1. health and fitness
2. disease

Inhoud
23e Internistendagen
Abstractboek
13-15 april 2011
MECC, MAASTRICHT
Voorwoord/Introduction
3
I
Oral Presentations Research
4
II
Oral Presentations Case reports
24
III
Endocrinology Research
48
IV
Endocrinology Case reports
50
V
Diabetes Mellitus Research
58
VI
Diabetes Mellitus Case reports
61
VII
Haematology Research
62
VIII
Haematology Case reports
63
IX
Oncology Research
71
X
Oncology Case reports
72
XI
Vascular Medicine Research
80
XII
Vascular Medicine Case reports
83
XIII
Gastro-Enterology Research
86
XIV
Gastro-Enterology Case reports
88
XV
Infectious Diseases Research
92
XVI
Infectious Diseases Case reports
93
XVII
Nephrology Research
XVIII
Nephrology Case reports
111
XIX
Intensive Care Research
113
XX
Intensive Care Case reports
115
XXI
Rheumatology Research
117
XXII
Rheumatology Case reports
118
XXIII
General Internal Medicine Research
120
XXIV
General Internal Medicine Case reports
124
XXV
Immunology/Allergology Research
136
XXVI
Immunology/Allergology Case report
136
109
XXVII Other Research
137
XXVIII Other Case reports
138
Index
139
1
V OO R W OO R D / I N T R ODU C T I ON
Voorbereidingscommissie
Mw. Dr. H.A.H. Kaasjager
Dr. M.A. van Agtmael
Prof.drs. J.F.W.M. Bartelsman
Prof.dr. J.W. Cohen Tervaert
Dr. P.W. Kamphuisen
Dr. E.J.P. de Koning
Mw. Dr. A. Reyners
Mw. Dr. A.W. Rijneveld
Mw. Dr. F. Waanders (JNIV)
Met genoegen presenteer ik u het abstractboek van de 23e Internistendagen, die worden gehouden van 13 tot 15 april 2011
in het MECC te Maastricht.
De abstracts betreffen zowel wetenschappelijk onderzoek als casereports. Uit alle windrichtingen zijn de abstracts in grote
getale ingestuurd. Er zijn 259 abstracts ingediend, die zijn opgenomen in dit abstractboek. Uit deze abstracts werden 84
abstracts geselecteerd voor orale presentatie. Deze worden eerst vermeld, gevolgd door de overige abstracts, geclassificeerd
per vakgebied. De selectie is gebaseerd op wetenschappelijke inhoud, originaliteit en presentatie. De selectie gebeurt
anoniem (auteurs en instituut worden geblindeerd) door drie leden van de commissie. De abstracts met de hoogste scores
zijn geselecteerd voor orale presentatie. Ook dit jaar is er voor gekozen de abstracts zoveel mogelijk per onderwerp te
bundelen in de verschillende sessies.
Deelnemende verenigingen
Nederlandse Internisten Vereniging (NIV)
Internistisch Vasculair Genootschap
Juniorafdeling Nederlandse Internisten Vereniging
Nederlandse Federatie voor Nefrologie
Nederlandse Vereniging voor Allergologie
Nederlandse Vereniging voor Diabetes Onderzoek
Nederlandse Vereniging voor Endocrinologie
Nederlandse Vereniging voor Gastro-Enterologie
Nederlandse Vereniging voor Haematologie
Nederlandse Vereniging voor Immunologie
Nederlandse Vereniging voor Intensive Care
Nederlandse Vereniging voor Klinische Farmacologie
Nederlandse Vereniging voor Medische Oncologie
Nederlandse Vereniging voor Medisch Onderwijs
Nederlandse Vereniging voor Oncologie
Nederlandse Vereniging voor Vasculaire Geneeskunde
NIV Sectie Acute Interne Geneeskunde
NIV Sectie Ouderengeneeskunde
Vereniging voor Infectieziekten
Het grote aantal ingezonden abstracts onderschrijft dat dit een belangrijk onderdeel is van de Internistendagen. In de
eerste plaats voor de arts-assistenten omdat de Internistendagen een uniek podium zijn om resultaten van onderzoek of
bijzondere observaties te presenteren aan een enthousiast publiek. In de tweede plaats voor de toehoorders, die kunnen
vernemen wat er gebeurt aan het front van de Interne Geneeskunde in Nederland en in de derde plaats om de diverse
onderzoeksgebieden binnen de Interne Geneeskunde met elkaar in contact te brengen. Ook dit jaar zal per sessie een
winnaar worden aangewezen die een prijs van 500 euro overhandigd zal krijgen!
Namens de hele Commissie Internistendagen wens ik u veel plezier toe met het lezen maar vooral aanhoren van de
vaak gloednieuwe onderzoeksresultaten en het oplossen van de leerzame puzzels in de casereports uit alle klinieken van
Nederland!
Organiserende vereniging
Dr. H.A.H. Kaasjager
Voorzitter Commissie Internistendagen
Nederlandse Internisten Vereniging
(Medicinae Internae B.V.)
Postbus 20066
3502 LB Utrecht
Tel.: 030-282 32 29
Fax: 030-282 32 25
www.internistendagen.nl/www.internisten.nl
This abstract book contains all abstracts that have been submitted to the Annual Meeting of the Netherlands Association of
Internal Medicine, 13-15 april 2011 in Maastricht, the Netherlands. Both research abstracts and case reports are included, representing all disciplines of Internal Medicine, 84 abstracts have been selected for oral presentation. These abstracts are printed first,
in the order of presentation. The remainder of abstracts is categorized according to discipline.
Congressecretariaat
Congress & Meeting Services Holland
Postbus 18
5298 ZG LIEMPDE
Tel. 0411-633476
Fax 0411-633805
E-mail: internistendagen@congresservice.nl
Dr. H.A.H Kaasjager
Chairman Organizing Committee
Uitgever
Van Zuiden Communications B.V.
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2400 CC Alphen aan den Rijn
Tel.: 0172-47 61 91
Fax: 0172-47 18 82
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© 2011
Overname van delen uit dit abstractboek kan alleen
plaatsvinden na schriftelijke toestemming van de
uitgever.
ISBN: 978-90-8523-153-0
2
3
I. ORAL PRESENTATIONS RESEARCH
1.
2.
CD20 directs cell positioning in secondary lymphoid
organs
T. van Meerten1 , R.S. van Rijn 2 , A. Hagenbeek 3 ,
A.C.M. Martens3, T. Mutis3
1
Gelderse Vallei Hospital, Department of Internal Medicine,
Willy Brandtlaan 10, 6716 RP EDE, the Netherlands,
e-mail: tvanmeerten@gmail.com, 2Erasmus Medical Centre,
ROTTERDAM, the Netherlands, 3University Medical Centre
Utrecht, UTRECHT, the Netherlands
Tipping the Noxa/Mcl-1 balance to overcome
ABT-737 resistance in chronic lymphocytic leukemia
M. Tromp, C.R Geest, T. Beaumont, A.P. Kater,
M.H.J. van Oers, E. Eldering
Academic Medical Centre, Department of Hematology,
Meibergdreef 9, 1105 AZ AMSTERDAM, the Netherlands,
e-mail: j.m.tromp@amc.uva.nl
Human CD20 is a B-cell restricted transmembrane
molecule and the most successful monoclonal antibody
targeted antigen, used worldwide to treat patients with
B-cell non-Hodgkin’s Lymphoma (B-NHL). Unfortunately,
the majority of B-NHL patients develops resistance to
anti-CD20 therapy, resulting in relapse of the disease.
Anti-CD20 antibody resistance is poorly understood and a
current focus of investigation.
Antibody resistance may be related to the interaction
of tumor cells via CD20 with the microenvironment.
However, although the CD20 molecule was discovered 30
years ago, its exact function is still unknown.
To explore the function of CD20, we used a system that
isolates human CD20 from
other B-cell surface molecules by retrovirally transferring
the human CD20 gene into normal human T-cells.
Initial in vitro assays comparing peptide-specific
CD20-positive T-cell clones with nontransduced parental
clones demonstrated no altered proliferative activity or
cytokine production associated with CD20 transduction.
We then injected a T-cell population containing 20%
CD20-positive T-cells into immune deficient RAG2-/-yc/-mice (n=10) to compare the distribution of the cells into
the organs with the distribution of normal human T-cells
(control mice n=10) and human B-cells (control mice n=5).
Immunohistochemical staining of the organs revealed
a remarkable phenomenon in all 10 spleens of the mice
that received the transduced T-cells: while normal T-cells
were scattered throughout the spleen, the CD20-positive
T-cells had positioned themselves periarteriolar in the
same way as the human B-cells do. In the other organs,
like the gut, liver and lungs, in contrast, the distribution
of the CD20-positive T cells did not differ from the normal
T-cells.
To confirm the hypothesis that the migration capacity of T
cells is altered following expression of the CD20 molecule,
we studied the influence of CD20 expression on T-cells
in in vitro transwell migration assays. In these assays
CD20-positive T-cells exhibited a 50% decreased migration
capacity towards stroma cells compared to the normal
T-cells (p=0.0075).
In summary, these data show that the CD20 molecule
directs the positioning of cells in secondary lymphoid
Introduction: Chronic Lymphocytic Leukemia (CLL)
is the most common leukemia in the Western world.
CLL is still an incurable disease despite new treatment
strategies developed in the last decade. Current treatment
of CLL is hampered by relapses, putatively originating
from lymph nodes (LNs) and novel therapeutic strategies
are warranted. In vitro CD40-stimulation of CLL cells
partially mimics the LN microenvironment by altering
levels of apoptosis-regulating Bcl-2 family members,
resulting in resistance to both known cytotoxic drugs as
well as novel drugs, such as the BH3 mimetic ABT-737,
that antagonizes the anti-apoptotic proteins Bcl-XL and
Bcl-2, but not Mcl-1 or Bfl-1. Currently, it is unclear which
anti-apoptotic proteins contribute to resistance towards
ABT-737 in CLL.
Aim: We used the CD40 in vitro system to investigate
the anti-apoptotic proteins associated with resistance to
ABT-737 and to determine whether combination of known
anti-leukemia drugs and ABT-737 resulted in apoptosis of
CLL cells.
Methods and results: To mimic the lymph node microenvironment, peripheral blood lymphocytes of CLL patients
were cultured in vitro on feeder cells expressing human
CD40L. We demonstrate that upon CD40-stimulation,
patient-specific variations towards resistance to ABT-737
developed, that correlated with differences in the relative
expression levels of Mcl-1 versus its antagonist Noxa (a
pro-apoptotic protein). Furthermore, Noxa knockdown,
as well as Mcl-1 overexpression, in human B cells by
retroviral transduction resulted in resistance to ABT-737,
corroborating the importance of the Noxa/Mcl-1 ratio in
the development of resistance to ABT-737. Promisingly,
increasing the Noxa/Mcl-1 balance, by lowering Mcl-1
with the tyrosine kinase inhibitor dasatinib or increasing
Noxa levels with the purine analogue fludarabine,
resulted in clear synergistic effects at low doses of
ABT-737.
Conclusions: Our in vitro data provide a rationale to
investigate the combination of fludarabine or dasatinib
with ABT-737 in a clinical setting as a novel treatment
modality for refractory CLL.
4
organs. Our findings indicate that CD20 holds back
further migration of the cells in order to take a periarteriolar position, which may be the optimal site for the physiological (T-cell independent) B-cell antigen recognition.
In addition, these data help to understand the role of
CD20-positive cells in their micro-environment, which
opens up new ways to conquer anti-CD20 antibody
resistance in the treatment of B-NHL.
of the AIx variation during tilting could be explained by
MAP and TR and 76% of the cfPWV variation by MAP
and by gender.
Conclusion: Instantaneous BP is a determinant of AIx
and cfPWV in AF patients. Moreover, changes in AIx
are unrelated to changes in cfPWV, indicating that
these measures of vascular stiffness provide different
information.
3.
4.
Instantaneous blood pressure is a determinant of
aortic augmentation index and pulse wave velocity:
observations in patients with autonomic failure
Near-peer teaching during the clerkship internal
medicine: a randomized cross-over trial
N. Wlazlo1 , B. Winkens2, C.P.M. van der Vleuten 2,
W.G. Peters1
1
Catharina Hospital, Department of Internal Medicine,
Michelangelolaan 2, 5623 EJ EINDHOVEN, the Netherlands,
e-mail: nick.wlazlo@cze.nl, 2 Maastricht University,
MAASTRICHT, the Netherlands
A.M.T. Huijben1 , F.U.S. Mattace-Raso2, J. Deinum3,
J. Lenders3, A.H. van de Meiracker2
1
St. Elisabeth Hospital, Department of Internal Medicine,
Tilburg, the Netherlands, e-mail: aukehuijben@hotmail.com,
2
Erasmus Medical Centre, ROTTERDAM, the Netherlands,
3
Radboud University Medical Centre, NIJMEGEN, the
Netherlands
Introduction and aim: The use of near-peer teaching in
procedural skills training and in PBL tutorial skills has
been proven equal to training by faculty or staff members.
However, it is unclear if senior students are also able to
teach theoretical matters in a clinical clerkship setting.
Therefore we compared the quality and desirability of
teacher-led versus student-led education in a randomized,
cross-over study.
Methods: Twenty-six fourth year medical students doing
an internship in internal medicine were given one hour
of theoretical education in general internal medicine once
a week. This training was alternatively provided by a final
year undergraduate medical student (senior student) and
a staff member (internist-haematologist). Students were
randomized into a group that started with the senior
student and a group that started with the internist. Topics
discussed were (differential) diagnosis and treatment of
common disorders in internal medicine, like anaemia,
jaundice, liver failure, fluid and electrolytes, thyroid
disorders, renal failure and haematological malignancies.
Each student evaluated 4 teaching sessions on a 16 item
questionnaire, and rated the session and the teacher.
Both grades and the mean score of the 16 items (overall
assessment) were compared using linear mixed models.
Results: Altogether, 92 questionnaires were obtained. The
grade for the senior student as tutor (8.38) was significantly
higher than for the internist (7.94; p=0.010). Moreover,
education sessions with the senior student received higher
grades than with the internist (8.28 vs. 7.80; p<0.001).
The overall assessment of the training (mean of 16 items)
was significantly higher for the senior student (8.31)
than for the internist (8.00; p=0.004). Scores at the item
level showed that this was due to more interactivity and
stimulation in a comfortable learning environment, as well
Introduction: Acute lowering of blood pressure (BP) with
vasodilating agents is associated with a reduction in
aortic augmentation index (AIx), whereas carotid-femoral
pulse-wave velocity (cfPWV) is largely unaffected.
Aim: We explored the effect of acute BP lowering on these
two indices of vascular aging, AIx and cfPWV, in patients
with autonomic failure (AF).
Materials and methods: In 10 AF patients (age 61±15 years,
4 males) and 14 age- and sex-matched controls finger
blood pressure was measured with the finometer device
(TNO-TPD Biomedical Instrumentation, Amsterdam)
and cfPWV, AIx, normalized for heart rate, and time to
aortic wave reflection (TR) with the SphygmoCor device
(AtCor Medical, Sydney). Measurements were performed
after subject had rested for 20 minutes in supine position
and during 300 and 600 passive head-up tilting by means
of motor-driven tilt table. Left ventricular ejection time
(LEVT) were derived from the finger blood pressure signal
using the BeatScope program (TNO-TPD Biomedical
Instrumentation, Amsterdam).
Results: At baseline mean BP (127.6±21.5 and
98.2±8.3 mmHg), AIx (32.4±13 and 20.4±12.2%) and
cfPWV (12.1±3.6 and 8.7±1.6 m.s-1) were higher in
patients than in controls. In patients, in response tot
30° en 60° MAP decreased by 18.7±9.8 and 39.6±11.6%,
LEVT by 11.5±3.2 and 20.4±5.5%, AIx by 39.2±27.5 and
100.9±78.1%, cfPWV by 12.0±10.5 and 27.5±13.5% and HR
increased by 5.2±7.7 and13.9±17.6% (all p<0.05), whereas
TR did not change. In patients the fall in BP and decreases
in AIx and cfPWV closely correlated (r=0.64, p=0.003
and r=0.74, p=<0.001). Postural decreases in AIx were not
related to changes in cfPWV. In adjusted analysis, 68%
5
as more overview and physiology in the senior student’s
training.
Conclusion: Teaching of theoretical matters by a senior
student received significantly higher assessments
compared with teaching by a staff member. However, it is
better to conclude that near-peer teaching produces similar
results, given the small differences in grades. These results
might be explained by cognitive and social congruence,
or teaching skills being more important than content
expertise. Near-peer teaching could therefore be implicated
in clinical internships, and might attenuate the work load
of specialists.
5.
related to the determination of ferritin (p<0.05). In total 75
(5.6%) patients were diagnosed with IDA and 181 (13,4%)
with ACD according to the DGPG. In only 1 patient with
ferritin levels between 15 and 100 mg/l an elevated serum
transferrin was established.
Conclusion: Anemia analysis according to Dutch General
Practitioners’ guidelines is followed only in the minority
of patients, possible leading to an underdiagnosis of for
instance IDA.
6.
Adherence to the protocollar approach in diagnosing
anemia in general practice; a retrospective cohort
study
Performance of four clinical decision rules in
the diagnostic management of acute pulmonary
embolism – the Prometheus diagnostic accuracy study
R.A. Douma1, I.C.M. Mos2, P.M.G. Erkens3, T.A.C. Nizet 4,
M.F. Durian5 , M.M. Hovens4 , A.A. van Houten6,
H.M.A. Hofstee7, F.A. Klok2, H. ten Cate3, E.F. Ullmann 4,
H.R. Büller1, P.W. Kamphuisen1, M.V. Huisman2
1
Academic Medical Centre, Department of Vascular Medicine,
Meibergdreef 9, 1105 AZ AMSTERDAM, the Netherlands,
e-mail: r.a.douma@amc.uva.nl, 2Leiden University Medical
Centre, LEIDEN, the Netherlands, 3Maastricht University
Medical Centre, MAASTRICHT, the Netherlands, 4Rijnstate
Hospital, ARNHEM, the Netherlands, 5Erasmus Medical
Centre, ROTTERDAM, the Netherlands, 6Maasstad Hospital,
ROTTERDAM, the Netherlands, 7VU University Medical
Centre, AMSTERDAM, the Netherlands
J. Droogendijk1, P.B. Berendes2, R. Beukers2, P. Sonneveld1,
M-D. Levin2
1
Erasmus Medical Centre, Department of Haematology,
’s-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: j.droogendijk@erasmusmc.nl, 2 Albert
Schweitzer Hospital, DORDRECHT, the Netherlands
Background: Iron deficiency anemia (IDA) is often
encountered by general practitioners and other clinicians.
Although IDA is a clinically relevant diagnosis, it often is
difficult to recognize and distinguish from other causes of
anemia such as anemia of chronic disease (ACD). For this
reason guidelines are developed such as the Dutch General
Practitioners’ guideline (DGPG).
Aim: To retrospectively study the adherence of general
practitioners to the DGPG in case of patients with newly
discovered anemia.
Materials and methods: We retrospectively evaluated all
laboratory tests of patients with a new anemia diagnosed by
general practitioners in the region of the Albert Schweitzer
hospital from January 1st 2004 until 31 December 2005.
We included women older than 50, in order to exclude a
predominance of iron deficiency due to menstrual blood
loss, and men 18 years and older with no diagnosis of
anemia in the previous two years.
Results: In two years time 1342 men and postmenopausal
women were diagnosed with a newly discovered anemia
by 63 participating general practitioners. 1103 patients
(82%) displayed a normocytic anemia (mean corpuscular
volume between 80 and 100), 131 (10%) microcytic (MCV
below 80) and 65 (5%) macrocytic (MCV higher than 100).
Ferritin, soluble iron, transferrin and total iron binding
capacity were determined in 396 (32%), 367 (30%), 344
(28%) and 338 (27%) of patients with normocytic and
microcytic anemia, respectively. Lower haemoglobin, lower
MCV, male gender and higher creatinin were significantly
Introduction: Pulmonary embolism (PE) is a frequently
occurring and potentially fatal condition. Correct exclusion
of the diagnosis demands a simple yet accurate diagnostic
strategy. Several clinical decision rules (CDRs) are available
for the exclusion of acute PE, including recently introduced
simplified scores. However, these scores have not been
directly compared.
Aim: To directly compare the performance of four CDRs
(Wells rule, revised Geneva score, simplified Wells rule
and simplified revised Geneva score) in excluding PE in
combination with D-dimer testing.
Materials and method: Design: A prospective cohort
study was performed including consecutive patients with
suspected acute PE from seven academic and non-academic
Dutch hospitals. The clinical probability of PE was assessed
using a computer program, which calculated all CDRs
and indicated the next diagnostic step. Clinical care was
guided by the results of the CDRs and D-dimer results. A
‘PE unlikely’ result according to all CDRs in combination
with a normal D-dimer result excluded PE, while patients
with ‘PE likely’ according to at least one of the CDRs or an
abnormal D-dimer result underwent CT-scanning. CDR
results were compared with PE prevalence indentified by
CT-scanning or venous thromboembolism during 3-month
follow-up.
6
Results: 807 consecutive patients were included; PE
prevalence was 23%. The number of patients categorized
as ‘PE unlikely’ ranged from 62% (simplified Wells
rule) to 72% (Wells rule); PE prevalence was comparable
(13-16%). Combined with a normal D-dimer level, the
CDRs excluded PE in 22-24% of patients. The total failure
rates of the CDR-D-dimer combinations were similar (1
failure, 0.5- 0.6%, upper 95% CI 2.9- 3.1%). Despite 30% of
the patients had discordant CDR outcomes, PE was missed
in none of the patients with discordant CDRs and a normal
D-dimer result.
Conclusions: All four CDRs show similar performance
for exclusion of acute PE in combination with a normal
D-dimer level. This prospective validation indicates that
the simplified scores may be used in clinical practice.
7.
Materials and methods: Open-label, single-arm,
multiCentre clinical trial of patients with objectively
proven acute pulmonary embolism, conducted in twelve
hospitals in the Netherlands from 2008 to 2010. Patients
with acute PE were triaged with eleven predefined Hestia
criteria for eligibility for outpatient treatment starting with
therapeutic weight adjusted doses of LMWH (Nadroparin),
followed by vitamin K antagonists. All patients eligible for
outpatient treatment according to the Hestia criteria, were
sent home either immediately or within 24 hours after
PE was objectively diagnosed. Outpatient treatment was
evaluated with respect to recurrent venous thromboembolism (VTE), including PE or deep venous thrombosis
(DVT), major haemorrhage and total mortality during
initial LMWH treatment and three months follow up. We
considered outpatient treatment to be effective if the upper
limit of the 95% confidence interval of the incidence of
recurrent VTE would not exceed 7%.
Results: Of 297 included patients, who all completed
follow-up, 6 patients (2.0%; 95% confidence interval [CI],
0.8-4.3) had recurrent VTE (5 PE (1.7%), 1 DVT (0.3%)).
Three patients (1.0%, 95% CI 0.2-2.9) died during three
months follow-up, but none as a result of fatal PE. One
patient died of fatal intracerebral haemorrhage, the other
two patients died of progressive malignancy. In addition
to the patient with intracranial bleeding, one other patient
had a major bleeding event (0.7%, 95% CI 0.08%-2.4%).
Conclusion: Outpatient anticoagulant treatment is
potentially effective and safe for patients with pulmonary
embolism who have been selected with the Hestia
criteria. These data have to be confirmed by a randomized
controlled trial. (Dutch Trial Register NTR1319)
Outpatient treatment in patients with acute
pulmonary embolism: the Hestia study
W. Zondag 1 , I.C.M. Mos 1 , D. Creemers 2 ,
A.D.M. Hoogerbrugge3, O.M. Dekkers1, J. Dolsma 4,
M. Eijsvogel5, L.M. Faber6, H.M.A. Hofstee 7, M.M.C.
Hovens8, G.J.P.M. Jonkers9, K.W. van Kralingen1, M.J.H.A.
Kruip10, T. Vlasveld11, M.J.M. de Vreede12, M.V. Huisman1
1
Leiden University Medical Centre, Department of Vascular
Medicine, Albinusdreef 2, 2333 ZA LEIDEN, the Netherlands,
e-mail: w.zondag@lumc.nl, 2Haga Hospital, THE HAGUE,
the Netherlands, 3Spaarne Hospital, HOOFDDORP, the
Netherlands, 4Diaconessenhuis, LEIDEN, the Netherlands,
5
Medical Spectrum Twente, ENSCHEDE, the Netherlands,
6
Rode Kruis Hospital, BEVERWIJK, the Netherlands, 7VU
University Medical Centre, AMSTERDAM, the Netherlands,
8
Rijnstate Hospital, ARNHEM, the Netherlands, 9Rijnland
Hospital, LEIDERDORP, the Netherlands, 10Erasmus Medical
Centre, ROTTERDAM, the Netherlands, 11Bronovo Hospital,
THE HAGUE, The Netherland, 12Haaglanden Medical
Centre, THE HAGUE, the Netherlands
8.
Somatostatin receptor scintigraphy in sarcoidosis
P.M. van Hagen1, L.S.J. Kamphuis1, J.A.M. van Laar1,
P.L.A. van Daele1, G.S. Baarsma2, D.J. Kwekkeboom1
1
Erasmus Medical Centre, Department of Internal Medicine,
’s-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: p.m.vanhagen@erasmusmc.nl, 2Het
OogHospital, ROTTERDAM, the Netherlands
Introduction: Patients with pulmonary embolism (PE)
are initially treated in the hospital with low molecular
weight heparin (LMWH). The most recent guideline of the
American College of Chest Physicians on Antithrombotic
therapy 2008 reports some small studies on outpatient
treatment in patients with pulmonary embolism, which
suggest outpatient treatment in selected patients with PE
is potentially effective and safe but firm recommendations for clinical practice are lacking. Clinicians urgently
need reliable, easy-to-use selection criteria for selection of
patients with pulmonary embolism eligible for outpatient
treatment.
Aim: To evaluate the efficacy and safety of outpatient
treatment according to predefined criteria (Hestia criteria)
in patients with acute PE.
Objectives: Somatostatin receptor scintigraphy (SRS)
localizes granulomas by binding to somatostatin receptors
that are expressed in sarcoidosis, a granulomatous disease
frequently involving lungs, skin or eyes. We correlated
uptake patterns on SRS and to disease parameters.
Materials and methods: The degree of intensity (DoI) of
uptake and localization of sarcoidosis associated lesion (SAL)
in 218 patients were determined. DoI was compared with
serum angiotensin converting enzyme (ACE) and serum
soluble interleukin-2 receptor (sIL-2R). Typical patterns on
SRS were compared to conventional chest CT and -x-ray.
7
Results: Therapeutic and symptomatic response was seen
in four out of five (80%) patients in the observational
period of 12 weeks. This was accompanied by decreased
uptake on SRS and more than 15% reduction of pathological lymph node volumes on the CT-scan. Clinical
symptoms improved followed by a fall of the inflammatory
cytokines interferon-? (IFN-?) and interleukin-8 (IL-8).
Conclusion: Four out of five patients (80%) patients
were considered to benefit from the adalimumab
treatment within 12 weeks. The clinical improvement
was accompanied by more than 18% decrease of initially
elevated serum IFN-? en IL-8 levels.
This is the first study demonstrating both a trend in
clinical and biochemical improvement after adalimumab
treatment in chronic sarcoidosis.
Results: SRS was negative in 28 patients, 10 patients had
one -and 180 patients had more SAL. The DoI correlated
significantly with ACE (p<0.001) sIL-2R levels (p<0.01).
Mediastinal lesions together with either eye, salivary
glands, clavicular or hilar localizations on SRS demonstrated a significant characteristic pattern. All patients with
abnormal conventional tests had SRS uptake. Moreover, of
94 patients with normal radiological findings 49 expressed
pathological SRS uptake. In 36 of these 49 patients a lung
biopsy was taken, which revealed sarcoidosis in 31.
Conclusion: The DoI in SRS correlates with sarcoidosis
activity. SRS is more sensitive in diagnosing sarcoidosis,
even in patients with normal chest radiology. SRS therefore
provides a useful and sensitive imaging technique to
monitor organ involvement and therapy in patients with
sarcoidosis.
10.
9
Efficacy of adalimumab in sarcoidosis
J.A.M. van Laar 1 , L.S.J. Kamphuis1, W.K. Lam-Tse2,
W.A. Dik1, J. Bastiaans3, P.L.A. van Daele1, P. van Biezen1,
D.J. Kwekkeboom, R.W.A.M. Kuijpers1, H. Hooijkaas1,
G.S. Baarsma3, P.M. Van Hagen1
1
Erasmus Medical Centre, ’s-Gravendijkwal 230,
3015 CE ROTTERDAM, the Netherlands, e-mail:
j.vanlaar@erasmusmc.nl, 2Sint Franciscus Gasthuis,
ROTTERDAM, the Netherlands, 3Het OogHospital,
ROTTERDAM, the Netherlands
Steroid use and polymyalgia rheumatica predict
redundant temporal artery biopsy in patients with
suspected giant cell arteritis
A.N. den Brok, I. Thomassen, C.J.A.M. Konings,
S.W. Nienhuis, M.C.G. van de Poll
Catharina Hospital Eindhoven, Department of Internal
Medicine, Michelangelolaan 2, 5623 EJ EINDHOVEN, the
Netherlands, e-mail: avalon.d.brok@catharina-Hospital.nl
Introduction: Temporal artery biopsy (TAB) is the golden
standard for the diagnosis of giant cell arteritis (GCA).
This invasive procedure is experienced as unpleasant and
upsetting for many patients. The yield of TAB is low (< 35%
positive findings reported in the literature). In addition
due to the relatively high rate of false negative outcomes,
negative histology is sometimes ignored, making the
biopsy redundant.
Aim: To investigate clinical predictors of negative TAB
and to assess clinical factors associated with not attaching
clinical implications to a negative TAB.
Materials and methods: One-hundred thirty consecutive
patients undergoing successful TAB in our hospital were
retrospectively analyzed. Univariate analyses (X2-test) and
multivariate analyses (logistic regression analysis) were
performed to identify associated factors and independent
predictors for negative or redundant TAB.
Results: Histological examination showed 33 positive and
97 negative TABs. Univariate analyses showed that the
proportion of male patients with a negative TAB (48.5%) was
significantly higher than the proportion of male patients with
a positive TAB (15.2%) (p=0.001). In addition mandibular
claudication was present in 8.2% of the patients with negative
TAB versus 39.4% in patients with a positive TAB (p<0.001).
Also the prevalence of headache was significantly lower
in patients with a negative TAB (p=0.016). Interestingly,
the prevalence of polymalgia rheumatica was significantly
Introduction: Adverse effects and lack of specificity often
hamper the use of conventional immunosuppressive
drugs in patients with systemic sarcoidosis. Adalimumab,
a monoclonal antibody directed against the key cytokine
involved in sarcoidosis, tumor necrosis factor (TNF)-a, is
used in patients with various immunological disorders.
Improved specificity, hence less adverse effects are the
major advantages of this new class of drugs leading to
an exponentially increasing role in their clinical use.
However, few reports involving adalimumab in patients
with sarcoidosis have been published so far and are
restricted to case reports.
Aim: To investigate clinical and biochemical effects
of adalimumab therapy in chronically active systemic
sarcoidosis patients.
Material and methods: Five patients with active,
symptomatic and biopsy-proven systemic sarcoidosis
received adalimumab with an induction scheme of 160mg
at week 0, 80mg at week 2 and 40mg every other week for
the observational period of 12 weeks. Therapeutic efficacy
was monitored by computered tomography (CT)-scan,
somatostatin receptor scintigraphy (SRS), pulmonary
function tests, physical examination and various inflammatory parameters.
8
higher in patients with a negative TAB (9.1% vs. 28.9%,
p=0.021). Multivariate analysis identified male gender
(p=0.003), the absence of mandibular claudication (p=0.010)
an erythrocyte sedimentation rate (ESR) < 60 mm (p=0.030)
and a diagnosis of polymyalgia rheumatica (PMR) (p=0.023)
as significant independent predictors of a negative TAB.
In 29 patients using steroids at the time of TAB steroids
were continued despite a negative TAB. In 15 cases steroids
were started despite a negative TAB. In these patients
TAB was considered redundant. Uni- and multivariate
analyses identified an ESR < 60 mm (p=0.055), a diagnosis
or suspicion of PMR (p<0.001) and the start of steroids
before the biopsy (p<0.001) as independent predictors of
redundant TAB.
Conclusion: Temporal artery biopsy is often performed
without attaching clinical consequences and could be
refrained from in patients with a high clinical suspicion of
giant cell arteritis or polymyalgia rheumatica. Steroid use
and polymyalgia rheumatica are independent predictors of
such redundant temporal artery biopsy.
11.
for both the serum creatinine measurements and the
MDRD-eGFRs were calculated. We created crosstabs
to evaluate classification of patients when a Jaffe or an
enzymatic assay was used to estimate MDRD-eGFR
compared to when the ID-MS traceable MDRD was used.
Results: Bias depended strongly on the creatinine concentration. Jaffe vs. an enzymatic technique showed a bias
of 19% vs. 0% for the reference 52 mmol/l, and 0.8 vs.
2.3% for reference category 262 mmol/l, respectively.
Such deviations in creatinine measurements resulted in
erroneous CKD-staging. 23.4% vs. 14% of the 40-year-old
subjects with a CKD stage of 60-90 ml/min/1.73m2
(when the ID-MS traceable MDRD was used) were
classified in CKD stage 45-60 ml/min/1.73m2, when a Jaffe
technique respectively an enzymatic technique was used
to measure SCr. In the CKD stage 45-60 ml/min/1.73m2
77% compared to 87% of the 60-year-old patients would
have been correctly staged when a Jaffe respectively an
enzymatic technique was used to estimate GFR.
Conclusion: Accurate and precise measurements of
creatinine are required for a reliable estimation of GFR.
The enzymatic technique to measure serum creatinine
results in substantial less variability than the Jaffe
technique compared to ID-MS reference values, leading to
more reliable estimates of GFR. To allow improvement of
reliability of eGFR calculations, the enzymatic technique to
measure creatinine is preferable over the Jaffe technique.
Effect of analytic variations in serum creatinine
on eGFR assessment and chronic kidney disease
staging
I. Drion1, C. Weykamp2, C. Cobbaert 3, N. Kleefstra1,
H.J.G. Bilo1
1
Isala Clinics, Thomas à Kempisstraat, 8021 BB ZWOLLE,
the Netherlands, e-mail: i.drion@isala.nl, 2Streek Hospital
Koningin Beatrix, WINTERSWIJK, the Netherlands,
3
Amphia Hospital, BREDA, the Netherlands
12.
The anti-proteinuric effect of indomethacin is
associated with a renoprotective urinary biomarker
profile
M.H. de Borst1, F.L. Nauta1, L. Vogt 2, R. Gansevoort1,
G. Navis1
1
University Medical Centre Groningen, Department of Internal
Medicine, PO Box 30.001, 9700 RB GRONINGEN, the
Netherlands, e-mail: m.h.de.borst@int.umcg.nl, 2 Academic
Medical Centre, AMSTERDAM, the Netherlands
Introduction: Measurements of serum creatinine (SCr)
are increasingly supplemented with creatinine-based
estimations of glomerular filtration rate (eGFR). There
are different methods to assess SCr, however. Estimates
of GFR might be biased, depending on the technique of
SCr measurement used. Aim: To examine the degree of
variation and reproducibility of different methods of SCr
assessment in Dutch laboratories and its consequences for
eGFR and chronic kidney disease (CKD) staging.
Materials and methods: Cross-sectional study evaluating
SCr data from the external quality assessment program in
2009 from the Dutch external quality assessment organization for laboratories. All 139 participating laboratories
measured serum creatinine using a Jaffe method and/or
an enzymatic method. Reference values for creatinine (a
linearity sequence ranging from 52-262 mmol/l as assessed
by ID-MS) were determined by a Joint Committee for
Traceability in Laboratory Medicine (JCTLM) accredited
laboratory. GFR was estimated using the Modification of
Diet in Renal Disease (MDRD) formula in three virtual
age categories (40, 60 and 80 years). Bias and precision
Background: Under specific conditions, non-steroidal
anti-inflammatory drugs (NSAIDs) may be used to lower
therapy-resistant proteinuria. Despite their favorable antiproteinuric effect, NSAIDs may also have deleterious
renal effects, e.g. decreased GFR. Large-scale randomized
trials investigating the long-term renoprotective effects
of NSAIDs are lacking. We investigated whether
indomethacin reduces urinary biomarkers of glomerular
damage and, subsequently, proximal and distal tubular
damage. We also investigated whether indomethacin
reduces proteinuria-induced tubulo-interstitial inflammation, known to mediate progressive renal damage.
Methods: Chronic kidney disease (CKD) patients (n=16)
with preserved renal function and stable residual
9
Introduction: Fetal exposure to maternal hypercholesterolemia increases the extent of fatty-streak formation in fetal
aortas as well as the rate of progression, and may therefore
increase coronary heart disease (CHD) risk later in life.
Aim: To determine whether the risk of CHD in untreated
individuals with familial hypercholesterolemia (FH) is
more extreme when the disease is transmitted maternally.
Materials and methods: In a large Dutch pedigree carrying
the V408M mutation in the low-density lipoprotein (LDL-)
receptor gene, 161 individuals over seven generations were
identified for which FH status and parent of origin of FH
was known. We calculated standardized mortality ratios
(SMR) and compared the consequences of maternal and
paternal inheritance of FH by Poisson regression analysis.
Results: Maternally inherited FH was associated with
significantly higher excess mortality than FH transmitted
by fathers (relative risk 2.2; p=0.048): the SMR of maternal
inheritance was 2.49 (95% confidence interval (CI)
1.45-3.99; p=0.001), whereas it was not significantly
increased in paternally inherited FH (SMR 1.30, 95% CI
0.65-2.32; p=0.234).
Conclusions: Mortality rates are more increased when
FH is inherited through the mother, supporting the fetal
origin of adulthood disease hypothesis with all cause
death, the most indisputable outcome measure. Future
research should explore safe options for cholesterollowering therapy of pregnant women with FH in order
to prevent unfavourable epigenetic consequences in their
children. When carefully extrapolating to the general
population, this study emphasizes the importance of a
healthy lifestyle and low LDL-cholesterol levels during
pregnancy.
proteinuria of 4.7±4.1 g/d were studied. After a wash-out
period of 4 wks without any RAAS blocking agents (CKD
baseline), patients received indomethacin 75 mg BID for 4
weeks (CKD+NSAID). Adequate and stable blood pressure
control was achieved during wash-out by non-RAAS
blocking antihypertensive agents. At the end of the study,
the 24h-excretion and plasma levels of total IgG, IgG4,
kidney injury molecule-1 (KIM-1), beta-2-microglobulin
(B2M), vitamin D binding protein (VDBP), neutrophil
gelatinase associated lipocalin (NGAL), N-acetyl-betaglucosaminidase (NAG), heart-fatty acid binding protein
(H-FABP) and monocyte chemotactic protein-1 (MCP-1)
were determined in duplo using ELISA. Biomarkers were
also determined in 24h urine of healthy kidney donors
(n=10). Data are presented as mean±SD.
Results: At baseline, proteinuria was 3.8±3.1 g/d and
reduced to 2.4±3.4 g/d by indomethacin (p<0.001). The
glomerular biomarkers total IgG (healthy controls 4±2 mg/d
vs.CKD baseline 299.2±361.5, p<0.0001, CKD+NSAID
163.2±247.0, p<0.01) and IgG4 (0.5±1.6 mg/d vs. 58.9±71.8,
p<0.0001 vs.17.4±18.8, p<0.001) were strongly increased
in CKD patients at baseline compared to healthy controls,
and strongly reduced by indomethacin. Some markers of
proximal tubular damage (KIM-1 [3.9±4.0 ug/d vs. 9.5±5.5,
p<0.01 vs.5.6±4.3, p<0.01], B2M [0.1±0.0 mg/d vs. 1.9±2.3,
p<0.05 vs.1.0±2.2, p<0.05], and VDBP [0.1±0.0 mg/d vs.
18.4±43.2, p<0.001 vs.14.3±37.1, p<0.05]) but not all (NGAL,
NAG) were reduced by the NSAID. The distal tubular
marker H-FABP was not affected by IND (0.3±1.6 ug/d vs.
60.1±62.4, p<0.0001 vs.60.6±107.6). Surprisingly the antiinflammatory drug indomethacin did not reduce urinary
excretion of the inflammation markers MCP-1 (1.0±0.9
ug/d vs. 1.9±1.1, p=0.01 vs.1.8±0.8) and NGAL, but did
reduce plasma MCP-1 levels (CKD baseline 0.23±0.13 ug/l,
CKD+NSAID 0.14±0.14, p=0.001).
Conclusion: The anti-proteinuric effect of indomethacin
is associated with strongly reduced urinary excretion of
biomarkers of glomerular damage. Although indomethacin
did not affect markers of tubulo-interstitial inflammation,
it did clearly reduce proximal tubular markers, probably as
a consequence of the anti-proteinuric effect.
13.
14.
Genetic variant of the scavenger receptor BI in
humans
M. Vergeer1 , S. Korporaal 2, R. Franssen1, I. Meurs2,
R. Out 2, G.K. Hovingh1, M. Hoekstra 2, J.A. Sierts1,
G.M. Dallinga-Thie1, M.M. Motazacker1, A.G. Holleboom1,
Th. van Berkel 2 , J.J.P. Kastelein 1, M. van Eck 2 ,
J.A. Kuivenhoven1
1
Academic Medical Centre, Department of Vascular Medicine,
Meibergdreef 9, 1105 AZ AMSTERDAM, the Netherlands,
e-mail: mennovergeer@hotmail.com, 2Gorlaeus Laboratories,
LEIDEN, the Netherlands
Maternal inheritance of familial hypercholesterolemia increases mortality
J. Versmissen 1 , I.P.G. Botden 1, R. Huijgen 2 ,
D.M. Oosterveer1, J.C. Defesche2, T.C. Heil1, A. Muntz1,
J.G. Langendonk 1, A.F.L. Schinkel1, J.J.P. Kastelein 2,
E.J.G. Sijbrands21
1
Erasmus Medical Centre, Department of Internal
Medicine, ’s-Gravendijkwal 230, 3015 CE ROTTERDAM,
the Netherlands, e-mail: Jorievers@hotmail.com, 2 Academic
Medical Centre, AMSTERDAM, the Netherlands
Introduction: In mice, the scavenger receptor class B
type I (SR-BI) is essential for the delivery of high-density
lipoprotein (HDL) cholesterol to the liver and steroidogenic
organs. Paradoxically, elevated HDL cholesterol levels
are associated with increased atherosclerosis in SR-BIknockout mice.
Aim: To elucidate the role of SR-BI in human metabolism.
10
Methods: We sequenced the gene encoding SR-BI in
persons with elevated HDL cholesterol levels and identified
a family with a new missense mutation (P297S). The
functional effects of the P297S mutation on HDL binding,
cellular cholesterol uptake and efflux, atherosclerosis,
platelet function, and adrenal function were studied.
Results: Cholesterol uptake from HDL by primary murine
hepatocytes that expressed mutant SR-BI was reduced to
half of that of hepatocytes expressing wild-type SR-BI.
Carriers of the P297S mutation had increased HDL
cholesterol levels (1.8 mmol per liter, vs. 1.4 mmol per liter
in noncarriers; p<0.001) and a reduced capacity for efflux
of cholesterol from macrophages, but the carotid artery
intima-media thickness was similar in carriers and in
family noncarriers. Platelets from carriers had increased
unesterified cholesterol content and impaired function.
In carriers, adrenal steroidogenesis was attenuated,
as evidenced by decreased urinary steroid excretion, a
decreased response to corticotropin stimulation, and
symptoms of diminished adrenal function.
Conclusion: We identified a family with a functional
mutation in SR-BI. The mutation carriers had increased
HDL cholesterol levels and a reduction in cholesterol efflux
from macrophages but no significant increase in atherosclerosis. Reduced SR-BI function was associated with altered
platelet function and decreased adrenal steroidogenesis.
15.
Aim: To investigate whether circulating PCSK9 levels
are associated with the FCHL phenotype and – when
positive – to determine the strength of its heritability.
Secondly, to study the response in PCSK9 levels to
treatment with standard lipid lowering therapy.
Materials and methods: Plasma PCSK9 levels were
measured with a sandwich ELISA (developed by Eli Lilly
and company) in FCHL patients (n=45), their normolipidemic relatives (n=139) and spouses (n=72). The heritability estimates for PCSK9, i.e. to what extent the variance
in plasma PCSK9 levels can be accounted for by genetic
factors, were calculated with SOLAR and FCOR. In
addition, PCSK9 levels were determined in eleven FCHL
patients before and after treatment with atorvastatin 40mg
once daily for eight weeks.
Results: Plasma PCSK9 levels (interquartile range) were
significantly higher in FCHL patients when compared to
normolipidemic relatives and their spouses: 96.1 (37.7132.9) versus 78.7 (60.6-100.3) and 82.0 (65.3-97.9) ng/ml,
p=0.004 and p=0.002, respectively. PCSK9 was positively
associated with both triglycerides and apolipoprotein B
levels (p<0.001). The latter relation was primarily accounted
for by LDL-apoliprotein B (r=0.31, p=0.02), but not by
VLDL-apolipoprotein B (r=0.09, p=0.49), as demonstrated
in a subgroup of subjects (n=59). Heritability calculations
for PCSK9 yielded estimates of 67 and 84% (p<0.0001).
Finally, circulating PCSK9 increased significantly from 122
to 150 ng/ml in eleven FCHL patients treated with atorvastatin 40mg once daily for 8 weeks (p=0.018).
Conclusion: This study demonstrates that plasma PCSK9
is a highly heritable trait that is associated with both FCHL
diagnostic hallmarks. These results warrant further studies
to unravel the exact role of PCSK9 in the pathogenesis this
genetic dyslipidemia. In this respect, the upstream sterol
regulatory element binding protein 2 (SREBP2) pathway
is of particular interest. Finally, the significant rise in
PCSK9 levels after statin treatment suggests that FCHL
patients could benefit from PCSK9 antagonizing therapy,
which is currently under development.
Circulating proprotein convertase subtilisin kexin
type 9 is a highly heritable trait of familial combined
hyperlipidemia
M.C.G.J. Brouwers1, M.M.J. van Greevenbroek1, J.S. Troutt2,
Angela Bonner Freeman2, Ake Lu3,
N.C. Schaper1, R.J. Konrad2, C.D.A. Stehouwer1
1
Maastricht University Medical Centre, Department
of General Internal Medicine and Endocrinology,
PO Box 5800, 6202 AZ MAASTRICHT, the
Netherlands,email:martijn.brouwers@maastrichtuniversity.nl,,
2
Eli Lilly and Company, INDIANAPOLIS, USA, 3University
of California Los Angeles, LOS ANGELES, USA
16.
Introduction: Familial combined hyperlipidemia (FCHL)
is the most prevalent genetic dyslipidemia in Western
Society. Its characteristic dyslipidemia is the consequence
of hepatic VLDL-overproduction – at a background of
insulin resistance – combined with an impaired clearance
of remnants and LDL-particles. Proprotein convertase
subtilisin kexin type 9 (PCSK9) is an important, inverse
regulator of LDL-particle clearance, since it promotes
the degradation of the LDL receptor in hepatocytes.
Furthermore, recent studies have suggested that PCSK9 is
also involved in VLDL-production. PCSK9 is therefore an
intriguing candidate to evaluate its involvement in FCHL.
Sensitivity, specificity and reproducibility of the
aldosterone-to-renin-ratio as a screening test for
primary aldosteronism – results of the dutch Arrat
study
P.M. Jansen, A.H.J. Danser, A.H. van den Meiracker
Erasmus Medical Centre, Department of Internal Medicine,
’s-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: jansen.pm@gmail.com
Background: The aldosterone-to-renin ratio (ARR) is a
widely used screening test for primary aldosteronism
(PA). A commonly adopted cut-off value according to
11
Objective: To describe the first results of renal sympathetic
nerve denervation for treatment of therapy resistant hypertension in Rotterdam, the Netherlands.
Design and methods: From September until December
2010 eight patients (mean age 48±8 years, 3 males) with
treatment resistant hypertension (defined as a blood
pressure above goal despite use of 3 or more antihypertensives) were treated with a new endovascular catheterguided technique, in which the renal nerves are denervated
through radiofrequency ablation via the lumen of the
renal arteries. Blood pressure and heart rate (mean of
10 automated measurements), estimated glomerular
filtration rate (GFR), plasma noradrenalin (as a marker for
sympathetic activity) and renin (as a marker for activity of
the renin-angiotensin system) were measured before and
1 week and 1 month after the procedure.
Results: Baseline blood pressure was 164±17/103±15 mmHg,
heart rate 83±24 bpm and GFR 72.9±14.5 ml/min. The
average number of antihypertensives was 5.3 (range 4-7).
Renal sympathetic nerve denervation was performed
uncomplicated in all patients. Four out of 8 patients
(baseline blood pressure 162±3/103±12 mmHg) showed a
marked decrease in blood pressure (136±16/84±16 mmHg
after 1 week and 137±9/85±7 mmHg after 1 month). The
other patients did not show any change in blood pressure.
Plasma noradrenalin concentration decreased from 402±97
to 308±103 pg/ml (p=NS) after 1 week and to 350±137 pg/
ml (p=NS) after 1 month. Plasma renin concentration at
baseline (median 13 uU/ml) did not change significantly
(16 uU/ml after 1 week and 18 uU/ml after 1 month). For
all 8 patients changes in SBP were not related to baseline
blood pressure or changes in plasma noradrenalin or
plasma renin concentration. Heart rate, GFR and number of
antihypertensives after 1 week and 1 month did not change.
Conclusion: In patients with therapy resistant hypertension
renal sympathetic nerve denervation was associated with
a response rate of 50%. The response was unrelated
to changes in plasma noradrenalin or plasma renin
concentration.
the Endocrine Society guidelines is 91 pmol/l per mU/l.
However, its sensitivity, specificity, and reproducibility have
not been studied extensively.
Objective: To characterize the main test characteristics of
the ARR.
Design and methods: In 99 patients with uncontrolled
hypertension (despite the use of at least 2 antihypertensive
drugs) plasma renin and aldosterone levels were assessed
twice with an interval of 2 to 4 weeks. Betablockers and/
or potassium sparing diuretics were discontinued at least
4 weeks before the first measurement. In all patients
an intravenous salt loading test (SLT) was performed.
Patients with a post-test plasma aldosterone concentration exceeding 235 pmol/l were considered to have PA.
Subsequently, aldosterone and renin measurements were
repeated in a subset of 64 patients after at least 4 weeks on
standardized treatment consisting of a calcium-channel
blocker and/or alphablocker. In the other 35 patients it
was not possible to change the antihypertensive regimen
due to very high blood pressure levels or side effects of
standardized treatment. Sensitivity and specificity were
calculated under random and standardized medication.
Reproducibility was evaluated by Bland-Altman analysis of
log-transformed ARR levels at the first (ARR1) and second
(ARR2) measurement. The 95% limits of agreement were
expressed as ARR1/ARR2 ratios.
Results: Fifteen patients had PA based on a positive SLT.
The other 84 patients were considered essential hypertensives (EH). The median ARR was 36.5 (range 6.2-295.5) in
PA patients versus 6.7 (0.2-65.7) in EH (p<0.001). Under
random medication the ARR had 33% sensitivity and 100%
specificity when a cut-off value of 91 was used. In the
subgroup receiving standardized treatment the ARR rose
from 10.3 (range 0.2-295.5) to 17.2 (0.9-438.6) (p<0.001).
However, sensitivity remained low at a level of 37.5% with
a specificity of 98.2%. Ninety-five percent of ARR1/ARR2
ratios were between 0.2 and 2.6 for PA patients, and
between 0.3 and 4.0 for EH patients.
Conclusion: When applying the commonly adopted ARR
cut-off value of 91, sensitivity for PA is low,even under
ARR-neutral medication,. Reproducibility is poor, stressing
the need for repeated measurement of the ARR.
On behalf of the Dutch ARRAT Investigators.
17.
18.
Renal sympathetic nerve denervation for the
treatment of resistant hypertension: first results in
Rotterdam, the Netherlands
The value of the mortality in emergency department
sepsis (MEDS) score, CRP, and lactate in predicting
28-day mortality of sepsis in a dutch emergency
department
M.A.W. Hermans, P. Leffers, L.M. Jansen,
Y.C.A. Keulemans, P.M. Stassen
Academic Hospital Maastricht, Department of Internal
Medicine, PO Box 5800, 6202 AZ MAASTRICHT, the
Netherlands, e-mail: p.stassen@mumc.nl
N.A.J. van der Linde, A.H. van den Meiracker
Erasmus Medical Centre, Department of Vascular Medicine,
’s-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: n.vanderlinde@erasmusmc.nl
Introduction: The tendency of sepsis to progress rapidly
and the benefit of early start of therapy emphasize the
12
importance of fast and adequate risk stratification in the
Emergency Department (ED). The Mortality in Emergency
Department Sepsis (MEDS) score was developed in the
U.S.A. to distinguish high- from low-risk patients that
present to the ED with sepsis.
Aim: This study aimed to (1) validate the MEDS score as a
predictor of 28-day mortality in ED sepsis patients in the
Netherlands, (2) investigate the value of C-reactive protein
(CRP) and lactate in predicting 28-day mortality and
compare these to the MEDS score.
Materials and methods: Cohort study in a Dutch secondary
and tertiary care university hospital. Patients were included
if they were seen by an internist in the ED, fulfilled the
criteria for (suspected) sepsis, and were admitted to the
hospital. Primary outcome was all-cause, in-hospital
mortality within 28 days of presentation.
Results: In our six-month study period, 331 patients
were included, of whom 38 (11.5%) died. Mortality varied
significantly per MEDS category: < 4 points (very low risk:
3.1%), 5-7 points (low risk: 5.3%), 8-12 points (moderate
risk 17.3%), 13-15 points (high risk: 40.0%), > 15 points
(very high risk: 77.8%). These mortality rates were higher
than those of the original validation study. The mortality
rate for CRP levels < 100 mg/ml was 7.6% (SD 2.2) vs.
14.9% for CRP levels > 100 mg/ml (p 0.039). For lactate
levels < 4, and > 4 mmol/l, mortality rates were 24.2% (SD
7.5) and 74.3 (SD 12.8), respectively. In ROC-analysis, the
MEDS score was better in predicting 28-day mortality than
CRP (AUCs 0.81 and 0.68, respectively). Lactate was not
measured in enough patients (47) for a valid evaluation, but
it seemed to predict mortality fairly (AUC 0.75).
Conclusion: The MEDS score is an adequate tool for
predicting mortality in patients with sepsis in a Dutch
ED population. CRP is less useful in this context. Lactate
appears to be a fair predictor of mortality, but needs to be
investigated more systematically in a larger population.
19.
of which endocarditis is the most common manifestation.
Q fever endocarditis requires long-term antibiotic treatment
and has poor prognosis if left untreated. The estimated risk
of developing Q fever endocarditis after primary infection
for patients with pre-existent valvulopathy was 39% in a
retrospective study, with the highest risk for patients with
prosthetic valves. In the Netherlands, there has been a large
outbreak of acute Q fever with over 4000 notified cases
since 2007, which allows a more precise estimation of the
risk for chronic Q fever in high-risk groups.
Aim: We studied the prevalence of chronic Q fever in an
endemic area in patients with a history of cardiac valve
surgery, including valve prosthesis.
Materials and methods: We identified patients with a
history of cardiac valve surgery from our cardiology
outpatient clinic and invited them by letter for microbiological screening. IgG antibodies to phase I and II antigens
of C. burnetii were tested by immunofluorescence assay.
If phase I IgG antibodies were present, polymerase chain
reaction (PCR) on blood for C. burnetii DNA was also
performed. Chronic Q fever was considered probable if
phase I IgG antibody titre was =1024 and proven in case of
positive C. burnetii PCR in blood.
Results: A total of 663 patients was identified with a history
of valve surgery and unknown C. burnetii serostatus. As of
January 2011, 200 patients had been invited for screening.
In total, 175 patients (87.5%) responded and were available
for serological screening. Of these, 31/175 patients (17.7%)
had phase I and/or phase II IgG antibodies against C.
burnetii, indicating a previous C. burnetii infection. In this
group, 2/31 patients (6.5%) had phase I antibodies titres
=1024, indicating probable chronic Q fever endocarditis.
C. burnetii PCR was negative for both patients.
Conclusion: Despite a seroprevalence of IgG antibodies against
C. burnetii of 17.7% in patients with a high risk of developing
chronic Q fever, only 6.5% of these patients had probable
chronic Q fever endocarditis. Compared to the previously
reported risk of 39% in case of valvulopathy, we found a
considerable lower percentage of patients who progressed to
chronic Q fever after C. burnetii infection. However, as chronic
Q fever can develop years after primary infection, further
follow-up of seropositive patients is warranted.
Low prevalence of Coxiella burnetii endocarditis in
patients with a history of cardiac valve surgery or
cardiac valve prosthesis in a Q fever endemic area
L.M. Kampschreur1 , J.J. Oosterheert 2, P.J. Lestrade3,
I.M. Hoepelman2, N.H.M. Nicole3, P. Elsman3, P.W. Wever3
1
University Medical Centre Utrecht/Jeroen Bosch Hospital,
Department of Internal Medicine and Infectious Diseases, PO
Box 85500, 3508 GA UTRECHT, the Netherlands, e-mail:
l.m.kampschreur@umcutrecht.nl, 2University Medical Centre
Utrecht, UTRECHT, the Netherlands 3Jeroen Bosch Hospital,
’s-HERTOGENBOSCH, the Netherlands
20.
A randomized study comparing no treatment with
24 or 60 weeks of antiretroviral treatment during
primary HIV infection
M.L. Grijsen1 , R. Steingrover2 , F.W.N.M. Wit 2 ,
S. Jurriaans1, A. Verbon3, K. Brinkman4, M.E. van der Ende5,
R. Soetekouw6, F. de Wolf7, J.M.A. Lange2, H. Schuitemaker1,
J.M. Prins1
1
Academic Medical Centre, Department of Internal Medicine,
Division of Infectious Diseases, Tropical Medicine and AIDS,
Introduction: Q fever is a zoonosis caused by Coxiella
burnetii. Following primary infection, which is often
asymptomatic, 1-5% of patients develop chronic Q fever,
13
Conclusions: Temporary cART during PHI lowers the viral
setpoint and defers the start of cART during chronic HIV
infection.
Meibergdreef 91, 1105 AZ AMSTERDAM, the Netherlands,
e-mail: m.l.grijsen@amc.nl, 2 Academic Medical Centre,
Amsterdam Institute for Global Health and Development,
AMSTERDAM, the Netherlands, 3Maastricht University
Medical Centre, MAASTRICHT, the Netherlands, 4Onze
Lieve Vrouwe Gasthuis, AMSTERDAM, the Netherlands,
5
Erasmus Medical Centre, ROTTERDAM, the Netherlands,
6
Kennemer Gasthuis, HAARLEM, the Netherlands, 7Stichting
HIV Monitoring, AMSTERDAM, the Netherlands
21.
Evaluation of a novel leptospirosis test in a Dutch
population
A.M. Zonneveld1, W.E. Fiets1, M.L. Hijmering2, J. Weel3
1
Medical Centre Leeuwarden, Department of Internal
Medicine, Henri Dunantweg 2, 8934 AD LEEUWARDEN,
the Netherlands, e-mail: a.m.zonneveld@mdl.umcg.nl, 2Isala
Clinics, ZWOLLE, the Netherlands, 3Izore, LEEUWARDEN,
the Netherlands
Background: Management of primary HIV infection (PHI)
remains controversial. We assessed the clinical benefit
of temporary combination antiretroviral therapy (cART)
during PHI.
Methods: Patients with laboratory evidence of PHI were
randomly assigned to receive no treatment, 24 or 60 weeks
of cART (3-way randomization). If therapy was clinically
indicated, subjects were randomized over the 2 treatment
arms. Primary endpoints were the viral setpoint, defined as
the plasma viral load (pVL) 36 weeks after randomization
in the no treatment arm and 36 weeks after treatment
interruption in the treatment arms, and the total time that
patients were off therapy, defined as the time between
randomization and start of cART in the no treatment arm,
and the time between treatment interruption and restart of
cART in the treatment arms. cART was (re)started in case
of confirmed CD4 count <350 cells/mm3 or symptomatic
HIV disease. Time off therapy was compared across
study arms using KM plots and multivariate Cox survival
analyses adjusted for confounding factors.
Results: 173 patients were randomized. The modified
ITT-analysis comprised 168 patients: 115 were 3-way
randomized and 53 2-way randomized. In the 3-way
randomized patients, mean age was 40 (SD 10) years, 96%
were men, 84% were MSM, 73% had a negative or indeterminate Western blot and 83% were symptomatic during
PHI. Mean viral setpoint was 4.8 (SD 0.6) log10 c/ml in the
no treatment arm, and 3.9 (1.1) and 4.2 (1.0) log10 c/ml in
the 24-and 60-week treatment arms (p<0.001). The mean
CD4 count at viral setpoint in the no treatment arm was
381 (SD 167) cells/mm3, and 571 (195) and 528 (263) cells/
mm3 in the 24- and 60-week treatment arms (p<0.001).
The median total time off therapy in the no treatment arm
was 0.7 (95% CI, 0.2-1.2) years compared to 3.1 (2.3-3.8) and
2.1 (0.4-3.8) years in the 24- and 60-week treatment arms
(Log-rank, p<0.001). Combining all treated patients, the
median total time off therapy was not different between the
24- and 60-week treated patients (p=0.14). In the adjusted
Cox analysis, independent predictors of time to (re)start
of cART were pVL at setpoint (HR for each 1 log10 c/ml
increase: 1.69 [95% CI 1.08-2.65], p=0.02), CD4 count at
viral setpoint (HR for 1 log10 cells/mm3 increase: 0.002
[0.0-0.03], p<0.001) and temporary cART during PHI (HR
0.36 [0.19-0.7], p=0.003).
Introduction: Leptospirosis is a bacterial infection which
is uncommon in the developed world. Most cases are mild
but some patients develop a severe infection with sepsis
and shock. The Microscopic Agglutination Test (MAT) is
the gold standard, however it is based upon serconversion,
which takes several weeks. The Leptocheck (Zephyr) is
a simple rapid serological test for leptospirosis, based
upon anti-IgM and can therefore be used in early disease.
Sensitivity and specificity have not been evaluated in a
non-endemic environment.
Aim: Evaluation of the sensitivity and specificity of the
Leptocheck and description of clinical features, treatment
and outcome leptospirosis in a Dutch cohort.
Materials and methods: Between January 2004 and
November 2008 we collected data for all patients with
a leptospirosis infection who were admitted to one
of the participating Centres. Data including clinical
features, treatment and outcome were collected from the
original medical records. The MAT was performed by the
laboratory of Tropical Diseases (KIT) in Amsterdam. The
Leptocheck was performed by experienced staff at the
Laboratory of Infectious Diseases in Leeuwarden (Izore)
and they were blinded for all previous test results. We
added 50 sera of patients with Borrelia (n=15), Treponema
(n=10), acute EBV (n=15) and acute CMV (n=10) to evaluate
the specificity. Statistical significance was calculated with
the McNemar test.
Results: 28 Patients with leptospirosis were included.
Eight patients were admitted to the ICU, three of them
died. Mortality in this cohort was 15% and we found
permanent impaired renal function in 10% of patients. The
first MAT was positive in 10 of 28 patients, resulting in a
sensitivity of 36%. The Leptocheck in the same sera was
definite positive in 20/28 patients at admission resulting
in a sensitivity of 71%. In 3/28 patients the test was weakly
positive. Overall we found a sensitivity of 81% a specificity
of 95% for the Leptocheck (p-value 0,0098).
Conclusion: Establishing the diagnosis leptospirosis is
mainly based upon medical history, clinical signs and
14
symptoms. Early and aggressive treatment should be
started immediately. The Leptocheck is an excellent
and statistical significant better test for leptospirosis
with a higher sensititvity and specificity than the gold
standard: the MAT. Hopefully better and faster diagnostics
will improve outcome in leptospirosis, which is still
unacceptably high.
22.
higher than those reported in the original studies, using
the MEDS and CURB-65. Feasibility-analysis showed
missing laboratory items were the main reason why
scoring systems could not be calculated completely. The
MEDS, REMS and RAPS were most feasible since they
could be calculated completely in more than 99%.
Conclusion:
In this study, the MEDS score predicted mortality in
patients with sepsis visiting the ED best, although other
scoring systems predicted mortality also fairly well. The
MEDS, RAPS and REMS turned out to be most feasible.
Overall, the MEDS score was the most adequate tool for
predicting 28-day mortality in septic patients at the ED.
Validity and feasibility of risk stratification scoring
systems to predict 28-day mortality of septic patients
in a Dutch emergency department
P.M. Stassen1, J.M. Hilderink1, P. Leffers2, A.W. Hermans1,
C. Keulemans1
1
Academic Hospital Maastricht, Department of Internal
Medicine, MAASTRICHT, the Netherlands, e-mail:
pstassen@home.nl, 2Department of Epidemiology, Maastricht
University, MAASTRICHT, the Netherlands
23.
Genito-urinary tuberculosis: easy to diagnose?
M. Janssen1, C. Richter1, K. Hendricksen1, P.C. Weijerman1,
J.W.R. Meijer1, C. Erkens2, R.C.G. Bruijnen1
1
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
m3janssen@alysis.nl, 2KNCV Tuberculosis Foundation, THE
HAGUE, the Netherlands
Sepsis is a clinical syndrome which tends to progress
rapidly to severe sepsis or septic shock and leads to high
mortality rates. Early therapy has proven to decrease
mortality; therefore a reliable risk stratification tool that
quickly quantifies a patient’s risk of bad outcome would
be helpful.
Objectives: We selected six scoring systems. Our objectives
were a) to investigate which scoring system predicts
28-day mortality best in septic patients in an emergency
department (ED); b) to identify which scoring system is the
most feasible score for the ED setting.
Methods: This historical cohort study was performed in
our secondary and tertiary university hospital. Patients
were included when they visited the ED between August
2009 and August 2010, were seen by an internist in
the ED, fulfilled the clinical criteria for sepsis, and were
admitted to the hospital. The six scoring systems MEDS,
CURB-65, SOFA, APACHE II, RAPS and REMS were
assessed from patient charts and hospital databases.
Primary outcome was all cause in-hospital mortality within
28 days. The discriminating ability of the scoring systems
expressed as the area under the receiver operating characteristics (ROC) curve. Our observed mortality rates were
compared with mortality reported in the original studies to
assess the external validation. We assessed the feasibility of
every scoring system by calculating the number of patients
in which the score could be filled out completely in the ED.
Results: A total of 664 patients were included, of whom
83 (12.5%) died within 28 days. The median age was 64
years. ROC-analysis showed that the MEDS score predicted
mortality significant better than the RAPS and REMS
score (p<0.005) and had the highest area under the curve
(AUC =0.82, CI 0.77-0.87), although the other scoring
systems were also fair predictors. Our mortality rates were
Introduction: Genito-urinary tuberculosis (GUTB) is rarely
seen. In the Netherlands about 25 cases every year have
been detected over the last 10 years. Data of the national
tuberculosis register indicate that the diagnosis is often
made with a long doctor’s delay. Moreover, the diagnosis
can easily be missed if it is not considered by the clinician
and urine is not sent for specific TB examinations. The
consequences of (especially late detected) GUTB can be
severe like renal failure or infertility. In our hospital we
diagnosed five patients in the last four years with GUTB.
In a coproduction with urologists, a pathologist, a senior
TB consultant at KNCV Tuberculosis Foundation and a
radiologist we described these cases and hoped to provide
some clues for physicians to diagnose GUTB.
Cases: Two patients presented with a painless swelling
of one of their testicles, after orchiectomy the pathology
results showed a granulomatous inflammation. One of
the patients had been treated for pulmonary tuberculosis
(TB) about 30 years ago. Another patient presented with
a, accidentally found, sterile leukocyturia. Urine was sent
for TB examination and was positive. Retrospectively
he had a renal calcification for about six years. A fourth
patient, a woman, had symptoms of abdominal discomfort,
urine incontinence and bladder retention. The fifth
patient presented with a rectovesical fistula which needed
operation. He developed disseminated TB shortly after the
operation. This patient turned out to be HIV-positive.
Background: As the cases describe, GUTB can present on
different ways. Most patients complain of local symptoms
like hematuria, abdominal pain and incontinence. About
15
23% has symptoms like fever and general discomfort.
In the patients’ history a previous pulmonary TBC or
originally being form a TBC endemic country can lead
to the suspicion of GUTB. Radiographic clues are renal
calcification or signs of (old) pulmonary TB. When
granulomatous inflammation is found by pathological
examination, tuberculosis should be considered as a
possible diagnosis. When UGTB is suspected morning
urine should be collected for three mornings in a row and
be examined for Ziehl Neelsen, TB-cultures and PCR for
tuberculosis. Once the diagnosis is established, therapy
with tuberculostatics (rifampicin, isoniazide pyrazinamide
and ethambutol) should be started. In general treatment of
GUTB in the Netherlands is successful.
Conclusion: GUTB is rarely seen, but can have severe
consequences. It’s important to establish the diagnosis in
an early stage and start with tuberculostatics.
24.
pathways. MBL binding to its ligand was dose dependently
prevented by recombinant rP8, however MASP-2 activity
was unaffected. In addition, rP8 reduced complementmediated killing of B. burgdorferi s.l. by inhibiting
formation of C5b-9 membrane attack complexes in vitro.
Other complement effector functions, such as migration
of human neutrophils towards Borrelia-induced inflammation and phagocytosis of B. burgdorferi s.l. by human
neutrophils, were also inhibited by rP8. Importantly,
in vivo experiments, in which mice were intradermally
inoculated with Borrelia in the presence or absence of
rP8, showed that rP8 inhibited inflammation and influx
of leukocytes 18 hours after inoculation and we observed
higher Borrelia numbers in murine skin 2 weeks post
infection in mice inoculated with Borrelia in the presence
of rP8.
Conclusions: We here demonstrate, for the first time, that
the MBL complement pathway is crucially important in
the clearance of B. burgdorferi s.l. and that the novel tick
salivary protein P8 facilitates survival of Borrelia by specifically inhibiting the MBL complement pathway. Currently,
by RNAi in ticks and passive immunization studies in
mice, we are determining the role of P8 in tick feeding
and also Borrelia transmission, potentially identifying
P8 as a candidate for an anti-tick vaccine to prevent Lyme
borreliosis.
A novel tick MBL complement pathway inhibitor
facilitates survival of the causative agent of Lyme
borreliosis
T.J. Schuijt1 , J. Coumou 1, S. Narasimhan 2, J. Dai 2,
T. van der Poll1, E. Fikrig2, J.W.R. Hovius1
1
Academic Medical Centre, Department of Internal
Medicine, AMSTERDAM, the Netherlands, e-mail:
j.w.hovius@amc.uva.nl, 2Yale University, School of Medicine,
NEW HAVEN, CONNECTICUT, USA
25.
Introduction: Lyme borreliosis – caused by Borrelia
burgdorferi sensu lato and transmitted through Ixodes
ticks – is the most prevalent arthropod-borne disease
in the Western world. The estimated yearly incidence
is approximately 133/100.000 inhabitants in the
Netherlands. Upon entry of the spirochete into the
host skin it is subjected to the host immune system.
The complement cascade is a fundamental part of the
mammalian innate immune response against both
ectoparasites, e.g. Ixodes ticks, as well as the microbes
they transmit, including the causative agent of Lyme
borreliosis. Both ticks and Borrelia spirochetes are known
to employ several strategies to circumvent activation of
the complement system. Recently, using yeast display
technology, we have identified multiple novel tick salivary
proteins. One of these proteins, designated P8, was found
to have anti-complement activity.
Methods and results: In the current study, we demonstrate
that p8 is expressed early during tick feeding and is
upregulated in the presence of B. burgdorferi. Using
standardized complement activity assays, we show that
Drosophila-expressed recombinant P8 (rP8) specifically
inhibited the human Mannose-binding lectin (MBL)
complement pathway, but not the classical and alternative
The lectin-like domain of thrombomodulin impairs
host defense in murine pneumococcal pneumonia
M. Schouten1, J. de Boer2, C. van ’t Veer2, J.J.T.H. Roelofs2,
J.J.C.M. Meijers2, M. Levi2, T. van der Poll2
1
St Lucas Andreas Hospital, Department of Internal
Medicine, AMSTERDAM, the Netherlands, e-mail:
m.schouten@amc.uva.nl, 2 Academic Medical Centre,
AMSTERDAM, the Netherlands
Introduction: Thrombomodulin (TM) is an endothelial cell
glycoprotein that, via distant structural domains, interacts
with multiple ligands, thereby modulating coagulation,
fibrinolysis, complement activation and inflammation.
Recently, the lectin-like domain (LeD) of TM has been
shown to interfere with monocyte and neutrophil adhesion,
with complement activation and to block the activity of the
pro-inflammatory cytokine HMGB1; factors which play an
important role in bacterial infection. To date, the role of
TMLeD in severe infection, like pneumonia and sepsis,
is unknown. Worldwide, pneumococcal pneumonia is a
frequent cause of sepsis and mortality. We here determined
the role of TMLeD in our well established model of murine
pneumococcal pneumonia.
Aim: To determine the role of TMLeD in murine pneumococcal pneumonia.
16
Materials and methods: Ten weeks old wild-type (WT) and
TMLeD KO mice were infected intranasally with viable
<i>S. pneumoniae</i>. Animals were either observed in
a survival study or sacrificed at 6, 24 or 48 hours after
induction of pneumonia. Bacterial loads were determined
in lung, blood, spleen and liver homogenates. Lung
pathology was assessed. Pulmonary influx of neutrophils
was determined by Ly-6G staining and measurement
of levels of myeloperioxidase (MPO). Cytokine and
chemokine levels were measured in lung homogenates
and plasma. Activation of coagulation was determined by
measurement of lung thrombin-antithrombin complexes
(TATc).
Results: TMLeD KO mice had a markedly better survival
in pneumococcal pneumonia as compared to WT mice.
Moreover, at 48 hours after induction of pneumonia,
TMLeD KO had lower bacterial loads in blood and liver. At
this time point, TMLeD KO mice showed less lung inflammation as evidenced by lower lung histopathology scores,
less pulmonary neutrophil influx, MPO and chemokine
levels. Moreover, at 24 and 48 hours plasma cytokine
levels were lower in TMLed KO mice than in WT mice. In
addition, at 48 hours after infection, lung TATc levels were
lower in TMLeD KO mice than in WT mice.
Conclusion: In pneumococcal pneumonia, TMLeD plays a
detrimental role by hampering antibacterial defense at later
time points, which results in higher bacterial loads, more
pulmonary inflammation and activition of coagulation,
more systemic inflammation and a higher mortality.
Whether this can be attributed to a direct role of TMLeD
in bacterial killing or to a role of TMLeD in modulating
the inflammatory response in a negative way, needs to be
addressed.
26.
Introduction: Venous thrombosis has frequently been
reported in patients with Cushing’s syndrome (CS).
Aim: To evaluate the incidence of venous thromboembolism (VTE) in patients with CS prior to treatment onset
and after surgery, in a multicentre cohort study
Materials and methods: Medical records of all patients
with endogenous CS of benign origin were reviewed
among all university medical centres in the Netherlands.
All objectively confirmed VTE’s during three years prior
to, and three years after treatment onset, within the
study period of January 1st, 1990 to June 6th, 2010,
were documented. Patients surgically treated for
non-functioning pituitary adenoma served as a control
group for the incidence of post-operative VTE in adrenocorticotropic hormone (ACTH)-dependent CS. Incidences
of VTE were expressed as incidence rates.
Results: A total of 473 patients with CS (mean age 42 years,
363 women) were included (360 with ACTH-dependent
CS). The total number of person years was 2526.
Thirty-seven patients experienced a VTE during the
study period, resulting in an incidence rate of 14.6
(95% confidence interval [CI] 10.3-20.1) per 1000 personyears. The incidence rate for first-ever VTE prior to
treatment was 12.9 (95% 7.5-12.6) per 1000 person-years
(17 events). The risk of post-operative VTE, defined as
the incidence rate in three months after surgery, was 0%
for ACTH-independent and 3.4 (95% CI 2.0-5.9%) for
ACTH- dependent CS (12 events in 350 patients); most
events occurred between 1 week and 2 month after surgery.
Compared to the control group, the incidence rate ratio was
4.6 (95% CI 1.4-15.1%) for post-operative VTE in patients
undergoing transsphenoidal surgery for ACTH-dependent
CS.
Conclusion: Patients with Cushing’s syndrome are at high
risk of venous thromboembolism, especially during active
disease and after surgery. General guidelines on the choice,
intensity and duration of thromboprophylaxis are urgently
needed.
Incidence of venous thromboembolism in patients
with Cushing’s syndrome: a multicentre cohort study
D.J.F. Stuijver1, B. van Zaane1, J. Debeij2, S.C. Cannegieter2,
R.A. Feelders3 , W. de Herder 3 , A.R. Hermus 4 ,
M.A. Wagenmakers4, G. van den Berg5, M.N. Kerstens5,
E. Fliers6, P.M.J. Zelissen7, N. Schaper 7, M.L. Drent8,
O.M. Dekkers2, V.E.A. Gerdes1, A.M. Pereira2
1
Academic Medical Centre/Slotervaarthospital Amsterdam,
Department of Vascular/Internal Medicin,AMSTERDAM,
the Netherlands, e-mail: d.j.stuijver@amc.uva.nl, 2Leiden
University Medical Centre, LEIDEN, the Netherlands,
3
Erasmus Medical Centre, ROTTERDAM, the Netherlands,
4
Radboud University Medical Centre, NIJMEGEN,
the Netherlands, 5University Medical Centre Groningen,
GRONINGEN, the Netherlands, 6Academic Medical Centre,
AMSTERDAM, the Netherlands, 7University Medical Centre
Utrecht, UTRECHT, the Netherlands, 8VU University Medical
Centre, AMSTERDAM, the Netherlands
27.
The clinical effects of GLP-1 analogues added to
insulin treated type 2 diabetes
K. Hoogenberg
Martini Hospital Groningen, Department of Internal
Medicine, PO Box 30033, 9700 RM GRONINGEN, the
Netherlands, e-mail: k.hoogenberg@mzh.nl
Introduction: Type 2 diabetes mellitus (T2DM) is often
complicated by obesity and insulin resistance. These are
difficult to treat as lifestyle changes are tough and as blood
glucose (BG) lowering is often accompanied by weight
gain. GLP-1 analogues are a new pharmacologic modality
registered for T2DM patient on oral antidiabetics (OAD)
17
Introduction: Results from our randomized controlled trial
(RCT) showed that with continuous intraperitoneal (IP)
insulin infusion with an implantable pump it is possible
to achieve better glycemic control and quality of life (QoL)
compared to subcutaneous insulin administration in
patients with type 1 diabetes (T1DM) after 6 months of
therapy.
Aim: The aim of this analysis was to investigate patients
therapy choice, QoL and glycemic control 30 months after
the end of the trial.
Materials and methods: The 23 patients that ended the
RCT in 2007/2008 all continued to use the IP pump.
Last known HbA1c values were collected in the 1st quarter
of 2010. Status regarding therapy mode were extracted
from hospital records. A questionnaire regarding QoL
(SF-36, WHO-5), treatment satisfaction (DTSQ) and other
parameters was sent to patients in the 2nd quarter of 2010.
Paired t-tests were used to compare HbA1c at the end of the
IP study phase with mean HbA1c at follow up.
Results: In March 2010, 22 (12 female, 10 male) patients
were still treated with IP insulin, 1 patient (female) was
back on subcutaneous insulin due to neuropathic pains,
which the patient blamed the IP pump for.
Mean (SD) age at follow up was 46.6 (12.0) years; mean
(SD) diabetes duration at the start of the study was 22.6
(10.6) years; mean HbA1c 8.6 (1.1)%; HbA1c > 7.5% in 20
subjects; hypoglycemic events =5/week in 14 subjects.
HbA1c was collected at 2.3 (0.6) years (mean (SD)) after the
end of the study. Mean (SD) HbA1c was 7.7 (1.1)%. Compared
to the baseline HbA1c value, this is a significant reduction of
0.83% (CI; -1.3, -0.4). Compared to the end of the IP phase
of the trial, the results are comparable (0.2% (CI; -0.3, 0.7).
Regarding QoL, compared to baseline, at follow up scores
on the SF-subscales ‘social functioning’, ‘vitality’, ‘bodily
pain’, ‘general health‘ were significantly higher. Compared
to the end of the IP trial, scores are at the same level at
follow up.
Conclusion: Our analysis shows that with IP therapy it is
possible not only to improve glycemic control in the short
term, but to achieve sustained improvement in glycemic
control in patients with T1DM who were insufficiently
controlled previously despite intensified subcutaneous
insulin regimens. IP insulin therapy also continues to
improves quality of life parameters and has a high patient
satisfaction, with a low drop out rate (1 out of 23 of patients).
that decrease HbA1c and body weight. These benefits may
also account for T2DM on insulin. Limited experience in
these patient show a variable weight loss and conflicting
HbA1c effects.
Aim: To investigate the effects of GLP-1 on HbA1c, insulin
needs, body weight and costs of BG lowering medication
in T2DM patients on insulin therapy.
Materials and methods: GLP-1 was given to overweight
(BMI > 35 kg/m2), insulin treated T2DM patients according
to a prespecified protocol. Patients that started GLP-1
with OAD served as a comparison. HbA1c, body weight,
daily insulin, OAD, and side-effects were recorded. Costs
of BG therapy were calculated. Analysis of the outcome
parameters was done at the time intervals of 0 to 3, 3 to 6,
6 to 9, 9 to 12 and 12 to 18 months.
Results: A total of 157 patients (122 on insulin, 35 on OAD)
started GLP-1 treatment. 142 continued GLP-1 therapy and
15 stopped.due to side-effects or lack of effects. 120 patients
were analysed at 3 months follow-up, 81 at 6 months,57
at 9 months, 36 at 12 months and 9 at =18 months. At
baseline, body weight was 118± 1,8 kg (mean±SE), BMI
was 39,9± 0,5 kg/m2, HbA1c was 8,1± 0,1% and daily
insulin was 123± 8 U. Body weight decreased linearly:
-4,8±0,4 kg at 3 months, -6,4± 0,6 kg at 6 months, -6.4±
0,7 kg at 9 months, 7.3± 1,0 kg at 12 months and 6± 1,9 kg
at =18 months, p<0.001 for all. HbA1c improved with -0,6±
0,09% at 3 months (p<0.001) and did not decline further.
Overall insulin doses dropped with 33±16 U/day. Costs
were approximately reduced by v 20,– so that overall
extra costs of GLP-1 therapy were v 60,– per month. 38%
Patients reported nausea and/or vomiting and 8% had
other adverse events whereas 54% patients had no adverse
events.
Conclusion: GLP-1 analogues added to insulin in T2DM
decreases body weight in a linear fashion, improves HbA1c
values and is associated with significant decrease in
insulin need leading to a modest decrease in the costs of
these medication.
28.
Sustained improvement of glycemic control and
quality of life with continuous intraperitoneal insulin
infusion in type 1 diabetes after 2.5 years of follow-up
S.J.J. Logtenberg 1 , N. Kleefstra 2 , S.T. Houweling 3 ,
K.H. Groenier4, H.J.G. Bilo2
1
Isala Clinics, Department of Internal Medicine,
PO Box, 8000 GK Zwolle, the Netherlands, e-mail:
s.j.j.logtenberg@isala.nl, 2Diabetes Centre, Isala Clinics,
ZWOLLE, the Netherlands, 3Langerhans Medical Research
Group, ZWOLLE, the Netherlands, 4General Practice,
University Medical Centre Groningen, GRONINGEN, the
Netherlands
29.
Risk of cancer in patients on insulin glargine in
comparison to those on human insulin: results from
a large population-based follow-up study
R. Ruiter 1 , E. Visser 1, M.P.P. van Herk Sukel 2 ,
J.W.W. Coebergh1, H.R. Haak3, P.H. Geelhoed-Duivestijn 4,
S.M.J.M. Straus5, R.M.C. Herings2, B.H.Ch. Stricker1
18
1
30.
Erasmus Medical Centre, Department of Epidemiology,
PO Box 2040, 3000 CA ROTTERDAM, the Netherlands,
e-mail: r.ruiter@erasmusmc.nl, 2PHARMO Institute for Drug
Outcomes Research, UTRECHT, the Netherlands, 3Máxima
Medical Centre, EINDHOVEN, the Netherlands, 4Medical
Centre Haaglanden, THE HAGUE, the Netherlands, 5College
ter Beoordeling van Geneesmiddelen, THE HAGUE, the
Netherlands
Sustained cardiac remodeling after a short-term very
low calorie diet in type 2 diabetes mellitus
J.T. Jonker, M. Snel, S. Hammer, I.M. Jazet,
R.W. van der Meer, H. Pijl, A.E. Meinders, A. de Roos,
H.J. Lamb, J.A. Romijn, J.W.A. Smit
Leiden University Medical Centre, Department of
Endocrinology, Albinusdreef 2, 2333 ZA LEIDEN, the
Netherlands, e-mail: j.t.jonker@lumc.nl
Introduction: Several publications suggest an association
between certain types of insulin and cancer but with
conflicting results. However, whether use of different types
of insulin may be a cause of cancer is an issue of ongoing
debate.
Aim: To analyze the hypothesis that the use of insulin
glargine is associated with an increased risk of cancer in
comparison to the use of human insulin.
Methods: Data for this study were obtained from the
PHARMO Record Linking System which includes drug
dispensing records from community pharmacies linked
on a patient level to hospital discharge records of approximately 2.5 million individuals in the Netherlands. Only
incident users of insulin with prior use of oral glucose
lowering drugs (OGLD) were included. The association
between use of insulin glargine and cancer in comparison
to use of human insulin was analyzed using Cox proportional hazard models with cumulative duration of drug
use as a time-varying determinant. A fixed cohort analysis
as well as an as treated analysis were performed. The first
hospital admission with a primary diagnosis of cancer
was considered as main outcome; specified cancers were
analyzed as secondary outcome. Results were adjusted or
stratified for age, sex, number of other unique drugs used
in the year prior start of insulin, number of hospitalizations in the year prior to start of insulin, calendar time, the
number of days of oral glucose lowering drug use in the
year prior to start of insulin and use as of 1998, the average
dosage per insulin category over the previously dispensed
prescriptions, baseline dosage of first prescription of
insulin and type of OGLD use prior to start of insulin.
Results: 19,337 incident insulin users were enrolled, of
whom 878 developed cancer. Use of insulin glargine was
associated with a lower risk of malignancies in general
in comparison to users with a similar length of use of
human insulin (HR 0.73, 95% CI: 0.69-0.77); in contrast,
an increased risk was found for breast cancer (HR 1.39,
95% CI 1.08-1.79).
Conclusion: Users of insulin glargine had a lower risk
of cancer in general than those on human insulin.
The association might be a consequence of residual
confounding or competing risk. However, like a previous
study, we demonstrated an increased risk of the use of
insulin glargine on the risk of breast cancer.
Background: A very low calorie diet (VLCD) in patients
with type 2 diabetes mellitus (T2DM) results in cardiac
remodeling and improved diastolic function. It is unknown
how long these effects sustain after reintroduction of a
regular diet.
Objective: To assess the long-term effects of initial weight
loss by a VLCD on cardiac dimensions and function in
T2DM patients.
Materials and methods: Fourteen patients with insulindependent T2DM (mean±SEM: age 53±2 years; body mass
index (BMI) 35±1 kg/m2) were treated by a VLCD (450 kcal/
day) during 16 weeks. Cardiac function was measured by
magnetic resonance imaging before and after the 16-week
VLCD and again after 14 months of follow-up on a regular diet.
Results: BMI decreased from 35±1 kg/m2 to 28±1 kg/m2 after
the VLCD and increased again to 32±1 kg/m2 at 18 months
(both p<0.05 vs. baseline). Left ventricular (LV) end-diastolic
volume index increased after the 16-week VLCD (80±3
to 89±4 ml/m2, p<0.05) and remained increased after
14 months of follow-up (90±3 ml/m2; p<0.05 vs. baseline)
at comparable filling pressures. The improvement in LV
diastolic function after the 16-week VLCD, was sustained
after 14 months of follow-up (early (E)/atrial (A) diastolic
filling phase ratio: 0.96±0.07 (baseline); 1.12±0.06 (after
VLCD); 1.06±0.07 (18 months, p<0.05 vs. baseline)).
Conclusion: Weight reduction by a 16-week VLCD in
T2DM patients results in sustained cardiac remodeling and
improved diastolic function after 14 months of follow-up,
despite weight regain on a regular diet.
31.
Familial longevity is marked by enhanced insulin
sensitivity
C.A. Wijsman, M.P. Rozing, T.C.M. Streef land,
S. Le Cessie, S.P. Mooijaart, P.E. Slagboom,
R.G.J. Westendorp, H. Pijl, D. van Heemst
Leiden University Medical Centre, Department of
Ouderengeneeskunde, PO Box 9600, 2300 RC LEIDEN, the
Netherlands, e-mail: c.a.wijsman@lumc.nl
Introduction: The mechanisms involved in human
longevity are largely unknown. In the Leiden Longevity
Study, we recruited long-lived siblings (aged 90 years or
19
older) and their offspring (mean age 60 years) to study
familial determinants of longevity. These offspring show
a 30% lower mortality rate compared to the general
population. Their partners, whith whom they share their
environment, do not have this mortality benefit, implying
that the offspring have a familial predisposition for
longevity. Previously we showed that the offspring had
better glucose tolerance compared to their partners as
controls.
Aim: To compare insulin action between offspring from
long-lived nonagenarian siblings and controls.
Methods: We performed a two step hyperinsulinemiceuglycemic clamp in a subgroup of the Leiden Longevity
Study comprising 24 subjects of which 12 offspring and
12 controls.
Results: Offspring and controls were similar with regard
to sex distribution, age and body composition. During the
clamp study, a higher glucose infusion rate was required
to maintain euglycemia during 40 mU/m2/min insulin
infusion in offspring compared to controls (p=0.036),
reflecting higher whole body insulin sensitivity. After
adjustment for sex, age and fat mass, the insulin-mediated
glucose disposal rate was higher in offspring than controls
(42.5±2.7 vs. 33.2±2.7 mmol/kg * min, mean±SE, p=0.025).
The insulin-mediated suppression of endogenous glucose
production and lipolysis did not differ between groups
(all p>0.05). Furthermore, the glucose disposal rate was
positively and significantly correlated with the mean age
of death of the parents in both the whole group (p=0.007)
and the group of controls only (p=0.022).
Conclusion: Offspring from long-lived siblings are marked
by enhanced insulin sensitivity, suggesting a relation
between familial longevity and insulin action. Future
research will focus on identifying the underlying biomolecular mechanisms involved, with the aim to promote
health in old age.
32.
to the intensive care unit (ICU) have hypomagnesemia. For
the emergency department (ED) setting, no information on
this subject exists.
Aim: This study aimed to (1) assess the number of serum
magnesium determinations in the ED, (2) investigate the
indication for determination of magnesium status, (3)
determine the clinical implications of hypomagnesemia
in the ED.
Materials and methods: During a 3 month period (June
until September 2010), we evaluated the charts of patients
who visited the internist in the ED and in whom serum
magnesium level was determined. From these charts,
we retrieved why the magnesium level was determined,
symptoms of hypomagnesemia, probable causes
(medication, underlying disease) and other electrolyte
imbalances, in-hospital mortality, cardiac dysrhythmias
and treatment.
Results: During 3 months, 1286 patients visited the
ED. In 28 patients (2.2%), serum magnesium level was
determined. In 27 patients admitted to the ICU/medium
care unit (MCU), magnesium level was determined in 2
patients (7.4%) (later in 3 additional patients). Main reasons
for determining magnesium level were chemotherapy
(28.6%), gastro-intestinal loss (25%) and hypocalcemia
(10.7%).
In 10 patients (8 female, 2 male), magnesium was below
0.7 mmol/l, while in 2 of these, serum magnesium was
below 0.5 mmol/l. Three patients (30%) had symptoms
related to hypomagnesemia. No differences in mortality,
ICU/MCU admission or admission duration were observed
in those with a normal or low magnesium level.
The probable causes of hypomagnesemia were gastro-intestinal loss (30%), renal loss due to cisplatin use (20%) and 2
(20%) used protonpump inhibitors. Less common causes
were malnutrition and malabsorption due to pancreatic
insufficiency. Magnesium suppletion was adequate in 4
patients (40%).
Conclusion: Determination of serum magnesium levels
is thought to be important in critically ill patients, but is
determined in only a minority of internistic patients (2.2%)
visiting the ED. Gastro-intestinal loss and medication
(cisplatin, protonpump inhibitor) were at least in part
responsible for low magnesium status in the majority of
cases. Last, hypomagnesemia remained untreated in 60%
of the patients.
Determination and clinical implications of serum
magnesium in the emergency department (ED)
P.M. Stassen, Y.H.A.M. Kusters, M.J. Noeverman
Academic Hospital Maastricht, Department of Internal
Medicine, Karposthegge 19, 6225 KJ MAASTRICHT, the
Netherlands, e-mail: pstassen@home.nl
Introduction: Magnesium is a critical cofactor in
ATP-powered reactions; therefore hypomagnesemia can
have dramatic effects on metabolism. It also acts as a
calcium channel antagonist, thereby affecting any activity
driven by intracellular calcium concentration fluxes.
Hypomagnesemia is described to be one of the most
common electrolyte deficiencies. Approximately 10 to 20%
of hospitalized patients and 50 to 60% of patients admitted
33.
Cardiovascular drugs and sex differences in adverse
drug reactions causing hospital admissions
E.M. Rodenburg, B.H.Ch. Stricker, L.E. Visser
Erasmus Medical Centre, Department of Epidemiology, PO
Box 2040, 3000 CA ROTTERDAM, the Netherlands, e-mail:
e.rodenburg@erasmusmc.nl
20
Background: Cardiovascular disease in women is often
undervalued and drug effects of cardiovascular drugs
differ between the sexes because of pharmacokinetic and
pharmacodynamic differences. Adverse drug reactions
(ADRs) within these drug classes may have serious consequences, leading to hospital admission.
Aim: To study differences between men and women in
hospital admissions for adverse drug reactions due to
cardiovascular drugs.
Methods: We conducted a nationwide study of all hospital
admissions between 2000 and 2005 with data from the
Dutch National Medical Register. Relative risks were
calculated of hospital admissions due to the different cardiovascular drug groups for women compared to men. Risks
were adjusted for the total number of hospital admissions,
age and total number of prescriptions.
Results: In total, 14,207 of the hospital admissions (34% of
all ADR related admissions) were attributed to cardiovascular drugs (7,690 in women (54%; 95% CI 53%, 55%)).
‘Anticoagulants and salicylates‘ (n=8988), ‘high and low
ceiling diuretics‘ (n=2242) and ‘cardiotonic glycosides’
(n=932) were responsible for the majority of the ADR-related
hospital admissions. The most pronounced sex-differences
were seen within low ceiling diuretics (RR 3.44; 95% CI
2.66, 4.43), cardiotonic glycosides (RR 1.92; 95% CI 1.66,
2.21), high ceiling diuretics (RR 1.73; 95% CI 1.57, 1.91) and
coronary vasodilators (RR 0.66; 95% CI 0.56, 0.78).
Conclusion: Clear sex differences exist in ADRs requiring
hospital admission for different cardiovascular drug
groups. Sex differences should be taken into account in the
prescription and evaluation of drugs.
34.
childhood cancer survivors described small populations,
included one type of cancer or had a short follow-up time.
Aim: This study assessed long-term effects on reproductive endocrine status in adult male five-year survivors
of childhood cancer, evaluated treatment-related risk
factors for the occurrence of disturbances in reproductive
endocrinology and assessed the association between the
FSH level and the later need for assisted reproductive
techniques.
Methods: The study cohort included adult male five-year
survivors of childhood cancer treated in the Emma
Children’s Hospital/Academic Medical Centre between
1966 and 2003. Survivors who had reached the age of at
least 18 years on January 1st 2008 were eligible for this
study. Data concerning patient and treatment characteristics, endocrine status (FSH, LH and testosterone
levels), fertility and pregnancy outcome were collected.
Multivariate regression analyses were performed to
evaluate treatment-related risk factors for disturbances in
reproductive endocrinology. The diagnostic and predictive
values of elevated FSH levels and later need for assisted
reproductive techniques were evaluated.
Results: Data on reproductive endocrine status were
available for 488 survivors (86.4%) of the 565 male
survivors who visited the outpatient clinic for the first
time after their 18th birthday. The median follow-up
time until first visit to the outpatient clinic was 15 years
(range: 5.0-39.0 years). The prevalence rates of elevated
FSH levels and decreased testosterone levels were 33% and
12%, respectively. Use of procarbazine, cyclophosphamide,
vinca-alkaloids, other alkylating agents, pelvic/abdominal
irradiation, total body irradiation (TBI) and surgery of
the testicular region were identified as treatment-related
risk factors for elevated FSH levels, and TBI was the only
risk factor for a decreased testosterone level. During
the follow-up period, 73 men reported 120 conceptions,
which resulted in 103 live births. All men whose partners
conceived by assisted reproductive techniques (n=13) had
elevated FSH levels (sensitivity: 100%; 95% CI: 71%-100%)
and all male survivors with a normal FSH level did not
need assisted reproductive techniques (negative predictive
value: 100%; 95% CI: 89%-100%).
Conclusion: One third of adult male survivors of childhood
cancer has elevated FSH levels. FSH is a sensitive marker
for the need of assisted reproductive techniques in male
childhood cancer survivors.
Reproductive status in adult male long-term
survivors of childhood cancer
J.J.M. Claessens1 , K. Tromp1,2 , S.L. Knijnenburg 2,3 ,
H.J.H. van der Pal2,3, F.E. van Leeuwen 4, H.N. Caron2,
C.C.M. Beerendonk1, L.C.M. Kremer5
1
Radboud University Medical Centre Nijmegen,
Department of Obstetrics and Gynaecology, PO Box
9101, 6500 HB NIJMEGEN, the Netherlands, e-mail:
j.claessens@obgyn.umcn.nl, 2Emma Children’s Hospital/
Academic Medical Centre, Amsterdam, the Netherlands,
3
Academic Medical Centre, AMSTERDAM, the Netherlands,
4
the Netherlands Cancer Institute, AMSTERDAM, the
Netherlands
Introduction: Between the 1960s and 1990s, five-year
survival for childhood cancer increased from 23% to 70%
due to advances in treatment. Unfortunately, iatrogenic
reproductive failure and endocrine disturbances are
frequently encountered late effects which have major
impact on quality of life. Previous studies on late effects in
35.
Patient selection for oncology phase i trials – a multiinstitutional study of prognostic factors
M.H.G. Langenberg1, D. Olmos2, R. A’Hern3, S. Marsoni 4,
J. Tabernero5, C. Gomez-Roca6, J. Verweij7, P. Schoffski8,
J. Ern Ang3, N. Penel9, J.H.M. Schellens10, L. Gianni11,
21
A.T. Brunneto2, J. Evans12, R. Wilson13, C. Sessa14 ,
R. Plummer 14 , R. Morales5, J.C. Soria6, S.B. Kaye2,
M. Lolkema15
1
University Medical Centre Utrecht, Department of Medical
Oncology, Heidelberglaan 100, 3584 AX UTRECHT, the
Netherlands, e-mail: m.langenberg@umcutrecht.nl, 2The
Royal Marshden NHS Foundation Trust, SUTTON,
United Kingdom, 3The Institute of Cancer Research,
SUTTON, United Kingdom, 4Southern Europe New Drug
Organization Foundation, MILAN, Italy, 5Vall d’Hebron
University Hospital, BARCELONA, Spain, 6Institut
Gustav Roussy, VILLEJUIF, France, 7Erasmus Medical
Centre, ROTTERDAM, the Netherlands, 8University
Hospital Gasthuisberg, LEUVEN, Belgium , 9 Centre
Oscar Lambret, LILLE, France, 10the Netherlands Cancer
Institute, AMSTERDAM, the Netherlands, 11Fondazione
IRCCS Instituto Nazionale dei Tumoni, MILAN, Italy,
12
The Beatson West of Scotland Cancer Centre, GLASGOW,
United Kingdom, 13Centre for Cancer Research & Cell
Biology, QUEEN’S UNIVERSITY BELFAST, United
Kingdom, 14Instituto Oncologico della Svizzera Italiana,
BELLINZONA, Switzerland, 15University Medical Centre
Utrecht, UTRECHT, the Netherlands
number of metastatic sites, clinical tumour growth rate,
lymphocytes and WBC. Prognostic models for 90-day
mortality derived from these factors achieved specificities
> 85% and sensitivities of ~50%. These overall were not
superior to a previously published RMH score.
Conclusions: Patient selection using scores comprising 3 to
7 prognostic factors will reduce 90-day mortality in Phase I
trials by half. However, their adoption should be balanced
against a reduction in recruitment to Phase I studies by
20%. These data show that we can modestly improve the
risk/benefit ratio for participants in early clinical trials.
A further major improvement in patient selection will
be derived by the application of predictive molecular
biomarkers which reflect tumour and host biology.
BMI was not associated with OS in 730 patients who
participated in the CAIRO2 study, although a trend was
observed (median OS 16.6, 17.8, 21.0, and 21.4 months for
BMI categories I, II, III and IV, respectively; p=0.8068).
Conclusions: These results show that BMI is an
independent prognostic factor for survival in patients
receiving chemotherapy, but not in patients receiving
chemotherapy and targeted therapy. The possible decreased
efficacy of bevacizumab in obese patients may explain this
discrepant result. The role of BMI in patients receiving
targeted therapy should be further tested
36.
J. Hofland1, R.A. Feelders1, R. van der Wal1, M.N. Kerstens2,
H.R. Haak3, W.W. de Herder1, F.H. de Jong1
1
Erasmus Medical Centre, Department of Internal Medicine,
Dr. Molenwaterplein 50-60, 3015 GE ROTTERDAM, the
Netherlands, e-mail: j.hofland@erasmusmc.nl, 2University
Medical Centre Groningen, GRONINGEN, the Netherlands,
3
Máxima Medical Centre, EINDHOVEN, the Netherlands
Influence of body mass index on outcome in
advanced colorectal cancer patients receiving chemotherapy with or without targeted therapy
L.H.J. Simkens1, M. Koopman2, L. Mol3, G.J. Veldhuis4,
D. ten Bokkel Huinink5, E.W. Muller6, V.A. Derleyn7,
S. Teerenstra1, C.J.A. Punt1
1
Radboud University Medical Centre Nijmegen, Department
of Medical Oncology, PO Box 9101, 5600 HB NIJMEGEN,
the Netherlands, e-mail: l.simkens@onco.umcn.nl, 2University
Medical Centre Utrecht, UTRECHT, the Netherlands,
3
Comprehensive Cancer Centre East (IKO), NIJMEGEN, the
Netherlands, 4 Antonius Hospital, SNEEK, the Netherlands,
5
Diakonessenhuis, UTRECHT, the Netherlands, 6Slingeland
Hospital, DOETINCHEM, the Netherlands, 7Elkerliek
Hospital, HELMOND, the Netherlands
Introduction: The selection of appropriate cancer patients
for early clinical trials represents a challenge due to the
difficult underlying risk/benefit assessments. The main
ethical challenge for these studies is that therapeutic
utility is not a conventional primary endpoint of these dose
and toxicity-finding studies while potential patients are
vulnerable due to the presence of advanced, progressive
malignant disease coupled to the lack of standard
treatment options. Many reported studies have attempted
to address these issues but are severely limited due to small
patient numbers and larger inter-practice heterogeneity.
Aim: This study aims to define prognostic factors to guide
risk/benefit assessments using a large patients database
from multiple Phase I units.
Methods: Data were collected from 2182 eligible patients
treated in Phase I trials between 2005 and 2007 in
14 different institutions. We derived and validated
independent prognostic factors for 90-day mortality.
Results: The 90-day mortality was 16.5% with a drugrelated death rate of 0.4%. Trial discontinuation within
3 weeks occurred in 14% of patients, due to disease
progression in the majority.
Overall objective radiologic response rate was 9.82%,
disease stabilization rate at 3 and 6 months were 26.05%
and 10.1%, respectively. The proportion of patients who had
progressive disease at first imaging evaluation was 49.53%.
The median PFS was 10.9 weeks (95% CI: 10.2-11.5).
We derived and validated eight different prognostic
variables for 90-day mortality: performance status,
albumin, lactate dehydrogenase, alkaline phosphatase,
Introduction: Obesity is associated with an increased
risk of development and recurrence of colorectal cancer.
However, the role of obesity in advanced colorectal cancer
(ACC) patients is unknown. We investigated the effect of
body mass index (BMI) on overall survival (OS) in ACC
patients receiving systemic treatment in two large phase
III studies (CAIRO and CAIRO2, Dutch Colorectal Cancer
Group).
Patients and methods: Treatment data were obtained
and analyzed from 796 ACC patients who were treated
with chemotherapy in the CAIRO study, and in 730
ACC patients who were treated with chemotherapy plus
targeted therapy in the CAIRO2 study. Baseline height and
weight were used to assign patients to one of the following
BMI categories: I (< 18.5 kg/m2), II (18.5-24.9 kg/m2), III
(25.0-29.9 kg/m2) and IV (= 30.0 kg/m2).
Results: In 796 patients of the CAIRO study a high BMI
was associated with better median OS (8.0, 14.9, 18.4, and
19.5 months for BMI categories I, II, III, and IV, respectively; p=0.001), and was an independent prognostic factor
for OS in a multivariate analysis.
22
37.
Conclusion: Inhibin pro-aC is produced by the adrenal
gland and its serum levels may serve as a tumor marker
for adrenocortical carcinomas.
38.
Surgery in adrenocortical carcinoma; importance of
national cooperation and centralized surgery
I.G.C. Hermsen1 , T.M.A. Kerkhofs2, G. den Butter2,
J. Kievit3, C. Eijck 4, E. Nieveen van Dijkum5, H.R. Haak2
1
Máxima Medical Centre Eindhoven/Veldoven, Department of
Internal Medicine, De run 4600, 5504 DB VELDHOVEN, the
Netherlands, e-mail: i.hermsen@mmc.nl, 2Máxima Medical
Centre, EINDHOVEN/VELDHOVEN, the Netherlands,
3
Leiden University Medical Centre, LEIDEN, the Netherlands,
4
Erasmus Medical Centre, ROTTERDAM, the Netherlands,
5
Academic Medical Centre, AMSTERDAM, the Netherlands
Serum inhibin pro-alphaC is a tumor marker for
adrenocortical carcinomas
Introduction: The low incidence rate of adrenocortical
carcinoma requires a multidisciplinary approach in which
specialised surgery has an essential role as complete
resection of the primary tumour is the only chance of cure.
In order to improve patient care, insight into surgical
results within the ACC population is essential. In 2007, a
Dutch Adrenal Network Registry has been created encompassing care and outcome of patients treated for ACC in
the Netherlands since 1965. Using this database a study
was performed with the following objectives: (1) to gain
insight into surgical performance in the Netherlands, (2) to
compare surgical data with international literature.
Patients and methods: The data of 175 patients treated from
1965 until January 2008, were studied. The following data
were collected; age, gender, functionality of the tumour,
stage at diagnosis (ENS@T staging), surgical procedure,
completeness of surgery, disease recurrence, adjuvant
mitotane therapy, recurrence free survival and overall
survival.
Results: 149 patients were operated. Patients with complete
resection had significantly longer survival than patients
with incomplete resection (p=0.01). Patients operated in
a Dutch Adrenal Network centre had significantly longer
survival in both univariate (p=0.01) and multivariate
analysis (p=0.01). Significant longer survival was observed
in operated stage IV patients compared to non-operated
patients (p=0.00).
Conclusion: Our data confirm the relevance of national
cooperation and centralized surgery in ACC. In selected
patients with stage 4 disease surgery can be beneficial
in extending survival. On the basis of the retrospective
analysis surgery in the Netherlands will and can be
improved.
Introduction: The increased detection rate of adrenal incidentalomas and the lack of diagnostic accuracy of currently
available tests for differentiation between benign and
malignant adrenocortical disease emphasize the need for
novel tumor markers for adrenocortical carcinoma (ACC).
Aim: Since the inhibin a-subunit is expressed within the
adrenal cortex and inhibins can serve as ovarian tumor
markers, the role of serum inhibin pro-aC as tumor marker
for ACC was studied.
Materials and methods: In vivo regulation of adrenal
pro-aC secretion was investigated by adrenocortical
function tests. Serum inhibin pro-aC levels were measured
in controls (n=181) and patients with adrenocortical
hyperplasia (n=45), adenoma (ADA, n=32), ACC (n=32)
or non-cortical tumors (n=12). Steroid hormone, adrenocorticotrophin (ACTH) and inhibin A and B levels were
also estimated in subsets of patients. In ten ACC patients
samples were collected before and after treatment.
Results: Serum inhibin pro-aC levels increased after
stimulation with ACTH (p=0.043). ACC patients had
higher serum inhibin pro-aC levels than controls
(p<0.0001) and patients with adrenocortical hyperplasia,
ADA or other adrenal tumors (p=0.0003). Inhibin pro-aC
measurement in ACC patients had a sensitivity of 59% and
specificity of 84% for differentiation from ADA patients.
ROC analysis displayed areas under the curve of 0.87 for
ACC versus controls and 0.81 for ACC versus ADA (both
p<0.0001). Surgery or mitotane therapy was followed by a
decrease of inhibin pro-aC levels in all ACC patients tested
(p=0.0065).
23
39.
Sunitinib-induced hypothyroidism is associated with
induction of deiodinase type 3 activity and capillary
regression
well as a decreased vessel-to-follicle ratio in 5 high power
fields compared to controls (0.31±0.02 vs. 0.96±0.10;
p<0.0001).
Conclusion: Sunitinib induces thyroid dysfunction in both
patients and rats which is due to the combination of thyroid
capillary regression and alterations in T4/T3 metabolism.
M.H.W. Kappers1, J.H.M. van Esch1, F.M.M. Smedts2,
R.R. de Krijger1, K. Eechoute1, R.H.J. Mathijssen1, S. Sleijfer1,
F. Leijten1, A.H.J. Danser1, A.H. van den Meiracker1
1
Erasmus Medical Centre, Department of Internal Medicine,
’s-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: m.h.w.kappers@erasmusmc.nl, 2Reinier
de Graaf Gasthuis, DELFT, the Netherlands
Introduction: Blocking vascular endothelial growth factor
(VEGF)-mediated signaling by the VEGF receptor tyrosine
kinase inhibitor sunitinib is an established treatment for
various types of cancer, but is associated with thyroid
dysfunction.
Aim: To obtain more insight into the mechanisms causing
thyroid dysfunction.
Materials and methods: The effects of sunitinib on thyroid
function and thyroid hormone metabolism were studied in
patients with metastatic renal cell carcinoma or gastrointestinal stromal tumors participating in a retro- (n=108) or
prospective (n=15) study. In addition, in Wistar Kyoto rats
the effects of sunitinib administration (n=9) for 8 days and
sunitinib withdrawal (n=7) for 11days on thyroid function,
hepatic type 1 (D1) and type 3 (D3) deiodinase, urinary
thyroid hormone excretion, and thyroid histology were
assessed and compared to control rats (n=6).
Results: Retrospective analysis in patients demonstrated
that 42% of the 83 evaluable patients developed elevated
TSH levels (TSH > 5.0 mU/l), which in 14% of patients
was preceded by TSH suppression, occurring equally in
men and women. In 20% of patients with elevated TSH
levels, TSH rose above 10 mU/l. Prospective analysis in 15
patients showed an increase in TSH levels from 1.12±0.26
to 4.27±1.23 mU/l already after 10 weeks of treatment,
accompanied by a decrease in T3/rT3-ratio, indicating
enhanced thyroid hormone metabolism. Anti-thyroid
peroxidase antibodies did not change during treatment
with sunitinib. In rats on sunitinib, hepatic D3 activity was
increased (0.22±0.01 fmol/min/mg vs. 0.14±0.02 fmol/
min/mg) and D1 activity was decreased (12.6±1.2 pmol/
min/ml vs. 20.6±0.9 pmol/min/ml; p<0.05), accompanied
by decreased serum T4 (43.9±1.8 nmol/l vs. 61.3±3.7
nmol/l; p<0.05) and T3 levels (0.74±0.05 nmol/l vs.
0.94±0.05 nmol/l; p<0.05) compared to control rats.
Changes in both deiodinase activities were reversible after
treatment discontinuation, but thyroid hormone levels did
not normalize. Urinary excretion of T3 and T4 was very low
at baseline and did not change during sunitinib administration. Histological examination of haematoxilin-eosinstained thyroid sections showed a decrease in total vessel
number in rats on sunitinib (36±3 vs. 71±8; p<0.0001) as
II.
ORAL PRESENTATIONS CASE REPORTS
40.
A rare cause of febris eci: intravascular large cell
lymphoma
J.L. Witmer, W.M. Smit, G.J. Kootstra, Chr.H.H. ten Napel,
J. van Baarlen
Medical Spectrum Twente, Department of Internal Medicine,
Ariensplein 1, 7500 KA ENSCHEDE, the Netherlands, e-mail:
jorindewitmer@hotmail.com
Case: A 83-year-old female with a history of hypertension, hysterectomy and subclinical hypothyroidism was admitted to the hospital because of fever
and malaise. No abnormalities were found on physical
examination. Laboratory testing showed a normocytic
anemia, erythrocyte sedimation rate of 59 mm/h, mild
hyponatremia (132 mmol/l), and LDH 645 U/l (n <450).
Chest-X-ray, ultrasound of liver and spleen, and CT-scan
of thorax and abdomen revealed no abnormalities and no
explanation for the fever. Cultures of feces, sputum and
blood were all negative. A bone marrow biopsy showed
no abnormalities; the mycobacterial culture was negative.
Additional laboratory test revealed panhypopituitarism
without involvement of the pituitary-adrenal axis (TSH
0.73 mU/l, FT4 6.5 pmol/l, T3 < 0.62 nmol/l, IGF-1 32 mg/l,
ACTH 3.6 pmol/l, cortisol 0.5 mmol/l, prolactine 0.57 U/l,
LH < 1.0 U/l, FSH 8.2 U/l, oestradiol 140 pmol/l, urine
cortisol 560 nmol/24h). An MRI of the brain showed a
considerably large pituitary gland (9 mm) compatible with
an adenoma probably ACTH-producing.
A few weeks later the patient was admitted again because
of persisting fever, headache and hypotension. The anemia
was progressive (4.8 mmol/l), trombocytes were 108 x 10?/l,
and LDH 1442 U/l, suggesting (micro-angiopathic) intravascular hemolysis. During fluid challenge, she developed
right-sided heart failure and acute renal failure, although
an ultrasound of the heart showed a normal left ventricular
function and only a slightly elevated serum NTproBNP.
The situation deteriorated quickly and she died.
Autopsy revealed a intravascular large B-cell-lymphoma in
the small en larger vessels of the lungs and pituitary gland.
Localization in the lung-vessels caused hypoxemia and
24
Initially, a cathastrophic antiphospholipid syndrome was
suspected, but could not be confirmed (LAC test, B2GP1
antibody test and ACA were all negative). Additional
diagnostic and laboratory investigations for (un)common
coagulation disorders like vasculitis, cardiac embolus,
factor V Leiden, prothrombin G20210A or JAK2 V617F
gene mutation and paroxysmal nocturnal hemoglobinuria
(PNH) showed no abnormalities.
Because we could not identify a disorder associated with
arterial thrombosis, we hypothesize that desmopressin in
an oral dose of at least 0.2mg must have been the cause
of this dramatic vascular complication (the exact dose she
took was unclear and unfortunately a desmopressin level
could not be measured). Indeed, factor VIII activity, vWF
activity ristocetin cofactor and vWF antigen were strikingly
elevated (268%, 590%, 740% respectively). We believe this
could be a desmopressin effect, although we realize that
major ischaemia may have contributed to this remarkable
elevation.
Thrombotic events (cerebrovascular accidents and
acute coronary syndromes) associated with the use of
desmopressin are rare and have only been described
after intravenous administration. Our patient used oral
desmopressin.
Conclusion: To the best of our knowledge this is the first
report suggesting a relationship between oral desmopressin use and life-threatening abdominal arterial
thrombosis.
probably leukostasis a, resulting in an elevated pressure in
pulmonary vessels which cardial ischemia and secondary
heart failure. There was only a minimal presence of the
lymphoma in the bone marrow.
Discussion: Intravascular large B-cell lymphoma (ILCL) is
a rare subtype of large cell lymphoma with an unknown
incidence. Patients present with a variety of symptoms
caused by occlusion of small vessels. The majority of
patients have B-symptoms and any organ can be involved.
The clinical presentation seems to be dependent of the
country of origin.
Conclusion: We present a patient with fever (of unknown
origin),heart failure and pituitary gland insufficiency
caused by infiltration of small and larger vessel by an intravascular large B-cell lymphoma.
41.
An unusual case of abdominal arterial thrombosis in
a young woman using desmopressin
E.J.M. Schrijver, W. Deenik, H. Chon, N.Koedam.,
A. Spoelstra-de Man
Tergooi Hospitals Hilversum, Department of Intensive
Care, Michelangelostraat 7-2, 1077 BN AMSTERDAM, the
Netherlands, e-mail: ejm.schrijver@gmail.com
Introduction: Desmopressin, a synthetic vasopressinanalogon, is prescribed for the treatment of nocturnal
enuresis. It stimulates the release of factor VIII and
promotes the release of Von Willebrand factor (vWF), also
making it an effective drug for coagulation disorders.
Case: A 27-year-old woman presented at the emergency
room with a 7-week history of abdominal pain and
diarrhoea. Her medical history included borderline
personality disorder with multiple hospital admissions.
Because of nocturnal enuresis, she used desmopressin
0.2 mg once daily since three months in combination
with aripiprazole, citalopram, alprazolam and topiramate.
On physical examination her vital signs were normal.
Abdominal examination revealed normal bowel sounds
with diffuse abdominal pain without muscular defense.
Rectal examination was normal. Her laboratory results
showed: sodium 132 mmol/l, potassium 3.3 mmol/l,
C-reactive protein 180 mg/l, leukocytes 23.7 x 109 IU/l
(10% band-forms), lactate 4.8 mmol/l and creatinine 47
umol/l. An abdominal CT scan was not conclusive. An
exploratory laparotomy revealed small bowel ischaemia due
to occlusion of the celiac trunk and superior mesenteric
artery. A thrombectomy of these arteries was performed.
The majority of the small bowel was resected, leaving
a residual small intestinal length of less than 100cm.
An aortahepatic bypass was made because remarkably,
thrombosis of the celiac trunk recurred during the
procedure, suggestive of a coagulation disorder.
42.
Thrombotic microangiopathy in new-onset systemic
lupus erythematosus
Y. Sandberg, M.F. Durian, S.P. Berger, E. Hoorn
Erasmus Medical Centre Rotterdam, Department of Internal
Medicine, S’-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: y.sandberg@erasmusmc.nl
Case: A 25-year-old Cambodian woman was admitted to a
general hospital because she had been feeling unwell for
two weeks and had a subfebrile temperature (38.0 °C). Her
previous medical history included tuberculosis in 1999
with vertrebral involvement leading to partial paraplegia.
Furthermore, a presumptive diagnosis of rheumatoid
arthritis (RA) was made based on an arthritis of her hands
and positive anti-cyclic citrullinated antibodies. She was
being treated with methotrexate (25 mg/week) and folic
acid. On admission, she was given antibiotics because
of suspected pneumonia. Pancytopenia was also noted,
which was ascribed to the use of methotrexate. Three days
later, however, she developed a sudden and transient loss
of vision and seizures, after which she was transferred
to the intensive care unit. There, hemolysis with schistocytes and renal insufficiency were noted, raising the
25
possibility of thrombotic thrombocytopenic purpura
(TTP). Her blood pressure was variable, but reached
a maximum of 160/110 mmHg. Although a normal
ADAMTS13 activity (58%) was detected, plasmapheresis
and prednisone were started. She was transferred to our
university hospital for further analysis and treatment.
After four days of plasmapheresis, an ADAMTS13 activity
of 91% was found and plasmapheresis was discontinued
and analysis for other causes was started. No known
association between methotrexate and TTP was found and
plasma levels of methotrexate were undetectable. Other
causes were also excluded, including human immunodeficiency and parvo B19 viruses, pregnancy, and the
antiphospholipid syndrome. Ultimately, a diagnosis of
systemic lupus erythematosus (SLE) could be established
based on the previously observed arthritis, pancytopenia,
positive antinuclear antibodies (1:2560 dilution, normal
< 1:80), anti double-stranded DNA antibodies (215 IU/ml,
normal < 10 IU/ml), and diffuse glomerulonephritis with
global involvement (class IV-G SLE nephritis). Treatment
with prednisone, mycophenolate mofetil and angiotensin
converting enzyme inhibitors led to complete remission.
Conclusions: New-onset SLE can be complicated by
thrombotic microangiopathy with normal ADAMTS13
activity. Possible explanations include a hypertensive
crisis and TTP. These were difficult to differentiate in this
particular case, because SLE nephritis was accompanied by
hypertension. It is important to recognize that TTP in SLE
is divided into two separate entities based on normal and
low ADAMTS13 activity. Only the latter category requires
plasmapheresis. Although incompletely understood, TTP
in SLE with normal ADAMTS13 activity carries a worse
overall prognosis. The second teaching point is that
anti-cyclic citrullinated antibodies can be positive in SLE
and therefore SLE should always be excluded prior to
diagnosing RA.
43.
He used salmeterol/fluticasone and mometasone furoate
for a mild COPD. Perindopril, metoprolol, spironolactone
and acenocoumarol were recently prescribed by the cardiologist. Physical examination showed a blood pressure of
90/60 mmHg and peripheral oedema. Initial aberrant
laboratory tests were haemoglobin 7.7 mmol/l, erythrocyte
sedimentation rate 63 mm/h, C-reactive protein 34 mg/l
and a total protein of 85 g/l (without M-protein).
Cardiomyopathy, polyneuropathy and eosinophilia each
have a large differential diagnosis. After a thorough work
up it was concluded that the underlying disorder was a
primary hypereosinophilia. Therefore the differential
diagnosis was narrowed to chronic eosinophilic leukaemia
(CEL), CEL unclassified, T-cell mediated hypereosinophilic
syndrome (HES) and HES.
Because testing for the FIP1-like-1-platelet-derived growth
factor receptor-fusion protein (FIP1L1-PDGFRalpha) was
negative, CEL was excluded. Bone marrow examination
showed 30% eosinophils; no blasts, mast cells, fibrosis
or cytogenetical abnormalities were found. There was a
normal T-cell subset at immunophenotyping. Molecular
cytogenetical studies were negative for JAK2, BCR-ABL
and KIT D816V mutations. A skin-fascia-muscle biopsy
showed eosinophilic fasciitis and eosinophilic myositis.
With those results a systemic mastcytosis, CEL unclassified
and T-cell associated HES were excluded and the diagnosis
HES was made. Our patient fulfilled the WHO criteria for
idiopathic HES; an eosinophil count > 1.5 x 109/l for more
than six months, exclusion of reactive eosinophilia as well
as eosinophilia associated with neoplasias, and evidence of
tissue damage as result of hypereosinophilia.
Although our patient was FIP1L1-PDGFRalpha negative,
treatment with imatinib 100 mg per day was started. After
10 weeks of therapy he experienced a better condition, less
neuropathy and a weight gain of 4 kg. His white blood
cell count normalized and the eosinophils dropped to < 2
x 109/l.
Discussion: There are some more case reports of patients
with FIP1L1-PDGFRalpha negative HES responsive to
imatinib, indicating that an as yet unidentified target of
imatinib is responsible for HES in these cases.
A patient with cardiomyopathy, polyneuropathy and
an eosinophilia: a diagnostic challenge
C. Bethlehem, P. Joosten
Medical Centre Leeuwarden, Department of Internal
Medicine, Henri Dunantweg 2, 8934 AD LEEUWARDEN,
the Netherlands, e-mail: carina.bethlehem@znb.nl
44.
Ungoing HIV replication in cerebrospinal fluid
under longterm ritonavir/lopinavir monotherapy
M. Bierhoff1, C.A.B. Boucher2, J. Kuster1, R.W. ten Kate1
Kennemer Gasthuis, Department of Internal Medicine,
Boerhaavelaan 22, 2035 RC HAARLEM, the Netherlands,
e-mail: m.bierhoff@kg.nl, 2Erasmus Medical Centre,
ROTTERDAM, the Netherlands
Case: A 56-year-old male patient with a recently diagnosed
cardiomyopathy and sensorimotor axonal polyneuropathy
was seen because of an eosinophilia (4.8-8.8 x 109/l),
existing for more than one year. During the past three
months he was complaining about dyspnoea d’effort,
deafness in his feet and progressive weight loss. There
were no signs of fever, cough, muscle pains, pruritus or
diarrhoea. Our patient did not smoke or use much alcohol.
1
Case: A 57- year HIV infected man was started on highly
active antiretroviral therapy (HAART) in 1999 at CD4
26
count of 620 x 106/ml and HIV-1 viral load of 114 copies/
ml on a regimen of lamivudine/zidovudine 150/300 mg
twice daily and nevirapine 200 mg twice daily. Due to
side effects of different regimens available at that time he
was ultimately successfully treated from 2001 with mono
therapy at first nelfinavir and subsequently ritonavir/
lopinavir (r/lPV) 50/200 twice daily 2. At that point his
HIV-1 viral load in serum was almost always beneath 400
copies/ml. This regimen was kept unchanged until he
presented in 2010 with dysarthria, dysfagia, dyskinesia
and tremor. A cerebral MRI showed changes in white
matter. A lumbar puncture was performed. Cerebrospinal
fluid (CSF) was negative for cytomegalovirus, Epstein-Barr
virus, herpes simplex virus, JC virus, varicella zoster virus,
enterovirus. HIV-1 viral load was 4500 copies/ml in CSF
with serum viral load of 400 copies/ml and a CD4 count
of 930 x 106/ml. LPV level in CSF 6 hours after intake was
0.07 mg/l and serum level 11.0 mg/l in plasma. This is a
normal plasma/CSF ratio.
His regimen was switched to etravirine 400mg twice
daily and lamivudine/zidovudine 150/300mg twice daily
and after two months the HIV-1 RNA viral load was again
undetectable in both serum as well as in CSF but the
patient remained clinically unchanged.
Conclusion: Despite a longstanding suppression of viral
replication in plasma we found substantial viral replication
in the CSF possibly responsible for the symptoms and
signs in our patient. Our observation support the
suggestion from recent literature that with mono therapy
with ritonavir/lopinavir is not
45.
Biopsies revealed chronic inflammation with granuloma
formation, suggestive for early Crohn’s disease (CD). After
exclusion of (latent) TBC infection using an IGRA-test
and X-thorax, a ‘top-down’ regimen was started consisting
of prednisone, azathioprine and remicade. However,
complaints remained and fever developed. A CT-scan
showed infiltration surrounding the coecum and terminal
ileum without abscess. The patient underwent an extensive
ileocecal resection. During surgery, multiple lesions on
the peritoneum and small intestine were found. Cultures
of resection material were positive for M. tuberculosis.
A Mantoux test was strongly positive. After initiation of
appropriate treatment, the patient recovered.
Case 2: A 75-year-old Italian man was admitted for general
malaise, chest pain and confusion. Physical examination
was normal. Laboratory revealed slightly elevated CRP,
blood cultures were negative. CT angiography showed a
thoracic aortic aneurysm of 7.2 cm and multiple perilymphatic pulmonary nodules. Sarcoidosis and tuberculosis
were considered. Bronchoalveolar lavage (BAL) and surgery
were postponed due to the aneurysm and the patient’s
poor condition, respectively. The patient had a BCG scar,
an IGRA test was negative. A liver biopsy showed granulomatous inflammation with a negative ZN stain. Treatment
for sarcoidosis was started with prednisone. Within days he
developed high spiking fever. Clinical diagnosis of miliary
TB was made, later confirmed by positive ZN staining,
BAL (PCR) and blood cultures. Appropriate treatment was
started, but unfortunately the patient died after a couple
months.
Discussion: Here we describe two cases in which a
false negative IGRA test had dramatic consequences for
the patients involved. IGRA tests have high specificity.
However, sensitivity for detecting (latent) infection is
variable and dependent on time since infection.
Conclusion: A negative IGRA test does not rule out
TBC and combined IGRA/Mantoux testing should be
considered in case of doubt.
Severe consequences of a missed diagnosis of TBC
infection due to a false negative Interferon Gamma
Release Assay
M. Kramer, A. Tan, G. den Hartog, E.H. Gisolf, C. Richter
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
m3kramer@alysis.nl
46.
Introduction: Interferon Gamma (IFNy) Release Assays
(IGRA’s) for the detection of (latent) TBC infection are
based on host IFNy production following recognition of
M. tuberculosis antigens and display superior specificity
compared to the Mantoux test. Sensitivity of the test,
however, is variable. Here, we describe 2 cases in which a
false-negative IGRA has led to a delayed onset of adequate
treatment with fatal outcome in one of the patients.
Case 1: A 42-year-old Dutch female presented with a
painful swelling in the lower right abdomen. Laboratory
analysis showed normal infection parameters and
ultrasound imaging was normal. Colonoscopy showed a
significant stenosis with ulceration in the ascending colon.
Put on the wrong track by Staphylococcus aureus
I.M.E. Wentholt, W.E.M. Schouten, P.H.J. Frissen
Onze Lieve Vrouwe Gasthuis, Department of Infectious
Diseases, Oosterpark 9, 1091 AC AMSTERDAM, the
Netherlands, e-mail: i.m.wentholt@amc.uva.nl
Introduction and anamnesis: A 44-yr old Somalian man
visited the Surgical outpatient clinic with a posttraumatic
haematoma in his right lower abdomen. Considered an
infected haematoma, the surgeon performed incision
and drainage of the mass, which appeared to be an
impressive subcutaneous abscess. Culture of the wound
demonstrated Staphylococcus aureus and coagulase-negative
27
Staphylococcus species, for which he received flucloxacillin.
Wound recovery was protracted for months. Therefore,
the infectiologist was consulted. In addition, the patient
reported 6 kg weight loss, night sweats and two painful
masses on the right side of his back.
Physical examination: A cachectic man with normal vital
parameters. Body temperature 37.2 °C, a granulating
wound (5 x 2 cm) at the right lower abdomen, two painful
masses (diameter 3 and 5 cm, respectively) on the right part
of his back and one (diameter 2 cm) in the right inguinal
area. No neurological abnormalities.
Laboratory findings: ESR 51 mm/h, Hb 7,5 mmol/l,
leucocytes 7,9 giga/l, CRP 124 mg/l
Microbiology: Smear of the abdominal wound and abscess
at the back demonstrated acid-fast bacilli in the Auraminerhodamine stain. PCR assay detected a weak signal of
Mycobacterium tuberculosis (TB) DNA. TB was isolated
from liquid culture. HIV serology was negative.
Imaging: Chest-X-ray: no abnormalities.
MRI: spondylitis of L1 with partial destruction.and
abscesses in musculus psoas and behind the musculus
erector spinae on the right side, with intraspinal and
epidural expansion at the level of the conus, with
compression.
Course and conclusion: Patient had TB spondylitis with
impressive soft tissue infection, stretching out over a
40 cm long abscess leading to a cutaneous fistula. The
abscesses were drained and tuberculostatic quadruple
therapy was initiated. Apparently, the surgeon had been
put on the wrong track by (1) the isolated Staphylococcus
aureus, which was erroneously assumed to be the causative
pathogen and (2) the absence of fever and acute illness,
which is typical for a “cold” TB abscess. The patient’s
ethnical origin should have raised strong suspicion for
TB and specific cultures should have been ordered. Even
though he recovered well, the patient had been at risk
of neurological function loss. In conclusion, whenever a
high risk patient presents with a persisting open wound,
the diagnosis of TB with formation of a cutaneous fistula
should be considered.
47.
symptom onset. She did not meet with the nation-wide
vaccination criteria, but decided herself to take the
vaccination proposed by her company.
Physical examination showed a somnolent patient with
meningeal signs and left sided hemiparesis. Laboratory
tests revealed leukocytes 19.4 x 109/l and CRP 100 mg/l.
Cerebral-CT-scan showed bilataral tempero-parietal edema.
Analysis of cerebrospinal fluid (CSF) revealed a leukocytosis and high protein- and glucose levels. As the diagnosis
meningoencephalitis was assumed, penicillin, ceftriaxone,
acyclovir and dexamethasone was started. Cultures of
cerebrospinal fluid, viral and mycobacterial PCR-tests were
negative.
After several days her clinical condition dramatically
deteriorated, leading to coma and respiratory insufficiency.
She was intubated and artificially ventilated in the ICU.
MRI showed extensive cerebral and brainstem white matter
lesions. By rising intracranial pressure, a decompressive
hemicraniectomy was performed, leaving a permanent
opening in the skull. Because of symptoms and MRI, acute
disseminated encephalomyelitis (ADEM) was suspected.
She was referred to an academic hospital where brainbiopsy confirmed the diagnosis. She was treated with high
dose steroids, immunglobulins and plasma-exchange.
Unfortunately, her clinical condition deteriorated, leading
to irreversible coma and severe epileptic activity.
ADEM, also known as post-infectious encephalomyelitis,
typically follows a (minor) infection or vaccination with
a latency period of 2-30 days. It is an immune-mediated
inflammatory demyelinating disorder with an acute onset
of focal neurological signs and encephalopathy. MRI is
essential for the diagnosis, showing diffuse or multifocal
lesions throughout the white matter on T2- and FLAIRweighted sequences. Viral infections like measles, rubella,
influenza, Epstein-Barr, HIV, herpes, CMV and West
Nile virus have been described as causative agent. Also
infections with streptococcus, mycoplasma, chlamydia,
rickettsia, leptospira and mycobacteria may induce ADEM.
Post-vaccination ADEM has been described after several,
especially primary, vaccinations for rabies, diphtheriatetanus-polio, smallpox, measles, mumps, rubella, Japanese
B-encephalitis, pertussis, influenza and hepatitis B.
There is no proven standard treatment for ADEM;
present therapy focuses on immunesuppression and
immunomodulation. Although the prognosis of ADEM is
generally favorable, fulminant untreatable cerebral edema
occurs occasionally. Predictors of poor outcome are older
age, female gender, high CSF protein level, spinal cord
involvement and poor response to corticosteroids.
This dramatic case of fulminant ADEM after
H1N1-vaccination illustrates the fact that the potential
benefit and adverse events of every medical treatment have
to be weighed carefully!
A breath-taking complication of H1N1-vaccination:
ADEM
L.M.H. van de Winkel, J. Buijs, T. Schreuder
Atrium Medical Centre, Department of Internal Medicine,
PO Box 4446, 6401 CX HEERLEN, the Netherlands, e-mail:
l.vandewinkel@alumni.maastrichtuniversity.nl
A 27-year-old woman presented at the emergency room
with fever, tachycardia and unconsciousness for several
minutes. Her medical history was unremarkable. She
recieved the influenza-H1N1-vaccine one week prior to
28
48.
Fishing for parasites
49.
A.M. Vondeling, J.W. Dorigo-Zetsma, S. Lobatto
Tergooi Hospitals, Department of Internal Medicine, Van
Riebeeckweg 212, 1213 XZ HILVERSUM, the Netherlands,
e-mail: arielvondeling@gmail.com
An unusual case of intermittend fever: chronical
meningococcemia
G.L. van Sluis1 , E.L.E de Bruijne1, L. Spanjaard 2 ,
B. Diederen3, E. Kerver1
1
Rode Kruis Hospital, Department of Internal Medicine,
Vondellaan 13, 1942 LE BEVERWIJK, the Netherlands, e-mail:
geertevansluis@gmail.com, 2Netherlands Reference Laboratory
of Bacterial Meningitis, AMSTERDAM, the Netherlands,
3
Regional Laboratoy of Public Health, HAARLEM, the
Netherlands
A 35-year-old female presented with complaints of fever
and malaise. She had no medical history. There were no
respiratory or urinary tract symptoms. She had recently
visited Northern Italy, but not the tropics. Her father had
similar complaints.
On physical examination the patient was afebrile and no
abnormalities were detected. Laboratory results showed
mildly elevated liver enzymes, CRPl 39 mg/l and leukocyte
count 11.2 x 109/l, 30 percent eosinophils. Chest X-ray and
abdominal ultrasound showed no liver abscess or other
abnormalities.
Because of the eosinophilia parasitological examination of
the stool was performed. On microscopy one liverfluke egg
was detected. PCR on the stools confirmed an Opistorchis
felineus infection.
World wide the number of human infections with
Opisthorchis felineus has been estimated to be 1.2 million,
most in south-east Asia. Infection in Western Europe is
extremely rare. The parasite lives in the biliary duct of
mammals where it reproduces. The eggs are excreted with
the faeces. Water snails eat these eggs and and are passed
on to freshwater fish such as the tench (member of the
carp family). By eating raw fish mammals can be infected.
The incubation period is 2-4 weeks. Acute symptoms are
abdominal pain, fever and malaise. Chronic complications
include liver abscess and biliary duct carcinoma.
The diagnosis is made by microscopic detection of eggs in
the faeces. It is impossible to differentiate microscopically
between species of liver flukes, hence specific PCR testing
is needed. The diagnosis can be confirmed by a positive
antibody test.
Our patient had eaten raw fish in a restaurant in Italy,
carpaccio of tench. After returning from holidays, she was
seen in a hospital 1500 km from where she was infected.
Local physicians contacted us about the diagnosis because
we were the first to diagnose opisthorchiasis..
Of the 52 people who had dinner in the restaurant
concerned, 45 presented with symptoms to the local
hospital. Eight of them were admitted. One patient
developed a liver abscess. All patients were treated with
praziquantel 75 mg/kg/dd. Our patient made a full
recovery. To our knowledge she is the first with opisthorchiasis in the Netherlands. Only a small number of outbreaks
has been reported to date.
Doctors, patients and caterers should be aware that
changing eating habits, e.g. consumption of raw fish in
Europe, can lead to an increase of parasitic infections.
A 19-year-old woman presented with intermittent fever
up to 39 °C and chills every 3 days and little red/blue
spots on her body. She also complained of joint pain, a
sore throat, headache and a neck stiffness. Her medical
history was uneventful. She used oral contraception as
medication. She was vaccinated according to the State
Vaccination Programme and had not visited foreign
countries recently. On physical examination we saw a
hemodynamically stable, moderately ill-looking young
woman with a temperature of 39 °C.
Purple skin lesions were observed on the extremities and
torso varying from several millimetres to one centimetre,
some with petechiae as well. Searches for a focus of
infection were unrevealing, and no signs of meningeal
irritation were found. Laboratory investigation revealed a
leukocytosis of 23 x 109/l with 21 x 109/l neutrophils and
an elevated C-reactive protein of 86 mg/l. IgA was found
repetitively low (< 0.4 g/l). Serological screening assays
for vasculitis were all negative. A skin biopsy showed a
leukocytoclastic vasculitis and the gram stain showed no
bacteria.
In the absence of persistent complaints and acute illness
she was admitted for observation and no antibiotics
were administered. The initial working diagnosis was
a post-infectious syndrome. After discharge she visited
the emergency department several times with the same
complaints and observations. Repetitive blood cultures
drawn during these visits grew Neisseria meningitidis
serogroup C.
She was treated with benzylpenicillin 12 million IU/24
hours intravenously for 14 days and her housemates were
treated with rifampicin 600mg two times a day during
two days. Her recovery was without remaining complaints.
In conclusion we saw a young woman with a chronic
meningococcemia due to group C N.meningitidis despite
vaccination. Probably due to IgA deficiency she had an
increased susceptibility to infection. Further investigation
into underlying immune deficiency is underway. In
the 8 years of vaccination with the menC vaccine in the
Netherlands (since 2002), there was only one other case of
vaccine failure.
29
50.
Fish-eye disease
51.
A.S.B. Conijn-Mensink, J.G. Schrama
Spaarne Hospital, Department of Internal Medicine,
Spaarnepoort 1, 2134 TM HOOFDDORP, the Netherlands,
e-mail: mensinkannemarie@hotmail.com
Introduction: Fish-eye disease (FED) is a rare genetic
disease (homozygous defect of the LCAT gene) clinically
characterized by the presence of corneal opacities,
markedly decreased plasma concentrations of high-density
lipoprotein (HDL) cholesterol and normal renal function.
We report a patient with corneal opacities and a low HDL
cholesterol, who was diagnosed with FED.
Case report: A 55-year-old man was seen on the outpatients’
department because of a low HDL cholesterol. He had no
coronary heart diseases and he did not use any drugs.
Physical examination showed a non acutely ill man with
a cornea opacification of both eyes. He indicated that
he has had this opacification since he was 20 years old.
His brother had the same eye problem. Blood pressure
was 136/90 mmHg. Examination of cor, pulmones and
abdomen was normal.
Laboratory tests showed a normal haematology, normal
renal function, normal glucose, normal liver enzymes and
normal thyroid function. He had a low HDL cholesterol of
0,1 mmol/l (normal range 0,9-1,7 mmol/l) with a normal
low-density lipoprotein (LDL) cholesterol and triglyceride
concentration. Urinalysis showed no protein.
The lecithin-cholesterol acyltransferase (LCAT) enzyme
activity was decreased to 0.75 nmol/ml x hour (normal
limit > 12,6 nmol/ml x hour). The genotype analysis
detected a homozygous defect of the LCAT gene. His
brother had the same defect. Patient and his brother were
diagnosed with FED.
Discussion: Because of a low HDL cholesterol and cornea
opacification, LCAT deficiency was considered in this
patient.
Several mutations have been described in the LCAT gene
and classified as FED or as familial LCAT deficiency (FLD).
Mutations in the LCAT gene associated with partial LCAT
deficiency lead to FED, whereas complete absence or very
low plasma LCAT activity leads to FLD. In FED, LCAT is
unable to esterify cholesterol in the HDL molecule, while
it retains its activity in very low density lipoprotein (VLDL)
and LDL. In FLD, plasma LCAT activity is nearly absent,
and plasma HDL and cholesteryl esters levels are very low.
Clinical manifestations include anaemia, corneal opacities
and renal disease with proteinuria.
Conclusion: In FED, the enzyme LCAT is unable to esterify
cholesterol in the HDL molecule. This leads to very low
HDL cholesterol and corneal opacities.
FED is distinguishable from familial LCAT deficiency by a
normal renal function and a partial LCAT deficiency.
30
Isolated elevated aspartate aminotransferase (ASAT),
a surprising outcome for clinicians
52.
Hyperhemolysis syndrome in a patient with anemia
caused by a gastric ulcer
R.R.L. Wener, F.J. Loupatty, W.E.M. Schouten
Onze Lieve Vrouwe Gasthuis, Department of Internal
Medicine, Oosterpark 9, 1091 AC AMSTERDAM, the
Netherlands, e-mail: r.r.l.wener@olvg.nl
H. Ytredal, H.J. Adriaansen, G.S. Madretsma, C.G. Schaar
Gelre Hospital Apeldoorn, Department of Internal Medicine,
Nieuwravenstraat 11, 3522 RK UTRECHT, the Netherlands,
e-mail: h.ytredal@gmail.com
Case report: A 34-year-old Polish woman, gravida 2, para
0, who was 34 weeks pregnant, was presented to the
gynecologist with pain in the right upper abdomen. Her
medical history revealed a severe trauma with abdominal
and pelvic injury, nephrolithiasis, benign ovarian cyst,
hematocolpos and pregnancy after Intracytoplasmatic
Sperm Injection procedure. In the past, she had seen
a doctor in Poland because of abdominal pain with
elevated liver enzymes. The gynecologist observed a
normal pregnancy and did not find a cause for the
abdominal pain. However, laboratory examination demonstrated a solitarily elevated ASAT (397 IU/l, reference
values ASAT < 30 IU/l). Consequently, the internist was
consulted. The patient had no other complaints, i.e. no
jaundice or fever. She used no medication, except an
antacid. Physical examination revealed no abnormalities.
Acute viral hepatitis was excluded by serological measurements for hepatitis A, B, C, EBV and CMV. An abdominal
ultrasound showed completely normal results. There was
no evidence for other sources of ASAT, such as myocardial
disease, skeletal muscle disorders, pancreatic disease or
hemolysis. The presence of macro-ASAT was suggested by
the clinical chemist and subsequently confirmed by means
of a polyethylene glycol precipitation assay.
Discussion: Acro-enzymes are enzymes in plasma that
have formed high-molecular-mass complexes, either
by self-polymerization or by association with plasma
components such as immunoglobulins. This benign
phenomenon is well characterized for macro-amylase
and macro-CK, but todate only 32 cases of macro-ASAT
have been reported in literature. The absence of pathology
over a long period of follow-up argues for the benign
nature of this phenomenon. Macro-enzymes are effectively
detected with a polyethylene glycol precipitation technique.
Considering the presence of macro-enzymes is important
to avoid diagnostic confusion and unnecessary investigations, as illustrated by our case. Hence, it is important to
record this information in patient’s notes.
Conclusion: Consider macro-enzymes in the differential
diagnosis of single elevated serum enzyme activity without
any evidence of disease.
Introduction: Hyperhemolysis syndrome is a well described
phenomenon in patients with sickle cell disease, however,
in patients without a hemoglobinopathy, it is rare.
A 64-year-old woman was admitted with a microcytic
anemia (hemoglobin 3.6 mmol/l) caused by a gastric
ulcer. She was treated with cross-matched red blood cell
concentrates (RBC) and a proton pump inhibitor. Ten
days later she was readmitted with jaundice and dyspnea.
Laboratory findings showed severe hemolysis (hemoglobin
2.4 mmol/l, haptoglobulin < 0.08 g/l) and newly present
anti-Jk(a) and anti-Kell antibodies, which were not
detectable at the pre-test screening before transfusion.
Despite nine compatible RBC’s and high dose corticosteroids the hemoglobin level did not increase further
than 3.1 mmol/l. In combination with progressive signs
of hemolysis a hyperhemolysis syndrome was diagnosed.
After addition of intravenous immunoglobulins (0.4 g/kg)
the hemoglobin level increased to 5.1 mmol/l and corticosteroids were tapered.
The latest antibody screening conducted eights months
after admission revealed only anti-Kell antibodies.
Discussion: Hyperhemolysis can be a life threatening
disease and early recognition is important. Patients with
hyperhemolysis have developed alloantibodies during
earlier RBC transfusion or pregnancy. This patient without
any previous RBC transfusions most likely developed
antibodies during one of her four pregnancies. However,
the titer of the alloantibodies decline and can become
undetectable, as is shown in this case with the anti-Jk(a)
antibodies.
In patients without known hemoglobinopathy, as far as we
know, hyperhemolysis has only been described in three
cases.
The cause of hyperhemolysis is still unknown.
Hemoglobinopathy itself and the high level of alloantibodies are suggested as a trigger. ‘Bystander hemolysis’
triggered by complement activation as well as inflammation with macrophage activation have been presumed
as causes of hemolysis. Furthermore suppression of the
erytropoiesis is being described with a decreased number
of reticulocytes or reticulopenia.
Treatment with prednisone is sufficient in some cases,
whereas intravenous immunoglobins have shown
additional effect.
Conclusion: Hyperhemolysis is a rare life threatening
transfusion reaction, mostly seen 5-10 days after
transfusion, with hemolysis of the transfused compatible
erythrocytes as well as the patient’s own cells. The
pathogenesis remains unclear and includes alloantibody mediated hemolysis, ‘bystander hemolysis’’, and
suppressed erytropoiesis.
This case confirms the importance of always considering
the pre-transfusion history of the patient, although alloantibodies could be undetectable. There is no standardized
treatment. In this case immunoglobulins were successful.
53.
A patient with ‘Coombs-negative’ auto-immune
mediated hemolytic anemia
A. de Haar-Holleman, L.A. Boven, S.K. Klein
Meander Medical Centre, Department of Internal Medicine,
PO Box 1502, 3800 BM Amersfoort, the Netherlands, e-mail:
a.de.haar@meandermc.nl
Case report: A 26-year-old male presented at our
emergency department with a 2-day history of fever,
jaundice, and hematuria. His history was blank. Physical
examination was notable for icterus and pallor. Laboratory
investigations revealed hemoglobin of 3.0 mmol/l, which
further decreased to 2.3 mmol/l within 2 hours. The MCV
was 109, erythroblasts 39/100 WBC and reticulocyte count
was at 0,18 * 1012/l. LDH could not be determined due to
extensive hemolysis. Blood smear examination showed
clear spherocytosis. Blood cultures as well as serology
were negative. Auto-immune hemolytic anemia (AIHA)
was suspected, but the direct Coomb’s test was negative.
Routine antiglobulin test (DAT) uses anti-human IgG
and C3d reagents. Therefore, the test was repeated using
anti-IgG, anti-complement and, additionally, anti-IgA.
The test with IgA was strongly positive, indicating a rare
IgA-mediated autoimmune hemolytic anemia. The IgA
antibodies were eluted from the red blood cells and further
characterized to determine specifity. Surprisingly, the
antibodies showed a clear and strong specificity for the
rhesus antigen e.
Discussion: AIHA is characterized by the destruction of
red blood cells (RBCs) associated with the presence of IgG,
IgM or IgA, and/or components of the complement system
on the RBC cell membrane. More than 70% of cases of
warm AIHA are caused by IgG. AIHA caused solely by
IgA, however, is very rare, i.e. 0.8-2.5% of cases. IgA
autoantibodies are usually warm-reacting. The proposed
mechanism of RBC destruction in IgA-mediated AIHA
appears to be trapping and subsequent sequestration of
agglutinated RBCs in the spleen rather than complement
activation or deposition or phagocytosis by monocytes.
Which makes our patient even more unique is the fact that
the IgA antibodies were directed against rhesus antigen
e, which is very uncommon as most AIHA with IgA
31
antibodies are directed against an antigen present on all
cells rather than blood type antigens. The patient required
multiple transfusions with matched e-negative typed red
cell concentrates. As therapy with high dose steroids and
gamma globulins were not successful, splenectomy was
performed. Relief of fever and jaundice followed and the
hemoglobin rose to 6 mmol/l. After discharge, the steroid
was tapered off and was discontinued 2 months later.
Conclusion:This case demonstrates the importance of
performing a monospecific antiglobulin test if there is a
strong suspicion of AIHA in apparently ‘Coombs-negative’
AIHA. Splenectomy and not steroids are curative in
IgA-mediated hemolysis.
54.
our patient, however, analysis of the pro-virus and genes of
the HTLV-1 in the skin has not been performed. A strongly
considered differential diagnosis was Sézary syndrome, a
leukemic variant of a cutaneous T-cell lymphoma, which
has marked similarities with ATLL but no association with
HTLV-1.
Although this retrovirus is not sufficient to induce T-cell
leukemia on its own, it drives cell growth of latentlyinfected cells through the expression of the pro-virus
coded oncoprotein TAX, which affects a variety of cellular
signalling pathways leading to transcriptional activation,
proliferation and transformation. Prognosis is ruled by
the clinical subtype; the chronic or smoldering subtypes
are considered indolent, whereas the acute subtype has a
worse overall survival.
Conclusion: We described a unique case of an ATLL
associated with HTLV-1 presenting as mammary swelling
and pruritic skin rash. Apart from clonally integration of
the virus, immunophenotyping and a peripheral blood
smear are useful in differentiating from Sézary syndrom
Adult T-cell leukemia-lymphoma presenting as a
mammary swelling
G.J. Tack, J.J. Hoefnagel, C.E.H. Siegert, W.L.E. Vasmel
Sint Lucas Andreas Hospital, Department of Internal
Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the
Netherlands, e-mail: g.tack@slaz.nl
55.
Introduction: Mammary swelling is commonly caused by
malignancy or infection of the mammary gland. We report
an interesting case of a rare cutaneous T-cell lymphoma
presenting as a mammary swelling.
Case: A 82-year-old black woman was admitted because
of tiredness, swelling of the left mamma and a pruritic
generalized rash. Medical history revealed type II diabetes
mellitus, hypertension, chronic renal insufficiency and a
pacemaker because of an atrioventricular block.
Physical examination showed diffuse swelling of the left
mamma and erythemateous lesions without papules
or plaques, mainly located on the arms, buttocks, left
mamma and lower back. Laboratory tests revealed an
increased LDH, normocalciemia, lymphocytosis with
so called flower-cells in the peripheral blood smear.
Immunophenotyping displayed CD25+T-cells, based on
the ex-pression of various T-cell lineage markers (CD3,
CD4, CD5 and T-cell receptor alpha/beta), without CD7
and CD8 positivity. In addition, a positive western-blot
for HTLV-1 was found. CT-scaning showed axillary and
inguinal lymphadenopathy without hepatosplenomegaly.
Mammography and ultrasound in-vestigations excluded
mamma carcinoma. A skin biopsy demonstrated dermal
perivascular infiltration and epidermal microabscesses.
Diagnosis: A diagnosis of adult T-cell leukemia-lymphoma
(ATLL) was made, an aggressive peripheral T-cell
lymphoma strongly associated with the human T-cell
leukemia virus-1 (HTLV-1). This rare disorder is characterized by lymphadenopathy, pathognomic flower cells
and CD4+/CD8-/CD7-CD25+ T-cell immunophenotype.
Skin involvement occurs in more than half of the cases. In
Walnut induced thrombocytopenia
R. Achterbergh, C. Daemen, H.J. Vermeer, S. Lobatto
Tergooi Hospitals Hilversum, Department of Internal
Medicine, Van Riebeeckweg 212, 1213 XZ HILVERSUM, the
Netherlands, e-mail: rachterbergh@tergooiziekenhuizen.nl
Introduction: Drug-induced thrombocytopenia, due to
antibodies binding to platelets in the presence of a drug, is
a well known phenomenon. Only a few case reports have
been published with a convincing level of evidence for a
causal relationship between thrombocytopenia and food or
beverage consumption, like tahin and cranberry juice. We
describe a case of thrombocytopenia as an adverse effect
of walnut consumption.
Case: A 70-year-old male was sent to the hospital because
after one night of nausea, vomiting and fever, a blood count
showed a platelet count of 32 x 109/l. He had no history of
bleeding disorder or low platelets. Four days later, in the
hospital, the count was normal (212 x 109/l) and it was
concluded that the initial low platelet count was probably
due to an incorrect test result.
However, a few months later, the same symptoms occurred
and again a low platelet count (37 x 109/l) was measured.
The platelet count recovered in a few days. The patient
recalled eating nuts before both events and suspected a
relation between his illness and eating walnuts. He did
not take quinine containing beverages and did not use
thrombocytopenia inducing medicines.
We decided to perform an in hospital walnut provocation
challenge. The platelet count before was 233 x 109/l.
The patient ate 100 grams of walnuts at 5.00 p.m. and
32
after 4 hours developed a fever (38.7 °C) and nausea
and vomiting. No other physical or systemic symptoms
were seen, especially no rash, angioedema or low blood
pressure. The nausea and fever gradually disappeared
during the next 8 hours, but the platelet count, measured
15 hours after walnut ingestion was 4 x 109/l and the
patient showed bleeding from an existing small wound and
large hematomas at venapuncture sites. Other laboratory
results, including specific IgE levels against tree nuts, were
normal. After four days the platelet count spontaneously
recovered to normal.
Discussion: Although walnut-induced thrombocytopenia has never been described before, this case is very
convincing. Exposure to walnuts resulted in acute thrombocytopenia that recovered to normal in a few days, in
absence of other thrombocytopenia inducing agents or
causes. This phenomenon was confirmed by an in hospital
provocation challenge. Further serological investigations
have been started and seem to confirm the presence of
specific walnut dependent IgG platelet antibodies in our
patients’ serum.
Conclusion: Transient thrombocytopenia might be induced
by consumption of walnuts.
56.
bleeds. Laboratory examination showed a PT-INR of 1.0.
Her aPTT, however, was 96 seconds. As mixing tests
only showed partial correction, we suspected a factor VIII
(fVIII) inhibitor. Indeed, fVIII activity was 1% and an fVIII
inhibitor of 64 BU/ml was established. A lupus anticoagulant was excluded. Interestingly, patient had a normal
factor IX and factor XI, while factor XII was significantly
reduced to 43%.
As 50% of patients with acquired hemophilia have comorbidities or underlying conditions (e.g. post-partum,
co-existing autoimmune diseases, malignancy), we
performed extensive laboratory testing and a computed
tomography of chest and abdomen. All returned negative.
Treatment consisted of recombinant factor VIIa for her
muscle bleeds and high dose prednisone. Subsequently,
her aPTT shortened and fVIII activity slowly increased.
Discussion: Acquired hemophilia A typically occurs in
elderly patients and may be masked by treatment with
vitamin K antagonists. Although anticoagulant therapy is
usually monitored using PT-INR, we recommend the determination of aPTT and PT in patients with disproportional
or unexplained subcutaneous bleeds. First-line bleeding
control consists of a bypassing agent (recombinant fVIIa
or activated prothrombin complex concentrate) with an
efficacy of 90%. Eradication of fVIII inhibitor may be
achieved using regimens of corticosteroids alone or in
combination with cyclophosphamide. In case of failure,
Rituximab (anti-CD20 antibodies) may be considered.
After achievement of remission, prolonged follow-up is
indicated as relapse occurs in 20% of patients.
A patient with a prolonged aPTT: to bleed or not to
bleed
G. Labots, F.J.S.H. Woei-A-Jin, P.F. Ypma
Haga Teaching Hospital, Department of Hematology,
Leyweg 275, 2545 CH THE HAGUE, the Netherlands, e-mail:
g.labots@hagaHospital.nl
57.
Introduction: Acquired hemophilia A is a rare, but
potentially life-threatening bleeding condition due to
formation of inhibitory antibodies against factor VIII
(mortality 9-22%). Unfortunately, diagnosis is frequently
delayed and bleedings undertreated. In this abstract, we
present an elderly patient, whose hemophiliac condition
was mistaken for a bleeding complication due to treatment
with vitamin K antagonists.
Case report: A 69-year-old female presented with
impressive subcutaneous bruising and right femoral
nerve palsy due to an iliopsoas hematoma. Her history
consisted of diabetes type 2 and atrial fibrillation, for which
she used vitamin K antagonists. Initially, domestic abuse
was suspected. Her husband, however, was wheelchair
dependent and both patient and spouse denied battering.
Prior to admission, patient had severe nose bleeds
ultimately resulting in a hemoglobin level of 3.6 mmol/l.
As her PT-INR was 4.3, patient was treated with vitamin K.
Shortly hereafter, patient was discharged from the hospital
with a PT-INR of 1.0. It was not long before patient was
readmitted because of generalized hematomas and muscle
Dancing eye syndrome
W.J. Wiersinga, J.M. Prins, D. van de Beek
Academic Medical Centre, Department of Infectious
Diseases, Tropical Medicine and AIDS, Meibergdreef 9,
1105 AZ AMSTERDAM, the Netherlands, e-mail:
w.j.wiersinga@amc.uva.nl
Introduction: Chaotic eye movements and myoclonus are
key features of the dancing eye syndrome, sometimes
referred to as the opsoclonus-myoclonus syndrome. The
etiology may be inflammatory and it can occur in many
settings, most notably paraneoplastic, in association with
autoimmune diseases, infectious diseases or drug toxicity.
Here we describe a unique case of therapy resistant
opsoclonus-myoclonus syndrome presenting in a patient
with HIV-1 de novo.
Case (including video presentation): A 27-year-old
previously healthy woman presented with a 3-week
history of uncontrolled eye movements with disabling
oscillopsia (see videotape registration). The complaints
started after a short flu-like illness. Vision was normal.
33
showed markedly elevated uptake of heat-damaged red
blood cells in the intraperitoneal and retroperitoneal
masses depicted on lowdose CT, corresponding to the
lesions visualised on ultrasonography and MRI and
confirming the diagnosis abdominal splenosis. Indeed,
a peripheral blood smear revealed no Howell-Jolly bodies.
Abdominal splenosis (AS) is a condition in which
autotransplantation of splenic tissue occurs after
iatrogenic/traumatic rupture of the spleen. AS differs from
accessory spleens that arise during embryogenesis. In AS,
depending on the amount of splenic pulpa that is spread
throughout the abdominal cavity, several to hundreds
of foci can be indentified. In addition, intrathoracal and
even intracerebral splenosis have been described. It is
estimated to arise in 65% of traumatic splenic ruptures
although usually not diagnosed until 10 years after
splenectomy. The borne again spleen can be functional
as has been suggested by mouse and human studies. AS
is often asymptomatic and is diagnosed by coincidence.
However, infarction, bleeding or obstruction can lead
to a symptomatic presentation. Usually AS requires no
treatment, but the diagnosis is warranted to exclude metastasised malignancy and to assess splenic function.
Physical examination was notable for uncontrolled eye
movements which were constantly present both at rest
and after fixation. Brain MRI, CT of thorax, abdomen
and pelvis, and examination of cerebrospinal fluid were
normal. However, nine months after presentation, she
was tested HIV-1 positive with a plasma HIV-1 RNA load
of 9971 copies per ml and CD4 count of 500 cells per mm3.
The diagnosis of HIV-associated opsoclonus-myoclonus
syndrome was made and she was started on combination
antiretroviral therapy (cART). Two years after presentation
the clinical picture remains unchanged despite treatment
with antiretroviral therapy, immunoglobulines, steroids
and gabapentin. Because of her complaints she is unable
to carry out her previous duties in the supermarket where
she worked.
Conclusion: In conclusion, we present a patient with the
dancing eye syndrome as a rare manifestation of HIV
infection at the time of seroconversion who does not
respond to treatment. The pathogenesis of this debilitating syndrome remains a mystery. The absence of
clinical improvement after initiation of therapy that target
the underlying disorder (cART) or the immune system
(immunoglobulines, steroids or gabapentin) has not been
described before. New insights are urgently needed for this
debilitating condition.
59.
58.
An unexpected cause of renal failure in a patient
with myelofibrosis
The borne again spleen
H.G. Jongsma-van Netten, M.B. Rookmaaker
University Medical Centre Utrecht, Department of
Department of Nephrology and Hypertension, Heidelberglaan
100, 3584 CX UTRECHT, the Netherlands, e-mail:
hnetten@umcutrecht.nl
J.W.R. Hovius1, H.J. Verberne1, R.J. Bennink1, W.L. Blok2
1
Academic Medical Centre, Department of Internal
Medicine, Bilderdijkkade 31 II, 1053 VH AMSTERDAM, the
Netherlands, e-mail: j.w.hovius@amc.uva.nl, 2Onze Lieve
Vrouwe Gasthuis, AMSTERDAM, the Netherlands
Case report: A 68-year-old woman was admitted because of
progressive renal failure and general weakness. Her history
comprised polycytemia vera 43 years ago, which had been
treated with splenic irradiation, busulphan, hydroxyurea
and phlebotomies and eventually transformed to myelofibrosis. She had recently been evaluated for renal masses
for which a kidney biopsy was performed. The pathology
report concluded ‘chronic inflammation’.
On physical examination her blood pressure was
172/90 mmHg, she had crackles over her lungs and
peripheral edema. Laboratory investigation showed a
microcytic anemia (Hb 7.8mmol/l), leukocytosis (39.7 x
109/l), increased circulating erythroblasts (25,8 x 109/l)
and mild thrombocytopenia (106 x 109/l). Her plasma
creatinine had suddenly increased from 253 umol/l to
410 umol/l in one month. A renal ultrasound showed
bilateral hydronephrosis. CT scanning confirmed the
hydronephrosis and revealed solid masses in the pyelum
and perirenal spaces of both kidneys. A nephrostomy
was inserted after which renal function improved slighty.
A 48-year-old man was referred to the outpatient clinic
with markedly elevated liver enzymes. His medical history
included splenectomy due to a car accident at the age of 5
years old and a gastric ulcer. Furthermore, he had a habit
of excessive alcohol abuse. Upon physical examination an
enlarged liver was observed. Blood tests were compatible
with alcoholic liver disease and alpha-fetoprotein levels
were marginally elevated. The patient was suspected of
alcoholic liver cirrhosis.
Further work-up included an ultrasound of the upper
abdomen, which revealed hepatomegaly and suggested
a central mass in the liver. MRI of the abdomen did not
show a hepatic mass, but revealed multiple (> 20) intraperitoneal and retroperitoneal structures with a maximum
diameter of 3 cm. The differential diagnosis included
metastasised malignancy and, with a medical history of
traumatic splenectomy, abdominal splenosis. A single
photon emission computed tomography (SPECT) with
99mTc-labelled heat-denatured autologous red blood cells
34
Unfortunately, soon after admission, the patient died of
sepsis. Autopsy showed extensive extramedullary hematopoiesis (EMH) in the liver and spleen, but also in the renal
parenchyma, pelvis and perirenal region. Revision of the
renal biopsy material also revealed renal EMH.
Discussion: EMH is the compensatory response to insufficient hematopoiesis in the bone marrow and can be
found in myelofibrosis, chronic myelogenous leukemia
and chronic hemolytic states. EMH is typically located
in spleen and liver, but can occur in almost any organ
including the kidneys. Renal EMH is often asymptomatic,
but can present with abdominal discomfort. It is mostly
bilateral and can cause renal failure due to either infiltration of the renal parenchyma, or urinary obstruction
through intrapelvic or perirenal masses. On ultrasonography, renal EMH presents as increased echogenicity of
the parenchyma or solid hypoechogenic masses in or
around the kidneys. On CT, renal EMH appears as welldefined soft tissue, moderately enhanced with intravenous
contrast. The differential diagnosis of bilateral renal
masses includes lymphomas, metastases, abcesses and
granulomatous diseases. The diagnosis renal EMH is
made by biopsy which shows hematopoiesis in all lineages
and can easily be confused with inflammatory tissue.
Treatment should be initiated in case of renal failure or
symptomatic EMH. Therapeutic options are chemotherapy
(i.e. busulfan, hydroxyurea) and high dose corticosteroids
aimed at the underlying condition or local radiotherapy of
the renal masses.
Conclusion: In patients with myelofibrosis and renal
failure, renal extramedullary hematopoiesis should be
considered as a cause of renal failure.
60.
HIV and hepatitis were negative and no M-proteine could
be detected. Chest X-ray and ultrasound of the abdomen
were normal, blood and stool cultures for parasites were
all negative.
Bone marrow biopsy showed 32% eosinophils, with
normal maturation of eosinophils. Chromosome studies
revealed no abnormalities; the RT-PCR was negatieve for
FIP1L/PDGRF a and ß mutations. A percutaneous kidney
biopsy specimen disclosed a dense tubular infiltrate
predominated by eosinophils and normal glomeruli.
Immunofluorescence was negative.
Based upon these findings, he was diagnosed with marked
central and peripheral eosinophilia most likely due to an
allergic reaction to mesalazine, as was supported by the
high levels of IgE. Concurrently, a nephrotic syndrome was
diagnosed whereas the kidney biopsy only showed interstitial nephritis. The latter only results in non-nephrotic
range proteinuria and cannot account for the observed
nephrotic syndrome. Based on the pathological data we
speculate that in addition to the mesalazine-induced
interstitial nephritis, mesalazine induced a minimal
change nephropathy as well, resulting in nephrotic-range
proteinuria. He was treated with 1 gr Methylprednisolone
for three days, followed by 60 mg of oral prednisone, which
quickly resolved his symptoms and resulted in complete
remission of the nephrotic syndrome and reversal of the
eosinophilia.
Allergic reactions to 5-ASA compounds are well known.
However, the combination of marked eosinophilia with
acute kidney failure with nephrotic range proteinuria
has been rarely described. Since these compounds are
frequently prescribed for prolonged periods, awareness
for these side-effects is important for the internist,
nephrologist, haematologist and last but not least the
gastroenterologist.
A young man with a bloated feeling
W.M. van der Deure, M.B.L. Leys, I.J.A.M. Verberk-Jonkers
Maasstad Hospital, Department of Internal Medicine, Groene
Hilledijk 315, 3075 EA ROTTERDAM, the Netherlands,
e-mail: wendyvanderdeure@hotmail.com
61.
Hypocalciuric hypercalcemia caused by chronic
lithium use, successfully treated with cinacalcet
A.E.C.A.B. Willemsen, A.G. Lieverse
Máxima Medical Centre, Department of Internal Medicine,
De run 4600, 5504 DB VELDHOVEN, the Netherlands,
e-mail: anneliekewillemsen@hotmail.com
A 21-year-old man presented with a bloated feeling,
nausea and vomiting since 2 weeks. He had a history
of ulcerative colitis, for which he used mesalazine
since 10 years. Except for peripheral edema, physical
examination was unremarkable. Laboratory data showed
marked eosinophilia (76,1%), with IgE levels higher
than 2000 kU/l. Blood results showed an increased
creatinine (160 mmol/l), a reduced albumin (14 g/l),
whereas urinalysis showed nephrotic-range proteinuria (15
gr/24 hrs) without microscopic hematuria. Anti-nuclear
antibodies, anti-double stranded DNA and ANCA were
negative. C3 and C4, immunoglobulin A, M and G levels
were within normal range, whereas serology for CMV, EBV,
Case: A 73-year-old woman was admitted to the psychiatric
ward with exacerbation of depression, anxiety and
confusion. She had a history of depression and anxiety,
for which she uses lithium for over 15 years. During
admission she developed nausea, vomiting and constipation. On physical examination there was nonspecific
tenderness in the lower abdomen. Laboratory examination
showed a corrected hypercalcemia of 2.68 mmol/l,
phosphate 1.00 mmol/l, albumin 47 g/l and an impaired
35
tration of plasma cells, fibrosis and increased serum
IgG4 levels. A frequent described form is auto-immune
pancreatitis, but a wide variety of tissues and organs can
be involved.
Case report: A 83-year-old man suffered from weight
loss, fatigue and decline in physical performance. He
did not have night-sweats or fever. Physical examination
was unremarkable except for a right-sided 1 cm large
supraclavicular lymph node. Laboratory findings were
normal except for a normocytic anemia (Hb 6.8 mmol/l),
renal insufficiency (serum creatinin 273 ug/l) without
proteinuria and hematuria and high serum total protein
(106 g/dl). Chest X-ray showed multiple densities
suspected for malignancy. PET and CT scan revealed
multiple hot spots, corresponding with pulmonary nodes
and extensive lymphadenopathy.
Bronchoscopy showed no abnormalities, cytologic
examination showed inflammatory changes. Culture
showed no growth of microbial organisms, culture and
PCR for tuberculosis were negative. Radiological guided
transbronchial biopsy of nodular lesions showed acute
inflammation and fibrosis with a polyclonal plasma cell
infiltrate. Plasmacells were predominant IgG4 positive.
Microscopy of the resected supraclavicular lymph node
showed inflammation and plasma cells with IgG4-positive
staining (> 30%). Renal biopsy revealed diffuse tubulointerstitial nephritis with infiltrate dominated by plasma
cells of which many were IgG4 positive. Serum IgG4 levels
were high (52.5 g/l, normal < 1.35 g/l), with concomitant
increase in IgG1 and IgG3. The diagnosis IgG4-related
disease with systemic manifestations, acute phase
response, lymphadenopathy, nodular pulmonary infiltrates
and renal manifestations was made. Treatment was started
with prednisolone 60 mg/day with a reduction of serum
creatinin to baseline value (112 umol/l) after 4 weeks. In
addition, the clinical condition strongly improved, the
patient gained bodyweight and lymphadenopathy and
pulmonary nodules resolved.
Conclusion: This case report describes a patient who
presented with abnormalities suspected for a disseminated
malignancy and acute renal failure. All abnormalities could
be attributed to pulmonary, nodal and renal involvement
of systemic IgG4-related disease. This disease is also
known as IgG4-related autoimmune disease and pancreatitis, IgG4-related plasmocytic disease or IgG4-positive
multi-organ lymphoproliferative syndrome and often
responds well to therapy with corticosteroids. This systemic
disease needs to be considered in patients with focal
infiltrating and fibrotic lesions and/or diffuse organ
involvement and malaise with elevated serum IgG4 levels
and in whom histological examination shows infiltration
with plasma cells. The diagnosis can be made by demonstrating a large fraction (> 30%) of IgG4-positive plasma
cells by specific staining.
renal function with a creatinine of 110 mmol/l, MDRD
42 ml/min/1.73m2. Further testing showed a parathyroid
hormone (PTH) of 6.8 pmol/l, 25-OH-vitamine D3 48
nmol/l and a decreased calcium urinary excretion of
0.8mmol/day. The urine calcium/creatinine clearance ratio
was low with 0.0078 mmol/mmol.
Discussion: In conclusion our patient has hypercalcemia
with a slightly elevated PTH, hypocalciuria and normal
vitamin D. Primary hyperparathyroidism was unlikely
considering the hypocalciuria. Hypocalciuria can be
caused by thiazide diuretics, milk-alkali syndrome or by
an inactivation of the calcium-sensing receptor (CaSR).
The patient did use thiazide diuretics, but the hypocalciuria did not resolve after discontinuation of this drug
and milk-alkali syndrome was ruled out. Therefore an
inactivation of the CaSR was the most likely cause.
Inactivation of the CaSR results in decreased calcium
sensing and therefore inappropriate PTH release with
respect to the serum calcium concentration. This inactivation can be caused by multiple mechanisms. There can
be a mutation in the gene of the CaSR, as is the case in
familial hypocalciuric hypercalcemia, auto-antibodies
against the CaSR can develop and chronic use of lithium
can cause a deactivation of the CaSR. The family history
was not contributory and since auto-antibodies against the
CaSR are very rare, in this patient the chronic lithium use
was most likely the cause.
Uncorrected, persistent hypercalcemia may exacerbate
psychiatric dysfunction, so there was an indication for
treatment. In some cases hypercalcemia resolves after
discontinuation of lithium, but considering her current
psychiatric problems discontinuation was contra-indicated.
A few case reports describe successful treatment of
lithium-induced hypocalciuria with cinacalcet. Cinacalcet
is a class II calcimetic agent that acts as an allosteric
modulator of the CaSR in the parathyroid glands. It
restores the calcium sensitivity of the CaSR. We started
our patient on cinacalcet 30 mg once daily and the serum
calcium successfully decreased to 2.41 mmol/l and the
PTH to 2.6 pmol/l.
This case illustrates how lithium-induced hypocalciuria
was successfully treated with cinacalcet.
62.
Tubulo-interstitial nephritis as part of systemic
IgG4-related disease
A.B. Kramer, C.A. Stegeman
University Medical Centre Groningen, Department of
Nephrology, Hanzeplein 1, 9713 GZ GRONINGEN, the
Netherlands, e-mail: a.b.kramer@int.umcg.nl
Introduction: IgG4-related systemic disease is characterized by tissue and organ inflammation with infil-
36
63.
Pro-active intoxication of a dialysis patient?
intake. At admission she was comatose (Glasgow Coma Scale
E1M4V2) and had normal sinusrythm of 102 beats/min,
blood pressure was 150/71 mmHg and respiratory rate was
30 breaths/min. Laboratory results included pH 7.28, pCO2
2.2 kPa, HCO3- 7.4 mmol/l, lactate 0.7 mmol/l, sodium
133 mmol/l, potassium 4.2 mmol/l, chloride 105 mmol/l,
glucose 4.1 mmol/l, albumin 33 g/l, osmol 281 mOsm/kg
and urine ketones were positive. Anion gap was 20.6 mmol/l,
where 4.8 was expected in view of albumin level. Strong
ion difference was 32 mEq/l, which is decreased. Osmolgap
was normal. Toxicology screening, analysis of liquor and
computed tomography of the brain showed no abnormalities.
Electroencephalography showed persistent epileptic activity.
Nonconvulsive status epilepticus was diagnosed, for which
the patient was treated with diphantoïn. This metabolic
acidosis was diagnosed as a ketoacidosis and treated by
dextrose infusions. Acidosis resolved within 3 days without
substantially increase in serum glucose during therapy.
Conclusion: This is a case of ketoacidosis due to starvation
in a pregnant woman with seizures the days before
admission and coma due to a non-convulsive status
epilepticus at presentation. Starvation leads to a decline in
insuline secretion, caused by an increase of sympathetic
drive, induced by dehydration. Furthermore, there is low
hepatic storage of glycogen due to an increased demand.
This will worsen the lipolysis and generate an excess of
acetyl coenzyme A, resulting in ketoacidosis. In case of
unexplained metabolic (keto)acidosis starvation is an
uncommon finding and clinicians should be aware of
this cause. Treatment consists of stimulating endogenous
insulin by dextrose infusion. Severe metabolic acidosis as
a consequence of acute starvation in pregnancy has been
described in the literature and is believed to be due to
frequent vomiting and an altered glucose metabolism. In
our patient the inadequate oral intake due to the seizures
and coma led to the ketoacidosis.
M.J.M.M. van der Steen, B. Veldman, S. Luderer
Canisius Wilhelmina Hospital, Department of Internal
Medicine, PO Box 9015, 6500 GS NIJMEGEN, the
Netherlands, e-mail: m.vandersteen@live.nl
A good medical history is essential for every patient. A
67-years-old hemodialysis-patient presented himself at
the emergency room after a sudden collapse with paralysis
of his legs. Electrocardiogram showed typical changes of
peaking of the T-wave, prolongation of the PR-interval, loss
of the P-wave amplitude and widening of the QRS complex.
Laboratory investigations revealed a hyperkalemia of
9,3 mmol/l. The patient was treated with calcium, insulin
and glucose and resonium. An acute dialysis was arranged.
Soon after treatment was initiated symptoms resolved and
the electrocardiogram normalized.
A thorough analysis took place of what could be the cause
of this life threatening hyperkalemia. The patient was
aware of potassium rich products and was compliant to
his dietary rules. The only recent change in his diet was
the addition of ‘Becel-Pro-Activ® voor de bloeddruk’. This
is a low-sodium margarine in which sodium is replaced by
potassiumgluconate.
By measuring the weight of a slice of bread before and after
addition of the margarine we calculated an extra potassium
intake of 40 mmol a day. It seemed that this was the cause of
the hyperkalemia. No other cause of the sudden increase of
potassium could be identified. After discontinuation of the
Becel Pro-activ, no excessive potassiumlevels were measured.
With this case report we would like to draw attention to the
importance of history taking in the patient with a hyperkalemia and the emergency treatment of hyperkalemia.
Low-sodium products can be a hidden source of potassium.
64.
Severe ketoacidosis caused by starvation during
pregnancy: a case report
65.
M. Kok, N.X. de Rijk, H. Endeman
Diakonessenhuis Utrecht, Department of Intensive Care,
Bosboomstraat 1, 3582 KE UTRECHT, the Netherlands,
e-mail: m_kok_@hotmail.com
Middle aortic syndrome, a rare cause of severe hypertension in a young adult
R.W. Andriessen, C.E.H. Siegert
St. Lucas Andreas Hospital, Department of Internal
Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the
Netherlands, e-mail: r.andriessen@slaz.nl
Introduction: Diabetic dysregulation is the most common
cause of ketoacidosis. This is a case of an uncommon cause
of ketoacidosis: starvation.
Case: A 37-year-old 34-weeks pregnant woman was admitted
to our intensive care unit because of unexplained loss of
consciousness. Medical history revealed epilepsy since
more than seven years, for which she was treated with
carbamazepin. She had suffered from several seizures the
days before presentation, which had led to a reduced oral
Case report: A 24-year-old man presented with severe
hypertension, chest pain, headache, and dizziness. The
patient was a non-smoker with no significant medical or
family history. Physical examination revealed a high blood
pressure 200/117 mmHg, measured in both arms, and a
pulse rate of 100 bpm. Besides the high blood pressure, the
physical examination was completely normal, with strong
and symmetric peripheral pulses.
37
Introduction: Intravascular lymphoma is a rare diagnosis,
most often diagnosed by autopsy. The disease is characterized by proliferation of clonal lymphocytes within
the lumen of small vessels, with little involvement of
surrounding tissue. Noteworthy is that intravascular tumor
cells are seldom identified in peripheral blood smear in
contrast to leukemia and other lymphomas. Diagnosis is
almost exclusively made by biopsies of a suspected site of
involvement. Clinical presentations are various; but have a
predilection to involve brain and skin.
We describe a patient diagnosed with intravascular
lymphoma ante-mortem.
Case-report: A 73-year-old man, with a history of
polycythaemia vera, presented himself with fever and
abdominal pain. On physical examination he had pain
in his right upper abdomen and petechiae on his legs.
Laboratory tests revealed a normal hemoglobin, leukocytosis 14,8 * 109/l, thrombocytopenia 38 * 109/l, c-reactive
protein 67 mg/l and elevated lactate dehydrogenasis
(LDH) 15530 IU/l. The patient was admitted with the
differential diagnosis of sepsis or hematologic malignancy.
X-rays did not show a focus and CT-scan of the abdomen
showed nothing but splenomegaly. During his stay, he
became hypotensive and anuric despite antiobiotic therapy.
Analyses were extended by CT-scan of the thorax, showing
some pleural effusion and bone marrow examination with
no morphological changes in the aspirate. Because of rapid
deterioration of the patient’s condition, antibiotics were
changed and hydrocortisone was started. Within two days
he became better and LDH decreased. In the mean time
bone marrow immunophenotyping showed evidence of
a monoclonal B-cell population suggesting lymphoma.
But surprisingly PET-CTscan showed no FDG-uptake,
nor any lymphadenopathy. As the patient became better
and no lymphoma could be located, hydrocortisone was
discontinued, with a worsening condition of the patient
and rapidly raising LDH-levels as result. At that time the
histo-pathological examination of the crista biopt revealed
myelofibrosis due to a myeloproliferative syndrome and
intravascular, atypical proliferation of B-cells, as did skin
biopsy. The diagnosis of intravascular lymphoma was
confirmed. We started reversed R-CHOP treatment being
afraid of tumorlysis. The patient became clinical better and
LDH decreased rapidly.
Unfortunately the patient deceased a few days later due to
peri- and epidural hemorrage caused by a lumbal puncture.
Conclusion: Intravascular lymphoma is a rare diagnosis
in life, as the clinical presentation is heterogeneous and
rapidly progressive. Diagnosis is confirmed with biopsy,
with intravascular tumor cells and little involvement
of surrounding tissue. Treatment consists of standard
lymphoma treatment (like R-CHOP) supplemented with
intrathecal chemotherapy.
Initial laboratory tests showed a hypokalemia (3.3 mmol/l;
normal range 3.5-4.5 mmol/l), the other results, including
complete blood count, esr, electrolytes, renal function,
thyroid profile and troponin, were normal. The urinalysis
showed no protein-uria.
Additional tests showed an elevated aldosteron level (1.41
nmol/l;normal range 0.11-0.87 nmol/l) and plasma renin
level (79 pg/ml; normal range 5.1-38.7 pg/ml), with normal
A/R ratio (6.4), which suggested the presence of secondary
hyperalostero-nism due to renovascular disease.
Because of the severe chest pain and hypertension a
computed tomography was made and excluded an aortic
dissection. The CT did demonstrate a severe narrowing
(diameter of 9mm) of the distal abdominal aorta, with signs
of bilateral renal artery stenosis and celiac artery stenosis.
Aortography confirmed abdominal aortic narrowing with
a significant bilateral stenosis of the renal arteries and
narrowing of the superior mesenteric artery.
Renography showed asymmetric renal function (left:right
=27:73%).
The patients blood pressure was controlled with
aggressive antihypertensive therapy (labetolol, enalapril
and nifedipine). Serum potassium normalised and his
headache and thoracic pains disappeared.
The patient was furthermore initially treated with PTA of
the right renal artery, and finally with aorticbypass surgery.
Discussion: Middle aortic syndrome (MAS) is a vascular
condition characterized by progressive segmental
narrowing of the abdominal or distal thoracic aorta. The
etiol-ogy has been described as congenital, acquired,
inflammatory or infectious. MAS can be found most
frequently in children and young adults, with no sex predilection. Symptoms typically occur within the first three
decades of life and include hyperten-sion, lower extremity
claudication, and mesenteric ischemia. The condition may
be considered as a life-threatening emergency as a result
of the complications associ-ated with severe hypertension.
Aortography remains the gold standard for diagnosis.
The timing of intervention is controversial and difficult
to decide. Hypertension refrac-tory to antihypertensive
treatment and severe ischemic symptoms are major
indica-tions in proceeding to intervention. When multiple
arteries appear to be involved in a young patient with a new
diagnosis of hypertension, the middle aortic syndrome
should be considered in the differential diagnosis.
66.
The almost invisible lymphoma
R.L. de Jager, K.L. van Rooijen, E.J.M. Ahsmann,
E.G. van Lochem, S.K. Klein
Meander Medical Centre, Department of Internal
Medicine, Utrechtseweg 160, 3800 BM AMERSFOORT, the
Netherlands, e-mail: dejager.rosa@gmail.com
38
67.
A rare cause of heparin-induced thrombocytopenia
complicated by venous pulmonary thromboembolism and adrenal hemorrhagic insufficiency
haemorhagic adrenal infarction with – a probably
transient – acute adrenal insufficiency has never been
described after HIT.
M.J.R. Quanjel, E. Beeldman, C.R.G.M. Daemen-Gubbels,
J.J.J. de Sonnaville
Tergooi Hospitals Hilversum, Department of Internal
Medicine, Van Riebeeckweg 212, 1213 XZ HILVERSUM, the
Netherlands, e-mail: marianquanjel@hotmail.com
68.
Bone lesions are not always what they seem to be
J.M. Sprangers, F.E. D. de Jongh, F. Croon-de Boer, A. Dees
Ikazia Hospital Rotterdam, Department of Internal Medicine,
Montessoriweg 1, 3083 AN ROTTERDAM, the Netherlands,
e-mail: melanie_sprangers@hotmail.com
Introduction: Heparin-induced thrombocytopenia (HIT)
is a well recognized disorder with severe thrombo-embolic
complications with a mortality rate of 25%, usually because
of venous thrombo-embolism, myocardial ischemia or
mesenterial infarction. HIT is caused by platelet-activating
antibodies that recognize complexes of platelet factor four
and heparin, resulting in activation of the coagulation
cascade leading to thrombin generation and induction of
vascular endothelial thrombogenic effects. The usual cause
of HIT is treatment with heparin or low molecular weight
heparin. We describe a patient with heparin-induced
thrombocytopenia linked to Fondaparinux prophylaxis
after elective knee surgery, complicated by venous thrombo
-embolism and bilateral adrenal hemorrhagic infarction.
Case report: A 67-year-old woman presented with back
pain, subfebrile temperature and vomiting eleven days
after a elective and uncomplicated total knee replacement.
She received Fondaparinux to prevent venous thromboembolic complications according to protocol. Physical
examination showed a slightly dyspneic women
with a temperature of 38,9 °C and blood pressure of
130/85 mmHg. Besides epigastric tenderness and a slightly
swollen knee further examination was unremarkable. A
CTA (after a normal X-ray of the chest) showed bilateral
pulmonary thrombo-embolism, and also bilateral
enlargement of the adrenal glands with peri-adrenal infiltration. Blood tests showed a progressive thrombocytopenia
(nadir 18 x 109/l) and hyponatremia (nadir 127 mmol/l)
and the Solid-Phase Enzyme Immunoassay for HIT was
positive, upon which treatment with fondaparinux was
discontinued and replaced by Danaparoïd and acenocoumarol. The persistence of vomiting, malaise and subfebrile
temperatures, associated with enlarged adrenals and a
decrease of sodium levels led to a possible diagnosis of
Addison’s disease which was confirmed by a Synacten
test (baseline, 30’, 60’ cortisol of 0.11, 0.11, 0.12 mmol/l,
with a baseline ACTH of 559 pg/ml). After initiation of
Hydrocortisone treatment the patient showed remarkable
clinical improvement. CT-scan of chest and abdomen
showed no signs of malignancy. Replacement therapy with
hydrocortisone was required.
Conclusion: This previously healthy patient showed an
extremely unusual cause of HIT, namely Fondaparinux,
with severe thromboembolic complications. A bilateral
Introduction: In hemato-oncology many patients present
with extensive bone lesions, which can be caused by many
different diseases, but mostly by metastatic carcinoma or
multiple myeloma.
Case: A 65-year-old woman presented at the surgical
emergency department with a (pathological) fracture of the
proximal humerus for which she had surgery.
Internal medicine was consulted because of abnormal
laboratory findings.
On physical examination we found a supraclavicular mass
on the left side, 6 cm in length together with scalp lesions.
Further examination revealed no other abnormalities.
Laboratory findings showed a hypercalciemia
(3.80 mmol/l), hemoglobin 7.5 mmol/l, ESR 112 mm/h,
LDH 213 IU/l, AF 269 IU/l and GGT 170 IU/l. M-protein
was detectable, IgG type lambda, 0.6 g/l.
Further investigation revealed numerous osseous lesions
in both humeri, the sternum, thoracic spine, femora and
multiple ribs. CT scan showed no signs of abdominal or
intra-pulmonary pathology or lymphadenopathy.
Bone marrow aspiration and biopsy was performed, which
showed no signs of multiple myeloma, carcinoma or
melanoma. In addition, biopsies of the supraclavicular mass
and the scalp lesions were analyzed and showed a CD30+
anaplastic large cell T-cell lymphoma, ALK-negative (ALCL).
Our patient was treated with radiotherapy of the humerus
followed by chemotherapy (CHOP + G-CSF) resulting in a
partial response after 3 cycles.
However, a few weeks later she presented with progressive
tetraparesis. MRI of the spine showed diffuse infiltration of
the spinal cord and extensive leptomeningeal involvement.
Despite treatment with dexamethasone and radiotherapy
her condition progressively worsened and she died within
several weeks.
ALK-negative ALCL counts for 2% of the Non-Hodgkin
lymphomas, typically have an aggressive behavior and a
rather poor prognosis. They often present in stage III or IV
with painless lymph node masses, anemia and high lactate
dehydrogenase. However, extranodal lesions as described
above in our patient are also reported.
Summary: We presented a middle age women with a pathological fracture, hypercalciemia and bone masses. Multiple
39
myeloma and metastatic carcinoma were excluded.
Biopsies of the supraclavicular mass and the skin lesions
revealed an anaplastic large cell T-cell lymphoma (ALCL).
Conclusion: We described an unusual presentation of
malignant lymphoma with extensive bone lesions, but
without involvement of blood, bone marrow and lymphoid
tissues.
69.
disease due to talcum inhalation have not been reported it
is not inconceivable.
Discussion: When analysing a patient with iron deficiency
it is important to ask for unusual cravings in order to
detect the pica syndrome, which has an incidence up
to forty percent in non pregnant iron deficient adults.
Furthermore, such behaviour may be copied by relatives
as well.
An unusual craving!
70.
E.G. Gerrits1, J.B. Schnog2
1
University Medical Centre Groningen, Department of
Internal Medicine, Hanzeplein 1, 9713 GZ GRONINGEN,
the Netherlands, e-mail: e.g.gerrits@int.umcg.nl, 2St. Elisabeth
Hospitaal, CURACAO, the Netherlands Antilles
New oral direct thrombin inhibitors: a coming
treatment option for paraneoplastic thrombotic
disease?
H.T. van der Boog, A. Goosens, A.C. Ogilvie
’t Lange Land Hospital, Department of Internal Medicine,
Toneellaan 1, 2725 NA ZOETERMEER, the Netherlands,
e-mail: ac.ogilvie@xs4all.nl
Introduction: Pica refers to an abnormal appetite for both
edible and non-edible substances usually occuring in
children with developmental disability or brain injury.
However, it is also associated with the iron deficiency state,
most often presenting with a craving for ice (pagophagia),
but substances like rubber, lemon peals and toothpicks
have been reported as well. The craving mostly rapidly
reverses with iron repletion. Here we present a case of
craving for Johnsons’ baby powder.
Case report: A 41-year-old woman was referred to the
outpatient clinic because of severe iron deficiency anemia.
She was supposed to take iron tablets because of anemia
caused by frequent epistaxis due to hereditary hemorrhagic
telangiectasia. Upon physical examination she had characteristic mucocutaneous telangiectasiae. In the past,
pulmonary and cerebral blood vessel abnormalities were
excluded elsewhere. She had discontinued her iron pills
for eight months. Laboratory results revealed severe iron
deficiency anemia. During the consult she asked whether
it was normal to consume one bottle of Johnsons’ baby
powder dayly, a behaviour subsequently picked up by
her 11-year-old daughter. She was diagnosed with pica
syndrome secondary to severe iron deficiency anemia.
After four weeks of iron supplementation she felt no
more craving and completely stopped its consumption.
Her general practitioner was informed and immediately
intervened pertaining to her daughter, in whom iron
deficiency was excluded. Johnsons’ baby powder or talcum
powder contains hydroxylated magnesium silicate and
zinc oxide, minerals that inhibit iron absorption. Talcum
powder craving associated with iron deficiency has not
previously been described. Pica for this powder might
be harmful for a patient ‘s health. As both mother and
daughter consumed the powder straight from its bottle
it is very likely that significant amounts have also been
inhaled. Acute respiratory problems secondary to talcum
inhalation have been described. Even though chronic lung
Introduction: Cancer patients are at increased risk
of developing venous thromboembolism (VTE). The
occurrence of VTE predicts worse prognosis in cancer
patients: whereas the 1-year survival in cancer patients
free of thrombosis is 36%, in patients with diagnosed
VTE it is 12%. The management of VTE in cancer patients
is challenging because the anticoagulant treatment in
these patients can be less effective and carry considerable
morbidity.
Case report: A 66-year-old woman was diagnosed with
a stadium IV ovarian cancer. She was on fenprocoumon
treatment after a deep venous thrombosis and a portal
vein thrombosis. During her Carboplatin Paclitaxel chemotherapy she developed a hematopericard and a deep venous
thrombosis, despite having a prolonged prothrombin
time (> 7,0 INR). During salvage treatment with subcutaneous Enoxiparin the thrombotic proces progressed and a
thrombopenia developted, due heparin-induced thrombocytopenia (confirmed by heparin-platelet factor 4 antibody
testing). Treatment with intravenous Argatroban was
initiated as a subsequent treatment and led to suppresion
of the ongoing thrombosis proces. After stabilisation the
treatment was switched to subcutaneous Fondaparinux,
in order to make it possible to discharge her. However,
the deep venous thrombosis progressed and intravenous
Argatroban had to be administered. During subsequentely
subcutaneous Danaparoid treatment she developed
again thrombopenia. She responded when intravenous
Argatroban was given as salvage treatment. The thrombopenia resolved. Unfortunately, her cancer progressed
and it was decided to stop the chemotherapy and to give
supportive care only. Because of the demonstration of
the clinical efficay of treatment with Argatroban, it was
decided to administer off-label Dabigatran, another direct
thrombin inhibitor with an oral formulation. Unexpectedly,
40
approximately 1 year later, she was in a much better
clinical condition and it was decided to start second
line Carboplatin Liposomal-Doxyrubicin treatment when
documented disease progression developed, while the
Dabigatran treatment was continued. No new thrombotic
event occurred.
Conclusion: This extra ordinary case suggests that direct
thrombin inhibitors may play also an important role in the
treatment VT-PE in cancer patients, reflecting the positive
results of recent clinical studies of oral direct thrombin
inhibitors as thromboprophylaxis after elective hip or knee
replacement surgery.
71.
thalassemia major) and much less pronounced in heterozygotes (ie beta thalassemia minor).
On electrophoresis in patients with beta-thalassemia
minor, over 90% of the hemoglobin will be hemoglobin
A along with an elevation in the hemoglobin A2 value,
sometimes as high as 7%, and an increase in HbF in about
50% of patients. However, some forms of beta-thalassemia
are not associated with elevated hemoglobin A2. This
may be the result of the presence of coinherited deltathalassemia from one of the common structural mutants
of the d gene or from mild beta-thalassemia mutations.
Therefore, a high-normal concentration of HbA2 does not
rule out the presence of beta-thalassemia trait, as shown
in our patient.
Anemia with persistent, unexplained low MCV with
normal Hb-electrophoresis and high-normal HbA2
prompts further evaluation of thalassemias.
The microcytic anemia in our patient does not have clinical
relevance. Because this hemoglobinopathy is hereditary, it
is an indication for screening of relatives to avoid the risk
of beta-thalassemia major in offspring of our index patient
or his relatives.
Unusual cause of beta-thalassemia minor
I.J.H. Vriens1, R.H. Olie1, Y. Kluiters1, C.L. Harteveld2,
L.V. Beerepoot1
1
St. Elisabeth Hospital, Department of Internal Medicine,
Hilvarenbeekseweg 60, 5022GC TILBURG, the Netherlands,
e-mail: ingeborgvriens@hotmail.com, 2Leiden University
Medical Centre, LEIDEN, the Netherlands
A 30-year-old kaukasian man without a medical history
was referred to our clinic because of fatigue. Physical
examination was unremarkable. Laboratory investigations
showed microcytic anemia (Haemoglobin 8.1 mmol/l
(8.5-11.0), MCV 71 fl (80-100), MCH 1,46 fmol/l (1.702.10)). Ferritin value was 51 mg/l (16-165). Serum iron
level was 10 mmol/l (11-28), total iron-binding capacity
59 mmol/l (45-75) and transferrin saturation 17% (18-38),
but our patient was taking iron supplements at that time.
We advised the patient to stop the iron supplements and
decided to evaluate the digestive tract for blood loss. The
results of evaluation by esophagogastroduodenoscopy,
colonoscopy, and videocapsule endoscopy were normal.
Biopsies taken from the duodenum didn’t show signs of
celiac disease. After cessation of the iron supplements,
haemoglobin, MCV and ferritin values didn’t further
decline. Iron deficiency hereby definitely wasn’t the cause
of the microcytic anemia. Hb-electrophoresis performed
in our clinic showed normal amounts of HbA2 (3,1%,
ref 2.5-3.5%), concluding that there were no signs of betathalassemia. No common mutations were found in the
alpha-globin chain, grossly ruling out alpha-thalassemia.
Further investigation on hemoglobinopathies however,
showed a heterozygous mutation in the HBB-gene and
HbA2 was high-normal (3,2%). Our patient therefore has
beta-thalassemia-minor.
Beta-thalassemia is due to impaired production of
beta-globin chains, leading to a relative excess of alphaglobin chains. The degree of alpha-globin chain excess
determines the severity of subsequent clinical manifestations, which are profound in homozygous patients (ie beta
72.
Recurrent vomiting stopped by taking a hot shower
W.A.G. van der Meijden, T.C. Minderhoud,
E.F.H. van Bommel, W. Lesterhuis
Albert Schweitzer Hospital, Department of Internal
Medicine/Gastroenterology, Albert Schweitzerplaats
25, 3318 AT DORDRECHT, the Netherlands, e-mail:
wagvdmeijden@kliksafe.nl
Case report: A 24-year-old male visited our emergency
department for the second time in three months with
hematemesis. His medical history included diabetes
mellitus type-I and depression. Three months ago a
grade-B-refluxoesophagitis was diagnosed. The patient
reported frequent vomiting with traces of blood since
one day and colicky abdominal pain. Meleana was not
reported. Physical examination showed a skinny patient.
Blood pressure was 145/75 mmHg, pulse rate 93 beats/
min. Abdominal examination revealed no abnormalities. Laboratory investigation included haemoglobin
level of 8,1 mmol/l; white-blood-cell count of 19,2 *
109/l and C-reactive protein level of 21 mg/l. Serum
creatinine amounted to 71 mmol/l, urea 6,2 mmol/l,
amylase 4 IU/l, glucose 15,3 mmol/l. Serum electrolytes
and venous bloodgas were within the normal range.
Chest X-ray showed no evidence of pneumomediastinum
or pneumoperitoneum. The patient was hospitalized
for observation and to perform duodenoscopy. The
next morning, nurses were amazed about the patient’s
behaviour, because he spent the whole night in the
41
bathroom taking many hot showers. Vomiting was not
reported over the night. Duodenoscopy revealed gradeD-(reflux)oesphagitis and prolaps by vomiting, no
hiatal hernia. His recurrent periods of severe vomiting
and frequently taking hot showers made us suspect
the ‘cannabinoid-hyperemesis-syndrome’. When asked,
the patient confirmed using cannabis for many years.
Subsequently his partner mentioned daily cannabis use
and many hospital admissions the last two years because
of dehydration by vomiting.
Discussion: ‘Cannaboid-hyperemesis-syndrome’ has been
described only recently in 2004. Patients with a history
of several years of cannabis abuse prior to the onset of
hyperemesis acquire cyclical vomiting illness. Cannaboids
have an anti-emetic effect. The paradoxical effects in
‘cannaboid-hyperemesis-syndrome’ are not understood.
Proposed mechanisms of cannabinoid hyperemesis
include toxicity due to marijuana’s long half-life, fat
solubility, delayed gastric emptying, and thermoregulatory
and autonomic disequilibrium via the limbic system.
Effects of cannabinoids on the limbic system might be the
underlying mechanism for the compulsive hot bathing
behaviour. Warm water improved the symptoms. Cessation
of cannabis stops the cyclic vomiting. Essential for the
diagnosis is a history of regular use of cannabis for years.
Major clinical features of this syndrome are: severe nausea
and vomiting; vomiting that recurs in a cyclic pattern over
months; resolution of symptoms after stopping cannabis
use. Supportive features are: compulsive hot baths with
symptom relief; colicky abdominal pain; no evidence of gall
bladder or pancreatic inflammation.
Conclusion: If patients presenting with cyclic severe
vomiting, accompanied by colicky abdominal pain and
compulsive hot bathing, the diagnosis of ‘cannabinoidhyperemesis-syndrome’ should be considered.
73.
before final diagnosis is made. We describe a patient
with submandibular and mediastinal lymphadenopathy
associated with AIP.
Case report: A 62-year-old male was analyzed for
non-painful submandibular lymphadenopathy since 2007.
At presentation, he reported a rapid development of
unilateral submandibular nodule in the absence of fever,
weight loss or nightly perspiration. Physical examination
was further unremarkable. Laboratory assessment of
blood chemistry, infection serological and bone marrow
tests were normal. Initial Computerised tomography (CT)
revealed no other localisation of pathological lymphoma.
Cytologic and histologic findings of submanidibular
lesion revealed inflammatory changes without evidence
of malignancy.
Three years later, patient presented with painless
obstructive jaundice. Physical examination showed
jaundice and firm swollen submandibular nodes. Blood
chemistry revealed elevated bilirubin 130 umol/l (n: 0-17
umol/l), AF 542 U/l (n:40-125 U/l), GGT 910 U/l (n:0-55
U/l), ALAT 840 U/l (n:0-45 U/l) and ASAT 467 U/l (n:0-35
U/l).
CT revealed a mass in the pancreatic head, mesenteric
peripancreatic and mediastinal lymfeadenopathy.
Endoscopic retrograde cholangiopancreatography (ERCP)
with insertion of an endoprosthesis was performed
and showed distal stenosis of the common bile duct.
Brush cytology of the stenosis showed no malignancy.
Endoscopic ultrasound revealed diffuse oedematous
pancreas, more prominent in the pancreatic head and
fine needle aspiration was again negative for malignancy.
Autoimmune serology, such as antinuclear antibody(ANA),
Anti-neutrophil cytoplasmic antibody (ANCA) was
negative. IgG4 was elevated (20.7 g/l; n:0.08-1.4 g/l),
highly suggestive of AIP. Treatment was started with
20 mg of prednisolone. After 2 weeks follow-up CT showed
resolution of pancreatic mass, mediastinal, peripancreatic
lymphadenopathy and IgG4 level dropped. Azathioprine
50mg was started and prednisolon was tapered slowly.
Complete resolution of submandibular lymphadenopathy
was noted after 6 weeks of treatment.
Conclusion: AIP should be considered in every patient who
presents with unexplained systemic disease in combination
with pancreatic abnormalities. Diagnosis is based on a
combination of diagnostic criteria based on histology,
imaging, serology and organ involvement. Since AIP
often mimics pancreatic or biliary cancer and in general
shows excellent response to corticosteroids, accurate
diagnosis is important. Consequently, it may prevent
unnecessary surgical intervention and potential morbidity
and mortality.
Sounds from the abdomen of cervical lymphadenopathy heralding autoimmune pancreatitis
F.M.F. Alidjan, J.W.J. van Esser, M.J. van Heerde
Amphia Hospital, Department of Internal Medicine,
Molengracht 21, 4800 RK BREDA, the Netherlands, e-mail:
falidjan@amphia.nl
Introduction: Autoimmune pancreatitis (AIP) is a rare
benign disorder of presumed autoimmune etiology that is
associated with characteristic clinical, histologic, imaging
and serum marker findings.
AIP may occur as a primary pancreatic disorder, but
is often associated with other autoimmune disorders.
Most often the diagnosis is made in case of overt
pancreatic disease. However, extrapancreatic manifestations may predominate clinical symptoms, even years
42
74.
Case: A 66-year-old woman was admitted for dyspnoea
and aching on the right side of the chest. She complained
of a gradual weight loss and an elevated temperature.
She has a history of pulmonary tuberculosis and visited
our out-patient clinic for several years because of lymfoplasmocellular lymphoma (Waldenström disease).
Previous treatment with chlorambucil leaded to sustained
remission. One year before admission she experienced a
painful volume increase of her right breast. Excision biopsy
showed lymfoplasmocellular lymphoma. During follow up
these complaints faded.
At presentation a moderately ill woman was seen.
Temperature was 37,3 °C, pulse 98/min, oxygen saturation
92% breathing ambient air. The axillary skin and lateral
side of the right breast were purple-red and felt hardened
on palpation. No palpable lymph nodes were found.
Chest examination revealed diminished breathing sounds
and dullness on percussion, notably on the right side
of the chest. Laboratory results showed elevated CRP
(218 mg/l) and BSE (89 mm/h), without leukocytosis
(8,9 * 109), anaemia with normal cell indices. Viscosity
was 2,5 mPascal/sec. and IgM 18,1 g/l, stable compared
to previous measurements. Chest X-ray revealed pleural
fluid predominantly on the right side. Antibiotics and
furosemide had no effect on dyspnoea, fever or CRP.
Multiple thoracic drainages were performed, without
lasting improvement.
Pleural fluid was characterised as an exudate, no
monoclonal cell population was detected, cultures and
PCR for tuberculosis were negative. On CT scanning
of the thorax we found an axillary lymphoma, eleven
cm in diameter and bilateral pleural fluid. Histologic
examination showed lymphoplasmocellular lymphoma
without evidence for evolution to a high grade lymphoma.
Systemic chemotherapeutic treatment with rituximab,
cyclophosphamide, vincristine and prednisone was started.
Sclerotherapy with talc and subsequently with bleomycin
failed to decrease the massive production of pleural fluid.
However instillation of 50 mg of rituximab through
the thoracic tube resulted in an immediate decline in
production. A second instillation of rituximab in the
pleural cavity was not possible. Now, two years later, the
patient is doing well without recurrence of the pleural
fluid.
Discussion: Rituximab is a chimeric monoclonal antibody
selectively binding to CD20 positive cells leading to cell
destruction. It is widely used for the systemic treatment
of CD20 positive non Hodgkin lymphoma. Only 2 case
histories describe the pleural instillation of rituximab.
Conclusion: In cases of therapy resistant pleural fluid
associated with CD20 positive lymphomatous pleuritis,
intrapleural rituximab is a possible treatment option.
Myelodysplastic syndrome and myelofibrosis
in a patient with multiple sclerosis treated with
natalizumab
M.A.E. Rab, P.C. De Bruin, S.T.F.M. Frequin, H.R. Koene
St. Antonius Hospital, Department of Hematology,
Koekoekslaan 1, 3435 CM NIEUWEGEIN, the Netherlands,
e-mail: minkerab@hotmail.com
Introduction: Multiple sclerosis (MS) is an auto-immune
disorder with limited therapeutic options. Natalizumab,
an anti-alpha4 integrin antibody, has shown effectivity
as second line treatment of relapsing-remitting MS.
Although the exact mechanism of this antibody remains
unclear, the most likely mechanism is thought to be the
prevention of leukocyte adhesion to vascular endothelium,
thus preventing migration of immune cells in the central
nervous system. Besides the positive results of natalizumab
on MS disease activity, severe adverse effects have been
reported.
Case report: A 32-year-old patient with MS visited our
outpatient clinic because of severe, transfusion-dependent
anemia. At presentation, he was being treated with
natalizumab for 15 months. Laboratory investigation
revealed no clear cause of the anemia. Bone marrow
investigation showed only mild dysplasia, cytogenetic
analysis revealed no abnormalities. Although anemia was
not a know adverse effect of natalizumab use, we discontinued the treatment. Six months after discontinuation,
the anemia resolved spontaneously to Hb-concentrations
of 9 mmol/l. Because MS disease activity increased
again, natalizumab was reintroduced 14 months later.
Unfortunately, the anemia recurred. This time it did not
improve after cessation of natalizumab therapy. Trephine
biopsy showed severe dysplasia and fibrosis. Cytogenetic
analysis was again normal. Myelodysplasia and/or myelofibrosis has not been reported as a side effect of natalizumab
in the literature, although two concisely described cases
were found in the online drug library DrugLib (www.
druglib.com).
Conclusion: Treatment with natalizumab is associated
with bone marrow dysplasia and fibrosis. Therapy
should immediately be discontinued upon occurrence of
unexplained anemia.
75.
Intrapleural rituximab for sclerotherapy resistant
pleural fluid in lymfoplasmocellular lymphoma
J.D. Sriram, W.G. Meijer
Westfries Gasthuis, Department of Internal Medicine,
Westfries Gasthuis, 1624 NP HOORN, the Netherlands,
e-mail: jd.sriram@gmail.com
43
76.
Kill two birds with one stone: rituximab as treatment
of refractory polymyositis associated with B-cell
chronic lymphocytic leukemia
prednisone was tapered, and completely withdrawn after
6 months. A few months later the patient is still doing well.
Conclusion: This case illustrates the rare co-occurrence of
myositis and B-CLL in which remission of both refractory
polymyositis and B-CLL was achieved after treatment
with rituximab. Despite the absence of histological confirmation, the parallel course of the diseases suggests an
association.
D. Boumans, B.W. Schot, H.J. Bernelot Moens
ZGT Hospital Almelo, Department of Internal Medicine,
Zilvermeeuw 1, 7609 PP ALMELO, the Netherlands, e-mail:
d.boumans@gmail.com
Introduction: Polymyositis is an uncommon skeletal
muscle disease belonging to the idiopathic inflammatory myopathies. It is associated with the occurrence
of solid malignancies and in rare cases with B-cell chronic
lymphocytic leukemia (B-CLL).
Patients generally present with subacute progressive
bilateral proximal muscle weakness. Several therapeutic
options are available if corticosteroid treatment fails.
Rituximab, an anti-CD20 antibody, is successfully used
for treating both hematologic malignancies and rheumatic
disorders. A number of case reports suggest that treatment
with rituximab is effective and safe in patients with
refractory polymyositis. Unfortunately, clinical trials are
lacking. We describe a patient in which prednisone
refractory polymyositis is probably associated with B-CLL
and successfully treated with rituximab.
Case report: A 70-year-old woman presented with subacute
progressive symmetrical proximal muscle weakness of
legs and arms. Physical examination was unremarkable
except for muscle weakness (MRC 4/5). Skin abnormalities,
lymphadenopathy and splenomegaly were absent. Medical
history reported diabetes for which she used glimepiride
and metformin. Laboratory investigation revealed a
remarkable increase of creatinine kinase (CK) (6329 U/l),
abnormal liver biochemistry (LDH 864 U/l, AST 161
U/l, ALT 331 U/l) and monoclonal B-cell lymphocytosis
(leukocytes 16 x 109/l). ANA and ENA-screening were
negative. Electromyography including needle examination
showed polyneuropathy with neuropathic and myopathic
changes. Treatment with prednisone was initiated (1 mg/
kg) as polymyositis was suspected. Three weeks later the
CK level decreased with 50%, but the muscle strength
did not improve. The leukocyte count increased up to 36
x 109/l and the patient met the criteria for B-CLL (RAI
stage 0) for which, however, treatment was not warranted.
Prednisone was tapered after eight weeks as the CK level
had decreased further. This was not accompanied with an
increase in muscle strength, which led to our conclusion
that the patient was refractive to prednisone. Due to the
synchronous development of B-CLL we suspected an
association with the myositis. To target both diseases we
started treatment with rituximab (four times 375 mg/m2/
month) and chlorambucil. Remission of both myositis
and B-CLL was achieved after a three month period.
Subsequently, rituximab and chlorambucil were ceased and
77.
Acquired recurrent angioedema in systematic lupus
erythematodes
N. Mehra, V.R. van der Pas, A.C. Venhuizen, E. Ton
University Medical Centre Utrecht, Department of Internal
Medicine, Rijnlaan 75-D, 3522 BD UTRECHT, the
Netherlands, e-mail: n.mehra@umcutrecht.nl
Introduction:Acquired angioedema (AAE), also called
deficiency of C1 inhibitor, is a rare syndrome of recurrent
episodes of angioedema. AAE is kinin-mediated, and
in contrast to mast-cell degranulation, characterised by
angioedema without urticaria or signs of anafylaxis. C1
inhibitor (C1-INH) acts by irreversible binding to activated
C1-subcompenents C1r and C1s. Deficiency leads to high
complement consumption and production of C2-kinin.
Furthermore C1-INH stimulates bradykinin release.
Activation of the kinin pathway increase endothelial
permeability via mechanisms involving nitric oxide, cyclic
GMP, and other effector molecules. In systemic lupus
erythematodus (SLE) auto-antibodies have been described
directed against C1-INH but also against C1q, leading to
AAE.
Case report: We present a female Caucasian patient
who was admitted to the Rheumatology ward for reconstructive hand and foot surgery. She had previously been
diagnosed with Sjogren’s disease and SLE with deformities
to the extremities (knees, hands). She had suffered from
pleuropericarditis, osteomyelitis, spondylodiscitis, interstitial lung disease and lungembolus. She was known with
allergies to antibiotics (clindamycin and cotrimoxazol).
Furthermore she had five previous post-operative episodes
of angioedema. The first three episodes she had manifest
swelling of the tongue, oral cavity, larynx and neck,
but without urticaria or signs of bronchoconstriction
and hypotension. Thereafter she had been thoroughly
examined for allergic responses to peri-operatively used
medication, of which all tested were negative, other
than the known allergies. Afterwards she was treated
pre-operatively before planned operations with a cocktail
of dexamethasone and tavegil, and post-operatively 3
consecutive days with xyzal. Still, there were mild episodes
of angioedema with pre-and postmedication, the third of
these episodes following reconstruction of the extensor
44
digitorum communis of the right hand and amputation of
her small toe. She had a nerve-block with local anesthesia,
found safe by earlier analyses. She was using no other
known medication that could cause bradykinin-induced
angioedema, such as ACE-inhibitiors or etanercept.
Investigation demonstrated normal tryptase, IgE and C3/
C4 levels, ruling out mast-cell induced angioedema and
hypocomplementaemia. Therefore we tested for C1-INH
serum levels, C1-INH function, C1q and C4. We found low
C1-INH function, demonstrating evidence for acquired
angioedema. If an future adverse event takes place, C1
inhibitor concentrate will be tested at an initial dose of 20
units/kg.
Conclusion: Angioedema in SLE can be caused by autoantibodies directed against inhibitors of the complement
pathway, leading to activation of the kinin-pathway,
increased vascular permeability and subsequent edema of
the skin, gastro-intestinal tract and upper airway.
resonance imaging of the brain showed symmetric
multifocal areas of white matter demyelination suggestive
for progressive multifocal leukoencephalopathy (PML).
Polymerase chain reaction for JC virus in the cerebrospinal
fluid was positive. In the meantime, she developed fever,
progressive dyspnea and coughing. Despite administration
of antibiotics, patient deteriorated clinically and died under
the suspicion of pneumonia. At autopsy, the differential
diagnosis of inflammatory myopathy with PML was
confirmed.
Discussion: PML is a severe demyelinating disease of
the central nervous system caused by reactivation of
JC virus, but is seldom reported in patients without
immunodeficiencies. The disease course of PML is
poor and usually progressive and fatal. The present case
underscores the intriguing possibility that PML may not
only occur in patients with immunodeficiencies, but also
in auto-immune disorders (polymyositis).
78.
79.
A woman with dysphagia, muscle weakness, and
cognitive impairment
J.L. Peters1 , L.D. Felius1, S.A. Danner 1, F. Stam 2 ,
J.M. Rozemuller1, A.W. Lemstra1, A.E. Voskuyl1
1
VU University Medical Centre, Department of Internal
Medicine, PO Box 7057, 1007 MB AMSTERDAM, the
Netherlands, e-mail: mjl.peters@vumc.nl, 2Medical Centre
Alkmaar, ALKMAAR, the Netherlands
A man with an ‘invisible’ primary tumor and
adenohypopituitarism
S.A.F. Streukens, J.P.W. van den Bergh, P.W.L. Thimister,
W.H.M. van Kuijk
Viecuri Medical Centre, Department of Internal Medicine,
Tegelseweg 210, 5912 BL VENLO, the Netherlands, e-mail:
bstreukens@me.com
Introduction: We describe a patient with severe endocrine
abnormalities in combination with liver metastasis,
but without signs of a primary tumor despite extensive
diagnostic testing.
Case: A 70-year-old male with a medical history of an
ischemic CVA, atrial fibrillation and type 2 diabetes,
was admitted because of progressive edema, dyspnea,
tiredness and marked hypertension. His medication
consisted of ramipril, atorvastatin, metformin and
acenocoumarol. Laboratory testing showed severe
hypokalemia with metabolic alkalosis, hyperglycemia
and liver enzyme abnormalities. The cardiologist ruled
out cardiac decompensation. Abdominal ultrasonography
showed multiple hepatic lesions suggestive of metastasis.
Additional laboratory testing showed marked hypercortisolism (plasma cortisol 4.7 umol/l, 24h-urine cortisol
excretion 20.000 nmol) combined with increased ACTH
(49.1 pmol/l) and adenohypopituitarism. There was no
suppression of cortisol after (high dose) dexamethason.
Plasma aldosterone and renin levels and 24h-urine (nor)
metanephrine excretion were normal. Glucose concentration was constantly between 15-30 mmol/l. Abdominal
and thoracic CT-scans confirmed multiple liver metastasis
with slight bilateral adrenal hyperplasia but no signs of
a primary tumor. Liver biopsy showed a poorly differen-
Casus: A 65-year-old patient was admitted to the hospital
with a 6-month history of progressive dysphagia, muscle
weakness, and cognitive impairment. During this period
she lost 10kg of weight. She also noticed muscle weakness
of the upper and lower extremities with gradual worsening
over the last period and gait ataxia. Her family reported
cognitive changes including an altered mental status,
impaired awareness and memory. The patient did not have
fever, nigh sweats, cough, skin lesions, or headaches. She
had previously been well, retired, lived alone, drank alcohol
socially, and smoked 10-15 cigarettes a day.
On examination, the patient was tired and had a lack of
attention complicating cognitive testing. There was muscle
atrophy and weakness of the hands and lower extremities.
No skin lesions were observed. The complete blood count
(with differential count), erythrocyte sedimentation rate,
C-reactive protein, serum levels of electrolytes, and tests
for renal and liver functions were normal. Serum levels of
creatine kinase were increased (2690 U/l), and the test for
antinuclear antibody (ANA) was positive, but additional
testing for specific antibodies was negative. Nailfold capillaroscopy demonstrated a ‘scleroderma’ spectrum with
mega-capillaries. Tissue (skin and muscle) biopsy of the
upper leg revealed an inflammatory myopathie. Magnetic
45
tiated carcinoma with neuroendocrine differentiation.
MRI showed no hypothalamic or pituitary abnormalities.
Based on these findings this patient was diagnosed
with multiple liver metastasis from an unknown ACTHor CRH-producing primary tumor with secondary
hyperglycemia, hypertension, hypokalemic metabolic
alkalosis and adenohypopituitarism due to extreme hypercortisolism. Our differential diagnosis regarding the
primary tumor was: carcinoma of the lung (small cell
(SCLC) or bronchial), thyroid, pancreas, stomach or a
carcinoid. Gastroscopy and colonoscopy were both normal.
A PET-CT-scan now showed marked bilateral adrenal
hyperplasia but no signs of FDG capturing metastasis or a
primary tumor. An additional octreotide scan was planned.
However the patient’s physical condition worsened and he
died before further diagnostic testing. Autopsy showed
extensive myocardial ischemia and a SCLC of the right
lower lobe (diameter 3.5cm) with pleural carcinomatosis
and extensive metastasis in the left lung, liver, pancreas,
adrenal glands, prostate and bone marrow. Reassessment
of both PET and CT-scan still did not reveal the metastasis
or the primary tumor.
Conclusion: SCLC is a known cause of ectopic
ACTH-secretion with clinical presentation of Cushing’s
syndrome. The present case has two distinctive characteristics. Firstly the adenohypopituitarism (without signs
of a pituitary mass) probably caused by suppression of
pituitary hormones due to the extreme hypercortisolism.
Secondly the ‘invisibility’ of the primary tumor on both the
PET and CT-scan despite its size at autopsy. Possibly it was
not FDG capturing due to the hypercortisolism-induced
hyperglycemia.
80.
of severe insulin resistance. In our outpatient clinic,
she had persistent hyperglycemias despite usage of a
total amount of insulin of about 250 units a day. In the
past three years her insulin necessity had been doubled.
Besides sporadic vaginal blood loss, she reported no
abnormalities. During admission she needed 440 units
of insulin per day. Laboratory testing showed an increased
level of estradiol and inhibin B. An additional CT scan
of the abdomen showed a solid tumor of the left ovary.
A bilateral salpingo-oophorectomy was performed, with
removal of the tumor. Pathological examination of the
left ovary showed a thecoma, a benign, solid, fibromatous
tumor. Postoperatively, the need for insulin dramatically
decreased. Glycosylated hemoglobin decreased from 12.6
to 6.7% in a few months. In this patient, severe insulin
resistance was caused by a thecoma.
Thecomas are usually confined to a single ovary and occur
predominantly in postmenopausal females. They may
produce estradiol and up to 20 percent of patients present
with synchronous endometrial cancer. These tumors have
a yellowish appearance from accumulated lipid and can
become very large (up to 40 cm). Histologically, they are
primarily composed of theca cells, but may also contain
granulosa cell components. The most common symptom
of thecomas is abnormal vaginal blood loss as a result of
endometrial stimulation from estroadiol produced by theca
cells.
Conclusion: Although ovarial stromal hyperthecosis and
PCOS are known to cause insulin resistance, no literature
exists on an association between a thecoma and insulin
resistance. Little is known about the pathophysiology of
insulin resistance in ovarial stromal hyperthecosis and
PCOS. Future studies might clarify a common pathway of
insulin resistance in ovarial stromal hyperthecosis, PCOS
and thecoma.
A thecoma as a cause of severe insulin resistance: a
case report
N.L. Verbeet, M.O. van Aken
Haga Hospital, Department of Internal Medicine, Leyweg
275, 2545 CH THE HAGUE, the Netherlands, e-mail:
nicoletteverbeet@yahoo.com
81.
A rare cause of hypophosphatemic osteomalacia
A.C. van de Ven, A.R. Hermus
Radboud University Medical Centre, Nijmegen, Department
of Endocrinology, Geert Grooteplein 10, 6525 GA NIJMEGEN,
the Netherlands, e-mail: ac.ven@aig.umcn.nl
Introduction: Insulin resistance is caused by several
diseases, some in which pathophysiology is known, such
as obesity and rare inherited diseases, like leprechaunism
and Rabson-Mendenhall syndrome, some in which the
mechanism remains unclear, such as polycystic ovary
syndrome (PCOS). In this report, we present a patient
with a thecoma causing severe insulin resistance. An
association which has not been reported previously in the
literature.
Case report: A 77-year-old female, known with type 2
Diabetes Mellitus, ischemic dilated cardiomyopathy and
atrial fibrillation, was admitted at our hospital because
A 38-year-old woman was referred to our outpatient
clinic by the rheumatologist. For the past 3 years, she
had suffered from progressive pain in the muscles and
bones. Due to the pain, she was sitting in a wheelchair
and she needed help with daily activities. She was using
Lynestrenol because of endometriosis and Fumaric Acid
because of psoriasis.
On physical examination, no signs of arthritis or other
abnormalities were noticed. Initial laboratory analyses
showed a severe hypophosphatemia (0.28 mmol/l, normal
46
value: 0.80-1.40 mmol/l) and a hypokalemia (2.9 mmol/l,
normal value: 3.5-4.7 mmol/l). Calcium, magnesium,
creatinin, vitamin D and parathyroid hormone were
normal. X-rays, already performed by the rheumatologist,
showed a decalcified aspect of the pelvis and revealed a
fracture of the third left metatarsal. Whole body scintigraphy showed a generally increased radiotracer uptake
and multiple foci of increased uptake in the rib cage
(rosary sign), tibia and feet. The diagnosis hypophosphatemic osteomalacia was made and further investigations were performed in order to assess the cause of the
hypophosphatemia.
Analysis of the urine showed a glucosuria and proteinuria.
The fractional phosphate excretion was inappropriately
high, suggestive for renal loss of phosphate. Also, a
generalized aminoaciduria was found. Serum uric acid and
bicarbonate were low. This combination of abnormalities
is consistent with Fanconi syndrome, a defect localized in
the proximal renal tubule.
Several diseases can cause Fanconi syndrome. Monoclonal
gammopathy, Wilson’s disease and cystinosis were ruled
out. A Pubmed search yielded 3 case reports of middle
aged German women who developed a Fanconi syndrome
with osteomalacia during the use of Fumaric Acid.
Fumaric Acid is an occasionally prescribed medicine for
the treatment of psoriasis in the Netherlands, although it
is not registered for this purpose. We stopped the Fumaric
Acid immediately and started with phosphate supplementation. Later on, vitamin D was added. Within a few
days, the patient noticed a decline of muscle pain. She was
able to walk all day, without the use of the wheelchair. At
this moment, 6 months after stopping the Fumaric Acid,
she has no complaints at all. Unfortunately, the Fanconi
syndrome is still present and the patient needs to take
daily high doses of a phosphate mixture in order to keep
the serum phosphate sufficient.
Diagnosis: hypophosphatemic osteomalacia due to Fanconi
syndrome, caused by Fumaric Acid use.
82.
there were no other people with osteoporosis. Physical
examination showed no abnormalities. The bone mineral
density measurement (using DXA) showed a T score of -4.1
SD for the lumbar spine and T -2.5 SD for the femoral neck.
The X-ray of the spine showed a fracture of Th 12.
Further evaluation for a secondary cause of his
osteoporosis showed no abnormalities besides an elevated
serum tryptase level (44.5 mg/l, normal value < 11.4 mg/l.).
In the bone biopsy several mast cells were seen. There was
a weak signal of the c-kit D816V mutation measurable.
It was concluded that the patient had osteoporosis and a
vertebral fracture because of systemic mastocytosis. He
was treated with peginferferon a, a bisfosfonate, cetirizine
and ranitidine. The results of one year of treatment and
some background information will be presented.
83.
Ain’t no sunshine when she’s gone…
C.R. van Rooijen, F. Stam, M.B. Kok
Medical Centre Alkmaar, Department of Internal Medicine,
Wilhelminalaan 21, 1815 JD ALKMAAR, the Netherlands,
e-mail: cleovanrooijen@gmail.com
Introduction: Serum calcium levels are hormonally
controlled, with a key role for parathyroid hormone (PTH)
and vitamin D. We present a patient with extremely
low calcium levels and an unusual disorder in calcium
metabolism.
Case report: An 18-year-old negroid woman presented with
progressive cramps in both hands for 2 days. She was born
in Jamaica and had moved to the Netherlands 8 months
ago. She had no relevant medical history. On physical
examination, we found her fingers to be cramped as well
as a positive Trousseau’s sign. No other abnormalities were
noticed. Laboratory analysis showed severe hypocalcaemia
(1.17 mmol/l) and hyperphosphatemia (2.0 mmol/l),
with normal blood levels of albumin (36 g/l), creatinin
(61 mmol/l) and alkaline phosphatase (96 U/l). Urinary
excretion of both calcium (0.8 mmol/day) and phosphate
(5 mmol/day) was low. We found this to be consistent
with hypoparathyroidism. However, the PTH level was
increased (22.1 pmol/l), whereas 25-(OH)-vitamin D was
low (31 nmol/l). An Ellsworth-Howard test was performed,
measuring urinary phosphate excretion after administration of synthetic PTH. This showed only a fivefold
increase in phosphate excretion, thereby supporting the
diagnosis of pseudohypoparathyroidism (PHP). Upon
treatment with calcium supplementation and 1a-(OH)vitamin D (alfacalcidol), her symptoms disappeared.
Serum calcium levels however remained in the low range,
as did her calcium excretion.
Discussion: Pseudohypoparathyroidism (PHP) is a rare
hereditary disorder with features resembling hypoparathy-
An unusual ca(u)se of osteoporosis
L.I. Arwert, P. Lips
VU University Medical Centre, Department of Endocrinology,
PO Box 7057, 1007 MB AMSTERDAM, the Netherlands,
e-mail: l.arwert@vumc.nl
This is a case report of a 46-year-old man who was seen
for evaluation of osteoporosis. He had a recent vertebral
fracture (Th12) after putting his motorbike in the upright
position. Thereafter he had back pain, but no other
complaints. In his history he had a wrist fracture at the
age of 9. In the last years he lost 5 centimetres of length.
He had no skin signs or abdominal problems. In his family
47
roidism, although plasma PTH levels are elevated. PHP is
caused by alterations in the PTH receptor, inducing target
tissue resistance to PTH. Normally, PTH increases serum
calcium levels by stimulating bone resorption and renal
calcium reabsorption and converting 25-(OH)-vitamin D
to the metabolic active 1,25-(OH)2-vitamin D (calcitriol).
PTH and calcitriol interact to increase intestinal calcium
and phosphate absorption, whereas PTH also stimulates
renal phosphate excretion. In PHP, tissue resistance to
PTH results in hypocalcaemia and hyperphosphatemia
in the presence of elevated PTH levels. The biochemical
abnormalities of PHP can be associated with Albright’s
hereditary osteodystrophy, which was not the case with
our patient.
The diagnosis of PHP is confirmed by the EllsworthHoward test. In hypoparathyroidism, administration of
synthetic PTH will cause a 100-fold increase in phosphate
excretion. Treatment is lifelong supplementation of both
calcium and alfacalcidol. In our patient, symptoms were
probably evoked by the lack of sunlight in Dutch winter,
decreasing vitamin D levels and thereby aggravating
hypocalcaemia.
Conclusion: Hypocalcaemia and hyperphosphatemia in the
presence of high PTH levels can be caused by alterations
in the PTH-receptor.
84.
treatment with a GLP-1 RA, primarily because of the
associated weight loss.
At presentation she used insulin aspart 8-12 IU with each
meal, insulin glargine 22 IU and metformin 850 mg bid.
She weighed 100 kg (BMI 34.6 kg/m2) and her HbA1c
was 69 mmol/mol (8.5%). We decided to treat her with
liraglutide at an initial dose of 0.6 mg per day. She was
instructed to stop insulin after taking 11 IU of insulin
glargine at bedtime prior to starting liraglutide the next
morning.
Results: Thirty-six hours after starting liraglutide, she
reported severe nausea and vomiting, with glucose
values between 12 and 20 mmol/l. At presentation in
our emergency department she had an acetone smell,
arterial pH of 7.29, bicarbonate level of 12.8 mmol/l, and
tested positive for ketones in her urine. She was treated
for diabetic ketoacidosis, and subsequently her insulin
regimen was restarted. Anti-GAD was positive (30 U/l).
She is now considered to have type 1 diabetes mellitus, and
she was instructed to never stop insulin again.
Conclusion: Our case shows that adequate classification
of diabetes is crucial before insulin is switched to GLP-1
RA. Diabetic ketoacidosis in a patient falsely classified as
having diabetes mellitus type 2 should be considered as
an alternative explanation for nausea and vomiting after
initiation of a GLP-1 RA.
Diabetic ketoacidosis after switching from insulin to
a glucagon like peptide-1 receptor agonist
T.M. Vriesendorp, F. Holleman, J.H. de Vries
Academic Medical Centre, Department of Internal
Medicine, 1105 AZ AMSTERDAM, the Netherlands, e-mail:
t.m.vriesendorp@amc.nl
Introduction: Glucagon like peptide-1 receptor agonists
(GLP-1 RA), a new class of glucose lowering agents, are
associated with weight loss. Their main mechanism
of action is glucose-dependent stimulation of insulin
secretion, but GLP-1 RA also inhibit gastric emptying
and promote satiety. The main side effects of GLP-1 RA
are nausea and vomiting. Currently, the combined use of
insulin and GLP-1 RA therapy is not approved.
Aim: To report a case of diabetic ketoacidosis after
switching from insulin to a GLP-1 RA
Materials and methods: A 34-year-old Caucasian female
visited our outpatient department for a second opinion.
Seven years before she had been diagnosed with type 2
diabetes mellitus, complicating her obesity with a BMI of
41.5 kg/m2. After 4 months she started insulin because of
poor control on oral agents. In the past year she had participated in an intensive weight loss program and had lost
20 kg of weight. Recently, her weight had stabilised and
her HbA1c had gone up after an initial fall. She proposed
III.
ENDOCRINOLOGY RESEARCH
85.
LHRH-antagonist cetrorelix may reduce postmenopausal flushing
P.M. van Gastel, M. van der Zanden, D. Telting, M. Filius,
L. Bansci, H. de Boer
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
petrivangastel@hotmail.com
Introduction: Estrogen replacement therapy is the most
effective treatment for postmenopausal (PMP) flushing,
but its use is often contraindicated. An effective and safe
alternative is urgently needed.
Aim: To explore the effects of the LHRH receptor
antagonist cetrorelix in women with severe PMP flushing
who have a mean daily flush score > 15.
Materials and methods: Open-label treatment with
cetrorelix 250 g twice a day in 9 women with severe
PMP flushing, for a period of 4-6 weeks. The response
to treatment was evaluated by monitoring serum gonadotropin levels, flush scores, and quality of life.
48
Results: 254 of 395 patients agreed to participate. The
results in this abstract are based on the patients that participated in the period April 2009 until June 2011 (n=170).
The response to the questionnaire at baseline was 100%.
106 patients completed the follow-up period of which 81
patients returned the follow-up questionnaire (76,5%). One
third of the patients had primary and two third secondary
adrenal insufficiency.
Conclusion: Glucocorticoid-education meetings could help
to improve patients’ knowledge and
self-management of illnesses and proper use of glucocorticoid stress doses.
Results: At baseline, the mean daily flush score was
35.9±2.0 (range 29-44). All subjects demonstrated a
decrease in serum LH and FSH during treatment, but
premenopausal levels of both gonadotropins were reached
in only 2 subjects. The mean daily flush score decreased
by 39.6±8.4% (p<0.005). This was caused by a decrease
in flush frequency of 25.4±7.1%, and a decrease in flush
severity of 17.3±7.5%.
Conclusion: Severe PMP flushing can be reduced by LHRH
receptor blockade. The data suggest that a longer treatment
period is required to capture the maximal effect.
86.
Knowledge and self-management of patients on
replacement therapy with glucocorticoids
87.
The role of Techneticum-99m methoxyisobutylisonitrile scanning in diagnostic imaging of patients with
primary hyperparathyroidism
J.W.J. Repping-Wuts, M.M.L. Stikkelbroeck, M.F. Kerstens,
M. vanTeeffelen-Lourens, A.R.M.M. Hermus
Radboud University Medical Centre, Department of Internal
Medicine, 6500 HB NIJMEGEN, the Netherlands, e-mail:
j.repping-wuts@reuma.umcn.nl
M. Maas, E.J. Postema, P.H.M. Reemst, H.R Haak
Máxima Medical Centre, PO Box 7777, 5500 MB Veldhoven,
the Netherlands, e-mail: M.Maas@mmc.nl
Objectives: To assess the knowledge and selfmanagement in patients receiving replacement
therapy with glucocorticoids before and 6 months after
glucocorticoid-education-meetings.
Method and design: A longitudinal questionnairebased survey at the Radboud University Medical Centre
Nijmegen.
Participants: 395 patients with primary or secondary
adrenal insufficiency on glucocorticoid replacement
therapy, received an invitation letter from their endocrinologist, to attend to a glucocorticoid-education-meeting.
Patients were invited to bring along a partner or a close
friend.
Intervention: The three-hour glucocorticoid-educationmeeting (12-14 patients per meeting) consisted of a
lecture about the disease, the treatment and specific stress
education. The nursing education consisted of instructions
how to inject hydrocortisone i.m.. Supervised by the nurse,
all patients and their guests could practice this action
during the meeting. Furthermore, during the meeting
patients could talk with other patients.
Measurement: Two weeks before, and 6 months after the
meeting, patients were invited to fill in a questionnaire.
This questionnaire (1), had been adapted and translated
into the Dutch language. Besides patients characteristics,
the questionnaire consisted of six hypothetical conditions
of illness and the patients were asked what action they
would take. Furthermore, patients were asked if they had
the glucocorticoid instruction leaflet and ampoules of
hydrocortisone at home. They were also asked about the
symptoms of an Addison crisis and if they had practiced
the intramuscular injection.
Objective: The aim of this study was to assess the
radiologic and nuclear diagnostic methods prior to surgery
in patients with primary hyperparathyroidism in Máxima
Medical Centre.
Methods: Between January 2005 and October 2010,
sixty-six patients with hyperparathyroidism underwent
a parathyroidectomy. Of these, we analysed fourty-six
patients with primary hyperparathyroidism who had a first
time parathyroidectomy with proven parathyroid adenoma
or hyperplasia. Primary hyperparathyroidism was defined
as having a serum PTH > 5.2 pmol/l, a serum calcium
> 2.55 mmol/l and a serum phosphate of < 0.80 mmol/l.
The forty-six patients were analysed retrospectively for
the used diagnostic method (ultrasound, MIBI, CT), the
sensitivity of these diagnostics for correctly predicting the
quadrant of the adenoma location and the obtained short
and long term remission.
Results: In thirty-four of the forty-six patients (74%) with
a proven parathyroid adenoma or hyperplasia, the MIBI
scan predicted the localisation of the adenoma correctly.
Of these thirty-four patients, twenty-five had additional
diagnostic procedures. In two of the remaining twelve
patients, the MIBI scan predicted the right side, but the
wrong quadrant. One of these two patients had a CT
scan that was normal, the other had an ultrasound which
did not show anything either. Both patients underwent
a minimally invasive parathyroidectomy (MIP) and had
normal serum calcium a year post-surgery. Nine of the
twelve patients (75%) with a negative MIBI scan also had
a CT scan, an ultrasound, or both. Only in 2 of these nine
patients, the additional diagnostic method predicted the
quadrant of the adenoma location correctly.
49
Conclusion: Our data indicate that a MIBI scan is a
reliable diagnostic method to predict the localisation
of a parathyroid adenoma or parathyroid hyperplasia.
Therefore, it should be the pre-operative diagnostic method
of first choice. There is very limited value of additional
diagnostic procedures.
Based on our study we would advise the following
pre-operative algorithm: Patients with a serum confirmed
PHP should first have a MIBI scan. If the MIBI scan shows
a parathyroid adenoma, the patients is eligible for having
a MIP. In case of a negative scan, the patients should
undergo an ultrasound of the neck. If the ultrasound
shows an adenoma in the neck, the patient is eligible for
an MIP. If this ultrasound is negative, the patient should
have a bilateral neck exploration.
88.
was within the normal range (NR 0.4-4.0 mE/l) in 93.2%
of cases, and in 91.8% of controls, respectively (p>0.05).
Mean TSH level did not differ significantly between groups
(cases: 2.0±1.7 mE/l vs. controls: 2.3±1.0 pmol/l; p>0.05).
Mean FT4 level was significantly lower in cases than in
controls (15.9±2.9 pmol/l vs. 17.7±3.2 pmol/l; p<0.001), but
there was no difference between the frequency of within
normal range FT4 levels (NR 9-24 pmol/l) between groups
(cases: 100% vs. controls: 98.6%; p>0.05). Frequency of
anti-TPO antibody positivity (i.e., anti-TPO titer >35 kIU/l)
was similar in both groups (cases: 8/73 [10.9%] vs. controls:
6/73 [8.2%]; p>0.05). Three iRPF patients and two control
patients had subclinical hypothyroidism (TSH >4 mE/l and
normal range FT4 level) associated with anti-TPO antibody
positivity (p>0.05). Three iRPF patients and two control
patients were positive for both ANA en anti-TPO antibody
(p>0.05). The overall frequency of ANA positivity did not
differ between groups (cases: 15/73 [20.54%] vs. controls:
13/73 [17.8%]; p>0.05).
Conclusion: In this unique case-control study we found
no association between iRPF and Hashimoto’s thyroiditis.
Our findings do not support the concept of iRPF being a
systemic autoimmune disorder.
Hashimoto’s thyroiditis and anti-thyroid peroxidase
antibody associated with idiopathic retroperitoneal
fibrosis: case-control study
C.E. Andreescu, E.F.H. van Bommel
Albert Schweitze Hospital, Department of Internal Medicine,
Albert Schweitzerplaats 25, 3318 AT DORDRECHT, the
Netherlands, e-mail: corina_andreescu@hotmail.com
Background: Idiopathic retroperitoneal fibrosis (iRPF)
is a rare disease of unknown origin, characterized by an
inflammatory proliferative fibrosing process occurring
in the retroperitoneum. Some case-reports suggest
an association of iRPF with Hashimoto’s thyroiditis,
which should support the hypothesis of an autoimmune
pathogenesis of iRPF. Our objective was to investigate
the frequency of Hashimoto’s thyroiditis, anti-thyroid
peroxidase antibody (anti-TPO) and antinuclear antibody
(ANA) positivity in iRPF patients.
Methods: In a case-control study, we evaluated prospectively 73 patients with a diagnosis of iRPF from April
1998 through October 2010 in our tertiary care referral
Centre. Controls were 73 randomly selected patients,
followed at the same outpatient department of internal
medicine, who volunteered to take part in the study.
Controls were not known with a history of iRPF and had
no evidence of iRPF by radiological examination. Groups
were matched for age and sex. In all patients, clinical
(including history regarding thyroid diseases and iRPF)
and physical examination were performed. In both groups,
we determined the presence of anti-TPO antibodies, ANA,
as well as thyroid hormone (FT4) and thyroid stimulating
hormone (TSH) levels.
Results: Demographic characteristics did not differ
between groups, including mean age (cases: 62.5±11.1year
vs. controls: 61.7±14.0 year) and percentage male sex
(cases: 73.9% vs. controls: 72.6%; both p>0.05). TSH level
IV.
ENDOCRINOLOGY CASE REPORTS
89.
Unexpected severe hypercortisolism leading to
ethical discussions at an intensive care unit
I.J.A. de Bruin 1 , A.J.C. Rokx 1, J.J. Weenink 2 ,
H.H. van Ojik1, W.A. Oranje1
1
TweeSteden Hospital, Department of Internal Medicine, Dr.
Deelenlaan 5, 5042 AD TILBURG, the Netherlands, e-mail:
idbruin@tsz.nl, 2Spaarne Hospital, HOOFDDORP, the
Netherlands
Case report: A 30-year-old man was referred to our
rheumatology department because of pain in both hands.
The patient was known with triple A syndrome and used
hydrocortisone replacement therapy, he used no other
medication. His mental capacities are limited, probably in
relation to the triple A syndrome. On physical examination
no signs of arthritis were found and further laboratory
analysis was performed. Inflammation parameters were
normal but there was a hypothyroidism (f T4 7,4 pmol/l,
TSH 94,2 mU/l). Only 4 months earlier his TSH had been
in the normal range (4.5 mU/l). On further evaluation
TPO antibodies were negative and the patient did not
have a goiter. He had never had radioiodine treatment and
had never had amiodaron, lithium or other drugs that
might interfere with thyroid function. Levothyroxine as
replacement therapy was initiated and after 4 months of
treatment he was euthyroid and free of pain in his hands.
Discussion: There are different mutations known in
the AAAS gene resulting in a heterogeneity of clinical
symptoms among patients. Often exhibited symptoms
(except for the alacrima, achalasia, adrenal insufficiency
and microcephaly) are abnormalities of pupils and cranial
nerves, optic atrophy and autonomic neuropathy. A
literature search revealed no known cases of patients with
triple A syndrome and hypothyroidism. The dysfunctional
protein caused by mutations in the AAAS gene is normally
part of the WD repeat protein family which has a wide
functional diversity. Possibly the mutation in this patient
is also responsible for the development of hypothyroidism
through still unknown mechanisms, because all features
of the syndrome appear to be neuro-endocrine in nature.
Our hypothesis is supported by the fact that no other
causes of hypothyroidism were identified.
Conclusion: Primary hypothyroidism diagnosed in a
30-year-old male patient known with triple A syndrome,
possibly because of a linked gene defect.
workup revealed renal rather than intestinal potassium
loss. This prompted us to investigate the possibility of
hyperaldosteronism or cortisol excess. No stigmata of
Cushings disease had been noticed. Serum ACTH was
356,7 ng/l and cortisol was 3,11 umol/l. A CT-scan showed
an intrapulmonary laesion and hepatic metastases. A liver
biopsy confirmed extensive small cell lung carcinoma
(SCLC). Ectopic ACTH overproduction from SCLC was
diagnosed.
We discussed extensively whether we should continue
treatment. However SCLC can be treated with chemotherapy with a high chance of durable responses. So
treatment was continued. First the high cortisol had to
be lowered. There are several possibilities: high dose
ketoconazol, metyrapone, mifepristone, etomidate, a
bilateral adrenalectomy or chemotherapy. Because the
condition of the patient deteriorated and he had to be
intubated, we choose for etomidate as a sedative and
therapeutic drug. Immediately after intubation we started
with substitution therapy with hydrocortison. Broad
antibiotic coverage including prophylaxis with trimethoprim-sulfamethoxazol and fluconazol was started in
this immunocompromised patient. Serum levels of both
ACTH and cortisol dramatically fell within 8 hours. After
the patient’s condition stabilized he was transferred to
a tertiary centre for a bilateral adrenalectomy. There the
patient was successfully weaned from the ventilator and
etomidate was substituted for ketoconazol orally with
good response. Finally no bilateral adrenalectomy was
performed since chemotherapy can induce rapid responses.
The condition of the patient stabilized so there could be
started with Cisplatin and Etoposide. Initially the patient
seemed to improve clinically. Unfortunately he died from
neutropenic sepsis.
Conclusion: This case illustrates the endocrine emergency
of malignant ectopic ACTH production leading to ethical
discussions at an ICU and different methods to treat it.
91.
Introduction: Severe hypercortisolism caused by malignant
ectopic ACTH production is a rare cause of hypokalaemia
and metabolic alkalosis and is difficult to treat. Treatment
options depend on the condition of the patient.
Case: A 66-year-old man with chronic diarrhoea and
recent onset diabetes and hypertension was referred to the
emergency department with general oedema and suspicion
of decompensated heart failure. Lately his diabetes was
difficult to manage. He experienced progressive loss of
muscular strength and despite the oedema there was a
weight loss of 10 kg. No other features of heart failure were
found. Blood analysis revealed serum levels of: potassium
1,6 mmol/l, sodium 141 mmol/l, bicarbonate 40 mmol/l
and arterial pH 7,59. He was admitted to the ICU for
treatment of hypokalaemia and alkalosis. The diagnostic
50
90.
Hypothyroidism in a patient with triple A syndrome,
due to the same gene defect?
Hypoglycaemia leading to a diagnosis of Non-Hodgkin
Lymphoma
F.J.C. Cuperus, R. Komdeur, D. Telting, H. de Boer
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
franscuperus@gmail.com
L.E. van der Wagen1, P.C. de Jong1, G.D. Valk2
1
St. Antonius Hospital, Department of Internal Medicine,
Koekoekslaan 1, 3435 CM NIEUWEGEIN, the Netherlands,
e-mail: lotte_vd_wagen@hotmail.com, 2University Medical
Centre Utrecht, UTRECHT, the Netherlands
Introduction: Hypoglycaemia is uncommon in non-diabetic
subjects. Its etiology can be established by appropriate
blood tests during prolonged diagnostic fasting. This
report describes a patient presenting with hypoglycemia as
the key symptom leading to a diagnosis of Non-Hodgkin
Lymphoma.
Case: A 72-year-old female was presented at the emergency
ward with a hypoglycemic coma (blood glucose 1.3 mmol/l),
Introduction: Triple A syndrome (‘Allgrove syndrome’) is
a rare autosomal recessive genetic disorder. Patients have
mutations in the AAAS (Alacrima Achalasia Adrenal
insufficiency syndrome) gene located on chromosome
12q13. They present with the above symptoms and also a
wide range of neurologic abnormalities.
51
which rapidly resolved after intravenous administration
of glucose 50%. Retrospectively, hypoglycemic episodes
had been present for 3 months. Medical history was
unremarkable, and the patient did not use any medication.
Night sweats, weight loss, or fever were not reported.
Physical examination and a general laboratory screening
were normal. Five hours after the start of a standardized
fasting procedure she developed hypoglycaemic symptoms
(blood glucose 2.3 mmol/l), upon which samples for the
measurement of glucoregulatory hormones were taken.
Plasma C-peptide, insulin, pro-insulin, insulin antibodies,
cortisol, and IGF-BP3 were within the normal range.
Plasma IGF-I and IGF-II were 279 (normal range 56-165)
and 706 (normal range 280-610), respectively. Plasma
E-peptide, a surrogate marker for pro-IGF-II, was within
normal range. Treatment with R-COP (rituximab, cyclophosphamide, doxorubicin, prednisolone) resulted in a
normalisation of glucose metabolism and plasma IGF-I and
IGF-II levels within one month.
Discussion: Malignancy-induced hypoglycaemia is very
rare, but should not be forgotten in the differential
diagnosis of non-hyperinsulinemic hypoglycemia.
The most common cause is tumoral overproduction of
pro-IGF-II, a precursor of IGF-II that stimulates the insulin
receptors and enhances glucose uptake. Less frequent
causes associated with malignant disease include tumoral
IGF-I or IGF-II production, tumoral insulin auto-antibody
production, and extensive destruction of the liver by
malignant cells. In our case no clear etiological agent was
found; E-peptide was within the normal range and IGF-I
and IGF-II were only mildly elevated.
Conclusion: A structured approach allows a rapid diagnosis
of non-islet cell tumor hypoglycaemia, finding the
etiological agent appears to be the major challenge.
92.
having any shortness of breath, coughing, oedema or
nycturia. Fevers and nocturnal transpiration were absent
and the patient followed a normal diet without gastrointestinal complaints.At physical examination, vital signs
were normal, and examination of the heart and lungs
did not reveal any abnormalities. Of note, the thoracic
pain was inducible by compression of the ribs of the left
hemithorax. No axial pain or pressure pain was present
in the extremities. Routine laboratory analysis, including
a complete blood cell count, renal function, and liver
enzymes, was normal.Chest X-ray and additional oblique
rib films were normal. A bone scintigram demonstrated
focal accumulation of activity in the left ribs and diffusely
elevated uptake in the mandible and cannon bones,
evidencing osteomalacia. Additional laboratory investigations revealed hypocalcaemia (1.72 mmol/l) with a
normal serum albumin (44 g/l) and a low-normal serum
phosphate (0.87 mmol/l). Serum 25-hydroxyvitamine
(vitamin D) level was 53 nmol/l (reference level 50-100
nmol/l), with a significantly elevated parathyroid hormone
(75 pmol/l). This was interpreted as secondary hyperparathyroidism as a result of a vitamin D deficiency, since
there was no evidence of malabsorption or osteoblastic
disease.After 2 months of oral calcium and vitamin D
suppletion, thoracic pain and facial spasms had resolved,
and serum calcium and phosphate levels were normalized.
Importantly, serum parathyroid hormone level had
decreased to 51 pmol/l after 2 months, and further to 6
pmol/l after 9 months of treatment. Serum vitamin D
level increased to 82 nmol/l after 9 months.In conclusion,
this patient was diagnosed with isolated hypocalcaemia
with secondary hyperparathyroidism and osteomalacia as
a result of vitamin D deficiency, whereas vitamin D levels
did not suggest severe vitamin D deficiency.The minimum
value of serum vitamin D has been subject of debate for
several years. However, most experts agree that a serum
vitamin D level < 50 nmol/l may be considered deficient.
Nonetheless, the current case demonstrates that serum
vitamin D levels must be interpreted in the in the clinical
context of each patient.
Hypocalcaemia and osteomalacia in a patient with a
normal vitamin D level
J. van Ramshorst, M.J.F.M. Janssen, C.F.A. EustatiaRutten, H. Dik, F. Smit, A.M. Schrander-van der Meer,
G.J.P.M. Jonkers
Rijnland Hospital, Department of Internal Medicine, Simon
Smitweg 1, 2353 GA LEIDERDORP, the Netherlands, e-mail:
j.van_ramshorst@lumc.nl
93.
Post-partum hypopituitarism and a sellar mass: not
always a Sheehan’s syndrome
S.M. Platvoet-Sijtsma, B.G. Ziedses des Plantes,
B.L.J. Kanen
Zaans Medical Centre, Department of Internal Medicine,
PO Box 210, 1500 EE ZAANDAM,, the Netherlands, e-mail:
smsijtsma@gmail.com
Case report: A 28-year-old women of Somalian origin
presented to the pulmonologist with thoracic pain. Her
medical history included treated pulmonary tuberculosis
10 years ago. She complained of a stinging, non-radiating
pain on the left hemithorax which worsened with
breathing, but was not radiating to the shoulder, upper
extremity or cheeks. Furthermore, the patient complained
of facial tingling sensations and spasms. She denied
94.
She had recently given birth to a healthy child. During
labour there was aproximately 500 cc bloodloss. In the
following days, lactation was difficult and had been
stopped.
One month later, our patient visited a neurologist because
of headaches. The analysis, including a computed
tomography scan of the brain, showed no explanation.
In the months following, our patient became anorectic
and nausious. She had fainted several times. Physical
examination was unremarkable, except for a blood pressure
of 105/78 mmHg, with evident orthostasis. Laboratory
findings include normal haemoglobin, kidney and liverfunction. Cortisol (< 0.01 mmol/l) and ACTH (2.0 pmol/l)
were compatible with secundary adrenal insufficiency, but
other pituitary functions seemed intact. The prolactine
level was normal (139 ml IU/l).
Magnetic resonance imaging (MRI) of the brain showed a
sellar mass iso-intense to brain tissue with homogeneous
gadolineum-contrast uptake which therefore was not
compatible with pituitary apoplexy as in Sheehan’s
syndrome. The diagnosis lymphocytic hypophysitis
was suspected and since there was no optic chiasm
compression, treatment with high dose glucocorticoids
was started. Recovery was quick and hydrocortison in
a substitution dose was continued. Pituitary gland- and
alpha-enolase autoantibodies all came back negative.
One month later, MRI showed a decrease in size of the
adenoma, supporting our diagnosis.
Discussion: Lymphocytic hypophysitis (LYH) is a very rare
disorder; the incidence is unknown. LYH typically occurs
during the third trimester of a pregnancy, or shortly after
pregnancy. It can be mistaken for a pituitary adenoma due
to its mass effect which can also result in optic chiasm
compression. It is characterized by lymphocytic infiltration
and destruction of the pituitary and typically results in
hypopituitarism. Usually the pituitary-adrenal axis is the
first to be affected, followed by the pituitary-thyoidal-axis.
The few cases reported describe disease courses from
complete recovery to permanent panhypopituitarism.
Few reports mention the presence of pituitary autoantbodies, especially anti-alpha-enolase, but the clinical
and etiological relevance is unclear. A confirmed diagnosis
can only be made with a biopsy of the pituitary. Treatment
with high-dose glucocorticosteroids is advocated, but due
to it’s rarity evidence is lacking.
Conclusion: When hypopituitarism is diagnosed in
a post-partum patient with a sellar mass, one should
consider lymphocytic hypophysits as a possible cause other
than Sheehan’s syndrome. Treatment with glucocorticoids
could be beneficial in preserving or recovering of pituitary
function.
H.M. de Wit, A.H. Mudde
Slingeland Hospital, Department of Internal Medicine, PO
Box 169, 7000 AD DOETINCHEM, the Netherlands, e-mail:
hmdewit@gmail.com
Introduction: MIDD and MELAS are both associated with
a 3,243 A>G mutation in mitochondrial DNA, which is
transmitted by maternal inheritance. MIDD patients often
present with progressive hearing loss, followed by diabetes
at 30-40 years of age. MELAS is characterized by stroke-like
episodes, encephalopathy causing seizures or dementia
and blood or cerebral spinal fluid lactic acidosis, often
presenting before 20 years of age. Both diseases are characterized by a broad spectrum of other symptoms including
renal, cardiovascular, neuromuscular and psychiatric
disease. We report on clinical details of the members of
a Dutch family with the 3,243 A>G mutation to make a
contribution to the phenotypic description of this mutation.
Family history: The mtDNA 3,243 A>G mutation was
discovered in 2002 in 2 generations of a family with a
high penetration of diabetes mellitus and deafness. The
mother of this family, who was positive for the mutation
(heteroplasmy 2,5%), was diagnosed as type 2 diabetes
at 53 years. She became insulin dependent 15 years later
and deafness became apparent at 79 years. Her husband,
negative for the mutation, had type 2 diabetes. Four of their
5 children developed diabetes and progressive hearing loss,
with heteroplasmy levels in leukocytes varying between
15 and 23%. In the course of their diseases remarkable
observations in these subjects were made. Firstly, extreme
insulin resistance gradually developed, which is unusual in
MIDD. The role of the paternally inherited diabetes, superimposed on the mtDNA mutation is discussed. Secondly,
the youngest brother (heteroplasmy in leukocytes and in
muscle 20% and 84%, respectively), showed a striking
deterioration of symptoms in time. He was diagnosed
with MIDD based on classical symptoms. Later in time
he seems to meet the criteria for MELAS, with stroke-like
episodes, declining cognitive function, blood lactic acidosis
and severe exercise intolerance, which we demonstrated
in a 6 minute walking test. His sister has recurrent
depressions and cerebral spinal fluid lactic acidosis. Muscle
biopsies in both patients showed abnormalities consistent
with MELAS, however no ragged red fibers were found.
Conclusion: This family history illustrates that MELAS and
MIDD could be regarded as two phenotypical expressions
of the same disease. The first may emerge from the second
in time. Moreover, extreme insulin resistance may be a
feature of the clinical picture.
Case report: A 28-year-old woman, with a history of subfertility, was admitted to our hospital because of fainting and
hypotension.
52
From MIDD (maternally inherited diabetes mellitus
and deafness) to MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like
episodes): two expressions of the same disease?
53
95.
Hypokalemic paralysis in a 22-year-old man
compartment, which leads to hyperpolarization of the
muscle membrane and inactivity of muscle fibres. The
paralysis may occur within an few hours-days usually
affecting lower extremities more than upper extremities.
Besides potassium suppletion, treatment aims for an
euthyroid state and antagonization of beta adrenergic
stimulation.
M.L. op de Weegh, H.E. van der Wiel
IJsselland Hospital, Department of Internal Medicine,
Spangesekade 75G, 3027 GK ROTTERDAM, the Netherlands,
e-mail: marlous33@hotmail.com
Introduction: Acute paralysis is usually reported in
neurologic, inflammatory, toxic, metabolic or endocrinological diseases. We present a patient with an acute
paralysis and a low serum potassium.
Case: A 22-year-old negroid man was referred to the
emergency ward with a symmetric paralysis of both
legs, and decreased strength in both arms. Additional
symptoms were nausea and vomiting. The day before
admission he had undergone an arthroscopy without
complications. His medical history yielded acute liver
failure of unknown origin, aplastic anemia and thrombocytopenia. The patient denied using illicit drugs, but was
using NSAIDs and pantoprazole. Physical examination
revealed an athletic male with symmetric paralysis of both
legs, and decreased strength in both arms with diminished
reflexes.
Laboratory results showed an extreme low serum
potassium (K 1.2 mmol/l), low TSH (0.020 m IU/l),
high FT4 (55.7 pmol/l), high TSI (111 IU/l) and urinary
potassium excretion was 20 mmol/l. The arterial blood
gas and serum renine activity were normal. Serum
aldosteron was slightly decreased (0.10 nmol/l). The ECG
showed U-waves. The MRI of the spinal cord showed no
abnormalities.
After treatment with strumazol, propanolol and
intravenous potassium, the serum potassium normalized
within hours with complete recovery of his paralysis. An
ultrasound of the thyroid gland was performed, which
showed a small inhomogeneous deviation of the left lobe
of the thyroid gland.
Discussion: This patient presented a thyrotoxic
hypokalemic periodic paralysis (TPP). Graves disease is
the underlying disorder in most cases of TPP. Thyrotoxic
hypokalemic periodic paralysis can be precipitated by
carbohydrate load, exercise or stress (in this case the
arthroscopy). TPP predominantly occurs in the early
morning. In most cases the paralysis is reversible. The
incidence of TPP is highest in Asian men. In non-Asian
populations the incidence of TPP is estimated to be
0.1-0.2%, mostly within the age of 20-40 years. Our
patient was from Caribbean origin in which TTP is rare.
It’s hypothesized that paralysis could occur because
thyroid hormone increases tissue responsiveness to
beta adrenergic stimulation. This response increases
sodium-potassium ATPase pump activity on the skeletal
muscle membrane. This is followed by a sudden shift of
potassium from the extracellular into the intracellular
96.
A harmless injection?
M.M. Oosterwerff, P. Lips, W. de Ronde
VU University Medical Centre, Department of Endocrinology,
De Boelelaan 1117, 1081 HV AMSTERDAM, the Netherlands,
e-mail: m.oosterwerff@vumc.nl
Introduction: Intra-articular corticosteroid injections are
well-known treatment modalities in rheumatic conditions.
Locally administered corticosteroid injections only sporadically evoke adverse effects. In this case report we present a
women with iatrogenic Cushing syndrome after two intraarticular injections with triamcinolon acetonide (TCA,
Kenacort®).
Case: A 31-year-old female was seen in the outpatient clinic
with a gradually developing moon face. Because of chronic
pain in the right shoulder, an injection with 40 mg TCA
was administered intra-articularly by her general practitioner four and two weeks prior to presentation.
Her medical history revealed a dilated cardiomyopathy with
tromboembolism and amputation of both legs caused by a
pheochromocytoma in the right adrenal gland in 2000.
The right adrenal gland was resected. In 2006 there
was a clinical and biochemical suspicion for a relapse of
pheochromocytoma close to the liver, which was resected,
but microscopic examination showed no abnormalities and
she had a good recovery.
At presentation, our patient complained of rapid weight
gain, hypertension, headache, irregular menses and
backache. Clinical examination showed a moon face,
high blood pressure 170/102 mmHg and multiple purple
striae. A 24-hour urine collection showed free cortisol
excretion of < 18 and < 14 nmol/24 hr. Morning plasma
cortisol and ACTH concentrations were very low at < 30
nmol/l and 2 pmol/l, respectively. A diagnosis of iatrogenic
Cushing’s syndrome was made. Our patient was treated
with metoprolol 50 mg once daily, hydrocortisone in case
of stress to avoid secondary adrenal insufficiency, no
replacement therapy in the abcence of severe symptoms. In
about five months symptoms and signs gradually regressed
and spontaneous recovery of HPA-axis was observed.
Conclusion: Supraphysiological amounts of exogenous
glucocorticoids are a cause of Cushing’s syndrome. In this
case report a iatrogenic Cushing’s syndrome is described
after two injections of TCA, which is an exceptional event.
54
Furthermore, exogenous corticosteroids can suppress the
HPA-axis and subsequently induce secondary adrenal
failure.
97.
due to takotsubo cardiomyopathy, which is a ventricular
dysfunction that is usually reversible. Treatment consists of
supportive care and resection of the adrenal tumor.
Conclusion: Takotsubo cardiomyopathy as initial presentation of a pheochromocytoma.
Cardiomyopathy and an adrenal mass
C.L. Boot, P. Lips
VU University Medical Centre, Department of Internal
Medicine, De Boelelaan 1117, 1081 HV AMSTERDAM, the
Netherlands, e-mail: c.boot@vumc.nl
98.
Successful treatment of insulinoma with endoscopic
ultrasound-guided alcohol ablation
M. Weijmans1 , F.P. Vleggaar2 , B.T. Rövekamp1,
E.A. bij de Vaate1
1
Zuwe Hofpoort Hospital Woerden, Department of Internal
Medicine, Polanerbaan 2, 3447 GN WOERDEN, the
Netherlands, e-mail: liez7@hotmail.com, 2University Medical
Centre Utrecht, Department of Gastroenterology, UTRECHT,
the Netherlands
Introduction: Most of the patients with a pheochromocytoma have hypertension. We present a case of a patient
with hypotension instead of hypertension as result of a
pheochromocytoma.
Case report: The patient is a 58-years-old woman, who once
had an episode of chest pain, without a clear diagnosis.
Since then she uses acetylsalicylic acid, bisoprolol and
simvastatin. Further medical history was unremarkable.
Since a couple of months before presentation she suffered
from heavy perspiration. She has had no hypertension,
headaches, palpitations or weight loss. Because of chest
pain and ST-elevations in leads V1, V2 and V3 on ECG
the patient was transferred from a hospital abroad to our
academic clinic to undergo a percutaneous coronary intervention. However, at the initial cardiac angiography no
abnormalities of the coronary arteries were seen. Because
blood pressure had fallen down, the patient needed
haemodynamic support. A transthoracic echocardiogram
showed a dilated left ventricle with akinetic segments
suggesting takotsubo cardiomyopathy. Ultrasonography
of the abdomen showed an adrenal mass at the right
side of 6 cm, which was also seen on the CT-scan. In
the urine an excessive excretion of catecholamines was
found, even after stopping haemodynamic support. On the
MIBG-scan intense uptake was seen in the right adrenal
mass, without any uptake elsewhere. After a short period
of time the patient became normotensive. Metyrosine
was given to reduce the production of catecholamines.
After starting doxazosine as a-blocking drug followed by
atenolol as ß-blocking drug to prevent hypertension during
operation a successful laparoscopic adrenal extirpation was
performed. Pathologic examination showed a pheochromocytoma of 7 cm. Postoperatively no complications were
seen and within a week the patient was sent home in good
clinical condition and with normal blood pressure. After
some weeks she was seen at the outpatient department.
Her sweats were gone, and blood pressure, catecholamine
excretion and echocardiogram were all normal.
Discussion: Pheochromocytoma is a rare diagnosis which
often presents with episodic haedache, sweating and hypertension. As we show in this case, sometimes the initial
presentation is chest pain combined with hypotension
Introduction: We present a case of a patient with recurrent
symptomatic episodes of insulinoma-induced hypoglycemia. Insulinoma is a rare beta-cell neoplasm of the
pancreatic islet that oversecretes insulin. Instead of
standard surgical therapy we performed EUS-guided
alcohol ablation.
Case report: In September 2010 an 82-year-old woman
was admitted to our hospital with a history of recurrent
episodes of hypoglycemia for more than one year. She
had no history of diabetes mellitus, did not use any
medication to regulate blood glucose levels, nor did she
have underlying liver failure. A fasting evaluation test
was performed and showed a spontaneous episode of
hypoglycemia. An inappropriately high serum insulin
concentration of 60.8 mU/l was measured during a
hypoglycemia of 2.5 mmol/l. This indicated excess insulin
and insulinoma was suspected. The preferred initial tests,
a transabdominal ultrasonography and a CT-pancreas, were
performed and showed no presence of a tumorous lesion in
the pancreas. The subsequent endoscopic ultrasonography
showed a neuroendocrine tumor of 10 mm size in the
corpus of the pancreas.
Because of the patient’s age, general condition and the
small size of the tumor, an EUS-guided alcohol ablation
instead of surgery was performed. There were no complications and a total of 3 ml 96% ethanol was injected into the
tumor. A histological biopsy taken during the procedure
showed a neuroendocrine tumor, which conformed
the diagnosis of insulinoma. Currently, the patient is
feeling well and has not experienced any recurrence of
hypoglycemia.
Conclusion: The standard therapy for patients with a
benign, solitary insulinoma is surgical excision of the
tumor. Only two cases1,2 of endoscopic ultrasound-guided
alcohol ablation of insulinoma have been reported. In our
patient the treatment showed good results: there was no
55
recurrence of hypoglycemia. Endoscopic ultrasound-guided
alcohol ablation is minimally invasive and appears to be
suitable for patients with a poor general condition and a
small insulinoma.
99.
may be often seen. The most frequent benign cause of
a recurrent laryngeal nerve paralysis is a multinodular
goitre. Thyroiditis causing recurrent laryngeal nerve
paralysis is extremely rare. Fortunately with modern
imaging techniques one rarely has to resort to surgery to
exclude a malignant cause.
Conclusion.: Recurrent nerve palsy when caused by
thyroid disease may be transient and have a benign cause,
especially when there is no apparent thyroid enlargement.
A rare cause of recurrent laryngeal nerve palsy in
thyroid disease
M. Sandovici1, C. Halma1, H. van den Berge2
1
Medical Centre Leeuwarden, Department of Internal
Medicine, Henri Dunantweg 2, 8934 AD LEEUWARDEN, the
Netherlands, e-mail: maria.sandovici@znb.nl, 2Department
of Otorhynolaringolog, Medical Centre Leeuwarden,
LEEUWARDEN, the Netherlands
100. Abdominal pain as the presenting symptom of
panhypopituitarism
S.H. Binnenmars, A.J.J. Woittiez
Hospital Group Twente, Department of Internal Medicine,
Zilvermeeuw 1, 7600 SZ ALMELO, the Netherlands, e-mail:
H.Binnenmars@zgt.nl
Introduction: Paralysis of a recurrent laryngeal nerve
in thyroid disease is classically associated with an
enlargement of the thyroid gland due to a malignant
process.
Case: A 60-year-old female with osteoporosis and Civatte’s
poikilodermia, presented with hoarseness. Six weeks
before, while on holiday in France, she got a sore throat
and fever up to 39.2 °C. She was initially treated with
Tragitol en strepsils and thereafter with Klacid and possibly
Prednison. At the moment of presentation the patient still
had a sore throat, a subfebrile temperature, night sweating
and fatigue. On physical examination a light dysphonia,
a slightly enlarged, painful thyroid gland without any
nodules and a heart rate of 85/min were found. Blood
analysis revealed an elevated sedimentation rate (> 9
0 mm/h) and CRP (107 mg/l), a normocytic anaemia (Hb
6.7 mmol/l), normal white blood cell counts, a slightly
decreased TSH (0.21 mU/l) and a normal FT4 (21.5 pmol/l),
and a negative anti-TPO. Flexible laryngoscopy showed a
palsy of the left vocal cord. A CT of the neck and thorax
showed signs of inflammation of the thyroid gland and
glottis, some reactive lymph nodes and no pathology in
the aortic-pulmonary window. A diagnosis of recurrent
laryngeal nerve palsy accompanying a subacute thyroiditis
was made. Ten days later the hoarseness subsided and
the pain clearly diminished. Four weeks later the CRP
normalized, the sedimentation rate decreased to 18 mm/h,
the anemia had spontaneously resolved and patient became
hypothyroid. A MRI showed a normal thyroid gland and no
signs of pathology along the left recurrent nerve.
Discussion: Paralysis of a recurrent laryngeal nerve is
only rarely associated with a benign thyroid disease. The
mechanisms involved herein are compression of the nerve
against the cervical spine or the trachea, stretching of the
nerve over an enlarged thyroid (such as in a goitre, thyroid
nodule or thyroiditis), inflammation of the nerve itself,
oedema or thrombosis of the minute arterial supply. In
the chronic phase, perineural fibrosis or calcifications
therapy was started. Almost one year after diagnosis the
patient is doing well.
Discussion: Abdominal pain is a well-known sign of
adrenal insufficiency. To the best of our knowledge
the underlying pathofysiological mechanism is poorly
understood. Abdominal pain is more often seen in primary
adrenal insufficiency than in secondary (or tertiary)
insufficiency. For this reason the pain is probably due to
mineralocorticoid deficiency rather than glucocorticoid
deficiency. This case illustrates that abdominal pain can
also be the presenting symptom in secondary adrenal
insufficiency.
Conclusion: It is important to look for other signs and
symptoms of primary adrenal insufficiency, as well
as secondary adrenal insufficiency in patients with
unexplained abdominal pain.
extensive investigation for the presence of endocrine
function disorders and neoplasia was performed. Blood
levels of TSH, prolactin, IGF-1,calcitonin, several tumor
markers, as well as urinary excretion of cortisol,and (nor)
metanefrine and 17-ketosteroids, were within the normal
range. A 1 mg dexamethasone overnight suppression test
was normal. However, the plasma level of chromogranine
A level was elevated (239 nmol/l; normal range 0-100).
Ultrasonography of the thyroid, magnetic resonance
imaging of the spine and pituitary gland, colonoscopy,
cystoscopy and gynaecological examination revealed no
signs of a malignancy. Genetic analysis for the regulatory
type I-a (RIa) subunit of protein kinase A (PRKAR1A)
tumor suppressor gene, characteristic for the Carney
complex, is still pending.
Conclusion: Carney complex should be suspected in case
of (multiple) neoplasias (mucocutaneous, cardiac, adrenal,
neural) in combination with endocrine overactivity and/
or pigmented mucocutaneous lesions. Early recognition
of the Carney complex may avert life-threatening embolic
complications of cardiac myxomas, which otherwise can
be the first manifestation. Any patient suspected of having
the Carney complex should be evaluated for the presence
of endocrine abnormalities and malignancies. When
confirmed, first degree relatives should also be screened.
101. Carney complex
Case: A 75-year-old man was admitted to our hospital
because of abdominal pain. His medical history included
benign prostatic hypertrophy, hypertension and polyarthrosis. His medications consisted of tamsulosin, losartan
potassium, furosemide and piroxicam with pantoprazole.
Besides a continuous chained pain around his upper
abdomen, the patient suffered from anorexia, nausea,
vomiting and lethargy since three months. On physical
examination the patient was pale with a blood pressure
of 111/65 mmHg. Auscultation of heart and lungs was
normal. Moderate tenderness was noted over the epigastric
area. Laboratory results revealed a mild normocytic
anaemia (7.2 mmol/l) and hyponatremia (129 mmol/l).
Renal function and potassium were normal.
At first, symptoms were assigned to gastric pathology.
However, gastroscopic examination revealed no abnormalities. Abdominal ultrasound was normal except for
liver steatosis. Because of the combination of abdominal
pain with hypotension and hyponatremia, adrenal insufficiency was suspected. A serum cortisol of 0.04 umol/l
confirmed this diagnosis. ACTH-level was 2.6 pmol/l,
suggestive of secondary (or tertiary) adrenal insufficiency.
All other hypothalamic-pituitary-endocrine axes were
suppressed. TSH level was 1.9 mU/l and FT4 level was
9.5 pmol/l. Testosterone level was 4.06 nmol/l with low
LH and FSH levels (2.2 and 2.9 U/l). Prolactin level was
slightly elevated (23.8 ug/l) and IGF-1 level was just normal
considering the patient’s age (68 ug/l). Magnetic resonance
imaging of the cerebrum showed a cystic pituitary tumor
extending to the right and to the optic chiasm, presumably
an adenoma with cystic degeneration, grade II to III-B/E
according to Hardy’s classification of pituitary adenomas.
The patient had no visual field deficits. He was started
on hydrocortisone and in a few days his abdominal pain
was dissolved. Levothyroxin and testosterone replacement
56
Z.A. Choudhry, J.J.M. van der Hoeven, S. Simsek, F. Stam
Medical Centre Alkmaar, Department of Internal Medicine,
Wilhelminalaan 12, 1815 JD ALKMAAR, the Netherlands,
e-mail: zichoudhry@hotmail.com
Introduction: Carney complex is a rare multiple neoplasia
syndrome assiociated with a variety of pigmented mucocutaneous lesions. Carney complex is inherited as an
autosomal dominant trait. We describe a case in which the
manifestations were an atrial myxoma, facial lentigines
and bilateral nodular masses.
Case report: A 63-year-old woman presented at our
outpatient department with a progressive inguinal
swelling. Her medical history consisted of a resected
atrial myxoma five years before, diabetes mellitus
type 2 and hypertension On physical examination, the
patient was obese (body mass index 36,4 kg/m2) with
a centripetal distribution of body fat. Investigation of
the skin showed facial lentigines and blue naevi in the
trunk. In the right groin a painless, hard mass of 5 cm
was felt. Further physical examination was remarkless. A
complete blood count, chemistry profile, liver and kidney
functions were normal. Positron emission tomography
(PET) with computed tomography demonstrated
enlargement of lymph nodes in the left para-iliac region
with F18-fluorodeoxyglucose (FDG) uptake. Furthermore,
bilateral adrenal nodularity without uptake of FDG was
seen, suggestive for primary pigmented adrenocortical
disease (PPNAD). Histopathological examination of the
inguinal lymph node revealed a poorly differentiated
neuro-endocrine carcinoma.
The coincidence of a neuro-endocrine carcinoma, atrial
myxoma (in the history), lentigines, blue naevi and possible
PPNAD, was suggestive for a Carney complex. Therefore,
102. Case report: uncommon cause of infertility
J.P.H. van Wijk1, W.L. de Ranitz-Greven1, F.A. Groenman2,
C. Kimmel2, E.W.M.T. ter Braak1
1
University Medical Centre Utrecht, Department of Internal
Medicine, Heidelberglaan 100, 3508 GA UTRECHT, the
Netherlands, e-mail: jwijk3@hotmail.com, 2FlevoHospital,
ALMERE, the Netherlands
We report a case of ovarian hyperstimulation syndrome
related to FSH secreting pituitary adenoma in a 21-year-old
female. The patient was referred to our hospital with a
2 year history of amenorrhea, abdominal pain, weight
gain and headache. On examination, she was obese, and
horizontally disposed striae were located on the breast,
abdomen and legs. Furthermore, there was a large mass
in the lower abdomen. Laboratory evaluation revealed
extremely high estradiol (23501 pmol/l, normal for follicular
phase: 180-600 pmol/l) with suppressed LH (< 0,5 IU/l,
normal for follicular phase: 2-11 IU/l) and inappropriately high FSH (27 IU/l, normal for follicular phase: 3-12
IU/l). Pelvic ultrasound showed bilateral enlarged ovaries
containing multiple giant cysts: the right ovary measured
10 x 18 cm and the left ovary 10 x 13 cm. The presence of
an endogenous ovarian hyperstimulation syndrome was
suspected. Subsequent MRI revealed pituitary macroadenoma with optic chiasm compression. Consultation of
57
the ophthalmologist confirmed bitemporal hemianopsia.
Transsphenoidal resection of the macro-adenoma was
performed, with an uneventful postoperative course.
Immunohistologic examination showed staining for FSH,
consistent with the diagnosis FSH secreting pituitary
adenoma. After surgery, laboratory values normalized
and the patient resumed regular menstrual cycles. Three
months after surgery, the MRI showed tumour disappearance. Pelvic ultrasound showed marked involution of
the ovarian masses. Within 6 months after surgery, the
patient conceived spontaneously. The pregnancy course was
uneventful. Recently, she gave birth to a healthy daughter.
In conclusion, ovarian hyperstimulation syndrome due to
a FSH secreting pituitary adenoma is a very rare medical
condition. Our patient resumed regular menstrual cycles
and conceived spontaneously after successful transsphenoidal resection of the adenoma.
V.
controlled trials (RCTs) using the total symptom score
(TSS) as the outcome measure were selected and assessed
for their methodological quality. A random-effect model
was used for pooling in case of heterogeneity, a fixed-effect
model in the absence of heterogeneity. Subgroup analyses
for intravenous and oral administration of alpha lipoic acid
versus placebo were conducted.
Results: The search yielded 242 publications. Six RCTs met
our inclusion criteria. Four RCTs were of good quality and
included for statistical pooling. Overall, the pooled standardized mean difference estimated from all trials revealed
a reduction in TSS scores of -2.26 (CI: -3.12 to -1.41;
p=0.00001) in favour of alpha lipoic acid administration.
Subgroup analyses of oral administration (-1.78 CI: -2.45
to -1.10; p=0.00001) and intravenous administration (-2.81
CI: -4.16 to -1.46; p=0.0001) confirmed the robustness of
the overall result.
Conclusion: Based on the currently available evidence, when
given intravenously at a dosage of 600 mg once daily over
a period of 3 weeks, alpha lipoic acid leads to a significant
and clinically relevant reduction in neuropathic pain (grade
of recommendation A). The significant improvements seen
after 3-5 weeks of oral administration at a dosage of <u>></
u> 600 mg daily are not clinically relevant.
DIABETES MELLITUS RESEARCH
103. Alpha lipoic acid for neuropathic pain in patients
with diabetes: a meta-analysis of randomised
controlled trials
104. Defining, measuring and improving perioperative
diabetes care
G.S. Mijnhout1, B.J. Kollen2, A. Alkhalaf1, N. Kleefstra3,
H.J.G Bilo1
1
Isala Clinics, Department of Internal Medicine, Dr. van
Heesweg 2, 8025 AB ZWOLLE, the Netherlands, e-mail:
g.s.mijnhout@isala.nl, 2University Medical Centre Groningen,
GRONINGEN, the Netherlands, 3Diabetes Centre and
Langerhans Medical Research Group, ZWOLLE, the Netherlands
I. Hommel, M.E.J.L. Hulscher, P.J.M. van Gurp
Radboud University Medical Centre, Department of Iq
Healthcare, Geert Grooteplein 21, route 114, 6500 HB
NIJMEGEN, the Netherlands, e-mail: i.hommel@iq.umcn.nl
Introduction: Optimal glycaemic control in surgical
patients reduces mortality, rate of infections and length
of stay. Guidelines and literature provide various recommendations on perioperative diabetes care. Optimal perioperative diabetes care, however, is often not achieved. This
probably reflects the difficulty of implementing best
practice recommendations into a complex multiprofessional setting.
Aim: To define and measure perioperative diabetes care in
terms of optimal professional, organizational and patientoriented quality, in order to guide development of an
improvement program.
Methods: To define optimal perioperative diabetes care, a
systematic RAND-modified Delphi method was used to
develop a set of key recommendations. Experts appraised
79 recommendations on perioperative diabetes care,
extracted from international guidelines and literature,
resulting in 17 indicators on professional performance, 9
indicators on organizational structure, and 4 indicators on
patient outcome. Twelve additional indicators on patient-
Background: Neuropathic pain is difficult to treat. The
medications currently used mainly include antidepressants, antiepileptics and opioids. These medications are
limited in their effectiveness, have considerable side
effects, and have no effect on the processes by which
hyperglycemia leads to cell damage. Alpha lipoic acid is a
potent antioxidant, reported to reduce diabetic micro- and
macrovacular complications in animal models.
Aim: We performed a systematic review and meta-analysis
of the literature in which the effectiveness of alpha lipoic
acid as a treatment for neuropathic pain in patients with
diabetes was evaluated. The aim of this meta-analysis was
to evaluate the effects of intravenous as well as oral administration of alpha lipoic acid versus placebo.
Methods: The databases MEDLINE and EMBASE were
searched using the key words ‘lipoic acid’’, ‘thioctic acid’,
‘diabet * ’, and the medical subject headings (MeSH)
‘thioctic acid‘ and ‘diabetes mellitus’. Randomised placebo-
58
metformin and a sulfonylurea. To evaluated from these
data if there is enough reason to conduct a prospective
study.
Patients and methods: 19 Overweight diabetic patients of
our outpatient clinic, whose therapy with a combination of
insulin and metformin was changed to the combination
of incretin mimetic, metformin and sulfonylurea (new
treatment), were evaluated in a retrospective study after
six months of the new treatment. HbA1c and weight were
measured in the beginning and after 6 months of the new
therapy. The patients were asked also about their quality of
life feelings after the six months of therapy.
Results: 6 Patients could not be evaluated, because two
patients were lost by failing and stopping the new therapy
during the six months treatment and four patients were
lost by lacking data. At the beginning of the new treatment
the remaining 13 patients had a body mass index higher
than 35.0 kg/m2, a mean HbA1c of 10.0% and a mean
weight of 116.1 kilograms. Six months after the start of the
new treatment the mean HbA1c was decreased to a mean
of 8.6%, and the mean weight to 111.0 kilograms. Only two
patients had an increase in HbA1c and only 1 patient gained
weight. All the patients said to feel a better quality of life
with the new treatment, than with the insulin treatment.
Conclusion: In this retrospective evaluation of a small
group of patients we showed in most patients a reduction
in HbA1c and weight and a better quality of life with a
treatment of incretin mimetics, metformin and sulfonylurea in stead of insulin and metformin. We recommend
a prospective study to confirm these results and to assess
which overweight diabetic patients treated with insulin can
benefit from incretin mimetics.
oriented quality were derived from an interview with an
expert panel of diabetic patients who underwent surgery
in the recent past.
To measure current perioperative diabetes care, in 6
Dutch hospitals, 400 diabetic patients were identified
based on the use of diabetic medication during hospitalization for a major surgical procedure. Diabetic patients
who had abdominal surgery during general anesthesia,
heart surgery or large joint orthopedic surgery with a
minimum operative time of one hour in the period march
2009-march 2010 were included. Selected patients were
approached by mail and by telephone to request permission
for a medical record search on professional performance,
and to complete a questionnaire on patient-oriented
items. Hospital organizational structure was assessed by
questionnaire.
Results: Preliminary results showed that there is ample
room for improvement regarding many of the indicators.
For example, medical records revealed information on
preoperative glycemic control in only 42% of patients.
Protocols on perioperative diabetes care were present in
all 6 hospitals; multiprofessional involvement in establishing and supporting adherence to these protocols varied,
however, considerable. Regarding patient-oriented quality,
17% of patients received complete information on perioperative diabetes management prior to surgery.
Conclusion: To improve perioperative diabetes care, we
are currently performing interviews with the various
professionals involved, revealing among others problems
in knowledge, insight into own performance and organizational problems like a lack of agreement on mutual responsibilities. Education, feedback on professional performance,
and a multiprofessionally established protocol will be part
of the improvement program. Patient-oriented care will
receive special attention to promote continuation of self
care of diabetes patients in hospital.
106. Vildagliptin improves endothelium-dependent
vasodilatation in subjects with type 2 diabetes
P.C.M. van Poppel, P. Smits, C.J. Tack
Radboud University Medical Centre, Department of Internal
Medicine, PO Box 9101, huispost 463, 6500 HB NIJMEGEN,
the Netherlands, e-mail: pleunvp@hotmail.com
105. Are incretin mimetics useful in obese insulin treated
diabetic patients?
C.M.L. Driessen, P.F.M.J. Spooren
TweeSteden Hospital Tilburg, Department of Internal
Medicine, Dr. Deelenlaan 5, 5042 AD TILBURG, the
Netherlands, e-mail: chantal_driessen@hotmail.com
Introduction: Cardiovascular complications are the leading
cause of morbidity and mortality associated with type 2
diabetes mellitus. Endothelial dysfunction is a marker of
and often precedes these vascular complications. Ideally,
pharmacotherapy for type 2 diabetes not only lowers
blood glucose levels but also has beneficial cardiovascular
effects. Recently, incretin-based therapy has become
available for the treatment of type 2 diabetes mellitus.
Dipeptidyl peptidase-4 (DPP-4) inhibits the breakdown
of incretin hormones including glucagon-like peptide-1
(GLP-1). GLP-1 improves endothelial function in both
animals and humans.
Introduction: Incretin mimetics (or GLP-1 analogs) are
approved for the treatment of type 2 diabetic patients. They
cause a significant reduction in HbA1c and in weight in
comparison to placebo.
Aim: To establish that poorly regulated obese type 2
diabetic patients using large quantities of insulin and
metformin are treated more effectively and show a better
quality of life with a combination of an incretin mimetic,
59
Aim: To determine the effect of the DPP-4 inhibitor
vildagliptin on endothelial function in patients with type
2 diabetes.
Materials and methods: 16 subjects with type 2 diabetes
(age 59.8±6.8year, BMI 29.1±4.8 kg/m2, HbA1c 6.97±0.61)
on oral blood glucose lowering treatment were included.
Participants received vildagliptin 50 mg bid or acarbose
100 mg tid for 4 consecutive weeks in a randomised, double
blind, cross-over design. At the end of each treatment
period we measured forearm vasodilator responses (plethysmography) to intra-arterially administered acetylcholine
(endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator).
Results: Baseline forearm blood flow (FBF) was higher
during vildagliptin treatment than during acarbose
(expe­r imental arm 3.3 ±0.3 vs.2.5±0.2 ml.dl1.min1, p=0.02).
Corresponding values in the non experimental arm
were 2.7±0.3 and 2.2±0.3 ml.dl1.min1 (p=0.07). Infusion
of acetylcholine induced a dose-dependent increase in
FBF in the experimental arm, which was higher during
vildagliptin (3.1±0.7, 7.9±1.1 and 12.6±1.4 ml.dl1.min1
in response to acetylcholine 0.5, 2.0 and 8.0 mg.dl-1.
min-1) than during acarbose (2.0±0.7, 5.0± 1.2 and 11.7±
1.6 ml.dl1.min1 respectively, p=0.01 by two-way ANOVA).
Treatment with vildagliptin did not significantly change
the vascular responses to sodium nitroprusside.
Conclusion: Vildagliptin improves endothelium-dependent
vasodilator responses in type 2 diabetic subjects on oral
treatment, while endothelium-independent responses are
unaffected. This effect might have favourable cardiovascular implications.
widespread access to the EU market, exposing large groups
of patients. This makes it of crucial importance to identify
safety concerns as soon as possible. Relevant safety signals
in the EU are regularly communicated in so-called ‘Direct
Healthcare Professional Communication’ (DHPC) or
European Medicines Authority (EMA) press releases. It is
unknown whether such safety signals effectively influence
prescribing and dispensing of drugs.
Aim: To analyse trends in dispensing patterns of rosiglitazone and pioglitazone following DHPCs and EMA press
releases in the EU member state the Netherlands.
Methods: Data for this study were obtained from the
PHARMO Record Linking System which includes, among
other issues, drug dispensing records from community
pharmacies of approximately 2.5 million individuals in
the Netherlands. We used linear regression analysis with
dispensing volume as the outcome and time as determinant
to assess the variance in dispensing volume over time.
Hypothesizing that this variance would not change, the beta’s
of this model were used as the outcome in a subsequent linear
regression. In this second model the DHPC letters or EMA
press releases were used as determinants to assess the impact
of these safety communications. Adjustments were made for
publication of certain relevant literature.
Results: 6,165,341 million prescriptions with an ATC code
for drugs used in diabetes mellitus (A10) were dispensed
to 158,599 participants during the period 1998-2008. After
applying exclusion criteria, 3,579,810 (58.1%) dispensed
prescriptions for 112,105 (70.7%) participants were left
for the analysis. The volume of rosiglitazone dispensings
decreased significantly after publication of DHPCs and
EMA press releases. This effect was more pronounced
for dispensings prescribed by specialists than for those
prescribed by general practitioners. Similar observations
were made for pioglitazone. However, adjustment for
certain relevant literature reduced the effect of the communicated safety issues on the proportion of dispensings.
Conclusion: Although it is difficult to disentangle the
effect of DHPCs and EMA press releases from the effect
of reports published in the literature, our results suggest
that prescribers also react to such safety communications.
107. Trends in dispensing patterns of rosiglitazone and
pioglitazone in the Netherlands following safety
signals during the period 1998-2008
R. Ruiter 1 , E. Visser 1, M.P.P. van Herk Sukel 2 ,
P.H. Geelhoed-Duivestijn3, S. de Bie1, S.M.J.M. Straus4,
P.G.M. Mol5 , S.A. Romio1, R.M.C. Herings2 ,
B.H.Ch. Stricker1
1
Erasmus Medical Centre, Department of Epidemiology,
PO Box 2040, 3000 CA ROTTERDAM, the Netherlands,
e-mail: r.ruiter@erasmusmc.nl, 2PHARMO Institute for
Drug Outcomes Research, UTRECHT, the Netherlands,
3
Medical Centre Haaglanden, THE HAGUE, the Netherlands,
4
College ter Beoordeling van Geneesmiddelen, THE HAGUE,
the Netherlands, 5University Medical Centre Groningen,
GRONINGEN, the Netherlands
108. The association between body fat and serum
C3 levels is largely explained by low-grade inflammation and insulin resistance: the CODAM study
N. Wlazlo1 , M. Greevenbroek 2 , I. Ferreira 2 ,
C.J.H. van der Kallen2, C. Schalkwijk 2, B. Bravenboer1,
C.D.A. Stehouwer2
1
Catharina Hospital, Department of Internal Medicine,
Michelangelolaan 2, 5623 EJ EINDHOVEN, the Netherlands,
e-mail: nick.wlazlo@cze.nl, 2Maastricht University Medical
Centre, MAASTRICHT, the Netherlands
Introduction: In the European Union (EU), the European
Medicines Agency (EMA) coordinates the centralised
authorisation procedure for medicinal products. Approval
through a centralized procedure facilitates a swift and
60
VI.
Introduction: Serum complement factor 3 (C3) is an
emerging risk marker for cardiovascular and metabolic
diseases. C3 levels are closely related to body fat, but the
underlying mechanisms explaining this association are
still unknown. We investigated the association between
several adiposity measurements and C3 and examined
the role of low-grade inflammation and insulin resistance
herein, since both are known correlates of adiposity and C3.
Methods: Body mass index (BMI), sum of 4 skinfolds
(subscapular, suprailiacal, biceps, triceps), waist circumference (WC), hip circumference (HC), waist-to-hip ratio
(WHR), sagittal diameter, serum C3, homeostastis model
assessment – insulin resistance (HOMA2-IR) and markers
of inflammation (high sensitivity C-reactive protein,
interleukin-6, serum amyloid A, haptoglobin, ceruloplasmin, soluble inter-cellular adhesion molecule-1) were
determined in the Cohort on Diabetes and Atherosclerosis
Maastricht (CODAM) study population (n=535; 62% men,
age 59±6.9 years, BMI 28.5±4.3 kg/m2, WC 99.3±11.8
cm). The markers of inflammation were standardized and
compiled into an average inflammation score. We used
linear regression analysis to examine the associations of
individual adiposity measurements with C3, adjusting
for age, sex, type 2-diabetes mellitus, cardiovascular
disease, smoking, alcohol intake and medication. Multiple
mediation analyses were performed to ascertain whether,
and the extent to which, these associations were independently explained by inflammation and HOMA2-IR.
Results: After adjustment for covariates, all adiposity
measurements were significantly and positively associated
with C3 levels, with the strongest associations found for
sagittal diameter (standardized regression coefficient
ß=0.451; 95% CI 0.374-0.528) and WC (ß=0.422; 95%
0.342-0.502). Further adjustments for inflammation and
HOMA2-IR attenuated these associations to ß=0.187
and ß=0.135 respectively. The independent mediation
(expressed as standardized ß) by inflammation in the
relation between WC and C3 was 0.097 (95% CI 0.0660.135), representing 23% of the total association between
WC and C3 (0.097/0.422 * 100%). Additionally, the
mediation by HOMA2-IR was 0.190 (95% CI 0.138-0.248),
which was 45% of the total association. For all adiposity
measures, 20-25% of the association with C3 was explained
by low-grade inflammation, and 40-55% by HOMA2-IR,
independently of one another.
Conclusion: Systemic low-grade inflammation and insulin
resistance may represent two independent pathways by
which body fat leads to elevated C3. Increases in serum
C3 may be due to changes at the level of C3 transcription in
response to e.g. increased (local) concentrations of inflammatory cytokines, or loss of inhibitory effect of insulin.
Moreover, decreased fatty acid storage in insulin-resistant
adipocytes may provide another potential stimulus for C3
production in fat.
DIABETES MELLITUS CASE REPORTS
109. Reversible loss of vision due to atorvastatin
W.J. Lammers, A.F.G. Jansen, A.A.M. Zandbergen,
A. Dees
Ikazia Hospital, Department of Internal Medicine, Willem
van Hillegaersbergstraat 12b, 3051 RJ ROTTERDAM, the
Netherlands, e-mail: w.j.lammers@gmail.com
Introduction: Atorvastatin is worldwide one of the most
used cholesterol lowering drugs, which blocks the
HMG-CoA-reductase, an important enzyme in the biosynthesis of cholesterol. A number of side effects have been
reported such as myalgia, nausea, constipation, diarrhea
and headache. Not much is known about visual loss as
major side effect. Here we describe a patient with the onset
of visual acuity problems after years of atorvastatin use.
Case report: A 60-year-old patient had been followed up
for many years at the Outpatient Clinic because of his
metabolic syndrome. His medical history comprised
hypertension, diabetes mellitus, hypercholesterolemia,
adipositas, atypical thoracic pain without evidence of
coronary artery disease, psychosocial problems and
epicondylitis lateralis. The treatment regimen consisted
of losartan, aliskiren, metoprolol, metformin and insulin,
four times daily. He had been treated with atorvastatin for
more than ten years.
The patient was known with hypermetropia, his visual
acuity after correction was 20/20. He underwent regular
ophthalmologic checks, without any significant signs of
diabetic retinopathy and with a first appearance of cataract
of the left eye. Despite these findings a slowly progressive
complaint of blurred vision of both eyes developed within
10 months. The ophthalmologist found that his visual
acuity decreased to 20/40. No other new ophthalmic abnormalities were noticed. The patient lost his driver licence.
Thinking of medicine-induced vision problems, the
ator­vastatin has been switched to simvastatin. After the
switch a dramatic clinical improvement occurred and the
blurred vision resolved slowly.
Discussion: Atorvastatin is a widely used drug with
some well-known side effects. However, ophthalmologic
problems have only been reported sporadically. Also, the
Dutch databank of medicine side effects, called Lareb,
reports three other cases of transient blurred vision due
to atorvastatin. There is nothing known about the pathophysiology of these ophthalmologic complications. Possibly,
opticus neuropathy is involved. Conclusively, in patients
who are on statin treatment for instance atorvastatin, drug
side effects must be considered when visual loss occurs,
even after many years of use.
61
110. Mastopathy: a rare complication in a young patient
with type 1 diabetes
VII. HAEMATOLOGY RESEARCH
N.C. de Clercq, M.E.M. Rentinck
Tergooi Hospitals, Department of Internal Medicine, Van
Riebeeckweg 212, 1213 XZ HILVERSUM, the Netherlands,
e-mail: nicoliendeclercq@gmail.com
111.
Increased numbers of microparticles and microparticle specific thrombin generation in patients with
myeloproliferative disease
M.C.
van
Aalderen 1 ,
M.C.
Trappenburg 1 ,
M. van Schilfgaarde1, P.J. Molenaar 1, H. ten Cate2,
A. Leyte1, W.E. Terpstra1
1
Onze Lieve Vrouwe Gasthuis, Department of Internal
Medicine, Oosterpark 9, 1090 HM AMSTERDAM, the
Netherlands, e-mail: m.c.vanaalderen@olvg.nl, 2Maastricht
University, MAASTRICHT, the Netherlands
Case: A 29-year-old woman was seen at the outpatient
clinic with a painless mass in the right breast. Her medical
history revealed type 1 diabetes mellitus from the age
of 12, with secondary complications of retinopathy and
nephropathy. The patient had noticed the mass 2 months
before, without signs of nipple discharge or retraction. She
had an aunt who died of breast cancer.
Physical examination of the breast showed a tumor behind the
right nipple, measuring approximately 2 cm. The left breast
was normal; no enlarged axillary lymph nodes were present.
Mammography showed dense fibroglandular tissue in the
central part of the right breast; no discrete lesions or pathological microcalcifications were found. Acoustic shadowing was
seen on ultrasound at the site of the palpable mass, measuring
3,6 by 2,1 cm. Cytology of the tumor was nonconclusive.
Histological biopsy under ultrasound guidance was performed.
Pathology demonstrated lymphoplasmocellular infiltration
around the acini and lobuli. No signs of malignancy were
seen. The clinical profile in combination with these pathologic
features was characteristic of diabetic mastopathy.
Discussion: Diabetic mastopathy is an unusual and often
not recognized complication of diabetes. Characteristic are
lymphocytic mastitis and stromal fibrosis that presents
in premenopausal women with long-standing type 1
diabetes mellitus with multiple microvascular complications. Clinicopathological features include the development
of irregular breast masses, which tend to be recurrent and
bilateral. Clinical distinction from a malignancy can be
difficult. However, the benign nature of this lesion is easily
recognized by histopathological examination. Microscopy
shows stromal fibrosis with signs of ductitis, lobulitis and
vasculitis. Although the pathogenesis is still unknown,
several mechanisms have been suggested. Possibly these
lesions are due to an auto-immune reaction to the accumulation of abnormal matrix induced by hyperglycemia. After
surgical excision, diabetic mastopathy tends to recur in
the same location and involves more breast tissue than the
preceding lesion; therefore surgical procedures should not
be considered unless neoplasia has not been ruled out.
Conclusion: The association between mastopathy and type
1 diabetes has been reported, but this clinical condition is
poorly recognized since breast examination is not routinely
performed in young diabetic patients. Recognition of this
complication in patients with long-standing type 1 diabetes is
important as it might save patients with documented diabetic
mastopathy from being subjected to repeated breast biopsies.
Introduction: Essential Thrombocythemia (ET) and
Polycythemia Vera (PV) are both myeloproliferative
neoplasms associated with an ill-understood high risk of
thromboembolic events. In a previous study we showed
elevated levels of platelet, endothelium and leukocyte
related microparticles (MPs) in ET.
Aim: To compare MP phenotypic profiles and
MP-dependent thrombin generation of ET and PV patients
to healthy controls to further explore the putative role of
MPs in myeloprolific thrombophilia.
Materials and methods: In plasma samples from 18 ET
patients, 24 PV patients and 20 controls, levels and cellular
origin of MPs were determined by flowcytometric analysis
and MP-dependent thrombin generation by our adaptation
of the Siemens ETP assay.
Results: ET patients had significantly higher numbers
of platelet derived MPs (CD41+) than PV patients and
controls (median: ET 9000, PV 5970, controls 4100 x 106/l;
p<0.001). MPs expressing the endothelial marker CD62E
were highly abundant in ET and moderately increased in
PV compared with controls (median ET 2975, PV 324,
controls 80 x 106/l; p<0.001 and p=0.02). Leukocyte
derived (CD45+) MP numbers were small but elevated in
all patients (median: ET 77, PV 112, controls 21 x 106/l;
p<0.001; p<0.001) and correlated with leukocyte count
(p<0.001). In line with their MP numbers, ET patients had
a higher MP-dependent endogenous thrombin potential
(ETP) than controls (median ET 278, PV 212, controls
147 milliAbsorbance; p<0.01).
Conclusion: ET and PV patients had elevated numbers of
MP with phenotypic profiles reflecting different degrees of
platelet, endothelium and leukocyte ancestry. MP specific
thrombin generation, which was highest for ET patients,
appeared equally proportional to ET, PV and control MP
numbers suggesting similar procoagulant properties.
VIII. HAEMATOLOGY CASE REPORTS
113.
Cholestasis as presenting symptom of Hodgkin
lymphoma
K. Boslooper1 , M. Hoogendoorn1, K. van der Linde1,
R.E. Kibbelaar2
1
Medical Centre Leeuwarden, Department of Internal
Medicine, Henri Dunantweg 2, 8934 AD LEEUWARDEN,
the Netherlands, e-mail: boslooperk@gmail.com, 2Pathologie
Friesland, LEEUWARDEN, the Netherlands
112. A woman with smoking Buttocks?!
N.A.F. Verheijden, T. Ermens, J.W.J. van Esser
Amphia Hospital Breda, Department of Internal Medicine,
Molengracht 21, 4818 CK BREDA, the Netherlands, e-mail:
NVerheijden@amphia.nl
Paraneoplastic features are frequently observed in patients
with Hodgkin lymphoma. These phenomena can mislead
clinicians and delay the diagnostic process. We describe a
case of a previously healthy 76-year-old men presenting with
fatigue, transient diarrhea and a skin rash in combination
with laboratory tests showing severe cholestasis. Extensive
diagnostic work-up including endoscopy, CT scan and liver
biopsy, performed by the hepatologist, did not reveal the
diagnosis. Several months later the patient was admitted
to our hospital with fever, weight loss and night sweats.
A FGD-PET/CT showed diffuse PET positive lymphadenopathy. Lymph node and bone marrow biopsy showed
Hodgkin lymphoma, stage IV-B. The patient was successfully treated with systemic chemotherapy consisted of
adriamycin, bleomycin, vinblastin and dacarbazin (ABVD)
and achieved complete remission after six cycles of
chemotherapy. The liver function test nearly normalized
after finalizing the treatment. Liver involvement can be
detected in Hodgkin lymphoma. It has a variable etiology,
including hepatic infiltration of lymphoma, extrahepatic obstruction by enlarged lymph nodes, hemolysis or
concurrent infectious hepatitis. However, jaundice and
severe cholestasis as the first presenting symptom is rare.
This may be due to a paraneoplastic phenomenon, which
is defined as vanishing bile duct syndrome or idiopathic
cholestasis. The pathogenesis of these entities is largely
unknown, but among the different hypotheses cytokine
release by lymphoma cells is frequently postulated. The
cholestasis may be fully reversible after successful treatment
of the disease. These paraneoplastic phenomena should
therefore be considered in cholestasis of unknown cause.
Case history: A 42-year-old woman, with a history of epilepsy,
had a routine visit to her neurologist. Laboratory check
up showed an abnormal leukocyte count and the patient
was referred. She had a smoking history of 30 pack
years and used no alcohol. Her father was known with
a non Hodgkin lymphoma and bladder carcinoma.
Physical examination was normal, especially no lymphadenopathy or hepatosplenomegaly were present. Laboratory
assessment showed: Hb 8.2 mmol/l (7.5-10.0 mmol/l),
leukocytes 16.5 x 109/l (4-10 x 109/l), leukocyte differentiation; lymphocytes 11.7, monocytes 0.7 and granulocytes
4,1 and a thrombocyte count of 198 x 109/l (150-400 x
109/l).
The peripheral blood smear showed ‘Buttock cells’.
Flowcytometry of peripheral blood revealed a polyclonal
increase of mature B-lymphocytes. A diagnosis of
persistent polyclonal B-cell lymphocytosis (PPBL) due to
nicotine abuse was made.
Discussion: Persistent polyclonal B-cell lymphocytosis
is a benign disease, characterized by the presence of
typical binucleated lymphocytes on peripheral blood
smear. These ‘Buttock cells’ are lymphoid cells with a
cleft and prominent nucleolus. PPBL is predominantly
seen in females and is associated with nicotine abuse. The
pathophysiology of PPBL is unknown, but its association
with HLA DR 7 suggests a genetic predisposition.
Flowcytometry is mandatory to differentiate PPBL from
monoclonal B cell proliferation as in chronic lymphatic
leukaemia and other lymphoproliferative diseases.
Reviewing the literature, three patients diagnosed with
PPBL, developed a non Hodgkin lymphoma. In all other
cases PPBL had a benign cause. Quit smoking should be
the therapy of choice.
Conclusion: Persistent polyclonal B-cell lymphocytosis is
a benign disease in which peripheral blood smear shows
binucleated lymphocytes (Buttock cells). PPBL is associated
with nicotine abuse, but there also seems to be a genetic
predisposition. To prevent extensive work-up, knowledge of
this disease entity is mandatory.
114. ‘Copycat’
D.G.J. Robbrecht, A.A.M. Ermens, R.S. Boersma,
J.W.J. van Esser
Amphia Hospital, Department of Internal Medicine,
Molengracht 21, 4818 CK BREDA, the Netherlands, e-mail:
DRobbrecht@amphia.nl
Introduction: We present two patients that illustrate how a
difficult but intriguing diagnostic process ultimately lead to
the diagnosis angioimmunoblastic T-cell Lymphoma (AITL).
62
63
Case report: Case 1: a 51-year-old male was referred because
of progressive red spots on both legs since 1 day. Preceding
referral he complained of malaise, pain in his wrists and
ankles, shortness of breath, and nocturnal transpiration
without fever, weight loss or itching. There was no history
of unsafe sex, blood transfusion, visits to foreign countries
nor did he use any medication. On physical examination
purpura were seen on both legs, furthermore multiple
enlarged lymph nodes and splenomegaly were present. He
had a normocytic anemia, kreatinin 102 umol/l (n: 59-104
umol/l, LDH 436 U/l (n: max. 250 U/l) and urinary screening
was unremarkable. Auto-immune serology was negative,
viral serology showed positive IgM for cytomegalovirus and
parvovirus. Serum elektrophoreses showed polyclonal hypergammaglobulinemia and complement profile was decreased.
Skin biopsy revealed leukocytoclastic vasculitis. Differential
diagnosis consisted of viral infection, auto immune disease
or lymphoma. Lymph node and bone marrow examination
revealed AITL and chemotherapy was initiated subsequently.
Case 2: a 63-year-old male presented with fever and rash.
On physical examination a palpable liver, generalised rash
and ankle edema were found. Laboratory examination
showed leukocytosis with marked eosinophilia and liverfunction abnormalities. Chest X ray was normal and
ultrasound of the abdomen showed a homogenously
enlarged liver. Liver biopsy and bone marrow examination
showed marked eosinophilia. Differential diagnosis
consisted of (drug) allergy, auto-immune disease, parasitic
infection, or hyper eosinophilic syndrome. A few days later
patient was readmitted because of a normocytic anemia of
4,2 mmol/l and reticulocytopenia, auto anti D and aspecific
cold and warmth auto antibodies were present. Computed
tomography showed lymphadenopathy and an enlarged
liver. Lymph node histology showed a reactive process
consisting of plasmacells, lymphocytes and eosinophils,
bone marrow examination showed a hypercellular marrow
with mature eosinophilia. Unfortunately patient died
secondary to a myocardial infarction. T cell receptor
rearrangement analysis showed monoclonal T cells. A
retrospective diagnosis of AITL was made.
Discussion: Cytokine production in AITL causes, amongst
others, polyclonal B-cell stimulation and a myriad of
symptoms mimicking infection, auto-immune disease,
allergy etc. Knowledge of this entity may prevent
unnecessary delay and initiation of treatment.
115.
Introduction: Portal vein thrombosis (PVT) is a rare
thrombosis that can be associated with Philadelphianegative myeloproliferative diseases (MPD). Diagnosing
MPD in patients with PVT can be difficult because of the
effects of portal hypertension, such as hypersplenism,
gastrointestinal bleeding and haemodilution. Since the
mutation in the Januskinase2 gene (JAK2 V617F) is
present in the majority of patients with MPD, testing is
an important diagnostic tool in recognizing atypical or
latent MPD. To illustrate the difficulties in the diagnostic
workup, we present a patient with thrombosis of the
splanchnic system as the presenting symptom of a latent
MPD.
Case: We saw a 68-year-old man, complaining of sub-acute
onset upper left quadrant abdominal pain, nausea and
fever. An abdominal CT-scan showed extensive portal
vein thrombosis along with splenic and superior
mesenteric vein thrombosis, as well as splenic infarction
in an enlarged spleen. Also, ascites and a thickened
mesenterium were observed.
Laboratory tests at presentation showed the following:
haemoglobin 7.8 mmol/l (8.0-10.6), haematocrit 40%,
MCV 76 fl (81-96) Leukocyte count 20.8 * 109/l (4.0-11.08
* 109), mainly neutrophils, CRP 142 mmol/l (<10.0).
Kidney function and electrolytes were unremarkable, liver
enzymes were slightly elevated. The initial thrombocyte
count was 622 * 109/l and ranged from 318 to 682 x 109/l
(150-400 * 109) during his stay in hospital.
Endoscopic studies revealed no gastrointestinal pathology.
Blood cultures were positive with bacteroides fragilis
indicating a concurrent peritonitis. We started treatment
with anticoagulants and antibiotics. Screening for thrombophilia revealed a lupus anticoagulans. Additional testing
for JAK-2 mutation was positive. Bone marrow biopsy was
consistent with MPD essential thrombocytemia.
However, in one year follow-up, no treatment targeting
the essential trombocytemia was initiated because of
completely normal blood cell counts, including the
platelets.
Discussion: In this case report we demonstrate pitfalls in
the diagnostic workup of patient with PVT. Concurrently
with extensive thrombosis of the splanchnic system,
our patient was diagnosed with splenic infarction and
peritonitis. In the setting of unreliable clinical and haematological parameters, the identification of JAK-2 mutation
can be pivotal in diagnosing latent MPD.
Furthermore, follow-up of our case with persistent normal
blood cell counts, illustrates that finding MPD underlying
a PVT does not inherently warrant initiating MPD
treatment. Whether the JAK mutation itself has intrinsic
prothrombotic capacity remains to be illuminated.
Pitfalls in diagnosing myeloproliferative disease in
the presence of portal vein thrombosis
G. Douma, M. Hoogendoorn
Medical Centre Leeuwarden, Department of Internal
Medicine, H. Dunantweg 2, 8934 AD LEEUWARDEN, the
Netherlands, e-mail: gea.douma@znb.nl
64
116. Right ventricular failure due to chloroma as
initial presentation of a patient with acute myeloid
leukemia
syndrome with multilineage dysplasia. Two weeks later
she presented with progressive fatigue and pancytopenia.
Another bone marrow puncture demonstrated progression
to MDS-RAEB type 2. Chromosomal analysis revealed
complex cytogenetic abnormalities. Due to her young age
doubt rose about the diagnosis and we investigated whether
the patient, despite her normal physical appearance,
suffered from Fanconi’s anemia. A chromosome breakage
test with mitomycine confirmed this diagnosis
Discussion: Fanconi’s Anemia (FA) is a rare autosomal
recessive disorder typically diagnosed at young age. Patients
have characteristic physical anomalies, including short
stature, café-au-lait spots and abnormalities of thumb,
radius and genitourinary tract. Bone marrow failure
typically develops during the first decade of life. In addition,
they have increased risk of developing malignancy, acute
myelogenous leukemia being the most frequent. Ear, nose
and throat tumors and gynecological malignancies are
much more prevalent as well. There are 13 genes involved
in FA, all of which cooperate in a common DNA-repair
pathway. The mutation in the FANCC gene is the most
abundant FA mutation occurring in the Netherlands. This
mutation is associated with a relatively mild phenotype.
Bone marrow transplantation is the only curative option
for these patients. Our patient will receive treatment with
azacitidine to reduce blast count followed by hematopoietic
stem-cell transplantation with myeloablative conditioning.
Conclusion: Fanconi’s anemia is a rare cause of pancytopenia which should be considered in young adults
presenting with pancytopenia.
M.L. Wumkes, W. Deenik
Tergooi Hospitals, Department of Internal Medicine,
Nachtegaalstraat 5c, 3581 AA UTRECHT, the Netherlands,
e-mail: mlwumkes@live.nl
Chloromas (granulocytic sarcomas) occur in 3-5% of
patients with acute myeloid leukemia (AML). A few
patients with chloroma involving cardiac structures have
been reported in literature so far.
We describe a 78-year-old female who presented with
dyspnoe, coughing, fatigue and weight loss. Her medical
history was besides ear problems unremarkable. At
physical examination she was dyspnoeic with signs of
right ventricular failure. Electrocardiography showed
atrial fibrillation without signs of cardiac ischemia. Chest
X-ray revealed interstitial edema and pleural effusion.
The patient was diagnosed with cardiac failure caused by
atrial fibrillation and was treated with diuretics, digitalization and anticoagulants. Transthoracic echocardiography
revealed right ventricular hypertrophy and a mass in the
right atrium. Peripheral blood revealed 5.2 x 109 leukocytes
with 35% blasts in the differential count. Flowcytometry
of the blasts in the peripheral blood showed CD11c, CD13,
CD33, CD34, CD117 and MPO positivity, consistent with
myeloid blasts. Analysis of the pleural effusion revealed
myeloblasts with identical immunophenotypic features.
Palliative radiotherapy of the right ventricle was scheduled,
because the patient was not a candidate for intensive
chemotherapy. However, the patient diseased shortly
after diagnoses due to cardiac failure before she received
radiation therapy. Right ventricular failure is a very rare
initial presentation of a patient with AML.
117.
118. Löffler endocarditis, a rare complication of a rare
disease
N.D. Niemeijer1 , P.L.A. van Daele1, O.J.L. Loosveld 2,
B.J.M. van der Meer2
1
Erasmus Medical Centre, Department of Internal
Medicine, ’s-Gravendijkwal 230, 3015 CE ROTTERDAM,
the Netherlands, e-mail: ndniemeijer@gmail.com, 2 Amphia
Hospital, BREDA, the Netherlands
A rare cause pancytopenia in an adult patient
A. de Haar-Holleman, S.K. Klein
Meander Medical Centre, Department of Internal Medicine,
PO Box 1502, 3800 BM Amersfoort, the Netherlands, e-mail:
a.de.haar@meandermc.nl
Introduction: The hypereosinophilic syndromes (HES) are
a rare group of disorders marked by the sustained overproduction of eosinophils. It is defined by an eosinophil
count of more than 1500 cells per microliter for at least
6 months, in addition to damage to target organs, such as
the heart and lungs. Eosinophilic myocarditis is a major
cause of morbidity en mortality among patients with HES.
We present a patient with idiopathic hypereosinophilic
syndrome and cardiac involvement.
Case report: A 37-year-old man presented to the emergency
department with one month of fatigue and five days of
progressive dyspnoea. Three months earlier he had been
Case report: A 24-year-old female presented at our
emergency department with deep anemia (hemoglobin
3.9 mmol/l). Her history was blank. Besides pallor, we
found no abnormalities with physical examination.
Laboratory investigations showed pancytopenia (leukocytes
1.5 * 109/l, thrombocytes 51 * 109/l). Thinking of acute
leukemia a bone marrow examination was performed
showing elevated cellularity and major abnormalities
in all three lineages consistent with myelodysplastic
65
Case: A 70-year-old man presented with normocytic
anemia (Hb 6.2 mmol/l) and progressive pain in the pelvic
girdle. Physical examination was normal. Laboratory investigation didn’t show any signs of hemolysis or deficiencies,
there were no signs of plasmaceldyscrasia, autoimmune
diseases or infections. Repeated X-rays and ultrasounds
were normal.
A bone marrow examination did not reveal any aberrations
besides minor dysplasia, too little for any diagnosis.
One year later myalgia worsened and ESR rose to 119mm/
hr; but a PET-CT scan yielded no abnormalities and a
temporal artery biopsy did not show giant cell artritis.
Therefore polymyalgia rheumatica was suspected and
prednisone 15mg was started. Symptoms vanished
promptly. But four months later, the patient was admitted
because of severe intermittent bone pain of the shoulder
and pelvic girdle and hence an elevated lactate dehydrogenase (LDH) of 1059 IU/l, without hemolysis. MRI
showed diffuse infiltration of the bone marrow and a
skeletscintigraphy showed multiple hot spots suggesting
metastases. Again bone marrow aspiration was performed,
showing normal morphology, but cytogenetic testing
showed 46 XY, add(12). Immunophenotyping revealed
that 9% of cells were large blast-like cells. One week
later a third bone marrow aspirate was performed in an
affected region and a monotonous cell population, without
classic hematopoietic features was seen with blue/grey
cytoplasm and round to oval nuclei without nucleoli.
Immunophenotyping showed 74% aberrant leukocytes
(weak CD45+/CD13+/CD15/CD16+/CD117/CD34-/partially
MPO positive), suggesting immature myeloid cells
with some degree of maturation. Bone biopsy revealed
immature myeloid cells. Finally, the diagnosis myeloid
sarcoma was made based on the cytogenetic testing, the
positive markers CD13, MPO and negative CD34 and the
remarkable findings on MRI and skeletscintigraphy.
The patient was treated with daunarubicin and cytarabine,
giving relieve of all complaints. Unfortunately he passed
away a few weeks later because of ileus and cardial
weakness.
Discussion: Myeloid sarcoma (MS) is an extramedullary
tumor composed of immature myeloid cells, which is
rarely diagnosed. Most of them occur with concurrent
bone marrow or blood involvement by a myelodysplastic
syndrome of a myeloproliferative disorder like acute
myeloid leukemia. MS is often associated with distinctive
cytogenetic and molecular abnormalities. It can be treated
like AML, but survival rates are low.
MS is an elusive disease, which may present in many
different forms and locations with subsequently a high
variety of clinical signs and symptoms.
diagnosed with severe eosinophilia. Extensive diagnostic
evaluation at that time revealed no cause of secondary
eosinophilia. High dose corticosteroids were prescribed
but later stopped because of ineffectiveness. On admission
we saw an ill-looking, dyspnoeic man, temperature 38.1
°C with signs of shock. Laboratory evaluation revealed a
high number of eosinophils of 84.2 x 109/l. Chest X-ray
showed pulmonary congestion. On the electrocardiogram
ST-elevations in V1-V3 and ST-depressions in various leads
were found. Transthoracic echocardiography revealed a
large mass in the left ventricle. In the intensive care unit,
the trachea was intubated and the patient mechanically
ventilated because of respiratory insufficiency. Cardiac
magnetic resonance imaging showed endomyocardial
fibrosis and necrosis and a large thrombus in the left
ventricle. Löffler endocarditis was diagnosed. Therapy
was initiated with diuretics, methylprednisolone and
anti-coagulation. Because of ineffectiveness interferon
alpha and hydroxycarbamide were added. After this the
eosinophils declined gradually. Recovery was complicated
by bone marrow depression with anemia and thrombocytopenia and haemoptysis with bilateral pulmonary consolidations, possibly eosinophilic consolidations.
Discussion: Idiopathic hypereosinophilic syndrome is
a rare systemic disease defined by the combination of
prolonged eosinophilia, evidence of organ involvement
and no evidence for other known causes of eosinophilia. It
affects mostly men between 20 and 50 years of age, with
a peak in the 4th decade of life. Cardiac involvement is
frequently found. The damage to the heart ranges from
early necrosis to subsequent thrombosis and fibrosis.
It is believed that eosinophils are directly cytotoxic and
release toxic substances like enzymes, reactive oxygen
species, pro-inflammatory cytokines and arachidonic acidderived factors. Prednisone and hydroxyurea constitute
the first-line therapy. In therapy-resistant cases interferon
alpha, which inhibits degranulation of eosinophils, is
a possibility. Besides this, routine cardiac therapy with
diuretics, afterload reduction and anticoagulation is
necessary. The prognosis is poor, and death is usually due
to congestive heart failure.
119. Myeloid sarcoma; a rare diagnosis after a challenging
diagnostic process
H.A. Polinder-Bos, N. Josephus Jitta, L.A. van Boven,
S.K. Klein
Meander Medical Centre, Department of Internal Medicine,
Postbus 1502, 3800 BM AMERSFOORT, the Netherlands,
e-mail: h.a.polinder@meandermc.nl
Introduction: Anemia is frequently seen, sometimes it
hides special diagnosis.
66
120. Dialysis using a Theralite filter in addition to chemotherapeutical treatment of multiple myeloma with
acute renal failure: a multidisciplinary approach.
Case report
showed a significant decrease compared to the pre-dialysis
level. In between dialysis, levels rose but an overall
reduction in sFLC levels was achieved.
Conclusion: The addition of intense dialysis using the
Theralite filter to chemotherapeutical treatment with
bortezomib/dexamethasone might be a very effective
approach to the treatment of patients with acute renal
failure due to multiple myeloma induced cast nephropathy.
E. Verweij, J.J. Beutler, R.M.J. Hoedemakers,
H.A.M. Sinnige
Jeroen Bosch Hospital, Department of Hematology/
Nephrology, Tolbrugstraat 11, 5211 RW ’s-HERTOGENBOSCH, the Netherlands, e-mail: mail@evaverweij.net
121. ITP and CMV: to treat, or not to treat?
Introduction: In September 2010 our patient was
diagnosed with multiple myeloma stage III B according
to Durie and Salmon (stage III according to the New
International Staging System) based on serum Free
Light Chain levels (sFLC, type Lambda) of 13300 mg/l.
Other laboratory abnormalities included a creatinin
of 808 umol/l, Hb 4,4 mmol/l, calcium 3,33 mmol/l
(normal albumin) and B2-microglobulin 33,30 mg/l. Upon
diagnosis patient had 44% monoclonal plasma cells in
the bone marrow aspirate and multiple osteolytic lesions.
Renal biopsy confirmed cast nephropathy combined with
deposition of free light chains.
Methods: Treatment with bortezomib 1,3 mg/m2 (day
1, 4, 8 and 11) and dexamethasone 20 mg (day 1, 2, 4, 5,
8, 9, 11 and 12) was started. On day 8, dialysis using a
Gambro Theralite filter started (daily the first week with
one non-dialysis day, followed by dialysis every other day).
sFLC levels were determined before and immediately after
dialysis.
The Gambro Theralite filter consists of a membrane
designed to target free light chains and other proteins up
to 15-65 kD. Regular filters are not permeable because of
much smaller pores. Theoretically the filter removes more
sFLC than plasma exchange (which is more expensive and
has not been proven effective).
During dialysis, frequent measurements of electrolytes
(phosphate, magnesium and calcium in particular) and
albumin are necessary to prevent (potentially severe)
deficiencies.
Bortezomib is a small molecule and concentrations may
be reduced during dialysis. However it has a short half-life
(?20 minutes). Therefore, determination of plasma levels is
not useful. Administering doses immediately after dialysis
or administration of bortezomib on non-dialysis days is
adequate.
Results: Bortezomib and dexamethasone treatment started
on day 1. On day 8, sFLC levels remained stable at
13300 mg/l and patient underwent the first dialysis with
the Theralite filter. sFLC level measurement immediately
after dialysis showed a spectacular decrease (of 78% to
2880 mg/l). Unfortunately levels rose within 24 hours
after dialysis. Patient underwent dialysis on day 9, 10,
12-15, 17, 18, 20, 22 and 25. Every sFLC level post-dialysis
M.L. Nijland, A.M. de Kreuk
Sint Lucas Andreas Hospital, Department of Internal
Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the
Netherlands, e-mail: m.nijland@slaz.nl
Introduction: Immune thrombocytopenic purpura (ITP)
is a common cause of acquired thrombocytopenia. ITP is
often considered to be idiopathic, but in some cases ITP is
associated with viral infections. In daily practice, results
of serological tests and/or viral load-assays only become
available after a few days. Management of CMV-associated
ITP may become a challenge if platelet counts do not
recover promptly after initial treatment.
Cases: We review two cases of CMV associated thrombocytopenia with a different clinical course.
Patient 1: A 63-year-old woman on adjuvant chemotherapy
for breast cancer, presented with large haematomas and a
febrile temperature. Physical examination showed multiple
large haematomas and petechiae. She had no signs of
hepatosplenomegaly or lymphadenopathy.
Patient 2: A 50-year-old man presented with petechiae
and gingival and rectal bleeding. He had complaints
of tiredness since a few months. Physical examination
showed petechiae but no other abnormalities.
In both cases, the initial laboratory tests showed a platelet
count of 2 x 109 IU/l, a mild lymphocytosis with atypical
lymphocytes, and a mild elevation of liver enzymes,
leading to the hypothesis of ITP, possibly induced by
CMV. Initially, we treated both patients with intravenous
immunoglobulins (IVIG) and a platelet transfusion, in
combination with methylprednisolone 1000mg/day for
3 days in patient 1 and with 40 mg prednisone/day in
patient 2.
In patient 1, CMV IgM was positive, and the viral load
at diagnosis was 10100 DNA-copies/ml. After 1 week
the platelet count was 177 and she received no further
treatment.
In patient 2, CMV IgM was also positive, and the viral load
was 61110 DNA-copies/ml. His platelet count remained
< 10 x 109 IU/l, and his bleeding only responded partially
to tranexaminic acid treat-ment. Subsequently, we started
prednisone (1mg/kg per day) treatment, however still
67
day, followed by oral prednisolone (1 mg/kg/day). Because
no universal guidelines were available, we decided to
treat the WM pragmatically as low-grade lymphoma with
chloorambucil and rituximab from July until December
2010. Renal function improved but remained moderately
impaired (creatinine 127 mmol/l; eGFR 38 ml/min). IgM
levels decreased and Hb increased to normal ranges (IgM
1.81 g/l; Hb 7.8 mmol/l). Corticosteroids were tapered and
stopped.
Discussion: WM is a lymphoplasmocytic proliferation
leading to the secretion of monoclonal IgM. Renal complications in WM are rare, and most often the result of
membranoproliferative type glomerulonephritis due to
intracapillary IgM deposition with or without the detection
of cryoglobulinaemia. However, AL-amyloidosis, cast
nephropathy and Fanconi’s syndrome have also been
described. Most reports describe complete recovery of
renal failure after steroid treatment. This case showed
that renal failure can be the only presentation of WM, and
that restoration of renal function can at least partially be
obtained with appropriate treatment.
without response. Treatment with valganciclovir resulted
in a decrease of CMV DNA, but not in improvement of
the platelet count. Only when prednisone was tapered and
discontinued under valganciclovir treatment, the platelet
count finally increased. After two months, CMV DNA was
negative and the platelet count was 51 x 109 IU/l.
Discussion: CMV infection can cause ITP, possibly through
molecular mimicry or immune dysregulation. CMV may
also directly infect megakaryocytes leading to diminished
platelet production. In this situation, immunosuppression
could actually worsen or prolong thrombocytopenia, as
probably happened in case 2. We recommend considering
non-immunosuppressive therapies for the initial treatment
of ITP in all cases where an underlying CMV-infection is
suspected.
122. A rare case of renal failure
R.B. Takkenberg, H.P. van den Berg, J.J. Weening
Tergooi Hospitals Blaricum, Department of Internal Medicine,
Rijksstraatweg 1, 1261 AN BLARICUM, the Netherlands,
e-mail: btakkenberg@tergooiziekenhuizen.nl
ymphoma and performed an additional liver biopsy. This
biopsy showed sinusoidal infiltration of atypical T-cells;
immunophenotyping confirmed the diagnosis of liver
involvement of the T-LGL.
T-LGL usually is an indolent non-Hodgkin lymphoma. It is
a clonal disease of large granular lymphocytes. The pathogenesis is unknown but the disease is often associated
with Human T-lymphotropic virus, cytokine disregulation and impaired apoptosis. Clinicians should consider
T-LGL in patients with recurrent neutropenia without
an other reasonable explanation or recurrent infections.
Seventy percent of the patients do need treatment with
methotrexate, or cyclophosphamide, or cyclosporin A
because of symptomatic disease. Combination chemotherapy can be started in case of more severe disease
activity.
Because of the extreme weight loss, our patient was treated
with a combination of cyclophosphamide, vincristine
and prednisone every three weeks. After four cycles
of CVP-chemotherapy a CT-scan showed a significant
decrease in hepatosplenomegaly compatible with a partial
remission.
Conclusion: T-LGL-leukemia is an indolent T-cell
malignancy that should be considered in case of
unexplained neutropenia. More aggressive variants should
be treated with combination chemotherapy.
colon. She underwent an extended right hemicolectomy
with ileodescendostomy. Histology showed no signs of
ischemia, but suggested a medication induced colitis.
Differential diagnosis suggested thalidomide or NSAID’s
as a possible initiating agent. Postoperatively the patient
was admitted to the intensive care unit. During this
admission she developed pneumocystis carinii pneumonia
and Adult Respiratory Distress Syndrome, anastomotic
leakage followed by relaparotomy and ascites infected with
candida albicans. She died 37 days after presentation. No
postmortem examination was performed.
Conclusion: In this case report a bowel perforation
following thalidomide treatment was described. There
is one literature report of four cases of thalidomide
associated bowel perforation in one hospital suggesting
that it is highly improbable that this is a co-incidental
finding. More reports of this possible side effect of
thalidomide can possibly contribute to unraveling its
causative mechanisms.
124. T-cell large granular lymphocyte leukemia; not
always indolent
123. Thalidomide and bowel perforation: a case report
Introduction: Waldenström’s macroglobulinaemia (WM)
or lymphoplasmocytic lymphoma is a rare lymphoid
neoplasia, accounting for 2% of all hematological
malignancies, with only 75 new cases per year in the
Netherlands. Renal function impairment can be found and
is most often the result from immunological light chain
nephrotoxicity. We describe a patient with renal failure,
based on a rare presentation of WM.
Case report: A 75-year-old woman presented with
progressive fatigue, shortness of breath on exercise and
weight loss. Her medical history revealed hypothyroidism
and M. Sjögren since 2008. Physical examination showed
a blood pressure of 90/45 mmHg with a pulse of 80/min.
There was no pitting edema on the extremities. Laboratory
investigations revealed an erythrocyte sedimentation rate
(ESR) of 40 mm/h, hemoglobin (Hb) 6.3 mmol/l with
a mean cell volume (MCV) of 85 fl, leukocytes of 6.2 x
109/l and platelets of 336 x 109/l, creatinine of 235 mmol/l
(eGFR 19 ml/min), with a urea of 13.7 mmol/l. Total
serum protein was 90 g/l, and electrophoresis revealed a
monoclonal IgM level of 22.1 g/l. Urine analysis showed no
abnormalities except for a high micro protein albumin of
120 mg/24 hours. A renal biopsy showed a profound interstitial cellular infiltrate composed of CD20+/IgM+ lymphoplasmocytic cells. Cytology and histology of bone marrow
showed no infiltration. The diagnosis WM with diffuse
renal infiltration and renal failure was established. The
anemia was interpreted as caused by renal impairment.
Because renal function deteriorated rapidly, she was
treated with three pulses of methylprednisolon 500mg/
F.M. van Haalen, I. van Dijk, F.H.M. Cluitmans,
A.M. Schrander-van der Meer
Rijnland Hospital, Department of Internal Medicine and
Intensive Care, Simon Smitweg 1, 2353 GA LEIDERDORP,
the Netherlands, e-mail: f.v.haalen@rijnland.nl
Introduction: Thalidomide is an oral agent with
immunomodulatory and antiangiogenic properties.
Besides its teratogenic side effects, thalidomide possesses
other important toxicities including constipation,
peripheral neuropathy, sedation, fatigue, thromboembolism, rash and pruritus. Bowel perforation is not a
frequent side effect of thalidomide. In the literature speculations are found that thalidomide may contribute to bowel
perforation by a number of mechanisms. Bowel perforation
following thalidomide has been previously described in
only a few cases.
Case-report: A 58-year-old female recently diagnosed
with multiple vertebral compression fractures presented
to the emergency room with hypercalcaemia. Bone
marrow cytology showed multiple myeloma. One week
after starting therapy with dexamethason 40 mg a day,
thalidomide 100mg a day and pamidronate (APD), she
became progressively dyspnoeic, developed peripheral
edema, clouding of consciousness and diarrhea with
rectal loss of blood. Computed tomography showed free
air formation intra-abdominal suspect of stomach or
proximal duodenal perforation. Subsequent surgery
demonstrated multiple perforated lesions in the transverse
68
M.C. Telgen1, J. Slomp1, J. van Baarlen2, W.M. Smit1
1
Medical Spectrum Twente, Department of Internal Medicine,
Ariensplein 1, 7511 JX ENSCHEDE, the Netherlands,
e-mail: m.telgen@mst.nl, 2Laboratorium Pathologie Oost,
ENSCHEDE, the Netherlands
125. A testicular tumor which turned out to be AML
R. Wester, V. Mattijssen
Rijnstate Hospital, Department of Internal Medicine,
Weurtseweg 69, 6541 AN NIJMEGEN, the Netherlands,
e-mail: westerruth@gmail.com
Case report: A formerly healthy 54-year-old woman was
referred to our outpatient clinic with a two months history
of an altered defecation pattern, night sweats and weight
loss of thirteen kilograms. Physical examination revealed
a hepatomegaly and an anal process. Although a gastrointestinal malignancy was the most probable diagnosis, a
colonoscopy did not show abnormalities. The anal process
appeared to be a thrombotic hemorrhoid. Laboratory
results showed a LDH 232 U/l, hemoglobin 5,8 mmol/l,
thrombocytes 331 109/l, leukocytes 6,6 109/l, with an
absolute neurophil count of 0,41 109/l. The differentiation
of the peripheral blood showed atypical lymphocytes with
granules. Immunophenotypic there was an abnormal
T-cell population (CD 3+, CD 8+, CD 57+, CD16weak,
TCR-AB+ and diminished expression of CD7 and loss of
expression of CD5) suggestive for T-cell large granular
lymphocyte leukemia (T-LGL). Additional T-cell gene
rearrangement showed a monoclonal population. A bone
marrow aspiration and biopsy confirmed this diagnosis.
Although T-LGL mostly has an indolent course, our
patient had an aggressive disease with B-symptoms and
hepatosplenomegaly on CT-scan. Therefore we wanted to
exclude a more aggressive lymphoma that could also fit the
phenotype, such as an alphabeta positive hepatosplenicl-
Introduction: Myeloid sarcoma is a rare manifestation
of acute myeloid leukemia (AML), characterized by the
occurrence of myeloid masses at an extramedullary
site. Despite the curiosity, it is important to recognize
this entity because of the fast clinical deterioration and
the important therapeutic consequences. That myeloid
sarcoma may occur at any site of the body is demonstrated
with this patient with AML, presenting as a testicular
tumor.
Case: A 65-year-old man presented at the urology department
with a growing mass in his right testicle. Testicular cancer
was suspected, and an orchidectomy was performed.
Serum tumor markers were normal. Histological
evaluation revealed a malignancy which could not be
classified. Two weeks later, the consulting internist
discovered pathologically enlarged lymph nodes in the
neck, and an elevated LDH. Malignant lymphoma was
suspected. Peripheral blood counts and bone marrow
examination at that moment were normal. A lymph
69
node biopsy was performed. Waiting for the results
the patient became progressively ill, with dyspnoea and
nausea. He developed pleural effusion. Four weeks after
the orchidectomy, the laboratorium results deteriorated,
with blasts appearing in his peripheral blood smear,
trombocytopenia, diffuse intravascular coagulation, and
renal failure. Another bone marrow biopsy revealed
more than 50% myelo-monoblasts. In the mean time
the pathologist concluded, that the malignant cells in
the testis and the lymph node were young monoblasts
(myeloid sarcoma). The combination of these results led
to the diagnosis of AML with extensive extramedullar
localisation, complicated by disseminated intravascular
coagulation and renal failure.
The patient’s condition deteriorated very quickly, and
remission induction chemotherapy for AML (ICE;
Idarubicine, Cytarabine and Etoposide) was started. Very
soon there was improvement in condition and in renal
function. Although it resulted in a complete remission of
bone marrow, lymph nodes and pleural effusion, we had
to refrain from further chemotherapy because of weak
general condition and a very small chance of curation,
because of the detrimental presentation of the AML in
combination with age of the patient.
Conclusion: We demonstrate a patient with AML who
presented with a tumor in his right testicle and lymphadenopathy. Differential diagnostic considerations included
testis carcinoma and non-Hodgkin-lymphoma. However,
occasionally patients with AML present with extramedullary disease. It may precede overt bone marrow disease,
as in our patient. Because of the fast clinical deterioration,
and the therapeutic consequences, being intensive chemotherapy with curative intent, it is of the utmost importance
to recognize myeloid sarcoma.
as were two PCR’s for Borrelia DNA. The patient was
treated with adjuvant radiotherapy and received two weeks
of doxycycline 100 mg once daily. He is in complete
remission for 2 years now.
PCMZL are indolent, extranodal lymphomas, classified
as marginal zone lymphomas (MZL’s) according to the
WHO-EORTC. MZL’s arise as extranodal acquisition
of lymphatic tissue at sites of chronic inflammation.
MZL’s are clearly associated with infectious, antigenic
stimuli that precede the transformation into a lymphoid
malignancy. The most common type of MZL is mucosaassociated lymphoid tissue (MALT)-lymphoma of the
stomach, which is associated with Helicobacter pylori
gastritis. Remarkably, in Helicobacter pylori associated
MALT-lymphoma of the stomach, the B-cell tumour clone
is not selected against a bacterial epitope, but carries autoreactive rheumatoid factor-immunoglobulins that undergo
somatic hypermutation. They develop as a secondary
lymphoid response to chronic inflammation. When typical
API2/MALT1 fusion cytogenic abnormalities are absent,
certain MALT-lymphomas have been known to show
complete histological remission after antibiotic eradication
therapy.
PCMZL has been associated with Borrelia Burgdorferi
infection, i.e. Lyme’s disease. There is a striking
geographical variation in the association between Borrelia
burgdorferi and PCMZL. While a clear association
has been seen in Europe, this association could not be
demonstrated in the United States and Asia-Pacific. The
geographical variation is interesting with regards to the
fact that different genotypes of spirochetes are responsible
for Lyme’s disease in Europe and the United States.
Furthermore the vector that transmits the spirochete to
humans differs from the one in Europe and studies within
the Ixodes ticks have demonstrated an influence of the
tick’s saliva on the differentiation of T-cells into either Th1
or Th2 lineage commitment.
The association between PCMZL and infection with
Borrelia Burgdorferi could have important clinical implications since, if the B-cell tumor clone is antigenically
driven, its progression into malignant lymphoma could
be arrested by antibiotic therapy or, at least, delayed to
prevent more aggressive therapies such as radiotherapy
and chemotherapy.
126. Primary cutaneous marginal zone lymphoma in the
presence of occult Borrelia infection.
P.G.N.J. Mutsaers, H.P.J. Visser
Medical Centre Alkmaar, Department of Internal Medicine,
Wilhelminalaan 12, 1815 JD ALKMAAR, the Netherlands,
e-mail: mutsaersp@gmail.com
A 54-year-old man presented with a solitary subcutaneous
tumour on the lateral side of the right leg present for six
months. Excision biopsy showed a primary cutaneous
marginal zone lymphoma (PCMZL), which was excised
with free margins. Dissemination examination did not
reveal metastatic disease. Although the medical history
was negative for a tick bite, the Borrelia serology was
strongly positive. Additional blood investigation showed
presence of rheumatoid factor. Direct staining of the
excision tissue for Borellia burgdoferi was negative,
127. Is early stage chronic lymfatic leukemia a risk factor
for severe cytomegalovirus infection?
E.H.C.J. Buster, E.F.S. van Velsen, D. Cheung, J. Keijman,
J.A. Riedl, M-D. Levin
Albert Schweitzer Hospital, Department of Internal Medicine,
Albert Schweitzerplaats 25, 3018 AT DORDRECHT, the
Netherlands, e-mail: e.buster@asz.nl
70
The second patient is a seventy-eight years old man who
was seen in the outpatient clinic because of a IgG kappa,
stage I multiple myeloma. One year after the first presentation he progressed into stage IIIB for which he was
treated with VAD-chemotherapy (vincristine, adriamycine,
dexamethason). Evaluation after three cycles showed a
markedly regression. After the fourth course the patient
complained of a light discomfort in the abdomen. After
the fifth course he was admitted to the hospital because
of progressive abdominal pain. At physical examination
a mass was palpable. A diagnostic CT of the abdomen
showed a very-large mass with encasement of the right
renal artery, vena cava inferior and the right ureter.
A biopsy revealed malignant plasma cells compatible
with an extra-medullary localization of the multiple
myeloma. Therapy was switched to bortezomib with
dexamethason. After two cycles patient developed slight
back pain and progressive lymphedema of the right leg. A
new CT-abdomen showed progression of the tumor mass.
Given that first and second line chemotherapy was not
successful, we switched to palliative treatment.
We showed two cases with an extraordinarily course of
a multiple myeloma. The first patient presented with an
extensive extra-medullary localization and the second
developed such during treatment. In both cases a rapidly
progressive course was observed.
A 56-year-old male with early stage chronic lymphocytic
leukemia (CLL) and COPD was admitted after five days of
high fever and chills without specific complaints indicating
a cause of the fever. The fever persisted for 18 days while
the patient was receiving broad-spectrum antibiotic therapy
and prednisone. During the hospital stay dyspnea progressively worsened and the patient underwent a bronchoscopy.
Bronchoalveolar lavage showed evidence of CMV
pneumonitis. Treatment with ganciclovir was initiated
and the patient’s body temperature gradually declined
and normalized, and dyspnea gradually resolved. Bone
marrow aspiration biopsy and CT-scan confirmed early
stage CLL (Rai stage 0, Binet stage A). There were no sign
of secondary immunoglobulin deficiency, paraprotein or
transformation to diffuse large B-cell lymphoma. CMV
pneumonitis is a rare presentation of CMV infection in
patients without evidence of immunodeficiency.
128. Two patients with an extraordinary course of a
multiple myeloma
I.H.A. Zegers
Catharina Hospital, Department of Internal Medicine,
Michelangelolaan 2, 5623 EJ EINDHOVEN, the Netherlands,
e-mail: ingrid_zegers@hotmail.com
We present two cases with an extraordinary course of
multiple myeloma. The first patient is a seventy-nine
years old man who presented himself with abdominal
pain, difficulties with urinating and a swollen left leg.
Laboratory investigation showed an acute renal insufficiency. Computer-tomography scanning (CT-scan) of
the abdomen showed widespread lymphadenopathy with
encasement of the ureters, arteria abdominalis, vena cava
inferior and both iliacofemoral arteries. On PositronEmission-Tomography (PET)scan there was widespread
metabolic active lymphadenopathy in the abdomen, pelvic
cavity and multiple small bone metastasis. Pathological
examination of a lymphnode revealed a multiple myeloma,
monoclonal for IgG lambda with blastair features. The
patient received three times CHOP-chemotherapy
(cyclofosfamide, vincristine, doxorubicine, prednisone).
Evaluation by means of CT-thorax/abdomen and PET-CT
showed a markedly reduced tumoractivity. After another
three cycles of CHOP-chemotherapy a new CT-scan was
performed. Except for a local laesion at the right urether no
abnormalities were found. However on a PET-CT accomplished four days later, widespread lymphadenopathy in
the abdomen with hydronephrosis of the right kidney, bone
metastasis and pleural effusion were seen. The patient was
admitted in the hospital but deteriorated very fast and died
ten days later.
IX.
ONCOLOGY RESEARCH
129. Screening for DPYD * 2A mutations: preventing
severe 5-fluorouracil related toxicity in Meander
Medical Centre
M.C. van der Goes, J.M. van Dodewaard, M. van Wijnen,
M.M. Malingre, H.J. Bloemendal, C.J. Rodenburg
Meander Medical Centre, Department of Internal Medicine,
Utrechtseweg 160, 3818 ES AMERSFOORT, the Netherlands,
e-mail: mc.vander.goes@meandermc.nl
Background: Capecitabine, an oral prodrug of 5-fluorouracil (5-FU), and 5-FU are frequently used chemotherapeutic agents and are catabolized by the enzyme
dihydropyrimidine dehydrogenase (DPD). Numerous
genetic mutations have been identified in the DPD gene
locus (DPYD). Few mutations, among which the DPYD *
2A with prevalence of 1.8 percent in the Dutch population,
result in decreased enzymatic activity and increase the
risk of severe toxicity. We screened patients planned for
treatment with 5-FU/capecitabine for the presence of the
DPYD * 2A mutation in order to prevent severe toxicity.
71
Methods: In the period from march 2009 until october 2010
259 cancer patients were screened for the presence of the
DPYD * 2A mutation prior to receiving chemotherapy. All
patients required treatment with monotherapy capeci­tabine
or combination chemotherapy including 5-FU/capecitabine.
A high-throughput real-time PCR test was used.
Results: In total 259 patients were screened. The mean age
was 62 years and 62% of the patients were female. Of the
259 patients 58% had colorectal cancer, 30% breast cancer
and 12% had other cancers (e.g. gastric and oesophageal
cancer). Fourty-eight percent of the patients were treated
in the adjuvant setting, 38% in the palliative setting and
14% in the neo-adjuvant setting. Monotherapy with capecitabine was given in 26% of the cases, combination therapy
including 5-FU/capecitabine in 74%.
Two patients were found to be DPYD * 2A heterozygote
and one was homozygote. In the homozygote patient, no
enzymatic activity was detected in the mononuclear cells
and chemotherapy was withheld. In one of the heterozygote patients capecitabine was given with a 50% dose
reduction, which resulted in minor toxicity. Chemotherapy
was withheld in the other patient. Of the 256 patients without
a DPYD * 2A mutation, still 8 percent required hospital
admission because of severe 5FU/capecitabine related toxicity.
Conclusions: Screening for DPYD * 2A mutations
presumably prevented severe or even lethal toxicity in
three patients. On the other hand, severe toxicity requiring
hospital admission developed in 8 percent of patients. A
possible explanation could be that these patients have another
mutation and/or have diminished DPD enzymatic activity.
Further analysis is in progress whether this is the case and
to see if screening for DPD deficiency is useful in the clinic.
and cyclophosphamide in clinical studies, which is most
frequently performed in selected patients. However, the
frequency of cardiotoxicity of trastuzumab in non-selected
patients in clinical practice is unknown. Here we describe
the cardiotoxicity in a retrospective study of breastcancer
patients treated with trastuzumab.
Materials and methods: In a retrospective single centre
study we considered all HER2Neu-receptor positive
breast cancer patients who underwent treatment with
trastuzumab from March 2001 until August 2010.
Trastuzumab was prescribed in two different settings:
adjuvant and palliative. In the adjuvant setting
trastuzumab was preceded by antracycline containing
treatment regiments. After this, trastuzumab was administered in combination with Paclitaxel, followed by
trastuzumab monotherapy for one year. Whereas in the
palliative setting trastuzumab was administered as initial
treatment in combination with Paclitaxel. Afterwards
trastuzumab was continued until relapse in the latter
patient population. Left ventricular ejection fraction (LVEF)
was assessed by MUGA-scan or 2 or 3D-echocardiography.
Results: In total 215 woman received treatment with
trastuzumab and had received follow-up by MUGA-scan
or echocardiography. Two hundred (93%) were treated with
trastuzumab after an anthracycline containing regimen
and fifteen (7%) received trastuzumab without previous
treatment with anthracyclines. Sixty-seven of all patients
(31%) had a decline in LVEF of moren than 10%. Of these
patients 18 demonstrated a decline of 10 to 14% and 49
demonstrated a decline of more than 15%. Seven of the
15 patients treated only with trastuzumab had a decline
in LVEF of more than 10%, of which six had a decline of
> 15%. Of the patients with a decline in LVEF two patients
received angiotensin-converting enzyme inhibitor because
of asymptomatic decreased LVEF. Forty-five of the forty-nine
patients who had a decline of > 15% recovered to an LVEF
> 45% during and after treatment with trastuzumab.
Conclusion: Cardiac follow-up is of critical importance in
the treament of patients with trastuzumab because of the
high incidence of cardiotoxicity.
130. Incidence of cardiotoxicity of trastuzumab in
Her2Neu positive breast cancer patients: a retrospective cohort study
C. Liesting, M.J.M. Kofflard, M-D. Levin
Albert Schweitzer Hospital, Department of Internal
Medicine, 3318 AT DORDRECHT, the Netherlands, e-mail:
c.liesting@asz.nl
Introduction: Chemotherapy has been proven to be a
helpful and efficient modality in the treatment of breast
cancer patients both in adjuvant and palliative settings.
HER2neu-receptor blocking agents, such as trastuzumab,
have evolved as promising agent in the treatment of breast
cancer with overexpression of the human epidermal
growth factor receptor 2 protein (HER2). A well-known
downside of treatment with trastuzumab is the increased
incidence of cardiotoxicity. The incidence of cardiotoxic
effects of trastuzumab varies from 2-5% when used as a
single agent to 25% when combined with anthracyclines
X. ONCOLOGY CASE REPORTS
131.
Bevacizumab associated caecal perforation in a
patient with advanced breast cancer: a bitter pill to
swallow
Introduction: Vascular endothelial growth factor (VEGF)
is a potent angiogenic factor that is overexpressed in
many human tumours and associated with tumour
progression and poor prognosis. Bevacizumab (Avastin®)
is a humanized monoclonal antibody that recognizes and
blocks VEGF-A. In clinical setting it has been shown to
be effective in the treatment of patients with advanced
colorectal, lung, renal, and breast cancer.
Case report: A 60-year-old female patient presented to our
emergency department with abdominal pain and fever.
Her medical history revealed advanced breast cancer with
bone and liver metastases for which she recently received 2
courses of paclitaxel and bevacizumab as first line palliative
chemotherapy (paclitaxel 90 mg/m2 i.v. on days 1, 8, and
15, and bevacizumab 10 mg/kg i.v. on days 1, and 15 of a
4 weekly cycle) On physical examination her abdomen
was tender, but neither signs of peritonitis nor ileus were
found. Extensive laboratory testing and abdominal CT
revealed no focus for her symptoms, which were then
attributed to chemotherapy-induced mucosal toxicity.
Despite increasing doses of morphine and antibiotic
treatment (cefuroxim and gentamicin), abdominal pain
progressed during the subsequent 2 days, with abdominal
rigidity and rebound tenderness. At that time intraperitoneal free air was shown on a repeated CT scan. At
emergency surgery, fecal peritonitis caused by a hand-size
proximal caecal perforation was noted, for which ileocecal
resection was performed. Pathological examination of
the resected specimen showed extensive necrosis due
to vascular ischemia; no evidence for thrombosis or
malignancy was found. After surgery, the patient had a
complicated 5 weeks lasting postoperative course attributable to poor wound healing, pneumonia and an infected
central venous access device.
Discussion: GI-perforation is a rare complication of
bevacizumab with an estimated incidence of 0-15%.
Its’ pathophysiology is not completely understood, but
potential mechanisms are ischemic perforation by
inducing regression of normal blood vessels in the GI
tract, regression and necrotisation of GI located tumours,
and inhibition of normal healing of ulcers and surgical
wounds. Risk factors mentioned in the literature are
recent bowel surgery, bowel obstruction, high doses of
bevacizumab, and treatment of patients with colorectal
and renal cell carcinoma. The mortality rate of this complication is reported to be as high as 50%.
Conclusion: We report the complicated clinical course
of a patient suffering from bevacizumab associated
GI-perforation, which should be suspected in all patients
treated with this agent and presenting with acute
abdominal pain.
132. Bone metastases from a granulosa cell tumour of the
ovary
C.J. Compaijen, M. Bierhoff, R.W. ten Kate,
P.W.G. van der Linden, M.I. Grootscholten
Kennemer Gasthuis, Department of Internal Medicine,
Boerhaavelaan 22, 2035 RC HAARLEM, the Netherlands,
e-mail: c.compaijen@kg.nl
Introduction: A granulosa cell tumour is a sex cord stroma
cell tumour. In general, granulosa cell tumours from the
ovary do not metastasise. They usually have a relatively
good prognosis and primary treatment is surgical excision.
Metastases are predominantly abdominal, whereas bone
metastases are extremely rare.
Case: A 63-year-old woman presented with back pain,
tingling of the abdominal skin and bladder dysfunction. Her
medical history showed a granulosa cell tumour in 1988 for
which total extirpation was performed. In 2007 a recurrence
was treated with debulking and chemotherapy (3 cycles of
BEP). A new a recurrence 2 years later was again treated
with chemotherapy (6 cycles of carboplatin/palcitaxel) with
a good response (inhibin B from 2083 to 159 ng/l).
Physical examination showed paresis of both legs and
dysesthaesia from the xyphoid downwards. Laboratory
analysis showed an increase of inhibin A and inhibin B
levels. A magnetic resonance imaging scan of the spine
was performed and showed a pathological fracture of
the first thoracal vertebra, with a tumour mass and
compression of the myelum. Further there where diffuse
bone metastases. Computer tomography of the thorax and
abdomen confirmed the bone metastases, besides growth
of pulmonary and lymph node metastases with a new mass
in the pelvis.
Because it is extremely rare for a granulosa cell tumour
to metastasise to the bone, a biopsy was performed to
exclude other causes of bone disease. The biopsy showed
granulosa cells, which were inhibin positive. There were
no more therapeutic options for our patient with extended
metastatic disease of a granulosa cell tumour and a high
risk of a transverse myelitis. She was transferred to a
hospice for palliative care and died several weeks later.
Conclusion: Metastases of a granulosa tumour may rarely
present with symptomatic bone lesions.
133. Paraneoplastic hypoglycemia in a patient with
gastrointestinal stromal tumour on palliative
imatinib treatment
H. Visser, C.E.H. Siegert, W.L.E. Vasmel
Sint Lucas Andreas Hospital, Department of Internal
Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the
Netherlands, e-mail: h.visser@slaz.nl
F.A. Klok, L.T. Vlasveld, N.I. Weijl
Bronovo Hospital,Bronovolaan 5, 2579 AX THE HAGUE, the
Netherlands, e-mail: f.a.klok@lumc.nl
72
73
Introduction: Non-islet cell tumor induced hypoglycemia
(NICTH) is a rare paraneoplastic syndrome characterized by recurrent fasting hypoglycemia in non diabetic
patients. Recently NICTH was de-scribed in patients with
gastrointestinal stromal tumours (GIST), with and without
imatinib treat-ment.
Case: A 84-year-old woman was admitted to our hospital
because of drowsiness. Her medical history revealed a
GIST of the stomach four years previously, for which she
underwent partial gastric resec-tion. Unfortunately, two
months before presentation, extensive intraperitoneal
and hepatogenic metastases of GIST were diagnosed.
She started imatinib (400 mg daily) treatment. One
week before admission her family noted she frequently
seemed to lose consciousness. Her drowsiness appeared
to be related to hypoglycemia’s. Her fasting glucose
was 1.6 mmol/l, although she did not use any antidiabetics. Additional laboratory findings showed low
levels of C peptide (0,18, nmol/l; normal range 0.30-2.35
nmol/l) and insulin (< 0,2 U/l; normal range 6-27 mU/l).
Also, IGF-I (36 ng/l; normal range 52-165 ng/l)) and
IGFBP-3 (0,84 mg/l; normal range 1.40-3.20 mg/l)) were
decreased, while IGF-II (511 ng/l; normal range 280-610
ng/l) was normal. She was treated with glucose infusions
and imatinib was discontinued. After a few days she was
euglycemic and could be discharged with dietary advises.
Discussion: GIST are the most common type of
mesenchymal malignant tumour of the gastrointesti-nal
tract. Patients with metastatic or unresectable GIST are
successfully treated with imatinib. Since 2003 occurrence
of NICTH in patients with GIST has been reported. In
contrast to patients with hy-perinsulinemic hypoglycemia,
these patients have low serum insuline and C-peptide
concentrations during hypoglycemia. Hypoglycemia is
induced by overproduction of proinsuline like growth
factor II (pro-IGF II) which stimulate insulin receptors.
IGF’s circulate in the blood bound to IGF-binding pro-teins
(IGFBP). In patients who suffer NICTH, serum concentrations of IGF II are normal, altough IGF-I and IGFBP-3 are
found to be reduced. Unfortunately pro-IGF II was not
measured in our patient, but other laboratory findings are
compatible with the diagnosis NICTH. Some case reports
mention pa-tients with GIST on imatinib treatment. The
specific pathogenetic role of imatinib in patients with GIST
and NICTH remains to be resolved.
Conclusion: Hypoglycemia due to NICTH in patients with
GIST is a very rare phenomenon. It has been described
even as the first symptom of GIST. Moreover, hypoglycemic
episodes can be trig-gered by imatinib treatment, as was
the case in our patient.
134. Incidental pulmonary embolism in oncology
patients; a frequent finding with unknown prognosis
M. van der Veer, A.P. Hamberg, W.E.J.J. Hanselaar
Sint Franciscus Gasthuis,Department of Internal Medicine,
Kleiweg 500, 3045 PM ROTTERDAM, the Netherlands,
e-mail: m.vanderveer@sfg.nl
Introduction: The association between cancer and venous
thromboembolism (VTE), compromising deep venous
thrombosis (DVT) and pulmonary embolism (PE) is well
known. Next to the malignancy, the presence of metastases
and anti-cancer therapy have a contributable risk for VTE.
Recently, there have been literature reports concerning PE
found by incidence in oncology patients. We describe the
occurrence of incidental PE in two patients with cancer and
summarize the data available on prevalence, risk factors
and prognosis of incidental PE.
Cases: The first case is a 40-year-old female who was
diagnosed with stage IV non small cell lung cancer.
Therefore she received Cisplatin and Gemcitabine. After
two cycles of these cytotoxic agents, a CT scan showed
tumorprogression and PE. Low molecular weight heparin
(LMWH) in a full therapeutic dose was applied. The
following months her malignancy was progressive and
four months after diagnosis she died of respiratory failure.
The second case is a 64-year-old male diagnosed with
a progressive castrate refractory prostate cancer and he
recently received radiation therapy because of painful bone
metastases. A CT scan was performed as baseline scan
before the commencement of first-line cytotoxic therapy
showing incidental PE. Treatment with LMWH was
initiated. He currently is receiving docetaxel as first-line
cytotoxic treatment.
Discussion: Incidental PE is a common finding in patients
suffering from cancer.Multiple studies show a prevalenco
of 6% incidental PE in inpatients and a 3-3.8% prevalence
in ambulatory patients. These studies also note that 75%
of the incidental PE was undetected at the initial CT image
interpretation, suggesting many cases are not diagnosed
in daily practice. Incidental PE is frequently observed in
patients with gynaecological, lung, genitourinary, ovarian
and pancreatic cancer. This matches the malignancies
associated with symptomatic PE. Metastatic disease, high
leukocyte count, platin-based chemotherapy and recent
diagnosis of cancer increase the risk for incidental PE.
One study showed a high mortality rate after asymptomatic
proximal DVT in patients with an acute medical illness,
including cancer. No specific data about the survival after
incidental PE in oncology patients alone are available.
Conclusion: Incidental PE in oncology patients is a
common finding and thus a part of daily practice of those
caring for these patients. The risk factors for incidental PE
in patients with cancer match those for symptomatic PE.
74
The survival after an incidental PE in oncology patients
remains unclear. Further research is needed to establish
the prognosis after incidental PE.
immediate therapy was started with high-dose cortico­
steroids and after broncho-alveolar lavage, broad spectrum
antibiotics were added. Within 24 hours symptoms and
radiologic findings diminished and oxygen requirement
decraesed. Antibiotics were stopped after two days of
therapy.
Both patients recovered fully from their gemcitabine
induced severe acute lung injury and corticosteroids could
be tapered out.
Conclusion: We describe two cases of pancreatic cancer
which both developed severe acute lung injury after
treatment with gemcitabine. Early recognition of the
gemcitabine induced pulmonary toxicity is vital as this
pneumonitis is rapidly progressive and with early adequate
treatment the condition can fully recover.
135. Gemcitabine induced pulmonary toxicity in two
patients with pancreatic cancer
J.W.T. van Enschot, G.J. Creemers
Catharina Hospital, Department of Internal Medicine,
Michelangelolaan 2, 5623 EJ EINDHOVEN, the Netherlands,
e-mail: joris.v.enschot@cze.nl
Introduction: Gemcitabine-associated acute lung injury is
a rare cause of dyspnea after treatment with gemcitabine.
The clinical symptoms are aspecific. Diffuse crackles can
be heard during auscultation of the lungs. The symptoms
may occur days to months after administration. Computed
tomography may show bilateral diffuse ground-glass
opacities. Discontinuation of the drug, administration of
corticosteroids and pulmonary support is the mainstay
of treatment. The mechanism of toxicity in gemcitabineinduced lung toxicity remains unclear.
Case 1: A 50-year-old man with a pT3N0Mx adenocarcinoma of the pancreas was treated adjuvantly with
gemcitabine (Gemcitabine 1000 mg/m2 day 1, 8, 14 every
4 weeks x6). After his fourth course of chemotherapy
he presented himself at the emergency department with
complaints of fever and dyspnea. Except from dyspnea,
physical examination revealed no abnormalities. Laboratory
investigation showed a C-reactive protein of 33 mg/l
(normal 0-10 mg/l) and leukocyte count of 8.7 x 109/l
(normal 4-10 x 109/l). Arterial blood gas analyses showed a
PaO2 of 88 mmHg (normal 80-100 mmHg). X-ray showed
minimal consolidations in the right upper lobe. Treatment
was started with broad-spectrum antibiotics. Despite this
therapy the condition of the patient deteriorated rapidly
with a PaO2 of 56 mmHg and the X ray showed diffuse
bilateral interstitial markings. Gemcitabine induced
pneumonitis was considered and high dose corticosteroids
were started. Within 24 hours the patient had less dyspnea
and during the next days radiographic findings improved
dramatically.
Case 2: A 56-year-old man diagnosed with a cT3N1M1
adenocarcinoma of the pancreas was treated palliatively
with gemcitabine. After his third course of chemotherapy he complained of dry cough, high fever and
severe dyspnea. Arterial blood gas analyses showed severe
hypoxemia with a PaO2 of 56 mmHg. C-reactive protein
was 140mg/l and leukocyte count was 7 x 109/l. Chest
radiography showed bilateral interstitial opacities and
computed tomography showed evident bilateral central
perihilar areas with ground-glass configuration. Given
the high suspicion of gemcitabine induced pneumonitis
136. Large bowel metastasis in metastatic renal cell
carcinoma 21 years after immunother
S.M. van Dorp, G.J.P.M. Jonkers, F.H.M. Cluitmans,
A.M. Schrander-van der Meer, M.J.F.M. Janssen
Rijnland Hospital, Department of Internal Medicine, Simon
Smitweg 1, 2353 GA LEIDERDORP, the Netherlands, e-mail:
s.v.dorp@rijnland.nl
Introduction: A man with rectal blood loss turned out to
have a late colonic metastasis of metastatic RCC with an
unique disease free interval of 21 years after treatment with
adoptive immunotherapy.
Case report: A 73-year-old man -transferred from the
regional academic centre- presented with rectal blood
loss without other symptoms. In 1989 he was diagnosed
with RCC with osseous and pulmonary metastasis. He
had a nephrectomy and extraction of the metacarpus I.
In addition, he was treated by intravenous interleukine-2
and LAK-cell therapy. He attained complete remission,
until January 2010. Because pulmonary embolism, the
patient was treated with warfarin. In August 2010 he
noticed rectal blood loss. Colonoscopy revealed a polypoid
tumor in the colon transversum. Pathologic examination
disclosed a localization of RCC, positive on S-100 marker.
CT scanning of chest and abdomen showed no signs of
metastatic disease. Because of obstruction he underwent
resection of the transverse colon.
Discussion: In 1985, S.A. Rosenberg reported his observations on the systemic administration of LAK cells and
recombinant interleukin-2 to patients with metastatic
cancer. During this treatment, referred to as adoptive
immunotherapy, lymphocytes from patients with advanced
metastatic cancer where obtained by repeated leucapheresis and incubated in interleukine-2 to generate
lymphokine-activated killer cells (LAK cells). These LAK
cells were reinfused in combination with the intravenous
75
administration of interleukine-2. In a study population
of 25 patients, 11 patients showed tumor regression and 1
patient showed complete remission. In 1987 these results
were confirmed in a population of 157 patients, of whom
36 patients with advanced RCC. In the latter 11% reached
complete remission. Unfortunately most patients with
complete remission relapsed later on. Because of the severe
toxic side effects due to capillary leakage, with a mortality
of 2,7%, its limited effectiveness and high financial burden
this treatment has been abandoned. In the Netherlands
only few patients have been treated according to this
method of which results are unknown. The latest Cochrane
review about immunotherapy for advanced RCC in 2005,
concluded that treatment with interferon-a complementary
to nephrectomy has proven to be the most effective form
of immunotherapy. The combination with interleukine-2
gives no additional effect.
Conclusion: This case report describes a late colonic
metastasis of metastatic RCC after treatment with adoptive
immunotherapy. Although gastrointestinal metastasis are
known and tend to occur later than metastasis at the usual
sites, the disease free interval of 21 years is exceptional.
of doxorubicin and cyclophophamide and 12 weekly cycles
of trastuzumab and paclitaxel the LVEF was 72%. Four
days after the 1st 3-weekly course of trastuzumab, she was
admitted to the hospital for rhythm observation on account
of recurrent syncopal episodes. A nine-seconds cardiac
arrest with sinoatrial block was observed at rest, followed
by a slow nodal escape rhythm. After pacemaker implantation trastuzumab monotherapy was continued.
Conclusion: This is the first reported case of asytole after
trastuzumab treatment. As the sinoatrial node does
not express HER2, there is no clear explanation for this
complication.
138. Long lasting pruritus as manifestation of a growing
colonic polyp
A. Wennemers, R. Heijligenberg, H.K. van Halteren
Gelderse Vallei Hospital, Department of Internal Medicine,
Willy Brandtlaan 10, 6716 RP EDE, the Netherlands, e-mail:
halterenh@zgv.nl
Introduction: Pruritus can be an epiphenomenon of
malignant disease, either because of skin infiltration by
tumor cells, or due to (epi)dermal autoimmune inflammation. We describe a case with an exceptionally long
interval between onset of pruritus and cancer diagnosis.
Case report: A 69-year-old male was referred for
colonoscopy because of iron-deficiency anemia. For the
past 4 years he had suffered from continuous burning
pruritus, which increased during hot showers and had
led to sleepless nights. The dermatologist had refrained
from skin biopsy, because the skin appeared macroscopically normal. The pruritus was refractory to treatment
with hydoxyzin, acrivastatin, desloratadin, lidocain
ointment and UV-light therapy. Colonoscopy revealed
an adenocarcinoma of the coecum. A laparoscopic right
hemicolectomy was performed and a pT3N1 adenocarcinoma was recovered. After the operation the pruritus
disappeared completely.
Conclusion: The temporal relation between hemicolectomy
and disappearance of pruritus strongly suggests that
pruritus onset was caused by a growing colonic polyp. The
immunogenicity of colonic polyps makes this hypothesis
plausible.
137. Asystole as complication of trastuzumab treatment
H.K. van Halteren, A. Wennemers, R. Walhout,
D. Agterhuis, R. Heijligenberg
Gelderse Vallei Hospital, Department of Internal Medicine,
Willy Brandtlaan 10, 6716 RP EDE, the Netherlands, e-mail:
halterenh@zgv.nl
Introduction: Trastuzumab is a monoclonal antibody
directed against the human epidermal growth factor
receptor 2 (HER2). It has proven to be highly effective
in the adjuvant/palliative treatment of breast cancers
with HER2 overexpression. Trastuzumab also binds to
HER2-expressing cardiomyocytes and treatment has been
shown to decrease left ventricle contractility in up to 25%
of patients. In contrast with anthracyclins, trastuzumab
cardiotoxocity does not appear to be cumulative and has
shown to be reversible with treatment discontinuation.
Rechallenge with trastuzumab may be well-tolerated.
There are no reports on trastuzumab treatment-related
arrythmias.
Case-report: A 65-year-old woman with no previous
history of cardiopulmonary events underwent a radical
mastectomy because of a pT1N1M0 infiltrating ductal
carcinoma of the left breast. Since the tumor appeared
HER2-positive, but hormone receptor-negative, she was
referred for chemoimmunotherapy with trastuzumab.
Before initiation of treatment the left ventricular ejection
fraction (LVEF), as estimated by means of Multi Gated
Acquisition Scanning, was 70%. After four 3-weekly cycles
139. Central nervous system involvement of multiple
myeloma
Introduction: Multiple myeloma (MM) is a clonal B-cell
malignancy, characterized by the presence of neoplastic
proliferating plasma cells. Primary MM is mainly located
in the bone marrow, but may invade other tissues and
organs, leading to an atypical clinical presentation as is
demonstrated in our case.
Case-report: A 71-year-old woman was presented to the
neurology department with unilateral sensory loss of the
face which had developed in several days. Her medical
history included MM, with an IgA lambda M-protein
level of 49 g/l at onset, one year before presentation.
The MM was treated with melphalan, thalidomide and
prednisolone, and became in complete remission five
months before presentation. On physical examination she
had an unilateral sensory loss of the face, without other
abnormalities. MRI of the brain and spine revealed a
mass close to the left nervus trigeminus, suggestive for a
schwannoma or a meningeoma. However, analysis of the
cerebrospinal fluid (CSF) showed an elevated protein level
of 950 mg/l with a monoclonal plasma cell population
with lambda-expression. The diagnosis of central nervous
system (CNS) involvement of MM was made. Despite the
start of intrathecal chemotherapy (cytarabine) the patient
died several days after the diagnosis due to progressive
neurologic symptoms and signs.
Discussion: CNS involvement in MM is a rare complication
with an estimated incidence of approximately 1%. It is
defined by the presence of monoclonal plasma cells in the
CSF. Evidence of monoclonality is mandatory, as plasma
cells can be seen in several infectious and non-infectious
conditions. The exact etiology remains unknown. Several
hypotheses are (1) direct continuous spread of osteolytic
skull lesions, (2) haematogenous spread of plasma cells
seen in plasma cell leukemia, or the spread of lymphoid
cells, progenitors of plasma cells, and (3) continuous
growth of plasma cells in the CNS during the course
and treatment of MM, while the drugs used in MM
cannot pass the blood-brain barrier. The clinical presentation covers a diffuse array of neurological symptoms
and signs. Treatment options include combinations of
systemic chemotherapy, intrathecal chemotherapy and
cranial irradiation. Despite treatment, CNS involvement
of MM has a poor prognosis with a median survival of two
months.
Conclusion: The presented case demonstrates a patient
with CNS involvement of MM after complete remission.
Although it is a rare manifestation, unexplained neurologic
signs and symptoms in a patient with MM, even when in
apparent remission, should prompt to look for monoclonal
plasma cells in the CSF.
140. Pleural and peritoneal effusion and an ovarian
tumour. Not always malignant
M.L. Wumkes, H.P. van den Berg
Tergooi Hospitals, Department of Internal Medicine,
Nachtegaalstraat 5c, 3581 AA UTRECHT, the Netherlands,
e-mail: mlwumkes@live.nl
The combination of a pelvic tumour, pleural effusion and
ascites has been known since the late 19th century. The
features of the disease were described by Meigs and Cass in
1937. Today, Meigs’ syndrome is defined as the co-existence
of benign ovarian fibroma, pleural effusion and ascites.
We describe a 55-year-old postmenopausal woman who
presented with dyspnea and recent abdominal pain. Her
medical history revealed hypertension, appendectomy,
cholecystectomy and melanoma. Examination of the lungs
revealed decreased respiratory sound and attenuation
at the right side. There was also an abdominal mass
just above the pubic bone. Laboratory investigation,
except CA-125 (300 kU/l), was unremarkable. Computed
tomography revealed right sided pleural effusion, ascites
and a large solid ovarian tumour of 11 x 10 x 8 cm as
well as an enlarged uterus. Cytologic examination of the
pleural effusion and ascites was negative for malignant
cells. Histologic analysis of the ovarian tumour biopsy
revealed fibroma. Shortly afterwards patient presented
with increasing abdominal pain caused by the tumour.
During surgery both ovaries including the tumour and
uterus were resected. Final histology revealed a fibrothecoma originating from the left adnex, without signs
of malignancy. She recovered uneventful. There’s no
indication for further treatment.
The trias of non-malignant pleural effusion, ascites and a
benign ovarian tumour is also known as Meigs’ Syndrome.
Fluid accumulation like pleural effusion and ascites is
related to substances like vascular endothelial growth
factor (VEGF) that raise capillary permeability. Resection
of the tumour results in elimination of ascites and pleural
effusion. Several cases of Meigs’ syndrome have been
reported in association with raised serum CA 125 levels.
Thus, neither ascites or pleural effusion, nor an elevated
CA 125 is necessarily indicative of an epithelial ovarian
cancer in a woman with a pelvic tumour.
141. Asystole as a complication of trastuzumab treatment
D.E. Agterhuis, M. Wennemers, H.K. van Halteren,
R.J. Walhout
Gelderse Vallei Hospital, Department of Internal Medicine,
Willy Brandtlaan 10, 6716 RP EDE, the Netherlands, e-mail:
Dinetteagterhuis@gmail.com
Y.H.M. Poel, H.P.J. Visser, W.A.T. Slieker
Medical Centre Alkmaar, Department of Internal Medicine,
Wilhelminalaan 12, 1815 JD ALKMAAR, the Netherlands,
e-mail: yvonne_poel@hotmail.com
76
77
Introduction: Trastuzumab is a monoclonal antibody
directed against the human epidermal growth factor
receptor 2 (HER2). It has proven to be highly effective
in the adjuvant/palliative treatment of breast cancers
with HER2 overexpression. Trastuzumab also binds to
HER2-expressing cardiomyocytes and treatment has been
shown to decrease left ventricle contractility in up to 25%
of patients. In contrast with anthracyclins, trastuzumab
cardiotoxocity does not appear to be cumulative and has
shown to be reversible with treatment discontinuation.
Rechallenge with trastuzumab may be well-tolerated. There
are no reports on trastuzumab treatment-related arrythmias.
Case-report: A 65-year-old woman without cardiopulmonary history underwent a radical mastectomy because
of a pT1N1M0 infiltrating ductal carcinoma of the left
breast. Since the tumor appeared hormone receptornegative but HER2-positive, she was referred for chemoimmunotherapy with trastuzumab. Before initiation of
treatment the left ventricular ejection fraction (LVEF), as
estimated by means of Multi Gated Acquisition Scanning,
was 70%. After four 3-weekly cycles of doxorubicin and
cyclophophamide and 12 weekly cycles of trastuzumab
and paclitaxel, the LVEF was 72%. Four days after the 1st
3-weekly course of trastuzumab, she was admitted to the
hospital for rhythm observation on account of recurrent
syncopal episodes. Routine ECG and laboratory tests
were normal. A nine second cardiac arrest with sinoatrial
block was observed at rest, consequently followed by a
slow nodal escape rhythm. After pacemaker implantation
trastuzumab monotherapy was continued.
Conclusion: This is the first reported case of asystole
after trastuzumab treatment. As the sinoatrial node does
not express HER2, there is no clear explanation for this
complication.
high aniongap (AG) metabolic acidosis (pH 7.38, pCO2
2.9kPa, pO2 14kPa, HCO3- 12.4 mmol/l, BE -10.6mmol/l,
albumin corrected AG 30.5 mmol/l) with elevated lactate
(20mmol/l), considerably elevated liver function tests (LD
2496 U/l, ASAT 352 U/l, ALAT 320 U/l, GGT 1850 U/l,
AF 464 U/l and Bilirubin 30mmol/l) and elevated albumin
corrected calcium (3.02 mmol/l). Contrast-enhanced
CT of chest and abdomen demonstrated a tumorous
process in the left hilus with mediastinal lymphadenopathy and extensive hepatic and adrenal metastases.
Histopathological examination of a biopsy obtained from
the liver confirmed small cell lung carcinoma. Despite
normal circulatory dynamics following volume resuscitation, lactate levels remained high. Respiratory distress
syndrome ensued compelling buffering with sodium
bicarbonate. Nevertheless the patient died 3 days after
admission.
Conclusion: Lactate has evolved into an important
biological marker for critical ill patients, lactic acidosis
being associated with a poor clinical outcome, in consideration of the fact that the underlying causes are often
difficult to manage. The disorder is related to a broad
range of possible etiological factors, a thorough knowledge
of which may assist clinicians in improving patient
management. The classification of Cohen and Woods
differentiates between type A en type B lactic acidosis: the
first one being related to hypoxia as in shock, the latter
being irrespective of the level of oxygenation and associated
with diseases like liver or renal insufficiency, malignancy,
pharmacological side effects or adverse reactions and
genetic defects. In our patient lactic acidosis was caused by
metastatic malignancy. The fact that cancer cells predominantly produce energy by high rate of glycolysis with
subsequently lactic acid fermentation even in an aerobic
situation is described as the Warburg effect. The pathophysiological mechanisms have been gradually unravelled
and are applied in PET scanning. Furthermore, pharmacological manipulation of intracellular lactate handling
opens novel therapeutic options. Recent studies have
demonstrated that dichloracetic acid may induce selective
apoptosis by mitochondrial toxicity in brain tumors,
opening new perspective in cancer treatment.
142. Type B lactic acidosis as severe complication of lung
cancer – review of pathophysiological mechanisms
may open new ways of cancer treatment
A. Hana, P.L. Rensma, L.V. Beerepoot
St. Elizabeth Hospital, Department of Internal Medicine,
Hilvarenbeekseweg 60, 5022 GC TILBURG, the Netherlands,
e-mail: a.hana@elisabeth.nl
143. No guts no glory: lifelong bevacizumab maintenance
therapy, an ethical dilemma in colon cancer?
Case report: A 72-year-old man with unremarkable
medical history besides nicotine abuse presented with
progressive dyspnoea, coughing, abdominal pain and
anorexia leading to a weight loss of 7 kg. Before admission
he had been given antibiotics because of a presumed
pneumonia, without clinical improvement. Physical
examination showed an ill and dehydrated patient with
Kussmaul breathing, tachycardia and hypotension.
Laboratory evaluation revealed respiratory compensated
A.C. Ogilvie, J.M. de Koning-Gans
’t Lange Land Hospital, Department of Internal Medicine,
Toneellaan 1, 2725 NA ZOETERMEER, the Netherlands,
e-mail: ac.ogilvie@xs4all.nl
Introduction: Due to the addition of tageted treatments as
bevacizumab to classic chemotherapy for metastatic colon
78
Background: After completion of a standard clinical
work up in patients with cancer, in less than 5% a
‘truly’ unknown primary cancer (UPC) is diagnosed.
The pathologic approach to UPC uses the clinical context,
morphology, and, where necessary, additional immunohistochemistry (IHC), electron microscopy and molecular
genetic testing like PCR. In female patients the IHC
panel includes staining for ER, PR, CK7 and CK20. IHC
should also include Her-2 staining, as is stated by standard
oncology textbooks.
Case: In 2008 a 44-year-old woman came to the emergency
department with abdominal pain, fatique, itching,
dyspnoea and jaundice. At physical examination the
cardinal findings were a WHO-PS of 4 and an enlarged
liver, there were no lymph node nor breast abnormalities.
Additional studies showed: elevated liver function tests,
liver lesions at ultrasound and biopsy of a metastatic
adenocarcinoma in the liver. Serum levels of CEA, CA-15.3
and CA-125 were elevated. However, additional studies
including CT scanning, Mammography and Sigmoidscopy
failed to identify a primary tumor site. She was diagnosed
as having a ‘locally advanced cholangiocarcinoma’ - which
was confirmed during a second opinion -, and treated
with gemcitabine and oxaliplatin. After her first treatment
cycle, when additional IHC demonstrated Her-2 positivity,
it was decided to add trastuzumab therapy. Her clinical
condition improved gradually thereafter, she gained a good
clinical remission and became free of symptoms. A year
later, during at the initiation of second line paclitaxel with
trastuzmab therapy because of progressive disease (liver
and the development of skeletal metastasis), she presented
with a mass in the right breast and a right axillar palpable
lymph node. After resection, it appeared that this was a
primary Her-2 negative breast cancer. A second liver biopsy
again demonstrated the Her-2 positivity of the metastases.
Due to disease progression, third-line vinorelbin and
trastuzumab treatment was initated early in 2011.
Discussion: This case highlights the clinical importance
of IHC staining studies in women suspected of having
UPC or a cholangiocarcinoma, as well as the high activity
of systemic chemotherapy regimes which inclcude
trastuzumab in this group of women with metastatic Her-2
positive adenocarcinoma, even when they appear clinically
to have entered the terminal stage of their illness.
cancer, response rates, progression-free and even overall
survival are improving. However, some times better than
anticipated responses leads to untill now an unknown
ethical dilemma: how to make good clinical decisions
without the guidance of the results evidence-based clinical
tests.
Case report: In 2006, a 64-year-old man presented with
abdominal pain, due to an obstructing sigmoid carcinoma.
After a sigmoid resection, additional studies showed supraclavicular, para iliac and mesentery lymph node as well as
liver and lungs metastases; of which the supraclavicular
site was cytologically proven. This patient was treated with
the experimental treatment arm of the Dutch CAIRO-2
study, consisting of capecitabine, oxaliplatin, bevacizumab
and cetuximab. Despite severe cutaneous toxicity grade III
which lead to the dose-reduction and discontinuation of
cetuximab and reduction of the capecitabine dose by 50%,
he gained a complete remission after the 6th treatment
cycle. Thereafter, in december 2006 he continued with the
study maintenance treatment untill disease progression
(according to the studyprotocol) consisting of capecitabine
and bevacuzimab. Capecitabine caused invalidating grade
III toxicity, including Pseudomonas A. infection of the toe
nail beds, which regressed after its discontinuation and
local antibiotic treatment. Thereafter the only remaining
toxicities were: hypertension (treated with enalapril),
hypothyriodism (with Thyroxine), the other asymptomatic
toxicities (mild hyponatremia and proteinuria) did not
needed treatment. The WHO-PS was 0, the patient led a
completely normal life. After the seond year of therapy the
question of the optimal treatment duration was dicussed
yearly with the patient and his family, after gaining expert
consultation from the regional comprehensive cancer
Centre and advice from the study investigators. Untill now,
both patient and his doctor has decided in every occasion
to continue bevacizumab untill progression, presumably
because they aim at the intuitive 5-year landmark of
complete remission duration.
Discussion: Given the absence of objective clinical
assessment instruments of the possibly persisting colon
cancer cells in our patient, such a good treatment outcome
results in tough ethical questions. Decisions regarding
treatment duration of bevacizumab maintenance can – to
our best knowledge – be only based on clinical judgment,
while eagerly awaiting further clinical research results.
145. Veno-occlusive disease (VOD) of the liver after
oxaliplatin treatment
144. Remember the Her-2 staining in woman with an
unknown primary cancer
H. Wolzak, M.P.J. Lolkema, A. Baars
University Medical Centre Utrecht, Department of Medical
Oncology, PO Box 85500, 3508 GA UTRECHT, the
Netherlands, e-mail: h.wolzak@gmail.com
A.C. Ogilvie, N. Buurma
’t Lange Land Hospital, Department of Internal Medicine,
Toneellaan 1, 2725 NA ZOETERMEER, the Netherlands,
e-mail: ac.ogilvie@xs4all.nl
79
XI.
Introduction: Veno-occlusive disease (VOD) of the liver is
a condition in which small veins in the liver are blocked,
which is causing liver failure. It is mainly observed in
relation to high dose chemotherapy followed by stem cell
transplantation, but incidentally occurs after regularly
dosed chemotherapy as well. VOD is thought to result
from injury to the endothelium of the liver veins causing
obstruction of the hepatic sinusoidal and centrolobular
venous outflow resulting in congestion of the liver. Clinical
signs include jaundice, weight gain caused by fluid
retention, hepatomegaly and spontanous hematoma. In the
medical literature seven other cases have been described
in which patients develop liver failure after oxaliplatin
therapy of whom 3 died due to progressive liver failure. In
this case report we present a patient with VOD of the liver
after oxaliplatin treatment that died from complications of
the VOD.
Case report: A 30 -year-old male patient with metastatic
extragonadal non-seminoma was treated with third line
chemotherapy consisting oxaliplatin and gemcitabine.
The first two cycles of gemcitibine and oxaliplatin were
uneventful, but four days after start of cycle three epistaxis
and dyspnea developed. The patient was dyspnoic and had
a distended abdomen. On physical examination his liver
was enlarged and ascites was present. Initial laboratory
results showed a severe thrombocytopenia as well as
elevated liver enzymes and hyperbilirubineamia of 205
umol/l. There was no sign of hemolysis. Abdominal
ultrasound showed ascites, hepatomegaly and absence
of portal vein thrombosis. Viral hepatitis was ruled out.
Veno-occlusive disease of the liver was suspected and the
patient was admitted to the intensive care unit for thrombolysis with alteplase and i.v. heparin through a femoralis
catheter. Platelet transfusion was given. After thirty hours
alteplase had to be discontinued because of severe blood
loss at the beginning of the central line. During 10 days
heparin treatment was continued. Although transaminases
slightly improved the bilirubin steadily rose from 40 to
300 umol/l, hepatic encephalopathy developed and need
for infusion of trombocytes persisted. The clinical and
neurological condition of the patient gradually worsened
without further treatment options. A few days later he
died. Autopsy was not performed. VOD of the liver after
oxalipaltin is a very rare complication and can be fatal.
Treatment mainly consists of supportive care including
diuretic treatment, paracentesis as clinically indicated,
correction of coagulopathy and stopping hepatotoxic
medication.
VASCULAR MEDICINE RESEARCH
146. Mannose binding lectin as cardiovascular risk factor:
a cohort study
B. Klop, A. Alipour, A. Westzaan, E. Birnie,
G.J.M. van de Geijn, T. Njo, J.W. Janssen, N. van der Meulen,
J.W.F. Elte, A.P. Rietveld, M. Castro Cabezas
Sint Franciscus Gasthuis, Department of Internal medicine,
PO Box 10900, 3004 BA ROTTERDAM, the Netherlands,
e-mail: b.klop@sfg.nl
Background: Mannose binding lectin (MBL) is linked to
atherosclerosis and both high and low levels have been
reported as risk factor. We measured MBL as part of our
standard cardiovascular risk (CVR) program and followed
patients prospectively.
Methods: MBL deficiency was established 0.8 mg/l.
Cardiovascular disease (CVD) was defined by coronary artery
disease (CAD), cerebrovascular disease (CVA) or peripheral
vascular disease (PVD) after initial MBL measurement.
Results: 478 patients were analyzed. The prevalence of
MBL deficiency was 44.4%. The median follow-up was
24.0 months (range 2.0-60.0 months). Age, gender and
medical history of CVD were comparable between patients
with and without MBL deficiency. Type 2 diabetes mellitus
(T2DM) was less prevalent in patients with MBL deficiency
(17.1% vs. 25.6%; p=0.016) in contrast to heterozygous
familial hypercholesterolemia (FH) (10.4% vs. 3.4%;
p=0.002). MBL deficient patients showed an incidence per
1000 person-years of 4.7 for CAD, 4.7 for CVA, 11.9 for PVD
and 21.3 for all CVD events combined. In patients with MBL
sufficiency, incidence density rates were respectively 16.2
for CAD, 9.0 for CVA, 16.2 for PVD and 41.3 for CVD. The
relative risk of MBL deficiency for CAD was 0.29 (95% CI
0.06-1.36), CVA 0.53 (95% CI 0.32-2.72), PVD 0.73 (95% CI
0.38-2.19) and for any CVD event 0.52 (95% CI 0.24-1.12).
Conclusion: MBL deficiency was unexpectedly prevalent
in our cohort. T2DM was less prevalent in MBL deficient
patients, but FH was more prevalent. Overall, our study
suggests a trend towards a protective effect of MBL
deficiency for atherosclerosis.
147. Variability of diurnal triglyceride levels in men and
women
B. Klop1, A.J.H.H.M. van Oostrom2, J.P.H. van Wijk3,
A. Alipour 1, E. Birnie1, J.W.F. Elte1, J.S. Cohn 4 ,
M. Castro Cabezas1
1
Sint Franciscus Gasthuis, Department of Internal medicine,
PO Box 10900, 3004 BA ROTTERDAM, the Netherlands,
80
e-mail: b.klop@sfg.nl, 2St. Antonius Hospital, NIEUWEGEIN,
the Netherlands, 3University Medical Centre Utrecht,
UTRECHT, the Netherlands, 4Heart Research Institute,
CAMPERDOWN, Australia
Aim: We assessed whether cardiovascular risk for these
individuals differs from that of hypercholesterolemic FH
heterozygotes and unaffected relatives.
Materials and methods: Individuals between 18-55 years
were recruited within 18 months after genetic screening.
Three groups were eligible: i.e. subjects with a molecular
diagnosis of FH and LDL-C levels at genetic screening
below the 75th percentile (FH-low), subjects with genetic
FH and an LDL-C level above the 90th percentile (FH-high)
and subjects without FH (No-FH). We measured carotid
intima-media thickness (IMT) by ultrasonography.
Differences in carotid IMT between the groups were
assessed using multivariate linear regression analyses.
Results: Mean carotid IMT of 114 subjects in the FH-low
group (0.623 mm 95% CI: 0.609 to 0.638 mm) was significantly smaller than that of 162 subjects in the FH-high
group (0.664 mm 95%CI: 0.648 to 0.679 mm; p<0.001)
and did not significantly differ from the mean carotid IMT
in 145 individuals in the No-FH group (0.628 mm 95% CI:
0.613 to 0.642 mm; <i>p</i>=0.67).
Conclusion: Our findings suggest that the risk of cardiovascular disease in patients with FH is to a large extent related
to LDL-C levels and not to the presence of a mutation
per se. Consequently, this study cautiously suggests that
individuals with an FH genotype without expression of
hypercholesterolemia may not require a pharmaceutical
intervention that is as aggressive as the standard for
subjects with FH.
Objective: Both increased fasting and non-fasting triglycerides (TG) predict cardiovascular events. However, TG
vary largely in the fasting state and possibly even more
postprandially. Only limited data are available on the intraindividual variability of non-fasting TG.
Methods: Capillary triglycerides (cTG) of 272 subjects were
measured in a free living situation at six standardized time
points (fasting, before lunch, after lunch, before dinner,
after dinner and at bedtime) for three days. Coefficients of
variation (CV) for cTG were calculated for each time-point.
Subjects were divided into tertiles based on their three-day
average fasting cTG.
Results: The CV for cTG gradually increased during the
day with a median ranging from 19.2% (IQR 10.2-33.4)
to 25.0% (IQR 13.2-40.4). CVfasting was significantly lower
compared to CVafter dinner and CVbedtime (p<0.05), but
CVbefore lunch, CVafter lunch and CVbefore dinner did not differ
significantly with other time-points including CVfasting.
Subjects from the first tertile showed a significantly lower
CVfasting and CVbefore lunch compared to subjects from the
second and third tertile (p<0.001). Within the second
and third tertile there were no significant differences in
CV between the different time-points. Average CV was
increased with 20.2% in men compared to women for
fasting and non-fasting time-points (p<0.05).
Conclusions: Men show a higher intra-individual variability
of fasting and non-fasting TG than women. Variability of
non-fasting TG compared to fasting TG is similar and only
slightly higher during the evening. Measuring non-fasting
TG instead of fasting TG could be easier for patients and
help in cardiovascular risk assessment.
149. Skin autofluorescence, a marker of tissue Advanced
Glycation Endproducts accumulation, is increased in
patients with carotid artery stenosis and peripheral
artery disease
D.J. Mulder1, M.J. Noordzij1, E. Loeffen1, B.R. Saleem1,
R. Meerwaldt2, H.L. Lutgers1, A.J. Smit1, C.J. Zeebregts1,
J.D. Lefrandt1
1
University Medical Centre Groningen, Department of Internal
Medicine, PO Box 30001, 9700 RB GRONINGEN, the
Netherlands, e-mail: udomulder@gmail.com, 2Medical
Spectrum Twente, ENSCHEDE, the Netherlands
148. Assessment of carotid atherosclerosis in normocholesterolemic individuals with proven mutations in
the LDL-receptor or apolipoprotein B genes
R. Huijgen1 , B.A. Hutten 2 , I. Kindt 3 , M.D. Trip2 ,
E. de Groot2, J.J.P. Kastelein2, M.N. Vissers2
1
Rode Kruis Hospital, Department of Internal Medicine,
Vondellaan 13, 1942 LE BEVERWIJK, the Netherlands,
e-mail: r.huijgen@amc.uva.nl, 2 Academic Medical Centre,
AMSTERDAM, the Netherlands, 3Stichting Opsporing Erfelijke
Hypercholesterolemie, AMSTERDAM, the Netherlands
Introduction: Advanced Glycation Endproducts (AGEs)
play an important role in development and progression
of atherosclerosis. Skin autofluorescence (SAF), a
non-invasive marker of tissue AGE accumulation, has
been shown to be a strong predictor of incident cardiovascular morbidity and mortality in patients with acute
myocardial infarction, diabetes mellitus, and kidney
failure, independent of classical risk factors.
Aim: We evaluated whether SAF is elevated in patients
with carotid artery stenosis (CAS) with and without
coexisting peripheral artery occlusive disease (PAOD).
Introduction: Genetic cascade screening for heterozygous
familial hypercholesterolemia (FH) revealed that fifteen
percent of diagnosed individuals do not exhibit elevated
low-density lipoprotein cholesterol (LDL-C) levels.
81
Materials and methods: SAF was measured using the
AGE Reader in 56 patients with CAS and in 56 age- and
sex-matched healthy controls without diabetes, renal
dysfunction, or known atherosclerotic disease.
Results: SAF was higher in patients with carotid artery
stenosis compared with controls: mean 2.81 versus 2.46
arbitrary units (AU) (p=0.002), especially in the younger
age group of 50 to 60 years old: mean 2.82 versus 1.94 AU
(p<0.001). Patients with CAS and PAOD proved to have an
even higher SAF than patients with CAS only: mean 3.28
versus 2.66 AU (p=0.003). Backward linear regression
analysis showed that age, smoking, diabetes mellitus, renal
function and the presence of PAOD were independent
determinants of SAF, whereas CAS alone was not.
Conclusion: SAF, a non-invasive marker of tissue AGE
accumulation, is increased in patients with CAS and even
more in those who also suffer from PAOD. It is associated
with established risk factors, including age, smoking,
diabetes, and renal insufficiency. The observation that SAF
increases with the extent of cardiovascular disease suggests
that it may be an indicator of the burden of atherosclerosis
and may potentially serve as a risk indicator in patients
with cardiovascular disease.
Using the Spacelabs oscillometer daytime MAP was
102±8,9 mmHg, i.e. 34,1±3,4% of PP above DBP.
MAPPWA was 103,8±11,4 mmHg; 38,8±4,4% above DBP.
This difference was significant (p<0,01).
Conclusion: MAP displayed by the Watch BP office and the
Spacelabs oscillometer, are too imprecise to be used for
calibration purposes. We suggest that devices should not
display MAP unless their accuracy is tested.
151.
Aldosterone-receptor antagonists lead to prolonged
blood pressure reduction in uncontrolled hypertension: a retrospective analysis
P.M. Jansen1, K. Verdonk1, B.P.M. Imholz2, A.H.J. Danser1,
A.H. van den Meiracker1
1
Erasmus Medical Centre, Department of Internal Medicine,
’s-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: jansen.pm@gmail.com, 2Twee Steden
Hospital, WAALWIJK, the Netherlands
Introduction: Aldosterone-receptor antagonists (ARAs)
have been shown to effectively reduce blood pressure (BP)
in patients with uncontrolled hypertension. However, the
long-term efficacy of ARAs as add-on treatment in uncontrolled hypertension has not yet been reported.
Methods: Data from 123 patients (21 with primary aldosteronism, 102 with essential hypertension) with difficultto-treat hypertension who received an ARA between May
2005 and September 2009 were analyzed retrospectively
for their effect on blood pressure (BP) and biochemistry at
first follow-up after start with ARA and the last follow-up
available. Possible predictors for a better BP response were
subsequently tested in a multivariate regression model.
Results: Systolic BP decreased by 22±20 and diastolic BP
by 9.4±12 mmHg after a median treatment duration of
25 months. In patients that received treatment > 5 years,
SBP was 33±20 and DBP 16±13 mmHg lower than at
baseline. Changes in BP were not significantly different for
PA and EH patients. Serum potassium increased from 4.0
to 4.4 mmol/l (p<0.001) in EH and from 3.4 to 4.3 mmol/l
(p<0.001) in PA patients. In addition, serum creatinine
showed a significant rise upon ARA treatment (85 to
94 mmol/l (p<0.001) in EH, and 86 to 96 mmol/l (p=0.01)
in PA). The total defined daily dose (DDD) of antihypertensive drugs remained unchanged (5 at baseline versus
4.5 at end of follow-up, p=0.459). Multivariate analysis
revealed that baseline BP and follow-up duration were
positively correlated with BP response.
Conclusion: Add-on ARA treatment in difficult-to-treat
hypertension results in a profound and sustained BP
reduction.
150. Inaccuracy in determining mean arterial pressure
with oscillometric blood pressure techniques
J. Vos1, H.H. Vincent1, M.C. Verhaar2, W.J.W. Bos1
1
St. Antonius Hospital Nieuwegein, Department of Internal
Medicine, Koekoekslaan 1, 3435 CM NIEUWEGEIN, the
Netherlands, e-mail: jornvos@hotmail.com, University
Medical Centre Utrecht, UTRECHT, the Netherlands
Objective: Accurate determination of MAP is important
in the calibration of pressure waveforms to calculate
central blood pressure. Currently a precise, individualized measurement of mean arterial pressure (MAP)
can only be obtained with intra-arterial BP measurements or with applanation tonometry. Objective was to
investigate whether easy to use oscillometric devices
validated for systolic and diastolic pressure measurements
(BHS protocol) give accurate determinations of MAP.
Methods: MAP measurements obtained with the WatchBP
Office oscillometric (Microlife) monitor (n=102) or with
the Spacelabs 90207 oscillometer (n=52) were compared
with MAP, assessed by pulse wave analysis (PWA)
(SphygmoCor).
Results: Average oscillometric MAPMicrolife was
97±12,5 mmHg (mean±SD), i.e. 23,6±9,1% of pulse
pressure (PP) above diastolic pressure (DBP). MAPPWA
was 106±14,6 mmHg (p<0,01), 37,7±3,9% of PP above
DBP. In simultaneous measurements on both arms with
Microlife we observed individual left-right differences.
82
XII. VASCULAR MEDICINE CASE REPORTS
rare. Furthermore, TA commonly affects young Asian
females, rarely occurring after age 40. Our case involves a
Caucasian woman, who was diagnosed with TA at age 49.
Conclusively, we here described a patient with concurrent
occurrence of RA and late onset TA. This association is
very rare and remains to be clarified.
152. Late onset Takayasu arteritis diagnosed in a patient
with rheumatoid arthritis
K.E. Verweij, J.G.J. Jonkman, A.A.M. Zandbergen, A. Dees
Ikazia Hospital, Department of Internal Medicine,
Montessoriweg 1, 3083 AN ROTTERDAM, the Netherlands,
e-mail: evelyneverweij@gmail.com
153. An unusual intrathoracal sharply defined mass
B. Tomlow, A. Boersma
Medical Centre Alkmaar, Department of Internal Medicine,
Wilhelminalaan 12, 1815 JD ALKMAAR, the Netherlands,
e-mail: 1000702@mca.nl
Introduction: Takayasu arteritis (TA) is a rare, chronic
vasculitis of unknown etiology that most frequently
involves the aorta and its branches. The highest incidence
is in Asians. In Europe the incidence is 1-3 per million per
year. TA mainly affects young women, with an age at onset
usually between 10 and 40 years.
Rheumatoid arthritis (RA) is characterized by chronic,
systemic inflammation of unknown etiology that primarily
involves joints. It can occur at any age with a peak onset
between 30 and 55 years.
Case report: A 48-year-old Caucasian woman with pain
and swelling in left knee and small joints in her hands
was diagnosed as having anti-CCP-positive rheumatoid
arthritis in October 2009. Treatment was started with
prednisolon (15 mg/day) and methotrexate (15 mg/week),
which improved her clinical condition. A year later, she
presented at the outpatient clinic with fatigue in both
upper extremities while in use. She did not experience
weight loss or low-grade fever. Upon physical examination,
a blood pressure difference between the left and the
right arm was noted, respectively 109/71 mmHg and
93/71 mmHg. Furthermore, a murmur was noticed over
the left carotid artery. Pulsations of both radial arteries
were reduced.
Laboratory tests were unremarkable, except for a slight
leukocytosis (15 x 109/l). Subsequent MRA showed
occlusion of the right truncus brachiocephalicus at its
origin from the aortic arch and a slight irregularity of the
aortic arch. There was also stenosis of the left subclavian
artery. PET-CT demonstrated increased FDG uptake along
both brachial arteries, suggestive of active vasculitis.
According to the ACR classification criteria the patient
was diagnosed with TA. The treatment she already used
for RA was continued. Within two months, the fatigue in
both arms improved, but the reduced pulsations and blood
pressure difference remained.
Conclusion: TA is a rare disease of which the pathogenesis
remains to be clarified. It has been suggested that the
vasculitis may deteriorate via an autoimmune mechanism.
Several studies have reported an association between
TA and systemic lupus erythematosus (SLE) or systemic
sclerosis, but the concurrent presence of TA and RA is
Introduction: If a sharply defined mass is found intrathoracal a CT thorax-abdomen should be performed to differentiate between the diagnosis of an infection, an empyema,
a vascular problem, malignancy (mesotheloma, pleuritis
carcinomatos, lymphoma), tuberculosis or a haemathorax.
In case of a mycotic aneurysma the in-hospital mortality
rate lies around 35%. A possible explanation for this can
be that operations are usually performed on an emergency
basis while patients are in a state of sepsis or shock and at
hightened risk of an aneurysmal rupture.
Case report: In July, 2010 a 79-year-old woman was
presented to our emergency department with fever, fatigue
and pain on the left side of the abdomen. Her medical
history revealed diabetes mellitus type 2, severe vascular
disease, and a smoking history of 30 pack years. Vital signs
revealed a body temperature of 38.5 °C, blood pressure of
188/117 mmHg, heart rate of 95 /min and a respiratory
rate of 18/min with a SO2 of 98% without supplemental
oxygen. Physical examination showed symmetrical normal
breathing with minor increase in vocal fremitus. The
left area of the abdomen showed tenderness, painful
at palpation, without muscular defence. Laboratory
results indicated an elevated C-reactive protein level of
279 mg/l (normal values: 0 to 10 mg/l), White blood cell
count of 12.7. * 109/l (normal values: 3.5 to10.0 * 109/l)
and a hemoglobin level of 5.5 mmol/l (normal values:
7.5-9.5 mmol/l) with a mean corpuscular volume of 86.0
fl (normal values: 80 to 100 fl). The chest x-ray showed a
sharply defined intrathoracal mass most prominent on
the lateral view. A thoracentesis was performed which
showed a green-brown gelatinous fluid with a pH of 7.4,
LDH of 1987 U/l, total protein of 39 g/l and a hemoglobin
level of 0.4 mmol/l. A CT thorax-abdomen which showed a
giant aneurysmata - 13 cm diameter – in the intra-thoracal
(TAA) as well as in the intra-abdominal aortic arch (AAA),
most likely a mycotic aneurysma which is a localized,
irreversible arterial dilatation caused by an infectious
destruction of the vessel wall. This is a serious condition
leading to significant morbidity and mortality rate which
83
and can trigger life-threatening ventricular arrhythmias.
A hypothesis is that calcium is also increased in the
pulmonary smooth muscle cells and can cause pulmonary
arterial vasoconstriction and in this manner genetic
susceptibility for developing pulmonary arterial hypertension in this patient. So a RYR-2 mutation is possibly a
new genetic risk factor. The risk for developing pulmonary
arterial hypertension is then further increased when a
patient uses amphetamines or cocaine.
Conclusion: Chronic use of amphetamines, cocaine and
appetite suppressants can cause severe pulmonary hypertension. Genetic susceptibility can play an important role.
can develop when a new aneurysm is produced by infection
of the arterial wall or when a pre-existing aneurysm
becomes infected. In spite of its name, which refers to the
appearance, like ‘fresh fungus vegetations’, the majority of
mycotic aneurysms are caused by bacteria.
154. Pulmonary arterial hypertension caused by chronic
use of amphetamines and cocaine
M. Ezzahti, N. Masalha
Amphia Hospital, Department of Internal Medicine,
Molengracht 21, 4818 CK BREDA, the Netherlands, e-mail:
ezzahti00@hotmail.com
155. Acute myocardial infarction in a young woman:
how a critical appraisal of the blood count led to a
treatable cause
Case: A 28-year-old woman diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT)
complained of progressive exertional dyspneu and fatigue
over two years. She had no chest pain and there was no
syncopal episode. The patient had used for more than
13 years amphetamines and cocaine. She had also used
for 3 months pseudoephedrine and caffeine for appetite
suppression. On physical examination the blood pressure
was 109/69 mmHg, her heart rate was 84 beats/min and
the oxygen saturation was 95% without use of oxygen.
Auscultation of the heart showed a split second heart
sound. Further physical examination was unremarkable.
Electrocardiography revealed signs of right ventricular
hypertrophy and a chest radiograph showed large central
pulmonary arteries. Echocardiography showed dilatation
of the right ventricle and right atrium, an estimated
pulmonary pressure of 105 mmHg, tricuspid regurgitation grade 2 and a normal left and right ventricular
function. Right cardiac catheterization revealed findings
consistent with pulmonary hypertension: pulmonary
arterial systolic pressure of 101 mmHg, mean right atrial
pressure of 8 mmHg and a cardiac output of 4,1 liter/
min. Pulmonary function testing was normal. Ventilation
perfusion scanning and a CT angiogram of the chest
revealed also no abnormalities. Lab results showed normal
liver function tests, negative ANA and ANCA and negative
HIV serology. The cause of pulmonary hypertension in
this patient was the chronic use of amphetamines, cocaine
and possibly appetite suppressants. Other causes were
excluded. The patient was treated with ambrisentan, an
endothelin receptor antagonist.
Discussion: Amphetamines may lead to pulmonary arterial
hypertension due to the release of serotonin, which
causes pulmonary vasoconstriction and the proliferation
of smooth muscle cells. Cocaine can cause endothelial
dysfunction and also proliferation of pulmonary smooth
muscle cells. The patient has a p.Val2178IIe mutation in
the RYR2-gen, which causes CPVT. The RYR2 mutation
increases calcium release in the muscle cells of the heart
D.J. Mulder, E.J. Houwerzijl, J.D. Lefrandt,
M.M.J.B.G. Beckers, A.J. Smit, K. Meijer
University Medical Centre Groningen, Department of Internal
Medicine, PO Box 30001, 9700 RB GRONINGEN, the
Netherlands, e-mail: udomulder@gmail.com
Introduction: Although acute myocardial infarction (AMI)
mainly occurs in elderly patients, young individuals can also
be affected. In young patients, most cases are still explained
by classical risk factors. However, in the absence of risk
factors, exceptional causes should never be overlooked.
Case report: At the age of 34, a previously healthy woman
was admitted to our hospital in cardiac arrest. Angiography
revealed a proximal 90% occlusion of the left main coronary
artery for which a drug eluting stent was placed. The
remaining coronary arteries did not show luminal stenosis
or apparent dissection, without signs of atherosclerosis
on CT-scan. Patient was treated according to protocol
after which she rapidly recovered. The usual secondary
prevention, including acetylsalicylic acid, was started.
Classical risk factors were absent, she had never smoked,
was athletic and not overweight, had no family history of
premature atherosclerosis, no hypertension, no diabetes,
and a normal lipid profile. Two months earlier, she had had
a short period of chest pain on exertion. In retrospection, her
hemoglobin and platelet levels appeared to be relative high
for a young woman. At the age of 27, her haemoglobin was
9.7 (7.5-9.9) mmol/l with platelets of 377 (150-350) x 109 IU/l
and at admission haemoglobin was 9.9 mmol/l, platelets
were 394 x 109 IU/l, and leukocytes were 12.7 x 109 IU/l, with
maximum values of 10.3 mmol/l, 467 and 18.6 x 109 IU/l.
Four years later, during regular follow-up, platelets had
increased to 575 109 IU/l. We considered the possibility
of an underlying myeloproliferative disorder (MPD), and
a JAK2 V617F mutation was detected. Bone marrow
aspiration demonstrated a low iron depot and panmyelosis,
84
matching the diagnosis MPD, without signs of primary
myelofibrosis of chronic myeloid leukemia. Based on
the 2008 WHO criteria, i.e. Hb > 10.2 for women and
JAK2 V617F mutation, polycythaemia vera was the most
appropriate diagnosis.
Conclusion: Our patient’s fulminant presentation of
AMI was almost certainly a thrombotic event following
a previously unrecognized MPD, already present many
years earlier. These are clonal marrow neoplasms that are
associated with arterial or venous thromboses, with AMI
being a rare complication. Untreated recurrence rates of
thrombotic events may be up to 60%. Cytoreductive therapy
is very effective in protecting against recurrent events, particularly after AMI. Therefore, in young patients with arterial
thrombosis, blood counts that are mildly but consistently
elevated should raise suspicion of MPD. This opportunity to
decrease the risk of recurrence should not be missed.
dehydrogenase (LDH, 971 U/l). A contrast-computed
tomography showed a left renal infarction. Cocaine
metabolites were found in a later performed drug screening.
It is generally accepted that cocaine has potent vasoconstrictive effects on vascular smooth muscle.
The release of vasoactive substances is influenced by
cocaine, for example the inhibition of vasodilatative nitric
oxide. It also blocks the re-uptake of catecholamines in
sympathetically innervated tissues, thereby leading to
sympathetic discharge. Extreme vasoconstriction causes
damage to the endothelial surface, resulting in platelet
activation and possibly formation of thrombi.
Beside the cardiac effects, renal injury is the most described
side effect of cocaine use. This involves renal failure and
infarction, mostly due to severe vasoconstriction. Less
often mentioned are gastrointestinal complications, despite
a mortality rate of almost 30%. Blocking the re-uptake of
norepinephrine may lead to mesenteric ischemia and focal
tissue ischemia, which may lead to perforation.
Conclusion: This case report shows renal and gastrointestinal side effects of cocaine use. It is important not to
underestimate these effects, as mortality rate can be high.
156. Unusual complications of cocaine
J.M. Hillen, F.H. Bosch
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6800 TA ARNHEM, the Netherlands, e-mail:
judithhillen@gmail.com
157. A life-threatening presentation of Wegener’s
granulomatosis
Introduction: The cardiac effects of cocaine are well
known. We report on two cases in which unusual
effects of cocaine are shown, induced by cocaine related
vasoconstriction.
Case report: The first patient, a 45-year-old male, presented
at the emergency department with abdominal pain,
vomiting and absence of defecation since 5 days. Medical
history revealed cocaine and marihuana abuse. Laboratory
results showed a serum creatinine of 542 mmol/l with a
blood urea nitrogen of 19.8 mmol/l. Liver enzymes were
slightly elevated and cocaine metabolites were found
in the urine. ECG showed negative T’s in II, III, V4-V6
but cardiac enzymes were not elevated. Two days after
admittance patient detoriated and developed acute gastrointestinal complaints. Laparotomy showed ischemia of the
mesentery and necrosis of the sigmoid. He was admitted
to the ICU, but died in five days because of an abdominal
sepsis with multi organ failure. Autopsy showed recent
myocardial infarction, as well as liver infarction and
extensive ischemia of the small intestine, colon and
omentum. In the left kidney, multiple older infarcts were
seen, all matching cocaine use.
Our second patient, a 36-year-old male, presented with
sudden pain in the left lower abdomen, characterized
as sharp and radiating to his left lower back. Physical
examination revealed a tenderness with percussion on
the left costovertebral angle. Laboratory analysis revealed
no abnormalities, except a remarkable increased lactate
J.A.J. Douma, F. Stam
Medical Centre Alkmaar, Department of Internal Medicine,
Wilhelminalaan 12, 1815 JD ALKMAAR, the Netherlands,
e-mail: joeridouma@gmail.com
Case report: A 64-year-old man presented at our emergency
department with symptoms of malaise. His complaints
consisted of loss of appetite, sensation of fever, night
sweats, painful legs and rhinorrhea since two weeks.
In addition, he had crusts in his nose for two years,
with periods of nose bleeding. The medical history
included schizophrenia, with three times a psychosis, and
ankylosing spondylitis, for which he received treatment
with etoricoxib. Physical examination showed a body
temperature of 38.1 °C, crustae in the nose and an oral
fetid odour. Laboratory investigation revealed an elevated
C-reactive protein (340 mg/l), thrombocytosis (1028 x
109/l), leukocytosis (20.1 x 109/l), and slight liver enzymes
disturbances. In addition, marked renal insufficiency
(serum creatinine 591 mmol/l) with proteinuria (1.1 g/l)
and dysmorphic erythrocyturia was demonstrated. A chest
X-ray showed a pulmonary infiltrate, whereas computed
tomography revealed mucosal swelling of the maxillary
and ethomidic sinuses, with partial destruction of the
nasal septum. A few days after presentation, the patient
developed acute pain on the left side of the abdomen with a
computed tomography showing subtotal splenic infarction.
85
Aim: Determine complaints in correlation with the use of
acid suppressive therapy ten years after diagnosis.
Materials and methods: 672 patients with oesophagitis
between 1998 and 2000 were reviewed to identify patients
suitable for this investigation. A total of 262 patients were
excluded because of pre-defined exclusion criteria (ie.
chronic cardiopulmonary disease, or treatment of cancer),
leaving a study population of 410 subjects. Patients received
a questionnaire regarding their use of acid suppressive
therapy, dosage, compliance and patient satisfaction. In
addition, use of ™ or gen was assessed. Presence of reflux
complaints was assessed via a validated questionnaire, and
a symptom score was calculated using a 5-point Likert scale.
Results: A total of 208 patients returned the questionnaire (51%), 161 (78%) of them used acid suppressive
therapy. Of the patients still on acid suppressive therapy
72% (116 patients, group 1) had reflux complaints, while
the remaining 45 patients (28%, group 2) were in complete
clinical remission. There was no difference in gender, age or
severity of the initially diagnosed reflux oesophagitis between
both groups. An equal number of patients in both groups
received the prescription from their general practitioner.
Patients in group 1 were significantly less compliant and
satisfied compared to patients from group 2, 73% vs. 96%
and 83% vs. 100% (p<0,001) respectively. An equal number
of patients in both groups used ™ or gen (p=ns). Presence of
reflux complaints as well as symptom score (although rather
low) showed no difference between users of ™ or gen. The
majority of patients always uses the prescribed dosage.
Conclusion: It is concluded that more than 10 years after
the diagnosis of reflux oesophagitis 22% of patients
stopped using acid suppressive therapy. From the patients
still on medication only a minority (28%) is in complete
clinical remission associated with significantly higher
patient satisfaction and compliance to therapy as compared
to their symptomatic counterparts. There appears to be no
difference in effect and usage of ™ versus gen preparations.
Another few days later the patient became dyspnoeic, due
to congestive heart failure as result of a non-ST-elevation
myocardial infarct. At that time, an obvious purple-red
discolouration of some parts of the fingers was noticed.
Cultures of blood and urine were negative.
Given the wide range of signs and symptoms in
combination with the participation of the upper airways
a systemic disease, like Wegener’s granulomatosis, was
suspected. Immunological investigation, showed a strongly
positive C-ANCA titre, as was the case for antiproteinase3-ANCA. This confirmed the diagnosis Wegener’s granulomatosis. Pathological investigation of tissue biopsy of
the nose displayed only necrosis, without granulomas.
Electromyography of the legs showed a mixed neuropathy
with degradation of both the motoric and sensory nerves.
After starting intravenous treatment with high doses of
prednisolone and cyclophosphamide the condition of the
patient improved. However, the patient needed to undergo
temporary haemodialysis because of renal failure and
some necrotic fingers needed to be amputated. Eight weeks
after admittances the patient could be discharged in good
general condition.
Conclusion: Wegener’s granulomatosis is a potential lifethreatening disease, that can affect multiple organ systems.
Our case represents the dramatic impact, when the disease
progresses without the correct diagnosis. When a patient
presents with signs and symptoms of multiple organs,
especially when combined with upper airway symptoms,
Wegener’s granulomatosis should always be considered.
XIII. GASTRO-ENTEROLOGY RESEARCH
158. Use of acid suppressive drugs, trademark versus
generic, more than 10 years after the endoscopical
diagnosis of reflux oesophagitis
159. Complaints in patients with reflux oesophagitis more
than 10 years after the diagnosis
G.M.H.E. Dackus, S.M.L.A. Loffeld, R.J.L.F. Loffeld
Zaans Medical Centre, Department of Internal Medicine,
PO Box 210, 1500 EE ZAANDAM, the Netherlands, e-mail:
loffeld.r@zaansmc.nl
S.M.L.A. Loffeld, G.M.H.E. Dackus, R.J.L.F. Loffeld
Zaans Medical Centre, PO Box 210, 1500 EE ZAANDAM, the
Netherlands, e-mail: loffeld.r@zaansmc.nl
Introduction: Reflux oesophagitis needs maintenance
therapy with acid suppressive drugs. Since generic
preparations (gen) became available, clinicians made the
observation that these drugs are probably less effective.
Most studies on the efficacy of acid suppressive therapy
report on short term follow-up after treatment with
trademark (™). Little data exist on the long term follow-up
of patients with reflux oesophagitis. Data on comparison
between these ™ and gen are not available.
Introduction: Treatment of reflux oesophagitis with
acid suppressive therapy is effective. Data on long term
follow-up are lacking.
Aim: A study was done in patients in order to assess
complaints more than 10 years after the endoscopic diagnosis.
Material and methods: All patients diagnosed in the years
1998, 1999 and 2000 were studied. Exclusion criteria were
chronic cardio-pulmonary disease, active treatment for any
86
collected. The cause and localisation of perforation was
determined. The cause was therapeutic (polypectomy or
coagulation), barotraumatic (the inflated air) or mechanical
(direct trauma). Results: In the period of 1992-2010 22376
consecutive procedures were done. Perforation of the
colon occurred in 29 patients (0.12%) (10 men, 19 women,
mean age 74.9 years, SD 10.3, median 76, range 33-89). In
15 cases (52%) the cause of perforation was mechanical,
in 9 (31%) barotraumatic (cecal blow-out), and in four
cases (13%) it was due to coagulation or polypectomy.
In one patient data was not available. Two sites were
prone to perforation: the sigmoid and the cecum. Cecal
blow-out occurred significantly more often as the result
of barotrauma, while perforation of the sigmoid was more
often the result of direct mechanical trauma. This occurred
more often in cases of diverticuli in the sigmoid.
Three perforations in patients with polyps were not the
direct result of a polypectomy or biopsy, two patients also
had diverticuli and one patient had a stenotic anastomosis.
Diverticuli are the most common diagnosis in relation to
mechanical trauma.
Two patients had a mechanical perforation of an otherwise
normal sigmoid. Both patients used high dosages of corticosteroids during a longer period of time. One perforation
of the sigmoid occurred during the dilatation of a stenotic
anastomosis, because the guide wire perforated a diverticulum 20 cm proximal to the stenosis. One patient
with overt bleeding due to active colitis was treated with
coagulation and had a sigmoid perforation one day later.
Successful cecal intubation was achieved in 14 out of these 29
patients with perforations (48%). In case of successful cecal
intubation the perforation was located in the sigmoid in 7
cases, in the transverse colon in one case and in the cecum in
4 cases. This was 10, 0, and 6 respectively in case the cecum
was not reached during the procedure. The majority of perforations were diagnosed within the first 24 hours.
Conclusion: It is concluded that the risk of perforation is
rather low. Mechanical trauma in cases of diverticuli and
barotrauma due to inflated air are very important causes.
Patients with a higher risk are those with diverticuli in the
sigmoid.
cancer, immigrants, Alzheimers, mental disability, and
psychiatric illnesses. All patients received a questionnaire by
mail. The questionnaire comprised four different, validated
lists of questions. A general questionnaire consisted of 20
questions on reflux complaints. Severity as well as frequency
was scored on a five and six point Likert scale respectively
(scores ranged from 0-40 and 0-60). The GerdQ list, a
symptom activity index (SAI), and the gastrointestinal
symptom rating scale (GSRS) were used as well.
Results: In a period of three years 672 patients were
diagnosed with reflux oesophagitis. After exclusions the
study population comprised of 410 patients. Of these 208
questionnaires (51%) were available for evaluation.
Complaints were reported by 130 patients (63%). The
majority of these, 115 (88%), use acid suppressive therapy.
Only 78 patients were in clinical remission, with or
without therapy. The respondents with complaints were
divided into two groups. Group 1: all patients with reflux
complaints and using acid suppressive therapy. Group 2: all
patients with complaints without medication.
Patients in group 1 were significantly older at time of the
endoscopic diagnosis compared with patients of group 2.
Patients in group 1 had significantly more often a hiatal
hernia (p<0.001). There was no difference in overall symptom
or frequency score per patient between both groups, mean
5.97 versus 6.8 and 13.4 versus 13.8 respectively. However,
heartburn, nausea, acid regurgitation, epigastric pain,
dysphagia, and nocturnal complaints showed a significant
higher prevalence in patients of group 2. Scores for specific
complaints were significantly lower in group 2. There was no
difference between the GERD-Q, SAI and GSRS.
Conclusion: Despite effective therapy only a 37% of patients
is in complete remission. However, the symptom score
per patient is rather low. Patients without medication have
more often reflux complaints but lower severity scores,
being a possible reason for not taking medication. Hence
it is to be expected that these patients regarded their
complaints very mild not necessitating therapy. Patients
who still had complaints and used medication had significantly more often a hiatal hernia.
160. Perforations after colonoscopy. Incidence and causes
161. Clinical and microbiological evaluation of liver
abscesses: 15-year single-centre experience in the
Netherlands
R.J.L.F. Loffeld, A. Engel, P.E.P. Dekkers
Zaans Medical Centre, Department of Internal Medicine,
PO Box 210, 1500 EE ZAANDAM, the Netherlands, e-mail:
loffeld.r@zaansmc.nl
I.L. Holster, A.C. de Vries, P. de Man, A.J.P. van Tilburg
Sint Franciscus Gasthuis, Department of Gastroenterology
and Hepatology, Kleiweg 500, 3045 PM ROTTERDAM, the
Netherlands, e-mail: i.holster@erasmusmc.nl
Introduction: The causes of perforations after colonoscopy
are largely unknown.
Aim: Study the causes leading to perforation.
Materials and methods: Data on sex, age, endoscopic
diagnosis, therapeutic actions, and cecal intubation were
Background: Liver abscesses are diagnosed infrequently
in the Western world. Escherichia coli, Streptococcus and
87
Case: A 64-year-old woman was admitted to our
department because of a 1-day history of diffuse abdominal
pain. She had no other complaints. The medical history
comprised limited cutaneous systemic sclerosis with
sclerodactyly, digital ulcers, calcinosis cutis and Raynaud
phenomenon, and GERD.
At physical examination, the abdomen was diffusely
tender. Laboratory examination showed a leukocyte count
of 16,0 x 109/l and C-reactive protein of 89 mg/l. Shortly
after admission the patient developed diarrhea, abdominal
distension and high-pitched borborygmi at auscultation.
Contrast enhanced abdominal CT revealed distention
of the small intestine and diffuse thickening of the
colonic wall with an intact splanchnic circulation. At
sigmoidoscopy, there was a moderate to severe ischemic
colitis of the sigmoid and descending colon. Repeated
faecal cultures were negative for SSYC and Clostridium
difficile. The patient was treated with a nasogastric tube,
TPN and analgesics.
One week after admission, abdominal pain declined
and auscultation revealed normalized bowel sounds, but
diarrhea persisted, with bowel movements up to ten times
per 24 hours. Sigmoidoscopy was repeated and showed
an unchanged endoscopic picture suggestive for severe
ischemic colitis.
Two days later, the patient developed an acute abdomen.
Abdominal CT was repeated and showed diffuse intestinal
distention, pneumatosis coli of the sigmoid and descending
colon and free intra-abdominal air. An emergency subtotal
colectomy was indicated. However, the patient refused
surgical intervention and died two days later. Autopsy
revealed a perforation of 3 centimeters at the splenic
flexure.
Discussion: Systemic sclerosis (SSc) is a chronic systemic
disorder of unknown etiology characterized by thickened,
hard skin (scleroderma) and distinctive involvement of
multiple internal organs, most notably the lungs, heart,
kidneys and gastrointestinal tract. The pathologic hallmark
of SSc is diffuse obliterative vasculopathy of small arteries
and arterioles and fibrosis in the skin and internal organs.
Nearly 90 procent of patients with SSc have some degree of
gastrointestinal (GI) involvement. Because of neuropathy,
smooth muscle atrophy and fibrosis, there is reduced
peristalsis throughout the gastrointestinal tract. GERD and
gastroparesis are frequently reported symptoms. Sever GI
problems, including bacterial overgrowth, malabsorption
and intestinal pseudo-obstruction, are much less common,
affecting less than 10 procent of patients.
Pneumatosis coli, that is the presence of air in the bowel
wall, is a very rare complication and a poor prognostic
sign. Although successful conservative treatment has been
described, the risk of colonic infarction and spontaneous
perforation with concomitant mortality is high, as seen in
our patient.
Staphylococcus species are the most recovered microorganisms in Europe, while Klebsiella pneumoniae is
predominant in puss cultures of pyogenic liver abscesses
in Southeast Asia and North America. In this report an
overview is provided on clinical presentation, etiology and
recovered microorganisms of liver abscesses in a general
hospital in the Netherlands.
Methods: All patients with a microbiologically proven
liver abscess during the period from December 1994
until December 2009 were included. Clinical, laboratory,
radiological, and microbiological data were systemically
collected and analyzed.
Results: A total of 35 patients (median age 69.5year; 63%
male) with an aspirated liver abscess (32 pyogenic (91%),
3 amoebic (9%)) were included. Frequently reported
symptoms in patients with pyogenic liver abscess at
presentation were fever or chills (72%) and abdominal
pain (66%). Twenty-one abscesses (60%) were solitary and
13 patients (40%) had multiple abscesses. The majority
of abscesses was right sided (43%), followed by multilocular (37%) and left sided (11%). The median size of the
largest abscess per patient was 7 cm (IQR 6-9 cm). The
most common etiologies of the abscesses were biliary
(31%) and diverticulitis (17%), while in 26% of cases
etiology remained unknown. Streptococcus species and
Escherichia coli were most frequently cultured, both in pure
cultures (resp. in 22% and 16% of patients), as well as in
mixed cultures (in 32% of patients). Resistance of microorganisms to amoxicillin clavunalate was found in cultures
of four patients (12%) and to combination treatment of
cefuroxime/metronidazole in three patients (9%) (two of
them were extensively pretreated with antibiotics).
Conclusion: Liver abscesses show large heterogeneity in
clinical presentation and microbiological culture results.
Streptococcus species and Escherichia coli are the most
common causative microorganisms in the setting of general
Dutch hospitals. In addition to drainage of the abscess,
empiric antibiotic treatment with cefuroxime/metronidazole seems an appropriate strategy, while resistance
occurs infrequently. These data support current Dutch
antibiotic guidelines for initial therapy of liver abscesses.
XIV. GASTRO-ENTEROLOGY CASE REPORTS
162. Systemic sclerosis complicated by pneumatosis coli
and intestinal perforation
M.C. van Veen, S.D. Kuiken
Sint Lucas Andreas Hospital, Department of Internal
Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the
Netherlands, e-mail: merkvanveen@hotmail.com
88
163. Amiodarone-induced hepatotoxicity eight years after
initation of therapy
Conclusion: Late hepatotoxity is a rare complication
of chronic amiodarone therapy. Regular liver enzyme
function testing remains warranted, even after years of
treatment.
J.G.P. Reijnders, S. Indhirajanti, A. Dees
Ikazia Hospital Rotterdam, Department of Internal Medicine,
Montessoriweg 1, 3083 AN ROTTERDAM, the Netherlands,
e-mail: jgp.reijnders@gmail.com
164. Pulmonary embolism in a patient with inflammatory
bowel disease (IBD), receiving adequate thrombosis
prophylaxis
Introduction: Hepatotoxicity is a relatively uncommon
side effect of amiodarone chlorhydrate, and, although
asymptomatic elevation of aminotransferases is reported
in up to a fourth of all patients, symptomatic hepatic
dysfunction occurs in less than 1% of the patients on
chronic amiodarone therapy.
Case: A 77-year-old man was referred for analysis of
slowly, progressive abnormal liver tests, which had started
15 months before. Medical history included mitral valve
plasty, and paroxysmal atrial fibrillation, which was
managed with initiation of fenprocoumaron and oral
amiodaron 200mg eight years before presentation. The
latter therapy had been complicated by type 2 painless
thyroiditis and persistent hypothyreoidy. There were only
complaints of long-term dyspepsia. He had no history of
jaundice, dark urine of pale stools, and denied alcohol
abuse or using any herbal or over-the-counter drugs.
He was a lean man without a family history of liver
disease. He had not received any blood transfusions.
On physical examination there were no signs of chronic
liver disease. Liver chemistries were abnormal: AST 171
U/l, ALT 191 U/l, alkaline phosphatase 115 U/l, GGT 259
U/l, bilirubin 9 mg/l, albumin 37 g/l, INR 3.7. Hepatitis
B and C serologies were negative, as were auto-immune
serologies. Serum Ig levels, ferritin, ceruloplasmin, and
a-1 antitrypsin were normal. Computed tomography of
the liver demonstrated no signs of liver cirrhosis or portal
hypertension, and no focal lesions, yet revealed a bright
texture of the liver, suggestive of diffuse liver fatty infiltration. Drug-induced hepatotoxicity with amiodarone
was considered as a possibility in view of the temporal
association of development of abnormal liver test values
after initiation of amiodarone, and the exclusion of other
causes of liver disease. Amiodarone was stopped, and
resulted in complete normalization of liver chemistries six
months after discontinuation of amiodarone.
Discussion: Amiodarone is a strong lipophilic compound,
which accumulates in tissue with high adipose content,
such as the liver. The latent period before aminotransferase
elevations develop, may vary from a few weeks to several
years, and probably reflects the time needed for drug
accumulation in the hepatocytes. Vice versa, because of its
long half life and huge volume of distribution, amiodarone
can persist in the liver for long periods after the drug is
stopped, and liver damage can thus progress despite drug
discontinuation.
L.H.A. Bonnie, A.J.G.H. Bindels, A.N. Roos
Catharina Hospital Eindhoven, Department of Intensive Care
Medicine, Michelangelolaan 2, 5623 EJ EINDHOVEN, the
Netherlands, e-mail: linda.bonnie@CZE.nl
Introduction: IBD patients are at increased risk for a
thrombo-embolic event, which should be prevented by
thrombosis prophylaxis.
We describe an IBD patient dying from a pulmonary
embolism, despite adequate prophylaxis.
Case report: A 68-year-old male was presented because
of fever, malaise and confusion. He had a medical history
of diabetes mellitus type 2, obesity and IBD, treated with
prednisone and methotrexate.
Physical examination showed a confused, dyspneic
man with an oxygen saturation of 90% without oxygen.
Laboratory findings were normal, except for signs of
inflammation (leukocytes 8.0 * 109/l (4,0-10,0 * 109/l),
CRP 110mg/l (< 6 mg/l)) and an elevated LDH (370 U/l
(150-300U/l)). Blood gas analysis showed a respiratory
acidosis with hypoxemia. A chest-X-ray showed bilateral
infiltrates. CT-angiography revealed diffuse alveolar
infiltrates without pulmonary embolism.
Patient was admitted to the ward; co-trimoxazole was
started under suspicion of a pneumocystis cariniipneumonia. The diagnosis was confirmed by a lavage and
cultures.
Three days later, patient’s condition deteriorated; he was
progressively confused, had low blood pressure, and was
respiratory insufficient. He was admitted to the ICU for
respiratory and hemodynamic support, antibiotics were
continued and standard ICU-care including prophylactic
dalteparine was started. During the following days, patient
slightly improved; inotropes were reduced and he was
weaned from the ventilator.
Eleven days after admission, CRP level and lactate
concentration were increasing, without a clear clinical
explanation. The next day, the clinical situation deteriorated progressively; patient had a high fever (40.7 °C)
and was hypotensive with poor peripheral circulation.
Fluid challenges were given and inotropes restarted.
Unfortunately, he remained hypotensive and bradycard,
and after all resuscitation had to be started. Despite
prolonged resuscitation, patient passed away.
89
treatment for recurrent cystitis. Discontinuation of the
drug caused an immediate fall in liver enzyme levels.
This major improvement after discontinuation of the drug
underlines the role of nitrofurantoine in the pathogenesis
of autoimmune hepatitis in this patient. We therefore
decided to refrain from corticosteroid treatment, taking
into account the posible side effects of long term immunosuppressive treatment. Our patient showed normalization
of liver values within three months after withdrawal of
nitrofurantoin.
Discussion: Nitrofurantoin is a commonly used antibiotic
in the treatment and prevention of urinary tract infections.
Although it is generally considered as a safe drug, hepatotoxicity occurs in 0.0003% of cases during long term use.
Different patterns of hepatotoxicity have been described,
including autoimmune hepatitis. It is postulated that drug
metabolites bind to cellular proteins which are susequently
recognized as neo antigens by the immune system.
Although corticosteroids are often used, withdrawal from
the drug alone can reverse the hepatic damage.
Conclusion: Nitrofurantoin induced autoimmune hepatitis
may resolve without immunosuppressive therapy.
The sudden clinical deterioration without overt explanation
gave reason to an autopsy; a massive pulmonary embolism
as the cause of death was found.
Discussion: Presence of IBD is associated with an
increased incidence of thrombo-embolic events, compared
to healthy subjects. The exact mechanism remains
unknown, but there is evidence of an altered haemostatic
situation. Also, it seems that tissue damage may lead to
simultaneous activation of both coagulation and inflammation. It is believed that factor Xa plays an important role
in this process. Inhibiting factor Xa may thus both reduce
the inflammatory response and the risk of thrombosis.
Literature is not informative about the incidence of
thrombo-embolic events in IBD patients using prophylaxis,
such as factor Xa-inhibitors. Therefore, it is difficult to
identify the optimal dose of thrombosis prophylaxis in
patients with IBD.
165. Autoimmune hepatitis triggered by nitrofurantoin;
recovery without immunosuppression
E.C. Gootjes, J.J.M. van Meyel, J. Veenstra
St Lucas Andreas Hospital, Department of Internal Medicine
and Gastroenterology, Jan Tooropstraat 164, 1061 AE
AMSTERDAM, the Netherlands, e-mail: e.gootjes@slaz.nl
166. A clinical manifestation of the Hepatopulmonary
Syndrome
Introduction: Autoimmune hepatitis is diagnosed based on
the presence of auto antibodies, total IgG levels and characteristic histopathological changes in the absence of viral
hepatitis. Immunosuppression is the first line of therapy.
Rarely, a toxic agent can be identified to be causative. We
present a case of autoimmune hepatitis, induced by long
term use of nitrofurantoin.
Case report: A 71-year-old woman was referred with
complaints of malaise, a raised erythrocyte sedimentation
rate (80 mm in first hour) and mildly elevated AST (82
u/l) and ALT (90 u/l). Previously she was diagnosed with
arthrosis, Raynaud syndrome and Sjögrens syndrome
and she was recently treated for cystitis. Besides eye
drops, she used esomeprazole and losartan/hydrochlorothiazide. She denied the use of alcohol. On physical
examination there were no diagnostic clues. Elaborate
laboratory testing did not show evidence of viral hepatitis
or storage disease. Autoimmune serology showed a positive
ANA (previously negative), but anti SMA, anti LKM and
anti SLA were negative. Levels of total IgG were elevated
(18 g/l). Imaging of the liver showed no abnormalities of
the liver parenchyma. As the liver enzyme levels further
increased (AST 252 u/l, ALT 274 u/l), a liver biopsy was
performed. The biopsy showed interface activity and
confluent necrosis compatible with autoimmune hepatitis.
Meanwhile, repeated careful questioning of the patient
revealed long term use of nitrofurantoin as prophylactic
S.M.C.H. Langenberg, D.M. Oude Hergelink,
M.J. Kerbert-Dreteler
Medical Spectrum Twente, Department of Internal Medicine,
Ariënsplein 1, 7511 JX ENSCHEDE, the Netherlands, e-mail:
s.langenberg@mst.nl
Introduction: There are no specific signs or symptoms
for the Hepatopulmonary Syndrome (HPS), although
abnormal oxygenation with dyspnea at rest and on exertion,
digital clubbing, spider naevi and cyanosis are strongly
suggestive for HPS. Diagnostic criteria for HPS are
liver disease with portal hypertension and/or cirrhosis,
pulmonary vascular dilatation (diameter 15-100 mm;
normal range 8-15 mm) and an oxygenation defect. Studies
show that, when diagnosed with HPS, the median survival
is 24 months and the 5-years survival rate is 23%. Liver
transplantation is the only treatment and shows a 5-years
survival rate of 76%.
Case report: a 70-years-old female with alcohol induced
liver cirrhosis was admitted because of hematemesis due
to esophageal varices grade 2. She also suffered from
dyspnea, especially in an upright position and on exertion.
Arterial blood gas analysis, breathing ambient air, showed
a severe oxygenation defect with a partial pressure of
oxygen of 56 mmHg (7.3 kPa) and an A-a gradient of
57 mmHg (7.4 kPa). X-ray computed tomography showed
no intrapulmonary abnormalities. Based on the history of
90
the patient, HPS was considered. In case of HPS, cut-off
values of abnormal oxygenation are a partial pressure
of oxygen < 80 mmHg (10.7 kPa) or an alveolar-arterial
oxygen gradient (A-a gradient) =15 mmHg (2.0 kPa)
breathing ambient air. The most practical and sensitive
way to detect pulmonary vascular dilatations and to a lesser
extend arteriovenous communications (shunts) is contrastenhanced echocardiography with agitated saline (shaken
to produce microbubbles > 10mm). In case of pulmonary
vascular dilatation, microbubbles opacification in the left
atrium occurs after three to six hearth beats. Contrastenhanced echocardiography in this case was positive
after five to six hearth beats. Administration of oxygen
relieved dyspnea and resulted in adequate oxygenation.
A classification of severity is vital because the severity
of HPS influences survival and is useful in determining
timing and risks of liver transplantation. Transplantation
in this case was considered and rejected, because of the
combination of severity of abnormal oxygenation, general
condition and age of the patient.
Conclusion: Although dyspnea in patients with portal
hypertension and/or cirrhosis can be due to other causes
such as anaemia, ascites, muscle wasting, hepatic
hydrothorax and/or chronic obstructive pulmonary disease,
HPS must be considered because of the consequences for
treatment.
be hepatic abscesses. An additional CT-scan showed two
liver abscesses of 8 cm and 3 cm in diameter, as well
as a thickened mucosa of the terminal ileum and the
suggestion of a Meckels diverticulitis. A Meckel-scan
showed no ectopic gastric acid production, which made
a Meckels diverticulum unlikely. A colonoscopy was
performed which showed an ileitis of (at least) the last 30
cm with ulcerations, and skip lesions matching Crohn’s
disease. Biopsies showed an active inflammation with
ulceration likely to be Crohn’s disease. Blood cultures
showed a Streptococcus intermedius. Faecal cultures
showed absence of protozoa and other bacteria. Treatment
consisted of antibiotics (Ceftriaxon and metronidazol)
initially intravenously and later on Ciproxin orally. At that
time no immune suppressive therapy was administrated.
The abscess size declined and the clinical condition of the
patient improved. After six weeks of antibiotic therapy
there was no evidence for an active infection and treatment
of Crohn´s disease was started with budesonide 9 mg and
Puri-Nethol 125 mg daily.
Conclusion: A liver abscess is a rare complication of
Crohn’s disease and it is even more seldom described as
the presenting symptom. The hypothesis of underlying
pathology is bacterial translocation across damaged
intestinal mucosa in Crohn’s disease followed by portal
bacteraemia.
167. A rare first presentation of Crohn’s disease
168. Freak of nature
J.W.G.M. Schreurs, M.E. Bartelink, M.A. van Herwaarden
Deventer Hospital, Department of Internal Medicine, Jan van
Arkelstraat 28, 8266 CN KAMPEN, the Netherlands, e-mail:
schreursjohn@live.nl
S. Boudewijns, C.M. Schweitzer, F.H.J. Wolfhagen
TweeSteden Hospital, Department of Internal Medicine, Dr.
Deelenlaan 5, 5042 AD TILBURG, the Netherlands, e-mail:
steve_boudewijns@hotmail.com
Introduction: A liver abscess is either an amoebic abscess
or an pyogenic abscess. However, only 7% of the pyogenic
liver abscesses are due to portal bacteraemia. A hepatic
abscess is a rare complication of Crohn’s disease, and
has to our knowledge only 3 times been described as the
presenting symptom in the last decades.
Case report: A previously healthy 43-year-old, male with
a history of two gastric bleedings was admitted to the
gastro-enterology ward with abdominal pain in the right
upper quadrant, fever, chills and anorexia for 3 days.
There were no symptoms of nausea, vomiting or changed
bowel habits. On physical examination temperature was
39.60C and there was slight tenderness in the upper
abdominal region without organomegaly. Laboratory
examination showed leukocytes of 33.5/nl, C-reactive
protein of 237 mg/l, normal electrolytes and renal function,
bilirubin 35/17 umol/l, Alkaline Phosphatase 208 U/l,
GGT 93 U/l, ASAT 40 U/l, ALAT 57 U/l, LDH 236 U/l.
Ultrasound examination showed two lesions suspect to
Introduction: Dysphagia is a frequently reported complaint
and has different causes. A thorough analysis is necessary
to achieve a correct diagnosis and appropriate therapy. We
report on a young woman with dysphagia and weight loss.
Case report: A 23-year-old woman, with a history of ADHD
and morbus Osgood-Schlatter, presented with dysphagia
and twelve kilograms loss of weight. She had trouble
swallowing food since a couple of months. Liquids had
not been a problem. She had been using methylphenidate
since 6 months. Physical examination was unremarkable
except for extreme nausea during palpation of the neck.
Laboratory results were all within the normal range and
an esophagogastroduodenoscopy was normal. At first a
barium swallow showed no pathology of the oesophagus
or stomach. Manometry of the oesophagus showed a
high-pressure zone with pulsations in the proximal
part of the oesophagus. This raised the suspicion of
compression of the oesophagus by an arteria lusoria, which
was confirmed by CT-scan. So, most likely the patient
91
deficiency. The test results for lysosomal storage diseases
were inconclusive. Histological examination of a liver
biopsy identified a normal liver. Finally, extensive revision
of the sagittal and coronal images of the CT scan revealed
a marked enlargment of the right liver lobe typical for a
Riedel’s lobe.
Riedel’s lobe is a tongue-shaped projection of the liver
from the inferior surface of the right lobe. It is a normal
anatomical variant and seen most frequently in women.
The lobe may be quite large, sometimes extending into the
right iliac fossa, and so, can be easily mistaken for pathological enlargement of the liver.
suffered from dysphagia lusoria. In retrospect the barium
swallow showed a possible compression of the proximal
oesophagus. Because of her severe complaints the patient
was presented to a vascular surgeon for reconstruction of
the vascular anatomy.
Discussion: Dysphagia secondary to extrinsic esophageal
compression by an aberrant right subclavian artery (arteria
lusoria) is known as dysphagia lusoria. David Bayford
first described it in 1794, and called it ‘lusus naturae’,
meaning ‘freak of nature’. The aberrant right subclavian
artery arises from the dorsal part of the aortic arch.
It is a relatively common congenital anomaly, with a
prevalence of up to 1,8%. This may be asymptomatic, but
symptoms varying from mild to severe dysphagia have
been reported. Usually a barium swallow reveals the
abnormality and sometimes it is seen with endoscopy.
Diagnosis is confirmed by CT-thorax or MR angiography.
Therapy depends on the severity of the symptoms. In some
cases dietary changes are sufficient, whereas in more
severe cases surgical transposition of the aberrant artery
is necessary. The results of surgical intervention are good
with relief of symptoms in nearly all patients.
Conclusion: An arteria lusoria as most likely cause of
dysphagia is described. Usually, an arteria lusoria is
discovered by a barium swallow investigation, but in this
case it was detected by manometry of the oesophagus.
Manometry may reveal unexpected and uncommon causes
of dysphagia.
2 mm skin biopsies from the eschars of all four patients.
Results were known within one week, where as positive
serology was not obtained until several weeks after patients
had completely recovered.
Conclusions: ATBF should be considered in travellers
returning from South Africa with (sub)febrile illness and
multiple skin lesions. The diagnosis can be confirmed by
(paired) serology, however PCR and sequencing on skin
biopsies could be a (better) alternative confirmatory test.
This will have to be validated in larger studies. Advantages
of molecular methods over serology are exact determination of the infectious agent and the timeframe within
which the diagnosis can be confirmed.
weeks with good clinical response. He was switched to oral
maintenance therapy with itraconazole and highly active
antiretroviral treatment was initiated.
Discussion: Sporotrichosis is caused by the dimorphic
fungus Sporothrix schenckii and is a rare invasive mycosis.
The fungus usually grows in decaying material, soil, or
hay. History usually reveals trauma to the skin, which
causes direct inoculation of the conidia (spores) into the
wound. Ulcerative nodules in the draining lymph-tract
are usually seen, but in immunocompromised patients
hematogenic dissemination can occur with meningeal,
osteoarticular, pulmonary, visceral, and rarely other
organ involvement. Presumably our patient also had
laryngeal infiltration. Diagnosis is based on culture and
microscopy of material obtained from involved tissue
sites. Histopathologic examination of tissue biopsies is
not sensitive nor specific, but can help to rule out other
pathology. There are no randomised studies addressing
treatment of disseminated sporotrichosis. Guidelines
recommend to start with lipid formulations of intravenous
amphotericin b and switch to oral itraconazole for
long-term maintenance therapy. In patients with persisting
immunosuppression, lifelong suppressive therapy with
itraconazole is advocated.
XV. INFECTIOUS DISEASES RESEARCH
XVI. INFECTIOUS DISEASES CASE REPORTS
170. Diagnosis of African tick-bite fever infection in
travellers returning from South-Africa
J.W.R. Hovius1 , R.W. Wieten 1, E. Tijsse-Klasen 2 ,
H. Sprong2, M.C. Beersma3, M.P. Grobusch1
1
Academic Medical Centre, Department of Internal
Medicine, Bilderdijkkade 31 II, 1053 VH AMSTERDAM,
the Netherlands, e-mail: j.w.hovius@amc.uva.nl, 2RIVM,
BILTHOVEN, the Netherlands, 3Erasmus Medical Centrum,
ROTTERDAM, the Netherlands
169. Too large but normal – Riedel’s lobe
Introduction: African tick-bite fever (ATBF) is frequently
diagnosed in travellers returning from South Africa. It
is the only tick-transmitted rickettsiosis in which several
inoculation eschars are observed in a high proportion
of cases. AFTB is caused by Rickettsia africae, a gramnegative bacterium, belonging to the spotted fever group
of Rickettsiae. The principal vectors for ATBF in southern
Africa are Amblyomma hebraeum ticks. The diagnosis is
based on the travel history and clinical presentation, but
is confirmed by detecting antibodies in serum against
Rickettsiae of the spotted fever group. However, these
serological tests have major shortcomings. Antibodies
typically occur late in the course of the disease and early
antibiotic treatment or a mild course of the disease can
diminish antibody production.
Methods and results: Here, we describe four male travellers
that presented with (sub)febrile temperature and multiple
skin lesions several days after returning from SouthAfrica. They were suspected of having contracted African
tick-bite fever. As we expected initial immunofluorescence
assays yielded no IgM/IgG antibodies directed against
Spotted Fever Rickettsiae. However, Rickettsia africae DNA,
using two independent polymerase chain reactions (PCRs,
i.e. and confirmed by sequencing, was amplified from
M. Kok, S. Lobatto, S.A. Luykx-de Bakker
Tergooi Hospitals, Department of Internal Medicine, Van
Riebeeckweg 212, 1213 XZ HILVERSUM, the Netherlands,
e-mail: kokmarleen@hotmail.com
Case: A 61-year-old woman without a significant medical
history was referred to our outpatient department with
hepatomegaly. The hepatomegaly was discovered over ten
years ago during a routine check-up. Besides a chronic
vague abdominal pain in the right upper quadrant,
the patient reported no medical problems. There was
no history of alcohol abuse and she did not take any
medication or supplement. On physical examination the
liver was palpable over 5 cm under the costal margin. No
icterus, stigmata of liver disease or signs of splenomegaly
or heart failure were present. Laboratory investigations
showed mildly elevated transaminases and gammaglutamyltransferase. Abdominal ultrasound and CT-scan
showed an enlarged liver extending into the right pelvis but
no further abnormalities. Additional biochemical investigation excluded viral and auto-immune causes, as well as
Wilson’s disease, hemochromatosis, alpha-1-antitrypsin-
92
171. Full of fungi
J.C. Dutilh1, E. de Barra2, J.J. Taljaard3
1
University Medical Centre Utrecht, Department of Internal
Medicine, Heidelberglaan 100, 3584 CX UTRECHT, the
Netherlands, e-mail: j.c.dutilh@umcutrecht.nl, 2Galway
University Hospital, GALWAY, Ireland, 3Tygerberg Academic
Hospital, KAAPSTAD, South Africa
172. Als de kat van huis is…
M.M.C. Lambregts, P.H. Rothbarth, M.B. Crijns, S. Anten,
N.M. Delfos
Rijnland Hospital, Department of Internal Medicine, Simon
Smitweg 1, 2353 GA LEIDERDORP, the Netherlands, e-mail:
merel_lambregts@hotmail.com
Introduction: Sporotrichosis is an invasive mycosis caused
by Sporothrix schenckii and is endemic in large parts
of Central- and South America and Africa. In severely
immunocompromised patients it can cause disseminated
disease.
Case: A 31-year-old HIV-positive man was referred to
Tygerberg Academic Hospital (Cape Town, South-Africa)
by a primary care facility with skin lesions. His CD4
count was 18 cells per cubic millimeter. He worked as a
construction worker and had been receiving antituberculous therapy for several months for pulmonary tuberculosis. The skin lesions had developed over a period of
three months. There were multiple painless, ulcerative,
and nodular lesions in the face, on the trunk, and on the
extremities. Three weeks prior to admission he developed
dysphonia. At presentation he was afebrile and not acutely
ill. On examination a swollen proximal interphalangeal
joint was noted on his right middle finger. X-ray of this
finger showed a lytic lesion with interruption of the cortex.
Laryngoscopy revealed ulcerating granulomas on the vocal
cords. A skin biopsy showed granulomatous inflammation.
A Ziehl-Neelsen-stain was negative and PAS-stain with
diastasis sporadically showed fungal conidia. Culture of
the skin biopsy grew Sporothrix schenckii. The patient
was treated with amphotericin b intravenously for two
Case: A 35-year-old woman presented with fever and a
crusting ulcer on her chest. The lesion occurred a few
weeks earlier when a vesicular eruption developed and
progressed to a brownish crusting ulcer with vesicles
on the borders followed by cellulitis and painful axillary
lymfadenopathy.
Recently, she had bought kittens at a nearby flowerfarm
and had frequently held them to her chest, petting them.
Since one of the kittens had contracted a skin disease, she
consulted a veterinarian. The cat was successfully treated
for a presumed bacterial and fungal infection, without
further testing. Other animal contacts were not reported.
Gram-stain and culture of the lesion were negative,
probably due to prior antibiotic treatment. While awaiting
further results the cellulitis improved on a regimen of
amoxicillin/clavunalate and ciprofloxacin for suspected
secondary bacterial infection or cat scratch disease.
Eventually cowpox virus was cultured from the lesion,
and confirmed by polymerase chain reaction (PCR). We
concluded that the patient was infected with the cowpox
93
virus by her kitten leading to a single skin lesion followed
by a secondary infection with common cellulitis.
Discussion: Cowpox virus is a DNA virus, part of the
orthopoxvirus family, as is smallpox. The name cowpox
historically originates from dairymaids getting infected
through infected teats of cows, which ultimately led to
the smallpox vaccine. Today, cowpox is a rare disease in
humans. However, the Netherlands have a relatively high
and rising prevalence, mainly affecting young people. This
can probably be attributed to the fact that routine smallpox
vaccination was abandoned in 1976 because of global
smallpox eradication.
Despite the name, most cowpox-infections are transmitted
by domesticated cats and mice. Rodents, but not cows, are
the reservoir hosts of cowpox virus. The kitten in this case
probably got infected by hunting voles. The incubation
period is 10-14 days, starting with localized vesicolopustular lesions at the site of contact, mostly the hands and
lower arms. After days to weeks the lesions ulcerate and
a crust develops. Secondary bacterial infection with local
lymphadenopathy is common.
The combination of a typical history and skinlesion should
raise suspicion of cowpox virus. However, other zoonotic
infections, particularly other orthopoxvirussen, parapoxvirussen and catscratch disease, may produce resembling
lesions. The disease is self-limiting in otherwise healthy
individuals. However, secondary lesions and generalized
eruption may occur in immunocompromised patients and
in patients with skin diseases.
Discussion: Rat bite fever, caused by Streptobacillus moniliformis, is characterized by fever, polyarthralgias and a rash.
The rash may appear petechial, purpuric or maculopapular, sometimes with hemorrhagic vesicles. The rash is
seen on the extremities, especially the hands and feet. Rat
bite fever typically follows a rat bite, but can also occur after
the ingestion of food or water that has been contaminated
with rat excrement. S. monilliformis is a Gram-negative
bacillus and is almost the exclusive cause of rat bite fever
in the United States and Europe. Spirillum minus can
also cause rat bite fever and accounts for most cases in
Asia. The incubation period of S. moniliformis-associated
rat bite fever ranges from 3 days to over 3 weeks, but is
in most cases less than 7 days. The mortality rate is 13%
when untreated and causes of death include endocarditis,
pneumonia and overwhelming sepsis. The differential
diagnosis include Lyme disease, Rickettsial infections,
Leptospirosis, secondary Syphilis, Meningococcemia
and sepsis from Staphylococcus aureus and Streptococcus
pyogenes. Diagnosis is made by culture of blood or synovial
fluid. Streptobaccillus requires culturing on enriched
media. Penicillin is the treatment of choice for 14 days. For
penicillin-allergic patients tetracyclines are also effective.
Conclusion: Rat bite fever should be considered in any
patient with a clinical triad of fever, arthralgias and a rash,
especially patients who are exposured to rats.
173. Rat bite fever
N. Josephus Jitta, B.M. van der Oord
Meander Medical Centre, Department of Intensive Care Unit,
Utrechtseweg 160, 3818 ES AMERSFOORT, the Netherlands,
e-mail: n.josephusjitta@gmail.com
174. A skin infection in an immunocompromised
patient – don’t miss odd pathogens!
M. Ezzahti, A.J.W. Kluytmans, I.M. Kuijpers, J.B. Heijns
Amphiahospital, Department of Internal Medicine,
Molengracht 21, 4818 CK BREDA, the Netherlands, e-mail:
ezzahti00@hotmail.com
Introduction: We present an immunocompromised patient
with a skin infection: a common combination, but caused
by an uncommon pathogen.
Case: A 79-year-old man was admitted to our ICU, after
initial presentation at the emergency ward. His medical
history included COPD and chronic kidney disease stage
3. Under suspicion of polymyalgia rheumatica, he had been
using steroids (prednisone 15 mg daily) for over five years.
A few hours before presentation he developed pain in his
left leg, later he noticed some redness. During the next
hours the pain increased and redness expanded. At presentation the patient was clearly in pain, his hemodynamics
were stable and his temperature was 37 °C. We noticed a
sharply demarcated rash, covering his left leg and the calf
of his right leg. During his stay at the emergency ward,
the redness rapidly expanded and the patient became
somnolent. He was treated with cefuroxim and gentamycin
(local protocol for sepsis of unknown origin), which was
Case: A 48-year-old man with no medical history presented
with a two-day history of fever, arthralgias and a pustular
rash. The man was bitten two weeks before by his pet rat
on his left thumb. On physical examination the blood
pressure was 136/80 mmHg, his heart rate was 108 beats/
min and the temperature was 38,6 °C. The patient had a
pustular rash on his palms of his hands and soles of his
feet. Further physical examination was unremarkable.
Lab results showed a CRP of 248 mg/l, leukocytes of 16,2
x 109/l and a normal renal function. Blood cultures were
negative. Streptobacillis moniliformis was identified from a
culture of a pustule on his left hand. A diagnosis of rat bite
fever was made. The patient was treated with amoxicillin/
clavulinic acid 1 week intravenously and 1 week orally. The
patient recovered completely.
94
shortly followed by penicillin and flucloxacillin (local
protocol for erysipelas). The patient was admitted to our
ICU. We continued penicillin and started clindamycin.
Under suspicion of necrotizing fasciitis, we performed a
biopsy of the fascia of his left calf. Surprisingly, Gram stain
was negative. During the next hours he patient’s condition
improved and the rash didn’t expand anymore.
After being stable for 24 hours, the rash expanded again
till it covered all four limbs, but the patient remained
otherwise stable. Blood cultures were negative. After 36
hours the biopsy showed grow of Pseudomonas Aeruginosa.
Pathological examination of the biopsy wasn’t typical
of fasciitis, but was more consistent with cellulitis.
Ceftazidim was started, combined with clindamycin,
because we couldn’t exclude coinfection with S. Pyogenes.
The rash gradually improved.
The patient slowly recovered. He was discharged from the
hospital after one month.
Discussion: We present a 79-year-old immunocompromised patient with a severe cellulitis, caused by P.
Aeruginosa. P. Aeruginosa is an aerobic, Gram negative
bacillus. It is a common pathogen in immunocompromised patient. P. Aeruginosa usually causes infections of
the respiratory or urinary tract, or infections of the eyes
or ears. Both fasciitis and cellulitis are rare. Cellulitis,
caused bij P. Aeruginosa usually presents with necrotic skin
ulcerations. In our patient, we saw a very painful, sharply
demarcated rash on both legs, which rapidly progressed,
and seemed to be more consistent with necrotizing
fasciitis.
not disinfected. Five days later, the patient developed fever
and progressive pain and swelling of the right shoulder,
which she could barely move.
At hospital admission, the patient was febrile (39.0 °C).
Blood pressure was 124/65 mmHg, heart rate 106 beats
per minute and respiratory rate 28 breaths per minute.
Physical examination revealed no heart murmurs,
abnormal lung sounds or petechiae. Her right shoulder
was swollen without redness, tender to palpation and
extremely painful to all active and passive movements.
The dorsal side of her right foot showed a small lesion that,
according to the patient, had been caused by the recent
acupuncture treatment. Laboratory investigation showed a
markedly raised C-reactive protein level (304 mg/l), without
leukocytosis. X-ray and ultrasound examination of the right
shoulder showed no abnormalities. A shoulder punctate
showed clear synovial fluid. After taking blood cultures,
the patient was treated with cefuroxim intravenously. Two
days later, she developed hypoxia. A chest-CT showed
large bilateral infiltrates. The presence of hematogenic
pneumonia was considered.
At that time, Staphylococcus aureus grew in multiple
blood cultures and the culture of the shoulder punctate.
Thereupon, the antibiotic regimen was switched to
flucloxacillin intravenously for three weeks. Ultrasound
investigation of the heart showed no signs of endocarditis.
She recovered gradually. The right shoulder improved
slowly with physical therapy. Two months later, she had
still not regained full function of her right arm.
Conclusion: Sepsis is a rare, but potentially fatal complication of acupuncture. The effectiveness of acupuncture
for the treatment of CFS is not proven.
175. An uncommon cause of Staphylococcus aureus
sepsis
176. An abdominal emergency
M.L. Maas, P.C. Wever, A.W. Plat, E.K. Hoogeveen
Jeroen Bosch Hospital, ’s-Hertogenbosch, Department of
Internal Medicine, Tolbrugstraat 11, 5211 RW ’s-HERTOGENBOSCH, the Netherlands, e-mail: m.maas@jbz.nl
C.S. Ootjers, M.J.F.M. Janssen, A.M. Schrander-van de Meer,
M.K. Vu
Rijnland Hospital, Department of Internal Medicine, Simon
Smitweg 1, 2353 GA LEIDERDORP, the Netherlands, e-mail:
claudia.ootjers@gmail.com
Introduction: Acupuncture is increasingly used to treat
a variety of conditions such as chronic fatigue syndrome
(CFS), for which there is no proof of effectiveness.
Therefore, it is important to establish whether its potential
benefits outweigh its risks. The risk of a serious adverse
event with acupuncture is estimated to be 0.05 per 10.000
treatments. We report a case of Staphylococcus aureus sepsis
due to acupuncture.
Case: A previously healthy 48-year-old woman was
admitted to hospital because of fever and severe pain of the
right shoulder since two days. A week before admission,
she had received acupuncture treatment for CFS. Sterile
needles had been inserted into the skin of her head,
shoulders and feet. With standard acupuncture, the skin is
Introduction: Atraumatic splenic rupture is a rare event
that has been associated with several infectious disease
processes and that requires immediate diagnosis and
prompt surgical treatment to ensure patient’s survival.
Case report: A previously healthy 55-year-old male
presented to the emergency department with fever and
chills since 5 days, without localizing signs. He collapsed
during his visit to the general physician earlier that
evening. Examination demonstrated beside fever and
hemodynamic instability minimal tenderness to palpation
over the left lower quadrant of the abdomen without
rebound or guarding. The remainder of his physical
95
fever. The pain was sharp and worsened on mobilization.
He had no diarrhea, and the stools appeared normal.
No family members were sick and there was no history
of a recent travel. He had a slightly productive cough
with white mucus. We saw an ill looking patient with a
temperature of 39 °C and a heart rate of 100/min. There
was a normal peristalsis and defense musculaire especially
around McBurney, with direct and rebound tenderness.
Laboratory findings: leukocytes 19.6 x 109/l and CRP
181 mg/l, normal liver and kidney functions. Ultrasound
was inconclusive. Because of clinically high suspicion on
appendicitis, an exploratory laparoscopy was performed.
A normal appendix was found. Further exploration of the
abdomen did not reveal another cause for the pain. After
surgery fever continued and an abdominal abscess was
suspected. On abdominal CT scan no abscess was found,
however, in the upper slice an empyema in the right lower
pulmonary lobe was seen. Culture of the pus was positive
for Staphylococcus aureus sensitive for flucloxacilline.
After drainage and antibiotic treatment the patient fully
recovered and was released one month after admittance.
Discussion: Although on physical examination an acute
abdomen was apparent, the relatively high levels of
infection parameters, temperature and the cough were a
clue that something else could be wrong. A chest X-ray
should have been made. Then adequate therapy could have
been started sooner, without an unnecessary operation.
Conclusion: Although every physician should know that
abdominal pain and fever may have a thoracic origin,
this case illustrates that in clinical practice there is not
always attention for this relationship. It can not be stressed
enough that especially pneumonia and pleural empyema
may present as an acute abdominal problem.
examination was unremarkable. Laboratory investigation
revealed pancytopenia (hemoglobin 6.9 mmol/l, leucocytes
3.9 mmol/l with 40% immature neutrophils; Platelet count
82 x 109/l) and increased C-reactive protein of 65. Chest
radiography and urine analysis were normal.
Because hemodynamic instability remained, despite
adequate resuscitation measures taken in the emergency
department, the patient was taken to the Intensive Care
Unit (ICU) for optimal support. Cefuroxime, gentamicin
and metronidazole was started on empirical base. During
his stay on the ICU the hemodynamic instability remained
and his abdominal pain increased with signs of peritonitis.
An abdominal focus of sepsis seemed most likely and
a CT-scan of the abdomen was performed on which a
diagnosis of atraumatic splenic rupture was ultimately
suspected. After exploratory laparotomy with confirmation
of multiple ruptures, splenectomy was performed, and the
patient made a full, uneventful recovery. Histopathologic
examination revealed increase of neutrophilic granulocytes
(consistent with sepsis), with bleeding and multiple ruptures
of the capsule. Results for serologic testing over the patient’s
hospital course and after discharge were negative.
Conclusion: Atraumatic splenic rupture is a rare event that
may lead to life-threatening hemorrhage if not diagnosed
and treated quickly. Although the infectious organism
which caused the sepsis of the patient’s case remains
unknown, atraumatic splenic rupture has been associated
with a variety of infectious diseases. Increased awareness
of atraumatic splenic rupture as a possible complication
of various infectious disease processes can enhance early
diagnosis and effective treatment.
177. Acute abdomen; not always appendicitis
J.E.M. Mellema, V. Mattijssen
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815AD ARNHEM, the Netherlands, e-mail:
liesbeth.mellema@hotmail.com
178. Abiotrophia defectiva: a very rare cause of
spondylodiscitis
J.B. van der Net, A.P. Rietveld, M. Castro Cabezas,
R.G. Wintermans, P. de Man1
Sint Franciscus Gasthuis, Department of Internal Medicine,
Zestienhovensekade 501, 3043 KT ROTTERDAM, the
Netherlands, e-mail: j.vandernet@sfg.nl
Introduction: Appendicitis is the most common cause for
acute abdomen. About 10-20% of patients operated because
of appendicitis eventually, are diagnosed otherwise. False
positive results are acceptable because of the severe complications of a perforated appendix, compared to the low
morbidity and mortality of an appendectomy. Anamnesis
and physical examination are as always, the cornerstones
of evaluating a patient. The next case report illustrates one
of the pitfalls in evaluating a patient with abdominal pain.
Case report: A 43-year-old man with no known medical
history was admitted to the emergency department with
abdominal pain which started about five days before,
located in the right lower quadrant and umbilical region.
He also had cold chills, nausea, vomiting, anorexia and
Introduction: Spondylodiscitis (or vertebral osteoarthritis) is an infection of the spinal vertebrae and the
adjacent intravertebral disc space. In developed countries
Staphylococcus aureus is the main cause. Here, we report a
very rare cause of spondylodiscitis.
Case report: A 46-year-old man with a history of hypertension was admitted to our hospital because of lower back
pain and abdominal pain in the lower left quadrant, which
had existed for three days and was worse at night. The pain
began gradually and progressively worsened. Because of the
96
back pain he had been bedridden for two days. There were
no signs of urinary tract infection. His stool was normal
en he did not have fever. There was no muscle weakness
or sensory change. On physical examination, there were
no remarkable findings, apart from local tenderness in the
lower left abdomen. There was no tenderness with palpation
or percussion of the spine. Laboratory results showed an
elevated C-reactive protein and an elevated leukocyte count
with immature bands. CT-scanning of the abdomen showed
no remarkable intra-abdominal findings, but did show a
degenerative aspect of the lumbar spine. An MRI of the
lumbar spine showed spondylodiscitis of L2-L3. The gram
stain of blood cultures showed gram-positive pleomorphic
bacterial growth, both coccoid and rod shaped. Some of
the rod-shaped forms had a central bulb. In expectation of
the definitive determination, our patient was treated with
amoxicillin intravenously. Aerobic and anaerobic growth
was very slow and poor. Biochemical identification with
the VITEK system (Biomerieux) revealed Abiotrophia, a
finding consistent with the gram stain, and poor growth.
Later, 16S rRNA sequencing confirmed that our isolate was
an Abiotrophia defectiva (A. defectiva) strain. Therapy was
switched to oral rifampicin and clindamycin for a total of
six weeks. There was considerable destruction of the lumbar
spine. Therefore, a brace was prescribed to reduce the pain
and stabilize the spine. Repeated transesophageal echocardiography did not reveal any sign of endocarditis.
Discussion: A. defectiva is part of the normal flora of the
intestinal and urogenital tract and is a very rare cause of
endocarditis. There are only a few case reports in literature
showing spondylodiscitis caused by A. defectiva, but all
secondary to endocarditis. To our knowledge, this case
report is the first to show spondylodiscitis caused by A.
defectiva, without signs of endocarditis.
pain and progressively loss of memory since three months.
Physical examination upon admission showed a man
normal habitus with a weight of 55 kg. His blood pressure
was 130/65 mmHg, pulse rate 70 beats/min and body
temperature 36.5 °C. There were no enlarged palpable
lymph nodes in the neck, supraclavicular, axillar or
inguinal. Auscultation of lungs and heart was normal.
Palpation of the abdomen revealed no abnormalities.
Neurological examination was normal. Laboratory investigation showed a microcytic anaemia with reduced serum
iron, transferrin and ferritin. Electrolytes, renal function
and liver tests were within the normal limits. Faecal fat
analysis demonstrated steatorrhoea: 5.4 g/24 h stools
and stool culture was normal. Chest X-ray showed mild
pleural effusion without other abnormalities. Abdominal
CT showed enlarged lipoid mass along the mesenteric
veins. Gastroduodenoscopy showed macroscopic
duodenitis and duodenal biopsies showed increased
histocytic macrophages laden with PAS-positive globulin,
without signs of malignancy or mycobacterial infection.
Cerebrospinal fluid obtained by lumbar puncture showed
a elevated protein level (0.46 g/l). Examinations of cell
pellets obtained by cytocentrifugation of CSF samples were
positive for PAS staining. Polymerase chain reaction testing
of the CSF was positive for Tropheryma whipplei resulting
in strong evidence of neuro-WD. Brain magnetic-resonance
imaging showed minimal loss of cerebral and cerebellum
tissue. Our patient was treated with intravenous ceftriaxone
(2 g daily) for two weeks and followed by oral co-trimoxazole
(trimethoprim plus sulphamethoxazole, 960 mg twice per
day) for at least one year. During antibiotics therapy patient
showed complete resolution of complaints together with
reversibility of cognitive impairment.
Conclusion: WD should be considered in any patient with,
diarrhoea, fever, malabsorption, weight loss, abdominal
pain or lymphadenopathy. CNS involvement may occur and
the prognosis for patients with neurological signs remains
poor. If the diagnosis is considered, this condition can be
readily diagnosed and shows good clinical response with
long-term antibiotics.
179. A patient with Neuro-Whipple’s disease
F.M.F. Alidjan, T. Seerden, B. Veldhuijzen
Amphia Hospital, Department of Internal Medicine,
Molengracht 21, 4800 RK BREDA, the Netherlands, e-mail:
falidjan@amphia.nl
180. The great pretender strikes again
Introduction: Whipple’s disease (WD) is a systemic disease
caused by a gram-positive bacterium, Tropheryma whippelii.
Although the first descriptions of the disorder described a
malabsorption syndrome with small intestine involvement,
the disease also affects the joints, cardiovascular system, and
central nervous system(CNS). CNS involvement may be silent
and its clinical expericience is sparsely reported. We report
a 68-year-old male with WD with involvement of the CNS.
Case: A 68-year-old man without a medical history was
admitted at our hospital with nonbloody diarrhoea, loss of
appetite, weight loss of ten kilogram, diffuse abdominal
Y. Eling, A.I.M. Hoepelman, D.J. Hijnen, V. Sigurdsson,
J.E. Arends
Utrecht University Medical Centre,Department of Internal
Medicine and Infectious Diseases, PO Box 85500, 3508 GA
UTRECHT, the Netherlands, e-mail: y_eling@hotmail.com
Introduction: Syphilis is a sexually transmitted disease
caused by the spirochete Treponema pallidum often seen
in men who have sex with men and shows a high rate of
HIV co-infection. We describe a patient with a very rare
97
Case: A 72-year-old female patient suffered from
arthralgias and arthritis for ten years. Analysis by rheumatologist, neurologist and internist did not led to a definite
diagnosis. Due to anaemia, increased ESR and substantial
weight loss multiple gastroduodenoscopies and colonoscopies were performed, but no explanatory macroscopic
abnormalities were observed. During these procedures
mucosal biopsy specimens were harvested, which did not
reveal histologic abnormalities. As part of a scientific study
in the analysis of intestinal microbiota, mucosal biopsy
specimens were subjected to a specific real-time qPCR
targeting an exclusive, repetitive sequence of T. whipplei.
Periodic acid schiff (PAS) staining of stored mucosal
biopsy specimens from both duodenum and colon showed
purple-stained foamy macrophages in the lamina propria.
Subsequently, patient underwent gastroduodenoscopy
with harvesting of mucosal biopsy specimens from the
duodenum. No histological abnormalities were observed,
with PAS-staining being negative. Nonetheless, qPCR was
positive for T. whipplei DNA. In addition, due to low back
pain for years with radiation to the right leg, suspicion of
infectious spondylodiscitis aroused. Therefore, an MRI
of the spinal column was performed which showed signs
of discitis localized at L2-L3. Bone biopsy from L2 was
harvested, in which no histological abnormalities were
present including negative PAS-staining. However, T.
whipplei DNA was detected by qPCR.
To exclude presence of T. whipplei in the cerebrospinal
fluid, lumbal puncture was performed, and proved to be
negative for T. whipplei DNA. Since convincing evidence
for Whipple’s disease was present, including an infectious
(spondylo)discitis but without central nervous system
involvement, patient received intravenous ceftriaxone for
two weeks, followed by trimethoprim-sulfamethoxazole
twice daily for a year.
Currently, situation of the patient has clinically improved
significantly with weight gain of 15 kg in five months and
absence of arthralgias. However, radiating pain persisted
because of which she is currently being treated by a
neurosurgeon. Obviously, not only CNS involvement could
lead to irreversible damage, but also the consequences of
spondylodiscitis due to T. whipplei infection.
In this case the coincident diagnosis of T.whipplei infection
as part of a scientific study led to accurate treatment of this
potentially lethal disease.
manifestation of syphilis which was initially misdiagnosed.
The incidence is increasing in the Netherlands from 250
cases in 2005 to 512 diagnoses in 2009 in STD clinics.
Case: A 34 year old homosexual man diagnosed with
HIV in 2009 and a normal CD4 count and no current
cART developed multiple nodular and ulcerative skin
lesions in a course of two weeks. Several weeks before
developing the lesions he experienced an episode of
fever in combination with chills. Shortly afterwards
several purple nodules appeared that progressed into
well demarcated ulcerations some covered by a dark
crust and others with necrotic material. His general
physician suspected a bacterial infection and started
a course of flucloxacillin, though promptly hereafter
new lesions formed. Laboratory studies revealed a slight
normocytic anemia and normal white blood cell counts
with a normal differentiation. The erythrocyte sedimentation rate was 75 mm/hour and C-reactive protein
was 18 mg/L. Liver and renal functions were normal.
A skin biopsy taken from the inside of the left thigh
showed hyperkeratosis of the epidermal layer. The upper
dermal layer revealed an increased vascularisation and
the lower dermal layer was characterized by leucocytoclasia and lymphohistiocytic infiltration, suggesting an
infectious etiology. Immunohistochemistry for HHV8
and spirochetes were however negative as were bacterial
cultures and PCR’s for Bartonella and mycobacteria. The
serum VDRL was positive (1:64) as was the CLIA for
Treponema pallidum and confirmation via Trepnonema
pallidum immunoblot having previously tested negative.
The diagnosis of secondary syphilis in the form of a
nodulo-ulcerative syphilis was made and the patient was
administered intramuscular penicillin-G. At a subsequent
visit one month later the patient showed significant clinical
improvement.
Discussion: Nodulo-ulcerative syphilis or lues maligna
is a form of secondary syphilis characterised by papules,
plaques as well as nodules which tend to ulcerate. Typically
the face is involved and contrary to other forms of secondary
syphilis the palms and soles are spared. Although this is a
rare presentation of a well known disease, due to the ever
increasing incidence of syphilis especially in the MSM
population it is yet again an entity to be reckoned with by a
disease known as the great pretender.
181. Science saved her life: diagnosis of severe T.whipplei
infection by coincidence
182. Acute abdominal pain as first sign of severe varicella
zoster in the immunocompromized patient
M.E. Grasman, A.M. Pettersson, N. Rabelink,
P.H.M. Savelkoul, A.A. van Bodegraven, E.A. bij de Vaate
VU Medical Centre, Department of MDL, De Boelelaan
1118, 1081 HV AMSTERDAM, the Netherlands, e-mail:
thijsgrasman@hotmail.com
A.H.W. Bruns, H.J. Bloemendal, R. Fijnheer
Meander Medical Centre, Utrechtseweg 160, 3818
ES AMERSFOORT, the Netherlands, e-mail:
ahw.bruns@meandermc.nl
98
Introduction: Tuberculosis is a chronic disease caused by
Mycobacterium tuberculosis. It usually infects the lungs but
may effect any part of the body. Most infected individuals
harbor the tuberculosis bacterium without symptoms, but
may later on develop active disease. Diagnosing tuberculosis may be very difficult.
Case: A 68-year-old Turkish woman, living in the
Netherlands, presented with fever, cold shivers, night
sweats, and abdominal pain. Her medical history revealed
Parkinson’s disease. On physical examination she had high
fever (40.7 °C) and abdominal tenderness. Her laboratory
results showed progressive anemia and thrombocytopenia,
with normal leukocyte counts, elevated C-reactive protein
levels (63 mg/l), elevated liver enzymes, and diffuse intravascular coagulation. CT scans showed thoracic para-aortal
lymphadenopathy.
Extended microbiological evaluation including blood and
urine cultures, viral hepatitis, HIV, EBV, CMV, malaria,
brucellosis, and leishmaniasis remained negative. The
IGRA test (Interferon Gamma Release Assay) was positive,
and active tuberculosis was suspected. A bone marrow
puncture and biopsy were performed, for pathological
examination and culture on tuberculosis. There were no
granulomas nor acid-fast rods in the bone marrow biopsy.
Remarkable was the presence of increased numbers of T
lymphocytes in the peripheral blood and bone-marrow.
Immunophenotyping of the peripheral blood showed that
this concerned a CD1a, CD4, aßTCR, CD56 restricted
T-cel population with loss of CD7 expression. This was
the reason to seriously consider a T cell lymfoproliferative
disease in the differential diagnosis. Meanwhile, the
patient had become very ill, and 13 days after admission
treatment for tuberculosis was started. Four days later she
died of multi-organ failure. Afterwards the bone marrow
culture on tuberculosis became positive.
Conclusion: This patient was admitted with high fever.
Tuberculosis was suspected because of her Turkish origin
and positive IGRA test, and ultimately proven in the bone
marrow culture. The remaining question was: how to
explain the pathological T cells in blood and bone marrow?
The immune response elicited after Mycobacterium tuberculosis infection is critically dependent on CD4+ T cells
during both acute and chronic infection. In addition to
CD4+ T cells, other T cell subsets such as gd, CD8+ and
CD1-restricted T cells have roles in the immune response
to M. tuberculosis. A diverse T cell response allows the
host to recognize a wider range of mycobacterial antigens
presented by different families of antigen-presenting
molecules, and thus greater ability to detect the pathogen.
Case report: A 63-year-old women was admitted with
nausea and acute onset of severe epigastric pain
referring to her back. She successfully had undergone
an autologous stem cell transplantation (SCT) for high
risk plasmacell leukemia one year ago. On admission,
physical examination revealed abdominal tenderness
localized to the epigastric region. She had no fever,
skin or mucosa lesions. Initial laboratory results showed
leucopenia (WBC 2.3 * 109/l) and thrombocytopenia
(50 * 109/l). The biochemistry levels including, liver
enzymes, bilirubin, amylase and C-reactive protein were
in the normal ranges. Chest radiography appeared normal.
Abdominal ultrasound showed prominent intra-hepatic
bile ducts and a distended ductus choledochus up to 1 cm
without concrements. During admission her pain rapidly
worsened, requiring intravenous morphine. Because of
the intensity of the pain, the dilation of bile ducts and
slightly raised bilirubin levels (18 umol/l) she underwent
on the second day of admission an ERCP, which except of
a dilated ductus choledochus turned out to be normal. On
day four, she developed fever and a disseminated vesicular
erythematous rash on her trunk, face and scalp and
treatment with acyclovir intravenous was initiated. PCR of
vesicular fluid turned out to be positive for varicella zoster
virus (VZV) and serology of VZV IgG was positive. After
initiating acyclovir she recovered within one week.
Discussion: Reactivation of varicella zoster virus (VZV)
is a common event after SCT. Visceral presentation
of generalized VZV infection is uncommon, although
probably an under-diagnosed event in post-SCT
patients. The interval from onset of abdominal pain
to the development of skin eruptions may delay the
initiation of specific antiviral therapy and symptoms may
be incorrectly diagnosed as gastro-intestinal or surgical
disease. Therefore, varicella zoster should be considered
in the differential diagnosis of abdominal pain in all
immunocompromized patients, particularly when the
cause is not obvious. Acyclovir therapy should be started as
soon as the clinical picture shows the typical manifestation
of the disease.
Conclusion: Recognizing severe abdominal pain as
primary sign of varicella zoster is of major importance,
since it allows prompt treatment of the infection and
prevents for invasive procedures.
183. Pathological T-cells in a patient with unexplained
fever: malignant lymphoma or tuberculosis?
S.N. Huttjes, E.J.M Mattijssen, J. Ruinemans-Koerts
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
sannehuttjes@hotmail.com
99
184. Brucellosis: an unpleasant travel companion
185. The balcony of death
W. Yassi, Dr. Zwart, A. van Tellingen
Zaandam Medical Centre, Department of Internal
Medicine, Koningin Julianaplein 58, 1502 DV Zaandam, the
Netherlands, e-mail: wisamyassi@yahoo.com
M.C. van Boreen1, J. Buijs2
1
Atrium Medical Centre Heerlen, Department of internal
medicine, Henri Dunantstraat 5, 6419 PC HEERLEN, the
Netherlands, e-mail: maritvanboreen@hotmail.com, 2 Atrium
Medical Centre, HEERLEN, the Netherlands
Case: A 67-year-old woman of Turkish origin, is admitted
to our internal medicine department for analysis of longstanding fever. Her medical history includes, end-stage
renal failure, due to malignant hypertension, for which
she recieves hemodialysis therapy. One and a half month
before admission, she was treated for suspected urinary
tract infection with amoxicillin, but without effect. On
further questioning she has a swinging fever, with peaks
in the evening. The patient is also depressed and has a
decreased appetite. On physical examination she has a
temperature of 39.8 °C, stable hemodynamics, flank pain
and an intense lower back pain increasing with movement.
She has tenderness over the lower lumbar vertebrae at the
location of the sacroiliac joint. Other physical examination
is not contributing, especially no heart murmurs. Blood
test shows a CRP of 171 mg/l and WBC of 8.0 x 109/l. Urine
analysis shows > 40 leukocytes per high powered field.
Under the suspicion of pyelonephritis, patient is treated with
amoxicillin /clavulanic acid intravenously, again without
effect. Ultrasonography shows no hydronephrosis or abcesses.
Chest and abdomen CT shows pathologically enlarged
mediastinal lymph nodes and a spondylodiscitis L3-L4.
Urine culture remains negative, however we switched to
cefuroxime and ciprofloxacin, guided by positive blood
cultures for gram-negative bacilli. The gram-negative
bacilli are hard to identify biochemically. Considering
the undulating temperature pattern, the ethnicity of the
patient and spondylodiscitis, brucellosis is highly probable
in our differential diagnosis. The Bang reaction in the
serum is markedly elevated. The complement-binding
reaction revealed a fourfold increase in three weeks. PCR
and 16S RNA sequencing of the blood culture colony give
a 99% identification as Brucella, on species level. Further
identification to species level is not possible by molecular
microbiology. Patient was treated with doxycyclin and
rifampicin for 6 weeks with good clinical respons also,
follow up CT after 6 weeks of therapy no longer shows
mediastinal lymphadenopathy, and a marked reduction in
spondylodiscitis. In the outpatient clinic, the patient has no
recurrence of fever nor lower back pain.
Discussion: In the Netherlands Brucellosis is a rare
cause of fever of unknown origin. The incidence is 3 per
10 million inhabitants. The typical undulating fever, the
country of origin and contact with animals may give the
clue for the diagnosis. Brucellosis is a disease which should
be reported to disease control authorities. Combination
therapy is chosen to reduce the risk of recurrence.
Case: A 73-year-old woman presented at the emergency
department with nausea, fatigue and melena. One month
earlier, analysis of anemia and inflammation revealed a
normal gastroscopy and colonoscopy. FDG-PET-CT-scan
showed abnormal metabolic activity in the upper abdomen
and a small aortic aneurysm. Her further medical history
was unremarkable.
We saw a pale patient with normal vital signs and a
pulsating abdominal mass. Laboratory tests demonstrated: hemoglobin 4.3 mmol/l, leukocytes 20.7 x 109/l.
CT-angiography showed no signs of a leaking aneurysm.
After admission, repeated gastroscopy because of haematemesis and hypotension revealed active duodenal bleeding.
CT showed an increased aneurysm size and thrombus
formation around the calcified aorta. Under suspicion
of aortaduodenal fistula patient underwent immediate
prosthesis-surgery. Bacterial cultures of blood and
the native aneurysm remained negative. The postoperative period was complicated by recurrent infectious
and ischemic problems, needing surgical closure of a
duodenal perforation, resection of necrotic jejunum, gall
bladder, right-sided colon and repair of multiple enterocutaneous fistulae. Due to a recent regional outbreak of
acute Q-fever, serology was determined, although there
was no documented primary infection. Serologic titers
were 1:2048 and 1:1024 for phase 1- and 2-IgG, respectively.
Despite of intensive medical and surgical treatment patient
died after 5 months of hospitalization due to respiratory
insufficiency and exhaustion.
Q-fever, a zoonosis caused by Coxiella burnetii, affects
various hosts, including humans, ruminants and pets. This
Gram-negative microorganism is very resistant to environmental influences and may survive for months outside
the host. Moreover, only a small inhalated inoculum may
lead to infection. Dry climate and direction of the wind are
closely related to human infection rate. In 2007/2008 the
Netherlands was faced with the largest epidemic of acute
Q-fever ever reported worldwide. In 3-5% of cases, chronic
Q-fever ensues, leading to vascular complications like
endocarditis and infected aneurysms or vascular prostheses.
Retrospectively, the patient did not recollect having any
contact with animals, nor did she live in the neighbourhood of an infected farm. The only clue was the fact
that she spent many hours on her balcony in the city,
6 kilometers east-ward to the rural region of Voerendaal,
the hot-spot of the Q-fever epidemic in the south of the
100
Netherlands. With the prevailing western winds, we
speculate that this may have caused transmission.
This dramatic case illustrates the importance of suspecting
chronic Q-fever in endemic regions, even when there is
no history of acute Q-fever or direct contact with infected
animals.
187. Fulminant hepatitis with coagulopathy due to HSV-1
in an immunocompetent man
186. Lemierre’s syndrome
Introduction: Herpes simplex infection (HSV-1) is a
common and most often a benign, self-limiting disease
presented with mucocutaneous lesions and mild viremia.
Systemic herpes simplex infection with acute hepatitis
is a rare complication of HSV-1 infection, especially in
immunocompetent patients. The diagnosis is often missed
due to the absence of specific signs or symptoms. Clinical
manifestations are nonspecific which include flu-like
illness, fever and abdominal discomfort. Fulminant HSV-1
hepatitis is usually marked by significant elevations in
transaminases (ASAT higher than ALAT), and a mild or
absent hyperbilirubinemia. The course of the disease is
often rapid and frequently fatal. The mortality rates vary
between 50 percent and 90 percent, mainly because of
delayed diagnosing and treatment with antiviral therapy.
We describe a patient with systemic HSV-1 infection with
a fulminant hepatitis and severe coagulopathy without
liver failure.
Case report: A 57-year-old man, with a history of recurrent
nephrolithiasis, was admitted to our hospital with fever
and chills after his return from Gambia. He had his vaccinations, and used malaria-prophylaxis. Two days before
presentation our patient had noticed itchy skin lesions
in the neck. On physical examination he had a fever of
38.5 °C. We saw a few vesicles in the neck. Laboratory
assessment revealed a low platelet count (102 x 109/l) and
elevated transaminases (ASAT 1348 U/l, ALAT 852 U/l).
A tropical associated disease was suspected. Because
of progressive fever intravenous amoxicillin/clavulanic
acid was started. Skin lesions suspected a disseminated
varicella zoster virus infection and acyclovir was added.
Patient’s condition worsened with the development of a
severe hepatitis (maximum levels of ASAT 4530 U/l, ALAT
1978 U/l, bilirubin 12 mmol/l). There were signs of disseminated intravascular coagulation with gastrointestinal and
urinary tract haemorrhages and respiratory failure with
pleural effusion.
PCR of serum and from a biopsy of the affected skin
revealed herpes simplex virus type I (HSV-1). CT scan,
thoracentesis and gastroscopy did not reveal other
pathology. Antibiotics were stopped and acyclovir was
continuated. On day 7 of acyclovir use patient started to
improve until full recovery, including full recovery of
hepatic enzymes.
Laboratory testing showed no signs of immunodeficiency.
Patient told he never experienced cold sores before; his wife
L.J.N. Wind, F.W. Folkert, M.N. Gerding
Deventer Hospital, Departement of Internal Medicine, Nico
Bolkesteinlaan 75, 7416 SE DEVENTER, the Netherlands,
e-mail: LJNWind@hotmail.com
N.P. Barlo, A.J. Meinders, B.M. de Jongh
St. Antonius Hospital, Department of Internal Medicine,
Koekoekslaan 1, 3435 CM NIEUWEGEIN, the Netherlands,
e-mail: n.barlo@antoniusHospital.nl
Introduction: Lemierre’s syndrome is a form of thrombophlebitis caused by Fusobacterium necrophorum. Patients
present with a sore throat caused by a streptococcus
infection, accompanied by a peritonsillar abcess. Anaerobic
bacteria like Fusobacterium grow inside the abcess and
penetrate into the jugular vein and cause thrombosis and
bacteremia. Fusobacterium bacteremia is uncommon,
accounting for less than 1% of positive blood cultures.
The majority of patients with positive blood cultures for
Fusobacterium present as Lemierre´s syndrome.
Case: A 27-year-old man with a blank medical history
presented at the emergency department with a sore
throat, vomiting and diarrhoea since 5 days. Two weeks
earlier he returned from a journey to Gambia and Liberia,
where he stayed for two months and did not experience
any symptoms. He presented with severe hypotension,
tachycardia en fever. On clinical examination he had a red
pharynx, painful cervical lymphadenopathy and a diffuse
painful abdomen on palpation. Laboratory tests showed
thrombocytopenia, abnormal liver and kidney function tests
and an increased lactate level and CRP. He was admitted
at the ICU and treated with cefuroxime and gentamicin
pending culture results. Extensive diagnostic research was
performed for tropical diseases. Blood cultures revealed
a Streptococcus milleri and Fusobacterium species. This
combination of bacteria led to the clue of Lemierre’s
syndrome. On CT scan there was indeed a parapharyngeal
abcess and thrombosis of the left internal jugular vein.
Furthermore, there were bibasilar pulmonary infiltrates,
which may be explained as septic emboli from the thrombophlebitis. His travel history could not explain this disease.
He was treated with penicillin and recovered well.
Conclusion: Lemierre’s syndrome is a rare disease,
classically presenting in otherwise healthy young
adults following a pharyngitis. Blood cultures showing
Fusobacterium species should point into the direction of
Lemierre´s syndrome and encourage further analysis for a
pharyngeal abcess, jugular vein thrombosis and metastatic
spread of septic emboli.
101
and daughter experienced cold sores a few weeks before
hospital admission.
Conclusion: This case illustrates that awareness of HSV
hepatitis, though extremely rare in immunocompetent
patients, is important, since timely recognition and early
initiation of antiviral therapy improves prognosis.
arthritis in the acute phase of hepatitis C infection has to
our knowledge never been described.
our case. When a complicated infection is suspected, it is
important to localize potential extraintestinal foci because
drainage is usually indicated, combined with prolonged
antimicrobial therapy.
with an increased risk of fulminant bacterial infections,
especially with encapsulated bacteria. Congenital asplenia
is usually seen in the context of recognised syndromes with
abnormalities in other organs, primarily cardiac abnormalities. Isolated congenital asplenia is rare. It is a condition
that is difficult to diagnose in the absence of other
indicators, and often diagnosed only after the patient has
had a serious, often fatal infection. Morphologic anomalies
of peripheral blood erythrocytes, such as Howell-Jolly
Bodies, may be the only evidence of a non-functional
spleen. It is not clear whether further investigation is
warranted if at a routine abdominal ultrasound the spleen
is not visualised.
189. Persistent shiver due to Salmonella
F.J. Voogd, A. Al Moujahid, M.D. Themmen
Medical Centre Leeuwarden, Department of Internal
Medicine, Henri Dunantweg 2, 8934 AD LEEUWARDEN,
the Netherlands, e-mail: fia.voogd@znb.nl
188. Arthritis and elevated liver enzymes in a patient with
HIV-infection: A rare presentation of acute Hepatitis
C
Introduction: Many primary enteric infections are mild,
selflimiting and not microbiologically diagnosed.
Case: Since four days, a 27-year-old male with no medical
history had a fever up to 40 °C with vomiting and
diarrhoea. Two weeks before admission to our hospital
he came back from a holiday in Turkey. On admission,
we saw an ill patient with fever and minimal abdominal
complaints without any other abnormity by physical
examination. Blood analysis showed a raised C-reactive
protein (171 mg/l), a normal white blood cell count and
elevated liver enzymes. Blood cultures showed Salmonella
oranienburg. Serological test for HIV was negative. Despite
adequately given antibiotic therapy with ciprofloxacin intravenously there was persistent fever with signs of relapsing
bacteremia. Computer tomography (CT) showed splenomegaly with splenic abscesses. After ultrasound-guided
percutaneous drainage was performed the clinical findings
quickly improved. Punctate showed Salmonella oranienburg.
After treatment with ciprofloxacin during four weeks the
abscesses completely resolved.
Discussion: Bacteremia with splenic abscesses are serious
complications of nontyphoidal Salmonella infection which
may not be suspected in the setting of mild primary
infection. The incidence of bacteremia is affected by
Salmonella serotype, geographic location, time of year and
host factors. Host risk factors include extremes of age and
any immunosuppressing condition. In series of adults with
nontyphoidal Salmonella bacteremia over 90 percent of
patients had an underlying medical illness.
Salmonella oranienburg is a foodborne pathogen and
the incidence of infections seems to be low overall, but
specific data are lacking. Infection is hardly complicated
by abscesses and mostly comparable with a Salmonella
enteritidis infection which hardly leads to bacteremia
but can behave like an opportunist in patients with any
immunosuppressing condition leading to infection at any
site.
In this case our patient was young without any predisposing comorbidities. HIV infection specifically was
excluded.
Conclusion: Primary enteric infections with nontyphoidal
Salmonella may be mild but can have serious complications
unexpectedly, even in otherwise healthy persons as in
S. Slavenburg, E.H. Elzinga, R.W. ten Kate, B.L. Herpers,
R. Soetekouw
Kennemer Gasthuis,Department of Internal Medicine,
Boerhaavelaan 22, 2035 RC HAARLEM, the Netherlands,
e-mail: s.slavenburg@kg.nl
Introduction: The incidence of acute hepatitis C infection
(HCV) in HIV-positive men who have sex with men (MSM)
has increased. Symptoms in the acute phase of HCV
infection are usually mild and aspecific such as fatique,
nausea, loss of apetite, flu-like symptoms or jaundice.
Herein we describe a HIV-positive patient with oligoarthritis of both knees as a manifestation of acute HCV
infection.
Case report: The patient is a 63-year-old HIV-positive man
who was successfully treated with combination antiretroviral therapy (c-ART) consisting of atazanavir/ritonavir,
emtricitabine and tenofovir. The viral load was undetectable and the CD-4 count was stable around 400 x 109/l.
There was no previous co-infection with hepatitis B or C.
He was admitted with arthritis of both knees and was
found to have abnormal liver function tests (bilirubin
72 mmol/l, AF 108 U/l, YGT 65 IU/l, ALAT 132 U/l, ASAT
130 U/l) consistent with acute HCV infection. Antibodies
against HCV were negative but the HCV-RNA assay in
plasma was positive (genotype 1A, viral load 4,5 x 106 cop/
ml).
The rheumatoid factor was < 3.0. The anti-nucleair factor
(ANF) was not measurable and anti-cyclic citrullinated
peptide antibody (anti-CCP) was 2.7 kU/l. The joint
radiograph showed osteoarthritis of both medial compartments. Crystals could not be identified in the synovial fluid
and bacterial cultures were negative. However, HCV-RNA
was demonstrable in the synovial fluid. In the course of
several weeks the arthritis resolved spontaneously. Twelve
weeks after presentation, HCV-RNA was still detectable in
plasma and treatment with peginterferon and ribavirin was
initiated. A rapid viral response was noted with undetectable HCV-RNA after 4 weeks of therapy.
Discussion: Arthritis, and indeed musculoskeletal
symptoms, are well known extrahepatic manifestations of
chronic hepatitis C virus infection. However, a self-limiting
102
190. Fulminant pneumococcal sepsis in a patient with
congenital asplenia
L.N. van den Hende1, F.G.C. Heilmann 2, T. Meys1,
Th.F. Veneman1
1
ZGT Hospital, Department of Internal Medicine, PO
Box 7600, 7600 SZ ALMELO, the Netherlands, e-mail:
L.vdHende@zgt.nl, 2Laboratorium Microbiologie Twente
Achterhoek, ENSCHEDE, the Netherlands
191. Varicella zoster virus induced paraparesis – a case
report
Case report: A 48-year-old woman was referred to our
emergency department because of flu-like symptoms
since three days, with dyspnoe and fever developing in
the last day. Her medical history revealed a laparoscopic
cholecystectomy. On physical examination she appeared
moderately ill, with a blood pressure of 130/80 mmHg,
regular pulse rate of 131 BPM, body temperature of 39.2
°C, oxygen saturation 99% (3 l O2). Auscultation revealed
normal breathing sounds bilaterally, without adventitious
sounds. Laboratory examination revealed CRP 305 mg/l,
leukocytosis 11.6 * 109/l, thrombocytopenia 90 * 109/l,
serumcreatinin 200 mmol/l and lactate 13.8 mmol/l.
Chest X-ray showed dubious infiltrates in both lower
fields. Under suspicion of pneumosepsis, intravenous
broad-spectrum antibiotics (amoxicillin/clavulanic acid
and ciprofloxacin) were administered. During her stay
at the emergency department her condition deteriorated
rapidly. She was transferred to our ICU for mechanical
ventilation and hemodynamic support. At that point she
also developed reddish/purple skin lesions diffusely on
her body. A CT scan of abdomen and thorax was made to
rule out any other focus of infection. Again, infiltrates were
seen in both lower lung fields. Surprisingly, near-complete
absence of the spleen was discovered. In hindsight an
abdominal ultrasound had been made a few years prior
at which her spleen was not visualised. The next day
blood cultures grew Streptococcus pneumonia for which
Benzylpenicillin was started.. During the following period
our patient developed a fulminant sepsis, with multi-organ
failure. Severe thrombopenia on account of DIC, inotropydependency and renal failure with the need for dialysis
developed. In blood smears Howell-Jolly Bodies were seen.
Furthermore the skin lesions progressed, with necrosis of
fingers and toes. She was eventually referred to a university
hospital for amputation of lower legs and fingers and
further treatment.
Conclusion: Asplenia is an uncommon condition that
may be acquired, functional or congenital. It is associated
J. Branger, J. Kliffen, J. van de Vlekkert, E. Bierdrager
Flevo Hospital,, Department of Internal Medicine,
Hospitaalweg 1, 1315 RA ALMERE, the Netherlands, e-mail:
jbranger@flevoHospital.nl
Introduction: Varicella zoster virus (VZV) is the well
known cause of shingles and herpes zoster infections.
However, in immunocompromised patients, such as in
HIV-infection, VZV can cause serious neurological disease
with permanent impairment, as illustrated in the case
report below.
Case report: A 37-year-old male presented with progressive
weakness of the right leg, numbness of the left leg,
and inability to urinate. Three months earlier, he was
diagnosed with toxoplasmosis encephalitis and an
advanced HIV-1 infection (CD4-count 80/ml). Both
infections were treated according to the current guidelines.
Two weeks before admission, the patient experienced
cramps and dysesthesia in his right leg. Since one week,
he developed loss of strength in his right leg and urine
retention. He reported no other symptoms, in particular
no fever or recent skin abnormalities. On examination
we saw an alert, a febrile male, hemodynamically stable.
Neurological examination showed a bilaterally disrupted
vital sensibility from the level Th8 downwards; gnostic
sensibility was intact. Furthermore, there was loss of
strength in the lower limbs, right more pronounced than
left, without hyperreflexia. Babinski’s reflex was present
on both lower extremities. Further physical examination
was uneventful. Laboratory tests showed a mild leucopenia
with 110 CD4-cells per ml. Biochemistry, including
C-reactive protein was normal. A MRI scan of the spine
was performed showing a diffuse myelopathy from C5 to
Th12 with thickening and/or swelling of the myelum and
gadolinium enhancement, suggestive of myelitis. Our
differential diagnosis comprised viral (herpesviridae, HIV),
103
fungal and parasitic infections. Furthermore, syphilis and
tuberculosis were considered. Finally, acute disseminated
encephalo-myelitis (ADEM) was thought of.
Liquor examination showed 96 mononuclear cells/ml,
an elevated total protein level (1.32 g/l), and a normal
glucose concentration of 2.9 mmol/l. A broad spectrum of
microbiological tests was performed, showing a positive
PCR and IgG antibodies for Varicella Zoster Virus in the
liquor. The diagnosis incomplete spinal cord lesion caused
by Varicella zoster myelitis was made. The patient was
treated with acyclovir and corticosteroids, with little clinical
improvement. Six months later, he is largely wheelchair
dependent and uses self catheterization.
Discussion and conclusion: In immunocompromised
patients, reactivation of VZV often occurs. This may
cause neurological sequelae including cranial nerve
palsy, meningo-encephalitis and myelitis. As in our
patient, herpes zoster may be absent: ‘zoster sine herpete’.
Unfortunately, VZV myelitis in HIV patients is often
progressive and frequently causes irreversible damage to
the CNS. When suspected, treatment should be started
without delay.
Twelve hours later he became respiratory insufficient and
was transferred to the intensive care unit, where he was
intubated and mechanically ventilated, eventually in prone
position. H1N1-infection was confirmed by PCR analysis,
serology for HIV was negative. His renal function deteriorated, levels of CK and LDH decreased in the following 4
days and the patient is slowly recovering.
Discussion: Pneumonia, complicated by rhabdomyolysis, is
primarily associated with legionella or influenza infection.
It was reported that 10% of the patients with influenza
pneumonia suffered from rhabdomyolysis and the
2009-H1N1-serotype may even have a greater propensity
for muscular inflammation than other seasonal influenza
serotypes. Mild to moderate CK elevation is seen in 62%
of patients with H1N1-pneumonia with respiratory failure.
Mechanisms underlying its pathogenesis remain unclear
and may include viral invasion, viral toxin, cytokines or
hypoxemia.
Conclusion: Physicians should be aware that rhabdomyolysis may present as a complication in a critically ill
patient with influenza A(H1N1)-induced respiratory failure.
193. Souvenir from Indonesia: an ameboma
192. A patient with pneumonia and rhabdomyolysis
M.J.T. Crobach, E.D. Beishuizen, J.W. van ’t Wout
Bronovo Hospital, Department of Internal Medicine,
Bronovolaan 5, 2597 AX THE HAGUE, the Netherlands,
e-mail: moniquecrobach@hotmail.com
A.D. Cornet, A.J. Kooter
VU Medical Centre, Department of Internal Medicine, De
Boelelaan 1117, 1081 HV AMSTERDAM, the Netherlands,
e-mail: cornet@vumc.nl
Introduction: Amebic infection is a rare cause of traveler’s
disease. Its clinical presentation is variable. An ameboma,
a mass of granulation tissue caused by localized amebic
infection, is one of the unusual presentations of amebic
infection. We present a patient with an ameboma after a
trip to Indonesia.
Case report: A 60-year-old woman was admitted with
malaise, fever and pain in the right lower abdomen. These
complaints started 3 days after a trip through Indonesia
(Java and Bali). Past medical history included gastroesophageal reflux disease and irritable bowel syndrome.
She was born in Indonesia. Before the trip, she had
received all recommended vaccinations.
On admission, physical examination showed a febrile
patient with a tender right lower abdomen at palpation.
Laboratory results and chest X-ray showed no abnormalities. Abdominal ultrasound showed an ileocecitis.
A preliminary diagnosis of bacterial ileocecitis was
considered and therapy with ceftriaxon IV was initiated.
A tuberculin skin test was positive but was considered
non-diagnostic as she was born in Indonesia. On therapy,
the patient recovered quickly and was discharged some
days later.
Case: A 56-year-old man, without a relevant medical
history, presented to the Emergency Department because
of shortness of breath, dry cough and a mild fever. He used
paracetamol because of myalgia and had been treated with
doxycylin for 3 days prior to presentation, but his condition
deteriorated. He had not traveled recently, did not smoke
or have pets. None of his relatives were ill and he had not
been vaccinated for seasonal flu. At presentation we saw
an obese man in respiratory distress, with a respiratory
rate of 38/min, cyanosis was absent using supplemental
oxygen with a nonrebreathing mask. His temperature was
37.6 oC, pulse 92/min and blood pressure 125/75 mmHg.
Breath sounds were bilaterally attenuated with fine crackles
up until the scapula. Laboratory results showed a CRP of
106 mg/l, leukocytes 5.0 x 109/l (10% lymphocytes) and
a normal renal function. Remarkable were the elevated
levels of both LDH (950 U/l) and CK (3080 U/l). Blood
gas analysis was as follows: pH 7.46, pCO2 37 mmHg,
BE +1 mmol/l, pO2 37 mmHg (room air) and urinalysis
demonstrated myoglobin. The chest X-ray showed bilateral
infiltrates. Amoxicillin-clavulanic acid and erythromycin
were started. The rhabdomyolysis raised the suspicion of
(H1N1-)influenza pneumonia and oseltamivir was started.
104
However, after this episode, the patient presented in the
outpatient clinic with persisting symptoms of right lower
abdominal pain, initially accompanied with fever. CT
scanning of the abdomen revealed slight inflammation
around the cecum and distal ileum. A colonoscopy revealed
no abnormalities, Auramine and Ziehl-Neelsen stains were
negative. One month later a CT scan showed localized
inflammation in the ileocecal region with accompanying
lymphadenopathy, findings which might also be suggestive
of an underlying tumour mass. At a second colonoscopy,
there were signs of inflammation in the ileocecal region,
biopsies showed amebic trophozoites. Amebic serology and
amebic PCR on feces were positive. We concluded that our
patient suffered from an ameboma. She was treated with
metronidazol and paromomycin. On a follow-up visit four
months later, she was asymptomatic. The CT scan of the
abdomen showed a nearly normalized ileocecal region.
Discussion: Amebic infection has a variable clinical
presentation. Many conditions, including colon cancer,
inflammatory bowel disease and tuberculosis, may have
overlapping clinical features. Not recognizing amebic
infection may have deleterious consequences, as patients
may for example be treated with steroids on suspicion of
inflammatory bowel disease. Given the present situation
with extensive foreign travel, amebic colitis and ameboma
must be included in the differential diagnosis of all
patients who present with colitis or a colonic mass after
travelling to the developing world.
and rifampicin. Patient started treatment with isoniazid,
rifampicine and moxifloxacin. In retrospect the abdominal
aneurysm, for which an EVAR was perfomed in 2009, had
shown some signs of a mycotic aneurysm. This diagnosis
was rejected because of the absense of fever and inflammatory parameters The psoas abcess was drained twice but
recurred. Therefore it was decided to replace the EVAR for
a graft of the great saphenous vein. Up until now patient
is doing well. He has to continue tuberculostatics for six
months after surgery. A recent MRI showed no signs of
activity in the spine
In international literature there are about 16 reported
cases of mycotic aneurysms due to M. bovis and several
cases of spondylodiscitis after BCG-immunotherapy. The
route of infection in our patient is most likely haemotogenous because the localisation in the spine is not related
to the psoas abces and the aorta. This case shows that in
doubt of a mycotic aneurysm or in case of an unexpected
osteoporosis in a patient with previous BCG installation
a low grade chronic infection like M. bovis must be
suspected.
195. A healthy female with Rhodococcus erythropolis
septicemia
J.M. van Hattem, S.A. Luykx-de Bakker, S. Lobatto
Tergooi Hospitals Hilversum, Department of Internal
Medicine, Van Riebeeckweg 212, 1213 XZ HILVERSUM, the
Netherlands, e-mail: jarne.vanhattem@gmail.com
194. Spondylodiscitis and a mycotic aneurysm:
complications of intravesical BCG (bacillus
Calmette-Guérin)-immunotherapy
Case: A 46-year-old female with a history of an appendectomy presented with stabbing pain in the left lower
abdomen of 2 weeks duration and fever (temperature 39.9
°C) since one day. An IUD for birth control was placed 6
years before. On physical examination a non-ill woman,
with a painful left lower abdominal quadrant without
rebound tenderness was seen. Laboratory examination
showed an elevated CRP (70 mg/l, a day later 146 mg/l)
and elevated leukocytes (13.4 x 109/l, a day later 16.6
x 109/l). Ultrasound showed a mass in the left lower
abdomen, possibly infiltrated fat tissue with abscesses. A
CT-scan was performed showing a para-iliac mass with a
diameter of 5 cm with central calcification, most likely an
ovarian abscess.
She was initially treated with oral amoxicillin/clavulanic
acid on an out-patient basis but was readmitted the next
day because of fever. Transvaginal drainage of the ovarian
abscess was performed and her IUD was removed.
Blood cultures identified a Rhodococcus species, further
determined by matrix assisted laser desorption/ionisation
(MALDI) as Rhodococcus erythropolis, penicillin sensitive
and trimethoprim-sulfamethoxazole resistant. Genital
swab cultures, PCR for Chlamydia trachomatis and
B. Santbergen, M.E.E. van Kasteren, P.H.W.E. Vriens
St. Elisabeth Hospital, Department of Internal Medicine,
Hilvarenbeekseweg 60, 5022 GC TILBURG, the Netherlands,
e-mail: bart_santbergen@hotmail.com
We report a case of a 58-year-old man with persisting back
pain after a vertebroplasty of vertebra Th8-Th9 because
of osteoporosis. Previous medical history included intravesical BCG-immunotherapy 3 years earlier for minimal
invasive bladder carcinoma and an EVAR for an abdominal
aneurysm 1 year earlier. Last months patient complained
of weight loss. A new MRI of the spine showed signs of a
low-grade spondylodiscitis at Th8-Th9 and a CT-guided
bone puncture was performed. Pathological analysis
showed necrotizing granuloma and microbiological
cultures grew Mycobacterium bovis. CT abdomen showed
a swelling around the EVAR and an abscess of the left
psoas muscle. A puncture of the psoas abscess also showed
acid fast bacilli and PCR for Mycobacterium complex was
positive. Culture grew M. bovis sensitive to isoniazid
105
Neisseria gonorrhoeae as well as culture of puss from the
abscess were all negative. The patient was treated with
penicillin intravenously and could be discharged after a
week.
Rhodococcus is a gram-positive pleomorphic organism
that appears coccoid on solid media but forms long rods
or short filaments in liquid media. The organism is
an occasional cause of disease in cattle and can cause
severe lung infections in foals. Most human infections
have been associated with immune system dysfunction.
Pulmonary infections are the most common form of
human disease. Little is known about the pathogenic
potential of Rhodococci other than R. equi.
We found two case reports of R. erythropolis septicemia: a
79-year-old man with esophageal cancer who had been treated
with radiotherapy followed by chemotherapy and a 7-year-old
child treated with chemotherapy for acute lymphocytic
leukemia. We know that colonization and pelvic infections
with Actinomyces are associated with IUD use, especially
prolonged IUD use. We could not find any literature about the
association between Rhodococcus and IUD use.
Conclusion: This is the third case report of Rhodococcus
erythropolis septicemia and the first in an immunocompetent
woman. It has been suggested that non-equi Rhodococcus
species may be of more importance in human disease than
previously thought. An association between Rhodoccus
infection and prolonged IUD use is very well possible.
above described skinlesions on the body and a conjunctivitis. He was hemodynamically stable, had a normal
temperature and a oxygen saturation of 95% with 5 liter
O2. On chest examination there were crackles at the right
lung base. Laboratory results showed elevated CRP 125
(< 10 mg/l) and a mild leukocyte count of 12.2 (< 10 x 109/l).
Chest X-ray showed a para-cardial infiltrate.
With the suspicion of a Stevens-Johnson Syndrome
triggered by a pneumonia, ciprofloxacin was started,
amoxicilin was continued without clavulanic acid and
aciclovir was added to cover a possible herpes simplex
co-infection. Initially he became septic en developed high
temperature. After a few days he recovered clinically and
the skin lesions resolved. Blood cultures were negative,
urine analysis for Legionella pneumophila was negative,
HIV serology was negative but sputum culture and
serology were positive for M. pneumoniae. Antibiotics were
switched to oral clarithromycin. Histologic findings of the
skin appeared evident for a Stevens Johnson syndrome.
The patient recovered quickly. Laboratory findings and
chest X-ray normalized after a couple of weeks.
Conclusion: One should keep in mind that when a patient
presents with symptoms suspected for a Stevens Johnsons
Syndrome, serology for M. pneumoniae should be obtained. If
there are respiratory symptoms, appropriate antibiotics should
be started covering M. pneumoniae prior to any test results.
of an ischaemic cerebral infarction. His medical history
further comprised multiple airway infections, a myocardial
infarction and an endovascular reconstruction for an
asymptomatic aortic aneurysm. His cardiovascular risk
factors included smoking, dyslipidemia, age and a positive
family history. Despite of risk factor reduction, the patient
experienced a series of strokes in the three years after his
first stroke, leaving him severely disabled. No other causes
for these recurrent events were found.
During follow-up at the internal medicine department the
patient complained of malaise and nightsweats without
fever. Several blood tests showed abnormalities: a slow
rise of the ESR to 97 mm/h and a slowly developing
anaemia of chronic disease (Hb 7.0 mmol/l). Also, levels
of all IgG subclasses were now raised, as well as the IgA
and IgM levels (previously normal). Based on the clinical
presentation and the labarotory tests a non-athesclerotic
endovasculitis was suspected. Serologic analysis showed
high phase 1 and phase 2 IgG and IgM antibody titers to
C. Burnetii (1:16000).
At last, the patients clinical condition could be explained
by chronic Q-fever infection, which was confirmed by high
antibody titers and biochemical signs of chronic infection.
Echocardiography showed no abnormalities, the patients
condition improved after treatment with doxycycline and
hydroxychloroquine.
Conclusion: 1. In this patient the diagnosis of chronic
Q-fever infection was delayed, due to the misrecognition
of the infectious cause of the vascular complications and
the lack of symptoms accompanying the acute phase of
the infection. 2. Possibly, the dysfunction of the cellular
immunity contributed to sustained infection. 3. In patients
with multiple vascular events and chronically increased
inflammatory parameters, a chronic bacterial infection
should be suspected as a cause.
encephalitis for which intravenous acyclovir was started.
Computed tomography of the brain showed asymmetric
edema mainly in the left temporal lobe. Cerebrospinal
fluid (CSF) analysis showed lymphocytosis (1540 cells
per ul), elevated protein (1.72 g/l) and a normal glucose
concentration (2.8 mmol/l). Polymerase chain reaction
(PCR) of CSF revealed herpes simplex virus type 1 (HSV-1).
The patient recovered quickly and was discharged home
ten days later. The non-fluent aphasia did not resolve
completely for which she received speech therapy.
Discussion: Herpes simplex encephalitis (HSE) is the most
common cause of sporadic viral encephalitis. It usually
affects the temporal and frontal lobes. In most cases HSV-1
is responsible for the disease, herpes simplex type 2 virus
(HSV-2) is involved in 4-6% of cases. Characteristically,
patients have behavioral changes, fever, confusion, speech
disturbances and, less frequently, seizures. MRI of the brain
is the preferred imaging study and may show changes in
the temporal and/or frontal lobe. Polymerase chain reaction
(PCR) of the CSF is the diagnostic method of choice.
Mortality rates reach 70% in the absence of therapy and only
a minority of individuals return to normal function.
Conclusion: Herpes encephalitis must be suspected in
case of fever, confusion and focal neurological deficit. In
this patient the key to the diagnosis lay in recognizing the
reported ‘confusion’ as aphasia. Plasma leukocytosis and
raised CRP, common signs of infection, were conspicuously absent.
197. A patient with herpes encephalitis
196. Rare presentation of a very common pneumonia
L.J.N. Wind, M. Ghiti, D.Q. Ngo, M.J.M. Diekman
Deventer Hospital, Departement of Internal Medicine, Nico
Bolkesteinlaan 75, 7416 SE DEVENTER, the Netherlands,
e-mail: LJNWind@hotmail.com
M.I. Ilik
ZGT Hospital, location Almelo, Department of Internal
Medicine, Zilvermeeuw 1, 7609 PP ALMELO, the
Netherlands, e-mail: m.ilik@zgt.nl
198. Late recognition of chronic Q-fever in an immunodeficient patient with multiple vascular complications
M.C. Buis1, G.J. Kootstra1, R. Klont2, Chr.H.H. ten Napel1
Medical Spectrum Twente, Department of Internal Medicine,
Ariënsplein 1, 7511 JX ENSCHEDE, the Netherlands, e-mail:
m.buis@mst.nl, 2Laboratorium Microbiologie Twente en
Achterhoek, ENSCHEDE, the Netherlands
1
Case report: A 58-year-old previously healthy women,
presented with fever, chills and vomiting since five days.
She had headaches, muscle pain and her family members
reported ‘confusion’ since two days. She used no alcohol or
illicit substances. On physical examination she had fever
of 38.9 °C, blood pressure of 126/68 mmHg and a pulse of
73 bpm. Further physical examination was unremarkable.
On neurological examination she was cooperative. She
seemed to respond adequately but was not fully oriented
with respect to time and place. There were no further
neurological signs.
Laboratory analysis showed normal C reactive protein
(CRP), leukocyte count and leukocyte differential. Apart
from a normocytic anemia (Hb 7.1 mmol/l) and mild
hyponatremia (133 mmol/l) electrolytes, glucose, liver
enzymes and renal function were normal as were urine
analysis and a chest X ray. The consulted neurologist
recognized the disorder in comprehension as a sign
of non-fluent aphasia and diagnosed clinically herpes
Introduction: Pneumonia due to Mycoplasma pneumoniae
are frequently found in young adults. Our patient had a
very rare presentation of a M. pneumoniae!
Case report: A 19-year-old male with no relevant medical
history presented with a nine days history of malaise,
cold chills, nausea and since three days diarrhea and
dyspnoea. Six days after his initial symptoms of cold chills
and nausea he developed blisters and erosions on his lips
and oral mucosa. He also developed erythematous and
purpuric macules with vesicles and bullae, which started
on his palms and symmetrically spread to the rest of the
body. His general physician had started with amoxicillin/
clavulanic acid orally two days before presentation. Despite
antibiotics the patients developed purulent coughing and
became more dyspnoeic.
He had not used any medication prior to his illness, worked
as a gardener and had not been bitten by insects, nor had
he been abroad recently. Physical examination showed the
106
199. A young healthy man with repeated episodes of
pericarditis
Introduction: Q-fever, a zoonosis caused bij Coxiella burnetii,
is a disease with a high morbidity but low mortality.
While acute Q-fever often presents with mild non-specific
symptoms and is a self-limiting condition, the infection can
become chronic and -when untreated- cause endovasculitis
with major vascular complications. Due to lack of specific
symptoms the diagnosis remains a clinical challenge.
We would like to present the case of an immunodeficient
patient with a complicated chronic Q-fever infection, which
was only recognised after multiple vascular events.
Case report: A 78-year-old male, with a medical history
of chronic oesophageal candidiasis after which he was
diagnosed with T-cell dysfunction in vitro, mannosebinding lectine deficiency en IgG-subclass deficiency
(low IgG1 and IgG3), was admitted to the hospital because
A.M.T. Huijben, S.J. van den Boogerd, J.M.G.H. van Riel
St. Elisabeth Hospital, Department of Internal Medicine,
Tilburg, the Netherlands, e-mail: aukehuijben@hotmail.com
Case: A 36-year-old non-smoking and previously healthy
male presented at the Emergency Room with fever,
dyspnoea and malaise. Psychical examination showed
fever (38.8 °C) and tachypnea. Laboratory investigation
showed an inflammatory response with elevated CRP
and leukocytes, and slightly elevated liver enzymes.
Urine analysis was normal. Chest-X-ray and abdominal
ultrasound at presentation were normal. Treatment was
started with amoxicillin and tobramycin with the suspicion
of fever with pulmonal or abdominal origin.
107
After 48 hours antibiotics fever persisted and patient
became oxygen dependent. As a consequence a CT-A was
performed showing bilateral pneumonia with atelectasis
and no lung embolism. Coincidental a pericardial cyst was
seen, suggested congenital. Electrocardiogram showed
atypical depolarization and heart enzymes were elevated.
With the suspicion of an acute coronary syndrome patient
was transmitted to the CCU. Echocardiography was
normal at that moment. Next day on cardiac examination
pericardial rub was heard and the diagnosis of pericarditis
secondary to pneumonia was hypothesized. Treatment
with high dose acetylsalicylic acid was started with initial
improvement. After seven days of decreasing inflammatory
markers and absence of fever, antibiotics were discontinued.
Meanwhile microbiological analysis did not show pathogens
and there was no evidence for autoimmune disease.
However, patient’s clinical situation worsened and he
developed thoracic pain. Repeated CT showed pericardial
effusion without signs of tamponade. Since patient was
hemodymanic stable, a pericardial punction was not
performed. One week later pericardium effusion progressed
and patient became hemodynamic instable with clinical
signs of a tamponade like pulsus paradoxus, hypotension
and elevated CVP. Patient underwent chirurgical intervention with drainage of 800 cc haemorrhagic fluid.
Microbiological analysis of the pericardium fluid and all the
blood cultivates did not show any bacterial or viral agent.
After all this, patient developed again a pneumonia,
which was treated with ciproxin, and also a pericarditis,
confirmed with CT, and colchicine was added to the
acetylsalicylic acid. The pericardium cyst, described as
congenital before, was not seen at this CT.
Discussion: Acute pericarditis is a common, not always
primary mentioned, disorder in several clinical settings.
Our patient had relapsing pericarditis due to a presumed
viral pneumonia. This case shows how pericarditis can
cause life-threatening clinical condition, even in a young
man without co-morbidity. However, retrospective we can
also hypothesize that there was an infected pericardial cyst
which is also described in literature.
resistance) is generally regarded to have a favorable safety
profile.
We report on two cases of severe cutaneous adverse
reactions following repeated exposure to this widely used
drug.
To the best of our knowledge, Stevens-Johnson syndrome
(SJS) has now been reported as an adverse reaction to
proguanil – atovaquone in three published cases.
Our patients (1 M, 1 F) - both healthy subjects with no
known history of apparent drug allergy had been exposed
to proguanil-atovaquone before. One of them on more
than ten occasions. Both patients were severely ill with
generalized involvement of skin and mucosal membranes.
Following withdrawal of all possibly offending drugs
treatment with steroids was initiated. Cutaneous adverse
events are frequent following the use of pharmaceutical
agents. The majority are caused by NSAIDs, anticonvulsants, and antimicrobials. SJS typically affects 10% of the
skin surface, but dermal detachment may progress and
overlap with the more severe and extensive form of the
disease, toxic epidermal necrolysis (TEN). The incidence
of SJS is 1-2 cases per million population per year with a
low mortality rate. In TEN it raises upto 15%-75%. SJS is
characterized an erythematous rash with macules, and,
occasionally, vesicles and bullae that may coalesce and
erode and mucous membrane lesions that involve the oral
cavity, anogenital regions, and conjunctivae. SJS can be
confused with erythema exudativum multiforme (EEM)
but EEM is typically limited to the extensor surfaces of
the extremities and the mucosal epithelium. Our patients
developed their symptoms while still on the drug with first
appearance on the
palate, gums and trunk region. In the next 72 hours
erythematous macules on the trunk, proximal extremities
and erosions in the genital region appeared. Prednisone
(60 mg) was started and virtually no new lesions developed
since.
The diagnosis of SJS was supported by the histopathological findings. As single agents both proguanil and
atovaquone have been rarely reported to provoke skin
rashes with JSJ mainly caused by atovaquone.
We conclude that proguanil – atovaquone were the
causative agents of SJS in our patients. There have been no
relapses or persisting complaints. Obviously (re)challenge
is thought to be unethical.
This report should alert physicians to add
proguanil – atovaquone to the list of drugs that can cause
SJS.
200. SCAR ‘severe cutaneous adverse reactions’ following
the use of proguanil-atovaquone (Malarone®)
malaria prophylaxis
P.J. Wismans, M. van Kats, D. Overbosch, P.J.J. van Genderen
Haven Hospital and Institute for Tropical Diseases,
Department of Internal Medicine, Haringvliet 2,
3011 TD ROTTERDAM, the Netherlands, e-mail:
pjwismans@planet.nl
201. Neuroschistosomiasis
C.R. Boeddha1, M. van Wolfswinkel1, J.J. van Hellemond2,
S. Rosso1, P.J.J. van Genderen1, P.J. Wismans1
The highly effective combination proguanil – atovaquone
to prevent malaria (even in areas of high level chloroquine
108
1
XVII.NEPHROLOGY RESEARCH
Haven Hospital and Institute for Tropical Diseases, Department
of Internal Medicine, Haringvliet 2, 3011 TD ROTTERDAM, the
Netherlands, e-mail: c_boeddha888@hotmail.com, 2Erasmus
Medical Centre, ROTTERDAM, the Netherlands
202. Improving medication safety in patients with renal
impairment; enhancing collaboration between
pharmacists and physicians
Introduction: Schistosomiasis (Bilharzia) is a parasitic
disease, caused by infection with a trematode of the
Schistosoma species. S. haematobium, S mansoni and S.
Japonicum are the most important pathogens. Humans are
infected by penetration of the skin by larval schistosomes
in snail infested water in specific regions. Chronic disease
occurs when adult worm pairs produce eggs, evoking an
inflammatory response. Neuroschistosomiasis is rare
complication, caused by migration of schistosoma eggs to
the central nervous system. We describe a case of neuroschistosomiasis that was recently seen in our hospital
Case report: A 41-year-old man with a history of hepatitis,
malaria and schistosomiasis, for which he was treated
adequately in 2006, presented with chest pain and a
numbed feeling of his abdomen en legs for the past 3
weeks. He also reported muscle weakness and urinary
hesitancy. From 1985-1990 he had worked in Liberia
and since 1990 he lived in Guinea. His vital signs were
normal. Neurological examination showed a decreased
sensibility from level Th 2 and the abdominal reflex
was absent. Decreased muscular strength of the legs
and bilateral Babinski’s sign were found. Magnetic
resonance imaging showed a transverse myelitis involving
C4-Th7. Laboratory results showed eosinophilia but were
otherwise unremarkable. A lumbar puncture was not
be performed in view of the swelling of the myeloma.
HIV screening was negative. Stool microscopy revealed
living S. Mansoni eggs. Schistosoma serology titers had
increased. A diagnosis of neuroschistosomiasis was made
and the patient was started on praziquantel 60 mg/kg for
3 days and prednisone 60 mg once daily. He soon noted
improvement of the neurological symptoms and made a
virtually complete recovery. After one month, repeated
MRI scanning showed normalisation of the abnormalities
and a lumbar puncture was performed which revealed
positive schistosoma serology, confirming the diagnosis.
Discussion: This patient presented with neurological
symptoms while suffering from schistosomiasis. A
detailed travel history is of utmost importance. To locate
the patients signs an accurate physical examination is
required. Other infectious causes such as TB, HIV, neurocysticercose etc. need to be excluded. An accurate approach
is needed to prevent persisting neurological damage.
Conclusion: The diagnosis of schistosomiasis should be
considered in any traveller from an endemic area with a
history of exposure to surface water. Eosinophilia, schistosomiasias serology and parasitological examination in
stools and urine supports the diagnosis. Praziquantel is the
drug treatment of choice.
J.M.H. Joosten1, I. Drion2, C.J. Boogerd3, E. van der Pijl3,
R.J. Slingerland 4, T.J. Jansen5, O. Schwantje5, J.P.J. Slaets6,
R.O.B. Gans7, H.J.G. Bilo2
1
Universitary Medical Centre Groningen, Department of
Internal Medicine, Hanzeplein 1, 9700 RB GRONINGEN,
the Netherlands, e-mail: j.m.h.joosten@int.umcg.nl, 2Diabetes
Centre, Isala Clinics, ZWOLLE, the Netherlands, 3Pharmacy
Boogerd-Kluin, ZWOLLE, the Netherlands, 4Isala Clinics,
ZWOLLE, the Netherlands, 5General Practitioner, ZWOLLE,
the Netherlands, 6Deparment of Geriatric Medicine, University
Medical Centre Groningen, GRONINGEN, the Netherlands,
7
Department of Internal Medicine, University Medical Centre
Groningen, GRONINGEN, the Netherlands
Introduction: Guidelines stress the importance of
monitoring prescriptions to prevent adverse drug events
(ADEs), especially in patients with polypharmacy or comorbidities like CKD. The Dutch HARM-study estimated an
incidence of 41.000 medication-related admissions in the
Netherlands (of which 19.000 possibly preventable). Renal
failure appeared an important risk factor, but is often not
recognized. More effective use of routinely collected data
from electronic patient records (like eGFR) was suggested
to improve medication monitoring.
Aim: To address medication errors from a preventive
perspective by linking laboratory data on eGFR to
pharmacy records and by introducing medication alerts for
renal impairment.
Materials and methods: Prospective intervention study
conducted between February 2009 and January 2010
in Zwolle. All community pharmacies (n=11) and GP
practices (n=24) in Zwolle participated. The regional
laboratory consecutively reported all (newly) identified
adults with an eGFR =40 ml/min/1.73 m2 towards participating pharmacies. Community pharmacists checked the
patients’ actual drug regimen on current contra-indications
with regard to eGFR and, if necessary, proposed an intervention in the drug regimen towards the prescribing
physician. Subsequently a low-eGFR-alert was activated
at the pharmacy record to warn for low eGFR in future
presciptions. Besides patients’ characteristics, all proposed
interventions, potential ADEs and ADEs were recorded.
Results: During the study period 1368 subjects with an
eGFR 40 ml/min/1.73m2 were identified. Median [IQR] age
was 78 years and median [IQR] eGFR 34 ml/min/1.73 m2.
Polypharmacy was present in 73% (n=993); the mean
109
number of drugs was 7 (range 0-21). Overall, 342 drug
errors triggered an intervention in 211 subjects (15%); this
mainly concerning diuretics (22%), antibiotics (21%) and
anti-gout therapy (15%). Subjects needing an intervention
had a significantly lower eGFR (median [IQR] 34 versus
29 ml/min/1.73 m2, p<0.001) and a higher polypharmacy
rate (89 versus 70%, p<0.001) versus those without.
Overall, 88% (n=300) of all drug errors were regarded as
potential ADEs. These potential ADEs were mainly judged
as significant or serious. Physicians complied with 67% of
the proposed interventions. In 21 cases an ADE occurred
after not implementing the proposed intervention.
Conclusion: After introducing low-eGFR-alerts in
pharmacies, intensified collaboration between community
pharmacists and physicians resulted in 229 drug
adjustments aiming to improve drug safety. Extending
the availability of renal function data revealed that 1.2%
of our city inhabitants is at risk for ADEs due to renal
impairment. Awareness of this risk factor is especially
relevant in elderly and subjects with polypharmacy.
136.9(2.0) and 137.3(1.7), NaISE 135.9(3.0), 135.4(1.9) and
135.3(1.7), KF 4.8(0.7), 3.9(0.4) and 3.7(0.3), KDSE 4.7(0.7),
3.9(0.5) and 3.6(0.3), KISE 4.7(0.7), 3.9(0.5) and 3.6(0.3)
mmol/l respectively.
NaC was lower after HD and was always higher than NaF,
NaDSE or NaISE. NaF was stable during HD. NaF was
always higher than NaISE but than NaDSE only after HD.
NaDSE was stable during HD and always higher than
NaISE. NaISE was stable during HD. K declined during
HD. KF was always higher than KISE and KDSE. KDSE
was slightly higher than KISE after HD. NaC before HD
was best explained (r2=0.72) by NaDSE, KDSE, TP and TG.
Conclusion: NaC is strongly affected by HD. An increasing
difference between NaDSE and NaISE suggests at least a
change in PW during HD. It is unknown whether changes
in other ions beside Na and K are relevant for NaC since
they were not measured. NaC is higher than NaDSE
and NaISE at any moment. This may be relevant to HD
practice. NaF and KF are structurally higher then Na- and
KDSE and -ISE. This can be explained by the fact that
flame photometry measures total Na and K whereas DSE
and ISE measure active Na and K.
203. Differences between methods for determining [na+]
and [k+] in hemodialysis patients at different times
during dialysis
204. Vitamin D levels in a cohort of patients on
hemodialysis
A.L.H.J. Aarnoudse, J.A. Riedl, G.M.T. de Jong
Albert Schweitzer Hospital, Department of Internal Medicine,
PO Box 444, 3300 AK DORDRECHT, the Netherlands,
e-mail: a.j.aarnoudse@asz.nl
E.R. van de Wal-Visscher, H. Bogers, B. Bravenboer,
C.J.A.M. Konings
Catharina Hospital Eindhoven, Department of
Internal Medicine, Michelangelolaan 2, 5623
EJ
EINDHOVEN,
the
Netherlands,
e-mail:
e.vandewal@alumni.maastrichtuniversity.nl
Introduction: Na and K can be measured with a flame
photometer (NaF, KF), direct ion-selective electrode
(NaDSE, KDSE) and indirect ion-selective electrode (NaISE,
KISE). Na represents the majority of electrolytes in blood.
This enables the AK200 ULTRA S (Gambro) dialysis
machine to derive a Na-concentration from the conductivity of blood (NaC). Hemodialysis (HD) may change
plasma water (PW) as well as it does plasma Na and K. The
different methods are differently affected by these changes.
Aim: To compare the different methods for measuring NA
and K during dialysis.
Methods: In 45 HD-patients (M/F 28/27) blood was drawn and
NaC was registered before, halfway and after a HD-session.
Blood was analyzed for Na, K, hematocrit, total protein (TP),
albumin, cholesterol, triglycerides (TG) and urea.
Mean Na and K were compared between methods and
between sampling times using paired tests. A backward
stepwise linear regression model was used to explain NaC
from NaF, NaDSE, NaISE and measured variables. All
statistics were performed using SPSS for Windows.
Results: Mean(SD) concentrations at start, during and after
HD were for NaC 141.2(2.6), 140.2(1.8), and 139.4(1.3), NaF
136.6(2.6), 136.8(1.7) and 136.2(1.7), NaDSE 136.9(2.8),
Introduction: Vitamin D deficiency in hemodialysis
patients is associated with a higher incidence of cardiovascular diseases, metabolic abnormalities and mortality.
Vitamin D deficiency has been linked to various problems
next to renal osteodystrophy, an alteration of bone
morphology, and as such it has been ignored as a source of
morbidity in the western world.
Aim: The purpose of this study is to identify vitamin D
deficiency in a large cohort of patients on hemodialysis in
one dialysis Centre, Catharina-hospital Eindhoven.
Patients and methods: Levels of 25 (OH)-vitamin D3, Ca,
PO4 and PTH were measured in 81 hemodialysis patients
in the Catharina-hospital Eindhoven, the Netherlands
in 2008. All patients received standard state of the art
counselling by qualified dieticians.
Results: The patients were tested in winter. The mean
vitamin D3 in 81 patients was 23.4 nmol/l +/- 13.2 nmol/l.
80 Patients (98.8%) had a level of vitamin D (25-hydroxyvitamin-D levels) below 75 nmol/l. Only one patient
had a normal vitamin D level. The mean calcium level
110
was 2.3 mmol/l +/- 0.2 mmol/l, mean PO4 level was
1.6 mmol/l, +/- 0.4 mmol/l. Calcium levels were higher than
2.54 mmol/l in 10 patients (13%) and 38 patients (46.9%) had
a phosphate level between 1.13-1.78 mmol/l. The mean PTH
concentration was 30.3 pmol/l, +/- 22.3 pmol/l. 40 Patients
(49.4%) had a PTH level in the normal range.
Conclusions: There is a very high prevalence of vitamin
D3 deficiency in hemodialysis patients. It is necessary to
screen on vitamin D3 dialysis patients and review standard
dietary care of dialysis patients and supply deficits to avoid
vitamin D3 deficiency and subsequent morbidity and
possible mortality. Further research must indicate whether
suppletion should lead to a lower mortality and morbidity
in dialysis patients.
result of ACE-inhibition, we concluded that the most likely
diagnosis was a stenosis in the remaining renal artery. A
CT-angiography showed a 98% renal artery stenosis, due to
five misplaced surgical clips. The cortex of the kidney was
still enhanced by contrast.
Two months after the initial nefrectomy, an uncomplicated hepato-renal bypass was created. Diuresis started
immediately after surgery. Three weeks later the blood
pressure had normalized, urinary production was more
than 2 liters/24 hrs and the creatinine had stabilized on
197 mmol/l (2.2 mg/dl) (MDRD clearance 23 ml/min).
To our knowledge, there has never been a report of
a successful renal revascularization procedure after
two months of reduced blood flow. It is known from
abdominal aortic surgery and kidney transplantation that
the maximum time the kidney can be deprived of blood is
fifty minutes. However, in this case report, occlusion of the
blood flow was incomplete, which resulted in revivability
of the kidney two months after reduction of the blood flow.
In conclusion we describe a patient with an iatrogenic,
incomplete renal artery stenosis, where a successful revascularization procedure was performed two months after
the initial event.
XVIII. NEPHROLOGY CASE REPORTS
205. A different kind of stenosis
K.J. Woittiez, M. van Buren
HAGA Hospital, Department of Internal Medicine/
Nephrology, Leyweg 275, 2545 CH THE HAGUE, the
Netherlands, e-mail: kwoittiez@hotmail.com
206. Primary focal and segmental glomerulosclerosis
successfully treated with immunosuppression and
plasmapheresis
A 54-year-old woman complained of back pain and
weight loss. A CT-scan revealed a mass in the left kidney,
suggestive of renal cell cancer with pulmonary and bone
metastases. She was immediately referred to the urologist
for a palliative nephrectomy. Pre-operatively our patient
had an excellent renal function, with a creatinine of
53 mmol/l (clearance MDRD 104 ml/min).
Surgery was complicated by hypotensive episodes due to an
estimated blood loss of 18 liters. To compensate, our patient
received multiple transfusions with washed erythrocytes,
fresh frozen plasma and voluven®.
After the operation, the patient produced no urine. An
ultrasound of the remaining kidney showed no signs of
hydronephrosis. It was concluded that the patient most
likely suffered from acute tubular necrosis, due to low
blood pressure during surgery, in combination with
possible nefrotoxicity due to the large amount of infused
voluven®. After four days, hemodialysis became necessary.
Several days later, the patient developed hypertension and
blurred vision. The ophthalmologist diagnosed hypertensive retinopathy grade 3. Calcium antagonist and efforts
to raise the ultrafiltration rate during dialysis were unsuccessful. Eventually, ACE-inhibition was started, which
resulted in lowering of the blood pressure.
After adding up the acute anuric kidney failure after
nephrectomy, the symptomatic hypertension and the good
D.A. Geerse1, C.J.A.M. Konings1, J.F.M. Wetzels2
1
Catharina Hospital, Department of Internal Medicine,
Michelangelollaan 2, 5623 ER EINDHOVEN, the Netherlands,
e-mail: dgeerse@hotmail.com, 2Radboud University Medical
Centrum, NIJMEGEN, the Netherlands
Introduction: primary focal and segmental glomerulosclerosis (FSGS) is a frequent cause of the nephrotic syndrome
in adults and is usually treated with immunosuppressive
drugs. Plasmapheresis is generally reserved for recurrence
of FSGS in renal transplants.
Case report: A 40-year-old man was admitted with severe
ischemic ulcers of both legs. He had peripheral arterial
disease with no surgical options for revascularization
and was diagnosed with nephrotic syndrome a year
earlier. Renal biopsy was compatible with FSGS and high
dose prednisolon was started. Three months before his
hospital admission he was admitted for exacerbation of
nephrotic syndrome due to bad treatment compliance.
Treatment with prednisolone (60 mg daily) was resumed.
The patient had ischemic ulcers on both legs with digital
necrosis. Amputation of the left lower leg was performed
several days later. Two weeks later, he developed a lung
abscess in the right upper lobe, multiple liver abscesses
and an acalculous cholecystitis. Cultures were drawn
111
and treatment was started with cefuroxim, metronidazol
and gentamycin. The prednisolone dose was decreased.
Subsequently, his nephrotic syndrome exacerbated and he
developed acute renal failure, for which hemodialysis was
started. He developed respiratory insufficiency and was
transferred to the Intensive Care Unit. A bronchoalveolar
lavage (BAL) fluid was obtained for culture. All cultures
remained negative. A sputum culture drawn three weeks
earlier showed aspergillus fumigatus. Echocardiography
showed no vegetations. There were no signs of osteomyelitis on X-ray.
The patient was transferred to a tertiary care hospital one
day after starting hemodialysis. Another renal biopsy was
performed to evaluate disease reversibility; active FSGS
was found without scarring. High dose prednisolone
was resumed, resulting in sufficient improvement to
stop hemodialysis. There was still massive proteinuria
though, requiring additional treatment. Because of the
lung abscess, no cyclophosphamide was given. Instead,
plasmapheresis was started, resulting in a significant
improvement of proteinuria. Meanwhile, his lung abscess
progressed to a cavitating lesion with characteristics of
an aspergilloma. Ultimately, a lobectomy was performed.
Pathologic examination confirmed an aspergilloma.
Postoperatively, the patient remained in partial remission,
with stable proteinuria. In attempt to obtain complete
remission, tacrolimus and ciclosporin were given, but
both were discontinued because of gastrointestinal sideeffects. Two years afterwards though, complete remission
was achieved, and the prednisolone dose was gradually
lowered. He is currently taking 5 mg daily, with proteinuria
of 140 mg/day.
Conclusions: We strongly suspect that plasmapheresis had
an important role in inducing remission of primary FSGS
in our patient.
in improving outcome of transplantation. Meta-analyses have
demonstrated superior effectiveness of bariatric surgery when
compared with conventional therapy in achieving sustained
weight loss in obese patients. Yet, further analysis shows
higher postoperative mortality rates after bariatric surgery
in patients with renal failure than in the general population.
Aim: To assess the feasibility of bariatric surgery prior to
renal transplantation in patients with ESRD.
Materials and methods: We report 2 female patients
(patient 1: age 28; patient 2: age 65), initially rejected for
renal transplantation because of morbid obesity, who
underwent a laparoscopic bariatric procedure followed by
kidney transplantation. Both patients had hypertension,
patient 1 suffered from insulin-dependent diabetes
mellitus and hypercholesterolemia, patient 2 suffered from
severe tapetoretinal degeneration. Patient 1 had diffuse
glomerulosclerosis, probably caused by hypertension, as
cause of ESRD and patient 2 had diabetic nephropathy.
Results: Laparoscopic gastric banding was performed in
patient 1 in 2008, 20 months prior to kidney transplantation, patient 2 underwent laparoscopic sleeve gastrectomy
in 2009, 7 months prior to kidney transplantation. BMI
values decreased from 46 to 36 kg/m2 in patient 1 and from
41 to 31 kg/m2 in patient 2 after bariatric surgery prior
to transplantation. Complications developed in patient
2: after the sleeve gastrectomy, the patient developed
respiratory failure probably based on opiate intoxication,
and was treated in the ICU for 14 days. However, both
patients recovered well and mean total weight loss was
22%. Subsequently, live donor kidney transplantation was
performed successfully in both patients.
Conclusions: Laparoscopic bariatric surgery is a viable
treatment option in morbidly obese patients with ESRD
to achieve sufficient weight loss prior to successful renal
transplantation. Larger prospective studies are necessary
to further investigate the potential risks and benefits of
bariatric surgery in patients with ESRD.
207. The feasibility of bariatric surgery prior to kidney
transplantation in two morbidly obese patients with
ESRD
Introduction: Preclinical studies have shown that the
endogenous nucleoside adenosine is able to modulate
inflammation and to prevent associated organ injury.
Dipyridamole, an adenosine reuptake inhibitor,
increases extracellular adenosine concentrations during
unfavourable conditions, e.g. inflammation, and as such
may attenuate the inflammatory response and subsequent
organ injury.
Aim: To examine the effects of oral dipyridamole treatment
on innate immunity and organ injury during human
experimental endotoxemia.
Material and methods: In a randomized double-blind
placebo-controlled study, 20 healthy male subjects received
2 ng/kg E. Coli endotoxin intravenously following seven
day pretreatment with dipyridamole, 200 mg retard twice
daily, or placebo.
Results: Nucleoside transporter activity was significantly
reduced by dipyridamole with 89±2% (p<0.0001), which
resulted in significantly augmented endogenous adenosine
levels at the start of the experiment. Experimental
endotoxemia induced flu-like symptoms and increased
concentrations of circulating cytokines. Dipyridamole
concentrations correlated with the peak adenosine
concentration, 2 hours after LPS administration (r=0.82,
p=0.0038). Moreover, this dipyridamole-induced increase
in adenosine concentrations resulted in an enhanced
IL-10 response (r=0.82; p=0.0035). IL-10 peak concentrations correlated with a more pronounced decline in TNF-a
(Pearson r=0.54, p=0.018), a phenomenon known as
negative feedback. Furthermore, dipyridamole treatment
resulted in less endotoxin-induced circulating plasma
markers of endothelial activation; intercellular adhesion
molecule (ICAM) and vascular cell adhesion molecule
(VCAM) (p=0.07 and p=0.018), and partial recovery
of vascular sensitivity to norepinephrine. No effect of
dipyridamole on the endotoxin-induced increased urinary
excretion of markers of renal tubular damage, nor on
oxidative stress was observed.
Conclusions: Dipyridamole treatment augments the antiinflammatory response associated with a faster decline
in TNF-a, during human experimental endotoxemia.
These actions of dipyridamole are mediated by increased
adenosine concentrations. Dipyridamole did not affect
LPS-induced end-organ damage.
our dialysis unit with renal failure. There was no evidence
of a pre- or post-renal cause, but ultrasound imaging did
show a large mass involving the right kidney. Dialysis was
commenced but was not tolerated due to severe hypotension
30 minutes after starting a dialysis session. Further history,
physical examination and initial laboratory studies did
not reveal a clear cause of the renal failure or the dialysisinduced hypotension. Microscopic examination of the blood
film showed monocytosis and blasts. Eventually a bone
marrow biopsy in combination with the presence of a c-kit
mutation and elevated serum tryptase levels confirmed a
diagnosis of systemic mastocytosis. Unfortunately, renal
biopsy to further evaluate the renal mass was not possible
due to a persistent coagulopathy, possibly due to mast-cell
heparin release. The acute renal failure was believed to
be multifactorial with mast cell infiltration of the kidney
and periods of mastocytosis-associated hypotension as
contributing factors. We hypothesised that the hypotensive
episodes were due to mast cell degranulation induced by
the haemodialysis and this was confirmed by increases in
serum mast cell tryptase during the first hour of dialysis
which returned to baseline after dialysis. To protect against
the effects of mast cell degranulation during dialysis
premedication with anti-histamines and hydrocortisone was
commenced resulting in an improved dialysis tolerance.
Unfortunately, the systemic mastocytosis transformed into
a secondary acute leukaemia and despite treatment and
eventually the decision was made to withdraw dialysis. She
died several days later.
Discussion: Systemic mastocytosis is a rare disorder
characterised by pathological mast cell accumulation in
extracutaneous organs. Symptoms occur due to release
of mast cell mediators, such as histamine or tryptase,
the effects of local infiltration of mast cells. Triggers of
mast cell mediator release include infections, surgical
procedures and various drugs resulting in symptoms
including pruritis and systemic vasodilation. We show
that dialysis can trigger mast cell degranulation and that
symptoms coincide with mast cell mediator release.
208. An unusual cause of dialysis-induced hypotension
M. Jalving1, D.J. Meredith2, G.P. Collins2, E. Sharples2
1
University Medical Centre Groningen, Department of Internal
medicine, PO Box 30.000, 9700 RB GRONINGEN, the
Netherlands, e-mail: m.jalving@int.umcg.nl, 2Oxford Radcliffe
Hospitals NHS Trust, OXFORD, United Kingdom
M. Zijlstra, B. Bravenboer, C. Konings
Catharina Hospital Eindhoven, Department of Internal
Medicine, Michelangelolaan 2, 5623 EJ EINDHOVEN, the
Netherlands, e-mail: myrte.zijlstra@gmail.com
Introduction: Obesity is a major contributing factor in the
aetiology of chronic renal failure, since end-stage renal disease
(ESRD) is most commonly caused by obesity-related diseases.
Survival rates in obese patients are higher after renal transplantation than on dialysis. However, obesity is associated
with increased peri- and postrenal transplantation morbidity
and mortality, and therefore is considered a (relative) contraindication for transplantation. Weight loss may play a key role
Introduction: A symptomatic reduction in blood pressure
occurs in up to 50% of dialysis sessions. Causes include
rapid fluid removal and cardiac compromise. We describe
a patient with severe dialysis-induced hypotension and an
unusual underlying cause.
Case: A 68-year-old woman, being analysed for leukocytosis at the haematology department, was transferred to
112
XIX. INTENSIVE CARE RESEARCH
209. Dipyridamole modulates the innate immune
response during human endotoxemia.
210. Assessing small bowel function in ICU patients with
multiple organ dysfunction syndrome using the
citrulline generation test
B.P.C. Ramakers, N.P. Riksen, T.H. Stal, S. Heemskerk,
P. van den Broek, J.G. van der Hoeven, P. Smits, P. Pickkers
Radboud University Medical Centre, Department of Intensive
Care, Geert Grooteplein 10, 6500 HB NIJMEGEN, the
Netherlands, e-mail: b.ramakers@ic.umcn.nl
M.B. Keur1, J.H. Peters2, N. Wierdsma3, A.R. Girbes3,
A.A. van Bodegraven3, A. Beishuizen3
1
VU University Medical Centre, Boelelaan 1117,
1081 HV AMSTERDAM, the Netherlands, e-mail:
113
martijnkeur@gmail.com, 2Rode Kruis Hospital, BEVERWIJK,
the Netherlands , 3VU University Medical Centre,
AMSTERDAM, the Netherlands
211. Causes and consequences of extremely low blood
glucose levels not caused by insulin
L.R. Woittiez1, M. Hoekstra2, R.F.M. Oude Elferink1,
M.W.N. Nijsten2, K. Hoogenberg1
1
Martini Hospital Groningen, Department of Internal
Medicine, Van Swietenplein 1, 9728 NT GRONINGEN, the
Netherlands, e-mail: lyckewoittiez@gmail.com, 2University
Medical Centre, GRONINGEN, the Netherlands
Introduction: Small bowel dysfunction is believed to be an
under diagnosed condition but it is difficult to diagnose
because there is no validated bed side test. However, it
is of high importance since small bowel dysfunction
can possibly lead to malabsorption, sepsis and multiple
organ dysfunction syndrome (MODS). Recently a novel
functional test was developed, the citrulline generation test
(CGT) which is suggested to quantify enterocyte function
and mass, making it an interesting test to assess small
bowel function. The aim of this study was to elaborate
the feasibility of the CGT in a group of ICU patients with
MODS and to compare results with a control group of
stable ICU patients.
Materials and methods: The CGT was performed in 19 ICU
patients with MODS (= 2 failing organs) and in a control
group of 16 stable ICU patients who were mechanically
ventilated but had no other organ support. Median age and
APACHE II score were respectively 69 years (64-76) and
28 (20-34) in the MODS group and 63 years (53-68) and
25 (20-27) in the control group. SOFA score was higher in
MODS patients when compared to the control group, 10
(8-14) vs. 4 (3-5) (p<0.001).
The CGT was performed after a 5 hour fast, after which
20 mg of glutamine-alanine was administered intravenously. Subsequently, arterial plasma was sampled at fixed
time points to measure plasma citrulline levels using
HPLC.
Small bowel function was defined by both the slope and
the incremental area under the curve of citrulline at T=75
(iAUCT75). The slope was calculated from baseline and
peak citrulline levels.
Results: Fasting citrulline plasma concentration was
37 mmol/l (23-45) in the MODS group and 31 mmol/l
(25-38) in the control group (p=0.5), respectively. Peak
citrulline concentration was 46 mmol/l (32-65) in MODS
and 52 mmol/l (37-59) in controls (p=0.8).
The slope in MODS patients was 0.17 mmol/l.min (0.1-0.25)
versus 0.22 mmol/l.min (0.19-0.3) in the control group,
p<0.05. The iAUCT75 was also lower in the MODS group,
461 mmol/l.min (289-726) vs.691 mmol/l/min (564-781) in
the control group (p<0.05).
Conclusion: Identifying patients with small bowel
dysfunction is of great concern, however no validated
tests existed until recently. The novel CGT is a test which
is able to quantify small bowel function in ICU patients
with MODS, being more sensitive than single fasting
citrulline determination. Future studies will further
elaborate feasibility and accuracy of the CGT for daily
clinical practice.
Introduction: The adverse effects of insulin-induced
hypoglycaemia have been repeatedly described, both in
diabetics and in patients in the intensive care unit (ICU).
Systematic evaluation of extremely low glucose levels
not caused by insulin has, to our knowledge, not been
performed before. Thus we examined our hospital records
for patients with extremely low blood glucose levels.
Aim: Determine the causes and consequences of blood
glucose levels ≤ 0.5 mmol/l in patients who did not receive
insulin.
Materials and methods: Glucoses from all patients
admitted over a 4 year period to our hospital were
evaluated. Patients with glucose levels of 0.5 mmol/l or
less who did not receive insuline were included in this
study. These patients were analyzed for organ failure and
other factors known to contribute to hypoglycaemia and
mortality rate.
Results: We identified 8 patients displaying glucose levels
of 0.5 mmol/l or less. All patients died during the same
hospital admission, 7 of them within one day. Analysis
of the patient histories demonstrated severe multiple
organ failure in all patients. With respect to the potential
mechanism involved in extremely low glucose levels, two
factors were present in all patients. Firstly, all patients had
severe disease existing for several days and thus compatible
with full exhaustion of glycogen supplies. Secondly, all
patients demonstrated significant laboratory signs of liver
failure, indicating impaired hepatic gluconeogenesis.
Conclusion: Very low blood glucose levels that are not
caused by insulin administration carry poor short-term
prognosis. This appears to be due primarily to exhaustion
of glycogen supplies and failing gluconeogenesis. As
hypoglycemia itself may contribute to the adverse outcome
timely intravenous administration of concentrated glucose
is warranted in patients at risk for hypoglycemia. We are
currently conducting a dual Centre study to confirm the
current findings and identify potentially protective factors.
114
XX. INTENSIVE CARE CASE REPORTS
third trimester pregnancy. It is important to have a local
protocol for this rare event.
212. Cardiac arrest in pregnancy
213. Reversal of severe tricyclic antidepressant-induced
cardiovascular toxicity with sodium bicarbonate in
two cases
V.H. van Waning, P.M.L.H. Vencken, P.W. de Feiter,
A.J.B.W. Brouwers
Sint Franciscus Gasthuis, Department of Internal Medicine,
Kleiweg 500, 3062 KW ROTTERDAM, the Netherlands,
e-mail: v.vanwaning@sfg.nl
P. Bijlstra, A.A.K. Jahn, P. van Driel, J.A.H. van Oers
St. Elisabeth Hospital, Department of Intensive Care Unit,
Hilvarenbeekseweg 60, 5022 GC TILBURG, the Netherlands,
e-mail: p.bijlstra@elisabeth.nl
Introduction: Cardiopulmonary arrest in pregnancy is
a rare event. However it is important for emergency
physicians to be familiar with the indications for
performing a perimortem caesarean section (PMCS). We
report 2 cases of PMCS performed during CPR.
Cases: The first case, a 37-year-old female, G1P0, had a
medical history of epilepsy. Her pregnancy was complicated
at 30 weeks gestation by a single uncomplicated grandmal
seizure as a result of a low valproate level. After doseadjustment no more seizures occurred. Two days after
admission for hypertension, at 35 weeks gestation, she was
found unresponsive. Basic life support was initiated. Upon
arrival of the resuscitation team she had pulseless electrical
activity. She was treated according to the standard advanced
cardiac life support protocol. After 8 minutes she was still
pulseless, so we decided to perform PMCS in the operating
theatre. Two days postoperatively she was still unresponsive,
with absent pupillary and cornea reflexes. A somato sensory
evoked potential (SSEP) showed bilateral absence of N20
signals, confirming the diagnosis of severe postanoxic
encephalopathy. Because of poor prognosis treatment was
withdrawn.
The male infant, with a birth weight of 2300 grams, had an
initial Apgar score of 0/6/7 and had seizures.
The baby was resuscitated and intubated. The baby
survived, and follow-up 12 months after delivery showed
normal growth and neurologic development.
The second case, a 35-year-old patient, G3 P1, had an
uneventful medical history and was referred to the
hospital for induction of labour at 41 weeks and 3 days
duration of pregnancy. Half an hour after spontaneous
rupture of membranes the patient suffered from dyspnoea,
hypotension, bradycardia and cyanosis. Upon arrival of
the resuscitation team the patient had pulseless electrical
activity. Three minutes after cardiopulmonary resuscitation the patient was still pulseless and PMCS was
performed in the delivery room, resulting in the birth of a
girl of 3450 grams with Apgar scores of 2/6/7. Two weeks
after the PMCS both mother and daughter were discharged
without any neurological or other abnormalities.
Conclusion: Timely use of PMCS is critical for obtaining
improved maternal and fetal outcomes in cardiac arrest in
Introduction: We present two cases of complete reversal of
serious tricyclic antidepressant (TCA) intoxication.
Case 1: A 51-year-old man was admitted to the ER 1 hour
after ingestion of 300 tablets Imipramine of 25 mg and
200 tablets Nortriptyline of 25 mg. BP 90/50 mmHg,
pulse rate 120/min. Within a few minutes he lost
consciousness, was intubated and mechanical ventilation
was started. He underwent gastric lavage and was given
charcoal. Crystalloid infusion and vasopressic drugs were
started. His ECG showed a sinus tachycardia at a rate of
120/min and a QRS of 180ms, QTc of 561 ms and a right
bundle branch block. Laboratory studies showed no abnormalities. No TCA plasma concentration was determined.
Sodium bicarbonate infusion was started. 200 ml sodium
bicarbonate 8.4% as bolus infusion, followed by 2 litres
of sodium bicarbonate 1.4% intravenously per day. This
resulted in pH values in the target range of 7.45 to 7.55.
QRS time normalized within 6 hours and the right bundle
branch block configuration disappeared. The patient was
discharged from the ICU after 6 days.
Case 2: A 20-year-old man was admitted to the ER after
ingestion of 150 tablets of Tryptizol 50 mg, 30 tablets of
Tryptizol 25 mg, 10 tablets Alprazolam 1 mg, 10 tablets
Alprazolam 0.25 mg and 10 tablets Tranxene 5 mg. Time
of intake was unknown. At arrival BP was 80/60, pulse 30/
min and Glascow Coma Scale 3. The patient was intubated
on site and transported to the ER. Because of the delayed
arrival no gastric lavage was performed, charcoal therapy
was started. Arterial bloodgas analysis showed a pH of 7.26
and 100 cc bolus sodium bicarbonate 8,4% was given and
2 times repeated until pH range was 7.45-7.55. At arrival
the QRS width was 138 ms and QTc was 541 ms. Both
normalized in 12 hours. Plasma concentration of TCA was
elevated. The patient was discharged from the ICU after
6 days.
Discussion: TCA induced cardiotoxicity is predominantly
due to blockade of cardiac fast sodium channels in the
His-Purkinje system and ventricular muscle, resulting
in conduction defects and decreased inotropy. Within 2
hours after ingestion gastric lavage is useful. Blood alkalization with Bicarbonate is the therapy of choice. The exact
115
mechanism is unresolved, suggested mechanisms being
both pH change and sodium loading. Because of the large
volume distribution and protein binding, dialysis cannot
help in disposition of TCA.
occur. Our patients required aggressive treatment with
high doses of sedatives, which lead to prolonged ventilation
and ICU stay. In the second case we considered administration of medical GHB as treatment.
214. Prolonged mechanical ventilation and ICU stay due
to GHB withdrawal syndrome in two cases
215. Relationship between Staphylococcus aureus sepsis,
orchidodynia and retroperitoneal disease: knowledge
of simple anatomy
P. Bijlstra, Q.L.M. Habes, J. van Rosmalen, J.A.H. van Oers
St. Elisabeth Hospital, Department of Intensive Care Unit,
Hilvarenbeekseweg 60, 5022 GC TILBURG, the Netherlands,
e-mail: p.bijlstra@elisabeth.nl
Y.M. Ahmed-Ousenkova 1 , H.J. van Leeuwen 2 ,
V. Mattijssen1
1
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
youlia-ahmed@hotmail.com, 2Rijnstate Hospital, 2Department
of Intensive Care, ARNHEM, the Netherlands
Introduction: We present two cases of mechanically
ventilated patients with Gamma-Hydroxybutyrate (GHB)
withdrawal syndrome.
Case 1: A 28-year-old man, with a history of alcohol and
cocaine abuse, presented to the ER with confusion and
agitation. Blood pressure 110/60 mmHg, pulse rate 110
beats/min, Glasgow Coma Scale Score of 9. Further
examination was without abnormalities. Because of his
fierce agitation he had to be intubated and sedated. A
cerebral CT, liquor analysis, laboratory studies and EEG
showed no abnormalities. At the ICU he became unmanageably aggressive, despite high doses of propofol 2.3 mg/
kg/h. Intravenous midazolam 1.5 mg/kg/h for 94 hours and
oral lorazepam 32 doses of 4 mg in 7 days had to be added,
with little improvement. The second day after admission
the patient’s family reported that he used an unknown
amount of street GHB 4 times every day. Therefore
intravenous clonidine (average 0.6 mg/kg/h) was given
for 77 hours, after which was switched to oral clonidine 3
x 200 mg/day. Finally, on day 7, his agitation resolved and
he could be detubated. The patient was discharged to the
psychiatric department with oral clonidine 3 x 200 mg/day
and lorazepam 6 x 4 mg/day at day 8.
Case 2: A 34-year-old man was admitted to the ICU after
a high-energy trauma with multiple rib fractures, left side
pneumothorax, pulmonary contusion and fractures of
cervical vertebrae C2-C6. Cerebral CT was without abnormalities. Due to a history of amphetamine and GHB abuse
he was treated with intravenous clonidine 0.59 mg/kg/h
for 273 hours and 0,47 mg/kg/h for 335 hours, propofol
2,4 mg/kg/h for 61 hours and 1,6 mg/kg/h for 546 hours and
midazolam average 0,1 mg/kg/h for 562 hours. Due to more
agitation on the third day lorazepam was added to the regime
(total 142 doses of 4 mg in 24 days),. Due to the regime of
sedatives he required prolonged mechanical ventilation (26
days). The patient was discharged with lorazepam 6 times
4 mg and clonidine 6 times 150 mg at day 27.
Discussion: GHB is an increasingly popular drug of abuse.
These cases highlight that after sudden cessation of GHB
use, a severe withdrawal syndrome with agitation may
Introduction: The incidence of Staphylococcus aureus sepsis
has significantly increased in the last twenty years. Twenty
percent of patients develop metastatic complications,
such as endocarditis, spondylodiscitis, metastatic abscess
formation and meningitis. The presenting symptoms can
sometimes be atypical, as is demonstrated in this case.
Case report: A 64-year-old man with a long history
of chronic lumbago and type 2 diabetes mellitus was
referred to the emergency department because of sudden
behavioural changes, worsening of back pain and pain
in the left testicle. Three days before admission, he had
consulted his general practitioner for worsening back pain,
and received increased pain medication.
On physical examination Glasgow Coma Score was 9.
Vital signs were: temperature 35 °C, blood pressure
171/96 mmHg, and a pulse rate of 126 beats/min.
Apart from a painful lower spine on palpation, physical
examination did not show any abnormalities, especially
inspection and palpation of the testicles. The results of
blood tests showed leukocytes 3.0 x 10/l, thrombocytes of
41 x 10/l, high lactate of 10,3 mmol/l and CRP 485 mg/l.
Chest X-ray and urine analysis showed no abnormalities.
Liquor was clear, and mixed with blood. The patient was
admitted at the Intensive Care Unit and treated according
to local protocol for sepsis of unknown origin with
cefuroxim. The pain in the testicle at first could not be
explained. CT scans of chest and abdomen showed spondylodiscitis L3-L4 with abscess formation and spread into the
left psoas muscle. Next day he was operated and the psoas
abscess was drained. From blood, cerebrospinal fluid and
psoas abcess Staphylococcus aureus was isolated. High dose
flucloxacillin was started. Transthoracic echocardiography
showed vegetations on the tricuspide valve. Four days after
admission, he died due to multiple organ failure.
Conclusion: We describe a patient who presented with
orchidodynia and lumbago and who proved to have severe
Staphyloccus aureus sepsis based on spondylodiscitis with
116
a psoas abscess. The orchidodynia can be explained as
referred pain from the retroperitoneal lumbar region.
This is due to the innervation of the testicle by the ilioinguinal and genitofemoral nerves, which descend from
level L1, partly along the psoas, to the testicle. Diagnosis
of spondylodiscitis is difficult in old patients because
they present with a wide variety of symptoms and signs.
Orchidodynia, without abnormalities of the testicle at
physical examination, should focus on the retroperitoneal
region, and in this patient might have revealed the psoas
abscess related to spondylodiscitis earlier.
was performed. All were negative. An osmol gap of
63,5 mOsm/kg is calculated (measured serum osmol
352 mOsm/kg minus calculated osmol 288,5 mOsm/
kg). This osmol gap is explained by the ethanol intoxication. Ethanol explains the osmoles, but is no acid. An
osmol gap of 63,5 mOsm/kg corresponds with an ethanol
intoxication of 2,9 ‰ (63,5 x 0,046). The measurement of
serum ethanol was 2 hours later performed. With this case
we tried to focus attention on the fact that a high anion
gap metabolic acidosis with an osmol gap is not always
the result of an intoxication with known intoxications as
methanol, ethylene glycol, aspirin or toluene (all acids).
216. High anion gap metabolic acidosis with osmol gap is
not always due to ingestion of known toxins
217. Use of terlipressin in amitriptyline overdose
P. Bijlstra, M. Samuels, J.A.H. van Oers
St. Elisabeth Hospital, Department of Intensive Care Unit,
Hilvarenbeekseweg 60, 5022 GC TILBURG, the Netherlands,
e-mail: p.bijlstra@elisabeth.nl
D.L.J. Moolenaar, A. Manten, B.M. van der Oord
Meander Medical Centre, Department of Internal Medicine,
Utrechtseweg 160, 3818 ES AMERSFOORT, the Netherlands,
e-mail: davidmoolenaar@gmail.com
Introduction: We present a case of a patient with a mixed
high anion gap metabolic acidosis with a osmol gap.
Case: A 29-year-old man, with a history of alcohol abuse,
presented to the ER after a fall from the stairs with a
short period of loss of consciousness and seizures. Due
to further loss of consciousness he had to be intubated
and artificial ventilation was started. A cerebral CT scan
showed bone fractures and a intracerebral haemorrhage
with blood in the ventricles. He was transported to
the ICU. Again seizures were observed and levetiracetam was started intravenously. Blood pressure 100/60,
pulse rate 111 beats/min, respiratory rate breaths 20/
min, temperature 36,4 °C, SaO2 93%, fully sedated.
Except for a haematoma on the skin of his scull no
further abnormalities on examination. Laboratory studies
included: Na+ 140 mmol/l; K+4,3 mmol/l; CL - 106 mmol/l;
ureum 1,8 mmol/l; glucose 6,7 mmol/l; ABG pH 7,33;
HCO3- 19,3 mmol/l; lactate 5,3 mmol/l; measured serum
osmol 352 mOsm /kg H2O. Urine analysis revealed no
ketones. Measured serum ethanol 1,7 ‰. Serum analysis
for methanol, ethylene glycol, aspirin and toluene were
negative. Calculated anion gap 19mmol/l, (Na+ + K+ Cl- - HCO3-) [N 8-16 mmol/l], calculated osmol (2 x Na+ +
glucose + ureum) 288,5 mOsm/kg.
Discussion: With an ethanol intoxication our patient fell
from the stairs and developed a traumatic subarchnoid
haemorrhage (SAH) The seizures are a result from the
SAH or ethanol intoxication and explain the high serum
lactate, which is released from the muscles. There were
no signs of sepsis or tissue hypoperfusion due to shock.
The lactate acidosis explains his high anion gap. Under
the suspicion of an intoxication serum analysis for known
toxins as methanol, ethylene glycol, aspirin and toluene
Introduction: Amitriptyline is an important member of the
tricyclic antidepressants and it is a commonly used drug in
intentional overdose.
Case: A patient is presented with severe hypotension due
to amitriptyline intoxication not responding to volumesuppletion, sodiumbicarbonate administration and high dose
vasopressive therapy. A very good response was elicited by
administering 2 mg of terlipressin leading to a quick and
uneventful recovery in the next hours.
Conclusion: We report a case of acute tricyclic-intoxication,
complicated by severe vasodilatory hypotension refractory
to volume and vasopressive therapy, successfully and safely
treated by terlipressin.
XXI RHEUMATOLOGY RESEARCH
218. Lymphocytopenia as a riskfactor for Pneumocystic
jiroveci pneumonia in dermatomyositis: two case
reports, a review and profylaxis recommendations
D.G. Beekman1, M.D. Kruif2, I. van Groenigen3, K. Saito4,
Y. Tanaka 4 , A. Voskuyl3, M. van Agtmael3, C. Slagt1,
B. Kanen1
1
Zaans Medical Centre, Department of Internal Medicine, PO
Box 210, 1500 EE AMSTERDAM, the Netherlands, e-mail:
djoekegonne@hotmail.com, 2 Academic Medical Centre,
AMSTERDAM, the Netherlands, 3VU University Medical
Centre, AMSTERDAM, the Netherlands, 4School of Medicine,
KITAKYUSHU, Japan
117
Introduction: We present two cases of DM, one fatal
of Pneumocystis jiroveci pneumonia in patients with
dermatomyositis. No consistent guidelines were found
for PCP-profylaxis in this patient group. We collected
expert opinions and we pooled data from previous studies,
in order to construct new, simple recommendations for
PCP-profylaxis in these patients.
Methods: Literature was reviewed using PubMed database
and references. Authors were contacted for sharing original
data, which were pooled in order to calculate incidence
figures of PCP, mortality rates and prognostic factors.
Results: Two cases from our hospital are presented, one of
them was fatal. In literature, 13 relevant case series were
found. Pooled incidence for PCP were 1% for all patients
with connective tissue disease (CTD) and 4.3% (p<0,001)
for the subset of patients with dermatomyositis and/or
polymyositis (DM/PM). Mortality in both groups was high
but not significantly different (45% vs. 55%). We found
a relation between a low lymphocyte count (< 1.5 x 109/l)
based on clinical parameters.
Conclusion: Based upon pooled data from 12 prospectiveen retrospective studies as well as 2 case-reports, we
recommend PCP-profylaxis for all patients diagnosed
with DM/PM with a low lymphocyte count (< 1.5 x 109/l)
at diagnosis.
joints. Blood investigation revealed a CRP of 141 mg/l,
ESR 114 mm/h, leukocyte count of 17.7 x 109/l and normal
renal and liver function tests. Diclofenac treatment was
started without success. Serologic examination for Borrelia,
Q-fever, Rubella, CMV and EBV as well as rheumatoid
factor were negative. Ferritin level was 3687 ug/l. At this
point AOSD was considered. Three months after initial
complaints, the patient developed acute liver test abnormalities with a total bilirubin level of 303 umol/l, AF 512
U/l, gGT 330 U/l, ASAT 1659 U/l, ALAT 1591 U/l and a
ferritin level of 7639 ug/l. Hepatitis A,B,C,E serology was
negative and she had no anti nuclear or anti mitochondrial
antibodies. Within a month her liver function returned to
normal. However, fever and arthralgia persisted and the
liver enzymes increased again. Definite diagnosis of AOSD
was made and prednisone was started which resulted in a
remarkable improvement. Eight months after her initial
complaints, the patient is nearly in remission.
Discussion: AOSD is an inflammatory disorder with
unknown etiology, characterized by fevers, arthritis, skin
rash and markedly elevated levels of serum ferritin. There
is no specific test to confirm the diagnosis. Therefore, a
combination of criteria, termed the Yamaguchi criteria, have
to be met. Liver involvement is one of the minor criteria, but
only a few cases describe extreme liver test abnormalities.
In this case, drug sensitivity for amoxicillin cannot be
completely ruled out but is considered unlikely because
of relapse of liver function disturbance and the fact that
development of liver test abnormalities was entirely in line
with the development of extreme levels of serum ferritin.
Conclusion: AOSD is often difficult to diagnose and can
lead to severe and long-lasting complaints.
XXII.RHEUMATOLOGY CASE REPORTS
219. Adult-onset Still’s Disease as a cause of extreme liver
test abnormalities
220. Painless joint deformities in a patient with renal
disease and diabetic polyneuropathy
P.M. van Gastel, C. Richter
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
petrivangastel@hotmail.com
J.J.M. Geelhoed, I.C. van Riemsdijk-van Overbeeke,
A. Dees
Ikazia Hospital, Department of Internal Medicine,
Scheepmakerskade 73, 3011 VX ROTTERDAM, the
Netherlands, e-mail: mgeelhoed@hotmail.com
Background: Adult onset Still’s Disease (AOSD) is a well
characterized rheumatoid disorder in which the liver is
frequently involved. This is generally asymptomatic, but
severe hepatic failure has occasionally been reported. We
describe a case of a woman who developed severe liver test
abnormalities three months after presenting symptoms
of AOSD.
Case-Report: A 52-year-old woman with a history of
endometrial carcinoma was referred to our outpatient
clinic because of fever. Complaints started five weeks
earlier, with fever, diffuse rash and a sore throat.
Amoxicillin therapy had been started two weeks before,
without remission. On examination she had erythema
on upper legs and red and swollen metacarpophalangeal
Introduction: Limited surgery of fingers or toes sometimes
is inevitable in diabetic and rheumatic patients, usually due
to persistent microvascular or infectious disease. Underlying
crystal arthropathies however, such as longstanding gout,
may mislead the pathologist and clinician.
Case: A 79-year-old male was sent to the nephrologist in
case of chronic kidney disease stage III. On admission,
marked, painless joint lesions of all fingers were noticed. He
had a history of TBC, hypertension, polyneuropathy, type II
diabetes mellitus, atrium flutter, and congestive heart failure.
Physical examination showed red and swollen joint lesions
118
of his fingers with yellow-white deposits (tophus lesions).
He missed his left digit V, which had been amputated. The
patient, who feared new surgery, told that the other fingers
had become worse since five months. The case was reconsidered: digit V had been amputated some years before,
because of persistent ulceration. The pathological diagnosis
was rheumatoid arthritis. X-ray imaging of the hands had
shown reactive changes with extensive erosions in nearly all
fingers. Because of the dramatic radiologic and microscopic
results, a diagnosis of rheumatic arthritis had been made.
Therapy with methotrexate and prednisone was started,
leading to an improvement of the clinical picture. Moreover,
older patient data revealed that at first, the lesions were
thought to be pseudo-gout caused by renal insufficiency.
However, in the past he had been diagnosed with gout flares
of his big toe and feet, accompanied by characteristic gout
pain and treated with Colchicine. Combining these contradicting data a new smear of the deposits was taken, showing
(surprisingly) massive uric acid crystals. Retrospectively,
the pathologist changed result of the amputated tissue from
rheumatoid arthritis to gout.
Discussion: Gout is a very painful urate crystal deposit
disease of the joints. Most often it presents as an acute
mono-arthritis with predilection for lower extremities,
especially the big toe. Longstanding progressive tophus
disease may present as low grade chronic poly-arthritis,
resembling rheumatoid arthritis. The diagnosis of gout
is confirmed by the presence of uric acid crystals in the
joint fluid or tophi. In our patient, doctors were misled by
the lack of pain, the pathological diagnosis of rheumatoid
arthritis and his renal insufficiency.
Conclusion: It illustrates that serious joint deformities do
not necessary lead to joint pain. In this atypical patient, his
diabetic polyneuropathy may have masked the pain and
thereby delayed the diagnosis.
muscle pain and muscle weakness. Laboratory results
at that time revealed no abnormalities, except for an
increased sedimentation rate (85 mm/h) and a leucopenia
(3.1 x 109/l), although creatininekinase was not determined.
Blood cultures were repeatedly negative.
On examination at our hospital the patient had severe
proximal muscleweakness and could hardly walk,
showed proximal muscle atrophy and most importantly a
heliotrope rash and Gottron’s plaques.
Based on these clinical observations, the most likely
diagnosis was dermatomyositis. The diagnosis was
confirmed by the presence of increased serum creatinekinase levels (1880 IU/l) and abnormalities shown
in the skinbiopsy (chronic perivascular and interstitial
dermatitis with vacuolar changes, edema and mucine
depositions) and in the muscle biopsy (lymphocytic
infiltrates in muscle, no specific abnormalities).
Additional imaging analysis revealed no signs of
malignancy and immunoserology showed positive antinuclear antibodies with antibodies against SS-A but not
against Jo-1. The patient was treated with corticosteroids.
Dermatomyositis is a rare inflammatory myopathy. Both
male and female of all ages may be affected. Symmetric
and proximal muscle weakness as well as characteristic
skin findings as heliotrope rash, shawl’s sign and Gottron’s
plaques are the typical symptoms. Systemic complaints
such as fatigue, fever, weight loss or non-erosive inflammatory polyarthritis may develop, especially as the disease
progresses. Interstitial lung disease develops in at least
ten percent of the cases and can rapidly lead to respiratory
failure and even death. Furthermore patients with
dermatomyositis have an increased risk of malignancies,
especially adenocarcinomas of the cervix, lung, ovaries,
pancreas, bladder and stomach. The treatment of choice
are glucocorticoids and if needed glucocorticoid-sparing
medications such as azathioprine or methotrexate.
In every patient with skin abnormalities on handjoints in
combination with muscle weakness the diagnosis dermatomyositis should be suspected.
221. Red fist without strength
I.K. van Groeningen1 , J. Arnoldus2 , D. Beekman 2 ,
M. van Agtmael1, A.E. Voskuyl1
1
VU University Medical Centre, Department of Internal
Medicine, De Boelelaan 1117, 1081 HV AMSTERDAM,
the Netherlands, e-mail: i.vangroeningen@vumc.nl, 2Zaans
Medical Centre, ZAANDAM, the Netherlands
222. Takayasu arteritis mimicking malignancy
A.E. Pulles, G.J.M. Herder, E.J. ter Borg, W.J.W. Bos
St. Antonius Hospital, Department of Internal Medicine,
Koekoekslaan 1, 3435 CM NIEUWEGEIN, the Netherlands,
e-mail: a.pulles@antoniusHospital.nl
Case: In July 2010, a 64-year-old man was presented to our
hospital for a diagnostic problem consisting fever, skin
lesions and musclepain. Six weeks before he presented
himself at another hospital with a submental swelling and
high fever and was treated with antibiotics on suspicion
of erysipelas. A week later skinlesions developed on the
metacarpophalangeal and proximal carpophalangeal joints
hands, nose and eyes. His mobility was impaired due to
Case report: A 69-year-old woman of Indonesian descent
was diagnosed with Takayasu arteritis in 2005 and is
regularly controlled in our outpatient department. For the
last couple of years there were no signs of disease activity;
blood pressure difference between both arms was stable.
Recently, she was evaluated because of weight loss.
119
Three weeks prior to presentation she was admitted to
a hospital in Bali (Indonesia) because of a suspected
pneumonia. The radiology report of the X-thorax described
a density in the left inferior lobe and possibly in the right
inferior lobe as well. She was treated with antibiotics and
her pulmonary symptoms disappeared completely.
A follow-up X-thorax in our clinic revealed a small density
in the right inferior lobe. Further analysis by CT disclosed
three nodules in the right inferior lobe, of which the
largest diameter was 1 cm. The lesions were suspect for
malignancy; therefore a PET-CT was made. However,
on PET-CT only one of the three nodules was visible and
barely active. Furthermore, there were no signs of active
metabolism in the large arteries. At that moment, CRP
(1 mg/l) en ESR (21 mm/h) were low. Subsequently a
bronchoscopy was performed. Cytology obtained by lavage
demonstrated no malignant cells and the cultures did not
grow any pathogenic micro-organisms. Since malignancy
could not be excluded, video-assisted thoracoscopic surgery
with a wedge resection of the right inferior lobe was
performed. Histopathological examination of the obtained
tissue showed mainly necrotic tissue surrounded by some
granulomatous inflammation. There were no malignant
features or signs of an active vasculitis. Stains for acid-fast
bacteria, fungi and other micro-organisms were negative.
The pathologist considered an old infarction to be the most
likely interpretation of this specimen.
Discussion: Takayasu arteritis primarily affects the aorta
and its main branches. In approximately 50 percent of
patients pulmonary arteries are involved as well, but
pulmonary symptoms occur less often. Pulmonary
infarction as the initial presentation of Takayasu disease is
well documented. However, to our knowledge pulmonary
infarction mimicking pulmonary malignancy in Takayasu
arteritis has not been described previously.
Conclusion: This case report illustrates that pulmonary
infarction due to Takayasu arteritis can mimic malignancy.
is thought to reduce morbidity and mortality. Early
warning systems (EWS) are based on this hypothesis.
In our hospital an EWS based on level of consciousness,
respiratory rate, heart rate, systolic blood pressure and
oxygen saturation was introduced.
Aim: To assess characteristics and outcome of patients with
clinical deterioration according to our EWS.
Methods: We performed a retrospective analysis of the
reports of the EWS during a ten-month period in 2009
and 2010 on a medical ward in a teaching hospital in the
Netherlands. Only first reports were included. Primary
endpoints were hospital mortality and adverse events in
the 24 hours after the report.
Results: During the study period there were 53 reports.
Two were not included because of incomplete data, 14
reports were excluded because they were second or third
reports. From the 37 reports which were analysed 59.5%
of the patients were male, the median age was 78 year
(range 44-91). 94.6% of the admissions were not planned.
Most frequent reasons for admission were suspicion of
infectious disease (45.9%), dyspnoea and kidney failure
(both 10.8%). In 56.8% there were no limitations on
treatment preceding the report. The parameter that
was most frequent changed was the respiratory rate
(RR >25/min, 26 times), followed by oxygen saturation
(oxygen saturation < 92%, 25 times) and changed level of
consciousness (decrease of GCS =2 points, 11 times). The
decline was in most cases thought to be due to a primary
problem in the circulation (37.8%) or to sepsis/infection
(37.8%). Medication and supportive care were started 28
times. In 9 cases there was consultation of an intensive
care specialist; 4 patients were transferred to the ICU, in
the other 5 cases a treatment limitation was adjusted. Two
other patients got a treatment limitation following the
report. Three patients (8.1%) died within 24 hours of the
report. All three of them had a treatment limitation and
their deaths were expected. Total hospital mortality was
32.4%. No cases of cardiopulmonary resuscitation were
found in the observed group.
Conclusion: In our study we found the respiratory rate as
most frequent reported changed physiological parameter,
as is previously described in other studies. The most
frequent causes for decline were circulatory problems and
sepsis/infection. It is notable that in almost 1 in 5 patients
a treatment limitation was arranged following the report.
XXIII. GENERAL INTERNAL MEDICINE RESEARCH
223. Early warning system on a medical ward; patient
characteristics and clinical outcome
C. Bethlehem, W.P. Kingma
Medical Centre Leeuwarden, Department of Internal
Medicine, Henri Dunantweg 2, 8934 AD LEEUWARDEN,
the Netherlands, e-mail: carina.bethlehem@znb.nl
224. The safety of winetasting: the Bac(chus) experiment
D.L.J. Moolenaar, A. van de Wiel, J.P.M. Wielders
Meander Medical Centre, Department of Internal Medicine,
Utrechtseweg 160, 3818 ES AMERSFOORT, the Netherlands,
e-mail: davidmoolenaar@gmail.com
Introduction: Clinical deterioration is often preceded by
changes in physiological parameters; early intervention
120
Introduction: During the last two decades wine has
become very popular even in non-wine growing countries
and winetasting sessions are organized regularly as part
of this social phenomenon. Although the wine is not
consumed, the contact of the wine with the buccal mucosa
may lead to alcohol absorption. In this experiment blood
alcohol concentrations (BAC’s) were measured after such
a winetasting session.
Methods: Ten healthy volunteers, five men and five
women, ages ranging from 30-60 years, participated in
the experiment. They tasted ten wines, five white and five
red ones, with alcohol percentages ranging from 11.5-13.5%
during 50 minutes. They were requested to hold fifteen
cc of each wine in the mouth during two periods of 15
seconds with an interval of one minute. The wine was spat
out to prevent gastro-intestinal uptake. The mouth was
washed with water before the next wine was tasted three
minutes later. Ten minutes after the last wine, so one hour
after the start of the experiment blood samples were taken
for BAC analysis by an enzymatic method on a Beckman
Counter Analyzer.
Results: In only one of the individuals, a woman of small
size, the alcohol concentration found (0.06 g/l) was above
the detection limit of 0.05 g/l. For the whole group concentrations ranged from 0.01-0.06 g/l, mean 0.025 g/l for
both men and women, well below the legal Dutch limit for
driving permission (0.5 g/l).
Conclusion: The tasting of ten wines during a one hour
period does not result in blood alcohol concentrations that
interfere with driving ability or daily activities.
in the Netherlands from May 2007-August 2007 were
studied.
2000 consecutive admissions were studied: 576 (29%,
26-32%) were classified as possibly iatrogenic; out of these
380 (19%, 17-22%) as definitely iatrogenic, out of whom
229 (12%, 10-14%) had already been classified as iatrogenic
by the admitting physicians. Patients with cardiac disease,
hypertension, gastrointestinal conditions, anticoagulant
treatment and use of NSAIDs were, particularly, at risk
of iatrogenic admission with percentages of 22 (16-24), 13
(11-18), 12 (9-15), and 7 (5-11)%. An independent predictor
of iatrogenic admissions was age with an odds ratio of 1.27
per 10 years (p=0.0001).
1. At least 19% of admissions to the departments of internal
medicine/cardiology/pulmonology, and, maybe, even
percentages up to 29% were due to adverse drug effects.
2. A large difference between the numbers of iatrogenic
admission according to the physicians in charge of
admission and the investigators, 229 versus 380 patients,
was observed.
3. Most often iatrogenic admissions were observed with
cardiac disease, hypertension, gastrointestinal conditions,
anticoagulant treatment, and use of NSAIDs.
226. Meta-analysis of recent studies on patients admitted
to hospital due to adverse drug effects
R. Atiqi1 , E.H.F. van Bommel1, A.M.J. Cleophas1,
A.H. Zwinderman2
1
Albert Schweitzer Hospital, Department of Internal Medicine,
Albert Schweitzerplaats 25, 3300 AK DORDRECHT, the
Netherlands, e-mail: r.atiqi@live.nl, 2 Academic Medical
Centre, AMSTERDAM, the Netherlands
225. Prevalence of iatrogenic admissions to the
departments of medicine/cardiology/pulmonology
in a 1250 beds general hospital
1
1
In the past decade the use of drugs has expanded. Earlier
studies on patients admitted for adverse drugs effects
(ADEs) were heterogeneous.
The objectives were to assess recent numbers of
admissions to hospital due to ADEs, to assess heterogeneity
of recent studies.
Prospective studies published in the past decade were
pooled and compared to the pooled results from earlier
studies.
The pooled overall percentage of the recent studies (n=20)
was 5.4% (5.0-5.8) and did not significantly differ from
that of the earlier studies (n=21, pooled percentage 4.7%,
3.1-6.2). The studies were clinically very heterogeneous
with percentages of ADEs between 3.4 and 33.2%. The
type of study group could be held largely responsible for
the clinical heterogeneity observed.
1
R. Atiqi , E.H.F. van Bommel , A.M.J Cleophas ,
A.H. Zwinderman2
1
Albert Schweitzer Hospital, Department of Internal Medicine,
Albert Schweitzerplaats 25, 3300 AK DORDRECHT, the
Netherlands, e-mail: r.atiqi@live.nl, 2 Academic Medical
Centre, AMSTERDAM, the Netherlands
A recent meta-analysis in this journal showed incidences
between 3.4 and 33.9%. Studies performed by pharmacists
and epidemiologists produced lower incidences than
internists’ studies.
We reassessed the prevalence of iatrogenic admissions
in a study of internists. Iatrogenic disease was defined
as adverse drug reactions according to the World Health
Organisation Definition and complications induced by
non-drug medical interventions.
Subsequent admissions at the departments of medicine/
cardiology/pulmonology in a 1250 beds general hospital
121
227. Anemia and its consequences in the LifeLines cohort
study
than 65 years. Less than half of the participants who were
informed contacted their GP. Among these patients several
serious diagnoses were found needing therapy. There was
no relationship between anemia and HR-QOL.
M.M. van der Klauw, H. van der Valk, L.J. van Pelt,
B.H.R. Wolffenbuttel
University Medical Centre Groningen, Department of
Endocrinology, PO Box 30001, 9700 RB GRONINGEN, the
Netherlands, e-mail: m.m.van.der.klauw@int.umcg.nl
228. Analyzing completion times in an academic
emergency department: decision making is the
weakest link
Introduction: Anemia is a common problem and is
associated with increased morbidity, mortality and a
decrease in quality of life.
Aim: To assess the prevalence of anemia in southwest
Friesland and East Groningen, and the diagnoses
established, and to compare the quality of life in participants with anemia with that of participants without
anemia.
Materials and methods: Case-control study within
the Dutch adult population who participated in the
LifeLines-cohort from November 2006 until June 2010.
We measured Hb, Ht and erythrocytes, and HR-QOL
(RAND-36 item Health Survey) in 11645 Caucasian participants, 4870 men and 6775 women (mean age 43.89, SD
11.44, range 18-89 years). Anemia was defined as a Hb
value of =0.5 mmol/l below the lower limit of the reference
interval of the University Medical Centre Groningen
laboratory (women < 7.0, men < 8.2 mmol/l). Both
the general practitioner (GP) and the participant were
informed of the finding. Of these participants, a chart
survey was performed in 41 general practices. The control
group consisted of a random selection of LifeLines participants, matched for age and gender.
Results: Prevalence of anemia was 2.2% among men and
2.1% among women. Among 644 participants older than
65 years, the prevalence in men was 8.4%, and in women
only 0.3%. Patient charts were checked in 196 anemia
cases. Only 96 (49%) participants contacted their GP for
further evaluation, 64 women and 32 men. Additional
examinations were performed in 68 participants, 22
received therapy directly, in 6 no analysis was performed
and no therapy started. 54 Participants had a known
anemia, and in 21 upon further analysis the anemia had
resolved. 4 Participants had recently donated blood, 32 had
hypermenorrhea, 3 vitamin B12 deficiency, 2 hemorrhoids,
1 nose bleeds, 1 a Barrett oesophagus, 3 thalassemia (of
which 2 were known), 1 oesophageal varices, and 5 were
found to have a carcinoma (1 renal cell, 1 stomach, 1
pancreatic and 2 coloncarcinomas).
The % of participants contacting their GP was larger if the
Hb was lower.
No relationship between the participants with anemia and
the control group regarding HR-QOL could be found.
Conclusions: The prevalence of anemia in this population
was 2.1%, and higher among male participants older
I.L. Vegting, M.C. Visser, M.H.H. Kramer, G.M. Koole,
E. van de Walle, P.W.B. Nanayakkara
VU University Medical Centre, PO Box 7057,
1007 MB AMSTERDAM, the Netherlands, e-mail:
p.nanayakkara@vumc.nl
Introdcution: Although, congestion with long waiting
times are frequently noticed in some emergency
departments (ED) in the Netherlands, no target for
completion time is defined or enforced. In our opinion,
it is preferable to keep the length of stay at the ED short,
so that patients can be transferred to a stable and a safe
environment as soon as possible. It has been demonstrated
that the length of stay in the ED is associated with the
length of stay in the hospital and even mortality
Aim: Investigating completion times in an academic
emergency department (ED) and the factors contributing
to long completion times.
Material and methods: Data of ED patients presenting at
VU university medical centre, was prospectively collected
during 4 weeks in February 2010. Presentation time,
referrer, discharge destination, and medical specialties
involved were registered. Additional detailed data about
relevant time-steps were collected from patients with triage
category Emergency Severity Index (ESI) 3. The Pearson’s
chi-square test and the Mann-Whitney test were used for
statistical analysis.
Results: 13% of patients had a completion time longer
than four hours (average 2:23 hours). In ESI 3 patients,
24% had a completion time longer than four hours
(p<0.001). Internal medicine had most patients exceeding
the four hour target (37%), followed by neurology (29%).
Undergoing a CT scan and hospital admission were
associated with exceeding the four hour target (p<0.001).
No association between arrival time on the ED and
completion time was found. The elapsed time between
receiving the results of all diagnostic tests and admission/
discharge had the most influence on the completion time
(p<0.001).
Conclusions: A significant percentage of vulnerable and
sick patients exceeded the four hour completion time
in our ED. The biggest contributor to this delay was
the process of decision making after completion of all
diagnostics on the ED. Improving the direct supervision
122
of junior colleagues will, in our opinion, speed up the
decision making process and lead to shortening of
completion times in many patients.
significant reduction in the diagnostic costs in the
department of internal medicine. Extending these
measures to the entire hospital and even entire country
will in our opinion lead to significant reduction in the
health care costs.
229. Increasing the awareness among the doctors lead
to a significant reduction in the costs spend on the
diagnostics
230. Risk factors influencing the outcome of community
acquired pneumonia
I.L. Vegting, M. van Beneden, M.H.H. Kramer, A Thijs,
P.W.B. Nanayakkara
VU University Medical Centre, PO Box 7057,
1007 MB AMSTERDAM, the Netherlands, e-mail:
p.nanayakkara@vumc.nl
L.M.A. Klieverik, R. So, D. Cheung, M.D. Levin
Albert Schweitzer Hospital, Department of Internal Medicine,
PO Box 444, 3300 AK DORDRECHT, the Netherlands,
e-mail: l.klieverik@asz.nl
Introduction: The burden of health care expenditure on
national budgets have increased dramatically over the past
decade. Hospital care consumes one of the largest portion
of the total healthcare costs. In hospitals a large portion of
the money is spent on diagnostic tools such as laboratory
and radiological tests. A pilot study performed in our
hospital demonstrated that unnecessary diagnostic tests
were performed frequently.
Aim: Reducing the costs of unnecessary diagnostic tests in
internal medicine patients
Materials and methods: In December 2008, a management
consultant evaluated all cost of all the diagnostics
(laboratory, radiology, nuclear medicine, pathology, microbiology) performed in the department of internal medicine
between 2006 and 2008. Doctors were then informed of
these findings. A target was set to reduce the costs spent on
diagnostics in the internal medicine department by 7,5% in
2009 compared to 2008. In 2009 multiple interventions
were introduced to improve awareness of unnecessary
diagnostic costs among physicians. This included: introduction of posters and pocket cards detailing the costs of
diagnostic tests, six weekly feedback on the diagnostics
costs, mentorship of junior doctors, unbundling panel
tests and increasing protocol adherence. Main outcome
measures were reduction in the total diagnostic costs
and the total number of laboratory tests performed in the
internal medicine department in 2009.
Results: The department of internal medicine spent
2.80 million euro and 2.45 million euro on the diagnostic
tests in 2008 and 2009 respectively (13% decline) and
thereby saved 350.000 euro in 2009. The largest reduction
was achieved by reducing the number of laboratory
tests performed.). In the rest of the hospital (internal
medicine department excluded), the total costs spent on
the diagnostics were 32,94 million euro in 2008 which
declined to 32,13 million euro in 2009, saving 389.000
euro in 2009 (2.4% reduction).
Conclusions: Introduction of a few simple measures
to improve awareness among the physicians led to a
Introduction: Community acquired pneumonia (CAP) has
worldwide high morbidity and mortality. In the literature
the mortality varies from 10% to 25%. In het Albert
Schweitzer Hospital in Dordrecht, the Netherlands the
morbidity and mortality are quite high as well.
Aim: The question remains what the underlying cause is
for these high numbers of hospital mortality.
Materials and methods: Between 01-2005 and 01-2010
2508 consecutive patients were admitted in our hospital
with a CAP. We evaluated patient characteristics, early
and late morbidity and mortality and predictors of adverse
outcome. Also the pneumonia severity index (PSI) en de
CURB-653 were used to predict mortality. Furthermore
we compared our outcome to the Dutch HSMR (Hospital
Standardized Mortality Ratio).
Results and conclusions are currently analyzed and will be
completed before the annual meeting of the Dutch College
of Physicians.
231. Physicians report barriers to deliver best practice care
for asplenic patients
A.J.J. Lammers, J.B.L. Hoekstra, P. Speelman,
M.J.M.H. Lombarts
Academic Medical Centre, Amsterdam, Department of
Internal Medicine, Meibergdreef 9, 1105 AZ AMSTERDAM,
the Netherlands, e-mail: a.j.lammers@amc.uva.nl
Introduction: Current management of asplenic patients
in the Netherlands is not in compliance with best practice
standards as defined by the British Committee for
Standards in Haematology. To improve quality of care,
factors inhibiting best practice care delivery need to be
identified first.
Aim: To identify and quantify physicians’ barriers to
adhere to best practice management of asplenic patients.
Materials and methods: A cross-sectional survey was
performed, preceded by multiple focus group discussions.
123
Dutch physicians responsible for prevention of infections
in asplenic patients, including internists, surgeons and
general practitioners (GPs) participated.
Results: Forty seven GPs and seventy three specialists
returned the questionnaire, yielding response rates of 47%
and 36,5% respectively. Physicians reported several barriers
to deliver best practice. For both GPs and specialists,
the most frequently listed barriers were: poor patient
knowledge (> 80% of specialists and GPs) and lack
of clarity about which physician is responsible for the
management of asplenic patients (50% of internists,
46% of surgeons, 55% of GPs). Both GPs and specialists
expressed to experience a lack of mutual trust: specialists
were uncertain whether the GP would follow their advice
given on patient discharge (33-59%), whereas half of
GPs was not convinced that specialists’ discharge letters
contained the correct recommendations. Almost all
physicians (> 90%) indicated that availability of a national
guideline would improve adherence to best practice,
especially if accessible online.
Conclusion: This study showed that care delivery for
asplenic patients in the Netherlands is suboptimal. We
identified and quantified perceived barriers by physicians
that prevent adherence to post-splenectomy guidelines.
Better transmural collaboration and better informed
patients are likely to improve the quality of care of the
asplenic patient population.
sation. The anion gap was elevated: 21 mmol/l. Presuming
a diagnosis of urosepsis, sodium bicarbonate was given
and the gynecologist decided to perform a Caesarean
delivery which passed uneventfully. Two girls were born,
one needing short cardiac massage and mechanical
ventilation. The next day both newborns were doing well
and no permanent disabilities were foreseen. Pathological
examination revealed no abnormalities of the placentae.
Lactate levels, measured shortly before caesarian section
were within normal range. A urine keton value of more
than 7,8 mmol/l was demonstrated (normal < 0.5 mmol/l).
Her husband stated that she had barely eaten for a week
previously and that she had been vomiting for two days
prior to admission. He confirmed her statement that she
had not taken salicylates, other medication or ingested
alcohol. She had no access to antifreeze. Toxicological
tests revealed a salicylate level of < 5 mg/l, an acetaminophen level < 1 mg/l, and an acetone level of 300 mg/l
(reference 5-20 mg/l), Methanol and ethanol tests were
both negative. No signs of renal disease or diabetes were
present. The metabolic acidosis resolved fully after glucose
5% infusion. Her vital parameters remained normal and
she was discharged to the obstetric ward the following
day. A non-diabetic starvation keto-acidosis in pregnancies
has been reported only in a few case reports. Pregnancy
is a high insulin resistant state, especially in third
trimester, accentuated in this case by obesity and a gemelli
pregnancy. The combination of (mild) starvation and a
state of insulin resistance may easily lead to metabolism
based on alternative sources, leading to overproduction of
ketons, and consequently ketoacidosis. Acute acidosis in
pregnancy is a risk for intra-uterine death and may lead to
abnormal neurological development. Treatment is glucose
and often delivery.
XXIV.GENERAL INTERNAL MEDICINE CASE REPORTS
232. A case of non-diabetic keto-acidosis in pregnancy
233. Rhabdomyolysis after dying hair with paraphenyl­
diamine-containing hair dye
J.B.J. Scholte, W.E. Boer
Atrium Medical Centre Parkstad, Department of Internal
Medicine-IC, Henri Dunantstraat 5, 6419 PC HEERLEN, the
Netherlands, e-mail: Janscholte@hotmail.com
M. Ezzahti1, P. Biezen2
1
Amphia Hospital, Department of Internal Medicine,
Molengracht 21, 4818 CK BREDA, the Netherlands,
e-mail: ezzahti00@hotmail.com, 2Erasmus Medical Centre
Rotterdam, ROTTERDAM, the Netherlands
Case: A 26-year-old patient presented with progressive
dyspnoea. She was pregnant with a dicorial, diamniotic
gemelli (35 weeks and 4 days). Initially (for one day)
she was treated with amoxicillin for a presumed lower
urinary tract infection. Physical examination revealed
no abnormalities except a body mass index of 39 kg/m2.
Cardiotocography revealed both normal and reactive heart
rates and no contractions. Chest X ray and electrocardiography showed no abnormalities. She was admitted for
further observation with a presumed diagnosis of chronic
hyperventilation and an unexplained mild elevation of
CRP (32 mg/l). The second day a new blood gas analysis
revealed a metabolic acidosis with respiratory compen-
Case-report: A 34-year-old female without medical history
was admitted to the hospital because of generalised
muscle pain and dysphagia. At physical examination
there was oedema of the face, no fever, the blood pressure
was 120/80 mmHg and respiratory rate 12/min. On
examination her hands were coloured deeply black.
Laboratory results showed a normal renal function, normal
CRP, CK 84446 U/l, ASAT 2619 U/l, ALAT 463 U/l
and lactate dehydrogenase of 6051 U/l. The urine was
124
Case presentation: An eighty-seven-year-old caucasian
woman presented with progressive fatigue and weakness
in the proximal extremity muscles. Because of an
elevated risk for cardiovascular events she used a statin.
Medical evaluation included high serum levels of creatine
phosphokinase (CK) and lactate dehydrogenase (LD).
Extensive evaluations for underlying malignancies, cardiac
and interstitial pulmonary disease were unremarkable.
Differential diagnosis included statin-induced myositis.
She was treated by prednisone and discontinuing the
statin. The laboratory results improved, but the muscle
weakness did not. An electromyogram (EMG) showed
axonal polyneuropathy with clues for an anterior horn
disease. A muscle biopsy revealed a necrotising myopathy.
Conclusion: Side-effects of statin use can follow a serious
course with muscle complaints, myositis, rhabdomyolysis,
and statin-induced myositis. One should always think
of such side-effects if a patient presents with muscle
complaints. Also, be aware of a possible underlying
(muscle) disease. Cessation of statin and monitoring CK
levels are important goals in treatment of statin-induced
myositis.
very dark and contained myoglobin. A chest radiograph
showed bilateral infiltrative shadows. The patient had a
combination of rhabdomyolysis, oedema of the face and
pneumonia. The patient used no medication or drugs.
There was no trauma or extreme physical exercise. There
were none electrolyte disturbances. The cause of her black
coloured hands was that she applicated with no gloves
traditional hair dye (Takawath) in combination with
Henna on her hair four hours before she got complaints.
She boiled the Takawath and this caused damps which
she inhaled. The Takawath contains paraphenyldiamine
(PPD). The urine of the patient was analysed qualitatively
for PPD and the result was positive. The patient was treated
with a high amount of 0.9% sodium chloride solution
with addition of bicarbonate. The renal function stayed
normal and CK decreased very rapidly. The complaints of
dysphagia and muscle pain disappeared in a couple of days.
After three days the chest radiograph showed spontaneous
reduction of the infiltrative shadows. The patient was
advised not to use PPD-containing hair dye anymore.
Discussion: Paraphenyldiamine is used very often in hair
dye and as an additive to Henna to give Henna a black
tattoo-like appearance. In Northern Africa and India hair
dye ingestion is a common problem. The ingestion of
PPD-containing hair dye is used to commit suicide and
can produce rhabdomyolysis, renal failure and severe
laryncheal oedema. The pathogenesis of renal failure is
through rhabdomyolysis and because of a direct toxic effect
of PPD in the tubules. Because the mechanism in which
PPD causes rhabdomyolysis is not known, we performed
in this patient a biopsy of the muscle of the right upper
leg. This showed a myositis with an allergic component
because of a great amount of eosinifolic granulocytes.
Conclusion: This case illustrates that paraphenyldiaminecontaining hair dye can cause rhabdomyolysis, oedema of
the face and a chemical pneumonia possibly through an
allergic mechanism. Every clinician should be aware that
this association exist.
235. A patient with back pain and inflammatory changes
on MRI due to polymyalgia rheumatica
N. Wlazlo, B. Bravenboer, H. Pijpers, M.C. de Rijk
Catharina Hospital, Department of Internal Medicine,
Michelangelolaan 2, 5623 EJ EINDHOVEN, the Netherlands,
e-mail: nick.wlazlo@cze.nl
Introduction: Polymyalgia rheumatica (PMR) is often
diagnosed by its typical presentation of pain and stiffness
in proximal joints. We present an atypical case of a man
with low back pain, in which imaging studies were
eventually helpful in establishing a diagnosis of PMR.
Case: A 64-year-old male was admitted to our hospital
with increasing low back pain, radiating to his upper
legs. Analgesics and physical therapy had not improved
his symptoms. In the past 5 months, he had visited our
emergency department twice with these complaints, but no
diagnosis had been established and the pain proved to be
self-limiting. The patient’s history showed type 2 diabetes
mellitus and several cardiovascular events.
The patient was not febrile and showed no abnormalities
on physical and neurological examination. Laboratory
investigation (reference values between parentheses)
showed an elevated erythrocyte sedimentation rate of
74 mm/h (0-20 mm/h) and a C-reactive protein of 74 mg/l
(0-6 mg/l). Our differential diagnosis included spondylodiscitis, epidural abscess, rheumatoid arthritis (RA),
unknown infection, spondylarthropathy, malignancy
(especially multiple myeloma), or auto-immune disease.
234. Statin-induced myositis
I.C. Kouwenberg, M.M.C. Hovens
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
ikouwenberg@alysis.nl
Introduction: Statins (HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor) are often used to
reduce the risk of cardiovascular events. Side effects of
statins can consist of muscle pain and remarkably elevated
serum creatine phosphokinase (CK) levels, or rhabdomyolysis, and can be life threatening.
125
unremarkable except for hypotension (BP 90/60 mmHg)
and a bradycardia of 45 beats/min. Electrocardiography
showed a sinus bradycardia of 50 beats/min with a first
degree atrioventricular block. Laboratory investigations
showed no abnormalities. Supportive treatment resulted
in rapid recovery in this case, too.
Discussion: We describe two patients that recently
presented at our emergency room with poisoning by
wild honey. Both patients had obtained the substance in
Turkey, where it is used as a complementary medicine for
gastrointestinal and cardiovascular symptoms. Wild honey
is made by bees from flowers of rhododendron species,
the most common being Rhododendron ponticum and
Rhododendron flavum. These rhododendrons can be found
in Turkey, Japan, Nepal, Brazil, and some parts of North
America and Europe. Grayanotoxins are believed to be the
toxic substances of these plants, and are found in its leaves,
flowers and nectar. Grayanotoxins in the honey may cause
the negative chronotropic effects. A possible mechanism
of action is binding of the toxin to sodium channels in the
cell membrane, resulting in a constant state of depolarization. This results in a decreased action potential, causing
dysfunction of the sinoatrial and atrioventricular nodes.
Another mechanism might be stimulation of the vagus
nerve. Both modes of action result in bradycardia and
hypotension. No deaths due to wild honey poisoning have
been documented so far. Supportive treatment, consisting
of infusion of normal saline and positive chronotropic
agents if needed, commonly facilitates recovery within 24
hours.
Conclusion: Although rare, wild honey poisoning should
be considered as a potential cause of hypotension and
bradycardia.
MRI of the lumbar spine was performed because of the
suspicion of spondylodiscitis, and showed inflammatory
changes dorsal of vertebrae L3-L5 with a small pocket at
L5. The patient was treated with i.v. flucloxacilline for 6
weeks, but did not recover. Several blood cultures and
a needle biopsy of the pocket at L5 showed no bacterial
agent. Auto-immune antibodies, rheumatoid factor and
anti-citrulline antibodies were all negative. Subsequently,
he developed pain at his neck and right shoulder. A
malignancy was ruled out by shoulder X-ray and bone
scintigraphy. We performed a FDG-PET-computed
tomography study in order to find a systemic inflammatory disease or infectious focus. This showed enhanced
FDG-uptake in shoulders, back and hips. This pattern has
been described in patients with polymyalgia rheumatica,
and so we started treatment with prednisone. The pain
decreased in 2 days and inflammatory markers declined.
Three months later the inflammatory changes on MRI had
disappeared as well.
Conclusion: Typical PMR is a clinical diagnosis after
exclusion of other disorders. When patients do not present
with the typical features, imaging studies like MRI or
PET-CT may be helpful in making a diagnosis by excluding
other possibilities, as in our case. Moreover, interspinal
bursitis on MRI and increased FDG-uptake in shoulders,
back and hips on FDG-PET-CT might be suggestive of
PMR in these patients.
236. Wild honey: not so sweet after all?
M. Wester, R. van Eijk, R.J. Walhout, J. Zeelenberg
Gelderse Vallei Hospital, Department of Internal Medicine,
Willy Brandtlaan 10, 6716 RP EDE, the Netherlands, e-mail:
westermaarten@gmail.com
was acetylsalicylic acid because of PTCA 10 years before.
There were no other complaints than fever and arthralgias,
particularly of both feet, but the hands en knees were
involved as well. On the first day of presentation he had
fever of 38.7 degrees centigrade, and a non-pruritic rash
on both legs, no obvious signs of arthritis. Laboratory
examination revealed a raised CRP, and a mild proteinuria.
Serological tests for ANA, ANCA, and reumatoid arthritis
remained negative. Further analysis, which included
blood cultures, an ultrasound of the abdomen, an X-ray of
the chest, an analysis of a urine specimen and testing for
multiple myeloma, revealed no abnormalities. A performed
skin biopsy showed a leukocytoclastic vasculitis with
the presence of C3 within the walls of small capillaries.
No antibiotics were administered, as our patient did not
appear very ill and did not fulfill the SIRS criteria. During
his hospital stay his daughter told us that a family trip to
Suriname was planned and that they had received DTP
and hepatitis A vaccination 10 days before. As other causes
for the clinical presentation were ruled out, we concluded
that the patient most probably suffered from a severe
serum sickness reaction against his recent vaccinations.
Because of the severely painful arthritis he had developed
during his hospital stay, oral corticosteroids were started.
A few days later the pain and arthritic pain resolved.
Unfortunately, their family vacation had to be skipped.
Conclusion: We present a man with a classic serum
sickness reaction with arthralgias, arthrititis and fever
after a vaccination against Hepatitis A and DTP. This case
shows that an extensive history is an important tool for
making this clinical diagnosis. Serum sickness is a known,
but rare complication of vaccinations.
change. Papilledema was not present. We were consulted
to evaluate for possible underlying internal causes of the
hydrocephalus. Chest imaging showed bihilar lymfadenopathy and histology of a mediastinal lymph node revealed
non-caseating granulomas, compatible with sarcoidosis.
At 37-weeks of gestation she delivered a healthy daughter.
After delivery, her neurologic complaints progressed.
Ventriculostomy did not reduce the symptoms. However,
prednisolone 1mg/kg resulted in rapid disappearance of
symptoms. MRI showed complete resolution of the hydrocephalus within 3 weeks after the start of prednisolone.
Literature review. Many internal diseases can cause a hydrocephalus. Particularly infections, tumours and autoimmune
disorders must be considered. Hydrocephalus is a rare
manifestation of sarcoidosis (0,25% of cases). Sarcoidosis
presenting with a hydrocephalus is even rarer and poses a
substantial diagnostic dilemma. Sarcoidosis can cause an
obstructive hydrocephalus by fourth ventricular outflow
obstruction or a communicative hydrocephalus due to
reduced absorption of liquor in the basal cisterns. Of all
manifestations of neurosacoidosis, hydrocephalus has the
worst long-term prognosis with a mortality rate of 75%.
Diagnostic criteria for neurosarcoidosis have been proposed
by Zajicek et al. who define possible, probable and definite
neurosarcoidosis. A nervous system biopsy is necessary to
establish a diagnosis of ‘definite’ neurosarcoidosis, however
this is not always feasible. Our patient met the criteria for
‘probable’ neurosarcoidosis. High-dose corticosteroids are
widely accepted as the first line of treatment.
Conclusion: Hydrocephalus can be the presenting manifestation of sarcoidosis. An acquired hydrocephalus in adults
can have many non-neurological causes. The internist
can play an important role in the differential diagnosis
of hydrocephalus. Adequate diagnosis of the underlying
disease requires a multidisciplinary approach. Treatment
of hydrocephalus due to neurosarcoidosis consists of high
dose steroids and on demand ventriculostomy.
238. Hydrocephalus, a rare manifestation of sarcoidosis
237. Serum sickness: vacation of vaccination?
Case report: Patient A is a 36-year-old male who presented
with palpitations, nausea, vomiting and sweating. He
had no relevant medical history and was not using any
medication. The symptoms occurred a few hours after
ingestion of wild honey for gastrointestinal symptoms.
Physical examination was unremarkable except for
hypotension (BP 98/48 mmHg) and a severe bradycardia
of 37 beats/min. Electrocardiography showed a sinus
bradycardia of 40 beats/min with normal conduction
times. Haematological and biochemical laboratory investigations were normal. Treatment consisted of normal
saline intravenously only. Within a few hours blood
pressure and pulse returned to normal values. Patient B is
a 42-year-old male who was referred because of weakness,
sweating, dizziness, nausea and vomiting. He had no
relevant medical history and did not use any medication.
His complaints started two hours after eating yoghurt
with wild honey. Physical examination once more was
M.J. Cruijsen, C. Richter, M.M.C. Hovens
Rijnstate Hospital,Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
mcruijsen@alysis.nl
Introduction: Classic serum sickness describes the
syndrome of a ‘type III’ of immune complex- mediated
hypersensitivity disease. The most common symptoms are
rash, fever, malaise, and polyarthralgias or polyarthritis.
They are caused by immunization of the host by heterologous (non-human) serum proteins, developing one to
two weeks after first exposure to the responsible agent.
Diagnosis is often delayed, as this syndrome resembles
more common infectious diseases
Case report: A 76-year-old man was presented to the
emergency ward because of fever, chills, and extremely
painful feet since 10 days. The only medication he used
126
G.S. Mijnhout, J.M. van Rooijen, T.T.A. Aalders
Isala Clinics, Department of Internal Medicine, Dr. van
Heesweg 2, 8025 AB ZWOLLE, the Netherlands, e-mail:
g.s.mijnhout@isala.nl
239. The unidentified angel
W. Vercoutere, J. Buijs, C. van Deursen
Atrium Medical Centre Parkstad, Department of Internal
Medicine, H. Dunantstraat 5, 6419 PC HEERLEN, the
Netherlands, e-mail: wardvercoutere@yahoo.com
Introduction: Sarcoidosis is a multisystem granulomatous
disorder of unknown origin typically affecting young
adults. The organs most commonly involved are the lungs,
skin and lymph nodes. Involvement of the nervous system
occurs in 5% of patients with sarcoidosis. We present a
patient with a hydrocephalus as the presenting manifestation of sarcoidosis. To our knowledge only few cases have
been reported.
Aim: Case report and review of the literature.
Case report: A 36 weeks pregnant woman developed a
symptomatic non-communicating hydrocephalus. She
had a 6-week history of progressive nausea, vomiting,
dizziness, diplopia and headache precipitated by position
Introduction: A 61-year-old man was referred to the
hospital with nausea, vomiting and watery diarrhoea. One
day before admission he received a present of his friend,
consisting of a collection of freshly picked mushrooms.
Being a connaisseur of mushrooms, he prepared
himself a meal consisting of Boletus edulis (penny bun),
Cantharellus cibarius (golden chanterelle) and two unidentifiable mushrooms.
127
Introduction: Worldwide, proton pump inhibitors (PPI’s)
are one of the most frequently prescribed drugs. Although
considered safe, the following case-report demonstrates a
rare but life-threatening skin-disease that can occur as an
adverse reaction to omeprazole.
Case report: A 50-year-old female presented to her general
practitioner with stinging eyes and a rash on her chest.
Four weeks earlier she had been started on omeprazole
for abdominal complaints. Since a toxic dermatitis was
suspected, omeprazole was terminated immediately. 48
hours later however the rash had worsened and the patient
was referred to our hospital. On examination a generalized
rash with erythematous macules and dusky centres was
noticed. She also had extensive oral and genital ulcerations,
conjunctivitis and blepharitis. Urine sediment analysis
showed signs of a cystitis. The most likely diagnosis
was erythema multiforme major (EMM) caused by an
urinary tract infection. The patient was admitted and
received antibiotics. Within the next 24 hours the rash
became confluent and desquamative, with multiple vesicles
growing into bullae followed by erosion of the skin and
mucous membranes, eventually affecting more than 40%
of her body-surface area (BSA). The clinical picture and
extensiveness of the BSA involved were now concomitant
with toxic epidermal necrolysis (TEN). A skin biopsy
revealed chronic inflammation suiting a diagnosis of either
TEN or EMM. Urine and blood cultures remained negative.
With the absence of other recently initiated drugs and no
sign of infection, TEN was attributed to omeprazole.
Treatment was initiated with high dose prednisolone,
hydration and nutritional support. Because of the specialized
wound care that was required the patient was transferred to
a dermatological ward in an academic hospital. Shortly after
her transfer the skin condition stabilized and the steroids
were weaned. Subsequently the denuded skin re-epithelialized. After two weeks she could be discharged with a
lifelong absolute contraindication for PPI’s.
Conclusion: Considering the incidence of 1 per one million
people annually and a mortality rate of 35%, TEN is a rare
but life-threatening adverse drug reaction. Although TEN
is mostly related to specific types of drugs (allopurinol,
penicillins, carbamazepine and NSAID’s), many other
agents have been implicated in a smaller number of cases.
So far only five cases of TEN caused by omeprazole have
been reported in literature. This case report illustrates that
even commonly prescribed drugs like PPI’s can cause severe
adverse drug reactions. Early recognition is important and
clinicians should be aware of the possibility of TEN.
Case report: On examination in the hospital he showed
normal vital signs and slight tenderness of the abdomen.
Serum alanine-aminotransferases were slightly elevated
(84 U/l), alkaline-phosphatase, bilirubin and coagulation
tests were normal. C-reactive protein and creatinine were
31 mg/l and 120 mmol/l, respectively.
Given the history and symptoms, amatoxin poisoning was
suspected. Silibinin (milk thistle, Silybum marianum) and
acetylcysteine were started as antidotum. The next days he
remained clinically stable, although laboratory tests revealed
increasing transaminases and declining liver synthesis
parameters. On day 4 he suffered from hemorrhagic
diarrhoea, hypotension, anuria, high-anion gap metabolic
acidosis and severe impairment of liver function (albumin
25.9 g/l, APTT 64 sec, INR 6.38, bilirubin 73.8 umol/l, LDH
5000 U/l, transaminases > 3000 U/l). He was referred to an
academic hospital and underwent an immediate liver transplantation. Nevertheless, he died after surgery. Pathological
examination of the native liver showed massive cellular
necrosis.
Discussion: This case illustrates the clinical course of a
lethal mushroom poisoning, caused by amatoxin (Amanita
phalloides, ‘death angel’). The LD50 of amatoxin is very
low, i.e. 0.1 mg/kg body weight, reflecting the weight
of only one mushroom. Amatoxin interacts with RNA
polymerase-II, leading to decreasing mRNA-concentrations, deficient protein synthesis and cell death. Intestinal
mucosa, liver and kidneys are the most susceptible organs.
Silibinin inhibits the enterohepatic cycle of amatoxin.
N-acetylcysteïne impairs toxicity by reducing glutathione
in hepatocytes. Amatoxin poisoning is classically divided
into four phases. After a latency period of 8-12 hours,
gastrointestinal symptoms start. Since non-hepatotoxic
mushrooms induce gastrointestinal symptoms 1-2 h after
ingestion, amatoxin intoxication should be considered
when a longer latency-period occurs. In the second phase,
oliguria, electrolyte/acid-base disturbances and renal
failure occur. In the third phase, diarrhoea ceases, leading
to clinical improvement. However, after 36-48 h signs of
liver involvement may appear, ranging from asymptomatic
increase of transaminases to full-blown acute liver failure.
Conclusion: The incidence of mushroom poisoning varies
over the world, depending on local traditions, life-style and
occurrence of wild mushrooms. Although the incidence of
mushroom intoxications is low in the Netherlands, patients
and clinicians should be aware of the hazardous consequences.
240. A rare side effect of a common drug
J. van der Kraan, S. Anten
Rijnland Hospital, Department of Internal Medicine, Simon
Smitweg 1, 2353 GA LEIDERDORP, the Netherlands, e-mail:
j.vd.kraan@rijnland.nl
241. First degree atrioventricular block due to acute
ethanol intoxication
D.A. Geerse, G.J. Creemers
128
with fever. Twenty hours before presentation, the father
had attempted to remove a colony of greenish Zoanthids
(soft corals) from a rock in his tropical sea aquarium by
putting the rock in a bucket of boiling tapwater. This
produced an offensive odour, which was inhaled by all four
family members. Immediately after touching the corals,
the man experienced paresthesias and pruritus in his right
arm lasting about ten minutes.
A few hours later, the man started to feel unwell. He
reported a metallic taste in his mouth, nausea, headache,
shivering and severe muscle cramps. On physical
examination, he had a blood pressure of 100/60 mmHg,
pulse rate 100/min and temperature 38 °C. Further
physical examination revealed no abnormalities. Blood
analysis showed leukocytosis (22.9 * 109/l) and elevated
CRP (174 mg/l). His wife and children had similar – but
less severe – symptoms and signs, all three had fever
> 38.5 °C. Based on the clinical history in combination
with the description of the soft coral, a clinical diagnosis
of palytoxin-intoxication secondary to (dermal and) inhalational exposure was made. All family members fully
recovered within 48 hours with supportive therapy.
Discussion: Palytoxin (PITX, PTX) is a very potent marine
toxin that converts the membrane sodium-potassium
pumps, responsible for maintaining ionic gradients critical
to cellular function (Na+/K+-ATPase), into nonspecific ion
channels. PTX has been found mainly in certain tropical
soft corals (Zoanthid) and bentic dinoflagellates (Ostreopsis
sp.). Cases of severe intoxication after ingestion of tropical
sea fish containing palytoxin (derived from eating these
corals/plankton) have been described, with symptoms
ranging from paresthesias, fever, dysguesia, myalgia and
nausea, to more severe with rhabdomyolysis, myocardial
damage and death. In the literature, two cases of toxicity
after dermal contact with Zoanthids from home sea aquaria
and two case reports describing intoxication after inhaling
a foul odour liberated by pouring boiling water on Zoanthids
from home aquaria were identified. There is no antidote
known for this toxin, supportive care is recommended.
Conclusion: Due to improved home marine aquarium
techniques, aquarians are potentially exposed to (un)
known sickening entities such as palytoxin. Aquarians
and their healthcare providers should be aware of these
potential risks.
Catharina Hospital, Department of Internal Medicine,
Michelangelollaan 2, 5623 ER EINDHOVEN, the Netherlands,
e-mail: dgeerse@hotmail.com
Introduction: Ethanol intoxication can lead to cardiac
conduction disturbances such as prolongation of the QTc
interval, possibly leading to lethal arrhythmias. It has
also been shown to increase the PR-interval in healthy
individuals. Few case reports exist of atrioventricular (AV)
block caused by acute ethanol intoxication.
Case report: A 26-year-old man was brought into the
emergency room with an acute ethanol intoxication. He
was found comatose after drinking large amounts of liquor.
On arrival of the ambulance, he was unresponsive to pain.
He regularly drank large amounts of alcohol, he did not use
illicit drugs and was otherwise healthy.
On physical examination he had an ethanol foetor and
was somnolent. Blood pressure was 120/75 mmHg, with a
regular pulse of 86/min. He had a snoring respiration with
a frequency of 12/min, with a SpO2 of 96% while breathing
ambient air. His core temperature was 34.7 °C and he had cold
extremities. Further examination showed no abnormalities.
Laboratory evaluation showed normal serum potassium,
sodium and calcium values. No other abnormalities were
found. An electrocardiogram showed a sinus rhythm
with a frequency of 88/min and a markedly prolonged
PR-interval of 300 msec. The QTc was 464 msec. There
were no other abnormalities and no second degree AV
block on continuous monitoring during the first hour in
the emergency room. After this hour, his consciousness
improved and he was able to answer questions.
He was given intravenous fluids and was admitted to the
ward for further observation. An electrocardiogram was
repeated 8 hours later; this showed normalization of the
PR-interval to 172 msec. He was feeling well at this time
and was discharged.
Discussion: This case describes a transient first degree AV
block in a patient with ethanol intoxication. Ethanol has a
direct inhibitory action on the cardiac conduction system and
may cause prolongation of the PR-interval, and even third
degree AV block. Clinicians should be aware of this possibility
when confronted with patients with ethanol intoxication.
242. A febrile family after handling soft corals from a
marine aquarium
243. How fast does an atrial myxoma grow?
L.L. Snoeks, J. Veenstra
Sint Lucas Andreas Hospital, Department of Internal
Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the
Netherlands, e-mail: l.snoeks@slaz.nl
J.M.J.B. Walpot 1 , B. Shivalkar2 , J. van Zwienen 1,
W.H. Pasteuning1
1
Admiraal De Ruyter Hospital, Department of Cardiology,
Koudekerkseweg 88, 4380 DD VLISSINGEN, the Netherlands,
e-mail: j.walpot@adrz.nl, 2University Hospital Antwerp,
EDEGEM-ANTWERP, Belgium
Case report: A family of four (father 37, mother 35, twins 10
years old) presented simultaneously to the emergency room
129
Introduction: The growth rate of atrial myxoma in humans
is not known, as the diagnosis of such lesions implies
surgical excision to prevent embolic events. Reports with
documented growth rate are very rare.
Case presentation: We report the case of a 65-year-old
woman, in whom a left atrial mass of 4.5 x 3.2 cm was
seen on a routine transthoracic echocardiogram. She was
in follow-up for mixed aortic valve disease. A year earlier,
the transthoracic echocardiogram could not document an
atrial mass.Histology diagnosed a myxoma. The calculated
growth rate was 0.375 cm/month.
The growth rate of cardiac myxoma is not known. We
performed a search in the medical literature and added
one new case. A Med-line search with the terms ’myxoma
and tumor growth’ was done. All case reports with
a documented growth rate were selected. Cases with
recurrent myxomas were excluded.
Twelve case studies were found. The calculated growth rate
was 0.49 cm (rang 0-1.36 cm) per month.
Conclusion: Reports with documented growth rate of
cardiac myxomas are very rare. These reports suggest the
growth rate of these lesions may be faster than we think.
was noticed that she had polyuria. Afterwards the patient
reported having polyuria and – polydipsia for three years.
A diagnosis of sarcoidosis was considered. Further analysis
with CT scan of the chest and MRI of the pituitary showed
small hilar and intrapulmonal lymphnodules, a thickened
aorta, and a mass in the pituitary gland. PET-CT showed
increased hilar and intrapulmonary tracer uptake, and
intense uptake in the aorta, suggesting aortitis. Histologic
examination of the extramedullary tumour revealed a
granulomatous inflammation. Auramine staining, PCR
and culture showed no mycobacteriae. In conclusion,
our patient had a rare presentation of a combination of
neurosarcoidosis with spinal as well as pituitary localisations, and systemic sarcoidosis complicated by aortitis. The
patient was treated with prednisolone, desmopressin and
anticoagulants. During therapy recovery of polyuria and
-dipsia and mild improvement of the neurologic symptoms
occured.
Discussion: Sarcoidosis is an inflammatory disease of
unknown aetiology characterised by the presence of noncaseating granulomas. Mycobacterial and fungal infections
as well as malignancy should be ruled out. Sarcoidosis
can effect any organ, most commonly lymph nodes, lung,
liver, skin and eye. On rare occasions the nervous system
and (large) blood vessels may be involved in the disease
process. Cornerstone in the treatment of sarcoidosis are
corticosteroids.
244. A woman with rare manifestations of a common
disease
J.P. Post, H.M.A. Hofstee
VU University Mmedical Centre, Department of Internal
Medicine, Boelelaan 1117, 1081 HV AMSTERDAM, the
Netherlands, e-mail: jp.post@vumc.nl
245. A rare case of dyspnea due to bisacodyl abuse
I.M. Dijkstra, H.R. Koene, V.H.M. Deneer, I.A. Eland,
I.M.M.J. Wakelkamp
St. Antonius Hospital, Department of Clinical Chemistry, PO
Box 2500, 3430 EM NIEUWEGEIN, the Netherlands, e-mail:
info@congresservice.nl
Case: A 58-year-old woman was admitted to the hospital
with a 3-month history of progressive muscle weakness,
sensory loss, and unsteady walk, eventually progressing
to paraplegia. Her past medical history included type
2 diabetes mellitus, hypertension, chronic obstructive
pulmonary disease, and pulmonary nodules that had not
changed in size for two years. The patient’s father died of
morbus Wegener. On physical examination the patient had
paralysed lower extremities, hypesthesia and hypalgesia
below the dermatome corresponding with the 6th thoracic
vertebra, bilateral Babinski’s response, and absent patellar
and achilles reflexes. Also there was swelling and redness
of the left leg. No other abnormalities were observed,
especially no lymphadenopathy, masses, skin changes,
hepatosplenomegaly, or swelling of the joints. MRI of the
spine showed a large epidural mass extending from the
2nd to the 6th and a smaller mass near the dorsal corpus
of the 10th thoracic vertebra. Compression ultrasonography
showed a deep vein thrombosis of the left vena poplitea.
After the insertion of a vena cava filter, a decompressive
and diagnostic laminectomy was performed. At the postoperative ward the patient developed hypernatremia, and it
Introduction: Bisacodyl, a contact laxative, can be obtained
without prescription. Adverse side effects of (excessive)
bisacodyl use are kidney stones, dehydration, hypovolemia
and secondary hyperaldosteronism.
Aim: We here present bisacodyl abuse as an explanation
for most clinical symptoms in a patient with a history of a
JAK2-V617F-negative thrombo- and erythrocytosis and a
recently discovered adrenal incidentaloma.
Case history: A 41-year-old woman was seen at our
emergency room with dyspnea, polydipsia and polyuria.
The medical history reported kidney stones and thromboand erythrocytosis most likely due to a myeloproliferative
disorder. However, no significant bone marrow abnormalities were observed and JAK-2 (V617F) mutation analysis
was negative. Three years earlier, a pulmonary embolism
was diagnosed and she was treated with fenprocoumon,
hydroxyureum, and occasional phlebotomy.
130
Physical examination revealed no abnormalities and
normal blood pressure (116/81 mmHg). Arterial blood
gas analysis showed a respiratory compensated metabolic
acidosis (pH 7.42, pO2: 14.2 kPa, pCO2: 3.8 kPa, HCO3:
18.4mmol/l, BE: -4.9). Besides hyponatremia (128 mmol/l),
elevated creatinin (94 mmol/l) and known erythro- and
thrombocytosis, no abnormalities were found in the lab. No
evidence of pulmonary embolism was seen on the CT scan.
However, an enlarged left adrenal gland was observed.
Hormonal evaluation excluded pheochromocytoma and
Cushing’s syndrome, but showed secondary hyperaldosteronism (plasma renin activity (PRA): 28,000 fmol/l/sec,
16x upper reference limit (URL)) and aldosteron: 40000
pmol/l, 47x URL). Although saline infusion markedly
decreased PRA (3500 fmol/l/sec, 5x URL) and aldosteron
(5000 pmol/l, 11x URL) levels, they remained significantly elevated. The patient repeatedly denied use of
laxatives or diuretics and reported normal stools and no
excessive sweating. A salt loading test was performed for 5
consecutive days during which she was asked to ingest 6
grams of salt per day, collect urine and register fluid intake.
Blood, urine, weight and blood pressure were analysed
daily. Average daily fluid intake was 3.5 litres, while urine
production was 1.2 litres. Her weight remained 59 kg
and blood pressure stayed normal. Because of persistent
low bicarbonate levels, screening for laxative in urine
was eventually conducted. All urine samples contained
bisacodyl metabolites.
Conclusion: Bisacodyl use was demonstrated in a patient
presenting with dyspnea, polydipsia, polyuria and adrenal
incidentaloma. Laxative abuse and subsequent dehydration
explains the electrolyte disturbances, metabolic acidosis,
shortness of breath and secondary hyperaldosteronism,
most probably causing adrenal hyperplasia. Also, the
haematological abnormalities and previously reported
kidney stones are possibly due to dehydration.
started in 2009, but no other actual complaints. On
examination a bradycardia of 46 beats per minute and a
relative hypotension of 106/54 mmHg were noted without
other abnormalities. EKG registration demonstrated an
AV-nodal rhythm without signs of ischemia. Hematology
and clinical chemistry were unremarkable. Within several
hours after admission, spontaneous recovery of sinus
rhythm and blood pressure was observed. Discharge
without a definite diagnosis followed. Both the Holter
registration and the exercise EKG subsequently performed
in the outpatient clinic appeared normal.
Strikingly, it turned out that the roommate of our patient
experienced a similar faintness during the admittance
of our patient. Though much milder in character, this
roommate too reported self-limiting symptoms that had
developed shortly after breakfast. As both our patient
and his roommate had consumed wild honey of Nepalese
origin, a suspicion on a food related toxic origin was
raised. With hindsight, the symptoms of both subjects
seemed highly characteristic for Mad Honey Poisoning.
Chemical analysis of the honey by the Dutch food authority
confirmed the presence grayanotoxin, the causative toxin.
Yet in Antiquity, the toxicity of honey and even its military
exploitation were reported. Currently, small amounts of
wild honey are being advocated as an alternative medicine
for gastrointestinal discomfort and sexual dysfunction.
The clinical picture of mad honey poisoning is grossly
cholinergic consisting of bradycardia, hypotension, perspiration, salivation, blurred vision, lightheadedness and
even loss of consciousness. Symptoms arise through
blockade of sodium channels by grayanotoxins originating
from Rhododendron nectar. Symptoms develop within
minutes to hours after ingestion, are rarely fatal and
generally last for no more than 24 hours. Treatment is
mainly supportive, consisting of atropine for symptomatic
bradycardia and intravenous administration of fluids in
case of hypotension.
Conclusion: Symptomatic bradycardia may be due to
atherosclerotic disease, especially in the presence of
cardiovascular risk factors. The differential diagnosis is
nevertheless extensive and includes food related toxins.
Given the increasing number of worldwide travelers in
addition, clinicians should be attentive to exotic causes of
intoxication.
246. A sweet surprise
D. Dekker1, P. Mulder2, R.F. van Es3, P. Smits1
1
Radboud University Medical Centrem, Department of
Farmacology/Toxicology, PO Box 9101, 6500 HB NIJMEGEN,
the Netherlands, e-mail: douwedekker@hotmail.com, 2Voedsel
en Waren Autoriteit, WAGENINGEN, the Netherlands,
3
Hospital Bethesda, HOOGEVEEN, the Netherlands
247. Rhabdomyolysis as complication of the new designer
drug MDPV
Case: a 64-year-old male presented at the emergency
department with a sudden faintness consisting of lightheadedness, perspiration and nausea which occurred
shortly after breakfast. Several days before, he returned
from a holiday in Nepal. The medical history revealed
obesity, systolic hypertension and thrombosis of the
central retinal vein of the left eye for which aspirin was
T.T.H. Nguyen, S.C.E. Klein Nagelvoort-Schuit, A. Govers
Erasmus Medical Centre, Department of Internal Medicine,
’s-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: hien277@hotmail.com
131
Introduction: In the fall of 2009 the health authorities
decided to start mass vaccination for the H1N1 virus
because of the ongoing pandemic in an attempt to prevent
excess deaths caused by infection by this new influenza
virus. Although the expected rate and morbidity of side
effects of the vaccine are very low, rapid mass vaccination
in groups at risk can lead to a wide range of problems. The
possibility of serious mistakes should at least be a matter
of consideration when rapid mass vaccination is initiated.
Safety protocols should be available and in routine use
wherever parenteral medication is administered.
Case report: A few weeks after the start of the
H1N1-vaccination campaign, 11 patients from a nursing
home were admitted to the emergency-department. During
the vaccination procedure in the nursing home 50 Units
of Insulin Glargine were mistakenly administered to all
11 patients instead of the H1N1 vaccine. In the emergency
department all patients were rapidly treated with intravenous
administration of glucose. In two patients a single episode of
hypoglycaemia was treated successfully. Four other patients
developed hypoglycaemia which persisted for 24 hours
despite glucose infusion. One of these four patients died
during admission, possibly of heart failure.
Conclusion: In the Netherlands drug-related physical
complaints lead to an estimated 19.000 admissions a
year and 1200 deaths. The number of cases of in-hospital
drug-related harm may rise up to 30.000 a year. We
report a serious and possibly very harmful mistake in
the administration of H1N1 vaccine which caused hospitalization in 11 patients, severe hypoglycaemia in at least
four patients and one death. Although the indication for
influenza vaccination in patients at risk is valid, as any
medical procedure, mass vaccination can lead to mistakes,
which can have very serious consequences. Especially in
patients with underlying morbidity, such as the population
in nursing homes, safety procedures should be followed to
prevent health damage.
Introductions: The use of psycho stimulant drugs
have been greatly increased since the last two decades.
‘Designer drugs‘ are new drugs, which are created to avoid
the current drug laws, and/or to enhance the psychoactive effect of existing drugs, usually by modifying
the molecular structures. Methylenedioxypyrovalerone
(MDPV) is a new designer drug; this recreational drug is
not as innocent as being said, as the next case illustrates.
Case report: A 21-year-old male, with a history of drugsinduced psychosis and possible schizophreniform disorder,
was seen in the Emergency Department because of an
auto-intoxication. Anamnestic evaluation reveals that he
used MDPV since 5 months, but now he has taken a much
larger dose than normal, the exactly amount was unclear.
At the Emergency Department he was anxious, agitated and
extremely paranoid, with hyperkinesia. His blood pressure
was 150/100 mmHg, with a pulse of 132 bpm, the rest of
the physical examination was unremarkablel. Laboratory
assessment revealed a creatinine of 214 umol/l, urea
11 mmol/l, creatininekinase 13.508 U/l, WBC 39 x 109/l,
CRP 12 mg/l. At the Emergency Department he refused
urine examination. An ultrasound of the kidneys didn’t
show any abnormalities. The diagnosis was rhabdomyolysis
due to MDPV-abuse and also a MDPV-induced psychosis.
The leukocytosis was attributed to extreme stress; there
were no signs of infection. Treatment consisted of proper
rehydration according to the guidelines for rhabdomyolysis, and Haloperidol for the psychosis. After a few days
the laboratory findings were fully normalized and he was
transferred to the psychiatric ward.
Discussion: MDPV is a new psychoactive drug chemically
related to Methylphenidate (but more potent), Pyrovalerone
(PV) and Methylenedioxymethamphetamine (MDMA). It
is assumed that it behaves as a norepinephrine-dopamine
reuptake inhibitor, and to a lesser extent as a serotonin
reuptake inhibitor. The acute physical effects include hypertension and tachycardia; the mental effects are euphoria,
increased awareness and arousal, anxiety and agitation. On
the internet forums high doses have been reported to give
prolonged panic attacks and even psychosis. Side effects are
presumed to be similar to PV and MDMA, long term effects
and toxic dose are not known yet.
Conclusion: Using the recreational drug MDPV is not
always without consequences, beware of adverse events
such as rhabdomyolysis and drugs induced psychosis.
transurethral resection of the prostate. This so called TUR
syndrome occurs in up to 20% of prostate operations.
The major risk factor for hyponatremia is the volume of
irrigant that is absorbed. Procedural risk factors for excess
fluid absorption during endoscopic procedures include the
type of procedure, introduction of fluid at high pressure,
visceral perforation, prolonged duration of the procedure
and type of anesthesia.
Case: A 45-year-old woman, with a history of hypertension was admitted to the hospital for hysteroscopic
resection of fibroids. Medication consisted of amlodipine,
valsartan, hydrochlorothiazide and amitryptilline. At
preoperative screening all laboratory results, including the
sodium level were normal. During hysteroscopy 6 liters of
non-conductive (non-electrolyte) distension fluids (1.5%
glycine) were used, of which 500 ml fluid was absorbed
during the procedure.
During postoperative recovery the patient complained
of nausea and malaise. Laboratory findings showed
a hyponatremia of 119 mmol/l. She was treated with
hypertonic saline and a furosemide. Her serum sodium
level increased to 124 mmol/l. With an 0.9% saline infusion,
her sodium level returned to normal, 140 mmol/l, by which
time she was asymptomatic. Hyponatremia in this patient
occurred shortly after hysteroscopic surgery, during which
she absorbed 500 ml of glycine irrigant. Hyponatremia is
most likely due to the absorption syndrome. It has been
described that symptomatic hyponatremia associated with
glycine irrigation requires fluid absorption of at least
1000 ml. However this case shows that it is also possible to
develop symptomatic hyponatremia with less fluid absorbed
during hysteroscopic procedure.
Conclusion: Hyponatremia should be suspected whenever
large volumes of nonconductive irrigation fluids have been
used or when patients develop new neurologic symptoms
during postoperative recovery, like nausea. This case
underlines the importance of monitoring the amount of
fluid absorbed during surgery so that patients at risk for
severe hyponatremia can be detected.
Tracheal compression may simulate asthma and warrants
further investigation.
Case-report: A 23-year-old woman was seen at our hospital
because of dyspnea and difficult swallowing. Physical
examination showed no stridor. Hemodynamics and
examination of heart and lungs were normal. Laboratory
results including arterial blood gas analysis was normal.
Chest X-ray showed possible compression of the trachea.
CT-thorax revealed a right sided aortic arch associated
with an aberrant left subclavian artery (LSA) originating
from a Kommerell’s diverticulum. The trachea and
esophagus were being compressed. Pulmonary function
test showed a flattened inspiratory pattern. The bronchoscopic examination showed stenosis of the lower part of
the trachea with a remaining lumen of 50%. A barium
esophageogram revealed extrinsic compression of the
esophagus. No congenital cardial abnormalities were
found. Because of her symptoms and the risk of rupture
of aneurysmal dilatation of the diverticulum surgical
treatment was indicated. A left lateral thoracotomy was
performed. The fibrous ligamentum arteriosum between
the left pulmonary artery and the inferior edge of diverticulum of Kommerell squeezed the trachea and esophagus
on their left lateral face against the retrotracheo-esophageal
subclavian artery in the back and the ascending aorta on
the right. The ligamentum arteriosum was cleaved and
the diverticulum of Kommerell was reefed. She recoverd
quickly and dyspnea and dysphagia disappeared.
Discussion: A right sided aortic arch is a rare congenital
defect of the aorta. The frequency is about 0.1%. In
50% there is an aberrant LSA. In 1936 Dr. Kommerell
first reported an aberrant right subclavian artery (RSA)
originating from the left descending thoracic aorta and
associated with persistence of a remnant of the right
dorsal aorta: a diverticulum from which the aberrant RSA
originated. In contrast to the anomaly of a left aortic arch
with an aberrant RSA patients with an right aortic arch
with aberrant LSA are symptomatic because the trachea
and esophagus are encircled by vascular structures.
5-10% have also cardial congenital abnormalities. Surgical
intervention is recommended in symptomatic patients or
asymptomatic patients with a large diverticulum. There is
an increased risk of rupture with large diverticuli and there
is an increased risk of thrombosis.
Conclusion: It is necessary for physicians to recognize that
the combination of tracheal or esophageal symptoms could
be caused by an vascular anomaly.
249. Hyponatremia following hysteroscopic surgery
I. Walhout, C.R.G.M. Daemen-Gubbels
Tergooi Hospitals, Department of Internal Medicine, Van
Riebeeckweg 212, 1213 XZ HILVERSUM, the Netherlands,
e-mail: iwalhout@tergooiziekenhuizen.nl
Introduction: Hysteroscopic procedures utilize large
volumes of irrigating solutions. The use of these nonconductive (non-electrolyte) containing fluids has been
associated with a number of complications including
heart failure and volume overload. Hyponatremia is
an uncommon complication following hysteroscopy.
Severe symptomatic hyponatremia occurs in 0.06 to 0.2
percent of women. It is a well known complication after
248. An unexpected side effect of vaccination against the
H1N1 virus. Safety first !
B. Flameling, W. de Graaff, M.H. Silbermann
Tergooi Hospitals Blaricum, Department of Internal Medicine,
PO Box 10016, 1201 DA HILVERSUM, the Netherlands,
e-mail: bflameling@tergooiziekenhuizen.nl
132
250. Don’t forget a congenital vascular anomaly in the
combination dyspnea and dysphagia
E.A.J.E. Braam1, J.C. Antons2
1
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
evelienbraam@gmail.com, 2Radboud University Medical
Centre, NIJMEGEN, the Netherlands
251. Giant cell arteritis: when to PET and when not to
PET?
Introduction: Developmental abnormalities of the aortic
arch affect approximately 3% of the general population.
Clinical manifestations are uncommon. Symptoms usually
occur because of compression of the trachea or esophagus.
N.L.H. Bekkali1 , K.D.F. Lensen 2 , C.E.H. Siegert 3 ,
E.H. van der Poest Clement1, J. Bosma1
133
1
St.Lucas Andreas Hospital, Department of Internal
Medicine-MDL, Jan Tooropstraat 164, 1061 DE AMSTERDAM,
the Netherlands, e-mail: noorbekkali@hotmail.com 2VUmc,
AMSTERDAM, the Netherlands
Conclusion: The 18-FDG PET-CT should be considered
in patients with high clinical suspicion for GCA despite
negative ultrasonography and biopsy.
Introduction: Early recognition of Giant cell arteritis
(GCA) and instant treatment with glucocorticosteroids are
essential to prevent severe organ dysfunction, blindness in
particular. While temporal artery biopsy is considered the
gold standard in diagnosing GCA, PET-CT is also gaining
a more important role in diagnosing GCA. Here we present
a patient who was diagnosed with GCA by PET-CT after
negative results from both, biopsy and ultrasonography.
Case report: A 50-year-old woman presented with a 2-weeks
history of fever, fatigue, chest pain and a dry cough.
The week prior to presentation she was treated with
amoxicilline-clavulanic acid by her general practioner for
bronchitis. Her medical history revealed asthma.
She also reported right-sided headache, fever with cold
chills and night sweats. After one week no infectious
cause was found for the fever. Thereafter the patient
started complaining of jaw claudication as well as painful
shoulders.
Biochemical tests showed an ESR of 117 mm/h with
a CRP level of 70 mg/l and mild normocytic anaemia
(haemoglobin level 6.7 mmol/l). Repeated blood cultures
were negative. Serological testing was positive for ANA
and negative for anti-dsDNA. Infectious serological
testing, including HIV, was negative. Tested M-protein
was negative.
After one week, given the new complaints amongst
which jaw claudication, GCA was considered. Therefore, a
bilateral temporal artery ultrasonography was performed
revealing no abnormalities. Also, a unilateral (right)
temporal artery biopsy showed no signs of inflammation.
Despite these negative findings, yet with significant
clinical suspicion for GCA, a 18-FDG PET-CT scan was
performed. The PET-CT revealed large-artery vasculitis,
showing increased FDG-uptake in the proximal branches
of the aortic root and entire aorta. MRA of the thorax
was performed to exclude Takayasu’s arteritis. No signs
of vascular narrowing or obstruction could be shown on
MRA.
Treatment with high doses of prednisone was started with
direct symptom relief and temperature normalisation.
Discussion: In this patient the combination of clinical
features and positive results obtained by PET-CT-scanning
were compatible with GCA. The presented patient demonstrates that negative temporal artery ultrasonography
and biopsy does not necessarily exclude the diagnosis
of temporal arteritis (Brack 1999 A&R, Janssen 2008 J
Vasc Surg). In cases of a strong suspicion of this classical
syndrome in internal medicine a 18-FDG PET-CT may be
a valuable new gold standard to diagnosis.
252. An unusual cause of post-renal kidney failure
P.J.E.J. van de Berg, V.C. Harris, P.S. van Dam
Onze Lieve Vrouwe Gasthuis, Department of Internal
Medicine, Oosterpark 9, 1091 AC AMSTERDAM, the
Netherlands, e-mail: p.j.e.j.vandeberg@olvg.nl
Introduction: In an elderly woman, the combination
of unintentional weight loss, loss of appetite, general
weakness and a retroperitoneal para-aortal mass leading
to obstructive kidney failure is highly suggestive for
malignancy. In the present case, however, an unusual
non-malignant condition was responsible for the
development of similar symptoms.
Case: A 74-year-old woman was admitted to the hospital
with generalized weakness, unintentional weight loss and
loss of appetite. Two months previously, she had undergone
bilateral angioplasty of the common iliac arteries.
Physical examination was significant for a solitary solid
mass that was palpable at the left sub-mandibular angle,
which had features suggesting a malignant lymph node
with ultrasound examination. Laboratory analysis of
blood and urine revealed renal insufficiency, which was
subsequently explained by the presence of a para-aortal
mass obstructing both ureters. Suspecting a malignant
lymphoma, an initial biopsy of the sub-mandibular
lymph node was performed, however pathology results
revealed a benign salivary gland tumor (Warthin tumor).
Consequently, biopsy of the para-aortal mass was
performed and revealed chronic fibrosing inflammation,
consistent with retroperitoneal fibrosis. To regain urinary
flow, pyelo-vesicular catheters were placed in both ureters.
This intervention relieved the patient’s malaise and loss of
appetite, and partly restored her kidney function (estimated
GFR 55 ml/min). The retroperitoneal fibrosis was treated
with high dose prednisolone for six weeks, slowly tapering
the dose hereafter to 10mg per day. After three months of
treatment, there was only a slight reduction in the size of
the retroperitoneal fibrosis. Our intention is to treat the
patient with prednisolone for the coming 1.5 years. During
this time, bilateral pyelo-vesicular catheters will assure
adequate urinary flow.
Discussion: This case demonstrates an unusual cause of
obstructive renal failure with a prevalence of 1.3 per 100.00
inhabitants. Although benign, the consequences of retroperitoneal fibrosis can be severe and treatment requires
long-term glucocorticoid treatment. The insidious onset of
the disease makes a quick diagnosis difficult. Interestingly,
this patient underwent a percutaneous procedure of the
134
Conclusion: This case shows an impressive presentation
of starvation causing hypotension, hypoglycemia and
metabolic acidosis. The starvation being caused by a
combination of reduced intake, gastric banding and
pregnancy. The complaint of popping ears caused by tuba
atrofy underlined her marked loss of fat supplies. Gastrical
banding is increasingly used as treatment for obesity, many
of these patients are women in a fertile age. This case
stresses the importance of monitoring their nutritional
state during pregnancy.
iliac arteries two months prior to when the retroperitoneal fibrosis became clinically apparent. Perhaps the
mechanical manipulation of the aorta and large arteries
resulted in the ‘periaortitis’ which is thought to play a role
in the pathogenesis of this disease.
253. A young woman with hypoglycemia, metabolic
acidosis and popping ears
M. Krikke, M. ten Wolde, N. Smit
Flevo Hospital, Department of Internal Medicine,
Hospitaalweg 1, 1315 RA ALMERE, the Netherlands, e-mail:
nsmit@flevoHospital.nl
254. Unusual use of nutmeg
C.G. Krol1, M.J.F.M. Janssen2
Leiden University Medical Centre, Department of
Internal Medicine, Albinusdreef 2, 2333 ZA LEIDEN, the
Netherlands, e-mail: cgkrol@hotmail.com, 2Rijnland Hospital,
LEIDERDORP, the Netherlands
1
Case report: A 35-year-old woman presented at the
emergency room with hypotension, nausea and vomiting.
She had consulted her doctor days before with dizzy
spells and general malaise. Four weeks earlier she had
given birth to her second child, the pregnancy and birth
had been without complications. Her symptoms started
in the last term of the pregnancy. In addition she lost
over 15 kilograms of weight in the last month and had
complaints of popping ears, closing and opening continuously. Her past medical history only notes a gastrical
band placing in 2000 due to obesity. Tachycardia, low
blood pressure and tachypneau were seen on physical
examination. Laboratory analysis showed a hypoglycemia of 2.7 mmol/l, metabolic acidosis with inadequate
respiratory compensation and increased aniongap
and ketonuria. The differential diagnosis considered
M. Addison, insulinoma, M. Sheehan, gastroenteritis,
infection, starvation, intoxication. Empiric hydrocortisone and fluids were started and further analysis was
requested; cortisol levels, thyroid function, ACTH levels,
all were within normal range. Cultures of blood and urine
were also negative. The general condition of our patient
improved. Further blood analysis revealed electrolyte
imbalances; hypomagnemesia, hypofosfatiemia, hypokaliemia. When deepening the history patient confesses
to low intake during her pregnancy. Also she notes
that she did not adjust her gastric band as instructed
during a pregnancy. This has resulted in starvation
during pregnancy and the breastfeeding period, afterwards
depleting her of her supplies. The starvation resulted in
a higher keton production, causing a metabolic acidosis
and her other symptoms and electrolyte imbalances. The
hypoglycemia is caused by insufficient substrate for gluconeogenesis and glycogenolysis due to glycogen depletion.
The ENT doctor was consulted. Her ears were clean of
wax on examination and the eardrum showed no signs of
pathology. Due to the loss of fat usually present in the tuba,
atrophy of the tuba is seen causing the tuba to collapse
causing a pressure difference resulting in popping ears.
Introduction: Nutmeg is a spice, frequently used in Dutch
and Asian cooking. Relatively unknown are the hallucinogenic and euphoric effects of nutmeg, and the adverse
effects in case of nutmeg intoxication.
Case: A 20-year-old woman with borderline personality
disorder was referred to the emergency department
by a psychiatric clinic. Her medical history included
several hospital admissions because of intoxications with
analgesics. On the day of the referral, she felt ‘down’
and searched the internet for a drug for self-harm when
she read about nutmeg, which she bought at a local
supermarket. After taking 10 g of nutmeg she complained
of stomach ache and dizziness. A physical examination
showed mild hypothermia and sinus tachycardia. She was
admitted for observation and discharged after 24 h to the
psychiatric clinic without sequelae.
Discussion: Nutmeg is a frequently used spice, of which
low quantity is generally enough to add flavour. In higher
dosage, nutmeg has hallucinogenic and euphoric effects
for which it is used mainly by drug abusers and students
because of its low costs and availability. Due to its strong
flavour and unpredictable and mild effects, wide-spread
usage has not been reported. Symptoms appear 6 h
after ingestion of at least 10 g of nutmeg and are related
to its effects on the central nervous system, leading to
agitation and lethargia. Anxiety, feelings of ‘doom’ and
psychosis are reported, accompanied by visual hallucinations. Dry mouth, nausea and dizziness may also occur.
Physical examination may show hypothermia, tachycardia
or hypertension or, in rarer cases, hypotension and shock.
Laboratory tests are usually unremarkable, and nutmeg
intoxication cannot be biochemically confirmed. There is
debate about the mechanism of toxicity. The symptoms
are probably caused by myristicine, which is metabolized
135
to amphetamine- like substance leading symptoms similar
to LSD intoxication. Symptoms disappear without sequelae
after 24-48 h. Death due to nutmeg intoxication has
not been described. Treatment consists of supportive
measures, including fluid infusion and anti-emetics. In
case of severe delirium, benzodiazepine treatment may
be considered. In the event of haemodynamic instability,
cardiovascular monitoring is indicated and other intoxications should be considered.
Conclusion: The course of nutmeg intoxication is generally
mild with disappearance of symptoms without sequelae
within 24-48 hours. Treatment is mainly supportive.
(75%) with SB lesions and in one (17%) without SB lesions.
Serum levels of TNF-a, IL1ß and IL-10 were also elevated
in one patient.
Conclusion: DBE is a valuable and safe tool to evaluate
the involvement of the entire gastrointestinal tract in
BD patients possibly leading to a change in therapy.
Inflammatory cytokines are involved, however no clear Th1
or Th17 profile was observed.
XXV. IMMUNOLOGY/ALLERGOLOGY RESEARCH
256. DRESS syndrome; a case-report
XXVI. IMMUNOLOGY/ALLERGOLOGY CASE REPORT
M. Janssen, G.S. Bleumink
Rijnstate Hospital, Department of Internal medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
m3janssen@alysis.nl
255. Clinical use of small bowel evaluation by double
balloon enteroscopy in Behçet’s patients with
abdominal complaints
Case: A 48-year-old man presented at the emergency
department with fever, rash and diarrhea of one week
duration. He also complained of headache and loss of
appetite. Five weeks earlier he had switched his antiepileptic medication from levetiracetam to carbamazepine.
He stopped using carbamazepine since start of the rash.
On physical examination the patient had a temperature of
39.2 °C, blood pressure of 125/87 mmHG and pulse of 108
bpm. Exanthema, impressing as toxicodermia, was seen
all over his body
Laboratory results showed an increased white blood cell
count of 19.8 x 109/l, high C-reactive protein (96 mg/l),
acute renal failure, increased liver enzymes and prolonged
coagulation tests, suggesting hepatic insufficiency.
Because of suspicion of sepsis, our patient was started
on cefuroxime and i.v. fluids. The rash was thought to be
caused by an allergic reaction to carbamazepine. Post renal
obstruction was excluded as a cause of renal failure.
During follow-up despite administration of i.v. fluids his
kidney function did not improve. Also, liverfunction tests,
fever and rash did not improve after antibiotics. Hence
the patient was started on methylprednison because of
suspicion of interstitial nephritis by DRESS syndrome
caused by carbamazepine. Eosinophils were determined
in the blood count and were elevated. During his stay
in the hospital repeated blood cultures stayed negative.
Shortly after the start of corticosteroids his kidney function
improved as did the other laboratory abnormalities. After
cessation of glucocorticoid treatment, his symptoms
recurred, therefore prednisone was started after another
infusion of solu-medrol, which again led to improvement of
laboratory abnormalities and clinical improvement.
J.H. Kappen, J.A.M. Laar, P.B.F. Mensink, W.A. Dik,
H. Hooijkaas, S. Lachman, P.L.A. Daele, P.M. Hagen
Erasmus Medical Centre, Department of Internal Medicine,
’s-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: j.kappen@erasmusmc.nl
Introduction: Gastrointestinal symptoms are often present
in patients with Behçet’s disease (BD), but objective
gastrointestinal inflammation occurs infrequently. Double
balloon enteroscopy (DBE) enables visualization of the
entire small bowel (SB) together with tissue sampling and
thus enhances the yield of gastroentestinal investigations
of BD patients with abdominal complaints. Evaluation of
Th1 and Th17 skewed key BD-cytokines might improve the
understanding of the pathophysiological processes in this
systemic vasculitis.
Aim: Evaluate small intestine involvement in BD using
DBE.
Patients and methods: 10 BD patients with therapy resistant
abdominal complaints were evaluated with DBE. Serum
cytokine profiles and lymphocyte subsets were analyzed.
Results: SB lesions were identified in four (40%) patients.
The SB lesions were located in the distal ileum in three,
and distal jejunum and terminal ileum in one patient. In
all patients the SB lesions were out of reach for conventional gastroduodeno- or ileocolonoscopy. No complications
occurred during or after the DBE procedure.
In two of the patients with SB lesion (50%) the serum
C-reactive protein (CRP) was elevated, while one patient
without SB lesions (17%) had an elevated CRP level. Serum
IFN-y levels were elevated (> 10 pg/ml) in three patients
136
Background: DRESS syndrome stands for Drug Rash (or
Reaction) with Eosinophilia and Systemic Symptoms.
Symptoms can be severe and include exanthema, fever and
involvement of one or more organs, including liver, kidneys
and lungs. Mortality is about 10%. Classically it develops 1
to 8 weeks after start of the causative drug. Anti-epileptics
are the most common drugs described as causing DRESS
syndrome.
It is hypothesized that hypersensitivity is induced as a
result of abnormalities in production and detoxification of
active metabolites of the causative drug.
Treatment consists of discontinuing the causative drug.
Often high-dose corticosteroids are given, but there is
no evidence in medical literature that this influences
the duration of symptoms or mortality of the DRESS
syndrome. In our case glucocorticoids seemed to be
effective in treating the DRESS syndrome, especially
because of recurrence of symptoms after cessation of
therapy.
the pharmacist reviewed the data and contacted the
prescribing physician, if necessary.
Results: During the study period, the computer reported
271 times that the drug dose needed correction because of
the renal function. However, in 210 cases the dose turned
out to be correct (or too low !) and no further action was
needed. In 36 cases improved renal function was a reason
not to contact the physician. In 25 cases the pharmacist
contacted the physician for advice. Drugs most frequently
reported were: low molecular weight heparin (LMWH),
various antibiotics, ACE inhibitors, metformin, pregabalin,
allopurinol and amantadin. The most important was
overdosage of LMWH in patients with renal failure, which
may cause serious bleeding.
Conclusion: In 60 days there were 246 reports, this
would be approximately 1650 reports in a year, but only
25 phone calls were necessary (152 calls/year). However,
very few serious problems were seen. Apparently, when
prescribing drugs, most doctors take renal function
into account. Still, drug surveillance such as described
here, may prevent morbidity and mortality, and should
therefore be continued. However, our system certainly
needs improvement in view of the many unnecessary
computer reports.
XXVII. OTHER RESEARCH
257. Improving safety in prescribing drugs in patients
with impaired renal function
258. Sarcopenia: can it be defined?
F.H. Woudstra, C. Halma, D. Vogel
Medical Centre Leeuwarden,Department of Internal Medicine,
Henry Dunantweg 2, 8934 AD LEEUWARDEN, the
Netherlands, e-mail: f hwoudstra@hotmail.com
A.Y. Bijlsma, C.G.M. Meskers, R.G.J. Westendorp,
A.B. Maier
Leiden University Medical Centre, Department of
Ouderengeneeskunde, Albinusdreef 2, 2333 ZA LEIDEN, the
Netherlands, e-mail: a.y.bijlsma@lumc.nl
Introduction: Because many drugs are excreted by the
kidneys, renal failure may cause accumulation and
unwanted drug toxicity. In hospitalized patients it is possible
to combine the pharmacy drug data base and clinical data
base (renal function) in order to track down inappropriately dosed drugs. By contacting the prescribing physician
dosages may be adjusted and morbidity may be prevented.
Aim: We examined retrospectively our programme to
detect inappropriately dosed drugs in our hospital.
Materials and methods: During a period of sixty days all
patients admitted to the Medical Centre Leeuwarden (657
beds/28.700 admittances a year) were screened on appropriateness of dosing according to the KNMP Kennisbank
‘verminderde nierfunctie’. Data from the pharmacy drug
database (Zamicom) and clinical database (GLIMS) were
combined into an Acces database. The renal function
was estimated by eGFR using the Modification of Diet in
Renal Disease (MDRD) formula, without correction for
body surface area (eGFR is in ml/min/1,73 m2). When the
computer indicated that the drug dose needed adjustment,
Introduction: Sarcopenia occurs as early as 30 years
of age and may result in a loss of about 50% of muscle
mass by the age of 80 years. Age related loss of muscle
mass is related to detrimental outcome, i.e. functional
impairments, falls and increased mortality.
Since the term ‘sarcopenia’ was launched in 1988 by
Rosenberg, not much progress has been made towards
a widely accepted, scientifically and clinically useful
definition.
The long way from the observation of a phenomenon to
a guidance for clinical decision making shows similarities with previous attempts to define the ‘age-related’
phenomenon osteoporosis. Even today physicians remain
critical and keep thinking of better strategies to define the
term osteoporosis.
Aim: To get a firm grip on and explain the status quo of a
definition of sarcopenia by a chronological comparison to
the development of a definition of osteoporosis.
Materials and methods: We first investigated the prevalence
of sarcopenia in a large cohort of subjects of the Leiden
137
Longevity Study, emerging from five different existing
definitions of sarcopenia using body composition values
as measured by bioimpedance analysis. Furthermore,
the chronology of the development of definitions for
osteoporosis was assessed from subsequent editions of
Harrison’s Principles of Internal Medicine and compared
to current definitions of sarcopenia.
Results: Within the Leiden Longevity study, comprising
311 middle aged women and 320 middle aged men a range
of 0-3.6% women and 0-26.4% men fulfilled the criteria
for sarcopenia depending on the applied definition. The
prevalence of sarcopenia was not related to chronological
age, when the five existing definitions were applied.
A timeline of milestones of the history of osteoporosis
definition development reflected the difficulties in defining
sarcopenia during recent years.
Conclusion: Prevalence of sarcopenia varies widely
depending on used definition or cut-off point. It even
can happen that no age-related loss of muscle mass is
found at all. Difficulties in definition of sarcopenia are
very similar to those of osteoporosis, e.g. in both cases it
appeared difficult to discern pathology from inevitable age
related decline and in both cases it is difficult to assess the
functional consequences on an individual base.
electrophoresis, glucose, and Troponin I were within
normal limits.
Rhythm monitoring was unable to detect arrhythmias or
high degree conduction disturbances. Even in the presence
of dizziness, the rhythm was normal. Neurological work-up
did not show relevant abnormalities. The transthoracic
echocardiographic (TTE) study showed mild to moderate
left ventricular hypertrophy with preserved systolic
function and impaired diastolic relaxation. There was left
atrial compression due to the hiatus hernia. A CT scan
of the chest documented that the stomach was nearly
completely localized above the diaphragm. Left atrial
compression was confirmed. TTE was repeated in fasting
condition and after a copious meal. After the meal, there
was severe compression of the left atrium, which could not
be documented in fasting condition.
A careful requestioning of the patient confirmed the time
relation between the postprandial period and the episodes
of dizziness and collapse. The patient was considered to be
too aged to be submitted for surgical correction. He was
told to use the same amount of calories in more frequent
smaller meals. Domperidon was initiated. The conservative
management resulted in complete relief of the symptoms.
The medical literature on left atrial compression is rather
limited. A Med-line search with the term ‘left atrial
compression’ showed 271 hits. Only 17 cases, of which
11 with hiatus hernia, of left atrial compression due to
structures of the gastrointestinal tract were found. Most
of the patients were successfully treated with conservative
management.
Noteworthy, the median age of these patients was 75 years,
suggesting that LAC due to a gastrointestinal structure is
a disease of the elderly.
Conclusion: We report the case of an 86-year-old man,
who suffered from recurrent syncope caused by LAC due
to a large hiatus hernia. Reports describing LAC are rare.
Echocardiography is a reliable tool to confirm LAC and
quantify the severity the compression.
XXVIII. OTHER CASE REPORTS
259. A rare cause of syncope: left atrial compression due
to a hiatus hernia
J.M.J.B. Walpot1, J. van Zwienen1, W.H. Pasteuning1,
B. Amsel2
1
Admiraal De Ruyter Hospital, Department of Cardiology,
Koudekerkseweg 88, 4380 DD VLISSINGEN, the Netherlands,
e-mail: j.walpot@adrz.nl, 2University Hospital Antwerp,
EDEGEM-ANTWERP, Belgium
Introduction: Symptomatic left atrial compression is a
rare clinical condition causing left ventriculair inflow
obstruction resulting in low output, with symptoms such
as syncope, and retrograde increase in pressure throughout
the pulmonary vessels with subsequent dyspnea.
Case report: An 86-year-old male, with a medical history
of a known asymptomatic hiatus hernia and polyneuropathy of unknown origin, was hospitalized because of
a syncope. After a meal, he had briefly lost consciousness.
The physical examination was unremarkable. The electrocardiogram showed sinus rhythm without ischemic or
hypertrophic changes. A complete blood count, renal an
liver function tests, inflammatory parameters, protein
138
I ND E X
FIRST AUTHOR
Aalderen, van
Aarnoudse
Achterbergh
Agterhuis
Ahmed-Ousenkova
Alidjan
Andreescu
Andriessen
Arwert
Atiqi
Barlo
Beekman
Bekkali
Berg, van de
Bethlehem
Bierhoff
Bijlsma
Bijlstra
Binnenmars
Boeddha
Bonnie
Boog, van der
Boot
Boreen, van
Borst, de
Boslooper
Boudewijns
Boumans
Braam
Branger
Brok, den
Brouwers
Bruin, de
Bruns
Buis
Buster
Choudhry
Claessens
Clercq, de
Compaijen
Conijn-Mensink
Cornet
Crobach
Cruijsen
Cuperus
Dackus
De Haar-Holleman
Dekker
Deure, van der
Dijkstra
Dorp, van
Douma
Douma
Douma
Driessen
Drion
FIRST AUTHOR
ABSTRACT NR
M.C.
A.L.H.J.
R.
D.E.
Y.M.
F.M.F
C.E.
R.W.
L.I.
R.
N.P.
D.G.
N.L.H.
P.J.E.J.
C.
M.
A.Y
P.
S.H.
C.R.
L.H.A.
H.T.
C.L.
M.C.
M.H.
K.
S.
D.
E.A.J.E
J.
A.N.
M.C.G.J.
I.J.A.
A.H.W.
M.C.
E.H.C.J.
Z.A.
J.J.M.
N.C.
C.J.
A.S.B.
A.D.
M.J.T.
M.J.
F.J.C.
G.M.H.E.
A.
D.
W.M.
I.M.
S.M.
R.A.
G.
J.A.J.
C.M.L.
I.
111
203
55
141
215
73, 179
88
65
82
225, 226
186
218
251
252
43, 223
44
258
213, 214, 216
100
201
164
70
97
185
12
113
168
76
250
191
10
15
89
182
198
127
101
34
110
132
50
192
193
237
91
158
53, 117
246
60
245
136
6
115
157
105
11
Droogendijk
Dutilh
Eling
Enschot, van
Ezzahti
Flameling
Gastel, van
Geelhoed
Geerse
Gerrits
Goes, van der
Gootjes
Grasman
Grijsen
Groeningen, van
Haalen, van
Hagen, van
Halteren, van
Hana
Hattem, van
Hende, van den
Hermans
Hermsen
Hillen
Hofland
Holster
Hommel
Hoogenberg
Hovius
Huijben
Huijgen
Huttjes
Ilik
Jager, de
Jalving
Jansen
Janssen
Jongsma-van Netten
Jonker
Joosten
Josephus Jitta
Kampschreur
Kappen
Kappers
Keur
Klauw, van der
Klieverik
Klok
Klop
Kok
Kouwenberg
Kraan, van der
Kramer
Kramer
Krikke
Krol
139
ABSTRACT NR
J.
J.C.
Y.
J.W.T.
M.
B.
P.M.
J.J.M.
D.A.
E.G.
M.C.
E.C.
M.E.
M.L.
I.K.
F.M.
P.M.
H.K.
A.
J.M.
L.N.
M.A.W.
I.G.C.
J.M.
J.
I.L.
I.
K.
J.W.R.
A.M.T.
R.
S.N.
M.I
R.L.
M.
P.M.
M.
H.G.
J.T.
J.M.H.
N.
L.M.
J.H.
M.H.W.
M.B.
M.M.
L.M.A.
F.A.
B.
M.
I.C.
J.
M.
A.B.
M.
C.G.
5
171
180
135
154, 173, 233
248
85, 219
220
206, 241
69
129
165
181
20
221
123
8
137
142
195
190
18
38
156
37
161
104
27
58, 170
3, 199
148
183
196
66
208
16, 151
23, 256
59
30
202
174
19
255
39
210
227
230
131
146, 147
64, 169
234
240
45
62
253
254
FIRST AUTHOR
Laar, van
Labots
Lambregts
Lammers
Lammers
Langenberg
Langenberg
Liesting
Linde, van der
Loffeld
Loffeld
Logtenberg
Maas
Maas
Meerten, van
Mehra
Meijden, van der
Mellema
Mijnhout
Moolenaar
Mulder
Mutsaers
Net, van der
Nguyen
Niemeijer
Nijland
Ogilvie
Oosterwerff
Ootjers
Peters
Platvoet-Sijtsma
Poel
Polinder- Bos
Poppel, van
Post
Pulles
Quanjel
Rab
Ramakers
Ramshorst, van
Reijnders
Repping-Wuts
Robbrecht
Rodenburg
Rooijen, van
Ruiter
Sandberg
Sandovici
Santbergen
Scholte
Schouten
Schreurs
Schrijver
Schuijt
Simkens
Slavenburg
Sluis, van
Snoeks
Sprangers
ABSTRACT NR
J.A.M.
G.
M.M.C.
W.J.
A.J.J.
M.H.G.
S.M.C.H.
C.
N.A.J.
S.M.L.A.
R.J.L.F.
S.J.J.
M.
M.L.
T.
N.
W.A.G.
J.E.M.
G.S.
D.L.J.
D.J.
P.G.N.J.
J.B.
T.T.H.
N.D.
M.L.
A.C.
M.M.
C.S.
J.L.
S.M.
Y.H.M.
H.A.
P.C.M.
J.P.
A.E.
M.J.R.
M.A.E.
B.P.C.
J.
J.G.P.
J.W.J.
D.G.J.
E.M.
C.R.
R.
Y.
M.
B.
J.B.J.
M.
J.W.G.M.
E.J.M.
T.J.
L.H.J.
S.
G.L.
L.L.
J.M.
FIRST AUTHOR
9
56
172
109
231
35
166
130
17
159
160
28
87
175
2
77
72
177
103, 238
217, 224
149, 155
126
178
247
118
121
143, 144
96
176
78
93
139
119
106
244
222
67
74
209
92
163
86
114
33
83
29, 107
42
99
194
232
25
167
41
24
36
188
49
242
68
Sriram
Stassen
Steen, van der
Streukens
Stuijver
Tack
Takkenberg
Telgen
Tomlow
Tromp
Veen, van
Veer, van der
Vegting
Ven, van de
Verbeet
Vercoutere
Vergeer
Verheijden
Versmissen
Verweij
Verweij
Visser
Vondeling
Voogd
Vos
Vriens
Vriesendorp
Wagen, van der
Wal-Visscher, van de
Walhout
Walpot
Waning, van
Weegh, op de
Weijmans
Wener
Wennemers
Wentholt
Wester
Wester
Wiersinga
Wijk, van
Wijsman
Willemsen
Wind
Winkel, van de
Wismans
Wit, de
Witmer
Wlazlo
Woittiez
Woittiez
Wolzak
Woudstra
Wumkes
Yassi
Ytredal
Zegers
Zijlstra
Zondag
Zonneveld
140
ABSTRACT NR
J.D.
P.M.
M.J.M.M.
S.A.F.
D.J.F
G.J.
R.B.
M.C.
B.
M.
M.C.
M.
I.L.
A.C.
N.L.
W.
M.
N.A.F.
J.
E.
K.E.
H.
A.M.
F.J.
J.
I.J.H.
T.M.
L.E.
E.R.
I.
J.M.J.B.
V.H.
M.L.
M.
R.R.L.
A.
I.M.E.
R.
M.
W.J.
J.P.H.
C.A.
A.E.C.A.B
L.J.N.
L.M.H
P.J.
H.M.
J.L.
N.
K.J.
L.R.
H.
F.H.
M.L
W.
H.
I.H.A.
M.
W.
A.M.
75
22, 32
63
79
26
54
122
124
153
1
162
134
228, 229
81
80
239
14
112
13
120
152
133
48
189
150
71
84
90
204
249
243, 259
212
95
98
51
138
46
125
236
57
102
31
61
187, 197
47
200
94
40
4, 108, 235
205
211
145
257
116, 140
184
52
128
207
7
21