1. health and fitness
2. disease

CHEST
Original Research
SARCOIDOSIS
The Treatment of Lupus Pernio*
Results of 116 Treatment Courses in 54 Patients
Eleni Stagaki, MD; William K. Mountford, PhD; Daniel T. Lackland, DrPH;
and Marc A. Judson, MD, FCCP
Background: Lupus pernio is a disfiguring sarcoidosis skin lesion that is difficult to treat and often
causes a major psychosocial impact that may adversely affect the patient’s quality of life. We
reviewed the treatment outcome of 54 patients with lupus pernio who received 116 individual
courses of treatment in our sarcoidosis clinic.
Methods: Lupus pernio patients were identified from an institution-approved database. All
patients were assessed at each clinic visit with facial photographs. By examining the photographs,
the percentage of face involved (< 10%, 10 to 25%, > 25 to 50%, > 50%) was determined as was
the effect of therapy (resolution, near resolution, improvement, no change, worsening). Medications included infliximab-containing regimens; systemic corticosteroids; noninfliximab, noncorticosteroid agents; and corticosteroids plus noncorticosteroid agents.
Results: In terms of achieving resolution or near resolution, infliximab regimens were superior to
all others (infliximab, 77%; corticosteroids plus noncorticosteroids, 29%; corticosteroids, 20%;
noncorticosteroids, 11%; infliximab vs other therapies: corticosteroids plus noncorticosteroids,
p ⴝ 0.0015; corticosteroids, p ⴝ 0.0005; noncorticosteroids, p ⴝ 0.0002). The percentage of facial
involvement also improved most with infliximab. Evaluating a secondary analysis of achieving
resolution, near resolution, or improvement, infliximab (92%) was superior to noncorticosteroids
(20%; p < 0.0001) and corticosteroids plus noncorticosteroids (56%; p ⴝ 0.0098), but not corticosteroids (72%; p ⴝ 0.2456); and noncorticosteroid agents were inferior to all other regimens.
Conclusions: Infliximab appears superior to systemic corticosteroids with or without additional agents
for the treatment of lupus pernio. Noninfliximab, noncorticosteroid-containing regimens are of
limited use for this condition.
(CHEST 2009; 135:468 – 476)
Key words: infliximab; lupus pernio; skin; systemic corticosteroids; therapy
Abbreviations: MUSC ⫽ Medical University of South Carolina; SASI ⫽ Sarcoidosis Activity and Severity Index
pernio is an indolent, red-to-purple, or
L upus
violaceous nodular or plaque-like sarcoidosis skin
lesion that may affect the cheeks, nose, chin, forehead, ears, perioral, or periocular regions.1 The
lesions are often disfiguring, and their psychosocial
impact may adversely affect the patient’s quality of
life. This form of sarcoidosis often portends a poor
prognosis.2– 4
Despite the gravity of this clinical entity, there is a
paucity of information concerning its treatment.
Treatment studies of lupus pernio include case
reports,5–10 case series,11–16 and one small (n ⫽ 14)
open label trial.17 This article summarizes our experience with the treatment of lupus pernio over the
past 8 years in our sarcoidosis clinic, describing the
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outcome of 54 sarcoidosis patients with lupus pernio
who received a total of 116 separate treatments.
Materials and Methods
This study was approved by the Medical University of South
Carolina (MUSC) Institutional Review Board.
Study Population
The patients were identified retrospectively from a clinical
sarcoidosis database approved by MUSC. Subjects were evaluated in the MUSC Sarcoidosis Clinic from May 12, 2000, until
January 07, 2008. All patients had biopsy-proven sarcoidosis and
definite lupus pernio based on the organ involvement instrument
from A Case Control Etiologic Study of Sarcoidosis.18 That is,
Original Research
Figure 1. A patient with lupus pernio skin lesions on the nose, forehead, and around the eyes: 10 to
25% of the face surface. The patient has given permission to use these pictures.
patients were defined as having lupus pernio if they had biopsyproven sarcoidosis and indolent, red-purple or violaceous, indurated, nodular, or plaque-like skin lesions affecting the nose,
cheeks, chin, forehead, ears, and perioral or periocular regions
that could not be attributed to another cause.1
Data Collection
Demographic data and clinical data related to extracutaneous
sarcoidosis were obtained from a review of each medical record.
The evaluation of lupus pernio lesions was based on information
extracted from the medical record and photographs of the lupus
pernio lesions taken at clinical visits. By using the medical record
and photographs, lupus pernio lesions were assessed by the
following: (1) the onset of lupus pernio; (2) the specific locations
of the face that were involved (forehead, cheeks, periocular, perioral,
chin, ears, and nose); and (3) the extent of the lesions characterized
by the amount of face surface involved (⬍ 10%, 10 to 25%, 25 to
50%, and ⬎ 50%). Photographic assessment of the skin lesions was
done with knowledge of which photograph was performed before
and after therapy. However, photographic assessment was blinded
*From the Third Pulmonary Department (Dr. Stagaki), Sismanoglio
General Hospital, Athens, Greece; and Department of Biostatistics,
Bioinformatics, and Epidemiology (Drs. Lackland and Mountford),
and Division of Pulmonary and Critical Care Medicine (Dr. Judson),
Department of Medicine, Medical University of South Carolina,
Charleston, SC.
Drs. Stagaki, Mountford, and Lackland have no conflicts of
interest to disclose. Dr. Judson has received research grants from
Celgene and Centocor.
Manuscript received May 27, 2008; revision accepted August 20,
2008.
Reproduction of this article is prohibited without written permission
from the American College of Chest Physicians (www.chestjournal.
org/misc/reprints.shtml).
Correspondence to: Marc A. Judson, MD, Division of Pulmonary
and Critical Care Medicine CSB-812, Medical University of
South Carolina, 96 Jonathan Lucas St, Charleston, SC 29425;
e-mail: judsonma@musc.edu
DOI: 10.1378/chest.08-1347
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in terms of the treatment regimen that was used. Figure 1 shows an
example of a lupus pernio patient assessed by this method.
Follow-up and Treatment
Subjects were examined and treated by the same physician
(M.A.J). Patients who were primarily receiving sarcoidosis treatment because of organ involvement other than lupus pernio were
excluded from the analysis. The schedule of follow-up visits and
the treatment plan were not standardized but were tailored to the
individual patient. The dosing of the major drugs administered is
outlined as follows. Corticosteroid dosing was usually 20 to 40
mg/d of prednisone equivalent. The dose of methotrexate ranged
between 10 to 20 mg/wk. Hydroxychloroquine doses ranged
between 200 mg/d and 400 mg/d. Infliximab dosing basically
followed a previously published dosing regimen19,20: 5 mg/kg IV
at weeks 0, 2, and 6, and then every 6 weeks. For the purposes of this
analysis, we characterized the treatment regimens used for the lupus
pernio patients as follows: (regimen 1) systemic corticosteroids
alone; (regimen 2) noninfliximab, noncorticosteroid drugs including
methotrexate, hydroxychloroquine or chloroquine, minocycline, azathioprine, thalidomide, pentoxyfylline, intralesional and topical corticosteroids, topical tacrolimus, and topical retinoic acid; (regimen 3)
systemic corticosteroids plus one or more of the agents above in
regimen 2; and (regimen 4) treatment regimens in which infliximab
was used: infliximab alone, infliximab plus systemic corticosteroids,
and/or plus agents above in regimen 2.
Treatment remained unchanged and uninterrupted in each
treatment course. If there was an addition or discontinuation of
one or more drugs, the treatment course was considered terminated and a new treatment regimen started. As a result, each
subject could have one or more treatment courses. If treatment was
interrupted more than a week, this was considered the end of a
treatment course. Patients were only analyzed if they had evidence
of lupus pernio after May 12, 2000 confirmed at our institution. If
such a patient had complete resolution of skin lesions, a new
treatment course would be analyzed if there was a de-escalation of
therapy in terms of the number of drugs and/or drug dosages. All
patients who received a course of infliximab had previously failed at
least one previous course of therapy for lupus pernio.
CHEST / 135 / 2 / FEBRUARY, 2009
469
Assessment of Response
The assessment of response to therapy was determined by the
change in the percentage of facial surface that was involved with
lupus pernio lesions. These were again determined by chart
review and by photographs of the lupus pernio lesions. The
response to therapy was also judged globally before and after a
treatment course by the same investigator and was classified into one
of the following five categories: (1) resolution: complete response
with disappearance of lesions; (2) near resolution: minimal active
lesions, plus possible hyperpigmentation/hypopigmentation or fibrosis; (3) improvement: partial response to treatment; (4) no change:
stable lesions; and (5) worse: extension of lesions.
Statistical Methods
Differences in means were tested using two-sample t tests; ␹2
tests were used to evaluate differences in proportions. When
expected cell counts were small, Fisher exact tests were used to
compare differences in proportions. Statistical tests were performed at two-sided ␣ levels of 0.05; thus, p values ⬍ 0.05 signified
statistical significance. All statistical analyses were performed using
statistical software (SAS Version 9.1; SAS Institute; Cary, NC).
Results
Ninety-two patients with lupus pernio were identified from the sarcoidosis database. Nine patients
had concomitant severe extracutaneous sarcoidosis
(cardiac sarcoidosis, neurosarcoidosis, and severe
pulmonary sarcoidosis) that was the primary reason
for therapy and so were excluded from this analysis.
Eleven patients had only a single visit and, therefore,
the effect of therapy could not be assessed. Two
patients had a history of lupus pernio but no active
lesions and were not treated. No data were found for
16 additional patients. This resulted in 54 patients
with lupus pernio who were included in our investigation. Demographic and clinical characteristics of
these patients are shown in Table 1. Most were
middle-aged, African-American women. The initial
evaluation of the lesions showed that the total face
surface involved with lupus pernio was ⬍ 25% in most
(83%) of the cases, and that the most frequent location
was the nose followed by the cheeks (Table 2).
Overall, the 54 patients with lupus pernio were
treated with 118 courses of therapy. Two of the 118
treatment courses could not be analyzed because no
posttherapy evaluation was identified. This left 116
treatment courses that were evaluated in this analysis. The types of treatment, number of treatment
courses, and duration of treatment courses are shown
in Tables 3, 4. The majority (87%) of the patients had
three or fewer treatment courses. The 13 courses of
infliximab-containing were administered to nine patients. In all cases in which a patient received two or
more infliximab-containing treatment courses, this was
not because of treatment failure but because a noninfliximab medication was discontinued that constituted
another treatment course by definition.
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Table 1—Demographic and Clinical Characteristics of
Patients (n ⴝ 54)*
Characteristics
Data
Age, yr
Sex
Male
Female
Race
White
African American
Initial chest radiograph stage (n ⫽ 47)
0
I
II
III
IV
Clinical characteristics
Extracutaneous involvement
Skin sarcoidosis other than lupus
pernio, erythema nodosum
Sarcoidosis of the upper respiratory
tract
Pulmonary function tests (n ⫽ 45)
FVC, % predicted
FEV1, % predicted
Time since lupus pernio diagnosis
before starting treatment
(n ⫽ 29), yr
44.6 ⫾ 9.2
5 (9)
49 (91)
9 (17)
45 (83)
12 (26)
20 (43)
7 (15)
5 (11)
3 (6)
47 (87)
24 (44)
15 (28)
89 ⫾ 22
85 ⫾ 21
3.7 ⫾ 5.1
*Data are presented as mean ⫾ SD or No. (%).
The final treatment outcome of the patients and
the outcome of each treatment course are summarized in Table 5. Complete resolution and near
resolution of lesions were recorded in 18 of 54
patients (33%) and 4 of 54 patients (7%), respectively. Conversely, in 15 of 54 patients (28%), the
lesions remained unchanged or deteriorated. There
was no difference (p ⫽ 0.96) in the percentage of
Table 2—Characteristics of Lupus Pernio at Baseline*
Patients
Characteristics
FA%
⬍ 10
10–25
25–50
⬎ 50
Total
Location
Nose
Cheeks
Eyes
Forehead
Lips
Chin
Ears
No.
%
37
8
7
2
54
68.5
14.8
13
3.7
100
39
24
16
11
8
4
3
72
44.5
29.6
20
15
7.4
5.6
*FA% ⫽ percentage of total facial surface involved.
Original Research
Table 3—Treatment Courses
Courses Per Patient, No.
Patients, No. (%)
1
2
3
4
5
6
Total
22 (41)
12 (22)
13 (24)
5 (9)
1 (2)
1 (2)
54 (100)
patients with resolution or near-resolution following
treatment who initially had ⬍ 10% of the face involved with lupus pernio (40%) compared to those
who had ⱖ 10% of the face involved (41%).
The qualitative outcome of treatment based on
the drug regimen is demonstrated in Figure 2.
Systemic corticosteroids resulted in at least some
improvement in 71% of patients, with 19% achieving resolution or near resolution. Treatment with
other therapies that did not include either systemic
corticosteroids or infliximab resulted in at least some
improvement in only 24% of patients, with only 14%
achieving resolution or near resolution. The combination of systemic corticosteroids plus another drug besides infliximab increased the likelihood of complete
resolution but did not change the overall likelihood of
some improvement. Treatment with infliximab resulted in resolution or near resolution in 77% of the
treatment courses. This was a statistically significant
difference in resolution or near resolution with infliximab courses compared to all other treatments (Fig 3).
The change in the percentage of total face surface
involved (quantitative assessment) before and after
the treatment courses is shown in Figure 4. No
significant change was recorded after noncorticosteroid, noninfliximab agent/s courses. Some improvement was evident after systemic corticosteroids alone
and corticosteroids plus additional noninfliximab
Table 5—Final Treatment Outcome for Each Patient
and Outcome for Each Course
Patients
Courses
Outcome
No.
%
No.
%
Resolution
Near resolution
Improvement
No change
Worse
Total
18
4
17
12
3
54
33
7
32
22
6
100
22
11
34
29
20
116
19
9
29
25
17
100
agent/s courses. Significant change was observed
after infliximab courses, in which the resultant total
face surface involved with lupus pernio was ⬍ 10%
in all cases. In terms of the treatment response based
on the locations of the lesions, there was resolution
or near resolution of 46% (18 of 39 nose lesions),
38% (6 of 16 eye lesions), and 21% (5 of 24 cheek
lesions). A treatment course that resulted in improvement or resolution/near resolution did so
within 5 months 75% of the time (data not shown).
Table 6 shows the outcome of treatment if a drug
was contained in the regimen. Table 6 should be
viewed with caution because 53% (62 of 116 treatment courses) contained two or more drugs. In
particular, only 19% (8 of 42 hydroxychloroquine
treatment courses) and 14% (3 of 21 methotrexate
courses) did not contain additional drugs.
The mean daily dose of prednisone with systemic
corticosteroids alone courses with a positive outcome
(improvement, near resolution, or resolution) was
16.4 mg/d; whereas with systemic corticosteroids plus
noncorticosteroid, noninfliximab agent/s courses with a
positive outcome, the mean daily dose was 12.7 mg/d
(p ⫽ 0.053). If median daily prednisone doses of the
above courses were used (18.5 mg/d and 12.7 mg/d,
respectively), there was a statistically significant difference (p ⫽ 0.044). When examining the use of systemic
Table 4 —Types of Treatment*
Duration, d
Treatment Category
Courses, No. (%)
Mean ⫾ SE
Median
Minimum
Maximum
Agent/s
Corticosteroids alone
Corticosteroids plus agent/s
Infliximab containing†
Total
19 (16)
35 (30)
49 (42)
13 (11)
116 (100)
292 ⫾ 50
415 ⫾ 74
385 ⫾ 44
579 ⫾ 176
231
257
290
353
82
18
33
61
815
1,659
1,403
2,262
*Agents included the following: noninfliximab, noncorticosteroid medications: hydroxychloroquine, 42 of 116 courses (36%); methotrexate, 21 of
116 courses (18%); topical corticosteroid creams, 10 of 116 courses (8%); minocycline, 8 of 116 courses (7%); corticosteroid injections, 4 of 116
courses (3%); azathioprine, 2 of 116 courses (2%); topical tacrolimus, 2 of 116 courses (2%); thalidomide, 1 of 116 courses (1%); pentoxifylline,
1 of 116 courses (1%); and retinoic acid, 1 of 116 courses (1%). More than one noninfliximab, noncorticosteroid agent could be used in a
noncorticosteroid treatment course.
†Includes seven additional treatments of infliximab plus corticosteroids.
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CHEST / 135 / 2 / FEBRUARY, 2009
471
60
% Courses
50
40
30
20
10
0
Resolution
Near
Improvement No Change
Resolution
Worse
Outcome
AG
CSS
CSS+AG
IFX
CSS: systemic corticosteroids; IFX: infliximab; AG: non-corticosteriod, non-infliximab
agent(s); CSS+AG: systemic corticosteroids plus non-corticosteriod, non-infliximab
agent(s)
Figure 2. Outcome of treatment courses of lupus pernio based on the drug regimen.
corticosteroids alone and systemic corticosteroids plus
noncorticosteroid, noninfliximab agent/s treatment
with a good outcome (improvement, near resolution, or
resolution), a mean daily dose of corticosteroids ⬍ 10
mg/d was found 12% and 42% of the time, respectively
(p ⫽ 0.0153). For the treatment courses with systemic
corticosteroids alone or systemic corticosteroids plus
noncorticosteroid, noninfliximab agent/s that had a
100
% Courses
80
60
40
20
0
AG
CSS
CSS+AG
IFX
Treatment Regimen
□ Resolution or Near Resolution
■ Improvement, No Change, or Worse
CSS: systemic corticosteroids; IFX: infliximab; AG: non-corticosteriod, non-infliximab
agent(s); CSS+AG: systemic corticosteroids plus non-corticosteriod, non-infliximab
agent(s)
Resolution or near resolution (black bars) versus improvement, no change, or worse
(white bars) for the various treatment regimens. Comparison of drug regimens in terms
of resolution or near resolution versus improvement, no change, or worse: IFX vs CSS:
p=0.0005; IFX vs CSS+AG: p=0.0015; IFX vs AG: p=0.0002; CSS vs CSS+AG:
p=0.371; CSS vs AG: p=0.468; AG vs CSS+AG: p=0.201
Figure 3. Comparison of treatment regimens: resolution or near resolution vs improvement, no
change, or worse.
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Original Research
AG
% AG courses
(N=19)
100%
CSS alone
% CS S courses
(N=35)
100%
>50
80%
>50
80%
25-50
25-50
60%
60%
10-25
10-25
40%
40%
<10
20%
0
<10
20%
0
0%
0%
BEFORE
BEFORE
AFTER
CSS + AG
%CS S +AG courses
(N=49)
AFTER
IFX
% IFX courses
(N=13)
100%
100%
>50
>50
80%
80%
25-50
25-50
60%
60%
10-25
10-25
40%
40%
<10
20%
0
<10
20%
0
0%
0%
BEFORE
AFTER
BEFORE
AFTER
Legend: Bar graph representing the change in percentage of each category of Face
Surface involved (FA%) before and after each of the four different treatment courses.
CSS: systemic corticosteroids; IFX: infliximab; AG: non-corticosteriod, non-infliximab
agent(s); CSS+AG: systemic corticosteroids plus non-corticosteriod, non-infliximab
agent(s). Note that on rare occasions (in the AG and IFX group) a treatment course
began when there was complete resolution of lupus pernio.
Figure 4. Change in face surface involved with lupus pernio before and after treatment courses.
negative outcome (no change or worse), there was no
statistically significant difference in the mean or median daily corticosteroid dose (p ⫽ 0.98).
Figure 5 examines a secondary analysis of resolution,
near resolution, or improvement vs no change or worse.
By this analysis, infliximab-containing regimens were statistically superior to corticosteroid plus noninfliximabcontaining regimens and to noninfliximab, noncorticosteroid-containing regimens. There was not a statistically
significant difference between infliximab-containing regiwww.chestjournal.org
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mens and regimens of systemic corticosteroids alone. In
addition, noncorticosteroid, noninfliximab-containing regimens were inferior to all other regimens.
Discussion
Our study is clearly the largest to examine the
treatment of lupus pernio with 116 separate treatment courses analyzed in 54 individual patients. The
CHEST / 135 / 2 / FEBRUARY, 2009
473
Table 6 —Outcome by Agent Contained in the Treatment Courses*
Outcome
Resolution
Near
Resolution
Improved
No
Change
Worse
Corticosteroids
Infliximab
Methotrexate
Hydroxychloroquine
Others
16
6
1
13
0
10
4
2
4
1
31
2
8
5
5
21
1
8
12
10
13
0
2
8
7
*Fifty-three percent (62 of 116 treatment courses) contained two or more drugs.
largest previous series13 of treatment of lupus pernio
that we identified reported 30 patients. However,
those authors13 mentioned that only 1 of their 30
patients had lupus pernio, although we believe that
most of them had lupus pernio by virtue of their
description of the skin lesions. In addition, the authors13 did not provide their methodology for
assessment of patient response, and the effect of
each specific drug therapy was not reported. Previous reports of the treatment of lupus pernio have
consisted of small cases series or case reports using the
following agents: corticosteroids,21 methotrexate,21,22 aza-
thioprine,23 chloroquine,24 hydroxychloroquine,25 thalidomide,17 infliximab,26 fumaric acid esters,27 minocycline,28
doxycycline,28 mycophenolate mofetil,29 allopuranol,30
transilast,31 and topical tacrolimus.32
Our results suggest that infliximab is an effective
agent for the treatment of lupus pernio, with ⬎ 75%
of all treatment regimens containing infliximab resulting in resolution or near resolution of lupus
pernio lesions. Treatment regimens that included
infliximab were statistically superior to all other
treatment regimens evaluated. It is notable that all of
the patients who received treatment including inflix-
100
% Courses
80
60
40
20
0
AG
CSS
CSS+AG
IFX
Treatment Regimen
□ Resolution, Near Resolution, or Improvement
■ No Change or Worse
CSS: systemic corticosteroids; IFX: infliximab; AG: non-corticosteriod, non-infliximab
agent(s); CSS+AG: systemic corticosteroids plus non-corticosteriod, non-infliximab
agent(s)
Resolution, near resolution, or improvement (black bars) versus no change or worse
(white bars) for the various treatment regimens. Comparison of drug regimens in terms
of resolution, near resolution, improvement, no change, or worse.
IFX was statistically superior to the other treatment regimens:
IFX vs AG: p < 0.0001; IFX vs CSS: p = 0.2456; CSS vs AG: p = 0.0004; IFX vs CSS+
AG: p = 0.0098; CSS+AG vs AG: p = 0.0171. All other regimen comparisons were not
statistically different.
Figure 5. Comparison of treatment courses: resolution, near resolution, or improvement vs no change,
or worse.
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Original Research
imab had already failed treatment with an alternate
treatment regimen, suggesting a therapeutic response in patients whose lupus pernio was relatively
recalcitrant to treatment.
Our results suggest that systemic corticosteroids
are effective in improving, but rarely resolving, lupus
pernio skin lesions. More than 70% of our patients at
least had improvement of their lupus pernio; however, ⬍ 25% had resolution or near resolution.
The use of alternate treatment regimens (ie, those
without systemic corticosteroids or infliximab) were
the least successful at improving lupus pernio lesions. It may be that the addition of these agents
(hydroxychloroquine or methotrexate were used
most in this series) to a systemic corticosteroids
regimen may allow a reduction in the overall corticosteroid dose without losing the overall treatment
benefit. Those patients on such a combination regimen had a lower median daily prednisone dose (12.7
mg/d) compared to those receiving corticosteroids
alone (18.5 mg/d). However, this was not a prospective study to test such a question.
We also observed that improvement occurred
within 5 months in 75% of the treatment regimens.
Our study did not have enough patients to determine
if there was a difference in the response rate between the different treatment regimens.
This study had several limitations. First, it was
retrospective and, therefore, subject to potential
selection biases. Our institution is a sarcoidosis referral clinic; therefore, our lupus pernio population
may reflect a more severe form of the disease.
However, we believe that this observation does not
detract from the significant findings. Also, 54 of the
92 original subjects identified from the database
were analyzed. Although we cannot exclude a potential difference between those who were excluded and
those who were analyzed, we cannot surmise a
plausible difference between these groups (reasons
for exclusion are outlined at the beginning of the
“Results” section).
Second, our method of quantitative and qualitative
assessment of lupus pernio has not been validated.
Frontal and left and right lateral photographs were
available from each clinic visit and were used to
make these assessments. The quantitative method
was based on the percentage of the face that was
involved with lupus pernio. A Sarcoidosis Activity
and Severity Index (SASI) has been reported for
quantitative assessment of lupus pernio skin lesions.33 However, this instrument was not available
when most of our patients were evaluated. We
cannot use the SASI retrospectively because it involves determination of the induration and desquamation of the skin lesions, which is problematic to
determine from photographs. Nevertheless, we did
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incorporate the percentage of face involvement with
lupus pernio using similar but not identical percentages as used with the SASI. Our qualitative assessment was not blinded as to which photograph represented the beginning and termination of a
treatment course. However, we were blinded to the
treatment regimen used, so we feel that this should
have a minimal impact on our results. We chose to
compare resolution or near resolution with all other
qualitative outcomes because we believed that these
two outcomes would be most important to the
patients (vide infra, health-related quality of life
issues).
Third, although we included numerous medications in our treatment of patients, we did not evaluate all drugs that have been reported to be useful for
lupus pernio. Also, many of these we used rarely, so
it is possible that we failed to identify an effective
treatment regimen. In addition, some medications
used for sarcoidosis such as methotrexate may take
several months to show efficacy.21 We might not
have allowed ample time to examine the final outcome of noncorticosteroid, noninfliximab regimens.
However, the median time of 231 days for noncorticosteroid, noninfliximab containing regimens
seems long enough to have observed a treatment
effect. Although infliximab treatment course durations were longer than for other regimens, this is
unlikely to explain their efficacy as most positive
responses were observed within 5 months. It is more
likely that the infliximab treatment durations were
longer because they were effective and did not
require change.
Fourth, the effectiveness of therapy might have
been related to the severity of disease at the initiation of a treatment course. However, we think that
this is unlikely. To support this contention, ⬎ 80% of
our patients had either 10 to 25% of their face or
⬍ 10% of their face involved with lupus pernio at the
onset of a treatment course (Table 2). When the
outcome of these two groups was compared in terms
of resolution or near resolution, we found no differences. This suggests that the baseline degree of facial
involvement has a minimal impact on outcome of
therapy.
Fifth, although these data suggest a superior benefit of certain agents for the treatment of lupus
pernio, because combination therapy was used in
more than half of the patients a definitive treatment
algorithm cannot be established from these data.
Indeed, as demonstrated in Table 6, regimens containing methotrexate and hydroxychloroquine did
result in resolution or near resolution in some instances, although they were usually combined with
CHEST / 135 / 2 / FEBRUARY, 2009
475
other agents on these occasions. Regimens that did
not contain infliximab or corticosteroids were rarely
effective (Fig 2).
Finally, our analysis did not account for the healthrelated quality of life of our patients. Lupus pernio is
not a life-threatening condition, but it often has a
major impact on the psychosocial status of the
patient. These disfiguring lesions affect patients in
their personal and professional interactions. It is
therefore important to measure how patients perceive their therapy and not solely rely on physician
assessment of the percentage of the face involved or
degree of resolution. We believe that all future
studies of lupus pernio should contain this component of assessment. In summary, our retrospective
review of a large series of lupus pernio patients who
were assessed carefully with photographs suggests
the following: (1) infliximab is very useful; (2) corticosteroids are effective although rarely result in
resolution; (3) adding noninfliximab agents to corticosteroids is often corticosteroid sparing: and (4)
treatment with noninfliximab, noncorticosteroid regimens is rarely beneficial.
ACKNOWLEDGMENT: The authors thank Dr. Sooyeon Kwon
for assistance with data analysis.
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Original Research