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Frequency and Severity of Systemic Disease in Patients With Subacute Cutaneous Lupus Erythematosus
Dana R. Black, MD;
Carlton A. Hornung, PhD, MPH;
Paul D. Schneider, MD;
Jeffrey P. Callen, MD
Arch Dermatol. 2002;138:1175-1178.
ABSTRACT
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Objective To compare the frequency and severity of systemic disease in patients
with subacute cutaneous lupus erythematosus (SCLE) followed up in a dermatology
practice vs patients with systemic lupus erythematosus (SLE) followed up in
a rheumatology practice.
Design Case-control comparison of patients matched for age, sex, and ethnicity.
Setting University-affiliated dermatology and rheumatology practices.
Patients Seventy-six patients with SCLE were compared with 24 patients with SLE.
Intervention All medical records were reviewed and the patients were interviewed.
Main Outcome Measures Systemic and serologic findings were compared between patients with
SCLE and those with SLE.
Results Hematologic disorders were present in 6 patients (8%) with SCLE and
in 13 patients (54%) with SLE (P<.001). Serositis
was present in 1 patient (1%) with SCLE and in 3 patients (12%) with SLE (P = .04). Renal involvement was present in 12 patients
(16%) with SCLE and in 6 patients (25%) with SLE (P
= .36). Antinuclear antibodies were found in 52 patients (68%) with SCLE compared
with 23 patients (96%) with SLE (P = .006). Anti-Ro
antibodies were found in 37 patients (49%) with SCLE compared with 10 patients
(42%) with SLE (P = .64). Other serologic abnormalities
(anti–native DNA, anti-Sm antibody, or anti-U1RNP) were present
in 6 patients (8%) with SCLE compared with 15 patients (62%) with SLE (P<.001). Photosensitivity was present in 65 patients
(86%) with SCLE, compared with 11 patients (46%) with SLE (P<.001).
Conclusions This analysis reveals a dissimilar frequency of internal organ involvement
between patients with SCLE and SLE. Renal disease was similar in frequency
and severity, and documented central nervous system involvement was rare in
both groups.
INTRODUCTION
SUBACUTE CUTANEOUS lupus erythematosus (SCLE) is a distinct form of
lupus erythematosus (LE) that is characterized by nonscarring, non–atrophy-producing
skin lesions.1 It is associated with anti-Ro/SS-A
antibodies. Many patients with SCLE fulfill 4 or more of the American College
of Rheumatology (ACR) diagnostic criteria2
for systemic lupus erythematosus (SLE).3-4
Most patients with SCLE are believed to have a chronic or relapsing but benign
process, with few of the serious manifestations of SLE, such as central nervous
system or renal disease.5 However, reports
of severe systemic disease occurring in patients with SCLE suggest that the
full spectrum of LE-associated disease is possible.4, 6
We are aware of only 1 case-control study7
of patients with SCLE and SLE, which revealed similar frequency and severity
of systemic disease in age- and sex-matched patients. The purpose of the present
investigation was to review a larger group of patients with SCLE (follow-up,
2 to >10 years) and to compare them with a cohort of patients (matched for
age, sex, and ethnicity) with SLE and without SCLE skin lesions and followed
up in a rheumatology practice.
PATIENTS AND METHODS
Seventy-six patients with SCLE were included in this study (follow-up,
2 to >10 years), which was conducted by physicians at a university-affiliated
private practice: Associates in Dermatology, PLLC, Louisville, Ky. The diagnosis
of SCLE was based on characteristic clinical features, combined with histopathologic
confirmation of an interface dermatitis, as previously described by Sontheimer
et al3 and Callen and Klein.4
The lesions were characterized as annular, papulosquamous, or tumid, based
on the major type of involvement present. We included tumid LE within this
study because these patients have photosensitive, nonscarring, non–atrophy-producing
lesions. Although some would classify such patients as having chronic cutaneous
LE because of the chronic nature of the disease, many of our patients with
other forms of SCLE also display a chronic or recurrent course. We did not
exclude patients with SCLE who fulfilled the ACR diagnostic criteria for SLE.6
Control subjects were selected from patients with SLE who were followed
up by physicians at Rheumatology Associates, Louisville. Patients with SLE
consenting to participate in our research project were matched by age (±2
years), sex, and ethnicity with at least 1 of our patients with SCLE. Criteria
for inclusion as a control subject were informed consent and nonparticipation
in dermatologic follow-up for SCLE. We did not exclude patients who had lesions
of discoid LE, malar erythema, or photosensitivity. The diagnosis of SLE was
based on fulfillment of 4 or more of the ACR criteria.6
Clinical and laboratory data were obtained from reviews of medical records
from the practices. Medical records were also obtained from each patient's
primary care physician, nephrologist, hematologist, and neurologist, when
applicable. The data collected included age, sex, ethnicity, age at onset
of disease, medications at onset, type of skin disease, activity of disease,
history of photosensitivity (abnormal reaction to light as observed by a physician
or as reported by the patient), joint disease (arthralgias or arthritis),
Sjögren syndrome (documented by a physician), serositis (pleuritis or
pericarditis), results of complete blood count and urinalysis, total hemolytic
complement studies, and serologic testing. We defined a hematologic disorder
as the presence of hemolytic anemia, leukopenia, or thrombocytopenia, and
a renal disorder as hematuria, proteinuria, or renal failure. Each patient
was interviewed to discuss his or her case at length. This study was reviewed
and approved by the Human Studies Committee of the University of Louisville.
Symptom or prevalence rates were compared using  2 and Fisher
exact tests, with  set at .05, 2-sided.
RESULTS
The mean age of the study population was 59.1 years for patients with
SCLE and 54.5 years for patients with SLE. The age at onset of SCLE ranged
from 19 to 85 years, and for SLE, 30 to 78 years. At the onset of disease,
3 patients with SCLE were taking medications that may have caused or exacerbated
their cutaneous disease; however, in all 3 patients the disease continued
after the medications were stopped. There were 58 women with SCLE (56 white
and 2 African American) and 18 men (all white). There were 22 women with SLE
(21 white and 1 African American) and 2 men (both white) (Table 1).
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Table 1. Patient Characteristics*
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The SCLE lesions were classified as annular (Figure 1), papulosquamous (Figure
2), or tumid. Annular disease occurred in 36 patients, papulosquamous
disease in 30, and tumid disease in 3. Six patients had lesions of mixed characteristics.
One patient's lesions were unclassified.
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Figure 1. Annular lesions of subacute cutaneous
lupus erythematosus. Erythematous plaques with a trailing scale and slight
central clearing are present on this patient's arm.
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Figure 2. Papulosquamous lesions of subacute
cutaneous lupus erythematosus. Scaly, erythematous plaques are present on
this patient's leg. These lesions simulated lichen planus.
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Forty-eight of the patients with SCLE fulfilled 4 or more ACR diagnostic
criteria for SLE. However, the frequency of systemic disease in patients with
SCLE varied from that observed in patients with SLE (Figure 3). Hematologic disorders, including leukopenia, hemolytic
anemia, and thrombocytopenia, were present in 13 (54%) of 24 patients with
SLE. Only 6 (8%) of 76 patients with SCLE experienced hematologic disorders
(P<.001).
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Figure 3. Manifestations of systemic disease
in patients with subacute cutaneous lupus erythematosus (SCLE) and systemic
lupus erythematosus (SLE). ANA indicates antinuclear antibody; asterisk, P<.05.
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Photosensitivity was more common in patients with SCLE (65 SCLE [86%]
vs 11 SLE [46%]) (P<.001). Forty-seven patients
(62%) with SCLE experienced arthritis vs 100% of the 24 patients with SLE
(P<.001). Serositis was present in 3 patients
(12%) with SLE vs 1 (1%) with SCLE (P = .04). Renal
disease, including hematuria, proteinuria, casts, and renal failure, occurred
in 12 patients (16%) with SCLE vs 6 patients (25%) with SLE (P = .36). Antinuclear antibody (ANA) was a common finding in both patient
groups (52 [68%] patients with SCLE vs 23 [96%] with SLE) (P = .006). Among the 24 patients with SCLE without ANAs, 17 (71%) were
photosensitive, 11 (46%) had arthritis, and 5 (21%) had anti-Ro/SS-A antibodies.
Serologic abnormalities other than a positive ANA or anti-Ro/SS-A were more
prevalent in patients with SLE (15 [62%] patients with SLE vs 6 [8%] with
SCLE) (P<.001). Anti-Ro/SS-A was pressent in 10
patients (42%) with SLE and in 37 patients (49%) with SCLE (P = .64). Thirty-three (51%) of 65 photosensitive patients were anti-Ro/SS-A–positive,
while 3 (27%) of 11 nonphotosensitive patients were positive for this antibody.
Renal disease was present in 4 (11%) of 37 anti-Ro/SS-A–positive patients.
Among our 3 patients with tumid LE, 2 were ANA-positive, 1 was anti-Ro/SS-A–positive,
and all 3 were photosensitive. Sjögren syndrome was present in 11 (46%)
of 24 patients with SLE vs 33 (43%) of 76 patients with SCLE (including all
3 of the patients with tumid LE).
The clinical and immunologic differences between patients with SCLE
with annular vs papulosquamous lesions are presented in Table 2. Patients with annular SCLE had more frequent photosensitivity,
more often developed arthritis, and were more frequently positive for ANA
and anti-Ro/SS-A).
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Table 2. Clinical and Serologic Differences Between Patients With Subacute
Cutaneous Lupus Erythematosus With Predominantly Annular vs Papulosquamous
Lesions*
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COMMENT
Subacute cutaneous lupus erythematosus is characterized
by nonscarring, non–atrophy-producing skin lesions. These lesions occur
predominantly on the face, upper chest, upper back, and arms in a photosensitive
distribution. An association with the anti-Ro/SS-A antibody has been established,
although the skin abnormalities are requisite for diagnosis. Most of our patients
with SCLE had 4 or more of the ACR diagnostic criteria for SLE.
Cohen and Crosby7 performed the first
case-control study of systemic disease associated with SCLE. Their data suggested
that the patients with SCLE might not be as clinically homogeneous as previously
believed. They demonstrated that the frequency and severity of renal and neurologic
disease in patients with SCLE were comparable to or greater than those found
in patients with SLE who did not have SCLE skin lesions. Despite these findings,
dermatologists generally perceive that patients with SCLE have a better prognosis
than those with SLE, with less frequent and less severe renal and central
nervous system disease.
Chlebus and colleagues8 attempted a comparative
study of patients with SCLE vs SLE. They found dissimilar frequency and severity
of internal organ involvement, with patients with SCLE being less severely
affected. However, their study had 2 biases that are addressed in the present
study. First, their cohorts were not age- and sex-matched; the SCLE group
was 10 years older and contained fewer women. Second, their definition of
the patients with SCLE was not the same as that used by Sontheimer et al1; the presence of photosensitivity was used to define
their patients with SCLE. Although photosensitivity is a common manifestation
of SCLE, its presence is not the defining characteristic.
López-Longo et al6 studied 128
patients with SLE selected from the rheumatology service at their hospital,
17 of whom had SCLE. They found significantly higher incidences of arthritis,
nephritis, central nervous system disease, and pleuritis among the 111 patients
with SLE and a significantly higher incidence of photosensitivity in the patients
with SCLE. Their 2 groups did not differ significantly in age or sex, but
they were not matched for these variables.
The purpose of the present study was to provide a prognostic prediction
for patients with SCLE. Seventy-six patients with SCLE were included in the
study. Controls, selected from patients with SLE who did not have SCLE, were
matched for age, sex, and ethnicity. Extensive reviews of medical records
were performed, including records from primary care providers and consultant
physicians. Patients with SLE had an increased frequency of serositis, hematologic
disorders, and anti–native DNA, anti-Sm, and anti-U, RNP antibodies.
Patients with SCLE had an increased frequency of photosensitivity. These results
show a dissimilar frequency of internal organ involvement and serologic abnormalities
and suggest that patients with SCLE are a distinct subset, with less frequent
systemic manifestations than comparable patients with SLE followed up in a
rheumatology practice. However, our patients were observed in an outpatient
setting rather than a hospital setting. Had we selected patients in a hospital
setting, we predict that more patients would have had renal, central nervous
system, and, possibly, pulmonary disease, as these patients are more often
admitted to the hospital.
AUTHOR INFORMATION
Accepted for publication December 4, 2001.
This study was supported by the University of Louisville School of Medicine
Summer Research Program.
Corresponding author and reprints: Jeffrey P. Callen, MD, 310 E Broadway,
Louisville, KY 40202 (e-mail: jefca{at}aol.com).
From the Divisions of Dermatology (Drs Black and Callen), General Medicine
(Dr Hornung), and Rheumatology (Dr Schneider), Department of Medicine, University
of Louisville School of Medicine, Louisville, Ky.
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