Lupus erythematosus (LE) is a chronic, relapsing autoimmune inflammatory disease. It has a wide clinical spectrum and the clinical course can vary considerably, ranging from serious systemic disease to chronic, indolent forms.1,2 The organs most frequently affected by LE are the skin, joints, and kidneys. Cutaneous lesions are often the first sign of the disease. The cutaneous manifestations of LE are classified as specific or nonspecific according to their clinical and histologic features.3 LE-specific lesions—that is, cutaneous lupus erythematosus (CLE)—are classified as acute (associated with systemic lupus erythematosus [SLE]), subacute, or chronic. Chronic discoid LE is the most common cutaneous form of LE.

Nearly all epidemiologic studies of patients with LE have involved patients with SLE. Few authors have investigated the characteristics of patients with CLE.

In this study, we describe the epidemiologic, clinical, and immunologic characteristics of a series of patients diagnosed with CLE who were treated in a specialized unit of a tertiary hospital and analyze the variation in these variables as a function of CLE subtype. We also consider the number of patients who had more than 1 distinct subtype of CLE and whether or not the presence of multiple CLE subtypes in a single patient is relevant to prognosis or therapeutic management.

We analyzed the patient data of all adults diagnosed with CLE who were seen for this disease between 1 January 2007 and 31 December 2011 in the specialized connective tissue disease unit of the dermatology department of Hospital General Universitario Gregorio Marañón, a hospital serving a catchment population of approximately 600 000 people in the Autonomous Community of Madrid. The diagnosis of CLE was histologically confirmed in all cases. Patients were classified according to clinical and histologic characteristics into 3 CLE subtypes: acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), or chronic discoid LE (CDLE).

Patients who had cutaneous manifestations associated with more than 1 CLE subtype were considered to have the subtype that appeared first or, if more than 1 subtype had appeared simultaneously, the subtype with the greatest extent and duration.

The study protocol excluded patients who met the criteria for SLE but did not have LE-specific cutaneous manifestations, patients who had one of the less common forms of CLE (LE tumidus [n=6], LE panniculitis [n=2], chilblain LE [n=2], bullous LE [n=1]), and patients who had clinical findings consistent with CLE but whose diagnosis was not confirmed on follow-up.

The following variables were included in the descriptive analysis: age at diagnosis, sex, site of lesions, the presence of antinuclear antibody (ANA) titers greater than 1:160, and the presence of LE-specific antibodies (anti-double-stranded-DNA antibody [anti-dsDNA], anti-Smith antibody [anti-Sm], anti-ribonucleoprotein antibody [anti-RNP], anti-Ro antibody, and anti-La antibody). Complement levels (C3, C4) were not included in the analysis because these tests were only requested for patients in whom SLE was suspected.

We also noted the systemic treatments received by the patients. The antimalarial agent initially prescribed was hydroxychloroquine in all cases. Chloroquine was prescribed for patients who did not show significant improvement after 4 months of treatment with hydroxychloroquine. When the patient did not improve after treatment with antimalarial agents, immunosuppressants (corticosteroids, methotrexate, azathioprine) or thalidomide were prescribed; the need for these treatments was only recorded for patients who received them for more than 3 consecutive weeks. The adverse effects associated with treatment with antimalarial agents (hydroxychloroquine, chloroquine) and thalidomide were also noted.

The statistical analysis was a retrospective, descriptive study. Univariate analysis of qualitative variables was performed using the Pearson χ2 test and the Fisher exact test. Qualitative and quantitative variables were analyzed using the t test. When necessary, the homogeneity of variance test and the Bonferroni test were applied. A P value of<.05 was considered statistically significant. The descriptive study and the analytic study of the variables were performed using the SPSS statistical package version 15 (SPSS, Chicago, Illinois, USA).

A total of 101 patients with a biopsy-confirmed diagnosis of CLE were included in the study. Table 1 shows the main epidemiologic, clinical, and immunologic characteristics of the patients. Patients with ACLE had a younger mean age at diagnosis than patients with any other subtype of CLE and were more likely to be positive for ANAs, anti-dsDNA, anti-Sm, and anti-RNP. All patients presented the characteristic facial rash. In 41 patients with CDLE (41%), the lesions were located only on the head and neck. Only 33% of patients with CDLE were positive for ANAs (titers ≥ 1:160).

Although women accounted for a majority of patients in all CLE subtypes, the highest percentage of female patients (94%) was in the SCLE group. Some 97% of patients in the SCLE group had lesions on the trunk, in most cases of the annular polycyclic type. The antibodies associated with photosensitivity (anti-Ro and anti-La) predominated in this group.

Fig. 1 shows the distribution of the patients by CLE subtype. A total of 17 patients had more than 1 subtype of CLE; the most common combination was CDLE and SCLE (8), followed by ACLE and CDLE (7) and ACLE and SCLE (2). Treatment with immunosuppressants was prescribed to 15 of the 17 patients with more than 1 CLE subtype (88%), compared with 44 of the 84 patients with just 1 CLE subtype (52%) (P=.006). Moreover, patients with more than 1 form of CLE were significantly more likely to be positive for antibodies associated with SLE, such as anti-dsDNA, anti-Sm, and anti-RNP (P=.034).

Figure 1.

Distribution of patients by subtype of cutaneous lupus erythematosus.

Abbreviations: ACLE, acute cutaneous lupus erythematosus; CDLE, chronic discoid lupus erythematosus; SCLE, subacute cutaneous lupus erythematosus.

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A total of 96 patients (96%) received systemic treatment with synthetic antimalarial agents (hydroxychloroquine or chloroquine). The main adverse effects associated with these drugs were reversible visual disturbances (6 patients), intolerance and/or gastritis (6 patients), tremors (2 patients), noncicatricial diffuse alopecia (3 patients), and pigmentation of the nail plate (1 patient). Thalidomide was prescribed to 13 patients, 4 of whom (31%) developed a peripheral neuropathy that necessitated discontinuation of the treatment. A total of 56 patients received treatment with immunosuppressants.

Most epidemiologic studies of patients with LE have focused on patients with SLE, and very few studies have been carried out on the various subtypes of CLE.4–8 While systemic involvement tends to be mild in most patients with CLE, the disease has a major impact on quality of life because the lesions are usually located on the face and the chronic forms can cause irreversible scarring. Moreover, up to 28% of patients with CDLE are susceptible to developing SLE.9

There is no consensus in the literature regarding the definition of CLE. The term is used interchangeably to refer to the independent primary cutaneous disease or to describe a series of specific manifestations that occur in patients with SLE. Sontheimer6 was the first author to propose the classification of skin lesions as either LE-specific or LE-nonspecific. Additionally, in 1979 he proposed the term subacute CLE to refer to a CLE subtype, distinct from the chronic cicatricial forms of the disease, characterized by annular or psoriasiform lesions in sun-exposed areas, the absence of systemic symptoms, and the presence of circulating anti-Ro antibodies.5,6 This subacute form of the disease appeared to occur more frequently in young women, with peak incidence rates in the fourth decade of life.7 Since SCLE was first described, only 1 new CLE subtype—LE tumidus—has been proposed10; however, this entity is still being defined and has not been unanimously accepted in the international literature.11

Very few epidemiologic studies on CLE have been carried out in Spain. Table 2 compares the most important epidemiologic characteristics of our patients with those reported in similar studies.12–14 However, there are important differences between our patients and those included in other studies. Our study does not include less common forms of CLE such as LE tumidus and LE panniculitis. Biazar et al.14 included patients from 13 European countries, and this could account for some of the differences between the results of their study and ours. Although Vera-Recabarren et al.12,13 studied Spanish patients, their analysis compared the clinical and immunologic characteristics of patients with CDLE with those of patients with SCLE12 but did not consider patients with ACLE. Despite these differences, our results are very similar to those of the other studies, especially with regard to epidemiologic characteristics. However, some significant differences did emerge, including the fact that our patients were diagnosed at a younger age and were more likely to be positive for anti-dsDNA than the patients studied by Biazar et al.14

In our study, 25 patients (17 with ACLE and 8 with SCLE) met at least 4 of the criteria for SLE established by the American Rheumatism Association (ARA). However, like other authors, we believe that these criteria should not be applied to patients with CLE because they are perhaps too sensitive but not very specific.15 Consequently, we believe that SLE is frequently diagnosed in patients who will never develop systemic manifestations associated with LE. Moreover, in such cases, any nonspecific symptoms reported by the patient—such as joint pain, headache, and fatigue—tend to be erroneously attributed to LE.

With this problem in mind, the European Academy of Dermatology (EADV) compared the 11 ARA criteria with a series of 13 additional criteria in a group of 140 patients who had LE with or without systemic involvement.16 The 13 additional criteria included the presence of histologic features such as the lupus band, complement and immunoglobulin G levels, and the presence of annular or papulosquamous lesions characteristic of SCLE. These additional criteria were later analyzed by other authors, who found them to be more specific but less sensitive.15,17 Since then, however, these criteria have not been used and they seem to have been forgotten by the international scientific community.

In conclusion, patients with different subtypes of CLE have distinct clinical and immunologic characteristics. In the absence of consensus on a definition that makes it possible to differentiate cutaneous forms of LE from SLE, the dermatologist's role in the correct diagnosis and classification of such patients is fundamental. Moreover, some patients with CLE present skin lesions that belong to different CLE subtypes. Systemic immunosuppressants are usually required to properly manage the disease in these patients.

The authors declare that they have no conflicts of interest.