We conducted a retrospective study with LET patients diagnosed in the Department of Dermatology of a Spanish tertiary referral center from January 2007 to May 2019. Clinical–epidemiological features, comorbidities, histological, DIF findings and response to treatment were recorded. Diagnosis of LET was based on clinical characteristics such as the presence of non-scarring erythematous, succulent and edematous papules and plaques located predominantly on sun-exposed areas along with histological features such as dermal edema, perivascular and periadnexal lymphocytic infiltration, and interstitial mucin deposition.

Diagnosis of SLE was based on the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria. All patients were monitored for, at least, 6 months. Response to treatment was defined as early clinical response (ECR) or late clinical response (LCR) when it was achieved within 3 months or after 3 months, respectively.

Autoantibodies tests were performed using a standard indirect immunofluorescence technique. Anti-double-stranded DNA (anti-dsDNA), anti-La and anti-Ro were determined by standardized enzyme-linked immunosorbent assays.

Dermoepidermal junction changes, type and pattern of inflammatory infiltrate, presence of interstitial mucin deposition and reactivity of CD123 immunohistochemical staining were evaluated by an expert dermatopathologist (AGH). Colloidal iron and/or Alcian blue were used to detect the presence of mucin. Positivity for CD123 was defined as the presence of clusters of CD123+ plasmacytoid dendritic cells (PDCs) arranged in aggregates of ≥15 CD123+ PDCs.

Four-micrometer thick cryostat sections from cutaneous biopsies obtained from lesional skin were stained with polyclonal fluorescein isothiocyanate-conjugated antibodies against human IgA, IgG, IgM, and C3, as per routine clinical testing.

Clinical–histological characteristics and outcomes were expressed as frequencies. The use of systemic therapy with corticosteroids or immunosuppressants and treatment response were analyzed using the Kruskal–Wallis One-Way Analysis of Variance (ANOVA) test. p<0.05 was considered statistically significant. Analyses were performed with SPSS Statistics version 18.0 (SPSS Inc., Chicago, IL, USA).

A total of 34 patients were included (52.9% [18/34] women). The median age was 53.5 years (range, 31–78). The median clinical follow-up was 47 months (range, 6–240). All patients presented with typical lesions of LET (erythematous edematous plaques or papules with no scarring). Lesions were located on the back [(82.4%) (28/34)] and face [(58.8%) (20/34)] in most patients. The median diagnostic delay was 6 months (range, 1–312).

Comorbidities (Table 1): autoimmune or rheumatologic disorders were found in 52.9% (18/34) of the patients, Sjögren's syndrome was the most frequently detected [17.4% (6/34) of cases). Other variants of CLE were observed in 26.5% (9/34) of patients. Of these, 66.7% (6/9) of cases were diagnosed with subacute CLE (SCLE), 44.4% (4/9) with discoid lupus erythematosus (DLE) and 22.2% (2/9) with chilblain lupus. Association with SLE—according to the 2019 EULAR/ACR classification criteria—was observed in 8.82% (3/34) of individuals: 2 had concomitant joint and kidney involvement and 1, lung and joint involvement. At least 1 positive autoantibody was detected in 64.7% (22/34) of patients: positive antinuclear antibodies (ANA) (titers>1/80) in 90.9% (20/22) of these cases, anti-DNA antibodies in 22.7% (5/22), anti-Ro, 40.9% (9/22) and anti-RNP in 9.1% (2/22) (Table 1).

Perivascular inflammatory lymphocytic infiltrate and the presence of interstitial mucin was evidenced in 100% (34/34) of the samples (Table 2). Mild involvement of the dermoepidermal junction with focal vacuolization of the basal layer was observed in 14.7% (5/34) of cases. Immunohistochemical study with CD123 was conducted in 29 specimens, showing positivity in 75.9% (22/29). DIF was performed in 64.7% (22/34) of cases turning out positive in 31.8% (7/22). The most common patterns observed were homogeneous deposit of IgG and granular deposit of C3 at the basement membrane (5/7).

Although all patients achieved a complete clinical response (CCR), multiple therapeutic agents were required. ECR was observed in 79.4% (27/34) of the patients, and LCR in 26.5% (9/34) of cases. All patients with SLE (3/3) and 80% (4/5) of the individuals with anti-DNA antibodies presented LCR.

All individuals received topical treatment (corticosteroids and/or calcineurin inhibitors). CCR was achieved exclusively with topical treatment in 23.5% (8/34). All of them showed ECR. Antimalarials were prescribed in 73.5% of cases (25/34), oral corticosteroids in 23.5% (8/34), and immunosuppressants in 14.7% (5/34) [mycophenolate (1/5), methotrexate (1/5), azathioprine+methotrexate (1/5) and mycophenolate+methotrexate (2/5)].

Regarding patients who received antimalarials, 45.7% (16/25) received them exclusively. Partial response (PR) was observed in 81.3% (13/16) and CCR in 18.7% (3/16); 20% (5/25) received antimalarial and oral corticosteroids, with PR in 40% (2/5) and CCR in 60% (3/5). Two patients received antimalarials and immunosuppressants (methotrexate or mycophenolate) and achieved CCR; another 2 patients, antimalarials, oral corticosteroids and immunosuppressants (methotrexate or mycophenolate), with PR in 1 patient and CCR in the other. Only 1 case was treated exclusively with oral corticosteroids and immunosuppressants (azathioprine and methotrexate since the patient had rheumatoid arthritis) and showed PR.

PR was significantly associated with age<50 years (p=0.034). LCR was significantly associated with the presence of SLE (p=0.002) and anti-DNA antibodies (p=0.003). Therapeutic response was not associated with sex, habitual smoking, age of LET presentation, concomitance with other types of CLE or autoimmune diseases, or presence of antinuclear antibodies, anti-Ro or anti-RNP, or positivity of CD123 or immunofluorescence.