Merle Haust

Cutaneous lupus erythematosus: First multicenter database analysis of 1002 patients from the European Society of Cutaneous Lupus Erythematosus (EUSCLE)

In this prospective, cross-sectional, multicenter study, we assessed clinical and laboratory characteristics from patients with cutaneous lupus erythematosus (CLE) using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). 1002 (768 females, 234 males) patients with different subtypes of CLE, such as acute CLE (ACLE, 304 patients), subacute CLE (SCLE, 236 patients), chronic CLE (CCLE, 397 patients), and intermittent CLE (ICLE, 65 patients), from 13 European countries were collected and statistically analyzed by an SPSS database. The main outcome measures included gender, age at onset of disease, LE-specific and LE-nonspecific skin lesions, photosensitivity, laboratory features, and the criteria of the American College of Rheumatology (ACR) for the classification of systemic lupus erythematosus. The mean age at onset of disease was 43.0±15.7 years and differed significantly between the CLE subtypes. In 347 (34.6%) of the 1002 patients, two or more CLE subtypes were diagnosed during the course of the disease and 453 (45.2%) presented with LE-nonspecific manifestations. Drug-induced CLE and Sjögrens Syndrome had the highest prevalence in SCLE patients (13.1% and 14.0%, respectively). Photosensitivity was significantly more frequent in patients with ACLE, SCLE, and ICLE compared with those with CCLE. The detection of antinuclear antibodies such as anti-Ro/SSA and anti-La/SSB antibodies revealed further significant differences between the CLE subtypes. In summary, the EUSCLE Core Set Questionnaire and its database facilitate the analysis of clinical and laboratory features in a high number of patients with CLE and will contribute to standardized assessment and monitoring of the disease in Europe.

Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI): a modified outcome instrument for cutaneous lupus erythematosus.

Summary Background  In 2005, a scoring system (CLASI, Cutaneous Lupus Erythematosus Disease Area and Severity Index) was developed for patients with cutaneous lupus erythematosus (CLE) to assess disease ‘activity’ and ‘damage’. However, the CLASI does not give an accurate assessment of the severity in all disease subtypes.

Photoprotective effects of a broad-spectrum sunscreen in ultraviolet-induced cutaneous lupus erythematosus: A randomized, vehicle-controlled, double-blind study

OBJECTIVE We sought to assess if the exclusive use of a broad-spectrum sunscreen can prevent skin lesions in patients with different subtypes of cutaneous lupus erythematosus (CLE) induced by ultraviolet (UV) irradiation under standardized conditions. METHODS A total of 25 patients with a medical history of photosensitive CLE were included in this monocentric, randomized, vehicle-controlled, double-blind, intraindividual study. The test product and its vehicle were applied 15 minutes before UVA and UVB irradiation of uninvolved skin areas on the upper aspect of the back in a random order, and standardized phototesting was performed daily for 3 consecutive days. RESULTS Characteristic skin lesions were induced by UVA and UVB irradiation in 16 patients with CLE in the untreated area, and 14 patients showed a positive test result in the vehicle-treated area. In contrast, no eruptions compatible with CLE were observed in the sunscreen-treated area in any of the 25 patients. This resulted in significant differences (P < .001) between UV-irradiated sunscreen-treated versus vehicle-treated areas, and between UV-irradiated sunscreen-treated versus untreated areas. Furthermore, a significant difference (P < .05) was observed concerning the age of disease onset and the patient history of photosensitivity. Patients who were younger than 40 years at onset of CLE reported photosensitivity significantly more often than patients with a higher age of disease onset. None of the patients showed any adverse events from application of the test product or the vehicle. LIMITATIONS Data resulting from standardized experimental phototesting might not be transferable to a clinical setting. CONCLUSION These results indicate clearly that the use of a highly protective broad-spectrum sunscreen can prevent skin lesions in photosensitive patients with different subtypes of CLE.

Lupus erythematosus tumidus is a separate subtype of cutaneous lupus erythematosus

Background  Lupus erythematosus tumidus (LET) is a rare disease which was first described in 1909 but has not always been considered as a separate entity of cutaneous lupus erythematosus (CLE) in the international literature.

Reduction of regulatory T cells in skin lesions but not in peripheral blood of patients with systemic scleroderma

Objective To determine the frequency and suppressive capacity of regulatory T cells (Treg) and their association with clinical parameters in patients with systemic scleroderma (SSc). Methods Peripheral blood from 25 patients with SSc, 15 patients with localised scleroderma (LS) and 29 healthy controls (HC) was studied. Analysis of CD4+ forkhead box P3 (Foxp3)+ and CD4+CD25++Foxp3+ Treg subpopulations was carried out by flow cytometry and cell proliferation was quantified by 3H-thymidine incorporation. Quantitative analysis of Treg was further performed in skin biopsies from 17 patients with SSc and 21 patients with LS using anti-CD4 and anti-Foxp3 monoclonal antibodies for immunohistochemistry. Results The frequency of CD4+Foxp3+ and CD4+CD25++Foxp3+ Treg in peripheral blood from patients with SSc was not significantly different from that of patients with LS or HC. The suppressive capacity of CD4+CD25++ Treg in SSc was also found to be similar to that of HC. Phenotypic and functional data revealed no significant difference between the limited or diffuse form of SSc. Moreover, therapy with bosentan showed no significant effect on the frequency of Treg during the course of the disease. However, the frequency of Treg in skin lesions from patients with SSc or LS, determined as the percentage of CD4+ cells expressing Foxp3 in the inflammatory infiltrate, was significantly reduced compared with other inflammatory skin diseases. Conclusion These results indicate that although the authors found no defect in the frequency or function of peripheral Treg subpopulations, the reduction of CD4+Foxp3+ Treg in the skin of patients with SSc may be important in the pathogenesis of the disease.

Photoprovocation in Cutaneous Lupus Erythematosus: A Multicenter Study Evaluating a Standardized Protocol

Photosensitivity is an important and distinguishing sign in various subtypes of cutaneous lupus erythematosus (CLE); however, it remains poorly defined. The purpose of this study was to evaluate whether standardized photoprovocation is a reproducible method to assess photosensitivity in subjects with CLE. A total of 47 subjects with CLE (subacute cutaneous lupus erythematosus (SCLE), n=14; discoid lupus erythematosus (DLE), n=20; lupus erythematosus tumidus (LET), n=13) and 13 healthy volunteers underwent photoprovocation at seven European sites. Of these, 22 (47%) subjects (57% SCLE, 35% DLE, and 54% LET) and none of the healthy volunteers developed photoprovoked lesions according to clinical analysis. Of these 22 subjects, 19 (86%) developed lesions that were histopathologically confirmed as specific for lupus erythematosus (LE). In CLE subjects who developed UV-induced lesions, 86% had Fitzpatricks phototypes I or II, and the mean minimal erythema dose (MED) was significantly lower compared with subjects without UV-induced lesions (P=0.004). No significant differences in photoprovocation results were observed between study sites. Safety parameters showed no clinically meaningful differences between CLE subjects and healthy volunteers after photoprovocation. In conclusion, a standardized, safe, and reproducible protocol for photoprovocation using UVA and UVB radiation induced skin lesions in approximately half of all CLE subjects and showed comparable results across multiple sites. This method may therefore be used for future diagnostic testing and clinical trials.

Development of a Core Set Questionnaire by the European Society of Cutaneous Lupus Erythematosus (EUSCLE)

A study group of the European Society of Cutaneous Lupus Erythematosus (EUSCLE) developed a Core Set Questionnaire for the evaluation of patients with cutaneous lupus erythematosus (CLE). The aim of the EUSCLE Core Set Questionnaire is to gain a broad and comparable data collection of patients with CLE from different European centers, to achieve consensus concerning evidence-based clinical standards for disease assessment, and to develop diagnostic and therapeutic guidelines. The authors designed the EUSCLE Core Set Questionnaire by including parameters considered most relevant for the evaluation of CLE and compiled from international literature, clinical praxis, and long-term experience with this disease. The compilation of the different parameters for the evaluation of CLE resulted in the 4-sided EUSCLE Core Set Questionnaire with six sections on patient data, diagnosis, skin involvement, activity and damage of disease, laboratory analysis, and treatment. Thus, the EUSCLE Core Set Questionnaire for CLE constitutes a useful tool for the collection and evaluation of epidemiological data from patients with this disease. It enables consistent statistical evaluation, exchange, and comparison of patients data within several European countries and provides a set of guidelines for standardized diagnostic and therapeutic strategies in CLE.

Anti-annexin 1 antibodies: A new diagnostic marker in the serum of patients with discoid lupus erythematosus

Abstract:  Annexin 1 is an anti‐inflammatory molecule and has also been described to be a common target of autoantibodies. In this study, we determined whether antibodies against annexin 1 can be detected in sera of patients with cutaneous lupus erythematosus (CLE). Levels of anti‐annexin 1 antibodies were evaluated by a new established enzyme‐linked immunosorbent assay and found to be significantly higher in sera of patients with CLE when compared to normal healthy donors (NHD). Moreover, the percentage of sera positively tested for anti‐annexin 1 antibodies was elevated in patients with CLE when compared to NHD. In particular, the percentage of positive sera for anti‐annexin 1 antibodies was significantly higher in patients with discoid lupus erythematosus (DLE); however, disease activity did not correlate with the antibody levels. The results of this study indicate that anti‐annexin 1 antibodies in sera of patients with DLE might be a valuable aid in the diagnosis of this subtype.

Updated Analysis of Standardized Photoprovocation in Patients With Cutaneous Lupus Erythematosus

To determine the frequency and reproducibility of standardized photoprovocation in patients with cutaneous lupus erythematosus (CLE) and report our long‐term experience.

Evaluation of disease activity and damage in different subtypes of cutaneous lupus erythematosus using the CLASI

Background  The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a scoring system for patients with cutaneous lupus erythematosus (CLE) to assess disease activity and damage.