ReviewCutaneous lupus erythematosus: First multicenter database analysis of 1002 patients from the European Society of Cutaneous Lupus Erythematosus (EUSCLE)
Introduction
The inflammatory autoimmune disease lupus erythematosus (LE) encompasses a great variety of clinical manifestations; however, the pathogenesis is not completely understood [1], [2], [3]. The American College of Rheumatology (ACR) introduced a set of criteria for the classification of systemic LE (SLE) that provides some degree of uniformity in classifying the patient populations of clinical studies [4]. Although 4 of the 11 criteria are muco-cutaneous manifestations (malar rash, discoid lesions, photosensitivity, and oral ulcers), the clinical presentation of skin involvement in LE presents with a much broader spectrum. Gilliam [5] suggested the differentiation of LE-specific and LE-nonspecific manifestations based on histopathological criteria of skin biopsy specimens. The LE-nonspecific skin lesions include, for example, vascular skin changes such as urticarial vasculitis and livedo reticularis, which are mostly associated with active SLE reflecting potentially internal organ manifestations and serious complications [6]. The LE-specific skin lesions encompass the subtypes of cutaneous LE (CLE). In 2004, the classification of CLE was modified (“Duesseldorf Classification 2004”) [7]; it now subdivides the skin manifestations into acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), and intermittent CLE (ICLE).
To date, no guidelines have been proposed for the diagnosis and treatment of patients with CLE in the international literature. As a result, varying diagnostic and therapeutic strategies exist in different European centers, impeding the standardized comparison of patient data. Therefore, a study group of the European Society of Cutaneous Lupus Erythematosus (EUSCLE) defined a core set of variables for the evaluation of the characteristic features of the disease, resulting in development of the four-page EUSCLE Core Set Questionnaire [8]. By collecting data from CLE patients all over Europe, the non-profit working group EUSCLE aims to achieve a general consensus concerning evidence-based clinical standards for disease assessment and to develop diagnostic and therapeutic guidelines. The EUSCLE Core Set Questionnaire includes various parameters that are considered the most relevant features of CLE. These parameters were chosen based on the international literature, clinical praxis, and long-term experience of the authors [9]. Moreover, the 11 clinical and laboratory ACR criteria for the classification of SLE [4] and the validated disease activity and damage scoring system “Cutaneous Lupus Erythematosus Disease Area and Severity Index” (CLASI) [10] are included in the EUSCLE Core Set Questionnaire.
In 2010, the EUSCLE working group published preliminary data on 50 patients from two European centers (Germany, Sweden) demonstrating that the EUSCLE Core Set Questionnaire provides a useful tool for standardized collection and statistical analysis of data on CLE in clinical practice [11], [12]. In the present study, data on 1002 patients with different disease subtypes from 14 countries were analyzed using the EUSCLE Core Set Questionnaire. The objectives included the analysis of clinical and laboratory characteristics, with particular regard to the different CLE subtypes. The results demonstrate that the EUSCLE Core Set Questionnaire and its database facilitate the analysis of diagnostic and therapeutic strategies in CLE and that they contribute to standardized assessment and monitoring of CLE in the future.
Section snippets
Study population
Between July 2006 and June 2010, a total of 1051 out- and in-patients with different subtypes of CLE was enrolled in the study using the EUSCLE Core Set Questionnaire at one point of time during the course of the disease. Classification and diagnosis of CLE were conducted with regard to clinical and histological criteria as well as serological parameters according to the “Duesseldorf Classification 2004” [7]. The data sets of 49 patients were excluded from the final statistical analysis as
Patients
The following subtypes of CLE were included in the analysis: ACLE (304 patients, mean age ± SD 46.6 ± 15.6 years), SCLE (236 patients, 57.2 ± 15.5), CCLE (397 patients, 49.7 ± 14.3), and ICLE (65 patients, 45.7 ± 12.2), which encompasses lupus erythematosus tumidus (LET). CCLE was sub-classified into discoid lupus erythematosus (DLE), lupus erythematosus panniculitis (LEP), and chilblain lupus erythematosus (CHLE). Two patients presented with neonatal lupus erythematosus (NLE) and were included in the
Epidemiology and gender
This study with a cohort of 1002 patients from 29 European centers using the four-page EUSCLE Core Set Questionnaire is, to our knowledge, the largest prospectively performed study of CLE patients that has ever been analyzed throughout Europe. The incidence of SLE in the general population varies according to the characteristics of the population studied, including age, sex, race, ethnicity, and national origin. In Europe, the annual incidence of SLE ranges from 3.3 to 4.8 cases per 100,000
Conclusion
This study of 1002 patients with CLE is the first multicenter analysis of the EUSCLE Core Set Questionnaire and, to our knowledge, includes the highest number of patients with CLE analyzed prospectively throughout Europe to date. The results of this study demonstrate that the EUSCLE Core Set Questionnaire allows prospective analysis of disease characteristics and diagnostic and therapeutic trends. The parameters included in the EUSCLE Core Set Questionnaire consider the most relevant features
Take-home messages
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In this prospective, cross-sectional, multicenter study, clinical and laboratory characteristics from patients with CLE were assessed using the EUSCLE Core Set Questionnaire.
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1002 (768 females, 234 males) patients with different subtypes of CLE from 14 countries were collected and statistically analyzed by an SPSS database.
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The main outcome measures included gender, age at onset of disease, LE-specific and LE-nonspecific skin lesions, photosensitivity, laboratory features, and the ACR criteria
Acknowledgments
We thank Anna Backmann and Ramona Weber, Department of Dermatology, University of Muenster, Germany, for their help in organizing the collection of the EUSCLE Core Set Questionnaires from all over Europe. We would also like to thank Aysche Landmann and Sonja Nozinic, Division of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany, for critical reading and their help in copy-editing the manuscript.
Other information
Ethical approval: The EUSCLE Core Set
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EUSCLE co-authors: M. Haust, Department of Dermatology, University of Duesseldorf, Duesseldorf, Germany; F. Nyberg, Department of Dermatology, University of Uppsala, Uppsala, Sweden; Z. Bata, L. Mihályi, Department of Dermatology, University of Szeged, Szeged, Hungary; R. Olteanu, Colentia Hospital, Dermatology, Bucharest, Romania; R.M. Pujol, J.M. Sánchez-Schmidt, Department of Dermatology, Parc de Salut Mar-IMAS, Barcelona, Spain; L. Medenica, D. Skiljevic, Department of Dermatovenereology, School of Medicine, University of Belgrade, Clinic of Dermatovenereology, Clinical Center of Serbia, Belgrade, Serbia; A. Reich, J.C. Szepietowski, Department of Dermatology, Venerology and Allergology, Wroclaw Medical University, Wroclaw, Poland; C. Dalle Vedove, G. Girolomoni, Department of Dermatology, University of Verona, Verona, Italy; T. Hawro, A. Zalewska-Janowska, Psychodermatology Department, Clinical Immunology and Microbiology, Medical University of Lodz, Lodz, Poland (the study was conducted at the Department of Dermatology and Venereology, Medical University of Lodz, Lodz, Poland); R. Glaeser, R. Huegel, Department of Dermatology of the University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany; H. Jedličková, Department of Dermatology, St. Anna University Hospital, Brno, Czech Republic; A. Bygum, R. Laurinaviciene, Department of Dermatology and Allergy Center, Odense University Hospital, Odense C, Denmark; S. Benoit, E. Broecker, Department of Dermatology, Venerology and Allergology, University Hospital Wuerzburg, Wuerzburg, Germany; F.A. Bahmer, Department of Dermatology, Hospital Bremen-Mitte, Bremen, Germany; E. Aberer, N. Wutte, Department of Dermatology, Medical University Graz, Graz, Austria; J. Lipozencic, B. Marinovic, University Hospital Center Zagreb, Department of Dermatology and Venerology, School of Medicine University of Zagreb, Zagreb, Croatia; M. Sárdy, V. Bekou, T. Ruzicka, Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany; C. Frances, B. Soutou, Tenon Hospital, Department of Dermatology, Paris, France; H. Lee, M. Worm, Department of Dermatology and Allergy, Charité Campus Mitte, Universitaetsmedizin Berlin, Berlin, Germany; A. Gruschke, N. Hunzelmann, Department of Dermatology and Venerology, University Hospital Cologne, Cologne, Germany; K. Steinbrink, Department of Dermatology, University Medical Center Mainz, Mainz, Germany; R. Romiti, Department of Dermatology, University of Sao Paulo, Sao Paulo, Brazil; M. Sticherling, C. Erfurt-Berge, Department of Dermatology, University Erlangen, Erlangen, Germany; G. Avgerinou, D. Papafragkaki, Department of Dermatology, University of Athens, A. Sygros Hospital, Athens, Greece; E. Antiga, M. Caproni, Department of Dermatology Sciences, University of Florence, Florence, Italy; B. Mayer, B. Volc-Platzer, Department of Dermatology, Donauspital Wien, Vienna, Austria; A. Kreuter, C. Tigges, Department of Dermatology, Venereology and Allergology, Ruhr University Bochum, Bochum, Germany; P.M. Heil, G. Stingl, Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University Vienna, Vienna, Austria.