Cutaneous lupus erythematosus (CLE) is a rare inflammatory autoimmune disease with heterogeneous clinical manifestations. To date, no therapeutic agents have been licensed specifically for patients with this disease entity, and topical and systemic drugs are mostly used 'off-label'. The aim of the present guideline was to achieve a broad consensus on treatment strategies for patients with CLE by a European subcommittee, guided by the European Dermatology Forum (EDF) and supported by the European Academy of Dermatology and Venereology (EADV). In total, 16 European participants were included in this project and agreed on all recommendations. Topical corticosteroids remain the mainstay of treatment for localized CLE, and further topical agents, such as calcineurin inhibitors, are listed as alternative first-line or second-line topical therapeutic option. Antimalarials are recommended as first-line and long-term systemic treatment in all CLE patients with severe and/or widespread skin lesions, particularly in patients with a high risk of scarring and/or the development of systemic disease. In addition to antimalarials, systemic corticosteroids are recommended as first-line treatment in highly active and/or severe CLE. Second-and third-line systemic treatments include methotrexate, retinoids, dapsone and mycophenolate mofetil or mycophenolate acid, respectively. Thalidomide should only be used in selected therapy-refractory CLE patients, preferably in addition to antimalarials. Several new therapeutic options, such as B-cell-or interferon a-targeted agents, need to be further evaluated in clinical trials to assess their efficacy and safety in the treatment of patients with CLE. JEADVAll authors are participants of the European Society for Cutaneous Lupus Erythematosus (EUSCLE), which received a grant by the European Academy of Dermatology and Venereology (EADV) to perform the project. This grant was used to organize the consensus conferences and to reimburse the travel fees and the accommodation of each participant. In addition, the grant by the EADV was used to partly reimburse the personnel costs of Aysche Landmann for coordination of the project; and drafting, copy-editing and formatting of the manuscript. Elisabeth Aberer, Zsuszanna Bata-Cs€ org€ o, Marcia Caproni, Andreas Dreher, Camille Frances, Regine Gl€ aser, Hans-Wilhelm Kl€ otgen, Annegret Kuhn, Aysche Landmann, Branka Marinovic, Filippa Nyberg, Rodica Olteanu, Annamari Ranki and Beatrix Volc-Platzer have no conflicts of interest with regard to fees for participation in review activities, such as data monitoring boards, statistical analysis, or end point committees. Jacek C. Szepietowski participated in the Novartis Steering Committee and the Sandoz Data Monitoring Committee. Elisabeth Aberer, Zsuszanna Bata-Cs€ org€ o, Marcia Caproni, Andreas Dreher, Camille Frances, Regine Gl€ aser, Hans-Wilhelm Kl€ otgen, Annegret Kuhn, Branka Marinovic, Filippa Nyberg, Rodica Olteanu, Annamari Ranki, Jacek C. Szepietowski and Beatrix Volc-Platzer have no confl...

Patients affected by Sjögren’s syndrome and systemic lupus erythematosus (SLE) carry autoantibodies to an intracellular protein denoted Ro52. Although the serologic presence of Ro52 autoantibodies is used clinically for diagnostic purposes, the function of the protein or why it is targeted as an autoantigen in several rheumatic conditions has not been elucidated. In this study, we show that the expression of Ro52 is significantly increased in PBMC of patients with Sjögren’s syndrome and SLE, and demonstrate that Ro52 is a RING-dependent E3 ligase involved in ubiquitination. Overexpression of Ro52, but not of Ro52 lacking the RING domain, in a mouse B cell line lead to decreased growth in steady state and increased cell death after activation via the CD40 pathway. The role of Ro52 in activation-mediated cell death was further confirmed as a reduction in Ro52 expression restored cell viability. These findings suggest that the increased expression of the Ro52 autoantigen in patients may be directly involved in the reduced cellular proliferation and increased apoptotic cell death observed in Sjögren’s syndrome and SLE, and may thus contribute to the autoantigenic load and induction of autoimmune B and T cell responses observed in rheumatic patients.

Maintenance treatment with a barrier-improving urea moisturizer on previous eczematous areas reduced the risk of relapse to approximately one third of that of no treatment.

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Objective. To investigate the role of the novel cytokine high mobility group box chromosomal protein 1 (HMGB-1) in the pathogenesis of cutaneous lupus erythematosus (CLE).Methods. Punch biopsy specimens of lesional and unaffected skin from 10 patients with CLE and 3 healthy control subjects were investigated. Immunohistochemical staining for HMGB-1, tumor necrosis factor ␣ (TNF␣), and interleukin-1␤ (IL-1␤) was performed on consecutive sections. Analysis of single-nucleotide polymorphisms of ؊308 TNF was performed on DNA extracted from peripheral blood mononuclear cells.Results. An altered expression of HMGB-1 was observed both in the epidermis and in the dermal infiltrates of lesional skin. Expression of HMGB-1 in the epidermis and dermis was increased (P < 0.01 and P < 0.001, respectively, versus unaffected skin), and translocation to the cytoplasm as well as the extracellular presence of secreted HMGB-1 were found. Increased levels of TNF␣ and IL-1␤ were also observed in the dermal infiltrates of lesional skin (P < 0.01 and P < 0.05, respectively, versus unaffected skin). The carrier frequency of the ؊308A TNF polymorphism was 80% in patients with subacute CLE, but this was not related to higher expression of TNF␣ in biopsy specimens from the CLE group.Conclusion. The high amount of extracellular HMGB-1 observed in skin lesions indicates that HMGB-1 is involved in the inflammatory process of CLE. TNF␣ and IL-1␤ may form a proinflammatory loop with HMGB-1, since they can induce the release of each other. The extracellular HMGB-1 observed by immunostaining of the epidermis indicates that keratinocytes may be an as yet unrecognized source of secreted HMGB-1, underscoring the role of the target organ in the rheumatoid autoimmune inflammatory process.The pathogenesis of cutaneous lupus erythematosus (CLE) remains to be fully understood, but ultraviolet (UV) radiation can trigger this autoimmune reaction in the skin. The different subsets of CLE include the acute, subacute, and chronic forms, and an individual patient may have more than 1 subset of CLE according to the currently accepted classifications (1). The lesions of subacute CLE have papulosquamous or annular features and are most commonly distributed on sunexposed areas of the skin, whereas the dermal manifestations of chronic CLE most often consist of coin-shaped scarring plaques, referred to as discoid lupus erythematosus (DLE). DLE lesions can, however, also occur in the skin of patients with systemic lupus erythematosus (SLE) and patients with subacute CLE (1). Subacute CLE is also frequently associated with the serologic presence of Ro/SSA autoantibodies (2-4).The diagnosis of different forms of CLE is confirmed histologically by the presence of epidermal hyperkeratosis, follicular plugging, and hydropic degeneration of the basal cell layer and a dermal lichenoid or patchy mononuclear infiltrate with perifollicular accen-