High expression of B lymphocyte stimulator in lesional keratinocytes of patients with cutaneous lupus erythematosus.

Belimumab, an anti-B lymphocyte stimulator (BLyS) monoclonal antibody, is approved for systemic lupus erythematosus; however, it is unclear if it can be used to treat specific skin lesions in this disease. In this analysis, we investigated the expression of BLyS and its receptors in skin lesions of different subtypes of cutaneous lupus erythematosus (CLE) using immunohistochemistry and gene expression analyses. Compared to healthy controls, the expression of BLyS was significantly higher in skin lesions of all included CLE subtypes. Similar results were seen for the BLyS receptors BAFF-R and BCMA. Moreover, CLE-typical pro-inflammatory mediators (immunostimulatory DNAs) significantly enhanced the BLyS expression of keratinocytes in vitro. This study suggests a potential role for BLyS as therapeutic target in the treatment of CLE skin lesions.

Ultraviolet light protection by a sunscreen prevents interferon-driven skin inflammation in cutaneous lupus erythematosus.

Irradiation with ultraviolet (UV) light is an important exacerbating factor in cutaneous lupus erythematosus (CLE) and induces various effects in the skin of patients with the disease, such as cell death and inflammation. Recently, we demonstrated the ability of a broad-spectrum sunscreen to prevent UV-induced damage both in patients with CLE and healthy controls (HCs). The aim of this study was to evaluate whether the UV-dependent activation of interferon (IFN)-driven inflammation in CLE can also be prevented by application of the sunscreen. In 20 patients with different subtypes of CLE and 10 HCs, defined areas on the upper back were treated with a broad-spectrum liposomal sunscreen 20 min prior to a combined standardized UVA/UVB irradiation. Immunohistological analyses using antibodies directed against MxA, CD11c, CD123 and CD68 were performed from skin biopsies taken from areas before UV irradiation as well as from sunscreen-treated and sunscreen-untreated areas 24 and 72 h after UV irradiation. The expression of MxA was completely prevented by the sunscreen applied prior to UV irradiation in CLE patients and HCs. Additionally, sunscreen protection significantly diminished the number of the CD11c- and CD123-positive dendritic cells, which are suggested to be a major source of type I/III IFNs, in UV-irradiated skin of patients with CLE. Moreover, the application of the sunscreen prevented the increase in CD68-positive macrophages in both groups 72 h after UV irradiation. The data of this study demonstrate that UV protection reduces lesional tissue damage and inhibits the typical IFN-driven inflammatory response in CLE.

The classification and diagnosis of cutaneous lupus erythematosus.

Lupus erythematosus (LE) is an inflammatory connective tissue disease of generalized autoimmunity characterized by pathogenic autoantibodies and immune complexes, attributed to loss of immune tolerance. Cutaneous involvement, which appears in the majority of patients with the disease, can present as LE-specific or LE-nonspecific manifestations. The LE-nonspecific manifestations include e.g. vascular skin changes and may be associated with systemic organ manifestations or other autoimmune diseases. In contrast, the LE-specific manifestations encompass the various subtypes of cutaneous lupus erythematosus (CLE), which are classified as separate entities without or with less severe systemic organ involvement. In the "Duesseldorf Classification", CLE is subdivided into four different categories: acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), and intermittent CLE (ICLE). Differentiation between these subtypes is based on clinical features and average duration of the cutaneous lesions, but can also consider histological changes of skin biopsy specimens and laboratory abnormalities. In addition, direct immunofluorescence and photoprovocation may be applied to confirm the diagnosis in specific cases. Further investigations should be considered dependent on the clinical symptoms of the CLE patient and the results of the laboratory tests. A revised scoring system, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) has recently been validated to assess disease activity and damage in CLE. In this review, we focus on the classification of CLE and the diagnostic procedures to identify and confirm the different subtypes of the disease.

Suppression of UV-induced damage by a liposomal sunscreen: a prospective, open-label study in patients with cutaneous lupus erythematosus and healthy controls.

This study aimed to determine whether a broad-spectrum liposomal sunscreen with a very high sun protection factor (Daylong actinica) can prevent damage induced by ultraviolet (UV) irradiation in patients with cutaneous lupus erythematosus (CLE) and healthy controls (HCs) under standardised conditions. In 20 patients with CLE and 10 HCs, defined areas of sunscreen-untreated and sunscreen-treated skin on the upper back were irradiated with combined UVA/UVB light. Disease-specific skin lesions were induced by UVA/UVB light in the untreated areas of nine patients with CLE; no specific eruptions or any sun damage was observed in the sunscreen-treated areas in any of the CLE patients, nor in the HCs. Histological analysis of skin biopsy specimens confirmed the clinical results. In conclusion, the use of a high-protection, broad-spectrum sunscreen can prevent UV-induced damage in patients with CLE and HCs.