Apoptotic signal molecules in skin biopsies of cutaneous lupus erythematosus: analysis using tissue microarray.

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease. Different pathogenetic mechanisms, including the accumulation of apoptotic keratinocytes in CLE, have been reported. Therefore, we investigated whether CLE and other inflammatory skin diseases differ with regard to the epidermal expression of molecules that are crucial for the initiation and regulation of apoptosis. In this study, 241 skin biopsies from patients with CLE, psoriasis (PSO), lichen planus (LP) and healthy controls (HCs) were analysed immunohistochemically using the tissue microarray (TMA) technique. The TUNEL assay and anti-activated caspase-3 antibodies revealed a significant increase of apoptotic keratinocytes in CLE lesions compared with HCs. Furthermore, we detected a significant increase in the epidermal expression of CD95 in CLE specimens compared with PSO, LP and HCs. These data suggest that the accumulation of apoptotic keratinocytes in CLE might be due to the increased epidermal expression of CD95, resulting in increased activity of the extrinsic apoptotic pathway in the disease.

Merkel cell carcinoma induces lymphatic microvessel formation.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, highly malignant neuroendocrine tumor of the skin characterized by frequent lymphatic metastasis. OBJECTIVE: We sought to identify lymphovascular anatomy and expression profiles of lymphangiogenic cytokines to give an opinion on lymphangiogenesis in MCC. METHODS: We studied lymphatic microanatomy and lymphangiogenic cytokines in 27 MCC by immunohistology or immunofluorescence (D2-40, lymphatic vessel endothelial hyaluronan receptor [LYVE-1], vascular endothelial growth factor [VEGF] receptor-3, VEGF-C, VEGF-D, Ki67/MiB-1, CD68/PG-M1, CD68/KP1, CD163), Merkel cell polyomavirus-specific polymerase chain reaction, and coanalysis with clinical and histologic data. RESULTS: We found a more than 3-fold increase in the mean density of absolute numbers of small lymphatic capillaries (diameter <10 µm) and a more than 8-fold increase in the median ratio of the number of small to large lymphatics (<10/≥10 µm) paratumorally compared with intraindividual controls. VEGF-C(+)CD68(+) CD163(+) cells (interpreted as M2 macrophages) could be identified as an important potentially lymphangiogenesis-inducing cell type. LIMITATIONS: Partially lacking follow-up data limited the analysis of the prognostic impact. CONCLUSIONS: Our findings strongly indicate lymphangiogenesis in MCC driven by VEGF-C(+)CD68(+) CD163(+) M2 macrophages.

Generalized interstitial granuloma annulare--response to adalimumab.

BACKGROUND: Cause and pathogenesis of granuloma annulare are poorly understood. A foreign-body granuloma formation induced by an unknown inciting antigen is suspected. Generalized forms often coincides with recalcitrant progression and frustrated experimental therapies. METHODS: We report a case of generalized interstitial granuloma annulare resolving completely after treatment with adalimumab. An initial dose of 80 mg was administered subcutaneously followed by a maintenance dose of 40 mg every two weeks. RESULTS: Already after two weeks, the eruptions became less infiltrated and paled. After a follow up of 7 weeks, only a residuum of postinflammatory hyperpigmented maculae without infiltration presented. The initially affected body surface area of over 35% reduced to less than 5%. Histopathological examination revealed a significant reduction in the interstitial histiocytic infiltration and the precipitations of mucin. CONCLUSION: Although adalimumab should not be first line therapy for granuloma annulare, our case showed that it may profit well-selected patients and shorten disease duration.