Histologic and Immunohistochemical Features of the Skin Lesions in CANDLE Syndrome

Trebes, A.; Twigg, S. R.; Uhlig, H. H.; Vyas, P.; Vyse, T.; Wall, S. A.; Watkins, H.; Whyte, M. P.; Witty, L.; Wright, B.; Yau, C.; Buck, D.; Humphray, S.; Ratcliffe, P. J.; Bell, J. I.; Wilkie, A. O.; Bentley, D.; Donnelly, P.; McVean, G.; Torrelo, A.; Colmenero, I.; Requena, L.; Paller, A. S.; Ramot, Y.; Richard Lee, C. C.; Vera, A.; Zlotogorski, A.; Goldbach-Mansky, R.; Kutzner, H.

Nat Genet. 2015 May 20; 37(7):517-22

Abstract

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a newly characterized autoinflammatory disorder, caused by mutations in PSMB8. It is characterized by early-onset fevers, accompanied by a widespread, violaceous, and often annular cutaneous eruption. Although the exact pathogenesis of this syndrome is still obscure, it is postulated that the inflammatory disease manifestations stem from excess secretion of interferons. Based on preliminary blood cytokine and gene expression studies, the signature seems to come mostly from type I interferons, which are proposed to lead to the recruitment of immature myeloid cells into the dermis and subcutis. In this study, we systematically analyzed skin biopsies from 6 patients with CANDLE syndrome by routine histopathology and immunohistochemistry methods. Skin lesions showed the presence of extensive mixed dermal and subcutaneous inflammatory infiltrate, composed of mononuclear cells, atypical myeloid cells, neutrophils, eosinophils, and some mature lymphocytes. Positive LEDER and myeloperoxidase staining supported the presence of myeloid cells. Positive CD68/PMG1 and CD163 staining confirmed the existence of histiocytes and monocytic macrophages in the inflammatory infiltrate. CD123 staining was positive, demonstrating the presence of plasmacytoid dendritic cells. Uncovering the unique histopathological and immunohistochemical features of CANDLE syndrome provides tools for rapid and specific diagnosis of this disorder and further insight into the pathogenesis of this severe life-threatening condition.

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