JAK-STAT Signaling Pathway in Pyoderma Gangrenosum

Cytokines are key molecules in the pathogenesis of inflammatory diseases. These molecules exert their effects through cell surface receptors and intracellular signaling pathways. Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway is implicated in the pathogenesis of several autoimmune diseases. Pyoderma gangrenosum (PG) is an inflammatory skin disease characterized by progressive and recurrent skin ulceration of destructive course. Treatment of PG requires aggressive immunosuppressive therapy but despite the use of several agents, including tumor necrosis factor inhibitory treatments there is still an unmet need in refractory PG. Recent reports suggested activation of JAK/STAT pathway in PG and some case-based studies suggested the beneficial effect of JAK-STAT inhibitory agent in the treatment of PG. Skin biopsies obtained from PG, hidradenitis suppurativa, psoriasis and healthy subjects will be studied to evaluate JAK/STAT pathway by using immunohistochemical methods. The following immunohistochemical stains will be used to evaluate the expression of JAK/STAT pathway: JAK1, JAK2, JAK3, Tyrosine Kinase 2, STAT1, STAT2, STAT3, STAT3, STAT4, STAT5 and STAT6. Staining intensity will be recorded categorically (negative and positive). The positive staining will also be graded semi-quantitively as follows: mildly positive, moderately positive and strongly positive.