Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects approximately 1 – 4% of the world population and is characterized by recurrent abscesses, nodules, and scars in the apocrine gland-bearing areas. The most frequently affected areas include the armpits, groin, genital area, abdomen, buttocks, and under the breasts.1-3 Overall, HS is a painful and disfiguring disease that is associated with a significantly impaired quality of life.  The underlying mechanisms which drive disease pathogenesis are not completely understood; therefore, limited targeted therapies exist for these patients with surgical management being the primary treatment for severe HS.  This study was conducted to improve our understanding of the downstream signaling pathways which are differentially expressed in patients with HS and may drive disease pathogenesis.  RNA was isolated from the skin of 16 healthy participants and 34 patients with mild to severe HS.  The expression of 15 genes was investigated using QuantiGene Plex assay with a focus on signaling molecules.  Overall, a majority of the genes tested (12 of 15) showed a significant (p<0.0001) increase in gene expression in the patients with HS compared to the healthy participants.  Specifically, patients with HS had elevated expression of kinases such as IRAK1 (fold change = 7.3), IRAK2 (fold change = 52.4), SYK (fold change = 4.7) and JAK-STAT signaling molecules JAK1 (fold change = 2.3), JAK3 (fold change = 68.9), TYK2 (fold change = 3.8), STAT1 (fold change = 12.0), STAT2 (fold change = 23.3), STAT3 (fold change = 2.1), STAT5A (fold change = 2.2), STAT5B (fold change = 32.2), and STAT6 (fold change = 8.2), compared to healthy participants.  These data suggest a role for JAK signaling in the pathogenesis of HS and support the rationale for their subsequent antagonism in this population.

Hidradenitis Suppurativa Lesions are Characterized by Increased Kinase Signaling Activity