Itch in dermatomyositis and the role of increased skin interleukin-31

Summary: Itch in Dermatomyositis and the Role of Increased Skin Interleukin-31 Hee Joo Kim, MD, PhD,1,2,3 Diletta Bonciani, MD,1,2,4 Majid Zeidi, MD,1,2 Sandra M Pena, BA,2 Victoria P. Werth, MD1,2 1Corporal Michael J. Crescenz VAMC, Philadelphia, PA 2Department of Dermatology, Perelman School of Medicine, University of Pennsylvania 3Department of Dermatology, Yonsei University College of Medicine, Seoul, Korea 4Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Florence, Italy Interleukin-31 (IL-31) has been implicated in pruritus associated with various skin diseases. Since pruritus is a prominent feature in dermatomyositis (DM), we hypothesized that IL-31 and IL-31 receptor contributed to the pathophysiology of itch in DM patients. Pruritus and disease activity of DM were evaluated by a visual analog scale (VAS) and the Cutaneous Disease and Activity Severity Index (CDASI), respectively. Half of 191 subjects had moderate to severe itch (28.8% moderate, 22.0% severe itch). Pruritus in DM was positively correlated with disease activity (r=0.325, p<0.001). The expression of IL-31 and IL-31 receptor alpha (IL-31RA) in lesional DM skin was evaluated by qRT-PCR and immunofluorescence. IL-31 gene expression was significantly higher in lesional DM skin than either non-lesional DM (p<0.05) or healthy control (HC) skin (p<0.01). IL-31RA gene expression was upregulated only in lesional DM skin compared to HC skin (p<0.05). IL-31 mRNA expression was positively correlated with VAS itch score (r= 0.5884, p=0.044). Immunoreactivity for IL-31 was also stronger in lesional skin of DM (p=0.0001). Flow cytometry to identify cellular sources of IL-31 in lesional DM skin showed that CD4+ cells are the most common cell types to produce IL-31 in DM, while other cell types that express CD8, CD68, CD11b, or CD11c also secrete IL-31 in DM. As a new therapeutic option for DM, the effect of ajulemic acid (AJA) on IL-31 production was evaluated. AJA significantly suppressed IL-31 secretion from CPG-stimulated PBMCs isolated from patients with DM at all AJA concentrations. In conclusion, we confirmed that skin IL-31 is significantly higher in itchy DM patients than in HC, suggesting its potential role in itch associated with DM. Keywords: dermatomyositis, IL-31 (interleukin), itch