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THU0352 THE ROLE OF PRURITOGENIC MEDIATORS IN DERMATOMYOSITIS RELATED ITCH

Background Pruritus is a common symptom in systemic autoimmune diseases like dermatomyositis (DM). Recent researches have indicated that interleukin-31 (IL-31), IL-33, IL-6, or inflammatory cytokines, such as tumor necrosis factor (TNFα), peroxisome proliferator-activated receptor γ (PPARγ) and ion channels belonging to the transient receptor potential (TRP) family are involved in pruriception. Objectives We examined targeted gene expression analysis of lesional versus non-lesional skin samples of patients affected with active DM. We looked for correlations between the examined pruriceptive signaling molecules, disease activity and itching sensation of DM patients. Methods Gene expression of TNFα, PPARγ, IL-33, IL-6 and TRPV channels in lesional DM skin was evaluated by RT-qPCR and was compared with non-lesional DM skin samples. Pruritus and disease activity of DM was evaluated by the 5-d itch scale and Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), respectively. Statistical analysis was performed with IBM SPSS 20.0 software. Results Skin samples of 17 active DM patients were analyzed. We could show, that itching index in DM was positively correlated with CDASI score with a correlation coefficient of 0.82 (p<0.001). TNFα gene expression was significantly higher (34.87%) in lesional DM skin than non-lesional DM skin (p=0.03). The normalized TNFα mRNA expression was positively correlated with itch scale (R= 0.605, p=0.022) and its level was significantly higher in skin samples of patients with severe itch (itching score: 15-20) versus mild itch (itching score: 5-10) (2.02±0.38 vs. 1.12±0.20; p<0.01). The level of PPARγ was decreased in lesional DM skin, but this was statistically not significant. The mRNA expression of normalized PPARγ was negatively correlated with itch scale (R= -0.618, p=0.019), and its level was significantly lower in skin samples of patients with severe itch versus mild itch (0.28±0.36 vs. 1.53±0.98; p=0.038). Lesional IL-6 mRNA levels were associated with CDASI activity score (R=0.619, p=0.018). The mRNA levels of TRPV1-4 channels were not associated with 5-D itch score, but normalized TRPV1 and TRPV4 mRNA expressions were positively correlated with CDASI damage score (R=0.699, p=0.008; R=0.789, p=0.001). Interestingly, itching sensation of DM patients was not correlated with IL-33 mRNA levels measured in skin samples. Conclusion Our results argue for that higher cutaneous disease activity generate pruritus. TNFα and PPARγ might play a determining, but opposite role in DM-associated itch. Furthermore IL-6, TRPV1 and TRPV4 channels might participate in pathomechanism of cutaneous manifestation of the disease. Disclosure of Interests: 