Sustained epithelial alarmin contribute to persistent hyperpigmentation after psoriasis remission by biologics.

Summary: Post-inflammatory hyperpigmentation (PIH) can develop following various skin conditions, external factors, and dermatological treatments. PIH after psoriasis can be particularly bothersome for patients, as the pigmentation may persist even after the complete resolution of psoriatic plaques. Our study aimed to examine the histopathologic and molecular characteristics of persistent hyperpigmentation following the clearance of psoriasis lesions. Two psoriasis patients treated with IL-23 monoclonal antibodies and reached PASI 100 underwent skin biopsies on both recovered lesions without PIH and lesions with persistent PIH. Compared to lesions that recovered without PIH, persistent PIH lesions showed more pronounced hyperkeratosis, epidermal acanthosis, and increased melanin deposition in the basal layer of the epidermis. Using spatial transcriptomics analysis, we observed heightened alarmin and cytokine signaling in the epidermis of persistent PIH lesions compared to non-PIH lesions. Furthermore, the alarmins were associated with increased expression of melanin-related proteins, suggesting a role for residual inflammatory signaling in the persistence of PIH. Together with our previous research, these findings indicate that persistent PIH in psoriasis patients represents an epidermal type of hyperpigmentation characterized by increased basal melanin and sustained hyperkeratosis, despite the absence of clinically visible scaling. Our data suggest that persistent hyperpigmentation may result from prolonged alarmin signaling. Targeting the alarmin signaling pathway could be a promising strategy for improving recalcitrant PIH. Young Joon Park¹, Se Gyoung Kim¹, Han-Seul Kim¹, Soo-Jin Lee¹, Eun-So Lee¹ 1. Department of Dermatology, Ajou University School of Medicine, Suwon-si, Gyeonggi-do, Korea (the Republic of). Translational Studies: Preclinical