Transcriptomic crossroads: Decoding genes and pathways that connect alopecia areata with chronic inflammatory skin disorders

Alopecia areata (AA) is an immune-mediated hair loss disorder that frequently co-occurs with chronic inflammatory skin disorders, such as atopic dermatitis, vitiligo, and psoriasis. Emerging evidence suggest that such comorbidity profiles represent clinical AA subtypes with distinct etiological underpinnings. However, mechanistic insights remain limited owing to a lack of molecular datasets from comorbid patient cohorts. In this study, we addressed this gap by leveraging publicly available case-control gene expression datasets from AA, atopic dermatitis, vitiligo, and psoriasis for an integrative analysis. Our results revealed a statistically significant overlap between gene expression signatures of AA and each chronic inflammatory skin disorder, suggesting that their co-occurrence is not coincidental. Downstream analyses of shared gene expression signatures suggested catecholamine signaling and hair/skin-pigmentation-related processes as possible drivers of AA and vitiligo codevelopment, whereas skin barrier defects and dysregulation of specific immune response pathways may underlie the comorbid development of AA with atopic dermatitis or psoriasis. This study provides a foundation for future mechanistic investigations into skin, hair follicle, and immune system interactions that drive distinct comorbid AA subtypes.