Risk of Th1-associated autoimmune skin diseases in people with Down syndrome: a large-scale retrospective cohort study

Down syndrome (DS), caused by trisomy 21, is associated with an increased frequency of some autoimmune and inflammatory diseases (1). Skin manifestations are part of this spectrum. Higher incidences of psoriasis in people with DS may indicate dysregulation of T-helper 1 (Th1)/Th17 responses; altered interferon (IFN) responses and downstream signaling were also reported in DS. Alopecia areata (AA), vitiligo and lichen planus (LP) are other primarily Th1-mediated skin diseases. In experimental AA, pathogenic CD4 T cells exhibit a Th1 profile and require interferon-γ (IFN-γ) activity for disease transfer. In vitiligo, IFN-γ-associated chemokine signaling and cytotoxic lymphocytes are likewise implicated in melanocyte injury. A systematic review of dermatologic disorders in DS reported mean prevalence estimates of 7.4% for AA and 4.4% for vitiligo (2). We hypothesize that Th1-skewed immune responses could be mechanistically altered in people with DS. Given the low evidence on rare skin diseases in people with DS, we conducted a large-scale retrospective study using real-world data to estimate the risk of Th1-associated skin diseases in DS. References 1. Lam M, Lu JD, Elhadad L, Sibbald C, Alhusayen R Common Dermatologic Disorders in Down Syndrome: Systematic Review JMIR Dermatol 2022;5(1):e33391 2. Hom, B., Boyd, N.K., Vogel, B.N. et al. Down Syndrome and Autoimmune Disease. Clinic Rev Allerg Immunol 66, 261–273 (2024).