Investigation of Clinical and Immunological Features of Alopecia Areata With Comorbid Atopic Dermatitis

BACKGROUND: Alopecia areata (AA) frequently co-occurs with atopic dermatitis (AD; AA-AD); however, AA-AD's features remain unclear. OBJECTIVE: To elucidate the clinical and immunological features of AA-AD. METHODS: Retrospective analysis of data from 123 AA-AD patients, 119 non-atopic AA patients, and 126 AD patients (2011-2024). Peripheral blood mononuclear cells (PBMCs), plasma, and scalp tissues from patients and healthy controls (HC) were examined by flow cytometry, multiplex cytokine assays, and immunofluorescence. RESULTS: Clinically, AA-AD patients were younger than non-atopic AA and AD-only patients, showed more severe alopecia and longer duration, but milder eczema, and exhibited higher dust-mite allergy, total IgE (tIgE), and Eos counts/percentages than non-atopic AA, while showing more intrinsic AD and lower tIgE and Eos counts/percentages than AD-only patients. AA severity and duration were positively correlated with those of AD. Compared with AA-AD patients with AA-first onset and AA with intrinsic AD (AA-IAD) patients, AA-AD patients with AD-first onset and AA with extrinsic AD (AA-EAD) patients were younger, had more severe eczema, higher tIgE levels, and dust-mite allergy. Compared with the non-atopic AA group and HC, the AA-AD group showed elevated plasma IL-4/6/10/13 levels and increased Th2 cells and ILC2s (group 2 innate lymphoid cells) proportions in PBMCs, along with their IL-13 production, all of which were positively correlated with AA course. AA-AD scalp also showed that Th2 cells and ILC2s were most abundant. CONCLUSION: AA-AD defines a distinct clinical-immunologic endotype of AA. AA and AD exhibit an asymmetric but bilateral interaction driven by Th2/ILC2s-IL-13-centered pathways, representing key mechanisms and targets for precision therapy.