Comorbidities of atopic dermatitis: Emerging evidence and clinical considerations

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and has traditionally been viewed as a disorder confined to the skin. However, emerging epidemiologic, genetic, and mechanistic evidence increasingly supports the concept that AD represents a systemic disease associated with a broad spectrum of immune-related comorbidities. This review synthesizes current literature on the comorbidities associated with AD, including dermatologic, respiratory, gastrointestinal, rheumatologic, neurologic, ophthalmologic, and endocrine disorders. Well-established associations include other atopic diseases such as asthma, allergic rhinitis, food allergy, and eosinophilic esophagitis, reflecting shared type 2 inflammatory pathways and epithelial barrier dysfunction. In addition, increasing evidence links AD with nonatopic autoimmune and immune-mediated conditions, including alopecia areata, chronic spontaneous urticaria, vitiligo, psoriasis, hidradenitis suppurativa, bullous pemphigoid, inflammatory bowel disease, autoimmune thyroid disease, and several rheumatologic disorders. Epidemiologic studies suggest that the risk of autoimmune comorbidity is influenced by AD severity, age, and sex, with more severe AD being associated with a higher risk of comorbidities. Shared pathogenic pathways-including epithelial barrier disruption, T_H2-driven immune activation, impaired immune tolerance, and autoreactive antibody responses-may underlie these associations. Recognition of these comorbidities has important implications for clinical practice, including early identification of systemic disease, multidisciplinary management, and selection of targeted therapies, including biologics and Janus kinase inhibitors, that may address overlapping inflammatory pathways. Improved understanding of these relationships may inform personalized treatment strategies and guide future research into shared mechanisms linking atopy and autoimmunity.