Autoimmune Diseases of the Eyelid Skin: Molecular Pathways, Clinical Manifestations, and Therapeutic Insights.

The eyelid skin represents a unique anatomical and immunological interface between the external environment and the ocular surface. Due to its structural delicacy, dense vascularization, and continuous exposure to microbial and environmental antigens, it is a primary target of inflammatory and autoimmune processes. This review aims to synthesize current molecular insights into eyelid skin inflammation, with particular emphasis on autoimmune mechanisms. We discuss autoimmune diseases such as ocular cicatricial pemphigoid, pemphigus, discoid and systemic lupus erythematosus, and thyroid-associated orbitopathy, focusing on the roles of T helper cell subsets, pro-inflammatory cytokines (IL-1β, IL-6, IL-17, TNF-α), and autoantibody-mediated complement activation. We further address the contribution of the periocular microbiome and meibomian gland dysfunction. Diagnostic advances, including confocal microscopy, in vivo molecular imaging, and tear proteomics, are highlighted alongside emerging targeted therapies such as biologics and small molecules directed at IL-17, TNF-α, and B-cell activity. Finally, we propose future perspectives for precision medicine approaches, integrating omics technologies and microbiome-based therapies to advance personalized management of eyelid skin inflammation.