Systemic Immune Dysregulation in Allergic Rhinitis: Mechanisms, Comorbidities, and Implications for Targeted Therapy.

Allergic rhinitis (AR) has traditionally been regarded as a localized inflammatory disorder of the nasal mucosa. However, accumulating evidence indicates that AR is associated with systemic immune dysregulation characterized by peripheral eosinophilia, altered T helper cell polarization, circulating cytokine imbalances, and widespread inflammatory signaling. This systemic immune disturbance contributes to the frequent coexistence of AR with asthma, atopic dermatitis, and other immune-mediated conditions. These associations support the concept of AR as part of a unified airway and systemic allergic disease spectrum. In this review, we summarize current insights into the immunopathogenesis of AR from both local and systemic perspectives. We focus on epithelial barrier dysfunction, type 2 immune responses, and immune cell trafficking between the upper and lower airways. We further discuss emerging systemic inflammatory biomarkers and their potential clinical relevance in disease stratification and management. Finally, we highlight recent advances in allergen immunotherapy and targeted biologic therapies, emphasizing their implications for precision treatment of AR and its comorbidities. Recognizing AR as a manifestation of systemic immune dysregulation may facilitate improved disease classification and support the development of more effective, individualized therapeutic strategies.