Background: Atopic dermatitis (AD), allergic rhinitis (AR), and chronic rhinosinusitis with nasal polyps (CRSwNP) represent interconnected conditions within the spectrum of type 2 inflammatory diseases. While these conditions share common genetic and epigenetic pathways, the precise molecular mechanisms remain underexplored. Methods: This review integrates the latest insights on the genetic and epigenetic factors linking AD, AR, and CRSwNP, focusing on genome-wide association studies, DNA methylation patterns, histone modifications, and microRNA regulation. Results: In all three conditions, epigenetic modifications, including DNA methylation (Me) and histone acetylation (Ac) and methylation, regulate inflammatory and barrier-related genes, influencing disease severity. Notably, miRNAs such as miR-146a and miR-155 play pivotal roles in modulating inflammation across all three diseases, while disease-specific miRNAs contribute to airway remodeling (miR-125b and miR-21 in AR and CRSwNP). Emerging evidence underscores the role of microbiome-driven inflammasome activation and matrix metalloproteinases (MMP-2, MMP-9, and MMP-12) in perpetuating chronic inflammation and remodeling. Conclusions: The interplay between genetic predispositions, epigenetic modifications, and exposomal factors underscores the systemic nature of type 2 inflammation. A deeper understanding of these interconnected mechanisms could lead to transformative, personalized diagnostic and therapeutic advancements.

Atopic dermatitis is a chronic inflammatory skin disease increasingly recognized as part of a broader atopic and type 2 inflammatory spectrum rather than a condition confined to the skin alone. Although its dermatologic burden is well established, its relevance to otorhinolaryngology remains relatively underrecognized. This narrative review examines atopic dermatitis from an otorhinolaryngology-centered perspective, focusing on ear, nose and throat (ENT) associations, clinical overlaps, shared inflammatory pathways, and practical implications for clinical care. Particular emphasis is placed on allergic rhinitis, chronic rhinosinusitis, ear-related eczematous manifestations, and the head and neck phenotype of atopic dermatitis. Shared pathophysiologic mechanisms, including epithelial barrier dysfunction, allergen sensitization, immune dysregulation, type 2 inflammation, microbiome alterations, and allergic multimorbidity, provide a framework for understanding these overlaps. Upper airway and ear-related conditions should not be interpreted as direct manifestations of atopic dermatitis in all patients, but as disorders that may coexist within a shared atopic or type 2 inflammatory background. The review further considers the implications of this perspective for targeted history-taking, differential diagnosis, referral decisions, therapeutic awareness, and multidisciplinary care. Overall, atopic dermatitis may serve as a clinically useful marker of broader allergic and inflammatory multimorbidity, with relevant implications for selected patients encountered in otorhinolaryngology practice.