Gender and Allergy: Mechanisms, Clinical Phenotypes, and Therapeutic Response-A Position Paper from the Società Italiana di Allergologia, Asma ed Immunologia Clinica (SIAAIC)

Sex and gender play a critical role in allergic diseases, influencing immune response, clinical phenotypes, treatment strategies, outcomes, and health-related quality of life. Despite mounting evidence across multiple studies examining sex/gender differences in a multitude of allergic diseases, most address isolated conditions, not taking into consideration the vast interplay of hormonal, genetic, immunological, and sociocultural factors and their unique consequences for clinicians and researchers. With this position paper, we aim to assess currently available evidence on the sex- and gender-specific characteristics of the most common allergic diseases, providing an overview of present knowledge and future areas of improvement for clinicians and researchers. This position paper was developed by the Società Italiana di Allergologia, Asma ed Immunologia Clinica (SIAAIC): a panel of experts who conducted a literature review focusing on sex and gender differences across major allergic diseases. A consensus-based approach was employed to assess the immunological, clinical, and therapeutic implications of available evidence, offering a recommendation for researchers and clinicians alike. Data highlights marked differences driven by sex and gender in disease prevalence, immune pathways, clinical phenotype and severity, as well as therapeutic outcomes. Female patients appear to show a higher prevalence of Th2-driven ailments, autoimmune overlap, and allergic drug reactions, whereas males are more likely to experience fatal anaphylaxis and severe mastocytosis. Sex hormones can modulate multiple immune pathways leading to mast cell activation, antibody production, and cytokine expression, thus contributing to divergent disease trajectories. In conclusion, sex and gender are a key determinant in allergic diseases, and their integration in future research is essential to develop a tailored approach to treatment. Efforts should prioritise the identification of sex- and gender-specific biomarkers, therapeutic strategies, and equitable access to healthcare services. A sex- and gender-aware approach could potentially improve outcomes, optimise treatment strategies, and address current gaps in allergy practice.