Sarcoidosis and Systemic Comorbidities: Sex-Related Differences in a Multicenter Italian Cohort

Introduction Sarcoidosis is a systemic granulomatous disease characterized by heterogeneous clinical presentation and variable organ involvement. Beyond pulmonary manifestations, extrapulmonary disease and associated comorbidities substantially contribute to disease burden and clinical complexity. Although sex-related differences in sarcoidosis phenotype have been reported, data on sex-specific patterns of systemic comorbidities remain limited. Methods We retrospectively analyzed 1,313 patients with sarcoidosis followed at five Italian referral centers. Systemic comorbidities, disease phenotype, and treatment exposure were systematically recorded and analyzed according to biological sex. Organ involvement was assessed using the WASOG Sarcoidosis Organ Assessment Instrument. Results Female patients showed a significantly higher prevalence of autoimmune, bone, and psychiatric comorbidities, as well as a greater burden of extrapulmonary sarcoidosis, particularly cutaneous and ocular involvement. Extrapulmonary disease was associated with increased systemic comorbidity burden. Malignancy occurred within the broader context of systemic comorbidities, was more frequent among female patients, and was not associated with treatment exposure. Conclusion Sarcoidosis is characterized by sex-specific patterns of systemic comorbidities and disease expression that extend beyond pulmonary involvement. These findings support the relevance of sex-aware clinical assessment and highlight the need for prospective studies to better define comorbidity trajectories and inform personalized management strategies.