Uncovering Sex and Gender Differences in Sarcoidosis: A Systematic Review of Current Evidence

Introduction: Sarcoidosis is a systemic granulomatous disorder classified among interstitial lung diseases (ILDs). While the lungs and intrathoracic lymph nodes are most affected, the disease can involve multiple organs. The heterogeneity of clinical presentation arises from complex interactions between environmental exposures and immune responses in genetically susceptible individuals. Sex-dependent genetic variations are associated with differences in phenotype and organ localization. Gender-related factors also influence the impact of sarcoidosis on quality of life and health perception, contributing to variability in disease burden and outcomes. Aim of the study: to provide an overview of sex- and gender-related differences in sarcoidosis, focusing on pathophysiological and clinical implications. Material and Methods: The systematic search was conducted on Medline database through Pubmed search engine. We included all clinical studies from 1992 to the present, and imposed language restrictions, accepting only English publications. Case reports, reviews, and pre-print studies were excluded. Results: A total of 35 studies were included. Sex differences significantly influenced both age of onset and clinical presentation of the disease. Women received a diagnosis of sarcoidosis at an older age and exhibited more frequently extrapulmonary localizations, with predominant involvement of the eyes, skin, and extra-thoracic lymph nodes. In contrast, men more commonly presented with limited pulmonary forms. Löfgren syndrome was more prevalent among women and appeared to be associated with sex-specific genetic variations, particularly within the MHC region. Gender differences also impacted quality of life and disease perception: women reported a lower quality of life and were more susceptible to anxiety and depression throughout the disease course. Conclusions: This report confirms that clinical presentation of sarcoidosis is significantly influenced by sex and gender. The identification of sex- and gender-specific clinical patterns supports a personalized medicine framework, in which diagnostic assessment, monitoring strategies, and therapeutic approaches may be tailored according to individual biological and gender-related characteristics.