Association between systemic sclerosis and atopic comorbidities: A case-control study of the All of Us database

Systemic sclerosis (SSc) is a rare, multisystem autoimmune connective tissue disease, with skewing of the T helper 1 (Th1) immune response associated with progression. In contrast, atopic disorders are common chronic diseases with the Th2 axis implicated in pathogenesis. Previous research suggests that Th2 cytokines, namely IL-4 and IL-13, may play a role in the inflammatory and fibrotic phases of SSc. A previous epidemiological study also showed an association between SSc and atopic dermatitis. Herein, we utilized the All of Us database to illuminate potential associations between SSc and atopy/allergic disease. We executed a nested case-control analysis, identifying 1,730 patients with SSc and matching each SSc patient to 4 age-, race-, ethnicity-, and sex- controls. χ2 test revealed that patients with SSc had significantly higher ( p <0.001) rates of atopic dermatitis, asthma, allergic rhinitis, and allergic conjunctivitis compared to matched controls. Logistic regression revealed that compared to controls, SSc patients were significantly more likely ( p <0.001) to be diagnosed with each aforementioned atopic disease, respectively. Revealing an association between SSc and atopic diseases, our study aligns with previous epidemiological research examining the overlap of these two entities, suggesting the role of the Th2 axis in SSc pathogenesis. Studies such as these are crucial, as they may enable potential repurposing of several highly efficacious biologics therapies available for treatment of Th2 axis predominant diseases, namely dupilumab, an IL-4Ra inhibitor approved for use in atopic dermatitis and asthma. Further investigation into the role of the Th2 axis and the potential of Th2-specific biologics in treating SSc may be warranted.