Association Between Type I Interferonopathies and the Development of Cutaneous Sarcoidosis, Morphea, Lichen Planus and Granuloma Annulare: A Retrospective Cohort Study

Dysregulated type I interferon (IFN-I) signalling is implicated in the pathogenesis of several systemic autoimmune conditions, collectively termed type I interferonopathies. Emerging evidence suggests that aberrant IFN-I pathway activity may similarly contribute to certain autoimmune dermatoses, namely granuloma annulare (GA), lichen planus (LP), cutaneous sarcoidosis (CS) and morphea. We sought to investigate this association using large, real-world cohorts, with type I interferonopathies serving as proxies for IFN-I-driven inflammation. Four retrospective cohort studies were conducted in parallel using the TriNetX Global Collaborative Network. Patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren's disease (SjD) and dermatomyositis (DM) were 1:1 propensity score-matched to healthy controls (HCs), and relative risks (RRs) for developing GA, CS, LP and morphea were calculated. Sensitivity analyses compared each interferonopathy cohort to patients with gout and ankylosing spondylitis, rheumatologic conditions not mediated by IFN-I pathways. Increased risk of morphea and LP was observed across all four interferonopathy cohorts relative to HCs. Patients with SLE, SSc and SjD had an increased risk of developing CS. GA risk was significantly increased only among patients with SLE and DM. Sensitivity analyses were broadly corroborative. These findings reveal consistent associations between type I interferonopathies and subsequent development of LP, CS and morphea. The results of these analyses are hypothesis-generating and complement existing evidence of an IFN-I mediated pathogenesis for these dermatoses. Prospective studies employing large, representative cohorts paired with transcriptomic and proteomic technologies for mechanistic confirmation are warranted.