First Meta-Analysis and Systematic Review of Relapse in Pulmonary Sarcoidosis: Prevalence, Risk Factors, and Future Directions

Background and AimRelapses are known to adversely affect the prognosis of patients with pulmonary sarcoidosis (PS). However, a systematic review or meta-analysis on the subject is not yet available in the literature. Research questionWhat are the global prevalence and underlying risk factors for relapse in PS patients? MethodsWe systematically searched PubMed, Google Scholar, Scopus, and Embase for eligible PS studies published until 31 January 2025. Eligible studies were peer-reviewed, English-language articles reporting relapse and risk factors in PS patients. Prevalence and risk factors were analysed via proportions and log odds ratios (LORs) with 95% confidence intervals (CIs). Quality was assessed via the Hoy et al. tool for prevalence studies. ResultsFifty studies with 5978 patients were included; 3646 patients were followed up for relapse analysis. Heterogeneity was significant (I{superscript 2}=94%). The pooled relapse incidence was 0.40 (95% CI: 0.34-0.46). The estimates were robust in the sensitivity analyses (0.35--0.41). The prevalence was lower in prospective studies (0.32, 95% CI: 0.26--0.38) than in retrospective studies (0.44, 95% CI: 0.36--0.54; meta-regression p=0.02). Relapse risk was greater in black patients (LOR 0.91, 95% CI: 0.44-1.37; p<0.001), those with stage II-III disease (0.55, 95% CI: 0.07-1.03; p=0.02), and those with stage IV disease (1.04, 95% CI: 0.25-1.83; p=0.01) but was comparable for age, sex, treatment type, and PS type (isolated or systemic). ConclusionThe pooled prevalence of PS relapse was 40%, but it was lower in prospective studies. A black race and higher-grade radiographic stages were the underlying risk factors for disease relapse. Take-Home MessageO_ST_ABSResearch QuestionC_ST_ABSWhat is the global occurrence and etiology of relapse among patients with pulmonary sarcoidosis illness? Relapse is a significant problem, with an overall pooled prevalence of 40%. The risk factors are advanced disease and black race. The prevalence of relapse was lower in prospective studies. Future prospective studies with proper relapse definitions are needed.