First Meta-Analysis and Systematic Review of Relapse in Pulmonary Sarcoidosis: Prevalence, Risk Factors, and Future Directions
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Background and Aim
Relapses 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 question
What are the global prevalence and risk factors for relapse in PS patients?
Methods
We systematically searched PubMed, Google Scholar, Scopus, and Embase electronic databases to collect eligible PS studies published until 31 January 2025. Eligible studies were peer-reviewed, English-language studies reporting relapse and risk factors in PS patients. Prevalence and risk factors were analyzed using proportions and log odds ratios (LORs) with 95% confidence intervals (CIs). Quality was assessed by Hoy et al tool for prevalence studies
Results
A total of 50 studies with 5978 patients were included in this meta-analysis. Among these patients, 3646 were followed up, and PS relapse was analyzed. Relapse prevalence heterogeneity was significant (Q test, p<0.01). The pooled prevalence of relapse was 0.40 (95% CI: 0.34, 0.46) in all included studies. Sensitivity analyses of the pooled prevalence estimate showed minimal variation, with estimates ranging from 35% to 41% across analyses removing outliers, performing leave-one-out, adjusting for study size, excluding lower-quality studies, and excluding studies without relapse definitions. The pooled prevalence of relapse in prospective vs. retrospective studies was 0.32 (95% CI: 0.26, 0.38) vs. 0.44 (95% CI: 0.36, 0.54), with a meta-regression coefficient of 0.14 (p = 0.02). The pooled LOR of relapse was greater for patients who were black [0.91 (95% CI: 0.44, 1.37); p<0.001], had stage II & III disease [0.55 (95% CI: 0.07, 1.03); p=0.02], and had stage IV disease [1.04 (95% CI: 0.25, 1.83); p=0.01], whereas it was comparable for age, sex, treatment type, and PS type (isolated or systemic PS).
Conclusion
The pooled prevalence of PS relapse in all studies 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 Message
Research Question
What is the global occurrence and etiology of relapse among patients with pulmonary sarcoidosis illness?
Interpretation
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Our first meta-analysis of 3,646 follow-up PS patients from 50 studies revealed that the pooled prevalence of PS relapse was 40% (95% CI: 0.34–0.46).
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The relapse prevalence was lower in prospective studies than in retrospective studies (0.32 [95% CI: 0.26, 0.38] vs. 0.44 [95% CI: 0.36, 0.54], with a meta-regression coefficient=0.14, p= 0.02), indicating the potential impact of study design on the occurrence or detection of relapses in patients with this disease.
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Black race (LOR: 0.91, p<0.001) and stage II & III PS (LOR: 0.55, p=0.02) and IV PS (LOR 1.04, p=0.01) were the underlying risk factors for relapse, whereas age, sex, treatment type, and type of PS (isolated or systemic) had no associations.
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This research emphasizes the critical need for a consensus definition of PS relapse and prospective large cohort studies identifying new biomarkers and treatments of relapse to improve the routine clinical practice and outcome of this disease.
