Sarcoidosis relapse risk factors: a single-centre retrospective cluster analysis

BACKGROUND: Sarcoidosis is a systemic granulomatous disease with an unpredictable course. While corticosteroids are the mainstay of treatment, recurrence is common and influenced by clinical, demographic and therapeutic factors. However, an integrated approach to patient stratification remains underdeveloped. RESEARCH QUESTION: What are the key clinical, demographic and therapeutic factors influencing sarcoidosis recurrence, and how can an integrated risk stratification model improve disease management? METHODS: We conducted a clustering analysis on 160 sarcoidosis patients to identify recurrence risk subgroups. Key variables included age, sex, body mass index, smoking history, Scadding stage, corticosteroid and immunosuppressant use, therapy duration and recurrence. K-means clustering was employed, with the optimal number of clusters determined using silhouette and elbow methods. RESULTS: Three distinct clusters emerged: Cluster 1 (n=110): predominantly Scadding stage I-II, low recurrence, favourable steroid response, minimal long-term complications. Cluster 0 (n=30): more smokers, advanced disease (Scadding III-IV), high recurrence despite treatment (p=0.003). Cluster 2 (n=20): patients with obesity with systemic symptoms (fatigue, dyspnoea), high recurrence, particularly in women (p=0.02).Multivariate analysis confirmed smoking (OR 2.3, p=0.002), obesity (OR 1.9, p=0.01) and prolonged steroid use (>12 months, OR 2.5, p=0.004) as independent predictors of recurrence. Sex differences were observed, with women showing more extrapulmonary involvement and men a higher risk of pulmonary fibrosis, though sex alone was not a significant predictor (p=0.08). INTERPRETATION: Distinct sarcoidosis phenotypes influence recurrence risk, underscoring the need for personalised management. While Cluster 1 may achieve remission with minimal therapy, Clusters 0 and 2 highlight smoking, obesity and advanced disease as recurrence drivers. Targeted interventions, including smoking cessation, weight management and early steroid-sparing therapy, could improve long-term outcomes and reduce disease burden.