Comorbidities in Juvenile-Onset Rheumatic Diseases: A Systematic Review and Meta-Analysis

Background/Objectives: Patients with childhood-onset rheumatic diseases may be at additional risk of developing other health conditions. This systematic review aimed to (i) identify and describe the comorbidities associated with three significant childhood-onset rheumatic diseases-Juvenile Idiopathic Arthritis (JIA), Juvenile-onset Systemic Lupus Erythematosus (jSLE), and Juvenile Dermatomyositis (JDM); (ii) describe comorbidity prevalence and incidence reported as apparent in childhood or adulthood, and (iii) compare these comorbidity estimates with control groups. Methods: PubMed, Web of Science, and Scopus databases were systematically searched without restrictions, in accordance with PRISMA guidelines. Where three or more studies reported the same comorbidity, a meta-analysis was performed using random-effect models. The risk of bias and study quality were assessed using an adjusted version of the Newcastle-Ottawa Scale. Results: Comorbidities were reported in 136,072 patients, of which 115,062 (84.56%) presented in childhood. There was significant heterogeneity within the results. The comorbidities presenting in childhood were uveitis (13.95%, 95% CI 11.79-16.43) in JIA patients, chronic kidney disease (48.38%, 95% CI 0.67-99.24) in jSLE patients, and calcinosis (29.70%, 95% CI 25.91-33.81) in JDM patients. The comorbidities identified in adult populations with childhood-onset rheumatic disease were uveitis (14.46%, 95% CI9.76-20.90) in JIA, hypertension (18.30%, 95% CI 7.52-38.16) in jSLE, and calcinosis (40.37%, 19.02-66.11) in JDM patients. Almost all comorbidities that were compared to control groups were more common in patients with childhood-onset rheumatic disease if statistically significant. Conclusions: Uveitis, chronic kidney disease/hypertension and calcinosis were most commonly identified among JIA, jSLE and JDM patients, respectively. Patients with the three childhood-onset rheumatic diseases evaluated in this systematic review were often found to be at higher risk of comorbidities compared to controls. This finding supports the need for the proactive, multidisciplinary management of comorbidities by clinicians and highlights the breadth of disease burden for patients.