Prepubertal to adolescent lupus: Age-related variations in clinical, laboratory, and outcome profiles

Abstract

Background: Childhood-onset systemic lupus erythematosus (cSLE) is a heterogeneous autoimmune disease with age-related variations. Older children often exhibit higher disease activity, whereas early-onset cSLE is associated with worse outcomes. However, most existing studies are retrospective and based on single-nation cohorts, yiedling inconsistent findings.ObjectiveTo investigate age-related variations in cSLE subgroups, namely prepubertal, peripubertal, and adolescent-onset cases.

Methods: This systematic review, registered in PROSPERO and conducted in accordance with PRISMA guidelines, searched PubMed, the Cochrane Library, and Web of Science for English-language studies pubslished between January 2000- February 2025. Eligible studies examined age-related variations in cSLE diagnosed before 18 years of age. Data were categorized into prepubertal, peri-pubertal, and adolescent-onset groups. Exclusion criteria included case reports, comments, editorials, viewpoint articles, conference abstracts, and incomplete studies. Four reviewers independently screened the articles, with discrepancies resolved by a fifth reviewer. Study quality was assessed using the NHLBI criteria.

Results: Of 16,313 studies screened, 13 met the inclusion criteria, comprising a total of 3920 cSLE cases. Among these, 464 (11.8%) were prepubertal, 1943 (49.6%) peripubertal, and 1513 (38.6%) adolescent-onset. The mean age at diagnosis was 5.8 ± 2.3, 9.4 ± 2.5, and 13.9 ± 1.1 years, respectively. The female-to-male ratio was highest in the adolescent-onset group ( = .002). Clinical manifestations showed no significant age-related differences; however, musculoskeletal involvement increased with age, while neuropsychiatric symptoms and fever decreased. Lymphopenia was more frequent in the adolescent-onset group (60% vs 25.6%, = .016). Although disease activity and damage did not differ significantly across age groups, mortality was signficantly higher in the prepubertal group (16.5%) compared to the adolescent-onset group (2.9%) ( = .014).

Conclusion: This review underscores both similarities and differences in cSLE across age groups. Prepubertal onset was associated with higher mortality, emphasizing the need for timely diagnosis and early intervention in this subgroup.