Neuropsychiatric Systemic Lupus Erythematosus in Children: A Scoping Review

Neuropsychiatric systemic lupus erythematosus (NPSLE) presents significant diagnostic and therapeutic challenges, particularly in childhood-onset SLE (cSLE), as there is limited pediatric-specific evidence, lack of specific diagnostic tests, and heavy reliance on adult data. This scoping review, the first dedicated specifically to the pediatric population, aims to evaluate the current literature on NPSLE in cSLE (cNPSLE), grade the level of evidence, and identify knowledge gaps in knowledge related to its manifestations, diagnosis, predictors, treatment and outcomes.

A search was performed in MEDLINE, Embase, Cochrane, and PsycINFO (PRISMA diagram). Articles were screened in Covidence. Clinical trials, systematic reviews, cohort, case-control and cross-sectional studies published between 2000 and 2023, involving patients aged ≤18 years diagnosed with NPSLE, and with original manuscript available in English were included. Five reviewers performed abstract and full-text screening. Eight reviewers performed full-text extraction. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology.

Sixty-five articles met eligibility criteria. Prevalence of cNPSLE ranged from 4.4% to 99.8%. Sociodemographic information was based on individual study metrics. Predictive factors for cNPSLE development were the most studied but were contradictory from study to study. Most frequent clinical manifestations were cognitive dysfunction, headaches and seizures. Common imaging findings were cerebral and cerebellar volume loss and white matter hyperintensities, though up to 50% of patients with active cNPSLE had normal imaging in 4 included studies. No pharmacologic clinical trials for cNPSLE are published. Outcomes from cNPSLE were variable.

This scoping review highlights the scarcity of articles on cNPSLE and identifies significant knowledge gaps. The 1999 ACR NPSLE case definitions, while providing a framework for classifying NPSLE, are not formally validated in children, resulting in heterogeneity in existing cNPSLE research and diagnostic criteria. Per the GRADE methodology, most studies were retrospective, single center, with low quality of evidence. The range in prevalence and frequency of cNPSLE manifestations highlights the lack of consensus in cNPSLE definition and evaluation as well as the heterogeneity of study populations. We highlight the need for high quality studies and consensus regarding cNPSLE definition, diagnosis, and management - a critical first step to guide the development of an international, multi-center prioritized research agenda for cNPSLE.