Recent advances in the management of pediatric neuropsychiatric lupus from conventional therapies to novel immunomodulators.

Abstract

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a severe and potentially life-threatening complication of systemic lupus erythematosus (SLE), particularly in pediatric populations, in whom central nervous system involvement is often more aggressive and associated with long-term neurocognitive sequelae. Diagnosis remains challenging due to heterogeneous clinical manifestations and the lack of specific biomarkers. Traditionally, management has relied on high-dose corticosteroids, intravenous cyclophosphamide, and plasma exchange for refractory cases. However, emerging evidence supports the potential role of targeted immunomodulatory therapies, including rituximab, belimumab, anifrolumab, and emerging B-cell-directed strategies, although pediatric NPSLE-specific evidence remains limited. Novel agents such as type I interferon inhibitors, JAK inhibitors, and BTK inhibitors are currently under investigation in both adult and pediatric populations, offering the promise of more precise and less toxic interventions. This review summarizes current diagnostic approaches, first- and second-line therapies, and recent advances in biologic and small-molecule therapies for pediatric NPSLE. We also highlight ongoing clinical trials and future directions, emphasizing the importance of early recognition, multidisciplinary management, and the development of pediatric-specific guidelines. As understanding of the immunopathogenesis of NPSLE evolves, personalized therapeutic strategies may substantially improve long-term neurological and developmental outcomes in affected children.