To analyze the clinical, radiological, therapeutic, and clinical outcomes of the leukodystrophy-like phenotype in neuropsychiatric systemic lupus erythematosus (NPSLE).

We conducted this systematic review following the Preferred Report Items for Systematic Review and Meta-analysis (PRISMA). We searched Pubmed, Embase, and Web of Science databases for articles published until May 31, 2025, using the terms “systemic lupus erythematosus” AND (“diffuse white matter lesions” OR “leukoencephalopathy” OR “leukodystrophies”). Additionally, we report five patients with leukodystrophy-like phenotype in early-onset NPSLE.

Thirty-three cases were reviewed. The mean age was 36.9 ± 14.9 years, and 28 (84.8%) were female patients. A previous diagnosis of SLE was present in 66% of cases. The main neurological symptoms included headache (33.3%), seizures (15.1%), and consciousness disturbances (15.1%). Among the 17 patients with cerebrospinal fluid (CSF) abnormalities, elevated protein levels were observed in 11 (40.7%) cases, and pleocytosis in 6 (22.2%). MRI findings were reported in 31 patients, typically showing cerebral white matter lesions characterized by hyperintense areas with T2-weighted or fluid-attenuated inversion recovery (FLAIR) sequences. Most patients were treated with high-dose corticosteroid pulse therapy (22/32), while others received cyclophosphamide pulses (18/32), therapeutic plasma exchange (PLEX) (4/32), or rituximab (6/32). Overall, the therapeutic response was satisfactory, with clinical improvement in 23 out of 33 patients.

In light of the severe clinical presentation of the leukodystrophy-like phenotype in NPSLE, early diagnosis and aggressive treatment are crucial for successful outcomes, as suggested by our review, which reported clinical improvement in 70% of patients. Future prospective studies are needed to confirm these findings.