Symmetric leukoencephalopathy associated with systemic lupus erythematosus: A systematic review of a distinctive neurorheumatologic syndrome

•Systemic lupus erythematosus can present with a distinct neurologic phenotype of symmetric leukoencephalopathy (SLE-SLE, or 2SLE), either with or without severe systemic manifestations.•2SLE can be the first presentation of SLE, and so should be suspected when this radiographic phenotype is seen regardless of patient medical history.•SLE should be excluded in any patient in whom a diagnosis of CLIPPERS is being considered.•When the imaging pattern of 2SLE is seen we recommend prompt initiation of immunomodulatory therapy in patients with known SLE, and systemic rheumatologic diagnostics in addition to neurologic autoimmune workup in patients without known SLE. A symmetric leukoencephalopathy can occur in the context of systemic lupus erythematosus (SLE), often as a first manifestation of underlying rheumatologic disease. Recognition of this distinctive syndrome can prompt investigation for SLE when undiagnosed, or prompt treatment initiation when the diagnosis is already known. Earlier recognition of this syndrome could lead to more effective treatment of the disease. Clinical, laboratory, and radiographic features of three patients were described from an academic medical center in the United States with treatment dates between 2015 and 2022. A systematic review of literature from 1991 to 2023 yielded data for an additional 23 patients. Twenty-six total patients with symmetric leukoencephalopathy were included in this study. The median age of the patients was 37 years (range 10–69), 22 patients (85 %) were female, and 4 (15 %) were male. Fourteen of 26 patients (54 %) had this as the first clinical manifestation of SLE. Contrast enhancement was present on MRI brain in 3/26 (88 %) patients. Twenty patients (77 %) were treated with pulse-dose steroids, and all but one patient received some immunomodulatory therapy. Seven patients (27 %) progressed to death. No meaningful predictive differences were found between patients who survived and those who did not. In this case series and literature review patients developed symmetric leukoencephalopathy in systemic lupus erythematosus most often as the first clinical manifestation of SLE. Clinicians should consider this syndrome in any patient with acute onset of symmetric leukoencephalopathy on brain magnetic resonance imaging.