Neuropsychiatric lupus: clinical challenges, brain-reactive autoantibodies and treatment strategies

Neurological manifestations in lupus can be due to active lupus disease affecting the brain or to other reasons. Reversible posterior leucoencephalopathy syndrome, primary lymphoma of the central nervous system, cerebral infections by bacteria (e.g. mycobacteria), viruses (e.g. JC virus), fungi (e.g. Cryptococcus) and parasites (e.g. Acanthamoeba), steroid-induced psychosis and reactive depression need to be excluded. Brain-reactive autoantibodies have been described as associating with neuropsychiatric lupus. The strongest associations described to date are with antiribosomal P protein and antiphospholipid antibodies. However these autoantibodies have not been shown to play significant roles in the pathogenesis. Treatment strategy for severe neuropsychiatric lupus include establishing definitive diagnosis, early identification and treatment of aggravating factors, appropriate symptomatic treatment, adequate immunosuppression, selective B-cell depletion and autologous haematopoietic stem cell transplant. Systematic reviews have shown that cyclophosphamide administration is superior to pulse methylprednisolone as a maintenance therapy. Mycophenolate mofetil has been shown to have modest effect and should only be considered if cyclophosphamide cannot be administered.