PURPOSE: Central nervous system (CNS) sarcoidosis often confers substantial morbidity and may cause death. Treatment of severe CNS sarcoidosis typically requires aggressive immunosuppression, but the optimal regimen is unknown. Cyclophosphamide (CYC) is generally reserved for cases refractory to steroids and/or methotrexate (MTX). Infliximab, a monoclonal tumor necrosis factor inhibitor, has also been used anecdotally in these patients. The relative efficacy of these medications is unclear.
METHODS: We recently observed dramatic responses to infliximab in 4 patients with severe CNS sarcoidosis failing CYC and steroids. All four had evidence of disease progression at the time of initiating infliximab. CNS manifestations in the cohort included: severe bilateral optic neuritis with complete loss of vision in one eye; extensive intra-and extradural cervical spine inflammatory mass causing left arm paresis, with concomitant basal meningitis and 6th cranial nerve involvement; meningitis with cranial wound dehiscence leading to severe headaches, paresthesias, vertigo, and cognitive impairment; and retro-orbital inflammatory mass with extension into the cranium associated with significant hemicranial paresthesias and proptosis. Three of the patients had failed treatment with steroids + MTX prior to CYC. Despite treatment with steroids and escalating doses of intravenous or oral CYC, all patients experienced progression of their disease. At the time infliximab was started, the patients had received 6.3-13.5 gm of CYC, and were also using Prednisone 20-40 mg daily. Infliximab 5mg/kg IV at 4-week intervals and methotrexate were initiated.
RESULTS: All patients experienced rapid and dramatic clinical improvements, with three improving between 2-4 weeks, and all patients by the 4th infusion. The response was quicker than would be expected for MTX. All patients were able to taper corticosteroids substantially early in the treatment course. Follow-up magnetic resonance imaging demonstrated marked resolution of radiologic disease, coinciding with the clinical improvement.
CONCLUSION: Review of our experience with these four patients with CNS sarcoidosis suggests that a regimen including infliximab may be more efficacious than CYC.
CLINICAL IMPLICATIONS: There is a need for prospective studies of infliximab in the treatment of CNS sarcoidosis.
DISCLOSURE: Karla Pearson, No Financial Disclosure Information; No Product/Research Disclosure Information