Rituximab in Granulomatosis with Polyangiitis: Challenging Equilibrium Between Therapeutic Efficacy and Iatrogenic Complications

Background: Granulomatosis with Polyangiitis is a renal-pulmonary syndrome that is treated with aggressive immunosuppressive therapy including high dose corticosteroids, cyclophosphamide, and plasmapheresis. Rituximab is also effective in inducing remission. Excess of immune suppressors may provoke generalized infections. Ultimate objective of therapy is to find equilibrium between the aggressive disease and avoidance of severe adverse effects of immune suppressors. Case presentation: We report a patient affected by rapidly evolving granulomatosis with polyangiitis, characterized by dialysis-dependent acute renal failure. The initial therapy based on high dose corticosteroids, oral cyclophosphamide and plasmapheresis was ineffective, while two infusions of 1 g of rituximab 15 days apart were effective in inducing remission. A few days after the second rituximab infusion, the patient presented cardiac arrest and tonic-clonic seizures and was admitted to the ICU. Brain MRI showed a severe and diffuse leukoencephalopathy that indicated a severe prognosis. A progressive multifocal leukoencephalopathy (PML) was excluded, since JC virus in liquor resulted negative. After a few days from the ICU admission, the patient showed a rapid clinical improvement, and was discharged a few weeks later with a mild residual renal insufficiency and complete disappearance of the neurological signs and normalization of the brain MRI pattern. Conclusion: In this case, it is uncertain whether the neurological and cardiac complications were a consequence of rituximab infusion or represented an evolution of the vasculitis. Anti-CD20 mab can be very effective in inducing remission of granulomatosis with polyangiitis; however, the exact dose regimen and interval between administrations need to be established.