Successful treatment of rheumatoid vasculitis-associated foot drop with rituximab

Sir, B-lymphocyte depletion with rituximab, either alone or in combination with cyclophosphamide or methotrexate, has been shown to have efficacy in rheumatoid arthritis [1]. Rituximab has also been used as an alternative agent for anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis [2, 3] and for giant cell arteritis [4]. We report our experience in using repeated courses of rituximab in a patient with severe refractory rheumatoid arthritis, complicated by vasculitis, who was unable to tolerate conventional disease modifying antirheumatic drug (DMARD) therapy and did not respond to other biological therapy. A 68-year-old white male presented with symmetric synovitis of both wrists, of the metacarpophalangeal and proximal interphalangeal joints of both hands, and synovitis of the right knee, associated with a rheumatoid factor of 495 IU/ml. Because of his history of a past liver biopsy showing non-specific inflammation and focal fibrosis, he was unable to take methotrexate or leflunomide. Multiple DMARD agents including sulfasalazine, plaquenil, etanercept and anakinra were tried, but the patient failed to respond. During this time, he lost approximately 35 pounds and 7 months after diagnosis, developed a left foot drop. Biopsy of the sural nerve showed necrotizing vasculitis; ANCA and cryoglobulins were negative. Cyclophosphamide at 75 mg daily and high dose prednisone were started, but he developed febrile neutropenia requiring discontinuation of cyclophosphamide. Azathioprine at 75 mg daily was tried, but caused severe leucopenia and was discontinued. Rituximab at 700 mg weekly for 4 weeks for a total dose of 2800 mg was given to the patient along with a daily dose of 40 mg prednisone; he tolerated this well without leucopenia and with resolution of synovitis, and his erythrocyte sedimentation rate (ESR) declined from 100 to 35 mm/h. Despite continuation of prednisone at 30–35 mg daily, 5 months later, he developed recurrence of his synovitis, peripheral-oedema and hypoalbuminaemia, with an increase in his ESR to 62 mm/h and an increase in the rheumatoid factor (RF) to 6810 IU/ml. He was treated with a second 4-week course of rituximab, and responded well with resolution of his synovitis and oedema and normalization of his serum albumin. Prednisone was slowly tapered, and the ESR normalized to 12 mm/h and RF declined to 2970 IU/ml over the course of 6 weeks. After another 3 months, however, he again developed synovitis, elevation in his ESR to 75 mm/h and the appearance of new nodules on his forearms. His RF, however, was lower at 1690 IU/ml. Rituximab was reinstituted with the same weekly regimen and he again responded well, though he was noted to have a rash after the third infusion, which resolved without treatment. Three months after the third course, the ESR was 30 mm/h, RF was 484 IU/ml, and he was without synovitis and had regained the strength in his left foot affected initially by the vasculitis-associated foot drop.