Rheumatology Advance Access originally published online on April 14, 2008
Rheumatology 2008 47(6):929-930; doi:10.1093/rheumatology/ken129
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Successful treatment of rheumatoid vasculitis-associated cutaneous ulcers using rituximab in two patients with rheumatoid arthritis
Department of Internal Medicine I, Division of Immunology and Rheumatology, University of Cologne, Cologne, Germany
Correspondence to: M. Hellmann, Department of Internal Medicine I, Division of Immunology and Rheumatology, University of Cologne, 50937 Cologne, Germany. E-mail: matthias.hellmann{at}uk-koeln.de
SIR, The course of RA may be complicated by rheumatoid vasculitis (RV), at least in a subset of patients who typically present with high titres of RFs [1]. RV has a predilection for the skin and may result in peripheral gangrene and deep cutaneous ulcers that tend to occur in unusual locations. Treatment mainly consists of the use of high-dose corticosteroids in addition to DMARDs, but controlled clinical trials are missing [2]. More recently, the successful use of TNF inhibitors in selected patients has been reported [3]. The use of rituximab (RTX), a monoclonal antibody that selectively targets CD20+ B cells, has resulted in significant improvement of articular symptoms in patients with active RA [4, 5] and is currently licenced for patients previously failing a TNF inhibitor. Small series and case reports have been published suggesting that RTX may be effective in ANCA-associated vasculitis and cryoglobulinaemia [6, 7]. However, the efficacy of RTX in patients with severe RV is largely unknown.
We here report on the successful use of RTX in two patients with severe refractory RV as a complication of long-standing RA.
A 65-yr-old white female with a 15-yr history of erosive seropositive RA received prednisolone (10 mg/day), NSAIDs and MTX (15 mg/week). A deep cutaneous ulceration close to her elbow (Fig. 1a) had persisted for more than 24 months. RV was diagnosed while other causes of cutaneous ulcers were excluded. The ESR was elevated to 64 mm/h and titres of RF were 826 kU/l and anti-CCP antibodies were 423 RE/ml, respectively. As the patient reported a history of recurrent soft tissue infections, we decided against the use of a TNF inhibitor.
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While MTX and steroids were continued, the patient received two infusions of 1000 mg RTX at a 2-week interval without any side-effects. During the following weeks, the vasculitic lesions started to heal and resolved completely within 5 months (Fig. 1b). In addition, articular symptoms improved with the 28-joint disease activity score (DAS28) decreasing from 5.05 to 2.97 at week 16, when the patient showed complete depletion of her peripheral B cells as determined by minimal residual disease flow cytometry (MRD-FLOW) as defined elsewhere [8]. ESR returned to normal and corticosteroids were slowly tapered.
The second patient is a 61-yr-old white female who was referred to us with severe erosive seropositive RA of 12-yr duration and a history of malignant melanoma. Her present medication consisted of oral prednisolone (10 mg/day), MTX (10 mg/week) and NSAIDs. Etanercept had previously been stopped after 12 months for inefficacy. At initial presentation, the patient had a DAS28 of 7.2 and several vasculitic ulcers of her legs (Fig. 1c). RV was confirmed by histopathology. Her ESR was elevated to 75 mm/h and titres of RF were 3070 kU/l. MTX and steroids were continued and two doses of 1000 mg RTX were given 2 weeks apart and well tolerated without any side-effects. During the subsequent 7 months, the vasculitic lesions of the lower limb resolved completely (Fig. 1d) in addition to the decreased DAS28 of 5.8. By week 16, the patient showed a complete depletion of peripheral B cells as determined by MRD-FACS. Retreatment with RTX was performed at week 24, resulting in a DAS28 of 4.1 after another 16 weeks. Finally, the ESR returned to almost normal (23 mm/h), titres of RF decreased to 256 kU/l and prednisolone was slowly tapered to 5 mg daily.
In patients with long-standing RA, RV may develop as a complication potentially involving skin, eyes or visceral organs. Despite the availability of a wide range of new and potent drugs for the treatment of RA, no evidence-based therapeutic guidelines for the management of RV have been developed and treatment therefore remains largely empirical. Although the successful use of TNF inhibitors in patients with RV has been reported [3], alternative treatment options for patients who are unresponsive or not eligible for TNF blockers are needed. Reports on the use of RTX in RV are rare. Recently, a patient with RV-associated foot drop was successfully treated with RTX [9]. Preliminary data from the French registry also suggests that RTX may represent a therapeutic option in patients suffering from RV [10].
In summary, we reported on two patients with long-standing RA suffering from severe RV-associated cutaneous ulcers who did not respond to conventional DMARD and steroid treatment. The course of these patients indicates the potential efficacy of RTX in improving both RV and articular symptoms as demonstrated by complete healing of ulcers within a few months and a concomitant decrease in DAS28. Although more research and clinical data is required to more fully delineate the role of RTX in patients with extra-articular RA manifestations. RTX may at present represent a suitable therapeutic option in patients who do not respond to TNF inhibitors or in whom TNF blockade is contraindicated.
Disclosure statement: The authors have declared no conflicts of interest.
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