Rheumatology Advance Access originally published online on July 4, 2006
Rheumatology 2006 45(9):1175-1176; doi:10.1093/rheumatology/kei248
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Successful treatment with leflunomide of arthritis in systemic sclerosis patients
Rheumatology Unit, University of Modena and Reggio Emilia and 1Rheumatology Unit, University of Pisa, Pisa, Italy
Correspondence to: C. Ferri, Cattedra e Servizio di Reumatologia, Università di Modena e Reggio Emilia, Policlinico di Modena, Via del Pozzo 71, 41100 Modena, Italy. E-mail: clferri{at}unimo.it
SIR, Systemic sclerosis (SSc) is a connective tissue disease clinically characterized by different degrees of skin fibrosis and visceral organ involvement [1]. Joint involvement with severe synovitis during SSc is relatively uncommon. About 11% of SSc patients present with arthritis at disease onset [2], usually characterized by mono-oligoarthritis, responsive to steroid therapy [3].
In some patients, arthritis is more aggressive; it can become erosive, simulating classical rheumatoid arthritis [1, 2]. Since leflunomide has been usefully employed in rheumatoid arthritis and other autoimmune systemic diseases [4–6], we undertook a preliminary investigation of the efficacy of this drug in patients with SSc complicated by active arthritis.
Three women with SSc, classified according to preliminary ACR criteria [7], were treated with leflunomide at the standard dosage of 20 mg/day (Table 1). In all patients arthritis had been unresponsive to other therapeutic attempts, including steroids, methotrexate, cyclosporin A and D-penicillamine. In two patients (cases 1 and 3) the articular involvement was asymmetrical and non-erosive, whereas the third (case 2) showed symmetrical and erosive polyarthritis with the presence of serum rheumatoid factor. This patient may be better classified as SSc/rheumatoid arthritis overlap syndrome. In no case was renal and/or hepatic involvement observed before or after the treatment. Leflunomide was well tolerated in all cases; only one patient developed moderate diarrhoea, which disappeared with the reduction of the leflunomide dosage to 20 mg every other day, without any relapse of arthritis. After few weeks of treatment, we observed resolution in cases 1 and 2 and a significant improvement in articular involvement in case 3, with normalization of inflammatory parameters; these variations remained stable after 1 yr of follow-up (Table 1).
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No significant modifications were observed for skin and visceral organ involvement in two of the three patients. Only one showed a reduction in the modified Rodnan skin score (from 25 to 14 after 1 yr of treatment) and a mild increase in lung carbon monoxide diffusion capacity (case 3).
Besides rheumatoid arthritis, leflunomide has been reported to be useful in some autoimmune diseases, such as systemic lupus erythematosus, Sjögren's syndrome and Wegener's granulomatosis [4–6]. Leflunomide is an isoxazole derivative with immunomodulating activity; it inhibits T-activated lymphocyte replication and reduces some cytokines, particularly IL-2 and TNF-
, that are probably involved in the early stages of scleroderma [8–10]. Many studies suggest that lymphocytes and cytokines play an important role in the pathogenesis of SSc; in particular, high levels of IL-2 and/or IL-2 receptor are observed in the early stages of the disease [9, 10]. According to its pharmacological activity, leflunomide could be usefully employed in SSc, particularly in patients with severe articular involvement.
In our patients, leflunomide was able to improve SSc-associated arthritis; it was well tolerated and in one case its efficacy persisted despite dosage tapering. Moreover, other SSc organ involvement remained stable in two cases, while skin sclerosis improved in the other one. On the whole, these data suggest the possible use of this drug in the SSc. This is the first study focusing on leflunomide in the treatment of SSc-associated arthritis; its actual efficacy should be ascertained in controlled trials including larger patient populations.
The authors have declared no conflicts of interest.
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