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Recurrent oral and genital aphthous ulcerations are the hallmarks of Behçet’s disease. Up to now the various clinical manifestations in Behçet’s disease have been treated with limited success. Recently, clinical observations have reported dramatic responses on clinical signs and symptoms in patients treated with tumour necrosis factor α (TNFα) blocking drugs, including severe mucocutaneous,1–3 gastrointestinal4,5 and ocular manifestations.6
We report the successful treatment with infliximab of a severe longstanding genital ulcer in a patient with Behçet’s disease.
The patient was a 29 year old woman with Behçet’s disease who had had recurrent oral ulcers from age 5 and genital ulcers, arthralgia, and uveitis from age 23. The outbreaks of uveitis were treated with local administration of dexamethasone only. From autumn 2000 the severity of the genital manifestations increased, and treatment with colchicine and prednisolone was started. However, during follow up she still had painful recurrent oral and genital ulcers. In December 2001 she had a new outbreak of a severe genital ulcer located at the left labium majus. No sign of spontaneous improvement was seen, and high dose prednisolone treatment (60 mg a day) was started in spring 2002. In summer, partial remission on per oral corticosteroid treatment had been achieved, but the painful ulcer was still present. During the following months the genital ulcer deteriorated despite high dose prednisolone treatment (initially 60 mg, which had to be reduced to 40 mg because of mental symptoms). In December 2002 treatment with azathioprine, 50 mg twice a day, was started in addition to prednisolone 30 mg daily. Treatment with azathioprine was stopped after 2 weeks because of a respiratory infection. Although non-selective immunosuppressive drugs—for example, thalidomide, azathioprine, and cyclosporin A, had not been tested sufficiently as monotherapy or in combination, we decided to treat her with infliximab, after full discussion and consent. This decision was judged justified owing to, firstly, the severe longstanding physical and psychological burden for the patient, secondly, to reports on successful treatment of genital ulcers with infliximab in Behçet’s disease,1–3 and, thirdly, to lack of response to high dose long term prednisolone treatment. The infliximab dose 5 mg/kg body weight infusion was given on four occasions at baseline, and after 2, 6, and 15 weeks. The fourth infusion, planned at 12 weeks’ follow up, was postponed owing to sinusitis treated with penicillin. No other possible infliximab side effects occurred. During treatment her general well being and fatigue improved.
At the time of the first infusion the ulcer was deep and had a diameter of 19 mm (fig 1A). After one infusion, at 2 weeks’ follow up, a marked improvement was seen (fig 1B), and at 6 weeks’ follow up, 4 weeks after the second infusion, only a scar of the ulcer was left (fig 1C). At 2 months’ follow up after the fourth infusion the patient was still in remission.
Recently, preliminary results from a double blind, placebo controlled study were presented on the effect of etanercept, another TNF blocking drug, on mucocutaneous manifestations in Behçet’s disease.7 In this 4 week study eight (40%) of the 20 etanercept treated patients achieved clinical remission of mucocutaneous manifestations compared with one (5%) patient in the 20 placebo treated patients.7 Interestingly, in the case by Estrach et al,3 the orogenital ulcerations in a patient with Behçet’s disease responded dramatically to treatment with infliximab after failure of etanercept. This raises the interesting question as to whether there is a difference in the efficacy in Behçet’s disease between etanercept (soluble receptor binding TNFα and -β) and infliximab (monoclonal antibody binding TNFα), drugs known to bind TNFα in different ways.
The experience so far with TNFα blocking treatment in Behçet’s disease is scarce as recently reviewed by Sfikakis.8 So far, significant side effects with the use of TNFα blocking drugs in Behçet’s disease have not been reported.8
Further clinical studies, especially double blind, randomised controlled trials designed with sufficient power are warranted before final conclusions can be drawn about the efficacy of treatment with TNFα blocking agents compared with conventional immunosuppressive agents.
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