Treatment of recalcitrant orogenital ulceration of Behçet's syndrome with infliximab

Sir, The recurrent oral and genital ulceration of Behçet's syndrome (BS) can be very distressing and is associated with considerable physical and psychological morbidity. We describe a case of Behçet's syndrome in a 65‐yr‐old woman whose orogenital ulceration was unresponsive to a wide range of topical and systemic treatments. Treatment with infliximab, a chimeric anti‐tumour necrosis factor α (anti‐TNF‐α) monoclonal antibody, in May 2000 resulted in the patient being free from ulceration for the first time in 10 yr.

A 48‐yr‐old woman was diagnosed with BS in 1983 on the basis of recurrent oral and genital ulceration for 2 yr, a 9‐month history of arthralgias affecting her elbows, wrists and fingers, several episodes of erythema nodosum and a positive pathergy test. Her tissue type was HLA A2, A11, B12(W44), B15(W62). Additional features seen over the subsequent years were thrombophlebitis of her legs in 1986 and synovitis of the left ankle in 1991. Her orogenital ulceration was initially treated with topical triamcinolone acetate, which had little effect. Oral thalidomide, dapsone, azathioprine, colchicine and cyclosporin were also tried over the subsequent years but they were either ineffective or resulted in intolerable side‐effects at therapeutic doses. In 1998 she developed a hoarse voice in conjunction with a fresh crop of oral ulcers. Nasolaryngoscopy showed there to be healed ulceration of the nasopharynx, but the pharynx and larynx appeared normal.

By March 2000, aged 65 yr, her orogenital ulceration had become very active despite oral doses of colchicine at 0.5 mg t.d.s., which also produced severe diarrhoea. There has recently been a case of BS with severe colitis and orogenital ulceration responding dramatically to treatment with infliximab, a chimeric anti‐TNF‐α monoclonal antibody (S. Travis, personal communication). As all other therapeutic avenues had been explored with very limited success it was decided, after full discussion with the patient, to initiate treatment with infliximab.

As 5 mg/kg infusion was given on three occasions at 0, 2 and 6 weeks. There was a marked improvement in both the oral and genital ulceration after the first infusion. By the time the third infusion was complete the patient was free from ulcers for the first time in 10 yr, which to date has been sustained.

T‐cell‐mediated immune responses are thought to play a major part in the immunopathogenesis of BS. Recently attention has been focused on the role of γδ T cells, which are thought to be involved in immunity at mucosal and epithelial surfaces. Increased numbers of γδ T cells in the peripheral blood of patients have been reported [1, 2]. Similar findings have been found in patients with recurrent aphthous stomatitis (RAS), in which the oral mucosa is the only site of ulceration [3]. It has been demonstrated recently that the γδ T cells in BS are activated in vivo and produce large amounts of TNF‐α [4]. This has been confirmed by another study, which found that γδ T cells in BS produce increased amounts of TNF‐α and interferon γ (IFN‐γ) compared with healthy controls, whereas in RAS only IFN‐γ production is increased [5]. This indicates that there is a qualitative difference between the γδ T cells in BS and RAS and also provides evidence as to why such dramatic therapeutic effects should occur when BS is treated with anti‐TNF‐α.

Therefore, we believe that anti‐TNF‐α therapy should be further investigated for its potential therapeutic use in the recalcitrant orogenital ulceration of BS when conventional modes of treatment have been unsuccessful in suppressing this often distressing and painful aspect of the condition.

Correspondence to: L. P. Robertson.