Recalcitrant, recurrent aphthous stomatitis successfully treated with adalimumab

Editor Recurrent aphthous stomatitis (RAS) is a chronic and debilitating disorder characterized by recurrent attacks of painful, erythematous ulcers covered by fibrin and surrounded by hyperaemic borders on the non-keratinized mucosa of the mouth. The aetiology is still not well understood, although one-third of patients have a positive family history. Furthermore, some patients may have an underlying disease, such as anaemia secondary to folic acid deficiency or cyclic neutropenia. The mainstay of treatment is topical therapy with anaesthetics, antiseptics, anti-inflammatories, tetracyclines, sucralfate or steroids. Nevertheless, these may not always suffice, and then systemic drugs are required, including colchicine, pentoxifylline, dapsone, steroids, thalidomide, azathioprine and methotrexate.1 We report a case of recalcitrant RAS with an impressive response to adalimumab. A 64-year-old man presented with a 26-month history of RAS. The lesions appeared on a 15-day basis, and healed within 7–12 days without scarring. They were painful and caused dysphagia, and were occasionally accompanied by fever. The patient denied any genital ulcers, as well as skin lesions and gastrointestinal or musculoskeletal symptoms. There was no history of trauma or food hypersensitivity. On physical examination, shallow erosions could be found on the floor of the mouth and buccal, soft palate, lower lip and oropharyngeal mucosae. They were minor and major in size, with fibrinous bases surrounded by erythematous halos. The rest of physical examination was otherwise normal. Complete blood count and biochemical profile were normal. No vitamin, iron or zinc deficiencies were found. Viral serologies, work-up for an associated autoimmune disease and pathergy test were all negative. No association with a certain human histocompatibility (HLA) surface antigen was found either. A biopsy specimen only revealed mucosal ulceration with non-specific inflammation. The patient’s condition was irresponsive to standard therapy, with only moderate improvement after 6-methylprednisolone boluses (Table 1). Hence, he was started on adalimumab 40 mg subcutaneously every other week in September 2007. Ever since the first dose, the patient experienced a dramatic improvement, with nearly all lesions clearing up. Complete remission was achieved following the second dose. After 5 months of follow-up, the patient remains free of aphtae and off any other medications aside from adalimumab. No adverse effects have been reported to date either. Recent data suggest that RAS may result from the cytotoxic effect of T cells on oral epithelial cells. In keeping with this, an increased expression of pro-inflammatory cytokines, tumour necrosis factor alpha (TNF-α) among them, have been observed in aphthous ulcer specimens compared with healthy controls.2 In fact, therapies that block TNF-α, such as pentoxifylline and thalidomide, have proved successful in treating RAS. Furthermore, the use of TNF-α monoclonal antibody blocking agents in RAS has been reported with success. The use of adalimumab yielded a complete remission in one patient, whereas partial improvement was achieved with etanercept in another one. RAS associated with Crohn’s disease has also been reported to dramatically improve with infliximab.3,4 Based on the in vitro evidence, and the previous use of anti-TNF therapies, we decided to try out adalimumab in our patient with an impressive outcome. To our knowledge, this is the second case of RAS responsive to adalimumab being reported. Should evidence continue, we believe that this agent may become an important therapeutic tool in the treatment of severe cases of RAS.