Sir, we were interested to read the letter on the new agent, apremilast, that has proved to be effective in treating idiopathic oral ulcers, the main manifestation of Behcet's syndrome.1 Acting as a selective inhibitor of phosphodiesterase 4, apremilast may partially supress the production of pro-inflammatory cytokines, stimulating the production of the anti-inflammatory cytokine IL-10.2 However, the full mechanism of action is not clear and the bioreceptor for this compound has not been identified. A preliminary, phase 2 study3 (NCT00866359) was not designed to assess a long-term efficacy of apremilast and unfortunately, until now, this drug is not formally approved for the treatment of Behcet's disease. Currently pending, a phase-3 randomised, placebo-controlled study aims to evaluate the efficacy and safety of apremilast in about 200 patients with active Behcet's disease.4 Apremilast is a novel analogue of thalidomide and pregnancy should be excluded before pharmacological treatment is considered to be initiated.5

Cimetidine, a well known drug used for the treatment of stomach ulcers as an H2 inhibitor, can be effective as a therapeutic agent for selected forms of aphthous stomatitis.6 When used regularly it may prevent future episodes aphthous ulcerations associated with PFAPA syndrome7 and has immunomodulatory effects that include blocking suppressor T-cells and facilitating cell-mediated immunity.8

As aphthous ulcers may result from the patient's immune system reacting against the mucosal epithelium, the more common systemic use of immunomodulatory drugs would bring clinical benefits, reducing recurrence and symptoms of oral ulcers.