Sir, because mouth ulceration has a wide range of causes, treatment is most likely to be effective if based on the diagnosis. Aphthous ulceration is common but generally poorly responsive to antibiotics and antipyretics, and the range of agents trialled is testimony to their low efficacy.1

Some ulceration that clinically mimics aphthae is serious and the differential diagnosis in a patient with oral ulceration and systemic lesions, such as genital ulceration, accompanied by fever, skin rashes and arthritis includes the possibility of aphthous-like ulceration2 such as seen in Behcet syndrome3 or other auto-inflammatory diseases.2 These are disorders of innate immunity characterised by an exaggerated inflammatory response in the absence of autoantibodies or any identifiable infection which manifest as recurring ulcers but closer scrutiny will reveal episodes of fever and systemic inflammation affecting other mucosae, skin and joints – and with raised inflammatory markers such as the erythrocyte sedimentation rate.4 These disorders may show dramatic responses to systemic anti-inflammatory agents such as corticosteroids, colchicine, thalidomide or biologics5 but unfortunately adverse effects – some serious – are possible with these agents.

Now a new agent apremilast, currently used in psoriasis, has appeared to give some hope at least in Behcet syndrome6 and has proved effective in treating oral ulcers, the cardinal manifestation of Behcet syndrome. Whether apremilast could be beneficial in aphthous ulceration is unclear as yet but this possible advance, appearing in the medical literature, should also be flagged up to the dental world. Apremilast specifically inhibits phosphodiesterase-4 inhibitor (PDE) that hydrolyses cyclic adenosine monophosphate (cAMP) within immune cells and thus modulates several inflammatory pathways and inhibits spontaneous production of tumor necrosis factor-alpha (TNF). Inhibition of PDE4 blocks hydrolysis of cAMP, thereby increasing levels of cAMP within cells of the immune system and CNS. Adverse effects may include weight loss and depression. More extensive evidence of efficacy in mouth ulceration is keenly awaited.