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February 2002
Major aphthous ulcer
Major aphthous ulcers are large (1 to 3 cm), painful ulcers that may be either solitary or multiple. They can occur anywhere in the oropharynx or elsewhere in the gastrointestinal tract of the HIV-infected child or adult. The lesions frequently heal slowly, if at all, over a period of weeks or months. The pathogenesis of aphthous ulcers is poorly understood. No specific infectious agent has been identified. Stress, vitamin deficiency, allergies, hormonal changes, diet, trauma, viral infection, and immune dysfunction have been implicated as precipitating factors. Bacteria may play a role in the progression of lesions. A negative correlation between tobacco use and the incidence of aphthous ulcers has been noted. It has been postulated that tobacco by-products increase keratinization of oral mucous membranes, thereby protecting against ulceration.
It is important to consider the broad array of infectious and non-infectious causes of oral ulcers in the HIV-infected child before making a presumptive diagnosis of aphthous ulcers and initiating therapy. Appropriate cultures should be obtained. Biopsy and histopathologic examination of tissue may be necessary in some cases.
Iatrogenic disease should be considered in the HIV-infected child with oral ulcers. Ulcers can result from prolonged granulocytopenia induced by myelosuppressive medications (e.g., zidovudine or ganciclovir). A high percentage of adults and children who receive zalcitabine (dideoxycytidine, ddC) therapy develop aphthous-like oral ulcers. This is a potentially debilitating and dose-limiting complication of therapy. If drug-induced oral ulcers are a consideration, temporary discontinuation or reduction in dose of the possible offending agent may be warranted. In the case of ulcers caused by zalcitabine, alternative antiretroviral therapy occasionally is necessary.
Recurrent aphthous ulcers generally are treated by application of topical steroids. Use of these agents with an oral base can enhance pain control and reduce dosing frequency. Fluocinonide ointment, 0.05 per cent, mixed 1:1 with Orabase (carboxymethylcellulose sodium in plasticized hydrocarbon gel), is commonly employed. It can be applied to ulcers four to six times daily. Miles' mixture, a liquid preparation containing tetracycline, hydrocortisone, and viscous lidocaine in Orabase, with nystatin added for Candida prophylaxis, has been recommended for treatment of adults with major aphthous ulcers. Older children also might be candidates for this therapy, but use of tetracycline and viscous lidocaine in young children is potentially problematic.
Because major aphthous ulcers tend to occur in the posterior oropharynx, topical application of any preparation can be difficult in young children. We have successfully treated several children using steroids intended for nasal inhalation (e.g., beclomethasone dipropionate, one or two puffs on to the area of the lesion three times daily). Parents generally can be instructed on the administration of the medication at home using a standard metered dose inhaler and a tongue blade, if necessary. Intralesional steroid injections or systemic steroid therapy (e.g., prednisone, 2 mg/kg/day in four divided doses) may be necessary if there is no response to topical steroid therapy. The usual duration of full-dose systemic therapy is about five to seven days, with a gradual tapering of the dose over the ensuing two weeks. Relapse is common following discontinuation of therapy.
Recent reports suggest that thalidomide may be useful in the therapy of refractory aphthous ulcers in HIV-infected adults. In one report, 19 of 20 patients responded subjectively and objectively to thalidomide, given in a dose of 200 mg per day for 14 days. There is no published information on use of the drug in HIV-infected children.
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