Thalidomide for aphthous ulcers in patients infected with the human immunodeficiency virus

Abstract

ACTG 251 confirmed the efficacy of thalidomide 200 mg/day for oral ulcers in HIV-infected patients. Thalidomide also appears to benefit most HIV- infected patients with aphthous ulcers of the esophagus or rectum. However, most of the available information is based on case reports and case series. None of these case reports has come from the United States, possibly because of the serious teratogenic consequences of thalidomide administration in the past and the restricted availability of thalidomide here. Aphthous ulcers are often diagnosed only after the exclusion of other treatable causes, including infection by bacterial, viral, and fungal pathogens. The first-line therapy for severe aphthous ulceration is systemic corticosteroids. However, these agents are contraindicated if an infectious process is present, since they may predispose the patient to worsening of the infection. It should also be noted that zalcitabine (dideoxycytidine) may cause ulceration of the lips and oral cavity within the first few months of therapy. The approach to ulceration in HIV-infected patients should include close visual examination, endoscopically if necessary. Cultures should be obtained from the lesions and histologic examination of samples obtained by biopsy performed to investigate for herpes simplex virus, cytomegalovirus, Candida species, and bacterial causes of infection, as well as for neoplastic processes. An empirical course of fluconazole and acyclovir or ganciclovir should be instituted. Often the empirical therapy precedes endoscopic evaluation and biopsy, but it should not precede culture of easily accessible lesions, such as those in the oral cavity or perianal region. If the empirical therapy produces no response and there is a lack of further diagnostic evidence of a cause treatable by other means, prednisone 0.5-1 mg/kg/day should be administered for two to four weeks. A decrease in pain may be noted within a few days, but ulcer healing should be confirmed visually. Only after all these measures have failed should thalidomide be considered. Approval in the United States for compassionate use of thalidomide may be obtained by filing an emergency treatment investigational new drug application with the FDA's Division of Antiviral Drug Products (301-443-9553). Patients who take thalidomide need to be educated about and monitored for somnolence, constipation, paresthesia, and rash. Also, the teratogenic potential of this drug must be explained to all patients. Pregnant women must never receive thalidomide. Women of childbearing potential must be using effective birth control. Patients must be instructed to not share thalidomide with others, especially young women. There must be strict accounting for all doses of the drug distributed. Informed consent recognizing all these precautions should be obtained. The optimal dosage of thalidomide for the treatment of aphthous ulcers is unknown. A dosage of 200 mg once daily at bedtime is reasonable. A response should be noted within a few days to weeks. An effort should be made to confirm the response, endoscopically if necessary. The optimal duration of therapy is also unknown. An initial course of four to eight weeks if the patient has a prompt response, or four to eight weeks after confirmed healing, is reasonable. A repeat course may be necessary should the patient relapse. Long-term uninterrupted maintenance therapy should be considered only for patients with very severe ulcerations or multiple recurrences.