Treatment Strategies for Recurrent Oral Aphthous Ulcers


Am J Health Syst Pharm. 2001;58(1) 

In This Article


An increase in T-helper cells (CD4+ cells) and a decrease in T-suppressor cells (CD8+ cells) may accompany RAU during periods of disease exacerbation and normalize during remission.[32] Levamisole is an immunopotentiating agent that has demonstrated the ability to normalize the CD4+ cell/CD8+ cell ratio and improve symptoms in RAU patients.[32] Correction of T-suppressor-cell deficiency may reduce the inflammatory response resulting from cellular immunity and promote resolution of aphthae.

Seven placebo-controlled clinical trials assessed the efficacy and safety of levamisole in patients with RAU (Table 2).[33,34,35,36,37,38,39] The RAU classification was reported for three of the seven trials.[33,34,38] More than 68% of the patients in these trials were diagnosed with minor RAU. The remaining studies did not categorize RAU but required at least one RAU episode per month. Use of concurrent drug therapies for RAU was prohibited in three trials.[34,36,39] Only two studies excluded drugs or diseases that might compromise immune function.[35,36] Levamisole was given either at the first sign of ulceration or prophylactically every one to two weeks. The trials lasted from six weeks to more than six months.

Four of the studies showed a reduction in the frequency and duration of aphthous ulcers during levamisole treatment, with ulcer recurrences decreasing by half in up to 43% of patients.[33,37,38,39] Efficacy did not differ whether levamisole was given routinely or started at the first sign of ulcers. In six trials, a complete absence of ulcers was found at the conclusion of the study in 16 of 144 patients receiving levamisole.[33,34,35,37,38,39] Follow-up of three of these studies[33,34,35,36,37,38] showed that 20 levamisole-treated patients were without ulcers for at least 103 days and that 4 patients were ulcer free for six months. In five trials, subjective improvement in a majority of patients taking levamisole was reported.[33,34,35,36,37] The disparity between subjective and objective responses evident in several trials was not discussed. In one trial, the subjective evaluations were performed by the investigator and may have differed from patient assessments.[36] Additionally, unidentified concurrent medications and illnesses may have altered patient perceptions of subjective improvement in the frequency and duration of ulcers.

Levamisole was well tolerated in a majority of the patients. Among 128 patients receiving levamisole, 2 withdrew as result of adverse effects (nausea and flu-like symptoms). The most frequent adverse effects were dysgeusia (21%) and nausea (16%). The other adverse effects occurred in fewer than 10% of the patients and included dysosmia, headaches, diarrhea, influenza-like symptoms, and rash. Some of these events occurred only on the days of treatment, and many may not have been attributable to levamisole.


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