|Clinical Guide > Comorbidities and Complications > Candidiasis|
Candidiasis, Oral and Esophageal
Guide for HIV/AIDS Clinical Care, HRSA HIV/AIDS Bureau
Oropharyngeal candidiasis ("thrush"), a fungal disease of the oral mucosa and tongue, is the most common intraoral lesion among persons infected with HIV. In the absence of other known causes of immunosuppression, oral thrush in an adult is highly suggestive of HIV infection. Although thrush in the absence of esophageal disease is not an AIDS-defining condition, it usually occurs with CD4 counts of <200 cells/µL. Three clinical presentations of thrush are common in people with HIV: pseudomembranous, erythematous, and angular cheilitis. Candida also may infect the esophagus in the form of esophageal candidiasis, which causes dysphagia (difficulty with swallowing) or odynophagia (pain with swallowing). Esophageal candidiasis is an AIDS-defining condition, generally occurring in individuals with CD4 counts of <200 cells/µL. It is the most common cause of esophageal infection in persons with AIDS.
Oropharyngeal and esophageal candidiasis are caused most commonly by Candida albicans, although non-albicans species increasingly may cause disease and may be resistant to first-line therapies.
The patient may complain of painless white patches on the tongue and oral mucosa, smooth red areas on the dorsal tongue, burning or painful areas in the mouth, a bad or unusual taste, sensitivity to spicy foods, or decreased appetite.
The patient complains of difficulty or pain with swallowing, or the sensation that food is "sticking" in the retrosternal chest. Weight loss is common, and nausea and vomiting may occur. Fever is not common with candidal esophagitis and suggests another cause. The patient may note symptoms of oral candidiasis (as above).
Perform a thorough oropharyngeal examination. Patients presenting with oral candidiasis may be totally asymptomatic, so it is important to inspect the oral cavity thoroughly. Patients with esophageal candidiasis usually have oral thrush and often experience weight loss.
Lesions can occur anywhere on the hard and soft palates, under the tongue, on the buccal mucosa or gums, or in the posterior pharynx.
Pseudomembranous oral candidiasis appears as creamy white, curdlike plaques on the buccal mucosa, tongue, and other mucosal surfaces. Typically, the plaques can be wiped away, leaving a red or bleeding underlying surface. Lesions may be as small as 1-2 mm, or they may form extensive plaques that cover the entire hard palate.
Erythematous oral candidiasis presents as one or more flat, red, subtle lesions on the dorsal surface of the tongue or the hard or soft palate. The dorsum of the tongue may show loss of filiform papillae.
Angular cheilitis causes fissuring and redness at one or both corners of the mouth and may appear alone or in conjunction with another form of oral Candida infection.
A partial differential diagnosis for the two conditions is as follows:
Clinical examination alone usually is diagnostic. If the diagnosis is unclear, organisms may be detected on smear or culture if necessary.
A presumptive diagnosis usually can be made with a recent onset of typical symptoms, especially in the presence of thrush, and empiric antifungal therapy may be started as a diagnostic trial. If the patient fails to improve clinically after 3-7 days of therapy, endoscopy should be performed for a definitive diagnosis.
Oral or esophageal candidiasis that does not improve after at least 7-14 days of appropriate antifungal therapy can be considered refractory to treatment. The primary risk factors for development of refractory candidiasis are CD4 counts of <50 cells/µL and prolonged, chronic antifungal therapy (especially with azoles). In such cases, it is important to confirm the diagnosis of candidiasis. As noted, other infections such as HSV, CMV, and aphthous ulcerations can cause similar symptoms. Once refractory candidiasis is confirmed, several treatment options are available, including the following:
The choice of treatment depends upon anticipated drug-drug interactions, the patient's preferences and tolerability, availability of medications, and the provider's experience. Consult with an HIV or infectious disease expert for advice about treatment regimens.
Use caution when considering chronic maintenance therapy, because it has been associated with refractory and azole-resistant candidiasis, as noted above. Fluconazole 100 mg PO daily or TIW or itraconazole oral solution 200 mg PO daily can be effective for patients who have had multiple or severe recurrences of oral disease (azole sensitive). Fluconazole 100-200 mg PO daily or posaconazole 400 mg PO BID (see Potential ARV Interactions," below) can be considered for patients who have had frequent or severe recurrent esophageal candidiasis.
There are no data to guide this decision; it is reasonable to discontinue maintenance therapy in patients who achieve immunologic responses on fully suppressive ART (i.e., with an increase in CD4 count to ≥200 cells/µL). Patients with fluconazole-refractory oropharyngeal or esophageal disease who respond to IV echinocandins are recommended to take posaconazole or voriconazole suppression until they achieve immune reconstitution on ART, because of high relapse rates.
Potential ARV Interactions
There may be significant drug-drug interactions between certain systemic antifungals, particularly itraconazole, voriconazole, and posaconazole, and ritonavir-boosted protease inhibitors (PIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), or maraviroc. Some combinations are contraindicated and others require dosage adjustment of the ARV, the antifungal, or both. Check for adverse drug interactions before prescribing. For example, voriconazole use is not recommended for patients taking ritonavir-boosted PIs, and dosage adjustment of both voriconazole and NNRTIs may be required when voriconazole is used concurrently with NNRTIs. See Tables 15a-e of the U.S. Department of Health and Human Services Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, or consult with an expert.
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