The Candida species are ubiquitous fungi that colonize more than 50 percent of healthy individuals. These strictly opportunistic pathogens result in various disease manifestations and severity determined by a combination of environmental factors, organism virulence, and host defenses. There are several Candida species (C. parapsilosis, C. tropicalis, C. glabrata, C. krusei, C. pseudotropicalis, C. guilliermondi, C. dubliniensis, and C. inconspicua), but the most commonly responsible for candidiasis is Candida albicans.

Candidiasis can be a limited skin infection or a devastating systemic disease. Immunocompetent individuals tend to have cutaneous infections of warm, moist mucous membranes, resulting in vaginitis, oral thrush, conjunctivitis, endophthalmitis, diaper rash, and infections of the nail and other skin folds. In immunocompromised patients, candidal infections can cause devastating systemic illnesses such as myocarditis, endocarditis, peritonitis, hepatosplenorenal abscesses, and pulmonary and CNS infections. Thrush, also known as acute pseudomembranous oral candidiasis, is the idiom used to describe the classic white-flecked lesions that allegedly resemble the brownish upper plumage and spotted breast of the thrush songbird (family Turdidae).

Oral candidiasis is a familiar mucosal infection frequently seen in the young, old, or those with compromised immunologic systems. It is estimated that 50 percent of patients undergoing radiotherapy and 70 percent undergoing chemotherapy for leukemia and solid tumors suffer from oral candidiasis. (Regezi JA, et al. [1999.] Oral Pathology: Clinical Pathologic Correlations. Saunders, Philadelphia.)

C. albicans is the most common Candida species isolated from the oral cavity in both health and disease conditions (Clin Dermatol 2000;18[5]:553) and the most common infectious cause of esophagitis. One study found 63.1 percent of adults were asymptomatic carriers of C. albicans, with the occurrence of thrush infection at 64.8 percent in adults and 66.7 percent in adults with dentures. (Adv Med Sci. 2006;51[Suppl 1]:77.) Ill-fitting dentures, inadequate oral hygiene, constant irritation by a prosthesis, higher salivary yeast counts, and adherence of C. albicans to denture base materials may explain the higher occurrence of thrush in patients who wear dentures. In children, 43.7 percent have been identified as asymptomatic carriers of C. albicans with a statistically significant higher rate (64%) in children with dental caries. (Adv Med Sci 2006;51[Suppl 1]:187.)

Candidiasis is the most common oral fungal infection seen in association with HIV infection, and has been described as a marker of poor prognosis. (AIDS 1991;5[11]:1339.) Interestingly, the first patient diagnosed with AIDS presented with oral candidiasis. (MMWR 1981;30:250.) Oral candidiasis occurs in more than 60 percent of HIV-infected patients (Oral Dis 1996;2:193), and more than 80 percent of patients diagnosed with AIDS have had thrush. (J Oral Pathol 1991;20: 332.)

Since the mid-1990s when highly active antiretroviral therapy (HAART) was introduced, rates of opportunistic infections in HIV have declined. In more recent studies, the rate of oropharyngeal, esophageal, and vaginal candidiasis was 34.5 percent in patients on initial presentation to a Ho Chi Minh City HIV clinic. (Int J STD AIDS 2007;18[7]:482.) Another recent study from a Chicago HIV dental clinic found the incidence of oral candidiasis to be 38 percent, with a slightly higher prevalence in men (39.2% versus 38.7% in women) and smokers (44.3% versus 34.5% nonsmokers). (Oral Dis 2007;13[3]:324.)

Many factors other than age and immunosupressed state (treatment for malignancy, HIV/AIDS, and DiGeorge syndrome, to name a few) predispose patients to developing thrush, including reduced salivary flow, epithelial changes, oral flora changes, high carbohydrate diet, diabetes, hypothyroidism, hyperparathyroidism, adrenal suppression, smoking, angular cheilitis, broad-spectrum antimicrobials, and deficiencies in iron, folate (Clin Dermatol 2000;18[5]:553), and other vitamins, and use of topical, systemic, and aerosolized corticosteroids.

Oral candidiasis has been arranged into two classification categories. Category I-primary oral candidiasis (confined to oral/perioral tissues). These are subclassified as:

▪ Acute/chronic pseudomembranous (confluent plaques resembling milk curds that can be wiped off revealing a raw erythematous possibly bleeding base, most commonly found in infants, the elderly, and terminally ill).

▪ Acute/chronic erythematous (painful erythematous areas, usually on the tongue, in the absence of white lesions, usually associated with HIV or use of steroids or antibiotics).

▪ Chronic hyperplastic (plaque-like nodular lesions usually on buccal mucosa that will not rub off that are premalignant).

▪ Candida-associated: denture stomatitis, angular cheilitis (painful erythematous fissured lesions at mouth angles), or median rhomboid glossitis (elliptical or rhomboid-like papillary atrophy at the tongue midline, anterior to the circumvallate papillae).

Category II-secondary oral candidiasis (oral candidiasis is a manifestation of a generalized systemic mucocutaneous candidal infection) is subdivided based on various immunological disease etiologies. (Clin Dermatol 2000;18[5]:553.)

Thrush is typically a clinical diagnosis. Findings on presentation to the ED depend on the type of lesion, ranging from discrete or confluent white plaques, to painful fissures to generalized oral erythema. Painful oral lesions may result in impaired nutritional intake, and delays in drug administration could have other clinically significant sequela on ED presentation. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103[Suppl:S6.e1].)

Gram-stain or cytology staining (showing hyphae or fungal spores) of a smear or oral rinse can confirm the diagnosis. Quantifying the fungal burden also may be useful in equivocal cases (typically normal carrier

<1000 CFU/mL versus infected patient 4000-20,000 CFU/mL burden). Immunohistochemical techniques may be needed to differentiate strains in patients refractory to treatment. (Clin Dermatol 2000;18[5]:553.)

If chronic hyperplastic candidiasis is suspected, a lesion biopsy is indicated. Because oral candidiasis is frequently associated with comorbid-immunocompromising conditions. In one study, 40 percent of patients with any type of oral candidiasis were found to have a hematological abnormality. (Int J Oral Maxillofac Surg 1986;15:72.) Screening blood work may be helpful (HIV test, thyroid studies, B-12, folate, ferritin, glucose, hemoglobin, lymphocyte, and WBC counts) to evaluate for possible underlying etiologies. Esophagography with contrast is indicated to diagnosis esophagitis.

The differential diagnosis of thrush includes hairy leukoplakia, leukoplakia, lichen planus, Fordyce spots, dermatitis, and herpetic infections.

Management in the ED is typically directed at identifying and treating the underlying etiology, if any, and topical lesion care. The majority of oral C. albicans infections can be treated with topical nystatin (oral suspension (100,000 U/mL) or lozenge (100,000 IU) four times daily for seven to 14 days) or amphotericin (suspension (100 mg/mL) or lozenges (10 mg) four times daily after meals). Withdrawal or substitution of broad-spectrum antibiotics alone can result in resolution, however. Patients with dentures should remove the dentures during treatment or coat the skin-contact surface with miconazole gel (20 mg/mL) three times a day for seven to 14 days or until inflammation resolves. Overnight, dentures should be soaked in 0.1% hypochlorite. Poorly fitting dentures should be replaced. In cases of chronic oral candidiasis in immunosuppressed patients, topical agents may not be effective. These cases may require systemic ketoconazole, fluconazole, itraconazole, or rarely, amphotericin. (Clin Dermatol 2000;18[5]:553.)

Most candidal infections are superficial, and patients fully recover. Death, however, can occur in as many as 77 percent of immunocompromised patients with systemic candidiasis. Patients with any form of candidiasis that requires more than simple oral treatment should be admitted for treatment of the fungal infection as well the underlying condition.

Wiler, Jennifer L. MD, MBA

Dr. Wiler is the assistant chief of clinical operations in the department of emergency medicine at Washington University in St. Louis.