Oral candidiasis is the most common fungal infection in both the immunocompetent and the immunocompromised populations. This article reviews the clinical presentations of the different forms of oral candidiasis, as well as the diagnosis and management.
Candidiasis is the most common oral fungal infection. Fungal infections of the oral cavity are caused by a group of saprophytic fungi that includes 8 species of the genus Candida . Candida albicans is the most common candidal species residing in the oral cavity of humans, accounting for 70% to 80% of oral isolates. Candida glabrata and Candida tropicalis account for approximately 5% and 8% of oral isolates, respectively. C albicans is a dimorphic fungus existing in both yeast and hyphal forms; however, only the hyphal form is associated with oral candidiasis. It may be a component of the normal oral microflora in approximately 30% to 50% of the population.
Predisposing factors
There are various predisposing factors for oral candidiasis, including systemic diseases that affect the immune status of the host, the local oral mucosal environment, and the specific strain of C albicans . Recurrent oral candidiasis is noted in patients with poorly controlled diabetes mellitus, human immunodeficiency virus (HIV)-positive patients (especially those with a CD4 cell count <200/μL), and patients with xerostomia. In one study, oral candidiasis was evident in 28.6% of HIV-positive patients and was the most common oral manifestation of HIV infection. The use of medications, especially among the elderly population, is one of the most common causes of xerostomia. Medications that are commonly associated with predisposition to xerostomia include antidepressants, diuretics, and those that possess anticholinergic effects. Other causes of xerostomia include radiation treatment to the head and neck region and Sjögren’s syndrome. A decrease in the salivary flow leads to a reduction in the cleansing capability of the saliva, in addition to a decrease in secretory immunoglobulin A levels, creating an environment that is more conducive to the growth of C albicans .
Additional predisposing factors for oral candidiasis include the use of broad-spectrum antibiotics that alter the normal microflora, corticosteroid medications, removable prostheses, and physical disabilities that impair proper oral hygiene or nutrition. The use of topical corticosteroids (eg, clobetasol), steroid inhalers, and systemic steroids are common iatrogenic causes of oral candidiasis.
Clinical manifestations
Patients with oral candidiasis may be asymptomatic or complain of a burning sensation or stomatodynia. They also occasionally report the presence of a metallic taste. Although the symptom of burning is a common complaint in patients with candidiasis, additional causes of oral burning should also be considered. These include xerostomia, as well as iron, vitamin B 12 , or zinc deficiency. If no definitive cause for the burning sensation is elucidated, a diagnosis of burning mouth syndrome is often rendered. Burning mouth syndrome is considered to be a diagnosis of exclusion once all other potential causes of burning mouth have been excluded.
The clinical presentation of oral candidiasis is variable and includes both white and erythematous forms. The white forms include pseudomembranous and hyperplastic candidiasis (candidal leukoplakia). The erythematous forms of the disease occur more commonly than the pseudomembranous or hyperplastic subtypes.
Pseudomembranous Candidiasis
Pseudomembranous candidiasis, also known as thrush, is the most commonly recognized form of candidiasis. It presents as adherent white wipeable plaques resembling curdled milk. The plaques occur anywhere on the oral mucosa, including the tongue, buccal mucosa, and hard palate. When the plaques are wiped off, the underlying mucosa often exhibits an erythematous appearance. This form of candidiasis is most commonly observed in infants and immunocompromised patients, including those who are HIV positive or who have undergone organ or tissue transplants. In patients with a compromised immune system, pseudomembranous candidiasis also affects regions other than the oral cavity, including the oropharynx and esophagus. Pseudomembranous candidiasis is the second most common AIDS-defining opportunistic infection following Pneumocystis carinii pneumonia, and results in significant morbidity in terms of weight loss, malaise, and reduced quality of life.
Erythematous Candidiasis
Erythematous candidiasis is the most common form of oral candidiasis and is categorized into several different forms depending on the cause and site of involvement. Causes include the use of medications, wearing removable prosthetic appliances for an extended period, and xerostomia. Erythematous candidiasis is categorized into the following subtypes: acute atrophic, chronic atrophic, angular cheilitis, median rhomboid glossitis, and chronic multifocal.
Acute atrophic candidiasis
Acute atrophic candidiasis has also been referred to as antibiotic sore mouth, as this subtype results from the use of broad-spectrum antibiotics. The clinical presentation is typically that of erythema of the involved tissues, including atrophy of the dorsal tongue papillae. Patients often present with a chief complaint of an oral burning sensation. The use of broad-spectrum antibiotics facilitates the overgrowth of C albicans by suppressing the normal oral bacterial microflora. The clinical presentation of an erythematous burning tongue demonstrating papillary atrophy also occurs in association with other disorders, including iron deficiency anemia, vitamin B 12 deficiency, and poorly controlled diabetes mellitus.
Chronic atrophic candidiasis
This form of candidiasis is commonly designated denture stomatitis, and as the name suggests, is noted in patients who wear primarily poorly fitting removable prosthetic appliances for extended periods, for example, by not removing them at night ( Fig. 1 ). Patients are most often asymptomatic and clinically present with erythema and petechiae of the mucosa coinciding with the denture-bearing area of the prosthesis. Denture stomatitis is primarily noted on the palatal denture-bearing mucosa where natural salivary flow is restricted.
Denture stomatitis is classified into 3 clinical subtypes or Newton classifications: (1) type I consists of localized inflammation or pinpoint petechial hemorrhages, (2) type II is a more diffuse erythema involving either a portion or the entire denture-bearing mucosa, and (3) type III is erythema in association with papillary hyperplasia of the denture-bearing mucosa. Culturing the tissue surface of the denture and the denture-bearing palatal mucosa often reveals a significantly greater extent of candidal growth from the denture itself. The acrylic porosities on the tissue surface of the denture provide an ideal environment for the growth of C albicans . Much of the observed erythematous tissue reaction is the result of the by-products of C albicans in contact with the mucosa. Petechial hemorrhages and papillary mucosal hyperplasia result from long-term irritation of the poorly fitting denture. In addition, patients with denture stomatitis often present with associated angular cheilitis.
Angular cheilitis
This variant of candidiasis most commonly represents a combination of fungal and bacterial infections ( Fig. 2 ). Most cases of angular cheilitis are caused by both C albicans and Staphylococcus aureus , and the remaining by either C albicans or S aureus . The clinical presentation consists of soreness along with erythema and fissuring at the commissures, most often bilaterally. Angular cheilitis is often noted in patients who are denture wearers, especially those with an old poorly fitting prosthesis. Over time, as alveolar bone recedes, there is a resultant decreased vertical dimension of occlusion, thereby allowing for the pooling and accumulation of saliva at the commissures. Thus, a favorable environment for the growth of C albicans and S aureus exists. Less common contributing factors for the development of angular cheilitis include nutritional deficiencies such as iron, vitamin B 12 , folic acid, thiamine, and riboflavin. Angular cheilitis is also seen in younger dentate patients who are HIV positive, most likely as a result of decreased immunity.
Median rhomboid glossitis
Median rhomboid glossitis is also known as central papillary atrophy. The clinical presentation consists of a well-demarcated, rhomboid region of atrophy of the dorsal tongue papillae localized to the midline posterior aspect of the tongue anterior to the circumvallate papillae. In some cases, an associated “kissing lesion” is present on the hard palate, resulting from direct inoculation that occurs when the dorsal tongue makes contact with the hard palate during deglutition. Median rhomboid glossitis was originally thought to be a developmental anomaly before being considered a variant of oral candidiasis.
Chronic multifocal candidiasis
Chronic multifocal candidiasis is defined as the presentation of candidiasis in more than one clinical location, such as concurrent denture stomatitis and angular cheilitis. Additional clinical criteria for this condition include the presence of lesions for more than 4 weeks, the absence of any predisposing medical conditions, and the exclusion of patients who have received radiation therapy; drugs such as antibiotics, antiinflammatory medications, or immunosuppressive drugs; and cytotoxic or psychotropic agents.
Hyperplastic Candidiasis
Hyperplastic candidiasis, also known as chronic hyperplastic candidiasis or candidal leukoplakia, presents clinically as a well-defined, white nonwipeable lesion most commonly on the buccal mucosa involving the commissural region and less frequently on the palate and lateral tongue. Clinically, hyperplastic candidiasis cannot be distinguished from leukoplakia. Leukoplakia is defined as the presence of a white nonwipeable well-defined lesion that cannot be characterized clinically or pathologically as any other disease entity and has no known etiology except tobacco and/or alcohol. If the lesion does not resolve after antifungal treatment, leukoplakia should be considered as a possible clinical diagnosis and it should be biopsied to rule out dysplasia or squamous cell carcinoma.
Hyperplastic candidiasis is the least common variant of oral candidiasis and remains somewhat controversial. Some consider it to be a preexisting leukoplakia that is colonized by candidal organisms. In other situations, Candida is determined to be the sole cause of the lesion, given that it resolves after antifungal treatment. Although many of these cases present as white lesions, occasionally there are focal areas of erythema in association with the white areas. Therefore, speckled leukoplakia, or erythroleukoplakia, should also be included in the differential diagnosis. Such lesions should be biopsied promptly because of the significantly increased frequency of the presence of either dysplasia or squamous cell carcinoma in lesions that demonstrate an erythematous clinical presentation.
Candidiasis and the Immunocompromised Host
Chronic candidiasis may present in immunocompromised patients with an inherited immune defect, such as chronic mucocutaneous candidiasis, or in patients who are immunocompromised as a result of an underlying disease process, including HIV infection, hematologic malignancies, and impaired immune status secondary to chemotherapy for cancer or immunosuppression subsequent to a transplant.
Chronic Mucocutaneous Candidiasis
This form of candidiasis presents as a long-term involvement of the mucosa, skin, and nails exhibiting a poor response to treatment with topical antifungal agents. The oral lesions are usually of the hyperplastic type, although other forms of candidiasis may be observed. Generally, the severity of the candidal infection correlates with the degree of immune dysfunction. Most cases are sporadic; however, an autosomal recessive inheritance pattern has been noted. Candidal infections usually present within the first few years of life. The underlying immune defect is thought to be cell mediated. Previous studies have shown that it may involve a defect in cytokine production in response to candidal and bacterial antigens.
Chronic mucocutaneous candidiasis has also been associated with various endocrinopathies, including endocrine-candidiasis syndrome and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, in addition to iron deficiency anemia. The endocrine abnormalities that have been noted include hypothyroidism, hypoparathyroidism, Addison disease, and diabetes mellitus. The endocrine disturbance often develops months or years after the onset of the candidal infection. In a study by Rautemaa and colleagues, an increased prevalence of oral and esophageal carcinoma was noted in patients with APECED syndrome, with 10% of adult patients affected by these malignancies.
HIV-Associated Candidiasis
Oral candidiasis is one of the most common opportunistic infections in HIV-positive patients. Studies have shown that more than 90% of HIV-positive individuals develop oral candidiasis some time during the course of their disease. It is also the most common oral fungal infection associated with HIV disease. HIV-associated oral candidiasis presents clinically as pseudomembranous, erythematous, or hyperplastic variants. The pseudomembranous form most frequently involves the tongue, hard and soft palate, and buccal mucosa, although any region of the oral mucosa may be involved. The erythematous form more often presents as an early oral manifestation of HIV infection, usually involving the palate and dorsal tongue.
Another form of HIV-associated oral candidiasis is linear gingival erythema. It is a nonplaque-induced gingivitis that presents as an erythematous band along the marginal gingiva and can be diffuse or generalized. Linear gingival erythema does not respond to the typical treatment regimen for gingivitis, which consists of scaling, professional tooth polishing with prophylaxis paste, and improved oral hygiene. It often results from a combination of candidal and bacterial infections. Linear gingival erythema is considered to be an oral manifestation of HIV infection; however, it is also noted in patients who are HIV-negative, although at a much lower frequency.
Clinical manifestations
Patients with oral candidiasis may be asymptomatic or complain of a burning sensation or stomatodynia. They also occasionally report the presence of a metallic taste. Although the symptom of burning is a common complaint in patients with candidiasis, additional causes of oral burning should also be considered. These include xerostomia, as well as iron, vitamin B 12 , or zinc deficiency. If no definitive cause for the burning sensation is elucidated, a diagnosis of burning mouth syndrome is often rendered. Burning mouth syndrome is considered to be a diagnosis of exclusion once all other potential causes of burning mouth have been excluded.
The clinical presentation of oral candidiasis is variable and includes both white and erythematous forms. The white forms include pseudomembranous and hyperplastic candidiasis (candidal leukoplakia). The erythematous forms of the disease occur more commonly than the pseudomembranous or hyperplastic subtypes.
Pseudomembranous Candidiasis
Pseudomembranous candidiasis, also known as thrush, is the most commonly recognized form of candidiasis. It presents as adherent white wipeable plaques resembling curdled milk. The plaques occur anywhere on the oral mucosa, including the tongue, buccal mucosa, and hard palate. When the plaques are wiped off, the underlying mucosa often exhibits an erythematous appearance. This form of candidiasis is most commonly observed in infants and immunocompromised patients, including those who are HIV positive or who have undergone organ or tissue transplants. In patients with a compromised immune system, pseudomembranous candidiasis also affects regions other than the oral cavity, including the oropharynx and esophagus. Pseudomembranous candidiasis is the second most common AIDS-defining opportunistic infection following Pneumocystis carinii pneumonia, and results in significant morbidity in terms of weight loss, malaise, and reduced quality of life.
Erythematous Candidiasis
Erythematous candidiasis is the most common form of oral candidiasis and is categorized into several different forms depending on the cause and site of involvement. Causes include the use of medications, wearing removable prosthetic appliances for an extended period, and xerostomia. Erythematous candidiasis is categorized into the following subtypes: acute atrophic, chronic atrophic, angular cheilitis, median rhomboid glossitis, and chronic multifocal.
Acute atrophic candidiasis
Acute atrophic candidiasis has also been referred to as antibiotic sore mouth, as this subtype results from the use of broad-spectrum antibiotics. The clinical presentation is typically that of erythema of the involved tissues, including atrophy of the dorsal tongue papillae. Patients often present with a chief complaint of an oral burning sensation. The use of broad-spectrum antibiotics facilitates the overgrowth of C albicans by suppressing the normal oral bacterial microflora. The clinical presentation of an erythematous burning tongue demonstrating papillary atrophy also occurs in association with other disorders, including iron deficiency anemia, vitamin B 12 deficiency, and poorly controlled diabetes mellitus.
Chronic atrophic candidiasis
This form of candidiasis is commonly designated denture stomatitis, and as the name suggests, is noted in patients who wear primarily poorly fitting removable prosthetic appliances for extended periods, for example, by not removing them at night ( Fig. 1 ). Patients are most often asymptomatic and clinically present with erythema and petechiae of the mucosa coinciding with the denture-bearing area of the prosthesis. Denture stomatitis is primarily noted on the palatal denture-bearing mucosa where natural salivary flow is restricted.
