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Oropharyngeal candidiasis occurs frequently among HIV-infected individuals, particularly those with more advanced immune suppression.
Among HIV-infected persons, four different manifestations of oral candidiasis can occur: pseudomembranous candidiasis (thrush), atrophic (erythematous) candidiasis, angular cheilitis (perleche), and rarely, hyperplastic candidiasis.
In most clinical situations, the presumptive diagnosis of oral candidiasis is made based on the typical clinical appearance[5]. Routine primary prophylaxis is not recommended[5], mainly because oropharyngeal candidiasis has a very low attributable mortality and regular use of antifungal agents can lead to the development of drug-resistant Candida species[6]. Multiple studies have compared different regimens for the treatment of oropharyngeal candidiasis. Extensive white plaques along the upper gums and lips in a patient with pseudomembranous candidiasis (thrush). Oral infections caused by yeast of the genus Candida and particularly Candida albicans (oral candidoses) have been recognised throughout recorded history.
A change from the harmless commensal existence of Candida to a pathogenic state can occur following alteration of the oral cavity environment to one that favours the growth of Candida.
Oral candidosis is not a single infection and generally four primary oral forms are described based on clinical presentation (Fig. In the case of AIDS, or other instances where the individual is immunocompromised long-term, chronic pseudomembranous candidosis can develop and whilst antifungal therapy can temporarily resolve the condition, recurrent infection is frequent. Chronic forms of erythematous candidosis can also occur and traditionally these infections encompassed the atrophic lesions associated with angular cheilitis and denture stomatitis. Chronic hyperplastic candidosis (occasionally referred to as candidal leukoplakia) can present on any oral mucosal surface and appears either as smooth (homogenous) or nodular white lesions (37). Secondary forms of oral candidosis can also occur and are frequently described as Candida-associated lesions.
Median rhomboid glossitis is a chronic condition that presents as a diamond-shaped lesion at the posterior midline on the dorsum of the tongue (31). The most prevalent oral infection involving Candida is Candida-associated denture stomatitis, which occurs in up to 65% of denture wearers, often asymptomatically (44). In a discussion on the oral forms of candidosis, mention needs to be made of chronic mucocutaneous candidosis (CMC), characterised by the widespread occurrence of superficial candidosis of the skin, nails, and mucosal membranes (including those of the oral cavity) of infected individuals (48, 49). In terms of oral candidosis, biofilms on an oral prosthesis, most commonly a denture, are a major predisposing factor to chronic oral candidosis. Immunocompetent individuals rarely suffer from oral candidosis even when Candida is present in the oral cavity. A priority in the treatment of oral candidosis is the alleviation of any identifiable predisposing factor. Both the physical and chemical reduction of Candida load in the oral cavity can be achieved by good oral hygiene practices including tooth brushing and the use of antimicrobial mouthwashes.
As the need to expand antifungal options increases, newer azole drugs such as itraconazole have been used in the treatment of oral candidosis, whilst others including voriconazole and pozoconazole are alternatives for invasive infections by Candida. Whilst Candida species are frequent members of the commensal oral microflora of humans, they are opportunistic pathogens that under conditions of host debilitation can cause a spectrum of oral infection.
Prevalence and antifungal drug sensitivity of non-albicans Candida in oral rinse samples of self-caring elderly. Carriage of Candida species in the oral cavity in diabetic patients: relationship to glycaemic control.
Risk factors of oral candidosis: a twofold approach of study by fuzzy logic and traditional statistic. Salivary IgA and oral candidiasis in asthmatic patients treated with inhaled corticosteroid.
Oral candidiasis associated with inhaled corticosteroid use: comparison of fluticasone and beclomethasone. Treatment of angular cheilitis: the significance of microbial analysis, antimicrobial treatment, and interfering factors. Incidence and anatomic localization of oral candidiasis in patients with AIDS hospitalized in a public hospital in Belo Horizonte, MG, Brazil.
Possible mycologic aetiology of oral mucosal cancer: catalytic potential of infecting Candida albicans and other yeasts in production of N-nitrosobenzylmethylamine. The relationship of candidiasis to linear gingival erythema in HIV-infected homosexual men and parenteral drug users. The diagnosis of oral candidiasis is a CDC category B diagnosis (in the 1993 CDC classification system)[1].

Pseudomembranous candidiasis typically manifests as creamy white plaque or patches on oral tissues that can usually be scraped off with a tongue blade (Figure 1.
For patients who have angular cheilitis with no evidence of intra-oral candidiasis, topical antifungal creams are generally sufficient for therapy (Figure 9. In one small study of patients with oropharyngeal candidiasis, fluconazole (50 mg once daily) appeared superior to ketoconazole (200 mg once daily)[7]. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Key to the increase in oral candidosis has, however, been the escalation of HIV-infection and AIDs (25). Of additional concern with chronic forms of pseudomembranous candidosis is the subsequent progression of infection to oesophageal involvement, which in turn can lead to difficulties in swallowing and chest pains. This form of oral candidosis frequently occurs after receipt of a broad-spectrum antibiotic, which, by lowering the oral bacterial population, facilitates subsequent overgrowth of Candida by alleviating competitive pressures. Unlike the lesions of pseudomembranous candidosis, those of chronic hyperplastic candidosis cannot be removed by gentle scraping. As this name suggests, denture wearing is the major predisposing factor, particularly in cases where the denture is not adequately cleansed or is retained overnight in the oral cavity.
Within the oral cavity, removal of loosely attached Candida by the physical flushing action of salivary flow or the process of sloughing off of epithelial cells from mucosal surfaces are important factors in host defence against Candida overgrowth.
The nature of these forces are in part governed by the local environment in the oral cavity; however, studies have shown that strain variation does occur in terms of cell surface hydrophobicity that may give certain isolates greater pathogenic potential (51). Manual tooth brushing is limited to accessible oral surfaces, although powered or electrical tooth brushing may be more effective as cavitation within surrounding fluids could disrupt Candida biofilms at otherwise inaccessible sites (92). Oral candidoses have been recognised throughout recorded history, although most attention has been given to the infections in the last few decades when the incidence increased greatly with the advent and escalation of the AIDs epidemic.
In addition, the presence of oropharyngeal candidiasis is an indication for initiating prophylaxis for Pneumocystis pneumonia and for initiating antiretroviral therapy.
Patients with pseudomembranous candidiasis can be destinguished from those with oral hairy leukoplakia by scraping the lesions with a tongue blade: the candidiasis plaques are usually removed whereas lesions caused by the oral hairy leukoplakia are not affected by scraping. In a study that involved 334 patients with oral candidiasis, fluconazole (100 mg once daily) and topical clotrimazole troches (10 mg 5 times per day) had similar initial clinical response rates, but clotrimazole was associated with a higher rate of return of symptoms during the second week of follow-up[8].
This has largely been due to an increased incidence of oral candidosis over this period, primarily because of the escalation in HIV-infection and the AIDS epidemic.
Pseudomembranous candidosis (oral thrush) presents as creamy white lesions on the oral mucosa and a diagnostic feature of this infection is that these plaques can be removed by gentle scraping leaving behind an underlying erythematous mucosal surface (31, 32). Chronic erythematous candidosis is prevalent in HIV-positive individuals and AIDS patients, and depending on the study can represent over a third of the Candida lesions encountered (36).
Most frequently, chronic hyperplastic candidosis occurs bilaterally in the commissural regions of the buccal mucosa with highest prevalence in middle-aged men who are smokers (38). Biofilm formation on denture surfaces is further promoted by poor oral hygiene and retention of dentures in the mouth whilst sleeping. An example of this are the recommendations made to patients suffering from chronic erythematous candidosis in order to improve oral hygiene through adequate denture cleansing.
Classification of antifungal agents is based on the target of activity, and in the treatment of candidosis the two classes most commonly used are the polyenes and the azoles (Table 4).
The development of oral candidiasis generally reflects an imbalance in the normal ecological environment of the oral cavity. Pseudomembranous Candidiasis (Thrush) on Lips and Gums">Figure 2); if the mouth is very dry or if the condition is more chronic, the plaques can be more adherent.
When the clinical diagnosis of oral candidiasis is not clear, the diagnosis can be confirmed by obtaining a direct smear and performing either a potassium hydroxide (KOH) wet mount or a Gram's stain. In the 2009 United States Guidelines for the Prevention and Treatment of Opportunistic Infections, fluconazole (Diflucan) is recommended as the drug of choice for patients with oropharyngeal candidiasis based on its good efficacy, convenience, and tolerance (Figure 10. A characteristic feature of this form of oral candidosis is the penetration of the oral epithelium by C.
Furthermore, the limited flow of saliva at this location means that loosely adherent Candida may not be efficiently removed from the site, as would be the case at other oral locations.
In addition, specific interaction of Candida with oral bacteria has also been demonstrated that could encourage biofilm formation on dentures and in dental plaque (54). Although HIV-related immune suppression is typically the most important risk factor for candidiasis, other factors can contribute, including use of antibiotics that change normal bacterial flora, use of corticosteroids, use of chemotherapeutic drugs, presence of diabetes, decreased salivary flow rates, and wearing dentures. Whilst oral candidosis has previously been considered to be a disease mainly of the elderly and very young, its occurrence throughout the general population is now recognised.

Candida albicans is the species most frequently associated with normal oral carriage in humans, occurring in the mouths of up to 80% of healthy individuals (13).
Where antibiotic treatment has been associated with predisposition, cessation of treatment leads to spontaneous resolution of the lesions once the bacterial population of the mouth recovers to pretreatment levels (22). The use of polyenes is limited further as they are poorly absorbed through the gut and, therefore, topical application in the form of lozenges and oral suspensions are the principle means of administration in oral infection.
The two most frequently administered azole antifungals in the treatment of oral candidosis are fluconazole and itraconazole and these drugs have the advantage of being readily absorbed through the gut with the result that oral administration is an effective means of delivery (97). Considering the strong association of HIV infection and oropharyngeal candidiasis, HIV assessment and testing is recommended for any person who presents with oropharyngeal candidiasis and does not have a known risk factor for oropharyngeal candidiasis[2]. Erythematous candidiasis manifests as flat red patches anywhere on the oral mucosa, most commonly on the hard palate (Figure 3.
Obtaining oral fungal cultures is generally reserved for situations when patients do not respond to therapy and anti-fungal resistance is suspected. Candidal biofilms in haemodialysis and peritoneal dialysis catheters are a common occurrence and associated with an infection rate of up to 20% in patients undergoing treatment (55). Polyenes are frequently used in the treatment of chronic erythematous candidosis, and oral suspension of amphotericin B may be employed in treating refractory oral candidosis frequently seen in HIV-infected and AIDs patients. Furthermore, fluconazole is secreted in high levels in saliva making the agent particularly suitable for treating oral infection (98).
Effective management of oral candidosis demands correction of any identified predisposing factor together with the administration of appropriate antifungal agents.
Among HIV-infected patients with oral candidiasis, Candida albicans is the most common species involved[3], but non-albicans species, such as such as C.
Erythematous (Atrophic) Candidiasis in Upper Mouth">Figure 3), attached gingival or buccal mucosa, or the dorsal surface of the tongue (Figure 4. Treatment of these infections has continued (and in some regards continues) to be problematic because of the potential toxicity of traditional antifungal agents against host cells.
Other possible strategies could involve the use of probiotics (107), which would induce an added microbiological pressure on Candida within the oral cavity and may also promote local immune function. Given the increasing incidence of NCAC species in oral infection and the development of resistance against some of the traditionally used antifungals, there is a constant need for research into new and effective agents to treat oral candidosis.
Alternative therapy consists of itraconazole (Sporanox) oral solution and posaconazole (Noxafil) oral solution. An important feature of chronic hyperplastic candidosis is its possible association with malignant transformation (40). The potential benefits of probiotics in the management of Candida biofilms have already been reported for indwelling voice box prostheses (108), as well as in lowering the Candida prevalence in the oral cavity (109).
For patients unlikely to adhere to a 7 to 14 day treatment, a study showed a single high dose of fluconazole (750 mg) was as effective as a standard 14-day course of fluconazole[15].
A confirmed link between Candida and the development of oral cancer remains to be established, although it has been shown in vitro that yeast can generate the carcinogenic nitrosamine, N-nitrosobenzylmethylamine from suitable precursor molecules (41). It should be noted that both filamentous and yeast forms are encountered in the oral cavity of healthy individuals, highlighting the importance of host factors in controlling Candida and the fact that no single predominant virulence factor is associated with the organism (64).
The aim of this review is to give the reader a contemporary overview of oral candidosis, the organisms involved, and the management strategies that are currently employed or could be utilised in the future. Patients with pseudomembranous or erythematous candidiasis often complain of a burning sensation in their mouth and of altered taste. Hyperplastic candidiasis is seen with chronic mucosal colonization by Candida with very superficial invasion of the epithelium. Episodic treatment of clinical episodes is strongly preferred over chronic suppressive therapy, mainly because of lower cost with episodic therapy and the concern for development of antifungal drug resistance with chronic therapy[2]. Initiating antiretroviral therapy would likely play a critical role in minimizing the need to treat recurrent episodes of oropharyngeal candidiasis. A detailed discussion of drug-resistant candidiasis will be reviewed in Case 4 in this same section (Oral Manifestations).
Angular cheilitis usually occurs in conjunction with other intra-oral manifestations of candidiasis.
Because patients with advanced HIV disease and oral candidiasis may have concomitant esophageal candidiasis, they should be asked about dysphagia and odynophagia.

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