Practice Essentials
Candidiasis describes a group of fungal infections involving the skin and mucous membranes. Infection is caused by Candida species, primarily Candida albicans. [1] C albicans is a dimorphic fungus that can asymptomatically colonize the gastrointestinal and genitourinary tracts (and their associated mucosae) in healthy individuals. [2] Oral colonization is estimated in 50% of healthy adults, [3] while genital colonization is seen in 21% of women. [4] When the local ecology is disturbed, or where there is an immune defect, Candida overgrowth may lead to an opportunistic infection. The mucosal surfaces primarily affected by candidiasis are the oral cavity, esophagus, angles of the mouth, and genitals (causing vulvovaginitis in females, balanitis in males).
Oral candidiasis may present as either white or erythematous lesions and either an acute or chronic infection. [5] Thus, the presentations can be divided into the following four subtypes:
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Acute pseudomembranous candidiasis (thrush): The classic multiple white-flecks on the tongue, buccal mucosa, and palate
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Chronic hyperplastic candidiasis: Thick white plaques on the buccal mucosa and labial commissures
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Acute atrophic (erythematous) candidiasis: Erythematous patches on the palate
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Chronic atrophic candidiasis (denture stomatitis): A form of erythematous candidiasis, resulting from poorly fitted dentures causing a burning, sore mouth
There are also conditions that may predispose individuals to chronic, multifocal infections from Candida. This can lead to syndromes such as chronic mucocutaneous candidiasis (CMC). See Risk Factors.
For further information, also see the Medscape articles Candidiasis, Chronic Mucocutaneous Candidiasis, Pediatric Candidiasis, Cutaneous Candidiasis, Candidiasis Empiric Therapy, Candidiasis Organism-Specific Therapy, and Candidiasis in Emergency Medicine.
Prognosis
The prognosis is good for most infections in the immunocompetent host, but in patients who are immunocompromised, antifungal resistance is commonplace. Oral candidiasis may predispose individuals to esophageal spread. Systemic spread is rare, but can occur in the severely immunocompromised.
Diagnostics
Diagnosis begins with a thorough history and physical examination.
Patients should be asked about immunosuppressive agents (local and systemic), antibiotics, other opportunistic infections, risky sexual contact, and dental procedures. Patients should be asked about difficulty or pain with swallowing, which can be an indication of esophageal spread. During the physical examination, directly visualize the lesions by examining all areas of the mouth or genitals.
Depending on the severity of the infection, potassium hydroxide (KOH) preparation, culture, and antimicrobial sensitivities should be done to confirm the diagnosis.
Also see Laboratory Studies.
Treatment
See Medical Care and Medication.
Prevention
Patients should be counseled about smoking, and they should be warned about the risk of developing mucosal candidiasis after taking medications that impair salivation, antibiotics, corticosteroids, and other immunosuppressants.
Pathophysiology
C albicans asymptomatically inhabits the mouths of almost 50% of the population. Overgrowth of Candida is protected against by local T cells and interleukin (IL)–17. [6] Thus, when immunity is compromised, growth proceeds unchecked and leads to opportunistic infections.
Candidiasis is seen in people with altered ecology, which in oral cases can be attributed to dental appliances, xerostomia, antimicrobials, nasopharyngeal steroids, oral cancer, or inflammatory diseases of the oral mucosa (e.g. pemphigus vulgaris). [7] Impaired systemic immunity is another major cause of infection, notably in patients who are on immunosuppressive therapy, infected by HIV, or have diabetes. [8, 9]
C albicans is the predominant causal organism of most candidiasis. Other species, such as Candidatropicalis and Candidastellatoidea, more often appear in persons who are severely immunocompromised.
Secreted aspartyl proteinases (SAPs) are hydrolytic enzymes secreted by Candida that contribute to virulence by degrading host cell mebranes and molecular mediators of host immunity. [10] The prevacuolar protein sorting gene, VPS4, is required for extracellular secretion of SAPs, and it is a key component of the virulence of Candida. [11] Additionally, studies have shown that women with vulvovaginal candidiasis have higher levels of SAPs in their vaginal fluid. [12]
In those with dental devices, Candida, upon attachment, can form a small subcolony of persister cells. These cells have been shown to be highly resistant to antimicrobials, and they provide a mechanism for the recurrent formation of biofilms. [13] In addition to providing drug resistance, these biofilms have been implicated as a virulence factor in candidias. [14]
Chronic mucocutaneous candidiasis
Chronic mucocutaneous candidiasis (CMC) describes a group of rare syndromes, in which persistent mucocutaneous candidiasis responds poorly to topical treatment. Extensive disease can recur even after systemic treatment. It is associated with immune defects, particularly in T-cell, dendritic cell, and T-helper 17 (Th17) cell function. Studies have demonstrated specific signals that when compromised, cause defects in the response to candidal antigens. Identified defects include overproduction of IL-6, underproduction of IL-23, and deficiency of IL-17. Some affected individuals have been shown to have muations in the Dectin/CARD9 signaling pathway, which is responsible for candidal antigen sensing in myeloid cells and the subsequent differentiation of naive CD4+ T cells toward a Th17 lineage. [15]
Risk Factors
There are many risk factors that increase the incidence of candidiasis. Immunosuppression is the most significant of these, and it can be due to diabetes, antibiotics, immunosuppression, systemic steroid use, and HIV infection, among others.
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Immunocompromise: Increased carriage rates are seen in several conditions, including novel coronavirus disease (COVID-19) [16] , HIV infection, diabetes, systemic steroid use, aerosolized steroid use, immunosuppression, and malignancy
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Hyposalivation: Increases carriage of Candida and can be due to drug effects (antipsychotics), Sjögren syndrome, radiotherapy, or chemotherapy
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Poor oral hygiene: Candida counts increase during sleep but are reduced by eating and brushing the teeth
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Dentures: Removal and reinsertion of dentures cause increases in salivary candidal counts, suggesting that plaque on the dentures harbors C albicans
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Missing teeth: Being edentulous increases the overlap of skin at the corners of the mouth, increasing the risk for angular cheilitis formation
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Smoking: Increases Candida carriage by 30-70%
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Antibiotic use: Increases carriage of Candida
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Vitamin deficiencies: Higher association of candidiasis with vitamin B-12 and iron deficiency
Patient Education
For patient education resources, see the following:
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Overview of oropharyngeal thrush from the Centers for Disease Control and Prevention (CDC): Candida infections of the mouth, throat, and esophagus
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Overview of vulvovaginal candidiasis from the CDC: Vaginal Candidiasis
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Pseudomembranous candidiasis.
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Erythematous candidiasis in HIV/AIDS.
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Denture-related stomatitis; a common form of oral candidiasis. From Scully C, Flint SF, Bagan JV, Porter SR, Moos K. Atlas of Oral and Maxillofacial Diseases. 2010. Informa, London.
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Angular cheilitis; a common form of oral candidiasis, typically seen in patients with denture-related stomatitis, especially those in whom the denture needs adjustment. In others, it may be a sign of diabetes, nutritional deficiency, or immune defect.
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Multifocal candidiasis; lingual lesions.
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Chronic hyperplastic candidiasis; typically affects the tongue dorsum or the commissures of the lips; potentially malignant.
