Oral candidiasis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Ahmed Younes M.B.B.CH [2]

Oral candidiasis of the mouth and throat is a fungal infection that occurs when there is an overgrowth of candida. Candida yeasts normally live on the skin or mucous membranes in small amounts. However, if the environment inside the mouth or throat becomes imbalanced, the yeasts can multiply and cause symptoms. Candida overgrowth can also develop in the esophagus, and cause esophageal candidiasis.

In 1839, B. Lagenbeck from Germany described a yeast-like fungus for the first time in the human oral infection thrush and its ability to cause it.

Candida species are normal inhabitants of the mouth, throat, and the rest of the gastrointestinal tract. Usually, candida yeasts live in and on the body in small amounts and do not cause any harm. However, the use of certain medications or immunosuppression can cause Candida to multiply, which may cause symptoms of infection.

Oral candidiasis is an infection of yeast fungus, Candida albicans, (or, less commonly, Candida glabrata or Candida tropicalis or C. parapsilosis or C. krusei or other candida species) in the mucous membranes of the mouth.

Oropharyngeal candidiasis must be differentiated from its different kinds and from various other diseases that can cause stomatitis or glossitisز

Oral candidiasis is not common among the general population but is frequently diagnosed in the immunocompromised patients.

People who have diabetes and had high blood sugar levels are more likely to get thrush in the mouth (oral thrush) because the extra sugar in saliva acts as a substrate for Candida. High doses of antibiotics or extended use of antibiotics also increases the risk of oral thrush. Antibiotics kill some of the healthy bacteria that help keep Candida from growing too much. People with poorly fitting dentures are also more likely to get thrush.

There are no sequelae with appropriate antifungal therapy. In contrast, among immunocompromised patients with disseminated infections, the mortality rate is almost 50%. Thrush in infants may be painful but is rarely serious. Because of discomfort, it can interfere with eating. If it does not resolve on its own within 2 weeks, a pediatrician should be notified. In adults, thrush that occurs in the mouth can be cured. However, the long-term outlook is dependent on immune status and the cause of the immune deficit.

In patients with a weakened immune system (for example, HIV-positive or receiving chemotherapy), Candida can spread throughout body, causing infection in esophagus (esophagitis), brain (meningitis), heart (endocarditis), joints (arthritis), or eyes (endophthalmitis).

Adults may experience discomfort or burning in the mouth. Symptoms of candidiasis in the esophagus may include pain and dysphagia (difficult swallowing). Candida infections of the mouth and throat can manifest in a variety of ways. The most common symptom of oral thrush is white patches or plaques on the tongue and other oral mucous membranes.

Oral infections of candida usually appear as thick white or cream color deposits. Underlying the deposits the mucosa of the mouth may appear inflamed (red and possibly slightly raised). Oral lesions are painless, white patches in the mouth.

A healthcare provider diagnoses the infection based on symptoms, and by taking a scraping of affected areas to examine under a microscope. A culture may also be performed; however, because Candida organisms are normal inhabitants of the human mouth, a positive culture by itself does not make the diagnosis.

Oral candidiasis can be treated with topical anti-fungal drugs, such as nystatin (Mycostatin), miconazole or amphotericin B. Patients who are immunocompromised, either with HIV/AIDS or as a result of chemotherapy, may require systemic treatment with oral or intravenous administered antifungals.

Good oral hygiene practices may help to prevent oral thrush in people with weakened immune systems. Some studies have shown that chlorhexidine (CHX) mouthwash can help to prevent oral candidiasis in people undergoing cancer treatment. People who use inhaled corticosteroids may be able to reduce the risk of developing thrush by washing out the mouth with water or mouthwash after using an inhaler.

Candida is usually a self-limiting disease unless concurrent immunosuppression is present.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2], Aravind Kuchkuntla, M.B.B.S[3], Ahmed Younes M.B.B.CH [4]

In 1839, B. Lagenbeck from Germany described a yeast-like fungus for the first time in the human oral infection thrush and its ability to cause it.

• In 1839, B. Lagenbeck from Germany described a yeast-like fungus for the first time in the human oral infection thrush and its ability to cause it.^[1]
• In 1923 the Candida albicans was described by Christine Marie Berkhout. Over the years the classification of the genera and species has evolved. Obsolete names for this genus include Mycotorula and Torulopsis. The species has also been known in the past as Monilia albicans and Oidium albicans. The current classification is nomen conservandum, which means the name is authorized for use by the International Botanical Congress (IBC).
• The full current taxonomic classification is available at Candida albicans.
• The genus Candida includes about 150 different species. However, only a few of those are known to cause human infections. c. albicans is the most significant pathogenic (disease-causing) species. Other Candida species causing diseases in humans include c. tropicalis, c. glabrata, c. krusei, c. parapsilosis, c. dubliniensis, and c. lusitaniae.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Ahmed Younes M.B.B.CH [2]

Candida is a normal commensal of the skin and mucous membranes. The balance between the virulence of the fungus and the host immune defense is responsible avoiding opportunistic infection of candida. Deficiency of cell-mediated immunity or poor general status are the main risk factors for having opportunistic candidiasis. Candidiasis is usually localized to skin and mucous membranes. In rare cases, candidiasis can spread causing candidemia and distant infection. These cases are usually associated with deficient immunity . C. albicans is the main species causing infection in humans more than any other candida species.

Candida is a normal commensal of skin and mucous membranes. A competent immune system and an intact regenerating healthy skin prevent the virulence of Candida.

The main virulence factors that mediate the infection:^[1]

• Secreting molecules that mediate adherence into host cells
• Production of hydrolases which has a lytic effect on tissues and facilitate the invasion by the fungus.
• Polymorphism: Candida has the ability to grow either as pseudohyphae (elongated ellipsoid form) or in a yeast form (rounded to oval budding form. While the role of polymorphism is not clearly understood in the virulence of Candida, it’s noted that the species that are capable of producing the most severe form of the disease has this ability.
• Biofilm production: which means the ability to form a thick layer of the organism on the mucosal surfaces or even on catheters and dentures.

Any condition that compromises cell-mediated immunity, worsens the general status of the patient or provide a favorable medium for Candida to form biofilms put the patient at increased risk for having candidiasis.^[2]

Candidal gene VPS4 plays an important role in mucosal candidiasis specifically. Moreover, fungi with mutations affecting this gene were found to be less virulent.^[3][4]

On speculum examination typical curdy white discharge is present. Usually present in newborns or in patients with deficient immunity, administering corticosteroids, etc.

Appears as erythema or edema without the characteristic white plaques. Usually, seen in patients with dental dentures.^[5]

Persistent tough, adherent, white lesions that are indistinguishable from other leukoplakia except through biopsy. Seen more in smokers, patients with iron deficiency anemia or deficient cell-mediated immunity.^[6][5]

• CMCC is a syndrome characterized by chronic or recurrent superficial candida infection in the skin and mucous membranes in association with endocrinal and autoimmune diseases.^[7]
• Characterized by the inability of T cells to react to candidal antigens.
• Presents with recurrent or chronic candidal infections. Infection is usually superficial though invasive candidiasis is encountered especially in immunocompromised patients.^[8]
• Endocrinopathies as hypoparathyroidism and adrenal insufficiency may accompany chronic candidiasis.

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• Microscopic examination of the wet mount with 10% KOH or saline demonstrates hyphae, pseudohyphae, and blastospores.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Ahmed Younes M.B.B.CH [2]

C. albicans is the main species causing infection in humans more than any other candida species.

Candida albicans is the most common cause of oropharyngeal candidiasis.^[1][2]

Other candida strains can cause oropharyngeal candidiasis:^[1][2]

• Candida krusei
• Candida glabrata
• Candida tropicalis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Ahmed Younes M.B.B.CH [2]

Oropharyngeal candidiasis must be differentiated from its different kinds and from various other diseases that can cause stomatitis or glossitis

Oropharyngeal candidiasis must be differentiated from its different kinds and from various other diseases that can cause stomatitis or glossitis:^[1][2]

• Aphthous ulcers
• Herpes simplex oral lesions
• Tumors of the tongue
  • Squamous cell carcinoma ^[3]
  • Leukoplakia^[4]
  • Melanoma^[5]
  • Torus Palatinus^[6]
• Autoimmune diseases^[7]
• Behcet’s syndrome^[8]
• CMV oral ulcers
• Blastomycosis oral lesions
• Crohn’s disease
• Agranulocytosis
• Fordyce’s spots
• Drug induced
• Burning mouth syndrome
• Syphilis
• Coxsackie virus accompanies involvement of the hands and the mouth
• HIV
• VZV or Chicken pox

Oral candidiasis must be differentiated from other diseases causing oral lesions such as leukoplakia and herpes simplex virus infection.

Disease	Presentation	Risk Factors	Diagnosis	Affected Organ Systems	Important features	Picture
Diseases predominantly affecting the oral cavity
Oral Candidiasis	Dysphagia or odynophagia White patches on the mouth and tongue	Newborn babies Denture users Poorly controlled diabetes As a side effect of medication, most commonly having taken antibiotics. Inhaled corticosteroids for the treatment of lung conditions (e.g, asthma or COPD) may also result in oral candidiasis which may be reduced by regularly rinsing the mouth with water after taking the medication. People with poor nutrition, specifically vitamin A, iron and folate deficiencies. People with an immune deficiency (e.g. as a result of AIDS/HIV or chemotherapy treatment). Women undergoing hormonal changes, like pregnancy or those on birth control pills. Organ transplantation patients	Clinical diagnosis Confirmatory tests rarely needed	Localized candidiasis Oral and esophageal candidasis Candida vulvovaginitis Chronic mucocutaneous candidiasis Invasive candidasis Candidaemia Candida endocarditis Candida osteoarticular disease	Oral candidiaisis is a benign self limiting disease unless accompanied by immunosuppression.
Herpes simplex oral lesions	Fever Sore throat Painful ulcers	Stress Recent URTI Female sex	Physical examination Viral culture Tzanck smear	Orofacial Infection Anogenital Infection Ocular Infection Herpes Encephalitis Neonatal Herpes Herpetic Whitlow Herpes Gladiatorum	The symptoms of primary HSV infection generally resolve within two weeks
Aphthous ulcers	Painful, red spot or bump that develops into an open ulcer	Being a female Between the ages of 10-40 Family history of aphthous ulcers	Physical examination Diagnosis of exclusion	Oral cavity	Self-limiting , Pain decreases in 7 to 10 days, with complete healing in 1 to 3 weeks
Squamous cell carcinoma	Non healing ulcer, nodule, indurated plaque or mass May involve skin, lips, inside the mouth, throat or esophagus	Chronic sun or UV exposure Fair skin Elderly age (>45 yrs) Male sex Smoking	Physical exam Biopsy	Oral Cavity Floor of mouth Lateral tongue Throat Esophagus	Malignant Can spread to TMJ Some times associated with leukoplakia
Leukoplakia	White leathery spots on the mucous membranes of the tongue and inside of the mouth Lateral borders of tongue	Atypical Tobacco use Chronic irritation Immunodeficiency Bloodroot (sanguinaria)	Physical exam Diagnosis of exclusion Biopsy	Vulvar lesions occur independent of oral lesions	Associated with HIV Persistant white spots Benign but can progress to carcinoma after almost 10 years Oral proliferative verrucous leukoplakia is an aggressive sub type with multiple lesions and higher conversion to warts or carcinoma[9]
Melanoma	A lesion with ABCD Asymmetry Border irregularity Color variation Diameter changes Bleeding from the lesion	UV radiations Genetic predisposition Old age Male gender Family or personal history of melanoma Multiple benign or atypical nevi	ABCD characteristics Bleeding or ulceration may show malignancy Serum LDH may be elevated in case of malignancy Biopsy	Can metastasize All UV radiation or sun exposed areas can be effected independently 1-2 to hundreds of granules	Neural crest cell derivative Development begins with disruption of nevus growth control Progression involves MAPK/ERK pathway N-RAS or BRAF oncogene also involved
Fordyce spots	Rice-like granules or spots Small, painless, raised, pale, red or white 1 to 3 mm in diameter	Greasy skin types Some rheumatic disorders Hereditary nonpolyposis colorectal cancer Lower gingiva (gums) Vestibular mucosa	Physical exam Small keratin-filled pseudocysts May be seen on incidental mucosal biopsy Biopsy not done for them primarily	Oral cavity Vermilion border of the lips Oral mucosa of the upper lip Buccal mucosa in the commissural region often bilaterally Genitals	Benign neoplasms with sebaceous features Visible sebaceous glands No surrounding mucosal change Several adjacent glands may coalesce into a larger cauliflower-like cluster
Burning mouth syndrome	Burning or tingling on the lips, tongue, or entire mouth	Nutritional deficiencies Chronic anxiety or depression Diabetes type 2 Menopause Oral thrush or dry mouth, or damaged nerves transmitting taste Female gender Menopause	Presentation Physical exam	Oral cavity	Pain typically is low in the morning and builds up over the day Low dosages of benzodiazepines, tricyclic antidepressants or anticonvulsants may be effective
Torus palatinus	Bony growth on midline of the hard palate Nodular mass covered with normal mucosa	Genetic predisposition Autosomal dominant	Physical exam Types Flat tori Spindle tori Nodular tori Lobular tori	Hard palate	More common in Asian and Inuit populations Twice more common in females Repeated trauma can cause bleeding Surgery may be required in symptomatic
Diseases involving oral cavity and other organ systems
Behcet’s disease	Painful mouth sores Acne like skin lesions Headache, fever, poor balance, disorientation Abdominal pain, diarrhea or bleeding Uveitis Joint swelling and joint pain Genital sores wit pain and scaring Aneurysms	Over active immune system	Physical examination	Mouth Genitals GIT Eye Joints Skin Vascular system Brain	Outbreaks of exaggerated inflammation Affects smaller blood vessels
Crohn’s disease	Chronic, episodic diarrhea or constipation Abdominal pain Vomiting Weight loss or weight gain	Smoking Whites and European Jews Hormonal contraception Diets high in microparticles, sweet, fatty or refined foods Industrialized country	Typical history and symptoms Skip lesions on biopsy Anti-Saccharomyces cerevisiae antibodies (ASCA) Anti-neutrophil cytoplasmic antibodies (ANCA)	Eyes Joints Skin	May lead to Obstructions Abscesses Free perforation Hemorrhage
Agranulocytosis	Fever or chills Frequent infections Unusual redness, pain, or swelling around a wound Mouth ulcers Abdominal pain Burning sensation when urinating Sore throat	Medications[10] Cytotoxic chemotherapy Hematologic malignancies Autoimmune disorders	Neutropenia <100 cells per micro litre Eosinopenia Basopenia	Oral cavity Skin GIT Urinary system Conjunctiva	Immunocompromization Types Drug-induced Malignant Autoimmune
Syphilis[11]	Chancre Regional lymphadenopathy	Multiple sexual partners Illicit drug use Unprotected sex Men who have sex with men Residence in highly prevalent areas HIV infection Presence of other STIs Previous history of STIs Intravenous drug use	Darkfield microscopy Non treponemal tests like VDRL and RPR test) Treponemal testsFTA-ABS tests, (TP-PA) assay, enzyme immunoassays, and chemiluminescence immunoassays)	Oral cavity Penis Cervix Labia Anal canal Rectum CNS CVS	Primary syphilis Chancre Secondary syphilis Condylomata lata Latent syphilis Asymptomatic Tertiary syphilis Gummas Neurosyphilis
Coxsackie virus	Fever Sores in the mouth Rash with blisters Aches	Pregnancy immunodeficiency	History and Physical exam Throat swabs Swabs from the lesion Tzanck test	Oral cavity Skin	Symptomatic treatment
Chicken pox	Conjunctival symptoms Catarrhal symptoms Characteristic spots on the trunk appearing in two or three waves Itching	Pregnancy Premature infants born to susceptible mothers All infants born at less than 28 weeks gestation or who weigh =1000 grams Immunocompromised	History and physical exam PCR to detect VZV in skin lesions (vesicles, scabs, maculopapular lesions)	Oral cavity Skin	Sodium bicarbonate in baths or antihistamines for itching Paracetamol (acetaminophen) for fever Prednisolone is contraindicated
Measles	Fever Rash Cough Coryza (runny nose) Conjunctivitis (pink eye) Malaise Koplick spots in mouth	Unvaccinated individuals[12][13] Crowded and/or unsanitary conditions Traveling to less developed and developing countries Immunocompromized Winter and spring seasons Born after 1956 and never fully vaccinated Health care workers	History and examination PCR for Measles-specific IgM antibody PCR for Measles RNA	Oral cavity Skin Respiratory tract Eyes Throat	Caused by Morbillivirus Primary site of infection is the respiratory epithelium of the nasopharynx Transmitted in respiratory secretions, via aerosol droplets containing virus particles

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Ahmed Younes M.B.B.CH [2]

Oral candidiasis is not common among the general population but is frequently diagnosed in the immunocompromised patients.

• The infection is not very common in the general population.
• It is estimated that between 5% and 7% of infants less than one month old will develop oral candidiasis.
• The prevalence of oral candidiasis among AIDS patients is estimated to be between 9% and 31%, and studies have documented clinical evidence of oral candidiasis in nearly 20% of cancer patients.^[1]
• Thrush is the fourth most common cause of nosocomial bloodstream infections.
• The incidence is 8 cases per 100,000 in the general population.
• There is a higher incidence among neonates and African-Americans.^[2]
• Oleander (OPC) used to be a common opportunistic infection in HIV-infected persons (prior to the introduction of highly active antiretroviral therapy HAART).
• Nosocomial disease surveillance is conducted by NNIS in selected hospitals. Active population-based surveillance for candidemia is being conducted in selected U.S. sites.^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Ahmed Younes M.B.B.CH [2]

Uncontrolled diabetes are more likely to get oral thrush, because the extra glucose in saliva acts as a substrate for Candida. High doses of antibiotics or extended use of antibiotics also increases the risk of oral thrush. Antibiotics kill bacterial flora that compete with candida. People with poorly fitting dentures are also more likely to get thrush.

• Thrush is commonly seen in infants.
• It is not considered abnormal in infants unless it lasts longer than 2 weeks.
• People who have uncontrolled diabetes are more likely to get oral thrush because the extra sugar in saliva acts as a substrate for Candida.
• High doses of antibiotics or extended use of antibiotics also increases the risk of oral thrush. Antibiotics kill bacterial flora that compete with candida.
• People with poorly fitting dentures are also more likely to get thrush.

• People with an immune deficiency (e.g. as a result of AIDS/HIV or chemotherapy treatment)
• Newborn babies
• Denture users
• Poorly controlled diabetes
• As a side effect of medication, most commonly having taken antibiotics. Inhaled corticosteroids for treatment of lung conditions (e.g, asthma or COPD) may also result in oral candidiasis which may be reduced by regularly rinsing the mouth with water after taking the medication.
• People with poor nutrition, specifically vitamin A, iron and folate deficiencies
• People with an immune deficiency (e.g. as a result of AIDS/HIV or chemotherapy treatment)
• Women undergoing hormonal changes, like pregnancy or those on birth control pills
• Organ transplantation patients

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Ahmed Younes M.B.B.CH [2]

There are no sequelae with appropriate antifungal therapy. In contrast, among immunocompromised patients with disseminated infections, the morbidity and mortality are very high.

• Thrush in infants may be painful, but is rarely serious. If it does not resolve on its own within 2 weeks, a pediatrician must be notified.
• In adults, thrush that occurs in the mouth can be cured. However, the long-term outlook is dependent on a persons immune status and the cause of the immune deficit.
• In patients with immunodeficiency (HIV-positive or receiving chemotherapy), Candida can spread throughout body, causing esophagitis,meningitis, endocarditis, arthritis, or endophthalmitis.

Oropharyngeal candidiasis is rarely complicated except in immunocompromised individuals.

• Thrush in infants may cause weight loss because of dysphagia and discomfort associated with it.
• Spread to the trachea or the esophagus (causing respiratory distress or esophagitis) is rarely seen in otherwise healthy individuals.
• Systemic spread causing candidaemia and distant candida infection is frequently seen in immunocompromised individuals.

• Prognosis of oropharyngeal candidiasis is excellent in otherwise immunocompetent individuals with no serious sequelae in the majority of cases.
• Special attention should be given to immunocompromised patients as local spread to the trachea or esophagus or systemic spread causing candidaemia or distant candidiasis can be very serious with very high mortality rate.

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