Esophageal candidiasis

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

Esophageal candidiasis is an opportunistic infection of the esophagus by Candida albicans. The disease occurs in patients in immunocompromised states, including post-chemotherapy and in AIDS. It is also known as candidal esophagitis or monilial esophagitis.

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.

Esophageal candidiasis is classified according to the severity of lesions seen during endoscopy into 6 grades.

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.

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

Esophageal candidiasis should be differentiated from other diseases causing dysphagia especially in immunocompromised patients (e.g. herpes simplex esophagitis, CMV esophagitis).

Candidiasis is the most common cause of infectious esophagitis followed by HSV esophagitis.

Immunodeficiency is the most important risk factor for candida esophagitis.

Candida esophagitis is very responsive to antifungal therapy. Complications can be systemic due to the spread of infection to the blood stream or local as esophageal stricture and obstruction.

The underlying predisposing factors are usually clear on obtaining history (HIV, chemotherapy, etc ..). Odynophagia is the most common encountered symptom of esophageal candidiasis. Examination reveals signs of immunocompromisation that was the primary cause of developing esophageal thrush.

Although the appearance of the patches during endoscopy is diagnostic for esophageal candidiasis, biopsies should be obtained to confirm the diagnosis. If the patient is not already diagnosed with HIV or another immunocompromising disease, screening should be done.

Esophageal candidiasis is almost always treated with systemic antifungals (either parentral or oral). A trial of antifungal therapy is done before performing endoscopy in HIV patients with esophagitis.

Surgical intervention is not recommended for the management of esophageal candidiasis unless complications ensue.​

There is no established method for prevention of candida esophagitis.​

There are no secondary preventive measures available for candida esophagitis.

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]

Esophageal candidiasis is classified according to the severity of lesions seen during endoscopy.

Esophageal candidiasis is graded according to severity of the lesions on endoscopy into:^[1]

1. Grade I: few raised lesions (< 2 mm) without surrounding edema nor laceration
2. Grade II: multiple raised lesions (> 2mm) without surrounding edema nor laceration
3. Grade III: linear, nodular and confluent lesions
4. Grade IV: same as grade III with narrowing of the lumen and friability of the mucosa
5. Grade V: thick white plaque covering the lumen in circumferential manner causing narrowing of the lumen
6. Grade VI: endoscopy can detect oropharyngeal candidiasis

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 mucosa oppose 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]

By upper endoscopy, candida esophagitis appears as white patches on the esophageal mucosa.

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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 Esophageal candidiasis.^[1][2]

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

• Candida krusei
• Candida glabrata
• Candida tropicalis

Specific species of candida were isolated from immunocompromised patients:^[3]

• Candida inconspicua
• Candida dubliniensis

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

Esophageal candidiasis should be differentiated from other diseases causing dysphagia especially in immunocompromised patients (e.g. herpes simplex esophagitis, CMV esophagitis)

Esophageal candidiasis should be differentiated from other diseases causing dysphagia especially in immunocompromised patients.

	Prominent clinical features	Endoscopy findings
Candida esophagitis	Odynophagia is the most prominent symptom May be accompanied by oropharyngeal candidiasis	Endoscopy shows characteristic white yellowish lesions over the mucosa.
HSV esophagitis	HSV esophagitis is due to reactivation of HSV usually in immunocompromised patients. HSV esophagitis usually presents acutely as dysphagia, odynophagia accompanied by fever and other constitutional symptoms. Oropharyngeal vesicles and ulcers may accompany HSV esophagitis.[1]	HSV lesions are usually present in the distal esophagus. Lesions start as vesicles but later on coalesce and form large ulcers. Ulcers are 8-10 mm in size, has a volcano like appearance and covered with a white exudate.
CMV esophagitis	CMV esophagitis is characterized by more insidious onset of nausea, vomiting, dysphagia and consequent weight loss. CMV esophagitis occurs more commonly in organ transplant patients more than in HIV patients.	As in HSV esophagitis, CMV lesions are usually in the distal esophagus. Lesions can be  multiple small ulcers or large single shallow ulcer. CMV esophagitis can present as esophageal necrosis with no ulcers.[2]
Esophageal lymphoma	Esophageal lymphoma has nonspecific symptoms of dysphagia, hoarseness and  retrosternal chest pain.	Endoscopy is useful in obtaining biopsies as visual findings are not specific as lymphoma can be accompanied by candidiasis or HSV esophagitis.[3]

• Gastroesophageal reflux disease (GERD)
• Barrett’s esophagus
• Esophageal achalasia
• Pill esophagitis
• Eosinophilic esophagitis

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

Candidiasis is the most common cause of infectious esophagitis followed by HSV esophagitis.

• Esophageal candidiasis has not been adequately studied in immunocompetent individuals.
• Candidiasis is the most common cause of infectious esophagitis followed by HSV esophagitis.^[1][2]

Candida esophagitis is more common in patients older than 55 years old.^[3][2]

• In a study conducted in 2015, the prevalence of esophageal candidiasis was 11.2% in HIV infected individuals and 2.9% in HIV infected individuals.^[4]
• Esophageal candidiasis has been reported in 10-15% of immunocompromised patients during their lifetime.^[5]
• Autopsies revealed isolation of candida in 43% of immunocompromised individuals.^[6]

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

Immunodeficiency is the most important risk factor for candida esophagitis.

Immunodeficiency is the most important risk factor for candida esophagitis^[1]

• People with an immune deficiency (e.g. as a result of AIDS/HIV)
• Organ transplantation patients
• Patients undergoing chemotherapy
• Patients undergoing radiotherapy
• Hematologic malagninacies

• Esophageal stasis (achalasia, esophageal cancer)^[2]
• Malnutrition
• Alcoholism

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

Candida esophagitis is very responsive to antifungal therapy. Complications can be systemic due to the spread of infection to the blood stream or local as esophageal stricture and obstruction.

If left untreated, complications as esophageal stricture and candidaemia ensue.

Complications can be systemic due to spread of candida or localized due to the local invasion of the fungus.^[1]

• Systemic spread and fungemia
• Esophageal perforation
• Tracheoesophageal fistula
• Esophageal stricture
• Esophageal obstruction

• Prognosis is excellent and Esophageal candidiaisis is usually responsive to antifungal treatment.
• Recurrence is common after treatment due to persistence of the predisposing immunosuppression.