Esophageal Candidiasis

Etiology

By far the highest risk factor for developing esophageal candidiasis is impaired cell-mediated immunity. Immunosuppressed patients at risk for esophageal candidiasis include HIV positive and AIDS patients, chemotherapy patients, patients with radiation to the neck region, antibiotic therapy, patients on chronic systemic or topical inhaled corticosteroids, diabetes mellitus, adrenal insufficiency, and advanced age.[1][2] Studies have shown that the use of proton-pump inhibitors is also a strong risk factor for esophageal candidiasis in immunocompetent patients.

Epidemiology

Studies have not shown a predominance of esophageal candida in either sex. Increasing age, HIV infection and the use of corticosteroids have been found to correlate with candidal esophagitis.  The median age of a person with esophageal candidiasis is 55.5 years. Several studies have shown esophageal candidiasis incidence rates ranging from 0.32 to 5.2% in the general population. There is a 9.8% prevalence in HIV-positive patients. The risk of esophageal candidiasis increases in HIV patients when the CD4 count is less than 200. The prevalence of esophageal candidiasis in HIV-infected patients appears to be decreasing due to the effectiveness of highly active antiretroviral therapy (HARRT). However, the incidence in non-HIV patients appears to be increasing, possibly due to comorbidities such as diabetes mellitus or from medications such as antibiotics and corticosteroids. Some studies show that smoking tobacco also correlates with developing esophageal candidiasis.[2][3][4]

Pathophysiology

Candida albicans can be part of the normal oral flora. Due to impaired cell-mediated immunity, the esophageal epithelial layer is susceptible to infection and colonization by candida. The candida proliferates and adheres to the esophageal mucosa forming white-yellow plaques. The plaques can be seen on upper endoscopy and do not wash from the mucosa with water irrigation. These plaques can be found diffusely throughout the entire esophagus or localized in the upper, mid, or distal esophagus.[2]

Histopathology

Histologic confirmation of candida in the esophagus is the gold standard for diagnosis. Hematoxylin and eosin stain of biopsies or brushing of esophageal candidiasis almost always show pseudohyphae which is diagnostic for esophageal candidiasis. The mucosa involved may exhibit desquamated parakeratosis which characteristically has groups of squamous cells that have detached or are in the process of detaching from the main squamous-lined tissue. This finding is not however specific to esophageal candidiasis. Pathology may demonstrate acute inflammation and/or intraepithelial lymphocytosis.[2]

History and Physical

Patients with esophageal candidiasis can have a multitude of complaints; however, patients are often asymptomatic. The most common symptoms associated with esophageal candidiasis are dysphagia, odynophagia, and retrosternal chest pain. Odynophagia is considered to be the hallmark of esophageal candidiasis. Other symptoms include abdominal pain, heartburn, weight loss, diarrhea, nausea, vomiting, melena.[1][2]

The only finding may be an associated infection of the oropharynx with candida.

Evaluation

Diagnosing esophageal candidiasis is via upper endoscopic evaluation. Visualizing the candida on the esophageal mucosa as white plaques or exudates confirms the diagnosis.  Plaques and exudates are adherent to the mucosa and do not wash off with water irrigation. There may also be mucosal breaks or ulcerations. Biopsies or brushings of the plaques can undergo testing for histologic confirmation of the infection.[1]

Treatment / Management

Treatment of esophageal candidiasis involves the use of antifungal therapy. Unlike oropharyngeal candidiasis, esophageal candidiasis should always be treated with systemic agents and not topical agents. The most commonly used medication to treat esophageal candidiasis is oral fluconazole 200 to 400 mg per day for 14 to 21 days.  If patients cannot tolerate oral intake, then intravenous Fluconazole 400 mg daily can be used and then de-escalated to oral Fluconazole when the patient can tolerate oral medications. Fluconazole 100 to 200 mg three times per week can be used to suppress recurrent esophageal candidiasis. Micafungin 150 mg IV daily has been shown to be non-inferior to fluconazole at 200 mg daily. Itraconazole 200 mg per day orally or Voriconazole 200 mg twice daily for 14 to 21 days are other treatment options. Amphotericin B deoxycholate 0.3 to 0.7 mg/kg daily can be used in patients with refractory candida esophagitis, but it has serious medication side effects and should be avoided if possible. Posaconazole 400 mg twice daily has been effective in refractory esophageal candidiasis as well. [5][6][7] (A1)

One may also use caspofungin as it is preferred over amphotericin.

Since esophageal candidiasis is an opportunistic infection and most often seen in immunocompromised persons, the cause of the immunosuppression should be diagnosed and treated as well.[8][9][10](A1)

Patients who are immunosuppressed and have symptoms of odynophagia or dysphagia can empirically be treated with a 14-21 day course of antifungal therapy. If no improvement in symptoms is seen after 72 hours of treatment then upper endoscopy should be performed.[11] (A1)

The dose of the azole agents does need modification in patients with renal insufficiency.

Azoles are considered teratogenic, so in pregnant patients with esophageal candidiasis, Amphotericin B is preferred.

Differential Diagnosis

Other common causes of esophagitis are as follows:[1][12][13]

• Cytomegalovirus
• Herpes simplex virus
• Eosinophilic esophagitis
• Pill-induced esophagitis
• Gastroesophageal reflux disease
• Radiation esophagitis
• Bacterial esophagitis (from Lactobacillus, B-hemolytic streptococci, Cryptosporidium, Pneumocystis carinii, Mycobacterium avium complex, Nocardia, Mycobacterium tuberculosis, Leishmania donovani)

Prognosis

There are no specific papers discussing the prognosis of esophageal candidiasis. It is usually treated successfully with antifungal agents. Resistant and refractory infections can occur and may require alternative agents for treatment or long term antifungal prophylaxis to reduce recurrence.[7]

Complications

Esophageal candidiasis complications include esophageal ulcerations with potential for esophageal perforation and upper gastrointestinal bleeding, weight loss, malnourishment, sepsis, candidemia, esophageal stricture, fistula formation into a bronchial tree.[14][15][16][2]