Hospital Medicine

Candidal esophagitis

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Candidal Esophagitis

I. What every physician needs to know.

Candidal esophagitis is a condition most commonly seen in the immunocompromised and those with esophageal motility disorders. Reasons for increased susceptibility in these patient populations include increased fungal burden and the breakdown of normal mucosal barriers. Candida albicans is almost always the causative organism. The key presenting feature is odynophagia. Frequently, affected patients will also present with oral thrush. However, the lack of associated oropharyngeal candidiasis does not rule out esophageal involvement.

II. Diagnostic Confirmation: Are you sure your patient has candidal esophagitis?

A. History Part I: Pattern Recognition.

The key symptom reported in those affected by candidal esophagitis is odynophagia with pain typically located in the retrosternal region. Other associated symptoms and signs include concurrent oral thrush, nausea and vomiting. Dysphagia is seen much less often. However, even when severe, esophageal candidiasis may be asymptomatic.

B. History Part 2: Prevalence:

Those most at risk for developing this disease include human immunodeficiency virus (HIV)-infected patients with a CD4 cell count of less than 200, those with hematologic malignancies, patients on immunosuppressive medications, the elderly, and those with esophageal motility disorders.

C. History Part 3: Competing diagnoses that can mimic candidal esophagitis.

Other differential considerations include alternate causes of infectious esophagitis (cytomegalovirus, herpes simplex virus), medication-induced (i.e. pill-induced) esophagitis and eosinophilic esophagitis.

D. Physical Examination Findings.

The only associated exam finding seen is the presence of concurrent oropharyngeal thrush, although this is not needed to be present for diagnosis.

E. What diagnostic tests should be performed?

When necessary, upper endoscopy with biopsy is typically the only diagnostic test utilized to confirm diagnosis.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

In those with appropriate risk factors and symptoms suggestive of candidal esophagitis it is reasonable to start empiric treatment with a systemic antifungal agent. If symptoms fail to improve after 72 hours of empiric treatment, upper endoscopy with biopsies is the diagnostic test of choice.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Imaging studies are typically not useful in the diagnosis of esophageal candidiasis. If patients fail to improve with empiric treatment or the suspicion of another underlying etiology is high, upper endoscopy with mucosal biopsy should be pursued to establish the diagnosis.

With endoscopy, local erythema, edema, white patches, and ulcerations can all be seen. Typically, the distal third of the esophagus is most often affected. Biopsy results reveal mucosal invasion of yeast and pseudohyphae. Cultures return positive for candida.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Barium esophagography may identify esophageal abnormalities in patients with this condition but the results are non-specific and of limited clinical utility.

III. Default Management.

A. Immediate management.

When esophageal candidiasis is suspected, empiric antifungal treatment should be initiated. Treatment always requires systemic antifungal therapy. Fluconazole is the agent of choice, either orally or intravenously. Intravenous therapy may be necessary initially for those who cannot take oral medication or those with severe disease. Typically, a loading dose of 400mg is given, followed by a dose of 200mg-400mg for 14-21 days after clinical improvement is noted.

B. Physical Examination Tips to Guide Management.

The patient can be monitored for resolution of associated oropharyngeal thrush, when present.

C. Laboratory Tests to Monitor Response to, and Adjustments in, Management.

Prolonged administration of azoles can cause hepatotoxicity. Liver function testing should be performed periodically in patients who require prolonged therapy.

D. Long-term management.

Long-term prophylaxis is seldom recommended. Exceptions to this are patients who have had multiple episodes of candidal esophagitis and remain immunosuppressed. However, development of resistance remains an ongoing consideration in the decision of whether to initiate antifungal prophylaxis.

E. Common Pitfalls and Side-Effects of Management.

If empiric treatment for candidal esophagitis is begun and no improvement is seen within 72 hours, upper endoscopy should be pursued to rule out alternate causes of esophagitis.

For patients who cannot take or are intolerant to fluconazole, or who have documented esophageal candidiasis that is refractory to treatment, other agents should be considered. Itraconazole has similar efficacy but its use is limited by side effects of severe nausea and the concern for drug interactions. Voriconazole and posaconazole represent reasonable options in outpatients who can tolerate oral medications and are maintaining hydration.

In those who require intravenous therapy and cannot tolerate fluconazole, an echinocandin such as caspofungin should be used. Echinocandins are generally preferred over amphotericin B when intravenous therapy is necessary due to increased incidence of toxicity.

IV. Management with Co-Morbidities.

A. Renal Insufficiency.

Azole therapy needs to be adjusted in those with renal insufficiency.

B. Liver Insufficiency.

Caution is advised with the use of azoles in patients with pre-existing liver insufficiency due to the risk of hepatotoxicity.

C. Systolic and Diastolic Heart Failure.

No change in standard management.

D. Coronary Artery Disease or Peripheral Vascular Disease.

No change in standard management.

E. Diabetes or other Endocrine issues.

No change in standard management.

F. Malignancy.

No change in standard management. Prophylactic antifungals may be considered in patients with recurrent episodes of esophageal candidiasis.

G. Immunosuppression (HIV, chronic steroids, etc.).

No change in standard management. Prophylactic antifungals may be considered in patients with recurrent episodes of esophageal candidiasis.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management.

I. Gastrointestinal or Nutrition Issues.

Azole therapy can cause gastrointestinal upset. Other agents may need to be considered depending on the severity of side effects.

J. Hematologic or Coagulation Issues.

Exercise caution with azole use in those on Coumadin due to the potential for interactions.

K. Dementia or Psychiatric Illness / Treatment.

No change in standard management.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

None

B. Anticipated Length of Stay.

Variable based on severity. Clinical improvement on treatment is expected within 72 hours.

C. When is the Patient Ready for Discharge.

Discharge should be considered when the patient is able to tolerate oral antibiotics, oral intake and maintain adequate hydration.

D. Arranging for Clinic Follow-up

1. When should clinic follow up be arranged and with whom?

Follow-up should occur with the patient's primary care provider within 2 weeks to determine ultimate duration of treatment.

2. What tests should be conducted prior to discharge to enable best clinic first visit?

None

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit?

None

E. Placement Considerations.

None

F. Prognosis and Patient Counseling.

Treatment of acute disease is very effective with clinical cure expected. Failure to respond to initial therapy should prompt consideration of resistance and a possible switch to an alternate therapy, along with endoscopy to rule out alternate etiologies for persistent symptoms. Prognosis relates more to underlying comorbidities.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

None

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Antifungal prophylaxis is only considered in those with recurrent episodes of candidal esophagitis who remain immunosuppressed.

What's the evidence?

Bennett, JE, Kasper, DL. "Candidiasis". Harrison's Principals of Internal Medicine.

Kaplan, JE, Benson, C, Holmes, KH. "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". MMWR Recomm Rep. vol. 58. 2009. pp. 1.

Norton, ML, Starlin, R, Lin, T. "Infections of the GI Tract". Infectious Diseases Subspecialty Consult. Lippincott Williams and Wilkins. 2005.

Pappas, PG, Kauffman, CA, Andes, D. "Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America". Clin Infect Dis. vol. 48. 2009. pp. 503.

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