Cytomegalovirus esophagitis

Cytomegalovirus esophagitis

I. What every physician needs to know.

Cytomegalovirus (CMV) esophagitis is most commonly a disease of patients who are immunocompromised. It should be suspected in an immunocompromised patient with odynophagia, persistent central chest/epigastric pain, nausea, vomiting, and/or hematemesis. It is most commonly related to reactivation of the virus in individuals infected, often asymptomatically, in childhood. In immunocompetent hosts, symptoms are generally milder and often do not prompt invasive (i.e., esophagogastroduodenoscopy [EGD]) evaluation.

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

Diagnosis is suspected clinically based upon symptoms, but confirmed upon EGD and biopsy.

A. History Part I: Pattern Recognition:

Usually an immunocompromised host presents with the following:

  • Chest pain

  • Nausea and/or vomiting

  • Odynophagia

  • Occasionally hematemesis

B. History Part 2: Prevalence:

Classically, CMV esophagitis is a disease of the immunocompromised. It is seen frequently in human immunodeficiency virus (HIV) positive patients, especially in those with a CD4+ count less than 200; it is also seen in transplant patients on immunosuppression, patients exposed to steroids for extended periods of time, and patients with malignancy, especially those treated with chemoradiotherapy.

Milder disease manifestations have been noted in patients who are not immunocompromised; the disease is often self-limited in these individuals.

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

Candidal esophagitis without evidence of oral thrush, herpes simplex virus (HSV) esophagitis and varicella zoster virus (VZV) esophagitis may all mimic CMV esophagitis. In HIV-positive patients with CD4 counts <200 with dysphagia and mild odynophagia (with or without oral thrush), many clinicians treat empirically for candidal esophagitis with a trial of oral fluconazole given its greater prevalence compared to CMV esophagitis. If no improvement in symptoms are seen in 5 to 7 days, upper endoscopy evaluating for ulcerative esophagitis from CMV infection is warranted.

In a broader context, presenting symptoms can also mimic gastroesophageal reflux disease (GERD) or peptic ulcer disease (PUD).

D. Physical Examination Findings.

Physical exam is of limited usefulness in diagnosing CMV esophagitis.

E. What diagnostic tests should be performed?

Several laboratory studies may be helpful in narrowing down the differential to CMV esophagitis; definitive diagnosis is made on the basis of biopsies of the lesions.

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

In-depth review of the serologic diagnosis of CMV can be found in the parent topic.

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

The gold standard for diagnosis is upper endoscopy with biopsy of the ulcerated lesions. Ulcers are often serpiginous, and surrounding mucosa is generally unaffected. Given its propensity for affecting the immunocompromised host, concurrent candidal plaques may be seen if candidal esophagitis is also present. Histology will reveal intranuclear and intracytoplasmic inclusions in fibroblasts and endothelial cells.

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

Laboratory tests including blood CMV antigen assays, cultures, and DNA polymerase chain reaction (PCR) are not useful for evaluation of suspected CMV esophagitis as blood levels of CMV do not reliably correlate with target organ involvement.

III. Default Management.

In immunocompetent patients, the disease may be self-limiting or very mild, requiring no therapy. Use of antivirals in immunocompetent individuals is a matter of debate.

In immunocompromised patients who have a definitive diagnosis of CMV esophagitis, induction therapy with intravenous (IV) antivirals, specifically ganciclovir, is warranted.

A. Immediate management.

The drug of choice is ganciclovir (5 mg/kg twice daily) for immunocompromised patients; this should be continued for 3 to 6 weeks, although conversion from IV to oral for completion of the course once symptoms have improved is acceptable. Alternatively, foscarnet (90 mg/kg twice daily) may be used for 3 to 6 weeks.

Oral maintenance therapy with valganciclovir after completion of the induction phase is generally reserved for immunocompromised individuals who have suffered a relapse of the CMV gastrointestinal (GI) disease. Valganciclovir should not be used for induction therapy in immunocompromised hosts.

B. Physical Examination Tips to Guide Management.


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

On ganciclovir, monitoring of biweekly complete blood count (CBC) and weekly serum creatinine is required. The drug may need to be stopped if cytopenias become problematic.

On foscarnet, biweekly basic metabolic panel (BMP) with magnesium and phosphorus should be monitored. There is a risk of nephrotoxicity.

D. Long-term management.

Maintenance therapy may be required if there is a relapse of CMV in the GI tract.

E. Common Pitfalls and Side-Effects of Management


IV. Management with Co-Morbidities

A. Renal Insufficiency.

Caution with use of foscarnet in renal insufficiency; drug dose adjustment required for impaired creatinine clearance.

B. Liver Insufficiency.

No change in standard management.

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.

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

In patients with newly diagnosed HIV, highly active antiretroviral (HAART) therapy should be initiated when initial GI symptoms (nausea/odynophagia) have resolved.

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

No change in standard management.

I. Gastrointestinal or Nutrition Issues

Concurrent CMV colitis: treatment recommendations are the same.

J. Hematologic or Coagulation Issues

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment

No change in standard management.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

No specific follow-up.

B. Anticipated Length of Stay.

For immunocompetent patients with CMV esophagitis, symptoms may not warrant an inpatient stay for IV antivirals. In the immunocompromised host, initial induction with antiviral therapy IV is recommended; induction therapy may last as long as 3 weeks, but if symptoms improve, the patient can be transitioned to oral antivirals for completion of the course.

C. When is the Patient Ready for Discharge.

Patients can be discharged when symptoms improve and the patient is able to tolerate diet, and therapy can be transitioned to oral or an appropriate IV outpatient regimen is established.

D. Arranging for Clinic Follow-up

A repeat endoscopy to document mucosal healing may be warranted, especially in patients who complete 2 to 3 weeks of therapy and still have symptoms. This can be particularly important in the immunocompromised host.

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

If there is concurrent HIV infection the patient should be referred to the infectious diseases clinic to establish or follow-up post-hospital discharge within 2 to 3 weeks.

If repeat endoscopy is desired, arrange GI follow-up within 2-3 weeks, or near the conclusion of the drug course prescribed.

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


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

Twice-weekly CBC and weekly BMP for patients on ganciclovir is indicated; twice-weekly BMP with magnesium and phosphorus levels are indicated for patients on foscarnet.

E. Placement Considerations.

If outpatient IV antivirals are planned, placement of central access prior to discharge will be important.

F. Prognosis and Patient Counseling.

CMV infection in the immunocompetent host often resolves spontaneously without intervention or sequelae. CMV esophagitis in the immunocompromised host can recur; this risk can be minimized by completing therapy as directed and being compliant with HAART therapy in HIV patients.

VI. Patient Safety and Quality Measures

A. Core Indicator Standards and Documentation.


B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

If related to HIV, please see the section on HIV for appropriate follow-up.

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