eMedicine Specialties > Gastroenterology > Esophagus

Cytomegalovirus Esophagitis

Author: Sandeep Mukherjee, MB, BCh, MPH, FRCPC, Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center
Coauthor(s): Vivek V Gumaste, MD, Associate Professor of Medicine, Mt Sinai School of Medicine; Adjunct Clinical Assistant, Mt Sinai Hospital; Director, Division of Gastroenterology, City Hospital Center
Contributor Information and Disclosures

Updated: Jan 3, 2010

Introduction

Background

Cytomegalovirus (CMV) is a member of the Herpesviridae family, along with herpes simplex viruses (HSVs) 1 and 2, Epstein-Barr virus, varicella-zoster virus, and others. CMV is a double-stranded DNA virus with a protein coat and lipoprotein envelope.


Characteristic giant cell with inclusion body in ...

Characteristic giant cell with inclusion body in a patient with cytomegalovirus esophagitis.

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Characteristic giant cell with inclusion body in ...

Characteristic giant cell with inclusion body in a patient with cytomegalovirus esophagitis.


Similar to other herpesviruses, CMV is icosahedral and replicates in the host's nucleus. Like the other members of this family, CMV has the ability to produce a latent infection. Replication in the host cell is typically represented by large intranuclear inclusion bodies and smaller cytoplasmic inclusions.

Studies have shown that 50-80% of the world's population is seropositive for CMV. The 2 peaks of primary CMV infection occur in preschool children and young adults. With the advent of immunosuppressive medications and the increased incidence of HIV infection and AIDS in the early 1980s, a new class of CMV infection has been described. CMV retinitis, adrenalitis, pneumonia, colitis, and esophagitis are some of the conditions observed in immunocompromised hosts.1 CMV is the third most common pathogen in patients with AIDS, superseded only by Pneumocystis carinii and Candida.

CMV GI disease was first described in the 1960s. Esophagitis is the second most common GI manifestation of CMV infection after colitis. CMV esophagitis has been reported in patients who have undergone transplantation, patients undergoing long-term renal dialysis, patients with HIV infection or AIDS, and patients with other debilitating diseases.

The average time to development of CMV esophagitis after solid organ transplantation is 5-7 months. Patients undergoing bone marrow transplantation may develop CMV disease much earlier, at an average of 2-3 months with symptoms occurring as early as 10 days after allogenic bone marrow transplantation.2 Patients with HIV infection are at increased risk because their CD4+ lymphocyte counts fall to less than 100 cells/µL.

Pathophysiology

Three major patterns of CMV infection are described.

The first is primary infection, in which the patient has never been exposed to the pathogen but becomes infected by a patient who is seropositive for the virus. This pattern accounts for 60% of cases. Primary infection in immunocompetent hosts causes few or no symptoms. Studies with in situ hybridization have shown that CMV DNA can persist in a latent form in most organs of the body.

The second pattern, reactivation, occurs in a patient who is seropositive with a latent virus that becomes reactivated when the host's immune system becomes compromised. This occurs in 10-20% of cases.

The third pattern is superinfection, which occurs in 20-40% of cases. A patient is seropositive for CMV and receives latently infected cells from another seropositive patient. The resulting CMV infection is from the latent donor cells, not the recipient cells.

Once a patient becomes infected, CMV can persist in the host tissues indefinitely. Both humoral and cellular mechanisms work in concert to control CMV infections and maintain the latent phase. However, if the host's T-cell response becomes compromised by disease or iatrogenic causes, the latent virus can be reactivated to cause a variety of syndromes.

Frequency

United States

Approximately 8-28% of patients with AIDS who undergo esophagogastroduodenoscopy (EGD) for dysphagia or odynophagia are found to have cultures positive for CMV. Approximately 38% of bone marrow transplant patients who undergo EGD for unexplained nausea and vomiting are positive for CMV esophagitis and/or small intestine involvement. CMV esophagitis has been described in only 3 patients immunocompromised by conditions other than transplantation, HIV infection, or AIDS. No cases have been reported in healthy hosts.

Mortality/Morbidity

Because CMV esophagitis occurs in immunocompromised hosts, the morbidity and mortality attributed to the esophagitis itself is difficult to quantitate.

  • Patients with CMV esophagitis may report severe dysphagia and/or odynophagia, preventing the already undernourished patient from obtaining much-needed nutrients. This can result in a progressive worsening of the patient's condition.
  • As the patient's condition worsens, the risk of disseminated CMV infection increases. Historically, however, the mortality rate associated with CMV disease in transplantation patients is 85%. With the advent of ganciclovir, the mortality rate has been markedly reduced.
  • In patients with HIV infection or AIDS, CMV infection is an opportunistic infection that signals a decline in patient immunity.

Race

CMV esophagitis has no racial predilection.

Sex

No sex predilection has been documented.

Age

No age-related predilection has been published; however, because immunocompetence generally decreases with age, older patients are at higher risk to develop CMV disease than younger patients.

Clinical

History

Patients with CMV esophagitis may also present with symptoms in other organs or systems (eg, colon, eyes, liver, lungs). Therefore, patients may present with multiple symptoms unrelated to the esophagitis.

Unlike HSV infection, patients present with a more gradual onset of symptoms.11 Nausea, vomiting, fever, epigastric pain, diarrhea, and weight loss are nonspecific symptoms but are more typical of CMV infection. By contrast, patients with HSV infection present with an abrupt onset of symptoms consisting of retrosternal chest pain and painful, difficult swallowing.

Keep in mind that CMV can coexist with HSV or any other cause of esophagitis; therefore, patient presentation may vary. Solid organ transplant recipients develop CMV disease 7-9 months after transplantation, while bone marrow transplant recipients develop disease after 2-3 months.

Presenting symptoms of patients with CMV esophagitis include the following:

  • Difficult or painful swallowing (ie, dysphagia, odynophagia, retrosternal pain)
  • Nausea and vomiting
  • Abdominal pain
  • Fever
  • Diarrhea
  • Weight loss
  • Chest pain
  • Hemoptysis

Physical

  • Adenopathy
  • Ulcerated oropharynx (uncommon)
  • Erythematous oropharynx

Causes

  • HIV infection or AIDS
  • High- or low-dose corticosteroid therapy
  • Immunosuppressive therapy following transplant
  • History of blood transfusion
  • Advancing age
  • Anything that can decrease the patient's immunity

More on Cytomegalovirus Esophagitis

Overview: Cytomegalovirus Esophagitis
Differential Diagnoses & Workup: Cytomegalovirus Esophagitis
Treatment & Medication: Cytomegalovirus Esophagitis
Follow-up: Cytomegalovirus Esophagitis
Multimedia: Cytomegalovirus Esophagitis
References
Further Reading
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References

  1. Sharma S, Gurakar A, Camci C, Jabbour N. Avoiding pitfalls: what an endoscopist should know in liver transplantation--part II. Dig Dis Sci. Jul 2009;54(7):1386-402. [Medline].

  2. Fiegl M, Gerbitz A, Gaeta A. Recovery from CMV esophagitis after allogeneic bone marrow transplantation using non-myeloablative conditioning: the role of immunosuppression. J Clin Virol. Nov 2005;34(3):219-23.

  3. Borges MC, Colares JK, Lima DM, Fonseca BA. Advantages and pitfalls of the polymerase chain reaction in the diagnosis of esophageal ulcers in AIDS patients. Dig Dis Sci. Sep 2009;54(9):1933-9. [Medline].

  4. Wilcox CM, Rodgers W, Lazenby A. Prospective comparison of brush cytology, viral culture, and histology for the diagnosis of ulcerative esophagitis in AIDS. Clin Gastroenterol Hepatol. Jul 2004;2(7):564-7. [Medline].

  5. Trappe R, Pohl H, Forberger A, Schindler R, Reinke P. Acute esophageal necrosis (black esophagus) in the renal transplant recipient: manifestation of primary cytomegalovirus infection. Transpl Infect Dis. Mar 2007;9(1):42-5. [Medline].

  6. Harada N, Shimada M, Suehiro T, et al. Unusual endoscopic findings of CMV esophagitis after liver transplantation. Hepatogastroenterology. Jul-Aug 2005;52(64):1236-9. [Medline].

  7. Baroco AL, Oldfield EC. Gastrointestinal cytomegalovirus disease in the immunocompromised patient. Curr Gastroenterol Rep. Aug 2008;10(4):409-16. [Medline].

  8. Len O, Gavalda J, Aguado JM, et al. Valganciclovir as treatment for cytomegalovirus disease in solid organ transplant recipients. Clin Infect Dis. Jan 1 2008;46(1):20-7. [Medline].

  9. Razonable RR. Cytomegalovirus infection after liver transplantation: current concepts and challenges. World J Gastroenterol. Aug 21 2008;14(31):4849-60. [Medline].

  10. Cvetkovic RS, Wellington K. Valganciclovir: a review of its use in the management of CMV infection and disease in immunocompromised patients. Drugs. 2005;65(6):859-78. [Medline].

  11. Attwood SE, Lamb CA. Eosinophilic oesophagitis and other non-reflux inflammatory conditions of the oesophagus: diagnostic imaging and management. Best Pract Res Clin Gastroenterol. 2008;22(4):639-60. [Medline].

  12. Baehr PH, McDonald GB. Esophageal infections: risk factors, presentation, diagnosis, and treatment. Gastroenterology. Feb 1994;106(2):509-32. [Medline].

  13. Brouillette DE, Alexander J, Yoo YK, et al. T-cell populations in liver and renal transplant recipients with infectious esophagitis. Dig Dis Sci. Jan 1989;34(1):92-6. [Medline].

  14. Garcia-Gallo CL, Gil PU, Laporta R. Is gammaglobulin anti-CMV warranted in lung transplantation?. Transplant Proc. Nov 2005;37(9):4043-5.

  15. Greenson JK. Macrophage aggregates in cytomegalovirus esophagitis. Hum Pathol. Mar 1997;28(3):375-8. [Medline].

  16. Laguna F, Garcia-Samaniego J, Alonso MJ, et al. Pseudotumoral appearance of cytomegalovirus esophagitis and gastritis in AIDS patients. Am J Gastroenterol. Jul 1993;88(7):1108-11. [Medline].

  17. Levine MS, Loercher G, Katzka DA, et al. Giant, human immunodeficiency virus-related ulcers in the esophagus. Radiology. Aug 1991;180(2):323-6. [Medline].

  18. Nelson MR, Connolly GM, Hawkins DA, Gazzard BG. Foscarnet in the treatment of cytomegalovirus infection of the esophagus and colon in patients with the acquired immune deficiency syndrome. Am J Gastroenterol. Jul 1991;86(7):876-81. [Medline].

  19. Parente F, Bianchi Porro G. Treatment of cytomegalovirus esophagitis in patients with acquired immune deficiency syndrome: a randomized controlled study of foscarnet versus ganciclovir. The Italian Cytomegalovirus Study Group. Am J Gastroenterol. Mar 1998;93(3):317-22. [Medline].

  20. Ponticelli C, Passerini P. Gastrointestinal complications in renal transplant recipients. Transpl Int. Jun 2005;18(6):643-50. [Medline].

  21. Spencer GD, Hackman RC, McDonald GB, et al. A prospective study of unexplained nausea and vomiting after marrow transplantation. Transplantation. Dec 1986;42(6):602-7. [Medline].

  22. Whitley RJ, Jacobson MA, Friedberg DN, et al. Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA. - Feinberg J. May 11 1998;158(9):957-69. [Medline].

  23. Wilcox CM. Esophageal strictures complicating ulcerative esophagitis in patients with AIDS. Am J Gastroenterol. Feb 1999;94(2):339-43. [Medline].

  24. Wilcox CM, Straub RF, Schwartz DA. Cytomegalovirus esophagitis in AIDS: a prospective evaluation of clinical response to ganciclovir therapy, relapse rate, and long-term outcome. Am J Med. Feb 1995;98(2):169-76. [Medline].

  25. Wilcox CM, Straub RF, Schwartz DA. Prospective endoscopic characterization of cytomegalovirus esophagitis in AIDS. Gastrointest Endosc. Jul-Aug 1994;40(4):481-4. [Medline].

  26. Wilcox CM, Straub RF, Schwartz DA. Prospective evaluation of biopsy number for the diagnosis of viral esophagitis in patients with HIV infection and esophageal ulcer. Gastrointest Endosc. Nov 1996;44(5):587-93. [Medline].

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Further Reading

Related eMedicine Topics

Clinical Trials
 Clinical Guidelines

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Keywords

cytomegalovirus esophagitis, CMV esophagitis, esophagitis, CMV infection, Herpesviridae, herpesvirus, herpes simplex virus, HSV, Epstein-Barr virus, varicella-zoster virus, EGD, esophagogastroduodenoscopy, dysphagia, odynophagia, HIV, AIDS, CMV esophagitis, CMV esophageal disease, HIV disease complications, AIDS complications, cytomegalovirus infection, cytomegalovirus, HIV/AIDS, esophageal disease

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Contributor Information and Disclosures

Author

Sandeep Mukherjee, MB, BCh, MPH, FRCPC, Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center
Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Coauthor(s)

Vivek V Gumaste, MD, Associate Professor of Medicine, Mt Sinai School of Medicine; Adjunct Clinical Assistant, Mt Sinai Hospital; Director, Division of Gastroenterology, City Hospital Center
Vivek V Gumaste, MD is a member of the following medical societies: American College of Gastroenterology and American Gastroenterological Association
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey D Band, MD, Clinical Professor of Medicine, Wayne State University School of Medicine; Director, Division of Infectious Diseases and International Medicine, William Beaumont Hospital Corporation
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

James L Achord, MD, Professor Emeritus, Department of Medicine, Division of Digestive Diseases, University of Mississippi School of Medicine
James L Achord, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Mississippi State Medical Association, New York Academy of Sciences, Sigma Xi, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

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