You are in: eMedicine Specialties > Gastroenterology > Esophagus Cytomegalovirus EsophagitisArticle Last Updated: Oct 10, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Deron J Tessier, MD, Staff Surgeon, Kaiser Permanente Medical Center, Fontana, CA Deron J Tessier is a member of the following medical societies: American College of Surgeons and American Medical Association Coauthor(s): Russell A Williams, MBBS, Program Director, Professor, Department of Surgery, University of California Medical Center at Irvine Editors: 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; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; James L Achord, MD, Professor Emeritus, Department of Medicine, Division of Digestive Diseases, University of Mississippi School of Medicine; Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine; 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 Author and Editor Disclosure Synonyms and related keywords: CMV, 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 INTRODUCTIONSection 2 of 11
  BackgroundCytomegalovirus (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. 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. 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. Patients with HIV infection are at increased risk because their CD4+ lymphocyte counts fall to less than 100 cells/µL. PathophysiologyThree 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. FrequencyUnited StatesApproximately 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/MorbidityBecause CMV esophagitis occurs in immunocompromised hosts, the morbidity and mortality attributed to the esophagitis itself is difficult to quantitate.
RaceCMV esophagitis has no racial predilection. SexNo sex predilection has been documented. AgeNo 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. CLINICALSection 3 of 11
HistoryPatients 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. 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:
Physical
Causes
DIFFERENTIALSSection 4 of 11
Achalasia Barrett Esophagus and Barrett Ulcer Candidiasis Cryptococcosis Esophageal Cancer Gastroesophageal Reflux Disease Herpes Simplex Histoplasmosis Tuberculosis
| |||||||||||||||||||||||||||||||||||||||
| Drug Name | Ganciclovir (Cytovene) |
|---|---|
| Description | Acyclic nucleoside analogue of 2'deoxyguanasine. Phosphorylated first to monophosphate form by a CMV-encoded protein kinase homologue, then to the diphosphate and triphosphate form by cellular kinases. This allows for a 100-times higher concentration in CMV-infected cells. Thought to inhibit CMV replication by competitive inhibition of viral DNA polymerases and by incorporating itself into viral DNA, causing termination of viral DNA elongation. |
| Adult Dose | Induction: 5 mg/kg IV q12h for at least 21 d, followed by maintenance therapy at 6 mg/kg IV 5 times/wk; role of PO ganciclovir maintenance at doses of 1 g tid uncertain |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Concomitant administration with cytotoxic drugs (eg, dapsone, vinblastine, doxorubicin, pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim-sulfamethoxazole combinations, other nucleoside analogs) may result in additive toxicity in bone marrow, spermatogonia, and germinal layers of skin and GI mucosa (coadminister only if potential benefits outweigh risks); coadministration with imipenem-cilastatin may cause generalized seizures (use only if potential benefits outweigh risks); serum creatinine may increase following concurrent use with either cyclosporine or amphotericin B; in presence of probenecid, renal clearance is reduced; bioavailability may increase when didanosine is administered either 2 h prior to or simultaneously; bioavailability may decrease in presence of zidovudine, while bioavailability of zidovudine is increased |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Clinical toxicity includes granulocytopenia, anemia, and thrombocytopenia; because PO ganciclovir is associated with higher rate of CMV retinitis progression compared with IV formulation, use only when benefits outweigh risks (advanced HIV disease); half-life and plasma/serum concentrations may increase as a result of reduced renal clearance; dosages > 6 mg/kg IV may result in increased toxicity; rapid infusions may result in increased toxicity; initially, reconstituted solutions of IV ganciclovir have a high pH (11); phlebitis or pain may occur at injection site despite further dilution in IV fluids; administration should be accompanied by adequate hydration; photosensitization (photoallergy or phototoxicity) may occur |
| Drug Name | Foscarnet (Foscavir) |
|---|---|
| Description | Organic analogue of inorganic pyrophosphate that inhibits replication of HSV, including CMV. Selectively inhibits at pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular polymerases. Unlike ganciclovir, does not require activation by a kinase and is active in vitro. |
| Adult Dose | Induction: 90 mg/kg IV q12h for 3-6 wk Maintenance: 90-120 mg/kg/d IV |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | Coadministration with potentially nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine) may increase nephrotoxicity (do not administer unless potential benefits outweigh risks); coadministration with IV pentamidine may cause hypocalcemia |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | May cause decline in renal function; for correct dosing, obtain 24-h serum creatinine at baseline and continue to monitor (discontinue if serum creatinine <0.4 mL/min/kg); hydration may reduce nephrotoxicity Carefully monitor electrolytes (eg, calcium, magnesium); assess for electrolyte and mineral level abnormalities if mild perioral numbness, paresthesias symptoms, or seizures occur; granulocytopenia and anemia may occur (regularly monitor CBC count) Infuse into veins with adequate blood flow to avoid local irritation; to avoid toxicity, do not administer by rapid or bolus IV injection |
| Media file 1: Characteristic giant cell with inclusion body in a patient with cytomegalovirus esophagitis. | |
 | View Full Size Image | Media type: Photo |
Cytomegalovirus Esophagitis excerpt
Article Last Updated: Oct 10, 2006
