Contents

Search

cytomegalovirus (CMV, human herpesvirus 5, HHV5)

Etiology: risk factors for CMV infection: 1) AIDS (especially in association with Pneumocystis carinii) - HIV1 infection with CD4 count < 50/uL [2] 2) organ transplantation - especially seronegative recipient, seropositive donor 3) lymphoreticular malignancy 4) cardiopulmonary bypass 5) multiple blood transfusions Epidemiology: 1) most common congenital infection [5] 1) 2nd most common infection in patients with AIDS 2) most common infectious complication of organ transplantation 3) can be transmitted by blood transfusions: - CMV is transmitted by granulocytes 4) may be introduced by transplantation of CMV-infected organ 5) disease may occur as reactivation of latent CMV infection Pathology: 1) retinitis (20-30% of patients with advanced AIDS) 2) pneumonia 3) gastrointestinal ulcerations 4) encephalitis 5) adrenalitis 6) infectious mononucleosis-like syndrome 7) putative receptor is beta-2 microglobulin/MHC [3] 8) cytomegalovirus glycoprotein UL16 binds to & causes sequestration of MICB in the endoplasmic reticulum 9) endothelial cells infected with CMV secrete renin, angiotensin-2 & pro-inflammatory cytokines & develop intimal hyperplasia & atherosclerosis (mouse model) [4] 10) hearing loss in early childhood with congenital infection [5] 11) virus latent in monocytes, lymphocytes, endothelial cells, epithelial cells [2] Clinical manifestations: 1) generally asymptomatic 2) mononucleosis-like syndrome a) fever b) lymphadenopathy c) fatigue 3) symptomatic CMV in organ transplant patients a) generally occurs within 1st few months following organ transplantation b) fever, malaise, anorexia, epigastric distress c) dry cough with progressive dyspnea in 1/3 (pneumonitis) d) gastrointestinal - diarrhea, bloody diarrhea (CMV colitis) & GI bleeding may occur - esophagitis, gastritis, colitis (multiple clean-based ulcers) e) hepatitis f) retinitis is uncommon in transplant patients 4) encephalitis, fever, dementia, brainstem manifestations & myelitis with CNS disease - uncommon, especially in patients with CD4 counts > 100/uL 5) CMV neuropathy a) polyradiculopathy 1] leg weakness 2] sensory loss 3] absent reflexes b) mononeuritis multiplex 6) CMV retinitis in immunosuppressed patients (AIDS, organ transplantation) 7) viral gastroenteritis in immunosuppressed patients - esophagitis, colitis [2] 8) bloody diarrhea in patients with ulcerative colitis Laboratory: 1) complete blood count (CBC) - leukopenia in renal transplant patients [2] 2) elevated liver function tests (LFTs) 3) serology for cytomegalovirus - heterophile antibody negative - most adults are seropositive - routine evaluation pre-organ transplantation - cytomegalovirus IgG in serum* 4) cytomegalovirus antigen - direct antigen immunostaining techiniques for CMV - cytomegalovirus early antigen - cytomegalovirus immediate-early antigen 5) cytomegalovirus DNA (PCR for CMV) a) useful for CMV viral load b) CSF viral load correlates with CNS disease c) not widely available (available at UCLA) 6) cytomegalovirus inclusion bodies (light microscropy) - "owl's eye" intracellular inclusions - seen on biopsy of infected tissue & in urine 7) culture for cytomegalovirus: a) isolation from respiratory tract does not always establish infection b) up to 4 weeks for diagnosis 8) HIV testing 9) CD4 count < 50/uL with encephalitis [2] 10) brain biopsy if encephalitis & diagnosis in question 11) see ARUP consult * a negative cytomegalovirus IgG in serum renders CMV infection unlikely - CMV infection is generally due to reactivation of latent virus Special laboratory: - ophthalmoscopy for CMV retinitis in patients with HIV1 infection & cytomegalovius infection (including CMV esophagitis) [14] - sigmoidoscopy may show severe colitis with multiple clean-based ulcers Radiology: - chest X-ray: a) diffuse small nodular or hazy infiltrates (15%) b) interstitial pneumonia in 50% of bone marrow transplants - neuroimaging (MRI of brain) if encephalitis - periventricular involvement [2] Differential diagnosis: - toxoplasmosis - Epstein-Barr virus usually presents with lymphadenopathy [2] - disseminated Mycobacterium avium complex associated with immune reconstitution inflammatory syndrome during initial implementation or re-initiation of antiretroviral therapy [2] Management: 1) ganciclovir or valganciclovir (IV) - add IV immune globulin for CMV pneumonia after bone marrow transplantation 2) foscarnet (IV) for ganciclovir resistance or intolerance 3) infusion of T-lymphocyte clones with cytolytic activity against CMV-infected cells into bone marrow recipients 4) CMV hyperimmune globulin within 1st 4 months of liver or renal may be of benefit 5) transplant patients - maribavir for post-transplantation CMV infection - reduction in immunosuppression 6) interferon-alpha plus hyperimmune globulin 7) prevention - letermovir (Prevymis) after hematopoietic stem cell transplantation - hyperimmune globulin administered to pregnant women not effective [10]

Related

cytomegalovirus (CMV) esophagitis cytomegalovirus (CMV) pneumonitis cytomegalovirus (CMV) retinitis cytomegalovirus DNA indications for CMV seronegative blood products

Specific

cytomegalovirus colitis; CMV colitis

General

herpesviridae

Properties

KINGDOM: virus GENOME-TYPE: deoxyribonucleic acid (DNA) DOUBLE-STRANDED GENOME-SIZE: 120-200 kB ENVELOPE: PRESENT CAPSID-SYMMETRY: ICOSAHEDRAL

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 515-16, 794
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2012, 2015, 2018, 2021.
  3. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 769
  4. Cheng J et al Cytomegalovirus infection causes an increase of arterial blood pressure. PLoS Pathog 2009 May; 5:e1000427. PMID: 19436702
  5. Boppana SB et al. Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N Engl J Med 2011 Jun 2; 364:2111 PMID: 21631323
  6. ARUP Consult: Cytomegalovirus - CMV The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/cytomegalovirus
  7. De Keyzer K, Van Laecke S, Peeters P, Vanholder R. Human cytomegalovirus and kidney transplantation: a clinician's update. Am J Kidney Dis. 2011 Jul;58(1):118-26. PMID: 21684438
  8. Eid AJ, Razonable RR. New developments in the management of cytomegalovirus infection after solid organ transplantation. Drugs. 2010 May 28;70(8):965-81 PMID: 20481654
  9. Helantera I, Lautenschlager I, Koskinen P. The risk of cytomegalovirus recurrence after kidney transplantation. Transpl Int. 2011 Dec;24(12):1170-8. PMID: 21902725
  10. Revello MG et al. A randomized, phase 2 trial of prevention of congenital cytomegalovirus. N Engl J Med 2014 Apr 2; 370:1316 PMID: 24693891 http://www.nejm.org/doi/full/10.1056/NEJMoa1310214
  11. Lemonovich TL, Watkins RR. Update on cytomegalovirus infections of the gastrointestinal system in solid organ transplant recipients. Curr Infect Dis Rep. 2012 Feb;14(1):33-40. PMID: 22125047
  12. Hodson EM, Ladhani M, Webster AC, Strippoli GF, Craig JC. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2013 Feb 28;2:CD003774. Review. PMID: 23450543
  13. Ariza-Heredia EJ, Nesher L, Chemaly RF. Cytomegalovirus diseases after hematopoietic stem cell transplantation: a mini-review. Cancer Lett. 2014 Jan 1;342(1):1-8. Review. PMID: 24041869
  14. NEJM Knowledge+ Gastroenterology
  15. Neurological Consequences of Cytomegalovirus Infection Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Neurological-Consequences-Cytomegalovirus-Infection-Information-Page