cytomegalovirus (CMV, human herpesvirus 5, HHV5)
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Etiology
risk factors for CMV infection:
- AIDS (especially in association with Pneumocystis carinii)
- HIV1 infection with CD4 count < 50/uL[2]
- organ transplantation
- especially seronegative recipient, seropositive donor
- lymphoreticular malignancy
- cardiopulmonary bypass
- multiple blood transfusions
Epidemiology
- most common congenital infection[5]
- 2nd most common infection in patients with AIDS
- most common infectious complication of organ transplantation
- can be transmitted by blood transfusions:
- CMV is transmitted by granulocytes
- may be introduced by transplantation of CMV-infected organ
- disease may occur as reactivation of latent CMV infection
Pathology
- retinitis (20-30% of patients with advanced AIDS)
- pneumonia
- gastrointestinal ulcerations
- encephalitis
- adrenalitis
- infectious mononucleosis-like syndrome
- putative receptor is beta-2 microglobulin/MHC[3]
- cytomegalovirus glycoprotein UL16 binds to & causes sequestration of MICB in the endoplasmic reticulum
- endothelial cells infected with CMV secrete renin, angiotensin-2 & pro-inflammatory cytokines & develop intimal hyperplasia & atherosclerosis (mouse model)[4]
- hearing loss in early childhood with congenital infection[5]
- virus latent in monocytes, lymphocytes, endothelial cells, epithelial cells[2]
Clinical manifestations
- generally asymptomatic
- mononucleosis-like syndrome
- symptomatic CMV in organ transplant patients
- generally occurs within 1st few months following organ transplantation
- fever, malaise, anorexia, epigastric distress
- dry cough with progressive dyspnea in 1/3 (pneumonitis)
- gastrointestinal
- diarrhea, bloody diarrhea (CMV colitis) & GI bleeding may occur
- esophagitis, gastritis, colitis (multiple clean-based ulcers)
- hepatitis
- retinitis is uncommon in transplant patients
- encephalitis, fever, dementia, brainstem manifestations & myelitis with CNS disease
- uncommon, especially in patients with CD4 counts > 100/uL
- CMV neuropathy
- polyradiculopathy
- leg weakness
- sensory loss
- absent reflexes
- mononeuritis multiplex
- polyradiculopathy
- CMV retinitis in immunosuppressed patients (AIDS, organ transplantation)
- viral gastroenteritis in immunosuppressed patients
- esophagitis, colitis[2]
- bloody diarrhea in patients with ulcerative colitis
Laboratory
- complete blood count (CBC)
- leukopenia in renal transplant patients[2]
- elevated liver function tests (LFTs)
- serology for cytomegalovirus
- heterophile antibody negative
- most adults are seropositive
- routine evaluation pre-organ transplantation
- cytomegalovirus IgG in serum*
- cytomegalovirus antigen
- direct antigen immunostaining techiniques for CMV
- cytomegalovirus early antigen
- cytomegalovirus immediate-early antigen
- cytomegalovirus DNA (PCR for CMV)
- useful for CMV viral load
- CSF viral load correlates with CNS disease
- not widely available (available at UCLA)
- cytomegalovirus inclusion bodies (light microscropy)
- "owl's eye" intracellular inclusions
- seen on biopsy of infected tissue & in urine
- culture for cytomegalovirus:
- isolation from respiratory tract does not always establish infection
- up to 4 weeks for diagnosis
- HIV testing
- CD4 count < 50/uL with encephalitis[2]
- brain biopsy if encephalitis & diagnosis in question
- see ARUP consult
* a negative cytomegalovirus IgG in serum renders CMV infection unlikely
- CMV infection is generally due to reactivation of latent virus
Diagnostic procedures
- 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:
- diffuse small nodular or hazy infiltrates (15%)
- 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
- ganciclovir or valganciclovir (IV)
- add IV immune globulin for CMV pneumonia after bone marrow transplantation
- foscarnet (IV) for ganciclovir resistance or intolerance
- infusion of T-lymphocyte clones with cytolytic activity against CMV-infected cells into bone marrow recipients
- CMV hyperimmune globulin within 1st 4 months of liver or renal may be of benefit
- transplant patients
- maribavir for post-transplantation CMV infection
- reduction in immunosuppression
- interferon-alpha plus hyperimmune globulin
- prevention
- letermovir (Prevymis) after hematopoietic stem cell transplantation
- hyperimmune globulin administered to pregnant women not effective[10]
More general terms
More specific terms
Additional terms
- cytomegalovirus (CMV) esophagitis
- cytomegalovirus (CMV) pneumonitis
- cytomegalovirus (CMV) retinitis
- cytomegalovirus DNA
- indications for CMV seronegative blood products
References
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 515-16, 794
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2012, 2015, 2018, 2021.
- ↑ 3.0 3.1 Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 769
- ↑ 4.0 4.1 Cheng J et al Cytomegalovirus infection causes an increase of arterial blood pressure. PLoS Pathog 2009 May; 5:e1000427. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19436702
- ↑ 5.0 5.1 5.2 Boppana SB et al. Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N Engl J Med 2011 Jun 2; 364:2111 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21631323
- ↑ ARUP Consult: Cytomegalovirus - CMV The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/cytomegalovirus
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/21684438
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/20481654
- ↑ Helantera I, Lautenschlager I, Koskinen P. The risk of cytomegalovirus recurrence after kidney transplantation. Transpl Int. 2011 Dec;24(12):1170-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21902725
- ↑ 10.0 10.1 Revello MG et al. A randomized, phase 2 trial of prevention of congenital cytomegalovirus. N Engl J Med 2014 Apr 2; 370:1316 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24693891 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1310214
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/22125047
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/23450543
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/24041869
- ↑ 14.0 14.1 NEJM Knowledge+ Gastroenterology
- ↑ Neurological Consequences of Cytomegalovirus Infection Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Neurological-Consequences-Cytomegalovirus-Infection-Information-Page