Cytomegalovirus (CMV)

Snapshot

• A 40-year-old man with a past medical history of HIV presents to the clinic for follow-up. He reports that he has had difficulty swallowing, fevers and chills, nausea, vomiting, and abdominal pain. He reports that he has been compliant with his HIV medications. On physical exam, he has ulcers in his oropharynx. His laboratory tests reveal positive CMV-specific immunoglobulin G but negative heterophile antibodies. He is given an antiviral treatment and is admitted for an endoscopy workup and close monitoring. (CMV esophagitis)

Introduction

• Classification
  • cytomegalovirus (CMV) or human herpesvirus-5 (HHV-5)  
    • linear, double-stranded DNA virus
    • largest virus that causes human infections
    • transmission via body fluids or vertical transmission
• Epidemiology
  • incidence
    • very common
  • risk factors
    • immunosuppression
    • men who have sex with other men
    • poor socioeconomic status
    • working in childcare
    • transplant recipients
      • prone to CMV pneumonia
• Pathogenesis
  • CMV-caused diseases can either result from a primary infection or reactivation of a latent infection
  • replication of host cells (including epithelial cells, macrophages, and neurons) result in viremia and symptoms from primary infection
  • cellular immunity is crucial in clearing this virus
• Associated conditions
  • congenital CMV infection 
    • jaundice
    • hepatosplenomegaly
    • thrombocytic purpura and petechial rash
    • hearing loss
      • most common cause of non-hereditary congenital sensorineural deafness
    • seizures
    • microcephaly
    • ventriculomegaly
    • intracranial calcifications
• Prognosis
• often self-limited in immunocompetent patients

Presentation

• Symptoms
  • immunocompetent patients
    • most cases are asymptomatic
    • if symptomatic, CMV infections often result in a mononucleosis syndrome with fevers, myalgias, arthralgias, and cough 
  • immunocompromised patients
    • esophagitis
      • results in linear ulcers vs the punched-out ulcers caused by HSV1
    • colitis (most common)
    • encephalitis
    • hepatitis
    • pneumonia
    • retinitis 
    • congenital CMV
    • hemolytic anemia
• Physical exam
  • fever
  • cervical lymphadenopathy
  • hepatosplenomegaly
• maculopapular rash

Studies

• Labs
  • lymphocytosis with atypical lymphocytes
  • thrombocytopenia
  • transaminitis
  • negative heterophile antibody
  • CMV-specific immunoglobulin M (persists for 4-6 months) 
  • CMV-specific immunoglobulin G (2-3 weeks)
    • active infection
  • viral load 
    • does not distinguish active vs past infection
• Histology 
  • if warranted, may reveal CMV on immunohistochemistry
  • classic “owl’s eye” appearance
• Making the diagnosis
• based on clinical presentation and laboratory studies

Differential

• Epstein-Barr viral (EBV) mononucleosis 
  • distinguishing factors
    • CMV mononucleosis often includes more myalgias, arthralgias, and cough than EBV infection
• CMV infection also does not typically present with sore throat or lymphadenopathy

Treatment

• Management approach
  • mainstay of treatment is supportive care
• Conservative
  • supportive care
    • indication
      • all patients
    • modalities
      • hydration
• Medical
  • antiviral medications 
    • indications
      • immunocompromised patients
      • severe disease or organ damage
    • drugs
      • ganciclovir
• valganciclovir 

Complications

• Thrombosis
• Colitis
• Permanent vision changes