What are the signs and symptoms of Cytomegalovirus (CMV) infection?

Signs and Symptoms of Cytomegalovirus (CMV) Infection

CMV infection presents with a wide spectrum of clinical manifestations ranging from asymptomatic infection to severe end-organ disease, with symptoms varying based on the patient's immune status and the affected organ systems. 1

General Manifestations

• Asymptomatic infection: Most common presentation in immunocompetent individuals
• Mononucleosis-like syndrome: Fever, malaise, lymphocytosis (with atypical lymphocytes), and elevated liver enzymes 2, 3
• Systemic symptoms: Fever, weight loss, fatigue, and malaise 1

Organ-Specific Manifestations

Ocular Manifestations (Most Common End-Organ Disease)

• Retinitis:
  • Floaters, scotomata, peripheral visual field defects
  • Central vision loss (if macula or optic nerve involved)
  • Characteristic appearance: perivascular fluffy yellow-white retinal infiltrates with/without intraretinal hemorrhage
  • "Brushfire pattern" progression with granular white leading edge advancing before atrophic scar
  • Often asymptomatic in young children, discovered on routine examination 1

Gastrointestinal Manifestations

• Colitis (second most common manifestation, 5-10% of cases):
  • Fever, weight loss, anorexia, abdominal pain
  • Debilitating diarrhea, malaise
  • Potential complications: mucosal hemorrhage, perforation 1
• Esophagitis (<5-10% of cases):
  • Fever, odynophagia, nausea
  • Mid-epigastric or retrosternal discomfort 1
• Other GI manifestations:
  • Oral and esophageal ulcers
  • Hepatic involvement (elevated transaminases)
  • Ascending cholangiopathy, gastritis 1

Pulmonary Manifestations

• Pneumonitis (uncommon):
  • Shortness of breath, dyspnea on exertion
  • Dry, nonproductive cough
  • Hypoxemia
  • Interstitial infiltrates on chest radiograph 1, 3

Neurological Manifestations

• Encephalitis/Dementia:
  • Lethargy, confusion, fever
  • May mimic HIV-related dementia
  • CSF: lymphocytic pleocytosis, low-to-normal glucose, normal-to-elevated protein 1, 4
• Ventriculoencephalitis:
  • Acute course with focal neurologic signs
  • Cranial nerve palsies, nystagmus
  • Rapid progression
  • Periventricular enhancement on CT/MRI 1
• Polyradiculomyelopathy:
  • Guillain-Barré-like syndrome
  • Urinary retention
  • Progressive bilateral leg weakness
  • Loss of bowel and bladder control
  • Flaccid paraplegia
  • CSF: neutrophilic pleocytosis (100-200 neutrophils/mL), hypoglycorrhachia, elevated protein 1, 5

Congenital CMV Infection

• Symptomatic disease (10% of in utero infections):
  • Small for gestational age
  • Purpura/petechiae, jaundice
  • Hepatosplenomegaly
  • Chorioretinitis
  • Microcephaly, intracranial calcifications
  • Hearing impairment
  • High mortality rate (up to 30%) 1, 6
• Late complications (in 90% of symptomatic survivors):
  • Substantial hearing loss
  • Mental retardation
  • Chorioretinitis, optic atrophy
  • Seizures, learning disabilities 1, 6

Laboratory Abnormalities

• Lymphocytosis (up to 50% lymphocytes)
• Atypical lymphocytes (up to 9%)
• Elevated liver transaminases
• Anemia, thrombocytopenia
• Elevated lactic dehydrogenase 1, 3

Special Considerations in Immunocompromised Patients

HIV-Infected Patients

• Higher rate of CMV viruria (up to 60% in those with AIDS)
• Accelerated progression of HIV disease
• Higher risk of CMV retinitis with CD4+ counts <100/μL
• Higher mortality rates compared to those without CMV coinfection 1

Transplant Recipients

• Higher risk of CMV end-organ disease (colitis, hepatitis, pneumonia)
• 4.9% 10-year cumulative incidence in liver transplant recipients
• 15-25% incidence after allogeneic hematopoietic stem cell transplantation 1

Clinical Pitfalls and Caveats

• CMV retinitis in young HIV-infected children is often asymptomatic and discovered only on routine examination
• CD4+ count is less predictive of CMV disease risk in young infants
• CMV pneumonia is difficult to diagnose as it often coexists with other pathogens
• Viremia may be present without end-organ disease, particularly in immunocompromised patients
• Negative CMV IgG generally rules out CMV as cause of symptoms, though seroreversion can occur in advanced immunosuppression 1, 7