What are the symptoms of cytomegalovirus (CMV) infection?

Symptoms of Cytomegalovirus (CMV) Infection

Cytomegalovirus (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.

General Symptoms of CMV Infection

CMV infection in immunocompetent individuals typically presents as:

• Malaise (67% of cases)
• Fever (46% of cases)
• Sweats (46% of cases)
• Abnormal liver function tests (69% of cases) 1
• Mononucleosis-like syndrome (accounts for up to 7% of mononucleosis cases) with symptoms similar to Epstein-Barr virus infection 2

The duration of symptoms can be prolonged, with an average of 7.8 weeks, and some patients experience a relapsing illness (12% of cases) 1.

CMV Disease in Immunocompromised Patients

In immunocompromised individuals, particularly those with CD4+ T lymphocyte counts <50 cells/μL, CMV can cause severe end-organ disease 3. The clinical manifestations by affected organ system include:

1. Ocular Manifestations (CMV Retinitis)

CMV retinitis is the most common manifestation of CMV end-organ disease 3 and presents with:

• Floaters
• Scotomata (blind spots)
• Peripheral visual field defects
• Decreased visual acuity (if central retina or macula is affected)
• Characteristic ophthalmologic appearance: perivascular fluffy yellow-white retinal infiltrates with or without intraretinal hemorrhage
• Progressive "brushfire pattern" with granular white leading edge advancing before an atrophic gliotic scar

2. Gastrointestinal Manifestations

CMV Colitis (5-10% of AIDS patients with CMV disease) 3:

• Fever
• Weight loss
• Anorexia
• Abdominal pain
• Debilitating diarrhea
• Malaise
• Potential complications: mucosal hemorrhage and perforation (life-threatening)

CMV Esophagitis (<5-10% of AIDS patients with CMV disease) 3:

• Fever
• Odynophagia (painful swallowing)
• Nausea
• Mid-epigastric or retrosternal discomfort

3. Pulmonary Manifestations (CMV Pneumonitis)

Though uncommon, CMV pneumonitis presents with 3:

• Shortness of breath
• Dyspnea on exertion
• Nonproductive cough
• Hypoxemia
• Interstitial infiltrates on chest radiograph

4. Neurologic Manifestations

CMV can cause various neurologic syndromes 3:

CMV Dementia:

• Lethargy
• Confusion
• Fever
• Clinical presentation may mimic HIV-1 dementia
• CSF findings: lymphocytic pleocytosis, low-to-normal glucose, normal-to-elevated protein

CMV Ventriculoencephalitis:

• Acute course with focal neurologic signs
• Cranial nerve palsies
• Nystagmus
• Rapid progression to death
• Periventricular enhancement on CT/MRI

CMV Polyradiculomyelopathy:

• Guillain-Barré-like syndrome
• Urinary retention
• Progressive bilateral leg weakness
• Progression to loss of bowel and bladder control
• Flaccid paraplegia
• CSF findings: neutrophilic pleocytosis (100-200 neutrophils/μL), hypoglycorrhachia, elevated protein

CMV Syndrome in Transplant Recipients

In solid organ transplant recipients, CMV syndrome is characterized by 3:

• Fever >38°C for at least 2 days
• New or increased malaise
• Leukopenia
• ≥5% atypical lymphocytes
• Thrombocytopenia
• Elevation of hepatic transaminases (ALT or AST) to 2× upper limit of normal

Congenital CMV Infection

Congenital CMV infection affects approximately 1 in 200 live births in high-income countries and presents with 4:

• Jaundice
• Rash
• Enlarged liver or spleen
• Small brain (microcephaly)
• Small for gestational age
• Only about 1 in 8 infected babies have clinically detectable signs at birth

Diagnostic Considerations

CMV viremia can be detected by PCR, antigen assays, or blood culture and is generally present in end-organ disease, though it may also be present without end-organ involvement 3. Specific diagnostic approaches vary by affected organ system:

• Retinitis: Diagnosis by ophthalmologic examination (95% positive predictive value)
• Colitis/Esophagitis: Endoscopic examination with biopsy showing characteristic intranuclear and intracytoplasmic inclusions
• Neurologic disease: CSF analysis, neuroimaging, and clinical presentation

Key Points to Remember

• CMV infection is often asymptomatic in immunocompetent individuals
• Symptoms can persist for weeks to months, with some patients experiencing relapsing illness
• The risk of severe disease is highest in immunocompromised patients, particularly those with CD4+ counts <50 cells/μL
• CMV can affect multiple organ systems, with retinitis being the most common manifestation in AIDS patients
• Congenital CMV is a major cause of hearing loss and brain damage in newborns