What is the clinical presentation of Cytomegalovirus (CMV) in pediatric patients?

Clinical Presentation of CMV in Children

CMV presents differently in children depending on timing of infection (congenital vs acquired) and immune status, with congenital infection causing the most severe disease and long-term sequelae, while acquired infection in immunocompetent children is typically mild or asymptomatic.

Congenital CMV Infection

Symptomatic Disease at Birth (10% of infected infants)

Approximately 10% of infants with in utero CMV infection are symptomatic at birth with congenital CMV syndrome, carrying a mortality rate as high as 30%. 1

Classic presenting features include:

• Small for gestational age 1
• Purpura/petechiae (most common cutaneous finding) 1, 2
• Jaundice 1, 2
• Hepatosplenomegaly (present in 45% of symptomatic cases) 1, 3, 2
• Microcephaly 1
• Intracranial calcifications 1
• Chorioretinitis 1
• Hearing impairment 1

Laboratory abnormalities commonly observed:

• Thrombocytopenia (50% of symptomatic cases) 3
• Elevated transaminases (50% of symptomatic cases) 3
• Anemia 1

Neuroimaging findings are highly prevalent and predictive:

• Abnormal cranial ultrasound in 56% (odds ratio 8.5 for adverse outcome) 3
• Abnormal head CT in 71% (odds ratio 21 for adverse outcome) 3
• Abnormal brain MRI in 89% 3

Long-Term Sequelae

Approximately 90% of infants with symptomatic disease at birth who survive develop late complications. 1

These include:

• Substantial hearing loss (most common sequela) 1
• Mental retardation/developmental delays 1
• Chorioretinitis 1
• Optic atrophy 1
• Seizures 1
• Learning disabilities 1

Asymptomatic Congenital Infection (90% of infected infants)

Although the majority of children with in utero CMV infection do not have symptoms at birth, 10-15% are at risk for developing later developmental abnormalities, sensorineural hearing loss, chorioretinitis, or neurologic defects. 1

CMV in HIV-Infected Children

Disease Acceleration and Mortality

HIV-infected children with CMV coinfection have accelerated progression of HIV disease with a relative risk of 2.6 (95% CI = 1.1-6.0) compared to those without CMV infection. 1

Key statistics:

• 53% of infants with HIV/CMV coinfection progress to AIDS or death by age 18 months compared to 22% without CMV 1
• Central nervous disease occurs in 36% with coinfection versus 9% without 1
• CMV causes 8-10% of pediatric AIDS-defining illness 1

CMV Retinitis

CMV retinitis is the most frequent severe manifestation of CMV disease among HIV-infected children, accounting for approximately 25% of CMV AIDS-defining illnesses. 1

Clinical presentation varies by age:

• Young HIV-infected children: Frequently asymptomatic, discovered on routine examination 1
• Older children: Present similarly to adults with floaters, loss of peripheral vision, or reduction in central vision 1

Diagnostic appearance includes white and yellow retinal infiltrates with associated retinal hemorrhages 1

End-Organ CMV Disease

In children with extraocular CMV disease, predominantly nonspecific symptoms are initially observed, including fever, poor weight gain, and loss of developmental milestones with laboratory abnormalities of anemia, thrombocytopenia, and elevated lactic dehydrogenase. 1

Gastrointestinal Manifestations

CMV colitis is the most common GI manifestation in HIV-infected children 1

Presentations include:

• Oral and esophageal ulcers 1
• Hepatic involvement 1
• Ascending cholangiopathy 1
• Gastritis 1

Sigmoidoscopy findings are nonspecific: diffuse erythema, submucosal hemorrhage, and diffuse mucosal ulcerations 1

Pulmonary Disease

CMV pneumonia is an interstitial process with gradual onset of shortness of breath and dry, nonproductive cough; auscultatory findings might be minimal. 1

Histologic evidence of CMV disease is needed to determine if active disease is present, as CMV is often isolated with other organisms (e.g., P. jiroveci). 1

CNS Manifestations

CNS manifestations include subacute encephalopathy, myelitis, and polyradiculopathy (primarily observed in adults but rarely reported among children) 1

CSF findings are nonspecific and may include:

• Polymorphonuclear predominance (>50% of patients) 1
• Elevated protein (75%) 1
• Low glucose (30%) 1
• However, up to 20% of children have completely normal CSF 1

Acquired CMV in Immunocompetent Children

Postnatal CMV results in liver symptoms in 67% of cases, followed by hematological disorders and gastrointestinal pathology in infants. 4

In older immunocompetent children, primary infection leads to liver disease in 51% of cases, with greater neurological and pulmonary involvement compared to infants. 4

Most acquired infections in immunocompetent children are asymptomatic or present with mild, nonspecific symptoms 2, 4

Critical Clinical Pitfalls

• CMV testing must be performed within the first 21 days of life to distinguish congenital from acquired postnatal infection 5, 6
• Do not assume asymptomatic infants at birth will remain unaffected - 10-15% develop sequelae later 1, 6
• Hearing loss may have late onset or be progressive, requiring long-term surveillance every 4-6 months through at least age 2 years 6
• CD4+ cell count is less predictive of risk for CMV disease in young infants, and systemic CMV disease can occur with higher age-adjusted CD4+ counts 1
• Abnormal brainstem auditory evoked responses (BAER) carry an odds ratio of 8.7 for adverse outcome 3