What are the clinical presentations of TORCH (Toxoplasmosis, Other, Rubella, Cytomegalovirus (CMV), and Herpes) infection in children over 2 months of age?

Clinical Presentations of TORCH Infections After 2 Months of Age in Children

The majority of children with TORCH infections who were asymptomatic at birth will develop late sequelae months to years later, with manifestations varying by specific pathogen but commonly including retinitis, visual impairment, neurologic deficits, and developmental delays. 1, 2

Key Principle: Delayed Manifestations Are the Rule

• 70-90% of infants with congenital TORCH infections (particularly toxoplasmosis) are asymptomatic at birth, but the majority will develop late sequelae with onset ranging from several months to years after birth. 1, 2, 3
• The interval until symptom onset is highly variable, ranging from months to years, making ongoing surveillance critical even in apparently healthy infants. 1

Toxoplasmosis Presentations After 2 Months

Ocular Disease (Most Common Late Manifestation)

• Chorioretinitis is the predominant late manifestation, appearing as white retinal lesions with minimal hemorrhage and potentially causing visual loss. 1
• New or recurrent eye lesions can develop years after birth, even in treated children—recurrence rates are approximately 36% in severely affected children and 9% in those with mild disease at birth. 1
• Isolated ocular toxoplasmosis is rare and usually occurs with CNS involvement, necessitating neurologic examination in all children with Toxoplasma chorioretinitis. 1

Neurologic Sequelae

• Seizures may develop de novo between 3-5 years of age, even in children who were initially seizure-free or had early seizures that resolved. 1, 4
• Progressive neurologic deterioration can occur, including development of microcephaly, intellectual impairment, and motor deficits if untreated. 1
• Toxoplasma encephalitis should be considered in HIV-infected children presenting with new neurologic findings (fever, reduced alertness, seizures, focal deficits), though this is uncommon in pediatric AIDS (<1% of cases). 1, 5

Developmental and Cognitive Issues

• Intellectual disability and cognitive decline can manifest over time, with some children showing deterioration in IQ scores between evaluations. 1
• Motor abnormalities and tone issues may persist or develop after the neonatal period. 4

Cytomegalovirus (CMV) Presentations After 2 Months

• Progressive sensorineural hearing loss is a hallmark late manifestation, often developing or worsening after the neonatal period. 6, 7
• Developmental delays, cerebral palsy, and epilepsy may become apparent as the child ages. 7
• Chorioretinitis can develop or progress beyond the neonatal period. 6

Rubella Presentations After 2 Months

• Deafness may not be detected until later in infancy when hearing assessment becomes more reliable. 6, 8
• Progressive rubella panencephalitis is a rare but devastating late complication occurring years after congenital infection. 7
• Retinopathy and visual impairment may become more apparent as visual demands increase. 8

Herpes Simplex Virus (HSV) Presentations After 2 Months

• HSV encephalitis can present acutely at any age with fever, altered consciousness, seizures, and focal neurologic deficits. 1
• In children, HSV encephalitis is more likely associated with primary infection and may present with labial herpes (unlike adults where cold sores lack diagnostic specificity). 1
• Recurrent skin lesions at sites of initial infection can occur. 8
• Long-term neurologic sequelae from neonatal HSV infection (developmental delays, seizures, motor deficits) become more apparent as developmental milestones are missed. 7

Varicella-Zoster Virus (VZV) Presentations

• Post-infectious cerebellitis is the most common neurologic presentation in young children, presenting with acute onset of ataxia, unsteadiness, and nystagmus. 1
• Arterial ischemic stroke associated with VZV can present months after the initial infection (mean 3 months, range 1 week to 48 months) with acute hemiparesis, seizures, or visual/speech disturbances. 1
• VZV encephalitis presents with fever, headache, altered consciousness, ataxia, and seizures, more common in immunocompromised children. 1

Critical Diagnostic Approach After 2 Months

• Maintain high clinical suspicion for TORCH infections in any child presenting with unexplained neurologic deterioration, new-onset seizures, visual complaints, developmental regression, or hearing loss. 1, 3
• Serologic testing remains the primary diagnostic method, though interpretation is complex and often requires reference laboratory expertise. 2, 5
• For suspected toxoplasmosis: obtain Toxoplasma-specific IgG (persistence beyond 12 months confirms congenital infection), ophthalmologic examination, neurologic assessment, and brain imaging. 1, 3
• Brain MRI is more sensitive than CT for detecting CNS lesions and should be performed when neurotoxoplasmosis is suspected. 2, 5

Treatment Considerations for Late Presentations

• For toxoplasmic encephalitis: pyrimethamine (2 mg/kg/day for 3 days, then 1 mg/kg/day) plus sulfadiazine (25-50 mg/kg/dose four times daily) and leucovorin (10-25 mg/day) for at least 6 weeks. 2, 5
• Leucovorin must always be administered with pyrimethamine to prevent bone marrow suppression, with weekly CBC monitoring. 2, 5
• For HSV encephalitis: acyclovir should be initiated immediately upon suspicion, even with atypical presentations. 1, 8

Common Pitfalls to Avoid

• Do not assume a normal newborn screen excludes TORCH infection—most affected infants are asymptomatic at birth and develop problems later. 1, 3
• Do not rely on maternal history alone; many infected mothers are asymptomatic during pregnancy. 3, 9
• Do not dismiss mild symptoms (single seizure, transient ataxia, headache) as they may represent milder forms of encephalitis requiring treatment. 1
• In HIV-infected children, do not exclude toxoplasmic encephalitis based on negative serology alone—cases have been reported without detectable IgG antibodies. 5