Case 1: Vesicular rash in an infant

A five-month-old term male infant was referred by his family doctor for evaluation of a vesicular rash. The mother first noticed several clusters of vesicles on the baby’s chest five days before presentation. In the subsequent four days, new adjacent vesicles erupted on the chest with clear discharge. He had slightly decreased appetite but normal voiding and stools, with no accompanying fever. A review of the infant’s systems was otherwise unremarkable.

The baby was born to a 32-year-old Pakistani-Canadian woman who remained in Pakistan during her pregnancy. Antenatal screening for HIV, hepatitis B and syphilis was negative, and a rubella immunoglobulin G test was positive. The baby was born at 39 weeks’ gestational age by spontaneous vaginal delivery with no perinatal complications. The birth weight was 3.2 kg and the baby was discharged home on the second day of life with a normal physical examination. He had received his two- and four-month routine immunizations uneventfully. There was no family history of immunodeficiency or recurrent infections.

A physical examination revealed a thriving, afebrile and well-appearing infant. Multiple crops of vesicles on an erythematous base were present on both the anterior and posterior right hemithorax (Figure 1). There were no satellite lesions.

Figure 1).

Vesicular rash on the (A) anterior and (B) posterior thorax. Permission to use the figure was obtained from the infant’s parent

One further detail on history suggested the diagnosis.

CASE 1 DIAGNOSIS: INFANTILE HERPES ZOSTER

The mother gave a history of having been exposed to a child with chicken pox at approximately 22 weeks’ gestation and subsequently developing a vesicular rash that was characteristic of varicella. She experienced no complications and did not receive treatment. Subsequent antenatal ultrasound examinations had not revealed any fetal abnormalities, although some ‘placental calcifications’ were noted. Based on this information, and combined with the infant’s findings of a classic vesicular rash in a dermatomal distribution, a diagnosis of infantile herpes zoster was highly suspected. Electron microscopy of lesion scrapings revealed herpes virus particles, and varicella zoster virus (VZV) DNA was detected by polymerase chain reaction (PCR). Serological testing of the infant’s blood revealed the presence of immunoglobulin G antibody to VZV and the absence of immunoglobulin M, suggesting a herpes zoster-type reactivation rather than primary VZV infection. Complete blood count and serum immunoglobulin levels were normal. The patient was managed with supportive care only, and his vesicular lesions spontaneously dried and crusted over a period of three weeks with no complications.

Infantile herpes zoster represents a reactivation of latent VZV infection after primary infection in utero or infancy. Approximately 70% of reported cases occur after maternal varicella during pregnancy, while 30% occur after post-natally acquired varicella (1). In paediatric populations, the reported incidence of herpes zoster is the lowest in the zero- to five-year age group (20 per 100,000 person-years) and highest in adolescents (63 per 100,000 person-years).

The development of herpes zoster in healthy immuno-competent infants is believed to be due to an age-related immature immune response (2). After varicella infection, infants younger than one year of age have lower VZV-specific cellular and humoral immune responses than older children (3). The short viral latency (with reactivation after only a few months) is attributed to infants’ immature cell-mediated immune response.

Maternal VZV infection is uncommon, occurring in two per 1000 pregnancies in temperate climates, where VZV is largely an infection of childhood (4). The epidemiology of VZV differs in the tropics (including Pakistan), where significant proportions of older children and young adults (including women of child-bearing age) remain susceptible to infection (2). When intrauterine infection occurs during pregnancy, the effect on the fetus depends on the timing of intrauterine infection. When maternal varicella infection occurs in the first or second trimester, approximately 1% to 2% of infants develop the congenital varicella syndrome (CVS) (2). The most common clinical manifestations of CVS are cicatricial scars and, less commonly, neurological (microcephaly and cortical atrophy), ophthalmological (chorioretinitis and congenital cataract) and limb (limb hypoplasia and joint contractures) abnormalities (4).

When maternal varicella occurs later in the second or third trimesters of pregnancy, the fetus can develop asymptomatic congenital infection. Twenty per cent of infants with intrauterine-acquired VZV primary infection will develop neonatal or infantile zoster in the first year of life, as demonstrated in the present case (4). No cases of CVS or infantile zoster have been observed following maternal varicella vaccination during or just before pregnancy, nor following maternal varicella infection with infantile postexposure prophylaxis with antivaricella zoster immune globulin (5,6).

The diagnosis of herpes zoster should be considered when vesicular lesions on an erythematous base are found in a dermatomal distribution. Clinical presentations in infants may include pruritis, localized pain, fever and lymphadenopathy (1). Complications such as secondary bacterial infections (impetigo) and ophthalmic herpes zoster have been described. The most commonly involved dermatomes are thoracic (33%), followed by cranial nerve (27%), cervical (20%) and lumbosacral (20%). The diagnosis can be confirmed by Tzanck smear or direct fluorescent antibody tests of scrapings from the floors of vesicles, high or rising VZV antibody titres, and definitively by culture or PCR for VZV.

In general, children with herpes zoster have an uncomplicated course, and disease is often mild, lasting one to three weeks (1). Treatment is generally supportive, with analgesia and appropriate skin care to minimize pain and the risk of secondary infection. Oral or intravenous acyclovir decreases the time to new vesicle formation and the number of days to crusting, and may be used in more severe cases.

CLINICAL PEARLS

• Infantile herpes zoster occurs in 20% of infants after congenital VZV infection in the second or third trimester, and can also occur after postnatal varicella.

• Infantile herpes zoster should be suspected when vesicular lesions in a dermatomal distribution are present, and can be confirmed definitively by culture or PCR for VZV from vesicular lesions.

• Supportive care is adequate for most infants and acyclovir may be used in severe cases.