Herpes Zoster in Healthy Infants and Toddlers after Perinatal Exposure To Varicella-Zoster Virus: A Case Series and Review of the Literature

From The Pediatric Infectious Disease Journal®
Xavier Rodríguez-Fanjul, MD; Antoni Noguera, MD, PhD; Asunción Vicente, MD; Maria Antònia González-Enseñat, MD; Rafael Jiménez, MD, PhD; Clàudia Fortuny, MD, PhD*

Abstract
Exposure to varicella-zoster virus in utero or during the first months of life is the main risk factor for the development of herpes zoster (HZ) in healthy children. We report a case series of 16 infants and toddlers who presented with HZ after early exposure to varicella-zoster virus. Two patients had recurrences. Despite the severity of the rash in some cases, the benign course and the long-term good prognosis of HZ in healthy children is noteworthy.

Introduction
Herpes zoster (HZ), also named shingles, is caused by the reactivation of latent varicella-zoster virus (VZV) infection within dorsal root and cranial nerve ganglia. While chickenpox usually occurs in the first years of life, HZ is uncommon in childhood and its incidence increases with age and with other causes of decreased cellular immunity.[1] Children infected with VZV in utero or before one year of age have an increased risk of developing HZ.[2,3] We report a case series of 16 previously healthy children who developed HZ after exposure to VZV during gestation or early infancy and who were referred to and followed up in a tertiary-care pediatric hospital in Barcelona (Spain) from 1993 to 2008.

Discussion
HZ is uncommon among children. In classic studies, its incidence in the pediatric age ranged from 0.2 to 0.74 cases per 1000 person-years.[2,3] A large population-based study from Iceland in the early 90s reported a higher incidence rate, up to 1.6 cases per 1000 person-years.[4] It is possible that the disease occurs more frequently than it is thought in children, but remains under reported because of its benign course, as many patients would not seek medical care.

In the largest published case series of HZ in children to date, only 10% of the patients were apparently healthy at inclusion.[5] Because that study was organized around a hospital-based surveillance system, the inclusion criteria probably biased these results. Despite this, and in the absence of updated population-based studies, most experts agree that HZ is more common among immunocompromised children,[1,3,6,7] especially in patients affected with acute leukemia.[8]

Among healthy children, primary VZV infection during gestation or the first year of life is the major risk factor for childhood onset HZ (incidence rate: 4.1 cases per 1000 person-years).[2,3] In our series, VZV primary infection had occurred in most patients by the age of 4 months. At this early age, the infant is protected by transplacentally transferred maternal VZV-specific antibodies[9] but is unable to develop adequate cellular and humoral immunity to VZV.[10,11] Not surprisingly, the age at onset of HZ has been reported to be lower after early primary VZV infection,[7] reflecting the blunting of VZV-specific immune memory in these patients. The median age at onset of HZ in our series was 22 months, clearly lower than the mean age in other large series of pediatric HZ.[3–5,7]

The diagnosis of HZ is based on clinical judgment.[12] Several sensitive microbiologic methods performed on blister fluid/scrapings are available in case of doubt, including viral cultures, polymerase chain reaction, and direct fluorescent antibody testing. Rashes that may resemble HZ are contact dermatitis, herpes simplex skin infection, and staphylococcal impetigo.[12] HZ in healthy children is mildly symptomatic and usually shows a benign and self-limited course in 1 to 3 weeks; its more common complications are bacterial secondary infection, depigmentation, and scarring. Thoracic dermatomes are involved in 65% to 75% of cases.[3,4] Ocular involvement, which is very frequent in the adult patient, must be always ruled out when the ophthalmic branch of the trigeminal nerve (V1) is affected.[13] Disseminated cutaneous HZ, neurologic complications, visceral dissemination, post-HZ neuralgia, and other sequelae have been very rarely reported in immunocompetent children.[5,7,14] Two of the patients in our series had a second episode of HZ in the same dermatome, which recovered uneventfully. Recurrences have not been previously reported in early childhood HZ and are also infrequent in the immunocompetent adult patient. Junker and Tilley[15] hypothesized that a failure to maintain or evoke a secondary VZV-specific immune response could explain recurrent chickenpox in a series of 23 healthy and apparently immunocompetent children.

Antiviral therapy and hospital admission are rarely needed.[4] In fact, acyclovir in the healthy child is only recommended when ophthalmic HZ or moderate-to-severe symptomatic rash occur; analgesics and appropriate skin care are more often required. In our series, a referral bias probably explains both the predominance of cranial nerve dermatome involvement and the high rates of hospital admission and acyclovir treatment. Despite the severity of the cases we report, a benign course and lack of sequelae ensued in all cases, reflecting the excellent prognosis of pediatric HZ.[4]

Although HIV infection and pediatric malignancies are commonly associated with HZ, childhood HZ has not been found to be the harbinger of an underlying immunodeficiency or malignancy.[4] Because of this, an immunologic work-up should not be routinely performed in previously healthy children affected with a first episode of HZ and would only be justified when recurrences occur.[6]
Finally, several cases of mild and uncomplicated HZ caused by the Oka vaccine strain of VZV have been reported, 65% of them in children <5 years of age.[16]

The incidence of HZ in children is higher after natural varicella infection than after varicella vaccination, in healthy and immunocompromised children.[17] Currently, varicella immunization with the Oka attenuated VZV strain is not publicly funded in Catalonia, despite the recommendation by the Asociación Española de Pediatría.[18] Universal vaccination programs will probably impact HZ epidemiology in the future, as has happened with varicella.[19]