Following primary infection, varicella zoster virus (VZV) establishes latency in cranial nerve and dorsal root ganglia and can subsequently reactivate to produce disease in infected individuals. Although wild-type VZV has been isolated from previously immunized children with herpes zoster, recent studies also indicate that vaccine strain VZV is a potential cause of herpes zoster in immunocompetent and immunocompromised children.1,2 Data from postlicensure surveillance indicate that clinical severity is milder in vaccinated children compared with children who have had the wild-type VZV infections.2 The central nervous system involvement in VZV reactivation is believed to be a rare complication. In this report, we describe herpes zoster and meningitis in an immunocompetent child with the vaccine strain of VZV.
A previously healthy 7-year-old boy presented with a 4-day history of right arm pain; a 2-day history of right arm rash; and a 1-day history of fever, headache, photophobia, and vomiting. The rash started on his right elbow and spread to the rest of his upper right arm and shoulder over 2 days. There was no history of sick contact. A review of his immunization record showed a varicella vaccination at 12 months of age.
On admission, his temperature was 37.1°C, pulse 96/min, respiratory rate 16/min, and blood pressure was 101/56. The physical examination was notable for multiple erythematous, maculopapular lesions without clear vesicles over the lateral side of his right arm. There was no nuchal rigidity, and there was no evidence of neurologic deficit or altered mental status.
Laboratory studies revealed a peripheral white blood cell count of 7000 cells/mm with 77% neutrophils, 13% lymphocytes, and 10% monocytes. His serum electrolytes, liver transaminases, hemoglobin, and platelet counts were within normal limits. Cerebrospinal fluid (CSF) revealed 16 white blood cells with 71% lymphocytes and 3 red blood cells/mm. The protein was 29 mg/dL, and the glucose was 57 mg/dL. The CSF Gram stain and culture were negative for bacterial pathogens. A swab from a skin lesion and CSF were positive for VZV by polymerase chain reaction. VZV from both sites was identified as vaccine strain according to genotyping performed at the National VZV Laboratory of the Centers for Disease Control and Prevention in Atlanta, GA. Subsequent immune evaluation showed normal numbers, percentages, and ratios of peripheral T and B cell subsets and a negative serology for human immunodeficiency virus.
The patient was treated with intravenous acyclovir (10 mg/kg every 8 hours). His symptoms improved, and he was discharged home on hospital day 3 with a peripherally inserted central catheter to complete a 21-day course of acyclovir. He was asymptomatic with a normal physical examination at 2 weeks after discharge.
The implementation of routine varicella vaccination has dramatically shifted the clinical epidemiology of primary VZV infection for children in the United States. The risk of herpes zoster has also been described as being decreased in vaccinated children.3 In postlicensure surveillance in the United States by the Centers for Disease Control and Prevention, 7 cases of herpes zoster due to wild-type VZV and 10 from vaccine strain VZV in patients hospitalized with herpes zoster have been identified.1 This data suggest that vaccine strain VZV is currently an important cause of herpes zoster among immunized children in the United States.
The incidence of neurologic complications in herpes zoster is not well defined in the medical literature, but they are believed to be rare complications. Although children with defects in cell-mediated immunity are expected to be more susceptible to neurologic complications, meningitis and meningoencephalitis resulting from reactivation of wild-type VZV have been reported in both immunocompetent and immunocompromised children.4–7 Notably, recent reports also identified meningitis as a complication in reactivation of vaccine strain VZV in immunocompetent and immunocompromised children.1,8,9 In this regard, our report represents the fifth laboratory confirmed case of vaccine strain VZV reactivation leading to meningitis in a previously vaccinated child.
The optimal therapy for meningitis and meningoencephalitis caused by reactivation of wild-type and vaccine strain VZV remains to be determined. Although 1 patient with a wild-type VZV meningitis recovered without antiviral therapy,6 recrudescence of symptoms after discontinuation of acyclovir after 2 days of therapy in an immunocompetent child with herpes zoster and meningitis due to a vaccine strain was reported by Levin et al,9 suggesting that antiviral therapy for some duration is prudent in these patients. A guideline from the Infectious Diseases Society of America suggests intravenous acyclovir at 10 to 15 mg/kg every 8 hours for 10 to 14 days for VZV encephalitis on the basis of case reports and small series.10 While awaiting the results of immunodeficiency evaluation and VZV virus genotyping, we opted for a 21-day course that mirrors the treatment duration of herpes simplex encephalitis in neonates.
No specific immune deficiency was identified in our patient, similar to what has been reported for 3 of the other 4 children with herpes zoster and meningitis caused by the vaccine strain.1,8,9 However, previously unrecognized primary immune deficiency such as in the toll-like receptor pathways is possible and should be explored particularly if the children present with recurrent episodes. It is interesting to note that 3 of the 4 immunocompetent children received a single dose of varicella vaccine at the age of 1 year. A previous study has suggested that primary varicella infection in the first year of life is a risk factor for childhood zoster.11 Based on our case and other recent reports, additional epidemiologic survey to determine whether early vaccination puts children at increasing risk for reactivation of the vaccine strain later in life may be warranted.
The etiologic agent in our case, as in other reported cases, was established by the VZV genotyping at the Centers for Disease Control and Prevention.12 Given the routine childhood immunization with varicella vaccine in the United States, we speculate that the incidence of meningitis caused by the reactivation of vaccine strain VZV may be on the increase. Appropriate testing to identify the VZV strain in future cases of patients presenting with herpes zoster meningitis will be important to establish the incidence and risk of this rare vaccine complication.
The authors thank Vicky Buttery at the Minnesota Department of Health for assistance in laboratory testing and critical reading of the manuscript. The authors also thank D. Scott Schmid, PhD, and Kay Radford at the National VZV Laboratory of the Centers for Disease Control and Prevention in Atlanta, GA, for laboratory testing and technical support.
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