Severe Herpes Zoster Following Varicella Vaccination in Immunocompetent Young Children

Abstract

Varicella vaccination is now virtually universal in North America, as well as in some European and Asian countries. Since varicella vaccine is a live attenuated virus, the virus replicates in the skin after administration and can travel via sensory nerves or viremia to become latent in the dorsal root ganglia. In some immunized children, virus reactivates within a few months to a few years to cause the dermatomal exanthem known as herpes zoster (shingles). Herpes zoster caused by vaccine virus often reactivates within the same dermatome as the site of the original varicella vaccine injection. We present evidence that occasional cases of herpes zoster following varicella vaccination in immunocompetent children can be as severe as herpes zoster following wild-type varicella. Analysis of the virus in one case disclosed that the vaccine virus causing herpes zoster was a wild-type variant with a mutation in ORF0. With regard to dermatomal localization of the viral eruption, we predict that herpes zoster of the lumbar dermatomes in children is likely to be caused by vaccine virus, because herpes zoster in those dermatomes is rare in children after wild-type varicella. One of the children with herpes zoster subsequently developed asthma, a known risk factor for herpes zoster, but none of the children had an autoimmune disease. Although postherpetic neuralgia is exceedingly rare, children who develop herpes zoster following varicella vaccination are at risk (albeit low) of developing meningoencephalitis and should be carefully observed for a few weeks.

Keywords: Oka vaccine; acyclovir; asthma; encephalitis; open reading frame 0; sequencing; shingles; varicella-zoster virus.

Figure 1.

Identification of an ORF0 mutation in the vaccine virus of patient 1. The structure of ORF0 in wild-type virus is shown in blue; there is a stop codon after residue 129. The structure of ORF0 in the vaccine virus is shown in red; a nucleotide transition (TGA to CGA) after residue 129 replaces the stop codon with an arginine at residue 130. The ORF0 protein product is longer. When ORF0 was sequenced from the vaccine virus recovered from patient 1, there was a stop codon after residue 129, as shown in green.

Figure 2.

Dermatomal rash of herpes zoster in patient 2. The rash was broadly distributed over the L3 dermatome on the anterior aspect of the right thigh (A); the location of the original varicella vaccine injection 9 months earlier is indicated by a white circle. The rash lessened as it extended around the flank and toward the spinal column (B).