Role of polymerase chain reaction in early diagnosisof herpes zoster ophthalmicus in childrenAjay Bhatnagar, FRCS, Paul Tomlins, MRCOphth, and Manoj V. Parulekar, FRCOphth

Herpes zoster ophthalmicus is uncommon in children, and diagno-sis may be delayed until the typical skin lesions become apparent.Delay in appropriate treatment may result in sight-threatening com-plications. We report a case of an 18-month-old child in whom wepromptly confirmed the clinical suspicion of herpes zoster ophthal-micus by the identification of viral DNA using polymerase chain re-action. This procedure enabled us to administer prompt antiviraltreatment, preventing sight-threatening sequelae. We review theliterature regarding the possible mechanism of herpes zoster oph-thalmicus in immunocompetent children and discuss the role ofpolymerase chain reaction in its diagnosis.

Case Report

An 18-month-old girl presented to the pediatricemergency department with an acute onsetvesicular skin eruption involving the left side of

the forehead, nose, and left upper eyelid. She was irritable,febrile, and not feeding well. Baseline blood investigationswere normal except for an increased total leukocyte count.Swabs obtained from the vesicular eruption were sent formicrobiological investigations. Although the diagnosis ofherpes zoster was considered, bacterial infection could notbe ruled out, and the patient was started on intravenous ce-furoxime.

During the next 24 hours, the skin lesions assumed thecharacteristic distribution of herpes zoster ophthalmicus(HZO) involving the nasociliary dermatome. Ophthalmicexamination performed with the use of a hand-held slitlamp showed conjunctival congestion, superficial punctatekeratitis, and a quiet anterior chamber. Culture of theswabs taken from the vesicles did not grow any organism.However, the use of polymerase chain reaction (PCR) en-abled us to identify varicella zoster viral (VZV) DNA. In-travenous acyclovir (10 mg/kg every 8 hours) therapy wasstarted immediately. Within 48 hours, the patient’s feversubsided, eyelid swelling started to improve, and skinlesions began to heal. Six days later, she was switched tooral acyclovir. After 4 weeks, the skin lesions had healedwith scarring, the lid edema had resolved, and the left cor-

Author affiliations: Birmingham Children’s Hospital, Steelhouse Lane, Birmingham,United Kingdom

Submitted July 1, 2008.Revision accepted October 7, 2008.Published online January 21, 2009.Reprint requests: A. Bhatnagar, FRCS, Eye Clinic, Birmingham Children’s Hospital,

Steelhouse Lane, Birmingham B4 6NH, UK (email: bhatnagar_ajay@hotmail.com).J AAPOS 2009;13:213-214.

Copyright � 2009 by the American Association for Pediatric Ophthalmology andStrabismus.

1091-8531/2009/$36.00 1 0doi:10.1016/j.jaapos.2008.10.006

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nea was clear. Visual acuity was 6/7.5 in both eyes using theCardiff acuity test. The child had not been vaccinatedagainst varicella nor did she have any known previous con-tact with chicken pox; her mother recalled having hadchicken pox as a child and was seropositive for VZV anti-bodies.

Discussion

After primary varicella infection, the herpes zoster virus liesdormant in the sensory ganglia. Herpes zoster occurs whenthe latent virus is reactivated. Although not uncommon inthe elderly (4.5/1,000 person-years in people 75 years orolder),1 herpes zoster is rare in children (estimated incidence0.2/1,000 person-years in children 0–5 years of age).2 Casesreported in children are mostly related to immunosuppres-sion3 and varicella infection acquired transplacentally orduring the first year of life.4 Binder and colleagues5 reporteda case of HZO in an immunocompetent 8-year-old patientwho had been previously immunized against varicella. Ourpatient was immunocompetent with no previous vaccinationagainst varicella or history suggesting intrauterine exposureto VZV; her mother had prenatal-acquired immunity tovaricella, making transplacental infection unlikely. It istherefore possible that the patient acquired primary varicellainfection during infancy that had remained unrecognized.Primary varicella infection in infants often is underdiag-nosed because of mild clinical manifestations and the expec-tation that maternal antibodies will be protective during thisperiod.4 However, the infant’s immune system is immature,and the cellular and humoral immune response to primaryvaricella infection may be inadequate,6 making such infantsprone to subsequent development of zoster. Primary infec-tion before 1 year of age is thus a well-recognized risk factorfor developing zoster during childhood.4

In a series of 10 cases of HZO in immunocompetentchildren, 5 patients developed corneal opacification, 2 ofwhom had severe visual impairment.7 Neither of these 2children received adequate antiviral therapy. Early diagno-sis and antiviral treatment is thus critical in preventingsight threatening disease.

Herpes zoster ophthalmicus can be a difficult and un-common diagnosis to make in a child. Children with earlyHZO presenting to the pediatric emergency departmentmay initially be diagnosed as having impetigo thus delayingappropriate antiviral therapy. The use of PCR has beenshown to be effective in identifying the viral DNA in95% of cases of herpes zoster.8 This technique has beenused to confirm the presence of varicella virus DNA fromoropharyngeal swabs,9 cerebrospinal fluid,10 and blood11

in atypical cases of herpes zoster. A plain swab of the

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vesicular fluid from the skin lesions is sufficient for the pur-pose of identifying viral DNA using PCR. Most moleculartesting laboratories are capable of testing for varicella zos-ter virus with the use of commercially available primers,and the result is available within a few hours. The initialskin lesions in our patient were suggestive, but not typical,of herpes zoster. This case highlights the value of PCR inconfirming the diagnosis of HZO in children early in theclinical course, ensuring systemic antiviral therapy isstarted without delay to prevent sight-threatening se-quelae.

References

1. Insinga RP, Itzler RF, Pellissier JM, Saddier P, Nikas AA. The inci-dence of herpes zoster in a United States administrative database.J Gen Intern Med 2005;20:748-53.

2. Guess HA, Broughton DD, Melton LJ III, Kurland LT. Epidemiol-ogy of herpes zoster in children and adolescents: A population basedstudy. Pediatrics 1985;76:512-17.

3. Kakourou T, Theodoridou M, Mostrou G, Syriopoulou V,Papadogeorgaki H, Constantopoulos A. Herpes zoster in children.J Am Acad Dermatol 1998;39:207-10.

4. Kurlan JG, Connelly BL, Lucky AW. Herpes zoster in the first yearof life following post-natal exposure to varicella zoster virus. ArchDermatol 2004;140:1268-72.

5. Binder NR, Holland GN, Hosea S, Silverberg ML. Herpes zosterophthalmicus in an otherwise healthy child. J AAPOS 2005;9:597-8.

6. Terada K, Kawano S, Yoshihiro K, Morita T. Varicella-zoster virus(VZV) reactivation is related to the low response of VZV-specific im-munity after chickenpox in infancy. J Infect Dis 1994;169:650-52.

7. De Freitas D, Martins EN, Adan C, Alvarenga LS, Pavan-Langston D. Herpes zoster ophthalmicus in otherwise healthy chil-dren. Am J Ophthalmol 2006;142:393-9.

8. Sauerbrei A, Sommer M, Wutzler P. Virologic diagnosis of herpeszoster. Hautarzt 1999;50:873-8.

9. Furuta Y, Fukuda S, Suzuki S, Takasu T, Inuyama Y, Nagashima K.Detection of varicella-zoster virus DNA in patients with acute periph-eral facial palsy by the polymerase chain reaction, and its use for earlydiagnosis of zoster sine herpete. J Med Virol 1997;52:316-9.

10. Bergstrom T. Polymerase chain reaction for diagnosis of varicella zos-ter virus central nervous system infections without skin manifesta-tions. Scand J Infect Dis Suppl 1996;100:41-5.

11. Rau R, Fitzhugh CD, Baird K Cortez KJ, Li L, Fischer SH, et al.Triad of severe abdominal pain, inappropriate antidiuretic hormonesecretion and disseminated varicella zoster virus infection precedingcutaneous manifestations after hematopoietic stem cell transplanta-tion: Utility of PCR for early recognition and therapy. Pediatr InfectDis J 2008;27:265-8.

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