Herpes Zoster in Childhood: A Review
Herpes zoster (HZ), significantly occurring as a dermatomal viral infection, is caused by the reactivation of varicella zoster virus (VZV) persisting in the posterior root ganglion. It is characterized by unilateral radicular pain and vesicular eruption limiting to a single dermatome innervated by that spinal or cranial sensory ganglion. In children, it may be due to intrauterine VZV infection or secondary to postnatal exposure to VZV at an early age. Diagnosis is mainly clinical, other options being pathological examination by Tzanck smear and immunofluorescence. Various treatment options depend on the patient’s age, immune status, duration of symptoms, and presentation.
Herpes zoster (HZ), significantly occurring as a dermatomal viral infection, is caused by reactivation of varicella zoster virus (VZV) persisting in the posterior root ganglion and is characterized by unilateral radicular pain and vesicular eruption limiting to a single dermatome innervated by that spinal or cranial sensory ganglion. HZ can occur in children, adults, old age and immunocompromised people. HZ is uncommonly reported in immunocompetent children. It may be due to intrauterine VZV infection or secondary to postnatal exposure to VZV at an early age.
The incidence of HZ is 1.5-3 per 1000 person years across all ages and 7-11 per 1000 person year in the age group above 60 years, without any seasonal variations noted. Herpes zoster is primarily a disease occurring between fourth and fifth decades of life. An overall rate in infants for HZ is of 3.4 cases per 1000 persons and the lowest incidence in individuals less than 10 years old (0.74/1000 person years). The earliest age reported is in a 3-month old infant.
Herpes zoster in childhood may be due to intrauterine VZV infection or secondary to postnatal exposure to VZV at an early age. Advancing age, immunocompromised state, malignancy, underlying systemic diseases like lung and kidney disease, are major factors for its occurrence. Vaccines are available, but a lot of concerns have arisen that the immunization might lead to an increased risk of vaccine-associated herpes zoster, particularly in the immunocompromised but enough data proving this is not available.
Herpes zoster is caused by the reactivation of a neurodermotropic virus called “varicella zoster virus” (VZV) lying dormant in the sensory ganglion following an earlier attack of varicella. During varicella infection, VZV passes from skin lesions into cutaneous sensory nerve endings and then travels centripetally to sensory ganglia where it remains in the latent stage. Many triggering factors like trauma, stress, sunburn, tumor of the ganglia, surgery, or irradiation, sinusitis, immunosuppression and old age on reactivation, it travels back along the sensory afferents to the skin associated with hematogenous dissemination. Depending upon the immune status of the patient, the presentation may vary from no clinical lesions to typical zoster, scattered vesicles, zoster sine herpete, or disseminated zoster. The overall prognosis in healthy children is usually good and as compared to adults, it is milder, without a prodrome, and is generally not associated with postherpetic neuralgia.
Multiple, grouped vesicles on erythematous base involving unilateral, single dermatome of the body with complaints of mild to moderate pain and burning sensation. Thoracic dermatomal involvement is observed in majority of cases, followed by lumbar, head, upper limbs and lower limbs. Ophthalmic, ear or face involvement is also seen.
Pain is the most common symptom along with prodromal symptoms such as headache, fever, fatigue and malaise. The pain has been described to be of burning, throbbing or stabbing sensation. The rash appears 3-4 days after the sensation of pain, starting as erythematous papules, quickly evolving into grouped vesicles or bullae and then into pustules. The lesions crust by 7-10 days, resolving in 2-3 weeks. The involved lymph nodes can be enlarged and tender.
Complications like post herpetic neuralgia, ocular complications, Ramsay-hunt syndrome, bacterial infection, Guillain-Barre Syndrome can occur. Earlier, herpes zoster in childhood was considered to be an indicator of an underlying malignancy, like acute lymphatic leukemia, but recent studies have shown that there is no increase in the incidence of malignancy in children with HZ.
Approximately 3% of the pediatric zoster cases occur in children with malignancies. Herpes zoster ophthalmicus in childhood with human immunodeficiency virus (HIV) can be a systemic disease and may be associated with tuberculosis and syphilis. Usually, the course of the disease is milder in children and the mean duration is 1 to 3 weeks. Herpes zoster in infancy or early childhood generally results from reactivation of VZV infection acquired either in utero or during early infancy while partially protected by maternal antibodies. The lesions usually heal completely in 10 days with slight hypopigmentation.
The timing of primary VZV infection in pregnancy determines the risk of fetal involvement with infection between 8 and 20 weeks of gestation leading to the congenital varicella syndrome in 12% of infants. These infants are born with cicatricial lesions, cutaneous defects and hypopigmentation in addition to multiorgan involvement. Intrauterine growth retardation and preterm birth may also occur.
Diagnosis of HZ is made by clinical examination of the lesions and it is confirmed by lab diagnosis by Tzanck smear of scrapings from the floor of the vesicles, which shows multinucleated giant cells on direct microscopy. The other methods of diagnosis are by direct fluorescent monoclonal antibody test or detection of serum specific IgM by the indirect fluorescent antibody method, presence of high or rising titers to VZV, or by culture studies. Ideally, in childhood HZ, lymphocyte counts, CD4/CD8 ratio, and serum immunoglobulin levels have also to be estimated to rule out undetected concurrent immunosuppression.
An important differential of HZ in childhood is zosteriform herpes simplex, which is more common, and can be diagnosed by direct fluorescent monoclonal antibody test or by detection of serum specific immunoglobulin M by the indirect fluorescent antibody method. The other differential diagnosis for dermatomal vesicular eruptions in children is bullous impetigo and bullous insect bite reaction.
The treatment options are based on the patient’s age, immune status, duration of symptoms, and presentation. Several studies indicate that antiviral medications decreased the duration of symptoms and the likelihood of post herpetic neuralgia, especially when initiated within 3 days of the onset of rash. Symptomatic treatment is important keeping in mind to prevent the complication of post herpetic neuralgia. Antiviral drugs may reduce the severity and duration of HZ. However, they do not prevent post herpetic neuralgia. Of these drugs, acyclovir has been the standard treatment in adults, but the new drugs valacyclovir and famcyclovir demonstrate similar or superior efficacy and good safety and tolerability.
The first line of therapy in childhood HZ is oral acyclovir, given at a dose of 20–40 mg/kg body weight, four times a day, (up to a maximum dose of 800 mg four times daily) for the duration of one week. An important study by Kubeyinje suggested that the use of acyclovir in healthy young children with zoster is not clearly justified, especially in situations of limited economic resources. Supportive measures include topical silver sulfadiazine cream, oral antibiotics, and paracetamol.
In most reported cases, there was a history of maternal varicella during gestation suggesting that the initial viral exposure occurred in utero. Treatment option is topical fusidic acid cream.
For prevention of VZV, there is a live vaccine which must be maintained at a temperature not exceeding minus 15 degrees Centigrade during storage, although it can be stored and transported at refrigerator temperature for up to 72 continuous hours before reconstitution. The lower age limit for vaccination is after first year of age but there is no recommended upper age limit. The vaccine reduced incidence of persistent, severe pain after shingles post herpetic neuralgia by 66% in people who contracted shingles despite vaccination. The vaccine associated side-effects are very less.
Patients with HIV infection are at a risk of developing severe illness from either varicella or herpes zoster. Progressive primary varicella, a syndrome with persistent new lesion formation and visceral dissemination, may occur in HIV infected patients and may be life threatening. In the remaining cases and in infections at a later stage of pregnancy, the fetus is either not infected or suffers a subclinical infection with persistence of immunoglobulin G (IgG) at 1-2 years of age. The low levels of lymphocytes, natural killer (NK) cells, cytokines and virus specific immunoglobulins seen in utero and in infancy may result in an inability to maintain the latency of VZV leading to the early appearance of zoster in children.
Rising incidence of herpes zoster is being observed in children due to primary varicella infection in utero, or in infancy, when the infant’s immunity is not fully developed. Most of them show no evidence of immunosuppression and the disease is generally mild and of shorter duration than its adult variety. Previous exposure to varicella is seen only in about half of the patients. Atypical presentations are very rare when compared to adults and elderly patients.
- Hope Simpson RE. The nature of herpes zoster: a long-term study and a new hypothesis. Proc Roy Soc Med. 1965;58:9-20.
- Handa S. Herpes zoster in a 3-month-old infant. Paed Dermatol. 1997;14:133.
- Straus SE, Schmader KE, Oxman MN. Varicella and herpes zoster. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, editors. Fitzpatrick’s Dermatology in General Medicine. 6th ed., Vol. 2. New York: McGrawHill. 2003. 2070-85.
- Talwar S, Shrivastava VK. Herpes zoster ophthalmicus with total ophthalmoplegia. Indian J Dermatol Venereol Leprol. 1991;56(6):454-455.
- Talwar S. Herpes zoster associated with varicelliform eruption. Indian J Dermatol Venereol Leprol. 1991;57(1):52.
- Aikenhead KJ, Johnson TL Jr. Herpes zoster in a 6-monthold infant with 13-year followup: A retrospective case report. J Chiropr Med. 2011; 10:3069.
- Kurlan JG, Connelly BL, Lucky AW. Herpes zoster in the first year of life following postnatal exposure to Varicella-zoster virus: Four case reports and a review of infantile herpes zoster. Arch Dermatol. 2004;140:1268-72.
- Gupta N, Sachdev R, Sinha R, Titiyal JS, Tandon R. Herpes zoster ophthalmicus: Disease spectrum in young adults. Middle East Afr J Ophthalmol. 2011;18:178-82.
- Laude TA, Rajkumar S. Herpes zoster in a 4-month-old infant. Arch Dermatol. 1980;116:160.
- Sanchez MA, BelloMunoz JC, Cebrecos I, Sanz TH, Martinez JS, Moratonas EC, et al. The prevalence of congenital varicella syndrome after a maternal infection, but before 20 weeks of pregnancy: A prospective cohort study. J Matern Fetal Neonatal Med. 2011; 24:341-7.
- Kakourou T, Theodoridou M, Mostrou G, Syriopoulou V, Papadogeorgaki H, Constantopoulos A. Herpes zoster in children. J Am Acad Dermatol. 1998;39(2 Pt 1):207-10.
- Gnann JW Jr., Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med. 2002;347(5):340-6.
- Berger R, Florent G, Just M. Decrease of the lymphoproliferative response to varicellazoster virus antigen in the aged. Infect Immun. 1981;32(1):24-27.
- Takayama N, Yamada H, Kaku H, Minamitani M. Herpes zoster in immunocompetent and immunocompromised Japanese children. Pediatr Int. 2000;42:275-9.
- Guess HA, Broughton DD, Melton LJ 3rd, Kurland LT. Epidemiology of herpes zoster in children and adolescents: A population based study. Pediatrics. 1985;76:512-7.
- Terada K, Kawano S, Yoshihiro K, Yokobayashi A, Miyashima H, Morita T. Characteristics of herpes zoster in otherwise normal children. Pediatr Infect Dis J. 1993;12(11):960.
- Papadopoulos AJ, Birnkrant AP, Schwartz RA, Janniger CK. Childhood herpes zoster. Cutis. 2001;68:213.
- Gupta LK, Khare AK, Mittal A, Kuldeep CM. Herpes zoster in infancy. Indian Dermatol Online J. 2013;4:252-4.
- Bhushan P, Sardana K, Mahajan S. Dermatomal vesicular eruption in an asymptomatic infant. Dermatol Online J. 2005; 11:26