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Background
The varicella zoster virus is the cause of this common childhood infection. It is a close relative of the herpes virus. After initial infection, the virus remains dormant in the dorsal root ganglia. During periods of stress or immunocompromised states, the virus may be reactivated and shingles (Herpes zoster) is the result. It is important to remember that a person with a shingles outbreak is infectious to anyone who has not been previously exposed to the virus.
OUTLINE
Epidemiology Disease Associations Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Prognosis Treatment Commonly Used Terms Internet Links
CLINICAL AND GROSS DISEASE VARIANTS CHARACTERIZATION INFANTILE 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
Julia G. Kurlan, MD ;Beverly L. Connelly, MD ;Anne W. Lucky, MD
From the Department of Dermatology, Wright State University, Dayton, Ohio (Dr Kurlan), and the Divisions of Infectious Diseases (Dr Connelly) and Pediatric Dermatology (Dr Lucky), Cincinnati Children's Hospital Medical Center, and Dermatology Associates of Cincinnati (Dr Lucky), Cincinnati, Ohio. The authors have no relevant financial interest in this article.Arch Dermatol. 2004;140:1268-1272. Abstract quote Background Herpes zoster, a painful vesicular dermatomal eruption, is the result of reactivation of the varicella-zoster virus (VZV) from infected sensory ganglia. Traditionally, it is considered to be a disease of adults, in contrast to primary infection with VZV, which tends to occur mainly in children.
Observations We report 4 cases of infantile herpes zoster in healthy immunocompetent children, all of whom were exposed to primary varicella infection within the first few months of life. A review of 62 cases from the literature reveals that postnatally acquired herpes zoster is less common than intrauterine infection (31% [n = 19] vs 69% [n = 43]) and that there is a 1.5:1 male predominance. All dermatomes are equally affected.
Conclusions Although uncommon, herpes zoster can develop in immunocompetent children as young as a few weeks of age and should be considered in the differential diagnosis of vesicular eruptions in infants. Most frequently, it is the result of intrauterine VZV infection, but it can be secondary to postnatal exposure to VZV at an early age.
RECURRENT
Atypical recurrent varicella in 4 patients with hemopathies.Nikkels AF, Simonart T, Kentos A, Liesnard C, Sadzot-Delvaux C, Feremans W, Pierard GE.
Department of Dermatopathology, University Medical Center of Liagege, Belgium.
J Am Acad Dermatol 2003 Mar;48(3):442-7 Abstract quote Relapsing varicella may occur in children with HIV infection and more rarely in younger adults.
Our aim was to report unusual clinical, histologic, and virologic aspects of 4 elderly patients with malignant hemopathies who had an unusual form of recurrent varicella develop. Conventional microscopy, immunohistochemistry, and in situ hybridization were applied to smears and skin biopsy specimens. The patients presented a few dozen, scattered, large, papulovesicular lesions with central crusting. No zoster-associated pain or dermatomal distribution of the lesions was noted. Conventional microscopy revealed vascular changes and epidermal alterations typical for alpha-herpes virus infection. The varicella zoster virus major viral envelope glycoproteins gE and gB, and the immediate-early varicella zoster virus IE63 protein and the corresponding genome sequence for gE were detected on Tzanck smears; they were localized in endothelial cells and keratinocytes on skin biopsy specimens.
The varicella zoster virus infection in endothelial cells, the vascular involvement, and the widespread distribution of the lesions suggest that the reported eruptions are vascular rather than neural in origin. These findings invalidate the diagnosis of herpes zoster but strongly support the diagnosis of recurrent varicella in an indolent and yet unreported presentation.
Furthermore, these eruptions differ from relapsing varicella in children and young adults by the age of the patients, the paucity of clinical lesions, the larger diameter of the lesions and their peculiar clinical aspect, the significantly longer time interval between primary varicella and the recurrence, the prolonged healing time of the lesions, their mild disease course, and the fact that all the lesions are in the same stage of development.
HISTOPATHOLOGY CHARACTERIZATION GENERAL
- Histopathologic features of cutaneous herpes virus infections (herpes simplex, herpes varicella/zoster): a broad spectrum of presentations with common pseudolymphomatous aspects.
Leinweber B, Kerl H, Cerroni L.
From the Department of Dermatology, Medical University of Graz, Graz, Austria.
Am J Surg Pathol. 2006 Jan;30(1):50-8. Abstract quote
Cutaneous eruptions caused by herpes simplex 1/2 (HSV-1/2) and herpes varicella/zoster (VZV) represent common dermatoses. In some cases, they present with atypical clinical and/or histopathologic features, including presence of dense lymphoid infiltrates with atypical lymphocytes simulating cutaneous lymphomas.
In this study, we reviewed the biopsy specimens of 65 patients (33 males, 32 females; mean age, 61.2 years; median age, 62 years; age range, 19-96 years) with cutaneous eruptions caused by HSV-1/2 or VZV.
Histologic examination revealed several atypical findings, including presence of dense lymphoid infiltrates, angiotropism, and atypical lymphocytes simulating malignant lymphoma. Immunohistochemistry performed in 22 cases showed a predominant T-cell infiltrate, in the majority of cases with variable numbers of CD30+ and CD56+ cells. Two cases with a pseudolymphomatous appearance and small clusters of CD30+ cells revealed a monoclonal population of T lymphocytes by PCR analysis, underlying the difficulties in classifying some of these cases correctly.
Our study indicates that cutaneous herpes infections can exhibit several atypical histopathologic, immunohistochemical, and molecular features, and that in given cases accurate clinicopathologic correlation and short-term follow-up controls are necessary for differentiation from cutaneous lymphomas.
VARIANTS CUTANEOUS LYMPHOID HYPERPLASIA
- Varicella-zoster-virus folliculitis promoted clonal cutaneous lymphoid hyperplasia.
Aram G, Rohwedder A, Nazeer T, Shoss R, Fisher A, Carlson JA.
Department of Pathology, Albany Medical College, Albany, New York 12208, USA.
Am J Dermatopathol. 2005 Oct;27(5):411-7. Abstract quote
Post herpes zoster (HZ) reactions have been associated with panoply of neoplastic, inflammatory, and fibro-inflammatory cutaneous disorders. Varicella zoster virus (VZV) DNA has not been identified in most of these reports.
After an episode of HZ, a healthy, active 90-year-old female developed ulcerative nodules in the affected trigeminal V1 dermatome and the contra-lateral trigeminal region over a 1-year period. Excision and/or biopsy of all these lesions showed similar pathologic changes that consisted of herpetic folliculitis, adjacent dense mixed nodular lymphocytic infiltrates with germinal centers (cutaneous lymphoid hyperplasia (CLH)), and in the deeper excision specimens, an obliterative vasculitis of a vessel with smooth muscle in its wall. Immunophenotype analysis revealed a mixed, predominate T- and B-cell population without loss of pan-T cell antigens or aberrant expression by B cells of T-cell antigens. Polymerase chain reaction for herpetic DNA was positive for VZV DNA. Lymphocyte gene rearrangement analysis revealed 2 distinct, anatomically and chronologically, monoclonal B-cell populations and a monoclonal T-cell population in one nodule. Treatment with valacyclovir has lead to almost complete resolution of her cutaneous nodules after 6 months of therapy.
In this case, it can be surmised that persistence of VZV infection and lack of effective cell-mediated immunity lead to development of both immunopathology (vasculitis) and excessive lymphoid cell proliferation (CLH).
LABORATORY/
RADIOLOGY/OTHER TESTSCHARACTERIZATION Detection of herpes simplex and varicella zoster viruses in clinical specimens using direct immunofluorescence and cell culture assays.
Meqdam MM, Todd D, Al-Abosi M.
Department of Applied Biology, Jordan University of Science and Technology, Irbid.
Microbios 2001;105(411):111-8 Abstract quote
Patients (33 in toto) with a clinical diagnosis of herpes infections (simplex, zoster or chickenpox) were investigated for the presence of herpes simplex virus (HSV) and varicella zoster virus (VZV) in skin samples, using direct immunofluorescence and cell culture assays.
Five patients with nonherpetic vesiculobullous disorders were included as negative controls. Of the 33 patients, nineteen (57.6%) were positive for HSV or VZV and fourteen (42.4%) were negative. Five controls were all negative for HSV or VZV. Of the nineteen positive patients, HSV was isolated from eight (42.1%) patients, by both direct immunofluorescence and cell culture assays. VZV was isolated from eleven (57.9%) patients, eleven (100%) by direct immunofluorescence assay, and six (54.5%) by cell culture assays. HSV was isolated from one patient clinically diagnosed as chickenpox (VZV), but otherwise the positive laboratory results were concordant with the clinical diagnosis.
For epidemiological studies, atypical cases and immunocompromised patients the clinical diagnosis should be confirmed in the laboratory.
PROGNOSIS AND TREATMENT CHARACTERIZATION VACCINATION Impact of Varicella Vaccination on Health Care Utilization .
JAMA. 2005;294:797-802. Abstract quote
Context Since varicella vaccine was first recommended for routine immunization in the United States in 1995, the incidence of disease has dropped substantially. However, national surveillance data are incomplete, and comprehensive data regarding outpatient as well as hospital utilization have not been reported.Objective To examine the impact of the varicella vaccination program on medical visits and associated expenditures.
Design, Setting, and Patients Retrospective population-based study examining the trends in varicella health care utilization, based on data from the MarketScan databases, which include enrollees (children and adults) of more than 100 health insurance plans of approximately 40 large US employers, from 1994 to 2002.
Main Outcome Measures Trends in rates of varicella-related hospitalizations and ambulatory visits and direct medical expenditures for hospitalizations and ambulatory visits, analyzed using 1994 and 1995 as the prevaccination baseline.
Results From the prevaccination period to 2002, hospitalizations due to varicella declined by 88% (from 2.3 to 0.3 per 100 000 population) and ambulatory visits declined by 59% (from 215 to 89 per 100 000 population). Hospitalizations and ambulatory visits declined in all age groups, with the greatest declines among infants younger than 1 year. Total estimated direct medical expenditures for varicella hospitalizations and ambulatory visits declined by 74%, from an average of $84.9 million in 1994 and 1995 to $22.1 million in 2002.
Conclusion Since the introduction of the varicella vaccination program, varicella hospitalizations, ambulatory visits, and their associated expenditures have declined dramatically among all age groups in the United States.
Effectiveness over time of varicella vaccine.
Vazquez M, LaRussa PS, Gershon AA, Niccolai LM, Muehlenbein CE, Steinberg SP, Shapiro ED.
Department of Pediatrics, Yale University School of Medicine, New Haven, Conn 06520-8064, USA.
JAMA. 2004 Feb 18;291(7):851-5 Abstract quote.
CONTEXT: Reports of outbreaks of varicella in highly immunized groups have increased concern about the effectiveness of varicella vaccine.
OBJECTIVE: To assess whether the effectiveness of varicella vaccine is affected either by time since vaccination or by age at the time of vaccination. DESIGN: Case-control study conducted from March 1997 through June 2003.
SETTING: Twenty different group practices in southern Connecticut.
PARTICIPANTS: Case subjects, identified by active surveillance of all practices, consisted of 339 eligible children 13 months or older who were clinically diagnosed as having chickenpox and who also had a polymerase chain reaction (PCR) test result that was positive for varicella-zoster virus DNA. For each case subject, 2 controls were selected, matched by both age and pediatric practice.
MAIN OUTCOME MEASURES: The effectiveness of the vaccine, especially the effects of time since vaccination and age at the time of vaccination, adjusted for possible confounders.
RESULTS: Although the adjusted overall effectiveness of the vaccine was 87% (95% confidence interval, 81%-91%; P<.001), there was a substantial difference in the vaccine's effectiveness in the first year after vaccination (97%) and in years 2 to 8 after vaccination (84%, P =.003). The vaccine's effectiveness in year 1 was substantially lower if the vaccine was administered at younger than 15 months (73%) than if it was administered at 15 months or older (99%, P =.01), although the difference in effectiveness overall for children immunized at younger than 15 months was not statistically significantly different than for those immunized at 15 months or older (81% vs 88%, P =.17). Most cases of chickenpox in vaccinees were mild.
CONCLUSIONS: Although varicella vaccine is effective, its effectiveness decreases significantly after 1 year, although most cases of breakthrough disease are mild. If administered at younger than 15 months, the vaccine's effectiveness was lower in the first year after vaccination, but the difference in effectiveness was not statistically significant for subsequent years.Childhood vaccination against varicella: persistence of antibody, duration of protection, and vaccine efficacy.
Vessey SJ, Chan CY, Kuter BJ, Kaplan KM, Waters M, Kutzler DP, Carfagno PA, Sadoff JC, Heyse JF, Matthews H, Li S, Chan IS.
Merck Research Laboratories, Merck & Co, Inc, West Point, Pennsylvania 19482, USA.
J Pediatr 2001 Aug;139(2):297-304 Abstract quote
OBJECTIVE: To document the duration of protection afforded by Oka/Merck varicella vaccine over a 7-year period.
STUDY DESIGN: The subjects were healthy children 1 to 12 years of age originally enrolled in clinical studies to evaluate the primary immune response to varicella vaccine 6 weeks after vaccination. Each was monitored for antibody persistence, breakthrough infection, and household exposure to varicella to produce estimates of vaccine efficacy.
RESULTS: The 6-year cumulative varicella antibody persistence rate was 99.5% (95% CI: 98.9%, 100.0%). The annual breakthrough rate through 7 years ranged from 0.2% to 2.3% per year; the estimated cumulative event rate was 6.5%. Comparison of the observed average annual breakthrough rate with the age-adjusted expected annual incidence rate of varicella in unvaccinated children corresponded to an estimated vaccine efficacy of 93.8% to 94.6%. Eighty vaccinated children were exposed to varicella in the household, resulting in 8 (10%) cases of infection. When compared with the historical attack rate of 86.8% in unvaccinated susceptible persons exposed to varicella in the household, this yields an estimated vaccine efficacy of 88.5% (95% CI: 80.9%, 96.1%). Varicella cases in vaccinated children generally were mild.
CONCLUSION: The live attenuated varicella vaccine is highly effective in inducing persistent immunity and long-term protection against breakthrough varicella infection.
Varicella vaccine exposure during pregnancy: data from the first 5 years of the pregnancy registry.
Shields KE, Galil K, Seward J, Sharrar RG, Cordero JF, Slater E.
Worldwide Product Safety & Epidemiology, Merck Research Laboratories, Merck & Co., Inc., USA.
Obstet Gynecol 2001 Jul;98(1):14-9 Abstract quote
OBJECTIVE: To assess the risks of congenital varicella syndrome and other birth defects in offspring of women who inadvertently received varicella vaccine during pregnancy or within 3 months of conception.
METHODS: Pregnant women inadvertently exposed to varicella vaccine, reported voluntarily, were enrolled in the Pregnancy Registry for VARIVAX (Merck & Co., Inc., West Point, PA). The pregnancies were monitored and the outcomes ascertained from questionnaires completed voluntarily by the health care providers. The rates of congenital varicella syndrome and congenital anomalies were calculated for seronegative women prospectively reported to the registry.
RESULTS: From March 17, 1995 through March 16, 2000, 362 pregnancy outcomes were identified from prospective reports. Ninety-two women were known to be seronegative to varicella, of whom 58 received their first dose of vaccine during the first or second trimester. No cases of congenital varicella syndrome were identified among 56 live births (rate 0%, 95% confidence interval [CI] 0, 15.6). Among all the prospective reports of live births, five congenital anomalies were reported. No specific pattern was identified in either the susceptible cohort or the sample population as a whole.
CONCLUSION: No abnormal features have been reported that suggested the occurrence of congenital varicella syndrome or other birth defects related to vaccine exposure during pregnancy. Because of the small numbers, this study has limited precision, so continued surveillance is warranted. However, these results should provide some assurance to health care providers and women with inadvertent exposure before or during pregnancy.
Immunization of HIV-infected children with varicella vaccine.
Levin MJ, Gershon AA, Weinberg A, Blanchard S, Nowak B, Palumbo P, Chan CY
AIDS Clinical Trials Group 265 Team. University of Colorado School of Medicine, Denver, USA.
J Pediatr 2001 Aug;139(2):305-10 Abstract quote
OBJECTIVE: To determine the safety and immunogenicity of varicella vaccine in children with human immunodeficiency virus (HIV) infection. Children (n = 41) who were mildly affected by HIV (Centers for Disease Control and Prevention stage N1 or A1) and had no history or serum antibody indicative of prior varicella infection were immunized with two doses of live attenuated varicella vaccine.
RESULTS: A minority of the vaccine recipients had mild local or systemic reactions. Vaccination had no effect on the clinical stage of HIV or the HIV RNA plasma load. CD4 cell percentage and CD4 cell count were marginally decreased at week 4 after the first vaccination; this effect was no longer present at week 8 after vaccination. Two months after the second dose of vaccine, 60% of vaccine recipients had anti-varicella antibody in their serum, and 83% had a positive lymphocyte proliferation assay response to varicella antigen.
CONCLUSION: On the basis of its safety and immunogenicity, varicella vaccine should be considered in the childhood vaccines given to mildly affected HIV-infected children.
Persistence of immunity to live attenuated varicella vaccine in healthy adults.Ampofo K, Saiman L, LaRussa P, Steinberg S, Annunziato P, Gershon A.
Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, NY, 10032, USA.
Clin Infect Dis 2002 Mar 15;34(6):774-9 Abstract quote The varicella vaccine was approved in 1995 for use in healthy varicella-susceptible children and adults.
Long-term immunity in 461 healthy adults who were enrolled in varicella vaccine trials in 1979-1999 were studied. Forty vaccinees (9%), including 19 (21%) of 89 vaccinees with household exposure (HHE) to chickenpox, developed breakthrough chickenpox 8 weeks to 11.8 years (mean, 3.3 years) after vaccination. The median number of skin lesions among the 36 untreated vaccinees was 20 (range, 1-240 lesions), and the number of lesions was essentially the same with time since vaccination. Breakthrough chickenpox was mild, even among vaccinees who did not have seroconversion or those recipients who lost detectable antibody. Lower varicella-zoster virus (VZV) antibody titers measured within 3 months of vaccination as well as at the time of HHE were associated with an increased risk of breakthrough disease.
This study demonstrated that the varicella vaccine was effective in providing adults with long-term protection from serious VZV disease.
Use of an inactivated varicella vaccine in recipients of hematopoietic-cell transplants.Hata A, Asanuma H, Rinki M, Sharp M, Wong RM, Blume K, Arvin AM.
Department of Pediatrics, Stanford University School of Medicine, Stanford, Calif 94305-5208, USA.
N Engl J Med 2002 Jul 4;347(1):26-34 Abstract quote BACKGROUND: The reactivation of varicella-zoster virus from latency causes zoster and is common among recipients of hematopoietic-cell transplants.
METHODS: We randomly assigned patients who were scheduled to undergo autologous hematopoietic-cell transplantation for non-Hodgkin's or Hodgkin's lymphoma to receive varicella vaccine or no vaccine. Heat-inactivated, live attenuated varicella vaccine was given within 30 days before transplantation and 30, 60, and 90 days after transplantation. The patients were monitored for zoster and for immunity against varicella-zoster virus for 12 months.
RESULTS: Of the 119 patients enrolled, 111 received a transplant. Zoster developed in 7 of 53 vaccinated patients (13 percent) and in 19 of 58 unvaccinated patients (33 percent) (P=0.01). After two patients in whom zoster developed before transplantation were excluded, the respective rates were 13 percent and 30 percent (P=0.02). In vitro CD4 T-cell proliferation in response to varicella-zoster virus (expressed as the mean stimulation index) was greater in patients who received the vaccine than in those who did not at 90 days, after three doses (P=0.04); at 120 days, after all four doses (P<0.001); at 6 months (P=0.004); and at 12 months (P=0.02). The risk of zoster was reduced for each unit increase in the stimulation index above 1.6; a stimulation index above 5.0 correlated with greater than 93 percent protection. Induration, erythema, or local pain at the injection site was observed in association with 10 percent of the doses.
CONCLUSIONS: Inactivated varicella vaccine given before hematopoietic-cell transplantation and during the first 90 days thereafter reduces the risk of zoster. The protection correlates with reconstitution of CD4 T-cell immunity against varicella-zoster virus.
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Tzank-This cytologic preparation utilizes a swab of a blister base smearing it on a glass slide. The characteristic viral inclusion bodies of herpes will be present in an active lesion.
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