CE/CME

Herpes Zoster Infection

Clinician Reviews. 2013 August;23(8):42-49

References

1. CDC. Shingles (herpes zoster). www.cdc.gov/shingles/hcp/clinical-overview.html. Accessed June 26, 2013.

2. Tseng HF, Smith N, Harpaz R, et al. Herpes zoster vaccine in older adults and the risk of subsequent herpes zoster disease. JAMA. 2011;305:160-166.

3. Weinberg JM. Herpes zoster: epidemiology, natural history, and common complications. J Am Acad Dermatol. 2007;57:S130-S135.

4. Kennedy PG, Cohrs RJ. Varicella-zoster virus human ganglionic latency: a current summary. J Neurovirol. 2010;16:411-418.

5. Wilson DD. Herpes zoster: prevention, diagnosis and treatment. Nurse Pract. 2007;32:19-24.

6. Chen TM, George S, Woodruff CA, Hsu S. Clinical manifestations of varicella-zoster virus infection. Dermatol Clin. 2002;20:267-282.

7. Gilden D, Mahalingam R, Nagel MA, et al. Review: the neurobiology of varicella zoster virus infection. Neuropathol Appl Neurobiol. 2011;37:441-463.

8. CDC. Chickenpox (varicella): monitoring the impact of varicella vaccination. www.cdc.gov/chickenpox/hcp/monitoring-varicella.html. Accessed June 26, 2013.

9. Civen R, Chaves SS, Jumaan A, et all. The incidence and clinical characteristics of herpes zoster among children and adolescents after implementation of varicella vaccination. Pediatr Infect Dis J. 2009;28:954-959.

10. Hardy I, Gershon AA, Steinberg SP, LaRussa P; Varicella Vaccine Collaborative Study Group. The incidence of zoster after immunization with live attenuated varicella vaccine: a study in children with leukemia. N Engl J Med. 1991;325:1545-1550.

11. Poletti P, Melegaro A, Ajelli M, et al. Perspectives on the impact of varicella immunization on herpes zoster: a model-based evaluation from three European countries. PLoS One. 2013;8:e60732.

12. Goldman GS, King PG. Review of the United States universal varicella vaccination program: herpes zoster incidence rates, cost-effectiveness, and vaccine efficacy based primarily on the Antelope Valley Varicella Active Surveillance Project data. Vaccine. 2013;31:1680-1694.

13. Leung J, Harpaz R, Molinari NA, et al. Herpes zoster incidence among insured persons in the United States, 1993-2006: evaluation of impact of varicella vaccination. Clin Infect Dis. 2011;52:332-340.

14. Donahue JG, Kieke BA, Gargiullo PM, et al. Herpes zoster and exposure to the varicella zoster virus in an era of varicella vaccination. Am J Public Health. 2010;100:1116-1122.

15. Schmader KE, Oxman MN. Varicella and herpes zoster. In: Goldsmith LA, Katz SI, Gilchrest BA, et al, eds. Fitzpatrick’s Dermatology in General Medicine. 8th ed. New York, NY: McGraw-Hill; 2012.

16. Wilson JF. Herpes zoster. Ann Intern Med. 2011;154:ITC31-ITC15.

17. Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008;57(RR-5):1-30.

18. Gnann JW Jr, Whitley RJ. Clinical practice: herpes zoster. N Engl J Med. 2002; 347:340-346.

19. Sauerbrei A, Eichhorn U, Schacke M, Wutzler P. Laboratory diagnosis of herpes zoster. J Clin Virol. 1999;14:31-36.

20. Whitley RJ. A 70-year-old woman with shingles. JAMA. 2009;302:73-80.

21. Galluzzi KE. Managing herpes zoster and postherpetic neuralgia. J Am Osteopath Assoc. 2009;109(6 suppl 2):S7-S12.

22. Fashner J, Bell AL. Herpes zoster and postherpetic neuralgia: prevention and management. Am Fam Physician. 2011;83:1432-1437.

23. Tyring S, Barbarash RA, Nahlik JE, et al; Collaborative Famciclovir Herpes Zoster Study Group. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995;123:89-96.

24. Pavan-Langston D. Herpes zoster: antivirals and pain management. Ophthalmology. 2008;115(2 suppl):S13-S20.

25. Opstelten W, Eekhof J, Neven AK, Verheij T. Treatment of herpes zoster. Can Fam Physician. 2008;54:373-377.

26. Tyring SK, Beutner KR, Tucker BA, et al. Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Arch Fam Med. 2000;9: 863-869.

27. Shafran SD, Tyring SK, Ashton R, et al. Once, twice, or three times daily famciclovir compared with aciclovir for the oral treatment of herpes zoster in immunocompetent adults: a randomized, multicenter, double-blind clinical trial. J Clin Virol. 2004;29:248-253.

28. Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007;44(suppl 1):S1-S26.

29. Benbernou A, Drolet M, Levin MJ, et al. Association between prodromal pain and the severity of acute herpes zoster and utilization of health care resources. Eur J Pain. 2011;15:1100-1106.

30. Gan EY, Tian EA, Tey HL. Management of herpes zoster and post-herpetic neuralgia. Am J Clin Dermatol. 2013;14:77-85.

31. Whitley RJ, Weiss H, Gnann JW Jr, et al; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Acyclovir with and without prednisone for the treatment of herpes zoster: a randomized, placebo-controlled trial. Ann Intern Med. 1996;125:376-383.

32. Wood MJ, Johnson RW, McKendrick MW, et al. A randomized trial of acyclovir for 7 days or 21 days with and without prednisolone for treatment of acute herpes zoster. N Engl J Med. 1994;330:896-900.

33. Wareham DW, Breuer J. Herpes zoster. BMJ. 2007;334:1211–1215.

34. Chen N, Yang M, He L, et al. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2010;(12):CD005582.

35. Shaikh S, Ta CN. Evaluation and management of herpes zoster ophthalmicus. Am Fam Physician. 2002;66:1723-1730.

36. Sweeney CJ, Gilden DH. Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry. 2001;71:149-154.

37. Tilki HE, Mutluer N, Selçuki D, Stålberg E. Zoster paresis. Electromyogr Clin Neurophysiol. 2003;43:231-234.

38. Oxman MN, Levin MJ, Johnson GR, et al; Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352:2271-2284.

39. Opstelten W, Zuithoff NP, van Essen GA, et al. Predicting postherpetic neuralgia in elderly primary care patients with herpes zoster: prospective prognostic study. Pain. 2007;132(suppl 1):S52-S59.

40. Mahamud A, Marin M, Nickell SP, et al. Herpes zoster-related deaths in the United States: validity of death certificates and mortality rates, 1979-2007. Clin Infect Dis. 2012;55:960-6.

41. Marin M, Güris D, Chaves SS, et al. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56(RR-4):1-40.

42. Zostavax® (zoster vaccine live). Highlights of prescribing information (2013). www.merck.com/product/usa/pi_circulars/z/zostavax/zostavax_pi2.pdf. Accessed June 26, 2013.

43. CDC. Update on herpes zoster vaccine: licensure for persons aged 50 through 59 years. MMWR Morb Mortal Wkly Rep. 2011;60:1528.

44. Simberkoff MS, Arbeit RD, Johnson GR, et al; Shingles Prevention Study Group. Safety of herpes zoster vaccine in the shingles prevention study: a randomized trial. Ann Intern Med. 2010;152:545-554.

45. Levin MJ, Oxman MN, Zhang JH, et al; Veterans Affairs Cooperative Studies Program Shingles Prevention Study Investigators. Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine. J Infect Dis. 2008;197:825-835.

46. Schmader KE, Oxman MN, Levin MJ, et al. Persistence of the efficacy of zoster vaccine in the Shingles Prevention Study and the Short-Term Persistence Substudy. Clin Infect Dis. 2012;55:1320-1328.

47. Singh A, Englund K. Q: Who should receive the shingles vaccine? Cleveland Clin J Med. 2009;76:45-48.

48. Mills R, Tyring SK, Levin MJ, et al. Safety, tolerability, and immunogenicity of zoster vaccine in subjects with a history of herpes zoster. Vaccine. 2010;28:4204-4209.

CLINICAL PRESENTATION
Identifying HZ infection is primarily a clinical diagnosis and not particularly difficult. Approximately 20% of patients will present with prodromal symptoms of fatigue, headache, malaise, and fever. Paresthesias in the involved dermatome often precede the rash by several days and may be manifested as itching, tingling, burning, or severe pain. Physical examination at this stage may reveal tenderness and hyperesthesia of the skin in the involved dermatome.^3,5,15,16

Pain and abnormal skin sensations are the most common symptoms of HZ. They often precede and usually accompany the rash. The prodromal pain of HZ can mimic a variety of other conditions, including pleurisy, myocardial infarction, peptic ulcer, appendicitis, or biliary or renal colic, prompting some clinicians to undertake an extensive workup and treatment plan.^15,17

Consistent with other herpes infections, the HZ rash initially starts in the form of erythematous papules, which quickly evolve into grouped vesicles or bullae. Within three to four days, these vesicular lesions can become more pustular. In contrast to chickenpox, the rash of shingles is manifested in a dermatomal distribution. The two most commonly affected dermatomes are the first (ophthalmic) division of the trigeminal nerve and the spinal sensory ganglia from T1 to L2.^3,5,15,16 The infection is generally limited to one dermatome in previously healthy hosts but can occasionally affect two or three neighboring dermatomes. Some patients have a few scattered vesicles located some distance away from the involved dermatome.¹⁵

In immunocompetent hosts, the lesions crust over within seven to 10 days and are no longer considered infectious. The development of new lesions more than a week after presentation should raise concerns regarding possible underlying immunodeficiency.^3,5,15,16

LABORATORY DIAGNOSIS
While HZ is generally a clinical diagnosis based on the history and physical exam findings, laboratory testing may be appropriate to confirm the diagnosis when the presentation is atypical, the host is immunocompromised, lesions recur, or serious complications are suspected.^17,18

Several laboratory tests are currently available (see Table 1^17,19). Detection of VZV DNA following amplification of appropriate specimens (most reliably, clear fluid from recently erupted vesicles) by polymerase chain reaction (PCR) is generally recommended if testing is required, because of its high sensitivity and specificity and quick turnaround. However, this test is not available at every laboratory.^17-19

When PCR is not available, a suitable alternative is direct fluorescent antibody (DFA) staining of cellular material from fresh vesicles or prevesicular lesions.¹ This test uses a modified Tzanck technique to view fluorescein-conjugated monoclonal antibodies. DFA staining can differentiate between herpes simplex and herpes zoster.^16,17,20

The original Tzanck smear is inexpensive and may reveal multinucleated giant cells and epithelial cells containing acidophilic intranuclear inclusion bodies.¹⁷ However, this test is not often used to confirm a diagnosis of HZ; rather, it is most helpful for distinguishing herpesvirus infections from vesicular lesions of other etiologies (eg, coxsackievirus, echovirus).^15,17

Serologic tests measuring immunoglobulin M and A titers (IgM, IgA) may be helpful in cases of zoster without rash (zoster sine herpete), but their sensitivity and specificity are low.¹⁵ Positive results may be indicative of primary infection, reinfection, or reactivation.¹

On the next page: Treatment >>