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By Jill Murphy, Associate Editor
Varicella-zoster virus (VZV) is a herpesvirus that causes 2 related but separate clinical illnesses.
Varicella-zoster virus (VZV) is a herpesvirus that causes 2 related but separate clinical illnesses. Primary exposure to VZV causes varicella infection (chickenpox). Once chickenpox resolves, VZV resides latent in neurons within the regional ganglia and may re-emerge at any time to cause herpes zoster infection (shingles).1
The incidence of chickenpox in the United States has decreased significantly since universal varicella vaccination began in 1995.2However, herpes zoster infection remains very common, with almost 1 of 3 individuals in the United States developing it in their lifetime.1Primary care providers should be able to diagnose both conditions and begin treatment promptly for uncomplicated infections. Moreover, clinicians should be able to recognize patients with signs and symptoms of severe VZV infection, as well as those at high risk for developing complications, and refer them to appropriate specialists.
Presentation and Pathogenesis
Following exposure, chickenpox has an incubation period ranging from 10 to 21 days.1Clinical illness starts with a short prodromal period of fever and malaise followed by the hallmark pruritic vesicular rash.3The lesions associated with the rash form crusts in about 6 days and then fall off after 1 to 2 weeks. Once the lesions have crusted, the individual is no longer considered contagious.4Usually, chickenpox confers lifelong immunity, although rare cases of reinfection have been reported.5
Humans are the only VZV reservoir, so chickenpox can only be transmitted from patient to patient.1It is highly contagious and may be transmitted via respiratory droplets and vesicular fluids; less commonly, the virus may become airborne.1,6Transmission of chickenpox is also possible from infected mother to her fetus in utero and to her newborn during birth.7 If an immunized individual develops breakthrough varicella infection, transmission to others is possible but uncommon.1
In healthy children, chickenpox is generally a mild, self-limiting illness that requires only symptomatic management. Typical symptoms include fever, malaise, and pruritic vesicular rash that starts on the head and face and spreads to the rest of the body.8However, in certain populations, varicella may cause significant morbidity and mortality. Groups at increased risk for complications include unvaccinated adolescents and adults, neonates, immunocompromised individuals, and pregnant women. Common serious complications from chickenpox include encephalitis, hepatitis, varicella pneumonia, and infection.9Additionally, maternal VZV infection during the first or second trimesters of pregnancy may lead to the fetus developing congenital varicella syndrome, which can cause severe birth defects.10
Mild varicella-like syndrome (MVLS), also called breakthrough varicella, is a milder version of varicella infection that develops occasionally when vaccinated patients are exposed to wild-type
VZV. Breakthrough infection may be caused by a failure to develop an effective immune response to the vaccine or by immunity diminishing over time.11Although the symptoms of MVLS are mild, the infected individual is still contagious to susceptible individuals.12
Complications from chickenpox include secondary bacterial skin infection, meningitis, encephalitis, cerebellar ataxia, pneumonia, glomerulonephritis, myocarditis, ocular disease, adrenal insufficiency, sepsis, and death.13Additionally, grave complications may develop if chickenpox is contracted during pregnancy, the most common of which is the aggressive varicella pneumonia, characterized by diffuse infiltration that often compromises both lungs and rapidly causes respiratory failure.14The fetus is also at risk of developing congenital varicella syndrome, which has a 30% mortality rate and can result in multiple birth defects. Common abnormalities caused by congenital varicella syndrome include mental retardation, microcephaly, hydrocephalus, seizures, limb hypoplasia or paresis, cataracts, optic nerve atrophy, micropthalmos, nystagmus, stenotic bowel, scarring, and low birth weight. Neonatal chickenpox may also cause severe disease and has a high mortality rate.15
Complicated Chickenpox Treatment
Groups considered to be at high risk for complications include immunocompromised patients, unvaccinated adults, pregnant women, and adolescents older than 12 years. For immunocompetent patients, oral valacyclovir or acyclovir are the treatments of choice. Immunocompromised patients should receive intravenous acyclovir. For greatest benefit, treatment should be started within 24 hours of development of rash. Regardless of age, treatment
should be initiated for any patient that presents with varicella-related complications such as encephalitis, hepatitis, or varicella pneumonia.16
Uncomplicated Chickenpox Treatment
The treatment for chickenpox varies widely based on the patient’s age and overall state of health. In general, symptomatic management is all that is required for immunocompetent children up to 12 years old. Recommended treatment for this group includes acetaminophen, antihistamines, and trimming fingernails to help discourage secondary skin infections.17Due to concerns of Reye syndrome, salicylates should be avoided with children and adolescents.18
Following exposure to VZV, pregnant women who have never received varicella vaccination and show no serologic proof of past VZV infection have a 96-hour window to receive post-exposure prophylaxis.19In the United States, the only FDA-approved product for passive immunity is VariZIG, which is used to prevent or attenuate varicella infection.20For pregnant women who develop varicella infection despite prophylaxis, there is no evidence that it prevents congenital varicella syndrome.19 VariZIG may also be used prophylactically in newborns who have been exposed to VZV to prevent or attenuate varicella infection.20
Chickenpox in Primary Care
When chickenpox is suspected, primary care providers should obtain vaccine history. If the patient has received 1 or 2 doses of vaccine, infection will likely be mild.11For patients older than 12 years, oral antivirals should be initiated within 24 hours of rash onset.17Patients should be advised that they are highly contagious until the lesions have crusted over, which usually takes 7 to 10 days.16,18They should be counseled to avoid unvaccinated individuals, immunocompromised individuals, newborns, and pregnant women since these groups have the greatest risk of complications.9 If an immunocompromised patient develops chickenpox, the individual should be closely monitored for prolonged fevers, extensive rashes, confusion, or other signs of distress.6 If chickenpox is suspected in a newborn, prompt referral for monitoring and treatment is warranted.4In general, once an individual has had chicken pox, immunity is conferred for life.7However, after varicella infection, the individual may develop shingles at any age.21
Presentation and Pathogenesis
Herpes zoster infection (shingles) is the reactivated illness caused by latent VZV. It can occur in individuals at any age, but is more likely to affect those 50 years and older.21It manifests as a pruritic vesicular rash that is typically unilateral and confined to a single dermatome. The rash associated with herpes zoster infection may be accompanied by acute neuritis, which may cause significant pain. The neuralgia can start days before the rash appears and can last for weeks after the rash resolves.22
Although there are multiple risk factors that contribute to VZV reactivation, the single greatest risk factor for developing shingles is being 60 years or older.23Other major risk factors for reactivation of VZV include physical trauma, female gender, depression, and various conditions that lead to host immunocompromise such as chronic lung disease, autoimmune disease, cancer,kidney disease, HIV infection, solid organ transplant, bone marrow transplant, inflammatory bowel disease, rheumatoid arthritis, and immunosuppressive medications.24-28
The exact mechanism and pathway of VZV from chickenpox to latency and then to reactivated herpes zoster infection is uncertain.29However, it is clear that decreased cell-mediated immunity contributes to reactivation. Therefore, primary risk factors for developing shingles are conditions that decrease cell-mediated immunity such as increased age and immunocompromise arising secondary to illness or medications.23
Herpes zoster infection is far less contagious than chickenpox. An individual with shingles cannot transmit shingles to another individual. However, they may transmit chicken pox to susceptible individuals.30Herpes zoster infection is transmitted via vesicular fluids and, less commonly, the virus may become airborne.30-31
Complications in Immunocompetent Patients
For immunocompetent patients, the most common complication of herpes zoster infection is postherpetic neuralgia. It is characterized by pain that recurs in the area of the initial outbreak for months to years after the infection has resolved. Patients older than 60 years account for half of the cases of postherpetic neuralgia.32In addition to nerve-related pain, there are several other serious neurologic complications which may develop from herpes zoster infection including aseptic meningitis, myelitis, peripheral motor neuropathy, encephalitis, Guillain-Barré syndrome, and stroke syndromes.33
Shingles infection in the eyes may cause herpes zoster opthalmicus or acute retinal necrosis, which are grave ophthalmic disorders that can result in permanent vision loss.34,35Patients with shingles lesions on the nose (Hutchinson’s Sign) are considered high risk for developing herpes zoster opthalmicus.36Clinicians should consider all patients with eye or nose involvement emergent because early detection and treatment are paramount for preserving vision.34Finally, there is Ramsay Hunt Syndrome, an optic complication which may involve multiple cranial nerves and result in facial paralysis, ear pain, vertigo, tinnitus, and taste disturbances.30Herpes zoster infection during pregnancy is not associated with congenital varicella syndrome. However, the mother may transmit chickenpox to her newborn during birth, and very rarely, the mother may transfer the virus to the fetus in utero.37
Complications in Immunocompromised Patients
In general, the immunocompromised, such as transplant recipients and HIV-positive patients, are at greatest risk of developing severe complications from herpes zoster infection.38In those patients, herpes zoster infection may even become a life-threatening syndrome with multi-organ involvement. Disseminated herpes zoster infection often involves multiple dermatomes and presents bilaterally.39It leads to rapidly progressing pneumonia, hepatitis, and encephalitis that often progresses to death even with treatment.40
Uncomplicated Shingles Treatment
Oral antiviral therapy is recommended for any patient without contraindications. Treatment should be initiated up to 72 hours after rash appears.30Antivirals are prescribed to lessen the severity and duration of illness, prevent post-herpetic neuralgia and reduce the risk of transmission.21Medications suitable for treatment of shingles are acyclovir, valacyclovir, and famciclovir. However, the second-generation antivirals, valacyclovir and famciclovir, are
preferred because of greater bioavailability and less frequent dosing.41Depending on the severity of neuritis and pain, patients may be treated with a range of pain medications. For mild pain, OTC acetaminophen or nonsteroidal anti-inflammatory drugs may suffice. Moderate to severe pain generally requires prescription pain medications such as tramadol, codeine, oxycodone, or morphine.30Adjunct medications such as glucocorticoids and tricyclic antidepressants are not recommended for initial treatment of shingles related pain since there is not enough evidence to support their use.42Pregnant women with herpes zoster infection are not considered high risk and are treated similar to other immunocompetent patients.30
Complicated Shingles Treatment
Postherpetic neuralgia is the most common complication of herpes zoster infection.43Current treatments for moderate to severe recurrent pain include amitriptyline, nortriptyline, desipramine, pregabalin, gabapentin, and valproic acid.44Topical capsaicin may also be used to augment any of these medications or as an alternative to systemic therapy.45For intractable pain, opioids may be prescribed. Other methods to control postherpetic neuralgia are intrathecal glucocorticoids, botulinim toxin injections, cryotherapy, and even surgery..46,47Severe complications from herpes zoster infection, such as those that involve cranial nerves and affect the eyes and ears, require early diagnosis and treatment with intravenous antivirals and ophthalmic steroids.30,32-34Additionally, immunocompromised individuals are at much greater risk of morbidity and mortality, and generally require hospitalized care where they may receive intravenous antiviral therapy as well as close monitoring for life-threatening complications.40
Shingles in Primary Care
When shingles is suspected, the primary care provider should obtain vaccine history. Previously vaccinated individuals tend to have milder infections and fewer complications than patients who have not been vaccinated.46Treatment with oral antivirals should be initiated within 72 hours of rash onset. If pain is present, pain-control measures should also be initiated.30Immunocompromised patients, as well as those with face or eye involvement, should be considered emergent and promptly referred to appropriate specialist.34,40Patients with shingles should be counseled that they are contagious until the rash has crusted over and that they can spread chickenpox to susceptible individuals.31Appropriate patients older than 50 years should be advised to receive the shingles vaccine to prevent or attenuate herpes zoster infection. Patients should also be counseled that past history of herpes zoster infection is not a contraindication to receiving the shingles vaccine. Providers should stay abreast of new vaccines since HZ/su may soon become available.43
1. CDC. Varicella. CDC website. cdc.gov/vaccines/pubs/pinkbook/downloads/varicella.pdf. Accessed May 3, 2016.
2. CDC. Evolution of varicella surveillance — selected states, 2000-2010. MMWR Morb Mortal Wkly Rep. 2012; 61(32):609-612. CDC website. cdc.gov/mmwr/preview/mmwrhtml/mm6132a2.htm. Accessed May 3, 2016.
3. Straus SE, Ostrove JM, Inchauspé G, et al. NIH conference. Varicella-zoster virus infections. Biology, natural history, treatment, and prevention. Ann Intern Med. 1988;108(2):221-237.
4. Heininger U, Seward JF. Varicella. Lancet. 2006;368(9544):1365-1376.
5. Martin KA, Junker AK, Thomas EE, Van Allen MI, Friedman JM. Occurrence of chickenpox during pregnancy in women seropositive for varicella-zoster virus. J Infect Dis. 1994;170(4):991-995.
6. Leclair JM, Zaia JA, Levin MJ, Congdon RG, Goldmann DA. Airborne transmission of chickenpox in a hospital. N Engl J Med. 1980;302(8):450-453.
7. Enright AM, Prober CG. Herpesviridae infections in newborns: varicella zoster virus, herpes simplex virus, and cytomegalovirus. Pediatr Clin North Am. 2004;51(4):889-908.
8. CDC. Chickenpox (varicella) signs & symptoms. CDC website. cdc.gov/chickenpox/about/symptoms.html. Accessed on May 3, 2016.
9. CDC. Chickenpox (varicella) complications. CDC website. cdc.gov/chickenpox/about/complications.html. Accessed on May 3, 2016.
10. CDC. Chickenpox (varicella) people at high risk for complications. CDC website. cdc.gov/chickenpox/hcp/high-risk.html. Accessed on May 3, 2016.
11. White CJ, Kuter BJ, Ngai A, et al. Modified cases of chickenpox after varicella vaccination: correlation of protection with antibody response. Pediatr Infect Dis J. 1992;11(1):19-23.
12. Gould PL, Leung J, Scott C, et al. An outbreak of varicella in elementary school children with two-dose varicella vaccine recipients--Arkansas, 2006. Pediatr Infect Dis J. 2009;28(8):678-681. doi: 10.1097/INF.0b013e31819c1041.
13. Fleisher G, Henry W, McSorley M, Arbeter A, Plotkin S. Life-threatening complications of varicella. Am J Dis Child. 1981;135(10):896-899.
14. Smego RA Jr, Asperilla MO. Use of acyclovir for varicella pneumonia during pregnancy. Obstet Gynecol. 1991;78(6):1112-1116.
15. Laforet EG, Lynch CL Jr. Multiple congenital defects following maternal varicella; report of a case. N Engl J Med. 1947;236(15):534-537. doi: 10.1056/NEJM194704102361504.
16. Ogilvie MM. Antiviral prophylaxis and treatment in chickenpox. A review prepared for the UK Advisory Group on Chickenpox on behalf of the British Society for the Study of Infection. J Infect. 1998;36(Suppl 1):31-38.
17. CDC. Varicella prevention & treatment. CDC website. cdc.gov/chickenpox/about/prevention-treatment.html. Accessed on May 6, 2016.
18. Belay ED, Bresee JS, Holman RC, Khan AS, Shahriari A, Schonberger LB. Reye's syndrome in the United States from 1981 through 1997. N Engl J Med. 1999;340(18):1377-1382. doi: 10.1056/NEJM199905063401801.
19. Cohen A, Moschopoulos P, Stiehm RE, Koren G. Congenital varicella syndrome: the evidence for secondary prevention with varicella-zoster immune globulin. CMAJ. 2011;183(2):204-208. doi: 10.1503/cmaj.100615.
20. CDC. FDA approval of an extended period for administering VariZIG for postexposure prophylaxis of varicella. MMWR Morb Mortal Wkly Rep. 2012;61(12):212.
21. Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med. 2002;347(5):340-346.
22. Oxman MN. Immunization to reduce the frequency and severity of herpes zoster and its complications. Neurology. 1995;45(Suppl 12):S41-S46. (Accessed on May 4, 2016).
23. Burke BL, Steele RW, Beard OW, Wood JS, Cain TD, Marmer DJ. Immune responses to varicella-zoster in the aged. Arch Intern Med. 1982;142(2):291-293. espace.library.uq.edu.au/view/UQ:242275/UQ242275_fulltext.pdf. Accessed on May 8, 2016.
24. Opstelten W, Van Essen GA, Schellevis F, Verheij TH, Moons KG. Gender as an independent risk factor for herpes zoster: a population-based prospective study. Ann Epidemiol. 2006;16(9):692-695.
25. Manuel O, Kumar D, Singer LG, Cobos I, Humar A. Incidence and clinical characteristics of herpes zoster after lung transplantation. J Heart Lung Transplant. 2008;27(1):11-16. doi: 10.1016/j.healun.2007.09.028.
26. Gupta G, Lautenbach E, Lewis JD. Incidence and risk factors for herpes zoster among patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2006;4(12):14831490.
27. Winthrop KL, Baddley JW, Chen L, et al. Association between the initiation of anti-tumor necrosis factor therapy and the risk of herpes zoster. JAMA. 2013;309(9):887-895. doi: 10.1001/jama.2013.1099.
28. Grabar S, Tattevin P, Selinger-Leneman H, et al. Incidence of herpes zoster in HIV-infected adults in the combined antiretroviral therapy era: results from the FHDH-ANRS CO4 cohort. Clin Infect Dis. 2015;60(8):1269-1277. doi: 10.1093/cid/ciu1161.
29. Ku CC, Padilla JA, Grose C, Butcher EC, Arvin AM. Tropism of varicella-zoster virus for human tonsillar CD4(+) T lymphocytes that express activation, memory, and skin homing markers. J Virol. 2002;76(22):11425-11433.
30. Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007;44(Suppl 1):S1-S26.
31. Josephson A, Gombert ME. Airborne transmission of nosocomial varicella from localized zoster. J Infect Dis. 1988;158(1):238-241.
32. Bowsher D. Postherpetic neuralgia and its treatment: a retrospective survey of 191 patients. J Pain Symptom Manage. 1996;12(5):290-299.
33. Galil K, Choo PW, Donahue JG, Platt R. The sequelae of herpes zoster. Arch Intern Med. 1997;157(11):1209-1213.
34. Severson EA, Baratz KH, Hodge DO, Burke JP. Herpes zoster ophthalmicus in olmsted county, Minnesota: have systemic antivirals made a difference? Arch Ophthalmol. 2003;121(3):386-390.
35. Lau CH, Missotten T, Salzmann J, Lightman SL. Acute retinal necrosis features, management, and outcomes. Ophthalmology. 2007;114(4):756-762.
36. Tomkinson A, Roblin DG, Brown MJ. Hutchinson's sign and its importance in rhinology. Rhinology. 1995;33(3):180-182.
37. Enders G, Miller E, Cradock-Watson J, Bolley I, Ridehalgh M. Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. Lancet. 1994;343(8912):1548-1551. 38. Cvjetkovic D1, Jovanovic J, Hrnjakovic-Cvjetkovic I, Brkic S, Bogdanovic M . [Reactivation of herpes zoster infection by varicella-zoster virus]. Med Pregl. 1999;52(3-5):125-128.
39. Miller GG, Dummer JS. Herpes simplex and varicella zoster viruses: forgotten but not gone. Am J Transplant. 2007;7(4):741-747.
40. Fleisher G, Henry W, McSorley M, Arbeter A, Plotkin S. Life-threatening complications of varicella. Am J Dis Child. 1981;135(10):896-899.
41. Gnann JW Jr. New antivirals with activity against varicella-zoster virus. Ann Neurol. 1994;35(Suppl):S69-S72.
42. Bowsher D. The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized, double-blind, placebo-controlled trial. J Pain Symptom Manage. 1997;13(6):327-331.
43. Bouhassira D, Chassany O, Gaillat J, et al. Patient perspective on herpes zoster and its complications: an observational prospective study in patients aged over 50 years in general practice. Pain. 2012;153(2):342-349. doi: 10.1016/j.pain.2011.10.026.
44. Hempenstall K, Nurmikko TJ, Johnson RW, A’Hern RP, Rice AS. Analgesic therapy in postherpetic neuralgia: a quantitative systematic review. PLoS Med. 2005;2(7):e164.
45. Derry S, Sven-Rice A, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2013;28(2):CD007393. doi: 10.1002/14651858.CD007393.pub3.
46. Kotani N, Kushikata T, Hashimoto H, et al. Intrathecal methylprednisolone for intractable postherpetic neuralgia. N Engl J Med. 2000;343(21):1514-1509.
47. Apalla Z, Sotiriou E, Lallas A, Lazaridou E, Ioannides D. Botulinum toxin A in postherpetic neuralgia: a parallel, randomized, double-blind, single-dose, placebo-controlled trial. Clin J Pain. 2013;29(10):857-864.