Herpes Zoster (Shingles)

Robert J. Hyde, MD, MA Reviewed 07/2016
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Subject: Herpes Zoster (Shingles)

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BASICS

DESCRIPTION

  • Results from reactivation of latent varicella-zoster virus (human herpesvirus type 3) infection

  • Postherpetic neuralgia (PHN) is defined as pain persisting at least 1 month after rash has healed. The term zoster-associated pain is more clinically useful.

  • Usually presents as a painful unilateral vesicular eruption with a dermatomal distribution

  • System(s) affected: nervous; integumentary; exocrine

  • Synonym(s): shingles

EPIDEMIOLOGY

Predominant sex: male = female 

Incidence

  • Incidence increases with age. ⅔; of cases occur in adults age ≥50 years. Incidence is increasing overall as the U.S. population ages.

  • Herpes zoster: 4/1,000 person-years (1)

  • PHN: 18% in adult patients with herpes zoster; 33% in patients ≥79 years of age

Prevalence

Nearly 1 million new cases of herpes zoster annually 
Pregnancy Considerations

May occur during pregnancy

 
Geriatric Considerations

  • Increased incidence of zoster outbreaks

  • Increased incidence of PHN

 
Pediatric Considerations

  • Occurs less frequently in children

  • Has been reported in newborns infected in utero

 

ETIOLOGY AND PATHOPHYSIOLOGY

Reactivation of varicella-zoster virus from dorsal root/cranial nerve ganglia. Upon reactivation, the virus replicates within neuronal cell bodies, and virions are carried along axons to dermatomal skin zones, causing local inflammation and vesicle formation. 

RISK FACTORS

  • Increasing age

  • Immunosuppression (malignancy or chemotherapy)

  • HIV infection

  • Use of immunosuppressant drugs (e.g., following organ transplant surgery)

  • Spinal surgery

GENERAL PREVENTION

  • Herpes zoster vaccination (Zostavax) is recommended by Advisory Committee on Immunization Practices (ACIP) for patients ≥60 years (FDA-approved for patients >50 years) (2,3 and 4):

    • Vaccine reduces cases of zoster and the incidence of PHN (5,6).

  • Patients with active zoster may transmit disease-causing varicella virus (chickenpox) to susceptible persons.

COMMONLY ASSOCIATED CONDITIONS

Immunocompromised individuals, HIV infection, posttransplantation, immunosuppressive drugs, and malignancy 

DIAGNOSIS

HISTORY

  • Prodromal phase (sensations over involved dermatome prior to rash)

    • Tingling, paresthesias

    • Itching

    • Boring “knifelike” pain

  • Acute phase

    • Constitutional symptoms (e.g., fatigue, malaise, headache, low-grade fever) are variable.

    • Dermatomal rash

PHYSICAL EXAM

  • Acute phase

    • Rash: initially erythematous and maculopapular; evolves rapidly to grouped vesicles

    • Vesicles become pustular and/or hemorrhagic in 3 to 4 days.

    • Weakness (1% have weakness in distribution of rash)

    • Resolution of rash, with crusts separating by 14 to 21 days

  • Possible sine herpete (zoster without rash) and other chronic disorders associated with varicella-zoster virus without the typical rash

    • Herpes zoster ophthalmicus (HZO). Vesicles on tip of the nose (Hutchinson sign) indicate involvement of the external branch of cranial nerve V; associated with increased incidence of ocular zoster.

  • Chronic phase

    • PHN (15% overall; increases with age)

    • A small percentage (1–5%) may affect the motor nerves, causing weakness (zoster motorius); facial nerve (e.g., Ramsay Hunt syndrome); spinal motor radiculopathies.

DIFFERENTIAL DIAGNOSIS

  • Rash

    • Herpes simplex virus

    • Coxsackievirus

    • Contact dermatitis

    • Superficial pyoderma

  • Pain

    • Cholecystitis

    • Appendicitis

    • Nephrolithiasis

    • Pleuritis

    • Myocardial infarction

    • Diabetic neuropathy

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

Rarely necessary because clinical appearance is sufficiently distinctive 
Follow-Up Tests & Special Considerations
  • Viral culture

  • Tzanck smear (does not distinguish from herpes simplex, and false-negative results occur)

  • Polymerase chain reaction

  • Immunofluorescent antigen staining

  • Varicella-zoster–specific IgM

Test Interpretation

  • Multinucleated giant cells with intralesional inclusion

  • Lymphatic infiltration of sensory ganglia with focal hemorrhage and nerve cell destruction

TREATMENT

GENERAL MEASURES

  • Treatment is directed to control symptoms and prevent complications.

  • Antiviral therapy decreases viral replication, lessens inflammation and nerve damage, and reduces the severity and duration of long-term pain.

  • Prompt analgesic control may shorten the duration of zoster-associated pain.

  • Lotions, such as calamine and colloidal oatmeal, may help reduce itching and burning sensation.

MEDICATION

First Line

  • Acute treatment

    • Antiviral agents initiated within 72 hours of skin lesions help relieve symptoms, speed resolution, and prevent or mitigate PHN (7)[A].

    • Valacyclovir: 1,000 mg PO TID for 7 days

    • Famciclovir: 500 mg PO TID for 7 days

    • Acyclovir: 800 mg q4h (5 doses daily) for 7 days

  • Analgesics (acetaminophen, NSAIDs)

  • Corticosteroids given acutely during zoster infection do not prevent PHN (8).

    • Tricyclic antidepressants (TCAs; amitriptyline 25 mg at bedtime and other low-dose TCAs) relieve pain acutely and may reduce pain duration; dose may be titrated up to 75 to 150 mg/day as tolerated.

    • Lidocaine patch 5% (Lidoderm) applied over painful areas (limit 3 patches simultaneously or trim a single patch) for up to 12 hours may be effective.

    • Gabapentin: 100 to 600 mg TID for pain and other quality-of-life indicators; limited by adverse effects

    • Capsaicin cream and other analgesics may be useful adjuncts. Use opioids sparingly.

    • Pregabalin: 50 to 100 mg TID reduces pain, but usefulness is limited by side effects.

  • Prevention of PHN and zoster-associated pain: No treatment has been shown to prevent PHN completely, but treatment may shorten duration and/or reduce severity of symptoms (9)[A].

    • Antiviral therapy with valacyclovir, famciclovir, or acyclovir given during acute skin eruption may decrease the duration of pain.

    • Low-dose amitriptyline (25 mg at bedtime) started within 72 hours of rash onset and continued for 90 days may reduce PHN incidence/duration.

    • Insufficient evidence to suggest that corticosteroids reduce incidence, severity, or duration of PHN (8)

  • Precautions

Second Line

Numerous therapies have been advocated, but supporting evidence to routinely recommend is lacking. 

COMPLEMENTARY & ALTERNATIVE MEDICINE

Studies on cupping therapy (traditional Chinese medicine) show potential benefit, but evidence is conflicting (10)[A]. 

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization

Outpatient treatment, unless disseminated or occurring as complication of serious underlying disease requiring hospitalization 

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Referral to ophthalmology if concern for involvement of ophthalmic branch of the trigeminal nerve 

Patient Monitoring

Follow duration of symptoms—particularly PHN. Consider hospitalization if symptoms are severe; patients are immunocompromised; >2 dermatomes are involved; serious bacterial superinfection, disseminated zoster, or meningoencephalitis develops. 

DIET

No special diet 

PATIENT EDUCATION

  • The duration of rash is typically 2 to 3 weeks.

  • Encourage good hygiene and proper skin care.

  • Warn of potential for dissemination (dissemination must be suspected with constitutional illness signs and/or spreading rash).

  • Warn of potential PHN.

  • Warn of potential risk of transmitting illness (chickenpox) to susceptible persons.

  • Seek medical attention if any eye involvement.

PROGNOSIS

  • Immunocompetent individuals should experience spontaneous and complete recovery within a few weeks.

  • Acute rash typically resolves within 14 to 21 days.

  • PHN may occur in patients despite antiviral treatment.

COMPLICATIONS

  • PHN

  • Herpes zoster ophthalmicus: 10–20%

  • Superinfection of skin lesions

  • Meningoencephalitis

  • Disseminated zoster

  • Hepatitis; pneumonitis; myelitis

  • Cranial and peripheral nerve palsies

  • Acute retinal necrosis

REFERENCES

Yawn BP, Saddier P, Wollan PC, et al. A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clin Proc.  2007;82(11):1341–1349.
Hales CM, Harpaz R, Ortega-Sanchez I, et al. Update on recommendations for use of herpes zoster vaccine. MMWR Morb Mortal Wkly Rep.  2014;63(33):729–731.
Schmader KE, Levin MJ, Gnann JWJr, et al. Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50-59 years. Clin Infect Dis.  2012;54(7):922–928.
Harpaz R, Ortega-Sanchez IR, Seward JF, et al. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep.  2008;57(RR-5):1–30.
Chen N, Li Q, Zhang Y, et al. Vaccination for preventing postherpetic neuralgia. Cochrane Database Syst Rev.  2011;(3):CD007795.
Langan SM, Smeeth L, Margolis DJ, et al. Herpes zoster vaccine effectiveness against incident herpes zoster and post-herpetic neuralgia in an older US population: a cohort study. PLoS Med.  2013;10(4):e1001420.
McDonald EM, de Kock J, Ram FS. Antivirals for management of herpes zoster including ophthalmicus: a systematic review of high-quality randomized controlled trials. Antivir Ther.  2012;17(2):255–264.
Chen N, Yang M, He L, et al. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database Syst Rev.  2010;(12):CD005582.
Li Q, Chen N, Yang J, et al. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev.  2009;(2):CD006866.
Cao H, Li X, Liu J. An updated review of the efficacy of cupping therapy. PLoS One.  2012;7(2):e31793.

SEE ALSO

  • Bell Palsy; Chickenpox (Varicella Zoster); Herpes Eye Infections; Herpes Simplex

  • Algorithm: Genital Ulcers

CODES

ICD10

  • B02.9 Zoster without complications

  • B02.29 Other postherpetic nervous system involvement

ICD9

  • 053.9 Herpes zoster without mention of complication

  • 053.10 Herpes zoster with unspecified nervous system complication

SNOMED

  • 4740000 Herpes zoster (disorder)

  • 2177002 Postherpetic neuralgia (disorder)

CLINICAL PEARLS

  • Zoster vaccine is recommended for patients ≥60 years of age and is approved for patients >50 years.

  • Patients with herpes zoster should begin antiviral therapy within 72 hours of the onset of rash to be most effective.

  • Patients with active herpes zoster can transmit clinically active disease (chickenpox) to susceptible individuals.

 
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