Herpes Zoster/Shingles

Background

Shingles is a skin or mucosal infection caused by the varicella-zoster virus (VZV) that occurs along a dermatome and represents a reactivation of varicella (chickenpox). Zoster is common in patients with HIV infection, including apparently healthy individuals before the onset of other HIV-related symptoms. The incidence may be higher among patients with low CD4 cell counts and during the 4 months after initiating potent antiretroviral therapy.

Zoster may be particularly painful or necrotic in HIV-infected individuals. Disseminated infection, defined as outbreaks with >20 vesicles outside the primary and immediately adjacent dermatomes, usually involves the skin and the visceral organs. Neurologic complications of zoster include encephalitis, aseptic meningitis, cranial nerve palsies, optic neuritis, transverse myelitis, and vasculitic stroke.

S: Subjective

The patient complains of painful skin blisters or ulcerations along one side of the face or body. Loss of vision may accompany the appearance of facial lesions. Pain in a dermatomal distribution may precede the appearance of lesions by many days (prodrome).

Assess the following during the history:

  • Duration of pain or blisters (average of 2-3 weeks if untreated)
  • Location of pain or blisters; severity of pain
  • History of chickenpox (usually in childhood)

O: Objective

Perform a skin and neurologic examination to include the following:

  • Vesicular lesions with erythematous bases in a dermatomal distribution; may be bullous or hemorrhagic
  • Necrotic lesions; may persist for as long as 6 weeks
  • Dermatomal scarring (particularly in dark-skinned individuals)
  • Lesions in the eye area or tip of nose, along the trigeminal nerve; these represent ophthalmic nerve involvement, which requires immediate evaluation and IV treatment (see below)

A: Assessment

  • Rule out other causes of vesicular skin eruptions (e.g., herpes simplex virus, severe drug reactions).
  • Assess contact exposures (see below).

P: Plan

Diagnostic Evaluation

The diagnosis usually is clinical and is based on the characteristic appearance and distribution of lesions. If the diagnosis is uncertain, perform viral cultures or direct fluorescent antigen or polymerase chain reaction test of samples from a freshly opened vesicle or biopsy from the border of a lesion.

Treatment

  • Treatment ideally should begin within 72 hours of an outbreak or while lesions are not yet fully crusted and should be continued for 7-10 days. Early treatment may attenuate a herpes zoster attack.

Localized dermatomal zoster

  • Preferred therapy
    • Valacyclovir 1 g PO TID
    • Famciclovir 500 mg PO TID
  • Alternative therapy
    • Acyclovir 800 mg PO 5 times daily
  • Dosage reductions of these drugs are required for patients with renal impairment.
  • If new blisters are still appearing at the end of treatment, repeat course of PO therapy or consider IV treatment. Adjunctive corticosteroids aimed at preventing postherpetic neuralgia are not recommended.
  • Consult an ophthalmologist immediately if lesions appear in the eye area or on the tip of the nose, or if the patient complains of visual disturbances, because VZV-related retinal necrosis can cause blindness. Because of the rapid progression associated with this diagnosis, hospitalization for administration of IV acyclovir and possibly foscarnet is recommended.
  • VZV from zoster lesions is contagious, and contact or airborne spread from vesicle fluid may cause chickenpox in nonimmune people. If a zoster patient's household includes a pregnant woman (HIV infected or uninfected) or an HIV-infected child, consult with a specialist immediately for advice on management of exposed household members. (See "Postcontact Chickenpox Prevention," below.)
  • Give analgesics for pain; narcotics may be required.
  • Postherpetic neuralgia (PHN) is a common sequela of zoster. Antiviral therapy may reduce the risk of PHN, but PHN often requires special treatment for pain control. Treatment options include:
    • Nortriptyline 10-25 mg. To be taken at bedtime and increased by 25 mg every 3-5 days to a maximum dosage of 150 mg QD until pain is controlled, assuming adverse effects remain tolerable. Other tricyclics may be used.
    • Gabapentin 100-300 mg PO BID; this may be increased by 300 mg every 3 days until reaching 3,600 mg total daily dosage. Adjust gabapentin dosage in patients with kidney disease.
    • Pregabalin 75 mg BID (or 50 mg TID) in patients with estimated creatinine clearance of >60 mL/minute; this may be increased to 300 mg total daily dosage over the course of a week as needed.
    • Lidocaine 5% patches provide good local relief with minimal systemic absorption. Up to 3 patches may be applied simultaneously to the affected area for up to 12 hours in a 24-hour period.
    • Capsaicin cream may be applied to the affected area TID or QID. Patients should wear gloves to apply the cream and wash their hands with soap and water afterward.
    • Sustained-release opiates may be required.

(See chapter Pain Syndrome and Peripheral Neuropathy for more options and specific recommendations.)

Severe or unresponsive cases

  • IV acyclovir may be indicated if:
    • The patient is severely immunocompromised
    • The ophthalmic branch of the trigeminal nerve is affected (as noted above)
    • Dissemination has occurred; visceral disease is suspected
    • Lesions are extensive
    • Lesions are not responsive to oral therapy
    • Pain is intractable in the setting of active skin lesions
  • The usual adult dosage is 10-15 mg/kg Q8H for 7-14 days based on clinical response; can switch to oral therapy when signs/symptoms are improving. Dosage reduction is required for patients with renal impairment. Refer to an infectious disease specialist.
  • Acyclovir resistance may occur in patients previously treated with acyclovir or related drugs, and foscarnet may be required for effective treatment. Resistance should be suspected if lesions are not resolving after 10 days of therapy or if they develop an atypical appearance. Such lesions should be cultured and drug sensitivities should be obtained.

Prevention

The vaccine for prevention of herpes zoster (Zostavax) has not been recommended by national guidelines for use in persons with HIV infection. Limited data in HIV-infected individuals with CD4 counts of >200 cells/µL show safety and immunogenicity. The zoster vaccination may be considered for select patients >50 years of age with CD4 counts of >200 cells/µL who have evidence of varicella immunity (if they have no evidence of varicella immunity, give the primary varicella vaccination). The vaccine is contraindicated in persons with AIDS or clinical manifestations of HIV.

Postcontact Chickenpox Prevention

All HIV-infected susceptible persons, including pregnant women, who have close contact with a patient who has chickenpox or zoster must be treated to prevent chickenpox. Exposed individuals who have no history of chickenpox or shingles or no detectable antibody against VZV should be administered varicella-zoster immune globulin (VariZIG) as soon as possible, but at least within 10 days after contact. Some experts also would recommend varicella vaccination for exposed patients with CD4 counts of ≥200 cells/µL, or preemptive treatment with acyclovir or valacyclovir; these approaches have not been studied in HIV-infected persons. Even immunocompetent adults with primary VZV (chickenpox) can develop viral dissemination to the visceral organs. HIV-infected patients may develop encephalitis, pneumonia, or polyradiculopathy during primary varicella (chickenpox) or reactivated zoster (shingles).

Patient Education

  • Patients should bathe the skin lesions in mild soap and water. For necrotic lesions, use warm, moist compresses 2-3 times a day to remove debris.
  • Antibiotic ointments may help prevent secondary infection and keep dressings from sticking.
  • Advise patients to take their medications as directed, and to contact the clinic if symptoms worsen.

References

  • ACIP Adult Immunization Work Group, Bridges CB, Woods L, et al.; Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP) recommended immunization schedule for adults aged 19 years and older - United States, 2013. MMWR Surveill Summ. 2013 Feb 1;62 Suppl 1:9-19.
  • Benson C, Hua L, Andersen J, et al. Zostavax is generally safe and immunogenic in HIV+ adults virologically suppressed on ART: results of a phase 2, randomized, double-blind, placebo-controlled trial. In: Program and abstracts of the 12th Conference on Retroviruses and Opportunistic Infections; March 5-8, 2012; Seattle. Abstract 96.
  • Fishman S. Post-Herpetic Neuralgia (Oxford American Pocket Notes). Oxford University Press; 2008.
  • Gebo KA, Kalyani R, Moore RD, et al. The incidence of, risk factors for, and sequelae of herpes zoster among HIV patients in the highly active antiretroviral therapy era. J Acquir Immune Defic Syndr. 2005 Oct 1;40(2):169-74.
  • Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of theInfectious Diseases Society of America. Available at aidsinfo.nih.gov/guidelines. Accessed December 1, 2013.

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Abbreviations for Dosing Terminology

BID
twice daily
BIW
twice weekly
IM
intramuscular (injection), intramuscularly
IV
intravenous (injection), intravenously
PO
oral, orally
Q2H, Q4H, etc.
every 2 hours, every 4 hours, etc.
QAM
every morning
QD
once daily
QH
every hour
QHS
every night at bedtime
QID
four times daily
QOD
every other day
QPM
every evening
TID
three times daily
TIW
three times weekly