23Nov

Herpes Zoster (“Shingles) and Postherpetic Neuralgia

Herpes zoster, commonly known as “shingles,” is caused by the varicella zoster virus (VZV). It occurs in about 1 million individuals each year in the US. Due to waning cell-mediated immunity over time, age is a major risk factor for herpes zoster with over half of unvaccinated patients 85 years and older being affected.

TIPS ABOUT THE MANAGEMENT AND PREVENTION OF HERPES ZOSTER AND POSTHERPETIC NEURALGIA

  • Acute herpes zoster (“shingles”) is a clinical diagnosis with best outcomes occurring when treatment is started within 72 hours using oral antiviral agents in combination with systemic glucocorticoids to decrease pain and shorten healing time.
  • The recently approved recombinant vaccine (RZV) is the first choice vaccine for preventing herpes zoster and postherpetic neuralgia (PHN) in adults age ≥50.
  • Consider vaccinating your patients with RZV even if they have been previously vaccinated with live varicella vaccine (VZL).

Herpes Zoster (“Shingles) and Postherpetic Neuralgia

Clinical Presentation & Diagnosis

Herpes Zoster
Herpes Zoster

VZV is usually acquired during childhood as chickenpox, which is typically symptomatic but occasionally has minimal symptoms. After this initial VZV infection, viral particles travel to cranial and dorsal root ganglia where they are shielded from antibodies. Under conditions of decreased cell-mediated immunity, which occur with aging and also due to disease-induced or medication-induce immune impairment, the virus reactivates and replicates, resulting in herpes zoster.

Zoster begins with a prodrome of malaise, headache, fever, and burning pain. The classic rash follows in two to three days. The rash starts as maculopapular lesions that appear in a single, unilateral dermatome (see figure below). The rash progresses to vesicles that crust over after seven to ten days. Herpes zoster is typically a clinical diagnosis, but polymerase chain reaction testing of vesicle fluid can be used with atypical presentations (95% sensitivity; 100% specificity).

The most common complication of zoster is postherpetic neuralgia (PHN), a syndrome of pain in a dermatomal distribution sustained for at least 90 days after the rash. While rare in young adults, PHN occurs in an estimated 10-13% of patients with herpes zoster age 50 years and older. PHN in older adults can last for years, causing severe and disabling pain. On rare occasions, shingles can cause blindness or hearing loss, and patients may develop pneumonia or encephalitis, which can be fatal.

Ideally, treatment should be initiated within 72 hours of presentation. Antiviral oral guanosine analogues are the mainstay of treatment, with additional medications serving as adjuncts (Table 1). If new lesions develop or ophthalmic or neurologic complications are present, treatment outside the 72-hour window is warranted. Antivirals decrease pain severity and appearance of new lesions by 12 hours, but do not reduce the incidence of PHN.

Table 1: Treatments for Acute Herpes Zoster *
AgentDosageSide EffectsComments
Acyclovir800mg PO 5x per day (7 days)Diarrhea, headache, malaiseMonitor INR in patients taking warfarin
Famciclovir500mg PO 3x per day (7 days)Confusion, headache, nauseaDose adjustment for CrCl <50ml/min
Valacyclovir1,000mg PO 3x daily (7 days)Diarrhea, headache, malaise, nausea, vomitingDose adjustment for CrCl <50ml/min
Prednisolone40mg PO daily (21 day taper)Dyspepsia, nausea, vomitingDoes not prevent post-herpetic neuralgia
Acetaminophen (Tylenol)325 q4-6 hours PRN; maximum dose in older adults is 3,000 mg/dayHeadache, hepatotoxicityUse lower doses in liver disease
Ibuprofen400mg PO q4hrs PRNAbdominal discomfort, dyspepsia,GI bleedingAvoid in history of renal disease
* None of these medications prevents or reduces the occurrence of postherpetic neuralgia

Glucocorticoids, in combination with antivirals, reduce acute pain and promote early healing, but they also do not reduce the incidence of PHN. Pain control depends on pain severity. Treatments typically used include acetaminophen, non-steroidal anti-inflammatory drugs, anticonvulsants, tricyclic antidepressants, and/or nerve blocks.

Management of Postherpetic Neuralgia

Postherpetic Neuralgia 
Postherpetic Neuralgia

Treatment options for PHN include both topical and systemic treatments. These are shown in Table 2.

Table 2: Treatments for Postherpetic Neuralgia 
AgentDosageSide EffectsComments
Lidocaine 5% patchUp to 3 patches dailyBlisters, local erythema, rashDo not use on broken skin
Capsaicin 0.075% creamFour applications per dayErythema, pain, rashAvoid contact with eyes and mucous membranes
Capsaicin 8% patchUp to 4 patches for up to 60 minutes

Do not apply more often than q3 months

Erythema, pain, rashPre-treat area with topical anesthetic prior to applying patch
Gabapentin300 to 600mg PO 3 times per dayDizziness, peripheral edema, sedation, weight gainWhen discontinuing, taper over 7 days (or longer  w/high doses); adjust dose for CrCl <60ml/min
Pregabalin150 to 300mg PO per day in 2 or 3 divided dosesDizziness, peripheral edema, sedation, weight gainTaper when discontinuing;
Dose adjustment for CrCl <60ml/min
Amitriptyline10-25mg PO at bedtime, increase 10 mg per week with goal of 75-150 mg/dayConstipation, blurred vision, dry mouth, sedation, urinary retentionNot recommended for older adults due to anticholinergic effects

Due to its favorable adverse effect profile, lidocaine 5% patches are considered the first-line therapy for PHN, although evidence supporting its effectiveness is inconsistent. Capsaicin 0.075% cream is another option, also with limited evidence. Capsaicin 8% patches, on the other hand, have shown clear evidence of benefit, but they are associated with skin irritation and pain with application.

Approved systemic treatments for PHN include anticonvulsants (gabapentin and pregabalin), which can achieve up to a 50% reduction in pain (NNT=8 and NNT=4, respectively). Titration to an effective dose can take weeks, however, and adverse effects such as somnolence, may limit their use in older adults. Amitriptyline is sometimes used in younger individuals, but should not be used in older adults due to its anticholinergic effects.

Prevention

Zoster and PHN can be prevented by vaccines, but vaccination rates in older adults are as low as 24% in some studies.

Zoster and PHN can be prevented by vaccines
Zoster and PHN can be prevented by vaccines

A live VZV vaccine (VZL-Zosatvax) and a recombinant vaccine (RZV-Shingrix) are available (Table 3), but RZV is more effective and it is considered the first-choice vaccine by the Centers for Disease Control and Prevention. RZV is 96%, 97%, and 91% effective in adults aged 50-59, 60-69, and ≥70 years, respectively, and protection lasts four years. RZV should be given to all patients in those age groups, including those with a past history of herpes zoster and those with a current acute episode, though in the latter group, vaccination should be delayed until the acute phase of illness is complete. The vaccine is also recommended for those with chronic conditions such as diabetes mellitus, rheumatoid arthritis, chronic kidney disease, and chronic obstructive pulmonary disease.

Table 3: Zoster Vaccines 
VaccineAgeDose/RouteEffectivenessComments
Shingrix (recombinant zoster vaccine)502 doses (0 months and 2-6months)
Intramuscular
96.6% efficacy (50-59)
97.4% (60-69)
91.3% (70)
This is the CDC-recommended vaccine
Store in refrigerator
Adverse events: Injection site redness, pain, swelling
Zostavax (zoster vaccine live)601 dose
Subcutaneously
70% (50-59)
64% (60-69)
38% (70)
Store in freezer
Protection decreases 1 year after vaccination
By 6 years effectiveness is <35%

Because of the more limited effectiveness of the VZL vaccine, the RZV vaccine should be given to patients who have already received VZL, though not sooner than 2 months after VZL.

Another aspect of prevention is avoiding spread of infection. Although shingles cannot be spread from one person to another, direct contact with fluid from the blisters in the zoster rash can transmit virus and cause chickenpox in individuals who have never had chickenpox or received the varicella vaccine. This is of particular concern for older adults who are interacting with unvaccinated grandchildren. Once the rash has crusted over, however, it is no longer infectious.

References and Resources

  • Saguil A, Kane S, Mercado M, Lauters R. Herpes Zoster and Postherpetic Neuralgia: Prevention and Management. Am Fam Physician. 2017;96(10):656-663.
  • Dooling K,  Guo A,  Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines.  MMWR. 2018;67(3):103-108.
  • Centers for Disease Control: provides useful clinical information.

 National Editorial Board:  Theodore M Johnson II, MD, MPH, Emory University; Jenny Jordan, PT, DPT, Sacred Heart Hospital, Spokane, WA;  Jane Marks, RN, MS, FNGNA, Johns Hopkins University; Josette Rivera, MD, University of California San Francisco; Jean Yudin, CRNP, University of Pennsylvania

 Interprofessional Associate Editors: Carleigh High, PT, DPT; David Coon, PhD; Marilyn Gilbert, MS, CHES; Jeannie Lee, PharmD, BCPS; Marisa Menchola, PhD;  Francisco Moreno, MD; Linnea Nagel, PA-C, MPAS; Lisa O’Neill, DBH, MPH; Floribella Redondo; Laura Vitkus, MPH, CHES

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