Mr. P, aged 64 years, had a history of coronary artery disease, hypertension, type 2 diabetes mellitus, and hyperlipidemia. He presented with a rash on the left side of the neck involving the C2-C3 dermatomes. At the time of presentation, he took aspirin, lisinopril (Prinivil, Zestril), metoprolol (Lopressor, Toprol), glipizide (Glucotrol), metformin (Fortamet, Glucophage, Glumetza), and simvastatin (Zocor) for his chronic medical problems, which were all well controlled.
1. Lab results
Laboratory workup revealed WBC 6,800/μl, hemoglobin 12.3 g/dL, platelets 207,000/μl, serum sodium 136 mEq/L, potassium 4.9 mEq/L, blood urea nitrogen 16 mg/dL, creatinine 1.1 mg/dL, thyroid-stimulating hormone 5.46 mIU/L, and free thyroxine 0.83 ng/dL. Liver function tests were within normal limits. Total cholesterol was 127 mg/dL, HDL 31 mg/dL, LDL 36 mg/dL, and tryglycerides 299 mg/dL.
After evaluation of the rash, the patient was diagnosed with herpes zoster (HZ), commonly known as shingles. Treatment with acyclovir 800 mg five times per day for 10 days initially improved the rash but left a hypopigmented area in the same dermatomal distribution. The patient then developed pain in the same location, a condition known as postherpetic neuralgia (PHN).
Primary infection with varicella zoster virus (VZV) typically occurs during childhood and results in varicella (chickenpox), which is manifested as cutaneous crops of pruritic vesicles that erupt and crust over in approximately one week. During the viremic phase, the virus accesses sensory nerves and, through retrograde axonal transport, establishes latency in the dorsal root ganglia.1
HZ occurs with reactivation of latent VZV, causing a painful blistering skin eruption along a dermatomal distribution that can take up to four weeks to heal. Reactivation most often occurs in immunocompromised patients and older adults during periods of stress.2 Persistent pain after resolution of the rash, or PHN, may occur, especially if there is continued viral replication leading to an intense spinal inflammatory reaction that manifests as axonal and cell-body degeneration, atrophy of the dorsal horn, scarring of the dorsal root ganglion, and loss of epidermal innervation of the affected area.1,3 PHN is severe and debilitating, and like most other neuropathic pain syndromes, is often refractory to treatment.
3. Presentation and diagnosis
Acute HZ. The diagnosis of HZ is usually clinical, as the skin findings are distinctive. The rash is typically localized to a single dermatome, is unilateral, and does not cross the midline. Adjacent dermatomes may be involved in approximately 20% of cases.2 Most commonly, the dermatomes corresponding to the ophthalmic division of the trigeminal nerve and thoracic and cervical dermatomes are affected.4 The classic HZ rash involves groups of lesions that progress through stages, from red macules and papules to vesicles and pustules that crust and scab over in seven to 10 days.2 A prodromal syndrome may precede the skin findings and can include headache; photophobia; such skin sensations as pain, itching, and burning in the dermatome of reactivation; and, less commonly, fever.1 These symptoms may precede the rash by days to three weeks.1 In some patients, the prodromal syndrome may be the only manifestation of HZ, in which case, the condition is known as zoster sine herpete.2 Shell vial culture is the gold-standard diagnostic test for HZ, but polymerase chain reaction or Tzanck smear may also be useful.2
PHN. Defined as pain persisting or recurring for at least three months after the healing of zoster skin lesions, PHN is characterized by constant or intermittent sharp, burning pain; allodynia; paresthesia; and hyperesthesia that can be significantly debilitating to the patient.4 Patients may also complain of mood and sleep disturbances, loss of appetite, chronic fatigue, anxiety, and even suicidal ideation.1
Acyclovir, famciclovir, and valacyclovir—nucleoside analogs that inhibit replication of human herpes viruses—are FDA-approved for treatment of acute HZ (even in immunocompromised patients). These agents decrease the duration of viral shedding, reduce the time to rash healing, and lessen the severity and risk of progression to PHN, especially when initiated within 2 days of the onset of rash.1
Additionally, a three-week tapering course of corticosteroids in conjunction with a nucleoside analog has been shown to decrease acute zoster pain and reduce healing time. Steroids, however, have not been shown to prevent PHN.1 Analgesics should be used for acute pain. Because nonsteroidal anti-inflammatory drugs are usually ineffective, many of the same modalities used in the treatment of PHN are also used in acute HZ (Table 1).2 Such narcotics as oxycodone (OxyContin) and also gabapentin (Fanatrex, Gabarone, Neurontin) are potential treatments for acute pain in patients with HZ. Controlled-release oxycodone was found to be superior to placebo in the early period of pain (Days 1-14). Gabapentin was not shown to yield a significantly greater relief of pain than placebo, although it offered modest pain relief during the first week.5
Although initial exposure to VZV produces antibody levels that remain relatively constant with age, the decline in cell-mediated immunity is the primary determinant for the development of HZ.6 The increased incidence of HZ in older adults is a result of the progressive decline in cell-mediated immunity that occurs with aging.6 Accordingly, preventive efforts are aimed at older adult populations. The zoster vaccine (Zostavax) is a live attenuated VZV that is most effective in patients aged 60 to 69 years and retains efficacy up to four years after vaccination. It is recommended by the Advisory Committee on Immunization Practices for immunocompetent adults aged 60 years and older as a single-dose vaccine, regardless of history of HZ.1,2
Since his diagnosis, Mr. P has been treated unsuccessfully with gabapentin, pregabalin (Lyrica), capsaicin cream, and transdermal fentanyl (Duragesic). He is currently taking duloxetine (Cymbalta), which provides some pain relief. The health-care team avoided amitriptyline (Elavil, Endep, Vanatrip) because of Mr. P’s history of a coronary artery bypass graft. If the patient’s pain does not completely resolve on this therapy, more invasive therapies — such as botulinum toxin injections or epidural nerve blocks — may be considered.
Dr. Willer is a first-year surgery resident, Dr. Siddiqui is a third-year family medicine resident, and Dr. Saxena is assistant professor of family medicine, all at Creighton University Medical Center in Omaha. Dr. Spangler is assistant professor and clinical pharmacist at Creighton University School of Pharmacy and Health Professions.
1. Harpaz R, Ortega-Sanchez IR, Seward JF; Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008;57(RR-5):1-30.
4. Irving G, Jensen M, Cramer M, et al. Efficacy and tolerability of gastric-retentive gabapentin for the treatment of postherpetic neuralgia: results of a double-blind, randomized, placebo-controlled clinical trial. Clin J Pain. 2009;25:185-192.
5. Dworkin RH, Barbano RL, Tyring SK, et al. A randomized, placebo-controlled trial of oxycodone and of gabapentin for acute pain in herpes zoster. Pain. 2009;142:209-217.
6. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352:2271-2284.
All electronic documents accessed June 15, 2011.