Minimal risk of currently approved meds and logic argue for expanding treatment recommendations.
Under the sponsorship of the International Society for the Study of Pain, an interdisciplinary group of physicians has developed Recommendations for the Management of Herpes Zoster—the first evidence-based, multispecialty consensus guidelines for the common condition, says Robert Dworkin, MD, who chaired the group.
With its diverse manifestations and complications, herpes zoster (HZ), aka shingles, may come to the attention of dermatologists, neurologists, ophthalmologists, infectious disease specialists, and pain specialists. But it is often diagnosed and first treated in primary care.
A dominant theme of the document is the importance of reducing pain, observes Dr. Dworkin, professor of anesthesiology, neurology, oncology, and psychiatry at the University of Rochester in New York. “Physicians should attend to pain for two reasons: Pain while the patient still has a rash is a clinical concern in its own right; it has a negative impact on quality of life and on physical and emotional function and needs to be reduced to the extent possible. Secondly, there are reasons to hypothesize that controlling the acute pain of zoster will lessen the risk of chronic pain.”
Antiviral therapy—start it quickly
Most patients should start taking an antiviral medication as soon as possible (see algorithm below). This is “the main take-home message of the Recommendations,” says Dr. Dworkin. Randomized controlled trials have repeatedly demonstrated that these agents shorten the period of acute pain and hasten resolution of the rash. The evidence that treatment forestalls postherpetic neuralgia (PHN) is also strong, although less conclusive.
Three antivirals—acyclovir, famciclovir, and valacyclovir—have been approved by the FDA for treating HZ. The Recommendations note that the latter two agents appeared more efficacious than the first in clinical trials and that their more convenient dosing schedule (three times vs. five times daily) probably fosters superior compliance.
Based on clinical trial data and product labeling, the authors advocate systemic antivirals as first-line treatment for HZ in immunocompetent patients who are aged 50 or older, who have moderate-to-severe pain or rash, or whose lesions appear in places other than the trunk. In light of the exceptional safety of these medications, however, the authors also suggest that antiviral treatment be considered even for patients who satisfy none of these criteria.
Similar logic applies to treatment timing. Controlled clinical trials have all initiated antiviral therapy within 72 hours of rash onset; its efficacy when started later is unproven. “But there's nothing magical about 72 hours—it's somewhat arbitrary as an inclusion criterion,” Dr. Dworkin notes.
Especially in light of the “minimal risks” of these drugs and the fact that diagnosis and acquisition of medication are often delayed, the authors recommend that physicians consider initiating treatment even after 72 hours if new vesicles continue to form (suggesting ongoing viral replication); cutaneous, neurologic, or ocular complications have developed; or pain is severe.
Similarly, labeling calls for a seven-day course of famciclovir or valacyclovir, and the efficacy of extending treatment is unknown. But the potential for further benefit with little risk justifies this extended approach for patients who have new vesicles or cutaneous complications after the first week. (Close monitoring and possibly further evaluation are also indicated, the Recommendations say.)
Pain control for short- and long-term benefit
The rationale for augmenting antiviral therapy is that enhanced relief of acute pain may reduce the risk of PHN still further. Evidence for the efficacy of corticosteroids, conventional analgesics, and certain antidepressants and antiepileptic drugs in this regard is limited. But as the authors point out, “Effective acute pain relief is [in itself] a very desirable treatment goal.” Pain severity determines whether and which drugs to add to antiviral treatment.
Oral corticosteroids may be considered “as soon as possible after diagnosis” when pain is moderately severe (and there are no contraindications), the authors say.
Acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs), alone or combined with codeine or another weak opioid analgesic, are indicated for mild-to-moderate pain. Prescribe them to maintain constant analgesia rather than as needed for exacerbations, the Recommendations advise. Stronger opioid analgesics (e.g., oxycodone or morphine) may be indicated for more severe pain; long-acting preparations have advantages for HZ patients.
Other approaches are generally best reserved for instances when standard analgesics have been inadequate, the authors state. The antiepileptic drugs gabapentin and pregabalin are approved for PHN, and they are safer and more tolerable than other drugs prescribed for neuropathic pain. While the data on efficacy in HZ per se are limited, the Recommendations suggest that adding gabapentin to an antiviral alleviates acute pain and reduces the risk of PHN. High doses (e.g., 3,600 mg gabapentin, 600 mg pregabalin) may be necessary.
Tricyclic antidepressants have established benefits for PHN, and one placebo-controlled trial found that adding amitriptyline to antiviral therapy for acute HZ reduced PHN incidence by half. Tolerability and safety concerns limit this agent's utility, however, particularly for the elderly. Nortriptyline is preferable, according to the authors.
Pain that remains substantial despite antiviral and adjunctive medication should be referred to a pain specialist or a pain center for evaluation and possible neural blockade.
Nondrug management is important too
Patient education and support are important in HZ management. These include explanations of the disease, the treatment plan, and the necessity of scrupulous adherence to the antiviral regimen. Any misconceptions and fears about HZ raised by the patient should be addressed, and patients should be cautioned about the risk of infecting individuals who have not had chickenpox. Counsel patients to keep the rash clean and dry to minimize the risk of bacterial superinfection, to report any increase in temperature, and to use sterile wet dressings to reduce discomfort.
Topical antibiotics and adhesive dressings can delay rash healing and should be avoided. There appears to be no role for topical antiviral or corticosteroid preparations.
When you encounter special cases
Immunocompromise by disease (e.g., HIV, malignancy) or medical intervention (e.g., organ transplantation, corticosteroid therapy) increases the risk of HZ and of dissemination and visceral involvement. IV acyclovir is the treatment of choice when immunocompromise is severe. Outpatient oral antiviral treatment has obvious advantages in less extreme cases, and data, though limited, support its safety and efficacy.
Elderly individuals in poor health or with diminished functional status are also vulnerable to viral dissemination, and the pain of HZ may initiate a spiral of inactivity, poor nutrition, cognitive impairment, and loss of independence. Dosages of adjunctive medications may need to be adjusted in light of physiologic changes and nonpharmacologic interventions ini-tiated to maintain nutrition and assist activities of daily living.
Failure of the rash to heal, neurologic or ophthalmologic complications, or symptoms suggesting dissemination usually merit referral to an appropriate specialist.
Recommendations for the Management of Herpes Zoster was published in Clinical Infectious Diseases (2007;44 [Suppl 1]:S1-S26) and is available online at www.journals.uchicago .edu/doi/pdf/ (accessed May 22, 2008).
Mr. Sherman is a medical writer in New York City.