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Prevention, treatment of herpes zoster pose challenges for patients with cancer
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Herpes zoster is the manifestation of reactivated latent varicella zoster virus in the sensory ganglia.
This syndrome often starts with a prodrome of malaise, headache and photophobia. The typical vesicular rash and pain is unilateral and develops in one to two adjacent dermatomes. The acute neuritis pain — which can range from mild to severe — has been described as burning, aching, stabbing or shock-like.
The vesicles form during a period of days, then heal through the pustular and crusting phases during a period of 2 to 4 weeks. There may be permanent changes in pigmentation of the area or scarring.
Lisa K. Lohr
In susceptible individuals, zoster can become disseminated, leading to pneumonia, encephalitis or hepatitis. The mortality associated with these conditions may range up to 15%. In addition, there may be ophthalmic involvement with serious ocular consequences.
Post-herpetic neuralgia (PHN) is the continuation of pain in the area of the zoster rash. It often lasts a few weeks or months, but it can persist for years. It occurs in about 10% to 30% of those with herpes zoster.
This pain may have burning, itching or sharp characteristics. PHN also is associated with psychosocial problems such as reduced appetite, depression, sleep disorders, and interference with activities of daily living and quality of life. The predictors of PHN include older age and greater rash severity and acute pain. The risk for developing PHN increases with age.
Herpes zoster development
The development of herpes zoster is triggered by the loss of varicella zoster virus–specific cell-mediated immunity, which is commonly seen as a person ages. This also is seen in immunocompromised patients, who are at risk for prolonged herpes zoster episodes and dissemination.
These immunocompromised patients include those with HIV, cancer — especially leukemia and lymphoma — bone marrow or solid organ transplantation, systemic lupus erythematosus, rheumatoid arthritis, Crohn’s disease and ulcerative colitis. These conditions increase the risk for developing herpes zoster by 20 to 100 times. Unfortunately, having a herpes zoster episode does not seem to protect against recurrence. In immunocompromised patients, zoster can be more severe and prolonged, and it is more likely to become disseminated. In contrast, the risk for PHN is not higher.
The annual incidence of herpes zoster in patients aged 60 years or older ranges from 7.2 to 11.8 cases per 1,000 persons, compared with 1.5 to four cases per 1,000 persons in the general population.
About 50% of individuals who live to age 85 years will develop herpes zoster. The risk is about 10% higher in women than in men, and the risk is much higher among whites than blacks.
The incidence of herpes zoster is increasing, independent of the aging of the population. This trend began before the introduction of the primary varicella vaccine (Varivax, Merck). Some reasons include the increasing proportion of immunocompromised persons and, perhaps, a decreased exposure of adults to children with chickenpox.
Treatment
The goal of herpes zoster treatment is to reduce the severity of the episode, speed healing of the lesions and reduce the acute neuritis pain.
Antiviral agents work by inhibiting viral replication, and all of those listed in Table 1 have demonstrated clinical efficacy. There is conflicting evidence regarding whether antiviral treatment reduces likelihood of PHN development. Oral antiviral agents include acyclovir, famciclovir and valacyclovir. The latter two have improved oral bioavailability and more convenient dosing.
In clinical trials, these agents were started within 72 hours of appearance of the vesicular rash. In clinical practice, not all patients present within that time frame. Most recommend starting the antiviral after this time period in immunocompromised patients, especially if new vesicles are still appearing. In uncomplicated situations, a 7-day course is sufficient, but there is no consensus as to whether treatment should continue beyond this if vesicles are still forming or if there are other complications. Topically applied antiviral agents are not effective for herpes zoster.
Those with disseminated herpes zoster or those who cannot tolerate oral medications should be treated with IV acyclovir 10 mg/kg every 8 hours, adjusted for renal dysfunction.
Use of corticosteroids in the treatment of acute herpes zoster is controversial. Some experts recommend a 3-week tapering course of prednisolone, starting at 1 mg/kg/day. This may reduce the acute neuritis pain of herpes zoster and hasten lesion healing. Steroids do not reduce the likelihood of PHN.
Providing adequate analgesia is vitally important. Mild to moderate herpes zoster pain might be managed with acetaminophen, tramadol or an NSAID. More severe cases may require the use of opioids, gabapentin, pregabalin or corticosteroids. Tricyclic antidepressants have not been shown to be of benefit in the acute phase or in preventing PHN.
Prevention
In the general population, the use of a live-attenuated zoster vaccine (Zostavax, Merck) has been shown to decrease the risk for herpes zoster development by about 50%. The number needed to vaccinate in the general population of those aged at least 60 years to prevent one herpes zoster episode during 3 years was 60 to 70 people. In addition, it has been shown to reduce the risk for PHN by about 60%. This vaccine is routinely recommended for those aged 60 years or older.
This vaccine is a one-time subcutaneous injection. There are conflicting recommendations about whether it can be administered during the same visit as the pneumococcal vaccine. The most common side effects were self-limiting injection site reactions. The varicella-zoster virus strain in Zostavax is the same strain as in the chickenpox vaccine, but at a 14-fold higher potency.
The efficacy of Zostavax wanes over time, and the precise duration of protection is unknown. No booster dose is recommended at this time. The optimal age for vaccination appears to be about 65 years.
There are no data to determine whether the herpes zoster vaccine is beneficial in those who already have had an episode of herpes zoster. Those enrolling in clinical studies were not asked about prior herpes zoster cases.
Vaccinations
Although immunocompromised patients are at greater risk for herpes zoster, the herpes zoster vaccine is not recommended for these patients. As it is a live-attenuated vaccine, there is a risk for developing varicella from the vaccination.
If possible, patients who anticipate immunosuppressive treatments should be vaccinated at least 14 to 30 days before starting treatment. Patients also should be off of antiviral therapy for 1 day before and at least 14 days after the vaccination. There is an inactivated zoster vaccine under development for use in immunocompromised patients.
Table 2 shows the patients for whom the herpes zoster vaccine is contraindicated. The Advisory Committee on Immunization Practices advises that patients with cancer whose disease is in remission and who have been off chemotherapy and radiation for at least 3 months may receive the herpes zoster vaccine.
In conclusion, herpes zoster is a condition that results in pain and decreases in quality of life. It primarily affects older individuals, as well as those with immunocompromising conditions or treatments.
Treatment with antiviral agents and analgesics is recommended to treat zoster episodes. The use of zoster vaccine decreases the risk for herpes zoster in those individuals, but it is contraindicated in those who are immunocompromised.
References:
Harpaz R. MMWR Recomm Rep. 2008;57:1-30.
Sanford M. Drugs Aging. 2010;27:159-176.
For more information:
Lisa K. Lohr, PharmD, BCPS, BCOP, is a clinical pharmacy specialist and oncology medication therapy management provider at the University of Minnesota Physicians Cancer Care at Fairview in Minneapolis. She may be reached at the University of Minnesota Physicians Cancer Care at Fairview, 424 Harvard St. SE (MMC 114), Minneapolis, MN 55455.
Disclosure: Lohr reports no relevant financial disclosures.