Correspondence
Herpes Zoster
N Engl J Med 2000; 343:221-223July 20, 2000
- Article
To the Editor:
Treatment of the pain that is frequently associated with acute herpes zoster and postherpetic neuralgia is a challenging clinical problem. Although in their review of the neurologic complications of the reactivation of varicella–zoster virus, Gilden et al. (March 2 issue)1 correctly note that there is no universally accepted protocol, they suggest using extra-strength acetaminophen and codeine to treat the pain resulting from acute zoster and avoiding the use of stronger narcotics. This approach contradicts scientifically based guidelines provided by the Agency for Health Care Policy and Research and the American Pain Society, which recommend selecting analgesic drugs and titrating the dose according to their efficacy and side effects.2,3
Acute herpes zoster causes mixed somatic and neuropathic pain of variable intensity. Although there is controversy about the preferred combination of adjuvant and opioid medications, the dose and drug should be selected according to the needs of the individual patient. If less potent analgesic medications are ineffective, stronger agents should be prescribed until pain is relieved or dose-limiting side effects occur. In addition, the effectiveness of the use of gabapentin for postherpetic neuralgia is no longer “anecdotal” but is supported by the results of a randomized, placebo-controlled clinical trial.4 In fact, in randomized, double-blind, placebo-controlled trials, oxycodone, gabapentin, and several tricyclic antidepressants have all demonstrated efficacy.4-6
6 ReferencesAlan Carver, M.D.
Richard Payne, M.D.
Kathleen Foley, M.D.
Memorial Sloan-Kettering Cancer Center, New York, NY 100211
Gilden DH ,Kleinschmidt-DeMasters BK ,LaGuardia JJ ,Mahalingham R ,Cohrs RJ . Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med 2000;342:635-645[Erratum, N Engl J Med 2000;342:1063.]
Full Text | Web of Science | Medline2
Jacox A ,Carr DB ,Payne R . New clinical-practice guidelines for the management of pain in patients with cancer. N Engl J Med 1994;330:651-655
Full Text | Web of Science | Medline3
Principles of analgesic use in the treatment of acute pain and chronic cancer pain: a concise guide to medical practice. 4th ed. Glenview, Ill.: American Pain Society, 1999.
4
Rowbotham M ,Harden N ,Stacey B ,Bernstein P ,Magnus-Miller L . Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA 1998;280:1837-1842
CrossRef | Web of Science | Medline5
Watson CPN ,Babul N . Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Neurology 1998;50:1837-1841
Web of Science | Medline6
Max MB . Thirteen consecutive well-designed randomized trials that show antidepressants reduce pain in diabetic neuropathy and postherpetic neuralgia. Pain Forum 1995;4:248-253
CrossRef | Web of Science
To the Editor:
The article by Gilden and colleagues on the neurologic complications of the reactivation of varicella–zoster virus contained several important inaccuracies and neglected to discuss the results of recent controlled clinical trials of postherpetic neuralgia.
Valacyclovir is an additional antiviral drug approved in the United States for the treatment of herpes zoster. The authors' statement that “trials of oral antiviral drugs to prevent postherpetic neuralgia have not been shown to be effective after six months of treatment” is potentially misleading. These drugs are used for the treatment of herpes zoster, not postherpetic neuralgia, and the placebo-controlled trials treated patients for 7 to 10 days, with 6 months of follow-up. Overall, the findings are consistent in demonstrating that antiviral drugs reduce the duration of pain from herpes zoster and the risk of postherpetic neuralgia. Whether antiviral drugs reduce the risk of pain that lasts more than six months has not been investigated. There is no evidence of the efficacy of antiviral drugs for the treatment of postherpetic neuralgia.
Postherpetic neuralgia can occur after herpes zoster in any distribution, not just in a trigeminal distribution, as implied by Gilden and colleagues, and an increased risk of postherpetic neuralgia after trigeminal zoster has not been found consistently.1 Postherpetic neuralgia can recur after pain-free intervals of various lengths of time.1 It is important to note that postherpetic neuralgia does occur before the age of 50 years; almost 10 percent of patients in their 30s and 40s who have herpes zoster report pain lasting more than one year.
Double-blind, vehicle-controlled studies have demonstrated that patients with postherpetic neuralgia obtain pain relief from a topical lidocaine patch.2 On the basis of these results, the Food and Drug Administration (FDA) recently approved a topical lidocaine patch for the treatment of postherpetic neuralgia; this is the only therapy with an FDA-approved indication for postherpetic neuralgia.
2 ReferencesRobert H. Dworkin, Ph.D.
University of Rochester, Rochester, NY 14642Bradley S. Galer, M.D.
Beth Israel Medical Center, New York, NY 10003Michael C. Rowbotham, M.D.
University of California, San Francisco, San Francisco, CA 941151
Dworkin RH ,Portenoy RK . Pain and its persistence in herpes zoster. Pain 1996;67:241-251
CrossRef | Web of Science | Medline2
Galer BS ,Rowbotham MC ,Perander J ,Friedman E . Topical lidocaine patch relieves postherpetic neuralgia more effectively than a vehicle topical patch: results of an enriched enrollment study. Pain 1999;80:533-538
CrossRef | Web of Science | Medline
To the Editor:
Dr. Gilden and his group are to be commended on their review of the neurologic complications of zoster. The subject is timely because of the increase in the population of elderly persons and of immunocompromised patients. We believe, however, that the authors greatly underestimate the magnitude of the problem. Our sources suggest that the annual incidence of zoster is close to 850,000 cases, not 300,000 cases.
The article also includes a misconception about the live attenuated varicella vaccine. It is true that millions of children have received this vaccine and that the virus in the vaccine has the potential to become reactivated. The incidence of reactivation, however, is clearly lower after immunization than after natural infection. This point has been shown in several studies involving immunocompromised children who were vaccinated. In addition, the incidence of zoster among immunized healthy children studied thus far also appears to be very low. Obviously, it will take many years of follow-up to be certain of this fact, but the experience thus far is that zoster is less frequent after vaccination than after natural infection. The public should be aware of this point, since more than one third of states now require children to be vaccinated against chickenpox before they are admitted to day-care programs or school.
The vaccine trials referred to by Dr. Gilden and his colleagues are taking place in “old-timers” like ourselves, who have latent infections with the natural, fully virulent virus.
Anne A. Gershon, M.D.
Columbia University College of Physicians and Surgeons, New York, NY 10032Richard T. Perkin
VZV Research Foundation, New York, NY 10021To the Editor:
The review article by Gilden et al. on the neurologic complications of varicella–zoster virus reactivation raises important questions concerning the diagnosis of these complications. The authors state that the diagnosis of neurologic disorders produced by varicella–zoster virus should be assessed by polymerase-chain-reaction analysis and antibody testing of cerebrospinal fluid and that, in cases of myelitis, the virus cannot be cultured from cerebrospinal fluid.
This statement conflicts with our experience and that of others. In 1987 we observed a case of varicella–zoster virus myelitis in a patient with severe immunodeficiency associated with AIDS (CD4+ cell count, 10 per cubic millimeter). The cerebrospinal fluid contained 6 lymphocytes per cubic millimeter and a normal level of protein. Varicella–zoster virus was recovered by culture of cerebrospinal fluid on human-fibroblast monolayers, and the isolate was shown to be acyclovir-resistant (by Dr. A.M. Fillet, Department of Virology, Hôpital Pitié–Salpêtrière, Paris). This information enabled us to use foscarnet instead of acyclovir, as previously reported.1
Varicella–zoster virus has also been recovered by culture of cerebrospinal fluid from four additional patients infected with the human immunodeficiency virus (HIV): two had subacute encephalitis,2 one had myelitis,3 and one had meningoradiculoneuritis.4 Interestingly, in the fourth patient, the varicella–zoster virus isolate in cerebrospinal fluid was also resistant to acyclovir.4 These cases show that varicella–zoster virus can be cultured from the cerebrospinal fluid of HIV-infected patients with neurologic complications and that isolation of the virus can facilitate treatment after drug-susceptibility testing.
4 ReferencesGuillaume Breton, M.D.
François Bricaire, M.D.
Eric Caumes, M.D.
Hôpital Pitié–Salpêtrière, 75651 Paris CEDEX 13, France1
Breton G ,Fillet AM ,Katlama C ,Bricaire F ,Caumes E . Acyclovir-resistant herpes zoster in human immunodeficiency virus-infected patients: results of foscarnet therapy. Clin Infect Dis 1998;27:1525-1527
CrossRef | Web of Science | Medline2
Dix RD ,Bredesen DE ,Erlich KS ,Mills J . Recovery of herpesviruses from cerebrospinal fluid of immunodeficient homosexual men. Ann Neurol 1985;18:611-614
CrossRef | Web of Science | Medline3
Gomez-Tortosa E ,Gadea I ,Gegundez MI , et al. Development of myelopathy before herpes zoster rash in a patient with AIDS. Clin Infect Dis 1994;18:810-812
CrossRef | Web of Science | Medline4
Snoeck R ,Gerard M ,Sadzot-Delvaux C , et al. Meningoradiculoneuritis due to acyclovir-resistant varicella-zoster virus in a patient with AIDS. J Infect Dis 1993;168:1330-1331
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Gershon and Perkin believe that our statement that “the widespread use of a vaccine against varicella–zoster virus is not likely to result in a reduced incidence of zoster and its attendant complications” is erroneous. They and others have shown that the incidence of zoster is lower among immunocompromised children who had been vaccinated than among children who had had chickenpox. Thus, they extrapolate that the incidence of zoster among adults who had been vaccinated in childhood will be lower than the incidence of zoster among adults who had naturally occurring chickenpox. We hope they are right. However, predictions based on these studies should be interpreted cautiously, since many children were vaccinated repeatedly, and immunity against varicella–zoster virus has been shown to be less complete in vaccinated persons than in those infected with wild-type virus.1 Because the incidence of zoster among elderly persons who were vaccinated in childhood will not be known for decades, we stand by our statement that current trials of a vaccine to boost immunity in middle-aged persons are valuable. It has already been shown that vaccination of prior vaccine recipients and persons who had chickenpox in childhood may extend the duration of immunity.1
Gershon and Perkin assert that the annual incidence of zoster is 850,000 cases, not 300,000 cases. Although no reference is given for this statistic, such a high incidence, if true, underscores the need for even more research into mechanisms of the latency and reactivation of varicella–zoster virus.
Dworkin et al. and Carver et al. correctly point out that many drugs have shown efficacy in double-blind, placebo-controlled trials in patients with postherpetic neuralgia. Unfortunately for patients and their doctors, no single drug or treatment regimen has emerged as clearly superior. We have cared for patients with postherpetic neuralgia for decades and have been frustrated by the lack of long-term efficacy and the side effects of carbamazepine, phenytoin, amitriptyline, and more recently, lidocaine patches, oxycodone, and gabapentin. Thus, we were reluctant to recommend a single protocol. We agree fully that the choice drug and dose should be tailored to each patient with postherpetic neuralgia and that pain control should be optimized. However, we stand by our statement that “stronger narcotics should be avoided” in this population of elderly patients who do not have cancer or other terminal illnesses. We have found narcotics, even when at an optimal dose, to be ineffective for the long-term control of pain from postherpetic neuralgia and to be associated with unacceptable side effects in the elderly, such as lethargy, confusion, unsteadiness, constipation, and headache. Finally, we recognize that valacyclovir has been approved for the treatment of zoster, but we are not aware that it is more effective than famciclovir.
Breton et al. correctly call our attention to several exceptional instances in which varicella–zoster virus was isolated by culture from the cerebrospinal fluid of severely immunocompromised patients. We did not mean to imply that culture of cerebrospinal fluid should never be used. However, it takes weeks to recover the virus from cerebrospinal fluid culture, as compared with one to two days in the case of polymerase-chain-reaction or antibody testing, and even after a characteristic herpesvirus cytopathic effect develops in tissue culture, the virus must still be identified with specific antiserum. The identification of drug-resistant varicella–zoster virus mutants is labor-intensive and not practical for the average hospital laboratory. Overall, because polymerase-chain-reaction testing and antibody testing of cerebrospinal fluid are sensitive, specific, and much faster than culture of cerebrospinal fluid, they have largely replaced this method and are the current diagnostic tools of choice for identifying varicella–zoster virus, as they are for many other viral infections of the central nervous system.
1 ReferencesDonald H. Gilden, M.D.
Bette K. Kleinschmidt-DeMasters, M.D.
University of Colorado Health Sciences Center, Denver, CO 802621
Krause PR ,Klinman DM . Varicella vaccination: evidence for frequent reactivation of the vaccine strain in healthy children. Nat Med 2000;6:451-454
CrossRef | Web of Science | Medline
- Citing Articles (2)
Citing Articles
1
P. L. Jacobson, J. D. Mann. (2003) Evolving Role of the Neurologist in the Diagnosis and Treatment of Chronic Noncancer Pain. Mayo Clinic Proceedings 78:1, 80-84
CrossRef2
Alan Carver, Kathleen Foley. (2001) Facts and an open mind should guide clinical practice. Current Neurology and Neuroscience Reports 1:2, 97-98
CrossRef
