Treatment of herpes zoster and postherpetic neuralgia

Author: J. Kevin Carmichael
Date: July, 1991

Herpez zoster results from reactivation of varicella-zoster virus that has been dormant in the dorsal root ganglia. The connection between varicella (chickenpox) and zoster was first suggested in 1892 by a Viennese physician, Janos Von Bokay, after observing several cases of varicella in persons exposed to zoster through household contact. [1] In 1984, restriction endonuclease digestion analysis of virus isolated from a patient who first had chickenpox and then had zoster demonstrated identical varicella-zoster virus DNA in both illnesses, thus confirming the etiologic role of varicella-zoster virus in both varicella and herpes zoster. [2]

Herpes zoster generally presents as a painful, unilateral vesicular eruption within a single dermatome. In young, immunocompetent patients, the course of zoster is usually benign. However, in elderly patients, acute neuritis and postherpetic neuralgia may develop, and can be debilitating. Immunocompromised persons are at risk for more serious disease and increased morbidity.

Treatment of acute zoster has been problematic. Acyclovir (Zovirax), given orally at high doses, now appears effective in limiting the duration of the acute infection if therapy is initiated early in the course. The problem of postherpetic neuralgia has received much attention, and a wide variety of therapies have been used for this condition. No one treatment is uniformly successful, but some offer significant benefits.


Zoster occurs at some time in 10 to 20 percent of the population. [3] An equal proportion of men and women are affected, and there is no racial predilection. Zoster has no seasonal variation or relation to epidemics of chickenpox. [4] It is important to remember that persons with zoster are contagious to persons not immune to chickenpox. Also, a previous history of zoster does not rule out recurrence of zoster, although recurrence is rare. [5]

Eighty percent of all cases of herpes zoster occur in persons 20 years of age or older. While persons in all age groups may be affected, the incidence clearly increase with age. Herpes zoster occurs at a constant rate of two to three cases per 1,000 persons between the ages of 20 and 50 years; the rate increases to five cases per 1,000 persons between the ages of 50 and 80 years and increases again to 10 cases per 1,000 persons over age 80. [3] The reason for the increased incidence zoster with increasing age remains unclear. The most common theory is that age-related impairment of cell-mediated immunity is responsible. [6]

Zoster is clearly associated with immune suppression. For example, bone marrow and other transplant recipients have high rates of zoster, particularly in the first two six months after transplantation. In addition, persons with malignancies, especially lymphoreticular malignancies, have an increased frequency of zoster; in two-year study, [7] zoster was found in 25 percent of persons with Hodgkin's disease. However, the longstanding notion that patients with zoster are likely to have an underlying malignancy does not appear to be true. Recent studies have conclusively disproved this belief. [8]

Zoster frequently occurs in patients infected with the human immunodeficiency virus (HIV). [9] In fact, zoster is often the first clinical manifestation of the disease. [10] The exact frequency of zoster in HIV infection is not known; however, in one series of 48 consecutive patients presenting with zoster, 70 percent had HIV infection. [11] Thus, the occurrence of zoster--particularly in persons under age 50 (in whom the frequency of zoster is otherwise low)--warrants consideration of HIV risk factors and possibly HIV antibody testing.

Patients with zoster may transmit varicella-zoster virus (as chickenpox) to persons at high risk (neonates, nonimmune persons, pregnant womane and immunocompromised patients). High-risk persons should be kept away from patients with active zoster.

Clinical Manifestations

The clinical features of zoster have been divided into three phases: the prodromal phase, the acute phase and the chronic phase. [12] Not every patient passes through each phase, and some patients may have unusual or atypical presentations.


Before the development of overt skin lesions, sensations described as burning, tingling, itching, boring, prickly or knifelike occur. These sensory changes appear to result from degeneration of cutaneous nerve fibrils from viral activity. Sensory changes in involved dermatomes precede the development of the rash of zoster by hours to days.


The rash of zoster is typically erythematous and maculopapular and evolves rapidly to grouped vesicles (Figure 1). The emergence of the rash may be accompanied by constitutional symptoms of fatigue, malaise, headache and low-grade fever. Generally, the vesicles become pustular and/or hemorrhagic by the third to the fourth day. Collapse of the vesicles, with drying and crust formation, occurs in abouth seven to 10 days. Resolution usually occurs in 14 to 21 days, with the crusts falling off, often leaving residual hyperpigmented or hypopigmented scarring.


In younger patients, the pain associated with acute zoster generally subsides as the rash resolves. Patients over 40 to 50 years of age, however, are at increased risk of developing postherpetic neuralgia. The overall incidence of this chronic pain syndrome is only about 15 percent. However, the percentage of affected persons increases dramatically with age; over 50 percent of those over age 60 will have pain lasting more than one month after the rash has healde. [13]


While zoster usually follows the typical course, immunocompetent or immunocompromised patients sometimes have unusual presentations or complications. Some of the complications are listed in Table 1.

In some patients, the prodromal symptoms are not followed by a rash. This is known as zoster sine herpete, of "zoster without the rash." The frequency of this syndrome is unknown because the diagnosis rests on serologic testing, which may not be performed unless zoster is a diagnostic consideration. [5]

TABLE 1 Complications of Herpes ZosterMeningoencephalitisCerebrovasculopathyCranial nerve syndromes Trigeminal (ophthalmic) branch (herpes zoster ophthalmicus) Facial and auditory nerve (Ramsay Hunt syndrome)Peripheral motor weaknessTransverse myelitisVisceral involvement Pneumonitis Hepatitis Pericarditis/myocarditis Pancreatitis Esophagitis Enterocolitis SynovitisCuttaneous disseminationSuperinfection of skin lesions


The diagnosis of zoster is clear when prodromal symptoms have occurred and the typical dermatomal vesicular rash is present. However, differentiating zoster from herpes simplex virus, coxsackievirus, contact dermatitis and superficial pyoderma is sometimes difficult.

Useful diagnostic procedures include viral culture, the Tzanck smear and monoclonal antibody tests. When available, viral culture is the most useful diagnostic test.

The Tzanck smear is prepared with scrapings from the base of a fresh vesicle. When positive, the smear reveals multinucleated giant cells, inclusion bodies and "balloon degeneration" of epithelial cells. Positive results confirm herpes virus etiology but do not distinguish between herpes simplex and herpes zoster. Viral cultures, direct immunofluorescence tests or assessment of acute and convalescent titers may be required to distinguish between herpes simplex virus and varicella-zoster virus. A negative Tzanck smear does not rule out herpes zoster, and many physicians are not skilled in performing this office diagnostic test.


The treatment goals in patients with zoster are to minimize discomfort, shorten the duration of symptoms, prevent dissemination or other complications, and prevent or minimize postherpetic neuralgia. The treatment of acute zoster may be divided into three areas of focus: local care, management of acute pain and antiviral drug therapy.


The two goals in management of zoster skin lesions are relief of itchings and reduction of bacterial colonization of damaged skin. Wet dressings or compresses, applied for 30 to 60 minutes four to six times daily, are soothing and help remove exudates or crusts. Either tap water or 5 percent aluminum acetate (Burow's solution) can be used for the dressings. Lotions such as calamine may be applied after the compresses are removed. Care should be taken not to apply so much lotion that the residual powder cakes and becomes difficult to remove.

The effectiveness of the various treatment modalities is difficult to assess because of deficiencies in the design of studies evaluating them. [21] No one therapy is uniformly effective. The best treatments available for postherpetic neuralgia may be capsaicin cream (Zostrix), transcutaneous nerve stimulation (TENS) and low-dose amitriptyline (Elavil, Endep). [21, 22]

Capsaicin. Capsaicin (trans-8-methyl-N-vanillyl-6-noneramide) is a naturally occurring irritant compound found in the fruit of several members of the nightshade plant family. Two recent studies found capsaicin effective in decreasing postherpetic neuralgia. [28, 29] One of these studies was double-blinded and placebo-controlled and showed that after four weeks of treatment, 77 percent of patients had a reduction in paid. [28]

Capsaicin is thought to act by depleting substance P from cell bodies and nerve terminals. Substance P is believed to be the primary chemomediator of painful impulses from the periphery to the central nervous system. [12] Interestingly, capsaicin blocks pain without affecting light touch of vibratory sensations. Capsaicin, available as a 0.025 percent cream, should be applied three to five times daily to affected skin. Local burning, stinging or redness of the skin is common, but generally self-limited. Results are usually achieved by day 14. The optimum duration of treatment is unknown. [28]

Transcutaneous Electrical Stimulation. TENS is believed to reduce pain by activating large low-threshold nerve fibers, thereby counteracting increased discharges from small unmyelinated fibers. One study showed pain reduction in about 30 percent of patients treated with TENS. [27] TENS treatments are usually carried out three or four times daily for 30 to 60 minutes. One to two weeks of therapy may be needed to assess response.

Amitriptyline. Amitriptyline was first recognized as effective in relieving post-herpetic neuralgia in 1965, when it was used for the treatment of depression in patients with the paid syndrome. [30] Tricyclic antidepressants (including amitriptyline) are believed to function as analgesics through their ability to block reuptake of serotonin and norepinephrine. Importantly, the analgesic effect of amitriptyline seems to be independent of the anti-depressant effect and can be achieved at lower doses. [31] Because of the side effects of amitriptyline, it is recommended that a low dosage be given, particularly in elderly patients; it should be started in doses of 10 to 25 mg per day and then increased slowly in 10-mg increments. [31, 32]

Final Comment

The safety and efficacy of high-dose acyclovir (800 mg orally five times daily) in decreasing the duration and severity of zoster represents a major breakthrough in clinical management. The earliest possible use of acyclovir will result in the best possible outcome, particularly in the elderly and in the immunosupprssed, groups that are at greatest risk of complications.

Postherpetic neuralgia will continue to be a problem, since acyclovir does not appear to be effective in prevention. No therapy is uniformly successful for this syndrome. Topical capsaicin, TENS and amitriptyline appear to provide the best results.

Finally, the common occurrence of zoster in HIV-infected persons, the concurrent increased risk of complications in these patients and the availability of therapy for HIV infection warrant a careful investigation of HIV risk factors and, perhaps, HIV antibody testing in persons with zoster, particularly those less than 50 years of age.


[1] Balfour HH Jr. Varicella zoster virus infections in immunocompromised hosts. A review of the natural history and management. Am J Med 1988;85 (2A):68-73.

[2] Straus SE, Reinhold W, Smith HA, et al. Endonuclease analysis of viral DNA from varicella and subsequent zoster infections in the same patient. N Engl J Med 1984;311:1362-4.

[3] Hope-Simpson R. The nature of herpes zoster: a long-term study and a new hypothesis. Proc R Soc Med 1965;58:9-20.

[4] Goldberg G. A treatment guide for herpes zoster. Mod Med 1987;56:66-75.

[5] Peto T. Shingles in general practice. Practioner 1989;233:398-403.

[6] Straus SE, Ostrove JM, Inchauspe G, et al. NIH conference. Varicella-zoster virus infections. Biology, natural history, treatment, and prevention. Ann Intern Med 1988;108:221-237 [Published erratum appears in Ann Intern Med 1988;109:438-9].

[7] Schimpff S, Serpick A, Stoler B, et al. Varicella-zoster infection in patients with cancer. Ann Intern Med 1972;76:241-54.

[8] Ragozzino MW, Melton LJ 3d, Kurland LT, Chu CP, Perry HO. Risk of cancer after herpes zoster: a population-based study. N Engl J Med 1982;307:393-7.

[9] Cohen PR, Grossman ME. Clinical features of human immunodeficiency virus-associated disseminated herpes zoster virus infection--a review of the literature. Clin Exp Dermatol 1989;14:273-6.

[10] Wilkerson MG, Jordan WP, Kerkering TM. Herpes zoster as a sign of AIDS-related complex. Am Fam Physician 1987;36(4):233-5.

[11] Friedman-Kien AE, Lafleur FL, Gendler E, et al. Herpes zoster: a possible early clinical sign for development of acquired immunodeficiency syndrome in high-risk individuals. J Am Acad Dermatol 1986;14:1023-8.

[12] Strommen GL, Pucino F, Tight RR, Beck CL. Human infection with herpes zoster: etiology, pathophysiology, diagnosis, clinical course, and treatment. Pharmacotherapy 1988;8:52-68.

[13] DeMoragas J, Kierland R. The outcome of patients with herpes zoster. Arch Dermatol 1957;75:193-6.

[14] Montes LF, Muchinik G, Fox CL Jr. Response of varicella zoster virus and herpes zoster to silver sulfadiazine. Cutis 1986;38;363-5.

[15] Elion GB. Mechanism of action and selectivity of acyclovir. Am J Med 1982;73(1A):7-13.

[16] Brigden D, Whiteman P. The clinical pharmacology of acyclovir and its prodrugs. Scand J Infect Dis 1985;47(Suppl):33-9.

[17] Tucker WE Jr. Preclinical toxicology profile of acyclovir: an overview. Am J Med 1982;73(1A):27-30.

[18] Huff JC, Bean B, Balfour HH Jr, et al. Therapy of herpes zoster with oral acyclovir. Am J Med 1988;85(2A):84-9.

[19] Morton P, Thomson AN. Oral acyclovir in the treatment of herpes zoster in general practice. NZ Med J 1989;102:93-5.

[20] Ljungman P, Lonnqvist B, Ringden O, Skinhoj P, Gahrton G. A randomized trial of oral versus intravenous acyclovir for treatment of herpes zoster in bone marrow transplant recipients. Nordic Bone Marrow Transplant Group. Bone Marrow Transplant 1989;4:613-5.

[21] Watson PN, Evans RJ. Postherpetic neuralgia. A review. Arch Neurol 1986;43:836-40.

[22] Robertson DR, George CF. Treatment of post herpetic neuralgia in the elderly. Br Med Bull 1990;46:113-23.

[23] Hope-Simpson R. Herpes zoster in general practice: post-herpetic neuralgia. J R Coll Gen Pract 1975;25:571-5.

[24] Hess TM, Lutz LJ, Nauss LA, Lamer TJ. Treatment of acute herpetic neuralgia. A case report and review of the literature. Minn Med 1990;73:37-40.

[25] Post BT, Philbrick JT. Do corticosteroids prevent postherpetic neuralgia? A review of the evidence. J Am Acad Dermatol 1988; 18:605-10.

[26] Schmader KE, Studenski S. Are current therapies useful for the prevention of postherpetic neuralgia? A critical analysis of the literature. J Gen Intern Med 1989;4:83-9.

[27] Nathan PW, Wall PD. Treatment of post-herpetic neuralgia by prolonged electrical stimulation. Br Med J 1974;3-645-7.

[28] Bernstein JE, Korman NJ, Bickers Dr, Dahl MV, Millikan LE. Topical capsaicin treatment of chronic postherpetic neuralgia. J Am Acad Dermatol 1989;21(2 Pt 1):265-70.

[29] Bernstein JE, Bickers DR, Dahl MV, Roshal JY. Treatment of chronic postherpetic neuralgia with topical capsaicin. A preliminary study. J Am Acad Dermatol 1987; 17:93-6.

[30] Woodforde JM, Dwyer B, McEwen BW, et al. Treatment of post-herpetic neuralgia. Med J Aust 1965;2:869-72.

[31] Watson CP. Therapeutic window for amitriptyline analgesia [Letter]. Can Med Assoc J 1984;130:105-6.

[32] Portenoy RK, Duma C, Foley KM. Acute herpetic and postherpetic neuralgia: clinical review and current management. Ann Neurol 1986;20:651-64.

J. KEVIN CARMICHAEL, M.D. is serving a fellowship in faculty development at the University of Arizona College of Medicine, Tucson, where he also is a member of the inter-disciplinary AIDS team. Dr. Carmichael graduated from the University of Miami School of Medicine and completed a residency in family medicine at Jackson Memorial Hospital, Miami.

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