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Unusual treatments for herpesvirus infections. II. Herpes zoster
Journal Club IIIIIII
II
.
III
II III II I
Unusual treatments for herpesvirus infections. II. Herpes zoster Bruce H. Thiers, M.D. Charleston, SC
As is the case with herpes simplex, the diverse array of remedies proposed for herpes zoster (HZ) raises doubts as to their overall efficacy. Three critical issues must be addressed in the therapy of patients with this disorder: (1) control of the pain of the acute eruption, (2) prevention of postherpetic neuralgia (PHN), i.e., pain persisting 2 months or longer after the attack of HZ, and (3) alleviation of the discomfort of PHN, should it occur. Unfortunately, many studies fail to distinguish between the clinical symptoms of acute HZ and those of the postherpetic syndrome. The usefulness of agents purported to control the pain of acute HZ must be assessed keeping in mind the natural tendency of the eruption to heal spontaneously. The site of the vesicles, concomitant infection, and the patient's immune status may all affect the clinical course. In addition, pain is a highly subjective sensation; uncontrolled studies are often unreliable, and the placebo effect may be marked. For a given drug to be clinically useful, it must be shown to be at least as safe and effective in controlling pain as the many analgesic agents now available. The beneficial effects of antiviral chemotherapy, if any, would be expected to be apparent only if used during the early stages of the illness. Idoxuridine ointment provides little relief. JuelJensen et al 1 found that continuous topical application of 40% idoxuridine in dimethyl sulfoxide (DMSO) reduced the duration of pain from the acute eruption. Wildenhoff et al z demonstrated
that the acute inflammatory reaction was greatly suppressed by such treatment, although they observed a less dramatic amelioration of pain. Unfortunately, 40% idoxuridine is exceedingly expensive, and the use of DMSO is restricted in many countries. (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) is a nucleoside analogue related to idoxuridine, and is highly active against the varicella zoster virus in vitro. 3 One practical advantage is that it can be taken by mouth. Treatment with orally administered BVDU caused prompt recovery of patients with severe HZ in a study reported by De Clercq et al. 4 Carefully controlled studies are needed to confirm the clinical value of BVDU as a systemic antiherpetic agent. Vidarabine, like idoxuridine, has been used to treat acute attacks of HZ. One studyp which appeared to demonstrate its efficacy in the therapy of ttZ in immunosuppressed patients, was not truly double blind and showed no significant effect on mortality or on the incidence of PHN. Other trials* have been more promising. An accurate assessment of the overall value of vidarabine in the treatment of HZ requires further investigation. Acyclovir is a nucleoside analogue which is unique in that it is preferentially absorbed and activated by infected cells. 6 This theoretically provides a much greater margin o f safety over many older antiviral agents, like idoxuridine, which may have significant effects on cellular DNA synthesis. Selby et al 7 used parenteral acyclovir to treat
From the Department of Dermatology, Medical University of South Carolina. No reprints available.
*Whitley R, Soong S, Dolin R, et al: Vidarabine therapy of herpes zoster infections in immunocornpromisedpatients. Presented at the 21st Interseience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, November, 1981.
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Thiers
seven patients with localized HZ and eight patients with disseminated HZ. All had an underlying malignancy and all had previously received cancer chemotherapy. When given early, the drug seemed to arrest progression of the infection and speed healing. Bean et al 8 conducted a randomized, placebocontrolled, double-blind trial of intravenous acyclovir for acute HZ and found that such treatment reduced pain, decreased erythema, prevented the formation of new vesicles, and healed skin faster than did the placebo. The duration of viral shedding was significantly shorter in patients receiving acyclovir. The drug did not seem to affect the incidence of PHN; in fact, six of seventeen acyclovir recipients suffered a recurrence of acute pain after the drug was discontinued. Acyclovir was associated with elevated serum creatinine in eleven of nineteen recipients during the 5-day treatment period. Peterslund et aP successfully treated HZ patients with intravenous doses of acyclovir about 40% lower than those used by Bean et al. No adverse reactions were noted. Lower daily doses of acyclovir administered over a longer period may be the ideal treatment for HZ. An oraI acyclovir preparation is currently under study. The incidence of PHN is roughly proportional to age, e.g., about 30% for patients 30 years of age, 50% for patients 50 years of age, and 70% for patients 70 years of age. It is especially common after attacks involving the trigeminal nerve. To confirm anecdotal reports of successful prevention of PHN with systemically administered corticosteroids, Eaglstein et aP ° treated thirty-five patients with either orally administered triamcinolone, 48 mg/day for 7 days, 24 mg/day for 7 days, and 16 mg/day for 7 days, or placebo. Benefits of steroid therapy were restricted to those 60 years of age or older, who experienced more rapid relief of pain and a decreased incidence (30% vs 73%) of PHN. Healing time and pain during the acute episode were similar in both the triamcinolone and the placebo groups. Keczkes and Basheed' treated twenty patients with early, severe HZ with prednisolone, 40 mg daily, and gradually reduced the dose over 4
Journal o f the American A c a d e m y of Dermatology
weeks. Carbamazepine, 100 mg four times daily, was prescribed for twenty similarly afflicted individuals. All patients were over 50 years of age. Only 15% of patients in the prednisolone group developed PHN, while 65% suffered this complication in the carbamazepine group. The authors concluded that the incidence and duration of PHN are considerably reduced by early administration of systemic corticosteroids. Epstein '2 used subcutaneous injections of triamcinolone to treat 400 patients with HZ or its sequelae. The group included 272 patients with active HZ and 128 patients with PHN. A 2 m g / m l concentration was injected subcutaneously under the areas of the eruption or at sites of pain, burning, or itching. In Epstein's uncontrolled group, the signs and symptoms of the acute eruption cleared in an average of less than 4 days. Although nearly 70% of his patients were 50 years of age or older, less than 3% developed PHN. Almost 64% of those with established PHN either cleared completely or improved significantly. The efficacy of subcutaneous injections of triamcinolone in the treatment of acute HZ and established PHN is difficult to evaluate without appropriate control groups. The usefulness of such injections in preventing PHN is predictable in light of the previously described studies by Eaglstein et al TM and Keczkes and Basheer. '1 The only real advantage of the injection method might be that a lower total dose of steroid is required in most cases. An intralesional corticosteroid-anesthetic mixture has also been tested in patients with PHN and appears to be as effective as intralesional corticosteroids alone. An anesthetic preparation without parabens must be used to prevent flocculation of the steroid.* Chaturvedi and Mathur la described six patients with recent-onset HZ who responded favorably to griseofulvin. Joubert's ~4 experience with this drug in HZ was "so phenomenal that (he) thought it should be brought to the notice of all those who deal with such cases." Similar results were re*Erickson L: Corticosteroids in zoster. Item 123 in The Schoch Letter, p. 32, August, 1981.
Volume 8 Number 3 March, 1983 ported by Joelson. 15 All patients noted early relief of pain and rapid healing after griseofulvin therapy. Increased sympathetic tone, with secondary regional vasoconstriction and ischemia, may be responsible for the characteristic pain of acute HZ and PHN. Such a phenomenon might explain the reported efficacy of griseofulvin, which, in addition to its antifungal properties, is also a vascular smooth muscle relaxant. Another method of decreasing sympathetic tone, regional sympathetic nerve block, has been investigated in patients with HZ. Colding la used 5 to 10 cc of 1% lidocaine with noradrenaline to perform sympathetic nerve block in patients with acute HZ or PHN. Injections, which were performed once daily for 2 to 4 days, were placed either midway between the affected ganglia or, in certain cases, into the ipsilateral stellate ganglia. Eruptions between the fourth and twelfth thoracic segment were treated by blocks applied directly to the affected sympathetic ganglia. Colding 16 found regional sympathetic block to be very effective for the pain of acute HZ, and the treatment appeared to prevent the lesions from progressing to the postherpetic syndrome. Early treatment was necessary to obtain favorable results. Sympathetic block seemed to be without benefit in the treatment of established PHN. Suzuki et aP 7 showed that the pain of PHN could be alleviated by application of dry ice. A stick of solid carbon dioxide was applied directly to the most hyperesthetic skin areas for 1 minute after infiltration with a local anesthetic. After blistering and crusting, healing took place within 2 to 3 weeks. Additional cryocautery was performed at adjacent painful areas during subsequent sessions. Patients were treated an average of eight times during a period of 2 to 3 weeks. At follow-up evaluation, five of 14 subjects experienced "excellent" pain relief, while five others described moderate benefits. The authors recommended that this procedure be used only in patients with painful regions localized to a relatively limited area of skin. Alleviation of pain by intracutaneous infiltration of local anesthetics may be useful in
Treatments for herpes zoster
435
predicting which patients will respond to cryocautery. The mechanism of action of freeze therapy is unclear; it may be due to changes in the abnormal sensitivity of previously involved skin, which results from viral damage to peripheral nerve receptors. Chlorprothixene is a phenothiazine-like drug used as a psychotherapeutic agent in emotional disorders. Farber and Burks 18 administered chlorprothixene to thirty patients with moderate to severe pain from acute HZ. No placebo controls were included. In the study group, twenty-seven patients experienced complete relief from all pain within 72 hours. The authors concluded that chlorprothixene can be used effectively as an anesthetic agent in the management of acute HZ. Kramer ~9 reported favorable responses in thirteen of sixteen patients with established PHN treated with chlorprothixene; the usual dose was 25 mg orally four times per day. Kembaum and Hauchecome2° administered capsules containing levodopa and benserazide (a peripheral decarboxylase inhibitor) or a placebo to forty-seven patients with HZ. They reported a significant decrease in the intensity of pain in the group receiving the study drug. Patients receiving the drag by the third day of the eruption experienced the most dramatic relief. Healing time was unaffected by treatment except in patients older than 65 years and in those with ophthalmic zoster, in whom the levodopa-benserazide combination appeared to accelerate healing. The only side effect noted was vomiting. It must be emphasized that while the preparation studied seemed to relieve the pain of acute HZ, little can be said of its ability to influence the development or course of chronic PHN. Hernandez-Perez 21 treated forty patients, all 60 years of age or older, with either dehydroemetine (a derivative of emetine), 60 mg daily given by intramuscular injection, usually for 3 to 6 days, or triamcinolone, given orally for 3 weeks, following the same schedule suggested by Eaglstein et al. 1° Skin lesions in patients treated with dehydroemetine seemed to heal faster than those in patients receiving triamcinolone. PHN did not develop in the patients treated with dehydroemetine.
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Thiers
However, eight of the twenty individuals treated with triamcinolone experienced this complication, which persisted for more than 6 months in four. Hoehn 22 successfully treated HZ with a regimen combining emetine and triamcinolone. The mechanism of action of dehydroemetine in HZ is unknown, but, it may be related to adrenergic blockade or the drug's antihyaluronidase activity. Caution is advised because of possible cardiotoxic effects reported from emetine and its derivatives. Lawrence '-a found autoimmune therapy to be an effective form of treatment for acute HZ. This technic consists of "injecting 20 ml of the patient's whole blood (obtained by venipuncture) into the buttocks, 10 ml being injected into each b u t t o c k . . , daily for 3-4 days . . . or every other day f o r . . . 3 times." The theoretical basis for this form of treatment remains a mystery. The immune response likely plays a critical role in the healing of HZ. Clinically significant dissemination of localized HZ occurs almost exclusively in immunosuppressed individuals. Attempts to augment the immune response to control HZ have been moderately successful. Of the agents studied, interferon seems to be the most promising. 24,~-sIts availability and cost limit its use; synthetic interferon inducers are under study. Zoster immune globulin is ineffective. 2~ REFERENCES
1. Juel-Jensen B, MacCallum F, Mackenzie A, et al: Treatment of zoster with idoxuridine in dimethyl sulphoxide. Results of two double blind controlled studies. Br Med J 4:776-780, 1970. 2. Wildenhoff K, Ipsen J, Essmann V, et al: Treatment of herpes zoster with idoxuridine ointment, including a multivariate analysis of symptoms and signs. Scand J Infect Dis 2:1-9, 1979. 3. De Clercq E, Descamps J, De Somer P, et al: (E)-5-(2Bromovinyl)-2'-deoxyuridine: A potent and selective anti-herpes agent. Proc Nati Acad Sci USA 76:29472951, 1979. 4. De Clercq E, DeGreef H, Wildiers J, et al: Oral (E)-5(2-bromovinyl)-2'-deoxyuridine in severe herpes zoster. Br Med J 281:1178, 1980. 5. Whitley R, Ch'ien L, Dolin R, et al: Adenine arabinoside therapy of herpes zoster in the immunosuppressed. N Engl J Med 294:1193-1199, 1976.
Journal of the American Academy of Dermatology
6. Elion G, Furman P, Fyfe J, et al: Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxmethyl) guanine. Proc Natl Acad Sci USA 74:5716-5729, 1977. 7. Selby P, Bowles R, Jameson B, et al: Parenteral acyclovir therapy for herpesvirus infections in man. Lancet 2:1267-1270, 1979. 8. Bean B, Braun C, Balfour H Jr: Acyclovir therapy for acute herpes zoster. Lancet 2:118-12 I, 1982. 9. Peterslund N, Seyer-Hansen K, Ipsen J, et al: Acyclovir in herpes zoster. Lancet 2:827-830, 1981. 10. Eaglstein W, Katz R, Brown J: The effects of corticostemid therapy on the skin eruption and pain of herpes zoster. JAMA 211:1681-1683, 1970. 11. Keczkes K, Basheer A: Do corticosteroids prevent postherpetic neuralgia? Br J Dermatol 102:551-555, 1980, 12. Epstein E: Treatment of herpes zoster and postzoster neuralgia by subcutaneous injections of triamcinolone. Int J Dermatol 20:65-68, 1981. 13. Chaturvedi U, Mathur A: Griseofulvin in herpes zoster. Br Med J 3:438, 1975. (Letter to Editor.) 14. Joubert J: Griseofulvin in the treatment of herpes zoster. S Aft Med J 54:224, 1978. (Letter to Editor.) 15. Joelson L: Griseofulvin in the treatment of herpes zoster. S Afr Med J 54:638, 1978. (Letter to Editor.) 16. Colding A: The effect of regional sympathetic blocks in the treatment of herpes zoster: A survey of 300 cases. Acta Anaesth Stand 13:133-140, 1969. 17. Suzuki H, Ogawa S, Nakagawa H, et al: Cryocautery of sensitized skin areas for the relief of pain due to postherpetic neuralgia. Pain 9:355-362, 1980. 18, Farber G, Burks J: Treatment for herpes zoster neuralgia. South Med J 67:808-812, 1974. 19. Kramer P: The management of post-herpetic neuralgia with chlorprothixene. Surg Neurol 15:102-104, 1981, 20. Kembaum S, Hauchecorne J: Administration of levodopa for relief of herpes zoster pain. JAMA 146:132134, 1981. 21. Hemandez-Perez E: Dehydroemetine therapy for herpes zoster. A comparison with corticosteroids. Cutis 25: 424-426, 1980. 22. Hoehn G: Emetine in herpes zoster. Cutis 27:40, 1981. (Letter to Editor.) 23. Lawrence R: Autoimmune treatment for herpes zoster. West J Med 130:271, 1979. (Letter to Editor.) 24. EmSdi G, Rufli T, Just M, et al: Human interferon therapy for herpes zoster in adults. Scand J Infect Dis 7:1-5, 1975. 25. Merigan T, Rand K, Pollard P, et al: Human leukocyte interferon for the treatment of herpes zoster in patients with cancer. N Engl J Med 298:981-987, 1978. 26. Groth K, McCullogh J, Marker S: Evaluation of zoster immune plasma: Treatment of cutaneous disseminated zoster in immunocompromised patients. JAMA 239: 1877-1879, 1978.
II
.
III
II III II I
Unusual treatments for herpesvirus infections. II. Herpes zoster Bruce H. Thiers, M.D. Charleston, SC
As is the case with herpes simplex, the diverse array of remedies proposed for herpes zoster (HZ) raises doubts as to their overall efficacy. Three critical issues must be addressed in the therapy of patients with this disorder: (1) control of the pain of the acute eruption, (2) prevention of postherpetic neuralgia (PHN), i.e., pain persisting 2 months or longer after the attack of HZ, and (3) alleviation of the discomfort of PHN, should it occur. Unfortunately, many studies fail to distinguish between the clinical symptoms of acute HZ and those of the postherpetic syndrome. The usefulness of agents purported to control the pain of acute HZ must be assessed keeping in mind the natural tendency of the eruption to heal spontaneously. The site of the vesicles, concomitant infection, and the patient's immune status may all affect the clinical course. In addition, pain is a highly subjective sensation; uncontrolled studies are often unreliable, and the placebo effect may be marked. For a given drug to be clinically useful, it must be shown to be at least as safe and effective in controlling pain as the many analgesic agents now available. The beneficial effects of antiviral chemotherapy, if any, would be expected to be apparent only if used during the early stages of the illness. Idoxuridine ointment provides little relief. JuelJensen et al 1 found that continuous topical application of 40% idoxuridine in dimethyl sulfoxide (DMSO) reduced the duration of pain from the acute eruption. Wildenhoff et al z demonstrated
that the acute inflammatory reaction was greatly suppressed by such treatment, although they observed a less dramatic amelioration of pain. Unfortunately, 40% idoxuridine is exceedingly expensive, and the use of DMSO is restricted in many countries. (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) is a nucleoside analogue related to idoxuridine, and is highly active against the varicella zoster virus in vitro. 3 One practical advantage is that it can be taken by mouth. Treatment with orally administered BVDU caused prompt recovery of patients with severe HZ in a study reported by De Clercq et al. 4 Carefully controlled studies are needed to confirm the clinical value of BVDU as a systemic antiherpetic agent. Vidarabine, like idoxuridine, has been used to treat acute attacks of HZ. One studyp which appeared to demonstrate its efficacy in the therapy of ttZ in immunosuppressed patients, was not truly double blind and showed no significant effect on mortality or on the incidence of PHN. Other trials* have been more promising. An accurate assessment of the overall value of vidarabine in the treatment of HZ requires further investigation. Acyclovir is a nucleoside analogue which is unique in that it is preferentially absorbed and activated by infected cells. 6 This theoretically provides a much greater margin o f safety over many older antiviral agents, like idoxuridine, which may have significant effects on cellular DNA synthesis. Selby et al 7 used parenteral acyclovir to treat
From the Department of Dermatology, Medical University of South Carolina. No reprints available.
*Whitley R, Soong S, Dolin R, et al: Vidarabine therapy of herpes zoster infections in immunocornpromisedpatients. Presented at the 21st Interseience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, November, 1981.
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434
Thiers
seven patients with localized HZ and eight patients with disseminated HZ. All had an underlying malignancy and all had previously received cancer chemotherapy. When given early, the drug seemed to arrest progression of the infection and speed healing. Bean et al 8 conducted a randomized, placebocontrolled, double-blind trial of intravenous acyclovir for acute HZ and found that such treatment reduced pain, decreased erythema, prevented the formation of new vesicles, and healed skin faster than did the placebo. The duration of viral shedding was significantly shorter in patients receiving acyclovir. The drug did not seem to affect the incidence of PHN; in fact, six of seventeen acyclovir recipients suffered a recurrence of acute pain after the drug was discontinued. Acyclovir was associated with elevated serum creatinine in eleven of nineteen recipients during the 5-day treatment period. Peterslund et aP successfully treated HZ patients with intravenous doses of acyclovir about 40% lower than those used by Bean et al. No adverse reactions were noted. Lower daily doses of acyclovir administered over a longer period may be the ideal treatment for HZ. An oraI acyclovir preparation is currently under study. The incidence of PHN is roughly proportional to age, e.g., about 30% for patients 30 years of age, 50% for patients 50 years of age, and 70% for patients 70 years of age. It is especially common after attacks involving the trigeminal nerve. To confirm anecdotal reports of successful prevention of PHN with systemically administered corticosteroids, Eaglstein et aP ° treated thirty-five patients with either orally administered triamcinolone, 48 mg/day for 7 days, 24 mg/day for 7 days, and 16 mg/day for 7 days, or placebo. Benefits of steroid therapy were restricted to those 60 years of age or older, who experienced more rapid relief of pain and a decreased incidence (30% vs 73%) of PHN. Healing time and pain during the acute episode were similar in both the triamcinolone and the placebo groups. Keczkes and Basheed' treated twenty patients with early, severe HZ with prednisolone, 40 mg daily, and gradually reduced the dose over 4
Journal o f the American A c a d e m y of Dermatology
weeks. Carbamazepine, 100 mg four times daily, was prescribed for twenty similarly afflicted individuals. All patients were over 50 years of age. Only 15% of patients in the prednisolone group developed PHN, while 65% suffered this complication in the carbamazepine group. The authors concluded that the incidence and duration of PHN are considerably reduced by early administration of systemic corticosteroids. Epstein '2 used subcutaneous injections of triamcinolone to treat 400 patients with HZ or its sequelae. The group included 272 patients with active HZ and 128 patients with PHN. A 2 m g / m l concentration was injected subcutaneously under the areas of the eruption or at sites of pain, burning, or itching. In Epstein's uncontrolled group, the signs and symptoms of the acute eruption cleared in an average of less than 4 days. Although nearly 70% of his patients were 50 years of age or older, less than 3% developed PHN. Almost 64% of those with established PHN either cleared completely or improved significantly. The efficacy of subcutaneous injections of triamcinolone in the treatment of acute HZ and established PHN is difficult to evaluate without appropriate control groups. The usefulness of such injections in preventing PHN is predictable in light of the previously described studies by Eaglstein et al TM and Keczkes and Basheer. '1 The only real advantage of the injection method might be that a lower total dose of steroid is required in most cases. An intralesional corticosteroid-anesthetic mixture has also been tested in patients with PHN and appears to be as effective as intralesional corticosteroids alone. An anesthetic preparation without parabens must be used to prevent flocculation of the steroid.* Chaturvedi and Mathur la described six patients with recent-onset HZ who responded favorably to griseofulvin. Joubert's ~4 experience with this drug in HZ was "so phenomenal that (he) thought it should be brought to the notice of all those who deal with such cases." Similar results were re*Erickson L: Corticosteroids in zoster. Item 123 in The Schoch Letter, p. 32, August, 1981.
Volume 8 Number 3 March, 1983 ported by Joelson. 15 All patients noted early relief of pain and rapid healing after griseofulvin therapy. Increased sympathetic tone, with secondary regional vasoconstriction and ischemia, may be responsible for the characteristic pain of acute HZ and PHN. Such a phenomenon might explain the reported efficacy of griseofulvin, which, in addition to its antifungal properties, is also a vascular smooth muscle relaxant. Another method of decreasing sympathetic tone, regional sympathetic nerve block, has been investigated in patients with HZ. Colding la used 5 to 10 cc of 1% lidocaine with noradrenaline to perform sympathetic nerve block in patients with acute HZ or PHN. Injections, which were performed once daily for 2 to 4 days, were placed either midway between the affected ganglia or, in certain cases, into the ipsilateral stellate ganglia. Eruptions between the fourth and twelfth thoracic segment were treated by blocks applied directly to the affected sympathetic ganglia. Colding 16 found regional sympathetic block to be very effective for the pain of acute HZ, and the treatment appeared to prevent the lesions from progressing to the postherpetic syndrome. Early treatment was necessary to obtain favorable results. Sympathetic block seemed to be without benefit in the treatment of established PHN. Suzuki et aP 7 showed that the pain of PHN could be alleviated by application of dry ice. A stick of solid carbon dioxide was applied directly to the most hyperesthetic skin areas for 1 minute after infiltration with a local anesthetic. After blistering and crusting, healing took place within 2 to 3 weeks. Additional cryocautery was performed at adjacent painful areas during subsequent sessions. Patients were treated an average of eight times during a period of 2 to 3 weeks. At follow-up evaluation, five of 14 subjects experienced "excellent" pain relief, while five others described moderate benefits. The authors recommended that this procedure be used only in patients with painful regions localized to a relatively limited area of skin. Alleviation of pain by intracutaneous infiltration of local anesthetics may be useful in
Treatments for herpes zoster
435
predicting which patients will respond to cryocautery. The mechanism of action of freeze therapy is unclear; it may be due to changes in the abnormal sensitivity of previously involved skin, which results from viral damage to peripheral nerve receptors. Chlorprothixene is a phenothiazine-like drug used as a psychotherapeutic agent in emotional disorders. Farber and Burks 18 administered chlorprothixene to thirty patients with moderate to severe pain from acute HZ. No placebo controls were included. In the study group, twenty-seven patients experienced complete relief from all pain within 72 hours. The authors concluded that chlorprothixene can be used effectively as an anesthetic agent in the management of acute HZ. Kramer ~9 reported favorable responses in thirteen of sixteen patients with established PHN treated with chlorprothixene; the usual dose was 25 mg orally four times per day. Kembaum and Hauchecome2° administered capsules containing levodopa and benserazide (a peripheral decarboxylase inhibitor) or a placebo to forty-seven patients with HZ. They reported a significant decrease in the intensity of pain in the group receiving the study drug. Patients receiving the drag by the third day of the eruption experienced the most dramatic relief. Healing time was unaffected by treatment except in patients older than 65 years and in those with ophthalmic zoster, in whom the levodopa-benserazide combination appeared to accelerate healing. The only side effect noted was vomiting. It must be emphasized that while the preparation studied seemed to relieve the pain of acute HZ, little can be said of its ability to influence the development or course of chronic PHN. Hernandez-Perez 21 treated forty patients, all 60 years of age or older, with either dehydroemetine (a derivative of emetine), 60 mg daily given by intramuscular injection, usually for 3 to 6 days, or triamcinolone, given orally for 3 weeks, following the same schedule suggested by Eaglstein et al. 1° Skin lesions in patients treated with dehydroemetine seemed to heal faster than those in patients receiving triamcinolone. PHN did not develop in the patients treated with dehydroemetine.
436
Thiers
However, eight of the twenty individuals treated with triamcinolone experienced this complication, which persisted for more than 6 months in four. Hoehn 22 successfully treated HZ with a regimen combining emetine and triamcinolone. The mechanism of action of dehydroemetine in HZ is unknown, but, it may be related to adrenergic blockade or the drug's antihyaluronidase activity. Caution is advised because of possible cardiotoxic effects reported from emetine and its derivatives. Lawrence '-a found autoimmune therapy to be an effective form of treatment for acute HZ. This technic consists of "injecting 20 ml of the patient's whole blood (obtained by venipuncture) into the buttocks, 10 ml being injected into each b u t t o c k . . , daily for 3-4 days . . . or every other day f o r . . . 3 times." The theoretical basis for this form of treatment remains a mystery. The immune response likely plays a critical role in the healing of HZ. Clinically significant dissemination of localized HZ occurs almost exclusively in immunosuppressed individuals. Attempts to augment the immune response to control HZ have been moderately successful. Of the agents studied, interferon seems to be the most promising. 24,~-sIts availability and cost limit its use; synthetic interferon inducers are under study. Zoster immune globulin is ineffective. 2~ REFERENCES
1. Juel-Jensen B, MacCallum F, Mackenzie A, et al: Treatment of zoster with idoxuridine in dimethyl sulphoxide. Results of two double blind controlled studies. Br Med J 4:776-780, 1970. 2. Wildenhoff K, Ipsen J, Essmann V, et al: Treatment of herpes zoster with idoxuridine ointment, including a multivariate analysis of symptoms and signs. Scand J Infect Dis 2:1-9, 1979. 3. De Clercq E, Descamps J, De Somer P, et al: (E)-5-(2Bromovinyl)-2'-deoxyuridine: A potent and selective anti-herpes agent. Proc Nati Acad Sci USA 76:29472951, 1979. 4. De Clercq E, DeGreef H, Wildiers J, et al: Oral (E)-5(2-bromovinyl)-2'-deoxyuridine in severe herpes zoster. Br Med J 281:1178, 1980. 5. Whitley R, Ch'ien L, Dolin R, et al: Adenine arabinoside therapy of herpes zoster in the immunosuppressed. N Engl J Med 294:1193-1199, 1976.
Journal of the American Academy of Dermatology
6. Elion G, Furman P, Fyfe J, et al: Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxmethyl) guanine. Proc Natl Acad Sci USA 74:5716-5729, 1977. 7. Selby P, Bowles R, Jameson B, et al: Parenteral acyclovir therapy for herpesvirus infections in man. Lancet 2:1267-1270, 1979. 8. Bean B, Braun C, Balfour H Jr: Acyclovir therapy for acute herpes zoster. Lancet 2:118-12 I, 1982. 9. Peterslund N, Seyer-Hansen K, Ipsen J, et al: Acyclovir in herpes zoster. Lancet 2:827-830, 1981. 10. Eaglstein W, Katz R, Brown J: The effects of corticostemid therapy on the skin eruption and pain of herpes zoster. JAMA 211:1681-1683, 1970. 11. Keczkes K, Basheer A: Do corticosteroids prevent postherpetic neuralgia? Br J Dermatol 102:551-555, 1980, 12. Epstein E: Treatment of herpes zoster and postzoster neuralgia by subcutaneous injections of triamcinolone. Int J Dermatol 20:65-68, 1981. 13. Chaturvedi U, Mathur A: Griseofulvin in herpes zoster. Br Med J 3:438, 1975. (Letter to Editor.) 14. Joubert J: Griseofulvin in the treatment of herpes zoster. S Aft Med J 54:224, 1978. (Letter to Editor.) 15. Joelson L: Griseofulvin in the treatment of herpes zoster. S Afr Med J 54:638, 1978. (Letter to Editor.) 16. Colding A: The effect of regional sympathetic blocks in the treatment of herpes zoster: A survey of 300 cases. Acta Anaesth Stand 13:133-140, 1969. 17. Suzuki H, Ogawa S, Nakagawa H, et al: Cryocautery of sensitized skin areas for the relief of pain due to postherpetic neuralgia. Pain 9:355-362, 1980. 18, Farber G, Burks J: Treatment for herpes zoster neuralgia. South Med J 67:808-812, 1974. 19. Kramer P: The management of post-herpetic neuralgia with chlorprothixene. Surg Neurol 15:102-104, 1981, 20. Kembaum S, Hauchecorne J: Administration of levodopa for relief of herpes zoster pain. JAMA 146:132134, 1981. 21. Hemandez-Perez E: Dehydroemetine therapy for herpes zoster. A comparison with corticosteroids. Cutis 25: 424-426, 1980. 22. Hoehn G: Emetine in herpes zoster. Cutis 27:40, 1981. (Letter to Editor.) 23. Lawrence R: Autoimmune treatment for herpes zoster. West J Med 130:271, 1979. (Letter to Editor.) 24. EmSdi G, Rufli T, Just M, et al: Human interferon therapy for herpes zoster in adults. Scand J Infect Dis 7:1-5, 1975. 25. Merigan T, Rand K, Pollard P, et al: Human leukocyte interferon for the treatment of herpes zoster in patients with cancer. N Engl J Med 298:981-987, 1978. 26. Groth K, McCullogh J, Marker S: Evaluation of zoster immune plasma: Treatment of cutaneous disseminated zoster in immunocompromised patients. JAMA 239: 1877-1879, 1978.