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Severe neutropenia associated with oral terbinafine therapy
Journal of the American Academy of Dermatology Volume 38, Number 5, Part 1
natural selection bias of the responders because those physicians with a history of HZ may have been more inclined to respond. Alternatively, the higher incidence rate may reflect a true increase in the incidence of HZ from that reported more than 30 years ago9 or be caused by being underreported.10 Given the statistically significant difference in incidence rates among pediatricians and the other physician groups, we conclude that an increased rate of exogenous reexposure to VZV may confer additional immunity against VZV, and subsequently a decreased incidence of HZ. We also suspect that the incidence of HZ in the general population is higher than previously estimated and is possibly equivalent to the 10.8% rate noted for psychiatrists.
Brief communications 765 2. Ragozzino MW, Milton LJ III, Kurland LT, Chu CP, Perry HO. Population based study of herpes zoster and its sequelae. Medicine 1982;61:310-6. 3. McGregor RM. Herpes zoster, chicken-pox, and cancer in general practice. Br Med J 1957; Jan-March: 84-7. 4. Miller AE. Selective decline in cellular immune response to varicella zoster in the elderly. Neurology 1980;30: 582-7. 5. Berger R, Florent G, Just M. Decrease of lymphoproliferative response to varicella zoster virus antigen in the aged. Infect Immun 1981;32:24-7. 6. Arvin AM. Cell mediated immunity to varicella zoster virus. J Infect Dis 1992;166:S35-S41. 7. Arvin AM, Koropchak CM, Witteck AE. Immunologic evidence of reinfection with varicella zoster virus. J Infect Dis 1983;148:200-5. 8. Siegel SS. Nonparametric statistics for the behavioral sciences. New York: McGraw-Hill; 1956. 9. Donahue J, Choo P, Manson J, et al. Herpes zoster. Arch Intern Med 1995;155:1605-9. 10. Williamson J, Stokoe IH, Gray S, Fisher M, Smith A, McGhee A, et al. Old people at home, their under-reported needs. Lancet 1964;1:1117-20.
REFERENCES 1. Hope-Simpson RE. The nature of herpes zoster: a long term study and new hypothesis. Proc R Soc Lond 1965;58:9-20.
Severe neutropenia associated with oral terbinafine therapy Aditya K. Gupta, MD, FRCPC,a Gamini S. Soori, MD,b James Q. Del Rosso, DO,c Paul B. Bartos, MD,d and Neil H. Shear, MD, FRCPCa Toronto, Ontario, Canada; Omaha, Nebraska; Las Vegas, Nevada; and Canton, Ohio
Terbinafine is an oral allylamine antifungal agent that was approved in the United States for the treatment of dermatophyte onychomycosis in May 1996. As of October 1997 it is estimated that terbinafine has been used in 7.5 million patients worldwide. It is an effective agent that is used extensively to treat dermatophyte infections. Terbinafine has been found to be safe, and adverse effects are usually mild and transient. We describe From the Division of Dermatology, Department of Medicine, Sunnybrook Health Science Center and the University of Toronto, Torontoa; the Department of Medicine, Creighton University, Omahab; the Las Vegas Skin and Cancer Clinicsc; and Altman Hospital, Canton.d Reprints not available from the authors. J Am Acad Dermatol 1998;38:765-7. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/54/87876
a patient in whom severe neutropenia developed during treatment with oral terbinafine. CASE REPORT A 60-year-old white man was treated with terbinafine, 250 mg daily, for onychomycosis of the toenails. He had been taking yohimbine 1 tablet (5.4 mg) three times a day for impotence, a drug that, to our knowledge, is not associated with myelosuppression. The pretherapy laboratory values (complete blood cell count [CBC]) were as follows: hemoglobin, 14.2 gm/dl (normal, 13.7 to 16.9 gm/dl); leukocytes, 6900/mm3 (normal, 3400/mm3 to 9900/mm3); and platelet count, 197,000/mm3 (normal, 150,000/mm3 to 400,000/mm3). The differential count was neutrophils, 60%; absolute neutrophil count, 4100/mm3 (range, 1300/mm3 to 6200/mm3); lymphocytes, 23%; monocytes, 10%; eosinophils, 0.7%; and basophils, 1%. After approximately 6 weeks of terbinafine therapy, a
766 Brief communications sore throat developed and the patient became febrile. Two days later tenderness and erythema developed in the web space of the left foot. The patient became progressively ill with chills, generalized weakness, and headaches. He was febrile (102.8° F) with a tender, warm, erythematous area on the dorsum of the left foot and the third web space, in which there was a draining ulcer. Stomatitis and gingivitis were present with scattered, tender, purpuric lesions on the gums. There was no exanthem or other features (e.g., myalgia or arthralgia) suggestive of a viral infection. The leukocyte count was 1600/mm3 (normal, 4000/mm3 to 11,000/mm3); hemoglobin, 13.1 gm/dl (normal, 13.3 to 17.7 gm/dl); platelet count, 200,000/mm3 (normal, 150,000/mm3 to 400,000/mm3). The differential count was as follows: granulocytes, 0.7% (normal, 38% to 80%; absolute granulocyte count, 11/mm3); lymphocytes, 26% (normal, 15% to 50%); and monocytes, 73% (normal, 2% to 14%). Bone marrow examination revealed neutropenia and mild anemia, as well as a hypocellular marrow with marked myeloid hypoplasia. Myeloid maturation arrest was present. Cultures revealed Pseudomonas aeruginosa septicemia. The cellulitis in the left foot was caused by a Staphylococcus infection. Treatment included rehydration, intravenous antibiotics, and filgrastim (granulocyte colony-stimulating factor). The terbinafine and yohimbine were discontinued. The leukocyte count increased to 10,800/mm3 with 80% granulocytes. The patient made an uneventful recovery. He resumed yohimbine without any adverse effects. DISCUSSION
The hematologic abnormalities associated with terbinafine therapy in immunocompetent patients include agranulocytosis or severe neutropenia, leukopenia, lymphopenia, pancytopenia, thrombocytopenia, and anemia.1-4 Of the estimated 1.5 million patients worldwide treated with terbinafine as of September 1994, eight cases of blood dyscrasias were reported, in particular agranulocytosis, pancytopenia, and thrombocytopenia, which were possibly or probably related to terbinafine (1:187,500 or 12 cases per million patients exposed).3 If the average duration for which terbinafine is generally used is 3 months, it is estimated that for these 1.5 million patients the corresponding number of patient-years is 0.375 million, giving a projected rate of blood dyscrasias with terbinafine to be 32 per million patient-years. Recent results indicate that the incidence of severe neutropenia, including agranulocytosis, may be of the order 1:400,000, with less severe forms of neutropenia being more
Journal of the American Academy of Dermatology May 1998
common.5 Furthermore, the frequency of thrombocytopenia may be of the order of 1 in 200,000 patients using terbinafine5 (also data on file, Novartis Pharma AG). However, the exact incidence of blood dyscrasias associated with terbinafine therapy is not known, in part because many patients do not have routine CBC monitoring performed. Furthermore, in general, only a proportion of adverse events with any drug are reported. In some instances estimates of blood dyscrasias in the general population are available. For example, the incidence rate of agranulocytosis has been estimated to be 9 per million per year in an age- and sex-adjusted U.S. population in Minnesota, Michigan, and Florida.6 In Sweden, in the normal population, the overall and drug-induced incidence rates of thrombocytopenia were estimated to be 55.0 and 12.5 per million per year, respectively.7 The corresponding rate for aplastic anemia or pancytopenia was estimated at 24.6 per million per year.7 With World Health Organization (WHO) data, the duration between the onset of terbinafine therapy and the development of blood dyscrasia is 6.9 ± 0.5 weeks (mean ± standard error).* This is an approximate value because a report to the WHO does not indicate a definite association between the adverse event and the drug. There is no requirement in the United States to conduct hematologic monitoring in immunocompetent patients treated with terbinafine. This is consistent with the very low incidence of blood dyscrasias reported with terbinafine. In general, routine monitoring only becomes rational when the incidence of a severe adverse event exceeds 1:1000.8 The U.S. product monograph indicates that in patients with known or suspected immunodeficiency, physicians should consider monitoring CBCs when using terbinafine for longer than 6 weeks.4 Our patient illustrates that a blood dyscrasia can occur in an immunocompetent patient receiving terbinafine and that this can be potentially serious. Some physicians perform CBCs at baseline after 4 to 6 weeks of continuous terbinafine therapy in immunocompetent patients; however, the pattern of monitoring varies considerably. Counseling the patient about potential blood dyscrasias during terbinafine therapy is *Information obtained from the WHO on Dec. 5, 1996. The information is not homogeneous at least with respect to origin or likelihood that the pharmaceutical product caused the adverse reaction. The information does not represent the opinion of the WHO.
Journal of the American Academy of Dermatology Volume 38, Number 5, Part 1
important regardless of the monitoring frequency. This could include informing the patient that the drug should be discontinued and medical attention sought on the development of fever, sore throat, dyspnea, unusual fatigue, bleeding from any source, lymphadenopathy, or secondary infection.3 The patient should be aware that the development of any symptoms or signs is a rare occurrence, which may have a delayed onset (e.g., 4 to 8 weeks after the start of therapy). REFERENCES 1. Kovacs MJ, Alshamarri S, Guenther L, Bourcier M. Neutropenia and pancytopenia associated with oral terbinafine. J Am Acad Dermatol 1994;31:806.
Brief communications 767 2. Terbinafine: hematological disorders. Can Med Assoc J 1994;151:64. 3. Lamisil (terbinafine hydrochloride) Canadian Product Monograph, Sandoz Canada Inc., Dorval, Quebec. November 1995. 4. Lamisil (terbinafine hydrochloride) U.S. Product Monograph. Sandoz Pharmaceuticals Corporation, East Hanover, New Jersey. 1996. 5. Suhonen R, Neuvonen PJ. The tolerability profile of terbinafine. Rev Contemp Pharmacother 1997;8:373-86. 6. Strom BL, Carson JL, Schinnar R, Snyder ES, Sahw M. Descriptive epidemiology of agranulocytosis. Arch Intern Med 1992;152:1475-80. 7. Böttiger LE, Böttiger B. Incidence and cause of aplastic anemia, hemolytic anemia, agranulocytosis and thrombocytopenia. Acta Med Scand 1981;210:475-9. 8. Gupta AK, Shear NH. Terbinafine: an update. J Am Acad Dermatol 1997;37:979-88.
Multiple basal cell carcinomas of the limb after adjuvant treatment of melanoma with isolated limb perfusion Philina M. Lamb, BS,a Gregg M. Menaker, MD,a and Ronald L. Moy, MDa,b Los Angeles, California Chemotherapy by isolated limb perfusion for the treatment of solid tumors, particularly malignant melanoma, was first described in 1958 by Creech et al.1 Single-agent limb perfusion with nitrogen mustard has been used in treating malignant melanoma confined to the extremities. Nitrogen mustard, an alkylating agent, has been demonstrated to be a carcinogen systemically and has been reported to induce epithelial cancers in both sun-protected and sun-exposed areas when applied topically. Alkylating agents act by forming highly reactive free radicals that permanently rupture the hydrogen bonds between DNA strands and RNA strands. The DNA is modified such that delayed cell death occurs 3 to 7 days after lethal exposure. No long-term effects of limb perfusion with nitrogen mustard have been described, but topical application has been reported to induce epithelial neoplasms such as basal cell carcinoma (BCC), squamous cell carcinoma, keratoacanthoma, and actinic keratosis.2-6 From the Division of Dermatology, University of California, Los Angeles,a and Dermatologic Surgery, Veterans Administration– West Los Angeles Medical Center.b Reprint requests: Ronald L. Moy, MD, 100 UCLA Medical Plaza, Suite 590, Los Angeles, CA 90024-6970. J Am Acad Dermatol 1998;38:767-8. 16/54/88864
We describe a patient with a history of malignant melanoma who has been experiencing BCCs at a rapid rate in the left lower limb. It is the same limb in which isolated limb perfusion with nitrogen mustard was given approximately 26 years earlier for the adjunctive treatment of melanoma. CASE REPORT A 62-year-old white man was seen because of multiple BCCs. In one year, seven confined to the left lower extremity had appeared. He subsequently experienced 14 BCCs during the next 3 years. They were treated with Mohs surgery or curettage and electrodesiccation. He had experienced melanoma of the left anterior medial thigh approximately 26 years before this. Treatment had included a wide resection with subsequent lymph node dissection and isolated limb perfusion with nitrogen mustard. The patient denied any radiation exposure to the left leg. The melanoma has not recurred, although the BCCs continue. DISCUSSION
Chemotherapy by isolated limb perfusion is designed to maximize the effects in the affected limb while minimizing systemic toxicity. With isolated limb perfusion, drug concentrations within the tumor are more than ten times that achievable by intravenous administration.
natural selection bias of the responders because those physicians with a history of HZ may have been more inclined to respond. Alternatively, the higher incidence rate may reflect a true increase in the incidence of HZ from that reported more than 30 years ago9 or be caused by being underreported.10 Given the statistically significant difference in incidence rates among pediatricians and the other physician groups, we conclude that an increased rate of exogenous reexposure to VZV may confer additional immunity against VZV, and subsequently a decreased incidence of HZ. We also suspect that the incidence of HZ in the general population is higher than previously estimated and is possibly equivalent to the 10.8% rate noted for psychiatrists.
Brief communications 765 2. Ragozzino MW, Milton LJ III, Kurland LT, Chu CP, Perry HO. Population based study of herpes zoster and its sequelae. Medicine 1982;61:310-6. 3. McGregor RM. Herpes zoster, chicken-pox, and cancer in general practice. Br Med J 1957; Jan-March: 84-7. 4. Miller AE. Selective decline in cellular immune response to varicella zoster in the elderly. Neurology 1980;30: 582-7. 5. Berger R, Florent G, Just M. Decrease of lymphoproliferative response to varicella zoster virus antigen in the aged. Infect Immun 1981;32:24-7. 6. Arvin AM. Cell mediated immunity to varicella zoster virus. J Infect Dis 1992;166:S35-S41. 7. Arvin AM, Koropchak CM, Witteck AE. Immunologic evidence of reinfection with varicella zoster virus. J Infect Dis 1983;148:200-5. 8. Siegel SS. Nonparametric statistics for the behavioral sciences. New York: McGraw-Hill; 1956. 9. Donahue J, Choo P, Manson J, et al. Herpes zoster. Arch Intern Med 1995;155:1605-9. 10. Williamson J, Stokoe IH, Gray S, Fisher M, Smith A, McGhee A, et al. Old people at home, their under-reported needs. Lancet 1964;1:1117-20.
REFERENCES 1. Hope-Simpson RE. The nature of herpes zoster: a long term study and new hypothesis. Proc R Soc Lond 1965;58:9-20.
Severe neutropenia associated with oral terbinafine therapy Aditya K. Gupta, MD, FRCPC,a Gamini S. Soori, MD,b James Q. Del Rosso, DO,c Paul B. Bartos, MD,d and Neil H. Shear, MD, FRCPCa Toronto, Ontario, Canada; Omaha, Nebraska; Las Vegas, Nevada; and Canton, Ohio
Terbinafine is an oral allylamine antifungal agent that was approved in the United States for the treatment of dermatophyte onychomycosis in May 1996. As of October 1997 it is estimated that terbinafine has been used in 7.5 million patients worldwide. It is an effective agent that is used extensively to treat dermatophyte infections. Terbinafine has been found to be safe, and adverse effects are usually mild and transient. We describe From the Division of Dermatology, Department of Medicine, Sunnybrook Health Science Center and the University of Toronto, Torontoa; the Department of Medicine, Creighton University, Omahab; the Las Vegas Skin and Cancer Clinicsc; and Altman Hospital, Canton.d Reprints not available from the authors. J Am Acad Dermatol 1998;38:765-7. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/54/87876
a patient in whom severe neutropenia developed during treatment with oral terbinafine. CASE REPORT A 60-year-old white man was treated with terbinafine, 250 mg daily, for onychomycosis of the toenails. He had been taking yohimbine 1 tablet (5.4 mg) three times a day for impotence, a drug that, to our knowledge, is not associated with myelosuppression. The pretherapy laboratory values (complete blood cell count [CBC]) were as follows: hemoglobin, 14.2 gm/dl (normal, 13.7 to 16.9 gm/dl); leukocytes, 6900/mm3 (normal, 3400/mm3 to 9900/mm3); and platelet count, 197,000/mm3 (normal, 150,000/mm3 to 400,000/mm3). The differential count was neutrophils, 60%; absolute neutrophil count, 4100/mm3 (range, 1300/mm3 to 6200/mm3); lymphocytes, 23%; monocytes, 10%; eosinophils, 0.7%; and basophils, 1%. After approximately 6 weeks of terbinafine therapy, a
766 Brief communications sore throat developed and the patient became febrile. Two days later tenderness and erythema developed in the web space of the left foot. The patient became progressively ill with chills, generalized weakness, and headaches. He was febrile (102.8° F) with a tender, warm, erythematous area on the dorsum of the left foot and the third web space, in which there was a draining ulcer. Stomatitis and gingivitis were present with scattered, tender, purpuric lesions on the gums. There was no exanthem or other features (e.g., myalgia or arthralgia) suggestive of a viral infection. The leukocyte count was 1600/mm3 (normal, 4000/mm3 to 11,000/mm3); hemoglobin, 13.1 gm/dl (normal, 13.3 to 17.7 gm/dl); platelet count, 200,000/mm3 (normal, 150,000/mm3 to 400,000/mm3). The differential count was as follows: granulocytes, 0.7% (normal, 38% to 80%; absolute granulocyte count, 11/mm3); lymphocytes, 26% (normal, 15% to 50%); and monocytes, 73% (normal, 2% to 14%). Bone marrow examination revealed neutropenia and mild anemia, as well as a hypocellular marrow with marked myeloid hypoplasia. Myeloid maturation arrest was present. Cultures revealed Pseudomonas aeruginosa septicemia. The cellulitis in the left foot was caused by a Staphylococcus infection. Treatment included rehydration, intravenous antibiotics, and filgrastim (granulocyte colony-stimulating factor). The terbinafine and yohimbine were discontinued. The leukocyte count increased to 10,800/mm3 with 80% granulocytes. The patient made an uneventful recovery. He resumed yohimbine without any adverse effects. DISCUSSION
The hematologic abnormalities associated with terbinafine therapy in immunocompetent patients include agranulocytosis or severe neutropenia, leukopenia, lymphopenia, pancytopenia, thrombocytopenia, and anemia.1-4 Of the estimated 1.5 million patients worldwide treated with terbinafine as of September 1994, eight cases of blood dyscrasias were reported, in particular agranulocytosis, pancytopenia, and thrombocytopenia, which were possibly or probably related to terbinafine (1:187,500 or 12 cases per million patients exposed).3 If the average duration for which terbinafine is generally used is 3 months, it is estimated that for these 1.5 million patients the corresponding number of patient-years is 0.375 million, giving a projected rate of blood dyscrasias with terbinafine to be 32 per million patient-years. Recent results indicate that the incidence of severe neutropenia, including agranulocytosis, may be of the order 1:400,000, with less severe forms of neutropenia being more
Journal of the American Academy of Dermatology May 1998
common.5 Furthermore, the frequency of thrombocytopenia may be of the order of 1 in 200,000 patients using terbinafine5 (also data on file, Novartis Pharma AG). However, the exact incidence of blood dyscrasias associated with terbinafine therapy is not known, in part because many patients do not have routine CBC monitoring performed. Furthermore, in general, only a proportion of adverse events with any drug are reported. In some instances estimates of blood dyscrasias in the general population are available. For example, the incidence rate of agranulocytosis has been estimated to be 9 per million per year in an age- and sex-adjusted U.S. population in Minnesota, Michigan, and Florida.6 In Sweden, in the normal population, the overall and drug-induced incidence rates of thrombocytopenia were estimated to be 55.0 and 12.5 per million per year, respectively.7 The corresponding rate for aplastic anemia or pancytopenia was estimated at 24.6 per million per year.7 With World Health Organization (WHO) data, the duration between the onset of terbinafine therapy and the development of blood dyscrasia is 6.9 ± 0.5 weeks (mean ± standard error).* This is an approximate value because a report to the WHO does not indicate a definite association between the adverse event and the drug. There is no requirement in the United States to conduct hematologic monitoring in immunocompetent patients treated with terbinafine. This is consistent with the very low incidence of blood dyscrasias reported with terbinafine. In general, routine monitoring only becomes rational when the incidence of a severe adverse event exceeds 1:1000.8 The U.S. product monograph indicates that in patients with known or suspected immunodeficiency, physicians should consider monitoring CBCs when using terbinafine for longer than 6 weeks.4 Our patient illustrates that a blood dyscrasia can occur in an immunocompetent patient receiving terbinafine and that this can be potentially serious. Some physicians perform CBCs at baseline after 4 to 6 weeks of continuous terbinafine therapy in immunocompetent patients; however, the pattern of monitoring varies considerably. Counseling the patient about potential blood dyscrasias during terbinafine therapy is *Information obtained from the WHO on Dec. 5, 1996. The information is not homogeneous at least with respect to origin or likelihood that the pharmaceutical product caused the adverse reaction. The information does not represent the opinion of the WHO.
Journal of the American Academy of Dermatology Volume 38, Number 5, Part 1
important regardless of the monitoring frequency. This could include informing the patient that the drug should be discontinued and medical attention sought on the development of fever, sore throat, dyspnea, unusual fatigue, bleeding from any source, lymphadenopathy, or secondary infection.3 The patient should be aware that the development of any symptoms or signs is a rare occurrence, which may have a delayed onset (e.g., 4 to 8 weeks after the start of therapy). REFERENCES 1. Kovacs MJ, Alshamarri S, Guenther L, Bourcier M. Neutropenia and pancytopenia associated with oral terbinafine. J Am Acad Dermatol 1994;31:806.
Brief communications 767 2. Terbinafine: hematological disorders. Can Med Assoc J 1994;151:64. 3. Lamisil (terbinafine hydrochloride) Canadian Product Monograph, Sandoz Canada Inc., Dorval, Quebec. November 1995. 4. Lamisil (terbinafine hydrochloride) U.S. Product Monograph. Sandoz Pharmaceuticals Corporation, East Hanover, New Jersey. 1996. 5. Suhonen R, Neuvonen PJ. The tolerability profile of terbinafine. Rev Contemp Pharmacother 1997;8:373-86. 6. Strom BL, Carson JL, Schinnar R, Snyder ES, Sahw M. Descriptive epidemiology of agranulocytosis. Arch Intern Med 1992;152:1475-80. 7. Böttiger LE, Böttiger B. Incidence and cause of aplastic anemia, hemolytic anemia, agranulocytosis and thrombocytopenia. Acta Med Scand 1981;210:475-9. 8. Gupta AK, Shear NH. Terbinafine: an update. J Am Acad Dermatol 1997;37:979-88.
Multiple basal cell carcinomas of the limb after adjuvant treatment of melanoma with isolated limb perfusion Philina M. Lamb, BS,a Gregg M. Menaker, MD,a and Ronald L. Moy, MDa,b Los Angeles, California Chemotherapy by isolated limb perfusion for the treatment of solid tumors, particularly malignant melanoma, was first described in 1958 by Creech et al.1 Single-agent limb perfusion with nitrogen mustard has been used in treating malignant melanoma confined to the extremities. Nitrogen mustard, an alkylating agent, has been demonstrated to be a carcinogen systemically and has been reported to induce epithelial cancers in both sun-protected and sun-exposed areas when applied topically. Alkylating agents act by forming highly reactive free radicals that permanently rupture the hydrogen bonds between DNA strands and RNA strands. The DNA is modified such that delayed cell death occurs 3 to 7 days after lethal exposure. No long-term effects of limb perfusion with nitrogen mustard have been described, but topical application has been reported to induce epithelial neoplasms such as basal cell carcinoma (BCC), squamous cell carcinoma, keratoacanthoma, and actinic keratosis.2-6 From the Division of Dermatology, University of California, Los Angeles,a and Dermatologic Surgery, Veterans Administration– West Los Angeles Medical Center.b Reprint requests: Ronald L. Moy, MD, 100 UCLA Medical Plaza, Suite 590, Los Angeles, CA 90024-6970. J Am Acad Dermatol 1998;38:767-8. 16/54/88864
We describe a patient with a history of malignant melanoma who has been experiencing BCCs at a rapid rate in the left lower limb. It is the same limb in which isolated limb perfusion with nitrogen mustard was given approximately 26 years earlier for the adjunctive treatment of melanoma. CASE REPORT A 62-year-old white man was seen because of multiple BCCs. In one year, seven confined to the left lower extremity had appeared. He subsequently experienced 14 BCCs during the next 3 years. They were treated with Mohs surgery or curettage and electrodesiccation. He had experienced melanoma of the left anterior medial thigh approximately 26 years before this. Treatment had included a wide resection with subsequent lymph node dissection and isolated limb perfusion with nitrogen mustard. The patient denied any radiation exposure to the left leg. The melanoma has not recurred, although the BCCs continue. DISCUSSION
Chemotherapy by isolated limb perfusion is designed to maximize the effects in the affected limb while minimizing systemic toxicity. With isolated limb perfusion, drug concentrations within the tumor are more than ten times that achievable by intravenous administration.