- Email: [email protected]
Dacarbazine but not temozolomide induces phototoxic dermatitis in patients with malignant melanoma
BRIEF
REPORTS
Dacarbazine but not temozolomide induces phototoxic dermatitis in patients with malignant melanoma Regina Treudler, MD, Juliana Georgieva, MD, Christoph C. Geilen, MD, and Constantin E. Orfanos, MD Berlin, Germany Ten patients with malignant melanoma and phototoxic reactions under dacarbazine or 5-(3,3-dimethyl-1triazeno) imidazole-4-carboxamide (DTIC) chemotherapy were investigated. All patients available for testing showed increased ultraviolet A-sensitivity (n ⫽ 5); patch testing revealed no type IV allergies (n ⫽ 6). In 5 patients intravenous DTIC was replaced by oral temozolomide, and no phototoxicity occurred. Temozolomide may represent an alternative for patients with DTIC-induced phototoxic skin reactions. (J Am Acad Dermatol 2004;50:783-5.)
D
acarbazine or 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC) is one of the most commonly administered chemotherapeutic drugs in malignant melanoma, often used in combination with interferon alfa and/or other cytotoxic agents.1 In addition to its wellknown side effects on the gastrointestinal and hematopoetic systems (nausea, vomiting, leukothrombopenia, eosinophilia), it may induce adverse skin reactions. In particular, pruritic maculourticarial erythemas may appear in the light-exposed areas including the face, neck, hands, and arms. Frequently, phototoxic reactions due to DTIC are clinically seen only after a few well tolerated sessions of chemotherapy.2 Also, urticaria,3 fixed drug eruption,4 and radiation recall dermatitis5 have been reported. Widespread phototoxic reactions often require discontinuation of DTIC therapy and introduction of another chemotherapeutic regimen. In this study, we investigated patients with phototoxic reactions due to DTIC and aimed to find out if temozolomide, a new chemotherapeutic agent considered to exert antimelanoma activities compaFrom the Department of Dermatology, Charite´—University Medical School Berlin, Campus Benjamin Franklin. Funding source: None. Conflicts of interest: None identified. Reprint requests: Regina Treudler, MD, Department of Dermatology, Charite´—University Medical School Berlin, Campus Benjamin Franklin, Fabeckstrasse 60-62, 14195 Berlin, Germany. E-mail: [email protected]. 0190-9622/$30.00 © 2004 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2003.12.016
rable to that of DTIC, could be an alternative in these patients.
CASES Ten patients with malignant melanoma (stage IIaIV, Table I), aged 34-75 years (median 59.5 years) who presented with phototoxic reactions under DTIC therapy were investigated. All patients had received a combined immunochemotherapeutic schedule with DTIC in light protected infusion bags. DTIC (150 mg/m2 intravenously day 1-5), was in most cases applied in combination with other agents such as carmustine (100 mg/m2 intravenously day 2 every second session) and hydroxyurea (1500 mg/m2 by mouth day 1-5) once a month. In addition, patients received low-dose interferon alfa-2a (Roferon) (3 MU subcutaneously 3⫻ weekly) during the intervals. All patients were instructed not to expose themselves to direct sunlight during the 5 days of chemotherapy sessions. First symptoms of skin phototoxicity became clinically relevant in all patients during the 3rd to 16th sessions (median 6.5), presenting with sharply demarcated maculourticarial erythemas, mainly on the face and/or the extremities. The skin reactions were treated with sunscreen and topical corticosteroids and cleared soon. If DTIC was continued for further therapy, new phototoxic reactions appeared in all cases (7 patients), mostly with enhanced severity, leading to interruption of the administration of DTIC. Tests with varying ultraviolet (UV)-spectra were performed in 5 patients during the eruption, with ultraviolet A (UVA) doses ranging from 1 J/cm2 to 20 J/cm2 and ultraviolet B (UVB) of 10 mJ/cm2 to 50 mJ/cm2. In all patients tested, increased photosensi783
784 Brief reports
J AM ACAD DERMATOL MAY 2004
Table I. Clinical characteristics and test results of 10 patients with phototoxic reactions under DTIC therapy
Patient No.
Age (y)
Sex
Stage of disease at time of reaction
Regimen of immunochemotherapy
Chemotherapy cycle when first phototoxic reaction occurred
1 2 3 4 5 6 7 8 9 10
59 56 37 75 56 34 56 60 61 62
F M F F F F M M M M
IV IIIb IIIc IIa IV IIIb IIIb IIIb IIIa IIIb
IFN/BHD IFN/BHD IFN/BHD DTIC IFN/BHD IFN/BHD IFN/BHD IFN/BHD IFN/BHD IFN/BHD
10 16 6 7 5 3 3 6 5 3
UVA sensitivity increase under DTIC
Patch testing with DTIC
Therapy was continued with
yes yes n.d. n.d. yes n.d. yes n.d. n.d. n.d.
n.d. neg. n.d. neg. neg. neg. neg. n.d. neg. n.d.
IFN/vindesine IFN/TMD IFN/vindesine IFN/vindesine none IFN/TMD IFN/TMD IFN/TMD IFN/TMD IFN
BHD, BCNU/carmustine, hydroxyurea; DTIC, darcabazine; F, female; IFN, interferon-alfa-2a; M, male; n.d., not done; neg, negative; TMD, temozolomide; UVA, ultraviolet A.
Table II. Photodecomposition products of DTIC ● Dimethylamine ● 5-Diazolmidazole-4-carboxamide (Diazo-IC) ● 4-Carbamoylimidazolium-5-olate ● 5-Carbamoyl-2-(4-carbamoyliimidazol-5-ylazo) imidazolium-5-olate ● 2-Azahypoxanthine
tivity mainly to UVA with minimal erythema doses in the range of 15-20 J/cm2 was found. In addition, 6 patients who gave their consent were patch tested 2-10 weeks after the eruption had cleared; by using a strong dilution of DTIC (300 mg in 250 mL 0.9% NaCl diluted 1:10, 1:100, 1:1000 with 0.9% NaCl) no positive reactions were seen (24-72 hour readings). In 5 patients, polychemotherapy was switched to monochemotherapy with temozolomide (Temodal 150 mg/m2 by mouth day 1-5 once a month; Essex Pharma, Munich, Germany), while low-dose Interferon alfa-2a and other supportive drugs such as antiemetics and/or analgetics were continued. None of these patients showed any phototoxic reaction after oral intake of temozolomide after a maximum of 10 sessions.
DISCUSSION DTIC is an anticancer agent for intravenous use, which is unstable in solutions and may show rapid photodegradation after direct exposure to sunlight (Table II). Phototoxic reactions are reported to be mainly due to 2-azahypoxanthine, while Diazo-IC has been made responsible for local venous pain when injected intravenously.6-8
We observed phototoxic reactions in 10 of our patients with malignant melanoma under combined immunochemotherapy including DTIC. In all cases, there was a clear clinical association between the onset of skin reactions and the administration of DTIC. Moreover, all skin reactions disappeared after having stopped DTIC. In 5 patients available for testing, increased sensitivity to UVA was demonstrated during DTIC therapy. Considering the fact that DTIC is frequently given in melanoma patients, only a small number of patients seem to develop phototoxic reactions. For prevention, the DTIC infusion bags were protected from light, and all patients were given instructions to ensure the avoidance of UV exposure. Even though we cannot fully exclude low compliance in some, there seems to be a special predisposing pharmacogenetic factor, leading to different metabolization products of DTIC in each individual. Remarkably, the phototoxic reactions appeared only after several sessions of well-tolerated DTIC treatment, suggesting some type of sensitization process. However, patch testing to DTIC was found negative in all cases. Taking into account the clinical picture showing sharply demarcated erythemas on the lightexposed areas, we favor a phototoxic rather than a photoallergic reaction. It is unclear whether there is an accumulation of phototoxic products in skin, leading to clinical manifestation of symptoms only after a number of sessions. As an alternative, an ongoing decrease of enzymes that metabolize DTIC to MTIC (5-3-methyltriazen-1-yl-imidazo-4-carboxamide) may result in higher levels of available DTIC for in vivo photodegradation.
Brief reports 785
J AM ACAD DERMATOL VOLUME 50, NUMBER 5
In all our patients showing phototoxic reactions, treatment with intravenous DTIC was discontinued because (1) the eruptions became intolerable with increasing number of sessions, and (2) the phototoxic metabolite 2-azahypoxanthine may lack anticancer activity.7 Five of our patients received temozolomide and none of them suffered new phototoxic eruptions. Temozolomide is a novel oral cytotoxic agent similar to DTIC in its mechanisms of action and efficacy. It is active against a broad spectrum of tumors and is currently marketed in the countries of the European Union for treatment of patients with glioblastoma and anaplastic astrocytoma. The drug has also been administered to patients with malignant melanoma and shown to be effective.9,10 Temozolomide has been postulated to exert in vivo activities via its degradation product MTIC; its cytotoxic action has been reported to result from alkylation on the O6 and N7 positions of guanine. In addition, it can be taken orally and penetrates through the blood-brain barrier. Finally, DTIC is metabolically converted to MTIC in the liver, whereas temozolomide degrades spontaneously, rapidly, and predictably to MTIC at physiological pH levels.11,12 REFERENCES 1. Hauschild A, Garbe C, Stolz W, Ellwanger U, Seiter S, Dummer R, et al. Dacarbazine and interferon alfa with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG). Br J Cancer 2001;84:1036-42.
2. Ippen H. [Light-caused skin reaction in dacarbazine therapy.] Dtsch Med Wochenschr 1980;105:531. German. 3. Bourry C, Naveau C, Lazrak K, Celerier P, Pasquiou C. First case of urticaria due to dacarbazine. Therapie 1995;50:588-589. 4. Giguere JK, Douglas DM, Lupton GP, Baker JR, Weiss RB. Procarbazine hypersensitivity manifested as a fixed drug eruption. Med Pediatr Oncol 1988;16:378-80. 5. Kennedy RD, McAleer JJ. Radiation recall dermatitis in a patient treated with dacarbazine. Clin Oncol 2001;13:470-2. 6. Kim H, Likhari P, Parker A¨D, Statkevich P, Marco A, Lin CD, et al. High-performance liquid chromatographic analysis and stability of anti-tumor agent temozolomide in human plasma. J Pharm Biomed Anal 2001;24:461-468. 7. Aatmani ME, Poujol S, Astre C, Malosse F, Pinguet F. Stability of dacarbazine in amber glass vials and polyvinyl chloride bags. Am J Health Syst Pharm 2002;59:1351-1356. 8. Asahi M, Matsushita R, Kawahara M, Ishida T, Emoto C, Suzuki N, et al. Causative agent of vascular pain among photodegradation products of dacarbazine. J Pharm Pharmacol 2002;54:11171122. 9. Frick S, Lischner S, Rosien F, Haacke TC, Schafer F, Christophers E, et al. Temozolomide as therapeutic option for patients with metastatic melanoma and poor prognosis. Hautarzt 2002;53:659-665. 10. Danson S, Lorigan P, Arance A, Clamp A, Ranson M, Hodgetts J, et al. Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma. J Clin Oncol 2003;21:2551-7. 11. Stevens MF, Hickman JA, Langdon SP, Chubb D, Vickers L, Stone R, et al. Antitumor activity and pharmacokinetics in mice of 8-carbamoyl-3-methyl-imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)one (CCRG 81045; M & B 39831), a novel drug with potential as an alternative to dacarbazine. Cancer Res 1987;47:5846-52. 12. Tsang LL, Quarterman CP, Gescher A, Slack JA. Comparison of the cytotoxicity in vitro of temozolomide and dacarbazine, prodrugs of 3-methyl-(triazen-1-yl)imidazole-4-carboxamide. Cancer Chemother Pharmacol 1991;27:342-6.
Pyodermatitis-pyostomatitis vegetans with circulating autoantibodies to bullous pemphigoid antigen 230 Bong Kyun Ahn, MD, and Soo-Chan Kim, MD Seoul, Korea We describe a woman from Korea with pyodermatitis-pyostomatitis vegetans associated with ulcerative colitis. On immunofluorescence examination, she demonstrated in vivo bound and circulating IgG antibasement membrane zone antibodies. The immunoelectron microscopy and immunoblot analysis showed that the antibodies reacted with the bullous pemphigoid antigen 230. We consider that the circulating autoantibodies to the bullous pemphigoid antigen 230 in this patient were an epiphenomenon, resulting from epidermal damage induced by inflammation of pyodermatitis-pyostomatitis vegetans. (J Am Acad Dermatol 2004;50:785-8.) From the Department of Dermatology and Cutaneous Biology Research Institute, Yongdong Severance Hospital, Yonsei University College of Medicine. Supported by Brain Korea 21 project for Medical Science, Yonsei University. Conflict of interest: None identified. Reprint requests: Soo-Chan Kim, MD, Department of Dermatology
and Cutaneous Biology Research Institute, Yongdong Severance Hospital, Yonsei University College of Medicine, 14692, Dogok-dong, Kangnam-gu, Seoul 135-720, Korea. E-mail: [email protected]. 0190-9622/$30.00 © 2004 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2003.09.007
REPORTS
Dacarbazine but not temozolomide induces phototoxic dermatitis in patients with malignant melanoma Regina Treudler, MD, Juliana Georgieva, MD, Christoph C. Geilen, MD, and Constantin E. Orfanos, MD Berlin, Germany Ten patients with malignant melanoma and phototoxic reactions under dacarbazine or 5-(3,3-dimethyl-1triazeno) imidazole-4-carboxamide (DTIC) chemotherapy were investigated. All patients available for testing showed increased ultraviolet A-sensitivity (n ⫽ 5); patch testing revealed no type IV allergies (n ⫽ 6). In 5 patients intravenous DTIC was replaced by oral temozolomide, and no phototoxicity occurred. Temozolomide may represent an alternative for patients with DTIC-induced phototoxic skin reactions. (J Am Acad Dermatol 2004;50:783-5.)
D
acarbazine or 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC) is one of the most commonly administered chemotherapeutic drugs in malignant melanoma, often used in combination with interferon alfa and/or other cytotoxic agents.1 In addition to its wellknown side effects on the gastrointestinal and hematopoetic systems (nausea, vomiting, leukothrombopenia, eosinophilia), it may induce adverse skin reactions. In particular, pruritic maculourticarial erythemas may appear in the light-exposed areas including the face, neck, hands, and arms. Frequently, phototoxic reactions due to DTIC are clinically seen only after a few well tolerated sessions of chemotherapy.2 Also, urticaria,3 fixed drug eruption,4 and radiation recall dermatitis5 have been reported. Widespread phototoxic reactions often require discontinuation of DTIC therapy and introduction of another chemotherapeutic regimen. In this study, we investigated patients with phototoxic reactions due to DTIC and aimed to find out if temozolomide, a new chemotherapeutic agent considered to exert antimelanoma activities compaFrom the Department of Dermatology, Charite´—University Medical School Berlin, Campus Benjamin Franklin. Funding source: None. Conflicts of interest: None identified. Reprint requests: Regina Treudler, MD, Department of Dermatology, Charite´—University Medical School Berlin, Campus Benjamin Franklin, Fabeckstrasse 60-62, 14195 Berlin, Germany. E-mail: [email protected]. 0190-9622/$30.00 © 2004 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2003.12.016
rable to that of DTIC, could be an alternative in these patients.
CASES Ten patients with malignant melanoma (stage IIaIV, Table I), aged 34-75 years (median 59.5 years) who presented with phototoxic reactions under DTIC therapy were investigated. All patients had received a combined immunochemotherapeutic schedule with DTIC in light protected infusion bags. DTIC (150 mg/m2 intravenously day 1-5), was in most cases applied in combination with other agents such as carmustine (100 mg/m2 intravenously day 2 every second session) and hydroxyurea (1500 mg/m2 by mouth day 1-5) once a month. In addition, patients received low-dose interferon alfa-2a (Roferon) (3 MU subcutaneously 3⫻ weekly) during the intervals. All patients were instructed not to expose themselves to direct sunlight during the 5 days of chemotherapy sessions. First symptoms of skin phototoxicity became clinically relevant in all patients during the 3rd to 16th sessions (median 6.5), presenting with sharply demarcated maculourticarial erythemas, mainly on the face and/or the extremities. The skin reactions were treated with sunscreen and topical corticosteroids and cleared soon. If DTIC was continued for further therapy, new phototoxic reactions appeared in all cases (7 patients), mostly with enhanced severity, leading to interruption of the administration of DTIC. Tests with varying ultraviolet (UV)-spectra were performed in 5 patients during the eruption, with ultraviolet A (UVA) doses ranging from 1 J/cm2 to 20 J/cm2 and ultraviolet B (UVB) of 10 mJ/cm2 to 50 mJ/cm2. In all patients tested, increased photosensi783
784 Brief reports
J AM ACAD DERMATOL MAY 2004
Table I. Clinical characteristics and test results of 10 patients with phototoxic reactions under DTIC therapy
Patient No.
Age (y)
Sex
Stage of disease at time of reaction
Regimen of immunochemotherapy
Chemotherapy cycle when first phototoxic reaction occurred
1 2 3 4 5 6 7 8 9 10
59 56 37 75 56 34 56 60 61 62
F M F F F F M M M M
IV IIIb IIIc IIa IV IIIb IIIb IIIb IIIa IIIb
IFN/BHD IFN/BHD IFN/BHD DTIC IFN/BHD IFN/BHD IFN/BHD IFN/BHD IFN/BHD IFN/BHD
10 16 6 7 5 3 3 6 5 3
UVA sensitivity increase under DTIC
Patch testing with DTIC
Therapy was continued with
yes yes n.d. n.d. yes n.d. yes n.d. n.d. n.d.
n.d. neg. n.d. neg. neg. neg. neg. n.d. neg. n.d.
IFN/vindesine IFN/TMD IFN/vindesine IFN/vindesine none IFN/TMD IFN/TMD IFN/TMD IFN/TMD IFN
BHD, BCNU/carmustine, hydroxyurea; DTIC, darcabazine; F, female; IFN, interferon-alfa-2a; M, male; n.d., not done; neg, negative; TMD, temozolomide; UVA, ultraviolet A.
Table II. Photodecomposition products of DTIC ● Dimethylamine ● 5-Diazolmidazole-4-carboxamide (Diazo-IC) ● 4-Carbamoylimidazolium-5-olate ● 5-Carbamoyl-2-(4-carbamoyliimidazol-5-ylazo) imidazolium-5-olate ● 2-Azahypoxanthine
tivity mainly to UVA with minimal erythema doses in the range of 15-20 J/cm2 was found. In addition, 6 patients who gave their consent were patch tested 2-10 weeks after the eruption had cleared; by using a strong dilution of DTIC (300 mg in 250 mL 0.9% NaCl diluted 1:10, 1:100, 1:1000 with 0.9% NaCl) no positive reactions were seen (24-72 hour readings). In 5 patients, polychemotherapy was switched to monochemotherapy with temozolomide (Temodal 150 mg/m2 by mouth day 1-5 once a month; Essex Pharma, Munich, Germany), while low-dose Interferon alfa-2a and other supportive drugs such as antiemetics and/or analgetics were continued. None of these patients showed any phototoxic reaction after oral intake of temozolomide after a maximum of 10 sessions.
DISCUSSION DTIC is an anticancer agent for intravenous use, which is unstable in solutions and may show rapid photodegradation after direct exposure to sunlight (Table II). Phototoxic reactions are reported to be mainly due to 2-azahypoxanthine, while Diazo-IC has been made responsible for local venous pain when injected intravenously.6-8
We observed phototoxic reactions in 10 of our patients with malignant melanoma under combined immunochemotherapy including DTIC. In all cases, there was a clear clinical association between the onset of skin reactions and the administration of DTIC. Moreover, all skin reactions disappeared after having stopped DTIC. In 5 patients available for testing, increased sensitivity to UVA was demonstrated during DTIC therapy. Considering the fact that DTIC is frequently given in melanoma patients, only a small number of patients seem to develop phototoxic reactions. For prevention, the DTIC infusion bags were protected from light, and all patients were given instructions to ensure the avoidance of UV exposure. Even though we cannot fully exclude low compliance in some, there seems to be a special predisposing pharmacogenetic factor, leading to different metabolization products of DTIC in each individual. Remarkably, the phototoxic reactions appeared only after several sessions of well-tolerated DTIC treatment, suggesting some type of sensitization process. However, patch testing to DTIC was found negative in all cases. Taking into account the clinical picture showing sharply demarcated erythemas on the lightexposed areas, we favor a phototoxic rather than a photoallergic reaction. It is unclear whether there is an accumulation of phototoxic products in skin, leading to clinical manifestation of symptoms only after a number of sessions. As an alternative, an ongoing decrease of enzymes that metabolize DTIC to MTIC (5-3-methyltriazen-1-yl-imidazo-4-carboxamide) may result in higher levels of available DTIC for in vivo photodegradation.
Brief reports 785
J AM ACAD DERMATOL VOLUME 50, NUMBER 5
In all our patients showing phototoxic reactions, treatment with intravenous DTIC was discontinued because (1) the eruptions became intolerable with increasing number of sessions, and (2) the phototoxic metabolite 2-azahypoxanthine may lack anticancer activity.7 Five of our patients received temozolomide and none of them suffered new phototoxic eruptions. Temozolomide is a novel oral cytotoxic agent similar to DTIC in its mechanisms of action and efficacy. It is active against a broad spectrum of tumors and is currently marketed in the countries of the European Union for treatment of patients with glioblastoma and anaplastic astrocytoma. The drug has also been administered to patients with malignant melanoma and shown to be effective.9,10 Temozolomide has been postulated to exert in vivo activities via its degradation product MTIC; its cytotoxic action has been reported to result from alkylation on the O6 and N7 positions of guanine. In addition, it can be taken orally and penetrates through the blood-brain barrier. Finally, DTIC is metabolically converted to MTIC in the liver, whereas temozolomide degrades spontaneously, rapidly, and predictably to MTIC at physiological pH levels.11,12 REFERENCES 1. Hauschild A, Garbe C, Stolz W, Ellwanger U, Seiter S, Dummer R, et al. Dacarbazine and interferon alfa with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG). Br J Cancer 2001;84:1036-42.
2. Ippen H. [Light-caused skin reaction in dacarbazine therapy.] Dtsch Med Wochenschr 1980;105:531. German. 3. Bourry C, Naveau C, Lazrak K, Celerier P, Pasquiou C. First case of urticaria due to dacarbazine. Therapie 1995;50:588-589. 4. Giguere JK, Douglas DM, Lupton GP, Baker JR, Weiss RB. Procarbazine hypersensitivity manifested as a fixed drug eruption. Med Pediatr Oncol 1988;16:378-80. 5. Kennedy RD, McAleer JJ. Radiation recall dermatitis in a patient treated with dacarbazine. Clin Oncol 2001;13:470-2. 6. Kim H, Likhari P, Parker A¨D, Statkevich P, Marco A, Lin CD, et al. High-performance liquid chromatographic analysis and stability of anti-tumor agent temozolomide in human plasma. J Pharm Biomed Anal 2001;24:461-468. 7. Aatmani ME, Poujol S, Astre C, Malosse F, Pinguet F. Stability of dacarbazine in amber glass vials and polyvinyl chloride bags. Am J Health Syst Pharm 2002;59:1351-1356. 8. Asahi M, Matsushita R, Kawahara M, Ishida T, Emoto C, Suzuki N, et al. Causative agent of vascular pain among photodegradation products of dacarbazine. J Pharm Pharmacol 2002;54:11171122. 9. Frick S, Lischner S, Rosien F, Haacke TC, Schafer F, Christophers E, et al. Temozolomide as therapeutic option for patients with metastatic melanoma and poor prognosis. Hautarzt 2002;53:659-665. 10. Danson S, Lorigan P, Arance A, Clamp A, Ranson M, Hodgetts J, et al. Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma. J Clin Oncol 2003;21:2551-7. 11. Stevens MF, Hickman JA, Langdon SP, Chubb D, Vickers L, Stone R, et al. Antitumor activity and pharmacokinetics in mice of 8-carbamoyl-3-methyl-imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)one (CCRG 81045; M & B 39831), a novel drug with potential as an alternative to dacarbazine. Cancer Res 1987;47:5846-52. 12. Tsang LL, Quarterman CP, Gescher A, Slack JA. Comparison of the cytotoxicity in vitro of temozolomide and dacarbazine, prodrugs of 3-methyl-(triazen-1-yl)imidazole-4-carboxamide. Cancer Chemother Pharmacol 1991;27:342-6.
Pyodermatitis-pyostomatitis vegetans with circulating autoantibodies to bullous pemphigoid antigen 230 Bong Kyun Ahn, MD, and Soo-Chan Kim, MD Seoul, Korea We describe a woman from Korea with pyodermatitis-pyostomatitis vegetans associated with ulcerative colitis. On immunofluorescence examination, she demonstrated in vivo bound and circulating IgG antibasement membrane zone antibodies. The immunoelectron microscopy and immunoblot analysis showed that the antibodies reacted with the bullous pemphigoid antigen 230. We consider that the circulating autoantibodies to the bullous pemphigoid antigen 230 in this patient were an epiphenomenon, resulting from epidermal damage induced by inflammation of pyodermatitis-pyostomatitis vegetans. (J Am Acad Dermatol 2004;50:785-8.) From the Department of Dermatology and Cutaneous Biology Research Institute, Yongdong Severance Hospital, Yonsei University College of Medicine. Supported by Brain Korea 21 project for Medical Science, Yonsei University. Conflict of interest: None identified. Reprint requests: Soo-Chan Kim, MD, Department of Dermatology
and Cutaneous Biology Research Institute, Yongdong Severance Hospital, Yonsei University College of Medicine, 14692, Dogok-dong, Kangnam-gu, Seoul 135-720, Korea. E-mail: [email protected]. 0190-9622/$30.00 © 2004 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2003.09.007