Acute necrotizing myopathy and podophyllin toxicity: report of a fatal case

Oliveira, Acary Souza Bulle; Calia, Leandro Cortoni; Kiyomoto, Beatriz Hitomi; Póvoa, Eliane Focaccia; Schmidt, Beny; Gabbai, Alberto Alain

doi:10.1590/S0004-282X1996000200017

Abstracts

A 21 year old male ingested podophyllin in a suicide attempt. The disorder was marked by seizures, coma, peripheral neuropathy, renal failure and acute necrotizing myopathy, an unusual finding. The coma and systemic disturbances resolved within three weeks. The myopathy resolved in 7 weeks, demonstrating a high capacity of muscle recuperation. The sensorimotor peripheral neuropathy persisted until the patient's death 9 weeks after the ingestion, due to septicemia. This report confirms the transient central neurotoxicity of podophyllin and persistent peripheral neurotoxicity of podophyllin, and describes a reversible necrotizing myopathy associated to mitochondrial abnormalities, a still unreported feature of podophyllin toxicity.

podophyllin; acute toxicity; myopathy

Paciente de 21 anos, sexo masculino, ingeriu 20 mL de podofilina a 25% como tentativa de suicídio. O quadro clínico caracterizou-se por crises convulsivas, coma, neuropatia periférica, insuficiência renal e miopatia necrotizante aguda. O estado de coma e os distúrbios sistêmicos resolveram-se em 3 semanas. A miopatia resolveu-se em 7 semanas, demonstrando uma alta capacidade de recuperação muscular. A neuropatia periférica sensitivo-motora persistiu até o óbito do paciente, por septicemia, 9 semanas após a ingestão da podofilina. Esta descrição confirma os achados de literatura com alterações transitórias do sistema nervoso central e persistentes do nervo periférico relacionadas à podofilina, e descreve uma miopatia necrotizante associada com anormalidades mitocondriais, mas de caráter reversível, característica até então não reportada de toxicidade pela podofilina.

podofilina; toxicidade aguda; miopatia

Acute necrotizing myopathy and podophyllin toxicity: report of a fatal case

Miopatia necrotizante aguda e toxicidade por podofilina: relato de caso fatal

Acary Souza Bulle Oliveira^I; Leandro Cortoni Calia^II; Beatriz Hitomi Kiyomoto^II; Eliane Focaccia Póvoa^III; Beny Schmidt^IV; Alberto Alain Gabbai^V

^IDoutor em Neurologia pela Escola Paulista de Medicina (EPM) Universidade Federal de São Paulo (UNIFESP)

^IIPós-graduando da Disciplina de Neurologia da EPM-UNIFESP

^IIIMedicado Hospital Arthur Ribeiro Saboya

^IVProfessor Adjunto do Departamento de Anatomia Patológica da EPM-UNIFESP

^VLivre Docente em Neurologia pela EPM-UNIFESP

ABSTRACT

A 21 year old male ingested podophyllin in a suicide attempt. The disorder was marked by seizures, coma, peripheral neuropathy, renal failure and acute necrotizing myopathy, an unusual finding. The coma and systemic disturbances resolved within three weeks. The myopathy resolved in 7 weeks, demonstrating a high capacity of muscle recuperation. The sensorimotor peripheral neuropathy persisted until the patient's death 9 weeks after the ingestion, due to septicemia. This report confirms the transient central neurotoxicity of podophyllin and persistent peripheral neurotoxicity of podophyllin, and describes a reversible necrotizing myopathy associated to mitochondrial abnormalities, a still unreported feature of podophyllin toxicity.

Key words: podophyllin, acute toxicity, myopathy.

RESUMO - Paciente de 21 anos, sexo masculino, ingeriu 20 mL de podofilina a 25% como tentativa de suicídio. O quadro clínico caracterizou-se por crises convulsivas, coma, neuropatia periférica, insuficiência renal e miopatia necrotizante aguda. O estado de coma e os distúrbios sistêmicos resolveram-se em 3 semanas. A miopatia resolveu-se em 7 semanas, demonstrando uma alta capacidade de recuperação muscular. A neuropatia periférica sensitivo-motora persistiu até o óbito do paciente, por septicemia, 9 semanas após a ingestão da podofilina. Esta descrição confirma os achados de literatura com alterações transitórias do sistema nervoso central e persistentes do nervo periférico relacionadas à podofilina, e descreve uma miopatia necrotizante associada com anormalidades mitocondriais, mas de caráter reversível, característica até então não reportada de toxicidade pela podofilina.

Palavras-chave: podofilina, toxicidade aguda, miopatia.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Aceite: 3-janeiro-1996.

Dr Acary S.B. Oliveira - Disciplina de Neurologia, Escola Paulista de Medicina, UNIFESP - Rua Botucatu 762-04023-900 São Paulo SP - Brasil.

1. Beumer HM, Porton WM. Studies on the morphologic effect of cytotoxic drugs on tumor cells. Oncology 1967;21:221-228.
2. Campbell AN. Accidental poisoning with podophyllin. Lancet 1980;1:206-207.
3. Cassidy DE, Drewry J, Fanning JP. Podophyllum toxicity: a report of a fatal case and a review of the literature. J Toxicol Clin Toxicol 1982;19:35-44.
4. Chamberlain MJ, Reynolds Al, Yeoman WB. Toxic effect of podophyllum application in pregnancy. Br Med J 1972;3:391-392.
5. Chan YW. Magnetic resonance imaging in toxic encephalopathy due to podophyllin poisoning. Neuradiology 1991;33:372-373.
6. Chang MH, Lin KP, Wu ZA, Liao KK. Acute ataxic sensory neuronopathy resulting from podophyllin intoxication. Muscle & Nerve 1992:15:513-514.
7. Chapon F, Dupuy YB, Gosset S, Carjuzaa A, Berthelin C, Viader F, Lechevalier B. Intoxication accidentelle à la podophylline: un cas avec étude du nerf périphérique. Rev Neurol (Paris) 1991; 147:240-243.
8. Clark ANG, Parsonage MJ. A case of podophyllum poisoning with involvement of the nervous system. Br Med J 1957, 2:1155-1157.
9. Claus EP. Pharmacognosy. Ed 4. Philadelphia: Lea & Febiger, 1961:254-258.
10. Coruh M, Argun G. Podophyllin poisoning: a case report. Turk J Pediatr 1965;7:100-103.
11. Dubowitz V. Muscle biopsy: a practical approach. Ed 2. London: Bailliere Tindall, 1985:19-40.
12. Dudley WH. Fatal podophyllin poisoning. Med Rec 1890;37:409.
13. Filley CM, Graff-Radford NR, Lacy JR, Heitner MA, Earnest MP. Neurologic manifestations of podophyllin toxicity. Neurology 1982;32:308-311.
14. Georgatsos JG, Karembyilis R. Action of podophylline acid on malignant tumors:II. Effects of podophyllic acid etyl hydrazide on the incorporation of precursors into the nucleic acids of mouse mammary tumors and livers in vivo. Biochem Pharmacol 1968;17:1489-1492.
15. Kelleher JK. Correlation of tubulin-binding and anti-tumor activities of podophyllotoxin analogs. Cancer Treat Rep 1978;62:1443-1447.
16. O'Mahony S, Keohane C, Jacobs J, O'Riordain D, Whelton M. Neuropathy due to podophyllin intoxication. J Neurol 1990;237:110-112.
17. Prentiss DW. Effect of an overdose of podophyllin: amount taken about sixty centigrams (ten grains). Phil Med Times 1982;12:520.
18. Rate RG, Leche J, Chervenak C. Podophyllin toxicity. Ann Intern Med 1979;90:723.
19. Schirren CF. Schwere Allgemeinvergiftung nach Ortlicher Anwendung von Podophyllinspiritus bel spitzen Condylomen. Hautarzt 1966;17:321-322.
20. Slater GE, Rumack BH, Peterson RG. Podophyllin poisoning: systemic toxicity following cutaneous application. Obst Gynecol 1978; 52:94-96.
21. Stoehr GP, Peterson Al, Taylor WJ. Systemic complications of local podophyllin therapy. Ann Intern Med 1978;89:362-363.
22. Ward JW, Clifford WS, Monaco AR, Bickesrstaff HS. Fatal systemic poisoning following podophyllin treatment of condyloma acuminatum. Southern Med J 1954; 47:1204-1206.
23. West WM, Ridgeway NA, Morris AJ, Sides PJ. Fatal podophyllin ingestion. Sourthern Med J 1982;75:1269-1270.
24. Wisniewski H, Shelanski ML, Terry RD. Effects of mitotic spindle inhibitors on neurotubules and neurofilaments in anterior horn cells. J Cell Biol 1968; 38:224-229.

Publication Dates

Publication in this collection
06 Dec 2010
Date of issue
June 1996

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Beumer HM, Porton WM. Studies on the morphologic effect of cytotoxic drugs on tumor cells. Oncology 1967;21:221-228.

[2] 2. Campbell AN. Accidental poisoning with podophyllin. Lancet 1980;1:206-207.

[3] 3. Cassidy DE, Drewry J, Fanning JP. Podophyllum toxicity: a report of a fatal case and a review of the literature. J Toxicol Clin Toxicol 1982;19:35-44.

[4] 4. Chamberlain MJ, Reynolds Al, Yeoman WB. Toxic effect of podophyllum application in pregnancy. Br Med J 1972;3:391-392.

[5] 5. Chan YW. Magnetic resonance imaging in toxic encephalopathy due to podophyllin poisoning. Neuradiology 1991;33:372-373.

[6] 6. Chang MH, Lin KP, Wu ZA, Liao KK. Acute ataxic sensory neuronopathy resulting from podophyllin intoxication. Muscle & Nerve 1992:15:513-514.

[7] 7. Chapon F, Dupuy YB, Gosset S, Carjuzaa A, Berthelin C, Viader F, Lechevalier B. Intoxication accidentelle à la podophylline: un cas avec étude du nerf périphérique. Rev Neurol (Paris) 1991; 147:240-243.

[8] 8. Clark ANG, Parsonage MJ. A case of podophyllum poisoning with involvement of the nervous system. Br Med J 1957, 2:1155-1157.

[9] 9. Claus EP. Pharmacognosy. Ed 4. Philadelphia: Lea & Febiger, 1961:254-258.

[10] 10. Coruh M, Argun G. Podophyllin poisoning: a case report. Turk J Pediatr 1965;7:100-103.

[11] 11. Dubowitz V. Muscle biopsy: a practical approach. Ed 2. London: Bailliere Tindall, 1985:19-40.

[12] 12. Dudley WH. Fatal podophyllin poisoning. Med Rec 1890;37:409.

[13] 13. Filley CM, Graff-Radford NR, Lacy JR, Heitner MA, Earnest MP. Neurologic manifestations of podophyllin toxicity. Neurology 1982;32:308-311.

[14] 14. Georgatsos JG, Karembyilis R. Action of podophylline acid on malignant tumors:II. Effects of podophyllic acid etyl hydrazide on the incorporation of precursors into the nucleic acids of mouse mammary tumors and livers in vivo. Biochem Pharmacol 1968;17:1489-1492.

[15] 15. Kelleher JK. Correlation of tubulin-binding and anti-tumor activities of podophyllotoxin analogs. Cancer Treat Rep 1978;62:1443-1447.

[16] 16. O'Mahony S, Keohane C, Jacobs J, O'Riordain D, Whelton M. Neuropathy due to podophyllin intoxication. J Neurol 1990;237:110-112.

[17] 17. Prentiss DW. Effect of an overdose of podophyllin: amount taken about sixty centigrams (ten grains). Phil Med Times 1982;12:520.

[18] 18. Rate RG, Leche J, Chervenak C. Podophyllin toxicity. Ann Intern Med 1979;90:723.

[19] 19. Schirren CF. Schwere Allgemeinvergiftung nach Ortlicher Anwendung von Podophyllinspiritus bel spitzen Condylomen. Hautarzt 1966;17:321-322.

[20] 20. Slater GE, Rumack BH, Peterson RG. Podophyllin poisoning: systemic toxicity following cutaneous application. Obst Gynecol 1978; 52:94-96.

[21] 21. Stoehr GP, Peterson Al, Taylor WJ. Systemic complications of local podophyllin therapy. Ann Intern Med 1978;89:362-363.

[22] 22. Ward JW, Clifford WS, Monaco AR, Bickesrstaff HS. Fatal systemic poisoning following podophyllin treatment of condyloma acuminatum. Southern Med J 1954; 47:1204-1206.

[23] 23. West WM, Ridgeway NA, Morris AJ, Sides PJ. Fatal podophyllin ingestion. Sourthern Med J 1982;75:1269-1270.

[24] 24. Wisniewski H, Shelanski ML, Terry RD. Effects of mitotic spindle inhibitors on neurotubules and neurofilaments in anterior horn cells. J Cell Biol 1968; 38:224-229.