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Toxic Myopathies

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Abstract

Toxic myopathies are myopathies induced by drugs or toxins. This chapter discusses the clinical features and morphological, electrophysiological, and metabolic evidence of these myopathies. Our goal is to provide a framework that can be used to better recognize categories of muscle toxins, understand the mechanisms by which they cause muscle damage, identify risk factors which predispose patients to myopathy, and thereby enhance the ability to diagnose these disorders.

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References

  1. Maningat P, Breslow JL. Needed: pragmatic clinical trials for ­statin-intolerant patients. N Engl J Med. 2011;365(24):2250–1.

    Article  CAS  PubMed  Google Scholar 

  2. Kuncl RW. Agents and mechanisms of toxic myopathy. Curr Opin Neurol. 2009;22:506–15.

    Article  CAS  PubMed  Google Scholar 

  3. Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003;289:1681–90.

    Article  CAS  PubMed  Google Scholar 

  4. SEARCH Collaborative. SLCO1B1 variants and statin-induced myopathy – a genomewide study. N Engl J Med. 2008;359:789–99.

    Article  Google Scholar 

  5. Egan A, Colman E. Weighing the benefits of high-dose simvastatin against the risk of myopathy. N Engl J Med. 2011;365(4):285–7.

    Article  CAS  PubMed  Google Scholar 

  6. Poels PJE, Gabreëls FJM. Rhabdomyolysis: a review of the literature. Clin Neurol Neurosurg. 1993;95:175–92.

    Article  CAS  PubMed  Google Scholar 

  7. Grable-Esposito P, Katzberg HD, Greenberg SA, et al. Immune-mediated necrotizing myopathy associated with statins. Muscle Nerve. 2010;41:185–90.

    CAS  PubMed  Google Scholar 

  8. Needham M, Fabian V, Knezevic W, et al. Progressive myopathy with up-regulation of MHC-1 associated with statin therapy. Neuromuscul Disord. 2008;17(2):194–200.

    Article  Google Scholar 

  9. Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol. 2006;97:52C–60.

    Article  CAS  PubMed  Google Scholar 

  10. Gaist D, Rodriguez LAG, Huerta C, et al. Lipid-lowering drugs and risk of myopathy: a population-based follow-up study. Epidemiology. 2001;12:565–9.

    Article  CAS  PubMed  Google Scholar 

  11. Pasternak RC, Smith Jr SC, Bairey-Merz CN, et al. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. Circulation. 2002;106:1024–8.

    Article  PubMed  Google Scholar 

  12. Hennekens CH. Statin-induced myopathy: hypothesis about randomized evidence and clinical impressions. Am J Med. 2009;122:4–5.

    Article  PubMed  Google Scholar 

  13. McAdams M, Staffa J, Dal Pan G. Estimating the extent of reporting to FDA: a case study of statin-associated rhabdomyolysis. Pharmacoepidemiol Drug Saf. 2008;17:229–39.

    Article  CAS  PubMed  Google Scholar 

  14. Davidson MH, Clark JA, Glass LM, Kanumalla A. Statin safety: an appraisal from the Adverse Event Reporting System. Am J Cardiol. 2006;97:S32–43.

    Article  CAS  Google Scholar 

  15. Silva MA, Swanson AC, Gandhi PJ, Tataronis GR. Statin-related adverse events: a meta-analysis. Clin Ther. 2006;28:26–35.

    Article  CAS  PubMed  Google Scholar 

  16. Ahmad S, Madsen CS, Stein PD, et al. (3R,5S,E)-7-(4-(4-fluorophenyl)-6-isopropyl-2-(methyl(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoic acid (BMS-644950): a rationally designed orally efficacious 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor with reduced myotoxicity potential. J Med Chem. 2008;51:2722–33.

    Article  CAS  PubMed  Google Scholar 

  17. Westwood FR, Bigley A, Randall K, et al. Statin-induced muscle necrosis in the rat: distribution, development, and fibre selectivity. Toxicol Pathol. 2005;33:246–57.

    Article  CAS  PubMed  Google Scholar 

  18. Corsini A, Bellosta S, Baetta R, et al. New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacol Ther. 1999;84:413–28.

    Article  CAS  PubMed  Google Scholar 

  19. Kobayashi M, Chisaki I, Narumi K, et al. Association between risk of myopathy and cholesterol lowering effect: a comparison of all statins. Life Sci. 2008;82:969–75.

    Article  CAS  PubMed  Google Scholar 

  20. Sakamoto K, Mikami H, Kimura J. Involvement of organic anion transporting polypeptides in the toxicity of hydrophilic pravastatin and lipophilic fluvastatin in rat skeletal myofibres. Br J Pharmacol. 2008;154:1482–90.

    Article  CAS  PubMed  Google Scholar 

  21. Flint OP, Masters BA, Gregg RE, Durham SK. Inhibition of cholesterol synthesis by squalene synthase inhibitors does not induce myotoxicity in vitro. Toxicol Appl Pharmacol. 1997;145:91–8.

    Article  CAS  PubMed  Google Scholar 

  22. Vaklavas C, Chatzizisis YS, Ziakas A, et al. Molecular basis of statin-associated myopathy. Atherosclerosis. 2009;202:18–28.

    Article  CAS  PubMed  Google Scholar 

  23. Sakamoto K, Wada I, Kimura J. Inhibition of Rab1 GTPase and endoplasmic reticulum-to-Golgi trafficking underlies statin’s toxicity in rat skeletal muscle. J Pharmacol Exp Ther. 2011;338:62–9.

    Article  CAS  PubMed  Google Scholar 

  24. Flint OP, Masters BA, Gregg RE, Durham SK. HMG Co-A reductase inhibitor-induced myotoxicity: pravastatin and lovastatin inhibit the geranylgeranylation of low-molecular-weight proteins in neonatal rat muscle cell cultures. Toxicol Appl Pharmacol. 1997;145:99–110.

    Article  CAS  PubMed  Google Scholar 

  25. Laaksonen R, Jokelainen K, Sahi T, et al. Decreases in serum ubiquinone concentrations do not result in reduced levels in muscle tissue during short-term simvastatin treatment in humans. Clin Pharmacol Ther. 1995;57:62–6.

    Article  CAS  PubMed  Google Scholar 

  26. Laaksonen R, Jokelainen K, Laakso J, et al. The effect of simvastatin treatment on natural antioxidants in low-density lipoproteins and high-energy phosphates and ubiquinone in skeletal muscle. Am J Cardiol. 1996;77:851–4.

    Article  CAS  PubMed  Google Scholar 

  27. Schaars CF, Stalenhoef AFH. Effects of ubiquinone (coenzyme Q10) on myopathy in statin users. Curr Opin Lipidol. 2008;19:553–7.

    Article  CAS  PubMed  Google Scholar 

  28. Waclawik AJ, Lindal S, Engel AG. Experimental lovastatin myopathy. J Neuropathol Exp Neurol. 1993;52:542–9.

    Article  CAS  PubMed  Google Scholar 

  29. Schaefer WH, Lawrence JW, Loughlin AE, et al. Evaluation of ubiquinone concentration and mitochondrial function relative to cerivastatin-induced skeletal muscle myopathy in rats. Toxicol Appl Pharmacol. 2004;194:10–23.

    Article  CAS  PubMed  Google Scholar 

  30. Nakahara K, Kuriyama M, Yoshidome H, et al. Experimental simvastatin-induced myopathy in rabbits. J Neurol Sci. 1992;113:114–7.

    Article  CAS  PubMed  Google Scholar 

  31. Phillips PS, Haas RH, Bannykh S, et al. Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med. 2002;137:581–5.

    Article  PubMed  Google Scholar 

  32. Liantonio A, Giannuzzi V, Cippone V, et al. Fluvastatin and atorvastatin affect calcium homeostasis of rat skeletal muscle fibers in vivo and in vitro by impairing the sarcoplasmic reticulum/mitochondria Ca2+-release system. J Pharmacol Exp Ther. 2007;321:626–34.

    Article  CAS  PubMed  Google Scholar 

  33. Sirvent P, Mercier J, Lacampagne A. New Insights into mechanisms of statin-associated myotoxicity. Curr Opin Pharmacol. 2008;8:333–8.

    Article  CAS  PubMed  Google Scholar 

  34. Nakamura Y. Pharmacogenomics and drug toxicity. N Engl J Med. 2008;359:856–8.

    Article  CAS  PubMed  Google Scholar 

  35. Voora D, Shah SH, Spasojevic I, et al. The SLC01B1*5 genetic variant is associated with statin-induced side effects. J Am Coll Cardiol. 2009;5(17):1609–16.

    Article  CAS  Google Scholar 

  36. Rodrigues AC, Hirata MH, Hirata RDC. The genetic determinants of atorvastatin response. Curr Opin Mol Ther. 2007;9:545–53.

    CAS  PubMed  Google Scholar 

  37. Vladutiu GD. Genetic predisposition to statin myopathy. Curr Opin Rheumatol. 2008;20:648–56.

    Article  CAS  PubMed  Google Scholar 

  38. Wilke RA, Lin DW, Roden DM, et al. Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges. Nat Rev Drug Discov. 2007;6:904–16.

    Article  CAS  PubMed  Google Scholar 

  39. Omar MA, Wilson JP, Cox RS. Rhabdomyolysis and HMG-CoA reductase inhibitors. Ann Pharmacother. 2001;35:1096–107.

    Article  CAS  PubMed  Google Scholar 

  40. Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006;80:565–81.

    Article  CAS  PubMed  Google Scholar 

  41. Desager JP, Horsmans Y. Clinical pharmacokinetics of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. Clin Pharmacokinet. 1996;31:348–71.

    Article  CAS  PubMed  Google Scholar 

  42. Beaird SL. HMG-CoA reductase inhibitors: assessing differences in drug interactions and safety profiles. J Am Pharm Assoc. 2000;40:637–44.

    CAS  Google Scholar 

  43. Vassallo JD, Janovitz EB, Wescott DM, et al. Biomarkers of drug-induced skeletal muscle injury in the rat: troponin I and myoglobin. Toxicol Sci. 2009;111(2):402–12.

    Article  CAS  PubMed  Google Scholar 

  44. Pritt NM, Hall DG, Recknor J, et al. Fabp3 as a biomarker of skeletal muscle toxicity in the rat: comparison with conventional ­biomarkers. Toxicol Sci. 2008;103(2):382–96.

    Article  CAS  PubMed  Google Scholar 

  45. Aranibar N, Vassallo JD, Rathmacher J, et al. Identification of 1- and 3-methylhistidine as biomarkers of skeletal muscle toxicity by nuclear magnetic resonance-based metabolic profiling. Anal Biochem. 2011;410(1):84–91.

    Article  CAS  PubMed  Google Scholar 

  46. Wu J, Buettner C, Smithline H, Ngo LH, Greenman RL. Evaluation of skeletal muscle during calf exercise by 31-phosphorous ­magnetic resonance spectroscopy in patients on statin medications. Muscle Nerve. 2011;43:76–81.

    Article  CAS  PubMed  Google Scholar 

  47. McKenney JM, Davidson MH, Jacobson TA, Guyton JR. Final conclusions and recommendations of the National Lipid Association statin safety assessment task force. Am J Cardiol. 2006;97(supp):89C–94.

    Article  CAS  PubMed  Google Scholar 

  48. Abd TT, Jacobson TA. Statin-induced myopathy: a review and update. Expert Opin Drug Saf. 2011;10(3):373–87.

    Article  CAS  PubMed  Google Scholar 

  49. Heber D, Yip I, Ashley JM, et al. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr. 1999;69:231–6.

    CAS  PubMed  Google Scholar 

  50. Prasad GVR, Wong T, Meliton G, Bhaloo S. Rhabdomyolysis due to red yeast rice (Monascus purpureus) in a renal transplant ­recipient. Transplantation. 2002;74:1200–1.

    Article  PubMed  Google Scholar 

  51. Xu D-Y, Shu J, Huang Q-Y, Wasti B, Chen C, Liu L, et al. Evaluation of the lipid lowering ability, anti-inflammatory effects and clinical safety of intensive therapy with Zhibitai, a Chinese traditional ­medicine. Atherosclerosis. 2010;211:237–41.

    Article  CAS  PubMed  Google Scholar 

  52. Lapi F, Gallo E, Bernasconi S, et al. Myopathies associated with red yeast rice and liquorice: spontaneous reports from the Italian Surveillance System of Natural Health Products. Br J Clin Pharmacol. 2008;66:572–4.

    Article  PubMed  Google Scholar 

  53. Smith DJ, Olive KE. Chinese red rice-induced myopathy. South Med J. 2003;96:1265–7.

    Article  PubMed  Google Scholar 

  54. Mueller PS. Symptomatic myopathy due to red yeast rice. Ann Intern Med. 2006;145:474–5.

    Article  PubMed  Google Scholar 

  55. Kwiecinski H. Myotonia induced with clofibrate in rats. J Neurol. 1978;219:107–16.

    Article  CAS  PubMed  Google Scholar 

  56. Dromgoole SH, Campion DS, Peter JB. Myotonia induced by clofibrate and sodium chlorophenoxy isobutyrate. Biochem Med. 1975;14:238–40.

    Article  CAS  PubMed  Google Scholar 

  57. Goldberg AP, Sherrard DJ, Haas LB, Brunzell JD. Control of clofibrate toxicity in uremic hypertriglyceridemia. Clin Pharmacol Ther. 1977;21:317–25.

    CAS  PubMed  Google Scholar 

  58. Bridgman JF, Rosen SM, Thorp JM. Complications during clofibrate treatment of nephrotic-syndrome hyperlipoproteinaemia. Lancet. 1972;2(7776):506–9.

    Article  CAS  PubMed  Google Scholar 

  59. Iliadis EA, Rosenson RS. Long-term safety of pravastatin-gemfibrozil therapy in mixed hyperlipidemia. Clin Cardiol. 1999;22:25–8.

    Article  CAS  PubMed  Google Scholar 

  60. Murdock DK, Murdock AK, Murdock RW, et al. Long-term safety and efficacy of combination gemfibrozil and HMG-CoA reductase inhibitors for the treatment of mixed lipid disorders. Am Heart J. 1999;138:151–5.

    Article  CAS  PubMed  Google Scholar 

  61. Rannels SR, Rannels DE, Pegg AE, Jefferson LS. Glucocorticoid effects on peptide-chain initiation in skeletal muscle and heart. Am J Physiol. 1978;235(2):E134–9.

    CAS  PubMed  Google Scholar 

  62. Wing SS, Goldberg AL. Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting. Am J Physiol. 1993;264(4 Pt 1):E668–76.

    CAS  PubMed  Google Scholar 

  63. Medina R, Wing SS, Goldberg AL. Increase in levels of polyubiquitin and proteasome mRNA in skeletal muscle during starvation and denervation atrophy. Biochem J. 1995;307:631–7.

    CAS  PubMed  Google Scholar 

  64. Mitch WE, Goldberg AL. Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. N Engl J Med. 1996;335:1897–905.

    Article  CAS  PubMed  Google Scholar 

  65. Rock KL, Gramm C, Rothstein L, et al. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell. 1994;78:761–71.

    Article  CAS  PubMed  Google Scholar 

  66. Minetto MA, Lanfranco F, Motta G, Allasia S, Arvat E, D’Antona GD. Steroid myopathy: some unresolved issues. J Endocrinol Invest. 2011;34:370–5.

    CAS  PubMed  Google Scholar 

  67. Rich MM, Pinter MJ, Kraner SD, Barchi RL. Loss of electrical excitability in an animal model of acute quadriplegic myopathy. Ann Neurol. 1998;43:171–9.

    Article  CAS  PubMed  Google Scholar 

  68. Ruff RL, Stuhmer W, Almers W. Effect of glucocorticoid treatment on the excitability of rat skeletal muscle. Pflugers Archiv – Eur J Physiol. 1982;395:132–7.

    Article  CAS  Google Scholar 

  69. Ruff RL, Martyn D, Gordon AM. Glucocorticoid-induced atrophy is not due to impaired excitability of rat muscle. Am J Physiol. 1982;243(6):E512–21.

    CAS  PubMed  Google Scholar 

  70. Pleasure DE, Walsh GO, Engel WK. Atrophy of skeletal muscle in patients with Cushing’s syndrome. Arch Neurol. 1970;22:118–25.

    Article  CAS  PubMed  Google Scholar 

  71. Bowyer SL, LaMothe MP, Hollister JR. Steroid myopathy: incidence and detection in a population with asthma. J Allergy Clin Immunol. 1985;76:234–42.

    Article  CAS  PubMed  Google Scholar 

  72. Afifi AK, Bergman RA, Harvey JC. Steroid myopathy. Clinical, histologic and cytologic observations. Johns Hopkins Med J. 1968;123(4):158–73.

    CAS  PubMed  Google Scholar 

  73. Engel AG. Electron microscopic observations in thyrotoxic and corticosteroid-induced myopathies. Mayo Clin Proc. 1966;41:785–96.

    CAS  PubMed  Google Scholar 

  74. Jaspers SR, Tischler ME. Role of glucocorticoids in the response of rat leg muscles to reduced activity. Muscle Nerve. 1986;9:554–61.

    Article  CAS  PubMed  Google Scholar 

  75. Horber FF, Hoopeler H, Scheidegger JR, et al. Impact of physical training on the ultrastructure of midthigh muscle in normal subjects and in patients treated with glucocorticoids. J Clin Invest. 1987;79:1181–90.

    Article  CAS  PubMed  Google Scholar 

  76. Kuncl RW, Wiggins WW. Toxic myopathies. Neurol Clin. 1988;6(3):593–619.

    CAS  PubMed  Google Scholar 

  77. Drenckhahn D, Lullmann-Rauch R. Experimental myopathy induced by amphiphilic cationic compounds including several psychotropic drugs. Neurosci. 1979;4:549–62.

    Article  CAS  Google Scholar 

  78. Hruban Z. Pulmonary and generalized lysosomal storage induced by amphiphilic drugs. Environ Health Perspect. 1984;55:53–76.

    Article  CAS  PubMed  Google Scholar 

  79. Saito K, Kakei M, Uchimura S, Kashima T, Tanaka H. Toxic effects of chlorpromazine on red and white muscles in rats: an ultrastructural study. Toxicol Appl Pharmacol. 1982;65:347–53.

    Article  CAS  PubMed  Google Scholar 

  80. Macdonald RD, Engel AG. Experimental chloroquine myopathy. J Neuropathol Exp Neurol. 1970;29:479–99.

    Article  CAS  PubMed  Google Scholar 

  81. Tsuzuki K, Fukatsu R, Takamaru Y, et al. Immunohistochemical evidence for amyloid beta in rat soleus muscle in chloroquine-induced myopathy. Neurosci Lett. 1994;182:151–4.

    Article  CAS  PubMed  Google Scholar 

  82. Tsuzuki K, Fukatsu R, Takamaru Y, et al. Co-localization of amyloid-associated proteins with amyloid beta in rat soleus muscle in chloroquine-induced myopathy: a possible model for amyloid beta formation in Alzheimer’s disease. Brain Res. 1995;699:260–5.

    Article  CAS  PubMed  Google Scholar 

  83. Tsuzuki K, Fukatsu R, Takamaru Y, et al. Amyloid beta protein in rat soleus muscle in chloroquine-induced myopathy using end-specific antibodies for A beta 40 and A beta 42: immunohistochemical evidence for amyloid beta protein. Neurosci Lett. 1995;202:77–80.

    Article  CAS  PubMed  Google Scholar 

  84. Tsuzuki K, Fukatsu R, Takamaru Y, et al. Snake coiled fibres in rat soleus muscle in chloroquine induced myopathy share immunohistochemical characteristics with amyloid depositions in Alzheimer’s disease brain tissue. Int J Exp Pathol. 1997;78:1–8.

    Article  CAS  PubMed  Google Scholar 

  85. Kumamoto T, Araki S, Watanabe S, et al. Experimental chloroquine myopathy: morphological and biochemical studies. Eur Neurol. 1989;29:202–7.

    Article  CAS  PubMed  Google Scholar 

  86. Kumamoto T, Ueyama H, Watanabe S, et al. Effect of denervation on overdevelopment of chloroquine-induced autophagic vacuoles in skeletal muscles. Muscle Nerve. 1993;16:819–26.

    Article  CAS  PubMed  Google Scholar 

  87. Murakami N, Oyama F, Gu Y, McLennan IS, Nonaka I, Ihara Y. Accumulation of tau in autophagic vacuoles in chloroquine myopathy. J Neuropathol Exp Neurol. 1998;57:664–73.

    Article  CAS  PubMed  Google Scholar 

  88. Murakami N, Ihara Y, Nonaka I. Chloroquine treated rat: a possible model for Alzheimer’s disease. Muscle Nerve. 1995;18:123–5.

    Article  CAS  PubMed  Google Scholar 

  89. Estes ML, Ewing-Wilson D, Chou SM, Mitsumoto H, Hanson M, Shirey E, et al. Chloroquine neuromyotoxicity. Clinical and pathologic perspective. Am J Med. 1987;82:447–55.

    Article  CAS  PubMed  Google Scholar 

  90. Clouston PD, Donnelly PE. Acute necrotising myopathy associated with amiodarone therapy. Aust N Z J Med. 1989;19:483–5.

    Article  CAS  PubMed  Google Scholar 

  91. Meier C, Kauer B, Muller U, Ludin HP. Neuromyopathy during chronic amiodarone treatment. A case report. J Neurol. 1979;220:231–9.

    Article  CAS  PubMed  Google Scholar 

  92. Fernando Roth R, Itabashi H, Louie J, et al. Amiodarone toxicity: myopathy and neuropathy. Am Heart J. 1990;119:1223–5.

    Article  CAS  PubMed  Google Scholar 

  93. Slotwiner P, Song SK, Anderson PJ. Spheromembranous degeneration of muscle induced by vincristine. Arch Neurol. 1966;15:172–6.

    Article  CAS  PubMed  Google Scholar 

  94. Bradley WG, Lassman LP, Pearce GW, Walton JN. The neuromyopathy of vincristine in man. Clinical, electrophysiological and pathological studies. J Neurol Sci. 1970;10:107–31.

    Article  CAS  PubMed  Google Scholar 

  95. Bradley WG. The neuromyopathy of vincristine in the guinea pig. An electrophysiological and pathological study. J Neurol Sci. 1970;10:133–62.

    Article  CAS  PubMed  Google Scholar 

  96. Wakayama Y, Sobue I. A tissue culture study of the toxic effect of vincristine on skeletal muscle. Exp Neurol. 1977;55:112–21.

    Article  CAS  PubMed  Google Scholar 

  97. Clarke JT, Karpati G, Carpenter S, Wolfe LS. The effect of vincristine on skeletal muscle in the rat. A correlative histochemical, ultrastructural and chemical study. J Neuropathol Exp Neurol. 1972;31:247–66.

    Article  CAS  PubMed  Google Scholar 

  98. Riggs JE, Schochet Jr SS, Gutmann L, et al. Chronic human colchicine neuropathy and myopathy. Arch Neurol. 1986;43:521–3.

    Article  CAS  PubMed  Google Scholar 

  99. Kuncl RW, Duncan G, Watson D, et al. Colchicine myopathy and neuropathy. N Engl J Med. 1987;316:1562–8.

    Article  CAS  PubMed  Google Scholar 

  100. Markand ON, D’Agostino AN. Ultrastructural changes in skeletal muscle induced by colchicine. Arch Neurol. 1971;24:72–82.

    Article  CAS  PubMed  Google Scholar 

  101. Himmelmann F, Schroder JM. Colchicine myopathy in a case of familial Mediterranean fever: immunohistochemical and ultrastructural study of accumulated tubulin-immunoreactive material. Acta Neuropathol. 1992;83:440–4.

    Article  CAS  PubMed  Google Scholar 

  102. Kuncl RW, Bilak MM, Craig SW, Adams R. Exocytotic “constipation” is a mechanism of tubulin/lysosomal interactions in colchicine myopathy. Exp Cell Res. 2003;285:196–207.

    Article  CAS  PubMed  Google Scholar 

  103. Kuncl RW, Cornblath DR, Avila O, Duncan G. Electrodiagnosis of human colchicine myoneuropathy. Muscle Nerve. 1989;12:360–4.

    Article  CAS  PubMed  Google Scholar 

  104. Wallace SL, Singer JZ, Duncan GJ, Wigley FM, Kuncl RW. Renal function predicts colchicine toxicity: guidelines for the prophylactic use of colchicine in gout. J Rheumatol. 1991;18:264–9.

    CAS  PubMed  Google Scholar 

  105. Cohen AS, Rubinow A, Anderson JJ, et al. Survival of patients with primary (AL) amyloidosis. Colchicine-treated cases from 1976 to 1983 compared with cases seen in previous years (1961 to 1973). Am J Med. 1987;82:1182–90.

    Article  CAS  PubMed  Google Scholar 

  106. Kaplan MM, Alling DW, Zimmerman HJ, et al. A prospective trial of colchicine for primary biliary cirrhosis. N Engl J Med. 1986;315:1448–54.

    Article  CAS  PubMed  Google Scholar 

  107. Lemor M, de Bustros S, Glaser BM. Low-dose colchicine inhibits astrocyte, fibroblast, and retinal pigment epithelial cell migration and proliferation. Arch Ophthalmol. 1986;104:1223–5.

    Article  CAS  PubMed  Google Scholar 

  108. Rieger EH, Halasz NA, Wahlstrom HE. Colchicine neuromyopathy after renal transplantation. Transplantation. 1990;49:1196–8.

    Article  CAS  PubMed  Google Scholar 

  109. Ducloux D, Schuller V, Bresson-Vautrin C, Chalopin JM. Colchicine myopathy in renal transplant recipients on cyclosporin. Nephrol Dial Transplant. 1997;12:2389–92.

    Article  CAS  PubMed  Google Scholar 

  110. Rana SS, Giuliani MJ, Oddis CV, Lacomis D. Acute onset of colchicine myoneuropathy in cardiac transplant recipients: case studies of three patients. Clin Neurol Neurosurg. 1997;99:266–70.

    Article  CAS  PubMed  Google Scholar 

  111. Hsu W-C, Chen W-H, Chang M-T, Chiu H-C. Colchicine-induced acute myopathy in a patient with concomitant use of simvastatin. Clin Neuropharmacol. 2002;25:266–8.

    Article  PubMed  Google Scholar 

  112. Tateishi T, Soucek P, Caraco Y, et al. Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation. Biochem Pharmacol. 1997;53:111–6.

    Article  CAS  PubMed  Google Scholar 

  113. Ucar M, Myorndal T, Dahlqvist R. HMG-CoA reductase inhibitors and myotoxicity. Drug Saf. 2000;22:441–57.

    Article  CAS  PubMed  Google Scholar 

  114. Simpson DM, Citak KA, Godfrey E, et al. Myopathies associated with human immunodeficiency virus and zidovudine: can their effects be distinguished? Neurology. 1993;43:971–6.

    Article  CAS  PubMed  Google Scholar 

  115. Kieburtz K. HIV or zidovudine myopathy? Neurology. 1994;44:361–4.

    Article  CAS  PubMed  Google Scholar 

  116. Gherardi RK, Florea-Strat A, Fromont G, et al. Cytokine expression in the muscle of HIV-infected patients: evidence for interleukin-1 alpha accumulation in mitochondria of AZT fibers. Ann Neurol. 1994;36:752–8.

    Article  CAS  PubMed  Google Scholar 

  117. Arnaudo E, Dalakas M, Shanske S, et al. Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy. Lancet. 1991;337(8740):508–10.

    Article  CAS  PubMed  Google Scholar 

  118. Mhiri C, Baudrimont M, Bonne G, et al. Zidovudine myopathy: a distinctive disorder associated with mitochondrial dysfunction. Ann Neurol. 1991;29(6)):606–14.

    Article  CAS  PubMed  Google Scholar 

  119. Dalakas MC, Leon-Monzon ME, Bernardini I, et al. Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage. Ann Neurol. 1994;35(4):482–7.

    Article  CAS  PubMed  Google Scholar 

  120. de la Asuncion JG, del Olmo ML, Sastre J, et al. AZT treatment induces molecular and ultrastructural oxidative damage to muscle mitochondria. Prevention by antioxidant vitamins. J Clin Invest. 1998;102:4–9.

    Article  PubMed  Google Scholar 

  121. Semino-Mora MC, Leon-Monzon ME, Dalakas MC. Effect of L-carnitine on the zidovudine-induced destruction of human myotubes. Part I: L-carnitine prevents the myotoxicity of AZT in vitro. Lab Invest. 1994;71:102–12.

    CAS  PubMed  Google Scholar 

  122. Semino-Mora MC, Leon-Monzon ME, Dalakas MC. The effect of L-carnitine on the AZT-induced destruction of human myotubes. Part II: Treatment with L-carnitine improves the AZT-induced changes and prevents further destruction. Lab Invest. 1994;71:773–81.

    CAS  PubMed  Google Scholar 

  123. Campos Y, Huertas R, Bautista J, et al. Muscle carnitine deficiency and lipid storage myopathy in patients with mitochondrial myopathy. Muscle Nerve. 1993;16:778–81.

    Article  CAS  PubMed  Google Scholar 

  124. Campos Y, Arenas J. Muscle carnitine deficiency associated with zidovudine-induced mitochondrial myopathy. Ann Neurol. 1994;36:680–1.

    Article  CAS  PubMed  Google Scholar 

  125. De Simone C, Tzantzoglou S, Jirillo E, et al. L-carnitine deficiency in AIDS patients. AIDS. 1992;6:203–5.

    Article  PubMed  Google Scholar 

  126. Lewis W, Dalakas MC. Mitochondrial toxicity of antiviral drugs. Nat Med. 1995;1:417–22.

    Article  CAS  PubMed  Google Scholar 

  127. Kiyomoto BH, Tengan CH, Godinho RO. Effects of short-term zidovudine exposure on mitochondrial DNA content and succinate dehydrogenase activity of rat skeletal muscle cells. J Neurol Sci. 2008;268:33–9.

    Article  CAS  PubMed  Google Scholar 

  128. Seok JI, Lee DK, Lee CH, et al. Long-term therapy with clevudine for chronic hepatitis B can be associated with myopathy characterized by depletion of mitochondrial DNA. Hepatology. 2009;49:2080–6.

    Article  CAS  PubMed  Google Scholar 

  129. Tak WY, Park SY, Jung MK, et al. Mitochondrial myopathy caused by clevudine therapy in chronic hepatitis B patients. Hepatol Res. 2009;39:944–7.

    Article  CAS  PubMed  Google Scholar 

  130. Fleischer RD, Lok AS. Myopathy and neuropathy associated with nucleos(t)ide analog therapy for hepatitis B. J Hepatol. 2009;51:787–91.

    Article  CAS  PubMed  Google Scholar 

  131. Kim BK, Oh J, Kwon SY, et al. Clevudine myopathy in patients with chronic hepatitis B. J Hepatol. 2009;51:829–34.

    Article  PubMed  Google Scholar 

  132. Manji H, Harrison MJ, Round JM, et al. Muscle disease, HIV and zidovudine: the spectrum of muscle disease in HIV-infected individuals treated with zidovudine. J Neurol. 1993;240:479–88.

    Article  CAS  PubMed  Google Scholar 

  133. Cupler EJ, Danon MJ, Jay C, et al. Early features of zidovudine-associated myopathy: histopathological findings and clinical correlations. Acta Neuropathol. 1995;90:1–6.

    Article  CAS  PubMed  Google Scholar 

  134. Chalmers AC, Greco CM, Miller RG. Prognosis in AZT myopathy. Neurology. 1991;41:1181–4.

    Article  CAS  PubMed  Google Scholar 

  135. Dalakas MC, Illa I, Pezeshkpour GH, et al. Mitochondrial myopathy caused by long-term zidovudine therapy. N Engl J Med. 1990;322:1098–105.

    Article  CAS  PubMed  Google Scholar 

  136. Masanes F, Barrientos A, Cebrian M, et al. Clinical, histological and molecular reversibility of zidovudine myopathy. J Neurol Sci. 1998;159:226–8.

    Article  CAS  PubMed  Google Scholar 

  137. Haller RC, Drachman DB. Alcoholic rhabdomyolysis: an experimental model in the rat. Science. 1980;208:412–5.

    Article  CAS  PubMed  Google Scholar 

  138. Drachman DB, Murphy SR, Nigam MP, Hills JR. “Myopathic” changes in chronically denervated muscle. Arch Neurol. 1967;16:14–24.

    Article  CAS  PubMed  Google Scholar 

  139. Victor M, Sieb JP. Myopathies due to drugs, toxins and nutritional deficiency. In: Engel A, Franzini-Armstrong C, editors. Myology. New York: McGraw-Hill; 1994. p. 1697–725.

    Google Scholar 

  140. Perkoff GT. Alcoholic myopathy. Annu Rev Med. 1971;22:125–32.

    Article  CAS  PubMed  Google Scholar 

  141. Urbano-Masquez A, Estruch R, Navarro-Lopez F, et al. The effects of alcoholism on skeletal and cardiac muscle. N Engl J Med. 1989;16:409–15.

    Article  Google Scholar 

  142. Munk ZM, Nantel A. Acute lindane poisoning with development of muscle necrosis. Can Med Assoc J. 1977;117:1050–4.

    CAS  PubMed  Google Scholar 

  143. Shemesh IY, Mishal Y, Baruchin AM, et al. Rhabdomyolysis in paraphenylenediamine intoxication. Vet Hum Toxicol. 1995;37:244–5.

    CAS  PubMed  Google Scholar 

  144. Rosenberg NL, Ringel SP. Myopathy from surreptitious ipecac ingestion. West J Med. 1986;145:386–8.

    CAS  PubMed  Google Scholar 

  145. Sugie H, Russin R, Verity MA. Emetine myopathy: two case reports with pathobiochemical analysis. Muscle Nerve. 1984;7:54–9.

    Article  CAS  PubMed  Google Scholar 

  146. Gutmann L, Besser R. Organophosphate intoxication: pharmacologic, neurophysiologic, clinical, and therapeutic considerations. Semin Neurol. 1990;10:46–51.

    Article  CAS  PubMed  Google Scholar 

  147. Meshul CK, Boyne AF, Deshpande SS, Albuquerque EX. Comparison of the ultrastructural myopathy induced by anticholinesterase agents at the end plates of rat soleus and extensor muscles. Exp Neurol. 1985;89:96–114.

    Article  CAS  PubMed  Google Scholar 

  148. Brodkin HM. Myoglobinuria following epsilon-aminocaproic acid (EACA) therapy. Case report. J Neurosurg. 1980;53:690–2.

    Article  CAS  PubMed  Google Scholar 

  149. Vanneste JA, van Wijngaarden GK. Epsilon-aminocaproic acid myopathy. Report of a case and literature review. Europ Neurol. 1982;21:242–8.

    Article  CAS  PubMed  Google Scholar 

  150. Bedry R, Baudrimont I, Deffieux G, et al. Wild-mushroom intoxication as a cause of rhabdomyolysis. N Engl J Med. 2001;345:798–802.

    Article  CAS  PubMed  Google Scholar 

  151. Nieminen P, Kirsi M, Mustonen A-M. Suspected myotoxicity of edible wild mushrooms. Exp Biol Med. 2006;231:221–8.

    CAS  Google Scholar 

  152. Matsumura T, Yuhara T, Yamane K, et al. D-penicillamine-induced polymyositis occurring in patients with rheumatoid arthritis: a report of two cases and demonstration of a positive lymphocyte stimulation test to D-penicillamine. Henry Ford Hosp Med J. 1986;34:123–6.

    CAS  PubMed  Google Scholar 

  153. Takahashi K, Ogita T, Okudaira H, et al. D-penicillamine-induced polymyositis in patients with rheumatoid arthritis. Arthritis Rheum. 1986;29:560–4.

    Article  CAS  PubMed  Google Scholar 

  154. Fontiveros ES, Cumming WJ, Hudgson P. Procainamide-induced myositis. J Neurol Sci. 1980;45:143–7.

    Article  CAS  PubMed  Google Scholar 

  155. Ricoy JR, Cabello A, Rodriguez J, Tellez I. Neuropathological studies on the toxic syndrome related to adulterated rapeseed oil in Spain. Brain. 1983;106:817–35.

    Article  PubMed  Google Scholar 

  156. Martin RW, Duffy J, Engel AG, et al. The clinical spectrum of the eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Clinical features in 20 patients and aspects of ­pathophysiology. Ann Intern Med. 1990;113:124–34.

    Article  CAS  PubMed  Google Scholar 

  157. Mebs D, Ownby CL. Myotoxic components of snake venoms: their biochemical and biological activities. Pharmacol Ther. 1990;48:223–36.

    Article  CAS  PubMed  Google Scholar 

  158. Steiner JC, Winkelman AC, De Jesus Jr PV. Pentazocine-induced myopathy. Arch Neurol. 1973;28:408–9.

    Article  CAS  PubMed  Google Scholar 

  159. Pan S, Wu X, Jiang J, et al. Discovery of NVP-LDE225, a potent and selective Smoothened antagonist. ACS Med Chem Lett. 2010;1:130–4.

    Article  CAS  Google Scholar 

  160. Tawbi HA, Ahnert JR, Dummer R, et al. Phase I study of LDE225 in advanced solid tumors: updated analysis of safety, preliminary efficacy, and pharmacokinetic-pharmacodynamic correlation. J Clin Oncol ASCO Meeting Abstracts. 2011;29(15 Suppl):abstract 3062.

    Google Scholar 

  161. Pedersen LM, Nygaard E, Nielsen OS, Saltin B. Solvent-induced occupational myopathy. J Occup Med. 1980;22:603–6.

    CAS  PubMed  Google Scholar 

  162. Teicher A, Rosenthal T, Kissin E, Sarova I. Labetalol-induced toxic myopathy. Br Med J (Clin Res Ed). 1981;282:1824–5.

    Article  CAS  Google Scholar 

  163. Hales DS, Scott R, Lewi HJ. Myopathy due to mercaptopropionyl glycine. Br Med J (Clin Res Ed). 1982;285:939.

    Article  CAS  Google Scholar 

  164. Schattner A, Geltner D, Bentwich Z. Immunocomplex nephritis and myopathy in a patient who works with vinyl chloride. Arch Intern Med. 1983;143:843.

    Article  CAS  PubMed  Google Scholar 

  165. Jenkins P, Emerson PA. Myopathy induced by rifampicin. Br Med J (Clin Res Ed). 1981;283:105–6.

    Article  CAS  Google Scholar 

  166. Sinclair D, Phillips C. Transient myopathy apparently due to ­tetracycline [letter]. N Engl J Med. 1982;307:821–2.

    CAS  PubMed  Google Scholar 

  167. Bregman H, Gelfand MC, Winchester JF, et al. Iron-overload-associated myopathy in patients on maintenance haemodialysis: a histocompatibility-linked disorder. Lancet. 1980;2(8200)):882–5.

    Article  CAS  PubMed  Google Scholar 

  168. Breil M, Chariot P. Muscle disorders associated with cyclosporine treatment. Muscle Nerve. 1999;22:1631–6.

    Article  CAS  PubMed  Google Scholar 

  169. Fernandez-Sola J, Campistol JM, Miro O, Garces N, Soy D, Grau JM. Acute toxic myopathy due to pyrazinamide in a patient with renal transplantation and cyclosporine therapy. Nephrol Dial Transplant. 1996;11:1850–2.

    Article  CAS  PubMed  Google Scholar 

  170. Norman DJ, Illingworth DR, Munson J, Hosenpud J. Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin. N Engl J Med. 1988;318:46–7.

    Article  CAS  PubMed  Google Scholar 

  171. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–45.

    Article  CAS  PubMed  Google Scholar 

  172. Tuccori M, Lombardo G, Lapi F, et al. Gabapentin-induced severe myopathy. Ann Pharmacother. 2007;41:1301–5.

    Article  CAS  PubMed  Google Scholar 

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Kuncl, R.W., Romano, G.J. (2014). Toxic Myopathies. In: Katirji, B., Kaminski, H., Ruff, R. (eds) Neuromuscular Disorders in Clinical Practice. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6567-6_68

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