BIOMAT Database Logo BIOMAT Database Logo

Mitochondrial myopathy caused by long-term zidovudine therapy. 1990

M C Dalakas, and I Illa, and G H Pezeshkpour, and J P Laukaitis, and B Cohen, and J L Griffin
Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Both infection with the human immunodeficiency virus type 1 (HIV) and zidovudine (formerly called azidothymidine [AZT]) cause myopathy. To identify criteria for distinguishing zidovudine-induced myopathy from that caused by primary HIV infection, we reviewed the histochemical, immunocytochemical, and electron-microscopical features of muscle-biopsy specimens from 20 HIV-positive patients with myopathy (15 of whom had been treated with zidovudine) and compared the findings with the patients' clinical course and response to various therapies. Among the zidovudine-treated patients, the myopathy responded to prednisone in four, to the discontinuation of zidovudine in eight, and to nonsteroidal anti-inflammatory drugs in two. Numerous "ragged-red" fibers, indicative of abnormal mitochondria with paracrystalline inclusions, were found in the biopsy specimens from the zidovudine-treated patients but not in those from the other patients. The number of these fibers appeared to correlate with the severity of the myopathy. All the patients, regardless of whether they had been treated with zidovudine, had inflammatory myopathy characterized by degenerating fibers, cytoplasmic bodies, and endomysial infiltrates consisting of CD8+ cells (mean +/- SD, 60.7 +/- 6.4 percent) and macrophages (39.2 +/- 6.4 percent) associated with Class I major histocompatibility complex (MHC-I) antigens (HLA-A, -B, and -C antigens) in the muscle fibers. The numbers and percentages of CD8+ cells and macrophages were similar in both the zidovudine-treated and the untreated HIV-positive patients. Specimens obtained on repeat muscle biopsy from two patients in whom the myopathy responded to the discontinuation of zidovudine showed remarkable histologic improvement. We conclude that long-term therapy with zidovudine can cause a toxic mitochondrial myopathy, which coexists with a T-cell-mediated inflammatory myopathy that is restricted to MHC-I antigen, and is indistinguishable from the myopathy associated with primary HIV infection or polymyositis in HIV-seronegative patients.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008285 Major Histocompatibility Complex The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. Histocompatibility Complex,Complex, Histocompatibility,Complex, Major Histocompatibility,Complices, Histocompatibility,Complices, Major Histocompatibility,Histocompatibility Complex, Major,Histocompatibility Complices,Histocompatibility Complices, Major,Major Histocompatibility Complices
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D008931 Mitochondria, Muscle Mitochondria of skeletal and smooth muscle. It does not include myocardial mitochondria for which MITOCHONDRIA, HEART is available. Sarcosomes,Mitochondrion, Muscle,Muscle Mitochondria,Muscle Mitochondrion,Sarcosome
D009135 Muscular Diseases Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE. Muscle Disorders,Myopathies,Myopathic Conditions,Muscle Disorder,Muscular Disease,Myopathic Condition,Myopathy
D003937 Diagnosis, Differential Determination of which one of two or more diseases or conditions a patient is suffering from by systematically comparing and contrasting results of diagnostic measures. Diagnoses, Differential,Differential Diagnoses,Differential Diagnosis
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000163 Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency

Related Publications

M C Dalakas, and I Illa, and G H Pezeshkpour, and J P Laukaitis, and B Cohen, and J L Griffin
Mitochondrial myopathy caused by long-term zidovudine therapy.
October 1990, The New England journal of medicine,
M C Dalakas, and I Illa, and G H Pezeshkpour, and J P Laukaitis, and B Cohen, and J L Griffin
Mitochondrial myopathy caused by arsenic trioxide therapy.
May 2012, Blood,
M C Dalakas, and I Illa, and G H Pezeshkpour, and J P Laukaitis, and B Cohen, and J L Griffin
Myopathy in human immunodeficiency virus-infected children receiving long-term zidovudine therapy.
July 1991, The Journal of pediatrics,
M C Dalakas, and I Illa, and G H Pezeshkpour, and J P Laukaitis, and B Cohen, and J L Griffin
Mitochondrial myopathy associated with chronic zidovudine therapy in AIDS.
January 1993, The Quarterly journal of medicine,
M C Dalakas, and I Illa, and G H Pezeshkpour, and J P Laukaitis, and B Cohen, and J L Griffin
Mitochondrial myopathy caused by clevudine therapy in chronic hepatitis B patients.
September 2009, Hepatology research : the official journal of the Japan Society of Hepatology,
M C Dalakas, and I Illa, and G H Pezeshkpour, and J P Laukaitis, and B Cohen, and J L Griffin
Mechanisms of zidovudine-induced mitochondrial toxicity and myopathy.
January 2008, Pharmacology,
M C Dalakas, and I Illa, and G H Pezeshkpour, and J P Laukaitis, and B Cohen, and J L Griffin
Zidovudine myopathy.
June 1992, Neurology,
M C Dalakas, and I Illa, and G H Pezeshkpour, and J P Laukaitis, and B Cohen, and J L Griffin
Zidovudine-induced experimental myopathy: dual mechanism of mitochondrial damage.
July 1999, Journal of the neurological sciences,
M C Dalakas, and I Illa, and G H Pezeshkpour, and J P Laukaitis, and B Cohen, and J L Griffin
Muscle carnitine deficiency associated with zidovudine-induced mitochondrial myopathy.
October 1994, Annals of neurology,
M C Dalakas, and I Illa, and G H Pezeshkpour, and J P Laukaitis, and B Cohen, and J L Griffin
Zidovudine myopathy: a distinctive disorder associated with mitochondrial dysfunction.
June 1991, Annals of neurology,
Copied contents to your clipboard!