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Hydroxychloroquine is being used for COVID-19 symptoms and in clinical trials, but can cause a toxic myopathy that leads to muscle weakness. A review of skeletal muscle biopsies from patients with hydroxychloroquine myopathy gives pointers of steps that can be taken to diagnose this toxic myopathy early and help differentiate it from COVID-19-related muscle weakness.

The goal of this article is to provide physiatrists, neurologists, and neuromuscular medicine physicians a framework that can be easily used in the process of evaluating, identifying, and treating patients with toxic myopathies. This review attempts to classify these rare but potentially deadly conditions in clinical patterns and distinguishes the cellular mechanisms in which the offending agents tend to impact the structure and function of myocytes.

Chloroquine and hydroxychloroquine, commonly used for rheumatologic conditions, are rare yet very important causes of toxic myopathy with vacuolar changes on muscle biopsy.

Drug-induced muscle dysfunction represents a significant and perhaps increasing subset of neuromuscular disorders that face the clinician. Whereas severe symptoms of proximal weakness and elevated muscle enzymes in an uncomplicated patient taking a single medication may lead to straightforward diagnosis, the tendency for patients with multisystem disease, on multiple medications, with multiple potential causes for weakness makes the diagnosis of toxic myopathy challenging. Furthermore, many toxic myopathies are characterized by nonspecific clinical and laboratory findings, ultimately requiring a trial of drug discontinuation in order to clarify the diagnosis. This review summarizes recent observations with regard to toxic effects on neuromuscular transmission and toxic myopathies.

Statins are commonly prescribed lipid-lowering medications that significantly reduce the risk of cardiovascular events. However, they can have myotoxic effects ranging in severity from myalgias to rhabdomyolysis. This review focuses on recent progress in defining the clinical features and mechanism(s) of statin-induced myopathy.Although severe myotoxicity is a very rare event, most recent studies suggest that myalgias and relatively low-level muscle damage may occur in a substantial number of patients treated with statins. Those taking medications that increase serum statin concentrations are at greater risk for severe muscle side-effects, as are those with a polymorphism in the gene encoding a hepatic statin transporter. Although the mechanism of muscle damage remains to be fully elucidated, a number of in-vitro studies suggest that inhibition of protein prenylation may underlie the myotoxic effects of statins, possibly through the induction of pro-apoptotic pathways. In addition, recent reports have indicated that statins may trigger an immune-mediated necrotizing myopathy with many features of polymyositis.Severe myopathy is a rare and generally self-limited side-effect of statin medications. However, myalgias are much more common and limit their use in many patients. Recent evidence also suggests that statins are associated with the development of a unique form of immune-mediated myopathy. Awareness of this newly described entity is important, as these patients may require immunosuppressive therapy.

The rosuvastatin inducing rhabdomyolysis in McArdle disease (MD) has not been reported to date. A 35-years-old man had exercise intolerance, muscular fatigue and cramps during physical activity since infancy. He presented severe rhabdomyolysis episode with seizure and coma after use of rosuvastatin. The investigation showed increased serum creatinekinase levels and the forearm ischemic exercise did not increased venous lactate. The muscle biopsy showed subsarcolemmal and central acummulation of glycogen and absence of the myophosphorylase enzyme. The statin induced myopathy is discussed and the danger of its use in MD is emphasized. Rosuvastatina induzindo rabdomiólise na doença de McArdle (MD) não foi relatada até o momento. Descrevemos o caso de um homem de 35 anos que desde a infância apresentava sintomas de intolerância aos exercícios, fadiga muscular e cãibras durante o esforço físico, porém após o uso de rosuvastatina apresentou episódio de rabdomiólise com crises convulsivas e coma. A investigação mostrou creatinoquinase sérica elevada e teste do esforço isquêmico sem aumento no lactato venoso. A biópsia muscular revelou acúmulo central e subsarcolemal de glicogênio nas fibras e ausência da enzima miofosforilase. Discutimos as estatinas induzindo miopatia, enfatizando o risco do seu uso na MD.

Several drugs and toxic substances can cause muscular abnormalities and are frequent causes of acquired myopathies. We present a series of 32 patients, predominance of young adult patients, diagnosed with toxic myopathy. The most common substances inducing myopathy were corticosteroids (56.2%) followed by the propoxyphene, neuroleptics, zidovudine and drug-induced hypokalemia. The investigation showed normal serum creatine kinase levels in 65.4%, myopathic pattern of the needle electromyography in 40% and the more frequent histological diagnosis of the muscle biopsy was type 2 fiber atrophy (59.3%). Clinical features, etiology, course of the disease, serum levels of muscular enzymes, electromyographic features and, especially, muscle biopsy features are discussed.

We report a case of subacute myopathy in a 47 years old man engaged on boiler maintenance at an oil-fired thermoelectric power station. The occupational history highlighted heavy exposure to inhalation of ash derived from mineral oil combustion and containing several elements, metals and metalloids, including vanadium and nickel. The presenting symptoms, clinical course and muscle histopathology suggest that exposure to toxic agents probably played an important part in the causation of the myopathy.

Labetalol has been successful in treating hypertension, and few side effects have been reported, although there have been cases of muscle pain during treatment. A patient with essential hypertension treated with labetalol 600 mg daily complained of muscle pains, particularly in the legs. No neurological abnormality was found, but the activity of muscle enzymes in the blood was high. Findings on electromyography were compatible with myositis and electron microscopical findings suggested toxic myopathy. Labetalol was stopped for 10 days, and the muscle pain disappeared and enzyme activity returned to normal. When labetalol was restarted the pain returned and enzyme activities rose. Myopathy should be considered in patients experiencing muscle pain after treatment with labetalol.

Nrf2 (nuclear factor [erythroid-d erived 2]-like 2 ; the transcriptional master regulator of the antioxidant stress response) is regulated through interaction with its cytoplasmic inhibitor Keap1 (Kelch-like ECH-associated protein 1), which under basal conditions targets Nrf2 for proteasomal degradation. Sequestosome 1 (SQSTM1)/p62–a multifunctional adapter protein that accumulates following autophagy inhibition and can serve as a diagnostic marker for human autophagic vacuolar myopathies (AVMs)–was recently shown to compete with Nrf2 for Keap1 binding, resulting in activation of the Nrf2 pathway. In this study, we used 55 human muscle biopsies divided into five groups [normal control, hydroxychloroquine- or colchicine-treated non-AVM control, hydroxychloroquine- or colchicine-induced toxic AVM, polymyositis, and inclusion body myositis (IBM)] to evaluate whether Keap1-SQSTM1 interaction led to increased Nrf2 signaling in human AVMs. In toxic AVMs and IBM, but not in control muscle groups or polymyositis, Keap1 antibody labeled sarcoplasmic protein aggregates that can be used as an alternate diagnostic marker for both AVM types; these Keap1-positive aggregates were co-labeled with the antibody against SQSTM1 but not with the antibody against autophagosome marker LC3 (microtubule-associated protein 1 light chain 3). In human AVM muscle, sequestration of Keap1 into the SQSTM1-positive protein aggregates was accompanied by an increase in mRNA and protein levels of Nrf2 target genes; similarly, treatment of differentiated C2C12 myotubes with autophagy inhibitor chloroquine led to an increase in the nuclear Nrf2 protein level and an increase in expression of the Nrf2-regulated genes. Taken together, our findings demonstrate that Nrf2 signaling is upregulated in autophagic muscle disorders and raise the possibility that autophagy disruption in skeletal muscle leads to dysregulation of cellular redox homeostasis. Electronic supplementary material The online version of this article (doi:10.1186/s40478-016-0384-6) contains supplementary material, which is available to authorized users.

We report the case of a patient who developed severe muscle pains due to acute toxic myopathy following intravenous urography. This is a previously unreported adverse reaction to intravenous contrast media and occurred with iopamidol 370, a low-osmolar, non-ionic agent. A 55-year-old man was referred for intravenous urography (IVU) during investigation for poorly controlled hypertension. His only medication was atenolol (50 mg mane) and slow-release nifedipine (20 mg bi-daily); there was no other past medical history of note.