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02 Hydroxychloroquine myopathy: cardiac and skeletal muscle toxicity
  1. Murray Urowitz
  1. University of Toronto, Canada


Antimalarial myopathic toxicities may involve both skeletal and cardiac muscles. In skeletal muscle it is a deposition myopathy and in cardiac muscle there may be a direct chemical action toxicity or a deposition myopathy.

In skeletal muscle there are isolated case reports of clinical myopathy and two prospective studies, one of 119 cases and the other of 21 cases.1 2 Both showed ±19% abnormal muscle enzymes. Clinical weakness was very uncommon but biopsies in 15 patients showed classic EM findings of antimalarial toxicity. All patients improved with cessation of antimalarials.

In chemical toxicity of cardiac muscle, antimalarials may cause QTc prolongation. This is based on isolated case reports. In one cross sectional case series of 90 patients there was no difference in QTc between those on antimalarials and those not.3 There are no reports of sudden death in lupus patients starting antimalarials. Perhaps the more significant findings are related to the deposition of antimalarials in cardiac muscle resulting in antimalarial induced cardiomyopathy (AMIC). Clinical, serologic, imaging and biopsy features of this complication will be described in 8 patients recently seen in the University of Toronto Lupus Clinic.4 A systematic review of 47 patients with biopsy proven AMIC will be presented.5 Features of AMIC include morphologic/structural changes (biventricular/septal hypertrophy, bi-atrial enlargement); functional defects (impaired systolic and diastolic function); conduction disorders (RBBB, LAFB, cAVB/SSS); elevated biomarkers (troponins [cTnI], BNP, CPK). In 151 lupus patients with no prior history of heart disease we found 16 (10.6%) had abnormal cTni and/or BNP.6 Of these six were diagnosed with AMIC, five with other diagnoses and five do not yet have a definite diagnosis. Cardiac biomarkers should be ordered in patients who are older, have a decreased eGFR, have elevated CK without clinical myositis, and who have taken antimalarials for more than 5 years.

Learning Objectives

  • Describe antimalarial muscle toxicity in skeletal and cardiac muscle

  • Discuss the possible association between antimalarial treatment and QTc prolongation and its possible consequences

  • Describe antimalarial deposition in cardiac muscle and its consequences

  • Differentiate the role of cardiac biomarkers in the early detection of antimalarial induced cardiomyopathy


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  2. Kalajian AH, Callen JP. Myopathy induced by antimalarial agents: the relevance of screening muscle enzyme levels. Arch Dermatol. 2009;145(5):597–600.

  3. Haj-Ali M, .Belmont H Hydroxychloroquine and QTc Prolongation in a Cohort of SLE Patients [abstract]. Arthritis Rheumatol. 2020;72:

  4. Tselios K, Deeb M, Gladman DD, et al. Antimalarial-induced Cardiomyopathy in Systemic Lupus Erythematosus: As Rare as Considered?J Rheumatol. 2019;46(4):391–6.

  5. Tselios K, Deeb M, Gladman DD, Harvey P, Urowitz MB. Antimalarial-induced cardiomyopathy: a systematic review of the literature. Lupus. 2018;27(4):591–9.

  6. Tselios K, Gladman DD, Harvey P, et al. Abnormal Cardiac Biomarkers in Patients with Systemic Lupus Erythematosus and No Prior Heart Disease: A Consequence of Antimalarials?J Rheumatol. 2019;46(1):64–9.

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