Chloroquine (CQ) and hydroxychloroquine (HCQ) have been associated with muscle toxicity, mostly described as a proximal myopathy with evidence of lysosomal dysfunction on muscle biopsy. In this retrospective study, we aimed to define the clinical phenotype, laboratory features, and treatment outcomes of CQ/HCQ myopathy, as well as the safety profile of these drugs. We identified 13 patients seen between 2000 and 2019, with a median age at presentation of 66 years (range 53–89); 11 were females. At onset of symptoms, patients were on CQ or HCQ for a minimum of 6 months and up to 21 years. Diagnosis was often delayed by a median of 6 months (range 3–48). At presentation, 13 patients reported limb weakness, with five requiring assistance in walking. Ten reported dysphagia, often severe, resulting in marked weight loss or aspiration pneumonia. Nine reported respiratory symptoms, which were multifactorial in four, and four reported severe neck weakness. Myopathy clinical phenotype showed predominant involvement of one or more of the following: proximal limb muscle weakness (12 patients), dysphagia (9), axial weakness (4), and respiratory failure (5). Eleven patients had a cardiac evaluation showing prolonged QT interval in 10 and CQ/HCQ cardiomyopathy (CMP) in four. Ten out of 12 patients markedly improved after discontinuing the medication, but most were left with some residual weakness. Eleven patients had a muscle biopsy showing a myopathy with rimmed vacuoles and marked acid phosphatase reactivity. Nine had elevated creatine kinase level up to 1,199 U/L. Twelve patients had an electromyography (EMG), which showed myopathic motor unit potentials with fibrillation potentials in 11 and myotonic discharges in 3. Higher cumulative dose and longer exposure duration were associated with more severe disability and more common cardiac and swallow involvement, indicating a cumulative dose effect. Herein, we demonstrate that long-term exposure to CQ and HCQ may result in a myopathy with a wide spectrum of clinical presentation and predilection for swallowing, respiratory, and cardiac muscles, often with marked associated morbidity. Once accurately diagnosed and the drug is discontinued, patients usually improve but often fail to return to baseline.
From Routine to Research Laboratory: Strategies for the Diagnosis of Congenital Fibrinogen Disorders
