氯喹(CQ)和羟氯喹(HCQ)与肌肉毒性有关,主要描述为近端肌病,肌肉活检显示溶酶体功能障碍。在这项回顾性研究中,我们的目的是定义临床表型,实验室特点,CQ/HCQ肌病的治疗结果,以及这些药物的安全性。我们确定了2000年至2019年之间的13例患者,中位年龄为66岁(范围53-89岁);11例为女性。在出现症状时,患者接受CQ或HCQ治疗的时间至少为6个月,最长为21年.诊断通常延迟中位数为6个月(范围3-48)。在介绍时,13例患者报告肢体无力,五个人需要帮助走路。十例报告吞咽困难,经常严重,导致明显的体重减轻或吸入性肺炎。九例报告了呼吸道症状,四个是多因素的,四个人报告严重的颈部无力。肌病临床表型表现为以下一种或多种主要受累:近端肢体肌无力(12例),吞咽困难(9),轴向薄弱(4),呼吸衰竭(5)。11名患者的心脏评估显示10名患者的QT间期延长,4名患者的CQ/HCQ心肌病(CMP)延长。12名患者中有10名在停药后明显改善,但大多数都留下了一些残余的弱点。11例患者的肌肉活检显示肌病,有边缘空泡和明显的酸性磷酸酶反应性。九个人的肌酸激酶水平升高至1,199U/L。12名患者进行了肌电图检查(EMG),显示肌病性运动单位电位,纤颤电位为11,强直放电为3。更高的累积剂量和更长的暴露时间与更严重的残疾和更常见的心脏和吞咽受累相关。表明累积剂量效应。在这里,我们证明,长期暴露于CQ和HCQ可能导致具有广泛临床表现和吞咽倾向的肌病,呼吸,和心肌,通常有明显的相关发病率。一旦准确诊断并停药,患者通常有所改善,但往往无法恢复到基线.
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.