A 64-year-old woman with a history of systemic lupus erythematosus, treated for more than 10 years with prednisone and hydroxychloroquine, presented with severe progressive dyspnea on exertion. She had no other significant medical history. Examination revealed an S3 gallop. Transthoracic echocardiogram (TTE) demonstrated a 46% ejection fraction (EF) with generalized left ventricular hypokinesis, grade 3/4 diastolic dysfunction, and elevated left ventricular filling pressure. Left ventricular chamber size was normal, with concentric wall thickening. The myocardium had a hyper-refractile appearance (Figure 1). Serum protein electrophoresis and abdominal fat aspiration with Congo red staining were negative. Endomyocardial biopsy revealed sarcoplasmic clearing and vacuolization on light microscopy and myelinoid and curvilinear bodies on electron microscopy (Figure 2). Hydroxychloroquine toxicity was diagnosed and the medication was discontinued. The patient was asymptomatic within 9 months. Followup TTE revealed a 74% EF with normal left ventricular systolic function and grade 2/4 diastolic dysfunction. Wall thickness had normalized.
Hyper-refractile appearance of the myocardium.
Endomyocardial biopsy revealed sarcoplasmic clearing and vacuolization on light microscopy and myelinoid and curvilinear bodies on electron microscopy. Bar = 500 nm.
Hydroxychloroquine cardiomyopathy is characterized by biatrial enlargement, biventricular thickening, and systolic and diastolic dysfunction1,2. Hydroxychloroquine induces the formation of sarcoplasmic myelinoid and curvilinear bodies that lead to myocyte dysfunction. Sarcoplasmic accumulation of myelinoid and curvilinear bodies expands the myocytes and interferes with their function. As a result, ventricular wall thickness is increased3,4. Definitive diagnosis requires electron microscopy of endomyocardial biopsy tissue revealing unique curvilinear bodies in the sarcoplasm1. These represent abnormal lysosomes replete with phospholipids and glucose. Withdrawal of hydroxychloroquine leads to symptomatic and echocardiographic improvement.
