Chloroquine cardiotoxicity: Clinicopathologic features in three patients and comparison with three patients with Fabry disease
Introduction
The antimalarial drug chloroquine and its derivative hydroxychloroquine have been used to treat autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus for several decades [1]. Their toxic effects include retinopathy, myopathy and neuropathy [2], [3], [4], [5], [6].
A rare yet serious complication of chloroquine therapy is cardiotoxicity [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. Acutely, chloroquine can induce hypotension and conduction disturbances, and fatal arrhythmias have been reported [15], [17]. Chronically, conduction disturbances, such as bundle-branch block and complete heart block, can occur [8], [14]. Congestive heart failure associated with biventricular hypertrophy or restrictive hemodynamics is also a common manifestation of chronic chloroquine cardiotoxicity [10], [11], [12], [15].
By light microscopy, cardiac myocytes appear vacuolated and, ultrastructurally, the vacuoles represent sarcoplasmic accumulations of myelinoid figures and curvilinear bodies [3], [7], [8], [9], [12], [13], [15], [16], [18]. These findings overlap with those described in Fabry disease [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33]. The aim of the current retrospective study was to report the clinical and pathologic features, including ultrastructural characteristics, in cases of chloroquine toxicity and compare them with cases of Fabry disease from Mayo Clinic Rochester.
Section snippets
Methods
The Mayo Clinic database and consultation files were searched for patients with a diagnosis of chloroquine toxicity or Fabry disease and with myocardial tissue available from biopsy or autopsy. Six patients were identified, three from each category. The study was approved by the Mayo Foundation Institutional Review Board.
Clinical and radiologic data were retrieved from medical histories or correspondence letters from referring pathologists. Data included the patient's age and gender, history of
Demographic features
Among the three patients with chloroquine cardiotoxicity, ages ranged from 53 to 73 years and two were women (Table 1). For the three with Fabry disease, ages ranged from 58 to 76 years and two were men. One Fabry patient has been previously reported [19].
Hydroxychloroquine was used for to treat rheumatoid arthritis in two patients and chloroquine was given to the one with systemic lupus erythematosus. The total dosage was 2 g daily for 2 years in one patient and was unknown in the other two
Common aspects
Patients with cardiac involvement due to chloroquine toxicity or Fabry disease have overlapping clinical characteristics. Patients from both groups commonly present with shortness of breath, chest pain, fatigue and arrhythmias or conduction disturbances. Echocardiographic findings in patients with chloroquine toxicity have included ventricular hypertrophy, with or without dilatation, and systolic or diastolic dysfunction [7], [8], [12], [13], [15], [16]. Patients with Fabry disease may exhibit
Summary
Patients with chloroquine cardiotoxicity or Fabry disease share numerous clinical and pathologic features. To distinguish between the two, the most useful clinical information is obviously a history of chloroquine usage, although this is not always provided to the pathologist. Although by transmission electron microscopy, both conditions have myelinoid bodies, only chloroquine toxicity is characterized by the presence of curvilinear bodies.
Acknowledgements
The authors would like to thank Patrice Abell-Aleff for her valuable work with the ultrastructural study.
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