Elsevier

Cardiovascular Pathology

Volume 11, Issue 5, September–October 2002, Pages 277-283
Cardiovascular Pathology

Chloroquine cardiotoxicity: Clinicopathologic features in three patients and comparison with three patients with Fabry disease

https://doi.org/10.1016/S1054-8807(02)00118-7Get rights and content

Abstract

Background: Microscopic features of chloroquine cardiotoxicity are similar to those of Fabry disease. The purpose of the study was to compare clinicopathologic findings in both disorders. Methods: Patients with a diagnosis of chloroquine cardiotoxicity or Fabry disease were identified who had undergone endomyocardial biopsy or autopsy at Mayo Clinic Rochester (1976–2000). Clinical information was collected from medical records and letters from referring physicians. Light and electron microscopy were performed in all cases. Results: Three patients (two women, one man) with chloroquine cardiotoxicity ranged in age from 53 to 73 years. Chloroquine was given for rheumatoid arthritis in two and systemic lupus erythematosus in one. Three patients (two men, one woman) with Fabry disease ranged in age from 58 to 76 years. Two had angiokeratomas, but only one had a previous diagnosis of Fabry disease. All six patients presented with dyspnea. Light microscopy from all six revealed myocyte enlargement due to perinuclear vacuolization. By transmission electron microscopy, all six showed abundant myelinoid figures within involved myocytes. Curvilinear bodies were observed in two patients with chloroquine cardiotoxicity and in none with Fabry disease. Conclusions: Patients with cardiac dysfunction due to chloroquine cardiotoxicity or Fabry disease have similar ages, presenting clinical symptoms, cardiac light microscopy and sarcoplasmic myelinoid bodies ultrastructurally. Patients with Fabry disease may not have a personal or family history of the disease. Similarly, a history of chloroquine usage may not be known to the pathologist. In these settings, the presence of curvilinear bodies ultrastructurally is useful for the diagnosis of chloroquine cardiotoxicity.

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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