Cardiomyopathy Caused by Longterm Treatment with Chloroquine: A Rare Disease, or a Rare Diagnosis?

Abstract

To the Editor: Chloroquine (CQ) has been used for the treatment and prophylaxis of malaria since World War II. Ten years later, the administration of CQ and hydroxychloroquine (HCQ) was introduced for the longterm therapy of rheumatic diseases. Although no reliable statistical data are available, HCQ, which differs from CQ only in a hydroxyl group at the end of the side chain, but not in pharmacokinetics or metabolism, is described in the literature as less toxic and has been staging a comeback, particularly in the treatment of systemic lupus erythematosus (SLE)1. CQ and HCQ induce a dysfunction of the lysosomal enzymes, leading to the impairment of intracellular degradation processes in conjunction with the accumulation of pathological metabolic products (glycogen and phospholipids). These appear histologically as granulovacuolar cell mutations and ultrastructurally as lamellar inclusion bodies (“myeloid bodies”) and as “curvilinear bodies” in cytoplasm (remnants of poorly digested membranes)2,3. Their pharmacokinetics are characterized by a long half-life and a high volume of distribution; they follow a multicompartment model with very slow distribution between plasma and tissue, leading to sustained organ sequestration and sometimes irreversible organ damage4. Severe toxicity in the form of irreversible retinopathy5 is well known under longterm treatment with these substances. In contrast, neuromyopathy6 and especially cardiac damage7 receive scant mention in the literature. Cardiac complications comprise conduction disturbances [bundle-branch block, atrioventricular (AV) block] and cardiomyopathy — often with hypertrophy, restrictive physiology, and congestive heart failure (literature reviews are found in Nord, et al 8 and Costedoat-Chalumeau, et al 9). Because the clinical features of cardiotoxicity are unspecific, the followup of potentially affected patients is of utmost importance. We report a case of a patient with rheumatoid arthritis (RA) and heart disease who was treated with CQ. A … Address correspondence to Dr. E. Tonnesmann, Kaiser-Karl-Klinik, Graurheindorfer Str. 137, D-53117 Bonn, Germany. E-mail: e.toennesmann{at}t-online.de