Morphologic Study of a Neuromyopathy Caused by Prolonged Chloroquine Treatment

Abstract

Two muscle biopsies were made in a case of chloroquine neuromyopathy in a 57-year-old woman with discoid lupus erythematosus. Histological study demonstrates widespread granulovacuolar degeneration and alterations of terminal innervation. Ultrastructural changes include formation of myelin figures and autophagic vacuoles. Of particular interest is the amount and mode of recovery from such alterations 2 months after cessation of the treatment.

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

“…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 damage 4 .…”

“…The range of differential diagnoses in the case of vacuolar myopathy revealed under light microscopy is considerably larger and includes the connective tissue diseases and steroid myopathy 2,3 (Table 2). Because rheumatic diseases often involve the cardiovascular system, and cortisone preparations are frequently prescribed, overlaps can occur and the symptoms of toxic damage are often ascribed to the underlying rheumatic disease and its complications.…”

Chloroquine-Induced Neuromyopathy

“…Blood chemistry disclosed anemia (3,350.000 red cells/ml. with 9.5% hemoglobin), leu kopenia (2,300/ml) with lymphopenia (1.089/ml), pe ripheral-patterned ANA, anti-dsDNA antibodies, pos itive LE cell preparations.…”

“…The presence of a granular deposition within the muscle fibers was observed and led to discontinuation of the drug and to a gradual recovery of muscle strength. The difficult differential diagnosis with polymy ositis, steroid-induced myopathy and SLE myositis is discussed.Myopathy with vacuolization and split ting of muscle fibers may occasionally occur in systemic lupus erythematosus (SLE) and in patients under treatment with both corti costeroids and chloroquine [1], This makes it difficult to establish the etiology of such a myopathy, and the presence of a granular deposition within the muscle fibers is usual ly considered as a possible discriminating feature [2,3].We describe the case of a patient in whom a neuromyopathy developed during steroid and chloroquine treatment for SLE. A gran ular deposition in muscle fibers was ob served and led to discontinuation of the antimalarial; this was followed by a gradual recovery of muscle strength.…”

Respiratory Failure Associated with Hydroxychloroquine Neuromyopathy

“…Recovery after discontinuation of therapy may be delayed. Chloroquine is known to produce vacuo lar myopathy affecting skeletal muscle [2,3] and heart [4]. Muscle alterations due to hydroxychloroquine are similar to those described with chloroquine but less severe [5,6], Various degrees of segmental demyclination and axonopathy may be associated.…”