Final Diagnosis -- Toxic Polyneuropathy Induced by Hydrochloroquine



Because of the complexity of the medical history of this patient, the differential diagnosis from the clinician's point of view included the vasculitides of collagen vascular disease, polyneuropathies associated with paraproteinemia, and iatrogenic causes. Chloroquine (together with Perhexiline maleate and Amiodarone) is an amphiphilic drug known to cause lipidosis both in animals and in humans (1,2,3) . The drug or its compounds interact with anionic groups of acidic phospholipids of cellular membranes forming a complex that is not diggested by lysosomes and is rearranged into concentric lamellar or crystaloid myeloid bodies. Complications of chloroquine when used in the treatment and prevention of malaria and in the treatment of connective tissue disorders include a vacuolar myopathy and sensory motor polyneuropathy. The development of chloroquine neuromyopathy may occur from several months (3) to several years (1) post-treatment. In nerve biopsy, the changes include segmental demyelination, axonal degeneration and the accumulation of pleomorphic osmophilic bodies with two distinct profiles; lamellar and curvilinear. They occur in the schwann cell cytoplasm, in perineural cells, in endothelial cells and smooth muscle cells but not in axons. The diagnosis of chloroquine neurotoxicity can be suspected by light microscopy, the inclusions being readily detected under oil immersion microscopy of semithin resin sections. In our patient, although the cause of neuropathy is probably multifactorial, the histology favors chloroquine neurotoxicity as significant pathogenesis of peripheral nerve dysfunction. Although some authors believe that chloroquine neuropathy is caused by primary involvement of schwann cells (1), in many cases a significant axonal component has been found, probably caused by degeneration of spinal ganglia neurons.


  1. Tegner R, Tome FM, Godeau P, Lhermitte F, Fardeau M: Morphological study of peripheral nerve changes induced by chloroquine treatment. Acta Neuropath 75:253-260, 1988.
  2. Estes ML, Ewing-Wilson D, Chou SM, et al: Chloroquine neuromyotoxicity. Clinical and pathogenic perspective. Am Jour Med 82:447-455, 1987.
  3. Leger JM, Pnifoulloux H, Dancea S, Hauw JJ, Bouche P, Rougemont D, Lapane D: Neuromyopathies a la chloroquine: 4 cas a cours d'une prophylaxie anti-paludeene. Revue Neurologique 142:745-752, 1986.

Contributed by Juan M. Bilbao, MD, FRCP(C)


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