Colchicine Myopathy Pathophysiology
March 1, 2002 2 minutes read
Colchicine Myopathy Pathophysiology
Abstract & Commentary
Source: Fernandez C, et al. Colchicine myopathy: A vacuolar myopathy with selective type 1 muscle fiber involvement. An immunohistochemical and electron microscopic study of two cases. Acta Neuropathol. 2002;103:100-106.
Colchicine blocks mitosis at metaphase and, rarely, produces a vacuolar myopathy by interfering with microtubular polymerization. Either acute overdose or long-term therapeutic usage may be responsible. It is often associated with polyneuropathy, and is more common in elderly patients with mild renal failure. Proximal weakness and areflexia, moderate creatine kinase elevation, and resolution of symptoms after withdrawal of the inciting agent fulfill the clinical picture. Pathophysiology remains unclear.
Two patients with muscle biopsy proven muscle colchicine myopathy demonstrated selective type 1 muscle fiber vacuolar change and microtubular disarray. Dystrophin and alpha-sarcoglycan, but not merosin, were expressed on the vacuolar membranes but not internally, the contents of which reacted with anti-alphaB-crystallin antibody. Membrane attack complex was observed on the surface of several muscle fibers, possibly due to complement activation resulting from vacuolar exocytosis. Calcium accumulation was not significant, in contrast to X-linked vacuolar myopathy, despite the presence of C5b-9 antibodies on the myofiber cell membrane. Colchicine myopathy is a treatable antimicrotubular myopathy, (by discontinuing the offending agent) selective for type 1 fibers, possibly due to the abundance of alpha tubulin in type 1 more than type 2 muscle cells. Overexpression of alphaB-crystallin in the vacuoles may be a cell protective effort, given that alphaB-crystallin is a heat shock protein shown to protect microtubules during simulated ischemia. Disruption of the microtubules may thus induce alphaB-crystallin synthesis.
Commentary
Microtubules (25 nm diameter), heterodimers of alpha and beta tubulin, comprise the skeletal muscle cytoskeleton, together with intermediate filaments (10 nm diameter) and microfilaments (4-8 nm diameter). Extending between myofibrils, the contractile element of muscle composed of an orderly array of actin and myosin filaments, microtubules run along the long axis of the myofiber, and are associated with MAPs (microtubule-associated proteins), including MAP-1, MAP-2, and tau which modify microtubular function. No known primary disease affects microtubular structure or function. —Michael Rubin.
Rubin, MD, Associate Professor of Clinical Neurology, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.
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