title: Colchicine myopathy: a vacuolar myopathy with selective type I muscle fiber involvement. An immunohistochemical and electron microscopic study of two cases.
abstract: Colchicine, a microtubule polymerization inhibitor, can very occasionally induce myopathy. We report two cases of colchicine myopathy. Both patients presented with myalgia and proximal muscle weakness. The first patient, an 80-year-old woman, had chronic renal failure related to renal amyloidosis. She had been treated by colchicine for 4 months. The second, a 75-year-old man with normal renal function, suffering from gout, was treated by colchicine for 3 weeks. Muscle biopsies displayed the same alterations, but the degree of severity was different. Conventional histology revealed vacuolar changes characterized by acid phosphatase-positive vacuoles and myofibrillar disarray foci. The lesions were selective for type I fibers. Ultrastructural study demonstrated autophagic vacuoles. Most of the vacuoles expressed dystrophin but not merosin. Several fibers reacted with anti-MHC class I antibody and granular deposits of membrane attack complex were observed on the surface of numerous myofibers. Anti-alphaB-crystallin antibody strongly reacted with vacuolar content. Physiopathologically, microtubules are primordial for vesicle movements and colchicine induces autophagic vacuole accumulation by preventing their fusion with lysosomes. The selective type I involvement is probably due to the higher tubulin amount in type I fibers. AlphaB-crystallin overexpression is related to its microtubule protection properties. Moreover, we suggest that vacuoles randomly floating in sarcoplasm might occasionally meet the plasma membrane and open in the extracellular space, leading to complement activation. Accurate diagnosis of colchicine myopathy is relevant because the treatment is based on colchicine interruption.
authors.affiliation: Department of Pathology and Neuropathology, Hôpital de la Timone, 264 rue Saint-Pierre, 13385 Marseille Cedex 05, France. carla.fernandez@wanadoo.fr
authors.forename: C
authors.initials: C
authors.lastname: Fernandez
authors.forename: D
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: P
authors.initials: P
authors.lastname: Alla
authors.forename: J-R
authors.initials: JR
authors.lastname: Harlé
authors.forename: J-F
authors.initials: JF
authors.lastname: Pellissier
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003078:Colchicine / Q000009:adverse effects*; D005260:Female; D006074:Gout Suppressants / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D009135:Muscular Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000378:metabolism*; D014617:Vacuoles / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D006074:Gout Suppressants; D003078:Colchicine