title: Dermal alterations in patients with Wilson's disease treated with D-penicillamine.
abstract: Wilson's disease is characterized by accumulation of copper and D-penicillamine favors its elimination. However, penicillamine binds to precursors of intermolecular crosslinks both in collagen and elastin, and could lead to alterations of these two fibrous proteins. In the present report skin biopsies from patients with Wilson's disease, treated with 900 mg/day of D-penicillamine, for 5, 9, 58 and 60 months, were studied by electron microscopy and compared with findings obtained from skin biopsies of age-matched normal subjects. Clinically, the elasticity and consistency of the skin of Wilson's patients was not modified by D-penicillamine treatment. The ultrastructural organization of collagen fibrils appeared normal in the adults treated with D-penicillamine for 5-9 months. In a 15-year-old girl, treated for 48 months, a high number of collagen fibrils were swollen and unreeved. Elastin fibers were altered in all patients. The alterations were mostly pronounced in the reticular dermis, were proportional to the time of treatment, and consisted of polymorphous aggregates of elastin connected to apparently normal elastin fibers. A stereological analysis, on EM pictures from the patient treated for 60 months, and from an age-matched control, showed a significant decrease in the percentage of collagen and of the mean area occupied by each collagen bundle in the reticular dermis of the patient compared to control; on the contrary, the number of elastin fibers per unit area increased significantly, and the mean area of each elastin fiber decreased. The volume density of elastin was similar to control. The results indicate that prolonged administration of penicillamine to humans induces alterations in the deposition of dermal collagen and elastin.
authors.affiliation: Institute of General Pathology, University of Modena, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Pasquali Ronchetti
authors.forename: D
authors.initials: D
authors.lastname: Quaglino
authors.forename: M
authors.initials: M
authors.lastname: Baccarani Contri
authors.forename: J
authors.initials: J
authors.lastname: Hayek
authors.forename: G
authors.initials: G
authors.lastname: Galassi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D003094:Collagen / Q000032:analysis; D004549:Elastin / Q000032:analysis; D005260:Female; D006025:Glycosaminoglycans / Q000032:analysis; D006527:Hepatolenticular Degeneration / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D010396:Penicillamine / Q000627:therapeutic use*; D012016:Reference Values; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure
chemical_list: D006025:Glycosaminoglycans; D003094:Collagen; D004549:Elastin; D010396:Penicillamine