title: D-penicillamine-induced ANA (+) ANCA (+) vasculitis in pediatric patients with Wilson's disease.
abstract: Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with systemic vasculitis. The pathophysiology of ANCA-associated vasculitis (AAV) has not been clearly proven, and drug-induced ANCA-associated vasculitis has been reported. Wilson's disease is an inborn error of copper metabolism caused by a mutation in the copper transporting gene ATP7B, and traditional treatment is based on copper chelation with agents such as D-penicillamine. There have been rare reports that prolonged D-penicillamine therapy might cause adverse renal events such as membranous nephropathy and minimal change disease, but it is questionable if D-penicillamine induces ANCA-associated vasculitis. We describe 2 patients with Wilson's disease treated with D-penicillamine who presented with ANCA (+) vasculitis and renal involvement. The 2 patients also showed positive results for antinuclear antibody (ANA). Their kidney biopsy findings were compatible with crescentic/necrotizing glomerulonephritis, pauci-immune type. After diagnosis of AAV, D-penicillamine was stopped. Patients were then treated with plasmapheresis and immunosuppressants, including methylprednisolone pulse therapy and intravenous cyclophosphamide. One patient progressed to end-stage renal disease and the other showed persistent proteinuria. These cases suggest that D-penicillamine may induce ANA (+) ANCA (+) vasculitis with severe renal involvement in pediatric patients, and plasmapheresis combined with immunosuppressant should be considered.
authors.forename: Yeonhee
authors.initials: Y
authors.lastname: Lee
authors.forename: Sang Taek
authors.initials: ST
authors.lastname: Lee
authors.forename: Heeyeon
authors.initials: H
authors.lastname: Cho
mesh_terms: D000293:Adolescent; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000139:chemically induced* / Q000188:drug therapy; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D002614:Chelating Agents / Q000009:adverse effects*; D005260:Female; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000188:drug therapy; D006527:Hepatolenticular Degeneration / Q000188:drug therapy*; D006801:Humans; D010396:Penicillamine / Q000009:adverse effects*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000974:Antibodies, Antinuclear; D002614:Chelating Agents; D010396:Penicillamine