title: Longstanding obliterative panarteritis in Kawasaki disease: lack of cyclosporin A effect.
abstract: Kawasaki disease is a childhood vasculitis of medium-sized vessels, affecting the coronary arteries in particular. We have treated a therapy-resistant child who met all diagnostic criteria for Kawasaki disease. After the boy was given intravenous immunoglobulins and salicylates, as well as several courses of pulsed methylprednisolone, disease recurred and coronary artery lesions became progressively detectable. Cyclosporin A was started and seemed clinically effective. In contrast to the positive effect on inflammatory parameters, ie, C-reactive protein and white blood cell counts, a novel plasma marker for cytotoxicity (granzyme B) remained elevated. Coronary disease progressed to fatal obstruction and myocardial infarction. Echocardiography, electrocardiograms, and myocardial creatine phosphokinase did not predict impending death. At autopsy an obliterative panarteritis was observed resulting from massive fibrointimal proliferation, affecting the aorta and several large and medium-sized arteries. Immunophenotypic analysis of the inflammatory infiltrates in arteries revealed mainly granzyme-positive cytotoxic T cells and macrophages in the intima and media, as well as nodular aggregates of T cells, B cells, and plasma cells in the adventitia of affected arteries. These findings further endorse the role of specific cellular and humoral immunity in Kawasaki disease. Unremitting coronary arteritis and excessive smooth muscle hyperplasia resulted in coronary occlusion despite the use of cyclosporin A.
authors.affiliation: Emma Children's Hospital, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. t.w.kuijpers@amc.uva.nl
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.forename: Maarten
authors.initials: M
authors.lastname: Biezeveld
authors.forename: Annemiek
authors.initials: A
authors.lastname: Achterhuis
authors.forename: Irene
authors.initials: I
authors.lastname: Kuipers
authors.forename: Jan
authors.initials: J
authors.lastname: Lam
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: Anton E
authors.initials: AE
authors.lastname: Becker
authors.forename: Allard C
authors.initials: AC
authors.lastname: van der Wal
mesh_terms: D000783:Aneurysm / Q000209:etiology / Q000473:pathology; D002097:C-Reactive Protein / Q000032:analysis; D003327:Coronary Disease / Q000209:etiology / Q000473:pathology*; D016572:Cyclosporine / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D004351:Drug Resistance; D017809:Fatal Outcome; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology; D012459:Salicylates / Q000627:therapeutic use; D012697:Serine Endopeptidases / Q000097:blood
chemical_list: D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D012459:Salicylates; D016572:Cyclosporine; D002097:C-Reactive Protein; D012697:Serine Endopeptidases; D008775:Methylprednisolone