title: Refractory Wegener's granulomatosis responds to tumor necrosis factor blockade.
abstract: Wegener's granulomatosis is a systemic necrotising vasculitis of small vessels that leads to severe impairment of affected organ systems. Conventional treatment is based on immunosuppression with a combination of steroids, cyclophosphamide, azathioprine or methotrexate over a prolonged time course. Early recurrence or disease refractory to therapy often results in a fatal outcome. As in other inflammatory disorders, tumor necrosis factor (TNF) plays an early and crucial role in progression of disease activity. We report on a patient with severe orbital Wegener's granulomatosis who developed acute renal failure despite intense conventional immunosuppression with cyclophosphamide and steroids. To stop vasculitic activity, by disrupting the autoimmune inflammatory cascade, a TNF-blocking antibody (Infliximab) was administered six times in a six-month period at 3 mg/kg body weight. Conventional immunosuppressive therapy with steroids and cyclophosphamide was continued, the latter being changed to azathioprine after three months. The first infusion of TNF antibody induced improvement of renal function, which continued throughout the course of therapy. The modification of diet in renal disease-glomerular filtration rate (MDRD-GFR) increased from 15.3 ml/min/1.73 m2 before the start of TNF-blockade to 55.5 ml/min/1.73 m2 after six months of therapy. Serum creatinine levels, proteinuria and cANCA titer decreased concomitantly. Clinical remission of Wegener's granulomatosis was induced without any major adverse events. A slight flare of orbital inflammation was successfully treated with an increased dose of azathioprine. Thus, in this case of refractory Wegener's granulomatosis TNF-blockade by monoclonal chimeric TNF-antibody (Infliximab) served as an effective tool to rescue kidney function and induce clinical remission.
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Kleinert
authors.forename: Matthias
authors.initials: M
authors.lastname: Lorenz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Köstler
authors.forename: Walter
authors.initials: W
authors.lastname: Hörl
authors.forename: Gere
authors.initials: G
authors.lastname: Sunder-Plassmann
authors.forename: Afschin
authors.initials: A
authors.lastname: Soleiman
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D001706:Biopsy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069285:Infliximab; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009916:Orbital Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D019233:Retreatment; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D003520:Cyclophosphamide; D011239:Prednisolone; D000069285:Infliximab; D008775:Methylprednisolone