2. Jason Kidd Morning Report 11/18/2009

3. Wegener: Controversy “Unlike doctors who joined the Nazi Party to be allowed to practice, Wegener joined the movement in 1932, before Hitler took power. He rose to a relatively high military rank and spent some of the war in a medical office three blocks from the Jewish ghetto in Lodz, Poland. Sketchy records suggest that he might have participated in experiments on concentration camp inmates.” Feder, NY Times 1/22/2008

4. Definition “A distinct clinicopathologic entity characterized by granulomatous vasculitis of the upper and lower respiratory tracts together with glomerulonephritis.” Harrison’s

5. Incidence and Prevalence Estimated prevalence: 3 per 100,000 1:1 male to female ratio Mean onset: 40 Harrison’s

6. Diagnostic Criteria: American College of Rheumatology proposed clinical criteria for diagnosis of WG: Nasal or oral inflammation Abnormal CXR Abnormal urinary sediment: hematuria with or without RBC casts Granulomatous inflammation on biopsy Adapted from UpToDate and Harrison’s

7. Diagnosis According to the Chapel Hill Consensus Conference: Granulomatous inflammation of respiratory tract Vasculitis of small to medium size vessels Jennette JC et al, Arthritis Rheum 1994

8. Upper Respiratory Tract Upper airway disease occurs in 90% of patients Nasal involvement may present with epistaxis, rhinorrhea, purulent discharge Otitis media and eustachian tube blockage can occur Nasal septal perforation may occur, leading to saddle nose deformity Subglottic tracheal stenosis can cause airway obstruction

9. Pulmonary Involvement Cough, hemoptysis, dyspnea Infiltrates and cavitary lesions can be seen on radiography Lung involvement typically appears as bilateral, nodular cavitary infiltrates Biopsy: necrotizing granulomatous vasculitis

11. Renal Involvement Generally manifested with acute renal failure Urine sediment: red cells, red cell casts, proteinuria Accounts for most of the mortality of this disease Renal biopsy: segmental necrotizing glomerulonephritis

12. Urine Sediment

13. Renal Biopsy

14. Laboratory tests Nonspecific Leukocytosis, thrombocytosis, elevated CRP, elevated ESR can all be seen 90-95% of patients with active Wegener’s are ANCA positive Diagnosis is confirmed by biopsy at site of active disease

15. Other Manifestations Joints: myalgias, arthralgias Eyes: episcleritis, uveitis Skin: palpable purpura, ulcerative lesions CNS: cranial nerve abnormalities Cardiac: pericarditis, coronary vasculitis High incidence of DVT

16. Treatment Diagnosis Remission Induction Remission maintenance Relapsing Disease Refractory Disease

17. Remission Induction Glucocorticoids Dosing has not been examined in randomized trials Generally start 1 mg/kg/day  10-20 mg daily at 12 weeks Cyclophosphamide Pulsed, IV is thought to be safer then oral Risk of myelosuppresion, infection, malignancy Plasma Exchange Shown in small studies to improve chances of renal recovery Recommended in lung hemorrhage Jayne, Nephrology 2009

18. Remission Maintenance Azathioprine or Methotrexate can be substituted for Cyclophosphamide after 3-6 months No standard length of treatment or regimen Relapses occur mostly in pt’s with continued ANCA positivity Relapse in WG has been assoc with nasal carriage of S. Aureus Utility of TMP/SMX prophylaxis? Jayne, Nephrology 2009

19. What happened? She received IV Cytoxan and Plex while hospitalized She has received a total of 3 doses of IV Cytoxan BAL grew Penicillium, currently being treated w/Vori She developed LE petechiae and RLE DVT She continues to be HD dependent

20. Sources Carruthers D et al, Evidence based management of ANCA vasculitis, Best Practice & Research Clinical Rheumatology 2009, 23:367-378 Feder B, A Nazi Past Casts a Pall on Name of Disease, New York Times, Jan 22 2008 Jayne D, Progress of treatment in ANCA-associated vasculitis, Nephrology 2009, 14: 42-48 Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CG, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994;37:187-92 Jennette JC, Falk RJ, Small Vessel Vasculitis, New England Journal of Medicine, 1997, 21: 1512-1523 Kasper et al, Harrison’s Principles of Internal Medicine, 2005 UpToDate 2009

21. Questions?

22. Anything is possible.