Granulomatosis de wegener


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Granulomatosis de wegener

  2. 2. 1.- Inflamacion granulomatosa de tracto respiratorio2.- glomerulonefritis progresiva3.- vasculitis necrotizante de arterias y venas de mediano y pequeño calibre
  3. 3. ORGANOS COMPROMETIDOS 95% Pulmón (vasos )  35% oído medio 90% senos  30% corazón 85% riñón  20% nervios 75% nasofaringe, periféricos bazo  20% SNC 70% articulaciones 50% piel 50% ojos
  4. 4. INCIDENCIA – PREVALENCIA Bastante rara > Hombres Edad 50-60 años > 95% Caucasicos Arthritis Rheum 2000 Feb;43(2):414 J Watch 2000 Mar 15;20(6):49)
  5. 5. CAUSAS Desconocida Probablemente inmunologica
  6. 6. PATOGENESIS Inmunidad tipo III hipersensibilidad mediada por inmunmocomplejos Vasculitis necrotizante de arterias y venas de mediano y pequeño calibre Matriz de metaloproteinasas (MMPs) y sus inhibidores endogenos han sido sugeridos en rol patologico Infeccion con Staphylococcus pueden provocar recaidas
  7. 7. CUADRO CLINICO Presentaciones comunes  Sinusitis , descarga nasal crónica  Pérdida de audición  Dolor articular  hemoptisis  Hematuria microscópica  Fiebre ( 90 %) Ocasionalmente  Glomerulonefritis, tos, rinitis, otitis, disnea , dolor muscular , neuritis, pérdida de peso Tervaert, JW. Anti-neutrophil cytoplasmic antibodies: Current diagnostic and pathophysiological potential. Kidney Int 2004 ; 46:1
  8. 8. DIAGNOSTICO 1.-Nasal or oral inflammation (painful or painless oral ulcers or purulent or bloody nasal discharge) 2.-Abnormal chest radiograph showing nodules, fixed infiltrates, or cavities 3.-Abnormal urinary sediment (microscopic hematuria with or without red cell casts) 4.- Granulomatous inflammation on biopsy of an artery or perivascular area American College of Rheumatology Arthritis Rheum 2009 Aug;33(8):1101
  9. 9. PRUEBAS A CONSIDERAR Hematometría ,creatinina sérica Examen completo de orina Factor reumatoideo ANA hepatitis serología (ANCA) anti-neutrophil cytoplasmic antibody biopsia  Piel (> rendim), anormalidades en uro análisis  Biopsia de nervio sural  Biopsia nasal (vasculitis and inflamación granulomatosa) Radiografía de tórax Angiografía Ecocardiografía Mayo Clin Proc 2005 Nov;80(11):1435
  10. 10. PRUEBAS SEROLOGICAS ANCA – C 90 % G W alta sensibilidad y especificidad (1,3) ANCA – p negativo (1, 5) ANCA –c  81% sensitivity, 98% specificity, 54% VPP and 99% VPN ; (2,3,4)  ELISA para ANCA –PR3 (5) Ann Intern Med 1997 Jun 1;126(11):866 Journal Club on the Web 1997 Jun 10) Arthritis Rheum 1998 Sep;41(9):1521 Arch Intern Med 2002 Jul 8;162(13):1509 (Ann Rheum Dis 2009 Feb;68(2):228 (5)
  11. 11. ANATOMIA PATOLOGICA PULMON : vasculitis granulomatosa , necrotizante (fibrinoide) , granulomas no caseificantes RIÑÓN : GMN focal y segmentaria con progresión a medias lunas GMN necrotizante VASOS : infiltrado inflamatorio y fibrosis ARTERITIS GRANULOMATOSA : predominantemente infiltrado monocítico con cell gigantes y formación de granuloma Koderisch, J, et al. Wegeners granulomatosis with renal involvement: Patient survival and correlations between initial renal function, renal histology, therapy and renal outcome. Clin Nephrol 2007; 35:139.
  12. 12. EULAR CLASSIFICATION classification of ANCA-associated vasculitis1.-Localized — Upper and/or lower respiratory tract disease without any other systemic involvement or constitutional symptoms.2.-Early systemic — Any, without organ-threatening or life-threatening disease.3.-Generalized — Renal or other organ-threatening disease, serum creatinine ≤ 5.6 mg/dL (500 micromol/L).4.-Severe — Renal or other vital organ failure, serum creatinine ≥ 5.7 mg/dL (500 micromol/L)5.-Refractory — Progressive disease unresponsive to glucocorticoids and cyclophosphamide. European League Against Rheumatism (EULAR) 2008 EULAR recommendation for the management of primary small vessel vasculitis. Ann Rheum Dis 2008
  13. 13. TRATAMIENTO INDUCCION - REMISION  Típicamente altas dosis de esteroides y ciclophosphamide ( oral pulsos IV )  methotrexate (o azatioprina si cr > 2 mg/dL ciclofosfamida i  IV IG 2 g/kg Mantenimiento de remisión  methotrexate 20-25 mg/sem o azathioprine 2 mg/kg/d x 12- 18 m (menos toxica q ciclofl )  trimethoprim-sulfamethoxazole 160/800 mg 2v/d x 24 m reduce el promedio de recaída
  14. 14. SUMMARY AND RECOMMENDATIONS— The treatment of Wegeners granulomatosis usually begins with cyclophosphamide and glucocorticoid therapy to induce remission. Cyclophosphamide is discontinued one to two months after complete remission is achieved, which usually occurs 3 a 6 m. After cyclophosphamide has been discontinued: Maintenance therapy should not be started until the white BCC is >4000 c and the absolute neutrophil count is >1500 c . Tatsis, E, et al. Therapy for the maintenance of remission in sixty-five patients with generalized Wegeners granulomatosis. Arthritis Rheum 2003 ; 39:2052.
  15. 15.  If these criteria are met, maintenance can be begun within days after cessation of oral cyclophosphamide and within two to four weeks after the last monthly dose of intravenous cyclophosphamide Initiation of maintenance therapy with methotrexate or azathioprine to sustain the remission (Grade 1A) Bacon, P. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003; 349:36.
  16. 16.  azathioprine rather than methotrexate for initial maintenance therapy GFR < 50 mL/´ (Grade 2B). - Azathioprine : initial dose of 2 mg/kg x d The dose can be lowered to 1.5 mg/kg x d at one year from the time of initiation of induction therapy - methotrexate : initial dose 0.3 mg/kg 1 v/sem (max 15 mg) increased by 2.5 mg x sem - max dose of 25 mg 1 v /sem + folic acid (1 to 2 mg/day) or folinic acid (2.5 to 5 mg/week, 24 hours after methotrexate) Maintenance immunosuppressive therapy should be continued for 12 to 18 ms. Longer term or indefinite maintenance therapy may be warranted in patients with multiple relapses. glucocorticoid therapy (prednisone or equivalent), using the lowest dose required for control of extrarenal symptoms (Grade 1C). Bacon, P. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2008; 349:36.
  17. 17. DIAGNOSTICO DIFERENCIAL hypersensitivity vasculitis, septic arthritis (fungal, tuberculosis), lymphomatoid granulomatosis other causes of granulomatous arteritis - Churg-Strauss vasculitis, temporal arteritis, Takayasus arteritis, seronegative spondylarthropathy (aortitis) other vasculitis of small-to-medium arteries - polyarteritis nodosa, inflammatory rheumatic diseases, HBV, HCV, HIV infection embolic disease - endocarditis (septic, marantic), atrial myxoma, cholesterol embolization vessel stenosis or spasm - atherosclerosis, fibromuscular dysplasia, drug- induced vasospasm (ergotamines, cocaine, phenylpropanolamine), intravascular lymphoma vessel thrombosis - disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), coumadin-associated necrosis, antiphospholipid antibody syndrome similar syndrome described in 5 adults with autosomal recessive defective surface expression of HLA class-I molecules. cocaine-induced pseudovasculitis described in case report Mayo Clin Proc 2005 May;80(5):671 Lancet 1999 Nov 6;354(9190):1598
  18. 18. COMPLICACIONES Glomerulonefritis (3) rápidamente progresiva  Hemorragia alveolar (gnrp)  pápulas, ulceras y Falla renal lesiones urticariales Sepsis  uveítis, neuritis óptica Anemia normocítica (2) normocrómica  cardiomiopatía dilatada CID y pericarditis Trombo embolismo  enfermedad orbital venoso (1) inflamatoria (4) Compromiso meníngeo Ann Intern Med 2005 Apr 19;142(8):620 Rheumatology (Oxford) 2008 Apr;47(4):530 Mayo Clin Proc 2000 Aug;75(8):856 Eye 2006 Oct;20(10):1196
  19. 19. RESISTENCIA A LA CICLOFOSFAMIDA the first step is to ensure that the cyclophosphamide regimen has been optimized and, if indicated, plasma exchange has been administered. Mycophenolate mofetil or rituximab (Grade 2C). mycophenolate mofetil 500 mg 2v/d which is increased, if there is no response, by 250 mg 2v/d c/2 sem to a max dose 500 mg 2v/d rituximab : 375 mg/m2 weekly for 4 weeks.