2. 1.- Inflamacion granulomatosa de tracto
respiratorio
2.- glomerulonefritis progresiva
3.- vasculitis necrotizante de arterias y venas de
mediano y pequeño calibre
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
10. 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
11. 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
12.
13. 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)
14.
15. 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. Wegener's granulomatosis with renal involvement: Patient
survival and correlations between initial renal function, renal histology, therapy
and renal outcome. Clin Nephrol 2007; 35:139.
16. EULAR CLASSIFICATION
classification of ANCA-associated vasculitis
1.-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
17.
18. 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
19. SUMMARY AND RECOMMENDATIONS
— The treatment of Wegener's 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 Wegener's granulomatosis. Arthritis Rheum 2003 ; 39:2052.
20. 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.
21. 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.
22. DIAGNOSTICO DIFERENCIAL
hypersensitivity vasculitis, septic arthritis
(fungal, tuberculosis), lymphomatoid granulomatosis
other causes of granulomatous arteritis - Churg-Strauss
vasculitis, temporal arteritis, Takayasu's 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
25. 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.