1. Vasculitis ANCA positivo
2015
Dr. Cristhian Mauricio Bueno Lara
Especialista en medicina interna – Universidad Autónoma de Bucaramanga
Fellow en Nefrología – Universidad del Valle

2. Conceptos
Comprenhensive Clinical Nephrology 4th Edition
11Para el
nefrólogo
1 2 3 4
5 6 7 8 9 10 11
91 caso por cada
1000 a 10000
habitantes/año
1
3 4 7 865 9
2
3Vasculitis ANCA
positivo 1 32

3. Conceptos
Síndrome riñón - Pulmón
Glomerulonefritis
rápidamente progresiva
Glomerulonefritis
pauciinmune
Vasculitis ANCA positivo
Glomerulonefritis rápidamente progresiva – Hemorragia
alveolar difusa
Disfunción renal en días/semanas
Proteinuria – Hematuria – Semilunas celulares
Presión arterial normal
Escasos depósitos de inmunoglobulinas o complemento en
glomérulo vasos renales
Poliangeítis granulomatosa
Poliangeítis microscópica
Poliangeítis granulomatosa eosinofílica
Stephen C West, Nishkantha Arulkumaran, Philip W Ind, Charles D Pusey. Pulmonary-renal syndrome: a life
threatening but treatable condition. Postgrad Med J 2013

4. Clasificación
American College of Rheumatology 1990

5. Clasificación
Chapel Hill Consensus Conference 1994

6. Clasificación
The European Medicines Agency 2008

7. Clasificación
Eoin F. McKinney & Lisa C. Willcocks & Verena Broecker. The immunopathology of ANCA-associated vasculitis. Semin
Immunopathol (2014) 36:461–478
99 Pacientes
ANCA positivo

8. Friedrich Wegener
• Nacimiento: 4 abril 1907, Noreste
de Alemania.
• Médico y asistente en patología
• Granulomatosis rinógena singular
• Retiro de la medicina en 1970 en
medio del reconocimiento.
• Muerte: 1990 a los 83 años.
• Título: Master Clinician of the
American College of Chest
Physician
Diagnosis and classification of granulomatosis with polyangiitis (aka Wegener’s granulomatosis). Journal of
Autoimmunity 48-49 (2014) 94e98
• 50 a 100 autopsias en judíos al mes
• Año 2007: Destitución de titulo de
Master por ACCP

9. Jacob Churg – Lotte Strauss
• 1951: 13 necropsias
en pacientes con
asma y vasculitis
sistémica.
• Chumbley y Lanham
han cambiado los
criterios.
Diagnosis and classication of eosinophilic granulomatosis with polyangiitis (formerly named Churge Strauss syndrome)
Journal of Autoimmunity 48-49 (2014) 99e103

10. Clasificación
Chapel Hill Consensus Conference 2012

11. Clasificación
Chapel Hill Consensus Conference 2012
Vasculitis de pequeño vaso
2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Vol. 65, No. 1, January
2013, pp 1–11

12. Clasificación
Chapel Hill Consensus Conference 2012
Vasculitis ANCA positivo
2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Vol. 65, No. 1, January
2013, pp 1–11
Vasculitis necrotizante
Sin o muy poco depósitos inmunes
Afectación de pequeño vaso
Asociado a ANCA Mieloperoxidasa o Proteinasa 3
Poliangeítis microscópica
Glomerulonefritis necrotizante
Capilaritis pulmonar es frecuente
No inflamación granulomatosa
Poliangeítis granulomatosa
Inflamación granulomatosa necrotizante
Compromiso respiratorio alto o bajo
Glomerulonefritis necrotizante
Poliangeítis granulomatosa
eosinofílica
Inflamación granulomatosa necrotizante y rica en eosinófilos
Asociada a asma con eosinofilia
Afectación del tracto respiratorio

13. Epidemiología
Classification, epidemiology and clinical subgrouping
of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Nephrol Dial Transplant (2015) 30: i14–i22
Por millón de habitantes

14. Epidemiología local
2015
85%
Hispanos
48%
Caucásicos

15. Fisiopatología
Diagnosis and classication of eosinophilic granulomatosis with polyangiitis (formerly named Churge Strauss syndrome)
Journal of Autoimmunity 48-49 (2014) 99e103

16. Fisiopatología
Comprenhensive Clinical Nephrology 4th Edition

17. Manifestaciones Clínicas
Comparison of disease activity measures for anti-neutrophil
cytoplasmic autoantibody (ANCA)-associated vasculitis
PA Merkel1, DD Cuthbertson2, B Hellmich3, GS Hoffman4, DRW Jayne5, CGM Kallenberg6,
JP Krischer2, R Luqmani7, AD Mahr8, EL Matteson9, U Specks9, and JH Stone10 for the
Vasculitis Clinical Research Consortium
1Boston University School of Medicine, Boston, Massachussets, USA 2University of South
Florida, Tampa, Florida, USA 3Kreiskrankenhaus Plochingen, Plochingen, Germany 4Cleveland
Clinic, Cleveland, Ohio, USA 5Addenbrookes Hospital, Cambridge, UK 6University Medical Center
Groningen, University of Groningen, Groningen, The Netherlands 7University of Oxford, Oxford,
UK 8Hospital Cochin, Paris, France 9Mayo Clinic, Rochester, Minnesota, USA 10Massachusetts
General Hospital, Boston, Massachussets, USA
Abstract
Aim—Currently, several different instruments are used to measure disease activity and extent in
clinical trials of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, leading
to division among investigative groups and difficulty comparing study results. An exercise
comparing six different vasculitis instruments was performed.
Methods—A total of 10 experienced vasculitis investigators from 5 countries scored 20 cases in
the literature of Wegener granulomatosis or microscopic polyangiitis using 6 disease assessment
NIH Public Access
Author Manuscript
Ann Rheum Dis. Author manuscript; available in PMC 2011 July 19.
Published in final edited form as:
Ann Rheum Dis. 2009 January ; 68(1): 103–106. doi:10.1136/ard.2008.097758.
Comparison of disease activity measures for anti-neutrophil
cytoplasmic autoantibody (ANCA)-associated vasculitis
PA Merkel1, DD Cuthbertson2, B Hellmich3, GS Hoffman4, DRW Jayne5, CGM Kallenberg6,
JP Krischer2, R Luqmani7, AD Mahr8, EL Matteson9, U Specks9, and JH Stone10 for the
Vasculitis Clinical Research Consortium
1Boston University School of Medicine, Boston, Massachussets, USA 2University of South
Florida, Tampa, Florida, USA 3Kreiskrankenhaus Plochingen, Plochingen, Germany 4Cleveland
Clinic, Cleveland, Ohio, USA 5Addenbrookes Hospital, Cambridge, UK 6University Medical Center
Groningen, University of Groningen, Groningen, The Netherlands 7University of Oxford, Oxford,
UK 8Hospital Cochin, Paris, France 9Mayo Clinic, Rochester, Minnesota, USA 10Massachusetts
General Hospital, Boston, Massachussets, USA
Abstract
Aim—Currently, several different instruments are used to measure disease activity and extent in
clinical trials of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, leading
to division among investigative groups and difficulty comparing study results. An exercise
comparing six different vasculitis instruments was performed.
Methods—A total of 10 experienced vasculitis investigators from 5 countries scored 20 cases in
NIH Public Access
Author Manuscript
Ann Rheum Dis. Author manuscript; available in PMC 2011 July 19.
Published in final edited form as:
Ann Rheum Dis. 2009 January ; 68(1): 103–106. doi:10.1136/ard.2008.097758.
2009
Poliangeítis microscópica
82% compromiso glomerular
Piel, Articulaciones y pulmonar
Poliangeítis granulomatosa
80% compromiso glomerular
90% compromiso pulmonar (Alto o bajo)
Poliangeítis granulomatosa
eosinofílica
50% frecuente compromiso glomerular
100% Asma
72% Sistema nervioso periférico

18. Manifestaciones Clínicas
Comprenhensive Clinical Nephrology 4th Edition

19. Diagnóstico
Estudio inicial
Exámenes iniciales
Hemograma tipo IV
Creatinina
Nitrógeno ureico en sangre
Uroanálisis
Anticuerpos antinucleares
Función hepática
Clínica ANCAs
Comprenhensive Clinical Nephrology 4th Edition

20. Diagnóstico
ANCA dirigido a auto-antígenos
Clinical features and diagnosis of small-vessel vasculitis. doi:10.3949/ccjm.79.s3.01
Mejor prueba para la evaluación de los ANCA
Valor pronóstico de los ANCA
Implicación clínica del tipo de ANCA
toemphasizethat t
usedintheselabora
whereIFTwithor w
A variety of dif
tionof ANCAshav
includingthird-ge
based multiplex a
for analysingANC
summarizesthem
methodologyand
testinginvasculitis
applyingthesetech
Automated ana
Despitetheemerge
IFTremainstherec
ingin vasculitis. H
dependsonanum
conjugatesandfixa
cells,storagecond
andwashing.7
Furt
consuming,requir
performance compared with conventional assays and can be used for PR3-ANCA
and MPO-ANCAdetection
The new methods for ANCAdetection and evaluation in ANCA-associated
vasculitis should be urgentlyevaluated in multicentre studies, in anticipation
of updating of standardization processes and a revision of existing strategies
a b
Figure 1 | ANCAIIFpattern differentiation byautomated signal intensityanalysis.
IIFimages, taken automatically byAKLIDES®, can discriminate a | P-ANCA-specific
and b | C-ANCA-specific staining of neutrophils byuse of mathematical algorithms
for pattern differentiation. Chromatin is stained byDAPI (blue) and specific ANCA

21. Diagnóstico
ANCA dirigido a auto-antígenos
Clinical features and diagnosis of small-vessel vasculitis. doi:10.3949/ccjm.79.s3.01
Mejor prueba para la evaluación de los ANCA
Inmunofluorescencia
Pruebas antígeno-
específicas

22. Diagnóstico
ANCA dirigido a auto-antígenos
Current and emerging techniques for ANCA detection in vasculitis Nat. Rev. Rheumatol. 10, 494–501 (2014)
rapidANCA testing.35
In thisassay,IFT iscombinedwitha
dot-blot test for PR3-ANCA and MPO-ANCA. However,
theresultsobtained areonly qualitativeand should be
confirmed and quantified by other ANCA assays.
patientswith suspected vasculitisneedstobeevaluated in
prospectivestudies.
Clinical usefulness of ANCA testing
Table 1 | Comparison of methods for testing for PR3-ANCA and MPO-ANCA in ANCA-associated vasculitis
Patient population
(n) vs comparison
group (n)
Method Sensitivity
(%)
Specificity
(%)
PPV
(%)
NPV
(%)
AUC/ ROC Comments
GPA (86) vs
non-vasculitic
disease (450)28
IFT
Direct PR3-ANCA ELISA
Capture ELISA
Anchor ELISA
92
60
72
96
99
99
99.3
98.5
Nd Nd 0.96 (0.94–0.98)
0.80 (0.76–0.83)
0.86 (0.82–0.89)
0.96 (0.94–0.98)
Histological
diagnosis
Retrospective
study
GPA (232) vs
in ammatory
diseases (661)29
IFT
Anchor ELISA
77.9
80.4
90.9
97.4
73
88
93
93
Nd Histological
diagnosis
Prospective
study
GPA (59* ) vs
in ammatory and
infectious diseases
(585)30
Hn–hr PR3-ANCA ELISA
Capture ELISA
Direct (hn) PR3-ANCA
94
66
64
99
(prede ned)
Nd Nd Nd Histological
diagnosis
Retrospective
study
GPA (34) vs SLE
(65)31
Direct PR3-ANCA
Anchor ELISA
97.1 98.4 Nd Nd 0.999
(0.947–1.00)
Clinical
diagnosis
Retrospective
study
GPA (40) vs RA
or SLE (20)32
IFT
Direct PR3-ANCA (n= 5 kits)
Capture ELISA (n=2 kits)
Anchor ELISA (n= 4 kits)
62.5
45–55
60–62.5
60–62.5
95–100 Nd Nd Nd Histological
diagnosis
Retrospective
study
MPA (40) vs RA
or SLE (20)32
IFT
Direct MPO-ANCA ELISA
(n= 8 kits)
Capture ELISA (n=2 kits)
Anchor ELISA (n= 1 kit)
82.5
62.5–85
80
75
95–100 Nd Nd Nd Histological
diagnosis
Retrospective
study
GPA (55) vs
suspected
vasculitis (175)33
IFT
Direct PR3-ANCA ELISA
(n= 2 kits)
Capture ELISA (n=2 kits)
Anchor ELISA (n= 3 kits)
Other assays (n=2)
69.1
61.8–72.7
70.9–72.7
61.8–72.7
72.7–74.5
100
95.4–96.4
95.9–99.5
98.5–99.0
95.9–97.9
Nd Nd Nd
0.856–0.879
0.862–0.878
0.833–0.881
0.878–0.902
Clinical
diagnosis
Retrospective
study
* 47 of 59 patients in the GPA group had a cytoplasmic ANCA pattern on IFT. Abbreviations: ANCA, antineutrophil cytoplasmic antibody; AUC, area under the
curve; GPA, granulomatosis with polyangiitis; hn, human native; hr, human recombinant; IFT, indirect immunofluorescence technique; MPA, microscopic
polyangiitis; MPO, myeloperoxidase; Nd, not determined; NPV, negative predictive value; PPV, positive predictive value; PR3, proteinase 3; RA, rheumatoid
arthritis; ROC, receiver operating characteristics; SLE, systemic lupus erythematosus.
REVIEWS

23. Diagnóstico
ANCA dirigido a auto-antígenos
Valor pronóstico de los ANCA
Comparison of disease activity measures for anti-neutrophil
cytoplasmic autoantibody (ANCA)-associated vasculitis
PA Merkel1, DD Cuthbertson2, B Hellmich3, GS Hoffman4, DRW Jayne5, CGM Kallenberg6,
JP Krischer2, R Luqmani7, AD Mahr8, EL Matteson9, U Specks9, and JH Stone10 for the
Vasculitis Clinical Research Consortium
1Boston University School of Medicine, Boston, Massachussets, USA 2University of South
Florida, Tampa, Florida, USA 3Kreiskrankenhaus Plochingen, Plochingen, Germany 4Cleveland
Clinic, Cleveland, Ohio, USA 5Addenbrookes Hospital, Cambridge, UK 6University Medical Center
Groningen, University of Groningen, Groningen, The Netherlands 7University of Oxford, Oxford,
UK 8Hospital Cochin, Paris, France 9Mayo Clinic, Rochester, Minnesota, USA 10Massachusetts
General Hospital, Boston, Massachussets, USA
Abstract
NIH Public Access
Author Manuscript
Ann Rheum Dis. Author manuscript; available in PMC 2011 July 19.
Published in final edited form as:
AnnRheumDis. 2009 January ; 68(1): 103–106. doi:10.1136/ard.2008.097758.
Comparison of disease activity measures for anti-neutrophil
cytoplasmic autoantibody (ANCA)-associated vasculitis
PA Merkel1, DD Cuthbertson2, B Hellmich3, GS Hoffman4, DRW Jayne5, CGM Kallenberg6,
JP Krischer2, R Luqmani7, AD Mahr8, EL Matteson9, U Specks9, and JH Stone10 for the
Vasculitis Clinical Research Consortium
1Boston University School of Medicine, Boston, Massachussets, USA 2University of South
Florida, Tampa, Florida, USA 3Kreiskrankenhaus Plochingen, Plochingen, Germany 4Cleveland
Clinic, Cleveland, Ohio, USA 5Addenbrookes Hospital, Cambridge, UK 6University Medical Center
Groningen, University of Groningen, Groningen, The Netherlands 7University of Oxford, Oxford,
UK 8Hospital Cochin, Paris, France 9Mayo Clinic, Rochester, Minnesota, USA 10Massachusetts
General Hospital, Boston, Massachussets, USA
NIH Public Access
Author Manuscript
Ann Rheum Dis. Author manuscript; available in PMC 2011 July 19.
Published in final edited form as:
Ann Rheum Dis. 2009 January ; 68(1): 103–106. doi:10.1136/ard.2008.097758.
NIH-PAAuthorManuscriptNIH-P
2009
NO

24. Diagnóstico
ANCA dirigido a auto-antígenos
Implicación clínica del tipo de ANCA
1995

25. Diagnóstico
Imágenes
Pathogenesis of ANCA-Associated Vasculitis: New Possibilities for Intervention. Am J Kidney Dis. 62(6):1176-1187
Nódulos pulmonares múltiples
Cavitaciones
Patrón en vidrio esmerilado

26. Diagnóstico
Histopatología
Focal
Creciente
Mixto
Esclerótica
2010

27. Diagnóstico
Histopatología
Histopathological classification of pauci-immune glomerulonephritis and its impact on outcome. Rheumatol Int
(2014) 34:1721–1727

28. Diagnóstico
Clinical features and diagnosis of small-vessel vasculitis. doi:10.3949/ccjm.79.s3.01

29. Diagnóstico
2008

30. Tratamiento
Ciclofosfamida
2009

31. Tratamiento
Treatment of ANCA-Associated Vasculitis: New Therapies and a Look at Old Entities. Advances in Chronic Kidney
Disease, Vol 21, No 2 (March), 2014: pp 182-193
1. Ciclofosfamida 15 mg/Kg/dosis cada 2 semanas por 3
dosis.
2. Continuar con Ciclofosfamida 15 mg/Kg/dosis cada 3
semanas hasta la remisión de la enfermedad
3. Continuar hasta 3 meses posterior a remisión de la
enfermedad con medicación oral o endovenosa
(Mantenimiento)
Ciclofosfamida

32. Tratamiento
Rituximab
2015

33. Tratamiento
Plasmaféresis
2013

34. Tratamiento
Inmunoglobulina
2009

35. Tratamiento
Inmunoglobulina
Intravenousimmunoglobulin asadjuvant therapy for
Wegener’sgranulomatosis(Review)
Fortin PM, Tejani AM, Bassett K, Musini VM
Figure 1. QUORUM (qualityof reportingmeta-analyses) flowchart of studyselection
Included studies
For detailsof theincluded study seeCharacteristicsof included
studies.
Thisstudywasaprospective,randomized,double-blind,placebo-
controlled multicenter trial. Thirty four patientswererandomly
assignedtoreceiveIVIg(total dose=2g/kg,n=17)or placebo(n
patientseither relapsing on steroidsalone(or steroidsin combi-
nation with immunosuppressant therapy) or thosethat did not
achievefull remission on steroidsin combination with immuno-
suppressant therapyfollowinginitial presentation.
Patients were excluded from participating in the trial if they
had any of the following characteristics: IVIg therapy during
the previous three months, history of anaphylaxis to properly
matchedbloodproducts,selectiveIgAdeficiency,rapidlyprogres-
Main results
WeincludedoneRCT with34participantswhowererandomlyassignedtoreceiveIVIgor placebooncedailyinaddition toazathioprine
and prednisolone for remission maintenance. Therewere no significant differencesbetween adjuvant IVIg and adjuvant placebo in
mortality, seriousadverseevents, timetorelapse, open-label rescuetherapy, and infection rates. Thefall in diseaseactivity score, derived
from patient-reported symptoms, was slightly greater in the IVIg group than in the placebo group at one month (MD 2.30; 95%
Confidenceinterval (CI) 1.12 to 3.48, P<0.01) and threemonths(MD 1.80; 95% CI 0.35 to 3.25, P=0.01). Therewasasignificant
increasein total adverseeventsin theIVIggroup (relativerisk (RR) 3.50; 95% CI 1.44 to 8.48, P< 0.01).
Authors’ conclusions
Thereisinsufficient evidencefromoneRCT that IVIgadjuvant therapyprovidesatherapeuticadvantagecomparedwiththecombination
of steroids and immunosuppressants for patients with WG. Given the high cost of IVIg (one dose at 2 g/kg for a 70 kg patient =
$8,400), it should belimited to treat WG in thecontext of awell conducted RCT powered to detect patient-relevant outcomes.
P L A I N L A N G U A G E S U M M A R Y
Intravenousimmunoglobulin in addition to standard treatmentsfor Wegener’sgranulomatosis
Wegener’sgranulomatosis isararedisorder that causesinflammation of theblood vessels. Thisinflammation restrictsblood flow to
2013

36. Tratamiento
Treatment of ANCA-Associated Vasculitis: New Therapies and a Look at Old Entities. Advances in Chronic Kidney
Disease, Vol 21, No 2 (March), 2014: pp 182-193

37. Futuro
2015