CLINICAL SCIENCE SESSION : VASCULITIS - Dr Paul Bacon
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Transcript of CLINICAL SCIENCE SESSION : VASCULITIS - Dr Paul Bacon
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Paul Bacon FRCPProfessor EmeritusRheumatology Research GroupCollege of Medicine & DentistryUniversity of Birmingham, UK
Area of special interest - SystemicVasculitis
Photo
Roadmaps toward the Classification of Vasculitis
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MAP of India
to show where
Kochi is located
Map of Ko-chi
Roadmaps for Vasculitis
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Roadmaps for Vasculitis
“to travel is better than to arrive”
No direct route-map – so need severalgetting steadily more comprehensive
Illustrate principals behind each attemptby going through the history
Current maps - sufficient to enable all physiciansto manage the majority of cases
- enough still unknown to entice young physicians
to specialise in vasculitis
sick pa-tient
Diagnosis of spe-cific vasculitis
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Classification of VasculitisVasculitis - inflammation in blood vessels
Defined by pathology
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Classification of Vasculitis
History of Vasculitis studies
Classification by vessel size & organ distribution
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Roadmap for VasculitisHistory - a disconnected set of discoveries
1866 PAN - Kussmaul & Maier“On a previously undescribed peculiar arterial disease (periarteritis nodosa), accompanied by Bright’s disease
and rapidly progressive general muscle weakness”
HPC. Male 27 -malaise fever & weakness; muscle pains ++numbness hand, then progressive paralysis
“nephritis” - haematuria/proteinuria; sc nodules - neck & abdo
PM. - multiple small nodules “like seeds” = aneurysmal thickening small muscular arteries
- sc & in bowel, kidney, spleen, heart & skeletal muscles
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History - a disconnected set of discoveriesRoadmap for Vasculitis
PAN - Kussmaul & Maier 1866
variants of “PAN”:“The only Microscopically recognisable form of Periarteritis Nodosa" - Wohlwill 1923PAN with predominant lung disease Wegener 1938 Churg & Strauss 1951PAN - predominant skin lesions - Henoch Schonleinlarge vv disease - Takayasu aorto-arteritis; Hortons Cranial GCAPAN due infection - HB Ag; Cryoglobulinaemia
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Periarteritis nodosa 1866 a rare new disease
Polyarteritis nodosa 1903 a series
Kussmaul & Maier
WG Wegener 1936
CSS
KS
Churg & Strauss 1951
Kawasaki 1957
Classification of Vasculitis - History
Microscopic form Wohlwill 1923
Historical Map 1.a
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Classification of Vasculitis
The spectrum of vasculitis - as perceived by a highly intelligent, experienced medical student
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Roadmap for Vasculitis
ACR 1990 criteria for classification of Vasculitis
ACR set up committee of interested rheumatologists to agree standard definitions
History - by 1970’s multiple forms of vasculitis need for definitions to aid classification cases
*****Huge collegiate effort.
Data collected at 47 centres from 1000 patients with one of 7 types of vasculitis
Data forms checked by committee, coded & analyseddata for each type compared to pooled data from rest
to select a specific criteria set for each
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Roadmap for Vasculitis ACR criteria 7 syndromes included
Polyarteritis NodosaChurg-Strauss syndromeWegeners granulomatosis
“Hypersensitivity vasculitis” Giant cell (temporal) arteritisTakayasu arteritis
Historical Map 1.b
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Roadmap for Vasculitis ACR criteria - GCA and TA
GCA – 214 pts compared to 593 “other vasculitis”5 criteria selected: Age > 50; localised headache;
Temporal tenderness/ loss pulse; ESR > 50;biopsy +ve
3 of 5 +ve sensitivity 93%; specificity 91%
TA – 63 pts compared to 744 controls6 criteria selected: Age < 40;limb claudication;
loss brachial pulse; BP difference >10mmHg;subclavian bruit; aortogram - aortic narrowing
3 of 6 +ve sensitivity 90%; specificity 98%
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Roadmaps for Vasculitis ACR 1990 criteria for classification of Vasculitis - misuse
Huge collegiate effort. Data driven, computer analysed- but problemsCriteria largely clinical in absence diagnostic testsData collected at 47 centers from 1000 patients - no standardisation of their diagnosis
- all established cases – so no criteria derived forearly cases or forme fruste
Classification criteria do not include full spectrum of disease manifestations
Inappropriate in diagnosis individual patients
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Classification of VasculitisACR criteria - further problems, not all specialities agreed
2. Variants of PAN - Nephrologists seeing “PAN" with predominant renal disease -
rejected criteria for PANSavage et al
“The only Microscopically recognisable form of Periarteritis Nodosa" - Wohlwill 1923
1. Hypersensitivity vasculitis
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2 day meeting driven by pathologists/nephrologists
only 3 rheumatologists
Chapel Hill Consensus Conference ’94
Definitions agreed for 9 major forms of Io systemic vasculitis • nb these are descriptions, not diagnostic
criteria• they utilise the old concept of vessel size• and emphasise the relevance of vessel size
Roadmaps for Vasculitis
Historical Map 2 .
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Chapel Hill Consensus Conference ’94Proposed Classification for 10 Systemic Vasculitis
Takayasu arteritisGiant Cell (Temporal) arteritis
Polyarteritis Nodosa (classic PAN)Kawasaki syndrome
Churg Strauss syndrome *Wegener syndrome *Microscopic polyangiitis (MPA) *
Henoch Schonlein purpura Essential Cryoglobulinaemic vasculitis
(EMC)Historical map 2.
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Medium-Sized Vessel Vasculitis
Microscopic Polyangiitis, Wegener’s Granulomatosis, and Churg-Strauss Syndrome
Aorta
Arteries
Arteriole
CapillaryVenule
Vein
Polyarteritis nodosa,
Chapel Hill Consensus Conference ’94
Medium VesselPAN & Kawasaki
Large VesselGCA & Takayasu
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Small Vessel Vasculitis
Necrotizing arteritis predominantly affecting medium-sized arteries defined as the main visceral arteries and their branches. Inflammatory aneurysms are common.
Vasculitis predominantly affecting small vessels, defined as small intraparenchymal arteries, arterioles, capillaries and venules. Medium sized arteries and veins may be affected.
Medium Vessel Vasculitis
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WGCSS KS
Classification - History to Chapel Hill Periarteritis nodosa 1866
Polyarteritis nodosa 1903
Microscopic Polyangiitis
MPAClassic PAN a rare disease
“Hyper sensitivity angiitis”
Cutaneous vasculitis
“Renal PAN”
“Microscopic polyarteritis”
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Classification of AASV and PAN
10 SV
CSS
MPA
cPAN
WG
yes
Unclassified Vasculitis
ACR criteria CSS
ACR criteria WG
Histology (CHCC) =WG
no
no
noSurrogate markers
Map 2 – how to get there. EMA algorhythm. Watts et al 2007
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2012 International Chapel Hill Consensus Conference
Map 3. – definitive, up-to-date and detailed
Names for adopted Vasculitides
Large Vessel Vasculitis - LVVMedium Vessel Vasculitis - MVVSmall Vessel Vasculitis - SVV
Variable Vessel Vasculitis - VVV eg Behcets
Single Organ Vasculitis - SOVVasculitis assoc Systemic Dis
RA, Lupus, Sarcoid, etcVasculitis assoc probable aetiology
Hep B, Hep C, Drugs, Cancer, etc
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2012 Revised CHCC – Types of vessels defined as large, medium, and small
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Chapel Hill Consensus Conference 2 ’2012
A A S V MPA GPA
EGPA
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1. Is “best therapy” the same for all small vessel vasculitis?
2. Is Cyc (cyclophosphamide) the best treatment for SV?
3. Is Iv Cyc better than oral cyc for SV?
Multi-choice questions
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Chapel Hill Consensus Conference 2 ’2012
A A S V MPA GPA
EGPA
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Classification of VasculitisVasculitis - inflammation in blood vessels
Defined by pathology. Pathogenetic mechanisms, trigger
agents,genetic background
all needed for proper understanding
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Adherence / entry of leukocytes
EC
T
T cell activation
LPS
TNFIL-1
Endothelial cell death
EC
ROSproteases
ANCA
Pathogenesis AA.SV
T
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ANCA - associated vasculitis Inflammation in wall of small blood vessels
type - acute necrotising inflammation trigger - unknown infection(s) pathology - anti-body mediated
polymorph degranulation
biomarkers ANCA + CRP surrogate marker - BVAS**
Treatment - immuno-suppression /B-cell depletion +/- steroids strong evidence base, prognosis improved ++
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Classification of VasculitisVasculitis - inflammation in blood vessels
Defined by pathology. Pathogenetic mechanisms, trigger
agents,genetic background
all needed for proper understanding
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What do we classify
vessel size & organ distribution
vessel wall – inflamed or scarred aetio-pathogenesis ?
Roadmaps for Vasculitis
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Roadmaps to Vasculitis Descriptions of Vasculitis – tour of history
Diagnostic criteria – standardised classification ACR criteria
Definitions of disease – standard nomenclatureChapel Hill 1
Diagnostic algorhythm – EMA practical guide
Definitions revisited – updated, comprehensiveChapel Hill 2
Why classify? what do you want it for ?
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Roadmaps for VasculitisFUTURE
what needs to be done now? It is up to you
Clinicians - use all these maps to derive individual patient-centred regimes
for the benefit of your patients
disease assessments & management recommendationsEULAR, ACR, etc
Researchers – focus on pathogenesis & biomarkers for each vasculitis syndrome
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What do we classify
vessel state - narrowed or blocked?
vessel size & organ distribution
vessel wall – inflamed/scarred aetio-pathogenesis ?
Roadmaps for Vasculitis
Disease Assessment - Activity v Damage
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Roadmaps for VasculitisFUTURE
It is up to clinicians to use these maps to derive individual patient-centred regimes relevant to diagnosis
management recommendationsEULAR recommendations for the management ofPrimary small and medium vessel vasculitis 2009
EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis 2016.
EULAR recommendations for the management of large vessel vasculitis 2009.
Indian Recommendations for management of Tak?
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Roadmaps for VasculitisDCVAS
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Roadmap for Vasculitis ACR 1990 criteria for 7 syndromes included
PAN, CSS, Wegeners, “Hypersensitivity vasc”,
GCA & Tak
nb used for studies & trials still not diagnostic criteria
ACR/EULAR 2017 CRITERIA for AA.SV & PANWeighted criteria, based on analysis of DCVAS data
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“not everything in the garden is roses”
Roadmaps for Vasculitis
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Assessment of aorto-arteritis - TA
• Metabolomics – unbiased approach
markers of a) sub-clinical disease b) predictors of relapse
c) response to therapy biomarkers still urgently needed in TA
• Detailed clinical assessment important start
- may help to understand pathology
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Classification of VasculitisWhat do we classify?
vessel size & organ distribution
vessel state - narrowed or blocked?
Disease AssessmentActivity v Damage
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Vasculitis Assessment, Therapy, & CVS disease
VASCULITIS - what is it ?
HISTORY
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Large Vessel VasculitisTakayasu arteritis
Aorta
Arteries
Arteriole
CapillaryVenule
Vein
Chapel Hill Consensus Conference ’94
CH definition
Granulomatous inflammationof the aorta and major branchesprogressing to chronic stenosis,
Usually in < 50’s, typically young women, commoner in Asians often with vessel occlusion
Aorta
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AA.SV - ANCA-associated Small Vessel Vasculitis
Chapel Hill Consensus Conference ’94
Small Vessel Vasculitis
Aorta
Arteriole
CapillaryVenule
Vein
Microscopic Polyangiitis, Wegener’s Granulomatosis, and Churg-Strauss Syndrome
LVV.Med.SVV.CHCC 2011.ppt
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Large Vessel VasculitisSmall Vessel Vasculitis
Vasculitis affecting large arteries more often than other vasculitides. Large arteries are the aorta and its major branches. Any size artery may be affected.
Vasculitis predominantly affecting small vessels, defined as small intraparenchymal arteries, arterioles, capillaries and venules. Medium sized arteries and veins may be affected.
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ANCA - associated vasculitis
inflammation in wall of small blood vessels type - acute necrotising inflammation trigger - unknown infection(s) pathology - antibody mediated
polymorph degranulation
Treatment - steroids +/- immuno-suppression strong evidence base
biomarkers needed
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AORTO
ARTERITIS
TAKAYASU
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AA.SV - ANCA-associated Small Vessel Vasculitis
Chapel Hill Consensus Conference ’94
Small Vessel Vasculitis
Aorta
Arteriole
CapillaryVenule
Vein
Microscopic Polyangiitis, Wegener’s Granulomatosis, and Churg-Strauss Syndrome
LVV.Med.SVV.CHCC 2011.ppt
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E L K ENT; LUNG;KIDNEY;
EY= eye
D E IE = upper airway L= lung K= Kidney
N=
H= S=
A= arthritis neuropathy
heart skin
organs score 2 each; constitutional symptoms 1; max 17
Disease Extent
Assessment of Vasculitis
Designed for Wegeners – useful only in WG
IRAVAS devised DEI.Tak to use in aorto-arteritis
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Spectrum of Vasculitis
CLASSIFICATION of VASCULITIS
1o Systemic Necrotising Vasculitis
2o SNV - infection, drugs, etc - CTD -RA , SLE , etc
Localised arteritis‘Pseudovasculitis’
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Roadmap for Vasculitis
how to get there Watts et al flow chart
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Chapel Hill Consensus Conference ’94Proposed Classification for 10 Systemic Vasculitis
Takayasu arteritisGiant Cell (Temporal) arteritis
Polyarteritis Nodosa (classic PAN)Kawasaki syndrome
Churg Strauss syndrome *Wegener syndrome *Microscopic polyangiitis (MPA) *
Henoch Schonlein purpura Essential Cryoglobulinaemic vasculitis
(EMC)Historical map 2.
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Chapel Hill Consensus Conference 2 ’2012
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Chapel Hill Consensus Conference 2 ’2012
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Roadmap for Vasculitis
CHAPEL HILL 2.an up-to-date modern map
far more detailed
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Roadmap for Vasculitis
Chapel Hill 2list of extras included
nb role of ANCA
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Large Vessel Vasculitis
Medium Vessel VasculitisSmall Vessel Vasculitis
Vasculitis affecting large arteries more often than other vasculitides. Large arteries are the aorta and its major branches. Any size artery may be affected.
Necrotizing arteritis predominantly affecting medium-sized arteries defined as the main visceral arteries and their branches. Inflammatory aneurysms are common.
Vasculitis predominantly affecting small vessels, defined as small intraparenchymal arteries, arterioles, capillaries and venules. Medium sized arteries and veins may be affected.
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Classification of VasculitisWhat do we classify?
vessel size & organ distribution
Type of inflammation, trigger factors, aetio-pathogenic mechanisms
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Paul Bacon FRCPProfessor EmeritusRheumatology Research GroupCollege of Medicine & DentistryUniversity of Birmingham, UK
Important achievementsFounder of Dept of Rheumatology at University
of BirminghamFounder Member of EUVAS (European
Vasculitis Group)Founder Member of IRAVAS, of BILAG and
SLICC: ACR Master Co-author of c 300 research papers – 140
vasculitis publications Areas of special interestAuto-inflammatory Rheumatic diseases;
disease assessmentVasculitis
Photo
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Map of Kochi – to show Bolgatty Island and Palace
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MAP of India
to show where
Kochi is located
Roadmaps for Vasculitis
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Roadmaps to Vasculitis• Map 1. - a plan of where we are
plan of Kochi or convention centre
• Map 2. - a route to plan how to get here- a practical guide for the general physician
• Map 3 – a guide to what to do when you arrive - your plan of what you want to do now you are here
1 a.) historical map to explain what was here before1 b.) new map to bring us up to date