clinical science session : vasculitis - dr paul bacon

Paul Bacon FRCPProfessor EmeritusRheumatology Research GroupCollege of Medicine & DentistryUniversity of Birmingham, UK

Area of special interest - SystemicVasculitis

Photo

Roadmaps toward the Classification of Vasculitis

MAP of India

to show where

Kochi is located

Map of Ko-chi

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

Classification of VasculitisVasculitis - inflammation in blood vessels

Defined by pathology

Classification of Vasculitis

History of Vasculitis studies

Classification by vessel size & organ distribution

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

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

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

Classification of Vasculitis

The spectrum of vasculitis - as perceived by a highly intelligent, experienced medical student

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

Roadmap for Vasculitis ACR criteria 7 syndromes included

Polyarteritis NodosaChurg-Strauss syndromeWegeners granulomatosis

“Hypersensitivity vasculitis” Giant cell (temporal) arteritisTakayasu arteritis

Historical Map 1.b

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%

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

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

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


Historical Map 2 .

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.

Medium-Sized Vessel Vasculitis

Microscopic Polyangiitis, Wegener’s Granulomatosis, and Churg-Strauss Syndrome

Aorta

Arteries

Arteriole

CapillaryVenule

Vein

Polyarteritis nodosa,


Medium VesselPAN & Kawasaki

Large VesselGCA & Takayasu

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

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”

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

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

2012 Revised CHCC – Types of vessels defined as large, medium, and small

Chapel Hill Consensus Conference 2 ’2012

A A S V MPA GPA

EGPA

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


A A S V MPA GPA

EGPA


Defined by pathology. Pathogenetic mechanisms, trigger

agents,genetic background

all needed for proper understanding

Adherence / entry of leukocytes

EC

T

T cell activation

LPS

TNFIL-1

Endothelial cell death

EC

ROSproteases

ANCA

Pathogenesis AA.SV

T

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 ++


Defined by pathology. Pathogenetic mechanisms, trigger

agents,genetic background

all needed for proper understanding

What do we classify

vessel size & organ distribution

vessel wall – inflamed or scarred aetio-pathogenesis ?


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 ?

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

What do we classify

vessel state - narrowed or blocked?


vessel wall – inflamed/scarred aetio-pathogenesis ?


Disease Assessment - Activity v Damage

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?

Roadmaps for VasculitisDCVAS

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

“not everything in the garden is roses”


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

Classification of VasculitisWhat do we classify?


vessel state - narrowed or blocked?

Disease AssessmentActivity v Damage

Vasculitis Assessment, Therapy, & CVS disease

VASCULITIS - what is it ?

HISTORY

Large Vessel VasculitisTakayasu arteritis

Aorta

Arteries

Arteriole

CapillaryVenule

Vein


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

AA.SV - ANCA-associated Small Vessel Vasculitis



Aorta

Arteriole

CapillaryVenule

Vein


LVV.Med.SVV.CHCC 2011.ppt

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.


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

AORTO

ARTERITIS

TAKAYASU

AA.SV - ANCA-associated Small Vessel Vasculitis



Aorta

Arteriole

CapillaryVenule

Vein


LVV.Med.SVV.CHCC 2011.ppt

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

Spectrum of Vasculitis

CLASSIFICATION of VASCULITIS

1o Systemic Necrotising Vasculitis

2o SNV - infection, drugs, etc - CTD -RA , SLE , etc

Localised arteritis‘Pseudovasculitis’


how to get there Watts et al flow chart

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.


CHAPEL HILL 2.an up-to-date modern map

far more detailed


Chapel Hill 2list of extras included

nb role of ANCA

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.


Classification of VasculitisWhat do we classify?


Type of inflammation, trigger factors, aetio-pathogenic mechanisms

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

Map of Kochi – to show Bolgatty Island and Palace

MAP of India

to show where

Kochi is located


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

clinical science session : vasculitis - dr paul bacon

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