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VASCULITIS - A DIAGNOSTIC

APPROACH

Dr Spencer EllisConsultant Rheumatologist

Lister Hospital

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Objectives

To summarise key points relevant tovasculitis for the physician

To outline a diagnostic approach

To review the use of ANCA

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The vasculitidies are mixed group ofuncommon diseases characterised byinflammation & necrosis of bloodvessels

Primary vasculitis

Secondary vasculitis

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Primary vasculitis:-

occurs in absence of recognisedprecipitating cause/associated disease

Secondary vasculitis secondary to established disease

secondary to infection

secondary to malignancy

secondary to drugs

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Consequence of vascular inflammationdepends on size/location/number ofblood vessels involved

May be relatively indolent with diseaseisolated to single organ/vessel or

rapidly fulminant multi-system disease

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Muscular arteries may develop

segmental or focal lesions segmental

affects whole vessel circumference stenosis/occlusion of vessel

results in infarction of distal organs focal

may lead to aneurysm formation aneurysms may rupture

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1990 ACR developed classification

1994 Chapel Hill consensus conferencedevised definitions for nomenclaturebased on:

1. Clinical & laboratory features

2. Size of involved vessels

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Alternative systems include classification based on:-

size of dominant vessels involved known aetiological factors ANCA

None provide diagnostic criteria or address theproblem of incomplete variants of the disease

For majority of vasculitidies specific diagnostic testsare lacking and diagnosis must be based on size ofvessel involved and associated non-specific clinicaland laboratory findings

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Diagnostic Approach

Should be suspected in any patient withmulti-system disease not readily explained byinfection or malignant process

Rarely clear at outset that vasculitis is the

cause

Establishing diagnosis consists of:-1. Documenting that vasculitis is present

2. Defining to fullest degree the possiblevasculitic syndromes that are responsible

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Differentiation of various syndromes is

important Some vasculidities are relatively benign & self

limiting eg: HSP Drug induced reactions

Many vasculidities are potentially lethal andrequire early use of high doseimmunosuppresion

Others require very different approaches eg Infective endocarditis

Atrial myxoma

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Diagnosis must first be suspected forappropriate treatment to be arranged

Much is known about pathogenesis ofsome vasculidities eg. SLE

Early diagnosis may lead to serologic

identification of patients at risk ofcertain clinical presentations

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ENT- epistaxis, crusting

sinusitis, deafness

Resp- cough, wheeze

haemoptysis, dyspnoea

Cardiac- chest pain, SOB

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Many syndromes are based on clinicalrather than lab criteria

Principle historical & clinical featureshelp to distinguish the major vasculiticsyndromes

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Initial evaluation should include detailed history of:

drug exposures

risk factors for Hep B/C/HIV

history of valvular heart disease

features that identify underlying Rheumaticdisease (eg SLE/APS)

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But what to ask?But what to ask?

Think in terms of disorders

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Any :- asthmasinus problemsnose bleedsdeafnesshaemoptysispins / needles

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Any :- skin rashphotosensitivitymouth ulcershair lossdry / gritty eyesdry mouthRaynauds

pleuritic painblood clotsmiscarriages

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Any:- weight lossfevers

night sweats

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2.Laboratory Investigations

Directed towards establishing

diagnosis

organs affected

disease activity

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Assessing Inflammation

Blood count & differential

total WCC - leucocytosis consistentwith infection & primaryvasculitis

- leucopaenia associatedwith CTDs

- eosinophils - elevated in CSS,drug reaction

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Assessing Inflammation (cont)

Acute phase response

ESR/CRP

Liver function- often non specific

- may also suggestviral infection

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Assessment of organ involvement Urine analysis - proteinuria

- haematuria- casts

Renal function - creatinine

clearance- 24hr protein

excretion- biopsy

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Assessment of organ involvement

Chest radiograph

Liver function

Nervous system - NCS

Cardiac function - ECG

- Echo

Gut - Angiography

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Immunological Tests

Complement - levels are low in SLE andinfection but high in primary vasculitis

Cryoglobulins

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Differential diagnosis

Important to exclude infection and other

conditions that may present as multi-systemdisease & mimic vasculitis

Blood cultures

Viral serology

Echo cardiography

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Specific Investigations

Imaging of sinuses

Biopsy of affected organs eg.skin/kidney/temporal artery

necessary to confirm diagnosis preferably taken prior to high doseimmunosuppression

yield is directly proportional to evidence ofinvolvement of specific tissue

skin biopsy should be reserved for whendiagnosis is unclear

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Important Mimics of Vasculitis

Infective Endocarditis

Atrial Myxoma

Cholesterol embolism

Antiphospholipid antibody syndrome

Vasoconstrictive drugs eg. ergot poisoning

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2 main staining patterns cytoplasmic C ANCA perinuclear P ANCA

Highly specific markers for several systemicvasculidities Wegners Granulomatosis microscopic polyangitis Churg-Strauss syndrome

idiopathic pauci-immune necrotising &cresenteric GN

Only moderately sensitive in limited orlocalised disease

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c ANCA correlates with proteinase 3

specificity most frequently observed in WG sensitivity for active WG approx 90% can be found in other systemic vasculitis

although p ANCA more common

Anti PR3 ANCA may have role in diseasepathogenesis in WG probably by enhancingdisease expression

In stable WG patients a rise in c ANCA mayherald a clinical exacerbation

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p ANCA in most cases induced by antibodies against

myeloperoxidase (MPO) less specific than c ANCA Anti MPO antibodies occur in:-

necrotising GN (65%) microscopic polyangitis (45%) CSS (60%) Wegners (10%)

can also occur in other conditionsbut target antigen rarely MPO RA IBD

Malignancy Infection

Conclusions

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Conclusions Vasculitis should be considered in

patients with multi-system disease

Classification can be difficult

Investigation should aim to Establish diagnosis

Assess organ involvement Assess disease activity Identify causes of secondary vasculitis Exclude vasculitis mimics