What

is vasculitis ?
s Vasculitis is a
s heterogeneous disorder s Vascular inammation

s Classied :
s Cause s Size of vessels s Ab-associated s Pathology

: primary, secondary : small, medium, large : ANCA, ANA : granulomatous, immune / pauci-immune

Classication of Vasculitis
Isolated vasculitis Systemic vasculitis

s Primary vasculitis
s Large vessel s Medium vessel s Small vessel s miscellaneous

s Secondary vasculitis
s Infection associated s CNTD associated s Drug induced s Malignancy associated s Post organ transplant

Secondary vasculitis
s Infection-associated
s Viral : HBV, HCV, HIV, Herpes, CMV , parvo B19 s Bacteria : strep, staph, salmonella s Mycobacteria : TB, atypical mycobacteria s Syphylis

Secondary vasculitis
s Infection-associated s CNTD-associated
s SLE s MCTD s Dermatomyositis s RA s Sjogrens syndrome

Secondary vasculitis
s Infection-associated s CNTD-associated s Drug induced
s Penicillin s Sulfonamide s Oral contraceptive agents s Allopurinol s PTU s Hydralazine

Secondary vasculitis
s Infection-associated s CNTD-associated s Drug induced s Malignancy-associated

Secondary vasculitis
s Infection-associated s CNTD-associated s Drug induced s Malignancy-associated s Post-organ transplant

Large

s aorta and its major branches (and the corresponding vessels in the venous circulation in some forms of vasculitis, e.g., Behet's disease). s smaller than the major aortic branches s contain four elements: (1) an intima, (2) a continuous internal elastic lamina, (3) a muscular media,(4) an adventitia. s In clinical terms, medium vessel vasculitis is generally macrovascular (i.e., involves vessels large enough to be observed in gross pathologic specimens or visualized by angiography). s all vessels below macroscopic disease, includes capillaries, postcapillary venules, and arterioles s less than 500 in outer diameter s Glomeruli: dierentiated capillaries

Medium

Small vessel

Classications
s ACR criteria 1990 s Chapel-Hill concensus conference 1994 s EULAR

American College of Rheumatology (ACR) 1990 criteria

s Classify 7 vascultis syndromes
s s s s s s s Giant cell arteritis Takayasu artieritis Henoch-Schonlein purpura Hypersensitivity vasculitis Polyarteritis nodosa Churg-Strauss Syndrome Wegeners granulomatosis

1994: CHCC classication ( Chapel Hill Consensus Conference) BV Size Large Primary Vasculitis GCA TK Medium PAN KW Small WG CSS MPA HSP Ess Cryo Cut. LCV Histology Granulomatous arteritis of aorta and its branch ( Ext Carotid A.) Granulomatous arteritis of aorta and its branch Necrotizing vasculitis of medium and small BV Large, meduim and small arteritis( Coronary a.) Granulomatous necrotizing vasculitis (sm- M) Granulomatous necrotizing vasculitis (Eo- sm-M) Necrotizing vasculitis of small BV IgA-deposit vasculits of small BV Cryoglobulin-deposit vasclitis of small BV Isolated cutaneous LCV no systemic

Classications
primary
Large artery

secondary

Giant cell arteritis Aortitis asso with RA Takayasus arteritis syphilis Isolated CNS angiitis PAN Kawasaki
WC CSS MPA HSP Cutaneous LCV Essential mixed cryoglobulinemia Hepatitis B SLE Sjogrens syndrome Drug HIV Drug Hepatitis B, C

Medium artery Small and medium vessel Small vessel

Miscellaneous : Cogan, Behcets, Relapsing polychondritis

Giant cell & Takayasu arteritis

aorta
Classic PAN, Kawasaki large & medium Wegener, MPA, Churg Strauss
Henoch Schonlein Cryoglobulinemia Buergers disease Small vessel angiitis

small
arteriole capillary venule vein vena cava

Behcets disease, Relapsing polychondritis,Cogans

Giant cell & Takayasu arteritis

aorta
Classic PAN, Kawasaki large & medium Wegener, MPA, Churg Strauss
Henoch Schonlein Cryoglobulinemia

small
arteriole capillary venule vein vena cava

Small vessel angiitis leukocytoclastic vasculitis cutaneous vasculitis hypersensitivity vasculitis

aorta
large & medium

small
arteriole capillary venule vein vena cava

less common in Westerns aseptic meningoencephalitis cerebral vasculitis recurrent phlebitis, arteritis, synovitis
Behcets disease

Tissue histopathology
s Granulomatous inammation s Immune complex - mediated s ANCA associated (pauci-immune)

Granulomatous Inammation
s Giant cell arteritis s Takayasu's arteritis s Cogan's syndrome s Wegener's granulomatosis s Churg-Strauss syndrome s Primary angiitis of CNS[] s Buerger's disease [] s Rheumatoid vasculitis
s Sometimes granulomatous. s Giant cells occur within inammatory thrombi (and are diagnostic of Buerger's disease), but do not occur within the blood vessel wall.

Immune complex associated vasculitis

s s s s s s s Anti-GBM disease (Goodpasture's disease) Henoch-Schnlein purpura : IgA1 Mixed Cryoglobulinemia : IgG, IgM, , HCV HBV-associated PAN CNTD-associated vasculitis Hypersensitivity vasculitis Erythema elevatum diutinum

ANCA associated
s WG s CSS s MPA s PAN

Approach to vasculitis
vIdentify common clinical features of vasculitis vExclude pseudo-vasculitis (mimics) vLook for causes of vasculitis (secondary vasculitis) vDene primary vasculitis (categorize group) vConrm denite diagnosis (tissue biopsy/angiogram) vStart appropriate treatment

Approach to vasculitis
vIdentify common clinical features of vasculitis vExclude pseudo-vasculitis (mimics) vLook for causes of vasculitis (secondary vasculitis) vDene primary vasculitis (categorize group) vConrm denite diagnosis (tissue biopsy/angiogram) vStart appropriate treatment

Clinical Features Suggesting Vasculitis

s FUO s Ischemic symptom (esp. in the young) s Suspecious rash s Mononeuritis multiplex s Unexplained multisystem involvement s Unexplained glomerulonephritis s Unexplained inammatory myositis/arthritis

Clinical Features Suggesting Vasculitis

vSkin Palpable purpura Livedoid vasculitis Urticarial vasculitis Panniculitis Chronic ulcers Digital gangrene vNervous system
PNS

s Mononeuritis multiplex s Peripheral neuropathy

CNS

s Stroke s Seizure s Visual disturbance s Cranial neuropathy

Clinical features suggesting vasculitis

vRespiratory tract Asthma, sinusitis Pulmonary hemorrhage Pulmonary inltration or nodules vGastrointestinal system Bowel angina Ischemic bowel GI hemorrhage vKidneys Renovascular hypertension Abnormal urine sediment Renal failure vMajor vessels Jaw claudication Extremity claudication Hypertension Aneurysm

Approach to vasculitis
vIdentify common clinical features of vasculitis vExclude pseudo-vasculitis (mimics) vLook for causes of vasculitis (secondary vasculitis) vDene primary vasculitis (categorize group) vConrm denite diagnosis (tissue biopsy/angiogram) vStart appropriate treatment

Mimic Vasculitis
Infec&ous diseases Bacterial endocardi-s ** DGI ** Pulmonary histoplasmosis Coccidioidomycosis Syphilis Lyme disease Rocky Mountain spo?ed fever Whipple's disease Drug toxicity Cocaine ** Amphetamines ** Ergot alkaloids ** Methysergide Arsenic Thrombosis ** An-phospholipid syndrome TTP Neoplasms ** Atrial myxoma Lymphoma Carcinomatosis Miscellaneous Atheroembolic disease ** Goodpasture's syndrome ** Sarcoidosis Amyloidosis Migraine Cryobrinogenemia

Approach to vasculitis
vIdentify common clinical features of vasculitis vExclude pseudo-vasculitis (mimics) vLook for causes of vasculitis (secondary vasculitis) vDene primary vasculitis (categorize group) vConrm denite diagnosis (tissue biopsy/angiogram) vStart appropriate treatment

Secondary vasculitis
Evaluate History s Infection-associated s CNTD-associated s Drug induced s Malignancy-associated s Post-organ transplant

Post-capillary venules
Palpable purpura Urticarial vasculitis

Arteriole small a.

Skin ulcer

Small medium sized a.

EN

Livedo reticularis

Gangrene

DDx : Erythema nodosum

s Infection s Drug s Inammation s Rheumato s Malignancy s Idiopathic

Mononeuritis multiplex

Typical Clinical Manifestations of Large, Medium, and Small Vessel Involvement by Vasculitis Constitutional symptoms: fever, weight loss, malaise, arthralgias/arthritis (all vessel sizes)
Large Limb claudication Asymmetric blood pressures Absence of pulses Bruits Aortic dilation Renovascular hypertension Medium Cutaneous nodules Ulcers Livedo reticularis Digital gangrene Mononeuritis multiplex Microaneurysms Renovascular hypertension Purpura Vesiculobullous lesions Urticaria Glomerulonephritis Alveolar hemorrhage Cutaneous extravascular necrotizing granulomas Splinter hemorrhages Uveitis/episcleritis/scleritis Small

Considerations in the Classications of systemic vasculitis

s Size of predominant blood vessels aected s Epidemiologic features
s Age s Gender s Ethnic background

s Pattern of organ involvement s Pathologic features

s Granulomatous inammation s Immune complex deposition VS pauci-immune histopathology s Linear staining along glomerular basement membrane

s Presence of ANCA, anti-GBM Ab, RF s Associated infection (hepatitis B or hepatitis C)

Epidermiology
s AGE, GENDER, AND ETHNICITY
s KW : 80% < 5 yrs s GCA : never occurs in < 50 yrs, mean age 72. s HSP :
s children (90%) self-limited s adults, higher chronicity & poor renal outcome

s Buerger's disease : only male predominance s TK : 9:1 female-to-male ratio

Epidermiology
Disease GCA United States Elsewhere Age/Gender/Ethnic Predispositions Age >50, mean age 72/ Females 3:1/Northern European ancestry Age <40/Females 9:1/Asian Silk Route countries Slight male predominance Children of Asian ancestry Whites >> Blacks Only 10% of cases occur in adults 240/1 million 220-270/1 million (Olmsted County, (Scandinavian MN) countries) 3/1 million 3/1 million 7/1 million 100/1 million 4/1 million
[]

TK Behets PAN KW WG HSP

200-300/1 million (India) 3000/1 million (Turkey) 7/1 million (Spain) 900/1 million (Japan) 8.5/1 million (United Kingdom)

In children: 135-180/1 million; in adults: 13/1 million

From Gonzalez-Gay MA, Garcia-Porrua: Epidemiology of the vasculitides. Rheum Dis Clin N Am 27:729-750, 2001.

Epidermiology
s GENES s Familial rare
s except GCA HLA-DRB10401 and HLA-DRB10101, tumor necrosis factor microsatellite polymorphisms

s Polygenic and complex. s Single gene and vasculitis

s HLA-B51 with Behet's disease,80% of Asian patients

s Rheumatoid vasculitis:
s HLA-DRB1 ,genotypes 0401/0401, 0401/0404, and 0401/0101 s HLA-C3 in patients lacking HLA-DRB104

s WG :
s functional polymorphism, 620W, in the intracellular tyrosine phosphatase gene PTPN22

Epidermiology
s ENVIRONMENT s cigarette smoking
s Buerger's disease and rheumatoid vasculitis

s IVDU s Infection
s HBV HCV VZV HIV

Investigations
1. Exclude mimic 2. Assess extent of vasculitis 3. Conrm diagnosis 4. Identify specic type of vasculitis

Investigations
1. Exclude mimic 2. Assess extent of vasculitis 3. Conrm diagnosis 4. Identify specic type of vasculitis
s H/C s Hepatitis prole s Anti HIV s Anti phspholipid chanel s ANA, RF s Echo s Anti GBM

Investigations
1. Exclude mimic 2. Assess extent of vasculitis 3. Conrm diagnosis 4. Identify specic type of vasculitis
UA CXR EMG / NCV EEG/ LP

Investigations
1. Exclude mimic 2. Assess extent of vasculitis 3. Conrm diagnosis 4. Identify specic type of vasculitis
s Biopsy s Angiogram

Investigations
1. Exclude mimic 2. Assess extent of vasculitis 3. Conrm diagnosis 4. Identify specic type of vasculitis
s ANCA s Cryoglobulin s Complement (C3 C4 CH50) s Eosinophilia / IgE (CBC) s Specic biopsy staining :
s s s s Necrotizing Granulomatous inam IgA deposit IC deposit

Antineutrophilic Cytoplasmic Ab (ANCA)

s rst described in 1982 by Davies and colleagues : necrotizing pauci-immune glomerulonephritis who were suspected of having viral infections. s Hall and colleagues : ANCA with systemic vasculitis. s In 1985, van der Woude and colleagues :ANCA & WG s Benet DDx small medium sized vasculitis

C-ANCA
>95% Proteinase-3 <5% others

P-ANCA

50-70% myeloperoxidase(MPO) 20-50% others

p-ANCA in selected disease

Giant cell & Takayasu arteritis

aorta
Classic PAN, Kawasaki large & medium Wegener, MPA, Churg Strauss
Henoch Schonlein Cryoglobulinemia

small
arteriole capillary venule vein vena cava

Small vessel angiitis leukocytoclastic vasculitis cutaneous vasculitis hypersensitivity vasculitis

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