VASCULITISVASCULITISPROF. DR. FERDA ÖZKANPROF. DR. FERDA ÖZKAN

VASCULITISVASCULITIS

This is a heterogenous group This is a heterogenous group of disorders characterized byof disorders characterized by inflammation & damageinflammation & damage of of blood vessels followed byblood vessels followed by thrombosis & ischemic thrombosis & ischemic manifestationsmanifestations in the tissues in the tissues supplied by the blood vessels.supplied by the blood vessels.

ClassificationClassification the the size and type of blood vessel size and type of blood vessel

involvedinvolvedvascular beds and organs affectedvascular beds and organs affectedassociated clinical featuresassociated clinical featuresetiologyetiologypathogenic mechanismspathogenic mechanismshypersensitivity – drugs, serum sicknesshypersensitivity – drugs, serum sickness infectionsinfections immune-mediated injuryimmune-mediated injury..

Classification of vasculitis Classification of vasculitis based on Pathogenesisbased on Pathogenesis

Direct infectionDirect infectionImmunologicImmunologicUnknownUnknown

1-Direct infection1-Direct infectionBacterial- NeisseraBacterial- NeisseraRickettsial-Rocky mountain spotted Rickettsial-Rocky mountain spotted

feverfeverSpirochetal-SyphilisSpirochetal-SyphilisFungal-aspergillosis, mucormycosisFungal-aspergillosis, mucormycosisViral-herpes zoster-varicellaViral-herpes zoster-varicella

Infectious arteritisInfectious arteritis

Rickettsial disease, syphilis, septic Rickettsial disease, syphilis, septic emboli, walls of abscesseemboli, walls of abscessess. .

A A mycotic aneurysmmycotic aneurysm is a spot at a is a spot at a branch-point of an artery where a branch-point of an artery where a septic embolus (usually) has lodged septic embolus (usually) has lodged and set up an infection, weakening and set up an infection, weakening the wall.the wall.

2-Immunologic2-ImmunologicImmune complex-mediated Immune complex-mediated Antineutrophil cytoplasmic antibody Antineutrophil cytoplasmic antibody

(ANCA)-mediated(ANCA)-mediatedDirect antibody mediatedDirect antibody mediatedCell-mediatedCell-mediatedInflammatory bowel diseaseInflammatory bowel diseaseParaneoplastic vasculitisParaneoplastic vasculitis

3-Unknown3-UnknownGiant cell (temporal) arteritisGiant cell (temporal) arteritisTakayasu arteritisTakayasu arteritisPolyarteritis nodosa Polyarteritis nodosa

Immunologic-Immune complex-Immunologic-Immune complex-mediated mediated

Infection induced-hepatitis B,CInfection induced-hepatitis B,C Henoch-Schönlein purpuraHenoch-Schönlein purpura SLE and RASLE and RA Drug inducedDrug induced CryoglobulinemiaCryoglobulinemia Serum sicknessSerum sickness

Immunologic-ANCA-mediatedImmunologic-ANCA-mediated

Wegener granulomatosisWegener granulomatosisMicroscopic polyangiitis Microscopic polyangiitis

(microscopic polyarteritis)(microscopic polyarteritis)Churg-Strauss syndromeChurg-Strauss syndrome

Immunologic-Direct antibody mediatedImmunologic-Direct antibody mediated

Goodpasture syndrome Goodpasture syndrome (anti-GBM antibodies)(anti-GBM antibodies)Kawasaki disease Kawasaki disease (anti-endothelial antibodies)(anti-endothelial antibodies)

Immunologic -Cell mediatedImmunologic -Cell mediated

Organ allograft rejectionOrgan allograft rejection

Pathogenesis of Noninfectious Pathogenesis of Noninfectious VasculitisVasculitis

Immune complex depositionImmune complex depositionANCA’sANCA’sAnti-endothelial cell antibodiesAnti-endothelial cell antibodiesAutoreactive T cellsAutoreactive T cells

Immune mediated vasculitisImmune mediated vasculitisVasculitis related to Vasculitis related to depositiondeposition of of

immune complexesimmune complexesConsequence of immune complex Consequence of immune complex

formation and localization formation and localization Ability of the immune complex to Ability of the immune complex to

activate complement activate complement Release of local Release of local vasoactive factorsvasoactive factors

which can increase vascular which can increase vascular permeabilitypermeability

Immune complex depositionImmune complex depositionThe vascular lesions resemble those found in The vascular lesions resemble those found in

experimental immune complex-mediated experimental immune complex-mediated conditions, such as conditions, such as the local Arthus the local Arthus phenomenon and serum sicknessphenomenon and serum sickness . .

Immune reactants and complement can be Immune reactants and complement can be detected in the serum or vessels of patients detected in the serum or vessels of patients with vasculitiswith vasculitis (e.g., DNA-anti-DNA (e.g., DNA-anti-DNA complexes are present in the vascular complexes are present in the vascular lesions of systemic lupus erythematosus-lesions of systemic lupus erythematosus-associated vasculitis and IgG, IgM, and associated vasculitis and IgG, IgM, and complement in cryoglobulinemic vasculitis). complement in cryoglobulinemic vasculitis).

Hypersensitivity to drugs causes Hypersensitivity to drugs causes approximately 10% of vasculitic skin lesions, approximately 10% of vasculitic skin lesions, largely through largely through vascular deposits of immune vascular deposits of immune complexescomplexes. Some, such as penicillin, . Some, such as penicillin, conjugate serum proteins; others, like conjugate serum proteins; others, like streptokinase ,, are themselves foreign are themselves foreign proteins. proteins.

The manifestations vary and range from The manifestations vary and range from small-vessel hypersensitivity and small-vessel hypersensitivity and leukocytoclastic vasculitis to polyarteritis leukocytoclastic vasculitis to polyarteritis nodosa, Wegener granulomatosis, and Churg-nodosa, Wegener granulomatosis, and Churg-Strauss syndromeStrauss syndrome and from mild and self- and from mild and self-limiting to severe and even fatal. limiting to severe and even fatal.

In vasculitis associated with viral In vasculitis associated with viral infections, immune complexes can infections, immune complexes can be found in the serum and in the be found in the serum and in the vascular lesions of some patients, vascular lesions of some patients, particularly in cases of polyarteritis particularly in cases of polyarteritis nodosa (for example, HBsAg-anti-nodosa (for example, HBsAg-anti-HbsAg in hepatitis-induced HbsAg in hepatitis-induced vasculitis).vasculitis).

ANCA’SANCA’SANCAs are a heterogeneous group of ANCAs are a heterogeneous group of

autoantibodies directed against autoantibodies directed against enzymes mainly found enzymes mainly found within the within the azurophil or primary granules in azurophil or primary granules in neutrophils, in the lysosomes of neutrophils, in the lysosomes of monocytes, and in ECs.monocytes, and in ECs.

The description of these The description of these autoantibodies is based on the autoantibodies is based on the immunofluorescent patterns of immunofluorescent patterns of staining of ethanol-fixed neutrophils. staining of ethanol-fixed neutrophils.

Two main patterns are recognized: Two main patterns are recognized: one shows cytoplasmic localization of one shows cytoplasmic localization of

the staining the staining (c-ANCA),(c-ANCA), and the most and the most common target antigen is common target antigen is proteinase-3 (PR3), a neutrophil proteinase-3 (PR3), a neutrophil granule constituent. granule constituent.

The second shows perinuclear The second shows perinuclear staining (p-ANCA) and is usually staining (p-ANCA) and is usually specific for myeloperoxidase (MPO). specific for myeloperoxidase (MPO).

AAntintinneutrophil eutrophil ccytoplasmic ytoplasmic aantibodyntibody (ANCA) (ANCA)

ANCA has been found in patients with: ANCA has been found in patients with: Wegener’s granulomatosis, microscopic Wegener’s granulomatosis, microscopic polyangitis; polyarteritis nodosa; Churg-Strauss polyangitis; polyarteritis nodosa; Churg-Strauss syndrome.syndrome.

c-ANCA:c-ANCA: classical, diffuse cytoplasmic ANCA; classical, diffuse cytoplasmic ANCA; stains the entire cytoplasm of alcohol fixed stains the entire cytoplasm of alcohol fixed white cells in a granular pattern;white cells in a granular pattern;associated with Wegener’s (found in 95%) associated with Wegener’s (found in 95%) p-ANCA:p-ANCA: anti-neutrophil a anti-neutrophil antibodientibodies to s to

myelooperoxidase; stain the peri-nuclear region myelooperoxidase; stain the peri-nuclear region associated with microscopic passociated with microscopic poolyangitis, lyangitis,

Churg-Strauss syndrome, and crescentic Churg-Strauss syndrome, and crescentic glomerulonephritisglomerulonephritis..

ANCA stainingANCA staining

c-ANCAc-ANCA pp-ANCA-ANCA

One plausible hypothesis for a causative role One plausible hypothesis for a causative role of ANCAs in vasculitis is summarized briefly of ANCAs in vasculitis is summarized briefly as follows:as follows:

(1) An underlying disorder (e.g., an infection) (1) An underlying disorder (e.g., an infection) elicits pro-inflammatory cytokines such as elicits pro-inflammatory cytokines such as TNF, and granulocyte-macrophage colony-TNF, and granulocyte-macrophage colony-stimulating factor, and microbial products stimulating factor, and microbial products such as endotoxin, which together cause such as endotoxin, which together cause neutrophils and other inflammatory cells to neutrophils and other inflammatory cells to express PR3 and MPO on their surfaces.express PR3 and MPO on their surfaces.

(2) These stimulate the formation of ANCAs.(2) These stimulate the formation of ANCAs. (3) ANCAs react with circulating cytokine-(3) ANCAs react with circulating cytokine-

primed neutrophils and cause them to primed neutrophils and cause them to degranulate degranulate

(4) PMNs activated by ANCA cause (4) PMNs activated by ANCA cause endothelial cell toxicity and other direct tissue endothelial cell toxicity and other direct tissue injury. injury.

ANCAs directed against neutrophil ANCAs directed against neutrophil constituents other than PR3 and MPO constituents other than PR3 and MPO are also found in some patients with a are also found in some patients with a wide range of inflammatory but wide range of inflammatory but nonvasculitic disorders such as nonvasculitic disorders such as inflammatory bowel disease, inflammatory bowel disease, autoimmune liver disease, primary autoimmune liver disease, primary sclerosing cholangitis, and rheumatoid sclerosing cholangitis, and rheumatoid arthritis, and in some patients with arthritis, and in some patients with malignancies and infectionsmalignancies and infections

Anti-endothelial Cell Anti-endothelial Cell AntibodiesAntibodies

Antibodies to ECs, perhaps induced Antibodies to ECs, perhaps induced by defects in immune regulation, by defects in immune regulation, may predispose to certain may predispose to certain vasculitides, such as those vasculitides, such as those associated with SLE and Kawasaki associated with SLE and Kawasaki disease.disease.

Diagrammatic representation of the sites of the vasculature involved Diagrammatic representation of the sites of the vasculature involved by the major forms of vasculitis. The widths of the trapezoids indicate by the major forms of vasculitis. The widths of the trapezoids indicate

the frequencies of involvement of various portions. LCA, the frequencies of involvement of various portions. LCA,

leukocytoclastic angiitis. Small-vessel vasculitisleukocytoclastic angiitis. Small-vessel vasculitis

VaVassculitisculitisImmune mediated vaculitidesImmune mediated vaculitidesWegener’s GranulomatosisWegener’s GranulomatosisBBüürger’s Diseaserger’s Disease ( (thromboangitis thromboangitis

obliteransobliterans))Takayasu ArteritisTakayasu ArteritisKawasaki’s diseaseKawasaki’s diseaseInfectious arteritisInfectious arteritisRaynaud’s diseaseRaynaud’s disease

PathologyPathology:: Small vesselsSmall vesselsHypersensitivity vasculitisHypersensitivity vasculitis

EExamples include serum sickness, xamples include serum sickness, drug-induced vasculitisdrug-induced vasculitis- - many of themany of the lesionslesions show immune complexes in show immune complexes in lesionslesions..

SSkin is most commonly affected, but a kin is most commonly affected, but a wide range of organs can bewide range of organs can be..

PPathology:athology:((in skin) in skin) fibrinoid necrosis – vessels break fibrinoid necrosis – vessels break

down; brisk inflammatory down; brisk inflammatory reaction reaction with PMN infiltratewith PMN infiltrate

leukocytoclastic vasculitis - leukocytoclastic vasculitis - karyorrhexis (nuclear karyorrhexis (nuclear fragmentation) of WBCs in fragmentation) of WBCs in vasculitic lesionvasculitic lesion

palpable purpura –palpable purpura – extravasation of RBCs from extravasation of RBCs from necrotic vessel + necrotic vessel + inflammationinflammation..

CausesCauses Connective tissue Connective tissue

diseases - SLE, RA diseases - SLE, RA Infections - Hepatitis B Infections - Hepatitis B Drugs Drugs (all 'P's) -(all 'P's) -

Penicillins, Penicillins, Phenothiazines, Phenothiazines, Phenylbutazones, Phenylbutazones, Propylthiouracil Propylthiouracil

Hematologic disease - Hematologic disease - Cryoglobulinemia, Cryoglobulinemia, Paraproteinemia - e.g. Paraproteinemia - e.g. multiple myeloma multiple myeloma

Idiopathic Idiopathic

AntigensAntigens microorganisms, microorganisms, drugsdrugs, , tumor, tumor, autoantigensautoantigens..

form of hypersensitivity vasculitis in kids, young adultsform of hypersensitivity vasculitis in kids, young adults clinical:clinical:

purpura on buttocks, arms, legspurpura on buttocks, arms, legs necrotizing vasculitis involving small dermal vesselsnecrotizing vasculitis involving small dermal vessels arthritisarthritis abdominal pain – often with bloody diarrhea/other evidence of abdominal pain – often with bloody diarrhea/other evidence of

intestinal bleeding, due to mucosal/submucosal vasculitisintestinal bleeding, due to mucosal/submucosal vasculitis kidney involvement in 1/3 – proteinuria, nephrotic syndrome, kidney involvement in 1/3 – proteinuria, nephrotic syndrome,

gross/microscopic hematuriagross/microscopic hematuria.. PPathology:athology:

glomerulonephritis is often focal, mesangial glomerulonephritis is often focal, mesangial proliferative in type; often self-limitingproliferative in type; often self-limiting

IgA is predominant Ab in glomerular and skin lesions.IgA is predominant Ab in glomerular and skin lesions.

PathologyPathology:: Small vesselsSmall vesselsHenoch-Schönlein PurpuraHenoch-Schönlein Purpura

CClinical:linical:widespread small vessel vasculitis, often widespread small vessel vasculitis, often

associated with severe glomerulonephritisassociated with severe glomerulonephritispurpurapurpuraarthralgia or arthritisarthralgia or arthritiscryoglobulinscryoglobulinsreversibly precipitatie in the coldreversibly precipitatie in the coldconsist of IgM rheumatoid factorsconsist of IgM rheumatoid factorsmost seen in patients with HCVmost seen in patients with HCV

PathologyPathology:: Small vesselsSmall vesselsMixed Cryoglobulinemia Mixed Cryoglobulinemia

syndromesyndrome

PPathology:athology:vessels show deposits containing vessels show deposits containing

cryoglobulins and complementcryoglobulins and complementleukocytoclastic vasculitis.leukocytoclastic vasculitis.

Leukocytoclastic vasculitisLeukocytoclastic vasculitis

can occur from teens can occur from teens toto old age; peak at age 40, old age; peak at age 40, slight male proponderance. 82% die in a year slight male proponderance. 82% die in a year without treatment.without treatment.

serious systemic disorder characterized by:serious systemic disorder characterized by: acute necrotizing granulomas in upper and/or lower acute necrotizing granulomas in upper and/or lower

respiratory tractrespiratory tract focal necrotizing or granulomatous vasculitis, focal necrotizing or granulomatous vasculitis,

affecting small to medium sized vessels in lungs affecting small to medium sized vessels in lungs mostlymostly

also skin, joints, nerves, earsalso skin, joints, nerves, ears glomerulonephritis, often crescenteric proliferative glomerulonephritis, often crescenteric proliferative

renal failurerenal failure

PathologyPathology:: Small to Small to Medium-sizedMedium-sized vessels vessels Wegener’s GranulomatosisWegener’s Granulomatosis

symptoms: symptoms: upper respiratory tract upper respiratory tract

(sinusitis, epistaxis, nasal (sinusitis, epistaxis, nasal obstruction, otitis media, obstruction, otitis media, deafness), deafness),

lower respiratory tract lower respiratory tract (productive cough, hemoptysis, (productive cough, hemoptysis, dyspnea), dyspnea),

renal failurerenal failure..

Inflammation (vasculitis) of a small artery Inflammation (vasculitis) of a small artery along with adjacent granulomatous along with adjacent granulomatous

inflammation, in which epithelioid cells and inflammation, in which epithelioid cells and giant cellsgiant cells

Clinical FindingsClinical Findings

Respiratory System – upper respiratory Respiratory System – upper respiratory tract infections, saddle nose deformity, tract infections, saddle nose deformity, pneumonitis, pleural effusion pneumonitis, pleural effusion

Renal - hematuria, hypertension, renal Renal - hematuria, hypertension, renal failure failure

Ocular - conjunctivitis, uveitis Ocular - conjunctivitis, uveitis Skin - urticaria, palpable purpura, livedo Skin - urticaria, palpable purpura, livedo

reticularisreticularis..

DDiagnosis: c-ANCA found in iagnosis: c-ANCA found in majority but not specificmajority but not specific

PPathologyathology:: lung lesions are lung lesions are most diagnosticmost diagnostic lesions usually multiple, well lesions usually multiple, well

circumscribed, variable sizecircumscribed, variable size coagulative necrosis coagulative necrosis

surrounded by granulation surrounded by granulation tissue; ghost outlines of tissue; ghost outlines of vessels in necrotic zone, vessels in necrotic zone, multinucleate giant cells may multinucleate giant cells may be presentbe present

extrapulmonary lesions – extrapulmonary lesions – same combo of granulomatous same combo of granulomatous inflammation and vasculitis in inflammation and vasculitis in upper respiratory tract, skin.upper respiratory tract, skin.

Elsewhere vasculitis Elsewhere vasculitis predominatespredominates..

The lung of a patient with fatal The lung of a patient with fatal Wegener granulomatosis, Wegener granulomatosis,

demonstrating large nodular lesionsdemonstrating large nodular lesions

predominates in young adult male (20-45) predominates in young adult male (20-45) tobacco smokers; female smokers as well. tobacco smokers; female smokers as well. Sligtly more common in Asians, Sligtly more common in Asians, Ashkenazi JewsAshkenazi Jews..

clinical:clinical:ischemiaischemia, usually of , usually of lower limbslower limbs, ,

progressing to progressing to gangrenegangreneabsence of atherosclerotic stigmataabsence of atherosclerotic stigmata

or risk factorsor risk factorsassociated with associated with migratory migratory

thrombophlebitisthrombophlebitis

PathologyPathology:: Medium-sizedMedium-sized vessels vesselsBBueuerger’s Diseaserger’s Disease ( (thromboangitis thromboangitis

obliteransobliterans))

The lumen is occluded by a The lumen is occluded by a thrombus containing two thrombus containing two abscessesabscesses

40-50s, M:F 2:1. May be life threatenting; 5 40-50s, M:F 2:1. May be life threatenting; 5 year survival <15%, 80% with therapy year survival <15%, 80% with therapy

fever, myalgia, weight loss, foot drop, fever, myalgia, weight loss, foot drop, weakness, abdominal pain, hypertension from weakness, abdominal pain, hypertension from renal arteriole involvementrenal arteriole involvement

mononeuritis complex - asymmetric peripheral mononeuritis complex - asymmetric peripheral neuropathy with sudden or subacute onset due neuropathy with sudden or subacute onset due to nerve infarction; many modalities lost in one to nerve infarction; many modalities lost in one nervenerve

local ischemia, inflammation of affected organslocal ischemia, inflammation of affected organskidney, GI tract, joints/muscles, heart, nervous kidney, GI tract, joints/muscles, heart, nervous

system, skin, lungs may be affectedsystem, skin, lungs may be affected..

PathologyPathology:: Medium-sizedMedium-sized vessels vesselsPolyarteritis NodosaPolyarteritis Nodosa

PathogenesisPathogenesis ( (no single mechanismno single mechanism, , some cases are idiopathic) some cases are idiopathic) : : IImmune mmune CComplexomplex deposition deposition: :

Hepatitis B AgHepatitis B Ag, tumor Ag, certain , tumor Ag, certain drugsdrugs

PPathologyathology AAll stages of activity may ll stages of activity may

coexist in different vessels, coexist in different vessels, even in one vesseleven in one vessel..

EEarly:arly: focal, fibrinoid focal, fibrinoid necrosis of necrosis of artery/arteriole wall; artery/arteriole wall; transmural inflammation transmural inflammation – PMN, eosinophilic poly – PMN, eosinophilic poly infiltrateinfiltrate

Intermediate:Intermediate: mural/occlusive thrombimural/occlusive thrombi

Late:Late: aneurysms if aneurysms if segmental involvementsegmental involvement with healing, wall infiltrated with healing, wall infiltrated

by fibroblasts -> fibrous by fibroblasts -> fibrous thickening of wall -> thickening of wall -> nodular appearancenodular appearance..

MMean age of onset 70 years; ean age of onset 70 years; CCommonly associated with clinical ommonly associated with clinical

syndrome syndrome polymyalgia rheumatica:polymyalgia rheumatica:pain, stiffness in shoulder & pelvic pain, stiffness in shoulder & pelvic

girdles in absence of evidence of girdles in absence of evidence of weakness or atrophyweakness or atrophy

ESRESRresponse to low-moderate steroid response to low-moderate steroid

dosesdoses..

PathologyPathology:: LargeLarge vessels vesselsGiant cell arteritis and temporal Giant cell arteritis and temporal

arteritisarteritis

Temporal (giant cell) Temporal (giant cell) arteritisarteritis

GGranulomatous inflammatory process can ranulomatous inflammatory process can affect affect any elastic and muscular arteryany elastic and muscular artery::

most often seen in most often seen in superficial temporal superficial temporal arteryartery, other cranial arteries, other cranial arterieschief clinical risk is blindnesschief clinical risk is blindnessclinical presentation: headache, scalp clinical presentation: headache, scalp tenderness, claudication of the jawtenderness, claudication of the jaw (tired jaw on chewing)(tired jaw on chewing), transient visual , transient visual disturbances, musculoskeletal disturbances, musculoskeletal symptoms symptoms (polymyalgia rheumatica) ,(polymyalgia rheumatica) , fever, malaise, weight loss, anemiafever, malaise, weight loss, anemia..

EExtracranial disease in 10-15%:xtracranial disease in 10-15%:intermittent claudication is commonintermittent claudication is commonarterial bruits, blood pressure arterial bruits, blood pressure

abnormalitiesabnormalities..TTreatment:reatment: responds well to steroids. responds well to steroids.CComplicationsomplications

coronary artery involvement coronary artery involvement myocardial ischemiamyocardial ischemia

aortic valve incompetenceaortic valve incompetenceaortic dissectionaortic dissectionaortic aneurysm, may ruptureaortic aneurysm, may rupture..

PPathologyathologyIInflammation nflammation

confined to media; confined to media; mixed cell infiltrate mixed cell infiltrate – lymphocytes, – lymphocytes, macrophagesmacrophages

GGiant cells may be iant cells may be present at junction present at junction of intima and media of intima and media (eating internal (eating internal elastic lamina)elastic lamina)

IIntimal proliferationntimal proliferation..

Elastic tissue stain demonstrating focal destruction Elastic tissue stain demonstrating focal destruction of internal elastic membrane (of internal elastic membrane (arrowarrow) and intimal ) and intimal thickening (IT) characteristic of long-standing or thickening (IT) characteristic of long-standing or

healed arteritishealed arteritis

CCommon in Far east; women 15-45 affectedommon in Far east; women 15-45 affectedChronic inflammatory disease involving both Chronic inflammatory disease involving both

systemic and pulmonary circulationssystemic and pulmonary circulationsAorta & major branches most commonly Aorta & major branches most commonly

affected – coronariesaffected – coronariesClinical: stenosis is characteristicClinical: stenosis is characteristicPPathology:athology: artery wall inflammation artery wall inflammation

fibromuscular intimal proliferation, mural fibromuscular intimal proliferation, mural thrombithrombi granulomatous panarteritisgranulomatous panarteritis vessel converted into rigid tube, associated with vessel converted into rigid tube, associated with

stenosis.stenosis.

PathologyPathology:: LargeLarge vessels vesselsTakayasu Arteritis or AortitisTakayasu Arteritis or Aortitis

The right carotid artery taken at autopsy of the patient demonstrating marked intimal

thickening with minimal residual lumen

Aortitis is literally inflammation of the Aortitis is literally inflammation of the aorta, and it is representative of a aorta, and it is representative of a cluster of large-vessel diseases that cluster of large-vessel diseases that have various or unknown etiologies. have various or unknown etiologies.

While inflammation can occur in While inflammation can occur in response to any injury, including response to any injury, including trauma, the most common known trauma, the most common known causes are infections or connective causes are infections or connective tissue disorders. tissue disorders.

Infections can trigger a noninfectious Infections can trigger a noninfectious vasculitis by generating immune vasculitis by generating immune complexes or by cross-reactivity. complexes or by cross-reactivity.

The etiology is important because The etiology is important because immunosuppressive therapy, the main immunosuppressive therapy, the main treatment for vasculitis, could treatment for vasculitis, could aggravate an active infectious process. aggravate an active infectious process.

Inflammation of the aorta can cause Inflammation of the aorta can cause aortic dilation, resulting in aortic aortic dilation, resulting in aortic insufficiency. insufficiency.

Also, it can cause fibrous thickening and Also, it can cause fibrous thickening and ostial stenosis of major branches, ostial stenosis of major branches, resulting in reduced or absent pulses, resulting in reduced or absent pulses, low blood pressure in the arms, possibly low blood pressure in the arms, possibly with central hypertension due to renal with central hypertension due to renal artery stenosis. artery stenosis.

Depending on what other vessels are Depending on what other vessels are involved, ocular disturbances, involved, ocular disturbances, neurological deficits, claudication, and neurological deficits, claudication, and other manifestations of vascular other manifestations of vascular impairment may accompany this impairment may accompany this disorder. disorder.

The disease has 3 phases:The disease has 3 phases:

Phase I is (prepulseless Phase I is (prepulseless inflammatory period) inflammatory period)

Phase II (vascular Phase II (vascular inflammation)inflammation)

Phase III (fibrosis stage) Phase III (fibrosis stage)

Pathologic changes involved in Takayasu Pathologic changes involved in Takayasu arteritis are the same as for giant cell arteritis are the same as for giant cell arteritis. arteritis. Involved vessel walls develop irregular Involved vessel walls develop irregular

thickening and intimal wrinkling. thickening and intimal wrinkling. Early in the disease, mononuclear Early in the disease, mononuclear

infiltration with perivascular cuffing is infiltration with perivascular cuffing is seen. seen.

That extends to the media, followed by That extends to the media, followed by granulomatous changes and patches of granulomatous changes and patches of necrosis and scarring (fibrosis) of all necrosis and scarring (fibrosis) of all layers, especially the intima. layers, especially the intima.

Late stages have lymphocytic infiltration. Late stages have lymphocytic infiltration.

When the abdominal aorta and its branches, When the abdominal aorta and its branches, eg, the renal arteries, are involved, central eg, the renal arteries, are involved, central hypertension may develop. hypertension may develop. Accurate blood pressure measurement may be Accurate blood pressure measurement may be

difficult because of arterial lesions affecting difficult because of arterial lesions affecting supply to the extremities. supply to the extremities.

Takayasu arteritis primarily involves the Takayasu arteritis primarily involves the aorta, its main branches, and, in 50% of aorta, its main branches, and, in 50% of cases, the pulmonary artery.cases, the pulmonary artery. The initial vascular lesions frequently occur in or The initial vascular lesions frequently occur in or

at the origin of the left subclavian artery, which at the origin of the left subclavian artery, which can cause weakened radial pulse and easy can cause weakened radial pulse and easy fatigability in the left arm. fatigability in the left arm.

As the disease progresses, the left common As the disease progresses, the left common carotid, vertebral, brachiocephalic, right-middle carotid, vertebral, brachiocephalic, right-middle or proximal subclavian, right carotid, and or proximal subclavian, right carotid, and vertebral arteries, as well as the aorta, also are vertebral arteries, as well as the aorta, also are affected, as well as retinal vesselsaffected, as well as retinal vessels. .

Destruction of the arterial media by Destruction of the arterial media by mononuclear inflammation with giant cellsmononuclear inflammation with giant cells

Complications:Complications:

Aortic insufficiency, Aortic insufficiency, angina pectoris, angina pectoris, myocardial infarction, myocardial infarction, stroke, stroke, limb ischemia, limb ischemia, renal artery hypertension, renal artery hypertension, all consequences of vascular all consequences of vascular

diseases.diseases.

Cogan's diseaseCogan's disease

Cogan's diseaseCogan's disease is another rare disease is another rare disease usually affecting young adults. usually affecting young adults.

It features abrupt onset of It features abrupt onset of nerve deafness, nerve deafness, iinterstitial keratitis, and/or nterstitial keratitis, and/or a systemic vasculitis often with a systemic vasculitis often with aortic aneurysm formation. aortic aneurysm formation.

It's apparently caused by an It's apparently caused by an autoantibody autoantibody against inner ear and endotheliumagainst inner ear and endothelium

Kawasaki's diseaseKawasaki's diseaseA febrile disease which resembles adult A febrile disease which resembles adult

polyarteritis nodosapolyarteritis nodosa histologically but occurs histologically but occurs in babiein babiess. .

Need Need to see five of these six signs: to see five of these six signs: fever (will last more than five days)fever (will last more than five days) non-purulent conjunctivitis in both eyesnon-purulent conjunctivitis in both eyes rashrash red cracked lips and/or strawberry tongue and/or red cracked lips and/or strawberry tongue and/or

red oral mucosared oral mucosa red palms and solesred palms and soles ( (later they desquamatelater they desquamate)) a big (1.5 cm or more) a big (1.5 cm or more) lymph lymph node in the necknode in the neck..

Most patients are of Japanese of Most patients are of Japanese of Korean ancestry, regardless of where Korean ancestry, regardless of where they live, but no HLA links are found. they live, but no HLA links are found.

The most serious concern is The most serious concern is coronary coronary vasculitisvasculitis,, which causes myocardial which causes myocardial infarcts. Healing can produce infarcts. Healing can produce coronary aneurysms, coronary aneurysms,

The cause remains obscure. The cause remains obscure.

Raynaud's disease & Raynaud's disease & phenomenonphenomenon

Spasm and occlusion of the arteriesSpasm and occlusion of the arteries supplying the fingers, which turn white, supplying the fingers, which turn white, then red, then blue. then red, then blue.

Triggered by cold weather, it's most often Triggered by cold weather, it's most often idiopathic; known causes range from idiopathic; known causes range from vasculitis syndromes to operating jack-vasculitis syndromes to operating jack-hammers. hammers.

SclerodermaScleroderma patients and some others patients and some others have this process greatly exacerbated by have this process greatly exacerbated by hyperplastic arteriolar sclerosis in the hyperplastic arteriolar sclerosis in the didigital gital arteries.arteries.

Type of Type of vasculitisvasculitis

Aorta and Aorta and its its

branchesbranches

Large and Large and medium-medium-

sized sized arteriesarteries

Medium-Medium-sized sized muscular muscular arteriesarteries

Small Small muscular muscular arteriesarteries

Venules, Venules, arteriolesarterioles

Takayasus Takayasus arteritisarteritis

++++++ ++

Giant cell Giant cell arteritisarteritis

++ ++++++ ++++++

PolyarteritisPolyarteritis ++++++ ++++++ ++

Wegeners Wegeners granulomatosgranulomatosisis

++++ ++++++ ++++++

Kawasaki Kawasaki diseasedisease

++++ ++

Vasculitis Vasculitis associated associated with with connective connective tissue tissue diseasedisease

++++ ++++++

LeukocytoclaLeukocytoclastic stic vasculitis: vasculitis: Henoch-Henoch-Schönlein Schönlein purpura, purpura, hypersensitivithypersensitivity vasculitis, y vasculitis, othersothers

++ ++++++

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