Vasculitis 2015 undergraduate

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DR. ABD EL AZEIM ALHEFNY MDProf. Internal Medicine, Rheumatology & Clinical immunology

Ain Shams University

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The vasculitides are a heterogeneous group of

systemic inflammatory disorders with structural

injury to the blood vessel walls & ischemia.

The major ischemic manifestations are defined

by the type and size of the involved blood

vessels and the tissue and organ damage

caused by vascular occlusion.

1) Immune complex formation.

2) Anti-endothelial cell antibodies.

3) Anti neutrophil cytoplasmic antibodies

(ANCA).

4) T cell dependent.

5) Infection of endothelial cells.

Possible Pathogenic Mechanisms

Fibrinoid necrosis (media)

Thrombosis

Inflammation

Classification

Vasculitis

Primary Secondary

Vessel size is the key

discriminator in the

definition of primary

systemic vasculitis.

CTD

Infection

Drug

Malignancy

Initial Assessment

Establish

the

Diagnosis

Biopsy

Imaging

Clinical

Features

Laboratory

Work Up

Establish

the

Diagnosis

Clinical

Features

Initial Assessment

J Allergy Clin Immunol 2009;123:1226-36

When to suspect Vasculitis?

(after excluding infection & neoplasm.)

Rule out vasculitis mimickers (DD)

1) Antiphospholipid syndrome.

2) Infective endocarditis + embolism

3) Atrial myxoma with emboli.

Others:-

• Cholesterol embolization.

• Chronic ergotism.

Establish

the

Diagnosis

Clinical

Features

Laboratory

Work Up

Initial Assessment

Laboratory workup

ESR & CRP

CBC

Transaminases & Liver function tests

Kidney Function tests

Urine analysis & P/C ratio…..

Blood & sputum cultures

Antibodies directed against neutrophil granule constituents

c-ANCA Stains cytoplasm (hence “c”)

Main target antigen: proteinase-3

Highly specific (>90%) for Wegener’s

p-ANCA Stains perinuclear (hence “p”)

Main target antigen: myeloperoxidase

A/w MPA and Churg-Strauss

Laboratory workup

Establish

the

Diagnosis

Imaging

Clinical

Features

Laboratory

Work Up

Initial Assessment

Imaging & Angiogaphy

Power Doppler & Duplex.

MRI, MRV & MRA.

CT & CT Angiography.

PET CT.

Establish

the

Diagnosis

Imaging

Clinical

Features

Laboratory

Work Up

Initial Assessment

Biopsy

Biopsy

Histopathological evidence of vasculitis is the gold

standard for the diagnosis.

Biopsy of involved sites:

Temporal Artery

Skin

Muscle

Nerve

Gut

Kidney

Renal biopsy in

patients with active

renal disease may show

specific diagnostic

lesions

Classification (ctd.)

Primary Vasculitis

Large

Vessel

Medium

Vessel

Small

Vessel

Classification (ctd.)

Classification (ctd.)

Classification (ctd.)

Many overlaps may occur

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Primary vasculitis Classified according to vessel size

Vessel size Disorder

1-Large vessels (Aorta &

its branchs)

*Giant cell arteritis (GCA- PMR)

*Takayasu's arteritis * Behcet

2-Medium-sized ves. (Main

visceral art.)

*Polyarteritis nodosa (PAN)

*Kawasaki disease

3-Small vessels (Venules,

capillaries, arterioles &

small ar)

ANCA- associated:

*Eosinophelic garnulomatosis with

Polyangiitis =EGPA

(Churg-Strauss syndrome (CSS)

*Granulomatosis With Polyangiitis (GPA)

=Wegener's granulomatosis (WG)

Immune compex vasulitis:

IgA Vas. *Henoch-Schőnlein purpura (HSP)

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It is a disease of the elderly (> 50 ys).

It affects primarily white people.

F > males.

Common presenting symptoms:

1. Fatigue, headache, and tenderness of the scalp.

2. Jaw & tongue claudication.

3. Temporal arteries (palpable, tender & nodular), with reduced pulsation.

4. Visual disturbances (optic arteritis) can lead to sudden & permanent blindness.

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Investigations

ESR usually elevated (> 100 mm/h).

Anemia and thrombocytosis.

A temporal artery biopsy should be performed

whenever a diagnosis of GCA is suspected, but this

should not delay the treatment.

Aortic imaging should be considered in GCA,

especially in patients with an AR murmur

The diagnosis of GCA:

Considered in any patient > 50Yrs + recent onset of

headache, disturbances of vision, myalgias, FUO, a

high ESR/CRP, or anemia.

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Characterized by proximal muscle aches

and stiffness (bilateral & symmetrical).

The ESR is usually elevated.

Some PMR pts. may develop GCA after

years.

50% of patients with GCA have symptoms

of PMR.

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Vessel size Disorder

1-Large vessels

(Aorta & its

branches)

*Giant cell arteritis (GCA- PMR)

*Takayasu's arteritis2-Medium-sized ves.

(Main visceral art.)*Polyarteritis nodosa (PAN)

*Kawasaki disease

3-Small vessels

(Venules, capillaries,

arterioles & small ar)

ANCA- associated:

*Eosinophelic garnulomatosis with

Polyangiitis =EGPA

(Churg-Strauss syndrome (P) CSS)

*Granulomatosis With Polyangiitis (GPA)

=Wegener's granulomatosis(C)WG

Immune compex vasulitis:

IgA Vas. *Henoch-Schőnlein purpura (HSP)

Classification of Primary vasculitis

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Chronic inflammatory disorder,

affecting the aorta & its major

branches.

Affects women mainly

(f:m = 9:1),

Ages 15 - 25.

ACR Classification criteria of TA

1. Age at disease onset ≤40 years

2. Claudication of the extremities

3. Decreased pulsation of one or both brachial

arteries

4. Difference of at least 10 mmHg in systolic

blood pressure between the arms

5. Bruit over one or both subclavian arteries or

the abdominal aorta

6. Arteriographic narrowing or occlusion of the

aorta or its large branches,

Disease is diagnosed if at least 3 of 6 criteria are +ve31

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Investigations High ESR in the early phase,

used for monitoring disease activity.

Chest X-ray:

Widened aortic shadow,

Irregularity of the descending

aorta,

Cardiac enlargement,

Hilar fullness.

• MRA or PET (positron emission tomography) can assist

diagnosis and document the extent of the thickened and

altered aorta & for monitoring disease activity. If not available

• Arteriography: will be helpful alternative.

Takayasu's arteritis

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Enlargement of the descending thoracic aorta & thickening of the vessel wall (arrows)

Multiple focal stenoses of

segmental pulmonary artery

branches

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Vessel size Disorder

1-Large vessels

(Aorta & its

branches)

*Giant cell arteritis (GCA- PMR)

*Takayasu's arteritis

2-Medium-sized ves.

(Main visceral art.)*Polyarteritis nodosa (PAN)

*Kawasaki disease

3-Small vessels

(Venules, capillaries,

arterioles & small ar)

ANCA- associated:

*Eosinophelic garnulomatosis with

Polyangiitis =EGPA

(Churg-Strauss syndrome (P) CSS)

*Granulomatosis With Polyangiitis (GPA)

=Wegener's granulomatosis(C)WG

Immune compex vasulitis:

IgA Vas. *Henoch-Schőnlein purpura (HSP)

Classification of Primary vasculitis

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PAN: Necrotizing inflammation of medium-

sized + small arteries causing segmental

transmural inflammation of muscular arteries,

but does not involve veins.

Without:- GN or ANCAs or vasculitis in

arterioles, capillaries, or venules.

Etiology: Unknown (1ry);

some cases have HBV infection (>30%), CTD

Also, HCV infection, and hairy cell leukemia =2ry

• PAN is twice commoner in males, around 40s.

• Constitutional symptoms: malaise, fever, weight loss &

musculo-sckeletal pain.

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Clinical presentation1. Kidneys are the most commonly involved organs,

glomerular ischemia (not GN) minimal proteinuria +modest hematuria (no red blood cell casts indicative of GN) sever HPT (RAA), renal imp & ESRD

2. Coronary arteritis with angina or MI (uncommon). Pericarditis is common. HF:- ischemic CM or Sever HTN

3. GIT abdominal pain, bleeding, and bowel obstruction or perforation. Rupture of mesenteric aneurysm intraperitoneal hemorrhage.

4. Asymmetric polyneuropathy (70%) : arteritis of vasa nervosa painful mononeuritis multiplex (M&S).

5. Vasculitis of CNS (5-10%) encephalopathy, convulsions, +/- CVS.

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Clinical presentation cont.

6. Cutaneous lesions:vascular purpura, livedo reticularis, peripheral gangrene & painful skin nodules.

7. Myalgias & arthralgias.

8. Orchitis & epididymitis

Gangrene

Livedo reticularis

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Investigations

ESR, CRP, WBCs, Platelets are

usually high.

Anemia, hematuria & ?mild proteinuria.

Hypocomplementemia.

ANCA is negative.

Hepatitis B surface antigen

(HBsAg) (>30%).

Angiography often shows microaneurysms and stenoses.

Biopsy to confirm diagnosis.

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Vessel size Disorder

1-Large vessels

(Aorta & its bran)*Giant cell arteritis (GCA- PMR)

*Takayasu's arteritis

2-Medium-sized ves.

(Main visceral art.)*Polyarteritis nodosa (PAN)

*Kawasaki disease

3-Small vessels

(Venules, capillaries,

arterioles & small ar)

ANCA- associated:

*Eosinophelic garnulomatosis with

Polyangiitis =EGPA

(Churg-Strauss syndrome (P) CSS)

*Granulomatosis With Polyangiitis (GPA)

=Wegener's granulomatosis(C)WG

Immune compex vasulitis:

IgA Vas. *Henoch-Schőnlein purpura (HSP)

Classification of Primary vasculitis

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= Mucocutaneous LN syndrome

Etiology: unknown.

Acute febrile disease

Affecting infants & children < 5 Yrs.

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Clinical presentation

The onset is abrupt, with high fever 1-2 W.

Painful cervical lymphadenopathy.

Bilateral conjunctival congestion.

Dryness, redness, and fissuring of the lips

"strawberry" tongue.

Exanthema of the trunk

Redness of the palms and soles /desquamation.

Carditis + heart murmurs + ECG changes.

CAD + dilatation or aneurysms.

Abdominal pain, vomiting, diarrhea.

Arthritis

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Treatment.

Supportive in uncomplicated cases.

Echocardiography to detect CAD.

Low-dose aspirin (3 to 5 mg/kg daily).

IV gamma globulin:

IVIG 400mg/kg/d for 4 days.

Follow-up coronary angiography.

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Mechanisms of action of IV gamma globulin

Decreases expression of adhesion molecules

on endothelial cells

Binds to inflammatory cytokines

Decrease number of activated T lymphocytes

(- CMI).

Blocking antibody binding sites.

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Vessel size Disorder

1-Large vessels

(Aorta & its bran)*Giant cell arteritis (GCA- PMR)

*Takayasu's arteritis

2-Medium-sized ves.

(Main visceral art.)*Polyarteritis nodosa (PAN)

*Kawasaki disease

3-Small vessels

(Venules, capillaries,

arterioles & small ar)

ANCA- associated:

*Eosinophelic garnulomatosis with

Polyangiitis =EGPA

(Churg-Strauss syndrome (CSS)

*Granulomatosis With Polyangiitis (GPA)

=Wegener's granulomatosis (WG)

Immune compex vasulitis:

IgA Vas. *Henoch-Schőnlein purpura (HSP)

Classification of Primary vasculitis

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pulmonary infiltrates

Hypereosinophilia

Asthma and allergic rhinitis.

Pulmonary infiltrates.

Cutaneous eruptions.

Pericarditis, cardiomyopathy & MI.

PN is found in 70% of patients.

Renal disease (generally mild).

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Laboratory findings.

70% of patients have anti-myeloperoxidase

antibodies (MPO-ANCA)= p-ANCA.

Eosinophilia.

Anemia .

Elevated ESR with activity.

Biopsy to confirm the diagnosis.

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Vessel size Disorder

1-Large vessels (Aorta &

its bran)

*Giant cell arteritis (GCA- PMR)

*Takayasu's arteritis

2-Medium-sized ves.

(Main visceral art.)

*Polyarteritis nodosa (PAN)

*Kawasaki disease

3-Small vessels

(Venules, capillaries,

arterioles & small ar)

ANCA- associated:

*Eosinophelic garnulomatosis with

Polyangiitis =EGPA

(Churg-Strauss syndrome (CSS)

*Granulomatosis With Polyangiitis

(GPA)

=Wegener's granulomatosis(WG)

Immune compex vasulitis:

IgA Vas. *Henoch-Schőnlein purpura (HSP)

Classification of Primary vasculitis

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Relatively rare disease, with classic triad:

1. Necrotizing granulomatous vasailitis of the upper and lower airways,

2. Systemic vasculitis,

3. Focal necrotizing GN. The spectrum and severity of the disease ranges from limited disease

involving only one site to severe/generalized multi-organ vasculitis

M/F ratio of 3:2, and mainly white with average age of 40yrs.

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Clinical presentation

Upper airway lesions: sinusitis, nasal drainage,

ulceration, septal perforation & cartilage destruction

(saddle nose deformity) and otitis media .

Tracheal inflammation subglottic stenosis.

Lung involvement cough, dyspnea, hemoptysis.

Massive pulmonary hemorrhage (life-threatening).

Renal involvement proteinuria, hematuria.

Chronic renal failure (CRF) most deaths.

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Cavity & infiltratesBilateral fluffy infiltrates d.to

pulmonary hemorrhage

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Clinical presentation

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Laboratory data

Normochromic, normocytic anemia

Leukocytosis, thrombocytosis,

Elevated ESR.

WG associated with c-ANCA;

{Antiproteinase-3 antibodies (PR-3)}

Titers associated with disease activity.

Biopsy specimens show diagnostic

granulomas.

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Vessel size Disorder

1-Large vessels

(Aorta & its bran)*Giant cell arteritis (GCA- PMR)

*Takayasu's arteritis

2-Medium-sized ves.

(Main visceral art.)*Polyarteritis nodosa (PAN)

*Kawasaki disease

3-Small vessels

(Venules, capillaries,

arterioles & small ar)

ANCA- associated:

*Eosinophelic garnulomatosis with Polyangiitis =EGPA

(Churg-Strauss syndrome (P) CSS)

*Granulomatosis With Polyangiitis (GPA)

=Wegener's granulomatosis(C)WG

Immune compex vasulitis:

IgA Vas. *Henoch-Schőnlein

purpura (HSP)

Classification of Primary vasculitis

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The most common hypersensitivity vasculitis of childhood & young adults.

Preceded by an upper respiratory tract infection, but the etiology IS ?unknown.

Boys and girls are affected equally.

The median age of onset is 4 years.

It follows a self-limiting course in most patients.

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Clinical presentation

The classic triad is palpable purpura with a normal platelet count, colicky abdominal pain, and arthritis + fever.

Purpura appears first on lower extremities & dependent areas and buttocks.

Arthritis is transient and usually involves the knees and ankles.

Hemoptysis in up to 1/3 of patients .

50% have occult gastrointestinal bleeding.

10-50% has renal involvement, from transient microscopic hematuria to RPGN.

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Made on clinical grounds + skin biopsy.

Laboratory results are variable (ESR,

complement, immune complexes & IgA).

Diagnosis

Largely supportive = hydration & monitoring.

NSAIDs for joint pain.

Corticosteroids 10-30 mg/d for abdominal pain,

edema, and nephritis.

Treatment

VARIABLE VESSEL VASCULITIS

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Behçet's syndromeOral ulcers Genital ulcers

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Diagnostic criteria of Behcet's syndromeDefinitionClinical Feature

observed by physician or patient that

recurred > 3 times/year

Recurrent oral ulceration

Plus two of the following criteria:

Aphthous ulceration or scarring observed

by patient or physician

Recurrent genital ulceration

Anterior uveitis, posterior uveitis, or cells

in vitreous on slit lamp examination, or

retinal vasculitis observed by

ophthalmologist

Ocular lesions

Erythema nodosum observed by patient

or physician, pseudofolliculitis or

papulopustular lesions, or acne form

nodules

Skin lesions

Performed with a ≤21-gauge needle under

sterile conditions, observed by a physician at 48 hours.

Positive pathergy test

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The positive pathergy

test is seen with pustular

lesion on injection area

Diagnostic criteria of Behcet's syndrome

Erythema Nodosum

Principles of Therapy

TREATMENTS SHOULD BE ADAPTED

TO DIAGNOSIS, SEVERITY AND

ETIOLOGY

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PROBLEM SOLVING

CASES

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A child complaining of:

Arthritis

Palpable purpuric eruptions in LL

Abdominal pain & GI bleeding

+ Hemoptysis

After upper RTI = ???

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IgA vas.

(HSP)

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A history of asthma,

allergic rhynitis,

atopy,

peripheral neuropathy,

cutaneous eruptions,

pericarditis,

cardiomyopathy,

myocardial infarction

Hypereosinophilia, P-ANCA

may suggest ???

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EPA

(CSS) Churg-Strauss syndrome

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Female patient over the age of 50

recent onset of headache,

Jaw claudication

scalp tenderness,

loss of vision,

myalgias,

fever (FUO),

a high ESR,

anemia. ????

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GCA

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Recurrent oral ulcers, > 3 times in 1yr.

Genital ulcer or scare,

Uveitis, cells in vitreous, retinal vasculitis,

Superficial thrombophlebitis,

Erythema nodosum,

Papulopustules

Pathergy (2mm eryth- 1-2days-25g-5mm depth).?????????

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Behcet

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Purulent or bloody nasal drainage,

Nasal mucosal ulceration,

Saddle nose deformity

Otitis media .

Cough, dyspnea, hemoptysis

Massive pulmonary hemorrhage

Hematuria, Proteinuria, CRF

Fever, weight loss,

Cutaneous purpura, peripheral

neuropathy, arthralgia/arthritis.

C-ANCA ???

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GPA (WG)

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A child <5yrs. complaining of:

Arthritis,

Acute onset of high fever,

Bilateral conjunctival congestion,

"strawberry" tongue.

Painful cervical LN,

Exanthema of the trunk,

Carditis + heart murmurs & IHD

Abdominal pain, vomiting & Diarrhea?

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Kawasaki

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A male, around 40s complaining of:

Myalgias, arthralgias, fever,

Sudden onset of sever HPT,

LL swelling & renal impairment,

Chest pain, dyspnea on exertion.

Abdominal pain, bleeding, and

bowel obstruction , abdominal

collection.

PN, painful mononeuritis multiplex,

seizures, strocks.

Palpable purpura, urticaria, livedo reticularis,

peripheral gangrene and skin nodules.

Orchitis and epididymitis.

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PAN

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young women complaining of:

Myalgias, arthralgias

Claudication,

Transient visual disturbances,

Syncope

Bruits, weak pulses,

Discrepancies of limb blood

pressure (LL>UL),

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Takayasu

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