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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
55
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 = ???
1
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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 ???
2
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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. ????
3
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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).?????????
4
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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 ???
5
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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?
6
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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.
7
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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),
8
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Takayasu
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