Vasculitis undergrad: diagnosis & treatment.

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DR. ABD EL AZEIM ALHEFNY MD
Prof. Internal Medicine, Rheumatology & Clinical immunology
Director of Rheumatology Unite
Ain Shams University

At the end of this lecture you have to know:-
 Vasculitis definition, shot note on pathophysiology
 When to suspect & the initial assessment
 Classification of vasculitides
 Clinical picture of some examples
 Lines of treatment.

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 The vasculitides are a heterogeneous group of
systemic inflammatory disorders with
demonstrable structural injury to the blood
vessel walls leading to ischemic manifestations .

1) Immune complex deposition.
2) Anti-endothelial cell antibodies.
3) Anti neutrophil cytoplasmic antibodies
(ANCA).
4) T cell dependent inflammatory reactions.
5) Infection of endothelial cells.
Possible Pathogenic Mechanisms

Fibrinoid necrosis
(media)
Thrombosis
Inflammation

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.)
branches

Establish
the
Diagnosis
Clinical
Features
Laboratory
Work Up
Initial Assessment

Laboratory workup
➢ ESR & CRP
➢ CBC
➢ Transaminases &Liver function tests
➢ Kidney Function tests
➢ Urine analysis & A/C ratio…..
➢ Blood & sputum cultures

Antibodies directed against :-
 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
 eg. MPA and Churg-Strauss
Laboratory workup

Establish
the
Diagnosis
Imaging
Clinical
Features
Laboratory
Work Up
Initial Assessment

Imaging & Angiogaphy
 Power Doppler & Duplex.
 MRI, MRA & MRV.
 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
Vasculitis
Primary Secondary
Vessel size is the key
discriminator in the
definition of primary
systemic vasculitis.
▪ CTD
▪ Infection
▪ Drug
▪ Malignancy

Classification (ctd.)
Primary Vasculitis
Large
Vessel
Medium
Vessel
Small
Vessel

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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 vasculitis:
* Eosinophelic garnulomatosis with
Polyangiitis =EGPA (Churg-Strauss
syndrome (P) CSS)
* Granulomatosis With Polyangiitis (GPA)
=Wegener's granulomatosis(C)WG
Immune complex vasculitis:

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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, anemia.

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 Characterized by proximal muscle aches
and stiffness (bilateral & symmetrical).
 The ESR is usually elevated.
50% have SS
GCA PMR.
Some develop

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1-Large vessels
(Aorta & its
branches)
*Giant cell arteritis (GCA- PMR)
*Takayasu's arteritis
2-Medium-sized ves.
(Main visceral art.)
*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)
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 ys.

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It has two phases:-
* Early systemic phase:
Malaise, fever, night sweats, weight loss,
myalgias, and arthralgias.
* Later occlusive phase:
 Claudicating pain (arms & neck),
headaches, BP difference >10 mmHg in
both arms, Bruit over subclavian,
syncope, and visual disturbances, + AR

ACR Classification criteria
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
entire aorta or its large branches,
Disease is diagnosed if at least 3 of 6 criteria are +ve
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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 & monitor 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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1-Large vessels
(Aorta & its
branches)
2-Medium-sized ves.
*Kawasaki disease
3-Small vessels
ANCA- associated:
Polyangiitis =EGPA

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 PAN: Necrotizing inflammation of medium-
sized arteries, but does not involve veins.
 Without:- GN or ANCAs.
 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 presentation
1. Kidneys are the most commonly involved organs,
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 presentationcont.
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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 ESR, CRP, WBCs, Platelets are
usually high.
 Anemia, hematuria & proteinuria.
 Hypocomplementemia.
 ANCA is negative.
 Hepatitis B surface antigen
(HBsAg) (>30%).
 Angiography often shows
microaneurysms and stenoses.
 Biopsy to confirm diagnosis.
Investigations

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1-Large vessels
(Aorta & its bran)
2-Medium-sized ves.
*Kawasaki disease
3-Small vessels
ANCA- associated:
Polyangiitis =EGPA

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 = Mucocutaneous LN syndrome
 Etiology: unknown.
 Acute febrile disease
 Affecting infants & children < 5 Yrs.

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❖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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1-Large vessels
(Aorta & its bran)
2-Medium-sized ves.
*Kawasaki disease
3-Small vessels
ANCA- associated:
Polyangiitis =EGPA
=Wegener's granulomatosis (C) WG

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pulmonary infiltrates
 Hypereosinophilia
 Asthma, sinusitis (61%) and allergic
rhinitis.
 Pulmonary infiltrates.
 Cutaneous eruptions (49%).
 Pericarditis, cardiomyopathy & MI.
 PN is found in 70% of patients.
 Renal disease (generally mild).
 Arthralgias (40%)
 GI symptoms (31%)

1990 ACR criteria for the diagnosis
of Churg-Strauss syndrome:
1. Asthma (wheezing, expiratory rhonchi)
2. Eosinophilia >10% in peripheral blood
3. Sinusitis
4. Pulmonary infiltrates (may be transient)
5. Histological proof of vasculitis with extravascular
eosinophils
6. Mononeuritis multiplex or polyneuropathy
The presence of four or more criteria yields a
sensitivity of 85% and a specificity of 99.7%.
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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.

Causes of bad prognosis
 Heart failure, &/or MI (most common cause)
 Renal failure
 Cerebral hemorrhage
 Gastrointestinal bleeding
 Status asthmaticus
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1-Large vessels (Aorta &
its bran)
2-Medium-sized ves.
*Kawasaki disease
3-Small vessels
ANCA- associated:
Polyangiitis =EGPA
*Granulomatosis With Polyangiitis
(GPA)

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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 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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 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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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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1-Large vessels
(Aorta & its bran)
2-Medium-sized ves.
*Kawasaki disease
3-Small vessels
ANCA- associated:
*Eosinophelic garnulomatosis with Polyangiitis =EGPA
* IgA Vas. = Henoch-Schőnlein
purpura (HSP)

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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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❖ 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

Behçet's syndrome
Oral ulcers Genital ulcers
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

Diagnostic criteria of Behcet's syndrome
DefinitionClinical 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
62

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The positive pathergy test is
seen with pustular lesion on
injection area
Diagnostic criteria of Behcet's syndrome
Erythema Nodosum

TREATMENTS SHOULD BEADAPTED
TO DIAGNOSIS, SEVERITYAND
ETIOLOGY

Principles of Therapy
 Identification and removal of the possible
causal agent (stop offending drug).
 Treat primary underlying disease
(i.e. Harvoni for hepatitis C or Lamivudin for
HBV).
 Limited cutaneous vasculitis:
 Antihistamines, colchicine or dapsone along
with supportive care.
 Corticosteroids if the lesions are wide spread.

 Glucocorticoids are usually sufficient to
manage giant cell arteritis and Takayasu's
arteritis and limited polyarteritis (no significant
visceral involvement).
 Indications for cytotoxic drug include:
1. Rapidly progressive disease with significant
visceral involvement.
2. Disease refractory to corticosteroids.
3. Inability to reduce the dose of
corticosteroid.

 Mycophenolate mofetil (MMF) has been
used as maintenance therapy for WG and
microscopic polyangiitis.
 IV immunoglobulins & TNF blockers may be
used in resistant cases of WG
 Plasmapheresis for acute management of
severe vasculitis remains controversial

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Approach to patient with
vasculitis
Characteristic clinical patterns
Tissue biopsy
Establish diagnosis
Patient with a multi system
disorders (suspected vasculitis)
AngiographySupporting laboratory testing
Look for underlying dis.Look for offending antigen
Specific
vasculitis syndrome NoNoYes Yes
Treat vasculitis
Remove antigen
TTT disease
Follow up
No further action
Syndrome resolved Syndrome resolved
No
No

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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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 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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 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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 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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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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❖ 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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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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Vasculitis undergrad: diagnosis & treatment.

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