Transcript Vasculitis [PPT]

23 - 09 - 2014
Vasculitis
Dr. Urmila Dhakad, MD
Assistant professor,
Dept. of Rheumatology
King George’s Medical University
Lucknow
What is Vasculitis?
•Vasculitis means inflammation of blood vessels.
•Heterogeneous group of diseases linked by common
clinical, laboratory, and pathophysiologic features.
•Clinicopathologic process characterized by
inflammatory destruction of blood vessels that results
in occlusion or destruction of vessel and ischemia of
tissues supplied by that vessel.
• All blood vessels can be affected from the largest
(Aorta) to smallest blood vessels in the skin
(capillaries)
• Any organ can be affected resulting in a wide variety
of signs and symptoms.
Aetiology of vasculitis
• Unknown, but is clearly multifactorial
• Vasculitis can occur independently (primary/ idiopathic) or
secondary vasculitides as a secondary feature of an established
disease, such as rheumatoid arthritis, malignancies, or infections .
Among the influences on disease expression are
 Ethnicity, genes (HLA and others),
 Gender and
 Environment (ultraviolet light, infections, toxins, drugs, allergy,
smoking, etc).
Diagnostic Classification of Vasculitis
There are appox. 20 different types of Vasculitis.
1. Large vessel vasculitis (Aorta /great vessels)
2. Medium-sized vessel vasculitis
(Arteries with muscular wall)
Small-vessel vasciulitis
(Capillaries, arterioles, venules)
Vessel size ?
• Large vessel - aorta and the largest branches directed
towards the major body regions (e.g.to the extremities
and the head and neck)
• Medium-sized vessel - main visceral arteries (e.g., renal,
hepatic, coronary and mesenteric arteries)
• Small vessel - venules, capillaries, arterioles and the
intraparenchymal distal arterial radicals that connect
with arterioles.
• Some small and large vessel vasculitides may involve
medium-sized arteries, but large and medium-sized
vessel vasculitides do not involve smaller arteries
Essential cryoglobulinemic vasculitis
Small-vessel vasculitis
ANCA associated vasculitis
•
Wegener’s
Immune complex mediated
•
vasculitis
granulomatosis
•
Churg-Strauss vasculitis
•
Microscopic polyangiitis
Hypersensitivity
•
Henoch-Schönlein
purpura
•
Behçet’s syndrome
•
Cryoglobulinemia
What Causes the Symptoms?
Inflammation : of the blood vessel itself and
Inflammation of tissues affected in the body.
Ischemia: From lack of blood flow through
swollen blood vessel.
Damage: From longstanding lack of blood
flow or inflammation.
Clinical Features Suggesting Vasculitis
Multisystem inflammatory disease - may involve
virtually every organ system in the body
Constitutional symptoms
Others
•Fever
•Mononeuritis multiplex
•Weight loss
•Mesenteric ischemia, bowel
•Fatigue
•Tachycardia
•Diffuse aches and pains
perforation.
•Cutaneous ulcers
•Renal insufficiency or failure
•Stroke
Clinical Features Suggesting Vasculitis
Small-vessel vasculitis - Palpable purpura,
glomerulonephritis, and pulmonary hemorrhage
Variety of Rashes –
•Palpable Purpura - most common rash
•Begin as non-palpable petechiae or
purpura which coalesce and become
palpable with time.
•Vary in size and usually found on lower
limbs.
•Do not blanche.
Clinical features suggesting
vasculitis
•
Pulmonary - Cough ,Shortness of breath , Hemoptysis
•
Neurological - inflammation of epi-neural arterioles
resulting in neural ischemia :
1. Mononeuritis (damage to a single nerve)
2. Mononeuritis - Multiplex (damage to many single
nerves), acute neurologic changes – foot drop/wrist
drop.
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Clinical features suggesting vasculitis
• Heart : Inflammation of coronary vessels ischemia,
infarction, pericarditis, myocarditis, endocarditis.
• Eyes : Sudden loss of vision, conjuctivitis , thinning of the
sclera, iritis and retinal vasculitis.
• Sinuses, Nose, & Ears : Inflammation of nasal septum –
ulcers, saddle nose deformity, hearing loss.
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Sequelae of vasculitis
• Necrosis of vessel walls resulting in
aneursymal dilatation and/or thrombosis
causing organ ischemia, infarction, or
hemorrhage
• Stenosis or occlusion of vessel with distal
ischemia / infarction
Diagnostic Approach to Patients With
Suspected Vasculitis
Diagnosis of a systemic vasculitis is often a
diagnosis of exclusion, based on recognition of
the clinical syndrome
e.g. Churg-Strauss: adult onset asthma x 2
years, followed by atypical pneumonias,
followed by peripheral nerve involvement
Diagnostic approach to patients
with suspected vasculitis
Biopsy of involved organ
•Gold standard method for establishing a diagnosis.
•May be helpful to exclude infection or malignancy.
•Helps in determination of vessel size.
•Histologic features like- necrosis, granulomas ,immune
complex and/or complements deposition.
Tests may be suggestive, but not diagnostic of vasculitis
• ESR, CRP
• CT: pulmonary hemorrhage, cavitary lesions
• Bronchoscopy: pulmonary hemorrhage
• Urinalysis: for patients with kidney vasculitis
• ANCA (antineutrophil cytoplasmic antibodies)
• Angiogram (including MRA, CT-angiogram)
Vasculitis mimics
• Diseases that can present as vasculitic syndromes
• Always look for mimics of vasculitis that have specific
treatments.
•
Infectious diseases - bacterial endocarditis,
HIV, viral hepatitis
• Paraneoplastic syndromes
• Atrial myxoma
• Cholesterol emboli syndrome
• Toxic drug effects – Ergots, cocaine,
amphetamine
Vasculitis : Treatment
principles
• Medium-vessel and small-vessel groups: respond
well to immunosuppression with cyclophosphamide
and corticosteroids.
• Large-vessel group: good response to moderate-tohigh-dose steroids alone.
• Small-vessel group: only sometimes require lowdose corticosteroids.
Vasculitis : Treatment principles
Remission induction:
Cyclophosphamide I V or orally x 6-12 months
Prednisone 1mg/ kg
Remission maintenance (minimum for 2 years)
–Methotrexate - 20-25 mg once a week
–Azathioprine - 2-3 mg/kg /day
–Mycophenolate mofetil - 2 g / day
–Leflunomide - 20 mg / day
Vasculitis: Monitoring
Investigations
• Lab tests - ESR , CBC, LFTs,
RFTs - every 4 weeks
• EMG
• NCV
• Otolaryngology: Sinusitis,
subglottic stenosis
• Nephrology : CRF
• CT scan
• PFTs
Consultation
6-12 months
• Gynecology: Fertility issues
• Neurology: peripheral
neuropathy
• Rehabilitation, pain
management
Important issues in care of patients with
vascultitis
PCP prophylaxis
• Co-trimoxazole
Anemia
• Check
erythropoietin
• Check iron stores
Osteoporosis
prophylaxis
• Base line DEXA scan
• Calcium and vitamin
D
• Bisphosfonates
Giant Cell Arteritis / Temporal arteritis
• Granulomatous arteritis of the aorta and its major branches,
with a predilection for the extra cranial branches of the
carotid artery.
• Often involves the temporal artery.
• Usually occurs in patients older than 50 years and often is
associated with polymyalgia rheumatica.
• Female : male -2:1
Giant Cell Arteritis / Temporal arteritis
•
A patient shall be said to have GCA if at least 3 of these 5
criteria are present -
1. Age at onset >50 years
2. New headache
3. Temporal artery abnormality - tenderness or decreased
pulsation
4. Increase ESR - >50 mm in first hour by WG method
5. Abnormal artery biopsy - characterised by mononuclear
cell infiltration or granulomatous inflammation.
Clinical Features of Giant Cell Arteritis
•Fever, fatigue, weight loss
•Headache, Scalp tenderness, jaw / tongue claudication
•Visual loss due to optic nerve ischemia from arteritis of
ocular vessels.
•Polymyalgia rheumatica : pain along shoulder and hip
girdle.
•Extremity claudication
•Aortic aneurysm
Takayasu arteritis
•Granulomatous inflammation of the aorta and its major
branches.
•Usually occurs in patients younger than 50 years.
•A patient shall be said to have TA if at least 3 of these 6
criteria are present 1. Age < 40 years old
2. Claudication of extremities - fatigue and discomfort in
muscles of extremities while in use, especially upper
extremities.
Takayasu arteritis
3. Decreased pulsation of one or both brachial arteries
4. BP difference >10 mm Hg in systolic BP between arms
5. Bruit over subclavian arteries or aorta
6. Arteriogram abnormality - narrowing or occlusion of entire
aorta, its proximal branches, or large arteries in proximal
upper or lower extremities
Magnetic resonance arteriogram
Irregularity and stenosis of
the infrarenal abdominal
aorta and right renal artery
Stenosis of Lt common
carotid and occlusion of Lt
subclavian artery coming off
the aortic arch.
Polyarteritis Nodosa
• Necrotising inflammation of medium-sized or small arteries
without glomerulonephritis or vasculitis in arterioles, capillaries
or venules.
• Often presents with acute severe ds.
• Systemic features - Fever, weight loss, arthralgias, night sweats
• Neurological - Mononeuritis multiplex (ie: foot drop, wrist drop)
• Renal - Hypertension, infarction
• GI tract - Pain, infarction, perforation, bleeding
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Polyarteritis Nodosa
A patient shall be said to have PAN if at least three of 10
criteria are present.
1.Weight loss - Loss of 4 kg or more since illness began.
2.Livedo reticularis - Mottled reticular pattern over skin of
3.Testicular pain or tenderness -
4. Myalgias, weakness, or leg tenderness .
5.Mononeuropathy or polyneuropathy
6.Diastolic BP >90 mm Hg
Polyarteritis Nodosa
7. Elevated blood urea >40 mg/dl or creatinine 1.5 mg/dl.
8. Hepatitis B virus - Presence of hepatitis B surface antigen
or antibody in serum.
9. Arteriographic abnormality - showing aneurysms or
occlusion of the visceral arteries
10. Biopsy of small or medium sized artery- showing the
presence of granulocytes or granulocytes and mononuclear
leucocytes in artery wall.
Livedo reticularis
Digital tip infarction
Angiogram showing microaneurysms in
polyarteritis nodosa
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Polyarteritis Nodosa
•Digital infarction - Ischemic finger / toe.
•Lab test:
-- Elevated ESR ,WBC and platelets count.
-- Anemia, LFT abnormalities, microscopic hematuria
-- can occur with hepatitis B or C
•Diagnosed by : Arteriography, biopsies
•Treatment : Prednisone + cyclophosphamide
Kawasaki disease
• Predominantly affects medium sized arteries but can
involve large, medium-sized, small arteries.
• Associated with mucocutaneous lymph node syndrome.
• Coronary arteries are often involved.
• Usually occurs in children
Kawasaki disease
Diagnostic criteria:
Fever for at least five days + any 4 of following:
1.Bilateral non purulent bulbar conjunctivitis.
2.Acute erythema of Palms, soles, hand & feet edema
3.Subacute periungual peeling of fingers & toes (2 & 3
week).
4.Changes in lips & oral cavity.
Kawasaki disease
5. Polymorphous rash, primarily truncal
6. Cervical lymphadenopathy (>1.5 cm), usually unilateral
Treatment of choice for Kawasaki
disease
•
Intravenous imune globuline
•
•
Aspirin
Steroid does not help
Kawasaki disease.
Periungual
desquamation
Polymorphous
exanthem
Conjunctivitis,
Red fissured lips,
Lt cervical
lymphadenopathy
Small Vessel Vasculitis
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Wegener’s Granulomatosis
Clinical features of WG
• Constitutional symptoms
• Skin rashes
• Neurological- Mononeuritis
multiplex
• Eyes - eye inflammation /
retro-orbital pseudo tumor
• Gastrointestinal- Ischemic
ulceration, Perforation,
intussusception , Pancreatitis
• Renal - 80% will progress to
GN
• Musculoskeletal
•Upper respiratory tract - Purulent
sinus drainage, nasal mucosal
ulceration with epistaxis , necrosis,
perforations of nasal septum, saddle
nose deformity, otitis media, hearing
loss, tracheal inflammation and
sclerosis of subglotic region.
•Lower respiratory tract - focal
infiltrates, Cavitary lesions, Massive
pulmonary hemorrhage and
hemoptysis - caused by alveolar
capillaritis
Wegener’s Granulomatosis
A patient shall be said to have Wegener’s granulomatosis
if at least two of these four criteria are present1. Nasal or oral inflammation - painful or painless oral
ulcers or purulent or bloody nasal discharge.
2. Abnormal chest radiograph - presence of nodules,
fixed infiltrates or cavities.
3. Urinary sediment - Microhaematuria (>5 red cells per
high power field) or red cell casts in urinary sediment.
Wegener’s Granulomatosis
4. Granulomatous inflammation on biopsygranulomatous inflammation within the wall of an artery
or in the perivascular or extravascular area (artery or
arteriole).
Granulomatous inflammation - Focal accumulations of
lymphocytes, macrophages, epithelioid cells and
multinucleated giant cells
Oral manifestations of Wegener granulomatosis
Tongue ulcer
“Strawberry gums” due to
gingival inflammation
Mononeuritis multiplex
Wasting of the interosseous muscle
between the thumb and first finger
A patient with weakness bilaterally
of foot dorsiflexion (“foot drop”)
Alveolar hemorrhage and a nodular lesion in the right lung
in a patient with WG
Microscopic polyangiitis
• Microscopic polyarteritis
• Necrotising vasculitis involving predominantely small,
but medium-sized vessels involvement may be present.
• It is associated with pANCA .
• There is few or no immune deposits in wall of effected
vessel.
• Necrotising glomerulonephritis is very common.
• Pulmonary haemorrhage because of capillaritis often
occurs.
Churg–Strauss syndrome
A person shall be said to have Churg–Strauss syndrome if at
least four of these six criteria are present.
1.Asthma
2.Eosinophilia >10% on white cell differential count
3.Mononeuropathy or polyneuropathy
4.Migratory or transient pulmonary infiltrates on radiographs
5.Paranasal sinus abnormality
6.Biopsy including artery, arteriole or venule showing
accumulations of eosinophils in extravascular areas.
Churg–Strauss syndrome
5. Paranasal sinus abnormality - History of acute or chronic
paranasal sinus pain or tenderness or radiographic opacification
of the paranasal sinuses
6. Biopsy including artery, arteriole or venule showing
accumulations of eosinophils in extravascular areas
Hypersensitivity vasculitis
A patient shall be said to have hypersensitivity vasculitis if at least
three of these five criteria are present.
1.Age at disease onset >16 years
2.Medication at disease onset - Medication was taken at the onset
of symptoms that may have been a precipitating factor
3. Palpable purpura - does not blanch and is not related to
thrombocytopenia
4. Maculopapular rash
5. Biopsy including arteriole and venule - showing granulocytes in
a perivascular or extravascular location
Palpable purpura representing hypersensitivity vasculitis
Henoch Schonlein Purpura
• Small vessel vasculitis, with IgA-dominant immune deposits.
• Typically involves skin, gut and glomeruli and joints.
• A pt shall be said to have HSP if at least 2 of these 4 features 1.
Palpable purpura
2. Bowel angina - Diffuse abdominal pain worse after meals,
or bowel ischaemia, usually bloody diarrhoea
3. Age at onset <20 years
4. Biopsy - histological changes showing granulocytes and IgAdeposits in walls of arteries or venules.
Henoch-Schönlein purpura
Palpable purpura over lower extremities
Essential cryoglobulinemic
vasculitis
• Small vessels vasculitis, with cryoglobulin immune
deposits.
• It is associated with cryoglobulins in serum.
• Cryoglobulins are immunoglobulin containing complex
which precipitate in serum spontaneously at low temp.
• 35-100 % of cases are associated with hepatitis C.
• Skin and glomeruli are often involved.
Major viruses associated with
vasculitis
• HBV - PAN
• HCV - Cryoglobulinaemic vasculitis
• HIV - PAN large/medium/small vessel vasculitis cerebral
vasculitis
• Parvovirus B19 – PAN, HSP-like
• Varicella zoster – Retinitis, meningoencephalomyelitis
• CMV – Retinitis, Colitis ,PAN
When you see a patient with a
possible vasculitis what do you need
to do?
1. Recognize if a patient is in a potentially
threatening situation
2. Confirm that this is vasculitis
3. Determine if there is an underlying
cause for the vasculitis
How do you do this ?
Recognition of Vasculitis
History
Exam
Labs
Imaging
Skin
+
+
Eye
+
+
ENT
+
+
+
Lung
+/-
+/-
+
Kidney
+
GI
+
+
Neuro
+
+
+
+
+
Summary points
• When a patient has a complex multisystem inflammatory
picture—think vasculitis!
• Vasculitides are inflammatory vessel diseases which include
around 15–20 distinct entities.
• They are categorised as primary or secondary.
• Further classified into 3 groups according to size of
predominantly involved vessels (large/medium/small-vessel).
Summary points
• Most cases of vasculitis are primary vasculitides.
• Most common causes of secondary vasculitides are
malignancies, infections or drug exposures.
• Some vasculitis entities (e.g. PN ) may present both as
primary and as secondary (e.g., HBV-related PAN ).
• It is important to consider vasculitis mimics in differential
diagnosis as they require different therapeutic approaches.
Assessment
MCQs
MCQ -1
Which of the following is not a ANCA associated vasulitis –
1.Churg–Strauss syndrome
2.Wegner’s Granulomatosis
3.Polyarteritis nodosa
4.Microscopic polyangitis
MCQ-2
Most common childhood vasculitis is –
1. Kawasaki disease
2.Churg strauss syndrome
3.Henoch-schonlein purpura
4.Childhood Poly arteritis Nodosa
MCQ -3
Which of the following is not a small vessel vasculitis a) Polyarteritis Nodosa
b) Wegener's granulomatosis
d) Henoch schonlein purpura
e) Churg-struass syndrome
MCQ - 4
A 65-year-old man suddenly becomes blind in one eye.
Angiography demonstrates occlusion of the central retinal
artery. Which of the following is the most likely cause A. Atheroma or embolism
B. Giant cell arteritis
C. Poly areritis nodosa
D. Takaysu’s arteritis
MCQ-5
A 30 years old female presents with fatigue and
claudication in Rt. upper limb. Her BP in Rt. and Lt. upper
limb is 180/90 and 130/90 mm Hg respectively. What is the
most likely clinical diagnosis –
1.Poly arteritis nodosa
2.Giant cell arteritis
3.Takayasu arteritis
4.Kawasaki disease
Thank you