11.10: Vasculitis Flashcards
Types of immune mediated inflammation leading to vasculitis?
- Immune complex associated
- ANCA: antineutrophil cytoplasmic antibody
- Anti endothelial cell antibodies: direct vasc. attack
- Cell mediated immunity
Broad categories that can cause vasculitis?
- Immune mediated
2. Invasion by infectious pathogens
Does vasculitis occur mainly in venous or arterial system?
Arterial
Layers of vessels from inside to out?
- Intima
- Internal elastic lamina
- Media
- Adventitia
How does vasculitis move in small vessels?
From inside out
How does vasculitis move in large vessels?
Vaso vasorum in the adventitia can allows immune cells and pathogens to infiltrate
**Inside out in medium vessels as well
Is vasculitis and inside out or outside in process? Which type of cells are responsible?
- Inside to outside: in small and medium vessels where most occurs
- Normally mediated by neutrophils
How are neutrophils involved?
- Neut is traveling in blood then adheres to vessel wall
- Something causes degranulation leading to inflammation
Pathway in large vessels?
- Naive T Cells activate DCs in adventitia
- Activation cause ROS = damage of media
- Non scarring arteritis: window of opportunity?
- Scarring and fibrosis break down elastic lamina and thicken Intima
- Fibrosis = stenosis / ischemia
- Breakdown of elastic lamina = aneurysm
Difference between instigating cells in small and large vessels?
Small: Neutrophils
Large: Macrophages
Pathway in small vessel vasculitis?
- Inflammatory state is first step
- Next several things could happen:
a. IC attaches and irritates endothelium
b. Anti neutrophil Ig could active neut
c. Ig directly bind endothelium leading to neut attack - Neutrophils then degranulate causing inflammation
- Small vessel comes apart leaking blood
What happens to endothelial cell when activated?
- Procoagulant: express adhesion factors
- Proinflammatory
- Leads to turbulent flow
What are features of all vasculitides?
- Fever
- Fatigue
- Myalgia
- Weight loss
- Organ dysfunction
What is CRP?
- Biomarker for inflammation
- Produced by liver
What occurs when levels of fibrinogen rise?
- Sedimentation rate goes up
What is leukocytoclasis?
- Neutrophils are exploding like kamikazes leaving nuclear debris in wake
Characteristics of small vessel vasculitis?
- Leukocytoclasis
- Fibrinoid necrosis
- Possible Immune complex deposition
What is fibrinoid necrosis?
- Dead neutrophils with fibrin deposition
Clinical signs of small vessel vasculitis?
- Palpable purpura: bumpy and does not blanch
- Bleeding in small vessels of lungs
- Necrotizing glomerulonephritis
What is special about purpura in vasculitis?
- It is bumpy from blood vessel inflammation causing them to pop up
Features of medium vessel vasculitis?
- Muscular layer offers great protection from obliteration
1. Fibrinoid necrosis with pleomorphic infiltrate
2. Fibrinoid necrosis is focal and segmental: not entire circumference, skip along vessel
3. Aneurysms from destruction of media
Clinical findings in medium cell vasculitis?
- Skin nodules in hands
- Livedo: Ringlike rash
- Ulcers instead of palpable purpura
- Abdominal pain
- Nerve infarcts: sensory and motor loss
What causes large vessel vasculitis?
- Usually not neutrophilic like small and medium
- Can be immune complex mediated
- Usually innate cells such as macs and T cells
Characteristics of large vessel vasculitis?
- Innate cell mediated
- Outside in
- Granulomas starting in adventitia usually present
- Intima becomes hyperplastic leading to stenosis / occlusion
- Neovascularization occurs to get some blood through
When does fibrinoid necrosis occur?
- Small and medium vasculitis, note large
Clinical findings in large vessel vasculitis?
- Loss of vision or 2x vision
- Claudication: cramps from low flow
- Chest pain
- Headaches and stroke symptoms
Diagnostic considerations in vasculitis?
- Vessel size based on presentation
- ANCA association
- Granulomas
- Possible disease association
Study performed with large vessel involvement?
- Angiography or MRA
- ESR
- CRP
Study performed with small vessel involvement?
- CT Chest
- Lung / kidney biopsy
- Skin biopsy
- Urinalysis
What are two types of ANCA? How to tell which kind?
- C-ANCA, “Cytoplasmic:” Elisa test positive for PR3
2. P-ANCA “Perinuclear:” Elisa test positive for MPO
What is Elisa test positive for PR3 indicative of?
C-ANCA
What is Elisa test positive for MPO indicative of?
P-ANCA
Pathogenesis of ANCA?
- Infection creating proinflammatory state
- Antibodies can be developed for neut granules
- Antibodies will later stimulate neut w/o infection
What can be used to treat ANCA?
Rituxan
Why does knowing if there are granulomas help?
There are small amount of vasculitis that form them
What are some non microbial antigens that can cause vasculitis?
- Drugs
- Allergens
- Tumor antigens
What can vasculitis be secondary to?
- HIV
- Lupus
3 Rheumatoid arthritis
What is GCA?
“Giant Cell Arteritis”
- > 50 yo, w/ 2/3 females
- More common in scandinavians: whites
- Less common in blacks, hispanics, asians
- Large / medium vessels
- Tender and tortuous temporal artery
Where does GCA usually occur?
- Usually in external carotid and temporal: tender and tortuous
- Can occur in ophthalmic c. off internal carotid
- Does NOT involve cerebral arteries
- Aorta
Pathologic features of GCA?
- Patchy and segmental
- Granulomatous
- Fragmented IEL: Aneurysm
- Can be chronic
Clinical features of GCA?
- Headaches
- Polymyalgia Rheumatic: stiff in morning
- Scalp tenderness
- TA pulse abnormality
- Ocular disturbance
- Claudication in extremities
- Cardiac or neurologic symptoms
Investigations for GCA?
- Temporal artery biopsy
- Test acute phase proteins
- Vessel imaging for claudication
Treatment for GCA?
Corticosteroids with SLOW taper
Another name for pulseless disease?
Takayasu’s ateritis
Typical ptn. with pulseless disease?
Japanese female
Vessel normally involved in Takayasu’s arteritis?
- Aorta, arch, and branches
- Pulmonary artery
- Renal artery
- Cerebral arteries with stroke
- **Likes to stenose in branching areas
Pathologic findings in Takayasu’s?
- Very similar to GCA
- Intense transmural scarring
- Hyperplastic intima with neovascularization
- Luminal narrowing
3 phases of Takayasu’s?
- Inflammatory period: ever, pain etc
- Vessel inflammation with pain and tenderness
- Fibrotic state with stenosis and bruits
Clinical features of Takayasu’s?
- Abnormal pulses
- Unequal blood pressure
- Bruits
- Claudication
- Ocular disturbance
- Pulmonary / renal htn
Key diagnostic test in Takayasu’s?
- Imaging of aorta and all vessels
What is most common cause of heart disease in kids?
Kawasaki’s
Pathologic characteristics of Kawasaki’s?
- Fibrinoid necrosis
- IEL destruction
- NO granulomas
- Aneurysm or acute thrombosis
When does kawasaki’s need to be treated?
2 weeks after first fever
Clinical features of Kawasaki’s disease?
- Fever
- Polymorphous rash
- Bilateral conjunctival w/o exudate
- Strawberry mouth and tongue
- Edema and erythema in extremities
- Swollen glands
- Coronary aneurysm
Treatment of Kawasaki’s disease?
- High dose aspirin
- IVIG: within first ten days of fever
What is PAN?
“Polyarteritis Nodosa”
- Small and medium muscular arteries
- Can be caused by hep B / C
What arteries does PAN prefer?
- Renal
- Coronary
- Hepatic
Pathologic features of PAN?
- Focal
- Segmental
- Transmural
- Fibrinoid necrosis
Clinical features of PAN?
- Organ infarct
- Abdominal pain
- Arthralgia
- Neuropathy: asymmetrically additive
- LUNGS ARE SPARED
What is characteristic of PAN neuropathy?
Asymmetrically additive: “Mononeuritis multiplex”
- Won’t be entire hand or foot as in diabetes
- Will just be individual parts
What is Mononeuritis multiplex?
- Asymmetrically additive neuropathy seen in PAN
Is PAN ANCA positive or negative?
Negative
Tests for PAN?
- ANCA negative
- Angiogram with smooth stenosis followed by aneurysm
How to treat PAN?
- Corticosteroids
- Plasma exchange if from Hep B
What are the 3 ANCA associated vasculitis?
- GPA: “Granulomatosis with Polyangiitis”
- MPA: “Microscopic polyangiitis”
- CS: Churg Strauss
Symptoms of ANCAs?
- Palpable purpura
- Renal / pulmonary syndrome
- Impact small vessels
What size vessels do ANCAs impact?
- Small and some medium
- Kidneys / lungs
Pathologic features of ANCAs?
- **All are Pauci immune
1. GPA: - Leukocytoclastic fibrinoid necrosis
- Granulomas in upper resp tract
2. MPA: “Microscopic polyangiitis - Leukocytoclastic fibrinoid necrosis
- NO granulomas
3. CS: Churg Strauss - Leukocytoclastic fibrinoid necrosis
- Granulomas
- Peripheral and tissue eosinophelia
Which ANCA shows no granuloma?
MPA
Which ANCA shows peripheral and tissue eosinophilia?
CS
What does pauci immune mean?
- Not much immune deposition
- Immunofluorescence is not positive
Clinical features of GPA?
- Destruction of upper airway: SADDLE NOSE
- Gingival hyperplasia
- Subepiglottic stenosis
- Eye issues
- Necrotic pulmonary cavities
- NCGN: Necrotizing crescentic glomerulonephritis
Clinical features of MPA?
- Alveolar
- NCGN
Clinical features of CS?
- Nasal polyps
- Asthma / allergy
- NCGN
- Can progress to cardiomyopathy from eosinophilic cardia infiltrate
Test indicating GPA?
- C ANCA and PR3 positive
What is C ANCA and PR3 positive indicative of?
GPA
Test indicating MPA?
- P ANCA and MPO positive
What does P ANCA and MPO positive indicate?
MPA
- Lesser likelihood of CS
What will ANCAs show on urine studies?
- Proteinuria
- RBCs
- Casts
What test is expected positive in Immune complex mediated vasculitis?
- Immunofluorescence
What is HSP?
“Henoch Schonlein Purpura”
- Usually in children: adults too
- More common in winter
- 50% of time preceded by URI
- Small vessels: IC mediated
What are the immune complex mediated diseases?
- SLE vasculitis
- HSP
- Cryoglobulin vasculitis
- Goodpasture disease
* *All occur in small vessels
What is IgA and C3 on immunofluorescence characteristic of?
HSP
How do you test for HSP?
- IgA and C3 on neutrophils
2. H and E shows neutrophils
HSP clinical features?
- Palpable purpura
- Arthritis
- Abdominal pain
- Renal impairment
What are the following characteristic of?
- Palpable purpura
- Arthritis
- Abdominal pain
- Renal impairment
HSP
HSP treatment?
- Hydration
- NSAIDs if no renal involvement
What is thromboangiitis obliterans?
- Seen in smokers
What are corkscrew collaterals indicative of?
Thromboangiitis obliterans
Treatment for thromboangiitis obliterans?
STOP SMOKING YOU IDIOT
Vasculitis treatment?
- Steroids
- Chemo
- Rituximab in B cell
When would you see granulomas at IEL?
GCA
When do you see leukocytoclastic vasculitis in glomerular capillaries?
ANCA associated / small vessel
When do you see extensive hyperplastic intima with neovascularization?
Takayasu’s
When do you see focal vasculitis with transmural fibrinoid necrosis?
PAN
What disease can cause aortic dissection?
GCA
