Vasculitis Flashcards
What are the 2 pathogenic mechanism of vasculitis?
- Immune‐Mediated Inflammation (more common)
* Direct invasion by infectious pathogens
What are the characteristics of small and medium vessel vasculitis?
i. “inside-out” pathogenesis
ii. endothelial disruption
iii. neutrophils predominate
iv. fibrin deposition
What are the characteristics of large vessel vasculitis?
i. “outside-in” pathogenesis
ii. Adventitial antigen presenting cells
iii. T-helper/cell-mediated, macrophage infiltrate.
iv. NO fibrin deposition
v. Hypertrophy & stenosis
What is the pathogenesis of small and medium vessel vasculitis?
Local or systemic inflammatory molecules trigger neutrophil & endothelial activation. Adhesion molecule upregulation with migration of the neutrophils into the
vessel walls which causes degranulation and damage.
What is the pathogenesis of large vessel vasculitis?
Tissue dendritic cells in adventitia start to stimulate T helper (likely Th1) cells that circulate in from vasa vasorum by displaying antigen+ giving the second activation signal leading to inflammation and eventual disruption of the internal elastic lamina and intimal hypertrophy.
What are the 3 ways that vasculitis can cause occlusion?
a. Thrombosis
b. Stenosis
c. Aneurysm + rupture or dissection
Which type of vasculitis is “leukocytoclastic”—neutrophil debris seen in?
Small Vessel
Where are the most common places where small vessel vasculitis is seen?
Most common places: skin, lungs, kidneys
Which type of vasculitis is fibrinoid necrosis seen in?
Small and Medium Vessel
What is a complication of vasculitis in medium vessels?
Aneurysms as there is a muscular layer that can cause extreme weakening of the wall when it is broken down
Which type of vasculitis is granuloma seen in?
Large Vessel
Which type of vasculitis are giant cells seen in?
Large Vessel
Which type of vasculitis is claudication seen in?
Large Vessel
Where is C-ANCA found and what is it associated with?
Cytoplasm. Usually associated with antibodies specific for proteinase-3. Very specific for an ANCA-associated vasculitis called granulomatous polyangiitis (i.e. Wegener’s)
Where is P-ANCA found and what is it associated with?
Perinuclear. Associated with antibodies specific for myeloperoxidase. In some GI conditions or with some drug hypersensitivity, can have P-ANCA on immunofluorescence, with negative MPO ELISA
What is the most common vasculitis?
Giant Cell Arteritis (GCA)
What vessels does GCA affect?
Large. Involves aorta and major branches to the head
What is the pathogenesis of GCA?
T-cell mediated
What are the findings with GCA?
- Nodular thickening of the artery, intimal proliferation resulting in narrowing of the lumen
- Acute, chronic, granulomatous inflammation
- Giant cells may be present
What is the typical patient of GCA?
Involves adults usually after age 50, most are female and Caucasian
What is a lab finding for GCA?
Patients have elevated serum ESR and/or CRP
What are clinical findings for GCA?
- Scalp tenderness
- TA pulse abnormality
- Ocular disturbance‐50%
What is the treatment for GCA?
Treatment is high dose corticosteroids (prednisone) with slow taper
What is Takayasu’s Arteritis AKA?
Pulseless Disease
What are the findings with Takayasu’s Arteritis?
- Thickening of arterial wall/intima, luminal narrowing
- Granulomatous inflammation
- Pulmonary Hypertension
- Claudication/Weakness
What are the vessels that Takayasu’s Arteritis involves?
Large. Involves Aortic Arch and its branches.
Who is the typical patient of Takayasu’s Arteritis?
East Asian women under 50 years of age
Why does the weakening of pulses occur with Takayasu’s Arteritis?
Weakening of pulses of upper extremities due to narrowing of lumen of vessels
What are the 3 phases of Takayasu’s Arteritis?
- Phase I: pre‐pulseless, inflammatory period characterized by nonspecific systemic complaints such as fever, arthralgias, and weight loss
- Phase II: vessel inflammation dominated by vessel pain and tenderness.
- Phase III: fibrotic stage, when bruits and ischemia dominate
What types of vessels does Kawasaki Syndrome affect?
Medium. Coronary arteries frequently involved.
What is the most common cause of acquired heart disease in children?
Kawasaki Syndrome
What is the main patient population for Kawasaki Syndrome?
Children under the age of 5 - more prevalent in Japan
What is the pathogenesis of Kawasaki Syndrome?
Anti‐endothelial/anti‐smooth muscle cell antibodies
What are some of the findings of Kawasaki Syndrome?
• Fever • Fibrinoid necrosis • Destruction of internal elastic lamina – No granulomas • Aneurysmal rupture or acute thrombosis
What is the window of opportunity to treat Kawasaki Syndrome?
0-2 weeks after fever
What is the treatment for Kawasaki Syndrome?
• High dose Aspirin - one of the few cases to treat a child with aspirin
What is Polyarteritis Nodosa (PAN) often associated with?
Hepatitis B and C
What vessels does PAN affect?
Medium to small muscular arteries
• Renal arteries
• Coronary arteries
• Hepatic arteries
What does PAN often spare?
Lungs
What are some of the clinical findings with PAN?
- Organ infarcts
- Abdominal pain
- Renal injury/Hypertension
- Cutaneous lesions
- Arthralgia/Arthritis
- Acute peripheral neuropathy
What are some of the lab findings of PAN?
- ANCA negative
* Hypocomplementemia
What is the progression of PAN?
Rapidly progressive & fatal if not treated
What types of vasculitis are ANCA associated?
Granulomatosis with Polyangiitis (GPA)
Microscopic Polyangiitis (MPA)
Churg‐Strauss (CS)
What vessels do ANCA associated vasculitis affect?
Small vessels:
• Glomerular capillaries
• Pulmonary capillaries
But can also affect medium sized vessels
What are the findings with granulomatosis with polyangiitis?
– Leukocytoclastic fibrinoid necrosis
– Granulomas in lung or upper respiratory tract
What are the findings with microscopic polyangiitis?
– Leukocytoclastic fibrinoid necrosis
– NO Granulomas
What are the findings with Churg Strauss?
– Leukocytoclastic fibrinoid necrosis
– Granulomas
– Peripheral & tissue eosinophilia
What will be absent in ANCA mediated vasculitis?
Immune complexes - “pauci-immune”
What does saddle nose indicate?
GPA
What does eosinophilic cardiac infiltration indicate?
CS
What does pulmonary hemorrhage indicate as a possible vasculitis?
MPA
What is the incidence of GPA by gender?
More in males than females
What type of ANCA is GPA associated with?
c-ANCA
What type of ANCA is CS associated with?
p-ANCA
What type of ANCA is MPA associated with?
p-ANCA
What vasculitis are nasal polyps associated with?
CS
What vessels does Henoch-Schonlein Purpura involve?
Small - arterioles, capillaries, venules
What is the pathogenesis of Henoch-Schonlein Purpura?
Infection or drug, or other environmental exposure causes IgA immune complexes to form & deposit in vessel walls, instigates complement cascade
What is the typical HSP patient?
Children - but CAN occur in adults
What is the triad of HSP symptoms?
Triad usually is arthritis, abdominal pain & palpable purpura
What are the lab findings with HSP?
- Immune complex deposition
- H&E shows neutrophils
- Immunofluorescence shows IgA & C3
What is the typical patient of thrombiangiitis obliterans?
Seen in SMOKERS younger than 40
What vessels does thrombiangiitis obliterans affect?
Inflammation of medium & small arteries
What can thromboangiitis obliterans result in?
Gangrenous extremities
What does imaging show about the vessel affected by thromboangiitis obliterans?
“Corkscrew” collaterals on imaging
