Vasculitis

Question 1

What are the 2 pathogenic mechanism of vasculitis?

Answer 1

• Immune‐Mediated Inflammation (more common)

* Direct invasion by infectious pathogens

Question 2

What are the characteristics of small and medium vessel vasculitis?

Answer 2

i. “inside-out” pathogenesis
ii. endothelial disruption
iii. neutrophils predominate
iv. fibrin deposition

Question 3

What are the characteristics of large vessel vasculitis?

Answer 3

i. “outside-in” pathogenesis
ii. Adventitial antigen presenting cells
iii. T-helper/cell-mediated, macrophage infiltrate.
iv. NO fibrin deposition
v. Hypertrophy & stenosis

Question 4

What is the pathogenesis of small and medium vessel vasculitis?

Answer 4

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.

Question 5

What is the pathogenesis of large vessel vasculitis?

Answer 5

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.

Question 6

What are the 3 ways that vasculitis can cause occlusion?

Answer 6

a. Thrombosis
b. Stenosis
c. Aneurysm + rupture or dissection

Question 7

Which type of vasculitis is “leukocytoclastic”—neutrophil debris seen in?

Answer 7

Small Vessel

Question 8

Where are the most common places where small vessel vasculitis is seen?

Answer 8

Most common places: skin, lungs, kidneys

Question 9

Which type of vasculitis is fibrinoid necrosis seen in?

Answer 9

Small and Medium Vessel

Question 10

What is a complication of vasculitis in medium vessels?

Answer 10

Aneurysms as there is a muscular layer that can cause extreme weakening of the wall when it is broken down

Question 11

Which type of vasculitis is granuloma seen in?

Answer 11

Large Vessel

Question 12

Which type of vasculitis are giant cells seen in?

Answer 12

Large Vessel

Question 13

Which type of vasculitis is claudication seen in?

Answer 13

Large Vessel

Question 14

Where is C-ANCA found and what is it associated with?

Answer 14

Cytoplasm. Usually associated with antibodies specific for proteinase-3. Very specific for an ANCA-associated vasculitis called granulomatous polyangiitis (i.e. Wegener’s)

Question 15

Where is P-ANCA found and what is it associated with?

Answer 15

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

Question 16

What is the most common vasculitis?

Answer 16

Giant Cell Arteritis (GCA)

Question 17

What vessels does GCA affect?

Answer 17

Large. Involves aorta and major branches to the head

Question 18

What is the pathogenesis of GCA?

Answer 18

T-cell mediated

Question 19

What are the findings with GCA?

Answer 19

1. Nodular thickening of the artery, intimal proliferation resulting in narrowing of the lumen
2. Acute, chronic, granulomatous inflammation
3. Giant cells may be present

Question 20

What is the typical patient of GCA?

Answer 20

Involves adults usually after age 50, most are female and Caucasian

Question 21

What is a lab finding for GCA?

Answer 21

Patients have elevated serum ESR and/or CRP

Question 22

What are clinical findings for GCA?

Answer 22

• Scalp tenderness
• TA pulse abnormality
• Ocular disturbance‐50%

Question 23

What is the treatment for GCA?

Answer 23

Treatment is high dose corticosteroids (prednisone) with slow taper

Question 24

What is Takayasu’s Arteritis AKA?

Answer 24

Pulseless Disease

Question 25

What are the findings with Takayasu's Arteritis?

Answer 25

- Thickening of arterial wall/intima, luminal narrowing - Granulomatous inflammation - Pulmonary Hypertension - Claudication/Weakness

Question 26

What are the vessels that Takayasu's Arteritis involves?

Answer 26

Large. Involves Aortic Arch and its branches.

Question 27

Who is the typical patient of Takayasu's Arteritis?

Answer 27

East Asian women under 50 years of age

Question 28

Why does the weakening of pulses occur with Takayasu's Arteritis?

Answer 28

Weakening of pulses of upper extremities due to narrowing of lumen of vessels

Question 29

What are the 3 phases of Takayasu's Arteritis?

Answer 29

* 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

Question 30

What types of vessels does Kawasaki Syndrome affect?

Answer 30

Medium. Coronary arteries frequently involved.

Question 31

What is the most common cause of acquired heart disease in children?

Answer 31

Kawasaki Syndrome

Question 32

What is the main patient population for Kawasaki Syndrome?

Answer 32

Children under the age of 5 - more prevalent in Japan

Question 33

What is the pathogenesis of Kawasaki Syndrome?

Answer 33

Anti‐endothelial/anti‐smooth muscle cell antibodies

Question 34

What are some of the findings of Kawasaki Syndrome?

Answer 34

``` • Fever • Fibrinoid necrosis • Destruction of internal elastic lamina – No granulomas • Aneurysmal rupture or acute thrombosis ```

Question 35

What is the window of opportunity to treat Kawasaki Syndrome?

Answer 35

0-2 weeks after fever

Question 36

What is the treatment for Kawasaki Syndrome?

Answer 36

• High dose Aspirin - one of the few cases to treat a child with aspirin

Question 37

What is Polyarteritis Nodosa (PAN) often associated with?

Answer 37

Hepatitis B and C

Question 38

What vessels does PAN affect?

Answer 38

Medium to small muscular arteries • Renal arteries • Coronary arteries • Hepatic arteries

Question 39

What does PAN often spare?

Answer 39

Lungs

Question 40

What are some of the clinical findings with PAN?

Answer 40

* Organ infarcts * Abdominal pain * Renal injury/Hypertension * Cutaneous lesions * Arthralgia/Arthritis * Acute peripheral neuropathy

Question 41

What are some of the lab findings of PAN?

Answer 41

* ANCA negative | * Hypocomplementemia

Question 42

What is the progression of PAN?

Answer 42

Rapidly progressive & fatal if not treated

Question 43

What types of vasculitis are ANCA associated?

Answer 43

Granulomatosis with Polyangiitis (GPA) Microscopic Polyangiitis (MPA) Churg‐Strauss (CS)

Question 44

What vessels do ANCA associated vasculitis affect?

Answer 44

Small vessels: • Glomerular capillaries • Pulmonary capillaries But can also affect medium sized vessels

Question 45

What are the findings with granulomatosis with polyangiitis?

Answer 45

– Leukocytoclastic fibrinoid necrosis | – Granulomas in lung or upper respiratory tract

Question 46

What are the findings with microscopic polyangiitis?

Answer 46

– Leukocytoclastic fibrinoid necrosis | – NO Granulomas

Question 47

What are the findings with Churg Strauss?

Answer 47

– Leukocytoclastic fibrinoid necrosis – Granulomas – Peripheral & tissue eosinophilia

Question 48

What will be absent in ANCA mediated vasculitis?

Answer 48

Immune complexes - "pauci-immune"

Question 49

What does saddle nose indicate?

Answer 49

GPA

Question 50

What does eosinophilic cardiac infiltration indicate?

Answer 50

CS

Question 51

What does pulmonary hemorrhage indicate as a possible vasculitis?

Answer 51

MPA

Question 52

What is the incidence of GPA by gender?

Answer 52

More in males than females

Question 53

What type of ANCA is GPA associated with?

Answer 53

c-ANCA

Question 54

What type of ANCA is CS associated with?

Answer 54

p-ANCA

Question 55

What type of ANCA is MPA associated with?

Answer 55

p-ANCA

Question 56

What vasculitis are nasal polyps associated with?

Answer 56

CS

Question 57

What vessels does Henoch-Schonlein Purpura involve?

Answer 57

Small - arterioles, capillaries, venules

Question 58

What is the pathogenesis of Henoch-Schonlein Purpura?

Answer 58

Infection or drug, or other environmental exposure causes IgA immune complexes to form & deposit in vessel walls, instigates complement cascade

Question 59

What is the typical HSP patient?

Answer 59

Children - but CAN occur in adults

Question 60

What is the triad of HSP symptoms?

Answer 60

Triad usually is arthritis, abdominal pain & palpable purpura

Question 61

What are the lab findings with HSP?

Answer 61

* Immune complex deposition * H&E shows neutrophils * Immunofluorescence shows IgA & C3

Question 62

What is the typical patient of thrombiangiitis obliterans?

Answer 62

Seen in SMOKERS younger than 40

Question 63

What vessels does thrombiangiitis obliterans affect?

Answer 63

Inflammation of medium & small arteries

Question 64

What can thromboangiitis obliterans result in?

Answer 64

Gangrenous extremities

Question 65

What does imaging show about the vessel affected by thromboangiitis obliterans?

Answer 65

“Corkscrew” collaterals on imaging