Pathophysiology of Vasculitis- Pyun

Question 1

What does ANCA stand for?

Answer 1

Anti-neutrophil Cytoplasmic Antibodies

-Results in antibodies directed against cytoplasmic proteins.

Question 2

What is Vasculitis?

Answer 2

Inflammation of blood vessel walls leading to end-organ damage, ischemia, and necrosis.

Question 3

What are Primary Vasculitides?

Answer 3

Forms of Vasculitis that are not a component of a major systemic disease like SLE or RA.

Question 4

Name the large Vessel vasculitides

Answer 4

• Giant cell (temporal) arteritis

- Takayasu’s arteritis

Question 5

Name the medium vessel vasculitides

Answer 5

• Polyarteritis Nodosa (PAN)

- Kawasaki’s Disease

Question 6

1. Name the Small vessel vasculitides. 2. Which ones are ANCA* associated? 3. Which one is Immune complex mediated**?

Answer 6

• Wegner’s Granulomatosis*
• Churg Strauss Syndrome*
• Microscopic Polyangiitis*

-Henoch Schonlein Purpura**

Question 7

Describe the types of ANCAs and which vasculitides are they seen in.

Answer 7

C-ANCA

• antibody against Protease 3
• Wegner’s

P- ANCA

• antibody against Myeloperoxidase (MPO)
• Churg Strauss
• Microscopic Polyangitis
• Drug induced Polyangitis

ANCAs are very specific for Vasculitis.

Question 8

Describe the Pathogenicity (not the mechanism) of ANCAs

Answer 8

• Very specific for vasculitis
• ANCA levels related to disease activity
• Persistent ANCAs associated with Wegner’s relapse
• ANCAs are proinflammatory on PMN, Monocytes, and endothelial cells.

Question 9

Describe the etiology of Wegener’s Granulomatosus

Answer 9

• Multi-organ disease of unknown etiology
• Anti-PR3 C-ANCA
• Granulomatous inflammation and Vasculitis of upper and lower respiratory tract; pauci-immune glomerulonephritis

Question 10

Describe the pathogenesis of ANCAs

Answer 10

• PR3 usually sequestered in PMN granules
• Infection/Tissue damage causes them to translocate to surface of PMN.
• Once expressed on surface, ANCA can interact with it –> resulting in Respiratory burst and degranulation of PMN.

-ANCAs also facilitate adhesion of PMN to Endothelial cell.

Released:

• Inflammatory Cytokines
• IL-1, 8 (Chemoattractants for other inflammatory cells)
• ROS and Proteases released (cause damage to endothelial cells)

Question 11

List the exact functions of ANCA

Answer 11

• Activation of PMN and monocytes
• Activation of Respiratory burst (release of lysosomal enzymes)
• Increased adhesion molecule levels
• Directly activate endothelial cells to increase their permeability and adhesiveness.

Question 12

Describe the clinical picture for Churg Strauss Syndrome

Answer 12

Churg Strauss in the CAVERNS RACES
-P-ANCA

• Cardiac involvement
• Asthma / Allergic Rhinitis/ Nasal Polyps
• Vasculitis
• Eosinophilia
• Rx: Rituximab, Azathioprine, Cyclophosphamide, Exchange plasma, Steroids
• Neuropathy
• Skin nodules

Question 13

Describe the clinical picture of Wegener’s Granulomatosis

Answer 13

Glomeulonephritis
Otitis
Deformity- Saddle Nose
Sinusitis

Pulmonary Infiltrate
Rhinitis
Epistaxis
Septal Perforation
Subglittic Stenosis

Note: GODS PRESS mnemonic

Question 14

Describe Henoch Schonlein Purpura

Answer 14

• Most common vasculitis in Children
• Usually occurs after URI
• Small vessel vasculitis (post-cap venules, arterioles, capillaries)
• IgA elevation and reduced clearance
• Complex deposition and compliment in tissues

Question 15

Describe the pathogenesis of Henoch Schonlein Purpura

Answer 15

• Increased IgA synthesis
• Reduced IgA clearance
• Capillary IgA immune complexes
• Abnormally O-glycosylated IgA (promotes mesangium deposition)

Question 16

Describe the Clinical Tetrad of Henoch Schonlein Purpura

Answer 16

• Palpable Purpura
• Arthritis/ Arthralgias
• Cramping/ Bloody stool
• Hematuria/ Protineuria

Question 17

How does Rituximab work?

Answer 17

• Monoclonal antibody against CD20 resulting in B cell depletion
• Proven efficacy in the Rx of Wegner’s and MPA