Vasculitis

Question 1

Types of vasculitis are organized by. . .

Answer 1

. . . the size of the blood vessels affected by the pathology

Question 2

Vasculitis diagram: Where is the inflammation?

Answer 2

Question 3

“Large” blood vessels

Answer 3

The aorta and its major branches

Question 4

Medium blood vessels

Answer 4

Visible to the naked eye or by angiography, often named arteries that branch off of the “major” central arteries.

Question 5

Small blood vessels

Answer 5

Arterioles, capillaries, and venules

Microscopic

Question 6

Etiologies of large vessel vasculitis

Answer 6

• Giant cell arteritis
• Takayasu arteritis

Question 7

Etiologies of medium vessel vasculitis

Answer 7

• Polyarteritis Nodosa

Question 8

Etiologies of small vessel vasculitis

Answer 8

• ANCA-associated vasculitis
• Cryoglobulinemic vasculitis
• IgA vasculitis

Question 9

Organs selectively affected by small vessel vasculitis and corresponding symptoms

Answer 9

• skin - purpura
• nerves - neuropathy
• lungs - coughing, nodules, hemoptysis
• kidneys - hematuria
• joints - synovitis, arthritis, arthralgia
• eyes - inflammatory symptoms

Question 10

Organs affected by medium vessel vasculitis and associated symptoms

Answer 10

• Mesenteric - abdominal pain
• Renal - kidney infarct, kidney pain
• Nerves - neuropathy
• Skin - ulcers, livedo, gangrene
• associated w/ insidious presentation

Question 11

Answer 11

Livedo

Question 12

Organs affected by large vessel vasculitis and associated symptoms

Answer 12

• Brain - headache
• Eyes - blindness
• Muscles of face - Jaw claudication
• Fever
• Extremity claudication

Question 13

Specific lab tests are available to test for ___.

Answer 13

Specific lab tests are available to test for small vessel vasculitis, but not medium or large vessel vasculitis.

Question 14

Small vessel vasculitis may be due to an underlying ___.

Answer 14

Small vessel vasculitis may be due to an underlying connective tissue disease.

Question 15

Tests for small vessel vasculitis

Answer 15

• Usually involve testing for glomerulonephritis
• Test for proteinuria
• Stain H and E for RBC casts
• Kidney biopsy for “crescent” of immune cells surrounding a glomerulus
• Full-body observation for purpura
• CT scan for diffuse alveolar hemorrhage

Question 16

Leukocytoclastic vasculitis

Answer 16

• When white blood cells attack blood vessels
• General term for any small-vessel vasculitis

Question 17

Answer 17

Small vesse vasculitis on H and E. Note the asterix in the vessel wall and extravasated RBCs (the histological equivalent to the finding of non-blanching erythema)

Question 18

Asterix

Answer 18

Firboid necrosis in a vessel wall

Question 19

Anti-neutrophil cytoplasmic antibodies (ANCA)

Answer 19

• Autoreactive antibodies against myeloperoxidase and proteinase-3
• Known to cause glomerulonephritis

Question 20

Indirect immunofluorescence test for ANCA

Answer 20

• Anti-MPO stains perinuclearly (pANCA)
• Anti-PR3 stains cytoplasmically (cANCA)
• Minor ANCAs such as elastase, Lamp-2, or lactoferrin may confound results (usually pANCA)
• ELISA used to confirm following indirect immunofluorescence screening test

Question 21

Three phenotypes of ANCA

Answer 21

• Microscopy polyangitis (MPA)
  
  • MPO > PR3, necrotizing vasculitis
• Granulomatosis with polyangitis (GPA)
  
  • PR3 > MPO, necrotizing vasculitis, granulomas
• Eosinophilic granulomatosis with polyangitis (EGPA)
  
  • MPO only, necrotizing vasculitis, granulomas, eosinophilia

Question 22

____ is central to ANCA

Answer 22

NETosis is central to ANCA

Question 23

NETosis model for ANCA

Answer 23

Question 24

Role of DNAse I in ANCA

Answer 24

Impaired DNAse I activity leads to NET persistence following physiological NETosis. This leads to some damage which is then associated with anti-PR3 and anti-MPO antibody development. These ANCAs then activate further NETosis via FcγRI binding.

The cycle goes on.

Question 25

IgA vasculitis

Answer 25

* Non-ANCA-mediated small cell vasculitis, rather IgA immune complex mediated * Generally preceded by the initiaton of a new medication (often antibiotics) * General presentation of **purpura, arthralgia/peri-arthralgia, abdominal pain (from interstitial vasculitis), glomerulonephritis**

Question 26

Diagnosing IgA vasculitis

Answer 26

Biopsy of area and direct immunofluorescence against IgA

Question 27

Cryoglobulinemic vasculitis

Answer 27

* Characterized by overabundance of cryoglobulins * May be primary, or may be secondary to: malignancy, connective tissue disease (steven-johnson syndrome), or Hep C infection * **Meltzer's triad: purpura, arthralgias, myalgias** * Membranoproliferative glomerulonephritis presenting as hematuria * Peripheral symmetric polyneuropathy (often painful) * Reynaud's phenomenon and acryocyanosis

Question 28

Cryoglobulin

Answer 28

Igs characterized by their ability to precipitate at low temperatures

Question 29

Acryocyanosis

Answer 29

Bluish or purple-coloring of the hands or feet caused by low circulation

Question 30

Diagnosis of cryoglobulinemic vasculitis

Answer 30

* Serum cryoglobulin measurement (must be collected in warm serum tube) * Hypocomplementemia (C4 depressed out of proportion to C3, due to C4 depletion) * High-titer Rheumatoid factor * Serum protein electrophoresis * Serum free light chain measurement

Question 31

Giant cell arteritis

Answer 31

* Form of large vessel vasculitis * Most common vasculitis in adults * Occurs more frequently w/ older age, almost all cases \>50 yr old * Majority of patients female Caucasian (due to HLA clustering) * Distinct clinical phenotypes * Headache, scalp tenderness, visual loss, jaw claudication * Visible superficial arteries with pulsation (often temporal artery) * Fever of unknown origin (likelihood increases w/ age) * Polymyalgia rheumatica (widespread myalgia, aches, and flu-like symptoms)

Question 32

Polymyalgia rheumatica

Answer 32

* Associated w/ giant cell arteritis (obsv. in 50% of GCA patients, but only 15-20% of PMR patients have GCA) * 2nd most common rheumatic disease in elderly * Symmetric \>30 min morning stiffness and aching pain in neck, shoulders, hips * Mostly due to bursitis, synovitis may be associated

Question 33

Answer 33

* H and E of giant cell arteritis * Characteristics: * Trans-mural mononuclear inflammation (mostly MΦ and CD4) * Occasional multinucleated giant cells * Predilection for internal elastic lamina * Intimal hyperplasia

Question 34

Immune cell infiltrate characteristics in GCA

Answer 34

* Dominated by oligoclonal CD4 T cells * Th1 and Th17 polarization * Assocaition w/ HLA-DRB1\*04 (note that this is the same family of HLA genes that predisposes to rheumatoid arthritis)

Question 35

Giant cell arteritis diagram

Answer 35

Question 36

CD4 T cell polarity

Answer 36

Question 37

Th17 polarization diagram

Answer 37

Question 38

Digital ischemia may be a presenting symptom of \_\_\_.

Answer 38

Digital ischemia may be a presenting symptom of **medium vessel arteritis**.

Question 39

\_\_\_ is a form of vasculitis associated with high titer rheumatoid factor.

Answer 39

**Cryoglobulinemia** is a form of vasculitis associated with high titer rheumatoid factor.