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Flashcards in Vasculitis Deck (60):
1

What is vascultis?

heterogenous group of uncommon (primarily autoimmune), occasionally life-threatening diseases having in common inflammation of blood vessels

2

What are the 2 major divisions of vasculitis?

1) infectious
2) non-infectous (primary)

3

What are the 3 most common causes of infectious vasculitis?

fungal- aspergillus
bacterial- pseudomonas
viral- CMV

4

How might giving steroid therapy to a patient with infectious vasculitis kill them?

steroids are anti-inflammatory and giving steroids to a patient with an infection will kill off all the things needed to mount an immune response to get rid of the infection

5

What is giant cell arteritis?

temporal arteritis - multinucleated giant cell attack on calcified internal elastic lamina in arteries or calcified media of thoracic aorta

6

What are the primary immune cells in arteries?

immature dendritic cells

7

How do dentritic cells get activated in he blood vessels?

antigens from pathogens or calcifications litigate TLRs which stimulate the PAMP/DAMP pathway whcih activates intracellular TRAM that stimulates NFkB to enter the nucleus and increase transcription of pro-inflammatory cells

8

What is the major dendritic receptor in adventitial cells?

TLR-4

9

Activated dendritic cells have what 3 functions?

1) Produce IL-12 and IL-18
2) Release lots of IFN-gamma, IL-2, and IL-6 that recruit inflammatory cells and increase T cell proliferation
3) Release "homing chemokines"

10

What is a "homing chemokine"? What does it do?

CCL19 and CCL21 bind to CCR7 and "trap" dendritic cells in the vessel

11

Progression of immune response in giant cell arteritis depends on what two cell types?

Th1
Th17

12

What does Th1 do to progress giant cell arteritis?

Release IL-12 and IFN-gamma that upregulates VEGF and PDGF which leads to lumen stenosis and an inflammatory loop where VEGF stimulates production of IFN-gamma that leads to giant cells and granuloma formation

13

How does Th17 progress giant cell arteritis?

release IL-1, -6, and -17 which create a proinflammatory environment that recruits activated monocytes to the arterial wall

14

What is released by macrophages and SM cells to destroy elastin and lead to matrix degeneration, intimal hyperplasia, and lumenal narrowing?

MMP-2 and MMP-9

15

What is the epidemiology of giant cell (temporal) arteritis?

Common, primarily in elderly white females (>50) of Northern European descent

16

What are the most common symptoms of giant cell arteritis?

headache
Visual disturbances--> can lead to blindness
Jaw claudicaiton
Swollen, tender artery
Scalp tenderness
FEVER

17

What vessels are affected in giant cell arteritis?

Involves temporal and ophthalmic arteries and thoracic aorta

18

What inflammatory disease is typically associated with temporal arteritis?

polymyalgia rheumatica (40% of cases)

19

How do you diagnose temporal arteritis?

high ESR (over 40 mm/hour) and positive biopsy (of temporal artery)

20

How do you treat temporal arteritis?

steroids (sometimes aspirin)

21

What is Takayasu Arteritis?

Granulomatous vasculitis of aortic arch at branch points with transmural scarring and thickening and severe luminal narrowing of branches (VERY similar to giant cell arteritis)

22

What factor is key in diagnosing Takayasu arteritis versus temporal arteritis?

AGE - same diagnosis and treatment, but Takayasu arteritis occurs in patients younger than 50 y/o

23

What are the symptoms of Takayasu arteritis

ocular disturbances and marked weakening of pulses in upper extremities, neurological problems

24

What is polyarteritis nodosa?

Vasculitis of small or medium-sized muscular arteries that typically involves renal and visceral vessels and spares pulmonary circulation. Healing of the lesions leaves behind some fibrosis

25

Polyarteritis Nodosa is commonly associated with what?

Hepatitis B immune complex formation

26

What is unique about the morphology of polyarteritis nodosa?

see lesions at all stages of activity suggesting ongoing & recurrent pathogenic insults

27

What are the signs/symptoms of polyarteritis nodosa?

HTN (renal involvement), melena and abdominal pain, neurologic disturbances, skin lesions (SYSTEMIC SYSTEMS)

28

What would a skin biopsy of polyarteritis nodosa show?

fibrinoid necrosis (NOT FIBRIN), inflammatory cells that surround the vessels and all the wall through the wall (transmural)

29

Who gets polyarteritis nodosa?

middle aged men

30

Why is polyarteritis nodosa a must-not-miss diagnosis?

because it is 90% treatable with immunosuppression (cyclophosphamide) and 100% fatal if non-treated

31

What leads to death in polyarteritis nodosa?

renal failure

32

What is Kawasaki disease?

(mucocutaneous lymph node syndrome) an acute childhood primary vasculitis of medium arteries (especially coronaries)

33

Who gets Kawasaki disease?

1-2 year old children, slightly more boys, an more common in Japanese

34

What are the symptoms of Kawasaki disease?

persistent high fever
conjunctivitis
mucosal and skin erythema
edema (palms and soles with peeling)
erythematous maculopapular skin rash
cervical lymphadenopathy
strawberry tongue

35

What are the complications of Kawasaki disease?

arterial rupture
MI
death

36

What is the proposed pathogenesis in Kawasaki disease?

aberrant immune reaction to a ubiquitous RNA virus that can become persistent in genetically predisposed individuals

37

What is the proposed treatment for Kawasaki disease?

aspirin with IV Ig but usually self-limited

38

What is Microscopic Polyangitis?

Necrotizing vasculitis that generally affects capillaries and is a feature of immune disorders like Henoch-Schonlein purpura, antibody responses to drugs, etc.

39

What is the immunologic cause of microscopic polyangitis?

MPO-ANCA lysosomal granule constituent involved in free-radical generation

40

What organs are typically affected by microscopic polyangitis?

kidney and lungs

41

What are the major complications of microscopic polyangitis?

necrotizing glomerulonephritis and pulmonary capillaritis

42

How do you treat microscopic polyangitis?

immmunosuppression and removal of offending agent.

43

What is the other name of Wenger’s Granulomatosis?

granulomatosis with polyangiitis

44

What is granulomatosis with polyangiitis?

Cell-mediated hypersensitivity response directed against inhaled infectious or environmental agents.

45

What is the immunologic cause of granulomatosis with polyangiitis?

Tissue injury driven by PR3-ANCA

46

What does a biopsy of granulomatosis with polyangiitis look like?

biopsy shows large necrotizing granulomas and geographic necrosis with basophilic debris (nuclear dust)

47

What organs are affected by granulomatosis with polyangiitis?

nasopharynx, lung, kidney

48

What is the typical presentation of granulomatosis with polyangiitis?

40 y/o man with pneumonitis, sinusitis, mucosal ulcerations, renal disease

49

What are the signs and symptoms of granulomatosis with polyangiitis?

Triad: granulomas of lung and URT, vasculitis, glomerulonephritis.

50

How do you treat granulomatosis with polyangiitis?

cyclophosphamide and steroids

51

What is Churg-Strauss Syndrome?

Hyperresponsiveness to normally innocuous allergic stimulus

52

What is the immunologic cause of Churg-Strauss Syndrome?

MPO-ANCAs

53

What are the signs and symptoms of Churg-Strauss Syndrome?

asthma, eosinophilia, necrotizing granulomatous inflammation!

54

What are the complications of Churg-Strauss symtome?

cardiomyopathy from cardiac involvemnt, palpable purpura, renal disease, GI bleeds

55

What are the possible immunologic causes of vasculitis?

Immune complex deposition
ANCAs
Anti-endothelial cell antibodies
Autoreactive T cells

56

What are the 2 types of vasculitis with immune complex eposition?

• Drug-hypersensitivity vasculitis (Ab’s against drug modified proteins)
• Vasculitis secondary to infections (Ab to microbial constituents form immune complexes that circulate and deposit in vascular lesions)--> ex. polyarteritis nodosa

57

What do ANCAs do?

directly activate neutrophils, stimulating the release of ROS and proteolytic enzymes leading to endothelial cell injury.

58

What is PR3-ANCA? When do you see it?

azurophilic granule constituent that shares homology with numerous microbial peptides (in Wenger granulomatosis)

59

What is MPO-ANCA? When do you see it?

lysosomal granule constituent involved in free-radical generation—associated with microscopic polyangiitis and C-S syndrome

60

When do you see anti-endothelial cell antibodies?

Kawasaki disease