Vasculitis, Noninfectious Vasculitis Flashcards

1
Q

What is vasculitis? What are the clinical SX?

A

Inflammation of vessels
Clinical symptomology depends on vascular bed affected (CNS VS. heart etc.)

Constitutional SX = fever, malaise, arthralgias, myalgias

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2
Q

In vasculitis, are more vessels more commonly affected than others?

A

Any type may be affected - more often arterioles, capillaries, & venules

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3
Q

What are the 2 types of vasculitis? Describe them.

A

Non-infectious vs. infectious - can be immune mediated inflammation vs. direct invasion by infectious pathogens (can provide immunosuppressive TX for immune-mediated)

Infections can also INDIRECTLY induce a noninfectious vasculitis (generating immune complexes or triggering cross-reactive immune response)

Physical & Chemical injury can also cause vasculitis ( irritation, mechanical trauma, toxins)

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4
Q

What is the major cause of noninfectious vasculitis? What are some examples?

A

Immune response - local or systemic

Giant cell (Temporal) arteritis 
Polyarteritis Nodosa (PAN) 
Granulomatosis with Polyangiitis 
Thromboangiitis Obliterans (Buerger Dz)
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5
Q

What are the characteristics of Giant Cell (temporal) Arteritis? Include sites of involvement, inflammatory cells present, and clinical Hx.

A

Sites = AORTA, medium sized arteries

Inflamm. cells = Lymphocytes, Macrophages (neutrophils/eosinophils rare)

Features:
Granulomas, Thrombosis , Giant cells (often, not required)
May present with constitutional Sx = fever, fatigue, weight loss
Facial Pain, Headache

Clinical Hx = >40 yo +- polymyalgia rheumatica

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6
Q

What are the characteristics of Churg-Strauss syndrome (allergic granulomatosis and angiitis? Include sites of involvement, inflammatory cells present, and clinical Hx.

A

Sites = Medium and Small sized arteries (small vessel necrotizing vasculitis) assoc with:
Clinical Hx = Asthma, allergic rhinitis, hypereosiniphilia

Inflamm cells = EOSINOPHILS required
+ Lymphocytes, Macrophages, Neutrophils

May resemble PAN/microscopic polyangiitis w/ addition of eosinophils and granulomas

Features:
Granulomas, thrombosis, Serum ANCA positivity (<1/2, mostly MPO)
Many organ systems involved = palpable purpura, GI tract bleeding, renal disease (focal/segmental glomerulosclerosis)
Myocardial involvement –> cardiomyopathy (60%, half deaths)

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7
Q

What are the characteristics of Leukocytoclastic vasculitis? Include sites of involvement and inflammatory cells present.

A

Sites = Small sized arteries, capillaries, veins

Inflamm cells = Lymphocytes, macrophages, neutrophils, eosinophils (all +-)

Features:
Thrombosis

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8
Q

What are the characteristics of Buerger Dz (thromboangiitis obliterans)? Include sites of involvement, inflammatory cells present, and clinical Hx.

A

Sites = Medium/small sized arteries, veins

  • Segmental, thrombosing
  • Tibial and Radial arteries
  • Occ secondary extension to veins and nerves of extremities (pain!)

May lead to vascular insufficiency of extremities
Chronic ulcerations –> may lead to gangrene

Inflamm cells = Lymphocytes, macrophages, neutrophils, eosinophils

Features:
THROMBOSIS Required

Clinical HX:
Young male smoker, <35 yo
Hypersensitivity to intradermally injected tobacco
Assoc. with HLA haplotypes of certain ethnic groups: Israeli, Indian, Japanese

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9
Q

What is immune complex vasculitis?

A

Autoantibody production and formation of immune complexes
Deposition of antigen-antibody complexes in vascular wall
-incites inflammatory reaction within the wall
-Ag is often unidentified

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10
Q

In what conditions may you see immune complex vasculitis?

A

Systemic immunologic diseases (ex: SLE)
Drug hypersensitivity
Secondary to exposure to infectious agent

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11
Q

Describe drug hypersensitivity in relation to immune complex vasculitis (ex: PCN). What may you see clinically? What happens if you stop the drug?

A

PCN acts as hapten binding to serum proteins of vessel walls
-Streptokinase acts as foreign protein

Clinically = mild to fatal; SKIN LESIONS most common

Always consider drug hypersensitivity. Stop drug –> resolution of vasculitis

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12
Q

How can you get immune complex vasculitis secondary to an infectious agent?

A

Ab to microbial constituents form immune complexes that deposit in vascular lesions

Polyarteritis nodosa = 30% associated with HBsAg and anti-HBsAg

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13
Q

What is Antineutrophil cytoplasmic antibodies (ANCA)?

A

A heterogenous group of antibodies reactant with cytoplasmic enzymes found in neutrophil granules, monocytes, and endothelial cells

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14
Q

What are the antibodies associated with ANCA?

A

Anti-proteinase-3 –> seen with PR3-ANCA

Anti-myeloperoxidase –> seen with MPO-ANCA

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15
Q

What dz is PR3-ANCA associated with?

A

Polyangiitis

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16
Q

What dz is MPO-ANCA associated with?

A

Microscopic polyangiitis and Churg-Strauss syndrome

Induced by RX: propylthiouracil

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17
Q

What do ANCA TITERS primary detect?

A

Disease SEVERITY

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18
Q

ANCA is pauci-immune. What does that mean?

A

ANCA Ab directed at cellular constituents and do not form circulating immune complexes.

You will not see a lot of immune cells

Vascular lesions do NOT typically contain Ab and complement

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19
Q

Describe the pathogenesis behind Giant cell (temporal) arteritis & aortitis.

A

Chronic (T-cell mediated, CD4>CD8) inflammation of arteries in the head, especially temporal arteries

Medial granulomatous inflammation, often with multinucleated giant cells
Fragmentation of the elastic lamina and intimal thickening
Site of involvement within an artery may be patchy and focal
Healed sites of inflammation show scarring of the media and intimal thickening
Double vision - involvement of ophthalmic artery may lead to vision loss

20
Q

What do you see with Takayasu arteritis? Location? Sx?

A

Characterized by ocular disturbances and marked weakening of pulses of the UPPER extermities

Sx: weak pulse and low BP in UE

Granulomatous vasculitis of medium and larger arteries

21
Q

Takayasu Arteritis is similar histologically to?

A

Giant cell arteritis

22
Q

How would you differentiate Takayasu arteritis with Giant cell arteritis?

A

Takayasu involves:

  • Aortic arch (aortitis) and major branch vessels - causes dilation and aortic valve insufficiency
  • Pulmonary artery (1/2 of cases), coronary & renal arteries
  • Younger age (<50), historically Japanese, now global
23
Q

What Symptoms do you see with Takayasu arteritis? Initially vs. later? Distally on the aorta? Quiescent stage sx?

A

Initially nonspecific - fatigue, wt loss, fever

Later - Vasc sx dominate = decreased BP, weak carotid and UE pulses, visual deficits, retinal hemorrhage, total blindness, neuro deficit

Distal aorta Sx = claudication of legs, pulm artery = pulm HTN, coronary artery = MI, renal artery = systemic HTN

Quiescent stage after few yrs permits long-term survival with visual and neuro deficits

24
Q

What are the most common causes of aortitis?

A

Giant cell arteritis and Takayasu arteritis

25
Q

Clinically, how would you diagnose GCA and Takayasu?

A

GCA = best is to do a biopsy at multiple places (b/c doesn’t occur everywhere) of the temporal artery, look to see if cells are abnormally large

Takayasu = Check BP in involved arteries arising form aorta, pulses + BP low/impossible to fine; generally brisk pulses in leg, bruits may be at narrowed arteries

26
Q

What vessels does polyarteritis nodose involve? (In decreasing order of frequency)

A

Renal vessels
Heart
Liver
GI tract

Pulm vessels spared

27
Q

What demographic does Polyarteritis Nodosa affect?

A

May affect any age group, but classically young adults

28
Q

What are some characteristics seen with Polyarteritis nodosa?

A

1/3 of pts have CHRONIC HEP-B = HBsAg-Ab complexes found in involved vessels

Immunosuppressive therapy usually effective

Segmental transmural necrotizing inflammation (neutrophils, eosinophils, lymphocytes, macrophages); predilection for branch points

Ulcerations, infarcts, ischemic atrophy or hemorrhage may be first sign of Dz

Sites of inflammation are typically not circumferential

29
Q

With Polyarteritis Nodosa, inflamed vessels are susceptible to?

A

Thrombus formation/occlusion
Aneurysm
Rupture

30
Q

What are the Sx seen with polyarteritis nodosa?

A

Result form ischemia and infarction of affected tissue
REMITTING AND EPISODIC with long Sx-free intervals, variable

Classic presentation:

  • rapidly accelerating HTN = renal artery involvement
  • abd pain and bloody stools = vascular gastrointestinal lesions
  • diffuse myalgias and peripheral neuritis - predom affecting motor nerves
  • Renal involvement prominent and major cause of mortality
  • Immunosuppression can help
31
Q

What is Kawasaki disease?

A

Acute arteritis of infants and small children (80% < 4 yrs)

Often involves coronary arteries
-Affected sites may form aneurysms –> thrombosis or rupture –> acute MI

Usually self-limited, but IVIg and aspirin are indicated to lower risk of coronary event

32
Q

How does Kawasaki Dz present? What are the Sx?

A

Sx:
Conjunctival and oral erythema and blistering
Edema of hands and feet
Erythema of palms and soles
Desquamative rash
Cervical lymph node enlargement - “Mucocutaneous lymph node syndrome”

20% of untreated pts develop cardiovasc sequelae, ranging from asymptomatic coronary arteritis –> ectasia –> aneurysms –> rupture/thrombosis, MI, death

33
Q

What is Microscopic Polyangiitis?

A

Necrotizing vasculitis involving arterioles, capillaries, and venules

Unlike polyarteritis nodosa, all lesions tend to be same age and distributed more widely
-Henoch-Schonlein pupura, essential mixed cyroglobinemia, vasculitis assoc with CT DOs

Affects vessels of many organ systems
-Renal glomeruli and lung capillaries most common (90% necrotizing glomerulonephritis)

Leukocytoclastic vasculitis or hypersensitivity vasculitis - immunosuppression helps

34
Q

What biomarker is Microscopic Polyangiitis associated with ?

A

MPO-ANCA

35
Q

What Sx will you observe with Microscopic Polyangiitis?

A

Segmental necrotizing inflammation with fibroid necrosis = Mainly apoptotic NEUTROPHILS (fragmented PMN - polymorphonuclear neutrophils)

Hemoptysis 
Hematuria &amp; proteinuria 
Bowel pain or bleeding 
Muscle pain or weakness 
Palpable cutaneous purpura
36
Q

What are the characteristics of Bechet Dz? Include sites of involvement, inflammatory cells present, and clinical Hx.

A

Sites = Medium and small sized arteries, capillaries, veins

Inflamm cells = NEUTROPHILS required, lymphocytes, neutrophils, macrophages
Neutrophilic and morphologically nonspecific, may involve visceral organ systems with subsequent aneurysm formation

Features: Thrombosis

Clinical Hx:
Orogenital Ulcers

37
Q

Bechet Dz has a classic triad of Sx. Name them.

A

Aphthous ulcers of oral cavity
Genital ulcers
Uveitis (also GI and Pulm manifestations)

38
Q

What gene is Bechet Dz associated with?

A

HLA-B51

39
Q

In Bechet Dz, mortality is related to ___. What Tx may be beneficial?

A

Neurologic involvement or rupture of aneurysm

Immunosuppression with steroid or TNF-antagonist tx is effective

40
Q

What are the characteristics of Granulomatosis with Polyangiitis? Include sites of involvement and inflammatory cells present.

A

Sites = Medium and Small sized arteries
Necrotizing vasculitis featuring:
-Necrotizing granulomas = upper/lower resp tracts
-Necrotizing or granulomatous vasculitis = resp tract
-Focal necrotizing, often Crescentric, glomerulonephritis

Inflamm cells = Lymphocytes, Macrophages, Neutrophils, and Eosinophils

Features:
GRANULOMAS required
Giant cells, Thrombosis, Serum ANCA positivity

41
Q

What biomarker is Granulomatosis w/ polyangiitis associated with?

A

PR3-ANCA (95% of cases)

42
Q

What reaction is occurring with Granulomatosis w/ polyangiitis?

A

T-cell mediated hypersensitivity response to normally “innocuous” inhaled microbial or other environmental agents

43
Q

What are the clinical features of Granulomatosis w/ polyangiitis?

A
M > F, Avg age 40 
Sx: 
Persistent pneumonitis &amp; sinusitis 
Renal dz
Nasopharyngeal ulceration 
Rashes, myalgias, articular involvement, neural inflammation and fever
44
Q

What happens if Granulomatosis w/ polyangiitis is untreated? What is the Tx?

A

Left untreated, rapidly fatal, 80% mortality at one year

Tx: steroids, cyclophosphamide, TNF antagonists
Once fatal, now chronic relapsing and remitting

45
Q

What is the morphology of Granulomatosis w/ polyangiitis at the upper and lower respiratory tracts?

A

Upper resp tract = sinonasal and pharyngral inflammation with granulomas & vasculitis
-Granulomas w/ geographic patterns of central necrosis and accompanying vasculitis

Lower resp tract = multiple necrotizing granulomas, which may coalesce and cavitate

46
Q

What are the Sx of Buerger Dz (thromboangitis obliterans?

A

Acute/chronic inflammation + luminal thrombosis
Thrombus = small microabscesses composed of neutrophils surrounded by granulomatous inflammation

Cold-induced Raynaud phenomenon
Intermittent claudication - leg pain induced by exercise, relieved on rest
Instep claudication
Superficial nodular phlebitis - venous inflammation
Sever pain - even at rest
Chronic extremity ulcerations - lead to frank gangrene