Vasculitis, Noninfectious Vasculitis Flashcards
What is vasculitis? What are the clinical SX?
Inflammation of vessels
Clinical symptomology depends on vascular bed affected (CNS VS. heart etc.)
Constitutional SX = fever, malaise, arthralgias, myalgias
In vasculitis, are more vessels more commonly affected than others?
Any type may be affected - more often arterioles, capillaries, & venules
What are the 2 types of vasculitis? Describe them.
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)
What is the major cause of noninfectious vasculitis? What are some examples?
Immune response - local or systemic
Giant cell (Temporal) arteritis Polyarteritis Nodosa (PAN) Granulomatosis with Polyangiitis Thromboangiitis Obliterans (Buerger Dz)
What are the characteristics of Giant Cell (temporal) Arteritis? Include sites of involvement, inflammatory cells present, and clinical Hx.
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
What are the characteristics of Churg-Strauss syndrome (allergic granulomatosis and angiitis? Include sites of involvement, inflammatory cells present, and clinical Hx.
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)
What are the characteristics of Leukocytoclastic vasculitis? Include sites of involvement and inflammatory cells present.
Sites = Small sized arteries, capillaries, veins
Inflamm cells = Lymphocytes, macrophages, neutrophils, eosinophils (all +-)
Features:
Thrombosis
What are the characteristics of Buerger Dz (thromboangiitis obliterans)? Include sites of involvement, inflammatory cells present, and clinical Hx.
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
What is immune complex vasculitis?
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
In what conditions may you see immune complex vasculitis?
Systemic immunologic diseases (ex: SLE)
Drug hypersensitivity
Secondary to exposure to infectious agent
Describe drug hypersensitivity in relation to immune complex vasculitis (ex: PCN). What may you see clinically? What happens if you stop the drug?
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
How can you get immune complex vasculitis secondary to an infectious agent?
Ab to microbial constituents form immune complexes that deposit in vascular lesions
Polyarteritis nodosa = 30% associated with HBsAg and anti-HBsAg
What is Antineutrophil cytoplasmic antibodies (ANCA)?
A heterogenous group of antibodies reactant with cytoplasmic enzymes found in neutrophil granules, monocytes, and endothelial cells
What are the antibodies associated with ANCA?
Anti-proteinase-3 –> seen with PR3-ANCA
Anti-myeloperoxidase –> seen with MPO-ANCA
What dz is PR3-ANCA associated with?
Polyangiitis
What dz is MPO-ANCA associated with?
Microscopic polyangiitis and Churg-Strauss syndrome
Induced by RX: propylthiouracil
What do ANCA TITERS primary detect?
Disease SEVERITY
ANCA is pauci-immune. What does that mean?
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
Describe the pathogenesis behind Giant cell (temporal) arteritis & aortitis.
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
What do you see with Takayasu arteritis? Location? Sx?
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
Takayasu Arteritis is similar histologically to?
Giant cell arteritis
How would you differentiate Takayasu arteritis with Giant cell arteritis?
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
What Symptoms do you see with Takayasu arteritis? Initially vs. later? Distally on the aorta? Quiescent stage sx?
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
What are the most common causes of aortitis?
Giant cell arteritis and Takayasu arteritis
Clinically, how would you diagnose GCA and Takayasu?
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
What vessels does polyarteritis nodose involve? (In decreasing order of frequency)
Renal vessels
Heart
Liver
GI tract
Pulm vessels spared
What demographic does Polyarteritis Nodosa affect?
May affect any age group, but classically young adults
What are some characteristics seen with Polyarteritis nodosa?
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
With Polyarteritis Nodosa, inflamed vessels are susceptible to?
Thrombus formation/occlusion
Aneurysm
Rupture
What are the Sx seen with polyarteritis nodosa?
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
What is Kawasaki disease?
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
How does Kawasaki Dz present? What are the Sx?
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
What is Microscopic Polyangiitis?
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
What biomarker is Microscopic Polyangiitis associated with ?
MPO-ANCA
What Sx will you observe with Microscopic Polyangiitis?
Segmental necrotizing inflammation with fibroid necrosis = Mainly apoptotic NEUTROPHILS (fragmented PMN - polymorphonuclear neutrophils)
Hemoptysis Hematuria & proteinuria Bowel pain or bleeding Muscle pain or weakness Palpable cutaneous purpura
What are the characteristics of Bechet Dz? Include sites of involvement, inflammatory cells present, and clinical Hx.
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
Bechet Dz has a classic triad of Sx. Name them.
Aphthous ulcers of oral cavity
Genital ulcers
Uveitis (also GI and Pulm manifestations)
What gene is Bechet Dz associated with?
HLA-B51
In Bechet Dz, mortality is related to ___. What Tx may be beneficial?
Neurologic involvement or rupture of aneurysm
Immunosuppression with steroid or TNF-antagonist tx is effective
What are the characteristics of Granulomatosis with Polyangiitis? Include sites of involvement and inflammatory cells present.
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
What biomarker is Granulomatosis w/ polyangiitis associated with?
PR3-ANCA (95% of cases)
What reaction is occurring with Granulomatosis w/ polyangiitis?
T-cell mediated hypersensitivity response to normally “innocuous” inhaled microbial or other environmental agents
What are the clinical features of Granulomatosis w/ polyangiitis?
M > F, Avg age 40 Sx: Persistent pneumonitis & sinusitis Renal dz Nasopharyngeal ulceration Rashes, myalgias, articular involvement, neural inflammation and fever
What happens if Granulomatosis w/ polyangiitis is untreated? What is the Tx?
Left untreated, rapidly fatal, 80% mortality at one year
Tx: steroids, cyclophosphamide, TNF antagonists
Once fatal, now chronic relapsing and remitting
What is the morphology of Granulomatosis w/ polyangiitis at the upper and lower respiratory tracts?
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
What are the Sx of Buerger Dz (thromboangitis obliterans?
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
