What does the clinical presentation of vasculitis depend on?
What type of vessel is most commonly affcted?
The vascular bed involved (CNS, heart, small bowel, etc.)
Arterioles, capillaries, venules.
Non-infectious vs. infectious vasculitis
Non-infectious: immune-mediated (immunosuppressive tx).
Infectious: direct invasion by pathogens.
How can infections indirectly induce non-infectious vasculitis?
By generating immune complexes or triggering cross-reactive immune response.
Immune complex vasculitis is a result of:
What diseases/states is it seen in? (3)
Deposition of Ag-Ab complexes in vascular walls.
SLE
Drug hypersensitivity (PCN, streptokinase)
Secondary exposure to infectious agent.
30% of Polyarteritis nodosa is associated w/:
HBsAg and anti-HBsAg
What are antineutrophil cytoplasmic Abs (ANCA)?
A group of Abs that react w/ cytoplasmic enzymes in neutrophil granules, monocytes and endothelial cells.
What are 2 major examples of ANCAs? Their associations?
Anti-proteinase-3 (PR3-ANCA) associated w/ polyangiitis
Anti-myeloperoxidase (MPO-ANCA) induced by RX propylthiouracil.
What do ANCA activate?
Neutrophils which release ROS
Why are ANCA considered “pauci-immune”?
Because the ANCA Ab directed against cellular constituents and do NOT form circulating immune complexes.
Giant cell arteritis and aortitis is most common vasculitis among which patients?
What is the presentation?
Older patients.
Constitutional complaints along w/ facial pain and headache.
What is Segmental Transmural necrotizing inflammation?
WBC inflammation/necrosis w/ a predilection for branch points. It spans the entire arterial wall.
What is the course of PAN?
Course is remitting and episodic.
What ANCA is microscopic polyangiitis associated with?
MPO-ANCA
What else is Microscopic polyangiitis known as? (2)
Leukocyte vasculitis or Hypersensitivity vasculitis
How does myocardial vessel vasospasm occur?
What is the outcome? (2)
Excessive vasoconstriction of myocardial as. or arterioles (cardiac Raynaud) and may cause ischemia or infarct. Usually occurs as a result of high levels of vasoactive mediators (epi, pheochromocytoma, cocaine).
Sudden cardiac death or Takotsubo cardiomyopathy (broken heart sybdrome assoc. w/ emotional distress).
What causes varicose veins?
Abn. dilation of veins w/ valvular incompetence, secondary to sustained intraluminal pressure.
Rarely embolizes.
What causes esophageal varices?
3 classes:
Portal HTN (often cirrhosis) opens a shunt to direct blood to veins at gastroesophageal junction.
Esophageal varices, hemorrhoids, caput medusae.
Thrombophlebitis is:
Includes which vessels?
Venous thrombosis and inflammation.
Almost always in deep vs. of leg.
What can cause Migratory thrombophlebitis (4)
Cancer pts. from a paraneoplastic syndrome.
Mucin-producing adenocarcinomas.
Spontaneous thromboses that form and resolve, etc.
Adenocarcinomas of lung, ovary, pancreas.
SVC syndrome cause:
Clinical picture:
Neoplasms compress or invade SVC.
Complex, but marked dilation of vs. in head, neck and arms w/ cyanosis.
Pulm. vessels can be compressed and lead to respiratory distress.
What 2 main cancers can lead to IVC syndrome?
Clinical picture?
Hepatocellular carcinoma and renal cell carcinoma tend to grow in the IVC and can lead all the way to the RA.
LE edema, venous distension in lower abdomen, massive proteinuria due to renal v. involvement*.
Most common agent in lymphangitis?
Grp A beta-hemolytic strep
Primary lymphedema cause:
Secondary or obstructive lymphedema cause:
Isolated congenital defect (Milroy DZ).
Blockage of normal lymph flow.
What is peau d’ orange?
Used to describe the skin overlying breast cancer where lymph is clogged with tumor cells.
Markers used to DX neoplasia of the venous system?
Endothelial cell-specific markers like CD31 or vWF.
Nevus flammeus means:
Birthmark
Cavernous hemangioma
Irregular dilated vascular channels make a lesion w/ indistint border.
More likely to involve deep tissue/bleed.
Pyogenic granuloma
Type of capillary hemangioma (neither pyogenic or hemangioma).
Rapidly growing, often in oral mucosa.
An example is granuloma gravidarum (pregnancy tumor) in gingiva of pregnant women.
Glomus tumor
Benign tumors from glomus bodies most often in distal fingers.
SM origin rather than endothelial.
Very painful.
Bacillary angiomatosis is from what bug?
Common in which pts.?
What is a classic appearance?
How can the bacteria be identified? (2)
What is an effective Tx?
Bartonella bacilli.
Immunocompromised pts.
Form red papules due to *proliferation of capillaries w/ plump endothelial cells.
PCR or visualized with a *Warthin-Starry stain.
Macrolide abx.
2 intermediate-grade (bordeline) vascular tumors
Epithelioid hemangioendothelioma
Kaposi sarcoma
Epithelioid hemangioendothelioma has what classic appearance at the cellular level?
What is the progression of DZ?
Neoplastic endothelial cells are plump and cuboidal and vascular channels may be hard to recognize.
Variable clinical behavior, but mets 20-30% of the time.
4 distinct clinical forms of KS
- AIDS-assoc. (most common AIDS related tumor)
- Classic KS: older men from middle east, Mediterranean. Tumors on skin.
- Endemic African KS: Pts < 40 yo. Can involve cervical LNs.
- Transplant-assoc. KS: assoc. w/ T cell immunosuppression. Can spread to LNs and viscera.
Angiosarcoma is malignant. Which age group is most affected?
What can cause it? (2)
Common sites: (4)
What is the prognosis at 5 yrs.?
Older pts. M=F.
Can be induced by radiation exposure. Can arise in setting of lymphedema.
Most common sites include skin, soft tissue, breast and liver.
5 yr. survival around 30%.
What is associated with hepatic angiosarcoma? (4)
Arsenic
Pesticides
Thorotrats
Polyvinyl chloride
3 ways to intervene in vascular defects via stenting
Balloon angioplasty
Coronary stent
Drug-eluting stents
Vascular replacement includes synthetic or autologous vascular grafts. What is an issue w/ synthetic large bora grafts?
They will work for aorta, but won’t work for smaller vessels (i.e. coronary as.) due to thrombosis or intimal hyperplasia at the junction of graft and native vasculature.
What vessels are used for small bore grafts? (2)
What are their patencies at 10 yrs.?
Saphenous vs. or left internal mammary as.
Saphenous vs. 50% patency at 10 yrs.
LIM as. 90% patency at 10 yrs.
Giant cell arteritis and aortitis: patient population
Older patients
Giant cell arteritis and aortitis: presenting symptoms
Facial pain
Headache
Giant cell arteritis and aortitis: major pathology
T-cell mediated (CD4+ > CD8+) inflammation of the temporal aa.
Giant cell arteritis and aortitis: histological features (3)
Multinucleated Giant cells
Fragmented elastic lamina and intimal thickening
Patchy and focal sites of involvement
Giant cell arteritis and aortitis: unique feature
Involvement of the ophthalmic a. may cause double vision.
Takayasu arteritis: patient population
Younger (< 50 y/o)
Takayasu arteritis: presenting symptoms
Weak pulses of the UE and UE BP.
Takayasu arteritis: major pathology
Granulomatous vasculitis of medium and larger aa. (pulmonary, coronary, renal aa.).
Takayasu arteritis: unique features (2)
Ocular disturbances may ensue
“Pulseless disease”
PAN: presenting population
Young adults
PAN: presenting symptoms
Accelerating HTN
Abdominal pain and bloody stool
Diffuse myalgias
Peripheral neuritis
PAN: major pathology
Systemic vasculitis of renal, heart, liver and GI tract vessels. (NO pulm.)
PAN: first sign of disease
Ulcerations, infarcts, ischemia and hemorrhage.
PAN: treatment
Immunosuppressive therapy
PAN: unique features (2)
1/3 of patients have Hep B
Segmental transmural necrotizing inflammation ensues w/ a predilection for branch points
Kawasaki disease: patient population
Infants and small children (< 4 y/o)
Kawasaki disease: presenting symptoms (3)
Erythema of conjunctive, oral mucosa, palms and soles
Desquamative rash
Cervical LN enlargement
Kawasaki disease: major pathology
Coronary a. -> aneurysm -> thrombosis/rupture -> acute MI
Kawasaki disease: treatment
IVIg and Aspirin to lower risk of MI
Microscopic polyangiitis: presenting symptoms
Hemoptysis Hematuria and proteinuria Bowel pain/bleeding Myalgias Palpable cutaneous purpura
Microscopic polyangiitis: major pathology
Necrotizing vasculitis involving arterioles, capillaries and venules.
Microscopic polyangiitis: most common sites of involvement (2)
Renal glomeruli
Lung capillaries
Microscopic polyangiitis: unique features (2)
Associated w/ MPO-ANCA
Segmental necrotizing inflammation w/ fibrinoid necrosis
Churg-Strauss syndrome: presenting symptoms
Asthma Allergic rhinitis Hypereosinophilia Lung infiltrates Palpable purpura
Churg-Strauss syndrome: major pathology
Small vessel necrotizing vasculitis w/ inflammation that includes eosinophils and granulomas.
Churg-Strauss syndrome: organ systems involved
Skin (purpura)
GI tract (GI bleed)
Kidneys (renal DZ)
Heart (cardiomyopathy)
Churg-Strauss syndrome: most common COD
Heart pathology for approx. 50%
PAN: most common COD
Renal disease
Behcet disease: presenting symptoms
Triad: oral ulcers, genital ulcers, uveitis
Behcet disease: major pathology
Vasculitis of small-medium vessels w/ neutrophilic inflammation
Behcet disease: disease mortality is related to…
Neurologic involvement or rupture of aneurysms.
Behcet disease: treatment (2)
Steroids
TNF-antagonists
Behcet disease: unique cell marker association
HLA-B51
Granulomatosis with polyangiitis: patient population
M>F with average of 40 y/o
Granulomatosis with polyangiitis: presenting symptoms
Pneumonitis
Sinusitis
Renal disease
Nasopharyngeal ulceration
Granulomatosis with polyangiitis: major pathology
Necrotizing vasculitis of URT and LRT.
May include focal necrotizing, often crescentic, glomerulonephritis.
It is a form of T cell mediated hypersensitivity response to innocuous microbes/insults.
Granulomatosis with polyangiitis: treatment (3)
Steroids
Cyclophosphamide
TNF-antagonists
Granulomatosis with polyangiitis: course
Chronic relapsing and remitting
Granulomatosis with polyangiitis: morphology in URT and LRT
URT: geographic patterns of central necrosis.
LRT: cavitory lesions.
Granulomatosis with polyangiitis: unique ANCA association
PR3-ANCA
Thromboangiitis obliterans: patient population
Heavy smokers, < 35 y/o, often Israeli, Indian and Japanese descent.
Thromboangiitis obliterans: presenting symptoms (3)
Cold-induced Raynaud’s
Leg pain at rest
Superficial nodular phlebitis
Chronic extremity ulcerations may lead to frank gangrene
Thromboangiitis obliterans: major pathology
Segmental, thrombosing, acute and chronic vasculitis of small and medium vessels, primarily the tibial and radial aa.
Thromboangiitis obliterans: unique features (2)
May produce a thrombus with small “microabscesses”.
Most affected patients have a hypersensitivity to injected tobacco products.
What 2 arteries are affected in Thromboangiitis obliterans?
Radial a.
Tibial a.
What DZ is associated w/ PR3-ANCA?
Granulomatosis with polyangiitis
Steroids
Cyclophosphamide
TNF-antagonists
Are treatments for?
Granulomatosis with polyangiitis
Steroids
TNF-antagonists
Are treatments for?
Behcet DZ
Skin (purpura)
GI tract (GI bleed)
Kidneys (renal DZ)
Heart (cardiomyopathy)
Are involved in which disease?
Churg-Strauss
Triad: oral ulcers, genital ulcers, uveitis
Behcet DZ
Which disease is associated w/ MPO-ANCA?
Microscopic polyangiitis
Which disease involves systemic vasculitis of renal, heart, liver and GI tract vessels?
PAN
What is a major symptom of IVC syndrome?
Massive proteinuria
Erythema of conjunctive, oral mucosa, palms and soles
Desquamative rash
Cervical LN enlargement
Are SX of?
Kawasaki DZ
Which DZs have palpable purpura? (2)
Microscopic polyangiitis
Churg-Strauss
What are 3 major arteries involved in Takayasu arteritis?
Pulm. a.
Coronary a.
Renal a.
Renal glomeruli
Lung capillaries
Are involved in which disease?
Microscopic polyangiitis
Eosinophilia, Rhinitis, Asthma
Churg-Strauss
Hemoptysis Hematuria and proteinuria Bowel pain/bleeding Myalgias Palpable cutaneous purpura
Microscopic polyangiitis