8/26- Path: Peripheral Vascular Disease (Vaculitis) Flashcards
What is vasculitis?
- Cause?
- Classified how
Inflammatory damage to blood vessels
- “Arteritis, “angitis”, “phlebitis” refer to vessel type affected
- Most common etiologies are infectious and autoimmune
- Classified by size of affected vessel
What are the large vessel vasculitises?
- Giant cell (Temporal) arteritis
- Takayasu arteritis)
What are the medium vessel vasculitis-es?
- Polyarteritis nodosa
- Kawasaki disease
What are the small vessel vasculitis-es?
- Wegener’s Granulomatosis
- Churg-Strauss Syndrome
- Microscopic Polyangiitis
- Thromboangiitis Obliterans (Buerger’s Disease)
What are the immune complex mediated vasculitis-es?
- SLE (SLE vasculitis)
- IgA (Henoch-Schonlen purpura)
- Cryoglobulin (cryoglobulin vasculitis)
- Goodpasture disease
Vasculitis naming table
What is Giant Cell (Temporal) Arteritis?
- Layers affected
- Epidemiology
- Associations
- Symptoms
- Treatment
- Granulomatous inflammation at the junction of the tunica intima and tunica media
- Most common vasculitis in elderly people
- Association with polymyalgia rheumatica
- Involvement of ophthalmic artery may lead to blindness; MEDICAL EMERGENCY
- If diagnosis is suspected, give corticosteroids immediately
What is Takayasu’s Pulseless Arteritis?
- Layers affected
- Epidemiology
- Symptoms
- Granulomatous inflammation involving the junction between the adventitia and tunica media
- Usually seen in young women (15-40)
- Manifests as weakened upper extremity pulses and ocular disturbances
What is Polyarteritis Nodosa?
- Layers affected
- Associations
- Symptoms
- Systemic, transmural! vasculitis involving muscular arterioles with sparing of pulmonary vasculature
- Usually involves renal, visceral arterioles (typically spares pulmonary vasculature)
- A spectrum of vasculitic changes are usually seen in one patient
- Associated with chronic hepatitis B
What is Kawasaki Disease?
- Epidemiology
- Symptoms
- Treatment
- Leading cause of acquired heart disease in children
- Most pts are less than 4 yo
Symptoms:
- Erythema of lips, hands, and feet
- Desquamation of skin
- Lymphadenopathy
- Vasculitis
Feared complication = aneurysm of the coronary arteries with rupture or MI
Treatment:
- IVIG
- Aspirin
What are ANCAs? Uses?
Anti-Neutrophil Cytoplasmic Antibodies
- These are Abs vs. inflammatory cell granule components
- P-ANCA (perinuclear) = MPO-ANCA
- C-ANCA (cytoplasmic) = PR3-ANCA
- Used to diagnose and track response to therapy, relapse, etc.
What is Wegener’s Granulomatosis?
- Vessel types affected
- Symptoms
- ANCA marker?
- Epidemiology
- Treatment
Varying manifestations:
- Necrotizing vasculitis of small to medium vessels within the lungs and upper airways
- Necrotizing extravascular granulomas in upper respiratory tract, lung, or both -> many pulmonary symptoms (sinus lesions, cavitating lung lesions)
- Renal disease (crescentic glomerulonephritis)
Pneumonitis, sinusitis, renal disease
Associated with C-ANCA (PR3-ANCA) More often in men than women
Treatment: Immunosuppression
Note: vessel becomes necrotic, but the granuloma itself occurs in the organ away from the vessel
What is Churg-Strauss Syndrome?
- Cause
- Symptoms
- Associations
- Morbidity
- ANCA marker?
- Allergic granulomatosis and angiitis
- Necrotizing vasculitis with infiltration by eosinophils (distinguish from Wegener’s with eos and the fact that granulomas are intravascular)
- Intra- and extravascular necrotizing granulomas
- Associated with asthma, allergic rhinitis, lung infiltrates, and peripheral eosinophilia
- Coronary arteritis & myocarditis are main causes of morbidity
- Associated with P-ANCA (MPO-ANCA)
What is Microscopic Polyangiitis
- Cause
- Vessels involved
- ANCA marker
- What is seen histologically
- Necrotizing vasculitis of small vessels
- Also known as leukocytoclastic vasculitis
- Can mimic PAN, but all lesions are the same age
- Can involve microvasculature of kidney, lung, skin, mucous membranes, brain, GI tract, heart
- Associated with P-ANCA (MPO-ANCA)
- Antibody response to foreign antigens
Luekocytoclastic vasculitis
- See neutrophil “carcasses” everywhere
What is Thromboangiitis Obliterans (Buerger’s Disease)?
- Epidemiology
- Vessels affected
- Manifestations
- Typical history: young males who smoke heavily
- Segmental, thrombosing vasculitis of small to medium arteries of extremities
- Leads to vascular insufficiency
Manifestations
- Chronic ulceration
- Gangrene
What are the benign, itermediate, and malignant tumors?
Benign:
- Hemangioma
Intermediate:
- Kaposi Sarcoma
- Hemangioendothelioma
Malignant
- Angiosarcoma
What is Hemangioma?
- Types
- Epidemiology
- Histological signs
- Locations
Benign tumor
Various types: capillary, cavernous…
Epidemiology:
- Infantile hemangiomas are 7% of all benign tumors of infancy and childhood
- Most are present from birth and expand along with the growth of the child
- Many of the capillary lesions eventually regress spontaneously
Histology:
- Unencapsulated aggregates of closely packed, thin-walled capillaries
- Caps usually blood-filled and lined by flattened endothelium
Often seen in liver, tongue, lips….
What is Kaposi’s Sarcoma?
- Cause
- Associations
- Stages/symptoms
- Common in patients with AIDS
- Associated with HHV-8
Patch, plaque, and nodule stages
- Nodule stage: sheets of plump spindle cells, mostly in the dermis or subcutaneous tissues, with small vessels and slitlike spaces containing red cells
What is a hemangioendothelioma?
NOT TESTED
Group of vascular neoplasms with clinical behavior intermediate between benign, well-differentiated hemangiomas and highly malignant angiosarcomas
- Epithelioid hemangioendothelioma
—-Adults
—-Occurs around medium-sized and large veins
—-Plump and often cuboidal neoplastic cells (resemble epithelial cells) with inconspicuous vascular channels
Clinical behavior: most are cured by excision, up to 40% recur, 20% to 30% eventually metastasize, and perhaps 15% of patients die of the tumor
What is an angiosarcoma?
- Epidemiology
- Location
- Associations
Epidemiology
- Older adults are more commonly affected
- Equal gender predilection
Occur at any site, but most often involve skin, soft tissue, breast, and liver
Hepatic angiosarcomas: associated with carcinogen exposures with long latency period
- Arsenic (arsenical pesticides), Thorotrast (a radioactive contrast agent formerly used for radiologic imaging), and polyvinyl chloride (a widely used plastic)
- Also seen in setting of lymphedema, e.g. in upper extremity several years after radical mastectomy (i.e., with lymph node resection) or after radiation
Case 1)
- 24 yo man with Hep B Ag+
- Diffuse muscle aches, acute abdominal pain
- BP = 180/100
- Abdominal arteriogram shows multiple mesenteric (medium) vessels with focal aneurysmal dilatation of the branch points and bifurcations
- Decreased perfusion of an affected bowel segment with suspected thrombotic occlusion
What form of vasculitis does he most likely have?
Poly-arteritis nodosa (PAN)
What sized arteries and what anatomic sites are most frequently invovled in PAN?
Small to medium sized muscular arteries of the visceral vasculature
- Main visceral arterial branches, e.g. renal, coronary, hepatic and mesenteric
- NOT renal, glomerulonephritis (hematuria) is not characteristic of this disease process
- Spares the pulmonary vasculature
What is seen here?
PAN
- A bunch of inflammation; affects entire wall (transumural)
Acute lesions:
- Fibrinoid necrosis (full thickness)—often eccentric and not the entire circumference
- neutrophils, eosinophils, and mononuclear cells in and around the vessel wall
What is seen here?
PAN
- A bunch of inflammation; affects entire wall (transumural)
Acute lesions:
- Fibrinoid necrosis (full thickness)—often eccentric and not the entire circumference
- neutrophils, eosinophils, and mononuclear cells in and around the vessel wall
What is seen here?
PAN: Healing lesions
- transmural scarring plus ongoing necrosis
- increased numbers of macrophages and plasma cells
- organized thrombosis
- fibrosis extending into surrounding adventitia
What is seen here?
PAN: Healed lesions
- marked fibrotic thickening of the arterial wall
- loss or fragmentation of the internal elastic lamina, with replacement by fibrosis.
What serologic test may be found in association with PAN?
Positive hepatitis B antigen serology (30%)
Case 2)
- 45-year-old male with persistent fever, muscle and joint pain, and shortness of breath (despite antibiotics)
- PMH: chronic sinusitis
- Physical Exam: Ulceration in the nasopharynx
- CXR: bilateral, nodular and cavitary pulmonary infiltrates
- Lab: hematuria and proteinuria
Basically: many pulmonary and renal symptoms
Take biopsy:
- Large cavitary regions
What is this?
Wegener’s granulomatosis
What is seen here?
Gross picture: granulomas
Necrotizing granulomatous inflammation corresponding to grossly identified granulomas
- “geographic outline” of necrosis
- Microabscess
***Granulomas= organized collections ofepithelioid histiocytes, often withmultinucleated giant cells, +/- cuff of lymphocytes
What is seen here?
Gross picture: granulomas
Necrotizing granulomatous inflammation corresponding to grossly identified granulomas
- “geographic outline” of necrosis
- Microabscess
***Granulomas = organized collections of epithelioid histiocytes, often with multinucleated giant cells, +/- cuff of lymphocytes
What is seen here?
Nongranulomatous vasculitis in the lung tissue (separate from the granulomas)
What is the triad seen in Wegener’s disease?
1. Granulomas: Acute necrotizing granulomas of the upper and lower respiratory tract (nose, sinuses, and lung)
2. Vasculature: Focal necrotizing (usually not granulomatous) vasculitis affecting small to medium–sized vessels; most prominent in the vessels of the lungs and upper airways, but affects other sites as well.
3. Renal disease (focal or diffuse necrotizing glomerulitis)
What is a good marker for Wegener’s disease?
C-ANCA (cytoplasmi anti-neutrophil cytoplasmic Ab)
- good marker for disease activity (93% of patients with active generalized disease)
- Patients in remission: negative test or a decrease in c-ANCA titer; rising titer of c-ANCA -> suggestive of relapse
Case 3)
- 60-year-old male w/ severe throbbing headache over his right temple and visual loss in right eye
- PE: tender, enlarged vessel palpated along the right temple with erythema in the overlying skin
- Lab: ESR = markedly elevated (erythrocyte sedimentation rate; marker of systemic/generalized inflammation)
What form of vasculitis does he most likely have?
Giant cell (temporal) arteritis
What is seen here?
Giant cell (temporal) arteritis
Classic pattern = focal granulomatous inflammation with:
- giant cell formation (2/3 of cases)- may need multiple sections
- fragmentation of the internal elastic membrane (as seen with the VVG stain for elastin)
May have thrombus in the vessel +/- organization and recanalization
Other patterns:
a) nonspecific inflammation (lymphocytes and eosinophils) in all layers of the arterial wall
b) intimal fibrosis without obvious disruption of the internal elastic lamina.
What is seen here?
Giant cell (temporal) arteritis
Classic pattern = focal granulomatous inflammation with:
- giant cell formation (2/3 of cases)- may need multiple sections
- fragmentation of the internal elastic membrane (as seen with the VVG stain for elastin)
May have thrombus in the vessel +/- organization and recanalization
Other patterns:
a) nonspecific inflammation (lymphocytes and eosinophils) in all layers of the arterial wall
b) intimal fibrosis without obvious disruption of the internal elastic lamina.
What is seen here?
Giant cell (temporal) arteritis
Classic pattern = focal granulomatous inflammation with:
- giant cell formation (2/3 of cases)- may need multiple sections
- fragmentation of the internal elastic membrane (as seen with the VVG stain for elastin)
May have thrombus in the vessel +/- organization and recanalization
Other patterns:
a) nonspecific inflammation (lymphocytes and eosinophils) in all layers of the arterial wall
b) intimal fibrosis without obvious disruption of the internal elastic lamina.
What is seen here?
Giant cell (temporal) arteritis
Classic pattern = focal granulomatous inflammation with:
- giant cell formation (2/3 of cases)- may need multiple sections
- fragmentation of the internal elastic membrane (as seen with the VVG stain for elastin)
May have thrombus in the vessel +/- organization and recanalization
Other patterns:
a) nonspecific inflammation (lymphocytes and eosinophils) in all layers of the arterial wall
b) intimal fibrosis without obvious disruption of the internal elastic lamina.
In general, what sized arteries would be involved in Giant cell (temporal) arteritis, and in what anatomic locations? Epidemiology?
Large to medium-sized cranial vessels, including:
- temporal arteries (most common)
- vertebral arteries
- ophthalmic arteries
- rarely, the aorta
Occurs in older individuals, rare below the age of 50 years
What accounts for this pt’s visual loss in the right eye?
- Involvement of the ophthalmic artery
- Visual symptoms may vary from blurred or double vision to the sudden onset of blindness (up to 40% of patients)
How could the visual loss have been prevented (Giant cell (temporal) arteritis)?
Corticosteroid therapy!
What laboratory tests and surgical procedures could aid in the diagnosis of Giant cell (temporal) arteritis?
- Markedly elevated erythrocyte sedimentation rate (ESR) is suggestive (supportive), but is non-specific
- Biopsy of the affected temporal artery is specific, but not entirely sensitive
- Go ahead and start treatment based on clinical picture
- don’t wait for the biopsy
Case 4)
- 28-year-old female w/ intermittent dizziness and blurred vision
- PE: low BP in arms, weakened radial pulse, retinal hemorrhages, and focal visual field defects
- Angiography: decreased dye in the upper extremities and narrowing at the origins of the great vessels in the aortic arch
What disease does she most likely have?
Takayasu’s (pulseless) arteritis
What sized vessels and what actual vessels are involved in Takayasu’s arteritis?
Large to medium–sized arteries (classically the aortic arch)
- In up to 1/3 of cases, the remainder of the aorta and its branches are also involved
- Some cases are limited to the descending thoracic and abdominal aorta
What is seen here?
Takayasu Vasculitis
- Early changes: mononuclear inflammation into the adventitia with perivascular cuffing of the vasa vasorum.
- Intermediate changes: intense mononuclear inflammation in the media, (+/-granulomatous changes with giant cells and central necrosis)
- Later stages: medial fibrosis and thickening of the intima by smooth muscle cells and associated extracellular matrix
What is seen here?
Takayasu Vasculitis
- Early changes: mononuclear inflammation into the adventitia with perivascular cuffing of the vasa vasorum.
- Intermediate changes: intense mononuclear inflammation in the media, (+/-granulomatous changes with giant cells and central necrosis)
- Later stages: medial fibrosis and thickening of the intima by smooth muscle cells and associated extracellular matrix
What is seen here?
Takayasu Vasculitis
- Early changes: mononuclear inflammation into the adventitia with perivascular cuffing of the vasa vasorum.
- Intermediate changes: intense mononuclear inflammation in the media, (+/-granulomatous changes with giant cells and central necrosis)
- Later stages: medial fibrosis and thickening of the intima by smooth muscle cells and associated extracellular matrix
What is seen here?
Takayasu Vasculitis
- Early changes: mononuclear inflammation into the adventitia with perivascular cuffing of the vasa vasorum.
- Intermediate changes: intense mononuclear inflammation in the media, (+/-granulomatous changes with giant cells and central necrosis)
- Later stages: medial fibrosis and thickening of the intima by smooth muscle cells and associated extracellular matrix
How do you distinguish Takayasu Vasculitis from Temporal Arteritis?
Largely based on clinical data!!!
- Age of the patient (females 15-40)
- More common in Asia
Takayasu’s arteritis: more likely to have inflammation in the adventitia (inflammation occurs more peripherally while Temporal arteritis is between intima and media?)
**Histologic changes of Takayasu’s arteritis may be indistinguishable from those of Giant cell (temporal) arteritis
What accounts for the ocular disturbances and weakening of the pulses with decreased blood pressure in the upper extremities in Takayasu’s vasculitis?
Fibrous thickening of the aortic arch -> narrowing or virtual obliteration of the origins of the great vessels arising in the arch -> orifices of the major arteries to the upper portions of the body are markedly stenosed or occluded -> “pulseless disease.”
Case 5)
- 30 yo man, Hx of heavy smoking
- Developed cold sensitivity in his fingertips and foot pain with exercise
- Eventually led to excrutiating pain and gangrenous necrosis of multiple fingers and toes
What form of angiitis do the history and physical findings imply?
Thromboangiitis obliterans (Buerger’s disease)
What is seen here?
Thromboangiitis obliterans (Buerger’s disease)
- Segmental, thrombosing, acute and chronic inflammation of small and medium sized arteries (occasionally veins) of the extremities
- Thrombus contains a central microabscess of neutrophils surrounded by granulomatous inflammation
With time, there is organization and recanalization
To what environmental exposure is Thromboangiitis obliterans (Buerger’s disease) most consistently related? Mechanism?
Heavy cigarette smoking!!
Possible mechanisms:
- Direct endothelial cell toxicity
- Vasoconstriction induced by catecholamine metabolism
- Hypercoagulability leading to thrombosis
How does this pathologic process (Thromboangiitis obliterans (Buerger’s disease) )contrast with that of atherosclerosis?
Buerger’s disease:
- Transmural inflammation and occlusive luminal thrombosis (with small micro-abscesses within the thrombus)
Atherosclerosis:
- Bland thrombosis
Case 6)
- 15 mo male
- Fever to 105
- Irritable, generalized erythematous papular rash, bilateral conjunctival injection, periorbital and pedal edema, “oral lesions”, perianal and inguinal desquamation; tachycardia
- CXR: cardiomegaly with 4-chamber enlargement and pericardial effusion
What type of arteritis is he likely to have?
Kawasaki Disease
What age groups are typically affected in Kawasaki Disease?
- Young children and infants (80% younger than 4 years old)
- Epidemics occur in Japan
- Increasingly in the U.S
What sized arteries does Kawasaki’s Disease usually involve? Where?
Medium-sized and small arteries
- Classically: coronary arteries!! (will see aneurysms here)
What do the cardiac catheterization results show in Kawasaki’s Disease?
Multiple aneurysmal dilatations of coronary arteries
Correlate the catheterization results with the gross findings in Kawasaki’s Disease
This shows a histologic section of a left coronary artery extending from the aortic sinus.
What are the abnormal findings?
Kawasaki’s Disease?
Aneurysmally dilated coronary artery with organized thrombus and possible more recent thrombus
What dreaded complication can result (from coronary artery aneurysm) and why (seen in Kawasaki)?
20% of kids with Kawasaki’s disease can develop cardiovascular problems
- Ranging from coronary artery ectasia or aneurysm formation to giant coronary artery aneurysms w/ rupture or thrombosis, myocardial infarction or sudden death
- Acute fatalities occur in 1–2% of patients
Case 7)
- 22 yo female with fatigue, myalgias, and a “rash” on her legs
- PMH: recent course of penicillin for suspected strep throat
- PE: scattered petechiae across the anterior aspects of both lower legs with some papular (“palpable”) purpuric lesions
- What is the diagnosis based on the examination of the biopsy?
What are the histological features?
Leukocytoclastic vasculitis (microscopic polyangiitis)
Histological features:
- Fibrinoid necrosis of the media
- Neutrophil infiltration and neutrophil fragmentation (leukocytoclasis) in and around the vessel wall (“neutrophil dust/chunks”)
- NO Granulomatous inflammation
How is Leukocytoclastic vasculitis (microscopic polyangiitis) disease different from Polyarteritis Nodosa (PAN)?
1. Size of the involved vessels
Leukocytoclastic vasculitis: small arterioles, capillaries, and venules
PAN: small to medium-sized arterioles
2. Evolution of the lesions:
- Leukocytoclastic vasculitis: all lesions are “same age”
- PAN: spectrum from acute to partially-healed to well-healed all in the same patient at the same time
3. Presence or absence of renal and/or lung disease:
- Leukocytoclastic vasculitis: glomerulonephritis and pulmonary capillaritis can be present
- PAN: not usually seen
In what clinical setting is leukocytoclastic vasculitis generally seen?
- Association with hypersensitivity response and circulating immune complexes sites most commonly affected: skin, mucous membranes, joints, muscle, kidneys, and gastrointestinal tract
- In this case, the exposure of this patient to Streptococcus or to the penicillin likely induced a systemic hypersensitivity response –> vasculitis.
