Vasculitis, Veins, Lymphatics, DVT, Vascular Tumors

Question 1

Clinical presentation of vasculitis

Answer 1

Depends on the vascular bed affected — but generally presents as constitutional sx: fever, malaise, arthralgias, myalgias

Question 2

What primary form of vasculitis affects the aorta?

Answer 2

Giant cell arteritis

Question 3

Diagnosis of what primary form of vasculitis REQUIRES the presence of neutrophils?

Answer 3

Behcet disease

Question 4

Diagnosis of what primary form of vasculitis REQUIRES the presence of eosinophils?

Answer 4

Churg-Strauss Syndrome

Question 5

Diagnosis of what primary form of vasculitis REQUIRES the presence of granulomas?

Answer 5

Granulomatosis with Polyangiitis

Question 6

Diagnosis of what primary form of vasculitis REQUIRES the feature of thrombosis?

Answer 6

Buerger disease

Question 7

A clinical history of >40 y/o, +/- polymyalgia rheumatica may clue you into what primary form of vasculitis?

Answer 7

Giant cell arteritis

Question 8

A clinical history including asthma and/or atopy may clue you into what primary form of vasculitis?

Answer 8

Churg-Strauss syndrome

Question 9

A clinical history including a young male smoker may clue you into what primary form of vasculitis?

Answer 9

Buerger disease

Question 10

A clinical history including orogenital ulcers may clue you into what primary form of vasculitis?

Answer 10

Behcet disease

Question 11

Pathogenesis of immune complex vasculitis

Answer 11

Autoantibody production and formation of immune complexes — deposition of Ag-Ab complexes in vascular walls — this incites an inflammatory reaction within the wall, the antigen is often unidentified

Question 12

Immune complex vasculitis may be seen in what conditions?

Answer 12

Systemic immunologic diseases (e.g.,SLE)

Drug hypersensitivity — e.g., penicillin (streptokinase acts as foreign protein) - always consider this because if drug is stopped, vasculitis resolves!

Exposure to infectious agent — so Abs to microbial constituents form immune complexes that deposit in vascular lesions (e.g., polyarteritis nodosa — associated with HBsAg and anti-HBsAg)

Question 13

Heterogenous group of antibodies reactant with cytoplasmic enzymes found in neutrophil granules, monocytes, and endothelial cells, —and associated with noninfectious vasculitis

Answer 13

Antineutrophil cytoplasmic antibodies (ANCA)

Question 14

2 types of ANCA antibodies and the conditions they are associated with

Answer 14

PR3-ANCA (anti-proteinase-3) — associated with polyangiitis

MPO-ANCA (anti-myeloperoxidase) — associated wtih microscopic polyangiitis and Churg-Strauss

Question 15

ANCA titers usually follow disease _____

Answer 15

Severity

Question 16

Why are ANCA-associated vasculitides considered “pauci-immune”?

Answer 16

ANCA Abs are directed against cellular constituents and DO NOT form circulating immune complexes — thus vascular lesions do not typically contain Ab and complement

Question 17

Most common vasculitis among older patients that may present with constitutional symptoms (fever, fatigue, weight loss), as well as facial pain and headache

Answer 17

Giant cell (temporal) arteritis and aortitis

Question 18

Pathogenesis of giant cell arteritis and aortitis

Answer 18

Chronic T-cell mediated inflammation of arteries in the head, especially temporal arteries

Medial granulomatous inflammation occurs, often with multinucleated giant cells

Fragmentation of elastic lamina and intimal thickening

Sites of involvement within an artery may be patchy and focal

Question 19

Why might pts with Giant cell arteritis complain of double vision?

Answer 19

Involvement of the ophthalmic artery — may lead to vision loss and is a medical emergency!

Question 20

Noninfectious vasculitis characterized by ocular disturbances and marked weakening of pulses of the upper extremities (pulseless disease); may present with weak pulse and low BP in upper extremities

Answer 20

Takayasu arteritis

Question 21

Takayasu has similar histologic findings (giant cells) as those seen in giant cell arteritis, with what exceptions?

Answer 21

It involves the aortic arch (aortitis) and major branch vessels — occasionally causing dilation and aortic valve insufficiency (leads to cardiac symptoms)

Pulmonary artery is involved in 1/2 the cases, coronary and renal arteries may also be involved

Younger age group (<50)

Question 22

Noninfectious, systemic vasculitis, likely immune-complex mediated, tends to involve renal vessels, heart, liver, and/or GI tract — BUT pulmonary vessels are spared

[most common is for just renal vessels to be involved]

Answer 22

Polyarteritis nodosa (PAN)

Question 23

Polyarteritis nodosa may affect any age group, but classically affects _______; almost 1/3 of the patients have _______

Answer 23

Young adult; chronic hepatitis B (HBsAg-HBsAb complexes are found in the involved vessels)

Question 24

What type of inflammation characterizes polyarteritis nodosa?

Answer 24

Segmental transmural necrotizing inflammation (neutrophils, eosinophils, lymphocytes, and macrophages) — with predilection for branch points

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

Sites of inflammation are typically NOT circumfirential; inflamed vessel walls are susceptible to thrombus formation/occlusion, aneurysm, rupture

Question 25

What type of necrosis is seen with polyarteritis nodosa?

Answer 25

Fibrinoid necrosis

Question 26

Acute arteritis of infants and small children (80% affecting < 4 years), often involving the coronary arteries which may end up forming aneurysms that thrombose or rupture leading to acute MI

Answer 26

Kawasaki disease

Question 27

Clinical presentation and prognosis of kawasaki disease

Answer 27

Usually erythema of the conjunctiva, oral mucosa, PALMS AND SOLES; desquamative rash Also may see cervical lymph node enlargement (“mucocutaneous lymph node syndrome”) Px: usually self-limited but IVIg and aspirin are indicated to lower the risk of a coronary event

Question 28

Necrotizing vasculitis involving arterioles, capillaries, and venules characterized by fragmented PMNs and associated with Henoch-Schonlein purpura, essential mixed cryoglobulinemia, and other CT disorders

Answer 28

Microscopic polyangiitis

Question 29

Microscopic polyangiitis affects vessels of many organ systems, but which are most common?

Answer 29

Renal glomeruli and lung capillaries

Question 30

Most cases of microscopic polyangiitis are associated with _______ Abs. Pathologic pattern includes segmental necrotizing inflammation with _____ necrosis. Many apoptotic _____ are usually seen — and it is often called “leukocytoclastic vasculitis”

Answer 30

MPO-ANCA; fibrinoid; neutrophils

Question 31

Small vessel necrotizing vasculitis associated with asthma, allergic rhinitis, hypereosinophilia, lung infiltrates, extravascular granulomas, and may resemble PAN or microscopic polyangiitis but with the addition of eosinophils and granulomas

Answer 31

Churg-Strauss syndrome

Question 32

T/F: less than 1/2 of Churg Strauss pts show ANCA positivity

Answer 32

True — when they do it is usually MPO-ANCA

Question 33

Organ systems involved with Churg Strauss syndrome and potentially fatal complication

Answer 33

Many organ systems may be involved; multisystem disease with cutaneous involvement (palpable purpura), GI tract bleeding, and renal disease (primarily as FSGS) Myocardial involvement may give rise to cardiomypathy; heart is involved in 60% of pts, and accounts for almost half of all deaths in the syndrome

Question 34

Behcet dz is a noninfectious vasculitis of small to medium vessels. What is the classic triad associated with this disease?

Answer 34

Aphthous ulcers of the oral cavity Genital ulcers Uveitis [there are also GI and pulmonary manifestations]

Question 35

Genetic marker of Behcet disease

Answer 35

HLA-B51

Question 36

In Behcet disease, the vessel inflammation is _______ and morphologically nonspecific. It may involve the visceral organ systems with subsequent aneurysm formation Disease mortality is related to severe ______involvement or rupture of ______

Answer 36

Neutrophilic Neurologic; aneurysms

Question 37

Noninfectious, necrotizing vasculitis featuring necrotizing granulomas of the upper and/or lower respiratory tracts, necrotizing or granulomatous vasculitis most prominently in respiratory trac, and focal necrotizing, often crescentic glomerulonephritis

Answer 37

Granulomatosus with polyangiitis (formerly known as Wegener granulomatosus)

Question 38

Granulomatosis with polyangiitis is associated with ______ Abs and is a form of ______-mediated hypersensitivity response to normally “innocuous” inhaled microbial or other environmental allergens

Answer 38

PR3-ANCA; T-cell

Question 39

Clinical features of granulomatosus with polyangiitis

Answer 39

M>F, avg age of 40 Most pts have persistent pneumonitis and sinusitis, renal disease, and NASOPHARYNGEAL ULCERATION May see rashes, myalgias, articular involvement, neural inflammation, and fever

Question 40

Prognosis associated with granulomatosis with polyangiitis

Answer 40

Left untreated, rapidly fatal — 80% mortality at one year Now tends to be more chronic relapsing/remitting w/ tx of steroids, cyclophosphamide, and TNF antagonists

Question 41

Morphology associated with granulomatosis with polyangiitis in upper vs. lower respiratory tract

Answer 41

Upper respiratory tract: sinonasal and pharyngeal inflammation with granulomas and vasculitis (granulomas with geographic patterns of central necrosis and accompanying vasculitis) Lower respiratory tract: multiple necrotizing granulomas, which may coalesce and cavitate

Question 42

Noninfectious acute and chronic vasculitis characterized by segmental, thrombosing pattern affecting small and medium vessels — especially the tibial and radial arteries with occasional extension to veins and nerves of the extremities

Answer 42

Thromboangiitis obliterans (Buerger disease)

Question 43

Complications of thromboangiitis obliterans

Answer 43

When there is extension to veins/nerves of extremities — associated with pain May lead to vascular insufficiency of the extremities Chronic ulcerations may lead to gangrene

Question 44

What risk factor has a strong correlation with thromboangiitis obliterans?

Answer 44

Smoking! Pts are almost always heavy smokers <35 y/o [most have hypersensitivity to intradermally injected tobacco products; assoc with HLA haplotypes of certain ethnic groups: Israeli, Indian subcontinent and Japanese]

Question 45

Morphology of thromboangiitis obliterans

Answer 45

Acute and chronic inflammation accompanied by luminal thrombosis Thrombus can contain small microabscesses composed of neutrophils surrounded by granulomatous inflammation

Question 46

What 3 organisms are associated with direct invasion of vessels leading to infectious vasculitis?

Answer 46

Pseudomonas Aspergillus Mucor

Question 47

Infectious vasculitis is characterized by localized tissue infection, but less commonly can be via hematogenous spread — what is an example of this?

Answer 47

Septicemia or embolization from infective endocarditis

Question 48

Vascular infections may weak arterial walls — leading to what complication?

Answer 48

Mycotic aneurysms [may also induce thrombosis or infarction]

Question 49

Disorder of blood vessel hyperreactivity characterized by excessive vasospasm of small arteries and arterioles, especially fingers and toes — causing proximal vasodilation, central vasoconstriction, and distal cyanosis

Answer 49

Raynaud phenomenon

Question 50

What is the difference between primary Raynaud and secondary Raynaud phenomenon?

Answer 50

Primary — induced by cold or emotion; SYMMETRIC involvement of the digits. Estimated 3-5% of general population - typically young women. BENIGN course Secondary — component of another arterial disease like SLE, SCLERODERMA, or thromboangiitis obliterans; ASYMMETRIC involvement of digits. WORSENS with time

Question 51

Define myocardial vessel vasospasm and its etiology

Answer 51

Excessive vasoconstriction of myocardial arteries or arterioles — may lead to ischemia or infarct High levels of vasoactive mediators can precipitate prolonged myocardial vessel contract — usually caused by vasoactive agents, which may be endogenous (epinephrine, pheochromocytoma), or exogenous (cocaine)

Question 52

Possible outcomes/complications with myocardial vessel vasospasm

Answer 52

Ischemia or infarct —> sudden cardiac death Takotsubo cardiomyopathy “broken heart syndrome”; associated with emotional duress

Question 53

Condition characterized by abnormal dilation of veins with valvular incompetence, secondary to sustained intraluminal pressure

Answer 53

Varicose veins

Question 54

Complications of varicose veins

Answer 54

Stasis, congestion, thrombus, edema, and ischemia of overlying skin (stasis dermatitis) [note that embolism from thrombi of SUPERFICIAL lower extremity veins is RARE]

Question 55

Increased luminal pressure in certain areas may lead to the formation of portosystemic shunts; what are some areas affected?

Answer 55

Esophagus — esophageal varices Rectum — hemorrhoids Periumbilicus — caput medusae

Question 56

Superior vena cava syndrome occurs when neoplasms compress or invade the SVC — what are some examples of neoplasms known to do this?

Answer 56

Bronchogenic carcinoma Mediastinal lymphoma Aortic aneurysm

Question 57

Obstruction associated with SVC syndrome produces what characteristic clinical complex?

Answer 57

Marked dilation of the veins of the head, neck, and arms with cyanosis Pulmonary vessels can also be compressed, leading to respiratory distress!

Question 58

What causes inferior vena cava syndrome?

Answer 58

Neoplasms that compress or invade the IVC; or thrombosis of the hepatic, renal, or lower extremity veins that propagate cephalad

Question 59

What 2 neoplasms are often associated with growth into veins and ultimate occlusion of the IVC —> IVC syndrome?

Answer 59

Hepatocellular carcinoma (HCC) Renal cell carcinoma (RCC)

Question 60

Clinical features of obstuction associated with IVC syndrome

Answer 60

Marked lower extremity edema Distention of the superficial collateral veins of the lower abdomen Renal vein involvement is associated with massive proteinuria

Question 61

Extremely common condition associated with dilation of the venous plexus at the anorectal junction causing pain, bleeding, and possible ulceration

Answer 61

Hemorrhoids

Question 62

Thrombophlebitis involves venous thrombosis and inflammation. It almost always involves deep veins in the legs and can be completely asymptomatic. What is the single most important risk factor for developing DVT in the LE?

Answer 62

Prolonged inactivity/immobilization Systemic hypercoagulability may also increase risk

Question 63

Most serious potential consequence of thrombophlebitis/DVT

Answer 63

Pulmonary embolism

Question 64

Migratory thrombophlebitis (Trousseau sign) involves a hypercoagulable state experienced as a paraneoplastic syndrome. It is particularly seen with what type of neoplasm?

Answer 64

Mucin-producing adenocarcinoma [associated with adenocarcinoma of the lung, ovary, and pancreas]

Question 65

Common benign vascular tumor characterized by localized increase in neoplastic blood vessels, most commonly affecting skin, mucous membranes of head and neck, and in the liver

Answer 65

Hemangiomas [note that these often regress when congenital]

Question 66

Most common benign vascular tumor

Answer 66

Capillary hemangioma [just thin-walled capillaries tightly packed together]

Question 67

Benign vascular tumor characterized by irregular, dilated vascular channels making a lesion with an indistinct border More likely to involve deep tissue and more likely to bleed

Answer 67

Cavernous hemangioma

Question 68

Type of capillary hemangioma that is rapidly growing and often seen in oral mucosa where they may ulcerate

Answer 68

Pyogenic granuloma [misnomer — not pyogenic, and not a granuloma]

Question 69

A simple lymphangioma appears very similar to capillary hemangiomas, but without _____; affects the subcutis of head/neck and axillae

Answer 69

RBCs

Question 70

Describe the lymphangioma that is associated with Turner syndrome

Answer 70

Cavernous lymphangioma (cystic hygroma) — appears in neck or axilla of children and can be up to 15cm Large cavernous lymphangiomas of the neck are often seen in Turner syndrome (X-)

Question 71

Painful, but otherwise benign tumors of smooth muscle origin that most often appear in distal fingers

Answer 71

Glomus tumor

Question 72

Benign vascular tumor associated with vascular proliferation in response to gram negative bartonella bacilli

Answer 72

Bacillary angiomatosus

Question 73

Clinical features of bacillary angiomatosus

Answer 73

Occurs on the skin of immunocompromised pts The lesions are localized, forming red papules Macrolide abx are effective

Question 74

Microscopy of Bacillary angiomatosus

Answer 74

Proliferation of capillaries with plump endothelial cells The bacteria can be identified with PCR or visualized with a Warthin-Starry stain

Question 75

Describe epithelioid hemangioendothelioma

Answer 75

Intermediate-grade (borderline) vascular tumor composed of neoplastic endothelial cells that are plump and cuboidal — so they resemble epithelium. Vascular channels may be difficult to recognize. Variable clinical behavior with metastasis in 20-30%

Question 76

Etiology of kaposi sarcoma

Answer 76

Human herpesvirus 8 (HHV8)

Question 77

Name the 4 distinct clinical forms of kaposi sarcoma — and which one is most common in US

Answer 77

AIDS-associated KS (most common form seen in US) Classic KS Endemic African KS Transplant-associated KS

Question 78

T/F: AIDS-associated KS is the most common AIDS-related malignant tumor and may spread to LNs and viscera

Answer 78

True

Question 79

What patient populations are affected by Classic KS?

Answer 79

Older men from Middle Eastern, Mediterranean or Eastern descent - NOT associated with HIV, tumors localized to skin

Question 80

Which type of KS is NOT associated with HIV, tends to affect pts <40, and can involve LNs?

Answer 80

Endemic African KS

Question 81

Type of KS NOT associated with HIV but with T-cell immunosuppression, can spread to LNs and viscera

Answer 81

Transplant-associated KS

Question 82

Characteristic histologic finding associated with Kaposi Sarcoma

Answer 82

Sheets of spindle cells

Question 83

Malignant endothelial vascular tumor associated with older age individuals and occurring equally in males and females; commonly associated with induction by radiation exposure, can arise in setting of lymphedema (such as lymphedema in upper extremity after radical mastectomy)

Answer 83

Angiosarcoma

Question 84

Environmental exposures associated with hepatic angiosarcoma

Answer 84

Arsenic Pesticides Thorotrast (contrast agent) Polyvinyl chloride

Question 85

Angiosarcoma may occur anywhere, but the most common sites are skin, soft tissue, breast, and liver. It is a locally invasive tumor that may metastasize and the 5 year survival rate is around 30% (it is aggressive). What is the characteristic pathologic marker of this disease?

Answer 85

CD31 endothelial marker

Question 86

Therapeutic interventions for vascular pathology can induce intimal thickening by recruiting smooth muscle cells, promoting extracellular matrix deposition, analagous to atherosclerosis. What are some endovascular stenting procedures associated with this complication? What is a potentially better option?

Answer 86

Balloon angioplasty —> rupture of occluding plaque and limited dissection produced. Abrupt reclosure can result from extensive dissection, so 90% of angioplasties followed by stent placement. Coronary stents —> may induce thrombosis, long term may exhibit in-stent restenosis (sometimes w/i 6 months-1year) bettter option: Drug-eluting stents block smooth muscle activation — decrease restenosis at 1 yr by 50-80%

Question 87

Vascular replacement may be done using synthetic or autologous vascular grafts. Synthetic large bore works for the aorta, but small bore fail d/t ______ or intimal hyperplasia at junction of the graft with the native vasculature. Thus, the _______ vein or _______ arteries (best px) are utilized for small bore grafts (coronary arteries)

Answer 87

Thrombosis Saphenous; left internal mammary