Vasculitis, Veins, Lymphatics, DVT, Vascular Tumors Flashcards
Clinical presentation of vasculitis
Depends on the vascular bed affected — but generally presents as constitutional sx: fever, malaise, arthralgias, myalgias
What primary form of vasculitis affects the aorta?
Giant cell arteritis
Diagnosis of what primary form of vasculitis REQUIRES the presence of neutrophils?
Behcet disease
Diagnosis of what primary form of vasculitis REQUIRES the presence of eosinophils?
Churg-Strauss Syndrome
Diagnosis of what primary form of vasculitis REQUIRES the presence of granulomas?
Granulomatosis with Polyangiitis
Diagnosis of what primary form of vasculitis REQUIRES the feature of thrombosis?
Buerger disease
A clinical history of >40 y/o, +/- polymyalgia rheumatica may clue you into what primary form of vasculitis?
Giant cell arteritis
A clinical history including asthma and/or atopy may clue you into what primary form of vasculitis?
Churg-Strauss syndrome
A clinical history including a young male smoker may clue you into what primary form of vasculitis?
Buerger disease
A clinical history including orogenital ulcers may clue you into what primary form of vasculitis?
Behcet disease
Pathogenesis of immune complex vasculitis
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
Immune complex vasculitis may be seen in what conditions?
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)
Heterogenous group of antibodies reactant with cytoplasmic enzymes found in neutrophil granules, monocytes, and endothelial cells, —and associated with noninfectious vasculitis
Antineutrophil cytoplasmic antibodies (ANCA)
2 types of ANCA antibodies and the conditions they are associated with
PR3-ANCA (anti-proteinase-3) — associated with polyangiitis
MPO-ANCA (anti-myeloperoxidase) — associated wtih microscopic polyangiitis and Churg-Strauss
ANCA titers usually follow disease _____
Severity
Why are ANCA-associated vasculitides considered “pauci-immune”?
ANCA Abs are directed against cellular constituents and DO NOT form circulating immune complexes — thus vascular lesions do not typically contain Ab and complement
Most common vasculitis among older patients that may present with constitutional symptoms (fever, fatigue, weight loss), as well as facial pain and headache
Giant cell (temporal) arteritis and aortitis
Pathogenesis of giant cell arteritis and aortitis
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
Why might pts with Giant cell arteritis complain of double vision?
Involvement of the ophthalmic artery — may lead to vision loss and is a medical emergency!
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
Takayasu arteritis
Takayasu has similar histologic findings (giant cells) as those seen in giant cell arteritis, with what exceptions?
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)
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]
Polyarteritis nodosa (PAN)
Polyarteritis nodosa may affect any age group, but classically affects _______; almost 1/3 of the patients have _______
Young adult; chronic hepatitis B (HBsAg-HBsAb complexes are found in the involved vessels)
What type of inflammation characterizes polyarteritis nodosa?
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
What type of necrosis is seen with polyarteritis nodosa?
Fibrinoid necrosis
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
Kawasaki disease
Clinical presentation and prognosis of kawasaki disease
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
Necrotizing vasculitis involving arterioles, capillaries, and venules characterized by fragmented PMNs and associated with Henoch-Schonlein purpura, essential mixed cryoglobulinemia, and other CT disorders
Microscopic polyangiitis
Microscopic polyangiitis affects vessels of many organ systems, but which are most common?
Renal glomeruli and lung capillaries
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”
MPO-ANCA; fibrinoid; neutrophils
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
Churg-Strauss syndrome
T/F: less than 1/2 of Churg Strauss pts show ANCA positivity
True — when they do it is usually MPO-ANCA
Organ systems involved with Churg Strauss syndrome and potentially fatal complication
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
Behcet dz is a noninfectious vasculitis of small to medium vessels. What is the classic triad associated with this disease?
Aphthous ulcers of the oral cavity
Genital ulcers
Uveitis
[there are also GI and pulmonary manifestations]
Genetic marker of Behcet disease
HLA-B51
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 ______
Neutrophilic
Neurologic; aneurysms
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
Granulomatosus with polyangiitis (formerly known as Wegener granulomatosus)
Granulomatosis with polyangiitis is associated with ______ Abs and is a form of ______-mediated hypersensitivity response to normally “innocuous” inhaled microbial or other environmental allergens
PR3-ANCA; T-cell
Clinical features of granulomatosus with polyangiitis
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
Prognosis associated with granulomatosis with polyangiitis
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
Morphology associated with granulomatosis with polyangiitis in upper vs. lower respiratory tract
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
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
Thromboangiitis obliterans (Buerger disease)
Complications of thromboangiitis obliterans
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
What risk factor has a strong correlation with thromboangiitis obliterans?
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]
Morphology of thromboangiitis obliterans
Acute and chronic inflammation accompanied by luminal thrombosis
Thrombus can contain small microabscesses composed of neutrophils surrounded by granulomatous inflammation
What 3 organisms are associated with direct invasion of vessels leading to infectious vasculitis?
Pseudomonas
Aspergillus
Mucor
Infectious vasculitis is characterized by localized tissue infection, but less commonly can be via hematogenous spread — what is an example of this?
Septicemia or embolization from infective endocarditis
Vascular infections may weak arterial walls — leading to what complication?
Mycotic aneurysms
[may also induce thrombosis or infarction]
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
Raynaud phenomenon
What is the difference between primary Raynaud and secondary Raynaud phenomenon?
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
Define myocardial vessel vasospasm and its etiology
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)
Possible outcomes/complications with myocardial vessel vasospasm
Ischemia or infarct —> sudden cardiac death
Takotsubo cardiomyopathy “broken heart syndrome”; associated with emotional duress
Condition characterized by abnormal dilation of veins with valvular incompetence, secondary to sustained intraluminal pressure
Varicose veins
Complications of varicose veins
Stasis, congestion, thrombus, edema, and ischemia of overlying skin (stasis dermatitis)
[note that embolism from thrombi of SUPERFICIAL lower extremity veins is RARE]
Increased luminal pressure in certain areas may lead to the formation of portosystemic shunts; what are some areas affected?
Esophagus — esophageal varices
Rectum — hemorrhoids
Periumbilicus — caput medusae
Superior vena cava syndrome occurs when neoplasms compress or invade the SVC — what are some examples of neoplasms known to do this?
Bronchogenic carcinoma
Mediastinal lymphoma
Aortic aneurysm
Obstruction associated with SVC syndrome produces what characteristic clinical complex?
Marked dilation of the veins of the head, neck, and arms with cyanosis
Pulmonary vessels can also be compressed, leading to respiratory distress!
What causes inferior vena cava syndrome?
Neoplasms that compress or invade the IVC; or thrombosis of the hepatic, renal, or lower extremity veins that propagate cephalad
What 2 neoplasms are often associated with growth into veins and ultimate occlusion of the IVC —> IVC syndrome?
Hepatocellular carcinoma (HCC)
Renal cell carcinoma (RCC)
Clinical features of obstuction associated with IVC syndrome
Marked lower extremity edema
Distention of the superficial collateral veins of the lower abdomen
Renal vein involvement is associated with massive proteinuria
Extremely common condition associated with dilation of the venous plexus at the anorectal junction causing pain, bleeding, and possible ulceration
Hemorrhoids
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?
Prolonged inactivity/immobilization
Systemic hypercoagulability may also increase risk
Most serious potential consequence of thrombophlebitis/DVT
Pulmonary embolism
Migratory thrombophlebitis (Trousseau sign) involves a hypercoagulable state experienced as a paraneoplastic syndrome. It is particularly seen with what type of neoplasm?
Mucin-producing adenocarcinoma
[associated with adenocarcinoma of the lung, ovary, and pancreas]
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
Hemangiomas
[note that these often regress when congenital]
Most common benign vascular tumor
Capillary hemangioma
[just thin-walled capillaries tightly packed together]
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
Cavernous hemangioma
Type of capillary hemangioma that is rapidly growing and often seen in oral mucosa where they may ulcerate
Pyogenic granuloma
[misnomer — not pyogenic, and not a granuloma]
A simple lymphangioma appears very similar to capillary hemangiomas, but without _____; affects the subcutis of head/neck and axillae
RBCs
Describe the lymphangioma that is associated with Turner syndrome
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-)
Painful, but otherwise benign tumors of smooth muscle origin that most often appear in distal fingers
Glomus tumor
Benign vascular tumor associated with vascular proliferation in response to gram negative bartonella bacilli
Bacillary angiomatosus
Clinical features of bacillary angiomatosus
Occurs on the skin of immunocompromised pts
The lesions are localized, forming red papules
Macrolide abx are effective
Microscopy of Bacillary angiomatosus
Proliferation of capillaries with plump endothelial cells
The bacteria can be identified with PCR or visualized with a Warthin-Starry stain
Describe epithelioid hemangioendothelioma
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%
Etiology of kaposi sarcoma
Human herpesvirus 8 (HHV8)
Name the 4 distinct clinical forms of kaposi sarcoma — and which one is most common in US
AIDS-associated KS (most common form seen in US)
Classic KS
Endemic African KS
Transplant-associated KS
T/F: AIDS-associated KS is the most common AIDS-related malignant tumor and may spread to LNs and viscera
True
What patient populations are affected by Classic KS?
Older men from Middle Eastern, Mediterranean or Eastern descent - NOT associated with HIV, tumors localized to skin
Which type of KS is NOT associated with HIV, tends to affect pts <40, and can involve LNs?
Endemic African KS
Type of KS NOT associated with HIV but with T-cell immunosuppression, can spread to LNs and viscera
Transplant-associated KS
Characteristic histologic finding associated with Kaposi Sarcoma
Sheets of spindle cells
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)
Angiosarcoma
Environmental exposures associated with hepatic angiosarcoma
Arsenic
Pesticides
Thorotrast (contrast agent)
Polyvinyl chloride
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?
CD31 endothelial marker
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?
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%
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)
Thrombosis
Saphenous; left internal mammary
