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66 Cards in this Set

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systemic vasculitis: primary systemic vasculitides

inflammatory disorders of blood vessels; characterized by IMMUNE MEDIATED INJURY leading to= vessel necrosis, vessel thrombosis, vessel stenosis, or a combo of these 3; further characterized by preferential vessel size or territory and tissue targeting; rare but may be organ or life threatening

vessel size determines vascular spectrum of vasculities (what are the names that are associated with vasculitides of the differently sized blood vessels)

aorta and large to medium sized arteries= giant cell (temportal) arteritis and takayasu's arteritis; large to medium sized arteries and small arteries= polyarthritis nodosa and kawasaki disease; small arteries all the way to veins= wegner's granulomatosis and churg-strauss syndrome; small arteries all the way to venules= microscopic polyangitis (microscopic polyartitis); arterioles all the way to venules= henoch-schonlein purpura and essential cryoglobulinemic vasculitis; capillaries and venules= cutaneous leukocytoclastic angitis

general pathogenesis of vasculitis: the players

humoral and cellular immune responses; cytokine release an chemokine activation; immune complex deposition; normal protective and repair processes= cellular migration and proliferation (intimal hyperplasia), procoagulant milieu (thrombosis and vessel occlusion), subsequent tissue ischemia and damage; for many vacsulitides association is speculative

stereotypical response to vascular injury

1. recruitment of smooth muscle cells or smooth muscle precursor cells to the intima from the media 2. smooth muscle cell mitosis 3. elaboration of extracellular matrix; intimal smooth muscle cells may derive from the underlying media or may be recruited from circulating precursors; so the intima is getting really large with muscle cells

pathological classification of vasculitis: noninfectious

aka immune mediated inflammation; immune complex deposition= drug hypersensitivity vasculitis, vasculitis secondary to infections; antineutrophil cytoplasmic antibodies= ANTIPROTEINASE 3 (PR3-ANCA or c-ANCA), ANTIMYELOPEROXIDASE (MPO-ANCA or p-ANCA), anti-endothelial cell antibodies, autoreactive T cells; we're focusing on these in this lecture

pathological classification of vasculitis: infectious

DIRECT INVASION of arteries by bacteria or fungi especially aspergillus and mucor spp; HEMATOGENOUS SPREAD OF BACTERIA DURING SEPTICEMIA OR EMOBOLIZATION from infective endocarditis; we already went over these on the last test

the vasculitides: size and pathogenesis

might want to look over this slide (slide 9)

the vasculitides: clinical presentation and diagnosis

manifestations are DIVERSE differing not only among disorders but also among pts; constitutional symptoms in all types= fever, fatigue, malaise, anorexia, weight loss, arthralgias, and myalgias

the vasculitides: typical clinical features in large vessels

limb claudication, asymmetrical blood pressure, absence of pulses, bruites, aortic dilation, aortic primary branch stenoses and/or aneurysms

the vasculitides: typical clinical features in medium vessels

cutaneous nodules, ulcers, livedo reticularis, digital gangrene, mononeuritis multiplex, microaneurysms of mesenteric and/or renal branch arteries

the vasculitides: typical clinical features in small vessels

purpura, vesiculobullous lesions, urticaria, glomerulonephritis, alveolar hemorrhage, cutaneous extravascular necrotizing granulomas, splinter hemorrhages, scleritis, episcleritis, uveitis

giant cell arteritis (GCA) (large vessel vasculitis): epidemiology

MOST COMMON form among the ELDERLY in developing countries; elderly; females more than males; 40% WILL DEVELOP POLYMYALGIA RHEUMATICA (PMR) (PMR= subacute onset of aching and stiffness in muscles of the neck, shoulder girdle, and hip girdle, only 10-25% of those with PMR will develop GCA)

giant cell arteritis (GCA): pathogenesis

HLA-DRB1 have increased risk; T cell mediated response (RNF, anti endothelial cell antibodies); affects branches of external carotid artery especially temporal arteries

giant cell arteritis (GCS): presentation

insidious or acute; NEW CONTINUOUS HEADACHE, JAW CLAUDICATION (aka jaw cramp); visual disturbances in 50% and diplopia to blindness in 10-15%; might present as a superficial temporal artery that is pulseless, nodular, and thickened

giant cell arteritis (GCA): diagnosis

erythrocyte sedimentation rate (ESR) >50mm/h; BIOPSY OF VESSEL IS DEFINITIVE BUT NEED 2-3 CM BIOPSY BECAUSE OF SKIP LESIONS= nodular intimal thickening reducing lumen diameter, granulomatous inflammation within inner media, fragmentation of the internal elastic lamina; will see giant cells near the fragmented internal elastic membrane; might see scarring between the interna and media layers

giant cell arteritis (GCA): treatment

need for urgent therapy within 24 hrs; GLUCOCORTICOIDS (E.G. PREDNISONE); LOW DOSE ASPIRIN TO PROTECT AGAINST CRANIAL ISCHEMIC EVENTS; risk of blindness, heart attack, stoke

Takayasu arteritis (TAK) (large vessel vasculitis): epidemiology

get in mid 20s; females more than males

Takayasu arteritis (TAK): pathogenesis

INVOLVES AORTIC ARCH AND PRIMARY BRANCHES; PULMONARY ARTERIES IN 50%; renal and coronary arteries may also be affected

Takayasu arteritis (TAK): presentation

unequal blood pressure (10 mm Hg between arms) with decreased brachial or radial artery pulses; bruits over subclavian arteries or aorta; limb claudication (pain caused by too little blood flow, usually during exercise); neck or jaw pain, headache, dizziness, pulmonary hypertension; aka 'pulseless disease' (because major pulses are missing unlike giant cell arteritis where it's only the temporal)

Takayasu arteritis (TAK): diagnosis

VASCULAR IMAGING= LONG TAPERING STENOTIC LESIONS OR ANEURYSMAL LESIONS; ESR>50 mm/h; biopsy of vessel shows adventitial mononuclear infiltrates, perivascular cuffing of vasa vasorum, intense transmural mononuclear inflammation to granulomatous inflammation, thickening of vessel wall, intimal hyperplasia, adventitial fibrosis; so massive intimal thickening again

Takayasu arteritis (TAK): treatment

GLUCOCORTICOIDS (E.G. PRODNISONE); steroid sparing immunosuppresive agents= mthotrexate, azathioprine; low dose aspiring; risk of aortic aneurysm with dissection and rupture; myocardial infarction

polyarteritis nodosa (PAN) (medium vessel vasulitis): epidemiology

primarily young adults but in all age groups; men more than women; 1/3 have HBV infection

polyarteritis nodosa (PAN): pathology/pathogenesis

SEGMENTAL TRANSMURAL NECROTIZING INFLAMMATION of small to medium sized arteries, thrombosis; affects vessels of KIDNEY, heart, liver, GI tract (descending order of frequency); lesions involve part of vessel circumference, predilection for branch points; arterial wall weakening and luminal obstruction; aneurysm formation on the non thickened side; downstream ischemic damage

polyarteritis nodosa (PAN): presentation

depends on site of involvement; RENAL= renal artery aneurysms or stenoses leading to HYPERTENSION OR RENAL DYSFUNCTION, prominent, major cause of death in PAN; heart= myocardial infarction, heart failure, pericarditis; GI= mesenteric aneurysms or stenoses resulting in gut ischemia lead to symptoms of ABDOMINAL PAIN or 'intestinal angina' (pain after eating), BLOODY STOOLS; nervous= MONONEURITIS MULTIPLEX= peripheral neuropathy with numbness, tingling, abnormal sensation, burning pain, paralysis, uncontrolled movement; skin= palpable purpura, TENDER NODULAR LESIONS, LIVEDO RETICULARIS, infarcts of fingertips

polyarteritis nodosa (PAN): diagnosis

biopsy= mixed inflammatory infiltrate of neutrophils and mononuclear cells, fibrinoid necrosis and luminal thrombosis, ALL STAGES OF ACTIVITY COEXIST in different vessels or within the same vessel; test for hep B, hep C, and HIV

polyarteritis nodosa (PAN): treatment

untreated, PAN typically is fatal; immunosuppression can yield remission or cure in 90% of the cases; GLUCOCORTICOSTEROIDS or NSAIDS or both; additional immunosuppressive agents= cyclophosphamide (GI and cardiac), methotrexate, colchicine, IVIG; if associated with HBV or HCV then antiviral therapy is required

Kawasaki disease (KD) (medium vessel vasculitis): epidemiology

85-90% in children 4 yrs or younger; asian/pacific origin highest incidence

kawasaki disease (KD): pathology/pathogenesis

acute febrile usually self limited or infancy and childhood that can lead to death from coronary artery aneurysm; pathology resembles PAN but confined to cardiovascular system; CORONARY ARTERY ANEURYSMS APPEAR WITHIN THE FIRST 4 WEEKS AFTER ONSET; they think this may have a bacterial etiology

kawasaki disease (KD): presentation

ACUTE FEBRILE PERIOD (up to 14 days)= fever >5 days, >38.5C and minimally responsive to antipyretics, conjunctival infection, strawberry tongue, cervical LAD, mucous membrane desquamation, rash on soles of feet; SUBACUTE PHASE of 2-4 weeks= fever, cutaneous desquamation, aneurysms; CONVALESCENT PHASE of months to yrs

kawasaki disease (KD): diagnosis

differentiate from viral infections, toxin mediated illness, systemic juvenile idiopathic arthritis, hypersensitivity reactions, and drug reactions (Stevens Johnson syndrome); anemia, LEUKEMIA W/ LEFT SHIFT (ACUTE PHASE) (again suggests bacterial component), THOMBOCYTOSIS (SUBACUTE PHASE) >1,500,000, CARDIOMEGALY on chest x ray, ABNORMAL ECG; echocardiogram for coronary artery aneurysms

kawasaki disease (KD): treatment

CORONARY ANEURYSMS develop in 20-25% if untreated and 4% with treatment; HIGH DOSE ASPIRIN (80-100 MG/KG/DAY FOR 2 DAYS AND THEN LOWERED TO 3-5 MG/KG/DAY; IVIG= STANDARD THERAPY

thromboangiitis obliterans (TAO) (medium vessel vasculitis): epidemiology

ALMOST EXCLUSIVELY IN HEAVY TOBACCO SMOKERS; onset before age 35 (20-45); more males than females

thromboangiitis obliterans (TAO): pathology/pathogenesis

focal acute and chronic inflammation of medium sized and small arteries especially the tibial and radial arteries; may be a hypersensitivity to component of tobacco; genetic predisposition= israeli, indian subcontinent, japanese, some HLA subtypes

thromboangiitis obliterans (TAO): presentation

early= cold induced raynaud phenomenon, instep foot pain induced by exercise, superficial nodular phlebitis; severe pain (neural involvement); intermittent claudication --> persistent ischemic ulcers --> gangrene (of fingers) (obliterates the vessels)

thromboangiitis obliterans (TAO): diagnosis

arterial doppler shows angiography; positive antiocardiolipin antibodies; biopsy= sharply segmental thrombosing vasculitis, luminal thrombosis, small microabscesses, inflammation extends into contiguous veins and nerves

thromboangiitis obliterans (TAO): treatment

STOP SMOKING IMMEDIATELY= only proven treatment to stop progression if done early in disease, 94% who quit avoid amputation, among those who do not quit amputation occurs in 43%; local ischemia ulceration= trial of calcium channel blockers; surgical debridement and potentially limb amputation; also known as BUERGER DISEASE

ANCA associated vasculitides: names

microscopic polyangiitis (MPA); granulomatosis with polyangiitis (GPA) previously knonw as wegener's granulomatosis; eosinophilic granulomatosis with polyangiitis (EGPA) previously known as Churd-straus syndrome; renal limited vasculitis (RLV)= acute renal failure pauci-immune necrotising cresentic glomerulonephritis

ANCA- associated vasculitides: what do they all affect, epidemiology

affect small and medium sized blood vessels; peak age of onset is 65-74 y/o; female more than males; EPGA least common and weaker association with ANCA than MPA and GPA

mechanism for ANCA vasculitis

1. drugs or cross reactive microbial antigens or leukocyte surface expression or release of PR3 and MPO (in the setting of infections) incites ANCA development; 2. subsequent infection, endotoxin exposure, or inflammatory stimulus elicits cytokines (TNF) that upregulate the surface expression of PR3 and MPO on neutrophils and other cell types; 3. ANCAs bind these cytokine activated cells causing further activation of neutrophils; 4. ANCA activated neutrophils cause endothelial cell injury by releasing granule contents and reactive oxygen species; NO immune complexes involved= pauci-immune

microscopic polyangiitis (MPA): epidemiology

white persons>black persons; males>females; 50 y/o

microscopic polyangiitis (MPA): pathology/pathogenesis

necrotizing vasculitis that affects caps as well as small arterioles and venules; all lesions of MPA tend to be of the same age in any given pt; kidneys= pauci immune necrotizing crescentic glomerulonephritis

microscopic polyangiitis (MPA): presentation

DEPENDS ON VASCULAR BED; palpable cutaneous purpura; hemoptysis; hematuria, proteinuria; abdominal pain or bleeding; muscle pain or weakness

microscopic polyangiitis (MPA): diagnosis

tissue biopsy; ANCA TESTING= most have perinuclear (pANCA) ANTIMYELOPEROXIDASE (anti-MPO) type

microscopic polyangiitis (MPA): treatment

induction of remissin (75-89%) glucocorticoids plus cyclophosphamide; remission maintenance= methotrexate or azathioprine

microscopic polyangiitis (MPA): also known as

hypersensitivity vasculitis or leukocytoclastic vasculitis

granulomatosis with polyangiitis (GPA): epidemiology

typical pt a 40 yr old male; women and other ages can be affected

granulomatosis with polyangiitis (GPA): pathology

granulomas of upper and lower respiratory tract; necrotizing granulomatous vasculitis with a surrounding fibroblastic proliferation; pauci- immune focal and segmental necrotixing or crescentic glomerulonephritis

granulomatosis with polyangiitis (GPA): presentation

bilateral pneumonitis with nodules and cavitary lesions (95%); chronic sinusitis (90%); mucosal ulcerations of nasopharynx (75%) with characteristic saddle nose deformity; renal disease (80%)

granulomatosis with polyangiitis (GPA): diangosis

tissue biosy; ANCA TESTING= most have cytoplasmic (cANCA) ANTIPROTEINASE 3 (anti-PR3) type (95%); urinalysis= hematuria, proteinuria, RBC casts

granulomatosis with polyangiitis (GPA): treatment

remission induction= glucocorticoids plus cyclophosphamide (with mesna) or rituximab plus glucocorticoids; remission maintenance= azithioprine or methotrexate; also give prophylaxis for pneumocystis jirovecii pneumonia= trimethroprime/sulframethoxazole

granulomatosis with polyangiitis (GPA): also known as

wegener's granulomatosis

eosinophilic granulomatosis with polyangiitis (EGPA): epidemiology

males>females; onset 15-70 yrs

eosinophilic granulomatosis with polyangiitis (EGPA): pathology

small vessel necrotizing vasculitis with granulomas and necrosis

eosinophilic granulomatosis with polyangiitis (EGPA): presentation

asthma and allergic rhinitis; paranasal sinusitis; lung infiltrates; palpable purpura; GI= pain, diarrhea, bleeding; cardiomyopathy (60%)

eosinophilic granulomatosis with polyangiitis (EGPA): diagnosis

70% have elevated IgE; eosinophilia >10%; 40% have anti-MPO; biopsy= transmural eosinophilic infiltrates with scattered plasma cells and lymphocytes; extravascular granulomas

eosinophilic granulomatosis with polyangiitis (EGPA): treatment

glucocorticoids; if life threatening add cyclophosphamide; follow with azathioprine or mycophenolate

eosinophilic granulomatosis with polyangiitis (EGPA): also known as

churg-straus syndrome

henoch-schonlein purpura (HSP): epidemiology

small vessel vasulitis; peak age at onset 4-6 y/o; females>males; about 50% of childhood vasculitis; more frequently in winter and spring often following URI, especially GAS

henoch-schonlein purpura (HSP): presentation in children

PALPABLE LOWER EXTREMITY PURPURA; arthritis (large joints) and abdominal pain (75%) that precedes purpura by 2 weeks; renal disease= microhematuria with or without proteinuria

henoch-schonlein purpura (HSP): pathophysiology

cutaneous leukocytoclastic vasculitis of small vessels with IgA deposition; IgA nephropathy

henoch-schonlein purpura (HSP): diagnosis

urinalysis, creatinine, serum IgA; coagulation studies (normal); ANCA (negative)

henoch-schonlein purpura (HSP): treatment

mild cases= hydration, analgesics; organ involvement (GI, renal)= glucocorticoids; life threatening GI or severe acute renal failure= plasmapheresis and/or additional immunosuppressive agents; <1% develop end stage renal disease with treatment

additional considerations in treatment

risks of immunosuppressive therapy= increased risk of infection (pts receiving moderate to high dose glucocorticoids plus another immunosuppressive agent should receive prophylaxis for pneumocystic jiroveci pneumonia), bone marrow suppression, long term risks of malignancy, methotrexate and cyclophosphamide are teratogenic, and cyclophosphamide may result in premature ovarian failure, consider when choosing therapies for women of child bearing age; glucocorticoid therapy complications= bone loss (osteopenia, osteoporosis) even within the first 6 months of therapy (calcium and vit D supplementation, baseline bone density study, consider additional bone protection therapies (e.g.bisphosphonates)), never discontinue glucocorticoid therapy abruptly (risk of adrenal crisis or disease relapse or both)

A 28-year-old woman of Japanese descent comes to her primary care doctor complaining of 4 months of vertigo, myalgia, weight loss, and arthralgias. The findings at physical exam were blood pressure 150/90 mm Hg, subclavian bruit, and no pulse in the upper extremities. Angiography showed narrowing of the aorta and some of its branches. What is the most probable diagnosis? A.Giant cell arteritis B.Granulomatosus with polyangiitis C.Kawasaki disease D.Takayasu arteritis E.Thromboagniitis obliterans

D. takayasu (attacks aorta, young people); a. giant cell arteritis attacks temporal artery and is in older people

A woman has been diagnosed with giant cell arteritis. Which additional syndrome is likely to occur in this woman? A.Fibromyalgia B.Gout C.Microscopic polyangiitis D.Polymyalgia rheumatica E.Rheumatoid arthritis

D. polymyalgia rheumatica (PMR) (shoulder pain, neck, pain, hip and shoulder girdle pain)

A25-year-old male is in his doctor's waiting room. He is smoking a cigarette using a claw hand (an artificial hand). The smoke is bothering the other patients, but he does not put the cigarette out until the nurse insists he do so before entering the exam room. On physical examination, he is found to have a decreased radial pulse. There is ulceration on the digits of his remaining hand. Arteriography shows involvement of small and medium arteries and veins. What is the most likely condition? A.Giantcell arteritis B.Polyarteritis nodosa C.Raynaud phenomenon D.Takayasu arteritis E.Thromboangiitis obliterans

E. thromboangiitis obliterans (if he doesn't stop smoking he's likely to lose his other hand and maybe his feet)