Large-Vessel Vasculitis

Takayasu's arteritis ("pulseless disease")

• Systemic granulomatous vasculitis involving aorta and its branches

• Most common in Asia and in young women of reproductive age

• Clinical manifestations

Phase I: inflammatory period with fever, arthralgias, weight loss

Phase II: vessel pain and tenderness.. and unequal pulses in extremities, bruits, limb claudication, renovascular hypertension (>50%). neurogenic syncope most often affects the subclavian and innominate arteries ( -90%). with carotid renal, pulmonary ( 50%). and coronary arteritis and aortitis also commonly seen Phase III: burnt out. fibrotic period

• Dx studies: T ESR (75%). CRP; arteriography — occlusion, stenosis, irregularity and aneurysms; carotid Doppler studies; MRI/MRA: pathology — focal panarteritis, cellular infiltrate with granulomas and giant cells

• Classification criteria (3 of 6 is 90.5% Se & 97.8% Sp^Wmm 199033:1129)

2. claudication of the extremities

3. decreased brachial artery pulse

4. systolic BP difference >10 mmHg between arms

5. bruit over subclavian arteries or aorta

6. arteriogram abnormality (Ao. primary branches, or prox. large arteries in extremities)

• Treatment: steroids, methotrexate, antiplatelet therapy

Giant cell arteritis (GCA) <nejm 2003349160)

• Vasculitis affecting cranial branches of aortic arch, especially temporal artery (thus also called "temporal arteritis"), but can cause aortitis as well

• Pts older than 50 (90% older than 60); female:male ratio 2:1

• Clinical manifestations (/ama 2002:28792)

constitutional symptoms: low-grade fevers, fatigue, weight loss, myalgias, anorexia headache (2/3); tender temporal arteries and scalp and absent temporal artery pulsation ophthalmic artery (20%) — optic neuritis, diplopia, amaurosis fugax and blindness facial arteries — jaw claudication

Raynaud's phenomenon; intermittent claudication of extremities; thoracic Ao aneurysm

• Dx studies: t ESR (though in 5% ESR <40 even before Rx): T CRP

ESR related to fgbn & Ig in blood; Ddx for >100: infxn, rheum. ESRD. malig temporal artery bx (3-5 cm sample length; vasculitis, granulomas)

• Classification criteria (3 of 5 is 93.5% Se & 91.2% Sp; arth Rheum 1990:33 1122)

2. new headache 5. biopsy — vasculitis & granulomas

3. temp artery tenderness or I pulsation

• Polymyalgia rheumatica (seen in 50% GCA Pts; 15% of Pts w/ PMR develop GCA)

no universal or validated diagnostic criteria exist; most follow general guidelines: age -50 y; ESR -40 mm/h (and/or elevated CRP)

bilateral aching and morning stiffness ( 30 min x .-1 mo), involving 2 of the following 3 areas: neck or torso, shoulders or prox. arms, hips or prox. thighs exclude other causes of sx (eg. RA); CK should be normal

• Treatment: steroids (if vision threatened do not await path results before starting Rx);

40-60 mg/d for GCA; 10-20 mg/d for PMR; follow clinical status and ESR

Medium-Vessel Vasculitis Polyarteritis nodosa ("classic" PAN) (/ama 2002:288 1632)

• Acute or chronic systemic necrotizing vasculitis, typically of renal and other visceral arteries, without granuloma formation

• More common in men; average age of onset 50 y; strongly associated with HBV

• Clinical manifestations (Cupps and Fauci. The VmtuMet. Philadelphia: Saunderv 1981)

constitutional symptoms: weight loss, fevers, fatigue musculoskeletal (64%): myalgias, arthralgias, arthritis renal involvement (60%) with active urinary sediment hypertension, renal failure nervous system (51%): peripheral neuropathies, mononeuritis multiplex, stroke gastrointestinal (44%): abdominal pain. Gl bleeding/infarction, cholecystitis cutaneous lesions (43%): livedo reticularis, purpura, nodules, Raynaud's cardiac (36%): coronary arteritis, cardiomyopathy, pericarditis GU (25%): ovarian or testicular pain

• Dx studies angiogram (mesenteric vessels) — microaneurysms and focal vessel narrowings MRA may not be adequate to make the diagnosis biopsy (sural nerve or skin) — vasculitis with fibrinoid necrosis without granulomas ' ESR. T WBC. rare eosinophil. © HBsAg (30%). p-ANCA (<20%)

• Classification criteria (3 of 10 criteria is 82% Se & 87% Sp: Arth Rheum 1990:33:1088)

1. weight loss a 4 kg

2. livedo reticularis

3. testicular pain/tenderness

4. myalgias, weakness, leg tenderness

5. mononeuropathy or polyneuropathy

6. diastolic BP >90 mmHg

8. Hepatitis B virus

9. Arteriographic abnormality (aneurysms, occlusion of visceral arteries) 10. Biopsy — vasculitis of small or medium-sized vessel

• Treatment: steroids, cyclophosphamide; antiviral therapy for HBV-related PAN

ANCA-Associated Small-Vessel Vasculitis






ANCA Type*


Wegener's granulomatosis





Microscopic polyangiitis





Churg-Strauss syndrome





•Predominant ANCA type: either p- or c-ANCA can be seen in all three disease». (NEJM 1997:337:1512)

•Predominant ANCA type: either p- or c-ANCA can be seen in all three disease». (NEJM 1997:337:1512)

Differential diagnosis of ANCA

• c-ANCA (anti-PR3): Wegener's granulomatosis, Churg-Strauss, microscopic polyangiitis

• p-ANCA (anti-MPO): microscopic polyangiitis. Churg-Strauss. PAN.Wegener's granulomatosis, drug-induced vasculitis, nonvasculitic rheumatic diseases

• atypical ANCA patterns: drug-induced vasculitis, nonvasculitic rheumatic diseases.

ulcerative colitis, primary sclerosing cholangitis, endocarditis, cystic fibrosis Wegener's granulomatosis

• Necrotizing granulomatous inflammatory disease with systemic vasculitis, particularly involving the upper and lower respiratory tract, and kidney

• Can occur at any age. but * incidence in young and middle-aged adults

• Clinical manifestations pulmonary (90%)

upper, sinusitis, otitis, rhinitis, nasal mucosal ulceration, saddle-nose deformity lower, pleurisy, pulmonary infiltrate, nodules, hemorrhage, hemoptysis renal (80%): hematuria. RPGN (pauci-immune) ocular (50%): episcleritis, uveitis and proptosis from orbital granulomas neurologic cranial and peripheral neuropathies, mononeuritis multiplex hematologic: t incidence DVT/PE (20x) when disease active (Anna's 2005:142:620)

• Dx studies: 90% © ANCA (80-95% c-ANCA. remainder p-ANCA)

CXR or CT -> nodules, infiltrates, cavities; sinus CT -» sinusitis ■ BUN & Cr, proteinuria, hematuria; sediment w/ RBC casts, dysmorphic RBCs biopsy necrotizing granulomatous inflammation of arterioles, capillaries, veins

• Classification criteria (2 of 4 criteria is 88% Se & 92% Sp;Arth RUvw 1990.331101)

1. nasal or oral inflammation: oral ulcers, purulent or bloody nasal discharge

2. CXR showing nodules, fixed infiltrates, or cavities

3. microscopic hematuria or urinary red cell casts

4. granulomatous inflammation on biopsy

• Treatment (Annok 1992:116:488; NCJM 2003:34936)

cyclophosphamide PO (2 mg/kg/d x 3-6 mos) & prednisone (1-2 mg/kg/d taper over 6 mos)

when prednisone s20mg/d. begin maintenance with MTX or AZA (< additional 18 mos)

for mild disease MTX/prednisone may be adequate for induction disease relapses: match aggressive diseose with aggressive Rx as needed TMP-SMX may prevent upper airway disease relapse incited by respiratory infections consider plasmapheresis for dialysis-dependent renal disease Microscopic polyangiitis (MPA)

• Necrotizing small-vessel vasculitis — glomerulonephritis, pulmonary capillary alveolitis. & dermal leukocytoclasdc venulitis. Similar to Wegener's but wlo granulomas.

• Not associated with HBV (unlike classic PAN)

• Clinical manifestations constitutional symptoms: weight loss, fevers, fatigue, myalgias renal: hematuria. RPGN (pauci-immune) pulmonary: cough and/or hemoptysis neurologic: mononeuritis multiplex

• Dx studies: 70% © ANCA (almost all p-ANCA). biopsy -♦ necrotizing, pauci-immune inflammation of arterioles, capillaries, & venules wlo granulomas or eosinophilic infiltrates urine sediment and CXR findings similar to those seen in Wegener's

• Treatment: as for Wegener's cyclophosphamide; high dose corticosteroids;

AZA for maintenance; plasmapheresis in some cases

Churg-Strauss syndrome

• Eosinophil-rich granulomatous inflammation involving lung, peripheral nerves, heart.

kidneys, and skin

• Rare condition that can present at any age. but typically 30-40

• Clinical manifestations asthma and allergic rhinitis (new asthma in an adult raises suspicion) eosinophilic infiltrative disease or eosinophilic pneumonia systemic small-vessel vasculitis with granulomas i neuropathy, coronary arteritis, and myocarditis frequent and severe glomerulonephritis and serositis less frequent and less severe

• Dx studies: 50% © ANCA (c-ANCA or p-ANCA). eosinophils (80%), biopsy . microgranulomas, fibrinoid necrosis and thrombosis of small arteries and veins with eosinophilic infiltrates; CXR may show shifting pulmonary infiltrates

• Classification criteria (4 of 6 criteria is 85% Se & 99.7% Sp; A/th Rheum 1990:33 1094)

1. asthma 4. migratory or transitory pulm-infiltrates

2. eosinophils >10% 5. paranasal sinus abnormality

3. mono- or polyneuropathy 6. extravascular eosinophils on biopsy

• Treatment: high-dose corticosteroids (- cyclophosphamide or other DMARDs if nec.)

Immune Complex-Associated Small-Vessel Vasculitis Henoch-Schonlein purpura (HSP)

• Most common systemic vasculitis in children. Rare in adults (SemmAnhnvi Rheum 1994:37.187;

• Begins after an upper respiratory tract infection or drug exposure; IgA-mediated

• Clinical manifestations: palpable purpura on extensor surfaces & buttocks; non-

deforming polyarthralgias especially involving hips, knees, and ankles; colicky abdominal pain • GIB or intussusception; nephritis ranging from microscopic hematuria and proteinuria to ESRD; many have fever

• Diagnostic studies: normal pit count; skin bx leukocytoclastic vasculitis with IgA

and C3 deposition in vessel wall; renal bx — mesangial IgA deposition

• Criteria for classification (2 of 4 is 87% Se and 88% Sp;Arth Rheum 1990:33:1114)

1. palpable purpura

2. age s20 y at disease onset

3. bowel angina

4. biopsy showing granulocytes in the walls of arterioles or venules

• Treatment: supportive; steroids • DMARDs for renal or severe disease

Cryoglobulinemic vasculitis: see "Cryoglobulinemia" Connective tissue disease-associated vasculitis

• Vasculitis associated with RA. SLE. or Sjogren's syndrome

• Clinical manifestations distal arteritis: digital ischemia, livedo reticularis, palpable purpura, cutaneous ulceration visceral arteritis: pericarditis and mesenteric ischemia peripheral neuropathy

• Diagnostic studies: skin and sural nerve biopsies, angiography. EMG

• Treatment: steroids, cyclophosphamide. MTX (other DMARDs) Cutaneous leukocytodastic angiitis

• Heterogeneous group of clinical syndromes due to immune complex deposition in capillaries, venules, and arterioles: includes hypersensitivity vasculitis

• Overall the most common type of vasculitis

• Etiologies drugs: penicillin, aspirin, amphetamines, thiazides, chemicals, immunizations infections: strep throat, bacterial endocarditis.TB. hepatitis, staphylococcal infections tumor antigens foreign proteins (serum sickness)

• Clinical manifestations: abrupt onset of palpable purpura, cutaneous ulceration and transient arthralgias after exposure to the offending agent, variably accompanied by fever, arthralgias and other organ involvement; peripheral neuropathy

• Dx studies: T ESR. 4 complement levels, eosinophil; skin biopsy leukocytodastic vasculitis with neutrophils, nuclear fragments 2° to karyorrhexis. Ig + complement deposition on direct immunofluorescence w/o IgA present, perivascular hemorrhage and fibrinoid deposits w/o cryoglobulin deposition

• Classification criteria (3 of 5 criteria is 71% Se & 84% Sp; Anh Rheum 1990.33 1108)

2. medication taken at disease onset

3. palpable purpura

4. maculopapular rash

5. biopsy showing granulocytes in a perivascular or extravascular location

• Treatment: withdrawal of offending agent • rapid prednisone taper Behcet's syndrome

• Multisystem vasculitis that may involve small-, medium- and large-sized vessels.

characterized by recurrent oral and genital ulcers with variable manifestations affecting the skin. eye. CNS. and musculoskeletal system

• Associated with HLA B51. highest prevalence on the old Silk Road (Turkey) and other Asian countries

• Classification criteria (#1 + ¿=2 others is 91% Se & 96% SpUorxet 1990;335 1078)

1. recurrent oral aphthous ulceration (at least 3 times in one year)

2. recurrent genital ulceration

3. eye lesions: uveitis (with hypopyon), scleritis. retinal vasculitis, optic neuritis 4 skin lesions: pustules, papules, folliculitis, erythema nodosum

5. © pathergy test (prick forearm with sterile needle pustule)

• Other clinical manifestations arthritis: mild, symmetric, chronic and nondestructive, involving knees and ankles neurologic: focal deficits, pleocytosis. inflammatory infiltrates w/o vasculitis vascular: superficial or deep vein thrombosis (25%); arterial stenosis, occlusion, and aneurysm can also occur

• Evaluation: ulcer bx. cerebral angio (rarely necessary); slit lamp exam and funduscopy

• Treatment (Arth Rheum 1997:40:769)

azathioprine early helps prevent ocular disease, ulcerations and improves prognosis mucocutaneous: steroids, colchicine, dapsone. thalidomide (males), etanercept ocular: steroids, AZA. IFN-«2a. infliximab. CsA. cyclophosphamide, chlorambucil CNS disease: oral/IV steroids, methotrexate. CsA. cyclophosphamide, chlorambucil arthritis: steroids, colchicine. iFN-«2a

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