Vasculitis and Connective Tissue
Disease
Evaldas Giedrimas, MD
Duane Pinto, MD
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Vasculitis Classification
• Based on size of the vessel and histology of
inflammatory cell:
• Large Vessel - mononuclear infiltrates and
inflammatory giant cells
– Temporal or Giant Cell Vasculitis/Arteritis
– Takayasu’s Arteritis
– Cogan’s Syndrome
• Medium Vessel
– Polyarteritis Nodosa
– Kawasaki’s Disease
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Vasculitis Classification (cont.)
• Small Vessel
–
–
–
–
Churg-Strauss
Hypersensitivity Vasculitis
Wegener’s Granulomatosis
Bechet’s Disease
• Scleroderma
• Lupus (SLE)
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Vasculitis Overview
• Definition
– inflammation and necrosis of blood vessels
• Idiopathic
• Secondary
• Etiology/Pathogenesis
– humoral or cellular immune-related injury
– Inflammation leads to narrowing or occlusion of the
vascular lumen (stenosis), corresponding ischemia,
local aneurysms, and possible ruptures
• Epidemiology
– rare
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Vasculitis Overview (cont.)
• Symptoms
• Physical Exam
• Presentation – “Red Flags”:
– Fever of unknown origin
– Unexplained arthritis or myositis
– Suspicious rash
• Palpable purpura
– Mononeuritis multiplex
– Glomerulonephritis
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Vasculitis Overview (cont.)
• Diagnosis
• Differential Diagnosis
• Treatment and Prognosis
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Large Vessel Vasculitis
Temporal Arteritis/Vasculitis
• Large branches of the carotid artery and aorta
• Epidemiology
– Age >50
– Women 3 X > Men
– Whites > non-whites
• Symptoms:
– slow to develop tenderness, erythema, nodularity
over the temporal artery; fever/headaches, PMR,
jaw claudication and visual loss
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Large Vessel Vasculitis
Temporal Arteritis/Vasculitis (cont.)
• Physical Exam:
– tender/thickened temporal arteries; bruits over carotid,
supraclavicular, brachial, axillary and rarely over the
orbits areas. May have associated distal joint synovitis
(15-20%)
• Diagnosis:
–
–
–
–
high ESR, CRP, anemia, thrombocytosis, elevated IL-6
Temporal biopsy is preferred form of diagnosis
Temporal arteritis patients should be screened for AAA
US findings of hypoechoic halo can be helpful
• Treatment:
– 40-60 mg daily prednisone immediately after diagnosis
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Large Vessel Vasculitis
Takayasu’s arteritis
• Aorta and main branches
• Epidemiology
– Young, Asian women
• Symptoms:
– HTN, decreased peripheral pulses, AR
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Large Vessel Vasculitis
Takayasu’s arteritis (cont.)
• Diagnosis:
– aortography/MRI, w/ narrowing of affected arteries and
collateral circulation
– associated with aorta coarctation and RAS – screening
• Treatment:
– glucocorticoids, cytoxic agents,
– angioplasty, bypass and invasive intervention
reserved for:
•
•
•
•
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HTN from RAS
CVA
Extremity ischemia with functional limitations
Cardiac ischemia
Large Vessel Vasculitis
Cogan’s Syndrome
• Mixed infiltrate of neutrophils and mononuclear cells
with disruption of elastic lamina and vessel wall necrosis
• Medium/small arteries, can extend to aortitis/carditis;
• Autoimmunity against ocular and audiovestibular
systems.
• Epidemiology
– Young
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Large Vessel Vasculitis
Cogan’s Syndrome (cont.)
• Symptoms:
– interstitial keratitis and audiovestibular symptoms,
often preceded by URI
• Physical Exam:
–
–
–
–
fever, myalgia, fatigue or weight loss,
vertigo, nausea, vomiting, tinnitus, hearing changes,
uveitis, optic neuritis, scleritis,
AR due to valve inflammation;
• Treatment:
– early Prednisone 40-60 mg QD; hearing aids; AVR;
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Medium Vessel Vasculitis
Polyarteritis Nodosa
• Disseminated necrotizing vasculitis, initially involves
intima and then progresses transmurally
• Medium-sized and small muscular arteries
• Symptoms:
– SOB, LE edema
– multi-organ: glomerulonephritis, mesenteric
ischemia, polyarthralgia, overlapping connective
tissue disease/myositis;
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Medium Vessel Vasculitis
Polyarteritis Nodosa (cont.)
• Physical Exam:
– HTN, palpable purpura, CHF, scleritis
• Diagnosis:
– renal dysfunction
– arteriographic documentation +/- biopsy
• Treatment:
– corticosteroids +/- cyclophosphamide
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Medium Vessel Vasculitis
Kawasaki’s Disease
• Mucocutaneous lymph node syndrome with
mononuclear infiltrate with endothelial cell
proliferation, elastic laminar disruption and
vessel wall necrosis and potential aneurysm
within 2 weeks
• Large, medium or small arteries, carditis in
50% of patients
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Medium Vessel Vasculitis
Kawasaki’s Disease (cont.)
• Epidemiology
– Male, children
• Symptoms:
– fever for 5+ days, and at least 4/5 of below:
– Rash
– Peripheral extremity changes such as erythema
or edema of palms/soles and periungal
desquamation
– Bilateral conjunctival injection
– Oral mucous membrane changes (fissured lips,
injected pharynx, strawberry tongue)
– Cervical lymphadenopathy
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Medium Vessel Vasculitis
Kawasaki’s Disease (cont.)
• Physical Exam:
– cervical lymphadenopathy, oral changes
• Diagnosis
– anemia, neutropenia, thrombocytosis
– EKG for MI findings with ruptured coronary aneurysm
– Echo for aortic aneurysm
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Medium Vessel Vasculitis
Kawasaki’s Disease (cont.)
• Treatment and Prognosis
– aspirin 80-100 mg/kg/day x 2 weeks AND
– single high-dose IV IgG infusion of 2 g/kg within
first 10 days of illness
– No steroids
– Echo at 8 weeks after diagnosis, if normal, then
therapy can be stopped, otherwise ASA
continued for at least 1 year.
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Small Vessel Vasculitis
Churgg-Straus
• Allergic
angitis and granulomatosis with
eosinophilia and extravascular
granulomas in patients with asthma
and/or allergic rhinitis
– Small/medium muscular arteries
• 40
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y.o. male
Small Vessel Vasculitis
Churgg-Straus (cont.)
•
Symptoms
– Respiratory: Initially URI, allergic rhinitis, asthma;
– GI: diarrhea (2/2 to eosinophils bowel infiltration)
+/- bleeding, bowel obstruction (due to nodules);
– CNS: similar to polyarteritis nodosa –
mononeuritis multiplex, symmetric peripheral
neuropathy, ischemic optic neuritis and CN
palsies;
– Cardiac: pericarditis, MI;
– Renal: UTI, FSGN;
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Small Vessel Vasculitis
Churgg-Straus (cont.)
• Physical Exam:
–
transient pulmonary findings, skin manifestations – purpura
with leukocytoclastic vasculitis, granulomatous nodules
• Diagnosis:
–
eosinophilia, + ANCA, extravascular granulomas, pulmonary
infiltrates, hilar shadows, large pulmonary nodules, necrotizing
vasculitis
• Differential Diagnosis:
–
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Wegener’s granulomatosis (no asthma, but more destructive
airway component), Loffler’s syndrome, sarcoidosis, allergic
bronchopulmonary aspergillosis.
Small Vessel Vasculitis
Churgg-Straus (cont.)
• Treatment and Prognosis:
– Corticosteroids
– Immunosuppressives
– Mean survival of 10 years after remission
– Mortality due to cardiac and pulmonary
failure
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Small Vessel Vasculitis
Hypersensitivity Vasculitis
•
Cutaneous necrotizing, allergic, leukocytoclastic
(small debris) vasculitis
• Small vessels with <1 mm necrotic inflammation
(PMNs +/- lymphocytes)
• Epidemiology:
– all ages, abrupt
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Small Vessel Vasculitis
Hypersensitivity Vasculitis (cont.)
• Physical Exam: - constellation of syndromes
– cutaneous signs: palpable purpura, petechiae, vesicles,
urticaria, papules, pustules, necrotic ulcerations,
nodules – usually grouped; arthralgias, arthritis – knees
ankles, wrists, elbows; hematuria
– Cryoglobulinemia – MSK/NS involvements along with
connective tissue disorders
– HSP – gastrointestinal/IBS
• Diagnosis:
– high ESR, leukocytosis, eosiniphilia, anemia, hemepositive stool, hematuria, proteinuria, cryoglobulinemia,
elevated LFTs/Cr.
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Small Vessel Vasculitis
Hypersensitivity Vasculitis (cont.)
• Differential Diagnosis: - collection of all or
individual syndromes
– Serums Sickness, drug hypersensitivity,
Henoch-Schonlein purpura (IgA dominated),
mixed cryoglobulinemia, and urticarial
vasculitis (hypocomplement)
•
Treatment:
– removal of offending agent, tx of systemic
illness, spontaneous resolution up to 4
weeks, may require corticosteroids;
hyperpigmentation scars
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Small Vessel Vasculitis
Wegener’s Granulomatosis
• Necrotizing granulomatous process of respiratory tract
with GN
– of unknown etiology, usually with FSGN
• Necrotizing small artery and vein (fibrinoid) vasculitis –
– at different healing stages, with mononuclear cell
involvement
• Young, middle-aged, male
• Symptoms
– upper and lower pulmonary involvement, cutaneous
lesions, ocular disease, peripheral and CNS, carditis
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Small Vessel Vasculitis
Wegener’s Granulomatosis (cont.)
•
Diagnosis:
– may require tissue biopsy
– high ESR, leukocytosis, thrombocytosis, anemia of
chronic disease;
– + Ab again proteinase 3, myeloperoxidase, human
leukocyte elastase; + ANCA (93% with active disease), ANA
• Differential Diagnosis:
– SLE, other vasculitides, cholesterol atheroemboli,
infective endocarditis, malignancies, fibromuscular
dysplasia, and radiation fibrosis
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Small Vessel Vasculitis
Wegener’s Granulomatosis (cont.)
• Treatment:
– cyclophosphamide and steroids;
requirement of HD can be reversed;
– if unTx, 90% of patients die within 2
years with respiratory or renal failure
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Small Vessel Vasculitis
Behcet’s Syndrome
• Vasoa vasorum vasculitis in large arteries
and veins of unknown etiology
– abnormal neutrophil and lymphocyte
dysfunction
• Eastern Mediterranean region, Turkey,
prevalent along “Silk Road”
– Associated with HLA-B51, HSV, parvovirus B19,
HCV infection
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Small Vessel Vasculitis
Behcet’s Syndrome (cont.)
• Presentation: - multi system
– oral aphthous and genital ulcers, skin
lesions, uveitis, synovitis, valvular and
coronary disease, meningioencephalitis,
renal vascular hypertension, CVA, cerebral
venous thrombosis, thrombophlebitis of both
superficial and DVT, claudication
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Small Vessel Vasculitis
Behcet’s Syndrome (cont.)
•
Diagnosis: CT, MRI, angiography, VQ scan
– Recurrent Oral ulceration - Aphthous or herpetiform
ulcers,
• observed by MD or patient, with >3 episodes over
12 months
– Recurrent Genital Ulceration - Aphthous ulceration
or scarring
– Eye lesions - detection by an ophthalmologist
• Anterior and posterior uveitis, retinal vasculitis,
vitreous cells on slit-lamp examination;
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Small Vessel Vasculitis
Behcet’s Syndrome (cont.)
•
Diagnosis (cont.)
– Skin lesions
• Erythema nodosum, papulopustular, pseudofollicular
lesions or acneform nodules in post-adolescent
patient w/out corticosteroids
– Positive pathergy test:
• + by MD at 24-48 hours (skin hypersensitivity to HLA
B5 Ag)
• Treatment:
– estradiol, dapsone, colchicine, cyclosporine,
levamisole
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Buerger’s Disease
(Thromboangiitis Obliterans)
• Non-atherosclerotic, segmental, inflammatory
thrombotic disease with sparing of vessel wall
– Small and medium arteries, veins and nerves
– Distal extremities, iliac arteries, renal, mesenteric,
internal thoracic arteries, pulmonary, coronary, aorta
and cerebral arteries,
• PMNs, micro-abscesses, and multinucleated giant cells,
progressive organization of thrombus, with subsequent
quieting of inflammation
• 40-45 y.o. men, Far & Middle East, Ashkenazi Jews,
tobacco use
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Buerger’s Disease
(Thromboangiitis Obliterans) (cont.)
• Symptoms:
–
ischemia of distal small arteries/veins in proximal
distribution, manifesting as ulcers and claudication
of the feet, legs, hands or arms, Raynaud’s.
• Diagnosis:
– Highly pathognemonic:
• (1) Age <45, (2) current/recent tobacco use, (3) distal
extremity ischemia and exclusion of autoimmune and
hypercoagulable diseases (4) Nl ESR, nl CRP, nl ANA,
RF, cryoglobulins, complements (5) Positive Allen test in
young smoker with leg ulcerations
– TTE to r/o embolization, arteriogram to assess
multiple limb involvement
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Buerger’s Disease
(Thromboangiitis Obliterans) (cont.)
• Differential Diagnosis:
– scleroderma, CREST, emboli,
hypercoagulable states, repetitive
trauma, other vasculitides
• Treatment:
– discontinuation of cigarette smoking
– Surgery is not recommended due to
diffuse segmental involvement
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Scleroderma
• Presence of thickened, sclerotic skin +/- vascular
involvement
– CREST (Calcinosis, Raynod’s, Esophageal
dysmotility, sclerodactyly, telangiectasia)
– Systemic sclerosis – includes skin and diffuse
disease/organ involvement
• Fibrosis of musculoskeletal, renal, pulmonary,
cardiac and GI systems
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Scleroderma (cont.)
• Immune system, endothelial dysfunction, enhanced
fibroblast activity
– Vascular injury occurs through endothelial cell injury
leading to eventual obliteration of the vessel lumen
and ensuing ischemia
• Activated cytokines (IL-2, TGF-b)
• Symptoms:
– Raynaud’s, digital ulcers or infarcts, arrhythmias
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Scleroderma (cont.)
• Diagnosis:
– clinical findings, skin Bx not necessary
– Systemic scleroderma - Should fulfill 1 major or
2/3 minor criteria
• Major criteria:
– proximal to MCP sclerodermitis skin
changes
• Minor criteria:
– sclerodactyly, digital pitting, scars of
fingertips or loss of substance
– of the finger pad, bibasilar pulmonary
fibrosis
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SLE
Affects skin, joints, kidneys, lungs, nervous system,
serous membranes
•
– unknown cause
– Chronic deposition of immune complexes, cytokine
effects, direct attack by Ab or leukocytes on renal
glomeruli, joins, pleural or pericardial serosa,
cardiac or vascular endothelium, cardiac valves,
and oral or conjuctival mucosa
– fatigue, fever, pleuritic chest pain, in a young
woman, found to have hypertension, mallar rash, a
pleural friction rub, several tender and swollen
joints, and mild peripheral edema
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SLE (cont.)
• Epidemiology
– Women in 20-30
– Genetic, environmental
– Meds: phenytoin, hydralazine,
procainamide, isoniazide can contribute to
SLE.
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SLE
• Vasculitis Presentation
– Small vessels - degenerative changes with minimal
inflammatory changes, chronic immune complex
deposition, cytokine effects on vascular endothelium
– Large to medium vessels - more classic vasculitis
with local thrombosis from anti-phospholipid Ab,
which can involve various sized arteries or veins.
– Endocarditis, with sterile inflammation with diffuse
microembolization
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