Pathogenesis Direct attack by an agent. A process directed
specifically at components in vascular tissue (e.g. ANCA,
anti-basement membrane disease). Secondary to an inflammatory
process (e.g. immune complex disease).
Antineutrophil cytoplasmic antibodies, ANCA Cause of
ANCA-associated vasculitis (AAV) C-antineutrophil cytoplasmic
antibodies (CANCA) against proteinase 3 (PR3) Associated with GPA
and MPA Disease activity is parallel to C-ANCA titer. P-ANCA
against myeloperoxidase (MPO) is non-specific marker for vascultiis
syndrome and other autoimmune diseases
Palpable purpura
Livido reticularis
mononeuritis multiplesx
MONONEURITIS MULTIPLEX Peripheral neuropathy of more than one
nerve roots. Pathogenesis: nerve infarction resulting from
widespread destruction of epineural arterioles. Causes: vasculitis
(esp PAN), diabetes or other autoimmune conditions (eg. SLE,
RA).
Vasculitis syndrome (Vasculitides) 1. 2. 3. Diagnostic triad:
Palpable purpura Glomerulonephritis More than three organs involved
Fever, fatigue, weight loss, granuloma Nerve Airway (ENT, Lung)
Allergy GI Musculoskeletal
Laboratory of vasculitis Screening CBC, ESR, CRP, Urine
analysis, ANA, Rheumatoid factor HBsAg, HCVAb, IgE, Eosonophil,
VDRL Confirmatory IgA, C3, C4 Anti-cardiolipin Ab (ACA),
anti-neutrophil cytoplasmic Ab (ANCA) Cryoglobulinemia
Giant Cell Arteritis (Temporal arteritis) Occurring primarily
over the age of 50 years. Frequent features include fatigue,
temporal headaches, jaw claudication, loss of vision, scalp
tenderness, polymyalgia rheumatica and aortic arch syndrome. Rarely
involves the skin, kidneys and lungs. The ESR is usually highly
elevated
Temporal arteritis
Temporal arteritis
Polymyalgia Rheumatica Myalgia, low-grade fever, fatigue,
weight loss and an elevated ESR. May combined with temporal
arteritis Morning stiffness is usually the predominant feature
Muscular pain is often diffuse and is accentuated by movement; pain
at night is common. Muscle strength is unimpaired although the pain
makes interpretation of muscle testing difficult. Rx:
Corticosteroid treatment is for at least 2 years.
TAKAYASUS ARTERITIS Affecting aorta and its major branches.
most commonly in females under 40 years of age. Clinical features
Systemic phase: malaise, fever, night sweats and fatigue. Occlusive
phase: upper limb claudication, headaches, postural dizziness and
visual disturbances. Reduced or absent upper limb pulses. Arterial
bruits over the carotid, abdominal and subclavian vessels.
At least 3 of 6 criteria
Polyarteritis nodosa (PAN) Medium-sized artery inflammation
involving the skin, kidney, peripheral nerves, muscle and gut.
Polyarteritis nodosa
Polyarteritis nodosa
Kawasaki disease An acute febrile disease occuring most
commonly in infants and children under 5 years of age. Sore red
eyes , red lips tongue or mouth. Redness or swelling of the hands
and feet. Rash all over the body. Vasculitis, especially of the
coronary arteries, is the most serious and life-threatening
complication of the disease.
Kawasaki disease
Granulomatosis with polyangiitis, GPA 2011-4 WEGENER'S
GRANULOMATOSIS (WG) Young and middle age adults Small and
occasionally medium-sized vessel vasculitis Midline granuloma
Necrosis, granuloma formation and vasculitis of the upper and lower
respiratory tracts. Glomerulonephritis in 75% of patients. Fever,
malaise, weight loss, arthralgia, , sinusitis, nasal or oral
ulceration, purpura C-ANCA related.
Eosinophilic granulomatous angiitis (CHURGSTRAUSS SYNDROME)
Small sized artery granulomatous inflammation. Clinical features
History of atopy. Constitutional symptoms fever, anorexia, weight
loss. Asthma. Peripheral neuropathy. Skin involvement nodular
lesions over pressure areas. Peripheral eosinophilia.
At least 4 of 6 criteria
Microscopic polyangiitis, MPA Pathogenesis is presumed to be
due to circulating immune complexes. Cutaneous involvement palpable
purpura or urticaria-like lesions are most common, less common are
livedo reticularis, ulcerations or necrosis. Systemic involvement
arthritis, glomerulonephritis, gastrointestinal hemorrhage or colic
are most common. Skin biopsy: leukocytoclastic vasculitis Kidney
biopsy: pauci-immune segmental necrotizing glomerulonephritis
IgA Vasculitis (HenochSchnlein purpura) A specific vasculitic
syndrome which is due to IgA immune complexes and IgA deposition
within the vessels and the kidney. mainly in children and young
adults The full spectrum includes palpable purpura, nephritis,
arthritis and gastrointestinal involvement.
Hypersensitivity vasculitis
Urticarial vasculitis
Antiphospholipid Antibodies Syndrome (APS) 1 clinical + 1 lab
criteria Clinical criteria 1. Vascular thrombosis arterial, venous,
or small-vessel thrombosis 1. Pregnancy morbidity One or more
late-term (>10 weeks gestation) spontaneous abortions One or
more premature births at or before 34 weeks gestation Three or more
spontaneous abortions before 10 weeks gestation Laboratory
criteria: on at least 2 occasions at least 12 weeks apart (1)
anticardiolipin (aCL), (2) antib2 glycoprotein I (anti-b2 GPI), (3)
Lupus anti-coagulant
Behcet disease 1. 2. 3. 1937: Turkish dermatologist Hulusi
Behcet first described. A type of vasculitis and pannivulitis
Symptom-complex of recurrent oral aphthous ulcers, genital ulcers,
and uveitis.
Recurrent oral ulceration Minor or major aphthous, or
herpetiform ulceration observed by physician or patient that
recurred at least 3 times in one 12-month period Plus 2 of the
following criteria: Recurrent genital ulceration Eye lesions
Aphthous ulceration or scarring observed by physician or patient
Skin lesions Positive pathergy test Anterior uveitis, posterior
uveitis, or cells in vitreous on slit lamp exam.; or retinal
vasculitis observed by ophthalmologist Erythema nodosum observed by
physician or patient, pseudofolliculitis or papulo- pustular
lesions; or acneiform nodules observed by physician in
postadolescent patients not receiving corticosteroid Tx Read by
physician at 24-48 hr International Study Group for Behcet's
Disease: Criteria for the diagnosis of Behcet's disease. Lancet
335:1078-1080, 1990.
Therapy of Vasculitis 1. Corticosteroid with or without 2.
Cytotoxic drugs
Steroid Therapy Glucocorticoids initially: 1 mg/kg/day
prednisone tapering of the dosis: 5-10 mg every week, from 15
mg/day only 1 mg every several week, treatment at least for 2 years
pulsus steroid: 1 g/day for 3 days 0.5 mg/kg/day after megadose
pulse therapy
Indication for addition of cytotoxic drug to prednisone on
initial evaluation, rapidly progressive vasculitis with significant
visceral involvement prednisone in high daily divided dosis is not
controlling the activity and progression of vasculitis prednisone
dose cannot be tapered to tolerable level and still controll the
disease
Other Treatment of Vasculitis 1. 2. 3. 4. 5. Aspirin
Anticoagulants Plasmapheresis Intravenous immunoglobulin, IVIG
Biological agents 1. Anti-TNF: () 2. Anti-CD20, Rituximab for
ANCA-associated vasculitis
Conclusion Vasculitis is a syndrome and disease spectrum
Classification depends on vascular size and clinical manifestations
ANCA, anti-cardiolipin antibody are key autoantibodies Treated by
steroid and cytotoxic drugs
