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40 - Systemic Vasculitis

Terms in this set (56)

- Heterogeneous group of disorders linked by the
primary finding of inflammation within the
walls of blood vessels
Definition of vasculitis
- 3 areas in normal vascular wall/involved in vasculitis
1. intima
2. media
3. adventitia
Histology of normal muscular artery
- inflammation within wall, BV become narrow or totally occluded--> tissue ischemia or infarction --> dilation could lead to rupture or bleeding
Pathophysiologic Mechanism of Vasculitis
...
Vasculitis classification
- aorta and its major branches
- HA, visual loss, aortitis
Large vessels and correlation with clinical symptoms
- vessels with all 3 layers
- tissue ischemia, infarction --> livedo reticularis, skin ulcerations, digital infarction, renovascular hypertension, intestinal angina/infarction, mononeuritis multiplex (infarction of the nerve), CVA, CAD
Medium sized vessels and correlation with clinical symptoms
- arterioles
- venules
- capillaries
- rupture, bleeding --> palpable purpura, alveolitis (ruptured of BV in lung), glomerulonephritis
Small vessels and correlation with clinical symptoms
- large and medium sized
- used to diagnose vasculitis
What sized vessels can an arteriography be performed on?
- inflammation of inflammatory cells in BV wall
- Giant cell arteritis
- Takayasu's arteritis
Large vessel vasculitis
= temporal arteritis
- >50, commonly elderly
- extracranial branches of carotid arteries including temporal artery
Giant cell arteritis (GCA)
- other name
- age
- arteries involved
- throbbing temporal headaches**
- jaw claudication (jaw pain with chewing)
- visual loss - external ophthalmic artery involvement (branch of carotid artery)
- constitutional symptoms - fever, weight loss,
night sweats
- aortitis - inflammation of aortic arch --> arm claudication (pain) with no pulse, aortic aneurism, aortic insufficiency
Giant cell arteritis (GCA) - clinical presentation
- GCA - thickened, tender blood vessels on Temporal Head
- GCA - ischemic retinopathy, visual loss
- seen in advanced phase of disease
- temporal artery biopsy*
- arteriography
Giant cell arteritis (GCA) Diagnosis
- high dose GC (prednisone)
Giant cell arteritis (GCA) Treatment
- >50, elderly
- pain and stiffness in muscles of neck, shoulders, lower back, hips
- elevated ESR and CRP (inflammation markers)
- treat - intermediate-dose GC
- associated with GCA in 10-15%
Polymyalgia rheumatica (PMR)
- age
- clinical symptoms
- lab
- treatment
- associated with
- young (< 40 years old), F, asian
- aortitis - arm claudication, pulselessness, aortic aneurysm, aortic insufficiency, renovascular hypertension
- carotid artery - headaches, visual loss
- Constitutional symptoms - fever, night sweats,
weight loss, myalgia
- Dx - arteriography
- Tx - high-dose glucocorticoids
Takayasu's arteritis
- age, gender, ethnicity
- clinical presentation
- diagnosis
- treatment
- polyarteritis nodosa (PAN)
- kawasaki disease
What are the medium size vessel vasculitis?
Takayasu's arteritis
- L - early stage
- R - late stage
Takayasu's arteritis
- aneurism, leaking of BV
- constitutional symptoms: fever, weight loss
- renovascular hypertension from renal artery involvement (high BP)
- intestinal angina or infarction from mesenteric
artery involvement (stomach pain)
- peripheral neuropathy: sensory and motor
neuropathy, mononeuritis multiplex
- skin ulcerations, nodules, livedo reticularis,
digital ulcerations
- No involvement of lungs (alveoli) and kidneys
(glomeruli)
Polyarteritis nodosa (PAN) clinical manifestations
- negative
Polyarteritis nodosa (PAN) ANCA+/- ?
- Hep B in 10%
Polyarteritis nodosa (PAN) viral association
Polyarteritis nodosa (angiogram)
- beading of BV due to vascular wall involvement
Microaneurysms of renal arteries in PAN
- small aneurisms in kidney due to PAN
- Arteriography
- Biopsy: skin biopsy (full thickness), sural nerve biopsy
PAN Dx
...
Diagnostic algorithm of small vessel vasculitis
- Induction: High dose Glucocorticoids + Cyclophosphamide
- Maintenance: Methotrexate or Azathioprine
PAN induction treatment and maintenance
- ANCA associated vasculitis
- immune-complex mediated vasculitis
What are the small vessel (+medium sized vessels) vasculitis?
1. Granulomatosis with Polyangiitis (GPA) (=Wegener's Granulomatosis)
2. Microscopic Polyangiitis (MPA)
3. Eosinophilic Granulomatosis with Polyangiitis
(EGPA) (=Churg-Straus Syndrome)
ANCA-associated vasculitis types
- detected by indirent immunofl
- substrate is neutrophils, patient serum added with fl tagged ab
- binds Fc portion of ab in patient
ANCA (Antineutrophil Cytoplasmic Antibody)
1. cytoplasmic C-ANCA- anti-PR3
2. perinuclear P-ANCA- anti-MPO, localized around nucleus
Two patterns of ANCA
ELISA test to ID antigen
- C-ANCA can be PR3
- P-ANCA
PR3 and MPO are pathogenic, direction against other antigens, significance unknown
- must combine IF and ELISA (either alone is NOT diagnostic)
- standard of care
- specificity > 95%
ANCA testing
- associated with C-ANCA and anti-PR3
- granulomatous lesions and vasculitis
Granulomatosis with Polyangiitis
- Pneumonitis
- Alveolar hemorrhage
- Interstitial lung disease
- Pulmonary nodules
- Pleural effusion
Granulomatosis with Polyangiitis clinical manifestations
- localized wegeners - isolated upper respiratory invovlement***
- kidney involvement
- sinusitis
- septal perforation
- oral ulcers
- otitis media
- subglottic stenosis
- acute or chronic
- causes vasculitis and extravascular involvement
- Neurologic - peripheral neuropathy, CNS vasculitis, sensoryneural hearing loss
- Gastrointestinal - mesenteric vasculitis
- Vascular - gangrene, venous thrombosis
- Musculoskeletal - arthritis
Granulomatosis with Polyangiitis clinical manifestations
Associated with P-ANCA and anti-MPO
• No granulomatous Lesions
• Involves Lungs and kidneys, not upper
respiratory tract
• Always acute
• Dx and Tx - same as GPA
Microscopic Polyangiitis (MPA)
- associated with?
- organ involvement?
-
- kidney invovlement in Granulomatosis with Polyangiitis
- Necrotizing GN (Crescent formation)
- No immune deposits (Pauci-immune)
- No granuloma
**helps distinguish between SLE
Granulomatosis with Polyangiitis clinical manifestations
- non-blanching
- cutaneous involvement of Granulomatosis with Polyangiitis
- Palpable purpura
- Subcutaneous nodules
Granulomatosis with Polyangiitis clinical manifestations
Granulomatosis with Polyangiitis
- Scleritis
- Conjunctivitis
- Uveitis
- Retro-orbital pseudotumor
clinical manifestations of...
- Retro-orbital peudotumor
- aggregation of inflammatory cells
Granulomatosis with Polyangiitis clinical manifestations
- activation of neutrophils
- inflammation cascade - inflammation of BV
Pathogenesis of GPA
- C-ANCA & Anti-PR3 (negative in 10% - 40% disease)
- Biopsy*
- Standard for diagnosis
- Not a dichotomous outcome
- Open lung biopsy (most informative), bronchoscopy guided lung biopsy, sinus biopsy, kidney biopsy, skin
biopsy
Diagnosis of GPA
- originally treatment for B cell lymphoma
- depletes naive and memory B ells which express CD20 (anti-CD20)
- spares pro B cells and plasma cells
- effective in ANCA vasculitis and RA
Rituximab - treats which vasculitis?
- type of ANCA vasculitis
- associated with P-ANCA and anti-MPA
- no granulomatous lesions
- involves lung, kidney, not upper resp tract
- always acute
- Dx and Tx- same as GPA
Microscopic Polyangiitis (MPA)
- Induction- high dose GD + Cyclophosphamide, Rituximab (anti-CD20) + Glucocorticoids
- Maintenance - Methotrexate, Azathioprine
Treatment of GPA
- Vasculitis with allergic rhinitis, asthma and eosinophilia
- Associated with p-ANCA (in 40-60%)
- Granulomatous lesions with eosinophilic infiltration
- Dx - biopsy (lung, endomyocardial)
- Tx - glucocorticoids, cyclophosphamide, methotrexate
Eosinophilic Granulomatosis with Polyangiitis (EGPA)
- what?
- associated with?
- histology?
- Dx?
- Treatment?
1. Hypersensitivity Vasculitis
2. Cryoglobulinemic Vasculitis
3. Henoch-Schonlein Purpura (IgA Vasculitis)
What is included in Immune Complex-Mediated Vasculitis?
- Hep C
What virus is Cryoglobulinemic vasculitis associated with?
- purpura in lower extremities
- Cutaneous ulcerations, digital gangrene, livedo
reticularis
- Arthralgia
- Membranoproliferative GN
- Peripheral neuropathy
Cryoglobulinemic vasculitis clinical presentation
- immunoglobulin that are characterized by their tendency to precipitate under conditions of cold; not always pathogenic
What is Cryoglobulin?
- Type I - hyperviscosity syndrome, IgG and IgM - MM, waldenstroms macroglobulinemia
- Type II (polyclonal IgG and monoclonal IgM)- vasculitis
- Type III (polyclonal IgG and IgM) - vasculitis, associated with Hep C
Cryoglobulinemic vasculitis - Type I, II, III
- Biopsy -skin biopsy, kidney biopsy
- Serum cryoglobulin
- Rheumatoid factor
- Complement - especially low C4
Cryoglobulinemic vasculitis diagnosis
...
• Immunosuppressive therapy:
- High dose glucocorticoids + Cyclophosphamide
- Rituximab (anti-CD20)
- Plasma exchange
• Treatment of hepatitis C if positive for hep C
Cryoglobulinemic vasculitis treatment
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