Vasculitides Flashcards
What are the three mechanisms of vasculitides?
- immune complex
- ANCA
- granulomatous
By which mechanism do the following disorders cause vasculitides?
(a) SLE
(b) GPA
(c) Cryoglobulinemia
(d) Hypersensitivity
(e) EGPA, Churg-Straus
(f) Microscopic Polyangiitis
(g) Takajasu’s
(h) Henoch-Schonlein Purpura
(i) Giant Cell Artritis
(j) RA
Mechanisms of vasculitides
(a) SLE => immune complex
(b) GPA => granulomatous and ANCA
(c) Cryoglobulinemia = immune complex
(d) Hypersensitivity = immune complex
(e) EGPA (Churg-Straus) = ANCA associated
(f) Microscopic Polyangiitis = MPA = ANCA
(g) Takajasu’s = granulomatous
(h) Henoch-Schonlein Purpura = immune complex
(i) Giant cell arteritis = granulomatous
(j) RA = immune complex mediated
Name two large vessel vasculitides?
Giant cell arteritis and Takajasu’s
What is the prototypical medium vessel arteritis?
PAN = polyarteritis nodosa
Describe the mechanism of immune complex vasculitis
Immune complexes form when there is an excess of antigens and antibodies (often from presence of autoantibodies => Ag-Ab complexes form in circulation then deposit in tissues, or less commonly may form directly in tissues
- immune complexes then activate complement which generates anaphylatoxins and chemoattracts for platelets and neutrophils
- neutrophils infiltrate and release superoxide anions and lysosomal enzymes that injure tissues
Overall:
Formation of immune complexes –> ICs deposit in BV wall –> Neutrophils release lysosomal enzymes –> Fibrinoid necrosis of BV wall
What is ANCA?
(a) Two ways to measure presence of ANCA
ANCA = anti-neutrophil cytoplasmic antibodies
a) ANCA presence can be detected by indirect immunofluorescence or ELISA to specific antibodies (to PR3 or MPO
C-ANCA vs. P-ANCA
(a) location of fluorescent staining
(b) associated with presence of which autoantibody
(c) associated most strongly w/ which vasculitides
C-ANCA vs. P-ANCA
C-ANCA
(a) cytoplasmic
(b) PR-3 autoantibody
(c) strongly associated w/ GPA (granulomatous vasculitis)
P-ANCA
(a) Perinuclear
(b) Anti-MPO (myeloperoxidase) enzyme
(c) More strongly seen in EGPA and MPA
Describe the pathogenicity of ANCA
- ANCA binds to neutrophils and monocytes, directly inducing ROS release and degranulation
- ANCA binds to endothelial cells and induces injury
In ANCA vasculitides what titers can be monitored to tract treatment response and predict relapse?
Can monitor anti-MPO (EGPA and MPA) and anti-PR3 (GPA) antibodies to monitor treatment response and predict relapse
Mechanism of granulomatous vasculitis
(a) Antigen
(b) Main cells involved
(c) Key cytokine and its fxn
(d) Key histological finding
Granulomatous vasculitis
(a) Unknown antigen activates
(b) Th1 cells to secrete
(c) Interferon gamma which activates macrophages to form mononuclear cell infiltrates w/ epithelioid cell transformation and granuloma formation
(d) Multinucleated giant cells
Common presentation of a granulomatous vasculitis
Constitutional symptoms: fever, fatigue, weakness
Ddxs to rule out when considering granulomatous vasculitis
Infection, Tb, malignancies (mets or paraneoplastic syndrome)
Describe the pathology of the large vessel vasculitides
Large vessel vasculitides = Giant cell/temporal arteritis + Takayasu’s
Pathologically: giant cells, granulomatous inflammation, obliteration of lumen by intimal hyperplasia
Differ the prototypical patient (age and ethnicity) in the large vessel vasculitides
Giant cell arteritis: pt > 50s, Caucasian
Takayasu’s: pt
Distinguish the typical distribution of the two large vessel vasculitides
Giant cell arteritis: most commonly seen in the extracranial branches of the carotid artery (ex: temporal artery)
Takayasu’s: typically involves the aorta or aortic main branches (abdominal aorta, arch of aorta)
Gold standard test to diagnose giant cell arterities
(a) Other tests used
Gold standard test for giant cell arteritis = temporal artery biopsy
(a) Less invasive alternatives = doppler ultrasound, angiogram
What is polymyalgia rheumatica (PMR)?
(a) Hallmark findings
(b) Closely associated w/ which vasculitides?
PMR = pelvic and shoulder pain, no vasculitis if just PMR alone
(a) Hallmark findings = pelvic and shoulder pain
(b) 40-60% of giant cell arteritis cases at some point have PMR
What symptoms can help you diagnose GCA over PMR?
How to tell pt has giant cell arteritis and not just polymyalgia rheumatica?
PGA
- unilateral headache
- possible change/loss of vision b/c of ischemic optic neuropathy
- jaw claudication
- system features: fever, weakness, fatigue, wt loss
PMR
-just hip/shoulder pain w/o any of the other symptoms associated w/ PGA
Differentiate the treatment of GCA and PMR
Both giant cell arteritis and polymyalgia rheumatic are responsive to steroids, but need to use very different doses (much higher in giant cell)
GCA: around 60 mg
PMR: around 15 mg
How is Takayasu’s arteritis diagnosed?
Not going to biopsy the aorta…=> use imaging
-CT angiogram, MRI angiogram: shows stenosis of aortic arch etc
2 key exam findings of Takayasu’s arteritis
Pts frequently present w/ arm claudication
- decreased radial pulses
- accelerated athosclerosis
Treatment for Takayasu’s arteritis
(a) Adjuvant therapy
Takayasu’s arteritis tx = steroids
Also can use steroid sparing agents: MTX and Azothiporine (IL-6Ra)
(a) Adjuvant therapy = aspirin or anti-platelet drug b/c there’s accelerated atherosclerosis in Takayasu’s
Why may a patient with polyarteritis nodosa have postprandial abdominal pain?
PAN = medium artery vasculitis w/ predilection for arterial bifurcation => ischemia of the gut => angina of the gut basically
-if arteries to the gut are blocked then can’t increase supply when needed after a meal
What type of arteritis is most likely: 50 yo white male w/ left hand numbness and right foot drop?
PAN = polyarteritis nodosa- medium vessel disease
