Vasculitis Flashcards
What is vascultis?
heterogenous group of uncommon (primarily autoimmune), occasionally life-threatening diseases having in common inflammation of blood vessels
What are the 2 major divisions of vasculitis?
1) infectious
2) non-infectous (primary)
What are the 3 most common causes of infectious vasculitis?
fungal- aspergillus
bacterial- pseudomonas
viral- CMV
How might giving steroid therapy to a patient with infectious vasculitis kill them?
steroids are anti-inflammatory and giving steroids to a patient with an infection will kill off all the things needed to mount an immune response to get rid of the infection
What is giant cell arteritis?
temporal arteritis - multinucleated giant cell attack on calcified internal elastic lamina in arteries or calcified media of thoracic aorta
What are the primary immune cells in arteries?
immature dendritic cells
How do dentritic cells get activated in he blood vessels?
antigens from pathogens or calcifications litigate TLRs which stimulate the PAMP/DAMP pathway whcih activates intracellular TRAM that stimulates NFkB to enter the nucleus and increase transcription of pro-inflammatory cells
What is the major dendritic receptor in adventitial cells?
TLR-4
Activated dendritic cells have what 3 functions?
1) Produce IL-12 and IL-18
2) Release lots of IFN-gamma, IL-2, and IL-6 that recruit inflammatory cells and increase T cell proliferation
3) Release “homing chemokines”
What is a “homing chemokine”? What does it do?
CCL19 and CCL21 bind to CCR7 and “trap” dendritic cells in the vessel
Progression of immune response in giant cell arteritis depends on what two cell types?
Th1
Th17
What does Th1 do to progress giant cell arteritis?
Release IL-12 and IFN-gamma that upregulates VEGF and PDGF which leads to lumen stenosis and an inflammatory loop where VEGF stimulates production of IFN-gamma that leads to giant cells and granuloma formation
How does Th17 progress giant cell arteritis?
release IL-1, -6, and -17 which create a proinflammatory environment that recruits activated monocytes to the arterial wall
What is released by macrophages and SM cells to destroy elastin and lead to matrix degeneration, intimal hyperplasia, and lumenal narrowing?
MMP-2 and MMP-9
What is the epidemiology of giant cell (temporal) arteritis?
Common, primarily in elderly white females (>50) of Northern European descent
What are the most common symptoms of giant cell arteritis?
headache Visual disturbances--> can lead to blindness Jaw claudicaiton Swollen, tender artery Scalp tenderness FEVER
What vessels are affected in giant cell arteritis?
Involves temporal and ophthalmic arteries and thoracic aorta
What inflammatory disease is typically associated with temporal arteritis?
polymyalgia rheumatica (40% of cases)
How do you diagnose temporal arteritis?
high ESR (over 40 mm/hour) and positive biopsy (of temporal artery)
How do you treat temporal arteritis?
steroids (sometimes aspirin)
What is Takayasu Arteritis?
Granulomatous vasculitis of aortic arch at branch points with transmural scarring and thickening and severe luminal narrowing of branches (VERY similar to giant cell arteritis)
What factor is key in diagnosing Takayasu arteritis versus temporal arteritis?
AGE - same diagnosis and treatment, but Takayasu arteritis occurs in patients younger than 50 y/o
What are the symptoms of Takayasu arteritis
ocular disturbances and marked weakening of pulses in upper extremities, neurological problems
What is polyarteritis nodosa?
Vasculitis of small or medium-sized muscular arteries that typically involves renal and visceral vessels and spares pulmonary circulation. Healing of the lesions leaves behind some fibrosis
Polyarteritis Nodosa is commonly associated with what?
Hepatitis B immune complex formation
What is unique about the morphology of polyarteritis nodosa?
see lesions at all stages of activity suggesting ongoing & recurrent pathogenic insults
What are the signs/symptoms of polyarteritis nodosa?
HTN (renal involvement), melena and abdominal pain, neurologic disturbances, skin lesions (SYSTEMIC SYSTEMS)
What would a skin biopsy of polyarteritis nodosa show?
fibrinoid necrosis (NOT FIBRIN), inflammatory cells that surround the vessels and all the wall through the wall (transmural)
Who gets polyarteritis nodosa?
middle aged men
Why is polyarteritis nodosa a must-not-miss diagnosis?
because it is 90% treatable with immunosuppression (cyclophosphamide) and 100% fatal if non-treated
What leads to death in polyarteritis nodosa?
renal failure
What is Kawasaki disease?
(mucocutaneous lymph node syndrome) an acute childhood primary vasculitis of medium arteries (especially coronaries)
Who gets Kawasaki disease?
1-2 year old children, slightly more boys, an more common in Japanese
What are the symptoms of Kawasaki disease?
persistent high fever conjunctivitis mucosal and skin erythema edema (palms and soles with peeling) erythematous maculopapular skin rash cervical lymphadenopathy strawberry tongue
What are the complications of Kawasaki disease?
arterial rupture
MI
death
What is the proposed pathogenesis in Kawasaki disease?
aberrant immune reaction to a ubiquitous RNA virus that can become persistent in genetically predisposed individuals
What is the proposed treatment for Kawasaki disease?
aspirin with IV Ig but usually self-limited
What is Microscopic Polyangitis?
Necrotizing vasculitis that generally affects capillaries and is a feature of immune disorders like Henoch-Schonlein purpura, antibody responses to drugs, etc.
What is the immunologic cause of microscopic polyangitis?
MPO-ANCA lysosomal granule constituent involved in free-radical generation
What organs are typically affected by microscopic polyangitis?
kidney and lungs
What are the major complications of microscopic polyangitis?
necrotizing glomerulonephritis and pulmonary capillaritis
How do you treat microscopic polyangitis?
immmunosuppression and removal of offending agent.
What is the other name of Wenger’s Granulomatosis?
granulomatosis with polyangiitis
What is granulomatosis with polyangiitis?
Cell-mediated hypersensitivity response directed against inhaled infectious or environmental agents.
What is the immunologic cause of granulomatosis with polyangiitis?
Tissue injury driven by PR3-ANCA
What does a biopsy of granulomatosis with polyangiitis look like?
biopsy shows large necrotizing granulomas and geographic necrosis with basophilic debris (nuclear dust)
What organs are affected by granulomatosis with polyangiitis?
nasopharynx, lung, kidney
What is the typical presentation of granulomatosis with polyangiitis?
40 y/o man with pneumonitis, sinusitis, mucosal ulcerations, renal disease
What are the signs and symptoms of granulomatosis with polyangiitis?
Triad: granulomas of lung and URT, vasculitis, glomerulonephritis.
How do you treat granulomatosis with polyangiitis?
cyclophosphamide and steroids
What is Churg-Strauss Syndrome?
Hyperresponsiveness to normally innocuous allergic stimulus
What is the immunologic cause of Churg-Strauss Syndrome?
MPO-ANCAs
What are the signs and symptoms of Churg-Strauss Syndrome?
asthma, eosinophilia, necrotizing granulomatous inflammation!
What are the complications of Churg-Strauss symtome?
cardiomyopathy from cardiac involvemnt, palpable purpura, renal disease, GI bleeds
What are the possible immunologic causes of vasculitis?
Immune complex deposition
ANCAs
Anti-endothelial cell antibodies
Autoreactive T cells
What are the 2 types of vasculitis with immune complex eposition?
- Drug-hypersensitivity vasculitis (Ab’s against drug modified proteins)
- Vasculitis secondary to infections (Ab to microbial constituents form immune complexes that circulate and deposit in vascular lesions)–> ex. polyarteritis nodosa
What do ANCAs do?
directly activate neutrophils, stimulating the release of ROS and proteolytic enzymes leading to endothelial cell injury.
What is PR3-ANCA? When do you see it?
azurophilic granule constituent that shares homology with numerous microbial peptides (in Wenger granulomatosis)
What is MPO-ANCA? When do you see it?
lysosomal granule constituent involved in free-radical generation—associated with microscopic polyangiitis and C-S syndrome
When do you see anti-endothelial cell antibodies?
Kawasaki disease
