Pathology of Vasculitis Flashcards
What is vasculitis?
a group of disorders that destroy blood vessels by inflammation
What things are important to keep in mind when considering vasculitis?
size (large, small) and type of vessel (artery, vein)
sex, age, ethnicity
clinical features (renal, GI symptoms)
histology
immune complexes
anti-neutrophil cytoplasmic antibodies: ANCA
anti-endothelial cell antibodies
If there are immune complexes associated with vasculitis, what will you see?
immune reactants and complement detected in serum or vessels.
What immune complexes will be found in systemic lupus erythematous (SLE)?
DNA-anti-DNA complexes found in vessels
Can hypersensitivities to drugs cause vasculitis?
YES
Can vasculitis be associated with viral infections?
YES
**What are anti-neutrophil cytoplasmic antibodies (ANCAs)?
group of antibodies that are formed against enzymes in the azurophil or primary granules in neutrophils, lysosomes of monocytes, and in endothelial cells due to defects in immune regulation. Titers reflect clinical severity. The etiology (cause) may be linked to neutrophils activated by ANCAs.
In what diseases are anti-neutrophil cytoplasmic antibodies (ANCAs) seen?
SLE and Kawasaki disease
Can ANCAs directly activate neutrophils?
YES, stimulating release of ROS and proteolytic enzymes. It is this activation that can cause destructive interactions between inflammatory cells and endothelial cells.
What are the 2 types of vasculitis?
- Anti-proteinase 3 (PR3-ANCA, formerly c-ANCA)= cytoplasmic localization of staining target antigen being proteinase 3 (PR3).
- Anti-myeloperoxidase (MPO-ANCA, formerly p-ANCA)= perinuclear staining specific for MPO
* Some vasculitis will be positive for both and some will be negative for both of these ANCAs.
What is polyarteritis nodosa (PAN)?
inflammation of many medium sized arteries with some nodularity to them. Renal and GI involvement is common. The pulmonary vessels are spared however.
How does polyarteritis nodosa present?
as acute, subacute, or chronic lesions with hypertension (renal involvement), wt. loss, fatigue, abdominal pain, GI hemorrhage, and melana (dark sticky feces) in young adults.
Will also see elevated ESR and leukocytosis (increase in WBCs).
Renal involvement is usually cause of death.
Does polyarteritis nodosa affect just segments of arteries?
YES, but it is transmural (entire thickness of wall) necrotizing inflammation. Early lesions are fibrinoid that cause fibrous thickening of the vessel wall.
** What is important to remember about stages of polyarteritis nodosa?
All stages coexist in different vessels or the same vessel!
Is the glomerulus involved in polyarteritis nodosa (PAN)?
NO! This is a small vessel, and even though the kidney is involved, it only affects MEDIUM vessels.
**For what antigen are many people with polyarteritis nodosa positive?
(board question)
Hepatitis B antigen
Is there an association with c-ANCA in polyarteritis nodosa?
NO!
What happens to a vessel when it becomes injured?
It becomes pro-thrombotic with mixed inflammatory infiltrates
Where specifically within the vascular system will PAN commonly affect?
arterial branch points
How do you treat PAN?
anti-inflammatory and immunosuppressive therapy is very effective
What is microscopic polyangiitis?
histologically similar to PAN, but the lesions will all be of the SAME age. You will see palpable purpura of the skin and may see hemoptysis, glomerulonephritis, and pulmonary capillaritis (because this affects SMALL vessels).
How do you diagnose microscopic polyangiitis?
skin biopsy
What ANCA is associated with microscopic polyangiitis?
MPO-ANCA (p-ANCA)
Is there granulomatous inflammation in microscopic polyangiitis?
NO.
Does microscopic polyangiitis have fragmented neutrophils?
YES
Does immunosuppression help to treat microscopic polyangiitis?
YES, just like PAN.
What is Churg-Strauss Syndrome?
Small-vessel vasculitis causing necrotizing granulomatous inflammation with eosinophils involving multiple organs, especially lungs and heart. Allergic rhinitis and bronchial asthma are also often present.
Can be positive for MPO/p-ANCAs and mimic PAN or microscopic polyangiitis.
What is Churg-Strauss syndrome also know as?
allergic granulomatosis and angitiis
In Churg-Strauss, will you see infiltration of vessels and perivascular tissue by neutrophils?
YES, not unlike PAN or microscopic polyangiitis
What is the primary cause of death in Churg-Strauss syndrome?
coronary arteritis and myocarditits (heart muscle due to perivascular infiltrates)
What is temporal (giant cell) arteritis?
most common large-vessel vasculitis among older individuals (usually females) commonly affecting the temporal or ophthalmic artery causing facial pain and headache. Can also affect the aorta.
Causes granulomatous inflammation and fragmentation of internal elastic membrane, reducing luminal diameter and can lead to ischemia.
How do you diagnose temporal (giant cell) arteritis?
biopsy
What is Takayasu arteritis?
large-vessel granulomatous vasculitis that classically involves the aortic arch at branch points, brachiocephalic, subclavian, or carotid arteries leading to weakening of the pulses in the extremities.
You will also see adventitial fibrosis of the affected arteries.
How does Takayasu arteritis present?
classically in young Asian females as visual and neurologic symptoms with weak or absent pulse “pulseless disease”..
How do you treat Takayasu arteritis?
corticosteroids.
Will you see giant cells in Takayasu arteritis?
YES because it is granulomatous
What is infectious arteritis?
localized arteritis from direct invasion of bacteria and fungi, most commonly Pseudomonas, Aspergillus and Mucor species.
Often seen after bacterial pneumonia and TB
What does infectious arteritis often cause?
mycotic aneurysms= weakening of the vessel wall from infections. This takes the endothelium from an anti-thrombotic state to a pro-thrombotic state inducing thrombosis and infarction
What diseases tend to be associated with vasculitis?
systemic diseases, lupus (SLE), RA, or malignancies. Many of these will resemble symptoms similar to PAN.
What is Kawasaki disease (mucocutaneous lymph node syndrome)?
medium-vessel vasculitis affecting asian children and presenting with oral erythema, conjunctivitis, and rash of palms and soles with enlarged cervical lymph nodes.
Thrombi and infarcts can also occur.
It is actually the leading cause of acquired heart disease in North America and Japan.
How do you treat Kawasaki disease?
aspirin and IVIG
What is important to remember with Kawasaki disease?
Kawasaki, Kids, Konjunctivitis, and Koronaries
What vasculitis does Kawasaki resemble?
PAN and has transmural inflammation.
What causes Kawasaki disease?
autobodies (not ANCAs) to smooth muscle cells and endothelial cells
What is Wegener Granulomatosis (granulomatosis with polyangiitis)?
small-vessel vasculitis causing necrotizing granulomatous (think giant cells) vasculitis involving nasopharynx (mucosal granulomas), lungs, and kidneys (glomerulonephritis). More males.
PR3/c-ANCA associated! Can cause death if untreated.
What can Wegener’s mimic?
TB. You may have significant alveolar hemorrhage.
What causes Wegener’s?
immunologic mechanism
How do you treat Wegener’s?
cyclophosphamide and steroids
What is Buerger disease (thromboangiitis obliterans)?
medium-vessel necrotizing vasculitis involving digits, seen in younger male smokers (due to hypersensitivity to tobacco extracts).
Inflammation will permeate the entire vessel wall and can lead to gangrene or amputation. Thrombosis occludes lumen and contains microabscesses.
DON’T CONFUSE WITH BERGER’S DISEASE
