Vasculitis Flashcards
(38 cards)
Vasculitis
General term for inflammation of blood vessel wall
Vasculitis Clinical Features
- Varied, depend on size and location of vessel targeted
- In addition to localized effects, vasculitis may frequently include systemic symptoms (fatigue, myalgias, arthralgias, malaise)
Vasculitis Classification Schemes
- Forms of vasculitis grouped according to:
1) size/diameter of vessel involved
2) role of immune complexes
3) presence of specific autoantibodies
4) presence/absence of granuloma formation
5) organ specificity
6) patient population most affected - Clinical and pathologic features of various entities can overlap
Vasculitis Main Pathological Mechanisms
- Immune-mediated inflammation (non-infectious)
- Direct invasion of blood vessel by infectious pathogens
Non Infectious Vasculitis
•Immunologic injury to blood vessels may be due to:
- Immune complex deposition
- Anti-neutrophil cytoplasmic antibodies (ANCA)
- Anti-endothelial cell antibodies
- Autoreactive T-cells
•Treatment generally involves various forms of immunosuppression: Corticosteroids, cyclophosphamide, anti-TNF agents, intravenous immunoglobulin (IVIg)
Non Infectious Vasculitis - Immune Complex-Associated Vasculitis
- Usually seen in systemic disorders, associated with autoantibody formation
a. SLE
b. Serum sickness
c. Arthus reaction - Also seen in:
a. Drug hypersensitivity vasculitis
i. Antibodies form against drug-modified self-proteins or against foreign molecules from drug
b. Immunologic vasculitis secondary to infection (not direct invasion of organism into vessel)
i. Antibodies form to circulating antigens related to microbes and subsequent complexes form and deposit in vessels, causing vasculitis
Non Infectious Vasculitis - Immune Complex-Associated Vasculitis Morphologc Features
a. Acute inflammation of vessels with associated immune complexes
i. If due to SLE – will have “full house” staining on immunofluorescence
b. Affected vessels may have fibrinoid necrosis
c. Renal manifestations of SLE vary by class
Non Infectious Vasculitis - Anti-Neutrophilic Cytoplasmic Antibody (ANCA) Associated Vasculitis
- ANCA = group of antibodies that react with neutrophil cytoplasmic antigens
a. Detection of ANCA very useful for diagnosis
b. Titer of ANCA usually correlates with disease severity, recurrence - Two types a. Anti-proteinase 3 (PR3) – i.e. c-ANCA (c = cytoplasmic staining pattern on immunofluorescence)
b. Anti-myeloperoxidase (MPO) – i.e. p-ANCA (p = perinuclear staining pattern on immunofluorescence) - ANCA’s thought to be implicated directly in pathogenesis of the vasculitis
a. ANCA can activate PMN’s, stimulate release of reactive oxygen species and proteolytic enzymes, and induce inflammation - ANCA’s are directed against cellular antigens and cause local injury (type II hypersensitivity) but do not form circulating immune complexes to any significant degree
a. Vascular lesions do not contain discrete immune complexes when visualized under immunofluorescence, therefore they are “pauci-immune” - ANCA-associated vasculitis tends to predominantly affect lung and kidney (“pulmonary renal syndrome”), although other organs can be involved
Non Infectious Vasculitis - Anti-Neutrophilic Cytoplasmic Antibody (ANCA) Associated Vasculitis - Granulomatosis with Polyangiitis
- Previously called “Wegener granulomatosis”
- Associated with cANCA (PR3)
- Males > Females affected, average age 40 yrs
- Rapidly fatal if untreated (80% mortality in 1 year)
Non Infectious Vasculitis - Anti-Neutrophilic Cytoplasmic Antibody (ANCA) Associated Vasculitis - Granulomatosis with Polyangiitis Classic Triad
• Necrotizing and/or granulomatous inflammation of upper respiratory tract, lung and kidney
Non Infectious Vasculitis - Anti-Neutrophilic Cytoplasmic Antibody (ANCA) Associated Vasculitis - Granulomatosis with Polyangiitis Morphologic Features
- Morphologic features
- Lung: Granulomas with necrosis, acute inflammation of alveolar capillaries with hemorrhage
- Renal: Pauci-immune necrotizing and crescentic glomerulonephritis
- General: No immune complexes (pauci-immune)
Non Infectious Vasculitis - Anti-Neutrophilic Cytoplasmic Antibody (ANCA) Associated Vasculitis - Microscopic Polyangiitis
- Associated with pANCA (MPO)
- Can triggered by drugs, infections, tumor proteins
- Necrotizing vasculitis of capillaries, small arterioles and venules
- Renal (90%) and lung
- May involve skin, mucous membranes, brain, heart, GI tract and muscle
Non Infectious Vasculitis - Anti-Neutrophilic Cytoplasmic Antibody (ANCA) Associated Vasculitis - Microscopic Polyangiitis Morphologic Features
- Renal: Necrotizing and crescentic glomerulonephritis
- Lung: Acute inflammation of pulmonary capillaries
- General:
- Fibrinoid necrosis of vessel walls, infiltrating PMN’s
- No granulomas or immune complexes (pauci-immune)
Non Infectious Vasculitis - Anti-Neutrophilic Cytoplasmic Antibody (ANCA) Associated Vasculitis - Churg Strauss Syndrome
- Also known as “allergic angiitis and granulomatosis”
- ANCA present in 50% (usually anti-MPO/pANCA)
- Small vessel necrotizing vasculitis with:
- Asthma
- Allergic rhinitis
- Skin rash/purpura
- Lung infiltrates with eosinophils, granulomas
- Blood eosinophilia
- Necrotizing granulomas of various organs
- Myocarditis, cardiomyopathy (60% of patients)
Non Infectious Vasculitis - Anti-Neutrophilic Cytoplasmic Antibody (ANCA) Associated Vasculitis - Churg Strauss Syndrome Morphologic Features
- Vessel inflammation and necrosis similar to microscopic polyangiitis and polyarteritis nodosa
- More involvement of eosinophils
- Granulomas usually present
Non Infectious Vasculitis - Giant Cell (Temporal) Arteritis
- Large to small size arteries in the head
- Temporal, vertebral and ophthalmic arteries
- Older patients (usually >50 years)
- Fatigue, fever, facial pain, headache, vision abnormalities
- Prompt therapy needed to prevent blindness
- Diagnosis:
- Vessel biopsy (at least 1 cm segment) to confirm vasculitis
- Granulomatous inflammation of vessel media with giant cells, disruption of internal elastic lamina
*Features may be difficult to identify in small biopsy specimen
Non Infectious Vasculitis - Giant Cell (Temporal) Arteritis Morphologic Features
i. Granulomatous inflammation of the vessel media and disruption of the internal elastic lamina
1. Multinucleated giant cells and granulomas may be difficult to find in small biopsies
ii. Healed vasculitis – intimal thickening, thinned media, fibrosis
Non Infectious Vasculitis - Takayasu Arteritis
• Granulomatous vasculitis of medium to larger sized arteries
-Aortic arch, great vessels off the aorta
- Older adults
- Etiology thought to be autoimmune
- Clinical signs/symptoms
- Vision changes, weakened pulse in upper extremities
- Pulmonary hypertension
- Myocardial infarction
- Renal artery stenosis with secondary hypertension
Non Infectious Vasculitis - Takayasu Arteritis Morphologic Features
- Similar to giant cell arteritis
- Irregular thickening of vessel with intimal hyperplasia
- Mononuclear inflammation of vessel; may see granulomas/giant cells
- Late: Fibrosis of vessel with dilation of lumen
Non Infectious Vasculitis - Polyarteritis Nodosa (PAN)
- Systemic vasculitis of small to medium sized muscular arteries
- Kidney > heart > liver > GI tract > nerves
- Ischemic injury: ulceration, infarcts, hemorrhage, atrophy (late)
- Clinical presentation:
*Hypertension, abdominal pain with bloody stool, diffuse myalgias, peripheral neuralgias, skin/soft tissue nodules
- No association with ANCA
- 30% patients have Hepatitis B virus
- Antibodies form to circulating viral antigens, form complexes and deposit in vessels (Type III hypersensitivity)
