Vasculitis Flashcards
- Name the different types of vasculitis per the Chapel Hill Consensus Conference classification
Large Cell Vasculitis
GCA
Giant cell arteritis (GCA):
Vessels most commonly affected: temporal arteries, vessels originating from the aortic arch, other arteries less common.
Demographic most commonly affected: older patients of northern European descent, 2-3 times more common in women
Most common symptoms/signs: temporal headache, scalp tenderness, jaw or tongue claudication, visual loss, double vision.
Pathology: giant cell arteritis with disruption of the internal elastic lamina.
- Name the different types of vasculitis per the Chapel Hill Consensus Conference classification
Large Cell Vasculitis
Takayasu’s arteritis
Takayasu’s arteritis:
Vessels most commonly affected: aorta including aortic arch and its branches
Demographic most commonly affected: young females, median age of onset 25 years, 8 times more common in women
Most common symptoms/signs: claudication of upper > lower extremities, CNS events.
Pathology: *granulomatous pan-arteritis
- Name the different types of vasculitis per the Chapel Hill Consensus Conference classification
Medium-vessel vasculitis:
Polyarteritis nodosa:
Vessels most commonly affected: small and medium-sized arteries;
Demographic most commonly affected: Adults in the 5th to 7th decade of life, all racial groups with no gender difference.
Most common symptoms/signs: May affect any organ, but skin, joints, peripheral nerves, gut, and kidney are most commonly involved
Pathology: focal but pan-mural necrotizing arteritis with a predilection for involvement at the v_essel bifurcation_.
- Name the different types of vasculitis per the Chapel Hill Consensus Conference classification
Medium-Cell Vasculitis:
Kawasaki’s disease
Vessels most commonly affected: small and medium-sized arteries Demographic most commonly affected: 80% of patients are children <5 years old. Two times more common in males.
Most common symptoms/signs: acute febrile illness primarily affecting infants and young children; fever, prominent mucocutaneous changes, cervical lymphadenopathy, polymorphous rash, erythema and edema of hands and feet, desquamation, myocarditis, coronary vasculitis
Pathology: probable infectious vector resulting in cytokine-mediated endothelial damage.
- Name the different types of vasculitis per the Chapel Hill Consensus Conference classification
Small-vessel vasculitis
a. Antineutrophil cytoplasmic antibody (ANCA) positive vasculitides:
Granulomatosis with polyangiitis (Wegener’s) abbreviated as GPA:
Vessels most commonly affected: small and medium-sized arteries Demographic most commonly affected: Wide range of ages. No gender difference.
Most common symptoms/signs: upper respiratory tract (sinuses), lungs, and kidneys, may affect other organs
Pathology: pauci-immune, necrotizing, granulomatous arteritis usually associated with serum cytoplasmic-ANCA (c-ANCA) with positive proteinase 3 (PR3)antibodies
- Name the different types of vasculitis per the Chapel Hill Consensus Conference classification
Small Cell Vasculitis:
Eosinophilic granulomatous with polyangiitis
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): Vessels most commonly affected: small arteries and venules Demographic most commonly affected: Onset 40s-50s.
No gender difference.
Most common symptoms/signs: asthma, *eosinophilia, multiorgan involvement – lungs, skin, peripheral nerves, gut, heart, renal (rare);
Pathology: necrotizing extravascular granulomas and vasculitis of small arteries and venules, eosinophils present in early stage
- Name the different types of vasculitis per the Chapel Hill Consensus Conference classification
Small Vessel Vasculitis:
Microscopic polyangiitis (MPA)
Microscopic polyangiitis (MPA):
Vessels most commonly affected: arterioles, capillaries, and venules Demographic most commonly affected: Onset 40s-50s.
No gender difference.
Most common symptoms/signs: pulmonary hemorrhage, glomerulonephritis, palpable purpura, peripheral neuropathy, joint and abdominal pain
Pathology: pauci-immune, necrotizing vasculitis, serum perinuclear- ANCA (p-ANCA) common with positive myeloperoxidase (MPO).
Antineutrophil cytoplasmic antibody (ANCA) negative vasculitides:
Henoch-Schönlein Purpura (HSP)
Vessels most commonly affected: arterioles and venules
Demographic most commonly affected: Young people < 20 years, but also can be seen in adults.
Most common symptoms/signs: palpable purpuric skin lesions lower extremities, arthritis, abdominal pain, hematuria
Pathology: leukocytoclastic (neutrophilic perivascular/transmural infiltrate) or necrotizing vasculitis often with IgA deposition
Antineutrophil cytoplasmic antibody (ANCA) negative vasculitides:
Cyoglobulinemic vasculitis
Cyoglobulinemic vasculitis: Of note, cryoglobulins are immunoglobulins that are reversibly precipitated by reduced temperatures.
Vessels most commonly affected: small vessels including glomerulocapillaries***
Demographic most commonly affected: Wide range of ages. M=F.
Most common symptoms/signs: purpura, arthralgias, weakness, peripheral neuropathy, Raynaud’s phenomenon, glomerulonephritis, pulmonary hemorrhage possible; often r_heumatoid factor (RF_) and hepatitis C antibody positive.
Pathology: leukocytoclastic vasculitis (LCV), intravascular hyaline thrombi, with immunoglobulin and complement 3 (C3) deposition on immunofluorescence (IF).
Antineutrophil cytoplasmic antibody (ANCA) negative vasculitides:
Cutaneous leukocytoclastic angiitis
Cutaneous leukocytoclastic angiitis:
Vessels most commonly affected: arterioles and venules
Demographic most commonly affected: Wide range of ages. M=F.
Most common symptoms/signs: palpable purpuric skin lesions, arthralgias, systemic symptoms may be present, usually secondary to an immune response [drugs, bugs (infections), connective tissue disease (CTD), malignancy]
Pathology: leukocytoclastic vasculitis (LCV)
- Describe the clinical features and the laboratory abnormalities suggestive of vasculitis.
Signs/Symptoms: Common clinical features, including skin lesions, constitutional symptoms (fever, anorexia, weight loss, weakness, and fatigue) and musculoskeletal symptoms (arthralgias, arthritis, myalgias, peripheral neuropathy) are found, to some extent, in all systemic vasculitides as noted above.
Laboratory features: reflect systemic inflammation – anemia of inflammatory disease, thrombocytosis, low albumin, elevated sedimentation rate (ESR) and C-reactive protein (CRP), polyclonal gammopathy; possibly elevated liver enzyme tests, low complement levels, cryoglobulins
Diagnosis: history and physical exam to determine extent of organ involvement, detection of serum autoantibodies (RF, ANA, ANCA), biopsy of affected organ; if biopsy inaccessible, angiogram to show segments of smooth arterial stenosis alternating with areas of normal or dilated artery; tapered occlusions; thrombosis
- Discuss the different immunopathogenic mechanisms that mediate vasculitis.
Pathology:
Considerable overlap exists in the patterns of pathologic involvement in the vasculitic syndromes. Vasculitic lesions tend to be both focal and segmental. The entire circumference of the vessel may not be involved.
Large and medium vessel vasculitis: typically, panarteritis with infiltration to a varying degree of lymphocytes, monocytes, histiocytes, eosinophils, and polymorphonuclear leukocytes (PMNs) through the vessel wall; can be associated with granuloma or giant cell formation in some disorders (see Section I); disruption of the elastic lamina: intimal thickening results in narrowing or obliteration of the vessel lumen
Small vessel vasculitis: typically fibrinoid necrosis of the vessel wall with a transmural inflammatory reaction; often referred to as “leukocytoclastic” vasculitis (LCV) – a pathologic term used to describe necrotizing vasculitis with PMN-derived nuclear debris that often accompanies the neutrophilic perivascular infiltrate of the vessel wall; immunoglobulin (IgM, IgA in HSP) and complement 3 (C3) vascular deposition are often noted in the vasculitic lesion
- Discuss the different immunopathogenic mechanisms that mediate vasculitis
Immune complexes (IC):
Immune complexes (IC): Animal models of serum sickness, human serum sickness induced by horse immunoglobulins (anti-venoms), and the demonstration of hepatitis B surface antigen and IgM in an arterial wall of a patient with polyarteritis nodosa suggest that IC can mediate inflammatory vessel disease.
In animal models, platelet activating factors and other vasoactive mediators released as part of the inflammatory and cytokine response probably induce vascular permeability. This is followed by deposition of circulating IC at the vascular endothelium, the activation of complement, and the attraction of PMNs.
Indirect evidence suggests the IC-induced vasculitis may be involved in hypersensitivity vasculitis, HSP, cryoglobulinemia, and hepatitis B– associated vasculitis.
- Discuss the different immunopathogenic mechanisms that mediate vasculitis
T Cell Dependent Mediated Endothelial Cell Injury:
T Cell Dependent Mediated Endothelial Cell Injury:
T-cell responses in the initiation and perpetuation of vascular injury have been suggested in Takayasu’s, granulomatosis with polyangiitis, and giant cell arteritis.
In patients with giant cell arteritis, there is an over-representation of the HLA-DR4 haplotype. This association has been mapped to a sequence polymorphism within the hypervariable region 2 of the HLA-7 DRB1 gene (a probable antigen-binding element of the HLA-DR molecule). This suggests antigen-driven vascular inflammation. This polymorphism is not shared by patients with rheumatoid arthritis.
- Distinguish the different types of anti-neutrophil cytoplasmic antibodies (ANCAs) and discuss their role in the pathogensis of vasculitis
Antineutrophil Cytoplasmic Antibodies (ANCA): ANCA are antibodies to antigens found in the cytoplasm of neutrophils.
The cytoplasmic staining or c-ANCA (granulomatosis with polyangiitis) binds to proteinase 3 (PR3) found in the primary granules of the PMN.
The perinuclear staining or p-ANCA (microscopic polyangiitis) binds to myeloperoxidase (MPO), another primary granule constituent which migrates to the perinuclear area with alcohol fixation of PMNs.
Potentially, inflammatory cytokines induced by infections or other insults activate PMNs to release and express PR3 and MPO on the cell surface. The binding of ANCA to the neutrophil cell surface leads to further neutrophil activation and possibly enhanced binding to vascular endothelial cells with resultant vascular damage. PR3 and MPO have also been found on the surface of activated endothelial cells. Although ANCA may not be essential for the initiation of the vasculitis, they may play a role in amplifying the inflammatory vascular response.
- Discuss the treatment of vasculitis as it relates to the extent of organ involvement.
Class notes:
