Vasculitis Syndromes Flashcards
What is the definition of vasculitis?
Inflammation and damage to blood vessels
Compromised lumen causing tissue ischaemia, either single organ or several organ-system
Syndromes have great heterogenicity but also considerable overlap
Classification of Vasculitis Syndromes
- Vessel size (Chapel Hill Classification)
- Primary vs secondary
A. Small vessel vasculitis
- Immune complex mediated: cryoglobulinaemia, urticarial, anti-GBM, IgA (HSP)
- Pauci-immune (ANCA): Wegener’s, Churg Strauss, MPA
B. Medium vessel vasculitis
- PAN
- Kawasaki
C. Large vessel vasculitis
- Takayasu
- Giant cell arteritis
Pathogenesis and pathophysiology of vasculitis syndromes
(Mechanisms of vessel damage)
A. Pathogenic immune complex formation
- IgA vasculitis (HSP)
- SLE vasculitis
- Serum sickness
- Hep C (cryoglobulinaemia) and Hep B vasculitis
B. Antineutrophil cytoplasmic antibodies (ANCA)
- Granulomatosis with polyangiitis (Wegener’s Granulomatosis)
- Microscopic polyangiitis
- Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
C. Pathogenic T lymphocyte responses and granuloma formation
- Giant cell arteritis
- Takayasu arteritis
- Wegener’s
- Churg Strauss
Describe the pathogenesis of immune complex formation/deposition
What are the factors influencing degree of vasculitis?
Pathogenesis
1. Antigen-antibody complexes formed in excess either in circulation or deposition
2. Increased permeability of vessel walls due to cytokines
3. Activation of complements (C5a) and chemotactic for neutrophils, resulting in infiltration into vessel wall, phagocytosis of immune complexes and release of intracytoplasmic enzymes that damage vessel walls
4. Subacute or chronic - mononuclear cells infiltration
Factors influencing degree of vasculitis
1. Ability of reticuloendothelial system to clear circulating complexes from blood
2. Size of immune complexes
3. Turbulence of blood flow
4. Intravascular hydrostatic pressure of vessel
5. Pre-existing integrity of vessel endothelium
Describe the pathogenesis of ANCA in vasculitis
Anti-neutrophil cytoplasmic antibodies (ANCAs) - antibodies against proteins in cytoplasmic granules of neutrophils and monocytes
- cANCA (cytoplasmic): diffuse, granula cytoplasmic staining pattern on IF, containing proteinase-3 antigen
- pANCA (perinuclear): localised perinuclear staining pattern on IF, containing myeloperoxidase
- Others: elastase, cathepsin G, lactoferrin, lysozyme, bactericidal increasing protein
Pathogenesis
1. Usually proteinase-3 and myeloperoxidase reside in granules of resting neutrophils/monocytes (inaccessible to antibodies)
- TNF-a or IL-1 priming of neu/mono causes translocation of proteinase-3 or myeloperoxidase to cell membrane, resultant interaction with antibodies -> development of ANCA
- Degranulation of neutrophils produces ROS leading to tissue damage
- Release of proinflammatory cytokines
Describe the pathogenesis of T lymphocyte response and granuloma formation
- INF-gamma activates vascular endothelial cells to express HLA class II molecules
- These cells then participate in interaction with CD4+ T lymphocytes immunologic reaction
- When activated endothelial cells secrete IL-1, T lymphocytes activated to initiate or propagate in situ
- Other endothelial adhesion molecules (ELAM-1, VCAM-1) enhance adhesion of leukocytes to endothelial cells in blood vessel wall
What are the specific abnormalities (alone or in combination) when present, is suspicious for vasculitis?
- Palpable purpura
- Pulmonary infiltrates
- Microscopic haematuria
- Chronic inflammatory sinusitis
- Mononeuritis multiplex
- Unexplained ischaemic events
- Glomerulonephritis
- Multisystem disease
What are conditions that mimic vasculitis
- Infections
- Coagulopathy
- Neoplasm
- Drug toxicity
- Others
Approach to patient with suspected diagnosis of vasculitis
- Presence of specific abormal features
- Excluded vasculitis mimics
- Recognising pattern and establishing diagnosis
- Pattern and extent of disease
- Specific treatment
What are the adverse effects of corticosteroids?
What are the adverse effects of cyclophosphamide?
What are the adverse effects of methotrexate?
What are the adverse effects of azathioprine?
What are the adverse effects of MMF?
What are the specific biologic agents for treatment of vasculitis?
Rituximab - Wegener’s and MPA
Tocilizumab - GCA
Mepolizumab - CS
Apremilast - Behcet
What are the adverse effects of specific biologic agents?
