Vasculitis Flashcards
Definition/epidemiology
A clinicopathologic process characterized by inflammation of the vessel wall, and associated tissue ischemia and necrosis
The distribution of the antigen responsible for vasculitis determine the pattern (type, size and location) of the blood vessel involved, and produce a group of clinical syndromes with considerable overlap
Vasculitic lesions are focal and segmental – may have skip lesions; important to be aware of this when doing a biopsy
Can be confined to a single organ system, or it may simultaneously involve multiple organ systems – typically will see kidney and lung involvement
Vasculitis in affected organs may be the primary manifestation of a disease process
Vasculitic syndromes are characterized by differences in age of onset, sexual predilection, ethnicity and incidence
Vasculitic syndromes produce a wide spectrum of clinical manifestations that are often serious and sometimes fatal.
Pathogenesis - overview
- genetics
- environmental stressors –> particularly infection
- epigenetics
- auto-antibodies
- complement
- neutrophils
- monocytes/macrophages
- T lymphocytes
- B lymphocytes
- endothelial cells
- TLRs
Pathogenesis - immune complexes
Immune complexes - complexes deposit in vessel walls formed in the circulation at selective vascular sites. Antigen-antibody complexes produce injury by binding complement and stimulating leukocyte infiltration
- Hypersensitivity vasculitis –> complexes formed to drugs or foreign proteins, i.e., penicillin conjugated serum proteins or streptokinase
- Systemic lupus erythematosus –> DNA-anti-DNA complexes
- Cryoglobulinemia –> IgG, IgM and complement
- Hepatitis B-associated vasculitis –> HBSAg-anti-HBSAg complexes and complement present in vascular lesions
Pathogenesis - endothelial cells
- antibodies to endothelial cells can induce the release of cytokines (IL1, IL6, IFN, etc) and promote local inflammatory response
- exposed endothelial cell antigens activate CD4 cells/T cell mediated vasculitis –> may be seen in SLE and Kawasaki disease
- non-endothelial structures of the vessel wall are involved in controlling the inflammatory process
Pathogenesis - ANCA
Anti-neutrophil cytoplasmic antibodies –> Autoantibodies directed against cytoplasmic antigens in neutrophils, primarily azurophils or primary granules.
- Can be detected by immuno-fluorescent staining techniques producing 2 main staining patterns:
- C-ANCA = Cytoplasmic staining of proteinase 3 (PR-3), a neutrophil granule constituent
- found in granulomatosis and polyangiitis GPA/Wegener’s (~ 90%) –> C-ANCA titers show close association with disease activity and may be important in the pathogenesis of disease - P-ANCA = target antigen is perinuclear and specific for myeloperoxidase (MPO).
- Found primarily in microscopic polyangiitis and Eosinophilic granulomatosis and angiitis (Churg-Strauss Syndrome)
Classification of vasculitis
Classically systemic vasculitis disorders are categorized by the size of the predominant blood vessel involved, but there is considerable overlap between these disorders
- large vessel vasculitis –> involves the aorta and its branches
- medium vessel vasculitis –> involves muscular arteries that supply organs
- small vessel vasculitis –> involves arterioles, capillaries and venules
The presence or absence of ANCA is an addition to classification criteria
Large vessel vasculites
- giant cell (temporal) arteritis
- takayasu arteritis
- IgG4 related syndrome
Medium vessel vasculites
- polyarteritis nodosa
- kawasaki disease
- primary central nervous system vasculitis
Small vessel vasculites
- eosinophilic granulomatosis with polyangiitis (churg strauss)
- granulomatosis with polyangiitis (wegeners)
- microscopic polyangiitis
- hypersensitivity vasculitis
- IgA vasculitis - henoch schonelin purpura
- cryoglobulonemic vasculitis
- vasculitis secondary to connective tissue diseases
Giant cell arteritis
Chronic vasculitis affecting large and medium sized vessels that originate from the aortic arch including cranial vessels branches –> especially temporal arteries and ophthalmic arteries
- patients will present with onset of blindness
- onset –> most common after age of 50, with a mean age of 72 years.
- greatest risk factors are aging and Scandinavian ethnicity
- often triggered by upper respiratory infection
Giant cell arteritis
- manifestations
- treatment
- complications
Manifestations
- Systemic symptoms –> fever, fatigue and weight loss
- Localized headache of new onset
- Jaw claudication
- Visual symptoms
- Tenderness or decreased pulse of the temporal artery
- Polymyalgia rheumatica – syndrome of diffuse stiffness of the upper and lower girdle
- elevated erythrocyte sedimentation rate (ESR) > 50 mm/hr
Biopsy of temporal artery –> necrotizing arteritis with predominance of mononuclear cells or granulomatous process with multinucleated giant cells (segmental disease) – skip lesions, might be missed
Treatment is high dose glucocorticoids (i.e., prednisone 60 mg QD or greater)
Complication of GCA: aneurysm, blindness and stroke –> Important to initiate treatment immediately – within 7 days, because if left untreated the patient will go blind
Takayasu arteritis
Chronic vasculitis affecting the aorta and its major branches, resulting in fibrosis of vessels and weakening of pulses (pulseless disease)
- Predominantly young women under 40, particularly common in the Asian populations
- The inflammatory process causes thickening of the wall of the arteries with dilatation, narrowing and obstruction. - Infiltrating cells are mostly gamma delta T lymphocytes
- Initial vascular lesions frequently involves the left middle or proximal subclavian artery
Takayasu arteritis
- manifestations
- treatment
Manifestations
- Decrease pulsation of one or both brachial arteries; differences of > 10 mm Hg blood pressure
- Claudication of the extremities
- Bruits over one or both subclavian arteries or abdominal aorta
- Ischemia of cranial vessels:
- arteriography revealing aneurysm formation, occlusion, collateral circulation
Treatment of acute disease with glucocorticoids, and surgical by-pass of occluded vessels
- depend on CT scan for follow up of these patients –> increased linear uptake in the aortic arch helps us know whether or not the disease is active
IgG4 related disease
A spectrum of multisystem autoimmune disease that can affect many organs with fibro-inflammatory conditions and has many manifestations –> including pancreatitis, sclerosing cholangiitis and sialadenitis.
Many organs are involved including –> thyroid, lung and pleura, renal, skin, lymph nodes, heart (pericarditis), and CNS (pachymeningitis)
IgG4-RD is characterized by a lymphoplasmacytic infiltrate composed of IgG4+ plasma cells, storiform fibrosis, obliterative phlebitis, and mild to moderate eosinophilia.
IgG4-RD lesions –> infiltrated by T helper cells - cause progressive fibrosis and organ damage.
Although autoreactive IgG4 antibodies are observed against various exocrine gland antigens, there is no evidence that they are directly pathogenic.
IgG4 associated vasculitis
IgG4RD has been recognized as one of the causes of non infectious aortitis and periaportitis involving the thoracic and abdominal aorta with lypmhoplasmacytic inflammatory reactions on pathological studies.
IgG4-associated aortitis is recognized at 1.6 % of all thoracic aortic resection in Japan
IgG4 deposition has been reported in cases with churg strauss
