What is vasculitis?
- Inflammation & necrosis of blood vessel walls.
- Associated w/ damage to skin, kidney, lung, heart, brain & gastrointestinal tract.
Examples of large, medium and small vessel vasculitides?
Large vessel:
- giant cell arteritis
- Takayasu’s arteritis
Medium vessel:
- Polyarteritis nodosa
- Kawasaki
Small vessel ANCA:
- Granulomatosis with polyangitis
- micro scoping polyangitis
- Churg-Strauss syndrome
Small vessel non-ANCA:
- Bechet disease
- Burgers disease
- Henoch-Schonlein Purpura
Epidemiology of Giant cell arteritis
More common in womenn
Co-exists w/ polymyalgia rheumatica
Must be over 50 y for diagnosis - average age of onset 70 y
Pathophysiology of giant cell arteritis
Immune-mediated vasculitis characterised by granulomatous inflammation
Affects large & medium sized arteries e.g. extra-cranial branches of carotid artery is common.
- Aorta& major branches common too.
Pathophysiology:
1. CD4+ T cells enter artery through the vasa vasorum (micro-vessels on muscular arteries).
2. They undergo clonal expansion in vessel wall.
3. T cells release cytokine interferon gamma which stimulates macrophages & induces formation of multinucleated giant cells
4. Macrophages produce inflammatory cytokines IL-1 & IL-6- cause systemic inflammation
5. Macrophages cause tissue damage so the internal elastic lamina becomes fragmented.
6. In response to injury, artery releases growth factors that result in thickening of vessels = causes narrowing
7. Occlusion & blood clots.
Presentation of giant cell arteritis
- Severe unilateral head ache (temporal or occipital) & scalp tenderness from skin ischaemia !
Pain on chewing food- jaw claudication from ischaemia.
Visual disturbance or blindness in 1 eye due to anterior ischaemic optic neuropathy!
- loss of vision= amaurosis fugax ( differentiated from other types of vision loss by being PAINLESS).
- if untreated, becomes painful & irreversible
Temporal arteries may be thickened & may be pulseless.
NOTE: Inflammation of temporal arteries prevents flow to jaw, vision and scalp, thus symptoms
-Neurological involvement - transient iscaemic attacks (TIA), stroke, hemiparesis (weakness of the body on one side).
-Systemic symptoms - weight loss, malaise, fatigue, night sweats.
Investigation for Giant cell arteritis: blood tests
- High ESR & CRP
- Rarely presents w/ normal ESR
- FBC - normocytic, normochromic anaemia
- Abnormal Liver function can occur.
Investigation for Giant cell arteritis: imaging & biopsy
Imaging:
- Ultrasound of arteries - halo sign (the dark band in A) Highly useful investigation.
- PET scans - looking for metabolic activity.
- MRI of cranial arteries - consider.
Biopsy:
Temporary artery biopsy - investigation of choice!
Characteristic findings:
- Luminalnarrowing
- fibrointimal thickening
- disruption of internal elastic lamina
- lymphohistiocytic inflammation in the media & intimacy
- Disruption of internal elastic lamina
NOTE: -ve biopsy does not exclude diagnosis
NOTE: view image on notes
Management for giant cell arteritis
URGENT DUE TO RISK OF BLINDNESS
- High dose steroids e.g. prednisolone (1mg/kg/day = 60-80mg)!!
- Dramatic response w/in 48-72 hours.
- Lack of response should challenge diagnosis.
- give even if you suspect but not fully confirmed its GCA- before biopsy - Bisphosphonates, Ca & Vitamin D - bone protective drugs (most patients are on steroids for more than a yr).
- Then reduce dose - guided by symptoms & ESR levels.
- not immediately- adissonian crisis
- unless co-existing infection- in which case double dose of prednisolone - Flare ups (recurrent) - methotrexate or azathioprine should be used to avoid long term steroid use.
- Biologic DMARDs - Tocilizumab.
Prognosis of giant cell arteritis
- Glucocorticoid-related side effects common e.g. diabetes or osteoporotic fractures.
- Risk of developing aortic aneurysms is increased & cardiovascular disease.
- Overall survival is similar to that of the general population
What are ANCAs?
Anti-neutrophil cytoplasmic antibodies
-The amount of ANCA mirrors clinical severity.
ANCAs can directly activate neutrophils = stimulating the release of ROCs & proteolytic enzymes.
What is Granulomatosis with polyangiitis (GPA)?
- Associated w/ necrotizing vasculitis
- Polyangiitis means multiple small vessel inflammation
- Granulmatas are a ball of chronic inflammatory tissue that deposits
- Formerly Wegener granulomatosis
Epidemiology of Granulomatosis with polyangiitis (GPA)?
30-40 y
1 in 25,000 people
What is the pathophysiology of Granulomatosis with polyangiitis (GPA)?
- Drugs or cross-reactive microbial antigens induce ANCA formation.
- Subsequent inflammatory stimuli cause release of cytokines e.g. TNF.
- TNF upregulates the surface expression of PR3 and MPO on neutrophils & other cell types.
- ANCAs bind to these cytokine-activated cells, causing further neutrophil activation
- ANCA-activated neutrophils cause endothelial cell injury by releasing granule contents & producing ROCs
Chronic inflammation & tissue necrosis occur in nose
- Lungs & kidneys also affected.
Presentation of Granulomatosis with polyangiitis (GPA)?
ENT involvement - Nasal discharge, collapsed nose (saddle-shaped deformity), hearing loss
Kidney- Glomerulonephritis ( inflammation of the glomeruli), Haematuria, Proteinuria
Respiratory:
- pulmonary infiltrates- pus, blood protein
- Cough & haemoptysis- coughing up blood
- Pulmonary haemorrhage
- High blood pressure
- Vasculitis rash
- cranial nerve lesions
- Fatal if untreated
Investigation for Granulomatosis with polyangiitis (GPA)?
- Serology- anti-proteinase 3 cANCA, high WCC, CRP & ESR.
ANCA = antineutrophil cytoplasmic antibodies.
- Urinalysis- haematuria & proteinuria.
- Chest X-ray - bilateral nodules, cavity infiltrates & tracheobrachial thickening.
- Biopsy of kidney or lesions in sinuses & upper airways.
renal biopsy: epithelial crescents in Bowman’s capsule
Management of Granulomatosis with polyangiitis (GPA)?
- Cyclophosphamide + corticosteroids - for bringing the condition under control.
NOTE: Methotrexate, MMF & Rituximab may be used instead.
- Immunosuppressants - Mycophenolate mofetil (MMF), methotrexate, azathioprine for keeping condition under control.
- Rituximab- for relapse.
