Vasculitis Flashcards
What is vasculitis
Inflammation of a blood vessel (arteries or veins), which is characterised by the presence of an inflammatory infiltrate and destruction of the vessel wall.
Heterogenous conditions
What does endothelial injury lead to
Results in thrombosis + ischaemia/infarction of dependent tissues
Types of Vasculitis Affecting The Large Vessels: arteries and major tributaries
- Giant cell arteritis
- Takayasu’s arteritis
Types of Vasculitis Affecting The Medium Sized Vessels: small arteries and arterioles
- Polyarteritis nodosa
- Kawasaki Disease
Types of Vasculitis Affecting The Small Vessels: small arteries, arterioles, venuoles and capillaries
ANCA +ve:
- Microscopic polyangiitis
- Granulomatosiswith polyangiitis (Wegener’s granulomatosis)
- Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss syndrome)
Types of Vasculitis Affecting The Small Vessels: small arteries, arterioles, venuoles and capillaries
ANCA -ve:
Henoch-Schonlein purpura
Cryoglobulinemic vasculitis
Anti-C1q vasculitis
Aetiology of vasculitis
May be primary (this may be due to direct or indirect damage of endothelial cells of the vessel) or secondary to other conditions such as RA, SLE, hepatitis B & C, HIV, polymyositis and some allergic drug reactions.
What is medium and large vessel vasculitis typically due to?
due to an autoimmune disease, where the immune system confuses a part of normal body as a foreign invader
body confuses the innermost layer of the blood vessel, which is the endothelial layer, with a foreign pathogen and directly attacks it
white blood cellsmix up the normal antigens on the endothelial cells with the antigens of foreign invaders like bacteria -
what are small vessel vasculitides due to?
immune system attacks healthy cells that are near the vascular endothelium, and the endothelial cells are only getting indirectly damaged.
situation in many small-vessel vasculitides, where theimmune system attacks white blood cell enzymes or other non-endothelial cell targets.
How do all vasculitis progress basically?
damaged endothelium exposes the underlying collagen and tissue factor, and these exposed materials increase the chance of blood coagulation
Blood vessels - weaker and become damaged - more likely aneurysms - as vessel wall heals becomes harder and stiffer as fibrin deposited in vessel wall as part of healing proces
What does presentation of vasculitis depend on?
vessel affected and the corresponding organ - could have ischaemia
- Blood cells clump onto the exposed tissue factor and collagen on the inside of blood vessels forming blood clots that can restrict blood flow.
- ## As fibrin is deposited in the vessel wall, the walls become thicker and bulge into the vessel, reducing the diameter of the vessel lumen, and restricting blood flow.
Typical general symptoms of vasculitis
- Fatigue
- Fever
- Weight loss
- Anorexia (loss of appetite)
- Anaemia
Typical specific presentations (depending on vessel and organ affected)
- Joint and muscle pain
- Peripheral neuropathy - vessels to the head are affected
- Anterior uveitis and scleritis - vessels to the head affected, causing ischaemia of the eye
- Gastrointestinal disturbance (diarrhoea, abdominal pain and bleeding)
- Renal impairment
- Hypertension
- Purpura. These are purple-coloured non-blanching spots caused by blood leaking from the vessels under the skin.
Markers for vasculitis
- Elevated ESR and CRP
- Anti neutrophil cytoplasmic antibodies (ANCA) - positive in most small vessel vasculitis
- 2 types: P-ANCA are also called anti-MPO antibodies. C-ANCA are also called anti-PR3 antibodies.
General management for vasculitis
Steroid:
Prednisolone - oral
Hydrocortisone - IV
Nasal sprays
Immunosuppressants:
- Cyclophosphamide
- Methotrexate
- Azathioprine
- Rituximab and other monoclonal antibodies
What is Giant cell arteritis (GCA)
Inflammation of the lining of your arteries
Sometimes called temporal arteritis as it commonly affects the temporal branch of the carotid artery.
What does giant cell arteritis co exist with normally?
Polymyalgia Rheumatica (PMR)
Epidemiology of GCA
- Common in elderly >55 years.
- F>M
- Associated with PMR in 50%
-0.4% of people - commonest vasculitis
- common in white people
Pathophysiology of GCA
- Arteries become inflamed, thickened and can obstruct blood flow
- Cerebral arteries affected in particular e.g. temporal artery
- Opthalmic artery can also be affected potentially resulting in permanent or
temporary vision loss - Blue dots around adventitia media and intima, cells blur margin between media and adventitia - intima proliferated into lumen causing it to narrow
S + S of GCA (non cranial)
- Malaise
- Dyspnoea
- Weight loss
- Morning stiffness
- Unequal or weak pulse
- anaemia
- limb claudication
Symptoms of GCA due to arteries in the head being affected (Cranial GCA)
- New Headache
- Scalp tenderness (pain when combing hair)
- Tongue/ jaw claudication - pain when chewing - lingual or facial artery involvement
- Amaurosis fugax - unable to see from one or both eyes
- Sudden unilateral blindness
Bloods in GCA
- Elevated ESR and CRP
- Elevated ALP
- Elevated platelets
- Reduced Hb
- ANCA -ve
Biopsy in GCA (temporal artery)
- Can see skip lesions - GCA is segmental so doesn’t affect the whole length of the artery
- Histology - giant cells (granulomas) seen in the internal elastic lamina
Specifity 100%, sensitivity 39%
Diagnostic criteria for GCA
- Age at disease onset ≥50 years
- New headache
- Temporal artery abnormality
- Elevated ESR(> 50 mm/hr)
- Abnormal temporal artery biopsy(typical vasculitis features)
3 of the following criteria have to be met
Treatment for GCA
Steroids - dampen down immune response - no delay in corticosteroid treatment
- Prednisolone
- IV methylprednisolone if evolving visual loss
Long term steroids need GI and bone protection:
- PPI
- Ca2+ and Vit D
- Biphosphonate
Prognosis for GCA
Typically a 2 year course and then complete remission. Can reduce prednisolone once symptoms have resolved. Symptoms may reoccur.
Main cause of death is long term steroid treatment!
What is Granulomatosiswith polyangiitis (Wegener’s granulomatosis) WG
multi-system disorder of unknown causes characterised by necrotising granulomatous inflammation and vasculitis of small and medium vessels.
Epidemiology of WG
Usually occurs in middle-aged men
What are cANCAs
B-cells target antibodies to granules made by a person’s neutrophils. The antibodies are called ‘cytoplasmic anti-neutrophilic cytoplasmic antibodies’ or cANCAs.
Pathophysiology of WG
c-ANCA targets and bind to a specific neutrophil granule called proteinase 3 which is embedded in the membrane of some neutrophils.
Once c-ANCA binds to the neutrophil, it causes the neutrophil to release oxygen free radicals, which can then indirectly damage the nearby endothelial cells, causing vasculitis.
Upper respiratory tract issues in WG
- Chronic pain caused by sinusitis
- Bloody mucus due to ulcers within the nose
- Saddle nose deformity: nose caves in
- Hearing loss
Lung issues in WG
- Breathing difficulty due to inflammation
- Wheeze
- **Ulcers can cause bloody coughing*
Kidney issues in WG
- Decreased urine production due to glomeruli death**
- Proteinuria**
- Haematuria**
- Increase in BP
Investigations for WG
FBC:
- cANCA +ve
- ESR and CRP raised
- Urinalysis - to look for proteinuria and haematuria
- Renal biopsy - can see granulomas and inflammation in blood vessel wall
- Chest x-ray - may show nodules +/- fluffy infiltrates of pulmonary haemorrhage
- CT - may reveal diffuse alveolar haemorrhage
Management of WG
- Steroids combined with cyclophosphamide
- Methotrexate and azathioprine usually used for maintenance
- Plasma exchange in patients with severe renal disease or pulmonary haemorrhage
What is Polyarteritis nodosa? PN
Necrotising vasculitis - causes aneurysms and thrombosis in medium sized arteries, leading to infarction in affected organs with severe systemic symptoms.
Epidemiology of PN
- M>F
- Rare in the UK
- May be associated to hepatitis B
Pathophysiology of PN
occur when the immune cells directly attack the endothelium, confusing it with hepatitis B virus.
Causes transmural inflammation - causes vascular wall to die through all 3 layers of artery - fibrosis occurs as vascular wall heals - process called fibrinoid necrosis
Fibrosed vessel wall left weak and prone to aneurysms
What is transmural inflammation
means the entire wall, the tunica intima, the media, and the adventitia are all affected.
General symptoms of PN
Fever, malaise, weight loss and myalgia
What happens if renal arteries affected in PN
- Hypertension
- Haematuria
- Proteinuria
What happens if mesenteric artery is affected in PN
Abdominal bleeding
GI bleeding
What happens if arteries supplying the brain are affected in PN
Neurological symptoms e.g. numbness, tingling, abnormal/lack of sensation and inability to move part of the body
What happens if arteries supplying the skin are affected?
- Skin lesions
- Rash - Livedo reticularis (pink blue mottling caused by stasis of blood in skin venules)
- Punched-out ulcers
- Nodules
Cardiac issues in PN
Coronary arteritis causes myocardial infarction and heart failure
Investigation for PN
FBC:
- Elevated WCC
- Eosinophilia
- Anaemia
- Raised ESR and CRP
- ANCA -ve
- Renal or mesenteric angiogram - can see string of beads pattern due to fibrotic aneurysms
- Renal biopsy
Management of PN
- Steroids e.g. prednisolone in combination with immunosuppressive drugs e.g. azathioprine or cyclophosphamide
- Control BP
- Hep B should be treated after treatment with steroids
Healthy vessel
Out to in
Adventitia - has vasa vasorum
Media
Intima
General pathophysiology of vasculitis
Primary phenomena = idopathic immune process
Secondary phenomena = drugs, RA, infection
Activated immune cell infiltrate vessel wall, direct damage and stimulates vascular smooth muscle remodelling
Infiltration, proliferation and damage causes weaking and occlusion of blood vessel
Complications for GCA
Strokes
Blindness - stroke affecting retinal vessels in optic nerve
Bilateral simultaneous or sequential loss
What other scans should be given for confirmatory test
Temporal artery US
Temporal artery biopsy
or both
PET- CT + Auxillary US to look for extra cranial disease
Managing steroid complication and pre existing co-morbidities
Steroid induced diabetes
Osteoporosis
Infection
Gi toxicity
Where are smooth muscle cells found
Tunica Media
Two forms of classificiation of vasculitis
1- by vessel size
2- consensus classification
Two most common clinical presentations of GCA
Cranial GCA
Large Vessel GCA
Physical signs of GCA
-Scalp tenderness
- temporal artery
