Vasculitis Flashcards
Define vasculitis?
Inflammation of blood vessels, often with ischaemia and necrosis, thrombosis and organ inflammation
Areas affected by vasculitis?
Any blood vessel, inc. capillaries
Define primary and secondary vasculitis?
Primary: results from an inflammatory response that targets the vessel walls and has an UNKNOWN CAUSE; it is sometimes autoimmune
Secondary: may be triggered by an infection, drug, toxin or it may occur as part of another inflammatory disorder of cancer, e.g: paraneoplastic vasculitis assoc. with cancer
Pathophysiology of vasculitis?
- Activated dendritic cells release cytokines that activate T cells and cause vascular inflammation
- T cells promote inflammation, GRANULOMA formation and macrophage activation
- Macrophages release mediators that cause progressive vascular inflammation, endothelial damage and intimal hyperplasia
Main classifications of vaculitis?
Large-vessel, inc. Takayasu arteritis and giant cell arteritis
Medium-vessel, inc. polyarteritis nodosa and Kawasaki disease
Small-vessel is split into two categories
PICTURE 1
2 categories of small vessel vasculitis?
ANCA-associated small-vessel vasculitis (AAV):
• Granulomatosis with polyangiitis (GPA)
• Eosinophilic granulomatosis with polyangiitis (EGPA)
• Microscopic polyangiitis (MPA)
Immune complex small-vessel vasculitis:
• Henoch-Schönlein (common)
• Others
Systemic symptoms common to all vasculitides?
Fever
Malaise
Fatigue
Weight loss
Two main causes of large vessel vasculitis and histopathology?
Takayasu arteritis (TA)
Giant Cell arteritis (GCA)
There is GRANULOMATOUS infiltration of the large vessel walls
Occurrence of takayasu arteritis?
Tends to affect those <40 YEARS
More common in FEMALES
It is much more prevalent in Asian populations
Occurrence of GCA?
Generally affects those > 50 YEARS
Typically causes temporal arteritis but the aorta and other large vessels may be affected
Signs on examination of large vessel vasculitis?
- Bruit (usually if carotid artery is affected)
- BP difference of extremities
- Claudication (in Takayasu, this occurs suspiciously in younger people)
- Carotydinia or vessel tenderness (painful to touch)
- Hypertension
Occurrence of temporal arteritis?
Assoc. with polymyalgia rheumatica
About 50% with GCA have PMR, and about 15% of individuals with PMR develop GCA
Classical symptoms of temporal arteritis?
- Unilateral temporal headache
- Scalp tenderness
- Jaw claudication
- Prominent temporal arteries with reduced pulsation
- Pain over temporal artery
Risks with temporal arteritis?
Of blindness due to ischaemia of the optic nerve
Ix of temporal arteritis?
Inflammatory markers (ESR, PV and CRP) are raised
Temporal artery biopsy shows granulomas; biopsy may be -ve as there are SKIP LESIONS
MR angiogram can show stenosis/thickening/aneurysm
PET CT can shows increased metabolic activity of inflammatory cells
Management of temporal arteritis?
If there are no visual problems, 40 mg prednisolone gradually reduced over 18 months to 2 years
If there are visual problems, 60 mg prednisolone gradually reduced over 18 months to 2 years
Occasionally, if the patient struggles with a reduced steroid dose, methotrexate/azathioprine may be considered
Types of medium vessel vasculitis?
Kawasaki disease
Polyarteritis nodosa
What is Kawasaki disease?
Seen in CHILDREN, usually < 5 years, often following an INFECTION
Causes vasculitis of various vessels but can affect CORONARY ARTERIES, leading to aneurysm development
Tends to be self-limiting
What is polyarteritis nodosa?
Characterised by necrotising inflammatory lesions that affect arteries at vessel bifurcations, leading to microaneurysm and aneurym formation, and often affecting skin, gut and kidneys
Assoc. with HEP B
What were the different types of small vessel vaculitis previously known as?
GPA was previously known as Wegener’s granulomatosis
EGPA was previously known as Churg-Strauss syndrome
Microscopic polyangiitis has not changed name
Pathology of GPA?
Granulomatous inflammation of respiratory tract, small and medium vessels
Necrotising GLOMERULONEPHRITIS common
Pathology of EGPA?
Eosinophilic granulomatous inflammation of respiratory tract, small and medium vessels; increased eosinophils in blood and tissues
Assoc. with asthma
Pathology of MPA?
Necrotising vasculitis with few immune deposits
Necrotising GLOMERULONEPHRITIS very common
Ecologic factors in development of AAV?
Bacteria - Staph. aureus carriage in the nose increases risk of GPA
Genetic factors
Environmental, e.g: silica
Drugs, e.g: hydralazine
Occurrence of GPA?
More common in northern european descent
SLIGHTLY MORE COMMON in MALES
Can occur at any age, usually between 35-55 years
GPA classification critera?
Must have at least 2 of the 4 criteria
ENT features of GPA?
There are the cardinal features:
• Sinusitis (stuffiness and discharge)
• Nasal crusting
• Epistaxis (nosebleed)
• Mouth ulcers
- Sensorineural deafness
- Otitis media (infection of middle ear) and deafness
• “Saddle nose” due to cartilage ischaemia
Respiratory signs of GPA?
Cough and haemoptysis
Diffuse alveolar hemorrhage (emergency)
Pulmonary infiltrates Cavitating nodules (usually, > 1) on CXR
Cutaneous signs of GPA?
NON-BLANCHING, raised/palpable purpura
These can join together and ulcerate
Renal issues in GPA?
NECROTISING GLOMERULONEPHRITIS manifests as blood and protein in the urine
Nervous system manifestations of GPA?
Mononeuritis multiplex commonly presents with wrist/foot drop
Sensorimotor polyneuropathy
Cranial nerve palsies (cannot move eye either due to granuloma invasion of a muscle or ischaemia of the nerve)
Ocular manifestations of GPA?
- Conjunctivitis, episcleritis, uveitis
- Optic nerve vasculitis
- Retinal artery occlusion
- Proptosis (eye is pushed outwards by a large granuloma)
Main differences between GPA and EGPA?
Late onset asthma
High eosinophil count
It does not have the same ENT signs that GPA does, e.g: nasal cartilage, collapse is not common
Criteria for EGPA?
Should have 4 or more of:
• Asthma (wheezing, expiratory rhonchi)
- Eosinophilia
- Paranasal sinusitis
- Pulmonary infiltrates (may be transient)
- Histological proof of vasculitis with extravascular eosinophils
- Mononeuritis multiplex or polyneuropathy
What is ANCA?
Anti-neutrophil cytoplasmic antibodies - group of antibodies in the cytoplasm of neutrophil grnaulocytes
Types of ANCA?
cANCA (cytoplasmic) is very specific to GPA
pANCA (perinuclear) is less specific and are present in MPA and EGPA
Other antibodies?
Anti-PR3 is very specific for GPA
Anti-MPO is seen in EGPA and MPA; it is not as useful for GPA
Antibodies present in GPA?
cANCA and anti-PR3
Antibodies present in EGPA?
pANCA and anti-MPO
How can disease be monitored?
ANCA, anti-PR3 and anti-MPO levels all vary with disease activity
Complement is consumed during active disease so C3/4 may fall
Management of AAV?
Localised/early systemic:
• Methotrexate + steroids
Generalised/systemic:
• 1st line - CYCLOPHOSPHAMIDE + STEROIDS
• Alternative - Rituximab + steroids
• This is followed by azathioprine; alternative inc. methotrexate, etc
Refractory (severe):
• IV Ig
• Rituximab
What is Henoch-Schönlein purpura (HSP)?
AKA acute IgA mediated disorder; it is a type of immune complex small-vessel vasculitis that tends to occur in CHILDREN between 2-11 YEARS (RARE in INFANTS)
It is a generalised vasculitis inv. small vessels of the skin, GI tract, kidneys and joints; rarely, vessel of the lungs and CNS
Triggers of HSP?
Most have a preceding URT, pharyngeal or GI infection. which usually occurs 1-3 weeks beforehand
Most common is group A Strep.
Presentation of HSP?
Purpuric rash typically over buttocks and lower limbs, sparing the upper body
Colicky abdominal pain
Bloody diarrhoea
Joint pain +/- swelling
Renal involvement (50%)
Management of HSP?
Usually, SELF-LIMITING and symptoms tend to resolve within 8 weeks; relapses may occur for months-years but will eventually stop
MUST PERFORM URINALYSIS to screen for renal inv.
