Autoimmune Conditions, Signs, Causes And Differentials Flashcards
What is vasculitis?
Strictly speaking it is inflammation of a blood vessel, vasculitis actually refers to a group of autoimmune conditions
Classification depends on size of vessel:
1. Large vessels = takayasu arteritis and giant cell arteritis - e.g. aorta and renal arteries
2. Medium vessels = polyarteritis nodosa and Kawasaki disease - e.g. renal arteries and interlobar arteries
3. Small vessels = Two categories - e.g. arcuate artery, arteriole and glomerular capillaries
A) circulating ANCA associated = microangiopathic polyangitis, wegeners granulomatosis and Chung Strauss syndrome
B) non-ANCA immune complexes= Lupus/rheumatoid, Henoch–Schönlein purpura, cryoglobulinaemia
What is takayasu vasculitis?
A large vessel vasculitis affecting the aorta and major branches, sometimes renal vasculature.
MOA: Granulomatous inflammation occurs due to immune reaction, WBC (mononuclear) infiltration of the endothelium, which heals with fibrosis causing scarring. This constricts the arteries and can cause ischemia. When this occurs in the renovasculature, the RAAS is activated and causes HTN.
What is giant cell arteritis?
A large vessel vasculitis, which affects the temporal arteries. This causes headaches, fever and polymyalgia.
Most important test is ESR, may present with jaw claudication and tender temporal areas.
What is polyarteritis nodosa (PAN)?
This is a medium sized vessel vasculitis. It acts on the visceral arteries causing necrotising arteritis.
It does not cause glomerulonephritis since it only acts on medium sized vessels.
Often associated with hepatitis B infection.
What are the signs of polyarteritis nodosa?
A skin rash - lived reticularis GI bleed Bowel infarction Renal artery aneurysms Renal artery infarction HTN
What is Kawasaki disease?
A medium vessel vasculitis disease of children.
Often presents with oral ulcerations (muco-cutaneous lymphadenopathy).
Can lead to coronary artery vasculitis.
What are the types of ANCA associated vasculitis?
GPA: Wegners granulomatosis (granulomatosis with polyangitis)
- most often ENT manifestations
MPA: Microscopic polyangitis
EGPA: Eosinophilic granulomatous polyangiitis (churg Strauss syndrome)
- most often respiratory symptoms and peripheral neuropathy
RLV: Renal limited vasculitis
Mostly characterised by circulating ANCA.
What is pANCA?
pANCA is an antineutrophil cytoplasmic autoantibody
It has perinuclear staining - hence ‘p’
The antibody is specific for (attacks) myeloperoxidase enzyme, contained within neutrophil granules - important enzyme for immune function.
What is cANCA?
cANCA is an antineutrophil cytoplasmic autoantibody
It has diffuse cytoplasmic staining - hence ‘c’ (stains entire cytoplasm)
The antibody is specific for (attacks) proteinase-3 enzyme; contained in neutrophil granules - important enzyme for immune function.
Which type of vasculitis is predominately c-ANCA positive?
Wegners granulomatosis (AKA granulomatosis with polyangitis)
Which type of vasculitis is often p-ANCA or c-ANCA positive?
Microscopic polyangitis is equally p-a ANCA and c-ANCA positive
Can also be ANCA negative
Which types of vasculitis is predominately p-ANCA positive?
Eosinophilic granulomatous polyangiitis (AKA Churg Strauss syndrome)
Pauci-immune glomerulonephritis
Both can also be ANCA negative
What are the causes of ANCA vasculitis?
The specific aetiology is unknown, however it appears to be multifactorial, like other autoimmune conditions.
Genetic predisposition
Environmental triggering; infection, silica and farming
What is the pathophysiology of ANCA vasculitis?
In short: neutrophils express weird antigen which acts as a switch to activate the neutrophil functions when bound by ANCA, the neutrophil then enters tissue and causes damage
- Priming of neutrophils (by infection etc)
- The neutrophils express autoantigen on their surfaces - visible to antibodies
- ANCA (antibodies) bind to the antigen and activate the neutrophils
- Activation causes adhesion and transmigration from blood to tissue
- Neutrophils then release ROS and cytokines
- Tissue damage occurs
What is the clinical presentation of ANCA vasculitis?
Kidney: Rapidly progressive glomerulonephritis
Lungs: Granuloma and alveolar haemorrhage, cough, Dyspnoea and haemoptysis (capillary damage)
ENT: Conductive deafness, rhinorrhoea, nasal crusting, epistaxis, nasal deformity and stenosis of subglottis and epiglottis (Granuloma formation)
Also: Skin rashes Myalgia and arthralgia GI symptoms Cardiac symptoms (mostly in churg Strauss) Peripheral neuropathy
