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Flashcards in Rheumatology - Vasculitis Deck (44)
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What is vasculitis? How is it classified?

The vasculitides are a group of systemic autoimmune conditions characterised by blood vessel wall inflammation. Damage is caused by ischaemia and necrosis of the tissue supplied.

Vasculitis is classified based on the size of the vessel it affects - small, medium or large or whether it expresses specific autoantibodies.

Vasculitis can arise as a primary process or secondary to other autoimmune diseases - especially RA and SLE.


What clinical features suggest a patient has systemic vasculitis?

Systemic vasculitis is suggested by:
- symptoms referable to > 1 organ
- constitutional symptoms (e.g. fever, weight loss, anorexia)
- increased ESR and CRP


What is the most common form of vasculitis? What is PAN associated with?

Wegener's granulomatosis (a form of small vessel vasculitis associated with c-ANCA) and giant cell arteritis are the 2 most common vasculitides.

Certain vasculitides are common at the extremes of age. For example, Kawasaki disease is almost paediatric whereas GCA generally occurs in the over 60s.

Some vasculitides are also associated with specific infections - e.g. PAN and hepatitis B.


What vasculitides are associated with granulomatous (caseating) necrosis of blood vessel walls?

These all have G in their name:
- GCA (large)
- BueGers (medium)
- ChurG-Strauss (small)
- WeGener's (small)

The only 2 exceptions are PAN (medium) and Takayasu's arteritis (large)


What pathological feature is often seen in vasculitis?

There is no exclusive pathology in vasculitis but leukocytoclastic vasculitis is often seen.
This is a characteristic histological appearance resulting from dissolution of leukocytes.

Suitable sites for biopsy are: blood vessels (e.g. superficial temporal arteries in suspected GCA), involved skin or other organs - e.g. kidney, lung, muscle


What antibodies are associated with vasculitis?

1) Antineutrophil cytoplasmic antibodies (ANCA)
2) RhF
3) Anti-double stranded DNA antibodies (Anti-dsDNA)

NB - only ANCA antibodies are associated with primary vasculitis and used to distinguish between the 2 types of small vessel vasculitis. RhF and SLE associated antibodies are used to diagnose vasculitis secondary to other autoimmune diseases


What are ANCA antibodies?

Antineutrophil cytoplasmic antibodies are circulating antibodies directed against cytoplasmic components of neutrophils.

They are classified according to the pattern of nuclear staining:
i) cytoplasmic (cANCA) associated with antibodies to proteinase 3 which are strongly associated with WG
ii) perinuclear (pANCA) directed against myeloperoxidase associated with other primary small vessel vasculitides and some other conditions


What conditions are pANCA antibodies associated with?

They are associated with the "PURGE" diseases:
- PAN, microscopic Polyangitis (or Churg-Strauss)
- UC
- RA with vasculitis
- Glomerulonephritis
- Endocarditis with HIV


What is rheumatoid factor?

Rheumatoid factors (RhFs) are antibodies directed against the Fc component of immunoglobulin (Ig). They occur in many patients with RA and are also found in many other vasculitides and chronic infections.


What are the primary large vessel vasculitides?

- Giant cell arteritis (GCA) and polymyalgia rheumatic (PMR)
- Takayasu's arteritis


What is the link between GCA and PMR?

The aetiology of GCA and PMR remains unclear. Both share common epidemiological, clinical and serological features although GCA is a granulomatous large vessel vasculitis, whilst PMR is an inflammatory disorder classically manifesting with shoulder and pelvic girdle muscular pain and stiffness in the absence of weakness.

Both conditions are more common in women over 50 and are associated with HLA-DR4 and HLADRB1 alleles, suggesting a genetic predisposition.


What is the clinical presentation of GCA?

Symptoms usually include the following:
- mild or severe, unilateral, temporal headaches often of abrupt onset
- burning sensation and tenderness over the scalp
- claudication of the jaw/ tongue muscles producing pain on chewing in 33-50% of cases
- systemic manifestations
- features of large vessel involvement: limb claudication
- symptoms of PMR


What is a serious complication of GCA?

Visual disturbances are the most serious complication of GCA. These can include blurring of vision, diplopia or amaurosis fugax. These are initially transient and ultimately progress to complete visual loss if not recognised and treated.

They occur in up to 20% of patients and reflect the arteries supplying the retina and/ or optic nerve.


What are the examination findings of GCA?

- ipsilateral temporal artery tenderness, thickened and irregular with reduced or absent pulsations
- scalp tenderness
- visual field defect
- relavent afferent pupillary defect
- anterior ischaemic optic neuritis (pale swollen optic disc with haemorrhages)
- asymmetry of pulses and blood pressure
- arterial bruits


What are the clinical features of polymyalgia rheumatica?

PMR is characterised by relatively abrupt onset of pain and stiffness in the shoulder and pelvic girdle. Symptoms are typically worse after periods of inactivity and there are few physical signs.

NB - restricted movement, weakness and tenderness are NOT features of PMR and should prompt consideration for other diagnoses (e.g. frozen shoulder, OA, or inflammatory myositis)


What investigations should be performed for GCA/ PMR?

There are no specific serological testes for GCA or PMA, but:
- ESR and CRP are usually raised, ESR typically > 60mm/h
- temporal artery biopsy is gold standard; arterial wall thickening with mononuclear cell infiltration or granulomatous infiltration with giant cells causing vessel occlusion
- duplex ultrasonography may show characteristic "hypoechoic halo", vessel occlusion and stenosis
- muscle enzymes, EMG, muscle biopsy all normal in PMR


Can GCA be diagnosed in the absence of positive biopsy?

Yes. Negative biopsy does not exclude GCA as skip lesions may occur. GCA should be diagnosed even with a negative biopsy if the clinical and biochemical features suggest the diagnosis.

Also, the biopsy often remains positive for 2-6 weeks after treatment is started so institution of corticosteroid therapy should not be delayed.


How should GCA and PMR be managed?

GCA and PMR are very sensitive to steroids.
- 60mg of prednisolone should be started without delay, and IV methylprednisolone should be used if there is visual disturbance
- treatment should continue for at least 12-24 months
- monitor CRP and ESR
- low dose aspirin may reduce the rate of visual loss and CVA in GCA

- 10-20mg of prednisolone daily is usually sufficient


What is Takayasu's arteritis?

This is a rare disorder (also called "pulseless disease") is characterised by inflammation and stenosis of large sized arteries with frequent involvement of the aortic arch and its branches producing aortic arch syndrome.

Its aetiology remains unclear but it is similar to GCA with focal granulomatous arteritis.


What are the clinical features of Takayasu's arteritis?

Clinical manifestations include:
- absent pulses - carotid, radial or ulnar arteries
- constitutional symptoms (fever, weight loss, anorexia)
- bruits: aortic, carotid and subclavian
- hypertension: majority of cases


How should Takayasu's arteritis be investigated?

ESR and CRP are typically raised, with anaemia and leucocytosis.

Aortic arch angiography and MR angiography are the imaging techniques of choice. They both reveal diffuse narrowing of the aorta and main arteries.


Management of Takayasu's arteritis

Treatment is with high dose corticosteroids (60-80mg) with gradual dose reduction guided by inflammatory markers.

Additional immunosuppression may be required in certain cases using azothioprine, methotrexate or cyclophosphamide.

Surgical intervention may be required for critical carotid or renal artery stenosis or significant aortic regurgitation.


What is polyarteritis nodosa? What is the characteristic pathological feature?

This is one of 2 medium vessel vasculitides (the other being Kawasaki's disease) that is characterised by necrotising immune complex inflammation of vessel walls.

Pathologically, it involves destruction of the arterial media and internal elastic lamina resulting in aneurysmal nodules.


What infection is associated with PAN?

PAN is of unknown aetiology but is associated with hepatitis B infection in 30% of cases.


What are the clinical features of PAN?

Clinical features often include constitutional symptoms such as fever, weight loss, and anorexia. PAN can also affect the following sites:
- kidneys: immune complex vasculitis in the arterioles of the glomeruli, renal lesions, and hypertension
- coronary arteries: ischaemic heart disease
- musculoskeletal system: myalgia, arthralgia, or arthritis
- GIT: nausea, vomiting or abdominal pain
- CNS: stroke
- PNS: peripheral neuropathy, areflexia, monoeuritis multiplex


How should PAN be managed?

Systemic disease (constitutional symptoms + symptoms reflecting >1 organ involvement) should be treated with a combination of corticosteroids and cytotoxic chemotherapy.

HBV infection should be treated promptly.


What is Kawasaki disease? What are the clinical features and how is it treated?

This disease is also called mucocutaneous lymph node syndrome. It is an acute, self limiting illness affecting infants and young children. It is characterised by acute necrotising vasculitis of medium sized vessels.

Clinically, the syndrome manifests by
1) fever, haemorrhagic oedema of the conjunctiva, lips and oral mucosa and cervical lymphadenopathy
2) It can be a cause of coronary artery vasculitis with aneurysm formation

It is treated with aspirin and IVIg.


How are small vessel vasculitides classified?

The small vessel vasculitides are distinguished based on whether they are associated with ANCA antibodies or not.

ANCA positive: these constitute Wegener's granulomatosis and microscopic polyangitis:
- cytoplasmic staining usually directed against proteinase 3 (c-ANCA) is Wegener's
- perinuclear staining directed against myeloperoxidase in microscopic polyangitis, and also a subset of patients with Churg-Strauss (amongst other conditions)

ANCA negative: these include hypersensitivity vasculitis, HSP and cryoglobulinaemia.


What is Wegener's granulomatosis?

This is a disease of unknown aetiology that is characterised by necrotising granulomatous vasculitis of the small vessels affecting the lungs and kidneys.

It affects both sexes equally, can occur at any age (commonly in middle age) and has an estimated annual incidence of between 10 to 20 million people. It is one of the most common vasculitides next to giant cell arteritis.


What are the clinical features of Wegener's?

The main feature of Wegener's are respiratory tract signs and symptoms especially of the paranasal sinuses and lungs. Necrotising glomerulonephritis (sometimes with immune complex deposition) is also common.

Microscopically, Wegener's is associated with fibrinoid necrosis of small arteries and veins, early infiltration by neutrophils, mononuclear cell infiltrate and granuloma formation with giant cells.