VASCULITIS

These are a heterogeneous group of diseases characterized by inflammation and necrosis of

blood-vessel walls, with associated damage to skin, kidney, lung, heart, brain and
gastrointestinal tract. There is a wide spectrum of involvement and disease severity,
ranging from mild and transient disease affecting only the skin, to life-threatening
fulminant disease with multiple organ failure.

clinical features result from a combination of local tissue ischaemia (due to vessel
inflammation and narrowing) and the systemic effects of widespread inflammation.
Systemic vasculitis should be considered in any patient with fever, weight loss, fatigue,
evidence of multisystem involvement, rashes, raised inflammatory markers and abnormal
urinalysis .

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Takayasu’s disease

Takayasu’s disease predominantly affects the aorta, its major branches and occasionally the
pulmonary arteries. The typical age at onset is between 25 and 30 years, with an 8 : 1
female preponderance.

It has a worldwide distribution but is most common in Asia. Takayasu’s is characterised by

granulomatous inflammation of the vessel wall, leading to vessel occlusion or weakening of
the vessel wall.

It presents with claudication, fever, arthralgia and weight loss. The vessels most commonly
affected are the aorta and carotid, ulnar, brachial, radial and axillary arteries.

Clinical examination may reveal loss of pulses, bruits, hypertension and aortic
incompetence.

Investigation will identify an acute phase response and normocytic, normochromic

anaemia, but the diagnosis is based on angiography, which reveals coarctation, occlusion
and aneurysmal dilatation.

The distribution of involvement is classified into four types:

• type 1: localised to the aorta and its branches

• type 2: localised to the descending thoracic and abdominal aorta

• type 3: combines features of 1 and 2

• type 4: involves the pulmonary artery.

Treatment is with high-dose steroids and immunosuppressants, as described for SLE. With
appropriate treatment, the 5-year survival is 83%.

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Kawasaki disease

Kawasaki disease is a vasculitis that mostly affects the coronary vessels. It presents as an
acute systemic disorder, usually affecting children under 5 years. It occurs mainly in Japan
and other Asian countries, such as China and Korea, but other ethnic groups may also be
affected.

Presentation is with fever, generalised rash, including palms and soles, inflamed oral
mucosa andconjunctival injection resembling a viral exanthem.

The cause is unknown but is thought to be the result of an abnormal immune response to
an infectious trigger.

Cardiovascular complications include coronary arteritis, leading to myocardial infarction,

transient coronary dilatation, myocarditis, pericarditis, peripheral vascular insufficiency and
gangrene.

Treatment is with aspirin (5 mg/kg daily for 14 days) and intravenous gammaglobulin (400
mg/kg daily for 4 days).

Polyarteritis nodosa
Polyarteritis nodosa has a peak incidence between the ages of 40 and 50, with a male
preponderance of 2 : 1. The annual incidence is around 2/1 000 000.
Hepatitis B is an important risk factor, and the incidence is 10 times higher in the Inuit of
Alaska, in whom hepatitis B infection is endemic.
Presentation is with fever, myalgia, arthralgia and weight loss, in combination with
manifestations of multisystem disease.
The most common skin lesions are palpable purpura ulceration, infarction and livedo
reticularis .

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Pathological changes comprise necrotising inflammation and vessel occlusion, and in 70% of
patients, arteritis of the vasa nervorum leads to neuropathy, which is typically symmetrical
and affects both sensory and motor function.
Severe hypertension and/or renal impairment may occur due to multiple renal infarctions,
but glomerulonephritis is rare (in contrast to microscopic polyangiitis).
The diagnosis is confirmed by angiography, which shows multiple aneurysms and smooth
narrowing of mesenteric, hepatic or renal systems, or by muscle or sural nerve biopsy,
which reveals the histological changes above.
Treatment is with high-dose steroids and immunosuppressants, as described for SLE.

Giant cell arteritis and polymyalgia rheumatica

Giant cell arteritis (GCA) is a granulomatous arteritis that predominantly affects medium-
sized arteries in the head and neck. It is commonly associated with polymyalgia rheumatica
(PMR), which presents with symmetrical muscle pain and stiffness affecting the shoulder
and pelvic girdles.

Since many patients with GCA have symptoms of PMR, and many patients with PMR go on
to develop GCA if untreated, many rheumatologists consider them to be different
manifestations of the same underlying disorder.

Both diseases are rare under the age of 60 years. The average age at onset is 70, with a
female preponderance of about 3 : 1. The overall prevalence is about 20 per 100 000 in
those over the age of 50 years.

Clinical features

The cardinal symptom of GCA is headache, which is often localised to the temporal or
occipital region and may be accompanied by scalp tenderness. Jaw pain develops in some
patients, brought on by chewing or talking, due to ischaemia of the masseter muscles.
Visual disturbance can occur and a catastrophic presentation is with blindness in one eye
due to occlusion of the posterior ciliary artery.

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On fundoscopy, the optic disc may appear pale and swollen with haemorrhages, but these
changes may take 24–36 hours to develop and the fundi may initially appear normal.

Other visual symptoms include loss of visual acuity, reduced colour perception and papillary
defects. Rarely, neurological involvement may occur, with transient ischaemic attacks,
brainstem infarcts and hemiparesis.

The cardinal features of PMR are symmetrical muscle pain and stiffness affecting the
shoulder and pelvic girdles.

Constitutional symptoms, such as weight loss, fatigue, malaise and night sweats, are
common. The onset of symptoms is usually fairly sudden over a few days, but may be more
insidious. On examination, there may be stiffness and painful restriction of active shoulder
movement but passive movements are preserved.

Muscles may be tender to palpation but weakness and muscle-wasting are absent.

Other conditions that mimic PMR are

• Fibromyalgia • Hypothyroidism • Cervical spondylosis • RA

• Systemic vasculitis • Inflammatory myopathy (particularly inclusion body myositis,) •

Malignancy

Investigations

The typical laboratory abnormality is an elevated ESR, often with a normochromic,

normocytic anaemia.

CRP may also be elevated and in some cases this precedes elevation of the ESR.

Rarely, PMR and GCA can present with a normal ESR.

The diagnosis is usually based on a combination of the typical clinical features, raised ESR
and prompt response to steroid.

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However, if there is doubt concerning the diagnosis of GCA, a temporal artery biopsy may
be undertaken.

Characteristic biopsy findings are fragmentation of the internal elastic lamina with necrosis
of the media in combination with a mixed inflammatory cell infiltrate.

Whilst a positive biopsy is helpful, a negative biopsy does not exclude the diagnosis because
the lesions are focal.

Ultrasound or arteriography may be used to help guide the biopsy.

Management

Corticosteroids are the treatment of choice and should be commenced urgently in

suspected GCA because of the risk of visual loss

Emergency management of giant cell arteritis

• Take blood for ESR and CRP • Commence prednisolone 40–60 mg daily

• Review patient in 3–4 days • Continue steroids in patients whose symptoms have
resolved, with gradual reduction in dose

• Organise temporal artery biopsy in patients with poor or equivocal response

Response to treatment is dramatic, such that symptoms will have completely resolved
within 48–72 hours of starting corticosteroid therapy in virtually all patients.

It is customary to use higher doses in GCA (60–80 mg prednisolone) than in PMR (15–30
mg), although the evidence base for this is weak.

In both conditions the steroid dose should be progressively reduced, guided by symptoms
and ESR, with the aim of reaching a dose of 10–15 mg by about 8 weeks. Thereafter, the
rate of reduction should be slower – by 1 mg per month – until an acceptable dose is
achieved (5–7.5 mg daily).

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If symptoms recur, the dose should be increased to that which previously controlled the
symptoms, and reduction attempted again in another few weeks.

Most patients need steroids for an average of 12–24 months.

Some patients also require steroid sparing agents, such as methotrexate or azathioprine, if
they require a maintenance dose of prednisolone of more than 7.5 mg daily.

Prophylaxis against osteoporosis should be given in patients with low BMD.

Antineutrophil cytoplasmic antibody-associated vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a life-threatening

disorder characterized by inflammatory infiltration of small blood vessels, fibrinoid necrosis
and the presence of circulating antibodies to ANCA.

The combined incidence is about 10– 15/1 000 000. Two subtypes are recognised.
Microscopic polyangiitis (MPA) is a necrotising small-vessel vasculitis found with rapidly
progressive glomerulonephritis, often in association with alveolar haemorrhage.

Cutaneous and gastrointestinal involvement is common and other features include

neuropathy (15%) and pleural effusions (15%).

Patients are usually myeloperoxidase (MPO) antibody-positive.

In granulomatosis with polyangiitis (also known as Wegener’s granulomatosis (WG)), the

vasculitis is characterised by granuloma formation, mainly affecting the nasal passages,
airways and kidney.

A minority of patients present with glomerulonephritis. The most common presentation of

WG is with epistaxis, nasal crusting and sinusitis, but haemoptysis and mucosal ulceration
may also occur.

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Deafness may be a feature due to inner ear involvement, and proptosis may occur because
of inflammation of the retro-orbital tissue.

This causes diplopia due to entrapment of the extra-ocular muscles, or loss of vision due to
optic nerve compression.

Disturbance of colour vision is an early feature of optic nerve compression. Untreated nasal
disease ultimately leads to destruction of bone and cartilage.

Migratory pulmonary infiltrates and nodules occur in 50% of patients.

Patients with WG are usually proteinase-3 (PR3) antibody-positive. Patients with active
disease usually have a leukocytosis with an elevated CRP and ESR, in association with raised
ANCA levels.

Complement levels are usually normal or slightly elevated.

Imaging of the upper airways or chest with MRI can be useful in localizing abnormalities
but, where possible, the diagnosis should be confirmed by biopsy of the kidney or lesions in
the sinuses and upper airways.

Management is with high-dose steroids and cyclophosphamide, as described for SLE,

followed by maintenance therapy with lower-dose steroids and azathioprine, methotrexate
or mycophenolate mofetil (MMF).

Rituximab in combination with high-dose steroids is equally effective as oral

cyclophosphamide at inducing remission in ANCA-associated vasculitis.

Both MPA and WG have a tendency to relapse, and patients must be followed on a regular
and long-term basis to check for clinical signs of recurrence.

Measurements of ESR, CRP and levels of ANCA antibodies are useful in monitoring disease
activity.

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Churg–Strauss syndrome

Churg–Strauss syndrome (CSS) is a small-vessel vasculitis with an incidence of about 1–3 per
1 000 000; it is associated with eosinophilia. Some patients have a prodromal period for
many years, characterised by allergic rhinitis, nasal polyposis and late-onset asthma that is
often difficult to control.

The typical acute presentation is with a triad of skin lesions (purpura or nodules),
asymmetric mononeuritis multiplex and eosinophilia.

Pulmonary infiltrates and pleural or pericardial effusions due to serositis may be present.
Up to 50% of patients have abdominal symptoms provoked by mesenteric vasculitis.
Patients with active disease have raised levels of ESR and CRP and an eosinophilia.

Although antibodies to MPO or PR3 can be detected in up to 60% of cases, CSS is

considered to be a distinct disorder from the other ANCA-associated vasculitides.

Biopsy of an affected site reveals a small-vessel vasculitis with eosinophilic infiltration of

the vessel wall.

Management is with high-dose steroids and cyclophosphamide, followed by maintenance

therapy with lowdose steroids and azathioprine, methotrexate or MMF.

Henoch–Scohnlein purpura

Henoch–Schonlein purpura (HSP) is a small-vessel vasculitis caused by immune complex

deposition following an infectious trigger. It is predominantly a disease of children and
young adults.

The usual presentation is with purpura over the buttocks and lower legs, accompanied by
abdominal pain, gastrointestinal bleeding and arthralgia.

Nephritis can also occur and may present up to 4 weeks after the onset of other symptoms.

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Biopsy of affected tissue shows a vasculitis with IgA deposits in the vessel wall. HSP is
usually a self-limiting disorder that settles spontaneously without specific treatment.
Corticosteroids and immunosuppressive therapy may be required in patients with more
severe disease, particularly in the presence of nephritis.

Cryoglobulinaemic vasculitis

This is a small-vessel vasculitis that can develop in some patients with circulating
cryoglobulins, which are immunoglobulins that precipitate out in the cold.

Cryoglobulins are classified into three types and types II and III are associated with
vasculitis. The typical presentation is with a vasculitic rash over the lower limbs, arthralgia,
Raynaud’s phenomenon and neuropathy.

Some cases are secondary to hepatitis infection and others are secondary to other
autoimmune diseases.

Affected patients should be screened for evidence of hepatitis B and C infection, and if the
results are positive, these should be treated appropriately .

There is no consensus as to how best to treat cryoglobulinaemic vasculitis in the absence of

an obvious trigger.

Corticosteroids and immunosuppressive therapy are often used empirically but their
efficacy is uncertain.

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