Vasculitis

Question 1

What is vasculitis

Answer 1

Vasculitis is the term applied to an inflammatory disorder of blood vessels which causes endothelial damage. Cutaneous vasculitis (confirmed by skin biopsy) mav be an isolated problem but occasionallv is associated with vasculitis in other organs. The most commonly used classification is based on the size of blood vessel involved

Question 2

What are some cutaneous features of vasculitis

Answer 2

The cutaneous features are of haemorrhagic papules. bustules. nodules or plaques which mav erode and ulcerate
These purpuric lesions do not blanch with pressure from a glass slide (*diascopy’). Occasionally, a fixed livedo reticularis pattern may appear which does not disappear on warming.

Question 3

What are the most common associations of vasculitis

Answer 3

Pyrexia and arthralgia are common associations even in the
absence of signItIcant systemic involvement. Other clinIcal features depend on the underlying cause

Question 4

What is the most common cutaneous vasculitis affecting small vessels

Answer 4

LeucocytocIastIc vasculItis (LCV) or anglitis

Question 5

Which part of the body is LCV most commonly found

Answer 5

Usually appears on the lower legs as a symmetrical palpable purpura. It is rarely associated with systemic involvement

Question 6

What are the causes of LCV

Answer 6

It can be caused by drugs (15%), infection (15%), inflammatory disease (10%) or malignant disease (<5%) but often no cause is found (55-60%)

Question 7

What are some investigations that need to be done for LCV

Answer 7

Investigations are only necessary with persistent lesions or associated signs and symptoms

Question 8

What is the treatment for LCV

Answer 8

Whilst LCV often settles spontaneously, treatment with analgesia, support stockings, dapsone or prednisolone may be needed to control the pain and to heal up any ulceration

Question 9

What are the two main features involved in the classification of vasculitis

Answer 9

The size of the blood vessels involved and the presence or absence of anti-neutrophil cytoplasmic antibodies (ANCA) in the blood

Question 10

Which blood vessels are affected in a large vessel vasculitis

Answer 10

Aorta and its maior tributaries

Question 11

Which blood vessels are affected in a medium-sized vasculitis

Answer 11

Small-sized arteries and arterioles.

Question 12

Which blood vessels are affected in a small vessel vasculitis

Answer 12

Small arteries, arterioles. venules and capillaries

Question 13

What are some examples of large vessel systemic vasculitis

Answer 13

Giant cell arteritis / Polymyalgia rheumatica
Takayasu’s arteritis

Question 14

Causes a sudden onset or severe pain and stiffness of the shoulders and neck, and of the hips and lumbar spine; a limb girdle pattern. These symptoms are worse in the morning, lasting from 30 minutes to several hours.

Clinical history is usually diagnostic and the patient is alwavs over su years old.
Approximately one-third of patients develop systemic features of tiredness, weight loss, depression and occasionally nocturnal sweats especially if PM is not diagnosed and treated early.
What condition could this be

Answer 14

Polymyalgia rheumatica

Question 15

What are some investigations for polymyalgia rheumatica

Answer 15

A raised ESR and/or CRP is a hallmark of this condition. It is rare to see PMR without an acute-phase response. If it is absent, the diagnosis should be questioned and the tests repeated a few weeks later before treatment is started.
• Serum alkaline phosphatase and y-glutamyl-transpeptidase may be raised as markers of the acute inflammation.
• Anaemia (mild normochromic, normocytic) is often present.
• Temporal artery biopsy shows giant cell arteritis in 10-30% of cases, but is rarely performed unless GCA is also suspected.

Question 16

What is giant cell arteritis

Answer 16

GCA is inflammatory granulomatous arteritis of large cerebral arteries which occurs in association with PM. The patient may have current PMR, a history of recent PMR, or be on treatment for PMR. It is extremely rare under 50 years of age.

Question 17

What are the presenting symptoms for giant cell arteritis

Answer 17

Presenting symptoms of GA include severe headaches
tenderness of the scalp (combing the hair may be painful) or of the temple, claudication of the jaw when eating, tenderness
swelling of one or more temporal or occipital arteries. The most feared manifestation is sudden painless temporary or permanent loss of vision in one eye due to involvement of the ophthalmic artery.
Systemic manifestations of severe malaise, tiredness and fever occur.

Question 18

What are some investigations of giant cell arteritis

Answer 18

• Normochromic, normocytic anaemia
• ESR is usually raised (in the region of 50-120 mm/h) and the CRP very high
• Liver biochemistry. Abnormalities occur, as in PMR. The albumin may be low
• A temporal artery biopsy from the affected side is the definitive diagnostic test. This should be taken before, or within 7 days of starting, high doses of corticosteroids.
The lesions are patchy and the whole length of the biopsy (>1 cm long) must be examined; even so, negative biopsies occur.

Question 19

What are the histological features of giant cell arteritis

Answer 19

Cellular infiltrates of CD4+ T lymphocytes, macrophages and giant cells in the vessel wall. Note that giant cells are not visible in all cases
• Granulomatous inflammation of the intima and media
Breaking up of the internal elastic lamina
Giant cells, lymphocytes and plasma cells in the internal elastic lamina.

Question 20

What is the treatment for polymyalgia rheumatica or giant cell arteritis

Answer 20

Corticosteroids produce a dramatic reduction of symptoms of PM within 24-48 hours of starting treatment, provided the dose is adequate. If this improvement does not occur, the diagnosis should be questioned and an alternative cause sought, such as RA, vasculitis, infection or malignancy. This treatment should reduce the risk of patients who have PMR developing GCA. NSAIDs are less effective and should not be used.
In GCA, corticosteroids are obligatory because they significantly reduce the risk of irreversible visual loss and other focal ischaemic lesions, but much higher doses are needed than in PMR. If GCA is suspected, it may not be possible to arrange a temporal artery biopsy rapidly. In these circum-stances, treatment should not be delayed, especially if there have already been episodes of visual loss or stroke.
Starting daily doses of prednisolone are:
• PMR: 10-15 mg prednisolone as a single dose in the morning
• GCA: 60-100 mg prednisolone, usually in divided doses.
The dose should then be reduced gradually in weekly or monthly steps. While the dose is above 20 mg, the step reductions are 5 mg, reducing the evening doses first.
Between 20 mg and 10 mg the reduction can be in 2.5 mg steps, but below 10 mg the rate should be slower and the steps each of 1 mg. Most patients will eventually be able to stop corticosteroids after 12-18 months but up to 25% may need low doses long-term. Steroid-sparing immunosuppressive agents are used in refractory cases where it is hard to reduce the corticosteroid dose without causing a flare of disease or a rise in ESR or CRP.
Calcium and vitamin D supplements and sometimes bisphosphonates are necessary to prevent osteoporosis while high-dose steroids are being used

Question 21

What is Takayasu arteritis

Answer 21

This is a granulomatous inflammation of the aorta and its major branches

Question 22

Give some examples of medium sized vessel vasculitis

Answer 22

Polyarteritis nodosa (PAN)
Kawasaki’s disease

Question 23

Rare condition which usually occurs in middle-aged men
Accompanied by severe systemic manifestations, and its occasional association with hepatitis B antigenaemia suggests a vasculitis secondary to the deposition of immune complexes.
Pathologically, there is fibrinoid necrosis of vessel walls with microaneurysm formation, thrombosis and infarction.
Which condition could this be

Answer 23

Polyarteritis nodosa (PAN)

Question 24

What are the clinical features of polyarteritis nodosa

Answer 24

These include fever, malaise, weight loss and myalgia. These initial symptoms are followed by dramatic acute features that are due to organ infarction
Neurological: mononeuritis multiplex is due to arteritis of the vasa nervorum.
• Abdominal: pain due to arterial involvement of the abdominal viscera, mimicking acute cholecystitis, pancreatitis or appendicitis. Gastrointestinal haemorrhage occurs because of mucosal ulceration.

•Renal: presents with haematuria and proteinuria.
Hypertension and acute/chronic kidney disease occur.
• Cardiac: coronary arteritis causes myocardial infarction
and heart failure. Pericarditis also occurs.
• Skin: subcutaneous haemorrhage and gangrene occur.
A persistent livedo reticularis is seen in chronic cases.
Cutaneous and subcutaneous palpable nodules occur,
but are uncommon.
• Lung: involvement is rare

Question 25

What is the investigation for PAN

Answer 25

Blood count. Anaemia, leucocytosis and a raised ESR occur. Biopsy material from an affected organ shows features listed above. • Angiography. Demonstration of microaneurysms in hepatic, intestinal or renal vessels if necessary. • Other investigations as appropriate (e.g. ECG and abdominal ultrasound), depending on the clinical problem. ANCA is positive only rarely in classic PAN.

Question 26

What is the treatment for PAN

Answer 26

Treatment is with corticosteroids, usually in combination with immunosuppressive drugs such as azathioprine.

Question 27

**This is an acute systemic vasculitis involving medium-sized vessels**, affecting mainly children under 5 years of age. It is very **frequent in Japan**, and an infective trigger is suspected. It occurs worldwide and is also seen in adults. What condition could this be

Answer 27

Kawasaki’s disease

Question 28

What are some clinical features of Kawasaki’s disease

Answer 28

Fever lasting 5 days or more • Bilateral conjunctival congestion 2-4 days after onset • Dryness and redness of the lips and oral cavity 3 days after onset • Acute cervical lymphadenopathy accompanying the fever • Polymorphic rash involving any part of the body • Redness and oedema of the palms and soles 2-5 davs after onset. The persistent fever plus at least four of the other five features should be present to make the diagnosis, or fewer than four if coronary aneurysms can be seen on two-dimensional echocardiography, MRI or angiography. Cardiovascular changes in the acute stage include pancar-dits and coronary arteritis leading to aneurysms or dilatation. Other features include diarrhea, albuminuria, aseptic meningitis and arthralgia and, in most, there is a leucocytosis, thrombocytosis and a raised CRP. Anti-endothelial cell autoantibodies are often detectable.

Question 29

What is the treatment for Kawasaki’s disease

Answer 29

Treatment is with a single dose of high-dose intravenous immunoglobulin (2 g/kg), which prevents the coronary artery disease, followed after the acute phase by aspirin 200-300 mg daily. There is no evidence that steroid treatment improves the outcome.

Question 30

This can be separated into those that are positive or negative for anti-neutrophil cytoplasmic antibody (ANCA) What is this

Answer 30

Small vessel vasculitis

Question 31

What are the ANCA-positive small cell vasculitis

Answer 31

- Wegener's granulomatosis - Churg-Strauss granulomatosis - Microscopic polyangitis

Question 32

List the ANCA-negative small cell vasculitis

Answer 32

- Henoch-Schönlein purpura - Cryoglobulinaemic vasculitis - Cutaneous leucocytoclastic vasculitis

Question 33

Characteristic acute **purpuric lesion** which histologically involves the dermal post-capillary venules Lesion affects only the skin and should be differentiated from similar lesions produced in systemic vasculitis The purpura may be accompanied by arthralgia and glomerulonephritis. Hepatitis C infection is common and may be an aetiological agent. **The condition can also be caused by drugs such as sulphonamides and penicilin.** What condition could this be

Answer 33

Cutaneous leucocytoclastic vasculitis

Question 34

What is the treatment for small cell vasculitis

Answer 34

The treatment depends on the organs involved. Vasculitis confined to the skin may not require systemic treatment whereas involvement of major organs (e.g. lungs or kidneys in Wegener's granulomatosis) requires high-dose cortico-steroids, immunosuppression and sometimes plasma exchange. Two recent clinical trials have shown that depletion of B cells with rituximab is as effective as cyclophosphamide in treating ANCA-associated vasculitis and it is likely that this will become a common form of treatment in the near future.

Question 35

**Inflammatory disorder of unknown cause.** There is a striking geographical distribution, it being most common in Turkey, Iran and Japan. **There is a link to the HLA-B51 allele, with a relative risk of 5-10; this association is not seen in patients in the USA and Europe.** What condition could this be

Answer 35

Behçet's disease

Question 36

What are the classical features of Behçet’s disease

Answer 36

The cardinal clinical feature is recurrent oral ulceration. The international criteria for diagnosis require oral ulceration and any two of the following: genital ulcers, defined eye lesions, defined skin lesions, or a positive skin pathergy test (see below). Oral ulcers can be aphthous or herpetiform. The eye lesions include an anterior or posterior uveitis or retinal vascular lesions. Cutaneous lesions consist of erythema nodosum, pseudofolliculitis and papulopustular lesions. Other manifestations include a self-limiting peripheral mono- or oligoarthritis affecting knees, ankles, wrists and elbows; gastrointestinal symptoms of diarrhea, abdominal pain and anorexia; pulmonary and renal lesions; thrombophlebitis (especially in the legs); vasculitis; a brainstem syndrome, organic confusional states and a meningoencephalitis. All the common manifestations are self-limiting except for the ocular attacks. Repeated attacks of uveitis can cause blindness. The pathergy reaction is highly specific to Behçet's disease. Skin injury, by a needle prick for example, leads to papule or pustule formation within 24-48 hours. Blood tests usually show raised ESR and CRP but not autoantibodies.

Question 37

What is the treatment for Behçet’s disease

Answer 37

Corticosteroids, immunosuppressive agents and ciclosporin are used for chronic uveitis and the rare neurological com-plications. Colchicine helps erythema nodosum and joint pain. Thalidomide may be useful in some cases although side-effects of drowsiness and peripheral neuropathy are common. It should not be used in pregnant women because of phocomelia (limb abnormalities). Anti-TNF agents can be used to control severe uveitis and serious manifestations such as neurological and gastrointestinal Behçet's disease.