Vasculitides

Question 1

What is vasculitis?

Answer 1

In its strictest sense, the term vasculitis denotes inflammation of a blood vessel, which is characterised by the presence of an inflammatory infiltrate and destruction of the vessel wall. Commonly, however, vasculitis refers to the systemic vasculitides, which are autoimmune disorders characterised by inflammation of blood vessels. The systemic vasculitides are a diverse group of disorders that demonstrate a wide range of organ involvement and clinical severity.

Question 2

! How are systemic primary vasculitides classified? (x2, x2, x6 and x1)

Answer 2

• LARGE: Giant cell arteritis (GCA), Takayasu’s arteritis (TA)
• MEDIUM: polyarteritis nodosa (PAN), Kawasaki’s disease (KD)
• SMALL: Churg-Strauss syndrome (CSS AKA eosinophilic granulomatosis with polyangiitis), microscopic polyangitis (MP), Henock-Schonlein purpura (HSP), Wegener’s granulomatosis (WG AKA granulomatosis with polyangiitis), mixed essential cryoglobulinaemia (MEC) and relapsing polychondritis (RP)
• VARIABLE VESSEL: Behcet’s disease

Question 3

What is the aetiology of primary vasculitides?

Answer 3

Autoimmune disorder of unknown origin.

Question 4

What are the associations of vasculitis? (x2)

Answer 4

PAN – Hep B. MEC – Hep C.

Question 5

What is the aetiology of systemic secondary vasculitides? (x3)

Answer 5

Infections, malignancies, connective tissue disorders such as RA and SLE.

Question 6

What is the pathophysiology of vasculitis? (x4 points)

Answer 6

• Autoimmune complex deposition in vessel walls that trigger classical complement activation and inflammation
• Some vasculitides such as WG, MP and CSS are not associated with this pathophysiology. Instead, autoantibodies are ANTI-NEUTROPHIL CYTOPLASMIC AUTOANTIBODIES (pANCA) which cause vascular damage indirectly by priming neutrophils to degranulate and produce free radicals
• Some have evidence of granulomatous inflammation (GCA, WG, CS and PAN) – aggregates of macrophages in chronic inflammation
• In both cases, necrosis of the vessel wall and RBC extravasation is characteristic of vasculitis

Question 7

What is fibrinoid necrosis?

Answer 7

When antigen-antibody complexes are deposited in the walls of blood vessels.

Question 8

What is the epidemiology of vasculitis: Age? Ethnicity?

Answer 8

Over 50. White ethnicity. Particular forms affect specific populations.

Question 9

What is the onset of vasculitis?

Answer 9

Sub-acute onset with symptoms and signs of chronic inflammation.

Question 10

Principle of differentiating between large, medium and small vessel vasculitides?

Answer 10

Large vasculitides have patterns resulting from the vessel affected. Medium and small vessel vasculitides are characterised by multi-organ involvement with less specific clinical features.

Question 11

GENERAL: What are the signs and symptoms of vasculitis?

Answer 11

• Constitutional symptoms: fever, night sweats, malaise, weight loss
• SKIN: purpuric, maculopapular, livedo reticularis rashes (small vessel)
• JOINT: arthralgia, myalgia, usually before onset of more specific symptoms
• GI: abdominal pain from ischaemia in medium vessel vasculitides, haemorrhage from mucosal ulceration, diarrhoea
• KIDNEY: glomerulonephritis, renal failure (small vessel)
• LUNG: dyspnoea, cough, chest pain, haemoptysis (small vessel)
• CVS: pericarditis, coronary arteritis, myocarditis
• CNS: mononeuritis multiplex, infarctions, meningeal involvement
• EYES: retinal haemorrhage, cotton wool spots, vision loss

Question 12

What is a purpuric rash?

Answer 12

Skin haemorrhages, more common at extremities.

Question 13

What is livedo reticularis?

Answer 13

Small blood clots that develop inside the blood vessels of the skin. It causes the skin to take on a blotchy red or blue appearance.

Question 14

What is mononeuritis multiplex?

Answer 14

Asymmetric, painful, sensory and motor peripheral neuropathic inflammation of two or more nerves in random areas of the body.

Question 15

What are the signs and symptoms characteristic of specific subtypes of vasculitis: large vessel vasculitides?

Answer 15

• GCA: see notes below
• TA: aka aortic arch syndrome; head/neck pain, tenderness over aorta and its major branches, dizziness, fainting, asymmetrical brachial pulses, reduced peripheral pulses, hypertension

Question 16

What are the signs and symptoms characteristic of specific subtypes of vasculitis: medium vessel vasculitides?

Answer 16

• PAN: microaneurysms, thrombosis, infarctions, hypertension and testicular pain.
• KD: age below 5 years, fever lasting over 5 days, fissured lips, red swollen palms and soles followed by desquamation, skin rash, inflamed oral cavity, conjunctival congestion, lymphadenopathy, coronary artery aneurysm

Question 17

What are the signs and symptoms characteristic of specific subtypes of vasculitis: small vessel vasculitides?

Answer 17

• CSS: allergic rhinitis, sinusitis, asthma, otorrhoea, ear pain
• (HSP: purpura on leg and buttocks, gut symptoms, glomerulonephritis with IgA deposition)
• MP: non-specific
• WG: granulomatous vasculitis of upper and lower respiratory tract, nasal discharge, sinusitis, corneal thinning
• (RP: affecting cartilage of ear, nose and larynx causing inflammation, hoarse voice)
• (MEC: splenomegaly, cryoglobulins)

Question 18

What are the investigations for vasculitis? (x5)

Answer 18

• BLOOD: high ESR (>100)/CRP, normocytic anaemia, thrombophilia, neutrophilia
• AUTOANTIBODIES: see next flashcard
• URINE: glomerulonephritis in small vessel vasculitis
• BIOPSY: best for diagnosis. If skin lesion is taken, subcutaneous tissue also taken as contains medium vessels. Direct immunofluorescence should also be performed as the pattern Ig deposition may provide clues to aetiology e.g., IgA deposition in HSP.
• ANGIOGRAPHY: beading, aneurysm, or smooth tapering vessel stenosis in medium and large vessel vasculitides

Question 19

What are the autoantibodies in vasculitis? (x3)

Answer 19

• cytoplasmic-ANCA: anti-proteinase-3 associated with WG
• perinuclear-ANCA: anti-myeloperoxidase associated with MP, CSS (but also IBD, PBC and chronic active hepatitis)
• Cryoglobulins (immunoglobulins (IgG, IgM) and complement components that precipitate at temperatures below 37 degrees) in MEC

Question 20

What is giant cell arteritis?

Answer 20

AKA temporal/cranial/granulomatous arteritis. Granulomatous inflammation of large arteries, particularly of the external carotid artery, most commonly the superficial temporal artery.

Question 21

What is the anatomy of the external carotid artery?

Answer 21

Some Anatomists Like Freaking Out Poor Medical Students

Question 22

What is the aetiology of giant cell arteritis? (x2)

Answer 22

Unknown. Genetic: HLA-DR4 and HLA-DRB1, and infective association (Mycoplasma pneumoniae, parvovirus B19, Chlamydia pneumoniae).

Question 23

! What is the pathophysiology of giant cell arteritis?

Answer 23

• Granulomatous inflammation in large arteries with preferential involvement of ECA but can also affect aorta and its other major branches.
• Initial immune insult occurs from resident dendritic cells presenting antigen to CD4+ T cells which release IFN-gamma that stimulates macrophage infiltration
• Granulomas are composed of T cells, macrophages, and multinucleated giant cells (fused macrophages)
• In response to damage, artery releases growth and angiogenic factors that result in myofibroblast proliferation, neovascularisation and marked thickening of the intimal layer
• This intimal expansion leads to occlusion of the vessel lumen leading to tissue ischaemia which leads to clinical symptoms

Question 24

What is the epidemiology of giant cell arteritis: Common? Age? Gender? Ethnicity?

Answer 24

Most common systemic vasculitis. Peak age 65-70 years. More common in females. Most common in white ethnicities.

Question 25

What are the signs and symptoms of giant cell arteritis? (x6) Onset?

Answer 25

• Subacute onset, usually over a few weeks
• Note that following signs and symptoms are not temporal artery exclusive. Giant cell arteritis can affect other arteries!
• HEADACHE: scalp and temporal tenderness (pain on combing hair), swelling and erythema over temporal artery.
• Thickened, non-pulsatile temporal artery
• Jaw and tongue claudication
• VISUAL DISTURBANCES: partial or complete, painless, sudden loss of vision in one eye due to ischaemia, called amaurosis fugax. From ophthalmic artery involvement – disease pathology of inflammation can also affect ophthalmic artery
• Symptoms of POLYMYALGIA RHEUMATICA: early morning pain and stiffness of the shoulders and pelvic girdle (associated with 50% of cases)
• Constitutional symptoms: low-grade fever, weight loss, lethargy

Question 26

What are the investigations for giant cell arteritis? (x3)

Answer 26

• BLOODS: ESR is elevated to at least 50mm/hour by the Westergren method is one of the diagnostic criteria. CRP also raised. ACD
• TEMPORAL ARTERY BIOPSY: definitive test. Shows granulomatous inflammation and multinucleated giant cells. Note may come back clear because skip lesions
• TEMPORAL ARTERY USS: wall thickening, stenosis and occlusion (preferred method early imaging)

Question 27

How is giant cell arteritis treated? (x5)

Answer 27

• High dose oral prednisolone immediately (60mg; BEFORE BIOPSY) to prevent visual loss. Most experience immense symptomatic relief within 48 hours
• Decrease dose gradually according to symptoms and ESR, to a maintenance dose of 7.5-10.0 mg/day. Many require prednisolone for 1-2 years
• Low-dose aspirin (plus PPIs for gastroprotection) to decrease risk of visual loss, TIAs or stroke
• Osteoporosis prevention (complication of high steroids): adequate dietary calcium, vitamin D and bisphosphonates (alendronic acid or risedronate sodium)
• Annual CXR to identify thoracic aortic aneurysms

Question 28

How is vision loss treated in giant cell arteritis?

Answer 28

IV pulse (intermittent high dose administration) methylprednisolone followed by high-dose oral prednisolone and regime described above.

Question 29

What are the complications of giant cell arteritis? (x2)

Answer 29

• Carotid artery or aortic aneurysms
• Thrombosis followed by recanalization (contraction and lysis of thrombus) or embolism

Question 30

What is the prognosis of giant cell arteritis?

Answer 30

Most cases last 2 years before complete remission.