Vasculitis

Question 1

What is vasculitis?

Answer 1

An inflammatory disorder of blood vessel walls.
- inflammation & necrosis of blood vessel walls with subsequent impaired blood flow.

Question 2

Briefly describe the pathophysiology of vasculitis.

Answer 2

Inflammation and necrosis of blood vessel walls with subsequent impaired blood flow resulting in:

1. Vessel wall destruction - aneurysm, rupture and stenosis:
   * Resulting in perforation and haemorrhage into tissues
2. Endothelial injury:
   * Resulting in thrombosis + ischaemia/infarction of dependent tissues

Question 3

According to which 2 factors is vasculitis classified?

Answer 3

1. Size of the blood vessel involved.
2. Presence or absence of anti-neutrophil cytoplasmic antibodies (ANCA).

Question 4

What does ANCA stand for?

Answer 4

Anti-neutrophil cytoplasmic antibodies.

Question 5

What are the 3 categories of vasculitis classified according to size?

Answer 5

1. Large-vessel vasculitis:
   - Refers to the aorta and its major tributaries
2. Medium-vessel vasculitis:
   - Refers to medium and small-sized arteries and arterioles
3. Small-vessel vasculitis:
   - Refers to small arteries, arterioles, VENULES and capillaries

Question 6

Give 2 examples of medium-vessel vasculitis.

Answer 6

1. Classical polyarteritis nodosa (PAN)
2. Kawasaki’s disease

Question 7

Give 2 examples of ANCA-associated small-vessel vasculitis.

Answer 7

1. Microscopic polyangitis
2. Granulomatosis with polyangitis

Question 8

Give 2 examples of ANCA-negative small-vessel vasculitis.

Answer 8

1. Essential cryoglobulinaemia
2. Cutaneous leucocytoclastic vasculitis

Question 9

Which 2 features are found in ALL forms of vasculitis?

Answer 9

1. Raised ESR
2. Anaemia

Question 10

Are the types of vasculitis common?

Answer 10

ALL RARE except giant cell (temporal) arteritis.

Question 11

Give an infective condition associated with vasculitis (risk factor).

Answer 11

Subacute infective endocarditis

Question 12

Giv 3 non-infective conditions associated with vasculitis (risk factors).

Answer 12

Non-infective:
1. Vasculitis with RA
2. SLE
3. Scleroderma
4. Polymyositis/dermatomyositis
5. Good pasture syndrome and Inflammatory bowel disease (UC/Crohn’s)

Question 13

Give 2 examples of large-vessel vasculitis.

Answer 13

1. Giant cell arteritis/polymyalgia rheumatic
2. Takayasu’s arteritis

Question 14

Describe the epidemiology of large-vessel vasculitis.

Answer 14

1. Affects those > 50 YO.
2. More common in FEMALES than males
3. Systemic disease of the elderly - incidence increases with age
4. Associated with polymyalgia & RA
5. In general - it’s rare; GCA is the most common type

Question 15

What is Polymyalgia Rheumatica (PMR)?

Answer 15

A condition that causes pain, stiffness and inflammation in the muscles around the shoulders, neck and hips.

Separate condition to GCA - but usually co-exist

Question 16

Give 2 risk factors for PMR.

Answer 16

1. SLE
2. Polymyositis/dermatomyositis

Question 17

Describe the clinical presentation of polymyalgia rheumatica (PMR).

Answer 17

Sudden onset of severe pain and stiffness of the shoulders
and neck, and of the hips and lumbar spine; a limb girdle
pattern.

Symptoms are worse in the morning, lasting from 30 mins -
several hours

Mild polyarthritis of peripheral joints.

1/3rd experience: fatigue, fever, weight loss, depression.

Question 18

Investigations for Polymyalgia Rheumatica (PMR).

Answer 18

1. Clinical history is usually diagnostic and the patient is ALWAYS OVER 50
2. BOTH ESR & CRP RAISED - diagnostic
3. ANCA negative
4. Serum alkaline phosphatase raised
5. Mild normochromic, normocytic anaemia may be present
6. Temporal artery biopsy:
   * Shows giant cell arteritis in 10-30% cases

• Note: creatinine kinase is normal - helps to distinguish from myositis / myopathies

Question 19

Treatment for Polymyalgia Rheumatica (PMR).

Answer 19

1. Corticosteroids with PPI + Alendronate + Ca2+ + Vit. D
   - e.g. Oral Prednisolone
   - Give a dramatic reduction of symptoms of PMR within
   24-48 hours of starting treatment

• PPI e.g. lansoprazole = GI protection due to long-term use of steroids
• Alendronate = bisphophonate for osteroporosis prevention dye to steroids
• Ca2+ and Vit. D = bone protection
• If improvement doesn’t occur: diagnosis should be questioned
• Decrease dose slowly

Question 20

Define giant cell arteritis (GCA).

Answer 20

Inflammatory granulomatous arteritis of large CEREBRAL ARTERIES as well as other large vessels e.g aorta, which occurs in association with PMR

*Arteritis = inflammation of the lining of the arteries

Question 21

Pathophysiology of GCA:
In GCA, which layers of the artery are affected?
What is the net effect of this?

Answer 21

Tunica media + interna.

Arteries become inflamed, thickened, cause narrowing of the lumen and can obstruct blood flow.

Question 22

Which arteries are commonly affected in GCA?

Answer 22

1. Cerebral arteries
   - Common temporal (splits into frontal + temporal)
   - Linguinal / facial
2. Opthalmic arteries
   - Cilliary (to retina)

Question 23

Give 5 cranial-related symptoms of GCA.

Answer 23

1. Severe headaches
   - Abrupt temporal unilateral headaches
2. Scalp tenderness
3. Jaw claudication (when eating)
4. Tenderness + swelling of one or more temporal or occipital arteries
   - Visible dilation of temporal artery on side of face
5. SUDDEN PAINLESS VISION LOSS - EMERGENCY
   - Arteritic anterior ischaemic optic neuropathy - optic disc is very pale/swollen

Question 24

Give 3 non-cranial-related symptoms of GCA.

Answer 24

1. Malaise, lethargy, chronic low grade fever
2. Associated symptoms of PMR
3. Dyspnoea, morning stiffness and unequal or weak pulses

Question 25

What might you find on clinical investigation in someone with giant cell arteritis?

Answer 25

1. Palpable and tender temporal arteries with reduced pulsation. 2. Sudden monocular visual loss, the optic disc is pale and swollen.

Question 26

What is the diagnostic criteria for GCA?

Answer 26

Diagnostic criteria - 3 or more of: 1. Age > 50 2. New headache 3. Temporal artery tenderness or decreased pulsation 4. ESR raised 5. Abnormal artery biopsy - inflammatory infiltrates present

Question 27

What investigations might you do in someone who you suspect has giant cell arteritis?

Answer 27

1. Bloods: - Normochromic, normocytic anaemia - HIGH inflammatory markers - ESR and CRP - ANCA negative - Serum alkaline phosphatase may be raised 2. Temporal artery biopsy - DIAGNOSTIC!! - Should be taken BEFORE or within 7 days of starting high dose corticosteroids * Lesions are patchy so take a big chunk! 3. Ultrasound - Halo sign on US of temporal and axillary artery

Question 28

Investigations for GCA: Temporal Artery Biopsy - what would you observe?

Answer 28

Lesions are patchy so take a big chunk! * Histological features: 1. Cellular infiltrates of CD4+ T lymphocytes, macrophages and giant cells (may not be visible in all cases) in the vessel wall = tightly-packed as if 1 giant cell 2. Granulomatous inflammation of the intima & media 3. Breaking up of the internal elastic lamina

Question 29

What cells might you see on a histological slide taken from someone with GCA?

Answer 29

Neutrophils and giant cells.

Question 30

Describe the treatment for GCA.

Answer 30

1. High-dose Corticosteroids RAPIDLY with PPI + Alendronate + Ca2+ + Vit. D e.g. PREDNISOLONE to stop vision loss - Gradual reduction of steroids over 12-18 months - PPI e.g. lansoprazole = GI protection due to long-term use of steroids - Alendronate = bisphophonate for osteroporosis prevention/prophylaxis due to steroids - Ca2+ and Vit. D = bone protection 2. Immunosuppressants that are used include: - Cyclophosphamide - Methotrexate - Azathioprine - Rituximab and other monoclonal antibodies 3. Monitor treatment progress by looking at ESR/CRP (should fall).

Question 31

Define Polyarteritis nodosa (PAN).

Answer 31

A rare multi-system disorder characterised by widespread inflammation, weakening, and damage to small and medium-sized arteries.

Question 32

Pathophysiology of Polyarteritis nodosa: what is the underlying pathology of PAN?

Answer 32

A vasculitis - fibrinoid necrosis of vessel walls with microaneurysm formation, thrombosis and infarction in medium sized arteries.

Question 33

Give 3 risk factors for PAN.

Answer 33

1. Male 2. Hepatitis B 3. RA, SLE, scleroderma

Question 34

Which vasculitis is most associated with Hep. B?

Answer 34

Polyarteritis nodosa (PAN).

Question 35

List some general + systemic features of polyarteritis nodosa (PAN).

Answer 35

General - fever, malaise, weight loss, myalgia. Skin - skin lesions, purpura, livedo reticularis (a mottled, purplish, lace like rash), ulcers, gangrene. Cardiac - angina, HF, pericarditis. Renal - hypertension, haematuria, renal failure. GI - pain or perforation, malabsorption. GU - orchitis. Neuro - Mononeuritis multiple (Numbness, tingling, abnormal / lack of sensation and inability to move part of the body)

Question 36

What investigations would you carry out in polyarteritis nodosa (PAN)?

Answer 36

1. Bloods: - Anaemia - WCC raised - ESR + CRP raised - ANCA negative (it's very rarely positive) 2. Angiography: * Demonstrates micro-aneurysms in hepatic, intestinal or renal vessels - "String of beads" pattern along the artery 3. Biopsy, of kidney in particular - To look for hypertension and other damage - can be diagnostic

Question 37

How would you treat polyarteritis nodosa (PAN)?

Answer 37

1. BP control - ACEi e.g. Ramipril 2. Corticosteroids with Immunosuppressants - Prednisolone with Azethioprine / Cyclophosphamide 3. Hep. B should be treated with an antiviral after initial treatment with steroids

Question 38

what size vessels does ANCA vasculitis affect?

Answer 38

small

Question 39

what are the two ANCA associated vasculitides?

Answer 39

p-ANCA: microscopic polyangiitis, eosinophillic, UC, primary schlerosing cholangitis c-ANCA: granulomatosis with polyangiitis (aka wegeners)

Question 40

eosinophilic granulomatosis presents similarly to

Answer 40

allergy | asthma

Question 41

What is Henoch-Schoenlein purpura?

Answer 41

IgA vasculitis (small-vessel vasculitis) 1. Rash 2. Abdominal pain 3. Glomerulonephritis 4. Arthritis/arthralgia

Question 42

Microscopic polyangiitis affects only the?

Answer 42

Kidney and lung

Question 43

What is Granulomatosis with polyangitis (Wegener's granulomatosis)?

Answer 43

Granulomatosis with polyangiitis is a small vessel vasculitis. It was previously known as Wegener’s granulomatosis.

Question 44

Is granulomatosis with polyangitis associated with c-ANCA or p-ANCA?

Answer 44

c-ANCA.

Question 45

What organ systems can be affected by granulomatosis with polyangitis?

Answer 45

1. URT. 2. Lungs. 3. Kidneys. 4. Skin. 5. Eyes.

Question 46

What is the affect of granulomatosis with polyangitis on the URT?

Answer 46

- Sinusitis. - Otitis. - Nasal crusting.

Question 47

What is the affect of granulomatosis with polyangitis on the lungs?

Answer 47

- Pulmonary haemorrhage/nodules. - Inflammatory infiltrates are seen on X-ray.

Question 48

What is the affect of granulomatosis with polyangitis on the kidney?

Answer 48

Glomerulonephritis.

Question 49

What is the affect of granulomatosis with polyangitis on the skin?

Answer 49

Ulcers.

Question 50

What is the affect of granulomatosis with polyangitis on the eyes?

Answer 50

- Uveitis. - Scleritis. - Episcleritis.

Question 51

Describe the clinical presentation of granulomatosis with polyangitis.

Answer 51

Classic sign on exams: saddle shaped nose Epistaxis Crusty nasal/ ear secretions 🡪 hearing loss Sinusitis Cough, wheeze, haemoptysis

Question 52

Diagnosis of granulomatosis with polyangitis.

Answer 52

High eosinophils on FBC. Histology shows granulomas. Presence of c-ANCA.

Question 53

What is the treatment for granulomatosis with polyangitis?

Answer 53

- If severe: high dose steroids with immunosuppressants e.g. cyclophosphamide - If non-end organ threatening: moderate steroids.