1. Dr Rachael Kilding Consultant Rheumatologist 29th February 2016
Vasculitis
Dr Rachael Kilding
Consultant Rheumatologist
29th February 2016

2. Outline Vasculitis Definition/Histology Classification Overview
Giant cell arteritis
Granulomatosis with polyangiitis (GPA)
(Wegener’s Granulomatosis)

3. What is vasculitis?
Inflammation and necrosis of blood vessel walls with subsequent impaired blood flow
Vessel wall destruction
perforation + haemorrhage into tissues
Endothelial injury
thrombosis + ischaemia/infarction of dependent tissues

4. Histology Vessel wall infiltration Fibrinoid necrosis
Neutrophils, mononuclear cells +/or giant cells
Fibrinoid necrosis
Leukocytoclasis (dissolution of leucocytes)

5. Classification of vasculitis
Difficult! - lots of overlap
Categorise by
Size of vessel affected
Small – medium - large vessel disease
Target organ(s)
Presence or absence of anti-neutrophil cytoplasmic antibodies (ANCA)
Primary vs secondary

6. Chapel Hill (Jennette JC et al A+R 1994)
Dominant vessel
Primary disorder
Secondary disorder
Large arteries
Giant cell arteritis
Takyasu’s
Isolated CNS angiitis
Aortitis in RA
Infection-syphilis
Medium arteries
Classical PAN
Kawasaki disease
Infection-hep B
Hairy cell leukaemia
Medium/small
Wegener’s granulomatosis
Churg Strauss
Microscopic polyangiitis
Vasculitis secondary to autoimmune disease
Malignancy
Drugs
Infection eg HIV
Small vessels
(leucocytoclastic)
Henoch Schonlein purpura
Essential mixed cyyoglobulinaemia
Cutaneous leucocytoclastic angiitis
Infection eg Hepatitis B/C

7. Chapel Hill (schematic)

8. How does vasculitis present?
No single typical presentation
Systemically unwell, fever, arthralgia/arthritis, rash, weight loss, headache, footdrop, major event eg stroke, bowel infarction
Easily confused with other diseases- mimickers
Must be excluded to ensure correct treatment
Sepsis-SBE, hepatitis
Malignancy
Other-eg cholesterol emboli

9. ANCA Small/medium vessel vasculitis
Anti-neutrophil cytoplasmic antibodies
Specific antibodies for antigens in cytoplasmic granules of neutrophils and monocyte lysosomes
Detected with indirect immunofluorescence microscopy
Two major patterns
Cytoplasmic ANCA (c-ANCA)
Peri-nuclear ANCA (p-ANCA)

10. cANCA
Granular cytoplasmic staining
Major antigen-
Proteinase 3 (PR3)

11. pANCA Homogeneous perinuclear staining
Major antigen - myeloperoxidase (MPO)

12. Large vessel vasculitis

13. Large vessel vasculitis
Primary
Giant cell (temporal) arteritis
Takyasu’s arteritis

14. Giant cell (temporal) arteritis
Granulomatous arteritis of aorta + larger vessels-extracranial branches of carotid arteries

15. Giant cell (temporal) arteritis
Primarily>50 yrs old
Incidence increases with age
Twice as common in women

16. Giant cell (temporal) arteritis
Presentation
Headache
Scalp tenderness
Jaw claudication
Acute blindness-medical emergency
Non specific malaise
Associated symptoms of polymyalgia rheumatica
At risk of CVA

17. American College of Rheumatology Diagnostic criteria
3 or more of:
Age>50
New headache
Temporal artery tenderness or decreased pulsation
ESR > 50 mm/h
Abnormal artery biopsies showing necrotizing arteritis with mononuclear infiltrate or granulomatous inflammation
(Sensitivity 93.5% specificity 91.2%)

18. Temporal Artery Biopsy

19. Temporal artery biopsy

20. Giant cell arteritis Temporal arteries Palpable Tender
Reduced pulsation

21. AION (Arteritic) anterior ischemic optic neuropathy
Sudden, painless, monocular and severe visual loss.
May be preceded by transient visual loss
The optic disc becomes pale and swollen, often with flame-shaped haemorrhages at the margin

22. Giant cell arteritis
Suspect in >50s developing new type of headache, jaw claudication, unexplained fever
Check ESR/CRP
Temporal artery biopsy

23. Treatment of GCA Prompt corticosteroids
Dramatic responses usually seen in 48 hr

24. GCA Prednisolone Initial dose of 30-40mg day if no visual disturbance
80 mg/day if visual disturbance

25. GCA Falling ESR/CRP and clinical improvement guide treatment
50% off steroids at 2 years

26. General Steroid sparing agents Prophylaxis of osteoporosis
Eg Azathioprine/Methotrexate/biologics
Prophylaxis of osteoporosis
Lifestyle advice
Calcium/Vitamin D + Bisphosphonate
DEXA scan

27. CASE 1

28. Case 1 65 year old woman Previously fit and well Ex smoker
3 month progressive history of malaise
Weight loss
General stiffness

29. Case 1 1 week history of headache Persistent
Not relieved with simple pain killers
Jaw pain on eating/chewing
1 episode of transient visual loss

30. Case 1 ESR 70 CRP 85 Tender scalp and temporal arteries
Referred urgently to hospital

31. Case 1 Commenced 60mg steroids Temporal artery biopsy arranged
Seen 2 weeks later
Dramatic improvement
ESR 30 CRP 25
Confirmed temporal arteritis on biopsy
Gradual steroid dose reduction over 3 years
Remained well

32. Small vessel vasculitis (ANCA associated)

33. Primary Churg Strauss Microscopic polyangiitis
Granulomatosis with polyangiitis (GPA)
(Wegener’s Granulomatosis)
Churg Strauss
Microscopic polyangiitis

34. Granulomatosis with polyangiitis (GPA)
Necrotizing, granulomatous vasculitis of arterioles, capilleries and post capillary venules
Associated with anti neutrophil cytoplasmic antibodies (c-ANCA)

35. Granulomatosis with polyangiitis (GPA)
Typically age years old
Prevalence 5-7/100,000
Affects vasculature of (all organ systems)
Upper respiratory tract
Lungs
Kidney
Skin
Nervous system
Eye

36. Granulomatosis with polyangiitis (GPA)
Upper respiratory tract
sinusitis/otitis/nasal crusting bleeding
Lungs
pulmonary nodules/haemorrhage
Kidney
Glomerulonephritis
(haematuria/proteinura)
Skin
purpura/ulcers
Nervous system
mononeuritis multiplex/CNS vasculitis
Eye
proptosis/scleritis/
episcleritis/uveitis
Other
synovitis/pericarditis/
GI/GU

37. Granulomatosis with polyangiitis (GPA)

38. Granulomatosis with polyangiitis (GPA)-small vessel vasculitis

39. Granulomatosis with polyangiitis (GPA)-eye disease
Marked bilateral periorbital edema
Chemosis (swelling of conjuctiva) of the left eye secondary to local granulomatous inflammation

40. Granulomatosis with polyangiitis (GPA)-eye disease
Granulomatous orbital disease

41. Granulomatosis with polyangiitis (GPA)-saddle nose deformity

42. Granulomatosis with polyangiitis (GPA)
Untreated mortality 90% at 2 years
Treatment
Severe
High dose steroids/cyclophosphamide/biologics
Non-end organ threatening
Moderate dose steroids + Methotrexate/Mycophenolate/Azathioprine etc

43. Case 2

44. Case 2 38 year old man No significant previous medical history
4 week history of fever
Weight loss
Joint pain and swelling
Rash
Diarrhoea
Cough

45. Case 2 On examination Unwell Febrile Florid rash over lower limbs
Synovitis of small joints
Abdominal tenderness

46. Case 2 ESR 100 CRP 120 Anaemic Renal impairment
Blood and protein in urine
CXR-multiple cavitating lung lesions

47. Case 2 Exclude infection Exclude malignancy cANCA positive Likely GPA
Biopsy

48. Case 2 Intravenous steroids-high dose Intravenous cyclophosphamide
Supportive care

49. Case 2 Gradual improvement ESR/CRP normalised Renal function improved
CXR cleared
ANCA negative
Long term immunosuppression and close review

50. Summary
Vasculitis is inflammation and necrosis of blood vessel walls resulting in tissue damage
Traditionally classified according to size of vessel involved (ANCA)
Disease presentation is highly variable resulting in diagnostic confusion & delay

51. Summary Giant cell arteritis is a primary large vessel vasculitis
ANCA negative
Treatment consists of immunosuppression with prednisolone +/- additional therapies

52. Summary Granulomatosis with polyangiitis (GPA) Small vessel
ANCA associated
High mortality/morbidity rates if untreated
Treatment tailored to disease severity
Steroids + immunosuppression

53. Thank you
Any questions??