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

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

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

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

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

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

Chapel Hill (schematic)

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

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)

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

pANCA Homogeneous perinuclear staining Major antigen - myeloperoxidase (MPO)

Large vessel vasculitis

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

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

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

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

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%)

Temporal Artery Biopsy

Temporal artery biopsy

Giant cell arteritis Temporal arteries Palpable Tender Reduced pulsation

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

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

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

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

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

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

CASE 1

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

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

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

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

Small vessel vasculitis (ANCA associated)

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

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

Granulomatosis with polyangiitis (GPA) Typically age 25-60 years old Prevalence 5-7/100,000 Affects vasculature of (all organ systems) Upper respiratory tract Lungs Kidney Skin Nervous system Eye

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

Granulomatosis with polyangiitis (GPA)

Granulomatosis with polyangiitis (GPA)-small vessel vasculitis

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

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

Granulomatosis with polyangiitis (GPA)-saddle nose deformity

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

Case 2

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

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

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

Case 2 Exclude infection Exclude malignancy cANCA positive Likely GPA Biopsy

Case 2 Intravenous steroids-high dose Intravenous cyclophosphamide Supportive care

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

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

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

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

Thank you Any questions??