1. Vasculitis Joanna Zalewska

2. Definition  Group of a rare conditions characterized by inflammation of blood vessels

3. Classification

4. Epidemiology  Diseases of the extremes age  Kawasaki diseases and Henoch- Schoenlein purpura occur in childhood, whilst GCA occurs in those aged >65 years  The other types are much rare, but also tend to occur in older people

5. Clinical features  In the early stages- the symptoms can be non- specific  The age is important (Takayasu, GCA)  Systemic- fever, weight loss, myalgia, arthralgia  ENT- epistaxis, nasal crusting, deaffness, sinusitis  Pulmonary- cough, haemoptysis, dyspnoea, wheeze  Late onset asthma- CSS  Cutaneous- purpuric rash, ulcers

6.  Neurological- peripheral neuropathy, headache- especially located in the temple, new onset or of a different character to previous haedache  Vascular- jaw claudication, limb claudication, carotidynia, difficulty in obtaining blood pressure readings

7. Key featues on examination  Cutaneous- purpuric rash, ulcers, digital gangrene  Musculoskeletal- synovitis  Neurological- motor or sensory neuropathy, mononeuritis multiplex  Vascular- tender non-pulstile temporal arteries, absent peripheral pulses, bruits, difficulty in obtaining BP measurement  ENT- nasal bridge collapse

8. General investigations  FBC anaemia, leucocytosis, eosinophilia  Acute phase response (ESR and CRP)  Liver function

9. Assessment of organ involvement  Urinalysis (proteinuria, haematuria, red cell casts)  Renal function (creatinine clearance, quantification of protein leak if present using either 24-h protein excretion or urine/ creatinine ratio)  CXR- infiltrates, haemorrhage, granuloma  Liver function  Nervous system  Cardiac function (ECG, echocardioography)  Gut (celiac axis angiography)

10. Serological investigations  cANCA- strongly associated with WG (>90%)  pANCA- MPA and CSS  ANA  RF- may be positive in cryoglobulinaemic vasculitis or systemic rheumatoid vasculitis  Anticardiolipin antibodies  Complement (low in cryoglobulinaemic vasculitis)  Cryoglobulins

11. Giant cell arteritis (GCA)  The most common of systemic vasculititides and is characterized by envolvement of large vessels particularly the extra cranial branches of the aorta  Often involves temporal artery, aorta and its major branches  Patients older than 50

12. ACR criteria of GCA (>3 criteria)  Age onste >50 years  New headache  Temporal artery abnormality (tenderness to plaplation or decreased pulsation)  Increase in ESR > 50 mm/h  Abnormal artery biopsy- predominance of mononuclear infiltration or granulomatous inflammation

13. Clinical features  In early stages the symptoms are non- specific (fever, weight loss, myalgia, morning stiffness)  Headache  Visual disturbance- suddenly, without warning and may be bilateral, transient visual loss  Jaw claudication- pain on eating  Arm or leg claudication

14. Examination  The temporal arteries- tender, thickened and non pulsatile  Eye- ischaemic optic neuropathy

15. Investigations  FBC anaemia, thrombocytosis  Acute phase response (ESR and CRP)  Temporal artery biopsy- as soon as possible  Ultrasonography  Angiography

16. Prognosis  Blindness risk (reduced by early corticosteroids therapy) Treatment  High dose of corticosteroids starting 0.7- 1 mg/kg (60- 80 mg) oral  Methylprednisolone (15 mg/kg) for 3 days – 1 g per day  Low dose of aspirin- reduces the risk of thrombosis  Azathioprine or methotrexate

17. Takayasu arteritis  Rare systemic, vasculitis of unknown aetiology, characterized by large vessel vasculitis  Granulomatous inflammation of the aorta and its major branches  Patients younger than 50

18. Criteria >3  Age <40 years old  Claudication of extremities- development and worsening of fatigue and discomfort in muscles of one or more extermity while in use, espacially the upper extremities  Decreased brachial arterialpulse  BP difference >10 mmHg in systolic BP between arms  Bruit over subclavian arteries or aorta  Arteriogram abnormality- narrowing or occlusion

19.  Occurence of stroke in a young person especcially when associated with a high ESR or CRP  Fever, weight loss, myalgia, arthralgia  Absence or asymmetry of peripheral pulses  Claudication of arms or legs  TIA and stroke

20. Examination  BP inequality between arms and legs  Hypertension new onset or evidence of renal artery stenosis  Vascular bruits most often heard over the carotid artries  Carotidynia  Neurological symptoms

21.  FBC anaemia  ESR and CRP elevation  Angiography- gold standard- localized narrowing or irregularity of the lumen, stenosis and aneurysms  MR- angiography  PET  High resolution Doppler ultrasound  ANCA, ANA, RF, anticardiolipin antibodies- negative

22.  Remisson can be achieved in the majority of patients using corticosteroids, but 73% of patients required additional immunosuppressants

23.  Oral corticosteroids start at 1 mg/kg (maximum dose 60- 80 mg) and taper quickly; aim for 10 mg/day at 6 months  Immunosuppression with methotrexate or azthioprine should be started at the same time as oral corticosteroids  Control hypertension  Surgery- bypass procedure or stenting

24. Wegener’s granulomatosis  Rare systemic vasculitis of unknown aetiology, characterized by involvement of the upper airways with granuloma formation  Granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affectin small to medium sized vessels

25. Criteria >2  Nasal or oral inflammation- oral ulcers or purulent/ bloody nasal discharge  Abnormal chest radiograph- nodules, fixed infiltrates or cavities  Urinary sediment- microhaematuria (>5 red cells per high power field) or red cell casts in urinary sediment  Granulomatous inflammation- histological changes showing granulomatous on biopsy inflammation within the wall artery or in the perivascular or extravascular area

26. Clinical features  Systemic- fever, weight loss, myalgia, arthralgia  ENT- epistaxis, nasal crusting, deaffness, sinusitis  Pilmonary- cough, haemoptysis, dyspnoea  Cutaneous- purpuric rash, ulcers  Peripheral neuropathy

27.  Skin- purpura, ulcers  Arthritis  Eye- scleritis, proptosis- retroorbital mass  ENT- nasal collapse, destructive sino-nasal disease

28.  Anaemia, leucocytosis, eosinophilia  ESR and CRP- elevation  Liver function  Urinalysis (proteinuria, haematuria, red cell casts)  Renal function (creatinine clearance, quantification of protein leak if present using either 24-h protein excretion or urine protein/creatinine ratio)  CXR- infiltrates, haemorrhage, granuloma  Nervous system- nerve conduction  Cardiac function- ECG, echocardiography  Skin- biopsy

29.  cANCA- strongly associated with WG >90%  ANA, RF, anticardiolipin antibodies, complement  cryoglobulins

30. Differential diagnosis  Other types of vasculitis  Vasculitis mimics- malignancy, atrial myxoma, calciphylaxis Infection Blood cultures Viral serology (HBV, HCV, HIV, CMV) Echocardiography

31. Churg- Strauss Syndrome  Eosinophil- rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small to medium- sized vessels associated with asthma and eosinophilia  Male  Peak age onset- 65- 74 years  Aetiology is unknown- leukotriene inhibitors

32. ACR Criteria >4  Asthma- history of wheezing or diffuse high pitch rales on expiration  Eosinophilia>10 % on white cell differential count  Mononeuropathy or polyneuropathy- development of mononeuropathy, multiple menoneuropathies or polyneuropathy  Pulmonary infiltrates  Paranasal sinus abnormality- history of acute or chronic paranasolor tenderness  Extravascular eosinophilis- biopsy including artery

33. Key points on history  Adult onset asthma- difficult to control  Systemic symptoms  Pulmonary- cough, wheeze, dyspnoea, upper respiratory tract symptoms  Cutaneous- purpuric rash or cutaneous granulomata occur in up to 50%  Neurological- peripheral neuropathy or mononeuritis multiplex  Cardiac- dyspnoea, cardiac failure, arrythmia

34. Key points on examination  Skin- purpuric vasculitic rash or palpable granulomata  Musculoskeletal- arthritis  Ophtalmic- scleritis  ENT- nasal polyps  Neurological- mononeuritis multiplex, sensory or motor neuropathy

35.  Anaemia, leucocytosis, eosinophilia >1.5 x10 9  ESR and CRP- elevation  Liver function  ANCA- 50% of patients are ANCA positive

36. Assessment of organ involvement  Urinalysis (proteinuria, haematuria, red cell casts)  Renal function (creatinine clearance, quantification of protein leak, 24-h protein excretion or urine protein/ creatinine ratio)  CXR- infiltrates, haemorrhage, granuloma  Liver function  Nervous system  Cardiac function  Skin- biopsy

37. Differential diagnosis  Other causes of hypereosinophilia- hypereosinophilic syndrome, eosinophilic leukaemia, chronic parasitic infection

38. Treatment  Induction, consolidation, maintenance of remission  immunosuppression

39. Microscopic polyangiitis  Necrotizing vasculitis, with few or no immune deposits affecting small vessels

40. Key features on history  Systemic- fever, weight loss, myalgia, arthralgia  Pulmonary- cough, haemoptysis, dyspnoea  Renal involvement  Cutaneous- purpuric rash  Neurological- peripheral neuropathy

41. Key features on examination  Cutaneous- purpuric rash, digital ischaemia, ulcers, livedo reticularis  Neurological- mononeuritis multiplex  Pulmonary- intersitial lung disease

42. Assessment of organ involvement  Urinalysis (proteinuria, haematuria, red cell casts)  Renal function (creatinine clearance, quantification of protein leak, 24-h protein excretion or urine protein/ creatinine ratio)  CXR- infiltrates, haemorrhage, granuloma  Liver function  Nervous system  Cardiac function  Skin- biopsy

43. Five factor score  Proteinuria >1g/ 24h  Serum creatinine> 140 umol/l  Gastrointestinal involvement  Cardiomyopathy  CNS involvement

44. Treatment- vasculitis  Induction- oral corticosteroids combined with methotrexate, mycophenolate mofetil or cyclophosphamide  Prophylaxis against pneumocystis carinii, PPI against gastric ulceration, Mesna against haemorrhagic cystitis, prophylaxis against osteoporosis  Plasma exchange  Azathioprine

45. Polyarteritis nodosa  Necrotizing inflammation of medium- sized or small arteries without glomerulonephritis or vasculitis in capillaries or venules

46. Criteria  Weight loss  Livedo reticularis  Testicular pain or tenderness  Myalgias, weakness or leg tenderness  Mononeuropathy or polyneuropathy  Diastolic BP>90 mmHg  Elevated blood urea or creatinine  Hepatitis B virus  Arteriographic abnormality  Biopsy of small or medium vessel