1. DANIEL CHIPETA RHEUMATOLOGY GSH
VASCULITIDES
DANIEL CHIPETA
RHEUMATOLOGY
GSH

2. VASCULITIDES
heterogenous group of diseases characterised by inflammatory cell infiltration and necrosis of blood vessel wall.
Manifestation and severity of vasculitis depends upon the site, type, and location of blood vessels.
Vasculitis can be:
primary with no known cause
secondary to underlying disease
pseudovasculitis- procoagulant/thrombogenic states

3. Histologically, there is inflammation in or through the blood vessel wall, with fibrinoid necrosis or granuloma formation
Nomenclature
Large vessel vasculitis – aorta and its major tributaries
Medium vessel vasculitis –medium and small-sized arteries and arterioles
Small vessel vasculitis – small arteries, arterioles, venules and capillaries .

4. EPIDEMIOLOGY
Vasculitides are rare disorders
UK studies found primary vasculitides(wegener’s granulomatosis, microscopic polyangiitis, PAN, Churg Strauss Sx) annual incidence of 19.8 per million
Peak age at diagnosis was 65-74
Male preponderance
SA data?
Geographical and ethnic differences in incidence of 10 systemic vasculitis

5. AETIOLOGY EXACT MECHANISMS UNCLEAR
WHY LESIONS FOUND IN SPECIFIC VESSELS
ANTIGEN DISTRIBUTED IN DIFF VESSELS
ENDOTHELIAL CELLS ATTRACT INFLAMMATORY CELLS
NONENDOTHELIAL STRUCTURES ARE INVOLVED IN CONTROLLING INFLAM PROCESS

6. CLASSIFICATION
Difficult and confusing becoz of even though there is heterogeneity of vasculitic disrorders there is ;
Overlap in clinical expression of diff vasculitic sx
Evolution of disease over time
Most classification use the dominant vessel size and types of blood vessels affected.

7. Classification of vasculitis
Dominant Vessel
Primary
Secondary
Large arteries
Giant cell arteritis
Takayasu’s arteritis
Aortitis assoc with RA
Infection – syphilis, TB
Medium arteries
Classical PAN
Kawasaki disease
Hep B assoc PAN
Small vessels and medium arteries
Wegener’s granulomatosis
Churg-Strauss syndrome
Microscopic polyangiitis
Vasculitis secondary to RA
SLE, Sjogren’s Syndrome
Drugs, Infections(HIV)
Small vessels
Leucocytoclastic
Henoch-Schonlein
Purpura, cryoglobulinaemia
Drugs, Hep C assoc
Infection

8. LARGE VESSEL VASCULITIS
Takayasu arteritis – affects aorta and its primary branches.
Giant cell(temporal) arteritis – chronic vasculitis of large and medium sized vessels. May be generalised but involves cranial branches of arteries originating from aortic arch.
MEDIUM SIZED VESSEL VASCULITIS
Polyarteritis nodosa – sytemic necrotizing vasculitis that affects the small and medium-sizeed muscular arteries.
When only small vessels are affected, it is called microscopic polyarteritis or polyangiitis

9. Kawasaki – arteritis of large, medium, and small arteries esp coronary arteries.
Isolated central nervous system vasculitis
SMALL VESSEL VASCULITIS
Churg-Strauss arteritis - aka allergic granulomatosis and angiitis.
Vasculitis of medium and small sized muscular arteries. Often found with vascular and extravascular granulomatosis.
Involves arteries of skin and lungs and may be generalised.

10. Wegener’s granulomatosis – systemic vasculitis of medium and small arteries, as well as venules and arterioles.
Typically produces granulomatous inflammation of the upper and lower resp tracts and necrotizing, pauci- immune GN.
Assoc with ANCA
Microscopic polyarteritis – thought to be part of Wegeners. Has ANCA and similar histo changes outside resp tract.
Henoch Schönlein Purpura – systemic vasculitis characterised by tissue deposition of Ig A – containing immune complexes in small vessels.

11. Essential cryoglobulinemic vasculitis – presence of cryoglobulins which are a mixture of immunoglobulins and complement proteins.
Precipitate in cold and dissolve upon warming.
Often due to Hep C infection
IC deposit in vessel wall resulting in small vessel inflammation
Hypersensitivity vasculitis
Vasculitis to a known or suspected substance eg drug reaction
Skin vasculitis with palpable petechiae or purpura
Biopsy shows inflammation of small blood vessels called leukocytoclastic vasculitis esp in post capillary venules.

12. Vasculitis secondary to connective tissue disorders – SLE, RA, Behcets etc.
Frequent involves small muscular arteries, arterioles, and venules.
Vasculitis secondary to viral infection
Hep B and C, HIV, EBV,CMV, Parvo B19

13. DIAGNOSTIC APPROACH
Establish diagnosis
Complaints and signs are nonspecific and include;
Fever, fatigue, weakness, arthralgias, abdominal pain, hypertension, acute nephritic sx, and neurologic dysfunction.
Suspect a vasculitis when sytemic symptoms occur in combination with single/multi-organ dysfunction(skin, musculoskeletal,renal,git, neurological systems)

14. History – drugs, hepatitis, disorder assoc with a vasculitis(SLE)
Age and sex may be imp in determining a vasculitic syndrome.
Exam – determine extent of vascular lesions, distribution of affected organs, presence of additional disease processes(mononeuritis multiplex, palpable purpura are highly suggestive).
Lab tests
Nonspecific
May ascertain type of vasculitis, and degree and types of organs involved

15. Tests include CEUG, Urinalysis, ESR, LFTs, Viral Serology, CXR, and PFTs, ECG, CSF analysis,Tissue and Blood Cultures, CNS Imaging
Specific tests
ANA suggest connective tissue disorder,
Low complement present in mixed cryoglobulinaemia, and SLE,
PR3(c)ANCA suggest Wegeners granulomatosis,
MPO(p)-ANCA favours microscopic polyarteritis
EMG if neuromuscular symptoms present and a vasculitis is suspected

16. Specific tests contd
Tissue biopsy – of most clinically involved tissue confirms diagnosis
Arteriograms useful in identifying vasculitis of large and medium sized arteries(Takayasu)
Categorise a specific vasculitic syndrome
Constellation of clinical laboratory, biopsy and radiographic findings usually allows categorisation to a specific syndrome and therapy should be initiated according to this information.

17. TREATMENT
Offending drug should be removed where possible ( eg drug hypersensitivity)
Treat underlying disease(infection, neoplasm, CTD)
Treatment should be initiated according to category of vasculitic syndrome
Broad Principles
Glucocoticoids and or immunosuppressive therapy should be instituted immediately in diseases that lead to irreversible organ dysfunction.
Longterm use of cyclophosphamide in lupus nephritis prevents ESRD while prednisone alone is less effective.

18. Steroids
Use in conditions not specifically categorised for which there is no standard therapy.
Add immunosuppressive only if there is
No adequate response
Remission can be achieved and maintained with toxic doses of steroids
Once remission is achieved, taper steroids and discontinue.
Usual starting dose is 1mg/kg/day

19. Immunosuppressives
Cyclophosphamide
Drug of choice in Wegeners and severe systemic vasculitides
Usual dose 2mg/kg/day orally
Watch for SE – bone marrow suppressioDose adjustment based on leucocyte count( >3000/μL), cystitis, bladder ca.
Cont Rx for 1 year after induction of remission then taper gradually over months
Methotrexate
Alternate drug
Start at 0.3mg/kg once weekly initially

20. Dose adjustments up to 20 – 25mg per week and maintain at that level.
Azathioprine
Dose 2mg/kg per day
Not as effective
Cyclosporine
MMF
Plasmapharesis + immunosupression

21. R E F E R E N C E S
1.UpToDate Version 15.1
2. Braunwald et al. Harrison’s Principles of Internal Medicine 15th Edition.vol USA;McGraw-hill.
3.Wegand CM, Goronzy Jorg. Medium and Large Vessel vasculitis.N.Engl J.Med.2003;349:160-9