medicine

1. APPROACH TO VASCULITIS

2. Introduction
• Vasculitis- Inflammation of blood vessels
characterised by leucocytic infiltration of the
vessel walls
• Different patterns of vessels’ involvement in
different entities
• Vessel lumen compromisedischemia of the
corresponding organ

3. Pathogenesis
• 3 main groups of pathogenetic mechanisms
behind vasculitis-
1.Immune complex formation
2.ANCA mediated
3.T lymphocyte mediated with Granuloma
formation

4. Immune complex formation
• Henoch Schonlein purpura- IgA mediated
• SLE & other collagen vascular diseases-
ANA
• Serum sickness
• Polyarteritis Nodosa- Hepatitis B ag
• Essential Mixed Cryoglobinemia- Hepatitis
C virion
*deposition of immune complexes in the
blood vesselsactivation of
complementsdestruction of vessel wall
(acute & chronic inflammation)

5. ANCA
• P-ANCA (anti-proteinase 3)- Wegener’s
• C-ANCA (anti-MPO)
- Churg Strauss vasculitis
- Microscopic Polyangiitis
- Wegener’s granulomatosis
* Aberrant expression of proteinase 3 and MPO
over the surface of the neutrophilsformation
of antibodiesdestruction of
neutrophilsvessel wall damage

7. Granuloma formation
(T lymphocyte mediated)
• Giant cell arteritis
• Takayasu’s arteritis
• Wegener’s granulomatosis
• Churg Strauss vasculitis
*classical granuloma formation (giant cells and
epitheloid cells in a backround of fibrinoid
necrosis) can be demonstrated in the
corresponding vessel biopsy

8. APPROACH TO VASCULITIS

9. STEP 1
“LEARN TO RECOGNISE VASCULITIS”

10. Know the common features
of vasculitis!!!
• Palpable purpura (cutaneous vasculitis)
• Pulmonary infiltrates
• Glomerulonephritis (microscopic hematuria)
• Mononeuritis multiplex
• Unexplained ischemic events- Myocardial
Infarction, Stroke, Raynaud’s phenomena,
Digital gangrene, Mesentric Ischemia

11. Palpable purpura

12. Pulmonary infiltrates

13. Microscopic hematuria

14. STEP 2
RULE OUT SECONDARY CAUSES OF VASCULITIS!!
i.e- diseases where vasculitis is one of the clinical
manifestations of the respective disease

15. Secondary Vasculitis
• Infections
• Malignancies
• Thrombotic Microangiopathies
• Drugs
• Others

16. Infections
• Bacterial endocarditis
• Gonococcal Infection
• Syphilis
• Rickettsial diseases
• Histoplasmosis
• Coccidiomycosis
• Whipple’s
• Lyme’s

17. Malignancies
• Atrial Myxomas
• Carcinomatosis
• Lymphomas
Thrombotic Microangiopathies
• TTP
• HUS

18. Drugs
• Cocaine
• Phenytoin
• Sulfa drugs
• Penicillins
• Hydralazine
• Allopurinol
• Propylthiouracil
• Thiazides

19. Others
• SLE
• Amyloidosis
• Sarcoidosis
• Migraine
• Atheroembolic Disease

20. STEP 3
THE PATTERN OF VESSEL INVOLVEMENT
(Large vessel, Medium vessel, Small vessel)

21. Large vessel vasculitis
• Giant cell arteritis
• Takayasu’s arteritis

22. Medium vessel Vasculitis
• Poly Arteritis Nodosa
• Kawasaki’s vasculitis

23. Small vessel Vasculitis
Pauci-immune (ANCA mediated)
Wegener’s Granulomatosis
Churg Strauss vasculitis
Microscopic Polyangiitis
Immune complex mediated
Henoch Schonlein Purpura
Essential Mixed Cryoglobulinemia
SLE and other collagen c=vascular diseases
related vascultis

24. Other primary vasculitides
• Thromb Angiitis Obliterans
• Behcet’s disease
• Idiopathic Cutaneous vasculitis
• Isolated Vasculitis of CNS
• Relapsing Polychondritis
• Polyangiitis overlap syndromes (features of
more than 1 vasculitis)

25. STEP 4
Learn the characteristic presentations of each vasculitis !!!

26. Giant cell arteritis
• Temporal arteritis
• Elderly persons more than 50 yrs. of age
• Non specific symptoms, Headache, Elevated
ESR
• BLINDNESS-most serious complication
• Jaw claudication, Scalp pain, Scalp Tenderness
• Polymyalgia Rheumatica- different end of the
spectrum of Giant Cell Arteritis

28. Takayasu’s Arteritis
• Pulseless Disease
• Middle aged females
• Aorta and its branches mainly involved
• Subclavian vessels, Carotid vessels, Mesentric
vessels
• Chronic and Relapsing course

30. Poly Arteritis Nodosa
• Renal arteries most commonly involved
leading to renovascular hypertension
• Pulmonary vessels NEVER involved
• Association with patients of
o Hepatitis B
o Hairy cell leukemia

31. Kawasaki’s Vasculitis
• MucoCutaneous Lymph node syndrome
• Children < 5 years of age mostly
• Desquamative erythematous rashes involving
the skin, mucus membranes, cervical
lymphadenopathy
• 25 % develop coronary artery aneurysms in
the convalescent stage of the illness

34. Pauci immune Vasculitis
Usually Pulmonary capillaritis PLUS
Glomerulonephritis
•Granulomas +, Asthma +  Churg Strauss
•Granulomas +, NO asthma  Wegener’s
•NO granulomas, NO asthma  Microscopic
Polyangiitis

35. Wegener’s Granulomatosis
• Classical triad  URT + LRT + renal
• Chronis sinusitis, Pulmonary nodules,
Pulmonary cavities, Rapidly Progressive
Glomerulonephritis
• Cutaneous vasculitis, Eye lesions may be
present
• Non specific symptoms may predominate

37. Churg Strauss Vasculitis
• Asthma, Eosinophilia with pulmonary infiltrates ,
glomerulonephritis
• Myocardial involvement  most common cause
of death
Microscopic Polyangiitis
• Pulmonary alveolar capillariitis,
glomerulonephritis

38. Henoch Schonlein Purpura
• 2nd decade
• Palpable purpura over lower limbs,
• Gastrointestinal complaints (abd.colicky pain,
blood in stools),
• Fever, polyarthralgia
• Increased IgA levels in blood

40. Essential Mixed Cryoglobulinemia
• 5 % of Chronic Hepatits C pts. Have EMC
• Cryoglobulins formed agianst HCV RNA
• Pulmonary, renal ( MPGN ), cutaneous
vasculitis
Thromb Angiitis Obliterans
• Chronic heavy Smokers
• Inflammation of arteries, veins, nerves
• Upper and lower limb gangrene, Instep
claudication, rest pain

41. Other primary vasculitides
• Behcet’s disease (Recurrent OculoOroGenital
ulcerations with vasculitis)
• Idiopathic Cutaneous vasculitis
• Isolated Vasculitis of CNS
• Relapsing Polychondritis
• Polyangiitis overlap syndromes (features of
more than 1 vasculitis)

42. Summary of 4 steps
• Step 1- Recognise vasculitis
• Step 2- Rule out Sec. Vasculitis
• Step 3- Study the pattern of vessels involved
in the patient
• Step 4- Remember the characteristic
presentations of each primary vasculitis

43. Step 5
How to diagnose vasculitis???

44. Common Blood Counts
• Mild Anemia – Anemia of Chronic Disease
• Differential Leucocyte Count:
Predominant eosinophils- Churg Strauss, HSP
ESR
• Non specific
• But useful test to suggest presence of
underlying inflammatory process

45. • Acute Phase Reactants
Highly sensitive C reactive Protein, Alpha 2
globulin
• Chest X ray / HRCT thorax:
-Pulmonary infiltrates- small vessel vasculitis
-Pulmonary cavities- Wegener’s granulomatosis
• Xray Para Nasal Sinuses
-Sinusitis of Wegener’s

47. • Urine routine- RBCs with active sediments
suggest Glomerulonephritis (Renal
involvement of small vessel vasculitis)
• Viral Markers
- Hep. B Poly Arteritis Nodosa
- Hep.C Essential Mixed Cryoglobulinemia

48. • Immunoglogulin levels (IgG, M, A)
- Usually hyper gammaglobulinemia seen
- Elevated IgA levelsHenoch Sconlein Purpura
• Cryoglobulins- Essential Mixed Cryoglobulinemia
• Rheumatoid Factors
-To detect secondary vasculitisRheumatoid
Arthrits
-Significantly raised in Essential Mixed
Cryoglobulinemia also

49. • Complement levels (reduced in immune compex
mediated diseases)- EMC, HSP
• ANCA
P-ANCA: Wegener’s Granulomatosis
C-ANCA: Microscopic polyangiitis, Churg Strauss,
Wegener’s vasculitis
• ANA
-screening of SLE, collagen vascular disorders in
suspicion of secondary vasculitis

50. BIOPSY
• Renal Biopsy- to detect glomerulonephritis
especially in small vessel vasculitis
RPGN- seen in pauci immune vasculitis
MPGN- seen in EMC
• Skin Biopsy- to detect “leukocytoclasis” in
cutaneous vasculitis all small vessel and
secondary vasculitides

51. BIOPSY
• Temporal Artery Biopsy- Giant Cell Arteritis
• Pulmonary tissue Biopsy- Small vessel vascultides
• Upper Airway biopsies- Wegener’s Vasculitis
* Main purpose of biopsy is to study presence of
leukocytoclasis, characterisitc pathological
alterations in tissues, GRANULOMAS
* Immunofluorescence also helps to study immune
complex deposition, IgA deposition, Complement
deposition

52. ARTERIOGRAPHY
Helps specially in in arteries that cannot be
biopsied easily like Aorta, Coronary artery,
Mesentric vessels
Presence of vascular patency, Aneurysms
• Aortic Angiography- Takayasu’s
• Cerebral Angiography- Isolated CNS vascultis
• Renal Angiography- PAN
• Coronary Angiography- Kawasaki’s
• Lower limb arteriography-Buerger’s Disease
(TAO)

54. The last step-STEP 6
TREATMENT

55. Principles of Treatment
• Immuno Suppression
Glucocorticoids- oral / IV methyl prednisolone
Cyclophosphamide
Methotrexate
Azathioprine
Cyclosporine
Rituximab- anti CD 20 ab
AntiTNF therapies- Infliximab, Adalimumab,
Etanacerpt, Certulizumab

56. Principles of Treatment
• Choice of therapy depends on
Severity of organ damage
Extent of Multi System Involvement
The vascular bed involved (renal, ocular,
coronary)
• Cyclophosphamide + Glucocorticoid therapy
preferred for severe / serious complications
• Glucocorticoids alone will suffice for isolated
mild vascultis like “idiopathic cutaneous
vascultis”

57. Principles of Treatment
• Wherever possible secondary causes
(infections, malignancies) should be sought
and treated
• Anti viral therapy (HCV, HBV)
• ASPIRIN therapy – Kawasaki’s, Giant cell
arteritis
• Intravenous Immunogloguloin Therapy-
Prevents coronary aneurysms in Kawasaki’s

58. Principles of Treatment
• Major toxic side effects of all prescribed drugs
need to be kept in mind
(Osteoporosis, growth retardation, bone
marrow suppression, hepatic toxicity, renal
toxicity, bladder cancer, cystitis …)
• Long term toxicities need to be prevented
• Long term prescription of a single group of
drug to be avoided change over to a drug
with lesser toxicity profile as soon as
symptoms are controlled

59. Principles of Treatment
• Regular Monitoring of Blood Counts, Renal
and hepatic functions
• Most of the Primary vasculitides have one
thing in common
“Chronic, Responsive to treatment, But
Notoriously Relapsing”

60. SUMMARY OF STEPS
• Step 1- Recognise vasculitis
• Step 2- Rule out Sec. Vasculitis
• Step 3- Study the pattern of vessels involved
in the patient
• Step 4- Remember the characteristic
presentations of each primary vasculitis
• Step 5- How to Diagnose
• Step 6- Principles of treatment