Systemic vasculitides - Wegener's Granulomatosis, Microscopic Polyangitis, Churg Strauss Syndrome, PAN, Giant cell arteritis, Polymyalgia rheumatica

1. SYSTEMIC VASCULITIDES
Dr.Rohit C K

2. DEFINITION
Heterogenous group of clinical syndromes
characterised by inflammation and necrosis
of blood vessels
NormalArtery
Artery: WBC in media and
adventitia

3. WHAT IS VASCULITIS?
1/20/2017
VASCULITIS IS A DIVERSE CATEGORY OF INFLAMMATORY
DISEASES OF BLOOD VESSELS.
• RANGE IN SEVERITY - SELF LIMITING DERMATOLOGIC
CONDITIONS TO ACUTE AND RAPIDLY FATAL MULTISYSTEM
DISEASES.
• CHARACTERISED BY ENDOTHELIAL DAMAGE, INTIMAL
PROLIFERATION, THROMBOSIS - > EVENTUAL
VASCULAR OCCLUSION.
• CAN AFFECT EVERY ORGAN SYSTEM.

6. PATHOGENIC IMMUNE COMPLEX
FORMATION
 Mechanisms of tissue damage resembles that in serum
sickness
 Ag-Ab complexes deposited in vessel walls with increased
permeability
 Activation on complement components ( mainly C5a)
 Chemotaxis for neutrophils infiltrate cell wall 
intracytoplasmic enzyme release  cell wall damage
 Once process is subacute/chrone  mononuclear
infiltration of cell wall

7. ANTINEUTROPHIL CYTOPLASMIC
ANTIBODIES (ANCA)
 High percentage of patients with active granulomatosis
with polyangiitis (Wegener’s) and microscopic polyangiitis
 Low percentage of pts with Churg Strauss (eosinophilic
granulomatosis with polyangiitis)
 Two major categories :
 Cytoplasmic ANCA (cANCA)
 Perinuclear (pANCA)

8. • c-ANCA
• Stains cytoplasm (hence “c”)
• Main target antigen: proteinase-3
• Highly specific (>90%) for Wegener’s
• p-ANCA
• Stains perinuclear (hence “p”)
• Main target antigen: myeloperoxidase
• A/w MPA and Churg-Strauss

9. Activation of neutrophils by ANCA  release of
proinflammatory cytokines IL-1, IL – 8.

10. PATHOGENIC T LYMPHOCYTE RESPONSES
AND GRANULOMA FORMATION
 Vascular endothelial cells activation by cytokines (IFN γ)  HLA class
II molecule expression  interaction with CD4+ T lymphocytes
 Endothelial cells secrete IL-1  activate lymphocytes.
 Also potent inducers of endothelial leukocyte adhesion molecule 1
(ELAM-1) and vascular cell adhesion molecule 1 (VCAM – 1)  adhesion
of leukocytes to endothelial cells in vessel wall

11. GRANULOMATOSIS WITH POLYANGIITIS
(WEGENER’S)
Granulomatous vasculitis of the upper and
lower respiratory tracts along with
glomerulonephritis

12. INCIDENCE AND PREVALENCE
Uncommon
Prevalence – 3 in 100,000
Whites > blacks
M:F = 1:1
Any age , mean age around 40 yr

13. PATHOLOGY AND PATHOGENESIS
Hallmarks – necrotizing vasculitis of small arteries
and veins + granuloma formation
Lung involvement – multiple, bilateral , nodular,
cavitary infiltrates
Upper airway – inflammation, necrosis, granuloma
formation, with or without vasculitis

14. Renal – focal and segmental glomerulonephritis 
evolve into RPGN/ crescentric.
No evidence of immune complex deposition in
renal lesion
High percentage – ANCA +ve

16. CLINICAL MANIFESTATIONS
 Upper airway involvement – 95%
 Paranasal sinus pain , purulent/bloody nasal discharge
 Nasal mucosal ulceration +/-
 Nasal septal perforation  saddle nose deformity
 Serous otitis media
 Subglottic tracheal stenosis – 16% of pts

18.  Pulmonary involvement
 Cough, hemoptysis, dyspnea, chest discomfort
 85-90% pts
 Endobronchial disease  obstruction
 Eye involvement
 Conjunctivitis, dacryocystitis, episcleritis, scleritis, uveitis, retroorbital
mass lesions  proptosis

20.  Skin lesions (46%)
 Papules, vesicles, palpable purpura, ulcers, subcutaneous nodules
 Cardiac (8%)
 Pericarditis, coronary vasculitis , cardiomyopathy (rare)
 Nervous system (23%)
 Cranial neuritis, mononeuritis multiplex, cerebral vasculitis
 Renal (77%)
 Proteinuria, hematuria, RBC casts
 RPGN ensues if not treated appropriately

22.  Nonspecific symptoms and signs
 Malaise
 Weakness
 Arthralgias
 Anorexia
 Weight loss
 Fever

23. Labs
ESR – markedly elevated
Mild anemia , leucocytosis
Mild hypergammaglobulinemia (mainly IgA)
Mildly elevated Rheumatoid factor
Thrombosytosis +/-
Antiproteinase 3 ANCA - +ve in 90% pts

24. Definitive diagnosis
Tissue biopsy – necrotizing granulomatous
vasculitis

25. TREATMENT
 Induction
 Glucocorticoids
 Prednisolone 1mg/kg/d – 1st month
 Taper and discontinue after 6 – 9 months
 Cyclophosphamide
 2mg/kg/day orally
 IV – 15mg/kg infusion – 3 infusions every 2 weeks x 3-6
months

26. Maintenance
 Methotrexate
 Orally or S/C
 0.3 mg/kg weekly dose, not to exceed 15mg/week
 If well tolerated, increase to dose of 20-25mg/week
 Azathioprine
 2mg/kg/day
 Mycophenolate mofetil – 1000mg BD
 Minimum duration of therapy – 2 years past remission, then can
gradually taper over 6 – 12 months

27. Rituximab
In severe disease
375mg/m2
Once weekly x 4 weeks + glucocorticoids

28. MICROSCOPIC POLYANGIITIS

29. DEFINITION
Necrotizing vasculitis with few or no immune
complexes affecting small vessels ( capillaries,
venules , arterioles)

30. INCIDENCE AND PREVALENCE
Mean age of onset ~ 57 yr
Males > females

31. PATHOPHYSIOLOGY
 Predilection to involve capillaries and venules
 Small and medium sized arteries
 Immune complex deposition – no role
 Renal lesion – similar to Wegener’s
 High association with ANCA

32. C/F AND LABS
 Shares similar features as Wegener’s
 Gradual onset – fever, wt loss, musculoskeletal pain
 Glomerulonephritis ~ 79% pts  rapidly progressive to
renal failure
 Hemoptysis
 Mononeuritis multiplex
 GI tract and cutaneous vasculitis
 ESR – raised, anemia , leucocytosis, thrombocytosis
 ANCA +ve in 75% - antimyeloperoxidase antibodies

33. DIAGNOSIS
 Histopathology  evidence of vasculitis or pauci immune
glomerulonephritis

34. TREATMENT
Same as Wegener’s

35. EOSINOPHILIC GRANULOMATOSIS WITH
POLYANGIITIS ( CHURG STRAUSS )

36. DEFINITION
 Characterized by asthma, peripheral and tissue eosinophilia
, extravascular granuloma formation , vasculitis of multiple
organ systems

37. INCIDENCE AND PREVALENCE
 1-3 per million
 Any age except infants
 Mean age of onset ~ 48yr
 Female : male = 1.2 : 1

38. PATHOPHYSIOLOGY
 Small and medium sized muscular arteries, capillaries, veins
, venules
 Characteristic feature – granulomatous reaction in tissues
or even in vessel walls
 Lung involvement – predominant
 Strong association with asthma  suggests aberrant
immunologic phenomena

39. CLINICAL FEATURES
 Nonspecific – fever , malaise , anorexia, weight loss
 Pulmonary findings predominate – severe asthmatic attacks
 Mononeuritis multiplex ~ 72 % pts
 Allergic rhinitis and sinusitis ~ 61% of pts – observed early
in disease course
 Skin lesions ~ 51% of pts – purpura, cutaneous,
subcutaneous nodules
 Renal disease – less common , less severe
 Cardiac – in 14% pts – imp cause of mortality

40. LABS
 Eosinophilia > 1000cells/ μL in >80% pts
 Raised ESR, fibrinogen , α2- globulins – 81% pts
 48% of patients – ANCA ( antimyeloperoxidase )

41. TREATMENT
 Prognosis – poor ( 5yr survival – 25%)
 Myocardial involvement – M/C cause of death
 Glucocorticoids alone – effective in many
 May require low dose for many years
 Those with multi system involvement – daily
cyclophosphamide+prednisolone

42. POLYARTERITIS NODOSA

43. DEFINITION
 Multisystem , necrotising vasculitis of small and medium
sized muscular arteries in which involvement of renal and
visceral arteries is characteristic

44. PATHOPHYSIOLOGY
 Necrotizing inflammation of small and medium sized
muscular arteries
 Segmental lesions – involve bifurcations and branches of
arteries
 Venule involvement – not seen
 Acute stage – PMN infiltration in all vessel wall layers and
perivascular areas  intimal proliferation  vessel wall
degeneration

45.  Mononuclear cells – subacute to chronic stages
 Fibrinoid necrosis ensues  thrombosis , infarction of
tissue, haemorrhage
 Aneurymal dilatation – characteristic of PAN
 Multisystem involvement +
 Pulmonary arteries – not involved
 Kidney involvement – arteritis without glomerulonephritis

47. LABS
 No diagnostic serologic tests
 Leukocytosis in 75% patients – neutrophil predominant
 Anemia of chronic disease maybe seen
 ESR – elevated
 Hypergammaglobulinemia maybe present
 Histopathology of the biopsy material – evidence of vasculitis
 Arteriography – demonstration of aneurysms of medium and
small sized arteries

49. TREATMENT
 Untreated – extremely poor prognosis ( 5 yr survival ~ 10-
20%)
 Death – usually from GI complications – bowel infarcts ,
perforation , CVS causes
 Favourable results – prednisolone + cyclophosphamide
 Less severe cases – glucocorticoids alone – sufficient
 Careful treatment of HTN – can reduce morbidity and
mortality
 Relapse – 10-20% patients

50. GIANT CELL ARTERITIS AND
POLYMYALGIA RHEUMATICA

51. INTRODUCTION
Inflammation of medium and large sized arteries
Characteristically involves – one/more branches of
carotid, particularly temporal A.
Closely associated with polymyalgia rheumatica ->
stiffness, aching , pain in muscles of neck ,
shoulders, lower back , hips , thighs

52. INCIDENCE AND PREVALENCE
> 50 yr age
Women > Men
HLA-DR4 association

53. PATHOPHYSIOLOGY
 Pan – arteritis with inflammatory mononuclear cell infiltrates within the
vessel wall with frequent giant cell formation
 Proliferation of intima + fragmentation of internal elastic lamina
 Process initiated in adventitia.
 CD4+T enter through vasa vasorum  activated  macrophage
differentiation.
 IL2 and IFN γ production  overt arteritis

54. CLINICAL MANIFESTATIONS
Fever, anemia , high ESR , headaches in pt > 50 yr age
Malaise, fatigue , anorexia , wt loss, sweats , arthralgia,
polymyalgia rheumatic
Cranial arterial involvement  headache – main symptom +
tender, thickened , nodular artery
Scalp pain + jaw claudication
Dreaded complication – ischemic optic neuropathy -> can
lead to blindness.

55. 1/3 pts – features of large vessel disease +
Subclavian artery stenosis ( arm claudication )
Aortic aneurysms involving thoracic / abdominal
aorta  risk of rupture / dissection

56. LABS
Elevated ESR
Normochromic / mildly hypochromic anemia
ALP elevated
IgG , complement levels elevated
CPK - normal

57. DIAGNOSIS
Temporal A biopsy
Biopsy segment – atleast 3-5 cm ( since
involvement maybe segmental )
Large vessel disease – by vascular imaging
(CT/MRI)

58. TREATMENT
 Very sensitive to glucocorticoid therapy
 Prednisolone 40-60mg/d x 1 month , followed by gradual
tapering
 If ocular signs/symptoms + -> IV methylprednisolone
1000mg/d x3 days
 Duration of treatment ~ 2 yr
 Recurrence during tapering of steroids 60-85% pts
 Aspirin 81 mg daily – reduce occurrence of cranial ischemic
complications

59. Polymyalgia rheumatica – prompt response to
prednisone
10-20 mg/day

60. TAKAYASU ARTERITIS

61. THANK YOU