1. N.Movaffagh MD Rheumatologist
The Vasculitis Syndromes
N.Movaffagh MD Rheumatologist

2. Vasculitis is a clinicopathologic process characterized by inflammation of and damage to blood vessels
The vessel lumen is usually compromised,
ischemia of the tissues supplied by
the involved vessel

3. Vasculitis Syndromes Vasculitis are primary & secondary
Vasculitis may be confined to a single organ,or it may simultaneously involve several organ systems

4. Primary Vasculitis Syndromes
Granulomatosis with polyangiitis (Wegener’s or GPA)
Microscopic polyangiitis(MPA)
Eosinophilic granulomatosis with polyangiitis(EGPA)
(Churg-Strauss)
IgA vasculitis (Henoch-Schönlein)
Cryoglobulinemic vasculitis
Polyarteritis nodosa
Kawasaki disease
Giant cell arteritis
Takayasu arteritis
Primary central nervous system vasculitis

5. Secondary Vasculitis Syndromes
Vasculitis associated with probable etiology
Drug-induced vasculitis
Hepatitis C virus–associated cryoglobulinemic vasculitis
Hepatitis B virus–associated vasculitis
Cancer-associated vasculitis
Lupus vasculitis
Rheumatoid vasculitis
Sarcoid vasculitis

6. Classification by Vessel Size
Large-Vessel Vasculitis
Takayasu’s arteritis
Giant cell arteritis
Medium-Vessel Vasculitis
Polyarteritis nodosa
Kawasaki’s disease
Small-Vessel Vasculitis
Anti-neutrophil Cytoplasmic Antibody–Associated Vasculitis
Microscopic polyangiitis
Granulomatosis with polyangiitis
Eosinophilic granulomatosis with polyangiitis
IgA vasculitis (Henoch-Schönlein)

7. PATHOPHYSIOLOGY AND PATHOGENESIS

8. Mechanisms of Vessel Damage in Vasculitis Syndromes
Pathogenic immune-complex formation and/or deposition
Production of antineutrophilic cytoplasmic antibodies
Pathogenic T lymphocyte responses and granuloma formation

9. Pathogenic immune-complex formation and/or deposition
IgA vasculitis (Henoch-Schönlein)
Lupus vasculitis
Serum sickness and cutaneous vasculitis syndromes
Hepatitis C virus–associated cryoglobulinemic vasculitis
Hepatitis B virus–associated vasculitis

10. PATHOGENIC IMMUNE-COMPLEX FORMATION
causal role of immune complexes has not been clearly established
actual antigen rarely been identified in vasculitic syndromes
Ag-AB Deposition in vessel walls permeability increased
deposition of complexes activation of complement (C5a)
Infiltration of N in the vessel wall
Phagocytose the immune complexes
release their intracytoplasmic enzymes
mononuclear cells infiltrate the vessel wall

11. Production of antineutrophilic cytoplasmic antibodies
Granulomatosis with polyangiitis (Wegener’s)
Microscopic polyangiitis(MPA)
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

12. ANCA cytoplasmic ANCA (cANCA) antibodies to proteinase-3
perinuclear ANCA (pANCA)Anti MPO
pANCA pattern inflammatory bowel disease, certain drugs,and infections (endocarditis)

13. p-ANCA
c-ANCA

14. ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA)
Neutrophils or monocytes are primed by (TNF-α) or (IL-1),
proteinase-3 and myeloperoxidase translocate to
the cell membrane
neutrophils then degranulate and produce reactive oxygen species ,cause tissue damage
Activation of neutrophils and monocytes by ANCA also induces the release of proinflammatory cytokines such as IL-1 and IL-8

16. Pathogenic T lymphocyte responses and granuloma formation
Giant cell arteritis
Takayasu arteritis
Granulomatosis with polyangiitis (Wegener’s)
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

17. PATHOGENIC T LYMPHOCYTE RESPONSES AND GRANULOMA FORMATION
cell-mediated immune injury
cytokines such as interferon (IFN) γ
Vascular endothelial cells can express
HLA class II
interaction with CD4+ T lymphocytes

18. Endothelial cells can secrete IL-1 which may activate T lymphocytes
IL-1 and TNF-α are potent inducers ELAM-1,
VCAM-1

19. General Principles of Diagnosis
The diagnosis of vasculitis is often considered in any patient with an unexplained systemic illness

20. Clinical abnormalities of vasculitis
palpable purpura
pulmonary infiltrates
microscopic hematuria
chronic inflammatory sinusitis
mononeuritis multiplex
unexplained ischemic events
GN with evidence of multisystem disease

21. Palpable purpura

22. workup of suspected vasculitis
1.exclude other diseases(Vasculitis Mimicars)
2.workup for follow a series of progressive steps that establish the diagnosis of vasculitis

23. Conditions That Can Mimic Vasculitis
Infectious diseases
Coagulopathies/thrombotic microangiopathies
Neoplasms
Drug toxicity(Cocaine,Levamisole,Amphetamines)
Sarcoidosis
Atheroembolic disease
Antiglomerular basement membrane disease
Amyloidosis
Migraine
Reversible cerebral vasoconstrictive syndrome

25. definitive diagnosis of vasculitis based on biopsy of involved tissue
For polyarteritis nodosa, Takayasu arteritis, primary (CNS) vasculitis arteriogram of organs

26. GENERAL PRINCIPLES OF TREATMENT
Glucocorticoids and/or other immunosuppressive agents

27. Isolated idiopathic cutaneous vasculitis usually resolves with symptomatic treatment

28. GRANULOMATOSIS WITH POLYANGIITIS (WEGENER’S)
DEFINITION
Wegener’ scharacterized by : granulomatous vasculitis of the upper and lower respiratory tracts together with GN

29. INCIDENCE AND PREVALENCE
uncommon disease
prevalence of 3 per 100,000
Rare in blacks
male-to-female ratio is 1:1
the mean age of onset is ∼40 years
∼15% of patients are <19 years

30. Wegener’s histopathologic hallmarks of Wegener’s:
necrotizing vasculitis of small arteries and veins together with granuloma formation
(intravascular or extravascular)

32. classic triad of disease : upper and lower respiratory tracts and kidney involvement

33. PATHOGENESIS immunopathogenesis of this disease is unclear
Chronic nasal carriage of Staphylococcus aureus associated with a higher relapse rate Wegener’s
there is no evidence for a role of this organism in the pathogenesis of the disease

34. PATHOLOGY AND PATHOGENESIS
IFN-γ
TNF-α
IL-12
ANCA

35. CLINICAL AND LABORATORY MANIFESTATIONS
Involvement of the upper airways in 95%
sinuses and nasopharyx
Nasal septal perforation
saddle nose deformity
Serous otitis media result of eustachian tube blockage
Subglottic tracheal stenosis(active disease or scarring) may result in severe airway obstruction

37. Pulmonary involvement% 85-90 asymptomatic infiltrates
cough, hemoptysis, dyspnea, chest discomfort

38. Lung involvement appears as:
multiple, bilateral, nodular cavitary infiltrates
Lung biopsy : necrotizing granulomatous vasculitis

41. Eye involvement 52%
Conjunctivitis dacryocystitis episcleritis scleritis, granulomatous sclerouveitis ciliary vessel vasculitis
retroorbital mass
proptosis

44. Skin lesions 46%
Papules vesicles palpable purpura ulcers subcutaneous nodules
Biopsy: vasculitis,granuloma

46. Cardiac involvement:
Pericarditis
coronary vasculitis
cardiomyopathy(rarely)

47. Renal disease 77% Renal involvement is characterized by:
Focal and segmental glomerulitis
Rapidly progressive crescentic GN
Granuloma formation is rare

48. malaise, weakness, arthralgias, anorexia, and
weight loss
Fever may indicate activity of the underlying disease & secondary infection,usually of the upper airway
deep venous thrombosis or pulmonary emboli

50. DIAGNOSIS necrotizing granulomatous vasculitis on tissue biopsy
Pulmonary tissue(highest diagnostic yield)
upper airway tissue usually reveals granulomatous
inflammation with necrosis but may not show vasculitis
Renal biopsy can confirm the presence of pauci-immune GN

51. specificity of a positive antiproteinase-3 ANCA for Wegener’s is very high(especially in active GN)
ANCA with rare exceptions, should not substitute for
tissue diagnosis
False-positive ANCA titers(certain infectious and neoplastic diseases)

52. Differential Diagnoses
Goodpasture’s syndrome
relapsing polychondritis
tumors of the upper airway or lung
infectious diseases such as histoplasmosis
noninfectious granulomatous diseases
midline destructive diseases
lymphomatoid granulomatosis

53. causes of midline destructive disease
Upper airway neoplasms specifically extranodal (NK)/T cell lymphoma (nasal type)
Cocaine-induced tissue injury
(cutaneous infarction and ANCA +)

54. Differential Diagnoses
lymphomatoid granulomatosis
An Epstein-Barr virus–positive B cell proliferation that is associated with an exuberant T cell reaction

55. laboratory findings Elevated ESR mild anemia Leukocytosis
mild hypergammaglobulinemia(particularly of the IgA class)
mildly elevated Rf
Thrombocytosis
90%positive antiproteinase-3 ANCA(active)
∼60–70%( Non active disease)
may antimyeloperoxidase

56. TREATMENT Glucocorticoids Cyclophosphamide
methotrexate (INDUCTION&maintenance)
Azathioprine
mycophenolate mofetil
RITUXIMAB
TMP-SMX on relapse regard to upper airway disease

57. EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS ((CHURG-STRAUSS

58. uncommon disease
annual incidence of 1–3 per million
occur at any age with the possible exception of infants
mean age of onset is 48 years
female-to-male ratio of 1.2:1

59. PATHOLOGY AND PATHOGENESIS
Involves small and medium-sized muscular
arteries, capillaries, veins, and venules
characteristic histopathologic feature:
granulomatous reactions in tissues or within the walls of the vessels.
infiltration of the tissues with eosinophils

60. CLINICAL MANIFESTATIONS
fever, malaise, anorexia, and weight loss
severe asthmatic attacks and pulmonary infiltrates
Mononeuritis multiplex is the second most common manifestation
Allergic rhinitis and sinusitis
heart disease
Skin lesions(purpura and subcutaneous nodules)
renal disease is less common

61. laboratory finding eosinophilia, levels >1000 cells/μL(>80%)
elevated ESR,fibrinogen, α2-globulins
ANCA antimyeloperoxidase(P-ANCA)

62. DIAGNOSIS
evidence of asthma peripheral blood eosinophilia clinical features consistent with vasculitis biopsy with clinical manifestations

63. TREATMENTE prognosis of untreated EGPA is poor
Echocardiography should performed in all new patients
Glucocorticoids
cyclophosphamide and prednisone

64. IgA VASCULITIS (HENOCH-SCHÖNLEIN)
a small-vessel vasculitis characterized by:
palpable purpura (most commonly over the buttocks and lower extremities)
Arthralgia
gastrointestinal signs & symptoms
glomerulonephritis

65. INCIDENCE AND PREVALENCE
usually seen in children (4 to 7 years)
however, the disease may also be seen in infants and adults
male-to-female ratio is 1.5:1
is not a rare disease
a peak incidence in spring has been noted.

66. PATHOLOGY AND PATHOGENESIS
number of inciting antigens have been suggested including:
upper respiratory tract infections,
various drugs, foods, insect bites, and immunizations
IgA is the antibody class most often seen in the immune complexes

67. CLINICAL MANIFESTATIONS
In pediatric patients, palpable purpura is seen in virtually all patients
Polyarthralgia
GI involvement
Colicky abdominal pain usually associated
with nausea, vomiting, diarrhea, constipation
Renal involvement occurs in 10–50%
(GN usually resolves spontaneously without
therapy)

68. CLINICAL MANIFESTATIONS
In adults, presenting symptoms are most frequently related to the skin and joints
initial complaints related to the gut are
less common
certain studies have found that renal disease is more frequent and more severe in adults, this has not been a consistent finding
Myocardial involvement

69. LABORATORY MANIFESTATIONS
mild leukocytosis, occasionally eosinophilia normal platelet count
Serum complement are normal
IgA levels are elevated in about one-half of patients

70. DIAGNOSIS Diagnosis is based on clinical signs and symptoms.
Skin biopsy specimen can be useful in confirming leukocytoclastic vasculitis with IgA and C3 deposition by immunofluorescence.
Renal biopsy is rarely needed for diagnosis

71. TREATMENT Most patients recover completely, and some
do not require therapy.
Treatment is similar for adults and children
glucocorticoid therapy (tissue edema, arthralgias, abdominal discomfort) however, it has not proved beneficial in the
treatment of skin or renal disease

72. In rapidly progressive glomerulonephritis :
plasma exchange combined with cytotoxic drugs