1. The Vasculitis Syndromes

2. Definition Inflammation and damage of blood vessels Single organ→ skin
Several organ systems
Primary
Secondary
Heterogeneity
Overlap

3. Primary Vasculitis Syndromes
Wegener´s granulomatosis
Churg-Strauss syndrome
Polyarteritis nodosa
Microscopic polyangitis
Giant cell arteritis
Takayasu´s arteritis
Henoch-Schönlein purpura
Idiopthic cutaneous vasculitis
Essential mixed cryoglobulinemia
Behcet´s syndrome
Isolated vasculitis of the CNS
Cogan´s syndrome
Kawasaki disease

4. Secondary Vasculitis Syndromes
Drug-induced vasculitis
Serum sickness
Vasculitis associted with other primary diseases, infection, malignancy, rheumatic disease

5. Pathophysiology and Pathogenesis
Immunpathogenic mechanisms
Pathogenic immune complex formation and/or deposition:Hepatitis B PAN, Hepatitis C Essential mixed cryoglob.
Production of antineutrophilic cytoplasmic antibodies: Wegener´s, Churg-Strauss, Microsc. polyang.
Pathogenic T lymphocyte responses and granuloma formation:Giant cell, Takayasu´s, Wegener, Churg-Strauss

6. Approach to the patient: Vasculitis
Unexplained systemic illness
Angiogram of organs
Definitive diagnosis→biopsy of involved tissue

7. Wegener´s granulomatosis

8. Incidence and Prevalence
Prevalence: 3 per
Age of onset: 40 years
Primary vasculitis syndrome→ damage of vessels
Immunopathogenic mechanisms
ANCA= antineutrophil cytoplasmic antibody
c-ANCA= cytoplasmic ANCA
(diffuse, granular cytoplasmic staining by immunofluorescence microscopy)
Detectable antibodies to proteinase-3
Granuloma formation

9. Pathology and pathogenesis
Necrotizing vasculitis of small arteries and veins + granuloma formation
Lung: multiple, bilateral, nodular cavitary infiltrates
Biopsy: necrotizing granulomatous vasculitis
Upper airway lasions: sinuses, nasopharynx
Kidney: rapidly progressive crescentic glomerulonephritis

10. Clinical manifestations
Upper airways 95%
Purulent or bloody nasal discharge
Nasal septal perforation
Saddle nose deformity
Serous oitis media, hearing loss
Subglottic tracheal stenosis→severe airway obstruction
Pulmonary involvement:hemoptysis, dyspnea 85-90%
Eye: scleritis, conjunctivitis, retroorbital mass laesion
Skin: palpable purpura, papules, vesicles, subcutaneous nodules
Heart: pericarditis, coronary vasculitis
CNS: mononeuritis multiplex, cerebral vasculitis
Kidney disease: 77%, proteinuria, hematuria, red blood cell casts, rapidly progressive renal failure

13. Laboratory findings ESR↑ Mild anemia, leukocytosis, thrombocytosis
90% positive antiproteinase-3 c-ANCA

14. Diagnosis of WG Tissue biopsy: necrotizing granulomatous vasculitis
c-ANCA positivity

15. Treatment of WG
Cyclophosphamide induction for severe disease: 2 mg/kg per day orally + steroids
Cyclophosphamide for 1 year following the induction of complete remission
Prednisone 1 mg/kg per day
Improvement: 90%
Complete remissions: 75%
Later relapses
Remission maintenance: Azathioprine, Methotrexate 2 years past remission

16. Treatment of WG 2 Mycophenolate mofetil 1000 mg twice a day
Rituximab (anti-CD20)
Trimethoprim-sulfamethoxazole

17. Churg-Strauss syndrome

18. Definition Allergic angiitis and granulomatosis
Asthma, peripheral and tissue eosinophilia, extravascular granuloma formation, vasculitis of multiple organs

19. Incidence and Prevalence
1-3 cases per million
Onset: 48 years

20. Pathology and Pathogenesis
Necrotizing vasculitis
Small and medium-sized muscular erteries, capillaries, veins, and venules
Granuloma formation
Infiltration of the tissues with eosinophils
Lung, skin, heart, kidney. Peripheralnervous system, GI

21. Clinical and Laboratory Manifesttions
Asthma, pulmonary infiltrates
Mononeuritis multiplex
Allergic rhinitis and sinusitis
Skin lesions: purpura, subcutaneous nodules
Eosinophilia
ESR↑
p-ANCA = perinuclear ANCA (antimyeloperoxidase)

22. Diagnosis
Asthma
Peripheral blood eosinophilia
Biopsy

23. Treatment
Steroids
Cyclophosphamide
Survival rate:72%

24. Polyarteritis nodosa

25. Definition Multisystem, necrotizing vasculitis
Small and medium-sized muscular arteries
Renal and visceral arteries

26. Incidence and Prevalence
Very uncommon disease

27. Pathology and Pathogenesis
Segmental lesions
Bifurcations and branching of arteries
Aneurysmal dilatations up to 1 cm in size
Kidney: arteritis without glomerulonephritis
Hepatitis B antigenemia: 10-30%
Circulating immune complexes composed of hepatitis B antigen

28. Clinical manifestations
Fever, weight loss
Kidney→renal failure, hypertension
Joint→arthritis, arthralgia, myalgia
Peripheral neuropathy, mononeuritis multiplex
GI→abdominal pain, bleeding, bowel infarction and perforation, liver infarction, pancreatic infarction
Skin→purpra, nodules, cutaneous infarcts, livedo reticularis
Heart→congestive heart failure, myocardial infarction, pericardiis
Testicular and ovarian pain
CNS→cerebral vascular accident, seizure, altered mental status

29. Laboratory tests Leukocyte count↑ ESR↑ Anemia of chronic disease
Hypergammaglobulinemia
HBsAg pozitivity 30%

30. Diagnosis Vasculitis on biopsy material of involved organs
Angiography→aneurysms of small and medium-sized arteries

31. Treatment Steroid Cyclophosphamide
PAN + Hepatitis B virus pozitivity: Antiviral drugs+ steroid+plasma exchange

32. Microscopic polyangitis
Glomerulonephritis→renal failure
Pulmonary capillaritis→hemoptysis
Mononeuritis multiplex
GI vasculitis
Cutaneous vasculitis
Age of onset: 57 years
pANCA positivity 75%

33. Diagnosis and Treatment
Kidney,lung: histologic evidence of vasculitis
Steroid +Cyclophosphamide

34. Giant cell arteritis and Polymyalgia rheumatica

35. Definition Temporal arteritis or Cranial arteritis
Inflammationof medium- and large-sized arteries
Temporal artery
Aorta and its main branches
Polymyalgia rheumatica: pain in the muscles of the neck, shouldersm lower back
>50 years

36. Clinical and Laboratory Manifestations
Fever,anemia
ESR↑
Headache
Temporal artery→tender, thickened, nodular
Ischemic optic neuropathy→visual loss→blindness
Increased risk of aortic aneurysm→ dissection

37. Diagnosis
Biopsy of the temporal artery
Giant cell arteritis

38. Treatment Steroid: Prednisone40-60 mg/day 1 month
Treatment for≥ 2 years
ESR↓
Polymyalgia rheumatica: Prednisone mg/day

39. Takayasu´s arteritis
Inflammatory and stenotic disease of medium- and large-sized arteries
Aortic arch and its branches
=Aortic arch syndrome
Incidence: 1-2 cases/million/year
Angiography

40. Frequency of angiographic abnormalities
Subclavian: 93%
Common carotid: 58%
Abdominal aorta: 47%
Aortic arch: 35%
Vertebral: 35%
Pulmonary: 10-40%
Coronary < 10%

41. Clinical manifestetions
Panarteritis with inflammatory mononuclear cell infiltrates
Narrowing of the lumen
Pulses absent
ESR↑, anemia, gammaglobulin↑

42. Diagnosis Young woman Decrease or absence ofperipheral pulses
Discrepancies in blood pressure
Arterial bruits
Arteriography→irregular vessel walls, stenosis, poststenotic dilatation, aneurysm formation, occlusion, evidence of increased collateral circulation

43. Treatment Steroid: prednisone 40-60 mg/day Methotrexate 25 mg/week
Surgical correction of stenosed arteries

44. Henoch-Schönlein purpura
Anaphylactoid purpura
Palpable purpura over the buttocks and lower extremities
Arthralgias
GI signs→colicky abdominal pain, melena/hematochesia
Glomerulonephritis→proteinuria, microscopic hematuria, red blood cell casts
Small-vessel vasculitis
Children 4-7 years
Immune-complex deposition
Serum IgA↑

45. Diagnosis
Clinical symptoms
Skin biopsy→ leukocytoclastic vasculitis

46. Treatment
Do not require therapy
Steroids: Prednisone 1 mg/kg/day

47. Idiopathic cutaneous vasculitis
=Hypersensitivity vasculitis
=Cutaneous leukocytoclastic vasculitis
Dermis, small vessels
Only skin involvement→palpable purpura, chronic urticaria
Diagnosis: biopsy→vasculitis
Etiology: drug, infection, underlying disease
Treatment:microbe→antimicrobal therapy, steroids

48. Essential mixed cryoglobulinemia
Cryoglobulins: cold-precipitable monoclonal or polyclonal immunoglobulins
Cutaneous vasculitis, palpable purpura, arthralgias, glomerulonephritis
Hepatitis C infection
Treatment:IFN-α, Ribavirin

49. Behcet´s syndrome
Recurrent, painful aphthous oral ulcerations in the oral cacity
Recurrent genital ulcers
Iritis
Cutaneous lesions
Treatment: topical steroids, Prednisone

50. Isolated vasculitis of the CNS
Severe headache, focal neurologic defects
Abnormal MRI of the brain
Abnormal liquor
Abnormal cerebral angiogram→vasculitis
Brain biopsy
Treatment:Prednisone+Cyclophosphamide

51. Kawasaki disease =Mucocutaneous lymph node syndrome
Nonsuppurative cervical adenitis
Children > 2 years
Coronary artery aneurysms 25%
Treatment:IVIG+ Aspirin

52. Raynaud´s Phenomenon Episodic vasoconstriction inthe fingers and toes
Tip of the nose and earlobes
Cold exposure
pallor→cyanosis→erythema rewarming of the fingers, vasoconstriction→ischemia→reperfusion
Normal population: 3-5%, women
Primary and/or secondary
Nailbed cutaneous capillaries viewed stereoscopic microscope

53. Treatment
Dress warmly, calcium channel blockers, ARBs (angiotensin II receptor blockers) Losartan, iv. prostaglandins, low-dose aspirin