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  • 1. TUTORIAL PRESENTATION APPROACH TO A CASE OF VASCULITIS Moderator :Dr. Saroj Purohit
  • 2. What is Vasculitis? Inflammation of blood vessels occlusion aneurysm ischemia hemorrhage
  • 3. WHICH BLOOD VESSELS ARE AFFECTED? • ANY BLOOD VESSEL CAN BE AFFECTED: – – – – – ARTERIES ATERIOLES CAPILLARIES VENULES VEINS • CAN DAMAGE VIRTUALLY ANY ORGAN OR TISSUE
  • 4. Predominantly Small Vessel Vasculitides Immune complex mediated 1.Goodpasture's disease (anti– glomerular basement membrane disease) 2.Cutaneous leukocytoclastic angiitis (“hypersensitivity vasculitis”) 3.Henoch-Schönlein purpura 4.Hypocomplementemic urticarial vasculitis 5.Essential cryoglobulinemia 6.Erythema elevatum diutinum ANCA-associated disorders 1.Wegener's granulomatosis 2.Microscopic polyangiitis 3.Churg-Strauss syndrome 4.Renal-limited vasculitis
  • 5. Secondary Forms of Vasculitis • Connective tissue disorders – rheumatoid vasculitis, – lupus erythematosus, – Sjögren's syndrome, – inflammatory myopathies • Inflammatory bowel disease • Paraneoplastic • Infection • Drug-induced vasculitis:
  • 6. Pathogenesis Antigens (Microbes, drugs, tumor, autoantigens) + Antibodies Formation of immune complexes ↓ Deposition of complexes in and around blood vessels ↓ Activation of complement cascade and generation of C3 and C5a (anaphylatoxins) ↓ Mast cell degranulation and generation of chemokines and cytokines
  • 7. cont….. Increased vascular permeability, neutrophil chemotaxis, further deposition of immune complexes ↓ Appearance of neutrophils with phagocytic activity, and release of proteolytic enzymes (e.g. collagenase and elastase) ↓ Destruction of vessels, formation of platelet thrombi ↓ Ischmia, hemorrhage, and necrosis of tissues involved ↓ Clinical signs and symptoms
  • 8. APPROACH TO A PATIENT OF VASCULITIS
  • 9. • The vasculitic syndrome display a multitude of variable presentations. • Hence there can be no uniform laid down guidelines or evaluation scale for the diagnosis of these disorders. • High degree of suspicion, a detailed history,meticulous physical examination and appropriate laboratory tests to determine organ systems involved and the extent of involvement are the components of the diagnostic process.
  • 10. When to suspect vasculitis Presence of following findings alone or in combination or other bizarre systemic manifestations should raise the suspicion of vasculitis – – – – – Occlusive arterial disease or hypertension in young adults. Unexplained fever, weight loss. Unexplained proteinuria with or without casts. Splinter haemorrhages in nails cutaneous lesions - palpable purpura, erythema, subcutaneous nodules or urticaria. – Sudden retinal vascular disease without hypertension or diabetes.
  • 11. • Persistent headache with sudden visual impairment (monocular blindness) in elderly. • Jaw claudication • Sudden appearance of peripheral neuropathy - wrist drop, foot drop. • Cerebrovascular/cardiovascular events in young. • Unexplained finding of pulmonary nodular/cavitatory lesions.
  • 12. Clinical presentation Predominantly cutaneous vasculitis • Usual presentation is in the form of palpable purpura, urticaria, bullous ulcers or splinter haemorrhages. • Mainly limited to lower extremities. • Salient features are:• • • • Absence of systemic involvement. Negative serology Small vessel leucocytoclastic vasculitis Better prognosis
  • 13. Manifestations of Systemic vasculitis
  • 14. Cont…
  • 15. DIAGNOSTIC WORKUP Laboratory investigations • • • • • • Full blood count with differential white cell count Markers of inflammation: ESR,CRP Electrolytes and hepatic transaminases, glucose Urinalysis for protein and blood Blood cultures (if pyrexial) Serology—ANA ,dsDNA , ANCA,C3 and C4,ASLO titre, viral titres (e.g. hepatitis B and hepatitis C, possibly HIV, CMV, parvovirus B19 and others if recent infection). • Others-rheumatoid factor, electrophoresis, immune complexes.
  • 16. • • • • • • • Skin biopsy Organ biopsy Angiography Other radiological investigations X-ray, CT scanning and MRI 2D Echocardiography Renal and hepatic function tests
  • 17. Mimicks of vasculitis
  • 18. Clinical finding according to vessel involvement
  • 19. LARGE VESSEL VASCULITIS
  • 20. GIANT CELL ARTERITIS (Temporal or Cranial Arteritis) • Transmural inflammation> intimal hyperplasia-> luminal occlusion • Fragmentation of internal elastic lamina • Cellular immune response involving T-cells, APCs, macrophages • Symptoms are due to end-organ ischemia
  • 21. GIANT CELL ARTERITIS Presentation • Temporal Headache • Scalp tenderness • Thickened temporal arteries • Jaw claudication • Acute visual loss • Weight loss, anorexia, fever, night sweats, malaise & depression
  • 22. Laboratory Findings • Erythrocyte sedimentation rate > 50 • 22% of patients with biopsy-proven GCA have normal ESR • Therefore, normal ESR does NOT rule out GCA • Mild-moderate anemia of chronic disease • Deranged LFT(1/3) • CRP- Raised
  • 23. GIANT CELL ARTERITIS Histopathology • Granulomatous cell infiltration • Giant cells • Disruption of internal elastic lamina • Proliferation of intima • Occlusion of lumen
  • 24. Treatment • Goal: Reduce the symptoms and to prevent visual loss • If clinical suspicion is high, treatment should NOT be delayed for biopsy • • • • • • Glucocorticoids Methotrexate Infliximab Azathioprine Imatinib mesylate Surgery
  • 25. MEDIUM VESSEL VASCULITIS
  • 26. Polyarteritis nodosa • Inflammatory necrotizing vasculitis • Tends to occur at bifurcations & branchings of small and medium sized muscular arteries but not venules • Involvement of the renal and visceral arteries is characteristic • involvement of the arterioles of the renal glomeruli or the pulmonary arteries does not occur but can involve bronchial arteries • Mediated by deposition of circulating immune complexes • Age 40-60 yrs • Association--hepatitis B ,Hairy cell leukemia • fibrinoid necrosis occlusion of the vessel lumen, thrombosis, and ischemia of the tissue supplied by the vessel. • Produces aneurysmal dilatation ( upto 1 cm ) of the artery
  • 27. • • • • • • • • • • • ACR classification Otherwise unexplained weight loss >4 kg Livedo reticularis Testicular pain or tenderness Myalgias (excluding that of the shoulder and hip girdle), weakness, or polyneuropathy Mononeuropathy or polyneuropathy New onset diastolic blood pressure >90 mmHg Elevated levels of serum blood urea nitrogen (>40 mg/dL) or creatinine (>1.5 mg/dL) Evidence of hepatitis B virus infection via serum antibody or antigen serology Characteristic arteriographic abnormalities not resulting from noninflammatory disease processes A biopsy of medium- or small-sized artery containing polymorphonuclear cells 3/10 sensitivity/specificity-82-87%
  • 28. TREATMENT • Less severe cases - glucocorticoids • Severe cases - combination of prednisone and cyclophosphamide • PAN with hepatitis B - antiviral therapy in combination with glucocorticoids and plasma exchange.
  • 29. SMALL VESSEL VASCULITIS
  • 30. Cutaneous small vessel vasculitis SYN : Cutaneous leukocytoclastic vasculitis • Hypersensitivity angiitis/vasculitis • Cutaneous necrotizing venulitis. • Affect mainly cutaneous post-capillary venules, • cutaneous small vessel vasculitis (CSVV) is the most common type of vasculitis in dermatology. • 50% of cases – idiopathic • 15–20% - infection • 15–20% - inflammatory diseases (collagen vascular disorders) • 10–15% - medications • 5% - malignancy.
  • 31. • Histopathology. • swelling of endothelium • fibrinoid necrosis of vessel walls • Extravasation of erythrocytes • Infiltrate of neutrophils with karyorrhexis of nuclei(i.e. leukocytoclasia)
  • 32. Clinical features • The major cutaneous manifestation of CSVV is palpable purpura, ranging in size from 1 mm to several centimetres. • Purpura may progress to papules, nodules, vesicles, plaques,bullae or pustules. • Other cutaneous findings include oedema, livedo reticularis and urticaria. Lesions typically occur in areas prone to stasis (ankles and lower legs). • Typically spare intertriginous regions. • Usually asymptomatic,pruritus,pain or burning may be experienced, as well as systemic symptoms including fever, arthralgia, myalgia and anorexia may occur.
  • 33. Wegener’s Granulomatosis Classical triad • • • systemic small vessel vasculitis Necrotizing granulomatous inflammation of both the upper and lower respiratory tracts, and Glomerulonephritis Pathology • • • • • Preferentially involves venules, capillaries and arterioles may involve medium sized arteries Characterized by the presence of granulomatous inflammatory lesions – Focal accumulations of lymphocytes, macrophages, epithelioid cells and multinucleated giant cells Granulomas are similar to granulomas associated with intracellular infections Predominant cell type is CD4+ T cells and macrophages
  • 34. • Upper • Respiratory tract – Purulent sinus drainage – Nasal mucosal ulceration with epistaxis / necrosis/perforations of nasal septum – Saddle nose deformity – Otitis media / hearing loss Tracheal inflammation and sclerosis of subglotic region : stridor and airway stenosis • Lower • – Fleeting focal infiltrates Cavitary lesions Massive pulmonary hemorrhage and hemoptysis - caused by alveolar capillaritis 80% will progress to paucimmune GN • Renal • GN is characterized by – Focal fibrinoid necrosis – Crescent formation – Absent/paucity of Ig/C3/C4 deposits
  • 35. Other signs and symptoms • Cutaneous manifestations – – Most common -palpable purpura – II most common- Oral ulcers • Other skin lesions– Tender subcutaneous nodules – Papules – Vesicles and petechiae – Non-specific ulcer – Pyoderma gangrenosum. • Migratory arthritis, ocular involvement (scleritis, corneal ulceration and orbital disease) • Peripheral (mononeuritis multiplex) or central nervous system involvement • Risk of venous thrombosis
  • 36. Treatment • Induction – Oral cyclophosphamide 2mg/kg with prednisone 1mg/kg – Usually for 3 to 6 months – IV cyclophosphamide 15mg/kg as monthly pulse • Maintenance – Azathioprine 2mg/kg and prednisone 5 to 10mg(low dose) – Methotrexate 15 to 20mg per week and low dose prednisone • Relapse – 80% experience one or more within 10yrs – Usually when treatment is being tapered or stopped – Need to re-start cyclophosphamide
  • 37. • • • Churg Strauss syndrome Also known as Allergic Granulomatosis Small vessel autoimmune vasculitis leading to necrosis Site: Blood vessels of the lungs (MC) GI Tract Peripheral nerves Heart, skin, and kidneys • ACR criteria for the diagnosis of Churg-Strauss syndrome • Presence of 4 or more criteria:(1) H/O Bronchial asthma (2) Eosinophilia >10% in Peripheral Blood (3) Paranasal sinusitis (4) Pulmonary infiltrates (Transient) (5) Histology: vasculitis with extravascular eosinophils (6) Mononeuritis multiplex or Polyneuropathy
  • 38. Pathology Necrotising vasculitis of small vessels Granulamatous reaction present in tissue and in the wall of vessels
  • 39. Clinical manifestation • Prodromal phase – – seen in second and third decades – characterized by atopic disease, allergic rhinitis, and asthma. • Eosinophilic phase – – peripheral blood eosinophilia – eosinophilic infiltration of multiple organs, especially the lung and GIT. • Vasculitic phase – – third & fourth decades – life-threatening systemic vasculitis of small vessels.
  • 40. • • • • • • Severe asthmatic attacks and migratory pulmonary infiltrates (MC) Mononeuritis multiplex (72%) Allergic rhinitis and sinusitis (60%) Skin lesions: Palpable purpura, cutaneous & subcutaneous nodules Gastrointestinal tract — abdominal pain , diarrhea , gastrointestinal bleeding. Musculoskeletal — Myalgias, migratory polyarthralgias, and frank arthritis. • Cardiovascular — Heart failure and cardiac rhythm abnormalities • Renal involvment: 50% patients have rapidly progressive or acute renal insufficiency , while the others isolated proteinuria or microscopic hematuria.
  • 41. • • • • • • Management Striking eosinophillia >1000 cells/µl (80%) Anaemia Raised ESR, Raised fibrinogen P-ANCA : Positive (48%) RFT:Elevated serum BUN and creatinine level Urine: proteinuria, microscopic hematuria & RBC casts • Corticosteroids - clinical remission in 90% • Severely affected patients, recalcitrant disease or those with poor prognostic factors such as cardiac, GI, renal or CNS involvement– Cyclophosphamide+ Corticosteroids – Intravenous immunoglobulin (IVIG)
  • 42. Henoch-Schönlein Purpura • • • • • Also referred to as anaphylactoid purpura characterized by – palpable purpura (most commonly distributed over the buttocks and lower extremities) – arthralgias – gastrointestinal signs and symptoms Glomerulonephritis Usually seen in children most patients range in age from 4 to 7 years; may also be seen in infants and adults male-to-female ratio is 1.5:1
  • 43. Pediatric patients Clinical features – palpable purpura (nearly all cases) – polyarthralgias  Gastrointestinal involvement (70%) • • • • • colicky abdominal pain nausea, vomiting diarrhea, or constipation passage of blood and mucus per rectum bowel intussusception  Renal – 10-50% Mild GN,proteinuria,microscopic hematuria Adults – Cutaneous vasculitis – Arthritis – Peripheral neuropathy – Glomerulonephritis (MPGN) – Life-threatening RPGN or vasculitis of the CNS, gastrointestinal tract, or heart occurs infrequently
  • 44. ACR criteria • • • • • • Palpable purpura Bowel angina Gastrointestinal bleeding Hematuria Age at onset ≤20 years No new medication • 3/6 carry sensitivity/specificity-87%
  • 45. • Management • Skin/renal biopsy( IFA)– Leucocytoclastic vasculutis with IgA and c 3 deposition Lab studies – Mild leucocytosis – Normal platelet count and complement level – Eosinophilia IgA level elevated • Prognosis is excellent and most patients recover completely • 1–5% of children progress to ESRD • Treatment is similar for adults and children. • Glucocorticoids - prednisone, in doses of 1 mg/kg per day and tapered according to clinical response effective in the treatment of abdominal pain and arthritis – not benefit in skin or renal disease – does not appear to shorten the duration of active disease or lessen the chance of recurrence. • • • • Dapsone (100 mg once daily)- shorten the duration, beneficial effect on the cutaneous lesions factor XIII replacement ranitidine RPGN - intensive plasma exchange combined with cytotoxic drugs. • Disease recurrences have been reported in 10–40% of patients. •
  • 46. Urticarial Vasculitis • 5–10% Of patients with chronic urticaria have urticarial vasculitis (UV). • Chronic disease,presents as urticarial lesions that most often occur on the trunk or proximal limbs, frequently with associated angio-oedema • Lesions persist for greater than 24 h, often demonstrate purpura and post-infl ammatory pigmentation. • Two types – – UV associated with hypocomplementaemia, and – UV without hypocomplementaemia(normocomplementaemic UV). Pathology – Histopathological features are those of leukocytoclastic vasculitis with a perivasculer neutrophilic infiltrate
  • 47. C/F • Fixed annular wheals • >24 hr • pain and burning sensation rather then itching • hyperpigmentation on resolution • Systemic symptoms and signs
  • 48. Treatment • majority of patients respond to systemic corticosteroids. • indomethacin 25mg three times daily to 50mg four times daily. • Colchicine 0.6mg two or three time daily. • Dapsone up to 200mg / day • Low dose oral methotrexate • Dapsone plus pentoxifylline