Tutorial vasculitis


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  • Dr Daulatram Dhaked, I am impressed by your clear understanding of rational diagnostic steps in such complicated issue as vasculitides. I have worked with vasculitides for 10 years. The problem is that you should keep in mind a big list of nosologies and criteria. I like your solution of this problem show in your presentation. I work with this issue too. I would be grateful if you look through my Quick Reference Guide on Diagnosis of vasculitides. My idea is to place all necessary data on two pages of A4 sheet. Please if you find time see http://www.slideshare.net/MikhailValivach/diagnosis-of-vasculitides-and-pseudovasculitides-a-quick-reference-guide-mikhail-valivach-pavlodar-2015 Mikhail Valivach, M.D., Kazakhstan, Pavlodar Regional Diagnostic Center
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Tutorial vasculitis

  2. 2. What is Vasculitis? Inflammation of blood vessels occlusion aneurysm ischemia hemorrhage
  4. 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. 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. 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. 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
  9. 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. 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. 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. 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. 13. Manifestations of Systemic vasculitis
  14. 14. Cont…
  15. 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. 16. • • • • • • • Skin biopsy Organ biopsy Angiography Other radiological investigations X-ray, CT scanning and MRI 2D Echocardiography Renal and hepatic function tests
  17. 17. Mimicks of vasculitis
  18. 18. Clinical finding according to vessel involvement
  20. 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. 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. 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. 23. GIANT CELL ARTERITIS Histopathology • Granulomatous cell infiltration • Giant cells • Disruption of internal elastic lamina • Proliferation of intima • Occlusion of lumen
  24. 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
  26. 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. 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. 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.
  30. 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. 31. • Histopathology. • swelling of endothelium • fibrinoid necrosis of vessel walls • Extravasation of erythrocytes • Infiltrate of neutrophils with karyorrhexis of nuclei(i.e. leukocytoclasia)
  32. 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. 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. 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. 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. 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. 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. 38. Pathology Necrotising vasculitis of small vessels Granulamatous reaction present in tissue and in the wall of vessels
  39. 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. 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. 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. 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. 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. 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. 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. 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. 47. C/F • Fixed annular wheals • >24 hr • pain and burning sensation rather then itching • hyperpigmentation on resolution • Systemic symptoms and signs
  48. 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