VASCULITIS. It means ―inflammation of the walls of thevessels‖ and can be associated to manydifferent clinical conditions...
VASCULITIS.CLASSIFICATION.(cont.) *Immunologic.A. Immune complex- mediated.-Infection-induced(Hepatitis B,C)-Henoch-Schon...
VASCULITIS.CLASSIFICATION.(cont.) B. ANCA-mediated.-Wegener granulomatosis-Microscopic polyangeitis-Churg-Strauss syndrom...
VASCULITIS.CLASSIFICATION.(cont.) D. Cell-mediated.-Organ-allograft rejection-Inflammatory bowel disease-Paraneoplastic v...
Classification
CLASSIFICATION TREEVasculitisLarge Blood Vessel• Temporal Arteritis• Takayasu ArteritisMedium Blood Vessel• Polyarteritis ...
GIANT CELL(TEMPORAL)ARTERITIS
GIANT CELL (TEMPORAL)ARTERITIS. A vasculitis of unknown etiology occurringprimarily in the elderly. Other termscommonly u...
GIANT CELL (TEMPORAL)ARTERITIS. CLINICAL: old patients with:◦ fever,◦ fatigue,◦ loss of weight,◦ with or w/o facial pain ...
GIANT CELL (TEMPORAL)ARTERITIS. Others, with more severe form andinvolvement of ophtalmic arterydiplopiaor blindness of ...
TAKAYASU ARTERITIS.
TAKAYASU ARTERITIS. Takayasu’s arteritis is a chronicinflammatory disorder of unknownetiology primarily affecting the aor...
Aortic archarteriogram in apatient withTakayasu‘s arteritis.Smooth taperedstenosis of bilateralcommon carotidarteries (upp...
TAKAYASU ARTERITIS.(cont.) MICROSCOPIC: mononuclear infiltration ofadventiciamid-layer with involvement ofvasa vasorum.
TAKAYASU ARTERITIS.(cont.) CLINICAL:◦ reduced brachial pulse,◦ difference in BP between R & L arm >10 mmHg,◦ Coldness + n...
POLYARTERITISNODOSA
POLYARTERITIS NODOSA Is a small/medium sized arteritis affectingmultiple organs (skin, peripheral nerves,gut, kidney and ...
POLYARTERITIS NODOSA CLINICAL: onset is gradual (wksmos.)and nonspecific:◦ malaise,◦ fever,◦ weight loss,◦ abdominal pai...
POLYARTERITIS NODOSA◦ diastolic pressure >90 mm Hg,◦ mononeuropathy or polyneuropathy◦ palpable purpura,◦ livedo reticular...
POLYARTERITIS NODOSA◦ Renal involvementhypertension.◦ In GI tract abdominal angina (hemorrhage,perforation).◦ In heart: ...
POLYARTERITIS NODOSA Dx.◦ Elevated BUN or creatinine◦ Proven hepatitis B/C virus infection◦ Angiographic signs ofaneuryms...
BUERGER´S DISEASE Also known as Thromboangiitis obliterans,is characterized by segmental thrombosis+ acute/chronic inflam...
BUERGER´S DISEASE Microscopically: acute + chronicinflammation in arterial walls +thrombosisorganization/recanalization....
BUERGER´S DISEASE CLINICAL:Claudication in feet and/or handssometimes centrallyradiated. Also, numbness and/or tinglingin...
KAWASAKI DISEASE
KAWASAKI DISEASE(Mucocutaneous lymph nodesyndrome). Is an arteritis that frequently affects coronaryarteries USUALLY in c...
KAWASAKI DISEASE Dx.:◦ Leukocytosis (PMN´s), thrombocytosis.◦ Some children have ANCA+ in plasmaand◦ Aprox.1/5 of patient...
Behçet’s Syndrome A systemic vasculitis of unknown causewith mucocutaneous and frequent ocularand musculoskeletal involve...
Behçet’s Syndrome: Clinicalfeatures Recurrent oral and/or genital aphthousulceration. Chronic relapsing uveitis leading ...
MICROSCOPICPOLYANGIITIS
MICROSCOPICPOLYANGIITIS It affects arterioles, capillaries andvenules (smaller than PAN) andthe leions are in the same st...
MICROSCOPIC POLYANGIITIS CLINICAL:◦ Necrotizing GN (90%)hematuria◦ Lungshemoptysis◦ GI tractabdominal pain◦ Jointsart...
MICROSCOPIC POLYANGIITIS About 70% of patients may have a clearrelation with a recent immunologicreaction to an Ag (drugs...
CHURG-STRAUSS SYNDROME Asthma is the cardinal clinical feature of CSS (8-10 yrs BEFORE symptoms of vasculitis) with 8-10y...
Wegener’sGranulomatosis
History of Wegener’s In 1936, Wegener first described a distinctsyndrome in three patients found to havenecrotizing granu...
Criteria for Classification Nasal or oral inflammation◦ Development of painful or painless oral ulcers or purulentor bloo...
Classic Symptoms Upper respiratory tract◦ sinuses◦ nose◦ ears◦ trachea Lungs Kidneys
EyeScleritisUveitisOrbitalpseudotumor/proptosis
Upper RespiratoryTractEarEar infections that are slow toresolve.Recurrent otitis media.Decrease in hearing.
Upper Respiratory TractNose Nasal crusting Frequentnosebleeds Erosion andperforation ofthe nasalseptum.◦ The bridge of ...
Upper Respiratory TractSinuses/Trachea Sinuses◦ Chronic sinusinflammation Trachea◦ subglottic stenosis
Lungs Nodules Alveolaropacities Pleuralopacities Diffuse hazyopacities (whichmay reflect alveolarhemorrhage)
Kidney Glomerulonephritis w/ associatedhematuria and proteinuria Can lead to renal failure if not treatedaggressively A...
RBC casts
Skin ―palpable purpura‖most common Raynaud‘sphenomenon—dueto inadequateblood flow tofingers and toes Ulcers
Miscellaneous Joints◦ Arthritis can occur, with joint swelling andpain Nerves◦ Peripheral nerve involvement leads tonumb...
Incidence of symptomsSymptom At OnsetTotal ENT 75% 95% Lung 50 85 Joints 30 70 Fever 25 50 Kidney 20 75 Cough 20 50...
PathogenesisANCA ANCAs may be not only markers forWegeners granulomatosis and relateddisorders, but they may also be acto...
Anti-Neutrophil CytoplasmicAntibody Immunofluorescencec-ANCA
Anti-Neutrophil CytoplasmicAntibody Immunofluorescence
Anti-Neutrophil CytoplasmicAntibody Immunofluorescencep-ANCA
Anti-Neutrophil CytoplasmicAntibody Immunofluorescence
Diagnosis Nasal or oral inflammation◦ Development of painful or painless oral ulcers orpurulent or bloody nasal discharge...
Management Vasculitides are often serious andsometimes fatal- require prompt recognition and therapy Treatment – helpful...
Management cont. Early deaths – due to active diseaseLate deaths – may be due to thecomplications of therapy The risk-ve...
Management cont. Glucocorticoides and/orimmunosuppressive therapy should beinstituted immediately in diseases whereirreve...
Management cont.Treatment of aggressive small vessel vasculitis1. Induction of remission2. Maintenance of remission3. Trea...
Management cont.In severe, life threatening disease(pulmonary haemorrhage, severecrescentic glomerulonephritis withcreatin...
Management cont.Maintenance therapy (to 18-24 months, longerif clinically indicated) Azathioprine, 2.0mg/kg/day (maximum2...
Management cont. Stop cyclophosphamide or azathioprine ifWBC < 4x109/L. Restart with a dose reduced by at least 25mgwhen...
Management cont. Most of other systemic vasculitides need atleast corticosteroidsUsual dose is 1mg/kg at the inductionGra...
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Vascul lecture

  1. 1. VASCULITIS. It means ―inflammation of the walls of thevessels‖ and can be associated to manydifferent clinical conditions.CLASSIFICATION.*Direct Infection.-Bacterial(Neisseria)-Rickettsial(spotted fever)-Spirochetal(Syphilis)-Fungal(aspergillosis)-Viral(herpes zoster)
  2. 2. VASCULITIS.CLASSIFICATION.(cont.) *Immunologic.A. Immune complex- mediated.-Infection-induced(Hepatitis B,C)-Henoch-Schonlein purpura-SLE, etc.-Drug-induced-Cryoglobulinemia(Ig, IgM)-Serum sickness
  3. 3. VASCULITIS.CLASSIFICATION.(cont.) B. ANCA-mediated.-Wegener granulomatosis-Microscopic polyangeitis-Churg-Strauss syndromeC. Direct Ab-induced-Goodpasture syndrome(anti-GBMAbs) -Kawasakidisease(anti-endoth.Ab)
  4. 4. VASCULITIS.CLASSIFICATION.(cont.) D. Cell-mediated.-Organ-allograft rejection-Inflammatory bowel disease-Paraneoplastic vasculitis*Unknown.-Giant.cell arteritis-Takayasu arteritis-Polyarteritis nodosa
  5. 5. Classification
  6. 6. CLASSIFICATION TREEVasculitisLarge Blood Vessel• Temporal Arteritis• Takayasu ArteritisMedium Blood Vessel• Polyarteritis Nodosa• Kawasaki’s DiseaseSmall Blood VesselANCAAssociated• Wegener’s Granulomatosis• Churg-Strauss Vasculitis• Microscopic Polyangiitis• Drug InducedNon-ANCAAssociatedImmune Complex• Hypersensitivity Vasculitis• Cryoglobulinemic Vasculitis• CTD related Vasculitis• Henoch Schonlein Purpura• Behcet’sMiscellaneous• Paraneoplastic Vasculitis• Inflammatory Bowel Disease
  7. 7. GIANT CELL(TEMPORAL)ARTERITIS
  8. 8. GIANT CELL (TEMPORAL)ARTERITIS. A vasculitis of unknown etiology occurringprimarily in the elderly. Other termscommonly used include temporal arteritis,cranial arteritis and granulomatous arteritis. Is the MOST common form of systemicvasculitis in adults, acute or chronic, oftengranulomatous inflammation of large/smallsize. It affects temporal arteries, but alsovertebral, ophtalmic (blindness) and aorta(aneurysm) Involved arteries have nodular thickeningreduction of lumenthrombosis.Granulomatous inflammation in inner half ofmedia with mononuclear cells+ giant cells.
  9. 9. GIANT CELL (TEMPORAL)ARTERITIS. CLINICAL: old patients with:◦ fever,◦ fatigue,◦ loss of weight,◦ with or w/o facial pain and headache.
  10. 10. GIANT CELL (TEMPORAL)ARTERITIS. Others, with more severe form andinvolvement of ophtalmic arterydiplopiaor blindness of abrupt onset.Dx.: significantly elevated ESR + arterialbiopsy.
  11. 11. TAKAYASU ARTERITIS.
  12. 12. TAKAYASU ARTERITIS. Takayasu’s arteritis is a chronicinflammatory disorder of unknownetiology primarily affecting the aortaand its major branches. Predominant in females below 40´sw/probable autoimmune mechanism, Arteritis may also affects pulmonaryarteries in ½ of cases as well ascoronary/renal arteries.
  13. 13. Aortic archarteriogram in apatient withTakayasu‘s arteritis.Smooth taperedstenosis of bilateralcommon carotidarteries (upperarrows) and of theright subclavianartery (lower arrow)can be seen. There ispoststenoticdilatation beyond theleft common carotidnarrowed segment.Total involvement isseen along the
  14. 14. TAKAYASU ARTERITIS.(cont.) MICROSCOPIC: mononuclear infiltration ofadventiciamid-layer with involvement ofvasa vasorum.
  15. 15. TAKAYASU ARTERITIS.(cont.) CLINICAL:◦ reduced brachial pulse,◦ difference in BP between R & L arm >10 mmHg,◦ Coldness + numbness of fingers,◦ bruising above a subclavia and/or aorta,◦ hypertension, visual defectsblindness.
  16. 16. POLYARTERITISNODOSA
  17. 17. POLYARTERITIS NODOSA Is a small/medium sized arteritis affectingmultiple organs (skin, peripheral nerves,gut, kidney and heart. Age of onset is from childhoodlateadulthood (average40´s) and it has been associatedw/Hepatitis B,C or both (most common ininjection drug abusers). Probably mediated by immune complexes(Igs + viral Ags)circulating anddeposited in inflammed vessels.
  18. 18. POLYARTERITIS NODOSA CLINICAL: onset is gradual (wksmos.)and nonspecific:◦ malaise,◦ fever,◦ weight loss,◦ abdominal pain,◦ melena,◦ myalgias,◦ muscular weakness
  19. 19. POLYARTERITIS NODOSA◦ diastolic pressure >90 mm Hg,◦ mononeuropathy or polyneuropathy◦ palpable purpura,◦ livedo reticularis,◦ digital gangrene or tender nodules
  20. 20. POLYARTERITIS NODOSA◦ Renal involvementhypertension.◦ In GI tract abdominal angina (hemorrhage,perforation).◦ In heart: myocarditis/myocardial infarction.◦ Eye: scleritis.
  21. 21. POLYARTERITIS NODOSA Dx.◦ Elevated BUN or creatinine◦ Proven hepatitis B/C virus infection◦ Angiographic signs ofaneuryms/vascularocclusion◦ Demonstration of granulocytes in smallor medium sized vessels (biopsy).
  22. 22. BUERGER´S DISEASE Also known as Thromboangiitis obliterans,is characterized by segmental thrombosis+ acute/chronic inflammation of mediumand small arteries MOSTLYtibial and radial arteries, and secondarilyinvolvement of veins and nerves of limbs. Apparently heavy cigarette-smokers areMOST frequently affected (endoth. cellshypersensitivity?)
  23. 23. BUERGER´S DISEASE Microscopically: acute + chronicinflammation in arterial walls +thrombosisorganization/recanalization. Also, thrombosis contains microabscesses+ granulomatous inflammationextensionto veins/nerves. Late complication: chronic ulceration oftoes or fingersgangrene.
  24. 24. BUERGER´S DISEASE CLINICAL:Claudication in feet and/or handssometimes centrallyradiated. Also, numbness and/or tinglingin limbs + Raynaud´s phenomenon.Skin ulcerations + gangrene of digits
  25. 25. KAWASAKI DISEASE
  26. 26. KAWASAKI DISEASE(Mucocutaneous lymph nodesyndrome). Is an arteritis that frequently affects coronaryarteries USUALLY in children/infants(about 80% are < 4 yrs old) Associated w/mucocutaneous lymph nodesyndrome of acute and self-limited evolution:◦ fever, conjunctivitis, sore throat,◦ generalized rash, redding of palms/soles,peeling of fingers/ toes and mucopurulentcervical lymphadenopathy. It is epidemic in Japan, Hawaii and US
  27. 27. KAWASAKI DISEASE Dx.:◦ Leukocytosis (PMN´s), thrombocytosis.◦ Some children have ANCA+ in plasmaand◦ Aprox.1/5 of patients involvement ofcoronary arteries/myocardium aneurysm/myocarditis that usuallyresolves spontaneously(mortality 2%).
  28. 28. Behçet’s Syndrome A systemic vasculitis of unknown causewith mucocutaneous and frequent ocularand musculoskeletal involvement. A marked geographic distribution ischaracterized by highest prevalence inTurkey, Iran and Japan.
  29. 29. Behçet’s Syndrome: Clinicalfeatures Recurrent oral and/or genital aphthousulceration. Chronic relapsing uveitis leading toblindness in 10% of all cases. A variety of skin manifestations, includingthe ‗pathergy‘ phenomenon. Musculoskeletal, neurologic, major arteryand vein involvement. An undulating course that generallyabates in intensity with the passage oftime.
  30. 30. MICROSCOPICPOLYANGIITIS
  31. 31. MICROSCOPICPOLYANGIITIS It affects arterioles, capillaries andvenules (smaller than PAN) andthe leions are in the same stage. Typically presents as ―palpable purpura‖(skin), but also with mucous membranes,lungs, brain, heart, GI tract, kidneys,muscle, PNS.
  32. 32. MICROSCOPIC POLYANGIITIS CLINICAL:◦ Necrotizing GN (90%)hematuria◦ Lungshemoptysis◦ GI tractabdominal pain◦ Jointsarthralgias◦ Weight loss(>70%)◦ Nerve damage(60%)numbness/tingling inlimbs.◦ Chronically: muscle wasting◦ Skin: purpura(>60%) in legs, feet, buttocks
  33. 33. MICROSCOPIC POLYANGIITIS About 70% of patients may have a clearrelation with a recent immunologicreaction to an Ag (drugs, microrganisms,tumor Ags,etc) having + pANCAS. MPA is quite similar histologically to PANmicroscopic changes EXCEPT thatmuscular/largearteries are usually spared. It reminds Wegener vasculitis BUT w/ogranulomatosis.
  34. 34. CHURG-STRAUSS SYNDROME Asthma is the cardinal clinical feature of CSS (8-10 yrs BEFORE symptoms of vasculitis) with 8-10yrs of evolutionrespiratory failure. Eosinophilia(>10% in CBC) Allergy Mono/polyneuropathy(ocular symptoms) Lung hemorrhage, pleural effusion, pulmonaryinfiltrates Changes in paranasal sinuses Eosinophilic granulomatosis vasculitis/perivasc. Abdominal cramps/heart failure(myocarditis)
  35. 35. Wegener’sGranulomatosis
  36. 36. History of Wegener’s In 1936, Wegener first described a distinctsyndrome in three patients found to havenecrotizing granulomas involving theupper and lower respiratory tract. In 1954, seven more patients described,resulting in definite criteria
  37. 37. Criteria for Classification Nasal or oral inflammation◦ Development of painful or painless oral ulcers or purulentor bloody nasal discharge Abnormal chest radiograph◦ Chest radiograph showing the presence of nodules, fixedinfiltrates, or cavities Abnormal Urinary sediment◦ Microhematuria (>5 red blood cells per high power field)or red cell casts in urine sediment Granulomatous inflammation onbiopsy◦ Histologic changes showing granulomatous inflammationwithin the wall of an artery or in the perivascular orextravascular area (artery or arteriole)* For purposes of classification, a patient shall be said to haveWegeners granulomatosis if at least 2 of these 4 criteria arepresent. The presence of any 2 or more criteria yields a sensitivityof 88.2% and a specificity of 92.0%
  38. 38. Classic Symptoms Upper respiratory tract◦ sinuses◦ nose◦ ears◦ trachea Lungs Kidneys
  39. 39. EyeScleritisUveitisOrbitalpseudotumor/proptosis
  40. 40. Upper RespiratoryTractEarEar infections that are slow toresolve.Recurrent otitis media.Decrease in hearing.
  41. 41. Upper Respiratory TractNose Nasal crusting Frequentnosebleeds Erosion andperforation ofthe nasalseptum.◦ The bridge of the nose cancollapse resulting in a―saddle–nose deformity‖.
  42. 42. Upper Respiratory TractSinuses/Trachea Sinuses◦ Chronic sinusinflammation Trachea◦ subglottic stenosis
  43. 43. Lungs Nodules Alveolaropacities Pleuralopacities Diffuse hazyopacities (whichmay reflect alveolarhemorrhage)
  44. 44. Kidney Glomerulonephritis w/ associatedhematuria and proteinuria Can lead to renal failure if not treatedaggressively Active urine sediment: red blood cell casts
  45. 45. RBC casts
  46. 46. Skin ―palpable purpura‖most common Raynaud‘sphenomenon—dueto inadequateblood flow tofingers and toes Ulcers
  47. 47. Miscellaneous Joints◦ Arthritis can occur, with joint swelling andpain Nerves◦ Peripheral nerve involvement leads tonumbness, tingling, shooting pains in theextremities, and sometimes to weakness ina foot, hand, arm, or leg Meninges Prostate gland Genito–urinary tract Constitutional symptoms of fatigue, low–grade fever, and weight loss
  48. 48. Incidence of symptomsSymptom At OnsetTotal ENT 75% 95% Lung 50 85 Joints 30 70 Fever 25 50 Kidney 20 75 Cough 20 50 Eye 15 50 Skin 15 45 Weight Loss 10 35 Nervous System (Central/Peripheral) 0 10/15One-third of patients may be without symptoms at onset ofdisease
  49. 49. PathogenesisANCA ANCAs may be not only markers forWegeners granulomatosis and relateddisorders, but they may also be actors inpathogenesis Neutrophils exposed to cytokines such asTNF, express PR3 & MPO (the targets forANCAs) Adding ANCAs to these cytokine-primedneutrophils causes them to generateoxygen radicals and release enzymescapable of damaging blood vessels.
  50. 50. Anti-Neutrophil CytoplasmicAntibody Immunofluorescencec-ANCA
  51. 51. Anti-Neutrophil CytoplasmicAntibody Immunofluorescence
  52. 52. Anti-Neutrophil CytoplasmicAntibody Immunofluorescencep-ANCA
  53. 53. Anti-Neutrophil CytoplasmicAntibody Immunofluorescence
  54. 54. Diagnosis Nasal or oral inflammation◦ Development of painful or painless oral ulcers orpurulent or bloody nasal discharge Abnormal chest radiograph◦ Chest radiograph showing the presence of nodules, fixedinfiltrates, or cavities Abnormal urinary sediment◦ Microhematuria (>5 red blood cells per high power field)or red cell casts in urine sediment Granulomatous inflammation onbiopsy◦ Histologic changes showing granulomatous inflammationwithin the wall of an artery or in the perivascular orextravascular area (artery or arteriole)Criteria for Classification
  55. 55. Management Vasculitides are often serious andsometimes fatal- require prompt recognition and therapy Treatment – helpful- particularly in the acute phase During maintenance therapy- adverse effects- superimposed infections
  56. 56. Management cont. Early deaths – due to active diseaseLate deaths – may be due to thecomplications of therapy The risk-versus-benefit ratio of anytherapeutic approach should be weighedcarefully
  57. 57. Management cont. Glucocorticoides and/orimmunosuppressive therapy should beinstituted immediately in diseases whereirreversible organ system dysfunction andhigh morbidity and mortality have beenclearly established Aggressive therapy should be avoided forvasculitic manifestations that rarelyresults in irreversible organ systemdysfunction and that usually do notrespond to such therapy
  58. 58. Management cont.Treatment of aggressive small vessel vasculitis1. Induction of remission2. Maintenance of remission3. Treatment of relapseInduction therapy (to 3 months after remission, usually 6months from diagnosis) Cyclophosphamide 2.0mg/kg/day (maximum200mg/day)Age > 60years, reduce dose by 25%> 75years, by 50% Prednisolone 1mg/kg/day (maximum 80mg/day)reduced weekly to 25mg/day by 8 weeks and thenmore slowly to 10mg/day by 6 months
  59. 59. Management cont.In severe, life threatening disease(pulmonary haemorrhage, severecrescentic glomerulonephritis withcreatinine > 500μmol/L) consider,◦ Plasma exchange, 7-10 treatments over14 days or◦ Three pulses of methylprednisolone,15mg/kg/day for 3 days
  60. 60. Management cont.Maintenance therapy (to 18-24 months, longerif clinically indicated) Azathioprine, 2.0mg/kg/day (maximum200mg/day)Age > 60yrs, reduce dose by 25%> 75yrs, by 50%Relapse therapy Major relapse: return to induction therapy Minor relapse: increase dose of corticosteroid
  61. 61. Management cont. Stop cyclophosphamide or azathioprine ifWBC < 4x109/L. Restart with a dose reduced by at least 25mgwhen WBC > 4x109/L on 2 consecutive tests.
  62. 62. Management cont. Most of other systemic vasculitides need atleast corticosteroidsUsual dose is 1mg/kg at the inductionGradual tapering during the remission

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