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Pediatric vasculitis dr inayat ullah

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Vasculitis in children pediatric rheumatology

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Pediatric vasculitis dr inayat ullah

  1. 1. VASCULITIS IN CHILDREN by DR. INAYAT ULLAH Shifa International Hospital Pediatric Department
  2. 2. VASCULITIS IN CHILDREN  Definition  Incidence  Pathogenesis  Classification  Pathology  Clinical features  Diagnosis  Treatment
  3. 3. VASCULITIS IN CHILDREN  Definition  Vasculitis is an inflammatory destructive process affecting arteries and veins.  Definition may include infiltration of the vessel wall by inflammatory cells without destruction.
  4. 4. VASCULITIS IN CHILDREN  Where is/are the lesions.  Site - Skin only e.g. Cutanous vasculitis - Internal organ only e.g. Isolated angiitis of CNS. - Both e.g. Systemic vasculitis  Vessel size - Small (Arterioles, Venules, Capillaries) - Medium (Main visceral arterioles + branches) - Large (Aorta and largest branches)  Lesion maybe - Focal (causing aneurysm) or - Segmental (Causing stenosis or occlusion)
  5. 5. VASCULITIS IN CHILDREN Pathogenesis  No single mechanism explain all vasculitidies.  Abnormalities noted in various vasculitides in: Polymorphs - Endothelial cells Lymphocytes - Humoral immunity Platelets  3 Mechanisms suggested: 1. Immune complex chemoattractant hypothesis(I.C.) 2. Adhesion molecular (A.M.) 3. Antibody – mediatedvascular injury
  6. 6. VASCULITIS IN CHILDREN Cont’d. Pathogenesis The Immune Complex Chemoattractant Hypothesis  Harlan 1987  I.C. deposits in the vessels at site of increased vascular permeability.  Trapping of I.C. + activation of complement complement breakdown product (CBP).  CBPs are chemoattractant to PMN leucocytes.  PMNs accumulate at the site of inflammation and release various enzymes and free radicals causing damage to vessel wall.  I.C. not demonstrated in all vasculitidies.  I.C. maybe found in tissue without inflammation.
  7. 7. VASCULITIS IN CHILDREN Cont’d.. Pathogenesis The adhesion molecules (AM) & inflammation  Aims are cell surface proteins found in surface of leukocytes and endothelium.  They mediate the interaction between the two cells.  3 classes of AM: 1. Selectins (L,P,E found in leukocytes, platelets and endothelial cell. - They slow the leukocytes in the vessels, and cause them to roll along the surface. 2. Integrins (many varieties) - They stop the leukocytes movement completely, allowing extravasation to the target tissue. 3. Members of immunoglobulin family.
  8. 8. VASCULITIS IN CHILDREN Pathogenesis e.g. - Good Pasture Syndrome (antiglomerular basement membrane antibody is responsible for G.N. & Pulmonary He - Antiendothelial cell antibodies (AEA) (demonstrated in several vasculitidies) - Van der Woude 1983 Anti-neutrophil Cytoplasmic antibodies as a useful diagnostic and prognostic marker for W.G. (C-ANCA = Antiprotinase 3 ab, P – ANCA= Antimyeloperoxidase)
  9. 9. VASCULITIS IN CHILDREN Classification  Overlap of signs & symptoms  Etiology is unknown  One etiology maybe associated with different vasculitidies. e.g. Hepatitis B was reported with – Cutaneous vasculitis Igower 1978) - Cryoglobulinaemia vasculitis (Levo 1977) - Glomerulonephritis (Combas 1971) - Polyarteritis (Gocke 1970)  Size of blood vessels involved (evolving diseases)  Classification based on pathology  No standard terms or definition  1993 Jennete et al reported the proposal of the Chapel Hill Consensur Conference (CHCC) on the nomenclature of systemic vasculitis
  10. 10. VASCULITIS IN CHILDREN Nomenclature of systemic vasculitis (CHCC 1993) Large vessel vasculitis Giant cell (temporal arteritis) Granulomatous arteritis of the aorta and its major branches with a predilection for the extracranial branches of the carotid artery. Often involved in the temporal artery. Usually occurs in patients older than 50 & often associated with polymyalgia rheumatica. Takayasu arteritis Granulomatous inflammation of the aorta and its major branches. Usually occurs in patients younger than 50.
  11. 11. VASCULITIS IN CHILDREN Cont’d. Nomenclature of systemic vasculitis (CHCC 1993) Medium size vessel vasculitis Polyarteritis nodosa Necrotizing inflammation of medium-sized or small arteries without glowmrulonephritis or vasculitis in arterioles, capillaries or venules. Kawasaki disease Arteries involving large, medium-sized and small arteries and associated with mucocutaneous lymph node syndrome. Coronary artery are often involved. Aorta and veins may be involved. Usually occurs in children.
  12. 12. VASCULITIS IN CHILDREN Cont’d. Nomenclature of systemic vasculitis (CHCC 1993) Small vessel vasculitis Weneger’s granulomatous Granulomatous inflammation involving the respiratory tract, and necrotizing vasculitis affecting small to medium-sized vessels (e.g. capillaries, venules, arterioles, and arteries). Necrotizing glomerulonephritis is common. Churg-Strauss syndrome Eosinophil-rich and granulomatous inflammation involving the respiratory tract, and necrotizing vasculitis affecting small to medium-sized vessels, and associated with asthma and eosinophilia. Microscopic polyangitis Necrotizing vasculitis, with few or no immune deposits, affecting small vessels (I.e. capillaries, venules, or arterioles). Necrotizing arteritis involving small and medium-sized arteries may be present. Necrotizing glomerulonephritis is very common.
  13. 13. VASCULITIS IN CHILDREN Cont’d. Nomenclature of systemic vasculitis (CHCC 1993) Small vessel vasculitis Henoch-Schonlein purpura Vasculitis wth IgA-dominant immune deposits, affecting small vessels (I.e. capillaries, venules, or arterioles). Typically involves skin, gut and glomeruli, and is associated with arthralgias or arthritis. Essential cryoglobulinemic vasculitis Vasculitis with cryoglobulin immune deposits, affecting small vessel (I.e. capillaries, venules, orarterioles), and associated with cryoglobulins in serum. Skin and glomeruli are often involved. Cutaneous leukocytoclastic angiitis Isolated cutaneous leukocytoclastic angiitis without systemic
  14. 14. VASCULITIS IN CHILDREN Pathology  Vasculitis induced injury to blood vessels may lead to: - Increased vascular permeability - Vessel weakening that cause aneurysm or hemorrhage. - Intimal proliferation and thrombosis which result in obstruction and local ischemia.  Cellular infiltrate (polymorphs, lymphocytes or eosinophils)  Vessel wall may show - Necrotizing vasculitis as in PAN. - Granulomatous vasculitis as in WG. - Perivascular cuffing as in embolic lesions.
  15. 15. VASCULITIS IN CHILDREN Pathology of Some Vasculitides POLYARTERITIS Polyarteritis nodosa (Syndrome) Vessels affected Characteristic Pathology Medium & small muscular Focal segmental arteries and sometimes arteries & (often near bifurcations) Fibrinoid sometimes arterioles necrosis, GI, renal, microaneursym; lesions at various necrosis, GI, renal microaneursym; Lesions at various stages of evolution. Kawasaki disease (Syndrome) Vessels affected Characteristic Pathology Coronary & other muscular Thrombosis, fibrosis, arteries aneurysm especially coronaries
  16. 16. VASCULITIS IN CHILDREN Cont’d. Pathology of Some Vasculitides LEUKOCYTOCLASTIC VASCULITIS Henoch-Schonlein Purpura (Syndrome) Vessels affected Characteristic Pathology Arterioles & venules Leukocytoclasis, mixed cell, eosinophils Often small arteries & veins eosinophil; IgA deposits in affected vessels (GI tract) Hypersensitivity angiitis Vessels affected Characteristic Pathology Arterioles and venules Leukocytoclasis or lymphocytic, varying eosinophils occasionally granulomatous; widespread lesions at same stage of evolution
  17. 17. VASCULITIS IN CHILDREN Cont’d. Pathology of Some Vasculitides GRANULOMATOUS VASCULITIS Allergic granulomatosis (Syndrome) Vessels affected Characteristic Pathology Small arteries and veins, Necrotizing extravascular granulomata; lung often arterioles and venules involvement; eosinophilia Weneger’s granulomatosis Vessels affected Characteristic Pathology Small arteries and veins, Upper and lower respiratory tract, necrotizing occasionally larger vessels granulomata, glomerulonephritis
  18. 18. VASCULITIS IN CHILDREN Cont’d. Pathology of Some Vasculitides GIANT CELL ARTERITIS Takayasu’s Arteritis (Syndrome) Vessels affected Characteristic Pathology Muscular and elastic arterities Granulomatous inflammation, giant cells, aortic arch and branches, aneurysms, dissection Temporal Arteritis (Syndrome) Vessels affected Characteristic Pathology Medium and large arteries Granulomatous inflammation, giant cell arteritis, carotid and branches
  19. 19. VASCULITIS IN CHILDREN Demographic Associations of the Vasculitides Age group Male-to- Female Ethnic origin Type of vasculitis Child M = F Any Henoch-Schonlein purpura Young adult M > F M = F F > M Asian > white > others Middle Eastern > others Asian >> others Kawasaki disease Behcet’s disease Takayasu’s arteritis Middle age M > F Any Wegeners granulomatosis, polyarteritis, /churg-Strauss vasculitis Elderly F > M Caucasian >> others Giant cell arteritis
  20. 20. VASCULITIS IN CHILDREN Common Presentations of the Vasculitic Syndromes Syndrome Presentation Constitutional Fever, weight loss, weakness, fatigue Musculoskeletal Arthralgia, myalgia, arthritis Cutaneous Palpable purpura, nodules, urticaria, livedo reticularis, superficial phlebitis, ischemic lesions Neurologic Headache, stroke, mononeuritis multiplex
  21. 21. VASCULITIS IN CHILDREN Cont’d Common Presentations of the Vasculitic Syndromes Syndrome Presentation Head and neck Sinusitis, chondritis,otitis, iritis Renal Nephritis, infarction, hypertension Pulmonary Hemorrhage, cavities, nodules, infiltrates Laboratory Anemia, elevated ESR, abnormal liver function tests, hematuria
  22. 22. VASCULITIS IN CHILDREN Approximate frequency of organ-system manifestations in several forms of small-vessel vasculitis Organ System Henoch- Schonlei n Purpura Cryoglo- bulinemic Vasculitis Microscopic Polyangitis Wegener’ s Granulo- matosis Churg- strauss Syndrom e percent Cutaneous 90 90 40 40 60 Renal 50 55 90 80 45 Pulmonary <5 <5 50 90 70 Ear, nose and throat <5 <5 35 90 50 Musculoskeletal 75 70 60 60 50 Neurologic 10 40 30 50 70 Gastrointestinal 60 30 50 50 50
  23. 23. VASCULITIS IN CHILDREN ACR 1990 criteria for the classification of Henoch- Schonlein purpura Criterion Definition 1) Palpable purpura Slightly raised “palpable” haemorrhagic skin lesions, 2) Age < 20 years 3) Bowel angina Diffuse abdominal pain, bowel ischaemia or bloody diarrhea 4) Wall granulocytes on biopsy Granulocytes in the walls of arterioles or venules
  24. 24. VASCULITIS IN CHILDREN Clinical characteristics of Henoch-Schonlein purpura Clinical Characteristic (%) Winter n = 43 Emery et al. n = 43 S. A. Al Rasheed et al n = 40 Purpura 97 100 100 Arthralgia/arthritis 65 79 58 Abdominal pain 100 63 58 Gastrointestinal bleeding 26 - 23 Nephritis - 37 38 Subcutaneous edema - 63 - Encephalopathy - - - Orchitis - - -
  25. 25. VASCULITIS IN CHILDREN Kawasaki Disease: frequency and clinical diagnostic criteria 1) Fever (100%) Duration of 5 days or more 2) Conjunctivitis Bilateral, bulbar, nonsuppurative 3) Lymph node enlargement (70%) Cervical, nonpurulent, >1.5 cm 4) Rash (80%) Polymorphous, no vesicles or crusts 5) Changes of lips or mucosa (90%) Dry, red, vertically fissured lips “Strawberry” tongue Diffuse erythema or oropharynx 6) Changes of extremities Erythema of palms or soles Indurative edema of hands and feet Desquamation of tips of fingers
  26. 26. VASCULITIS IN CHILDREN Other Clinical Findings in Kawasaki Disease Relatively common abnormalities:  Arthralgia / arthritis  Meningitis  Pneumonitis  Anterior uveitis with photophobia  Gastroenteritis  Meatitis and dysuria  Otitis
  27. 27. VASCULITIS IN CHILDREN Cont’d. Other Clinical Findings in Kawasaki Disease Relatively uncommon abnormalities:  Hydrops of the gallbladder  Gastrointestinal ischemia  Jaundice  Central nervous system disease Febrile convulsions Encephalopathy or ataxia  Cardiac disease Coronary thrombosis or aneurysms Cardiac tamponade Cardiac failure Myocarditis Pericarditis  Petechial rash
  28. 28. VASCULITIS IN CHILDREN ACR 1990 criteria for the classification of hypersensitivity vasculitis Criterion Definition 1) Age at onset > 16 years Development of symptoms after age 16 years 2) Medication at disease onset Medication that may be a precipitating factor 3) Palpable purpura Over one or more areas of the skin 4) Maculopapular rash Over one or more areas of the skin 5) Biopsy including arteriole and venule Granulocytes in a perivascular or extravascular location
  29. 29. VASCULITIS IN CHILDREN ACR 1990 criteria for the classification of polyarteritis nodosa Criterion Definition 1. Weight loss > 4 kg Not due to dieting or other factor 2. Livedo reticularis Mottled reticular pattern over the skin 3. Testicular pain or tenderness Not due to infection, trauma or other causes 4. Myalgias, weakness, or leg tenderness Diffuse myalgias (excluding shoulder and hip girldle) 5. Mononeuropathy or polyneuropathy 6. Diastolic BP > 90 mmHg
  30. 30. VASCULITIS IN CHILDREN Criterion Definition 7. Elevated blood urea or creatinine Elevation of BUN > 40 mg/dl or creatinine > 1.5 mg/dl, not due to dehydration or obstruction 8. Hepatitis B virus Presence of hepatitis B surface antigen or antibody in serum 9. Arteriographic abnormality Arteriogram showing aneurysms or occlusions of the visceral arteries, not due to other non-inflammatory causes 10. Biopsy of small or medium sized artery containing PMN Histologic changes showing the presence of granulocytes and mononuclear leukocytes in the artery wall Cont’d. ACR 1990 criteria for the classification of polyarteritis nodosa Three or more criteria yields a sensitivity of 82.2%and a specificity of 86.6%
  31. 31. VASCULITIS IN CHILDREN Criterion Definition 1. Age at disease onset < 40 years 2. Claudication of extremities Development of fatigue and discomfort in muscles of extremity 3. Decreased brachial artery pulse Decreased pulsation of one or both brachial arteries. 4. BP difference > 10 mmHg Difference of > 10mmHg in systolic blood pressure between arms 5. Bruit over subclavian arteries or aorta Bruit over subclavian arteries or abdominal aorta 6. Arteriogram abnormality Arteriographic narrowing or occlusion of the entire aorta, its proximal branches or large arteries. ACR 1990 criteria for the classification of Takayasu arteritis Three or more criteria yields a sensitivity of 90.5% and a specificity of 97.8%
  32. 32. VASCULITIS IN CHILDREN Criterion Definition 1. Nasal or oral inflammation Painful or painless oral ulcers or purulent or bloody nasal discharge 2. Abnormal chest radiograph Nodules, fixed infiltrates or cavities 3. Urinary sediment Microhaematuria or red cell casts 4. Granulomatous inflammation on biopsy Granulomatous inflammation within the wall of an artery or in the perivascular or extravascular area ACR 1990 criteria for the classification of Wergener’s granulomatosis Two or more criteria yields a sensitivity of 88.2% and a specificity of 92.0%
  33. 33. VASCULITIS IN CHILDREN Criterion Definition 1. Asthma History of wheezing or diffuse high pitched rales on expiration 2. Eosinophilia Eosinophilia > 10% on white blood cell differential count 3. History of allergy * History of seasonal allergy or other documented allergy 4. Mononeuropathy or polyneuropathy (i.e. glove/stocking distribution) attributable to a systemic vasculitis 5. Pulmonary infiltrates, non- fixed Migratory or transitory pulmonary infiltrates on radiographs 6. Paranasal sinus abnormality radiographic opacification of the paranasal sinuses or history 7. Extravascular eosinophils Biopsy showing accumulations of eosinophils in extravascular areas ACR 1990 criteria for the classification of Churg-Strauss syndrome
  34. 34. VASCULITIS IN CHILDREN D. ANGIOGRAPHY:  Large and medium vessels vasculitis  Do selected angiogram according to clinical findings  False positive results - Drug induced vasospasm - Fibromuscular dysplasia  Look for narrowing, obstruction or aneurysmal dilatation
  35. 35. VASCULITIS IN CHILDREN Con’t. Laboratory studies in vasculitis E. Biopsy:  Avoid blind biopsy  Lesions may be segmental  Skin changes do it prove systemic or visceral involvement  Pathological findings must be interpreted with clinical picture.
  36. 36. VASCULITIS IN CHILDREN Disease Primary treatment  Vasculitis of small vessels  Hypersensitivity vasculitis Often self-limited if offending agent is removed, steroids in severe cases.  Henoch-Schonlein purpura Often no treatment. Steroid for some gastrointestinal and steroids cyclophosphamide for renal involvements.  Cryoglobulinemia Corticosteroids; plasmapheresis for severe involvement. Antiviral therapy for hepatitis C. Treatment of the major systemic vasculitidies
  37. 37. VASCULITIS IN CHILDREN Disease Primary treatment Vasculitis of small and medium-sized vessles  Polyarteritis nodosa Steroids + cyclophosphamide  Microscopic polyangiitis Steroids + cyclophosphamide  Churg-Strauss vasculitis Steroids + cyclophosphamide  Wegener’s granulomatosis Steroids + cyclophosphamide or steroids + methotrexate for less severe involvement + septrin  Kawasaki disease High dose aspirin and intravenous immune globulin, ? steroids Cont’d. Treatment of the major systemic vasculitidies
  38. 38. VASCULITIS IN CHILDREN Disease Primary treatment Vasculitis of large vessels Giant cell, or temporal, arteritis High-dose steroids Takayasu’s arteritis High-dose steroids Cont’d. Treatment of the major systemic vasculitidies
  39. 39. VASCULITIS IN CHILDREN CONCLUSION:  There is a wide spectrum of vasculitis affecting children.  Although we know some etiological agents, still we are behind in majority.  The names and definitions proposed by CHCC will be helpful if adopted by different centers.  Classification still does not cover the whole spectrum of vasculitis  New discovery on etiopathogenesis still awaited.  Steroids and cytotoxic drugs improved the prognosis.
  40. 40. VASCULITIS IN CHILDREN General Approach to Diagnosis: 1. Suspect the diagnosis. 2. Exclude other processes. 3. Determine the organs and vessels involved. 4. Attempt to reach specific type of vasculitis on basis of clinical features and helpful laboratory tests.
  41. 41. VASCULITIS IN CHILDREN Conditions that may mimic systemic vasculitis.  Drug exposure Coccaine Amphethamine Penicillins, supha drugs Anticonvulsants Hydralazine, Propylthiouracil  Infections  Malignant disease  Atrial myxoma  Cholesterol emboli  Antiphospholipid antibody syndrome  Other connective tissue disorders
  42. 42. VASCULITIS IN CHILDREN Infection-related vasculitis  Viral HIV Hepatitis B,C EBV, herpes zoster Parvovirus B19, CMV  Bacterial/fungal SBE  Mycobacterial Tuberculosis  Spirochetal Syphilis  Rickettsial Rocky Mountain spotted fever
  43. 43. VASCULITIS IN CHILDREN Clues for Identifying the Type of Vessels Involvement in Vasculitis Clinical feature Affected vessels Associated vasculitis CUTANEOUS Palpable purpura Postcapillary venules Any vasculitis except giant cell Skin ulcers Arterioles to small Polyarteritis, Churg-Strauss arteries hypersensitivityvasculitis, WG Gangrene in a Small to medium- Polyarteritis, Churg- Strauss Extremity sized arteries WG
  44. 44. VASCULITIS IN CHILDREN Clues for Identifying the Type of Vessels Involvement in Vasculitis Clinical feature Affected vessels Associated vasculitis G.I. TRACT Abdominal pain Small to medium-sized HSP, PAN arteries Churg-Strauss Gastrointestinal Capillaries to medium- HSP, PAN Bleeding sized arteries Churg-Strauss
  45. 45. VASCULITIS IN CHILDREN Clues for Identifying the Type of Vessels Involvement in Vasculitis Clinical feature Affected vessels Associated vasculitis RENAL Glomerulo- Capillaries Microscopic polyangiitis nephritis HSP, WG, cryoglobulinemia Churg-Strauss Ischemic renal Small to medium- Polyarteritis, TA, less Failure sized arteries commonly , Churg- Strauss, WG
  46. 46. VASCULITIS IN CHILDREN Clues for Identifying the Type of Vessels Involvement in Vasculitis Clinical feature Affected vessels Associated vasculitis PULMONARY Pulmonary Capillaries; less Microscopic polyangiitis, WG Hemorrhage commonly small to medium-sized arteries Pulmonary Small to medium- Churg-Strauss, WG, Infiltrates or sized arteries Microscopic polyangiitis cavities
  47. 47. VASCULITIS IN CHILDREN Clues for Identifying the Type of Vessels Involvement in Vasculitis Clinical feature Affected vessels Associated vasculitis NEUROLOGIC Peripheral Small arteries Polyarteritis, Churg- Strauss neuropathy WG, cryoglobulinenia Stroke Small, medium- Giant cell arteritis, SLE sized or large arteries
  48. 48. VASCULITIS IN CHILDREN Laboratory studies in Vasculitis A. Nonspecific - Complete blood count - Erythrocyte sedimentation rate (ESR) - C-reactive protein B. Organ involvement - Creatinine - Urinalysis – Liver enzymes - Electrocardiogram - Echocardiogram - Creatinine phosphokinase - Chest roentgenogram - Sinus roentgenograms - Electromyography/nerve conduction studies D. Angiography E. Biopsy
  49. 49. VASCULITIS IN CHILDREN Laboratory studies in Vasculitis C. Etiology/pathogenesis  HIV Hepatitis B & C antibodies  Antinuclear antibody, DNA binding, extractable nuclear antigen  Cryoglobulins  Serum complement  Rheumatoid factor  Blood cultures  Antiglomerular basement membrane antibodies (anti- GBM-Ab)  Antineutrophil cytoplasmic autoantibodies (ANCA)

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