1. VASCULITIS IN CHILDREN by: DR. ABDULLAH S. AL MAZYAD King Saud University Pediatric Department

2. VASCULITIS IN CHILDREN Definition Definition Incidence Incidence Pathogenesis Pathogenesis Classification Classification Pathology Pathology Clinical features Clinical features Diagnosis Diagnosis Treatment Treatment

3. VASCULITIS IN CHILDREN Definition Definition Vasculitis is an inflammatory destructive process affecting arteries and veins. Vasculitis is an inflammatory destructive process affecting arteries and veins. Definition may include infiltration of the vessel wall by inflammatory cells without destruction. Definition may include infiltration of the vessel wall by inflammatory cells without destruction.

4. VASCULITIS IN CHILDREN Where is/are the lesions. Where is/are the lesions. Site - Skin onlye.g. Cutanous vasculitis Site - Skin onlye.g. Cutanous vasculitis - Internal organ onlye.g. Isolated angiitis of CNS. - Internal organ onlye.g. Isolated angiitis of CNS. - Bothe.g. Systemic vasculitis - Bothe.g. Systemic vasculitis Vessel size - Small (Arterioles, Venules, Capillaries) Vessel size - Small (Arterioles, Venules, Capillaries) - Medium (Main visceral arterioles + branches) - Medium (Main visceral arterioles + branches) - Large (Aorta and largest branches) - Large (Aorta and largest branches) Lesion maybe - Focal (causing aneurysm) Lesion maybe - Focal (causing aneurysm) or - Segmental (Causing stenosis or occlusion) or - Segmental (Causing stenosis or occlusion)

5. VASCULITIS IN CHILDREN From the Pediatric Rheumatology Data Base group, 4,348 patients seen in 1992 at 26 centres in USA. Only 174 (4%) had some form of vasculitis. From the Pediatric Rheumatology Data Base group, 4,348 patients seen in 1992 at 26 centres in USA. Only 174 (4%) had some form of vasculitis. Underestimated 1 st – Only academic centre involved. Underestimated 1 st – Only academic centre involved. 2 nd – Kawasaki diseases Henoch- Schonlein purpura not referred to rheumatology clinics. 2 nd – Kawasaki diseases Henoch- Schonlein purpura not referred to rheumatology clinics. During 1970’s in UK the annual incidence of systemic vasculitis is 10 per million. During 1970’s in UK the annual incidence of systemic vasculitis is 10 per million. In Norwich (1988 – 1994) the annual incidence is 39 per million. In Norwich (1988 – 1994) the annual incidence is 39 per million.

6. VASCULITIS IN CHILDREN Pathogenesis No single mechanism explain all vasculitidies. No single mechanism explain all vasculitidies. Abnormalities noted in various vasculitides in: Abnormalities noted in various vasculitides in: Polymorphs- Endothelial cells Lymphocytes- Humoral immunity Platelets 3 Mechanisms suggested: 3 Mechanisms suggested: 1. Immune complex chemoattractant hypothesis(I.C.) 2. Adhesion molecular (A.M.) 3. Antibody – mediatedvascular injury

7. VASCULITIS IN CHILDREN Cont’d.Pathogenesis The Immune Complex Chemoattractant Hypothesis Harlan 1987 Harlan 1987 I.C. deposits in the vessels at site of increased vascular permeability. I.C. deposits in the vessels at site of increased vascular permeability. Trapping of I.C. + activation of complement complement breakdown product (CBP). Trapping of I.C. + activation of complement complement breakdown product (CBP). CBPs are chemoattractant to PMN leucocytes. 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. 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. not demonstrated in all vasculitidies. I.C. maybe found in tissue without inflammation. I.C. maybe found in tissue without inflammation.

8. VASCULITIS IN CHILDREN Cont’d..Pathogenesis The adhesion molecules (AM) & inflammation Aims are cell surface proteins found in surface of leukocytes and endothelium. Aims are cell surface proteins found in surface of leukocytes and endothelium. They mediate the interaction between the two cells. They mediate the interaction between the two cells. 3 classes of AM: 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. the surface. 2.Integrins (many varieties) - They stop the leukocytes movement completely, allowing extravasation to the target tissue. extravasation to the target tissue. 3.Members of immunoglobulin family. - They act as attachment sites for integrins on endothelial cells.

9. VASCULITIS IN CHILDREN Pathogenesis e.g. - Good Pasture Syndrome (antiglomerular basement membrane antibody is responsible for G.N. & Pulmonary Hge.) -Leung 1986 -Leung 1986 Serum of Kawasaki patients causes significant complement mediated kindling of IL-1 or (TNF) stimulated endothelial cells. - Antiendothelial cell antibodies (AEA) (demonstrated in several vasculitidies) - Antiendothelial cell antibodies (AEA) (demonstrated in several vasculitidies) - Van der Woude 1983 - 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)

10. VASCULITIS IN CHILDREN Classification Overlap of signs & symptoms Overlap of signs & symptoms Etiology is unknown Etiology is unknown One etiology maybe associated with different vasculitidies. 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) Size of blood vessels involved (evolving diseases) Classification based on pathology Classification based on pathology No standard terms or definition 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 1993 Jennete et al reported the proposal of the Chapel Hill Consensur Conference (CHCC) on the nomenclature of systemic vasculitis

11. 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.

12. 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.

13. 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. Pulmonary capillaries often occurs.

14. 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 vasculitis or glomerulonephritis

15. VASCULITIS IN CHILDREN Classification of vasculitis First attempt at classification by Zeek 1952. First attempt at classification by Zeek 1952. She proposed the term necrotizing angiitis to include: She proposed the term necrotizing angiitis to include: 1. Hypersensitiviy angiitis 2. Allegic granulomatous angiitis 3. Rheumatic arteritis 4. Periarteritis nodosa 5. Temporal arteritis Weneger’s granulomatosis and Takayasu’s were not included. Weneger’s granulomatosis and Takayasu’s were not included. 1952 – 1994, nine different classified reported. 1952 – 1994, nine different classified reported.

16. VASCULITIS IN CHILDREN Cont’d. Revised, PRACTICAL CLASSIFICATION OF VASCULITIS from Lie JT 1994 Primary vasculitides Affecting large, medium and small blood vessels. Affecting large, medium and small blood vessels. o Takayasu arteritis o Giant cell (temporal) arteritis o Isolated angiitis of the central nervous system Affecting predominantly medium and small blood vessels. Affecting predominantly medium and small blood vessels. o Polyarteritis nodosa o Churg-Strauss syndrome o Weneger’s granulomatous

17. VASCULITIS IN CHILDREN Cont’d. Revised, PRACTICAL CLASSIFICATION OF VASCULITIS from Lie JT 1994 Primary vasculitides Affecting predominantly small blood vessels Affecting predominantly small blood vessels o Microscopic polyangiitis o Schonlein-Henoch Syndrome o Cutaneous leukocyclastic angiitis Miscelleneous conditions Miscelleneous conditions o Buerger’s disease o Cogan syndrome o Kawasaki Disease

18. VASCULITIS IN CHILDREN Classification of system in vasculitis from Scot and Watts 1994. Dominant vessel involved Large arteries Large arteries Primary Secondary Primary Secondary Giant cell arteritisAortitis asscociated w/ RA Takayasu’s arteritisInfection (e.g. syphilis) Isolated CNS angiitis Medium Arteries Medium Arteries Primary Secondary Primary Secondary Classical PANInfection (e.g. Hepatitis B) Kawasaki disease

19. VASCULITIS IN CHILDREN Cont’d. Classification of system in vasculitis from Scot and Watts 1994. Dominant vessel involved Small vessels and medium arteries Small vessels and medium arteries Primary Secondary Primary Secondary Weneger’s granulomatosis Vasculitis 20 to RA, SLE Churg-Strauss syndrome Sjogren syndrome Microscopic polyangiitis Drugs Small vessels (leukocytoclastic) Small vessels (leukocytoclastic) Primary Secondary Primary Secondary Henoch Schonlein purpura Drugs Essential mixed cryoglobulenemia Infection (e.g. Hepatitis B, C) Cutaneous leukocytoclastic angiitis angiitis

20. 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.

21. VASCULITIS IN CHILDREN Pathology of Some Vasculitides POLYARTERITIS Polyarteritis nodosa (Syndrome) Vessels affectedCharacteristic Pathology Vessels affectedCharacteristic Pathology Medium & small muscular Focal segmental Medium & small muscular Focal segmental arteries and sometimes arteries & (often near bifurcations) Fibrinoid 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. sometimes arterioles necrosis, GI, renal, microaneursym; lesions at various necrosis, GI, renal microaneursym; Lesions at various stages of evolution. Kawasaki disease (Syndrome) Vessels affectedCharacteristic Pathology Vessels affectedCharacteristic Pathology Coronary & other muscularThrombosis, fibrosis, Coronary & other muscularThrombosis, fibrosis, arteriesaneurysm especially coronaries arteriesaneurysm especially coronaries

22. VASCULITIS IN CHILDREN Cont’d. Revised, PRACTICAL CLASSIFICATION OF VASCULITIS from Lie JT 1994 Secondary vasculitides Infection-related vasculitis Infection-related vasculitis Vasculitis secondary to connective tissue disease Vasculitis secondary to connective tissue disease Drug hypersensitivity-related vasculitis Drug hypersensitivity-related vasculitis Vasculitis secondary to mixed essential cryoglobulinemia Vasculitis secondary to mixed essential cryoglobulinemia Malignancy-related vasculitis Malignancy-related vasculitis Hypocomplementemic urticaria vasculitis Hypocomplementemic urticaria vasculitis Postorgan transplant vasculitis Postorgan transplant vasculitis Pseudovasculitic syndrome (myxoma, endocarditis) Pseudovasculitic syndrome (myxoma, endocarditis)

23. VASCULITIS IN CHILDREN Cont’d. Pathology of Some Vasculitides LEUKOCYTOCLASTIC VASCULITIS Henoch-Schonlein Purpura (Syndrome) Vessels affectedCharacteristic Pathology Vessels affectedCharacteristic Pathology Arterioles & venulesLeukocytoclasis, mixed cell, eosinophils Often small arteries & veinseosinophil; IgA deposits in affected vessels (GI tract) Hypersensitivity angiitis Vessels affectedCharacteristic Pathology Arterioles and venules Leukocytoclasis or lymphocytic, varying eosinophils occasionally granulomatous; widespread lesions at same stage of evolution occasionally granulomatous; widespread lesions at same stage of evolution

24. VASCULITIS IN CHILDREN Cont’d. Pathology of Some Vasculitides GRANULOMATOUS VASCULITIS Allergic granulomatosis (Syndrome) Vessels affectedCharacteristic Pathology Small arteries and veins, Necrotizing extravascular granulomata; lung often arterioles and venulesinvolvement; eosinophilia Weneger’s granulomatosis Vessels affectedCharacteristic Pathology Small arteries and veins, Upper and lower respiratory tract, necrotizing occasionally larger vesselsgranulomata, glomerulonephritis

25. VASCULITIS IN CHILDREN Cont’d. Pathology of Some Vasculitides GIANT CELL ARTERITIS Takayasu’s Arteritis (Syndrome) Vessels affectedCharacteristic Pathology Muscular and elastic arteritiesGranulomatous inflammation, giant cells, aortic arch and branches, aneurysms, dissection Temporal Arteritis (Syndrome) Vessels affectedCharacteristic Pathology Medium and large arteriesGranulomatous inflammation, giant cell arteritis, carotid and branches

26. 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 > F 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

27. VASCULITIS IN CHILDREN Common Presentations of the Vasculitic Syndromes SyndromePresentation 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

28. VASCULITIS IN CHILDREN Cont’d Common Presentations of the Vasculitic Syndromes SyndromePresentation 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

29. 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 Cutaneous9090404060 Renal5055908045 Pulmonary<5<5509070 Ear, nose and throat <5<5359050 Musculoskeletal7570606050 Neurologic1040305070 Gastrointestinal6030505050

30. VASCULITIS IN CHILDREN ACR 1990 criteria for the classification of Henoch- Schonlein purpura CriterionDefinition 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

31. 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 Purpura97100100 Arthralgia/arthritis657958 Abdominal pain 1006358 Gastrointestinal bleeding 26-23 Nephritis-3738 Subcutaneous edema -63- Encephalopathy--- Orchitis---

32. 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

33. VASCULITIS IN CHILDREN Other Clinical Findings in Kawasaki Disease Relatively common abnormalities: Arthralgia / arthritis Arthralgia / arthritis Meningitis Meningitis Pneumonitis Pneumonitis Anterior uveitis with photophobia Anterior uveitis with photophobia Gastroenteritis Gastroenteritis Meatitis and dysuria Meatitis and dysuria Otitis Otitis

34. VASCULITIS IN CHILDREN Cont’d. Other Clinical Findings in Kawasaki Disease Other Clinical Findings in Kawasaki Disease Relatively uncommon abnormalities: Hydrops of the gallbladder Hydrops of the gallbladder Gastrointestinal ischemia Gastrointestinal ischemia Jaundice Jaundice Central nervous system disease Central nervous system disease Febrile convulsions Encephalopathy or ataxia Cardiac disease Cardiac disease Coronary thrombosis or aneurysms Cardiac tamponade Cardiac failure MyocarditisPericarditis Petechial rash Petechial rash

35. VASCULITIS IN CHILDREN ACR 1990 criteria for the classification of hypersensitivity vasculitis CriterionDefinition 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 Three or more criteria yields a sensitivity of 71% and a specificity of 83.9%

36. VASCULITIS IN CHILDREN ACR 1990 criteria for the classification of polyarteritis nodosa CriterionDefinition 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

37. VASCULITIS IN CHILDREN Cont’d. ACR 1990 criteria for the classification of polyarteritis nodosa CriterionDefinition 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 Three or more criteria yields a sensitivity of 82.2%and a specificity of 86.6%

38. VASCULITIS IN CHILDREN ACR 1990 criteria for the classification of Takayasu arteritis CriterionDefinition 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. Three or more criteria yields a sensitivity of 90.5% and a specificity of 97.8%

39. VASCULITIS IN CHILDREN ACR 1990 criteria for the classification of Wergener’s granulomatosis CriterionDefinition 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 Two or more criteria yields a sensitivity of 88.2% and a specificity of 92.0%

40. VASCULITIS IN CHILDREN ACR 1990 criteria for the classification of Churg-Strauss syndrome CriterionDefinition 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

41. VASCULITIS IN CHILDREN D. ANGIOGRAPHY: Large and medium vessels vasculitis Large and medium vessels vasculitis Do selected angiogram according to clinical findings Do selected angiogram according to clinical findings False positive results False positive results -Drug induced vasospasm -Fibromuscular dysplesia Look for narrowing, obstruction or aneurysmal dilatation Look for narrowing, obstruction or aneurysmal dilatation

42. VASCULITIS IN CHILDREN Con’t. Laboratory studies in vasculitis E. Biopsy: Avoid blind biopsy Avoid blind biopsy Lesions may be segmental Lesions may be segmental Skin changes do it prove systemic or visceral involvement Skin changes do it prove systemic or visceral involvement Pathological findings must be interpreted with clinical picture. Pathological findings must be interpreted with clinical picture.

43. VASCULITIS IN CHILDREN Treatment of the major systemic vasculitidies Disease Primary treatment Vasculitis of small vessels Vasculitis of small vessels Hypersensitivity vasculitis Hypersensitivity vasculitis Often self-limited if offending agent is removed, steroids in severe cases. Henoch-Schonlein purpura Henoch-Schonlein purpura Often no treatment. Steroid for some gastrointestinal and steroids cyclophosphamide for renal involvements. Cryoglobulinemia Cryoglobulinemia Corticosteroids; plasmapheresis for severe involvement. Antivial therapy for hepatitis C.

44. VASCULITIS IN CHILDREN Cont’d. Treatment of the major systemic vasculitidies Disease Primary treatment Vasculitis of small and medium-sized vessles Polyarteritis nodosa Polyarteritis nodosa Steroids + cyclophosphamide Microscopic polyangiitis Microscopic polyangiitis Steroids + cyclophosphamide Churg-Strauss vasculitis Churg-Strauss vasculitis Steroids + cyclophosphamide Wegener’s granulomatosis Wegener’s granulomatosis Steroids + cyclophosphamide or steroids + methotrexate for less severe involvement + septrin Kawasaki disease Kawasaki disease High dose aspirin and intravenous immune globulin, ? steroids

45. VASCULITIS IN CHILDREN Cont’d. Treatment of the major systemic vasculitidies Disease Primary treatment Vasculitis of large vessels Giant cell, or temporal, arteritis High-dose steroids Takayasu’s arteritis High-dose steroids

46. VASCULITIS IN CHILDREN CONCLUSION: There is a wide spectrum of vasculitis affecting children. There is a wide spectrum of vasculitis affecting children. Although we know some etiological agents, still we are behind in majority. 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. 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 Classification still does not cover the whole spectrum of vasculitis New discovery on etiopathogenesis still awaited. New discovery on etiopathogenesis still awaited. Steroids and cytotoxic drugs improved the prognosis. Steroids and cytotoxic drugs improved the prognosis.

47. 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.

48. VASCULITIS IN CHILDREN Conditions that may mimic systemic vasculitis. Drug exposure Drug exposureCoccaineAmphethamine Penicillins, supha drugs Anticonvulsants Hydralazine, Propylthiouracil Infections Infections Malignant disease Malignant disease Atrial myxoma Atrial myxoma Cholesterol emboli Cholesterol emboli Antiphospholipid antibody syndrome Antiphospholipid antibody syndrome Other connective tissue disorders Other connective tissue disorders

49. VASCULITIS IN CHILDREN Infection-related vasculitis Viral HIV Hepatitis B,C Viral HIV Hepatitis B,C EBV, herpes zoster Parvovirus B19, CMV Bacterial/fungalSBE Bacterial/fungalSBE MycobacterialTuberculosis MycobacterialTuberculosis SpirochetalSyphilis SpirochetalSyphilis RickettsialRocky Mountain spotted fever RickettsialRocky Mountain spotted fever

50. VASCULITIS IN CHILDREN Clues for Identifying the Type of Vessels Involvement in Vasculitis Clinical feature Affected vesselsAssociated vasculitis CUTANEOUS Palpable purpura Postcapillary venulesAny vasculitis except giant cell Skin ulcers Arterioles to smallPolyarteritis, Churg-Strauss arterieshypersensitivity vasculitis, WG arterieshypersensitivity vasculitis, WG Gangrenein an Small to medium-Polyarteritis, Churg- Strauss Extremity sized arteriesWG

51. VASCULITIS IN CHILDREN Clues for Identifying the Type of Vessels Involvement in Vasculitis Clinical feature Affected vesselsAssociated vasculitis G.I. TRACT Abdominal pain Small to medium-sized HSP, PAN arteriesChurg-Strauss arteriesChurg-Strauss Gastrointestinal Capillaries to medium-HSP, PAN Bleeding sized arteriesChurg-Strauss

52. VASCULITIS IN CHILDREN Clues for Identifying the Type of Vessels Involvement in Vasculitis Clinical feature Affected vesselsAssociated vasculitis RENAL Glomerulo- CapillariesMicroscopic polyangiitis nephritis HSP, WG, cryoglobulinemia Churg-Strauss Ischemic renal Small to medium-Polyarteritis, TA, less Failure sized arteriescommonly, Churg-Strauss, WG

53. 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 medium-sized arteries Pulmonary Small to medium- Churg-Strauss, WG, Infiltrates or sized arteries Microscopic polyangiitis cavities

54. 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 sized or large arteries arteries

55. VASCULITIS IN CHILDREN Laboratory studies in Vasculitis A.Nonspecific - Complete blood count - Complete blood count - Erythrocyte sedimentation rate (ESR) - Erythrocyte sedimentation rate (ESR) - C-reactive protein - 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

56. VASCULITIS IN CHILDREN Laboratory studies in Vasculitis C. Etiology/pathogenesis HIV Hepatitis B & C antibodies HIV Hepatitis B & C antibodies Antinuclear antibody, DNA binding, extractable nuclear antigen Antinuclear antibody, DNA binding, extractable nuclear antigen Cryoglobulins Cryoglobulins Serum complement Serum complement Rheumatoid factor Rheumatoid factor Blood cultures Blood cultures Antiglomerular basement membrane antibodies (anti- GBM-Ab) Antiglomerular basement membrane antibodies (anti- GBM-Ab) Antineutrophil cytoplasmic autoantibodies (ANCA) Antineutrophil cytoplasmic autoantibodies (ANCA)