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VASCULITIS IN CHILDREN
by
DR. INAYAT ULLAHShifa International Hospital
Pediatric Department
VASCULITIS IN CHILDREN
Definition Incidence Pathogenesis Classification Pathology Clinical features Diagnosis Treatment
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.
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)
VASCULITIS IN CHILDRENPathogenesis No single mechanism explain all vasculitidies. Abnormalities noted in various vasculitides in:
Polymorphs - Endothelial cellsLymphocytes - Humoral immunityPlatelets
3 Mechanisms suggested:1. Immune complex chemoattractant hypothesis(I.C.)2. Adhesion molecular (A.M.)3. Antibody – mediatedvascular injury
VASCULITIS IN CHILDRENCont’d.PathogenesisThe 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.
VASCULITIS IN CHILDRENCont’d..PathogenesisThe 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.
VASCULITIS IN CHILDRENPathogenesise.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 1983Anti-neutrophil Cytoplasmic antibodies as a
useful diagnostic and prognostic marker for W.G.(C-ANCA = Antiprotinase 3 ab, P – ANCA=
Antimyeloperoxidase)
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
VASCULITIS IN CHILDRENNomenclature of systemic vasculitis (CHCC
1993)Large vessel vasculitisGiant 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 arteritisGranulomatous inflammation of the aorta and its major branches. Usually occurs in patients younger than 50.
VASCULITIS IN CHILDREN Cont’d.
Nomenclature of systemic vasculitis (CHCC 1993)Medium size vessel vasculitisPolyarteritis nodosa
Necrotizing inflammation of medium-sized or small arteries without glowmrulonephritis or vasculitis in arterioles, capillaries or venules.
Kawasaki diseaseArteries 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.
VASCULITIS IN CHILDREN Cont’d.
Nomenclature of systemic vasculitis (CHCC 1993)Small vessel vasculitisWeneger’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 syndromeEosinophil-rich and granulomatous inflammation involving the respiratory tract, and necrotizing vasculitis affecting small to medium-sized vessels, and associated with asthma and eosinophilia.
Microscopic polyangitisNecrotizing 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.
VASCULITIS IN CHILDREN Cont’d.
Nomenclature of systemic vasculitis (CHCC 1993)
Small vessel vasculitisHenoch-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 vasculitisVasculitis 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 angiitisIsolated cutaneous leukocytoclastic angiitis without systemic vasculitis or glomerulonephritis
VASCULITIS IN CHILDRENPathology 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.
VASCULITIS IN CHILDRENPathology of Some Vasculitides
POLYARTERITISPolyarteritis 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
VASCULITIS IN CHILDREN Cont’d.
Pathology of Some Vasculitides LEUKOCYTOCLASTIC VASCULITISHenoch-Schonlein Purpura (Syndrome) Vessels affected Characteristic Pathology Arterioles & venules Leukocytoclasis, mixed cell, eosinophilsOften small arteries & veins eosinophil; IgA deposits in affected
vessels(GI tract)
Hypersensitivity angiitisVessels affected Characteristic PathologyArterioles and venules Leukocytoclasis or lymphocytic,
varying eosinophils occasionally granulomatous; widespread lesions at same stage of evolution
VASCULITIS IN CHILDREN Cont’d.
Pathology of Some Vasculitides GRANULOMATOUS VASCULITISAllergic granulomatosis (Syndrome) Vessels affected Characteristic PathologySmall arteries and veins, Necrotizing extravascular granulomata;
lung often arterioles and venules involvement; eosinophilia
Weneger’s granulomatosisVessels affected Characteristic PathologySmall arteries and veins, Upper and lower respiratory tract,
necrotizing occasionally larger vessels granulomata, glomerulonephritis
VASCULITIS IN CHILDREN Cont’d.
Pathology of Some Vasculitides GIANT CELL ARTERITISTakayasu’s Arteritis (Syndrome) Vessels affected Characteristic
PathologyMuscular and elastic arterities Granulomatous inflammation,
giant cells, aortic arch and branches, aneurysms, dissection
Temporal Arteritis (Syndrome) Vessels affected Characteristic
PathologyMedium and large arteries Granulomatous
inflammation, giantcell arteritis, carotid and
branches
VASCULITIS IN CHILDRENDemographic Associations of the Vasculitides
Age group Male-to-Female
Ethnic origin Type of vasculitis
Child M = F Any Henoch-Schonlein purpura
Young adult M > FM = FF > M
Asian > white > othersMiddle Eastern > othersAsian >> others
Kawasaki diseaseBehcet’s diseaseTakayasu’s arteritis
Middle age M > F Any Wegeners granulomatosis, polyarteritis, /churg-Strauss vasculitis
Elderly F > M Caucasian >> others
Giant cell arteritis
VASCULITIS IN CHILDRENCommon Presentations of the Vasculitic Syndromes
Syndrome PresentationConstitutional Fever, weight loss, weakness,
fatigueMusculoskeletal Arthralgia, myalgia, arthritis
Cutaneous Palpable purpura, nodules, urticaria, livedo reticularis, superficial phlebitis, ischemic lesions
Neurologic Headache, stroke, mononeuritis multiplex
VASCULITIS IN CHILDRENCont’dCommon 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
VASCULITIS IN CHILDRENApproximate frequency of organ-system manifestations in several forms of small-vessel vasculitis
Organ System
Henoch-Schonle
in Purpura
Cryoglo-bulinemi
c Vasculiti
s
Microscopic
Polyangitis
Wegener’s
Granulo-matosis
Churg-strauss Syndro
me
percentCutaneous 90 90 40 40 60Renal 50 55 90 80 45Pulmonary <5 <5 50 90 70Ear, nose and throat
<5 <5 35 90 50
Musculoskeletal 75 70 60 60 50Neurologic 10 40 30 50 70Gastrointestinal 60 30 50 50 50
VASCULITIS IN CHILDRENACR 1990 criteria for the classification of Henoch-Schonlein purpura
Criterion Definition1) 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
VASCULITIS IN CHILDRENClinical characteristics of Henoch-Schonlein purpura
Clinical Characteristic
(%)
Wintern = 43
Emery et al.
n = 43
S. A. Al Rasheed et al
n = 40Purpura 97 100 100Arthralgia/arthritis 65 79 58Abdominal pain 100 63 58Gastrointestinal bleeding
26 - 23
Nephritis - 37 38Subcutaneous edema - 63 -Encephalopathy - - -Orchitis - - -
VASCULITIS IN CHILDRENKawasaki 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” tongueDiffuse erythema or oropharynx
6) Changes of extremities Erythema of palms or solesIndurative edema of hands and feetDesquamation of tips of fingers
VASCULITIS IN CHILDRENOther Clinical Findings in Kawasaki
Disease
Relatively common abnormalities: Arthralgia / arthritis Meningitis Pneumonitis Anterior uveitis with photophobia Gastroenteritis Meatitis and dysuria Otitis
VASCULITIS IN CHILDRENCont’d.
Other Clinical Findings in Kawasaki Disease
Relatively uncommon abnormalities: Hydrops of the gallbladder Gastrointestinal ischemia Jaundice Central nervous system disease
Febrile convulsionsEncephalopathy or ataxia
Cardiac diseaseCoronary thrombosis or aneurysmsCardiac tamponadeCardiac failureMyocarditisPericarditis
Petechial rash
VASCULITIS IN CHILDRENACR 1990 criteria for the classification of hypersensitivity vasculitis
Criterion Definition1) 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
VASCULITIS IN CHILDRENACR 1990 criteria for the classification of polyarteritis nodosa
Criterion Definition1. Weight loss > 4 kg Not due to dieting or other
factor 2. Livedo reticularis Mottled reticular pattern over
the skin3. 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 polyneuropathy6. Diastolic BP > 90 mmHg
VASCULITIS IN CHILDREN
Criterion Definition7. 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%
VASCULITIS IN CHILDREN
Criterion Definition1. Age at disease onset < 40 years2. 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%
VASCULITIS IN CHILDREN
Criterion Definition1. 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%
VASCULITIS IN CHILDREN
Criterion Definition1. Asthma History of wheezing or diffuse high
pitched rales on expiration2. Eosinophilia Eosinophilia > 10% on white blood cell
differential count3. History of allergy * History of seasonal allergy or other
documented allergy4. 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 history7. Extravascular eosinophils Biopsy showing accumulations of
eosinophils in extravascular areas
ACR 1990 criteria for the classification of Churg-Strauss syndrome
VASCULITIS IN CHILDREND. 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
VASCULITIS IN CHILDRENCon’t.
Laboratory studies in vasculitisE. 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.
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
VASCULITIS IN CHILDREN
Disease Primary treatmentVasculitis 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
VASCULITIS IN CHILDREN
Disease Primary treatment
Vasculitis of large vesselsGiant cell, or temporal, arteritis
High-dose steroids
Takayasu’s arteritis High-dose steroids
Cont’d.
Treatment of the major systemic vasculitidies
VASCULITIS IN CHILDRENCONCLUSION: 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.
VASCULITIS IN CHILDRENGeneral 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.
VASCULITIS IN CHILDRENConditions that may mimic systemic
vasculitis. Drug exposure
CoccaineAmphethaminePenicillins, supha drugsAnticonvulsants Hydralazine, Propylthiouracil
Infections Malignant disease Atrial myxoma Cholesterol emboli Antiphospholipid antibody syndrome Other connective tissue disorders
VASCULITIS IN CHILDRENInfection-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
VASCULITIS IN CHILDRENClues for Identifying the Type of Vessels
Involvement in VasculitisClinical feature Affected vessels Associated
vasculitisCUTANEOUSPalpable 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
VASCULITIS IN CHILDRENClues for Identifying the Type of Vessels
Involvement in VasculitisClinical feature Affected vessels
Associated vasculitisG.I. TRACTAbdominal pain Small to medium-sized HSP, PAN
arteries Churg-Strauss
Gastrointestinal Capillaries to medium- HSP, PANBleeding sized arteries Churg-
Strauss
VASCULITIS IN CHILDRENClues for Identifying the Type of Vessels
Involvement in Vasculitis
Clinical feature Affected vesselsAssociated vasculitis
RENALGlomerulo- Capillaries Microscopic
polyangiitisnephritis HSP, WG,
cryoglobulinemiaChurg-Strauss
Ischemic renal Small to medium- Polyarteritis, TA, less
Failure sized arteries commonly , Churg-Strauss,
WG
VASCULITIS IN CHILDRENClues for Identifying the Type of Vessels
Involvement in VasculitisClinical feature Affected vessels Associated
vasculitisPULMONARYPulmonary Capillaries; less Microscopic
polyangiitis, WGHemorrhage commonly small to
medium-sized arteries
Pulmonary Small to medium- Churg-Strauss, WG,
Infiltrates or sized arteries Microscopic polyangiitis
cavities
VASCULITIS IN CHILDRENClues for Identifying the Type of Vessels
Involvement in Vasculitis
Clinical feature Affected vessels Associated vasculitis
NEUROLOGICPeripheral Small arteries Polyarteritis, Churg-
Straussneuropathy WG,
cryoglobulinenia
Stroke Small, medium- Giant cell arteritis, SLE
sized or large arteries
VASCULITIS IN CHILDRENLaboratory studies in VasculitisA. 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. AngiographyE. Biopsy
VASCULITIS IN CHILDRENLaboratory studies in VasculitisC. 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)