pediatric vasculitis dr inayat ullah

VASCULITIS IN CHILDREN

by

DR. INAYAT ULLAHShifa International Hospital

Pediatric Department


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)


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.


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.


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


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


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


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


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%


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%


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%


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.


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


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


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


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


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


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


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)

pediatric vasculitis dr inayat ullah

Health & Medicine