Pediatric vasculitis dr inayat ullah

VASCULITIS IN CHILDREN
by
DR. INAYAT ULLAH
Shifa International Hospital
Pediatric Department

 Definition
 Incidence
 Pathogenesis
 Classification
 Pathology
 Clinical features
 Diagnosis
 Treatment

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

 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)

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

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.

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.

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)

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

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.

Cont’d.
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.

Cont’d.
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.

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

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.

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)
Coronary & other muscular Thrombosis, fibrosis,
arteries aneurysm especially coronaries

Cont’d.
LEUKOCYTOCLASTIC VASCULITIS
Henoch-Schonlein Purpura (Syndrome)
Arterioles & venules Leukocytoclasis, mixed cell, eosinophils
Often small arteries & veins eosinophil; IgA deposits in affected
vessels
(GI tract)
Hypersensitivity angiitis
Arterioles and venules Leukocytoclasis or lymphocytic, varying
eosinophils
occasionally granulomatous; widespread
lesions at same stage of evolution

Cont’d.
GRANULOMATOUS VASCULITIS
Allergic granulomatosis (Syndrome)
Small arteries and veins, Necrotizing extravascular
granulomata; lung
often arterioles and venules involvement; eosinophilia
Weneger’s granulomatosis
Small arteries and veins, Upper and lower respiratory tract,
necrotizing
occasionally larger vessels granulomata, glomerulonephritis

Cont’d.
GIANT CELL ARTERITIS
Takayasu’s Arteritis (Syndrome)
Muscular and elastic arterities Granulomatous inflammation,
giant cells, aortic arch and branches,
aneurysms, dissection
Temporal Arteritis (Syndrome)
Medium and large arteries Granulomatous inflammation,
giant
cell arteritis, carotid and branches

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

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

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

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

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

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 - - -

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

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

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

ACR 1990 criteria for the classification of
hypersensitivity vasculitis
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

polyarteritis nodosa
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

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%

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%

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
Wergener’s granulomatosis
Two or more criteria yields a sensitivity of 88.2% and a specificity of 92.0%

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

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

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.

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 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.

Vasculitis of large vessels
Giant cell, or temporal,
arteritis
High-dose steroids
Takayasu’s arteritis High-dose steroids
Cont’d.

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.

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.

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

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

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

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

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

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

NEUROLOGIC
Peripheral Small arteries Polyarteritis, Churg-
Strauss
neuropathy WG, cryoglobulinenia
Stroke Small, medium- Giant cell arteritis,
SLE
sized or large
arteries

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

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)

Pediatric vasculitis dr inayat ullah

Pediatric vasculitis dr inayat ullah

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