Download Childhood Vasculitis

Childhood Vasculitis
• Characterised by the presence of inflammation
in the walls of blood vessels, with resultant
tissue ischaemia and necrosis.
• incidence : 53.3 per 100,000 children under 17
years of age
• Henoch-Schönlein purpura (HSP):20,4 ,Kawasaki
disease 5,5
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• A number of factors have been reported to be associated with
the development of vasculitis,
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infections,
drugs,
allergy,
vaccination
desensitisation procedures.
EULAR/PRES endorsed consensus criteria for
the classification of childhood vasculitides.
Ann Rheum Dis 2006
Changes suggested by the 2012 Conference
were use of the term eosinophilic
granulomatosis with polyangiitis (EGPA), in
place of Churg Strauss syndrome, and formal
adoption of the term antineutrophil
cytoplasmic antibody (ANCA) associated
vasculitis (AAV) for the three disorders
microscopic polyangiitis, granulomatosis with
polyangiitis (Wegener’s), and EGPA
Henoch Schönlein Purpura
• Most common vasculitis in children.
• Incidence 20,4/100000 year
• Occurs most frequently between the ages of 3 and 10
years
• Diagnostic criteria: purpura with lower limb
predominance and the presence of at least one of the
following four features
• arthralgia or arthritis,
• diffuse abdominal pain,
• any biopsy showing predominant IgA deposition,
• renal involvement (any proteinuria and/or hematuria)
• Skin or renal biopsies demonstrate the
deposition of IgA (mainly IgA1) in the wall of
dermal capillaries and post capillary venules and
mesangium
• Children with HSP and with IgA nephritis have
abnormal glycosylation in IgA1 O-linked glycans,
an abnormality that facilitates the deposition of
IgA in tissues
• Mainly infectious diseases triggers HSP (esp.
upper respiratory tract infections )
Clinical features
• Palpabl purpura,
• Arthritis,
• Abdominal pain,
• Gastrointestinal bleeding,
• Nephritis/Hematuria.(hematuria and
proteinuria, is seen in 20% to 50% of
affected children with 2% to 5%
progressing to end-stage renal failure)
• Risk factors for nephritis
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- children older than 4 years,
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- purpura lasting more than 1 month,
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- gastrointestinal bleeding,
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- factor XIII activity less than 80% of normal
Extrarenal manifestations
• Joint complaints respond well to on steroid antiinflammatory drugs (NSAID).
• Cutaneous manifestations are often self-limited,
but may have a relapsing pattern.
• Abdominal pain is common and usually selflimited.
Diagnosis
• Diagnosis is established by the pattern of clinical
manifestations.
• No spesific laboratory test is available.
• Skin biopsy reveals leukocytoclastic vasculitis
with IgA deposition in blood vessel walls but is
not required in typical presentation
• Renal biopsy is rarely necessary for diagnosis but
may have prognostic utility
Treatment
• NSAID (ibuprofen): Artritis and artralgia
• Glucocorticoids: Lessen tissue edema, arthritis, and
abdominal pain and decrease the rate of intussusception.
BUT
• Glucocorticoid therapy does not prevent recurrence of
abdominal symptoms, skin involvement, or renal disease and
does not appear to shorten the duration or lessen the
likelihood of relapse
• Glucocorticoids combined with a cytotoxic agent (cyclosporine
A, azathioprine and cyclophosphamide) might be beneficial in
patients with active glomerulonephritis and progressive renal
insufficiency.
Kawasaki Disease
• An acute, systemic medium and small
vessels vasculitis occurring primarily in
children.
• Approximately 80% of children with
Kawasaki disease are less than 5 years old
• Asians are at the highest risk
The classification criteria for Kawasaki Disease,
• Fever for 5 days or longer and least four of the following five
signs:
- nonpurulent conjunctivitis,
- rash (polymorphous erythematous),
- hyperemic lips
and/or mucous membranes,
- changes to the extremities (peripheral edema,
peripheral erythema and periungual desquamation), and
- cervical adenopathy (usually unilateral).
• Coronary artery lesions are responsible for most
of the disease-related morbidity and mortality.
• Aneurysms appear 1 to 4 weeks after the onset
of fever and develop in 15% to 25% of untreated
children.
• All children with known or suspected KD should
have an echocardiogram at the time of
presentation and again after 2 to 3 weeks of
illness.
Laboratory
• Marked elevations in the levels of acute-phase reactants are
present in the first week of illness.
• Elevated leukocyte count or a normal leukocyte count with a
left shift is typical
• The platelet count is generally normal in the first week of
illness. Thrombocytosis during the second to third week of
illness is classically associated with KD
Treatment
• Shown to reduction significantly the
development of coronary artery complications.
• Standard treatment
- IVIG (2 g/kg single dose in a 10-12 hour
infusion) and
- Aspirin (50-80 mg/kg daily divided into four
doses)
When the inflamatuar markers (sedimantation
rate or CRP) returned to normal levels, aspirin
dose is reduced (3-5 mg/kg daily as a single dose)
Treatment
• IVIG should be administered to children
presenting after day 10 of illness (i.e., patient
with delayed diagnosis) if they have either
persistent fever without explanation or
aneurysms and ongoing systemic inflammation
(elevated ESR or CRP)
• Intravenous methylprednisolone (IVMP) is
considered for KD patients with persistently poor
responses to the second IVIG treatment
• Infliximab
Polyarteritis Nodosa (PAN)
• Characterised by necrotizing inflammatory
changes in medium and/or small sized arteries.
• Rare in childhood
• Etiopathogenesis of PAN is is unknown, but
infections such as viral hepatitis, streptococcal
infections, and parvovirus infections have been
implicated.
• Criteria for childhood PAN: Histologic evidence of necrotizing
vasculitis in medium or small- sized arteries or angiographic
abnormalities (aneurysm or occlusion) plus two of the
following seven;
• muscle tenderness or myalgia,
• skin involvement (livedo reticularis, tender subcutaneous
nodules, other vasculitic lesions),
• systemic hypertension,
• mononeuropaty or polyneuropathy,
• abnormal urine analysis and/or impaired renal function,
• testicular pain or tenderness,
• signs or symptoms suggesting vasculitis of any other major organ
system (gastrointestinal, cardiac, pulmonary, or central nervous
system
• Disease manifestations are ranging from the
benign cutaneous form to the severe
disseminated multi-systemic form
• The most common clinical manifestations:
Constitutional symptoms (fever, weight loss,
malaise), Arthralgia, Myalgia, mononeuritis
multiplex, gastrointestinal disease (ischaemia,
infarction, haemorrhage or perforation), cardiac
disease (ischaemic heart disease), hypertension,
livedo reticularis and testicular pain
• Laboratory evaluation usually reflects the ongoing systemic
inflammation including
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anemia,
leukocytosis,
thrombocytosis,
elevated ESR, CRP.
Antineutrophil cytoplasmic antibodies are expected to be
negative.
• Therapy includes steroids and various immunosuppressive
medications
• Therapy includes steroids and various immuno
suppressive medications
• For induction of remission, cyclophosphamide and high
doses of corticosteroids are used until remission is
achieved
• Azathioprine and cyclophosphamide
• Adjunctive plasma exchange certainly still plays an
important role in some children for gaining rapid disease
control where life or critical organs are threatened
• Cutaneous PAN characterised by the presence of painful
subcutaneous nodules, non-purpuriclesions with or without
livedo reticularis, with no syste
• It commonly occurs after a sore throat or streptococcal
pharyngitis.
• ANCA tests are negative
• Skin biopsy shows necrotizing, non-granulomatous vasculitis.
mic involvement
• Treatment is typically much less aggressive. Low dose
prednisolone, anti-platelet agents, colchicine,
hydroxychloroquine, or azathioprine
ANCA-Associated Vasculitis (AAV)
• Microscopic polyangiitis, (MPA)
• Granulomatosis with polyangiitis(GPA) (Wegener’s),
• EGPA (Churg Strauss syndrome)
• Two types of ANCA have been identified in patients with
vasculitis
• cANCA
• pANCA
Granulomatous polyangiitis (GPA)
• uncommon in children. Median age at diagnosis was 14.5
years
• necrotizing granulomatous inflammation of small to mediumsized vessels involving the kidneys and upper and lower
respiratory tracts.
• The proposed classification criteria for GPA were that three of
the following six criteria should be present:
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abnormal urinalysis,
granulomatous inflammation on biopsy,
naso-sinus inflammation,
subglottic, tracheal or endobronchial stenosis,
Abnormal chest X-ray or computed tomography (CT)
PR3 ANCA or cytoplasmic ANCA staining
Patients with GPA frequently present with
• sinusitis,otitis media, persistent rhinorrhea, purulent/
bloody nasal discharge, oral and/or nasal ulcers.
• Nasal and sinus mucosal inflammation can produce
• sinus pressure and pain,
• epistaxis,
• persistent otitis media with effusion or decreased hearing,
• cartilage ischemia with nasal septal perforation, resulting
• in a saddle nose deformity.
• Pulmonary radiographic abnormalities can include nodules or
infiltrates, cavities and ground-glass infiltrates.
• Renal involvement occurs as microscopic hematuria, proteinuria,
and rapidly progressive renal failure.
• The characteristic renal histology is focal, segmental
necrotizing, crescentic glomerulonephritis with few to no
immune complexes on immunofluorescence and electron
microscopy
• The diagnosis of WG is usually based on biopsy results, with
nonrenal tissues demonstrating the presence of
granulomatous inflammation and necrosis, with necrotizing or
granulomatous vasculitis
• Initial immunosuppressive therapy in GPA typically consists of
cyclophosphamide and glucocorticoids.
• Mortality is as high as 90% if untreated
Microscopic polyangiitis (MPA)
• MPA is characterized by necrotizing vasculitis with few or no
immune deposits affecting small vessels.
• Clinical features: involving the kidneys, lungs, joints, skin,
gastrointestinal tract, and peripheral nerves.
• Cardinal features:
-glomerulonephritis,
-pulmonary hemorrhage,
-fever,
-mononeuritis multiplex.
Takayasu disease (giant cell)
• Affects the aorta, its main branches, and the pulmonary
arteries in which granulomatous vasculitis results in stenosis,
occlusion, or aneurysms of affected vessels
• Female predominancy (80-905 of cases)
• Criteria for childhood TA are angiographic abnormalities
(conventional, CT, MR) of the aorta or its main branches plus
at least one of the following four features:
• decreased peripheral artery pulse (s) and/or claudication of
extremities,
• bruits over aorta and/or its major branches,
• hypertension
• blood pressure difference >10 mm Hg.
• Pathologically TA lesions consist of granulomatous changes
progressing from the vascular adventitia to the media
• Systemic symptoms are common: fatigue, weight loss, and
low-grade fever
• Vascular symptoms are related to the location and nature of
the lesion
• Laboratory changes reflect the inflammatory process but are
mostly nonspecific. A normochromic normocytic anemia is
present in most patients.
• Acute-phase reactants (ESR and CRP) are usually elevated.
• The mainstay of therapy for Takayasu arteritis is
glucocorticoids.