Early in the course of a vasculitis, nonspecific findings reflecting systemic inflammation

• fever

• malaise

• fatigue

• failure to thrive

• elevated acute-phase reactants

As vessel damage progresses…

• evidence of vascular compromise

• elevation of markers of vascular injury

– von Willebrand’s factor antigen,

– pentraxin 3

• distinctive autoantibodies

– especially antineutrophil cytoplasmic antibodies [ANCA]

– or anti-endothelial antibodies

‘‘Catch-22’’

• becomes more evident only after severe and irreversible morbidity is present.

• little information suggestive of vasculitis when the diagnosis needs to be made.

Size of vessel

• Large vessels to the extremities – claudication.

• visceral vessels.

– hypertension (renal arteries),

– abdominal pain (mesenteric and celiac axes),

– chest pain (aortic or coronary artery involvement),

– neurologic symptoms (focal neurologic deficits or neuropathic pain).

Inflammation of smaller arteries and arterioles

Symptoms in richly vascularized organs.

Skin involvement.

livedo reticularis,

purpuric (generally palpable) or nonblanching lesions,

palmar or plantar rashes.

Pulmonary, renal, and gastrointestinal arterial.

hemoptysis,

hematuria,

hypertension.

abdominal pain, or melena.

Capillary and venous.

less of an acute emergency than arteritis.

Clues to Dg

• history and general physical examination

• recent illnesses, in particular infections,

• over-the-counter drugs

• travel

• family history

• All pulses must be palpated carefully

• Allen’s tests

• auscultation for bruits,

• blood pressures in all four extremities

• skin nodules

• ocular fundi and nailbed capillaries

Laboratory studies specific for the diagnosis of vasculitis are not yet available.

• CBC

• ESR

• C-reactive protein [CRP])

• Immunoglobulines

• ANCA

• Von Willebrand factor antigen

•

• PTX3, a pentraxin expressed by endothelial cells and monocytes

Imaging procedures

large- or medium-sized vessels

• Vascular imaging

• Doppler US studies

• CT or MRI angiograms

Histopathologic demonstration of vascular inflammation

• The reference standard for diagnosing a vasculitis.

• Inaccessibility of lesions or patchiness of the vascular involvement.

Classification

• Clinical manifestations.

• Size of blood vessels involved.

• Histology of vascular damage.

• Presumed disease pathogenesis.

An etiologic classification

• TNF seems to be effective in TA

• But apparently is less so in Wegener’s

• Rituximab effective in ANCA-associated vasculitides

Classification of pediatric vasculitides

• Primary vasculitides

• Large vessel diseases

• Takayasu arteritis

• Giant cell (temporal) arteritis

Medium vessel disease

• Polyarteritis nodosa

– Cutaneous

– Systemic

• Cogan’s syndrome

• Kawasaki disease

Small-vessel disease

• Henoch-Schonlein purpura

• Hypersensitivity vasculitis

• Primary angiitis of the central nervous system

• ANCA-positive vasculitis

• Wegener’s granulomatosis

• Microscopic periarteritis

• Churg–Strauss syndrome

Secondary vasculitides

• Infection-related vasculitis

• Hepatitis viruses

• Herpes viruses (EBV, CMV, varicella)

Vasculitis secondary to connective tissue disease

• Dermatomyositis,

• Systemic lupus erythematosus,

• Rheumatoid arthritis

• Hypocomplementemic uticarial vasculitis

• Drug hypersensitivity –related vasculitis

•

• Malignancy-related vasculitis

•

• Post–organ transplant vasculitis

•

• Pseudovasculitic syndromes

– Myxoma

– Endocarditis

– Sneddon syndrome

Vasculitides with strong genetic component

• Periodic fever syndromes.

• Behet’s disease.

Modified from Hunder GG, Wilking AP.

Classification of the vasculitides.

in children. UpToDate, 2005. Available at: http://www.utdol.com/application/search.asp.

Epidemiology

• Primary vasculitis among children < 17 years of age was 20.4/100 000,

• Henoch-Schfnlein purpura (HSP) the most prevalent.

Pathogenesis

Generally not understood

1. Humoral factors:

• Vascular damage secondary to specific antibodies is best demonstrated in the ANCA-associated vasculitides

• Activate neutrophils, causing vascular inflammation,

• Antiendothelial antibodies are also present in a variety of vasculitides

2. Immune complexes:

• The size, charge, and immunoreactivity of immune complexes help explain aspects of the pathogenesis of HSP and cryoglobulinemic vasculitis

• Similarly, PAN associated with hepatitis B or C seems to be triggered by inflammation incited by immune complexes deposited upon vessel walls

3. T lymphocytes attracted to damaged or infected endothelium

• Suppression of autoreactive lymphocytes.

• T-regulatory cells - breaking of tolerance and development of autoimmunity.

• Biopsy samples from different types of vasculitis demonstrate different populations of cells invading vessel walls (eg, macrophages in KD and eosinophils in Churg–Strauss syndrome [CSS])

4. The characteristic predilection of different vasculitides for different anatomic sites

• Remains unexplained,

• Depend on a variety of factors, including.

– specificity of the triggering antigen,

– regional variations in cell surface receptors,

– and unidentified contributions of surrounding tissues.

Recluse Spiders

• Genus Loxosceles

• Family Sicariidae

• Six-eyed sicariid spiders

• Necrotic arachnidism

• Loxoscelism “gangrenous spot of Chile"

• At least 56 species

• One from the Mediterranean region

• Inside houses

• Hiding in the folds of clothing, shoes, or underneath boxes in storage rooms

Henoch-Schonlein purpura

• IgA immune complex–mediated small-vessel.

• leukocytoclastic vasculitis.

• Triad of:

– nonthrombocytopenic palpable purpura,

– colicky abdominal pain.

– arthritis.

• May progress to chronic renal failure in 1%.

A wide variety of infections may trigger HSP.

• Group A streptococcus is the most common precipitant, (one third).

• Bartonella,

• Haemophilus parainfluenza, and numerous vaccines and drugs.

In rare cases, CNS or respiratory lesions may.

lead to hemorrhage with serious sequelae.

HSP

• Slightly more common in boys

• More commonly during winter and spring

• May begin as urticaria, progresses to dramatic purple, nonblanching lesions

Predilection to lower body

• Activation of the alternate pathway of complement by large IgA containing immune complexes.

• Gravity causes immune complexes to deposit and incite inflammation in dependent areas.

Gastrointestinal involvement

• Ranges from colicky abdominal pain to profuse bleeding, intussusception (typically ilio-ilial) and perforation

• Pancreatitis, cholecystitis, and protein-losing enteropathy

Renal disease

• In most cases, the first days or weeks.

• First 3 months of the illness in 97% of patients.

Risk factors:

• age over 47 years,

• gastrointestinal bleeding,

• purpura of more than 1 month’s duration,

• factor XIII activity < 80% of normal,

• factor XIII concentrate treatment.

Recurrence

• HSP recurs in about one third of patients,

• especially those with nephritis.

• first 4 to 6 months.

Outcome

• Patients demonstrating both nephritic and nephrotic changes at greatest risk.

• Renal biopsy is useful for confirming the extent and severity of nephritis and planning treatment:

• The higher the percentage of glomeruli with crescents, the more likely is development of end-stage renal disease.

• High serum levels of nitric oxide and urinary nitrate excretion.

• Increased urinary excretion of the tubular proteins N-acetyl b-d-glucoseaminidase and a-1-microglobulin also proved useful in identifying.

• Patients at higher risk of long-term renal disease.

• 1% to 5% of HSP patients develop some degree of chronic renal disease.

Acute hemorrhagic edema of infancy

• Fever,

• Large purpuric lesions, and edema.

• A self-limited condition,

• Likely to resolve within weeks.

Hypersensitivity vasculitis

Clinical features.

• Fever,

• Urticaria,

• Lymphadenopathy,

• Arthralgias,

• low serum complement levels, and elevated ESR.

• Low serum concentrations of C3 and C4 and the absence of IgA.

• deposition in vessel walls help to distinguish this entity from HSP.

Therapy of HSP is primarily supportive

• NSAIDs, no evidence of increased likelihood of GI hemorrhage in HSP.

• Use of steroids continues to be controversial.

Prednisone

• Prednisone, 2 mg/kg/day,

• Relieve symptoms rapidly in most cases,

• Must avoid excessively rapid tapering of the steroids,

• precipitate a flare of symptoms

Immunosuppressive agents

• Such as cyclophosphamide or azathioprine,

• Reserved for children with biopsy-proven crescentic glomerulonephritis

• other life-threatening complications such as cerebral or pulmonary hemorrhage

Kawasaki disease

• Although KD or mucocutaneous lymph node syndrome it is a self-limited condition, with fever and manifestations of.

• Acute inflammation lasting for an average of 12 days without therapy.

• Diagnosed by clinical criteria not histology or angiography.

Kawasaki disease

• 80% to 90% of >fifth birthday.

• 1.5% of untreated children died from KD.

• More than 140,837 cases of KD have been registered in Japan since its initial description in 1967.

Kawasaki disease

• susceptibility of different ethnic groups to KD

• Genetic factors,

• polymorphisms of chemokines

• and TNF receptors

• variations in HLA haplotypes

•

• Overall, Asians are affected 5 to 10 times as frequently as whites;

• blacks and Hispanics have an intermediate risk

The cause of KD remains unknown.

Criteria for diagnosis of Kawasaki disease

• Fever lasting 5 days or more (4 days if treatment with IVIG

• eradicates fever) plus at least four of the following clinical signs

• not explained by another disease process

Modified from Centers for Disease Control. Revised diagnostic criteria
for Kawasaki disease. MMWR Morb Mortal Wkly Rpt 1990;
39(No. 44-13):27–8.

1. Bilateral conjunctival injection (80%–90%)

2. Changes in the oropharyngeal mucous membranes (including

one or more of the following symptoms: injected or fissured

lips, strawberry tongue, injected pharynx) (80%–90%)

3. Changes in the peripheral extremities, including erythema

or edema of the hands and feet (acute phase) or periungual

desquamation (convalescent phase) (80%)

4. Polymorphous rash, primarily truncal; nonvesicular (N 90%)