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KAWASAKI DISEASE
Definition/Epidemiology/Etiology/ Pathology Clinical Criteria typical manifestations/clinical phases associated findings/laboratory Atypical KD Complications Treatment Natural History/ Follow-up
KAWASAKI DISEASE
Mucocutaneous Lymph Node Syndrome
an acute, self-limited, multisystem vasculitis of infancy and childhood Infantile Polyarteritis Nodosa
KAWASAKI DISEASE
Peak onset: 6-11 months 80% are under 4y/o Male/female ratio:1.35:1 Recurrence rate: 3%
KAWASAKI DISEASE
ETIOLOGY: still UNKNOWN
clinical & epidemiological features suggest infectious cause Probable immunologic response triggered by several different microbial agents
identification of cytoplasmic inclusion bodies (aggregates of viral proteins & RNA) & virus-like particles in KD tissues
KAWASAKI DISEASE
Possible role of genetic predisposition:
1% with positive family history 50% of 2nd cases develop within 10 days of the first case 13% occurrence in twins
Genomic studies: functional single nucleotide polymorphism of ITPKC gene that confers susceptiblity to KD (Onouchi, 2008)
KAWASAKI DISEASE:
Acute Phase: a) induration (swelling) of hands & feet (dorsal edema); sometimes painful
KAWASAKI DISEASE:
Changes in the Peripheral Extremities Acute phase: b) Erythema of palms & soles; abrupt change to normal skin at wrist & ankle (stocking & glove areas)
Convalescent phase
(1 to 2 months after onset): transverse grooves across nails (Beaus lines)
KAWASAKI DISEASE:
RASH
Polymorphous rash on trunk & extremities most common: non-specific diffuse maculopapular erythematous rash No bullous & vesicular eruptions
Congestive heart failure Myocarditis, pericarditis, valvulitis Coronary artery findings: arteritis Aneurysms of medium-size noncoronary arteries Raynauds phenomenon Peripheral gangrene
KAWASAKI DISEASE
Rare findings: Testicular swelling, pulmonary nodules and infiltrates, pleural effusions, and hemophagocyctic syndrome
KAWASAKI DISEASE
Gangrene of toes
KAWASAKI DISEASE: CLINICAL PHASES Acute Febrile Phase (1-10 days) 2. Subacute Phase (11-20 days) 3. Convalescent Phase (21-60 days)
1.
4. Chronic Phase (7 years)
1-2 weeks which lasts up to 4 weeks after onset of fever resolution of fever, rash & lympadenopathy irritability, anorexia & conjunctival injection may persists Desquamation
illness when all the clinical signs have disappeared continues until the ESR returns to normal
Partially-treated UTI
Viral meningitis
Acute abdomen
Viral infections (measles, adenovirus, enterovirus, Epstein-Barr virus) Scarlet fever Staphylococcal scalded skin syndrome Toxic shock syndrome Bacterial cervical lymphadenitis Drug hypersensitivity reactions Steven-Johnson syndrome Juvenile Rheumatoid Arthritis Leptospirosis Mercury hypersensitivity reaction (acrodynia)
Higher risk of coronary artery lesions in patients < 6 mons old 20-25% of untreated cases develop coronary artery abnormalities Mortality rate drops from 1-2% to 0.08% with IVIG Death usually due to myocardial infarction secondary to:
a) Thrombosis of a coronary aneurysm b) Rupture of a large coronary artery
Koren G, et al , J Pediatr (1986) Beiser AS, et al, Am J Cardiol (!998) Daniels SR, et al Am J Dis Child (1987)
6. 7.
Anemia Thrombocytopenia early in the disease & thrombocytosis in a later stage 8. WBC >30,000/mm2 9. ESR > 101 mm/hr and high CRP 10. Elevated ESR and CRP > 30 days or recurrent elevation 11. Low serum albumin & adjusted IgG levels
Koren G, et al , J Pediatr (1986) Beiser AS, et al, Am J Cardiol (!998) Daniels SR, et al Am J Dis Child (1987)
Left coronary angiogram (LAO): huge aneurysm of left anterior descending artery
CT scan
coronary aneurysms, stenosis, intimal hypertrophy, wall abnormalities
MRI
myocardial ischemia
Multi-slice CT scan
Anti-inflammatory dose in acute phase= 80-100 mg/kg/day given every 6 hours Antiplatelet / anti-thrombotic dose: 3-5 mg/kg/day single dose 2-3 days after the fever lyzes; given for 6 weeks & continued indefinitely if coronary abnormalities are observed
KAWASAKI DISEASE
Mechanism of action of IVIG: UNKNOWN With generalized anti-inflammatory effect Possible:
1. 2. 3. 4. 5.
Modulation of cytokine production Neutralization of bacterial superantigens or other etiologic agents Augmentation of T-cell suppressor activity Suppression of antibody synthesis Provision of anti-idiotypic antibodies
Circulation, 2004; 110
Kawasaki Disease:Treatment
3. Heparin/ Warfarin Indicated in large coronary aneurysms with or without thrombus IV heparin or subcutaneous low molecular weight (LMWH) heparin Warfarin dose titrated to target INR of 2 2.5; should be given with low dose aspirin Disadvantage: interactions with Vit K rich food and many drugs
IKI 2008:T. Suzuki et al: as prime therapy, beneficial in those who have high risk of being IVIG non-responders H. Suzuki et al: worse coronary outcomes
KAWASAKI DISEASE
TREATMENT of Patients Who Failed to Respond to Initial Therapy:
Steroids: should be restricted to children in whom 2 infusions of IVIG have been given IV Methylprednisolone: 30 mg/kg for 2-3 hours once daily for 1 to 3 days
Circulation 2004;110
KAWASAKI DISEASE
TREATMENT of Patients Who Failed to Respond to Initial Therapy: Infliximab (anti-TNF-alpha agent)- given with 2nd dose of IVIG in IVIG resistant patients
Others: Plasma exchange Ulinastatin Abciximab Monoclonal antibodies Cytototoxic agents: cyclophosphamide
Circulation, 2004:110
KAWASAKI DISEASE: Long-Term Follow-up Spontaneous regression of aneurysms (50-70%) in 1-2 years Factors which favor regression:
< 1 year age of onset of KD Aneurysm: small size, fusiform morphology, location in distal coronary segment
Kawasaki Disease: Long-Term Follow-up Atherosclerosis, lipid abnormalities, late coronary artery lesions Need for counselling for healthy life-style (proper diet & exercise)
KAWASAKI DISEASE: Important Parameters for Follow-up 1. After baseline 2D-echo, repeat study:
2-4 weeks after onset of illness 4-6 months after illness 9-12 months after illness
Summary
Kawasaki Disease is an acute multisystem vasculitis of infancy and childhood. The standard criteria for diagnosis includes: fever for 5days or more plus the presence of 4/5 of the ff: nonpurulent conjunctivitis, oral mucosal changes, unilateral cervical lymphadenopathy, polymorphous rashes and swelling of hands/feet.
Summary
Treatment is intravenous immunoglobulin and aspirin. Long-term follow-up of children with Kawasaki Disease is advisable.
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