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Pediatrics›Condition·Updated Jul 11, 2026·v1

Kawasaki Disease

Kawasaki disease is an acute self-limited vasculitis of young children that requires prompt recognition and treatment with IVIG and aspirin within 10 days of fever onset to prevent coronary artery aneurysms. Risk stratification using the Kobayashi score identifies patients who benefit from adjunctive corticosteroids or ciclosporin. Long-term management is dictated by coronary artery status, with lifelong surveillance and antithrombotic therapy for persistent aneurysms.

High Evidence234 references·5,263 words·22 min read·v1
Kawasaki diseasevasculitiscoronary artery aneurysmpediatricsIVIGincomplete KawasakiKobayashi scoreMIS-C

Quick Reference

RxDrug of choiceIVIG 2 g/kg single dose plus aspirin (high-dose acutely, then low-dose)
AltAlternativesInfliximab 5 mg/kg (IVIG resistance); prednisolone 2 mg/kg/day for 15 days (high-risk); ciclosporin 5 mg/kg/day for 5 days (high-risk); methylprednisolone pulse 30 mg/kg/day (refractory)
⊘AvoidNon-dihydropyridine CCBs (diltiazem, verapamil); high-dose aspirin beyond acute phase; live vaccines within 11 months of IVIG
DxTest of choiceEchocardiography with coronary artery z-score measurement
ScKey scoreKobayashi score (≥4 points predicts IVIG resistance; sensitivity 71% in Japanese, poor in non-Asian)
→When to referPediatric cardiology for any coronary artery abnormality; pediatric rheumatology for refractory disease or MAS; interventional cardiology for ischemia or stenosis
Early IVIG (within 10 days of fever) reduces coronary aneurysm risk from 25% to 5%; add corticosteroids or ciclosporin for high-risk patients (Kobayashi ≥5); lifelong surveillance for persistent aneurysms.
Kawasaki disease (KD) is an acute, self-limited systemic vasculitis of unknown etiology, primarily affecting children <5 years, and the leading cause of acquired heart disease in developed countries [2,8]. Early recognition and treatment with IVIG within 10 days of fever onset are critical to prevent coronary artery aneurysms (CAA).

Overview and Recommendations

Background

  • •Kawasaki disease (KD) is an acute, self-limited systemic vasculitis of unknown etiology that predominantly affects children under 5 years of age, with a peak incidence at 12-24 months; it is the leading cause of acquired heart disease in children in developed countries, accounting for 20 per 100,000 children <5 years in the United States and up to 359 per 100,000 in Japan.
  • •The pathophysiologic hallmark is a dysregulated immune response, likely triggered by an infectious pathogen in a genetically susceptible host, that drives a cascade of endothelial activation, neutrophilic infiltration, and pro-inflammatory cytokine release (IL-1, TNF-α, IL-6) targeting medium-sized arteries, especially the coronary arteries. This cytokine storm leads to destruction of the internal elastic lamina and collagen degradation, resulting in coronary artery aneurysms (CAA) if unchecked.
  • •Genome-wide association studies have identified susceptibility loci (e.g., ITPKC, CASP3) that dysregulate immune cell activation and apoptosis, explaining the striking ethnic predilection: children of Japanese and Korean ancestry have the highest incidence, and familial clustering is observed.
  • •Untreated KD carries a 15-25% risk of coronary artery aneurysms; with timely IVIG (within 10 days of fever onset), the risk drops to 5-7%. The paradigm shift from aspirin alone to IVIG-based therapy, established by the landmark Newburger trial (1991), reduced CAA incidence dramatically and remains the cornerstone of management.
  • •Cases are classified as complete KD (fever ≥5 days plus ≥4 of 5 principal clinical criteria), incomplete KD (fewer criteria but with ancillary laboratory or echocardiographic evidence), and Kawasaki disease shock syndrome (KDSS), a severe variant with hypotension and poor perfusion seen in ~5% of cases.

Evaluation

  • •Suspect KD in any child with unexplained fever for ≥5 days, especially if the fever is high-spiking (>39°C), remittent, and unresponsive to antipyretics. Ask about the five principal clinical features: bilateral non-exudative conjunctival injection, oral mucous membrane changes (erythema, cracked lips, strawberry tongue, pharyngeal injection), polymorphous truncal rash, extremity changes (erythema/edema of palms/soles in acute phase, periungual desquamation in subacute phase), and cervical lymphadenopathy (≥1.5 cm, usually unilateral, anterior).
  • •Examine for the classic mucocutaneous findings: painless conjunctival injection without exudate; strawberry tongue; diffuse oropharyngeal erythema; erythematous, non-vesicular rash; and non-pitting edema of hands and feet. Note that lymphadenopathy is the least frequent classic sign (present in only ~24% of cases). In infants <6 months, the presentation may be incomplete with only fever and irritability, yet these infants carry the highest risk of CAA.
  • •Order baseline laboratory studies: CRP (typically ≥3 mg/dL, often >10 mg/dL), ESR (≥40 mm/h), complete blood count with differential (WBC ≥15,000/mm³ with left shift, normocytic anemia, platelet count ≥450,000 after day 7), serum albumin (≤3.0 g/dL suggests inflammation), liver enzymes (ALT elevation), and urinalysis (sterile pyuria ≥10 WBC/hpf). Also check sodium (≤135 mmol/L is associated with IVIG resistance).
  • •Obtain a transthoracic echocardiogram at diagnosis to measure coronary artery internal diameters and calculate z-scores adjusted for body surface area. A z-score ≥2.5 defines coronary artery dilation or aneurysm. Repeat echocardiography at 1-2 weeks and 4-6 weeks after treatment; if initially normal, the likelihood of later abnormality is only 1.7%.
  • •Diagnose complete KD when fever ≥5 days plus ≥4 of 5 principal clinical features are present. Diagnose incomplete KD when fever is present with 2-3 principal features but echocardiography shows coronary z-score ≥2.5, or when supplemental laboratory criteria are met (CRP ≥3 mg/dL or ESR ≥40 mm/h plus ≥3 of: albumin ≤3.0 g/dL, anemia for age, elevated ALT, thrombocytosis ≥450,000, WBC ≥15,000, urine WBC ≥10/hpf).
  • •Consider the differential diagnosis: multisystem inflammatory syndrome in children (MIS-C), older age, more cardiac dysfunction, shock, lymphopenia, positive SARS-CoV-2 serology; viral exanthems (adenovirus, measles, enterovirus), conjunctival exudate, lower fever, respiratory symptoms, positive PCR; scarlet fever, sore throat, sandpaper rash, group A streptococcus on culture; staphylococcal/streptococcal toxic shock syndrome, hypotension, multisystem organ failure, desquamation; juvenile idiopathic arthritis (systemic onset), quotidian fever, salmon-pink rash, arthritis, serositis; drug reaction with eosinophilia (DRESS), eosinophilia, lymphadenopathy, medication history. A positive respiratory viral PCR does not exclude KD.
  • •Stratify risk for IVIG resistance using validated scoring systems: the Kobayashi score (≥4 points indicates high risk) uses sodium, neutrophil percentage, AST, platelet count, CRP, age, and illness days; the Egami score (≥3 points) uses similar variables. These scores perform best in Japanese populations and have limited sensitivity in non-Asian cohorts; therefore, clinical judgment remains essential. The neutrophil percentage-to-albumin ratio (NPAR) is a strong predictor of IVIG resistance (OR 15.53 per unit increase).
  • •Identify red flags for severe disease: hypotension or shock (KDSS) requiring vasoactive support, macrophage activation syndrome (MAS) with persistent fever, hepatosplenomegaly, cytopenias, and hyperferritinemia, and giant coronary artery aneurysms (internal diameter ≥8 mm or z-score ≥10). These patients require immediate escalation of care and intensive monitoring.

Management

  • •Initiate IVIG 2 g/kg as a single intravenous dose over 10-12 hours as soon as the diagnosis of KD is established, and within 10 days of fever onset. Do not delay treatment for further testing once the diagnosis is likely.
  • •Start high-dose aspirin 80-100 mg/kg/day orally divided every 6 hours during the acute phase; continue until the patient is afebrile for 48 hours, then reduce to low-dose aspirin 3-5 mg/kg/day once daily. A recent RCT (Kuo et al., 2025) demonstrated noninferiority of IVIG alone vs IVIG plus high-dose aspirin for preventing coronary artery lesions at 6 weeks, suggesting that high-dose aspirin may be omitted in the acute phase, but current guidelines still recommend it for anti-inflammatory and antipyretic effects.
  • •For patients predicted to be at high risk for IVIG resistance (e.g., Kobayashi score ≥5, Egami score ≥3), consider adding adjunctive therapy from the outset. The RAISE trial showed that prednisolone 2 mg/kg/day for 15 days after normalization of C-reactive protein, added to IVIG and aspirin, reduced CAA incidence from 23% to 3% (NNT=5). The KAICA trial demonstrated that ciclosporin 5 mg/kg/day for 5 days plus IVIG reduced CAA from 31% to 14% (NNT=6).
  • •If fever persists or recurs 36 hours to 7 days after completion of IVIG (IVIG resistance), administer a second IVIG dose (2 g/kg) OR infliximab 5 mg/kg IV over 2 hours. Infliximab may provide faster fever resolution and shorter hospitalization. For highly refractory cases, consider methylprednisolone pulse 30 mg/kg IV (max 1 g) daily for 1-3 days, often combined with another IVIG dose.
  • •Monitor laboratory markers (CRP, ESR, CBC) daily during the acute phase. Watch for IVIG adverse effects: infusion reactions, aseptic meningitis, hemolysis. For aspirin, monitor for GI bleeding and Reye syndrome (avoid during influenza or varicella). For corticosteroids, monitor for hyperglycemia and hypertension. For infliximab, watch for infusion reactions and infections. For ciclosporin, monitor renal function and blood pressure.
  • •Perform echocardiography at baseline, 1-2 weeks, and 4-6 weeks after treatment. Measure coronary artery z-scores. If no coronary abnormalities are detected at 6 weeks, low-dose aspirin can be discontinued. If small or medium aneurysms persist (z-score 2.5 to <10), continue low-dose aspirin indefinitely and perform echocardiography every 6-12 months. For giant aneurysms (z-score ≥10 or absolute diameter ≥8 mm), add anticoagulation with warfarin (target INR 2.0-3.0) or edoxaban (weight-based dosing) to low-dose aspirin, and perform echocardiography every 3-6 months plus stress imaging after age 10.
  • •Consider atorvastatin 0.5 mg/kg/day (max 20 mg) for persistent aneurysms, especially giant aneurysms, for its anti-inflammatory effects; titrate to LDL reduction >30% if tolerated. A phase I/IIa trial showed safety in children with CAA, but efficacy data are pending.
  • •What NOT to do: Do not use corticosteroids as primary therapy in unselected patients (the 2026 NEJM trial of 3208 patients showed no benefit in CAA reduction). Do not use high-dose aspirin beyond the acute febrile phase (increases risk of Reye syndrome). Do not use non-dihydropyridine CCBs (diltiazem, verapamil) as they exacerbate heart failure. Do not administer live virus vaccines (MMR, varicella) for 11 months after IVIG due to potential interference.
  • •Refer to pediatric cardiology promptly if any coronary artery abnormality is detected. Refer to pediatric rheumatology for refractory disease or suspected MAS. Refer for interventional cardiology or cardiac surgery if significant coronary stenosis or ischemia develops. Discharge criteria: afebrile for 24-48 hours, tolerating oral intake, no evidence of cardiac complications, and follow-up echocardiography scheduled.

Board Review — High Yield

  • •Complete KD criteria, Fever ≥5 days plus ≥4 of 5: bilateral conjunctivitis, oral changes, rash, extremity changes, cervical lymphadenopathy.
  • •Incomplete KD, Fever ≥5 days with 2-3 criteria + echocardiographic (z-score ≥2.5) or laboratory evidence (CRP ≥3, ESR ≥40, albumin ≤3.0, anemia, ALT elevation, thrombocytosis, sterile pyuria).
  • •IVIG dose, 2 g/kg single infusion; must be given within 10 days of fever onset to prevent coronary aneurysms.
  • •Kobayashi score, Predicts IVIG resistance; includes sodium, neutrophil %, AST, platelet count, CRP, age, illness days; score ≥4 identifies high-risk patients.
  • •RAISE trial, Prednisolone 2 mg/kg/day for 15 days added to IVIG in high-risk patients reduced CAA from 23% to 3% (NNT=5).
  • •IVIG resistance management, Second IVIG or infliximab 5 mg/kg; methylprednisolone pulse for refractory cases.
  • •Giant aneurysm definition, Internal diameter ≥8 mm or z-score ≥10; requires dual antithrombotic therapy (aspirin + warfarin/edoxaban) and lifelong surveillance.
  • •Aspirin pearls, High-dose (80-100 mg/kg/day) for anti-inflammatory effect acutely; low-dose (3-5 mg/kg/day) for antiplatelet effect long-term. Avoid Reye syndrome by discontinuing during viral illness.
  • •MIS-C vs KD, MIS-C patients are older, have more cardiac dysfunction and shock, lymphopenia, thrombocytopenia, and positive SARS-CoV-2 serology; management differs with steroids often first-line.
  • •Live vaccine delay, Defer MMR and varicella for 11 months after IVIG due to antibody interference.

Deep Dive — Evidence Details

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