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Kawasaki Disease

Learning Objectives

By the end of this rotation, the resident should be able to:

Recognize and Diagnose

  1. Identify the 5 principal clinical features of KD and recognize key pattern details that support KD (bilateral nonexudative conjunctival injection; polymorphous—not vesicular—rash; extremity edema/erythema with later periungual desquamation)
  2. Apply complete KD criteria and the 2024 "don't-wait" update: with ≥4 principal features, diagnosis can be made with 4 days of fever (experienced clinicians may diagnose at 3 days) to avoid treatment delay
  3. Define illness day correctly (Day 1 = first day of fever) and prioritize treatment within 10 days of fever onset, ideally by illness day 4-5 for complete KD
  4. Order and interpret a resident-appropriate initial evaluation (CBC, CMP with albumin/ALT, CRP/ESR, urinalysis) and use results to support/argue against KD
  5. Recognize findings that are not characteristic of KD (elevate alternate diagnoses): oral ulcerations, exudative pharyngitis, exudative or unilateral conjunctivitis, vesicular rash

Handle Incomplete KD and "Can't-Miss" Presentations

  1. Suspect and evaluate incomplete KD when fever ≥5 days with only 2-3 features, particularly in infants <6 months who present atypically
  2. Act on the principle that KD is a clinical diagnosis without a pathognomonic test—clinical reasoning must drive timely treatment decisions
  3. Recognize Kawasaki Disease Shock Syndrome (KDSS) as a severe phenotype (vasodilatory shock, hypotension, poor perfusion ± myocardial dysfunction) and initiate stabilization + urgent escalation
  4. Differentiate KD from MIS-C: MIS-C has more prominent GI symptoms, cytopenias, and myocardial dysfunction; KD has classic mucocutaneous features and coronary abnormalities

Risk Stratify

  1. Interpret coronary Z-scores from the echo report and classify using AHA categories: normal (<2), dilation (2-2.5), small (2.5-<5), medium (5-<10 and <8 mm), large/giant (≥10 or ≥8 mm)
  2. Identify "high-risk KD at diagnosis": age <6 months and/or RCA or LAD Z-score ≥2.5 → communicate to cardiology early as it may change initial therapy
  3. Recognize IVIG resistance as fever ≥36 hours after completion of initial IVIG infusion—a time-sensitive escalation problem (occurs in 10-20%)
  4. For patients with Z ≥2.5, anticipate more frequent echo surveillance (at least twice weekly during hospitalization until stable)

Initiate Treatment and Escalate Safely

  1. Initiate first-line therapy: IVIG 2 g/kg over 8-12 hours
  2. Apply contemporary aspirin strategy: 30-50 mg/kg/day ÷ q6h (many centers) OR 80-100 mg/kg/day until afebrile, then 3-5 mg/kg/day; avoid NSAIDs while on aspirin
  3. Recognize when primary intensification is indicated (high-risk features) and coordinate early with cardiology for IVIG + adjunctive anti-inflammatory therapy
  4. Know second-line options for IVIG-resistant KD: infliximab 10 mg/kg (KIDCARE showed faster fever resolution vs second IVIG), second IVIG (hemolytic anemia risk), corticosteroids
  5. Monitor for treatment complications: IVIG reactions, hemolysis, aspirin bleeding/gastritis, steroid effects

Antithrombotic Therapy

  1. State the antithrombotic approach by coronary category:
    • Small aneurysm: low-dose aspirin
    • Medium aneurysm: low-dose aspirin + clopidogrel
    • Large/giant aneurysm: low-dose aspirin + anticoagulation (warfarin, LMWH, or DOAC per cardiology)
  2. Recognize the key distinction: medium aneurysm = dual antiplatelet; anticoagulation is reserved for large/giant

Communicate and Coordinate

  1. Explain to families the "why we follow you" logic: coronary status drives prognosis, surveillance, antithrombotic strategy, and activity counseling
  2. Recognize and escalate chest pain/syncope in a patient with known aneurysms as a potential coronary emergency requiring immediate cardiology/PICU evaluation
  3. Consult cardiology appropriately: at diagnosis (all cases), urgently (CAA or IVIG resistance), emergently (shock, myocardial dysfunction, coronary ischemia)
  4. Provide vaccine guidance: defer live vaccines (MMR, varicella) for 11 months after high-dose IVIG

Key Guidelines

2024 AHA Scientific Statement: Update on Diagnosis and Management of Kawasaki Disease Jone PN, Tremoulet A, et al. Circulation. 2024;150(23):e481-e500. PMID: 39534969 | DOI: 10.1161/CIR.0000000000001295

Quick Reference: Kawasaki Treatment Algorithm

Key Updates (Resident-Facing)

  • KD remains a clinical diagnosis (no single confirmatory test); diagnose and treat within 10 days of fever onset (ideal ~day 4-5 for complete KD)
  • Early diagnosis: with ≥4 principal features, diagnosis can be made with 4 days of fever (experienced clinicians may diagnose at 3 days)
  • High-risk features in North American practice include age <6 months and/or baseline RCA or LAD Z-score ≥2.5 → consider intensified primary therapy
  • IVIG resistance definition: fever ≥36 hours after completion of initial IVIG
  • Aspirin dose in acute phase is institution-dependent; many centers use 30-50 mg/kg/day (evidence has not shown clear coronary outcome differences vs higher doses)
  • Medium aneurysm thromboprophylaxis: aspirin + clopidogrel (not routine anticoagulation)
  • Large/giant aneurysm: anticoagulation options include warfarin, LMWH, or DOAC (cardiology-directed)

Diagnostic Criteria

Complete Kawasaki Disease

Fever ≥5 days PLUS ≥4 of 5 principal features: 1. Bilateral bulbar conjunctival injection (non-exudative) 2. Oral mucous membrane changes (strawberry tongue, cracked lips) 3. Polymorphous rash 4. Extremity changes (erythema, edema, desquamation) 5. Cervical lymphadenopathy (≥1.5 cm, usually unilateral)

Incomplete Kawasaki Disease

Fever ≥5 days + 2-3 features + laboratory/echo findings supporting diagnosis

Coronary Artery Classification (Z-scores)

Category Z-score Management Implications
No involvement <2.0 Standard treatment
Dilation only 2.0 to <2.5 Standard + closer follow-up
Small aneurysm 2.5 to <5.0 Consider intensification; ASA alone
Medium aneurysm 5.0 to <10 and <8 mm Intensify; ASA + clopidogrel
Large/Giant aneurysm ≥10 or ≥8 mm Aggressive therapy; ASA + anticoagulation

Treatment

Initial Treatment (All Patients)

  • IVIG 2 g/kg single infusion over 8-12 hours
  • Aspirin (follow institutional pathway):
  • Acute phase: 30-50 mg/kg/day ÷ q6h (many North American centers) OR 80-100 mg/kg/day ÷ q6h (traditional)
  • Evidence has not shown clear coronary outcome differences between high- vs low-dose strategies
  • Continue until afebrile 48-72 hours
  • Then low-dose: 3-5 mg/kg/day for 6-8 weeks minimum (if no CAA)
  • Avoid NSAIDs (e.g., ibuprofen) while on aspirin — reduces antiplatelet effect

Treatment Intensification (High-Risk Patients)

High-risk = Z-score ≥2.5 OR age <6 months OR KDSS

Options (coordinate with cardiology): 1. Corticosteroids: IV methylprednisolone 2 mg/kg/day × 3 days → oral prednisone taper over 2-3 weeks (per RAISE protocol) 2. Infliximab: 10 mg/kg IV (per KIDCARE trial) 3. Second IVIG dose: 2 g/kg 4. Anakinra: IL-1 receptor antagonist (refractory cases) 5. Cyclosporine: For refractory cases

IVIG Resistance

Definition: Persistent or recrudescent fever ≥36 hours after completion of IVIG infusion

Second-line options (institution/cardiology-directed): - Infliximab 10 mg/kg — KIDCARE showed faster fever resolution and shorter hospitalization vs second IVIG - Second IVIG dose (2 g/kg) — risk of hemolytic anemia with additional IVIG - Corticosteroids (if not already given) - Anakinra, cyclosporine for refractory disease

Thromboprophylaxis by Z-score

Coronary Category Z-score Antithrombotic (Resident-Level Summary)
No involvement <2.0 Low-dose ASA × 6 weeks, then stop if normal
Dilation only 2.0-2.5 Low-dose ASA; stop if normal at follow-up
Small aneurysm 2.5 to <5.0 Low-dose ASA until regression
Medium aneurysm 5.0 to <10 and <8 mm Low-dose ASA + clopidogrel
Large/Giant aneurysm ≥10 or ≥8 mm Low-dose ASA + anticoagulation (warfarin INR 2-3, LMWH, or DOAC) ± dual antiplatelet

Key Distinction

Medium aneurysm = dual antiplatelet therapy (aspirin + clopidogrel). Anticoagulation is reserved for large/giant aneurysms only.

Long-term Surveillance

CAA Category Imaging Frequency
No CAA Echo at 1-2 weeks and 4-6 weeks; discharge if normal
Small CAA Echo every 3-6 months until regression
Medium CAA Echo + stress imaging every 6-12 months
Giant CAA Echo every 3-6 months + CT/MR angiography annually

Critical Points

  • Z-score system: Use same equation across time (PHN recommended)
  • Most coronary abnormalities regress (especially if Z-score <5)
  • Giant CAAs rarely regress and have highest risk for MI
  • Long-term cardiovascular risk even after CAA regression

Board Pearls

Pearl: Z-score ≥2.5 or age <6 months = HIGH RISK

Intensify initial treatment beyond standard IVIG alone

Pearl: IVIG resistance occurs in ~15-20% of patients

Options: second IVIG, steroids, infliximab, anakinra, cyclosporine

Pearl: Use PHN Z-scores consistently

Same equation must be used over time for accurate trending

Self-Assessment

Q1: A 4-month-old presents with 5 days of fever, bilateral conjunctival injection, and rash (only 2 principal features). Labs show CRP 8 mg/dL, albumin 2.8, platelets 450K. What is the most important next step?

Answer **Answer**: Treat as **incomplete Kawasaki disease** with IVIG 2 g/kg + consider treatment intensification **Rationale**: This infant has incomplete KD (fever ≥5 days + 2-3 features + supportive labs). Age <6 months is a **high-risk feature** per 2024 AHA guidelines—infants often present atypically with fewer features. High-risk patients warrant treatment intensification (IVIG + corticosteroids or infliximab). Don't wait for more features to develop. **Key learning point**: Infants <6 months are the highest-risk group and often missed because they present atypically.

Q2: A 3-year-old with Kawasaki disease received IVIG starting at 8 AM; the infusion finished at 6 PM. At 10 AM the next day (16 hours later), the child still has fever. The team wants to give a second IVIG dose. Is this appropriate?

Answer **Answer**: **No—it is too early to diagnose IVIG resistance** **Rationale**: IVIG resistance is defined as persistent or recrudescent fever **≥36 hours after completion** of the initial IVIG infusion. This child is only 16 hours post-completion. The 2024 AHA update emphasizes waiting the full 36 hours before declaring resistance. Premature retreatment exposes patients to unnecessary risk (hemolytic anemia with additional IVIG) and cost. **Key learning point**: Count from when IVIG **finishes**, not when it starts. Wait 36 hours.

Q3: A 5-year-old with prior Kawasaki disease has a known medium-sized coronary aneurysm (LAD Z-score 7.2). What antithrombotic regimen is indicated per 2024 AHA guidelines?

Answer **Answer**: Low-dose aspirin **+ clopidogrel** (dual antiplatelet therapy) **Rationale**: Medium aneurysm (Z 5-<10 and <8 mm) = **dual antiplatelet therapy** (aspirin + clopidogrel or ticagrelor). Anticoagulation is reserved for **large/giant aneurysms** (Z ≥10 or ≥8 mm). This is a common board/clinical confusion point—many assume anticoagulation is needed for medium aneurysms, but the 2024 AHA statement clarifies: medium = dual antiplatelet, large/giant = anticoagulation. **Key learning point**: Medium aneurysm = ASA + clopidogrel. Anticoagulation is for large/giant only.

References

  • Jone PN, Tremoulet A, et al. Circulation. 2024;150:e481-e500. PMID: 39534969 — 2024 AHA Scientific Statement
  • McCrindle BW, et al. Circulation. 2017;135:e927-e999. PMID: 28356445 — 2017 AHA Scientific Statement (prior guideline)
  • Kobayashi T, et al. Lancet. 2012;379:1613-20. PMID: 22405251 — RAISE study (corticosteroids)
  • Tremoulet AH, et al. J Pediatr. 2023;262:113594. PMID: 37480965 — KIDCARE trial (infliximab vs second IVIG)