Summary

Kawasaki Disease (KD) is an acute, self-limiting systemic vasculitis affecting medium-sized arteries, predominantly occurring in children under 5 years. It is the leading cause of acquired heart disease in children in developed countries. The primary concern is the development of coronary artery aneurysms (CAAs), which occur in 15-25% of untreated cases but can be reduced to less than 5% with prompt treatment. Diagnosis is clinical, based on fever for ≥5 days plus ≥4 of 5 principal features (the "CREAM" criteria). Treatment must be initiated within 10 days of fever onset with IV Immunoglobulin (IVIG) and Aspirin. [1,2]

Clinical Pearls

"Fever = Clock Ticking": The 10-day treatment window is critical. Every day of untreated Kawasaki increases coronary artery risk.

Incomplete Kawasaki is Still Kawasaki: Children with fever ≥5 days and only 2-3 criteria may have "incomplete" KD. Have a low threshold to treat if inflammatory markers elevated and other causes excluded.

"CREAM" Mnemonic: Conjunctivitis, Rash, Extremity changes, Adenopathy, Mucosal changes.

Aspirin in a Child: Kawasaki is one of the FEW paediatric conditions where Aspirin is used (risk of Reye's syndrome applies only in influenza/varicella context).

Kawasaki Disease is a Medical Emergency. It is the only common paediatric vasculitis where a single therapeutic intervention (IVIG) can prevent lifelong cardiac disease.

• The Window of Opportunity: Efficacy of IVIG is highest in the first 10 days. After this, the inflammatory cascade may become autonomous.
• The Silent Killer: A child may look "well" between fevers, but their coronary arteries are actively inflamed.

The "Incomplete" Trap

The term "Atypical Kawasaki" is outdated. Use "Incomplete KD".

• Scenario: Infant < 6 months with fever > 7 days and only red lips.
• Risk: Infants have the highest risk of aneurysms yet often present with fewest clinical signs.
• Guideline: Mandatory Echo for any infant with prolonged unexplained fever.

Despite 50 years of research, the cause remains elusive. The prevailing theory is:

1. Genetic Susceptibility:
   • Asian ancestry confers higher risk.
   • polymorphisms in ITPKC (T-cell activation) and CASP3 (apoptosis) are linked.
   • Siblings have 10x higher risk.
2. Infectious Trigger:
   • The disease behaves like an infection (epidemics, seasonality, rare in <3 months due to maternal antibody).
   • Candidates: Retroviruses, Superantigens (Staph/Strep), Candida, RNA viruses.
3. Abnormal Immune Response:
   • Instead of clearing the pathogen, the immune system launches a "Superantigen" response.
   • Massive T-cell activation + Cytokine Storm (TNF-a, IL-1, IL-6).

The destruction of the coronary artery occurs in 4 stages (Naoe Classification):

Stage 1: Acute Necrotizing Arteritis (Days 0-12)

• Neutrophils infiltrate the vessel wall (Intima and Media).
• Endothelium is stripped away.
• The internal elastic lamina begins to fragment.
• Clinical: High fever, rash.

Stage 2: Subacute / Chronic Vasculitis (Days 12-25)

• Inflammation shifts to Lymphocytes (T-cells, Plasma cells).
• Pan-arteritis: The entire wall is inflamed.
• Myofibroblast Proliferation: The wall weakens and dilates (Aneurysm forms).
• Clinical: Fever settles (usually), peeling fingers, thrombocytosis.

Stage 3: Luminal Myointimal Proliferation (Days 28-60)

• The body attempts to heal.
• Smooth muscle cells proliferate in the lumen.
• Risk: This thickening can cause Stenosis of the coronary artery.

Stage 4: Scarring (Months to Years)

• Fibrosis leads to stiff, non-compliant vessels.
• Aneurysms may "remodel" (shrink) but the vessel is never normal.
• Risk: Calcification and Early Atherosclerosis.

Why the Coronary Arteries?

Why not the renal or femoral arteries?

• Theory: The coronary arteries are under high shear stress and have specific endothelial receptors that matched the pathogenic trigger.
• Note: Other vessels (Axillary, Iliac, Renal) can be affected but are rare ("Systemic KD").

Diagnosis requires Fever ≥ 5 days + 4 of 5 features.

• Note: In expert hands, fewer criteria are needed (Incomplete KD).

1. Fever (The Engine)

• Character: High grade (>39°C), Remittent (doesn't touch baseline).
• Response: Minimally responsive to antipyretics (Paracetamol/Ibuprofen). Antibiotics have NO effect.
• Duration: Without treatment, lasts 11-14 days. With IVIG, resolves in 24 hours.

2. Conjunctivitis

• Type: Bilateral, Bulbar injection.
• Appearance: "Dry" (Non-purulent, no discharge).
• The Sign: Limbic Sparing (A clear halo of white sclera immediately around the iris, distinguishing it from viral conjunctivitis).
• Uveitis: Anterior uveitis is present in 70% (seen on slit lamp).

3. Rash

• Appearance: Polymorphous (can look like anything... EXCEPT vesicles/bullae).
• Distribution: Generalised.
• The Sign: Perineal Desquamation (Redness and peeling in the nappy area). Often the first sign.
• BCG Site: Reactivation (Induration and erythema) at the old BCG scar. (Specific to KD).

4. Extremity Changes

• Acute Phase (Week 1):
  • Erythema: Palms and Soles turn fuschia red.
  • Oedema: Indurated swelling of hands/feet. The child refuses to walk or hold things (painful).
• Subacute Phase (Week 2-3):
  • Periungual Desquamation: Sheets of skin peel from the fingertips and toes.

5. Adenopathy (Cervical)

• Frequency: The LEAST common feature (50%).
• Character: Unilateral, >1.5cm, Anterior Cervical triangle.
• Consistency: Firm, non-fluctuant. (Differentiates from Bacterial Lymphadenitis which is fluctuant/tender).

6. Mucosal Changes

• Lips: Bright red, cracked, fissured, bleeding.
• Tongue: Strawberry Tongue (Hypertrophy of fungiform pappilae on a red base).
• Pharynx: Diffuse erythema.
• Exclusions: NO ulcers (Herpes), NO exudate (Strep/EBV).

Crucial for preventing missed diagnoses in infants. Scenario: Child with Fever ≥ 5 days and only 2 or 3 criteria. Action:

1. Assess Patient: Is there another explanation? (Viral swab? Urine?).
2. Blood Test: Check CRP and ESR.
   • If CRP < 30 and ESR < 40: Monitor daily.
   • If CRP ≥ 30 or ESR ≥ 40: Proceed to Step 3.
3. Supplemental Laboratory Criteria (Need ≥ 3):
   • Albumin < 30 g/L.
   • Anaemia for age.
   • Elevation of ALT.
   • Platelets > 450 (after day 7).
   • WBC > 15,000.
   • Urine WBC > 10/hpf.
4. Decision:
   • If ≥ 3 supplemental criteria: TREAT with IVIG.
   • If < 3: Echocardiogram. If positive -> Treat.

KD is not just skin deep.

• Neurological: Extreme Irritability is classic (Aseptic meningitis).
• Gastrointestinal: Hydrops of Gallbladder (RUQ pain, jaundice). Diarrhoea (Common diagnostic confusion).
• Musculoskeletal: Arthritis (small joints).
• Genitourinary: Sterile Pyuria (Urethritis/Cystitis).
  • Trap: A child with fever and pyuria is diagnosed with UTI -> given antibiotics -> Fever persists -> Missed KD.
  • Clue: Pyuria is Sterile (Negative culture).

Classic Kawasaki Disease Criteria

Diagnosis requires: Fever ≥5 days PLUS ≥4 of 5 Principal Features (CREAM):

Incomplete Kawasaki Disease

• Definition: Fever ≥5 days + 2 or 3 principal criteria (not the full 4).
• Importance: Still at risk for coronary aneurysms. Requires high index of suspicion.
• Workup: CRP/ESR, FBC, LFTs, Urine (sterile pyuria), Echo. Treat if inflammatory markers elevated and no other diagnosis.

Other Clinical Features (Supportive)

1. The "Golden Hour" (Diagnostic Workup)

• Admit: All suspected cases.
• Cardiac Monitor: Watch for arrhythmias.
• Echocardiogram:
  • Must not delay treatment. If high suspicion, treat before Echo.
  • Sedation: Often required for young children (Chloral Hydrate).
  • Views: Assessment of LCA, LAD, LCx, and RCA. Z-scores calculated.

2. IVIG Infusion Protocol

• Dose: 2 grams/kg (A massive fluid load).
• Calculation: A 10kg child receives 20g (Often 4 bottles).
• Administration:
  • Start slow (0.01 ml/kg/min) for 30 mins to watch for anaphylaxis.
  • Increase rate every 30 mins.
  • Total infusion time: 10-12 hours.
• Warning: Aseptic Meningitis is a common side effect of high-dose IVIG (Severe headache 24h later).
• Vaccines: Defer live vaccines (MMR, Varicella) for 11 months after IVIG (Antibodies neutralise the vaccine).

3. Aspirin Taper Strategy

• Acute Phase (Anti-inflammatory):
  • Dose: 30-50 mg/kg/day (divided 4 times daily).
  • Target: Until child is afebrile for 48 hours.
• Convalescent Phase (Anti-platelet):
  • Dose: 3-5 mg/kg/day (Once daily).
  • Target: Continue for 6-8 weeks until follow-up Echo confirms normal coronaries.
• Reye's Syndrome Warning: If the child gets Influenza or Chickenpox while on Aspirin, risk of Reye's (Liver failure/Encephalopathy).
  • Advice: Varicella vaccine recommended? Stop Aspirin and switch to Clopidogrel (requires specialist advice) if chickenpox develops?

4. Corticosteroids (The RAISE Study)

• Indication: High risk of IVIG resistance (Kobayashi Score > 5 - mainly validated in Japan).
• Regimen: IV Methylprednisolone alongside primary IVIG.
• Rescue: First line for IVIG-resistant cases.

Case 1: The "Antibiotic Fail"

History: 3-year-old boy. 6 days fever. Seen by GP, given Amoxicillin for "Tonsillitis". Fever persisted. Exam: Red cracked lips. BCG scar inflamed. Management: Admitted. IVIG started Day 7. Result: Fever broke within 4 hours ("Lazarus Effect"). Echo normal. Learning: Antibiotics do NOT touch Kawasaki fever.

Case 2: The "Incomplete" Infant

History: 4-month-old girl. 8 days fever. Irritable. No rash. Urine dip: Leucocytes ++ (Sterile). Trap: Treated for UTI. Urine culture came back negative. Fever continued. Investigation: Echo done on Day 10 showed Giant Aneurosomes. Learning: Infants with prolonged fever and sterile pyuria MUST have an Echo.

Case 3: The "Shock" Presentation (Kawasaki Shock Syndrome)

History: 5-year-old. Hypotensive, Tachycardic. Suspected Sepsis. Features: Rash, Strawberry tongue. Troponin elevated. Diagnosis: Kawasaki Shock Syndrome (subset with severe myocardial inflammation). Management: ICU support + IVIG + Steroids immediately.

Management Algorithm

       SUSPECTED KAWASAKI DISEASE
       (Child less than 5yrs + Fever ≥5 days + Clinical Features)
                     ↓
       DOES CHILD MEET DIAGNOSTIC CRITERIA?
       (Fever ≥5 days + ≥4/5 CREAM features)
    ┌────────────────┴────────────────┐
   YES (Classic KD)              NO (Incomplete KD?)
    ↓                                 ↓
 CONFIRM DIAGNOSIS            CHECK CRP/ESR + FBC
 BASELINE ECHO                (If CRP≥3 or ESR≥40 + 2-3 features +
 START TREATMENT              no other diagnosis → Treat as KD)
    ↓                                 ↓
       TREATMENT (WITHIN 10 DAYS OF FEVER)
    ┌──────────────────────────────────────┐
    │  IV IMMUNOGLOBULIN (IVIG)            │
    │  - 2 g/kg as SINGLE DOSE over 12h    │
    │                                      │
    │  HIGH-DOSE ASPIRIN                   │
    │  - 30-50 mg/kg/day in 4 doses        │
    │  - Continue until afebrile 48h       │
    │                                      │
    │  THEN LOW-DOSE ASPIRIN               │
    │  - 3-5 mg/kg/day                     │
    │  - Continue for 6-8 weeks            │
    │  - Lifelong if coronary aneurysm     │
    └──────────────────────────────────────┘
                     ↓
       IVIG RESISTANT?
       (Fever persists/recurs 36h after IVIG)
    ┌────────────────┴────────────────┐
   YES                               NO
    ↓                                 ↓
 SECOND DOSE IVIG              FOLLOW-UP ECHO
 (2 g/kg)                      (2 weeks, 6-8 weeks)
 +/- IV METHYLPREDNISOLONE
 +/- INFLIXIMAB (Anti-TNF)
                     ↓
       CORONARY ARTERY ANEURYSM?
    ┌────────────────┴────────────────┐
   YES                               NO
    ↓                                 ↓
 ANTIPLATELET +/- ANTICOAGULANT    LOW-DOSE ASPIRIN
 (Aspirin + Warfarin/LMWH           for 6-8 weeks
  for medium/giant aneurysms)       (Then stop if Echo normal)
 + Cardiology Follow-Up

First-Line Treatment

IVIG-Resistant Kawasaki

• Definition: Fever persisting or recurring ≥36 hours after completing IVIG.
• Occurs in 10-20%.
• Management:
  • Second Dose IVIG (2 g/kg).
  • IV Methylprednisolone (30 mg/kg/day for 1-3 days).
  • Infliximab (Anti-TNF, 5 mg/kg) – increasingly used.
  • Consider Cyclosporine in refractory cases.

Management of Coronary Artery Aneurysms

• With Treatment (less than 10 days): CAA risk less than 5%. Excellent prognosis.
• Without Treatment: CAA risk ~25%. Long-term risk of MI, sudden death.
• Small Aneurysms: 50-70% regress within 1-2 years.
• Giant Aneurysms: Do NOT regress. Lifelong cardiology follow-up and anticoagulation.
• Late Complications: MI can occur years/decades after acute illness, especially if CAA persists.

Key Guidelines

Landmark Trials

• Newburger et al. (1991): IVIG reduces CAA from 23% to 5%.

Standards for Paediatric Units treating Kawasaki Disease:

What is Kawasaki Disease?

Kawasaki Disease is an illness that causes inflammation of blood vessels throughout the body, particularly affecting the heart's blood vessels (coronary arteries). It mainly affects children under 5 years old.

What are the symptoms?

The main features are a high fever lasting at least 5 days, along with red eyes, a rash, swollen hands and feet, a swollen lymph node in the neck, and red lips and tongue.

Why is it serious?

If not treated quickly, Kawasaki Disease can cause weakening and ballooning (aneurysms) of the coronary arteries. This can lead to heart problems later in life. Fortunately, with early treatment, this risk is greatly reduced.

How is it treated?

We give a medication called Immunoglobulin (IVIG) through a drip, along with Aspirin. This calms down the inflammation and protects the heart. Most children recover fully, especially if treated within 10 days of the fever starting.

OSCE Station: Counselling Parents

Scenario: You are the Registrar. 3-year-old child diagnosed with Kawasaki Disease. Explain the diagnosis and treatment (IVIG) to the parents. Key Explanations:

1. The Disease: "It is an inflammation of the blood vessels. We don't know the exact cause, but it behaves like an infection."
2. The Heart: "The main reason we treat this aggressively is to protect the heart. Without treatment, 1 in 4 children develop widening of the coronary arteries."
3. The Treatment (IVIG):
   • "It is a blood product (antibodies from donors)."
   • "It works by 'mopping up' the inflammation."
   • Risks: Transfusion reaction (chivers, fever), Anaphylaxis (rare), Fluid overload.
4. Vaccines: "You must delay MMR and Chickenpox vaccines for 11 months, as the treatment stops them working."
5. Follow-up: "He will need heart scans (Echos) at 2 weeks and 6 weeks."

Viva: The "Mechanism" of IVIG

Examiner: "How does IVIG actually work in Kawasaki Disease?" Candidate: "The exact mechanism is unknown, but theories include:

1. Fc Receptor Saturation: Blocking the receptors on macrophages so they stop destroying tissue.
2. Neutralisation: Binding to the superantigen or pathogen.
3. suppression of Cytokines: Downregulating IL-1 and TNF-alpha."

Viva: Atypical Presentations

Examiner: "Tell me about Kawasaki in infants." Candidate:

• "It is the highest risk group for aneurysms."
• "Often have incomplete criteria (e.g., just fever + pyuria)."
• "Any infant <6 months with >7 days fever needs an Echo."