Kawasaki Disease

Kawasaki disease (KD) is an acute, self-limiting medium-vessel systemic vasculitis of early childhood, notorious for one devastating sequela — coronary artery aneurysms (CAA). It is the leading cause of acquired heart disease in children in the developed world, having overtaken acute rheumatic fever. For NEET PG, the highest-yield clusters are the diagnostic criteria, the strawberry tongue/peeling fingertips imagery, CAA as the feared complication, and IVIG + aspirin as treatment.

Definition & overview

KD (formerly mucocutaneous lymph node syndrome, described by Tomisaku Kawasaki in 1967) is a febrile vasculitis predominantly affecting medium-sized muscular arteries, with a striking predilection for the coronary arteries. It is most common in children 6 months to 5 years (peak at 18–24 months), with a slight male preponderance and highest incidence in children of Japanese/East-Asian ancestry. Untreated, ~20–25% develop coronary aneurysms; with timely IVIG this drops to ~3–5%.

High-yield: KD is a medium-vessel vasculitis (same vessel size as polyarteritis nodosa). It is the commonest cause of acquired heart disease in children in developed countries.

Etiology & pathophysiology

The exact cause is unknown, but the leading hypothesis is an abnormal immune response to an infectious trigger in a genetically susceptible host. Key threads:

• Genetic susceptibility: polymorphisms in ITPKC (a negative regulator of T-cell activation) and CASP3 are strongly associated; high recurrence among siblings and the Japanese predominance support this.
• Infectious trigger: seasonal/epidemic clustering (winter–spring) suggests an infectious agent, possibly entering via the respiratory tract. No single organism is confirmed.
• Immune activation: massive activation of T cells and monocytes/macrophages, raised pro-inflammatory cytokines (TNF-α, IL-1, IL-6), and matrix metalloproteinase (MMP-9) that degrades the arterial wall.

Pathologically the inflammation progresses through three vascular phases:

1. Necrotising arteritis (first ~2 weeks) — neutrophilic destruction of the media → aneurysm formation.
2. Subacute/chronic vasculitis — lymphocyte/eosinophil/plasma-cell infiltration; may persist months to years.
3. Luminal myofibroblastic proliferation (LMP) — progressive stenosis, the substrate for late ischaemia and thrombosis.

The media is weakened → ballooning → aneurysm; turbulent flow in the aneurysm → thrombosis → myocardial infarction, the chief cause of death.

Clinical features & diagnostic criteria

KD is a clinical diagnosis — there is no confirmatory test. The classic (complete) criteria require fever ≥ 5 days PLUS ≥ 4 of 5 principal clinical features.

Feature	Description / exam buzzword
Conjunctivitis	Bilateral, bulbar, non-exudative (non-purulent), with limbal sparing
Oral changes	Strawberry tongue, dry/cracked fissured red lips, diffuse oropharyngeal erythema — NO discrete oral ulcers/exudate
Rash	Polymorphous (maculopapular, morbilliform, scarlatiniform) — never vesicular/bullous; accentuated in groin
Extremity changes	Acute: erythema/oedema of palms & soles. Subacute: periungual/membranous desquamation (peeling fingertips, weeks 2–3)
Cervical lymphadenopathy	Unilateral, ≥ 1.5 cm, usually single node — the least common feature

High-yield mnemonic — "CRASH and burn": Conjunctivitis, Rash, Adenopathy, Strawberry tongue, Hands/feet changes, and burn = fever. Need fever + 4 of 5.

High-yield: Cervical lymphadenopathy is the least frequent principal feature (~50–75%), whereas conjunctival injection and oral changes are the most common.

Other supportive (non-criteria) findings — heavily tested as "associated":

• Extreme irritability (out of proportion; aseptic meningitis common).
• Erythema/induration at the BCG scar site — a near-pathognomonic clue, especially relevant in India.
• Perineal desquamation in the acute phase.
• Arthritis/arthralgia, sterile pyuria (urethritis), hydrops of gallbladder, anterior uveitis, diarrhoea.
• Beau's lines (transverse nail grooves) appear later.

The clinical course classically runs in three phases:

Acute febrile (1–2 wk) → Subacute (2–4 wk: desquamation, thrombocytosis, highest aneurysm + sudden-death risk) → Convalescent (weeks–months: clinical normalisation, ESR normalises)

Incomplete (atypical) Kawasaki disease

This is a favourite exam trap. Incomplete KD = prolonged fever with fewer than 4 principal features. It is commoner in infants < 6 months and in older children > 5 years — exactly the groups at highest risk of coronary aneurysms because diagnosis is delayed.

Per the AHA algorithm, suspect incomplete KD when there is fever ≥ 5 days + 2–3 clinical features, then use laboratory criteria: if CRP ≥ 3 mg/dL and/or ESR ≥ 40 mm/hr, look for ≥ 3 supplemental lab findings:

1. Anaemia for age
2. Platelets ≥ 4,50,000 after day 7 (thrombocytosis)
3. Albumin ≤ 3.0 g/dL
4. Elevated ALT
5. WBC ≥ 15,000
6. Urine ≥ 10 WBC/hpf (sterile pyuria)

If criteria met or echocardiogram positive, treat as KD.

High-yield: Infants < 6 months with prolonged unexplained fever should have an echocardiogram even with few features — they get incomplete KD and the worst coronary outcomes.

Investigations

There is no diagnostic test; labs support the diagnosis and the inflammatory picture is characteristic.

Investigation	Typical finding
ESR / CRP	Markedly raised (acute-phase response)
Platelets	Normal/raised early; marked thrombocytosis (often > 5–10 lakh) in 2nd week
WBC	Leukocytosis with left shift
Hb	Normocytic normochromic anaemia
LFT	↑ Transaminases, ↓ albumin, mild hyperbilirubinaemia
Urine	Sterile pyuria (no bacteria)
CSF (if done)	Aseptic (lymphocytic) meningitis
NT-proBNP	Often elevated; supportive of myocarditis

High-yield: Thrombocytosis is characteristic but appears in the second week (subacute phase) — early platelets may be normal. Thrombocytopenia, conversely, is a poor prognostic sign (DIC / macrophage activation / KD shock syndrome).

Investigation of choice for cardiac involvement

Two-dimensional transthoracic ECHOCARDIOGRAPHY is the investigation of choice for detecting coronary artery abnormalities. It is non-invasive, assesses the proximal LAD and right coronary well, and also detects pericardial effusion, valve regurgitation and ventricular function.

Echo schedule: at diagnosis, then at 1–2 weeks and 4–6 weeks after onset in uncomplicated cases. Children with aneurysms need more frequent follow-up. Coronary size is reported using body-surface-area-adjusted Z-scores.

Coronary status	Z-score / size
Normal	Z < 2
Dilation only	Z 2 to < 2.5
Small aneurysm	Z 2.5 to < 5
Medium aneurysm	Z 5 to < 10 (and < 8 mm absolute)
Giant aneurysm	Z ≥ 10 or ≥ 8 mm absolute

High-yield: Giant coronary aneurysms (≥ 8 mm) carry the worst prognosis — highest risk of thrombosis, stenosis, MI and need lifelong anticoagulation. Coronary angiography/CT-coronary angiography is reserved for defining complex aneurysmal anatomy.

Management / drug of choice

The two pillars are IVIG + aspirin, ideally started within 10 days of fever onset (best results within 7 days) to prevent coronary aneurysms.

1. Intravenous immunoglobulin (IVIG) — drug of choice. Single dose 2 g/kg over 10–12 hours. Reduces CAA incidence from ~25% to ~3–5%. Mechanism is immunomodulatory (not fully understood).
2. Aspirin.
   • High/moderate dose (anti-inflammatory): 30–50 mg/kg/day (some protocols up to 80–100) during the acute febrile phase.
   • Low dose (antiplatelet): 3–5 mg/kg/day once afebrile, continued 6–8 weeks (until inflammatory markers and platelets normalise and follow-up echo is normal). Continued indefinitely if aneurysms persist.

High-yield: IVIG is the drug of choice; aspirin is adjunctive. KD is the classic paediatric exception to avoiding aspirin in children (despite the Reye syndrome concern) — its benefit outweighs the risk here. Live vaccines (MMR, varicella) are deferred ~11 months after IVIG because passive antibody blunts the response.

IVIG resistance & escalation

About 10–20% have IVIG-resistant KD (persistent or recrudescent fever ≥ 36 hours after the first infusion). The flow is:

IVIG 2 g/kg → if fever persists ≥ 36 h → second IVIG 2 g/kg → still refractory → IV corticosteroids (methylprednisolone pulse) ± infliximab (anti-TNF-α); other agents: ciclosporin, anakinra.

High-risk children (e.g., aneurysm already present, very young infants) may receive corticosteroids upfront with IVIG. Anticoagulation (warfarin/LMWH ± antiplatelets) is added for giant aneurysms.

High-yield: The single most important determinant of outcome is timely IVIG (within 10 days). Delayed treatment is the chief modifiable risk factor for aneurysms.

Complications

• Coronary artery aneurysms — the hallmark and most feared; → thrombosis, stenosis, myocardial infarction, sudden death. CAA is the leading cause of mortality.
• Myocarditis (almost universal in acute phase), pericardial effusion, valvulitis (mitral regurgitation).
• Kawasaki disease shock syndrome (KDSS) — hypotension/poor perfusion, often with thrombocytopenia; mimics septic/toxic shock and predicts IVIG resistance and CAA.
• Macrophage activation syndrome (MAS) — hyperferritinaemia, cytopenias, falling ESR.
• Peripheral artery aneurysms (axillary, iliac), arrhythmias, and long-term endothelial dysfunction.

High-yield: A falling ESR with worsening clinical state in KD should raise suspicion of MAS/HLH. Beau's lines of the nails are a late, benign convalescent finding.

Key differentials

Condition	Distinguishing clues vs KD
Measles	Koplik spots, exudative conjunctivitis, cough/coryza, cephalocaudal rash; CRP usually not as high
Scarlet fever	Strep throat, sandpaper rash, perioral pallor; rapid response to penicillin; ASO ↑
Staphylococcal/streptococcal toxic shock	Hypotension, diffuse erythroderma, multi-organ; positive cultures
Stevens–Johnson syndrome	Mucosal ulceration/erosions, target lesions, drug history — KD spares discrete oral ulcers
Juvenile idiopathic arthritis (systemic)	Quotidian fever spikes, salmon-pink evanescent rash, arthritis; ferritin very high
MIS-C (post-COVID)	Older children, prominent GI symptoms, myocardial dysfunction, SARS-CoV-2 link — considerable overlap with KD

High-yield: KD oral involvement is diffuse erythema/strawberry tongue WITHOUT discrete ulcers or exudate — discrete ulcers point to SJS/herpetic stomatitis, and exudative conjunctivitis points to measles/adenovirus.

Recently asked / exam angle

• Diagnostic criteria is the perennial favourite: fever ≥ 5 days + 4 of 5 features — questions test the exact features and that cervical adenopathy is least common.
• Image-based questions: strawberry tongue, cracked red lips, periungual desquamation of fingertips, bilateral non-exudative conjunctivitis.
• Most feared complication / cause of death: coronary artery aneurysm → MI.
• Investigation of choice for cardiac involvement: 2-D echocardiography (not angiography first-line).
• Drug of choice: IVIG 2 g/kg; aspirin is the paediatric exception to the Reye-syndrome rule.
• Incomplete KD in infants < 6 months — recognise that they have the highest aneurysm risk and need echo with prolonged unexplained fever.
• BCG scar reactivation — high-yield in Indian/Japanese exams as a supportive sign.
• Vessel size: medium-vessel vasculitis (group it with polyarteritis nodosa).
• MIS-C vs KD overlap is an increasingly common newer-pattern question.
• IVIG resistance management ladder and delaying live vaccines for ~11 months after IVIG.

Rapid revision

1. KD = acute medium-vessel vasculitis; commonest in 6 months–5 years, peak ~2 yrs, East-Asian predominance.
2. Diagnosis is clinical: fever ≥ 5 days + 4 of 5 — Conjunctivitis, Rash, Adenopathy, Strawberry tongue/lips, Hands-feet changes ("CRASH and burn").
3. Conjunctivitis is bilateral, non-exudative, limbal-sparing; adenopathy is unilateral ≥ 1.5 cm and the least common feature.
4. Periungual/membranous desquamation of fingertips in week 2–3 is classic; BCG scar erythema is a near-pathognomonic clue.
5. Labs: ↑ESR/CRP, thrombocytosis in the 2nd week, anaemia, ↑ALT, ↓albumin, sterile pyuria.
6. Echocardiography is the investigation of choice for coronary involvement; done at diagnosis, 1–2 wk, 4–6 wk.
7. Coronary artery aneurysm is the hallmark complication and leading cause of death; giant aneurysm ≥ 8 mm = worst prognosis.
8. IVIG 2 g/kg single dose is the drug of choice, ideally within 10 days; cuts CAA from ~25% to ~4%.
9. Aspirin — high dose (anti-inflammatory) acutely, then low dose antiplatelet for ≥ 6–8 weeks; KD is the paediatric aspirin exception.
10. IVIG resistance (~10–20%) → repeat IVIG → steroids ± infliximab.
11. Incomplete KD is commonest and most dangerous in infants < 6 months and children > 5 years — use AHA lab criteria (CRP ≥ 3 / ESR ≥ 40 + supplemental labs).
12. Defer live vaccines ~11 months post-IVIG; a falling ESR with deterioration suggests MAS.