What is the most likely diagnosis for an afebrile 2‑year‑old boy with a diffuse maculopapular erythematous rash on the torso, neck and face, bilateral non‑purulent conjunctivitis, and cracked erythematous lips, without other symptoms or prior illness?

Most Likely Diagnosis: Kawasaki Disease

The most likely diagnosis is Kawasaki disease, despite the absence of fever, which represents an incomplete presentation that still warrants urgent evaluation and treatment. 1

Clinical Reasoning

This 2-year-old boy presents with 4 of the 5 principal clinical features of Kawasaki disease:

• Bilateral non-purulent conjunctivitis (bulbar conjunctival injection without exudate) 1
• Oral mucosal changes (cracked lips, consistent with erythema and fissuring) 1
• Polymorphous exanthem (maculopapular erythematous rash on torso, neck, and face) 1
• Likely extremity changes (though not explicitly described, should be examined for erythema of palms/soles or edema) 1

The critical missing criterion is fever persisting at least 5 days, which is typically an absolute requirement for classic Kawasaki disease diagnosis. 1

Why This Still Suggests Kawasaki Disease

The American Heart Association explicitly states that incomplete Kawasaki disease can present with fewer than 4 principal features if coronary artery disease is detected on echocardiography, and some patients develop coronary aneurysms even with incomplete presentations. 2 The absence of fever makes classic Kawasaki disease extremely unlikely, but the constellation of findings—particularly the combination of conjunctivitis, oral changes, and rash—is highly characteristic and should not be dismissed. 2

The age (2 years) falls within the peak incidence range, as 80% of Kawasaki disease cases occur in children under 5 years. 1

Critical Differential Diagnoses to Exclude

Multisystem Inflammatory Syndrome in Children (MIS-C)

• MIS-C presents with similar features: polymorphic rash, conjunctivitis, oral mucosal changes (red/cracked lips, strawberry tongue), and gastrointestinal symptoms. 1
• Key distinguishing feature: MIS-C requires an epidemiologic link to SARS-CoV-2 (positive PCR/serology, preceding COVID-19-like illness, or close contact within 4 weeks). 1
• If no COVID exposure history exists, MIS-C is less likely. 1

Viral Exanthems

• Human herpesvirus 6 (HHV6) is the most common viral cause (24%) of fever with maculopapular rash in children, with mean age 1.6 years. 3
• However, viral exanthems typically do not cause the specific combination of conjunctivitis, oral mucosal changes, and characteristic rash pattern seen here. 4
• The absence of respiratory symptoms makes common viral infections less likely. 3

Drug Hypersensitivity Reaction

• Delayed-onset maculopapular rashes from β-lactams are common in children but are only reproducible in 6.8% of cases on rechallenge. 5
• The statement "no previous illness or known allergies" and "no other symptoms" makes drug reaction less likely unless there was recent medication exposure not mentioned. 1

Immediate Diagnostic Workup Required

Urgent pediatric cardiology consultation and echocardiography are necessary, as coronary artery disease can occur even with incomplete presentations. 2

Tier 1 Laboratory Evaluation:

• Complete blood count (looking for leukocytosis, thrombocytosis in subacute phase) 1
• Comprehensive metabolic panel (hypoalbuminemia, elevated transaminases) 1
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (both typically markedly elevated) 1
• SARS-CoV-2 PCR and serology (to exclude MIS-C) 1

Tier 2 Evaluation if Initial Tests Suggestive:

• Echocardiography to assess for coronary artery abnormalities, pericardial effusion, or decreased contractility 1
• Urinalysis (sterile pyuria of urethral origin) 1
• ECG (arrhythmias, ST-T wave changes) 1

Physical Examination Priorities

Examine specifically for:

• Extremity changes: Erythema of palms and soles, firm or painful induration of hands or feet (acute phase findings) 1
• Cervical lymphadenopathy: Unilateral node ≥1.5 cm diameter 1
• Perineal involvement: Early desquamation may occur in the perineal region 1
• Cardiovascular findings: Gallop rhythm, distant heart sounds, or signs of cardiac dysfunction 1

Treatment Considerations

If clinical suspicion for Kawasaki disease is high, empiric treatment with IVIG (2 g/kg) and aspirin should be considered even before definitive diagnosis, as early intervention decreases the approximately 20% risk of developing coronary artery abnormalities. 1, 2

The American Heart Association recommends that in the presence of 4 principal criteria, diagnosis can be made on day 4 of illness (before the traditional 5-day fever requirement). 1 However, this child is afebrile, creating diagnostic uncertainty that necessitates echocardiographic evaluation. 2

Critical Pitfalls to Avoid

Never dismiss the absence of fever as completely excluding Kawasaki disease; some patients present with incomplete criteria and develop coronary aneurysms. 2 The combination of conjunctivitis, oral changes, and characteristic rash in a 2-year-old warrants aggressive evaluation regardless of fever status. 2

Never assume a benign viral exanthem without excluding Kawasaki disease in any child with rash and the specific mucocutaneous findings described here. 2 The consequences of missed diagnosis—coronary artery aneurysms, myocardial infarction, and death—are too severe to adopt a "wait and see" approach. 1

Document whether fever has truly been absent or simply not measured/reported. Parents may not recognize low-grade fevers, and the child may have had fever earlier in the illness course that has now resolved. 1