What are the differential diagnoses to consider in a pediatric patient under 5 years old presenting with symptoms consistent with Kawasaki disease?

Differential Diagnoses for Kawasaki Disease in Pediatric Patients Under 5 Years

The most critical differentials to consider are scarlet fever, adenovirus infection, drug reactions, bacterial lymphadenitis, measles, and multisystem inflammatory syndrome in children (MIS-C), as these conditions share overlapping clinical features with Kawasaki disease but require different management approaches. 1, 2

Primary Infectious Differentials

Scarlet Fever

• Presents with high fever, strawberry tongue (initially white-coated, then bright red with prominent papillae), and characteristic sandpaper-like rash, most commonly affecting children aged 5-15 years. 2
• Key distinguishing feature: exudative pharyngitis is present in scarlet fever but should prompt exclusion of Kawasaki disease if present. 1
• The rash distribution differs—scarlet fever typically spares the face while Kawasaki disease rash is truncal with groin accentuation. 1

Viral Infections (Adenovirus, Measles)

• Adenovirus is specifically mentioned as mimicking Kawasaki disease features and represents one of the most common childhood illnesses in the differential. 1
• Measles can present with conjunctivitis, rash, and fever but can be differentiated based on clinical presentation and laboratory tests. 3
• Critical distinction: exudative conjunctivitis suggests viral infection rather than Kawasaki disease, which presents with bilateral non-purulent bulbar conjunctival injection with limbus sparing. 1, 2

Bacterial Infections

• Bacterial lymphadenitis is a common misdiagnosis, especially in older children where cervical lymphadenopathy ≥1.5 cm may be the presenting and most prominent sign. 1
• Staphylococcal scalded skin syndrome can mimic the rash and extremity changes of Kawasaki disease. 3

Multisystem Inflammatory Syndrome in Children (MIS-C)

MIS-C presents with overlapping features but requires different management intensity—patients typically have more prominent gastrointestinal symptoms, lower platelet counts, and higher CRP levels than classic Kawasaki disease. 2

• All patients with suspected Kawasaki disease should have SARS-CoV-2 PCR and serology testing to rule out MIS-C. 2
• This distinction is critical as MIS-C emerged as a significant differential following the COVID-19 pandemic. 2

Drug Reactions

Drug reactions can mimic many features of Kawasaki disease, particularly in children initially treated with antibiotics for presumed bacterial infection—this represents a classic missed diagnosis scenario. 1, 2

• Do not attribute strawberry tongue and rash solely to antibiotic reaction if the patient was initially treated for presumed bacterial infection. 2

Key Clinical Features That Help Exclude Kawasaki Disease

The presence of any of the following should prompt consideration of alternative diagnoses: 1

• Exudative conjunctivitis or pharyngitis (suggests bacterial or viral infection rather than Kawasaki disease)
• Discrete intraoral lesions (Kawasaki disease presents with diffuse erythema without focal lesions or ulcerations)
• Bullous or vesicular rash (Kawasaki disease rash is polymorphous but never bullous or vesicular)
• Generalized lymphadenopathy (Kawasaki disease typically presents with unilateral cervical lymphadenopathy ≥1.5 cm)

Diagnostic Algorithm for Distinguishing Differentials

When Fever ≥5 Days with 2-3 Kawasaki Features Present:

Immediately measure ESR and CRP—if ESR ≥40 mm/hr and/or CRP ≥3 mg/dL, obtain complete blood count, comprehensive metabolic panel (albumin, transaminases), urinalysis, and echocardiography. 2, 1

• The degree of inflammatory marker elevation helps distinguish Kawasaki disease from common viral infections—ESR often exceeds 100 mm/hr and CRP typically reaches ≥3 mg/dL (30.0 mg/L) in Kawasaki disease. 1

High-Risk Populations Requiring Lower Threshold for Diagnosis:

Infants <6 months may present with only prolonged fever and irritability yet have the highest risk of coronary abnormalities—these patients require echocardiography even with minimal clinical features if fever persists ≥7 days. 2, 3, 4

• Do not dismiss Kawasaki disease because conjunctivitis is absent—incomplete Kawasaki disease is more common in infants <1 year and can present with fewer than 4 principal features. 2, 1

Common Diagnostic Pitfalls to Avoid

The most dangerous pitfall is attributing prolonged fever to a common viral illness or drug reaction without considering Kawasaki disease, as the consequences of missed diagnosis include serious morbidity from coronary artery aneurysms or, in rare cases, death. 1

• Without treatment, coronary artery abnormalities develop in 15-25% of patients with Kawasaki disease; with prompt IVIG therapy this decreases to ~5%. 1, 2
• Young infants (<6 months) with prolonged fever (≥7 days) and systemic inflammation require echocardiography even with minimal clinical features due to high risk of coronary complications. 2
• Older children and adolescents often have delayed diagnosis and higher prevalence of coronary artery abnormalities. 3, 4

Laboratory Testing to Differentiate Conditions

When Kawasaki disease is suspected, obtain: complete blood count with differential, complete metabolic panel, ESR, CRP, and SARS-CoV-2 PCR and serology. 2

• Platelet count is typically elevated in Kawasaki disease but may be normal early in the disease course. 2
• Sterile pyuria may be present in Kawasaki disease, helping distinguish it from urinary tract infection. 3
• Thrombocytosis is common in the second week after fever onset in Kawasaki disease. 4