What are the differential diagnoses for Kawasaki disease?

Differential Diagnoses for Kawasaki Disease

The key differential diagnoses that must be excluded before diagnosing Kawasaki disease include viral infections (measles, adenovirus, enterovirus, Epstein-Barr virus), scarlet fever, toxic shock syndrome, staphylococcal scalded skin syndrome, Stevens-Johnson syndrome, drug hypersensitivity reactions, bacterial cervical lymphadenitis, juvenile rheumatoid arthritis, Rocky Mountain spotted fever, leptospirosis, and mercury hypersensitivity reaction (acrodynia). 1

Infectious Differentials

Viral Infections

• Measles shares many clinical features with Kawasaki disease and should be strongly considered in any unimmunized infant or child presenting with fever, rash, and conjunctivitis 1
• Adenovirus, enterovirus, and Epstein-Barr virus can present with prolonged fever, rash, and conjunctivitis, mimicking Kawasaki disease 1
• Kawasaki disease occurs more commonly in winter and spring when many respiratory viruses circulate, making concurrent viral infection possible 1

Bacterial Infections

• Scarlet fever (Group A Streptococcal infection) presents with fever, rash, and strawberry tongue similar to Kawasaki disease, but is distinguished by circumoral pallor, Pastia's lines, and peripheral eosinophilia 1, 2
• Toxic shock syndrome shares conjunctival injection, oropharyngeal erythema, and extremity edema with Kawasaki disease, but is characterized by thrombocytopenia (not thrombocytosis), absence of cervical adenopathy, and absence of splenomegaly 2
• Bacterial cervical lymphadenitis can be confused with Kawasaki disease when cervical lymphadenopathy is the predominant feature; bacterial adenitis typically presents with a single hypoechoic node on ultrasound, whereas Kawasaki disease shows multiple enlarged nodes with retropharyngeal edema or phlegmon 1
• Staphylococcal scalded skin syndrome presents with diffuse erythema and desquamation but lacks the mucosal changes and conjunctivitis of Kawasaki disease 1

Other Infectious Causes

• Rocky Mountain spotted fever presents with fever, maculopapular rash becoming petechial (starting on wrists/ankles), conjunctival suffusion, splenomegaly, and extremity swelling, but includes prominent headache and periorbital edema 1, 2
• Leptospirosis can mimic Kawasaki disease with fever and conjunctival injection 1

Non-Infectious Differentials

Rheumatologic/Inflammatory

• Juvenile rheumatoid arthritis can present with fever, rash, and arthritis, but typically has a different pattern of joint involvement and lacks the characteristic mucosal changes of Kawasaki disease 1
• Stevens-Johnson syndrome presents with mucosal involvement and rash but is distinguished by vesiculobullous lesions, oral ulcerations, and targetoid lesions—features that should prompt consideration of an alternative diagnosis to Kawasaki disease 1

Hypersensitivity Reactions

• Drug hypersensitivity reactions can mimic Kawasaki disease with fever, rash, and conjunctivitis; this is a common pitfall when fever and pyuria are attributed to urinary tract infection and subsequent rash is mistakenly attributed to antibiotic reaction 1
• Mercury hypersensitivity reaction (acrodynia) is a rare differential that can present with extremity changes and irritability 1

Critical Distinguishing Features

Features That Argue AGAINST Kawasaki Disease

The presence of the following should prompt strong consideration of an alternative diagnosis 1:

• Exudative conjunctivitis (Kawasaki disease has non-exudative bilateral bulbar conjunctival injection)
• Exudative pharyngitis (Kawasaki disease has diffuse oropharyngeal erythema without exudate)
• Oral ulcerations (not seen in Kawasaki disease)
• Vesiculobullous or petechial rashes (Kawasaki disease has polymorphous rash but not vesicular/bullous)
• Splenomegaly (not typical of Kawasaki disease)
• Generalized lymphadenopathy (Kawasaki disease typically has unilateral cervical lymphadenopathy ≥1.5 cm)

Features That Support Kawasaki Disease

• Non-exudative bilateral bulbar conjunctival injection with limbal sparing 1, 3
• Absence of pharyngeal exudate despite oropharyngeal erythema 1
• Thrombocytosis in the second week (not thrombocytopenia) 1, 3
• Markedly elevated inflammatory markers (ESR often >100 mm/hr, CRP ≥3 mg/dL) 1, 3

Common Diagnostic Pitfalls

High-Risk Populations for Missed Diagnosis

• Infants <6 months may present with only prolonged fever and irritability, yet have the highest risk of coronary abnormalities; these cases are frequently missed 1, 3
• Older children and adolescents often have delayed diagnosis and higher prevalence of coronary artery abnormalities 1, 3

Clinical Scenarios Leading to Misdiagnosis

• Fever and pyuria mistakenly attributed to urinary tract infection, with subsequent rash attributed to antibiotic reaction 1
• Irritability and culture-negative CSF pleocytosis misdiagnosed as aseptic meningitis 1
• Cervical lymphadenitis as primary manifestation misdiagnosed as bacterial adenitis, often with concurrent retropharyngeal phlegmon attributed to bacterial infection 1
• Prominent gastrointestinal symptoms leading to surgical admission with other Kawasaki features overlooked 1
• Patients presenting with shock misdiagnosed as sepsis 1