What is the differential diagnosis for a patient presenting with hyperpyrexia (fever), strawberry tongue, and rash, without cough or conjunctivitis?

Differential Diagnosis for Fever up to 40°C, Strawberry Tongue, and Rash Without Cough or Conjunctivitis

The primary differential diagnosis is Kawasaki disease (KD), scarlet fever, and toxic shock syndrome, with the absence of conjunctivitis making incomplete Kawasaki disease or scarlet fever most likely. 1

Primary Diagnostic Considerations

Kawasaki Disease (Classic or Incomplete)

• Classic KD requires fever ≥5 days plus 4 of 5 principal features: bilateral non-purulent conjunctival injection, oral changes (strawberry tongue, cracked lips), polymorphous rash, extremity changes (erythema/edema), and cervical lymphadenopathy ≥1.5 cm. 1
• This patient has fever up to 40°C (typical for KD), strawberry tongue, and rash but lacks conjunctivitis, meeting only 2-3 criteria, suggesting incomplete (atypical) KD. 1
• Incomplete KD is particularly important to recognize because coronary artery aneurysms develop in up to 25% of untreated patients, reduced to ~5% with prompt IVIG therapy. 1
• The absence of conjunctivitis does NOT exclude KD—conjunctivitis may appear later or be absent entirely in incomplete presentations. 1
• Check for additional KD features: extremity changes (erythema, edema of hands/feet), cervical lymphadenopathy, perineal desquamation, irritability, sterile pyuria, and elevated inflammatory markers (ESR >40 mm/hr, CRP ≥3 mg/dL). 1

Scarlet Fever (Group A Streptococcal Infection)

• Scarlet fever presents with high fever, strawberry tongue (initially white-coated, then bright red with prominent papillae), and characteristic sandpaper-like rash, most common in children aged 5-15 years. 2, 3
• Key distinguishing features from KD: exudative pharyngitis (sore throat with exudate), absence of conjunctivitis, and the rash typically starts in the groin/axillae and spreads. 1, 2
• The absence of conjunctivitis actually favors scarlet fever over classic KD. 2
• Rapid strep testing and throat culture are diagnostic. 2

Multisystem Inflammatory Syndrome in Children (MIS-C)

• MIS-C shares overlapping features with KD including fever, strawberry tongue, rash, and conjunctivitis, but occurs 2-6 weeks after SARS-CoV-2 infection. 1
• MIS-C patients have more prominent gastrointestinal symptoms (abdominal pain, vomiting, diarrhea), neurologic symptoms, present more frequently in shock, and have cardiac dysfunction. 1
• Laboratory differences: MIS-C patients tend to have lower platelet counts, lower absolute lymphocyte counts, and higher CRP levels than KD patients at presentation. 1
• SARS-CoV-2 PCR or serology (IgG, IgM, IgA) is essential for diagnosis. 1

Toxic Shock Syndrome (TSS)

• TSS presents with high fever, diffuse erythematous rash, and multisystem involvement but typically includes hypotension/shock, which helps distinguish it from early KD. 1
• Strawberry tongue can occur but is less characteristic than in KD or scarlet fever.

Critical Diagnostic Algorithm

Step 1: Assess fever duration and obtain complete history

• If fever ≥5 days with 2-3 KD features (including strawberry tongue and rash), measure ESR and CRP immediately. 1
• If ESR ≥40 mm/hr and/or CRP ≥3 mg/dL, obtain: complete blood count, comprehensive metabolic panel (albumin, transaminases), urinalysis, and echocardiography. 1

Step 2: Perform targeted testing

• Rapid strep test and throat culture to evaluate for scarlet fever. 2
• SARS-CoV-2 PCR and serology if MIS-C is suspected based on timing or gastrointestinal/cardiac symptoms. 1
• Blood cultures if toxic shock syndrome or bacterial infection is considered. 2

Step 3: Echocardiography interpretation

• If coronary artery abnormalities are present on echo with fever and ≥3 clinical features, KD can be diagnosed even without meeting full criteria. 1
• Echocardiography may also reveal pericardial effusion, decreased ventricular function, or valvular regurgitation supporting KD diagnosis. 1

Common Diagnostic Pitfalls

• Do not dismiss KD because conjunctivitis is absent—incomplete KD is more common in infants <1 year and can present with fewer than 4 principal features. 1
• Do not attribute strawberry tongue and rash solely to antibiotic reaction if the patient was initially treated for presumed bacterial infection—this is a classic missed diagnosis scenario for KD. 1
• Do not wait for all KD features to appear simultaneously—a careful history may reveal that features were present at different times during the illness. 1
• Exudative pharyngitis, oral ulcerations, and vesicular/bullous rash argue AGAINST KD and suggest alternative diagnoses like scarlet fever or viral infections. 1
• 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. 1

Additional Differential Considerations

• Drug reaction/hypersensitivity: Can cause fever, rash, and oral changes but typically lacks the specific strawberry tongue appearance and high-grade fever pattern of KD. 1
• Viral exanthems (adenovirus, EBV): May mimic KD but typically have shorter fever duration and lack the characteristic oral mucosal changes. 1
• Staphylococcal scalded skin syndrome: Presents with fever and rash but has characteristic skin sloughing rather than polymorphous rash. 1