What is the differential diagnosis for a 1-year-old patient with fever, multiple aphthous ulcers, gingival inflammation, and rashes on the dorsal surface of the tongue, considering foot and mouth disease?

Differential Diagnosis for a 1-Year-Old with Fever, Oral Ulcers, Gingival Inflammation, and Tongue Rash

The most critical differential diagnoses to immediately exclude in this 1-year-old are primary herpetic gingivostomatitis (HSV-1), Kawasaki disease, and hand-foot-and-mouth disease (HFMD), with HSV-1 and Kawasaki disease requiring urgent recognition due to potential for severe complications and specific treatment needs. 1, 2

Primary Diagnostic Considerations

Primary Herpetic Gingivostomatitis (HSV-1)

• HSV-1 is the most common herpes virus infection in children outside the neonatal period and presents with fever, irritability, gingival inflammation with bleeding, and superficial painful ulcers throughout the oral mucosa and perioral area. 1, 3
• The presence of tender submandibular lymphadenopathy strongly suggests HSV-1 rather than HFMD. 3
• Severe irritability and difficulty eating beyond what would be expected from fever alone, combined with prominent gingival involvement, are key distinguishing features. 3
• Clinical diagnosis based on appearance alone is unreliable—obtain viral culture or HSV DNA PCR from lesion swabs for definitive diagnosis. 1, 3

Kawasaki Disease

• This diagnosis is critical to exclude in any 1-year-old with fever and oral changes, as untreated Kawasaki disease leads to coronary artery aneurysms in up to 25% of cases, reduced to ~5% with prompt IVIG therapy. 2
• Incomplete Kawasaki disease is particularly common in infants under 1 year and can present with fewer than 4 principal features. 4, 2
• Immediately assess for: bilateral non-purulent conjunctival injection, polymorphous rash on trunk/extremities, extremity changes (erythema/edema of hands/feet), and cervical lymphadenopathy ≥1.5 cm. 1, 2
• Document exact fever duration—Kawasaki disease requires fever ≥5 days, though treatment should not be delayed if other features are compelling. 4, 2
• If fever ≥5 days with 2-3 features present, immediately measure ESR and CRP; if ESR ≥40 mm/hr and/or CRP ≥3 mg/dL, obtain CBC, comprehensive metabolic panel, urinalysis, and echocardiography. 2

Hand-Foot-and-Mouth Disease (HFMD)

• HFMD presents with low-grade fever, painful oral ulcerations, and characteristic maculopapular or papulovesicular rash on palms and soles of feet. 5
• Oral lesions in HFMD typically involve the posterior pharynx and soft palate, whereas HSV-1 prominently affects the gingiva and anterior oral mucosa. 1, 5
• Lesions usually resolve in 7-10 days with supportive care only. 5
• The absence of palmar/plantar lesions makes HFMD less likely but does not exclude it, as oral lesions may precede skin findings. 5

Critical Diagnostic Algorithm

Step 1: Assess Fever Duration and Kawasaki Criteria

• If fever ≥5 days: Immediately evaluate for all 5 principal Kawasaki features (conjunctivitis, oral changes, rash, extremity changes, lymphadenopathy ≥1.5 cm). 2
• If fever <5 days but ≥7 days in an infant <6 months: Obtain echocardiography even with minimal clinical features due to high risk of coronary complications. 2
• Do not dismiss Kawasaki disease because conjunctivitis is absent—this is a classic missed diagnosis scenario. 2

Step 2: Distinguish HSV-1 from HFMD

• Examine for gingival inflammation/bleeding and tender submandibular lymphadenopathy (suggests HSV-1). 3
• Check palms and soles for vesicular lesions (suggests HFMD). 5
• If clinical presentation is uncertain or child appears systemically ill, obtain viral culture or PCR from oral lesions to definitively distinguish between HFMD and HSV-1. 3

Step 3: Laboratory Evaluation Based on Clinical Suspicion

For suspected Kawasaki disease:

• CBC with differential, comprehensive metabolic panel (albumin, transaminases), ESR, CRP, urinalysis, and echocardiography. 2
• Consider SARS-CoV-2 PCR and serology to rule out MIS-C, which presents with overlapping features but typically has more prominent GI symptoms and higher CRP levels. 2

For suspected HSV-1:

• Viral culture from vesicle fluid or ulcer base (detectable within 1-3 days) or HSV DNA PCR (most sensitive method). 3

Additional Differential Diagnoses to Consider

Enteroviral Infections (Herpangina)

• Herpangina presents with fever and oral lesions located specifically on the posterior pharynx and soft palate, sparing the gingiva and anterior mouth. 1
• This distribution pattern helps distinguish it from HSV-1 gingivostomatitis. 1

Other Viral Exanthems

• Maculopapular rashes can occur with human herpesvirus 6 (roseola), parvovirus B19, Epstein-Barr virus, and other enteroviruses (coxsackievirus, echovirus). 4
• These typically lack the prominent oral ulceration and gingival inflammation seen in this case. 4

Streptococcal Pharyngitis

• Presents with tonsillopharyngeal erythema, exudates, and cervical lymphadenopathy, but discrete oral ulcers are more suggestive of viral etiology. 1

Management Implications

For HSV-1 gingivostomatitis:

• Oral acyclovir 20 mg/kg/dose three times daily for 7-14 days is effective if started within the first 3 days of disease onset. 1, 3
• For severe disease or immunocompromised children, IV acyclovir 5-10 mg/kg/dose three times daily for 7-14 days. 3

For Kawasaki disease:

• Immediate hospitalization for multidisciplinary team involvement, serial cardiac monitoring, and IVIG therapy (2 g/kg) once diagnosis is confirmed. 2

For HFMD:

• Treatment is supportive with hydration and pain relief using acetaminophen or ibuprofen; oral lidocaine is not recommended. 5

Common Pitfalls to Avoid

• Do not attribute oral changes and rash to antibiotic reaction if the patient was initially treated for presumed bacterial infection—this is a classic scenario for missing Kawasaki disease. 2
• Do not assume HSV-1 can be ruled out based on clinical appearance alone—atypical presentations are common and laboratory confirmation is essential when diagnosis impacts treatment decisions. 3
• Do not wait for all 5 Kawasaki criteria in a 1-year-old with prolonged fever—incomplete Kawasaki disease is more common in this age group and carries the same risk of coronary complications. 4, 2
• Sterile pyuria may be mistaken for partially treated urinary tract infection; consider this as supporting evidence for Kawasaki disease rather than dismissing it. 4