In a 2‑year‑old child who is mildly febrile and slightly unwell, presenting with a unilateral macular‑papular rash confined to one arm and no other viral symptoms, what are the most likely diagnoses and appropriate management?

Unilateral Maculopapular Rash on One Arm in a 2-Year-Old with Mild Fever

This presentation is most consistent with a localized viral exanthem, but you must urgently exclude incomplete Kawasaki disease, which can present with unilateral or asymmetric rash and carries a 20% risk of coronary artery aneurysms if untreated. 1

Immediate Diagnostic Priorities

Rule Out Incomplete Kawasaki Disease First

Kawasaki disease is the critical diagnosis to exclude because 80% of cases occur in children under 5 years, making your 2-year-old patient fall squarely in the peak incidence range. 1 The American Heart Association acknowledges that incomplete presentations may lack the traditional 5-day fever requirement yet still warrant urgent evaluation. 1

Examine immediately for these principal Kawasaki features:

• Bilateral non-purulent conjunctivitis (bulbar injection without discharge) 1
• Oral mucosal changes: cracked lips, erythema, fissuring 1
• Extremity changes: erythema of palms/soles, edema, or early perineal desquamation 2, 1
• Unilateral cervical lymphadenopathy ≥1.5 cm 1
• Polymorphous exanthem on torso, neck, or face (can be unilateral initially) 1

Critical pitfall: Do not dismiss Kawasaki disease based on the unilateral distribution of the rash alone—the polymorphous exanthem can begin asymmetrically. 1 Children may present with fever and unilateral findings that are mistaken for other conditions, and the rash that follows is often attributed to antibiotic reactions. 2

If ≥2 Principal Features Present: Urgent Laboratory Workup

Order immediately:

• Complete blood count (leukocytosis, later thrombocytosis) 1
• ESR and CRP (typically markedly elevated) 1
• Comprehensive metabolic panel (hypoalbuminemia, elevated transaminases) 1
• Echocardiography to assess coronary arteries, even before day 10 of illness 2, 1
• Urinalysis for sterile pyuria 1

The American Heart Association states that when clinical suspicion is high, empiric IVIG (2 g/kg) plus aspirin should be administered promptly, as early treatment reduces the ~20% risk of coronary artery abnormalities. 1 Failure to recognize and treat can lead to coronary aneurysms, myocardial infarction, and death. 1

Secondary Differential Diagnoses

Localized Viral Exanthem (Most Likely if Kawasaki Excluded)

If Kawasaki features are absent, a benign viral exanthem is the most probable diagnosis. 3, 4 Human herpesvirus 6 (HHV-6) is the most common cause of fever with maculopapular rash in children aged 2 months to 14 years (24% of cases), with a mean age of 1.6 years. 5 HHV-7 and EBV are less common. 5

Supportive features:

• Mildly unwell appearance with low-grade fever 3
• Absence of respiratory symptoms 5
• Self-limited course, typically resolving within 5–14 days 3, 4

Management: Supportive care only with observation for development of additional symptoms or fever persistence beyond 5 days. 1

Unilateral Laterothoracic Exanthem (Asymmetric Periflexural Exanthem)

This benign viral exanthem can present with unilateral distribution, typically starting in the axilla or groin and spreading asymmetrically. 6 It is self-limited and requires no specific treatment. 6

Molluscum Contagiosum with Secondary Dermatitis

Molluscum can cause a unilateral follicular reaction and associated eczematous dermatitis, though the distinctive dome-shaped umbilicated lesions should be visible on examination. 2 This would not explain the fever. 2

Herpes Simplex Virus (HSV) – Less Likely

HSV conjunctivitis typically presents with unilateral bulbar injection, watery discharge, and vesicular eyelid lesions, not isolated arm rash. 7 However, primary HSV can cause systemic symptoms with localized vesicular eruptions. 7 The absence of vesicles makes this unlikely. 7

Red Flags Requiring Immediate Escalation

Refer urgently to pediatric cardiology if:

• Any 2 or more principal Kawasaki features are present 1
• Fever persists beyond 5 days, even without other features 1
• Rash progresses to involve palms, soles, or becomes generalized 1

Consider SARS-CoV-2/MIS-C if:

• Recent COVID-19 exposure or positive serology within 4 weeks 1
• Gastrointestinal symptoms develop 1

Management Algorithm

1. Perform focused physical examination for all Kawasaki principal features (conjunctivitis, oral changes, extremity changes, lymphadenopathy) 1

2. If ≥2 features present: Order urgent labs (CBC, ESR, CRP, CMP, urinalysis) and echocardiography; consult pediatric cardiology same-day 1

3. If <2 features and child appears well: Provide reassurance, supportive care, and schedule follow-up within 24–48 hours to reassess for evolving Kawasaki features or fever persistence 1

4. Instruct caregivers to return immediately if: Fever persists >5 days, new conjunctivitis or oral changes develop, extremity swelling occurs, or child becomes more unwell 1

Never assume a benign viral exanthem without excluding Kawasaki disease in any child with rash and fever, especially in the high-risk age group under 5 years. 1