What is the best course of treatment for a 20-month-old child with diffuse hives and erythema multiforme, no fever, no coastal involvement, and no blistering, who has not responded to antihistamines (diphenhydramine) for 3 days and is worsening?

Treatment of Diffuse Hives with Erythema Multiforme in a 20-Month-Old Child

This child requires immediate escalation to systemic corticosteroids given the failure of antihistamines and worsening symptoms over 3 days, with prednisolone 1-2 mg/kg/day as the appropriate treatment, along with discontinuation of diphenhydramine due to significant safety concerns in children under 6 years. 1, 2

Critical Safety Issue: Discontinue Diphenhydramine Immediately

• Diphenhydramine should be avoided in children under 6 years of age due to significant safety concerns, with 33 deaths associated with its use in children under 6 years between 1969-2006, and 41 deaths in children under 2 years. 1
• The FDA and pediatric advisory committees explicitly recommend against using over-the-counter cough and cold medications, including first-generation antihistamines like diphenhydramine, in children below 6 years of age. 1
• First-generation antihistamines induce sedation in more than 50% of patients and may adversely affect learning ability in children. 3

Recommended Treatment Algorithm

Step 1: Switch to Second-Generation Antihistamine

• Replace diphenhydramine with cetirizine 2.5 mg twice daily (approved for ages 2-5 years) as the safer antihistamine option. 1
• Alternatively, loratadine 5 mg once daily can be used for children aged 2-5 years. 1
• Second-generation antihistamines have superior safety profiles with very low rates of serious adverse events in young children and lack the sedating effects of first-generation agents. 1, 4

Step 2: Add Systemic Corticosteroids for Worsening Symptoms

• Given the 3-day duration with worsening despite antihistamines, initiate prednisolone 1-2 mg/kg/day in divided doses (equivalent to approximately 10-20 mg daily for a 20-month-old weighing 10-12 kg). 2
• The FDA label for prednisolone indicates the initial dose may range from 0.14 to 2 mg/kg/day in three or four divided doses (4 to 60 mg/m²/day) for pediatric patients depending on disease severity. 2
• Continue corticosteroids for 3-10 days until symptoms resolve, with no evidence that tapering prevents relapse in short-course therapy. 2

Step 3: Monitor and Reassess

• Assess response to treatment within 24-48 hours; if no improvement or continued worsening, urgent referral to pediatric dermatology or allergy is indicated. 5
• Failure to respond to first-line management (topical measures and antihistamines) is an explicit indication for specialist referral. 5

Clinical Reasoning for This Approach

• Antihistamines alone have limited efficacy when symptoms are progressive and severe, as their therapeutic value resides principally in sedative properties for pruritus rather than treating the underlying inflammatory process. 5
• The worsening course over 3 days despite antihistamine therapy indicates a more aggressive inflammatory process requiring systemic anti-inflammatory treatment. 5
• Systemic corticosteroids have a definite role in severe acute urticarial/erythema multiforme presentations in children when first-line measures fail. 5, 2

Important Caveats and Pitfalls

• Do not use systemic corticosteroids as maintenance therapy; they are appropriate only for short-term control of acute flares. 5
• Monitor for secondary bacterial infection, which would require antibiotics (flucloxacillin for S. aureus or erythromycin if penicillin allergy). 5
• If fever develops or the child appears systemically unwell, consider eczema herpeticum (requires oral acyclovir) or other serious complications requiring immediate medical evaluation. 5
• Liquid formulations of medications are preferred in young children for easier administration and better absorption. 1
• The absence of fever, mucosal involvement, and blistering makes Stevens-Johnson syndrome less likely, but continued monitoring is essential as erythema multiforme can evolve. 5

Why Not Continue Antihistamines Alone?

• Antihistamines show only 42-65% good or very good response rates even in optimal conditions, and their value may be progressively reduced due to tachyphylaxis. 5
• Non-sedating antihistamines have little value in severe inflammatory skin conditions beyond symptomatic pruritus relief. 5
• The 3-day failure to respond with worsening symptoms indicates the need for escalation rather than continuation of ineffective therapy. 5