How should I assess and manage a 10‑month‑old infant with a single episode of diffuse urticaria at night that resolved after Benadryl (diphenhydramine)?

Assessment and Management of Single Episode of Diffuse Urticaria in a 10-Month-Old

For a 10-month-old infant with a single episode of widespread hives that resolved with Benadryl, you should transition immediately to a second-generation antihistamine (cetirizine 2.5 mg once or twice daily) and discontinue diphenhydramine, as first-generation antihistamines are associated with significant safety concerns in children under 6 years, including 33 deaths between 1969-2006. 1

Immediate Safety Concerns with Diphenhydramine

• Diphenhydramine should be avoided in children under 6 years of age for routine allergic symptoms due to documented mortality risk, with the FDA and pediatric advisory committees recommending against OTC cough and cold medications (including first-generation antihistamines) in this age group 1
• The medication carries risks of respiratory depression, cardiac toxicity (including cardiac arrest), and central nervous system effects, particularly when given intravenously or in higher doses 2, 3
• While diphenhydramine may be used as adjunctive therapy in true anaphylaxis under direct medical supervision at 1.25 mg/kg, it should never be first-line treatment even in emergencies 1

Recommended Treatment Approach

Switch to second-generation antihistamines:

• Cetirizine 2.5 mg once or twice daily (preferred for ages 6 months to 2 years) 1
• Loratadine 5 mg once daily (alternative option for ages 2-5 years) 1
• These agents have superior safety profiles with very low rates of serious adverse events in young children and lack the sedating/anticholinergic effects of first-generation antihistamines 1

Use liquid formulations as they are preferred in young children for easier administration and better absorption 1

Clinical Assessment to Determine Etiology

Identify the most likely trigger:

• Viral infection (most common): Benign viral illnesses account for approximately 81% of acute urticaria in infants and young children, often associated with antibiotic therapy 4
• Food allergens: Responsible for approximately 11% of cases, particularly in infants with atopic dermatitis or family history of atopy 4
• Drug reactions: Consider any medications given within 24-48 hours before the episode 4

Key clinical features to document:

• Presence of angioedema (occurs in 60% of acute urticaria cases in infants) 4
• Hemorrhagic or geographic lesions (seen in 49% of cases, more common with infectious causes) 4
• Associated symptoms such as fever, respiratory symptoms, or joint complaints 4
• Personal or family history of atopy (present in 58% of cases) 4

When to Prescribe Epinephrine Auto-Injector

Epinephrine is NOT indicated for this presentation because:

• The episode involved only urticaria without respiratory compromise, cardiovascular symptoms, or angioedema of the tongue/lips 5
• Self-injectable epinephrine is reserved for patients with history of anaphylaxis characterized by respiratory or cardiovascular compromise, or for those with generalized urticaria after insect stings (10% risk of severe future reaction) 5
• Acute generalized urticaria alone does not warrant a diagnosis of anaphylaxis or prescription of epinephrine 5

Follow-Up and Prognosis

Continue antihistamine therapy for 2 weeks as this is the standard treatment duration for acute urticaria in infants 4

Counsel parents that:

• 20-30% of infants with acute urticaria develop chronic or recurrent disease at 1-2 year follow-up 4
• Most cases are caused by benign viral illnesses and do not require extensive laboratory investigations 4
• If urticaria recurs or becomes chronic, referral to a pediatric allergist is indicated for proper diagnostic testing and identification of specific triggers 1

Common Pitfalls to Avoid

• Do not continue diphenhydramine for routine management despite its initial effectiveness—the safety risks outweigh benefits in this age group 1
• Do not prescribe epinephrine unless there is clear history of anaphylaxis with respiratory/cardiovascular involvement 5
• Do not order extensive laboratory workup for a single episode of acute urticaria, as the cause is typically viral and self-limited 4
• Do not use antihistamines prophylactically for prevention of future allergic disease, as this practice is contraindicated and provides no proven benefit 1