What is the initial treatment for a patient presenting with hives in the Emergency Department (ED)?

Initial Treatment for Hives in the Emergency Department

For isolated hives (urticaria) without signs of anaphylaxis, start with an H1 antihistamine such as diphenhydramine 50 mg IV or oral, and consider adding an H2 antihistamine like ranitidine or famotidine for enhanced symptom relief. 1, 2

Critical First Step: Distinguish Hives from Anaphylaxis

Before initiating treatment, you must immediately assess whether the patient has isolated urticaria or anaphylaxis, as this fundamentally changes management:

Signs that indicate anaphylaxis requiring epinephrine first 3:

• Respiratory symptoms (wheezing, stridor, dyspnea, laryngospasm)
• Cardiovascular symptoms (hypotension, syncope, tachycardia with weak pulse)
• Gastrointestinal symptoms (vomiting, diarrhea, abdominal cramping)
• Airway swelling or angioedema involving lips, tongue, or eyelids
• Any systemic symptoms beyond skin findings

If any of these are present, this is anaphylaxis—give intramuscular epinephrine 0.3-0.5 mg (1:1000 solution) immediately before any other medications. 4, 1, 3

Treatment Algorithm for Isolated Hives (No Anaphylaxis)

First-Line Therapy

H1 Antihistamine 1, 2:

• Diphenhydramine 1-2 mg/kg per dose (maximum 50 mg) IV or oral
• Oral liquid formulation is absorbed more rapidly than tablets 4
• Alternative: Use a second-generation, less-sedating H1 antihistamine 4

Enhanced Therapy for Moderate-Severe Urticaria

Add H2 Antihistamine 1, 2:

• Ranitidine 1-2 mg/kg per dose (maximum 75-150 mg) oral or IV 4, 1
• Alternative: Famotidine at equivalent dosing 1
• The combination of H1 plus H2 antihistamines is more effective than either alone for urticaria relief 1, 2

Research evidence strongly supports this combination approach: a randomized controlled trial demonstrated that diphenhydramine plus cimetidine provided clinically significant relief in 92% of patients with urticaria compared to only 46% with diphenhydramine alone (P = 0.027). 2 Another study showed cimetidine alone was as effective as diphenhydramine but caused significantly less sedation. 5

Adjunctive Corticosteroids (Selective Use)

Consider adding corticosteroids for 4, 1:

• Severe, extensive urticaria
• Anticipated prolonged symptoms
• Recurrent urticaria episodes

Dosing 4, 1:

• Prednisone 1 mg/kg oral (maximum 60-80 mg), OR
• Methylprednisolone 1 mg/kg IV (maximum 60-80 mg)

Important caveat: Corticosteroids have no immediate effect on acute urticaria due to delayed onset of action (hours), but may prevent symptom recurrence over the following 1-2 days. 4, 1, 6

Common Pitfalls to Avoid

Never use antihistamines or corticosteroids as first-line treatment if there is any concern for anaphylaxis. 4, 1 The 2020 AAAAI practice parameter emphasizes that using antihistamines as primary treatment is the most common reason for failure to administer epinephrine, which significantly increases risk of progression to life-threatening reactions. 4, 1

Do not assume isolated hives will remain isolated. 6 Severe life-threatening respiratory or cardiovascular symptoms can appear suddenly even after hives have improved. 6 Maintain vigilance during the observation period.

Observation and Discharge Planning

Observation period 4, 6:

• Minimum 2-4 hours for isolated urticaria that responds promptly to treatment 4
• Patients with minimal residual symptoms may be discharged after 4 hours of stability 4

Discharge medications 4, 1:

• H1 antihistamine (diphenhydramine) every 6 hours for 2-3 days 4, 1
• H2 antihistamine (ranitidine or famotidine) twice daily for 2-3 days 4, 1
• Corticosteroid (prednisone) daily for 2-3 days if prescribed 4, 1

Critical discharge instructions 4, 1:

• Warn patients about possible recurrent urticaria over 1-2 days 4, 6
• Provide return precautions for any respiratory, cardiovascular, or systemic symptoms
• Consider prescribing epinephrine auto-injector if trigger is unknown or unavoidable 4
• Arrange follow-up with primary care or allergist 4, 1

Special Considerations

If the patient has a history of anaphylaxis or the trigger is unknown, strongly consider prescribing an epinephrine auto-injector even if current presentation is isolated urticaria. 4 Patients with food allergies (especially peanuts, tree nuts, fish, shellfish) and concurrent asthma are at highest risk for progression. 4

Sedation warning: Diphenhydramine causes significantly more sedation than H2 antihistamines or second-generation H1 antihistamines. 5 Consider this when selecting agents, particularly for patients who need to drive or operate machinery.