What is the treatment for exercise-induced urticaria?

Treatment of Exercise-Induced Urticaria

Start with second-generation non-sedating H1 antihistamines at standard dose, and if symptoms persist after 2-4 weeks, increase up to 4 times the standard dose before considering escalation to omalizumab or other therapies. 1

Critical First Step: Distinguish Exercise-Induced Urticaria from Exercise-Induced Anaphylaxis

Before initiating treatment, you must differentiate isolated exercise-induced urticaria from exercise-induced anaphylaxis, as the latter requires immediate epinephrine and represents a medical emergency. 2, 3

Exercise-induced urticaria presents with:

• Isolated hives (10-15 mm conventional wheals) triggered only by exercise 2, 4
• Generalized pruritus, flushing, and warmth without systemic progression 4, 5
• No vascular collapse, laryngeal edema, or bronchospasm 2

Exercise-induced anaphylaxis progresses to:

• Angioedema, gastrointestinal symptoms, laryngeal edema, and/or vascular collapse 2
• Approximately one-third experience transient loss of consciousness 2
• Nearly two-thirds develop upper respiratory obstruction 2
• Requires immediate intramuscular epinephrine 3, 5

Also exclude cholinergic urticaria, which presents with characteristic punctate wheals (1-3 mm, not 10-15 mm) triggered by core body temperature increase from exercise OR passive warming (hot shower, sauna), whereas exercise-induced urticaria requires actual exercise. 1, 2, 4

First-Line Treatment: Antihistamine Therapy

Begin with a second-generation non-sedating H1 antihistamine at standard dose, as recommended by the American College of Allergy, Asthma, and Immunology. 1

Preferred agents include:

• Cetirizine 10 mg daily (shortest time to maximum concentration for rapid relief) 6
• Loratadine 10 mg daily 1, 6
• Fexofenadine, desloratadine, or levocetirizine 1

Offer at least two different non-sedating antihistamines to each patient, as individual responses and tolerance vary significantly between agents. 1, 6

If inadequate symptom control after 2-4 weeks, increase the dose up to 4 times the standard dose (e.g., cetirizine 40 mg daily or loratadine 40 mg daily). 1, 6

Avoid first-generation antihistamines (diphenhydramine, hydroxyzine) in routine management due to marked sedation and anticholinergic effects, though hydroxyzine may be effective for cholinergic urticaria specifically. 7, 4, 8

Second-Line Treatment: Omalizumab

For urticaria unresponsive to high-dose antihistamines, add omalizumab at 300 mg subcutaneously every 4 weeks. 1, 6

• Allow up to 6 months for patients to respond before considering treatment failure 1, 6
• If insufficient response at standard dosing, increase to 600 mg every 2 weeks as the maximum recommended dose 1

Third-Line Treatment: Cyclosporine

For patients who fail both high-dose antihistamines and 6 months of omalizumab, add cyclosporine to the antihistamine regimen at up to 5 mg/kg body weight. 1, 6

• Effective in approximately 65-70% of patients with severe urticaria 1, 6
• Monitor blood pressure and renal function every 6 weeks due to nephrotoxicity and hypertension risk 1, 6

Role of Corticosteroids

Restrict oral corticosteroids to short courses (3-10 days) for severe acute exacerbations only—never use chronically due to cumulative toxicity. 1

For acute management of urticarial reactions, hydrocortisone 200 mg IV may be administered if symptoms do not improve after 15 minutes of observation. 7

Essential Adjunctive Measures

Identify and minimize aggravating factors:

• Overheating and environmental heat exposure 1, 6
• Stress 1, 6
• Alcohol consumption 1, 6
• Aspirin and NSAIDs (avoid in all patients, as 13% of exercise-induced anaphylaxis cases involve NSAID use) 1, 2, 6
• Codeine 1, 6

Screen for food-dependent exercise-induced anaphylaxis (FDEIA):

• Ask about temporal relationship between specific food ingestion and exercise within 4-6 hours 2
• Common culprits include wheat and soy 2, 9
• If FDEIA is suspected, patients can consume culprit foods safely if they avoid exercise for 4-6 hours afterward 2

Symptomatic relief:

• Cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) provide symptomatic relief 1, 6

Critical Pitfall to Avoid

Never confuse exercise-induced urticaria with cholinergic urticaria, as the latter responds well to hydroxyzine and presents with punctate wheals triggered by any core temperature increase (including hot showers), not just exercise. 1, 4 Exercise-induced urticaria requires actual physical exertion and presents with larger conventional wheals. 2, 4

Emergency Preparedness

All patients with exercise-induced urticaria should be counseled about the potential for progression to exercise-induced anaphylaxis, though this is uncommon in isolated urticaria. 2, 5

If systemic symptoms develop (dyspnea, throat tightness, hypotension, gastrointestinal symptoms):

• Stop exercise immediately 4, 5
• Administer epinephrine intramuscularly (Adrenalin®) 3, 5
• Seek emergency medical care 5