What is the treatment for urticarial angioedema?

Treatment of Urticarial Angioedema

Begin with second-generation non-sedating H1-antihistamines (cetirizine, desloratadine, fexofenadine, levocetirizine, or loratadine) at standard doses, and if inadequate response occurs after 2-4 weeks, increase the dose up to four times the standard dose before considering alternative therapies. 1

First-Line Treatment Approach

• Start with a single second-generation H1-antihistamine at standard dosing for 2-4 weeks to assess initial response 1
• Second-generation antihistamines are the mainstay of therapy for both acute and chronic urticaria with angioedema, with over 40% of patients showing good response to antihistamines alone 2, 3
• These agents work by blocking histamine release from mast cells and basophils, which drives the vasodilation and increased vascular permeability causing urticaria and angioedema 4

Preferred agents include:

• Cetirizine (shortest time to maximum concentration, advantageous for rapid symptom relief) 5
• Loratadine 1
• Desloratadine 1
• Fexofenadine 1
• Levocetirizine 1

Dose Escalation Strategy

• If standard dosing provides inadequate control after 2-4 weeks, increase the antihistamine dose up to 4 times the standard dose 1, 6
• This up-dosing strategy yields sufficient response in approximately 23% of patients who failed standard dosing 6
• If still insufficient, consider increasing beyond fourfold dosing (median effective dose of 8 times standard, range 5-12 times), which provides adequate control in an additional 49% of refractory patients 6
• Side effects remain minimal even at higher-than-fourfold dosing, with only 10% reporting adverse effects (primarily somnolence) 6

Second-Line Adjunctive Therapies

If antihistamine monotherapy fails despite dose escalation:

• Add H2-antihistamines (ranitidine or famotidine) for resistant cases 1, 2
• Add leukotriene receptor antagonists (montelukast) as adjunctive therapy, particularly beneficial for aspirin-sensitive and autoimmune urticaria 1, 2
• Consider switching to a different second-generation antihistamine, as individual responses vary significantly 5

Role of Corticosteroids

• Use short courses of oral corticosteroids only for severe acute urticaria or life-threatening angioedema (e.g., prednisolone 50 mg daily for 3 days in adults, or 3-10 days maximum) 1, 2
• Restrict corticosteroid courses to 3-4 weeks maximum 2
• Avoid long-term corticosteroid use in chronic urticaria except in very selected cases under specialist supervision due to cumulative toxicity 1, 5

Emergency Management of Life-Threatening Angioedema

• Administer intramuscular epinephrine immediately for anaphylaxis or severe laryngeal angioedema 7, 5, 8
• Adult/adolescent dose: 0.5 mL of 1:1000 (500 µg) epinephrine intramuscularly 7
• Pediatric dose (15-30 kg): 150 µg via fixed-dose epinephrine pen 7, 5
• If no significant relief after first dose, administer a second dose 7
• Epinephrine alleviates pruritus, urticaria, and angioedema through its effects on alpha-adrenergic receptors (reducing vasodilation and vascular permeability) and beta-adrenergic receptors (causing bronchial smooth muscle relaxation) 9

Third-Line Therapies for Severe Refractory Cases

For severe antihistamine-resistant chronic urticaria:

• Consider omalizumab 300 mg subcutaneously every 4 weeks 1
• Cyclosporine 4 mg/kg daily is effective in approximately two-thirds of patients with severe autoimmune urticaria, though optimal duration remains 16 weeks rather than 8 weeks 7, 1
• Monitor blood pressure and renal function every 6 weeks for patients on cyclosporine 1

Critical Pitfalls to Avoid

• Avoid aspirin and NSAIDs in urticaria patients, as they inhibit cyclooxygenase and can exacerbate symptoms 2
• Avoid ACE inhibitors in patients with angioedema without wheals, and use cautiously when angioedema accompanies urticaria 2
• Do not use epinephrine for angioedema caused by C1 inhibitor deficiency (hereditary angioedema), as it is not considered helpful 7
• Screen for hereditary angioedema with serum C4 levels in patients presenting with recurrent angioedema without wheals, as this requires different management (C1 inhibitor concentrate, tranexamic acid, or anabolic steroids rather than antihistamines) 2

Adjunctive Symptomatic Measures

• Minimize non-specific aggravating factors including overheating, stress, and alcohol 1
• Apply cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) for symptomatic relief 1
• Consider pseudoallergen-free diet in chronic cases, though only 19% demonstrate confirmed exacerbations on provocation testing 7

Monitoring and Follow-Up

• Regularly assess disease activity, impact on quality of life, and treatment response 1
• Consider stepping down therapy after achieving complete control for at least 3 consecutive months 1
• For patients requiring cyclosporine, monitor blood pressure and renal function every 6 weeks 1