What is the treatment for urticaria?

Treatment of Urticaria

Second-generation H1-antihistamines at standard doses are the first-line treatment for all forms of urticaria, and should be increased up to 4-fold if symptoms persist after 2-4 weeks. 1, 2

First-Line Treatment: Second-Generation H1-Antihistamines

• Start with standard-dose second-generation H1-antihistamines such as cetirizine, desloratadine, fexofenadine, levocetirizine, or loratadine 1, 3, 2
• Offer patients at least two different non-sedating antihistamine options, as individual responses vary significantly 1, 2
• Second-generation agents are preferred over first-generation antihistamines due to longer duration of action, fewer anticholinergic effects, and significantly less sedation 1, 4, 5

Why Second-Generation Antihistamines Work

• These agents act as inverse agonists at H1 receptors and effectively treat pruritus, flushing, and urticaria 1
• They have similar onset of action to first-generation agents but superior safety profiles 1
• Peak plasma concentrations occur at 60-120 minutes, with maximal tissue effect requiring an additional 60-90 minutes 1

Step-Up Approach for Inadequate Control

Dose Escalation (After 2-4 Weeks)

• If symptoms remain inadequately controlled after 2-4 weeks, increase the second-generation H1-antihistamine dose up to 4 times the standard dose 1, 6, 2
• This updosing approach is now common practice when potential benefits outweigh risks 1
• If one antihistamine fails at high doses, trial a different second-generation antihistamine before advancing therapy 6

Adjunctive Therapies for Resistant Cases

• Add H2-antihistamines (such as ranitidine or cimetidine) to H1-antihistamines for additional histamine receptor blockade 1, 6
• Consider adding leukotriene receptor antagonists (such as montelukast) as combination therapy 1, 6
• Add first-generation antihistamines at night (such as hydroxyzine) to help with sleep and provide additional symptom control 1, 2

Second-Line Treatment: Omalizumab

• For chronic spontaneous urticaria unresponsive to high-dose antihistamines, initiate omalizumab 300 mg subcutaneously every 4 weeks 1, 2
• Allow up to 6 months for patients to respond to omalizumab before considering it a treatment failure 1, 2
• In patients with insufficient response, consider updosing by shortening the interval and/or increasing the dosage, with a maximum recommended dose of 600 mg every 14 days 1
• Higher doses are particularly beneficial in patients with high body mass index 1

Third-Line Treatment: Cyclosporine

• For patients who do not respond to high-dose antihistamines and omalizumab, initiate cyclosporine 4 mg/kg daily for up to 2 months 1, 2
• Cyclosporine is effective in approximately 65-70% of patients with severe antihistamine-resistant urticaria 2
• Monitor blood pressure and renal function (blood urea nitrogen and creatinine) every 6 weeks due to risks of hypertension and renal failure 1, 2
• Be aware of other potential adverse effects including epilepsy in predisposed individuals, hirsutism, and gum hypertrophy 1

Role of Corticosteroids

When to Use Corticosteroids

• Restrict oral corticosteroids to short courses (3-10 days maximum) for severe acute urticaria or angioedema affecting the mouth 1, 6, 2
• More prolonged treatment may be necessary for delayed pressure urticaria or urticarial vasculitis 1
• Do not administer corticosteroids before or in place of epinephrine in anaphylaxis 1

Why Corticosteroids Have Limited Role

• Glucocorticoids have slow onset of action, working by binding to receptors, translocating to the nucleus, and inhibiting gene expression of inflammatory mediators 1
• They are nonselective, ineffective in treating acute symptoms, and have multiple adverse effects with prolonged use 1
• Recent evidence shows that adding corticosteroids to antihistamines does not improve outcomes in acute urticaria in 2 out of 3 randomized controlled trials 7

General Measures and Trigger Avoidance

• Identify and avoid specific triggers including overheating, stress, alcohol, aspirin, NSAIDs, codeine, and ACE inhibitors 1, 6, 2
• Apply cooling antipruritic lotions such as calamine or 1% menthol in aqueous cream for symptomatic relief 1, 2
• NSAIDs should be avoided in aspirin-sensitive patients with urticaria 2
• ACE inhibitors should be avoided in patients with angioedema without wheals 2

Special Considerations by Urticaria Type

Physical Urticaria

• Physical urticaria weals typically resolve within 1 hour (except delayed pressure urticaria which can last up to 48 hours) 1, 3
• Treatment follows the same stepwise approach as ordinary urticaria 3
• In cholinergic urticaria, focus on avoiding core temperature increases 3

Urticarial Vasculitis

• If weals last longer than 24 hours, perform skin biopsy to evaluate for urticarial vasculitis, which requires different management 1, 6
• Ordinary urticaria weals typically last 2-24 hours 1, 6

Critical Distinction: Urticaria vs. Anaphylaxis

When Epinephrine Is Required

• Administer intramuscular epinephrine 0.5 mL of 1:1000 (500 µg) immediately for urticaria associated with anaphylaxis or angioedema affecting the airway 2, 8
• Epinephrine is the first-line treatment of anaphylaxis due to its vasoconstrictive, bronchodilatory, ionotropic, and mast cell stabilization properties 1
• Antihistamines should never be administered before or in place of epinephrine in anaphylaxis 1
• Epinephrine alleviates pruritus, urticaria, and angioedema through its action on alpha and beta-adrenergic receptors 9

Why Antihistamines Alone Are Insufficient in Anaphylaxis

• Unlike epinephrine, antihistamines are poorly effective in treating cardiovascular and respiratory symptoms such as hypotension or bronchospasm when used acutely as monotherapy 1
• The onset of action for oral antihistamines (30 minutes to peak effect at 60-120 minutes) is too slow for the rapid and potentially fatal nature of anaphylaxis 1

Monitoring and Step-Down Strategy

When to Step Down Treatment

• Consider stepping down therapy after achieving complete symptom control for at least 3 consecutive months 1
• Reduce the daily dose gradually, no more than 1 tablet per month 1, 6
• If symptoms recur during step-down, return to the last effective dose that provided complete control 1, 6

Use of Disease Control Assessment

• Regularly assess disease activity using the Urticaria Control Test (UCT) 1
• In patients with UCT score ≤16, increase treatment intensity 1
• Step-down protocols should be implemented with prudence and patience 1

Prognosis

• Approximately 50% of patients with chronic urticaria presenting with wheals alone will be clear by 6 months 1, 6, 2
• Patients with both wheals and angioedema have a poorer outlook, with over 50% still having active disease after 5 years 1, 2
• Over 40% of hospitalized patients with urticaria show a good response to antihistamines 1

Common Pitfalls to Avoid

• Do not perform extensive laboratory workup unless history or physical examination suggests specific underlying conditions, as chronic urticaria is idiopathic in 80-90% of cases 10
• Do not use first-generation antihistamines as first-line monotherapy due to marked sedative and anticholinergic effects 4, 5
• Do not continue corticosteroids beyond short courses due to cumulative toxicity that is dose and time dependent 6
• Do not delay epinephrine administration in anaphylaxis to give antihistamines or corticosteroids first 1