What is the recommended treatment for a patient with urticaria, considering their past medical history and demographics?

Treatment of Urticaria

Second-generation non-sedating H1 antihistamines are the first-line treatment for urticaria, with cetirizine or loratadine as preferred initial options, and doses can be escalated up to 4 times the standard dose if symptoms remain inadequately controlled after 2-4 weeks. 1, 2

First-Line Treatment: Antihistamines

Initial Antihistamine Selection

• Offer patients a choice between at least two different second-generation antihistamines (cetirizine, loratadine, desloratadine, fexofenadine, or levocetirizine), as individual responses and tolerance vary significantly between patients 1, 3
• Cetirizine has the shortest time to maximum concentration, making it advantageous when rapid symptom relief is needed 1, 3
• Avoid first-generation antihistamines (diphenhydramine, hydroxyzine) as monotherapy due to marked sedation and anticholinergic effects, though they may be added at night if the H1 receptor is not already saturated 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 before adding other therapies 1, 3, 2
• This dose escalation is common practice when potential benefits outweigh risks, though it exceeds manufacturer's licensed recommendations 1
• Adjust timing of medication to ensure highest drug levels coincide with anticipated urticaria symptoms 1

Adjunctive H2 Antihistamines

• Adding an H2 antihistamine (cimetidine, ranitidine) to an H1 antihistamine may provide better control than H1 antihistamine alone, though evidence is limited 1, 2
• This combination is particularly effective for symptomatic dermatographism 4

Second-Line Treatment: Omalizumab

For chronic spontaneous urticaria unresponsive to high-dose antihistamines, omalizumab 300 mg subcutaneously every 4 weeks is the next step. 2, 5, 6

• Omalizumab is FDA-approved for adults and adolescents 12 years and older with chronic spontaneous urticaria who remain symptomatic despite H1 antihistamine treatment 5
• Allow up to 6 months to evaluate response before considering alternative treatments 3, 2
• Omalizumab is effective in approximately 70% of antihistamine-refractory patients 6
• Dosing for chronic spontaneous urticaria is not dependent on serum IgE level or body weight, unlike dosing for asthma 5

Important Safety Consideration

• Omalizumab carries a risk of anaphylaxis (presenting as bronchospasm, hypotension, syncope, urticaria, and/or angioedema), which can occur after the first dose or beyond 1 year of treatment 5
• Initiate therapy in a healthcare setting and observe patients for an appropriate period after administration 5

Third-Line Treatment: Cyclosporine

For patients who fail both high-dose antihistamines and omalizumab, cyclosporine at 4 mg/kg daily for up to 2 months is recommended. 1, 2, 6

• Cyclosporine is effective in approximately 65-70% of patients with severe autoimmune urticaria 1, 6
• Monitor blood pressure and renal function regularly (every 6 weeks) due to potential side effects 2, 6
• Optimal duration may be 16 weeks rather than 8 weeks based on recent evidence, with fewer therapeutic failures at longer duration 1
• Only 25% of responders remain clear or much improved 4-5 months after stopping treatment 1

Role of Corticosteroids

Short-Term Use Only

• Oral corticosteroids (prednisone, hydrocortisone 200 mg IV) should be restricted to short courses of 3-10 days only for severe acute exacerbations or angioedema involving the mouth 1, 3, 2
• Corticosteroids can shorten the duration of acute urticaria episodes 3
• Long-term or maintenance corticosteroid therapy should never be used in chronic urticaria due to cumulative toxicity (adrenal suppression, growth interference in children, dermal thinning, hypertension, diabetes, Cushing syndrome, cataracts, muscle weakness, impaired immune function) 2, 6

Acute Urticaria Evidence

• Recent systematic review evidence is mixed: addition of prednisone to cetirizine or levocetirizine did not improve symptoms compared to antihistamine alone in two out of three RCTs 7
• Despite limited evidence, short courses remain reasonable for severe acute presentations with significant angioedema 3

Adjunctive Measures and Trigger Avoidance

• Identify and minimize aggravating factors including overheating, stress, alcohol, aspirin, NSAIDs, and codeine 1, 2
• Avoid NSAIDs in aspirin-sensitive patients with urticaria 1, 2
• Control environmental temperature to decrease symptoms and reduce antihistamine requirements 3
• Cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) can provide symptomatic relief 2

Emergency Management

Intramuscular epinephrine is life-saving in anaphylaxis and severe laryngeal angioedema. 1, 3

• Dosing is weight-dependent: 0.5 mL of 1:1000 (500 µg) for adults and adolescents older than 12 years 1
• Fixed-dose epinephrine auto-injector pens deliver 300 µg for adults or 150 µg for children weighing 15-30 kg 1, 3
• If no significant relief after the first dose, administer a further dose 1
• Epinephrine is not helpful for angioedema caused by C1 inhibitor deficiency 1

Special Populations

Pediatric Considerations

• Second-generation antihistamines (cetirizine, loratadine) are first-line for children 6 years and older 3
• For infants, cetirizine is particularly well-studied and has the shortest time to maximum concentration 8
• Approximately 50% of children with chronic urticaria presenting with wheals alone will be symptom-free within 6 months 3, 8
• Patients with both wheals and angioedema have poorer prognosis, with over 50% still having active disease after 5 years 3

Pregnancy

• Avoid all antihistamines in pregnancy when possible, especially during the first trimester 1
• Chlorpheniramine is often chosen when antihistamine therapy is necessary due to its long safety record 1
• Hydroxyzine is specifically contraindicated during early pregnancy 1

Renal Impairment

• Halve the dose of cetirizine, levocetirizine, and hydroxyzine in moderate renal impairment 1
• Avoid acrivastine in moderate renal impairment (creatinine clearance 10-20 mL/min) 1
• Avoid cetirizine, levocetirizine in severe renal impairment (creatinine clearance <10 mL/min) 1

Hepatic Impairment

• Mizolastine is contraindicated in significant hepatic impairment 1
• Avoid chlorphenamine and hydroxyzine in severe liver disease due to inappropriate sedating effects 1

Common Pitfalls to Avoid

• Do not use first-generation antihistamines (diphenhydramine) or vasopressors during infusion reactions, as these can convert minor reactions into hemodynamically significant serious adverse events including exacerbation of hypotension, tachycardia, and shock 1
• Do not add H2 antihistamines or leukotriene antagonists routinely, as literature does not support significant added efficacy in most cases 6
• Do not use topical crotamiton cream or capsaicin for chronic urticaria, as evidence does not support their use 2
• Do not retest IgE levels during omalizumab treatment for dose determination, as total IgE levels remain elevated for up to one year after discontinuation 5

Prognosis

• The prognosis for eventual recovery from ordinary, physical, and vasculitic urticarias is excellent, though some physical urticarias may be especially persistent 1
• In chronic urticaria, a cause is unlikely to be found in most cases 1