What is the management of chronic urticaria?

Management of Chronic Urticaria

Start with a standard-dose second-generation H1 antihistamine as first-line therapy, escalate to up to 4 times the standard dose if inadequate control after 2-4 weeks, add omalizumab 300 mg subcutaneously every 4 weeks if symptoms persist despite high-dose antihistamines, and reserve cyclosporine (up to 5 mg/kg) for patients who fail both antihistamines and omalizumab after 6 months. 1, 2

First-Line Treatment: Second-Generation H1 Antihistamines

• Begin with standard-dose second-generation non-sedating H1 antihistamines (cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, or mizolastine), which are the mainstay of therapy for chronic urticaria 1, 2

• Offer patients at least two different non-sedating antihistamines to choose from, as individual responses and tolerance vary significantly between agents 2, 3

• If symptoms remain inadequately controlled after 2-4 weeks, increase the antihistamine dose up to 4 times the standard dose when potential benefits outweigh risks 1, 2

• This dose escalation strategy is now common practice and supported by international guidelines, even though it exceeds manufacturer's licensed recommendations 1

• First-generation sedating antihistamines (like hydroxyzine or chlorphenamine) can be added at night for additional symptom control and to help with sleep disturbance, but should not be used as first-line monotherapy due to sedation and anticholinergic effects 3, 4

Second-Line Treatment: Omalizumab

• For chronic spontaneous urticaria unresponsive to high-dose antihistamines, add omalizumab (anti-IgE monoclonal antibody) at 300 mg subcutaneously every 4 weeks 1, 2, 5

• Allow up to 6 months for patients to respond to omalizumab before considering it a treatment failure 1, 6, 2

• If insufficient response at standard dosing, the dose can be increased to 600 mg every 2 weeks as the maximum recommended dose 1, 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

• Critical pitfall: Omalizumab carries a black box warning for anaphylaxis, which can occur after the first dose or beyond 1 year of treatment; therefore, initiate therapy in a healthcare setting and observe patients for an appropriate period after administration 5

Third-Line Treatment: Cyclosporine

• For patients who do not respond to high-dose antihistamines and omalizumab within 6 months, add cyclosporine to the antihistamine regimen at a dose of up to 5 mg/kg body weight 1, 6, 2

• Cyclosporine is effective in approximately 65-75% of patients with severe autoimmune urticaria 6, 7

• Monitor blood pressure and renal function every 6 weeks due to potential nephrotoxicity and hypertension 6, 2

• A treatment duration of 16 weeks with cyclosporine is superior to 8 weeks for reducing therapeutic failures 6

Adjunctive Therapies for Resistant Cases

• Combinations of non-sedating H1 antihistamines with H2 antihistamines (like cimetidine or ranitidine) can be useful for resistant cases, though evidence is mixed 1

• Addition of leukotriene receptor antagonists (montelukast) may provide benefit in some refractory patients 1

Role of Corticosteroids

• Restrict oral corticosteroids to short courses (3-10 days) for severe acute exacerbations or angioedema affecting the mouth only—they should not be used chronically due to cumulative toxicity 1, 6, 3

• More prolonged corticosteroid treatment may be necessary for delayed pressure urticaria or urticarial vasculitis, but long-term use should be avoided except in very selected cases under regular specialist supervision 1, 6

General Measures and Trigger Avoidance

• Identify and minimize aggravating factors including overheating, stress, alcohol, aspirin, NSAIDs, and codeine 6, 2, 3

• NSAIDs should be avoided in aspirin-sensitive patients with urticaria 2, 3

• ACE inhibitors should be avoided in patients with angioedema without wheals 2, 3

• Cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) can provide symptomatic relief 6, 2

• Patient education about the generally favorable prognosis is important: approximately 50% of patients with chronic urticaria presenting with wheals alone will be clear by 6 months, though those with wheals and angioedema have a poorer outlook with over 50% still having active disease after 5 years 3

Treatment Step-Down Protocol

• In patients with complete disease control (UCT score >16), step-down should be considered to reduce treatment burden and assess for spontaneous remission 1

• Patients should not step down from higher-than-standard antihistamine doses before completing at least 3 consecutive months of complete control 1

• The daily antihistamine dose should not be reduced by more than 1 tablet per month 1

• When control is lost during treatment step-down, return to the last dose that previously provided complete control 1

Special Population Considerations

Renal Impairment

• Avoid acrivastine in moderate renal impairment; halve the dose of cetirizine, levocetirizine, and hydroxyzine in moderate renal impairment 2, 3
• Avoid cetirizine, levocetirizine, and alimemazine in severe renal impairment 2

Hepatic Impairment

• Avoid mizolastine in significant hepatic impairment 2, 3
• Avoid alimemazine, chlorphenamine, and hydroxyzine in severe liver disease 2, 3

Pregnancy

• Avoid antihistamines during pregnancy if possible, especially during the first trimester 2, 3
• If necessary, choose chlorphenamine due to its long safety record 2, 3
• Loratadine and cetirizine are FDA Pregnancy Category B drugs 2

Diagnostic Considerations

• Urticaria can usually be classified on clinical presentation without extensive investigation 1

• The wheals of ordinary chronic urticaria typically last from 2 to 24 hours 1

• If wheals last longer than 24 hours, urticarial vasculitis should be sought by skin biopsy 1

• At least 30% of patients with chronic urticaria appear to have an autoimmune etiology; the autologous serum skin test (ASST) is a reasonably sensitive and specific marker for histamine-releasing autoantibodies in this group 1

• Only a limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions 8

Immunomodulating Therapies

• Immunomodulating therapies for chronic autoimmune urticaria should be restricted to patients with disabling disease who have not responded to optimal conventional treatments (high-dose antihistamines, omalizumab, and cyclosporine) 1