What is the recommended management for urticaria?

Urticaria Management

Start with a standard-dose second-generation H1-antihistamine (cetirizine, desloratadine, fexofenadine, levocetirizine, or loratadine) as first-line therapy, and if inadequate control persists after 2-4 weeks, increase the dose up to 4-fold before considering other treatments. 1, 2

Initial Classification and Assessment

Distinguish between acute urticaria (≤6 weeks) and chronic urticaria (>6 weeks), as management strategies differ. 2

• Weal duration helps differentiate types: physical urticaria weals typically resolve within 1 hour (except delayed pressure urticaria), while ordinary urticaria weals last 2-24 hours 1
• If weals persist beyond 24 hours, perform a skin biopsy to evaluate for urticarial vasculitis, which requires different management 1, 3
• Obtain baseline testing including differential blood count, C-reactive protein or ESR, total IgE, and IgG-anti-TPO levels to identify autoallergic or autoimmune mechanisms 1

Stepwise Treatment Algorithm

Step 1: First-Line Treatment (Standard-Dose Antihistamines)

Initiate treatment with a standard dose of a second-generation H1-antihistamine taken once daily. 1, 2

• Offer patients a choice of at least two different non-sedating antihistamines, as individual responses and tolerance vary significantly 1, 2
• Standard doses: cetirizine 10 mg, desloratadine 5 mg, fexofenadine 180 mg, levocetirizine 5 mg, or loratadine 10 mg daily 1, 4
• Approximately 43% of patients achieve remission with standard-dose antihistamines 5
• Continue for 2-4 weeks to assess response before escalating therapy 1, 2

Step 2: Dose Escalation and Combination Therapy

If symptoms remain inadequately controlled after 2-4 weeks, increase the antihistamine dose up to 4 times the standard dose. 1, 2, 3

• This updosing approach is common practice when potential benefits outweigh risks, though it exceeds manufacturer's licensed recommendations 1
• Consider switching to a different second-generation antihistamine if one fails at high doses, as 15% of patients benefit from switching 5
• Updosing provides remission in approximately 38% of patients who failed standard doses 5

For resistant cases, add adjunctive therapies:

• Add an H2-antihistamine (ranitidine or famotidine) for additional histamine receptor blockade 1, 2
• Consider adding a leukotriene receptor antagonist (montelukast), which provides remission in approximately 25% of resistant patients 1, 2, 5
• Combination of two different second-generation antihistamines achieves remission in approximately 36% of patients 5
• Adding a sedating antihistamine at night (chlorphenamine 4-12 mg or hydroxyzine 10-50 mg) may help sleep, though it adds little additional urticaria control if H1 receptors are already saturated 1

Step 3: Second-Line Treatment (Omalizumab)

For patients who fail high-dose antihistamines and combination therapy, add omalizumab 300 mg subcutaneously every 4 weeks. 1, 2

• Allow up to 6 months for patients to respond to omalizumab 1
• If insufficient response occurs, consider updosing by shortening the interval and/or increasing the dose 1
• Maximum recommended dose is 600 mg every 2 weeks, particularly beneficial in patients with high body mass index 1
• The risk-benefit profile of high-dose omalizumab is superior to cyclosporine 1

Step 4: Third-Line Treatment (Cyclosporine)

For patients who do not respond to higher-than-standard doses of omalizumab, consider cyclosporine at 4-5 mg/kg body weight daily. 1, 2

• Cyclosporine provides remission in approximately two-thirds of patients with severe autoimmune urticaria 2
• Monitor blood pressure and renal function (blood urea nitrogen and creatinine) every 6 weeks during treatment 1, 2
• Be aware of potential risks: hypertension, seizures in predisposed patients, hirsutism, gum hypertrophy, and renal failure 1
• Restrict immunomodulating therapies to patients with disabling disease who have not responded to optimal conventional treatments 1

Role of Corticosteroids

Restrict oral corticosteroids to short courses (3-10 days) for severe acute urticaria or angioedema affecting the mouth. 1, 2, 3

• Do not continue corticosteroids beyond 3-10 days due to cumulative toxicity that is dose and time dependent 3
• More prolonged corticosteroid treatment may be necessary only for delayed pressure urticaria or urticarial vasculitis 1
• Avoid long-term use in chronic urticaria except in very selected cases under specialist supervision 2

General Measures and Trigger Avoidance

Counsel patients to minimize non-specific aggravating factors and avoid known triggers. 1, 2, 3

• Avoid overheating, stress, and alcohol 2, 3
• Discontinue medications that worsen urticaria: aspirin, NSAIDs, codeine, and ACE inhibitors 2, 3
• Apply cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) for symptomatic relief 2

Treatment Step-Down Protocol

Once complete disease control is achieved for at least 3 consecutive months, consider stepping down therapy to assess for spontaneous remission. 1, 2

• Reduce the daily antihistamine dose gradually, no more than 1 tablet per month 1, 2
• If symptoms recur during step-down, return to the last effective dose that provided complete control 1, 2
• Use the Urticaria Control Test (UCT) to assess disease control; a score >16 indicates complete control 1

Special Population Considerations

Pregnancy

• Avoid all antihistamines if possible, especially during the first trimester 1, 2
• If treatment is necessary, chlorphenamine has the longest safety record in the UK, while loratadine and cetirizine are FDA Pregnancy Category B 1, 2
• Hydroxyzine is specifically contraindicated during early pregnancy 1

Renal Impairment

• Avoid acrivastine in moderate renal impairment (creatinine clearance 10-20 mL/min) 1, 2
• Halve the dose of cetirizine, levocetirizine, and hydroxyzine in moderate impairment 1, 2
• Avoid cetirizine, levocetirizine, and alimemazine in severe renal impairment (creatinine clearance <10 mL/min) 1, 2

Hepatic Impairment

• Mizolastine is contraindicated in significant hepatic impairment 1, 2
• Avoid alimemazine, chlorphenamine, and hydroxyzine in severe liver disease due to hepatotoxicity and inappropriate sedating effects 1, 2

Pediatric Patients

• Second-generation H1-antihistamines remain the cornerstone of management in children 2, 6
• Dose and age restrictions vary for younger children 2
• Acute episodic urticaria is the most prevalent form in the pediatric population, often triggered by viruses, food allergies, or physical stimuli 6

Predictors of Antihistamine Refractoriness

Identify patients at higher risk for antihistamine failure who may require earlier escalation to third-line treatments. 5

• Baseline UCT score ≤4 predicts antihistamine refractoriness 5
• Emergency department referral is associated with treatment resistance 5
• Family history of chronic spontaneous urticaria increases risk of antihistamine failure 5

Prognosis

• Approximately 50% of patients with chronic urticaria presenting with weals alone are clear by 6 months 1
• Patients with both weals and angioedema have a poorer outlook, with over 50% still having active disease after 5 years 1
• The prognosis for complete recovery has likely not changed over 40 years, though newer antihistamines provide better disease control 1