What is the treatment for urticaria?

Treatment of Urticaria

Start with second-generation non-sedating H1 antihistamines as first-line therapy, escalate the dose up to 4 times standard if needed, add omalizumab 300 mg every 4 weeks for chronic cases unresponsive to high-dose antihistamines, and reserve cyclosporine for patients who fail omalizumab. 1, 2

First-Line Treatment: Second-Generation Antihistamines

• Begin immediately with a second-generation non-sedating H1 antihistamine (cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, or mizolastine) for both acute and chronic urticaria 1, 3, 2

• Offer patients at least two different antihistamine options, as individual responses and tolerance vary significantly between agents 1, 3

• Use antihistamines on a regular scheduled basis, not just after hives appear 4

• First-generation antihistamines (diphenhydramine, hydroxyzine, chlorpheniramine) should be avoided as primary therapy due to significant sedation and anticholinergic effects, though they may be added at night for additional symptom control if needed 3, 2

Dose Escalation Strategy

• If standard dosing provides inadequate control within 24-48 hours for acute urticaria or 2-4 weeks for chronic urticaria, increase the antihistamine dose up to 4 times the standard dose when benefits outweigh risks 1, 3, 2

• This updosing strategy is strongly supported by international guidelines and should be attempted before adding additional agents 5, 6

Corticosteroids for Acute Urticaria

• Add a short course of oral corticosteroids (prednisolone 50 mg daily for 3 days) for moderate to severe acute urticaria, rather than waiting for antihistamine failure 3

• Restrict corticosteroid use to short 3-10 day courses only due to cumulative dose- and time-dependent toxicity 3

• For chronic urticaria, oral corticosteroids should only be used for short courses in severe cases or angioedema affecting the mouth 2

Second-Line Treatment: Omalizumab

• For chronic spontaneous urticaria (CSU) unresponsive to high-dose antihistamines, add omalizumab (anti-IgE monoclonal antibody) 300 mg subcutaneously every 4 weeks 5, 1, 7

• Omalizumab is FDA-approved for adults and adolescents 12 years and older with CSU who remain symptomatic despite H1 antihistamine treatment 7

• Allow up to 6 months for patients to respond to omalizumab before considering it a treatment failure 5, 1

• If insufficient response occurs, consider updosing by shortening the interval and/or increasing the dosage up to a maximum of 600 mg every 14 days 5

• Higher doses are particularly beneficial in patients with high body mass index 5

• The dosage for CSU is not dependent on serum IgE level or body weight, unlike its use in asthma 7

Omalizumab Safety Considerations

• Omalizumab carries a risk of anaphylaxis, which can occur as early as the first dose or beyond 1 year of treatment 7

• Initiate therapy in a healthcare setting and observe patients for an appropriate period after administration 7

• Healthcare providers must be prepared to manage life-threatening anaphylaxis 7

Third-Line Treatment: Cyclosporine

• For patients who do not respond to high-dose antihistamines and omalizumab, add cyclosporine 4 mg/kg daily (up to 5 mg/kg) for up to 2 months 5, 1, 2

• Cyclosporine is effective in approximately 65-70% of patients with severe autoimmune urticaria 1, 2

• Treatment duration of 16 weeks is superior to 8 weeks for reducing therapeutic failures 2

• Monitor blood pressure and renal function (blood urea nitrogen and creatinine) every 6 weeks while on cyclosporine due to risks of hypertension, nephrotoxicity, epilepsy in predisposed patients, hirsutism, and gum hypertrophy 5, 1

• The risk-benefit profile of high-dose omalizumab is superior to cyclosporine, making cyclosporine truly a last-resort option 5

Treatment Algorithm Summary

Follow this stepwise approach:

1. Start with standard-dose second-generation H1 antihistamine 1, 2
2. If inadequate control after 2-4 weeks, increase dose up to 4x standard 5, 1
3. If still inadequate control, add omalizumab 300 mg every 4 weeks 5, 1
4. If inadequate response to omalizumab within 6 months, consider cyclosporine 5, 1

Use an "as much as needed and as little as possible" approach by stepping up and stepping down treatment based on disease control 5

General 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

• Avoid ACE inhibitors in patients with angioedema without wheals, as they can precipitate or worsen angioedema 1, 2

• Apply cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) for symptomatic relief 1, 3

• Prevent skin from drying, avoid hot showers, scrubbing, and excessive sun exposure to minimize hyperresponsive skin 6

Emergency Management

• For acute urticaria with signs of anaphylaxis or angioedema affecting the airway, immediately administer intramuscular epinephrine 0.5 mL of 1:1000 solution (500 µg) into the anterolateral thigh 3, 2

• Follow with antihistamines and corticosteroids as adjunctive therapy 3

• Prescribe fixed-dose epinephrine auto-injectors (300 µg for adults) for patients at risk of life-threatening attacks 2

Special Population Considerations

Renal Impairment

• Avoid acrivastine in moderate renal impairment 1
• Halve the dose of cetirizine, levocetirizine, and hydroxyzine in moderate renal impairment 1, 2
• Avoid cetirizine, levocetirizine, and alimemazine in severe renal impairment 1

Hepatic Impairment

• Avoid mizolastine in significant hepatic impairment 1, 2
• Avoid alimemazine, chlorphenamine, and hydroxyzine in severe liver disease 1, 2

Pregnancy

• Avoid antihistamines during pregnancy if possible, especially during the first trimester 1, 2
• If necessary, choose chlorphenamine due to its long safety record 1, 2
• Loratadine and cetirizine are FDA Pregnancy Category B drugs 1

Diagnostic Workup for Chronic Spontaneous Urticaria

• Perform thorough history and physical examination, including review of pictures of wheals and/or angioedema 5

• Basic tests should include differential blood count, C-reactive protein or ESR, total IgE, and IgG-anti-thyroid peroxidase (TPO) levels 5

• Testing for IgG-anti-TPO and total IgE helps identify autoimmune CSU: patients with autoimmune CSU typically have low or very low total IgE levels and elevated IgG-anti-TPO 5

• A high ratio of IgG-anti-TPO to total IgE is currently the best surrogate marker for autoimmune CSU 5

• Routine extensive laboratory investigation is not cost-effective in CSU unless clinical features suggest autoimmune diseases 6

Common Pitfalls to Avoid

• Do not use first-generation antihistamines as monotherapy due to sedation and lack of proven superiority over second-generation agents 3, 6

• Do not use antihistamines on an as-needed basis; they must be taken regularly for optimal effect 4

• Do not abandon omalizumab too early; allow the full 6 months for response before declaring treatment failure 5, 1

• Do not use prolonged courses of systemic corticosteroids for chronic urticaria due to significant long-term toxicity 3

• Do not re-test IgE levels during omalizumab treatment for dose adjustment, as levels remain elevated for up to one year after discontinuation 7