What is the treatment for severe hives (urticaria)?

Treatment of Severe Hives (Urticaria)

For severe hives (urticaria), the treatment approach should follow a stepwise algorithm starting with high-dose second-generation H1 antihistamines, progressing to omalizumab for refractory cases, and considering cyclosporine as third-line therapy. 1

First-Line Treatment

• Second-generation non-sedating H1 antihistamines are the mainstay of therapy for severe urticaria, with options including cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, and mizolastine 1
• For severe cases (generalized involvement with >30% body surface area affected), increase the dose up to 4 times the standard dose when potential benefits outweigh risks 1, 2
• Patients should be offered at least two different non-sedating antihistamines, as responses and tolerance vary between individuals 1
• First-generation antihistamines (like diphenhydramine) should generally be avoided due to sedation and potential to convert minor reactions into hemodynamically significant events 3

Second-Line Treatment

• For severe urticaria unresponsive to high-dose antihistamines, omalizumab (anti-IgE monoclonal antibody) is recommended 1
• The standard starting dose is 300 mg every 4 weeks, with the option to increase up to 600 mg every 14 days in patients with insufficient response 1
• Allow up to 6 months for patients to respond to omalizumab before considering alternative treatments 1
• Omalizumab is particularly effective for recurrent anaphylaxis and skin symptoms associated with severe urticaria 3

Third-Line Treatment

• Cyclosporine is recommended for patients who do not respond to high-dose antihistamines and omalizumab 1
• It is effective in about two-thirds of patients with severe autoimmune urticaria at 4 mg/kg daily for up to 2 months 3, 1
• Regular monitoring of blood pressure and renal function is required due to potential side effects 1
• Similar overall responses have been seen with tacrolimus and mycophenolate mofetil in open studies 3

Adjunctive Treatments

• Short courses of systemic corticosteroids (prednisone 0.5-1 mg/kg/day) may be used until hives resolve to grade 1 for severe cases 2
• Cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) can provide symptomatic relief 1, 2
• H2 antihistamines can be added to H1 antihistamines in some cases, though the benefits of such practice are not clearly established 4, 5
• Antileukotrienes may be beneficial in a small subgroup of patients with severe chronic urticaria 4

Management of Anaphylaxis

• For severe urticaria with signs of anaphylaxis (hypotension, laryngeal edema, vasomotor collapse, oxygen desaturation), epinephrine is the first-line treatment 3, 6
• Epinephrine acts on both alpha and beta-adrenergic receptors to alleviate pruritus, urticaria, and angioedema through its effects on smooth muscle 6
• After epinephrine administration, antihistamines and corticosteroids can be added as required 3

Special Considerations

• Identify and minimize aggravating factors such as overheating, stress, alcohol, and certain medications (aspirin, NSAIDs, codeine) 1, 2
• NSAIDs should be avoided in aspirin-sensitive patients with urticaria, and ACE inhibitors should be avoided in patients with angioedema without weals 1
• For patients with renal impairment, avoid acrivastine in moderate renal impairment, and halve the dose of cetirizine, levocetirizine, and hydroxyzine 1
• For patients with hepatic impairment, avoid mizolastine in significant hepatic impairment, and avoid alimemazine, chlorphenamine, and hydroxyzine in severe liver disease 1

Treatment Algorithm for Severe Urticaria

1. Start with standard dose of second-generation H1 antihistamine
2. If inadequate control after 2 weeks, increase dose up to 4x standard dose
3. If still inadequate control after 1-4 weeks of high-dose antihistamine, add omalizumab
4. If inadequate response to omalizumab within 6 months, consider cyclosporine
5. For breakthrough symptoms, consider short courses of systemic corticosteroids 1, 7

Remember that more than one-half of patients with chronic urticaria will have resolution or improvement of symptoms within a year, so patient education about the generally favorable prognosis is important 7.