What is the management of severe urticaria (hives)?

From the Guidelines

Management of severe urticaria involves a stepwise approach starting with high-dose second-generation H1 antihistamines as first-line therapy. Begin with medications like cetirizine 10-20 mg, fexofenadine 180-360 mg, or loratadine 10-20 mg daily 1. If symptoms persist after 2-4 weeks, increase the dose up to four times the standard dose (e.g., cetirizine 40 mg daily). For inadequate response, add omalizumab 300 mg subcutaneously every 4 weeks, which targets IgE antibodies and is highly effective for refractory cases. Cyclosporine 3-5 mg/kg/day can be considered as a third-line option for 3-6 months in resistant cases. During acute severe flares, a short course of oral corticosteroids (prednisone 40-60 mg daily for 3-7 days with taper) may provide temporary relief, but should not be used long-term due to side effects.

Key considerations in managing severe urticaria include:

• Identifying and avoiding triggers, including certain foods, medications, physical stimuli, or stress
• Patients should be advised to keep a symptom diary to track potential triggers and treatment response
• H2 antihistamines (ranitidine 150 mg twice daily) or leukotriene receptor antagonists (montelukast 10 mg daily) can be added as adjunctive therapy
• This approach targets different inflammatory pathways involved in urticaria pathogenesis, including histamine release from mast cells and broader inflammatory cascades that contribute to chronic symptoms

It is essential to note that the use of epinephrine may be necessary in cases of anaphylaxis, which can be a life-threatening condition 1. However, the primary focus of managing severe urticaria is on the stepwise approach with antihistamines, omalizumab, and cyclosporine, as well as identifying and avoiding triggers.

In terms of specific medications and dosages, the following can be considered:

• Cetirizine: 10-20 mg daily, increasing to 40 mg daily if necessary
• Fexofenadine: 180-360 mg daily
• Loratadine: 10-20 mg daily
• Omalizumab: 300 mg subcutaneously every 4 weeks
• Cyclosporine: 3-5 mg/kg/day for 3-6 months in resistant cases
• Prednisone: 40-60 mg daily for 3-7 days with taper during acute severe flares
• Ranitidine: 150 mg twice daily as adjunctive therapy
• Montelukast: 10 mg daily as adjunctive therapy

Overall, the management of severe urticaria requires a comprehensive approach that takes into account the patient's individual needs and response to treatment. By following a stepwise approach and considering the use of adjunctive therapies, healthcare providers can help patients achieve optimal symptom control and improve their quality of life.

From the FDA Drug Label

The initial suppressive dose level should be continued until satisfactory clinical response is obtained, usually four to ten days in the case of many allergic and collagen diseases. In the event of an acute flare-up of the disease process, it may be necessary to return to a full suppressive daily divided corticoid dose for control.

The management of severe urticaria (hives) may involve initial high-dose therapy for control of the disease process, which can be administered for 4 to 10 days. If an acute flare-up occurs, it may be necessary to return to a full suppressive daily divided corticoid dose for control 2.

From the Research

Management of Severe Urticaria

The management of severe urticaria involves a step-by-step approach, with the primary goal of alleviating symptoms and preventing further episodes.

• The first-line treatment for severe urticaria is the use of non-sedating H1 receptor antagonists (antihistamines), such as cetirizine, fexofenadine, and loratadine 3.
• In cases where symptoms are severe and not controlled by antihistamines, corticosteroid therapy with prednisone or methylprednisolone may be administered for a short period (7-14 days) 3.
• Leukotriene receptor antagonists, such as montelukast and zafirlukast, may be tried in cases of relapse after corticosteroid suspension 3.
• For patients with severe, unremitting urticaria, immunosuppressive treatment with low-dose cyclosporine may be considered, which has a corticosteroid-sparing effect and is generally effective in these patients 3.

Treatment of Acute Urticaria

The treatment of acute urticaria is less clear, with limited evidence-based approaches available.

• A systematic review of existing evidence-based approaches for acute urticaria treatment found that the addition of corticosteroids to antihistamines did not improve symptoms in most cases 4.
• Another study found that the combination of diphenhydramine and ranitidine or cimetidine was most efficient for relief of urticaria in some cases 4.
• A randomized controlled trial found that adding intravenous corticosteroids to H1 antihistamines in patients with acute urticaria did not improve treatment outcomes and may be associated with persistent urticaria activity 5.

Treatment of Chronic Urticaria

The treatment of chronic urticaria involves a similar approach to that of severe urticaria.

• The mainstay of treatment is avoidance of triggers, if identified, and the use of second-generation H1 antihistamines, which can be titrated to greater than standard doses 6.
• First-generation H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists, and brief corticosteroid bursts may be used as adjunctive treatment 6.
• In refractory chronic urticaria, patients can be referred to subspecialists for additional treatments, such as omalizumab or cyclosporine 6.