What is the next best step in managing an acute urticarial rash that is pruritic and unresponsive to diphenhydramine (Benadryl) or cetirizine (Reactine)?

From the Guidelines

The next best step in managing an acute urticarial rash that is not responding to cetirizine (Reactine) or diphenhydramine (Benadryl) is to add a short course of oral corticosteroids, such as prednisone 50 mg daily for 3 days, as recommended by the British Journal of Dermatology guidelines 1. This approach helps to quickly reduce inflammation and control symptoms when antihistamines alone are insufficient. While taking prednisone, continue the antihistamines, preferably a non-sedating second-generation option like cetirizine at the maximum dose of 10 mg twice daily, as suggested by the guidelines for evaluation and management of urticaria in adults and children 1. For better symptom control, consider adding a second antihistamine, such as ranitidine (H2 blocker) 150 mg twice daily. If the rash is extensive or severe, seek immediate medical attention to rule out anaphylaxis or angioedema. After the acute phase resolves, work with a healthcare provider to identify potential triggers through a detailed history and possibly allergy testing. Corticosteroids are effective because they suppress multiple inflammatory pathways involved in urticaria, whereas antihistamines only block one mediator (histamine). For persistent urticaria beyond 6 weeks, referral to an allergist or dermatologist may be necessary to consider additional treatments such as omalizumab or immunosuppressants, as recommended by the latest update of the international urticaria guideline 1.

Some key points to consider when managing acute urticarial rash include:

• The use of oral corticosteroids to quickly reduce inflammation and control symptoms
• The continuation of antihistamines, preferably non-sedating second-generation options, to block histamine receptors
• The potential addition of a second antihistamine, such as an H2 blocker, to improve symptom control
• The importance of seeking immediate medical attention if the rash is extensive or severe
• The need to identify potential triggers through a detailed history and possibly allergy testing after the acute phase resolves.

It is also important to note that the treatment of urticaria should be individualized, and the "as much as needed and as little as possible" approach should be used, as recommended by the latest update of the international urticaria guideline 1. This approach involves stepping up and stepping down the treatment of urticaria based on levels of disease control assessed with the Urticaria Control Test (UCT). In patients who are treated with a standard-dosed second-generation antihistamine and whose urticaria cannot be completely controlled, a higher dose (up to 4-fold higher) should be used. In patients with complete disease control, step-down should be considered to reduce the treatment burden and assess patients for spontaneous remission.

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. The next best step in managing an acute urticarial rash that is pruritic and unresponsive to diphenhydramine (Benadryl) or cetirizine (Reactine) is to consider corticosteroid therapy, such as prednisone, at a daily dose for initial control of the disease process, for a period of 4 to 10 days 2.

From the Research

Management of Acute Urticarial Rash

The next best step in managing an acute urticarial rash that is pruritic and unresponsive to diphenhydramine (Benadryl) or cetirizine (Reactine) involves several considerations:

• Assessment and Diagnosis: The diagnosis of urticaria is based on clinical examination, and an allergic etiology for acute urticaria should always be considered and ruled out 3.
• First-Line Treatment: The mainstay of treatment is avoidance of triggers, if identified, and the first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses 4, 3.
• Adjunctive Treatment: For cases unresponsive to first-line treatment, adjunctive treatments such as first-generation H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists, or brief corticosteroid bursts may be considered 4, 5.
• Corticosteroid Therapy: Corticosteroid therapy with prednisone or methylprednisolone can be administered for a few days if urticarial symptoms are not controlled by antihistamines and a rapid clinical response is needed 5.
• Immunomodulatory Treatments: In cases of refractory chronic urticaria, patients can be referred to subspecialists for additional treatments, such as omalizumab or cyclosporine 4, 5.
• Recent Guidelines: Recent guidelines on urticaria treatment mainly focus on chronic urticaria rather than on acute urticaria, and the addition of corticosteroids to an antihistamine as treatment for acute urticaria needs to be further investigated 6, 7.

Treatment Options

Treatment options for acute urticarial rash that is pruritic and unresponsive to diphenhydramine or cetirizine include:

• Increasing the dose of second-generation H1 antihistamines up to 4 times 7
• Adding first-generation H1 antihistamines, H2 antihistamines, or leukotriene receptor antagonists 4, 5
• Brief corticosteroid bursts 5
• Referral to subspecialists for immunomodulatory treatments such as omalizumab or cyclosporine 4, 5