Medication Summary
The goals of pharmacotherapy are to reduce morbidity and to prevent complications. The mainstay agents used in the management of pressure urticaria include antihistamines and corticosteroids. The benefit of omalizumab has been established in chronic idiopathic urticaria (CIU) and shows benefit for patients with delayed pressure urticaria (DPU). Other medications such as leukotriene antagonists, dapsone, sulfasalazine, methotrexate, cyclosporine, and intravenous immunoglobin (IVIg) have limited data, with only few case reports.
Antihistamines, 2nd Generation
Class Summary
Antihistamines may be useful in helping control symptoms of chronic urticaria, which frequently coexists with delayed pressure urticaria (DPU). Second-generation antihistamines, also known as less-sedating or low-sedation antihistamines, produce less sedation than traditional H1 blockers because they are less lipid-soluble and only cross the blood-brain barrier in small amounts. They also have longer half-lives, allowing less frequent dosing. Many H1 antagonists are metabolized through the cytochrome P-450 system. Important exceptions include cetirizine, levocetirizine, and fexofenadine.
Fexofenadine (Allegra, Allegra Allergy 12 Hour, Allegra Allergy 24 Hour)
Fexofenadine is a nonsedating second-generation medication that has fewer adverse effects than first-generation medications. It competes with histamine for H1 receptors in the gastrointestinal (GI) tract, blood vessels, and the respiratory tract, reducing hypersensitivity reactions. Fexofenadine does not sedate. It is available in once-daily and twice-daily preparations.
Cetirizine (Aller-Tec, Children's Zyrtec Allergy, Children's Zyrtec Hives Relief)
Cetirizine selectively inhibits H1 receptor sites in blood vessels, the GI tract, and the respiratory tract, thereby inhibiting the physiologic effects that histamine normally induces at H1 receptor sites. Once-daily dosing is convenient; bedtime dosing may be useful if sedation is a problem.
Loratadine (Claritin, Claritin RediTabs, QlearQuil All Day & All Night 24 Hour Allergy Relief)
Loratadine selectively inhibits peripheral histamine H1 receptors.
Levocetirizine (Xyzal)
Levocetirizine is an H1-receptor antagonist and an active enantiomer of cetirizine. Peak plasma levels are reached within 1 hour, and the half-life is approximately 8 hours. Levocetirizine is available as a 5-mg breakable (scored) tablet and a 0.5 mg/mL oral solution. It is indicated for uncomplicated skin manifestations of chronic idiopathic urticaria (CIU).
Desloratadine (Clarinex, Clarinex RediTabs)
Desloratadine is a long-acting tricyclic histamine antagonist that is selective for H1 receptors. It is a major metabolite of loratadine, which, after ingestion, is extensively metabolized to the active metabolite 3-hydroxydesloratadine.
Antihistamines, 1st Generation
Class Summary
First-generation antihistamines compete with histamine at the tissue-receptor level, preventing it from carrying out its mediator functions in urticaria.
Diphenhydramine (Alka-Seltzer Plus Allergy, Benadryl, Benadryl Allergy Dye-Free LiquiGels)
Diphenhydramine is a first-generation antihistamine with anticholinergic effects. It binds to H1 receptors in the central nervous system (CNS) and the body, competitively blocking histamine from binding to these receptors.
Diphenhydramine is employed for symptomatic relief of pruritus caused by release of histamine in inflammatory reactions. It has significant antimuscarinic activity and penetrates the CNS and thus has a pronounced tendency to induce sedation. Approximately half of those treated with conventional doses experience some degree of somnolence. A small percentage of children paradoxically respond to diphenhydramine with agitation.
Hydroxyzine (Vistaril)
Hydroxyzine antagonizes H1 receptors in the periphery. It may suppress histamine activity in the subcortical region of the CNS.
Monoclonal Antibodies
Class Summary
Monoclonal antibodies directed to immunoglobulin E (IgE) binding may reduce the release of mediators that provoke an allergic response. These agents may be considered when H 1 -receptor antagonists are ineffective.
Omalizumab (Xolair)
Omalizumab is a recombinant humanized monoclonal antibody administered by subcutaneous injection every 4 weeks. It selectively binds to IgE and inhibits binding to IgE receptors on the surface of mast cells and basophils. It is indicated for chronic idiopathic urticaria in adults and children aged 12 years or older who remain symptomatic despite anti-H1 antihistamine treatment.
Corticosteroids
Class Summary
Because of their anti-inflammatory properties, corticosteroids have been used in the management of pressure urticaria, with variable success.
Prednisone (Deltasone, Prednisone Intensol, Rayos)
Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte (PMN) activity. It stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.
Prednisolone (FloPred, Millipred, Millipred DP)
This glucosteroid occurs naturally and synthetically. It is used for both acute and chronic asthma. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity.
Antihistamines, H2 Blockers
Class Summary
H2 antagonist therapy can be used as an adjunct to H1 antagonist therapy.
Famotidine (Acid Controller, Act, Dyspep HB)
Famotidine is an H2 antagonist that, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.
Ranitidine (Zantac, Zantac 150 Maximum Strength, Zantac 75)
Ranitidine is a second-generation agent that is effective for the treatment of urticaria. It is tolerated very well, with a rate of sedation that is not significantly different from that seen with placebo.
Nizatidine (Axid)
This agent competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.
Cimetidine (Tagamet HB)
This agent inhibits histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
Class Summary
NSAIDs are the medications most commonly used to control mild to moderate pain and to decrease inflammation. Sulfasalazine, steroids, and immunosuppressive agents are sometimes used, with varying degrees of success. NSAIDs can also be a nonimmunologic trigger of mast cell degranulation and subsequent urticaria.
Ibuprofen (Advil, Motrin, PediaCare Children's Pain Reliever/Fever Reducer IB)
Ibuprofen is an NSAID with analgesic, anti-inflammatory, and antipyretic properties. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Naproxen (Aleve, Anaprox, Anaprox DS)
Naproxen inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
5-Aminosalicylic Acid Derivatives
Class Summary
These agents have anti-inflammatory effects.
Sulfasalazine
Sulfasalazine decreases the inflammatory response and systemically inhibits prostaglandin synthesis.
Antidepressants, TCAs
Class Summary
Agents in this class that antagonize the H1 receptor preventing histamine from causing urticaria. The tricyclic antidepressant doxepin is used in urticaria for its sedative and antihistaminic properties. Oral doxepin may be considered if oral antihistamines are not helpful.
Doxepin (Silenor)
Doxepin is a tricyclic antidepressant that has potent H1-blocking activity, which makes it quite useful for urticaria. However, doxepin has very potent sedative and anticholinergic effects. It can be quite effective if given at bedtime because its sedative effects can make it easier for patients with pruritus to sleep.
Corticosteroids, Topical
Class Summary
Some small studies have shown topical corticosteroids to be efficacious in reducing the size of pressure urticaria lesions, as well as the erythema and pruritus associated with them.
Clobetasol (Clarelux, Clobex, Clobex Spray)
Clobetasol propionate is a class I superpotent topical steroid; it suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction. Clobetasol decreases inflammation by stabilizing lysosomal membranes, inhibiting PMN leukocytes and mast cell degranulation.
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Delayed pressure urticaria. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/reactions/pressure2.jpg).
