Medical treatment is required for patients who are annoyed by wheals appearance and pruritus. First line treatment is H1 antihistamine medications, such as diphenhydramine, hydroxyzine, cetirizine and other H1 antihistamine. Some patients might require high doses of antihistamines for a complete control of their symptoms, but fortunately it’s high doses are tolerated by most patients. If antihistamines as the first line treatment didn’t successfully controlled the symptoms, omalizumab and cyclosporine should be tried as the second line treatment. Omalizumab has been effective in different sub-types of urticaria, such as solar urticaria, cold urticaria, cholinergic urticaria, urticarial vasculitis and symptomatic dermatographic urticaria. There are some other alternatives if the aforementioned medications didn’t help, alternatives such as dapsone, hydroxychloroquine, sulfasalazine, colchicine, methotrexate, intravenous gamma globulin, plasmapheresis, corticosteroids, H2 antagonists and leukotriene antagonists. Some studies recommended specific alternative treatment for each subtypes of urticaria.

• Antihistamines, such as diphenhydramine, hydroxyzine, cetirizine and other H1 antihistamines are recommended as the first line treatment for urticaria. These are taken on a regular basis for their protective effect, lessening or halting attacks.^[1]
• Antihistamines are effective on high doses and most of the time are tolerated by patients.^[2]
• Furthermore H2 antagonists, such as cimetidine and ranitidine, may help to control symptoms either prophylactically or by relieving symptoms during an attack.^[3]
• When H2 antagonists are taken in combination with H1 antihistamines, a synergistic effect is expected, which may be more effective than either treatment alone in some cases.
• The use of ranitidine (or other H2 antagonists) for urticaria is considered an off-label use, since these drugs are primarily used for the treatment of peptic ulcer disease and gastroesophageal reflux disease.
• If the disease doesn’t response to antihistamines, second line treatments are recommended.

• Omalizumab is a monoclonal antibody against immunoglobulin E which is a good option for most patients with urticaria (effective in more than 80% of cases).^[4][5]
• It lessens the function of mast cells and helps eosinophil apoptosis. It also decreases cytokine release from basophils.
• Nevertheless high price of this medication is considered a drawback that decreases it’s use.
• It is used subcutaneously and has been effective in different sub-types of urticaria, such as solar urticaria, cold urticaria, cholinergic urticaria, urticarial vasculitis and symptomatic dermatographic.

• Cyclosporine A has been effective in some cases of urticaria by it’s direct effect on liberation of the mast cell mediators, nevertheless due to it’s high cost it is usually considered as an alternate treatment.^[2][6]
• Cyclosporine has been related to longer remission in long term, compared to corticosteroids.
• Based on numerous studies cyclosporine is 64%-95% effective in patients with urticaria.^[7]
• Due to it’s side effects in long period of use, it is usually reserved for patients resistant to high doses of antihistamine and omalizumab.

• An oral corticosteroid, such as prednisone can sometimes be prescribed. In a randomized controlled trial done on adult who had urticaria with a duration less than 24 hours, a comparison between prednisone plus levocetirizine and levocetirizine alone, yielded 62% and 72% rates of resolution within two days, respectively.^[8]
• Long term treatment must be avoided, due to high rates of adverse effects.^[2]

• Beta blockers, such as propranolol, have been effective in treatment of adrenergic urticaria.^[9]
• In simultaneous mastocytosis, PUVA showed to be effective due to it’s effect on mast cell reduction.^[10][11][12]
• Tricyclic antidepressants such as doxepin, which act as a potent H₁ and H₂ antagonists and may have a role in therapy, although their side effects usually limit their use.
• An Australian company performed a clinical trials with an analogue of alpha-melanocyte-stimulating hormone called melanotan (CUV1647) for the treatment of solar urticaria.^[13][14]

The following table is a summary of first and second line urticaria treatments and other alternatives:^[15]

The following table is a summary of recommended treatment in different types of urticaria:^[2]

Urticaria is considered an absolute contraindication to the use of the following medications:

• Erythromycin/Benzoyl Peroxide
• Indomethacin
• Nabumetone