Treatment of chronic spontaneous urticaria with an inadequate response to H1-antihistamine

The second-generation H1-antihistamines (sgAH) are the first-line symptomatic treatment of patients with chronic spontaneous urticaria (CSU). Up to 50% of the patients will not respond to licensed doses of sgAH. According to the guidelines, the dose of sgAH may be increased up to 4 times the conventional dose. However, even at higher doses, there is a subgroup of patients refractory to the antihistamine treatment. The purpose of this article was to review the different treatment options of antihistamine-refractory CSU patients. This revision examines the available literature for therapies used in chronic urticaria, including omalizumab, ciclosporin A, oral glucocorticoids, leukotriene receptor antagonists, H2 antihistamines, doxepin, dapsone, hydroxychloroquine, phototherapy, methotrexate, mycophenolate mofetil, azathioprine, autohemotherapy, intravenous immunoglobulins and rituximab, between others. After the exhaustive review of the medical literature only few high-quality studies have been identified, mostly for omalizumab. Omalizumab is an anti-immunoglobulin E monoclonal antibody, approved for the treatment of CSU, that has radically changed the management of the patients without good response to sgAH, allowing to reach complete responses in a high percentage of patients. Although actually the therapeutic management of CSU is more effective and safer than before 2014, there is place even for new and more effective treatments. A good number of partial responders and slow responders to omalizumab and a little percentage still of non-responders to available therapies stimulate the development of new drugs that will also be discussed.