News, Views, & Reviews
Chronic Urticaria: Omalizumab and Review of Therapeutic Options
June 2013 | Volume 12 | Issue 6 | Features | 715 | Copyright © June 2013
Kendra Gail Bergstrom MD FAAD
Chronic idiopathic urticaria is a rare but significantly life-altering
skin disease. Recent developments in immunology have
promoted our understanding of its autoimmune pathology, but
treatment options have not yet developed at the same pace.
When antihistamines aren't sufficient, the next steps for treatment
have less evidence for support. Fortunately, a Phase III
clinical trial has shown that the monoclonal antibody omalizumab,
approved for use in asthma, can reduce symptoms of
chronic idiopathic urticaria when added to maximal doses of
H1-antihistamines. Therapeutic options for chronic idiopathic
urticaria are reviewed. J Drugs Dermatol.
While rare, chronic idiopathic urticaria is a cause of significant suffering and morbidity for those affected. Formally, chronic urticaria is defined as lasting longer than six weeks. In practice, many people suffer for months or years. While an underlying etiology can sometimes
be found, in over 50% of cases the cause remains obscure and is labeled chronic idiopathic urticaria (CIU). The identification
of the IgG anti-Fc epsilon R1 antibody helped to understand
the etiology of chronic idiopathic urticaria up to 60% of cases.1 Individuals with the receptor antibody generally have a longer disease course and are less likely to have an underlying
treatable cause for urticaria. Treatment options are few and most are used as off-label indications. However, this discovery has not yet affected therapeutic options.
Therapeutic Options for Chronic Idiopathic UrticariaH1 antihistamines, both sedating and non-sedatingH2 histamine antagonists: cimitidine, ranitidine, famotidineTricyclic antidepressant: doxepin2Calcium channel blocker: nifedipine3Leukotriene receptor antagonists: montelukast, zafirlukast4oral corticosteroidsInosine monophosphate dehydrogenase inhibitor: mycophenolate
mofetil5Calcineurin inhibitor: cyclosporine (may be effective at doses < 3 mg/kg daily)6methotrexateIntravenous immunoglobuin, IVIgCase reports: plasmaphoresis, cyclophosphamideMonoclonal antibody: omalizumabIn pregnancy: chlorpheniramine, diphenhydramine7
The use of sedating and non-sedating H1 antihistamines for all types of urticaria is well established. Doses much higher than those approved by the FDA, usually 2 to 4 times higher, is often needed for control of CIU. While dosing regimens vary, many physicians treat morning and evening with the FDA approved dose of antihistamine then titrate upwards to control of disease or until side effects occur. While the side effects of antihistamines may vary, the most common are dry mucous membranes, anticholinergic
symptoms including tachycardia, urinary retention, and blurry vision, and exacerbation of narrow-angle glaucoma. It is important to note that all studies used the above agents in addition to maximally tolerated doses of antihistamines.
Because basophils have H2 receptors that mediate histamine release, the use of H2 antihistamines has a plausible mechanism
for efficacy. Their relatively safe toxicity profile and there is a paucity of clinical data to support their use other than as an adjunct. One study in 2002 showed famotidine to be as effective
as diphenhydramine for acute urticaria among a group of twenty-five patients an emergency department setting. Given that these patients received intramuscular medications within 72 hours of the onset of acute urticaria, it is harder to apply this data for treating CIU.
The most recent retrospective case series using an H2 antagonist
for CIU was in 2013 in Japan.9 The authors did show subjective efficacy of a newer second generation H2 antagonist, lafutidine, added to antihistamines over a three month period. Seventy-five percent of a group of 46 patients showed improvement
at three months after adding lafutidine; no adverse events were reported. Lafutidine is a second-generation H2 antagonist currently available in Japan, China, and India; dose is 10 mg given once or twice daily.
Leukotriene Receptor Antagonists: Montelukast, Zafirlukast
Leukotrienes are signaling molecules from the arachadonic acid inflammatory pathway. Leukotriene receptors are present on mast cells and cause mast cell degranulation and histamine release. While originally developed for asthma, the leukotriene receptor antagonists montelukast and zafirlukast have shown efficacy in urticaria as well. Dosing is daily for both medications,
and adverse events are rare. Response rates in published studies4,10range from 30 to 50 percent, though it may be higher among patients with more recalcitrant disease.10
Publications in the 1980s and 1990s supported the use of nifedipine to treat chronic idiopathic urticaria. Studies of patients with active CIU on maximally tolerated doses of antihistamines were studied