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Concept: Urticaria


Background Many patients with chronic idiopathic urticaria (also called chronic spontaneous urticaria) do not have a response to therapy with H(1)-antihistamines, even at high doses. In phase 2 trials, omalizumab, an IgE monoclonal antibody that targets IgE and affects mast-cell and basophil function, has shown efficacy in such patients. Methods In this phase 3, multicenter, randomized, double-blind study, we evaluated the efficacy and safety of omalizumab in patients with moderate-to-severe chronic idiopathic urticaria who remained symptomatic despite H(1)-antihistamine therapy (licensed doses). We randomly assigned 323 patients to receive three subcutaneous injections, spaced 4 weeks apart, of omalizumab at doses of 75 mg, 150 mg, or 300 mg or placebo, followed by a 16-week observation period. The primary efficacy outcome was the change from baseline in a weekly itch-severity score (ranging from 0 to 21, with higher scores indicating more severe itching). Results The baseline weekly itch-severity score was approximately 14 in all four study groups. At week 12, the mean (±SD) change from baseline in the weekly itch-severity score was -5.1±5.6 in the placebo group, -5.9±6.5 in the 75-mg group (P=0.46), -8.1±6.4 in the 150-mg group (P=0.001), and -9.8±6.0 in the 300-mg group (P<0.001). Most prespecified secondary outcomes at week 12 showed similar dose-dependent effects. The frequency of adverse events was similar across groups. The frequency of serious adverse events was low, although the rate was higher in the 300-mg group (6%) than in the placebo group (3%) or in either the 75-mg or 150-mg group (1% for each). Conclusions Omalizumab diminished clinical symptoms and signs of chronic idiopathic urticaria in patients who had remained symptomatic despite the use of approved doses of H(1)-antihistamines. (Funded by Genentech and Novartis Pharma; number, NCT01292473 .).

Concepts: Urticaria, Pharmacology, Medical terms, Clinical research, Clinical trial


Several guidelines for urticaria and angioedema have been published in Europe and United States since 1997. General principles for diagnosis and treatments of them are similar. However, each guideline has its own characteristics and shows differences in areas such as the coverage of urticaria subtypes, nomenclatures, and hierarchy of the medications. In Japan, the Japanese Dermatological Association (JDA) published its first guideline for urticaria and angioedema in 2005. It established a new classification of urticaria and angioedema together with the definition of each subtype. It emphasized the importance of discriminating idiopathic urticaria, consisting of acute urticaria and chronic urticaria from inducible urticaria, such as allergic urticaria, physical urticaria and cholinergic urticaria. It contains several unique algorithms for diagnosis and treatment of urticaria from a view point of clinical practices, and was further enforced by a style of EBM in 2011. Nevertheless, these guidelines have not been recognized outside of Japan, because of a language barrier. In this article, the outline of the newest guidelines by JDA are introduced and compared with the guidelines in other countries published in English.

Concepts: Angioedema, Cholinergic urticaria, Urticaria and angioedema, Urticaria


Hereditary angioedema (HAE) is a rare autosomal dominant disease that usually occurs in adolescence and early adulthood. It is characterized by recurrent non-pitting edema involving the skin and intestinal tract, especially the extremities and face. It is not associated with urticaria and pruritus. The cause is known to be the deficiency of C1 inhibitor. We herein report a 7-year-old girl with HAE who had recurrent episodes of swelling of the extremities and face without urticaria and pruritus. Her great grandmother had suffered from the same symptoms. The level of serum C4 was 8.01 mg/dL (normal: 10-40 mg/dL). The level of C1 inhibitor was 5.0 mg/dL (normal: 18-40 mg/dL). To our knowledge, this is the first pediatric case with typical clinical symptoms of HAE and C1 esterase inhibitor deficiency in Korea.

Concepts: Hereditary angioedema, C1-inhibitor, Cetirizine, Allergy, Gastroenterology, Urticaria, Angioedema


Patients with autosomal dominant vibratory urticaria have localized hives and systemic manifestations in response to dermal vibration, with coincident degranulation of mast cells and increased histamine levels in serum. We identified a previously unknown missense substitution in ADGRE2 (also known as EMR2), which was predicted to result in the replacement of cysteine with tyrosine at amino acid position 492 (p.C492Y), as the only nonsynonymous variant cosegregating with vibratory urticaria in two large kindreds. The ADGRE2 receptor undergoes autocatalytic cleavage, producing an extracellular subunit that noncovalently binds a transmembrane subunit. We showed that the variant probably destabilizes an autoinhibitory subunit interaction, sensitizing mast cells to IgE-independent vibration-induced degranulation. (Funded by the National Institutes of Health.).

Concepts: Cell biology, Urticaria, Degranulation, Immune system, Mast cell, Protein, Amino acid, Histamine


Treatment of chronic urticaria is challenging because many patients are refractory to or experience adverse effects with conventional therapy. Recently, short-term efficacy of omalizumab has been demonstrated.

Concepts: Medical terms, Adverse drug reaction, Chronic urticaria, Urticaria, Term


Introduction: Urticaria is a highly prevalent disease among people. First-choice treatment continues to be centred on the second-generation H1 antihistamines, including a wide group of drugs with a better therapeutic index (or risk:benefit ratio) than the classic ones, even in the high, off-label dosage occasionally required in chronic urticaria. Bilastine is a newly registered H1-antihistamine for treatment of allergic rhinoconjunctivitis and urticaria. With established antihistaminic and antiallergic properties, it is widely reviewed in the medical literature; however, to our knowledge, a specific review of bilastine’s role in the treatment of urticaria was lacking. Areas covered: This article reviews the medical literature on the effectiveness and safety of bilastine in urticarial syndromes, either spontaneous or inducible, by means of a Medline search from 1990 to present, completed with some nonpublished data provided by the manufacturer. Expert opinion: Once-daily treatment with bilastine 20 mg is effective in managing symptoms and improving patient’s quality of life in chronic urticaria, with at least comparable efficacy to levocetirizine. As far as studies in healthy volunteers, clinical assays, and recent clinical experience can establish, bilastine’s safety profile is adequate, appearing to be entirely free from cardiovascular effects, and not impairing psychomotor performance or actual driving, even at twice the therapeutic dose.

Concepts: Efficacy, H1 antagonist, Histamine antagonist, Asthma, Urticaria, Pharmacology, Effectiveness, Medicine


Edema is tissue swelling and is a common symptom in a variety of diseases. Edema form due to accumulation of fluids, either through reduced drainage or increased vascular permeability. There are multiple vascular signalling pathways that regulate vessel permeability. An important mediator that increases vascular leak is the peptide hormone bradykinin, which is the principal agent in the swelling disorder hereditary angioedema. The disease is autosomal dominant inherited and presents clinically with recurrent episodes of acute swelling that can be life-threatening involving the skin, the oropharyngeal, laryngeal, and gastrointestinal mucosa. Three different types of hereditary angiodema exist in patients. The review summarises current knowledge on the pathophysiology of hereditary angiodema and focuses on recent experimental and pharmacological findings that have led to a better understanding and new treatments for the disease.

Concepts: Angiotensin II receptor antagonist, Urticaria, Skin, Disease, ACE inhibitor, Hereditary angioedema, Bradykinin, Angioedema


A 43 year old caucasion gentleman had been receiving Botulinum toxin type A injections (BOTOX(®) , Allergan) for his axillary hyperhidrosis since 2004 with good effect. In June 2009 he gave an 18 month history of developing small prutitic wheals on his chest, arms and to a lesser extent his legs and back.. The lesions lasted between 5 and 120mins. There was no dermographism. Triggers included anxiety, physical exercise and hot showers.

Concepts: Physical exercise, Insomnia, Microbial toxins, Allergan, Cholinergic urticaria, Urticaria, Hyperhidrosis, Botulinum toxin


Adrenergic urticaria (AU) is a rare type of stress-induced physical urticaria characterized by widespread pruritic urticarial papules. Diagnosis can be made by i.d. injection of adrenaline or noradrenaline, which produces the characteristic rash. Although the lesions of AU typically respond to beta-blockers such as propranolol, the therapeutic options for AU are limited. Here, we report a case of AU that was resistant to beta-blockers and successfully treated with clotiazepam. The clinical picture of AU resembles that of cholinergic urticaria (CU), however, positive noradrenaline test and negative acetylcholine skin test were useful for the differential diagnosis of AU and CU. Although his symptoms were resistant to several therapeutic methods including olopatadine (H1 antagonist), lafutidine (H2 antagonist) and propranolol, the severity and frequency of his attacks and his subjective symptoms were reduced by oral clotiazepam, an anxiolytic benzodiazepine. Dermatologists should be aware that anxiolytic benzodiazepines may be a therapeutic option in AU.

Concepts: Pruritic urticarial papules and plaques of pregnancy, Differential diagnosis, Norepinephrine, Beta blocker, Neurotransmitter, Cholinergic urticaria, Urticaria, Adrenergic receptor


Because omalizumab was only recently approved for refractory chronic urticaria (CU), there are few studies that have evaluated patients using omalizumab for longer than 1 year.

Concepts: Asthma, Chronic urticaria, Urticaria