Generation H1-antihistamines Research Articles

Efficacy and safety of switching to bilastine, an H1-antihistamine, in patients with refractory chronic spontaneous urticaria (H1-SWITCH): a multicenter, open-label, randomized, parallel-group comparative study.

For treating patients with refractory chronic spontaneous urticaria (CSU) resistant to standard doses of 2nd generation H1-antihistamines (H1AH) the International and Japanese guidelines recommend increasing H1AH dose. The latter also recommends switching to a different H1AH. This study explored if the efficacy of the standard dose of bilastine 20 mg is non-inferior to that of double-dose of H1AH in patients with refractory CSU. This phase IV, multicenter, open-label, randomized, parallel-group trial evaluated the efficacy and safety of switching treatment to bilastine compared to treatment with a 2-fold dose of H1AH in patients with CSU refractory to standard dose H1AH. The primary endpoint was the mean total symptom score (TSS) at Day 5-7 after the start of administration. Treatment efficacy and safety were evaluated in 128 patients (bilastine, n=64; 2-fold dose of H1AH, n=64). The mean TSS at Day 5-7 after the start of administration was smaller than the non-inferiority margin of 0.8, demonstrating non-inferiority of the bilastine switching group to the double-dose H1AH group (0.17 (95% CI -0.32, 0.67)). No difference in Japanese version of Epworth Sleepiness Scale (JESS), DLQI, and urticaria activity score over 7 consecutive days (UAS7) was observed between the two groups. There were no serious adverse events in either group. H1AH-related adverse events occurred in 5 subjects (8 cases) and 2 subjects (3 cases) in the double-dose H1AH and bilastine groups, respectively. Switching treatment to bilastine demonstrated non-inferiority to a double-dose of H1AH in terms of efficacy in patients with CSU refractory to standard dose H1AH with a favorable safety profile. https://jrct.niph.go.jp/latest-detail/jRCTs051180105, identifier jRCTs051180105.

Omalizumab for Patients with Chronic Spontaneous Urticaria: A Narrative Review of Current Status.

Chronic spontaneous urticaria (CSU) is a debilitating inflammatory disorder of the skin, characterized by a fluctuating natural history, a complex mechanism of action, and a significant burden on patients, including effect on quality of life, development of psychosocial disorders, and a range of comorbidities. Recent international guidelines recommend a therapeutic approach of first-line treatment with second generation H1-antihistamines and second-line treatment with the biologic omalizumab. Here, the salient aspects of CSU and current status of data for omalizumab for patients with CSU are reviewed, with a focus on mechanism of action, efficacy and real-world effectiveness (including patient outcomes, response, relapse, and remission), and safety (including consideration of the risk of anaphylaxis). The review also considers recent data on COVID-19, CSU, and omalizumab and presents our perspective on future needs. Overall, the data suggest that omalizumab is an effective and well-tolerated treatment for patients with CSU that provides benefits for a wide range of patients.

Fexofenadine: A review of its use in the treatment of urticaria in pediatric and adult populations

Urticaria is an inflammatory skin disorder primarily resulting from activation of cutaneous mast cells. The released inflammatory mediators and histamine are responsible for the development of wheals and/or angioedema. Current guidelines recommend non-sedating second generation H1 antihistamines such as fexofenadine hydrochloride as first-line therapy. A recent review by Ansotegui et al. provides an update on urticaria, both in adult and pediatric populations, and on the safety and efficacy of fexofenadine hydrochloride as a treatment option.

Aquagenic Urticaria in an Adolescent Following COVID-19 Vaccine

A subset of patients receiving COVID-19 vaccinations develops cutaneous reactions. The majority are delayed hypersensitivity reactions that resolve spontaneously without treatment. More rarely, cutaneous manifestations such as urticaria, vasculitis, and morbilliform eruptions have been reported. Aquagenic urticaria is a form of chronic inducible urticaria caused by skin contact with water. Characteristic 1-2mm folliculopapular urticarial papules appear 20-30 minutes following water exposure and spontaneously resolve within 30-60 minutes of water removal. A water provocation test is the gold standard of diagnosis. The mainstay of treatment is 2nd generation H1 antihistamines taken before water exposure. We report the development of aquagenic urticaria in a 12-year-old African American male patient following the Pfizer-BioNTech mRNA COVID-19 vaccine.

Prevalence, Clinical Manifestations, Treatment, and Clinical Course of Chronic Urticaria in Elderly: A Systematic Review.

PurposeData specific to the epidemiology, clinical features, and management of chronic urticaria (CU) in the geriatric population remain limited and not well understood. We aim to systematically review the prevalence, clinical manifestations, treatment, and clinical course of elderly patients with CU.Patients and methodsOriginal articles that included data of elderly (aged >60 years) with CU that were published until February 2021 were searched in PubMed, Scopus, and Embase using predfefined search terms. Related articles were evaluated according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.ResultsAmong the included 85 studies and 1,112,066 elderly CU patients, most (57.4%) were women. The prevalence of elderly CU in the general population ranged from 0.2–2.8%, and from 0.7–33.3% among all CU patients. Compared to adult CU, elderly CU patients had a higher percentage of wheal alone (73.9%), and lower rate of positive autologous serum skin test and atopy. Gastrointestinal diseases were the most common comorbidity (71.9%), and there was a high rate of malignancies and autoimmune diseases. Second generation H1-antihistamines were commonly used, and achievement of complete control was most often reported. Omalizumab was prescribed in 59 refractory patients, and a significant response to treatment was reported in most patients. The treatment of comorbidities also yielded significant improvement in CU.ConclusionElderly CU was found to be different from adult CU in both clinical and laboratory aspects. H1- antihistamines are effective as first-line therapy with minimal side-effects at licensed doses. Treatment of secondary causes is important since the elderly usually have age-related comorbidities.

Integrative lipidomic features identify plasma lipid signatures in chronic urticaria.

Chronic urticaria (CU) is a chronic inflammatory skin disease mainly mediated by mast cells. Lipids exert essential functions in biological processes; however, the role of lipids in CU remains unclear. Nontargeted lipidomics was performed to investigate the differential lipid profiles between CU patients and healthy control (HC) subjects. Functional validation studies were performed in vitro and in vivo including β-hexosaminidase release examination from mast cells and passive cutaneous anaphylaxis (PCA) mouse model. We detected dramatically altered glycerophospholipids in CU patients compared with HCs. Phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) were increased, while phosphatidylcholine (PC) was reduced in CU patients. The reduction in PC was related to a high weekly urticaria activity score (UAS7), while PS was positively associated with the dermatology life quality index (DLQI). We also identified the differential lipid profiles between chronic spontaneous urticaria (CSU), symptomatic dermographism (SD), and CSU coexist with SD. CU patients were classified into two subtypes (subtype 1 and subtype 2) based on consensus clustering of lipid profiling. Compared with patients in subtype 2, patients in subtype 1 had elevated levels of PC (18:0e/18:2) and PE (38:2), and lower urticaria control test (UCT) scores indicated worse clinical efficiency of secondary generation H1 antihistamines treatment. Importantly, we found that supplementation with PC could attenuate IgE-induced immune responses in mast cells. In general, We described the landscape of plasma lipid alterations in CU patients and provided novel insights into the role of PC in mast cells.

Natural history and clinical course of patients with dermographism in a tropical country: a questionnaire-based survey.

Dermographism is the most common form of chronic inducible urticaria. However, the natural history and clinical course of patients with dermographism in tropical countries has not fully been described. To examine clinical features, natural history and clinical course of dermographism in Thai patients according to their experiences. A cross-sectional, internet-based survey was conducted in 2021. All study respondents completed a 45-item questionnaire that was circulated on social media regarding dermographism. Among the 2,456 respondents who reported dermographism, 1,900 had symptomatic dermographism (SD), while 556 had simple dermographism (SimD). Of the respondents who reported SD and SimD, the female to male ratio was 2.2:1 and 2.4:1, respectively. The median age of the first episode of SD and SimD was 16 and 15 years, respectively. Older age, greater body weight, cardiovascular diseases, allergic conjunctivitis, atopic dermatitis, changes in temperature, and family history of dermographism were all factors linked to an increased probability of SD. Half of the respondents with SD reported moderate itch severity. Moreover, about half of SD and almost all of SimD respondents let the wheal resolve on its own. Second generation H1-antihistamines were most commonly prescribed while over-the-counter medicines were taken by both SD and SimD respondents. This survey highlights several aspects of dermographism in Thai patients which can be useful for healthcare providers. SD is troublesome and affects the quality of life of many patients, leading some to seek medication themselves.

Neuropsychiatric side reactions of leukotriene receptor antagonist, antihistamine, and inhaled corticosteroid: A real-world analysis of the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS)

BackgroundThere are limited real-world studies on the differences in leukotriene receptor antagonists (LTRA), H1-antihistamines (H1-AH), and inhaled corticosteroids (ICS) associated neuropsychiatric events. In this study, we aimed to analyze the characteristics of drug associated neuropsychiatric events, and compare the differences among different drug categories. MethodsDisproportionality analysis and Bayesian analysis were used in data mining to identify suspected neuropsychiatric events associated with LTRA, H1-AH, and ICS based on the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from January 2004 to September 2020. Demographic information, time interval to onset, and death rates of LTRA, H1-AH, and ICS-associated neuropsychiatric events were also analyzed. ResultsA total of 9475 neuropsychiatric events were identified. The number of neuropsychiatric events related to LTRA, H1-AH, and ICS were 5201 (54.89%), 3226 (34.05%), and 1048 (11.06%), respectively. LTRA related neuropsychiatric events were more common in patients aged 4–6 years (18.66%). H1-AH and ICS related neuropsychiatric events were more common in patients aged 18–44 years (29.92%) and older than 65 years (30.60%), respectively. Montelukast was highly associated with neuropsychiatric events, with a high reporting odds ratio (ROR). Most neuropsychiatric symptoms occurred within the first 10 days after drug initiation (78.63% for LTRA, 91.39% for H1-AH, and 84.07% for ICS). The death rate due to neuropsychiatric events of first generation H1-AH was significantly higher than that of LTRA and ICS (p < 0.001). ConclusionsLTRA associated neuropsychiatric events reported in FAERS were most frequent in 4 to 6-year-old children. Most reported cases occurred within the first 10 days after drug initiation. The second generation H1-AH was relatively safe for neuropsychiatric events compared with the first generation. The fatality rate due to first generation H1-AH associated neuropsychiatric events was higher than that of LTRA and ICS. More attention should be paid to specific patients treated with LTRA and H1-AH.

Epileptic convulsions probably induced by desloratadine: a case report

Desloratadine, a second generation H1-antihistamine, is generally considered to be safe. We found only one article reporting four children with a family or disease history of epilepsy who developed the...

Anti-inflammatory activity of the antiallergic drug 7-[4-(4-benzhydrylpiperazinyl-1)butyl]-3-methylxanthine succinate (theoritin)

BACKGROUND: Many antagonists of histamine (H1) receptor, in addition to antihistamine action, suppress allergic inflammation by inhibiting the formation and secretion of proinflammatory cytokines. The new antiallergic drug benzhydrylpiperazinyl butylmethylxanthine succinate (theoritin), which has an antihistamine activity comparable to the known second generation H1-antihistamines, surpasses them in the ability to suppress the allergic inflammatory reaction, which allows this drug to have additional anti-inflammatory properties associated with the inhibition of the formation of proinflammatory cytokines.&#x0D; AIM: This study aimed to determine the effect of theoritin on the induced release of proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)- in cell culture in comparison with the action of the inverse agonist of H1 receptor cetirizine and a known inflammation inhibitor glucocorticosteroid dexamethasone.&#x0D; MATERIALS AND METHODS: U937 cells differentiated toward macrophage-like cells were used. Cytotoxicity of the substances used was assessed in the methyltetrazolium test at different incubation times (up to 24 h). Cells were stimulated with lipopolysaccharide (LPS). The tested compounds (theoritin and cetirizine) were evaluated at concentrations from 0.001 to 100 M and dexamethasone at 10 M was tested when added to cells 1 h before (prophylactic effect) or 1 h after (therapeutic effect) the addition of LPS. The presence of IL-6, IL-8, and TNF in the supernatants was determined by enzyme immunoassay.&#x0D; RESULTS: For cetirizine and theoritin, no cytotoxic action was found in the tested concentrations and time points. Dexamethasone inhibited the formation of IL-6 and TNF to the initial level and IL-8 to 50%60%. Theoritin led to a significant concentration-dependent decrease in the LPS-induced production of IL-6, IL-8, and TNF, and at a concentration of 100 M, the effect of theoritin was comparable with that of dexamethasone at a concentration of 10 M. The prophylactic test scheme for theoritin was more effective in suppressing LPS-induced production of proinflammatory cytokines than the curative one. The described effect of theoritin on LPS-induced production of proinflammatory cytokines exceeded that of the reference drug cetirizine.&#x0D; CONCLUSION: In addition to its antihistaminic action, theoritin, a new antiallergic agent, inhibits LPS-induced production of proinflammatory cytokines, which may be of clinical importance in suppressing allergic inflammation.

Bilastine for the treatment of chronic spontaneous urticaria: Consensus statement for Indian patients

Urticaria or hives is a common skin condition that affects population with a lifetime prevalence of up to 22% and point prevalence of 1%. Antihistamines play a very important role in the treatment of chronic urticaria. International guidelines recommend second-generation, non-sedating H1-antihistamines as the first line therapy for management of chronic urticaria. Uncontrolled symptoms in many patients demand a new antihistamine which offers significant efficacy without or with minimal adverse events especially sedation. Bilastine, a second generation H1-antihistamine, offers significant benefits over most antihistamines including once daily dosage, significant efficacy in relieving symptom, minimal risk of drug to drug interactions and adverse events. This consensus statement is prepared to discuss the role of bilastine in the management of chronic urticaria among Indian patients. Comprehensive review of published literature was done to prepare a draft of consensus statement. The draft was circulated to the experts for their review and comments. Final document was prepared with incorporation of their comments. Keywords: Bilastine, C hronic urticaria, Consensus statement.

Antihistamínicos en el tratamiento de la urticaria en México

There are four types of histamine receptors. Allergic symptoms, especially those in rhinoconjunctivitis and urticaria, are mainly caused by activation of histamine receptor 1 (H1). Consequently, oral H1-antihistamines form and integral part of the treatment of these diseases. Antihistamines are inverse agonists that stabilize the non-active configuration of the histamine receptor. First generation H1-antihistamines cause a variety of adverse effects via several mechanisms: sedation (accumulation in the central nervous system), dry mouth, urinary retention, weight gain (low selectivity: stimulation of serotonin/muscarinic/alpha-adrenergic receptors) and drug interactions (substrate of CYP450-3A4). Generally second generation H1-antihistamines have a better safety profile. New guidelines on allergic rhinitis and urticaria recommend second generation H1-antihistamines as first line drugs, with -if necessary- four-times updosing to obtain control in urticaria. The enhanced efficacy of quadruple doses in urticaria, while maintaining a good safety profile, has been shown for bilastine, desloratadine and levocetirizine (rupatadine). For ebastine and fexofenadine only the safety of quadruple doses has been shown till now. Extreme precaution should be taken with astemizol and terfenadine that never should be up-dosed, as high serum concentrations can cause potentially fatal ventricular tachycardia. First generation antihistamines are not recommended as first line treatment and updosing is not safe.

Two Cases of Well Controlled Chronic Spontaneous Urticaria Triggered by the Moderna COVID-19 Vaccine

Chronic spontaneous urticaria (CSU, chronic idiopathic urticaria) is a clinical diagnosis characterized by recurrent urticaria of unknown origin, with or without angioedema, that occurs for six weeks or longer. Management of CSU includes a second-generation H1 antihistamine and/or elimination of exacerbating factors. If initial treatment is unsuccessful, trials of first generation H1 antihistamine, H2 blocking antihistamine, leukotriene-receptor antagonist, anti-inflammatory or immunosuppressive agents may be administered. Exacerbating factors include stress, environmental conditions, medications, physical stimuli, and infections. We report the first two cases of a COVID-19 vaccine triggered relapse of CSU that was previously well controlled on therapy.

Fresh look on the urticaria problem.

Introduction. Nowadays urticaria is one of the most common diseases. According to the International Guidelines for the definition, classification, diagnosis and management of urticaria, 2nd-generation H1-antihistamines are recommended to be used as the first-line and second-line therapy. Omalizumab, a humanized monoclonal anti-IgE antibody, is assumed to be the third-line therapy in urticaria treatment.&#x0D; Summary. In this review we discuss the latest data on pathogenetic mechanisms of urticaria, focusing on the search of the new targets for the therapy. We represent the latest clinical trials of the new biological treatment for urticaria. Safety and efficiency of 4-folds higher therapeutical dose of the 2nd generation H1-antihistamines, and criteria for personalized selection of the antihistamines are discussed.

Allergic rhinitis: are there any problems? Case from clinical practice

Allergic rhinitis (AR) is found in the practice of doctors of various specialties, but making the correct diagnosis and prescribing adequate therapy can take many months and sometimes years. Currently, the problem of AR remains relevant, due to the extreme prevalence of AR, late diagnosis, underestimation of the possible risks of disease progression, complications, and the addition of such a formidable pathology as bronchial asthma. The path of the patient presented in the clinical case is quite typical for many patients with AR and concomitant pathology of nose. A young patient with allergic rhinitis received conservative treatment, and was later operated, but the effect was incomplete and short-lived. Only after 4 years, the patient was first examined by an allergist. Symptoms of AR indicate that the patient has an atopic status that promotes the involvement of various organs and systems in the inflammatory process. To verify the diagnosis and clarify the entire spectrum of “guilty” allergens, a specific allergological examination was carried out, which included skin testing and determination of specific IgE antibodies. The main participants in allergic inflammation are mast cells, eosinophils, lymphocytes, epithelial and endothelial cells. The effect of mediators on vascular endothelial cells and neuroreceptors of the nasal mucosa leads to the formation of allergic inflammation and the onset of clinical symptoms of AR. One of the main mediators released upon repeated contact with an allergen in a sensitized body is histamine, therefore antihistamines are first-line drugs at any stage of AR therapy. In our clinical case, taking into account complaints, medical history, clinical manifestations, results of laboratory (specific, nonspecific) and instrumental methods, the patient needs treatment of the corresponding first stage of therapy based on symptom control. The effectiveness of 2nd generation H1-antihistamines in the management of symptoms such as pruritus, sneezing, and rhinorrhea is due to histamine-mediated development of the early phase of the allergic reaction, which in turn leads to the onset of the late phase and the chronic co Bilastine can be considered as the drug that most fully meets the requirements of ARIA experts for 2nd generation H1-antihistamines : selective blockade of H1 receptors, high antiallergic effect, rapid onset of clinical effect, duration of action 24 hours, lack of tachyphylaxis and good tolerance. The results of the studies and their analysis show that bilastine is the preferred choice for monotherapy of allergic rhinitis.urse of allergic inflammation in the nasal mucosa.

Omalizumab in children and adolescents with chronic spontaneous urticaria: Case series and review of the literature.

The recent EAACI/GA2 LEN/EDF/WAO guidelines recommend omalizumab (anti-IgE) for the management of patients aged ≥12 years with chronic urticaria unresponsive to high-doses second-generation H1 -antihistamines (antiH1 ). However, there is little published information on the success of omalizumab for such a treatment in children. We reported our experience of six patients with chronic spontaneous urticaria (CSU) treated with omalizumab. Mean age of our case series was 14.7 years (range 11-16 years) with a prevalence of male gender (66.7%). All six patients were treated with at least one 6-months course of omalizumab. The average follow-up period was 13 ± 6 months. Only one patient was no responder to omalizumab therapy. Thus far, two patients have experienced a complete CSU regression over 12 months after the final omalizumab administration. The remaining three patients needed a second course of treatment. Our experience demonstrates that omalizumab is effective and safe as treatment option for CSU unresponsive to antiH1 , even in adolescent age.

Phase II trial of levocetirizine with capecitabine and bevacizumab to overcome the resistance of antiangiogenic therapies in refractory metastatic colorectal cancer.

Despite the clinical success of vascular endothelial growth factor (VEGF) blockade in metastatic colorectal cancers (mCRC), resistance to anti-angiogenic drugs invariably develops. IL-8 and other cytokines have been implicated in development of resistance to anti-angiogenic therapy. Levocetirizine is a second generation H1 antihistamine with anti-inflammatory and IL-8 suppression properties. We conducted a phase II trial combining levocetirizine with capecitabine and bevacizumab to potentially overcome anti-angiogenic therapy resistance in patients with refractory mCRC. This was a single-center open-label prospective trial in refractory mCRC patients. Treatment consisted of oral capecitabine 850 mg/m2 twice daily administered as 7 days on and 7 days off, intravenous (IV) bevacizumab 5 mg/kg every 14 days and oral levocetirizine 5 mg daily. The primary end point was progression free survival (PFS) and secondary endpoints included objective response rate (ORR) and tolerability. An exploratory endpoint included correlation of PFS with cytokine levels. A sample size of 36 evaluable patients could identify a median PFS of 3.4 months at a 0.05 significance level. To examine cytokine changes related to levocetirizine treatment, patients were randomized to Arm A where levocetirizine was started 7 days after starting chemotherapy and to Arm B where levocetirizine was started 7 days prior to chemotherapy. Cytokine levels were measured at baseline and with each cycle of chemotherapy (up to three cycles). Forty-seven patients were enrolled in the trial to have 36 evaluable patients. Arm A enrolled 23 patients and Arm B enrolled 24 patients. Fifty percent of patients had progressive disease and 62% of patients had stable disease in each arm as best response. There was no demonstrable difference in PFS between the two arms (log-rank test P=0.83). Median time to progression was 3.4 months in Arm A and 3.5 months in Arm B. Median PFS in the trial was comparable to and appeared to be better than other regimens used in the refractory setting (e.g., median PFS of 1.9 months for regorafenib). Cytokine measurement with IL-8 levels did not show any correlation with progression free survival but patients with stable disease showed overall lower levels of IL-8 as compared to patients with progressive disease in the cytokine analysis.

Formulation, characterization and cytotoxicity evaluation of ketotifen-loaded nanostructured lipid carriers

Abstracts Ketotifen (KT) as a second generation H1-antihistamine is used to relieve allergic conjunctivitis and allergies. To improve KT systemic bioavailability and reduce cellular toxicity, it was formulated into nanostructured lipid carriers (NLCs). KT-loaded NLCs were prepared using hot homogenization and ultrasonication methods and characterized using Zetasizer and transmission electron microscopy (TEM). The particle size and encapsulation efficiency (EE) of KT-loaded NLCs were around 100 nm and 70%, respectively. TEM image of NLCs revealed spherical shaped particles and verified the Zetasizer results. MTT and DAPI staining assays confirmed the low toxicity of KT-loaded NLCs. Finally, the prepared delivery system can be a surrogate for the traditionally available products used in the treatment of allergic symptoms.

Bilastine: A novel antihistamine

Bilastine is a new second generation H1-antihistamine approved for the symptomatic treatment of allergic rhinitis (AR) and chronic urticaria (CU) in patients older than 12 years of age. AR and urticaria are very common clinical conditions that represent one of the most frequent reasons for a patient to visit their general practitioner or allergist or dermatologist. Bilastine, with its efficacy and safety profile epitomizes the evolution of research on antihistamines.

Chronic Urticaria in Children: A Review

Chronic urticaria (CU) is characterised by the recurrence of hives/angioedema for &gt;6 weeks. It affects children and adults and has a worldwide distribution. In children, CU is substantially less common than acute urticaria but is associated with larger decrease in quality of life. The current classification divides CU into two groups: 1) chronic spontaneous urticaria, which includes idiopathic urticaria (by far the most common type), autoimmune urticaria, and those associated with drugs, food, or additives allergies; and 2) chronic inducible urticaria, constituted by cholinergic urticaria and physical urticarias. Diagnosis of CU is based on the history and characteristics of the lesions. Although laboratory and specific testing could establish the diagnosis of some subtypes of CU, frequently the aetiology is never found; therefore, an extensive workup is not recommended. Once the trigger has been identified, it must be avoided. Specific treatment may be tried, but unfortunately this is not always possible. Currently, the first-line treatment for children with CU are second generation H1-antihistamines (SG-H1AH), such as cetirizine, fexofenadine, desloratadine, and rupatadine, among others. If, after 2–4 weeks, the patient has not improved, an increment from 2 to 4-times the regular dose is recommended. Patients that fail to respond to this treatment may be switched to another SG-H1AH or a second agent, such as H2-antihistamines (e.g., cimetidine, ranitidine), ketotifen, cyclosporine, or a leukotriene receptor inhibitor (e.g., montelukast), may be added to the H1-antihistamine therapy. Recently, omalizumab, an anti-immunoglobin-E monoclonal antibody has been approved in several jurisdictions for patients 12 years or older with recalcitrant CU; however, its high cost has limited its use.