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[Display omitted] Chronic spontaneous urticaria (CSU) is a chronic inflammatory disease characterized by recurrent pruritic wheals (hives) and/or angioedema. Patients with CSU could remain symptomatic despite standard-of-care H 1 antihistamines (H1-AH) or anti-IgE (omalizumab) treatment. Dupilumab blocks IL-4/IL-13 signaling and is approved for multiple type 2/atopic indications. We conducted two phase 3, randomized, placebo-controlled, double-blind trials comparing dupilumab with placebo in patients with symptomatic CSU despite H1-AH. In LIBERTY-CSU CUPID Study A, patients were omalizumab-naive (n = 138, aged ≥6 years). In Study B, patients were omalizumab-intolerant/incomplete responders (n = 108, aged ≥12 years). The primary end point was either change from baseline over 7 days in the Urticaria Activity Score (UAS7) or Itch Severity Score (ISS7) at week 24, with the other as a key secondary end point, depending on regional regulatory requirements. Studies were pooled for safety assessment. In Study A, UAS7 and ISS7 improved with dupilumab versus placebo (difference −8.5 [95% CI, −13.2 to −3.9; P =.0003] and −4.2 [95% CI, −6.6 to −1.8; P =.0005]). In Study B, tested at α = 0.043 after interim analysis, UAS7 improved (difference −5.8 [95% CI, −11.4 to −0.3; P =.0390]), with a numerical trend in ISS7 (difference −2.9 [95% CI, −5.7 to −0.07; nominal P =.0449, not significant]). Pooled safety data were consistent between dupilumab and placebo and with the known dupilumab safety profile. Dupilumab reduced urticaria activity by reducing itch and hives severity in omalizumab-naive patients with CSU uncontrolled with H1-AH. Although the primary end point for Study B was not met, dupilumab effects were small in patients who were omalizumab-intolerant/incomplete responders. [ABSTRACT FROM AUTHOR]

Chronic spontaneous urticaria (CSU) is an inflammatory skin disorder that manifests with itchy wheals, angioedema, or both for more than 6 weeks. Mast cells and basophils are the key pathogenic drivers of CSU; their activation results in histamine and cytokine release with subsequent dermal inflammation. Two overlapping mechanisms of mast cell and basophil activation have been proposed in CSU: type I autoimmunity, also called autoallergy, which is mediated via IgE against various autoallergens, and type IIb autoimmunity, which is mediated predominantly via IgG directed against the IgE receptor FcεRI or FcεRI-bound IgE. Both mechanisms involve cross-linking of FcεRI and activation of downstream signaling pathways, and they may co-occur in the same patient. In addition, B-cell receptor signaling has been postulated to play a key role in CSU by generating autoreactive B cells and autoantibody production. A cornerstone of FcεRI and B-cell receptor signaling is Bruton tyrosine kinase (BTK), making BTK inhibition a clear therapeutic target in CSU. The potential application of early-generation BTK inhibitors, including ibrutinib, in allergic and autoimmune diseases is limited owing to their unfavorable benefit-risk profile. However, novel BTK inhibitors with improved selectivity and safety profiles have been developed and are under clinical investigation in autoimmune diseases, including CSU. In phase 2 trials, the BTK inhibitors remibrutinib and fenebrutinib have demonstrated rapid and sustained improvements in CSU disease activity. With phase 3 studies of remibrutinib ongoing, it is hoped that BTK inhibitors will present an effective, well-tolerated option for patients with antihistamine-refractory CSU, a phenotype that presents a considerable clinical challenge. [ABSTRACT FROM AUTHOR]

Physical urticaria is a type of urticaria in which recurrent wheals and/or angioedema occur following exposure of the skin to a physical stimulus. It is classified according to its triggers, which may be mechanical (friction, pressure, and vibration), thermal (cold and heat), or solar electromagnetic radiation. Symptoms of different physical urticarias can develop following specific activities that expose patients to an eliciting stimulus and may be variably accompanied by mucosal involvement and systemic symptoms, including nausea, headache, or even anaphylaxis. Differentiation of physical urticaria from other chronic urticarias requires careful clinical assessment and confirmatory provocation testing, which in turn can inform appropriate management. This clinical review provides an evidence-based summary of the epidemiology, clinical features, pathogenesis, diagnostic work-up, and management of physical urticaria. [ABSTRACT FROM AUTHOR]

Urticaria is a heterogeneous inflammatory disorder that can be acute or chronic and is defined by the appearance of wheals, angioedema, or both. Very recently, the newest update and revision of the international European Academy of Allergy and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum/Asia Pacific Association of Allergy Asthma Clinical Immunology guideline for the definition, classification, diagnosis, and management of urticaria was published. It aims to help primary care physicians and specialists in the management of their patients with urticaria. The guideline applied the Grading of Recommendations Assessment Development and Evaluations approach to developing consensus recommendations. These recommendations were then discussed in a Delphi conference that included more than 250 specialists in the field, and they are endorsed by more than 50 international societies. Here, we highlight changes from previous versions of the international urticaria guideline and their impact on clinical practice. [ABSTRACT FROM AUTHOR]

The binding of IL-33 to its receptor ST2 (alias of IL1RL1) leads to the release of inflammatory mediators and may play a role in the pathogenesis of atopic dermatitis. Astegolimab is a fully human, IgG 2 mAb that binds to ST2 and inhibits IL-33 signaling. This study sought to assess the efficacy, safety, and pharmacokinetics of astegolimab in patients with atopic dermatitis. This was a randomized, placebo-controlled, phase 2 study in which adults with chronic atopic dermatitis were randomized 1:1 to receive astegolimab 490 mg every 4 weeks or placebo, for 16 weeks. The primary outcome was the percentage of change from baseline to week 16 of the Eczema Area and Severity Index score. A total of 65 patients were enrolled in the study (placebo, n = 32; astegolimab, n = 33). The adjusted mean percentage of change from baseline to week 16 in the Eczema Area and Severity Index score was −51.47% for astegolimab compared with −58.24% for placebo, with a nonsignificant treatment difference of 6.77% (95% CI: −16.57-30.11; P =.5624). No differences were observed between treatment groups for secondary efficacy outcomes and in exploratory biomarkers (blood eosinophils, serum IL-5, serum CCL13). With the use of loading dose, pharmacokinetic exposure was sufficient from week 1. Astegolimab was well-tolerated, with a safety profile consistent with that observed in previous clinical trials. In patients with atopic dermatitis, astegolimab did not show a significant difference compared to placebo for the primary or secondary outcomes. [ABSTRACT FROM AUTHOR]

Chronic spontaneous urticaria (CSU) is a debilitating mast cell–driven disease characterized by recurrent wheals and/or angioedema. Substantial progress has been made in dissecting the 2 main autoimmune mechanisms that drive the pathogenesis of CSU. Type I autoimmune (autoallergic) CSU is associated with IgE antibodies against autoantigens, for example, thyroid peroxidase and IL-24. Type IIb autoimmune CSU is mediated by autoantibodies that activate mast cells, for example, via IgE and FcεRI, and is present in less than 10% of patients with CSU when strict criteria are used, that is, triple positivity of autologous serum skin test, immunoassays for IgG autoantibodies, and basophil activation tests. A subpopulation of patients with CSU has both types. Type IIb autoimmune CSU is characterized by higher disease severity, concomitant autoimmune diseases, low levels of total IgE, elevated levels of IgG-anti–thyroid peroxidase, basopenia, eosinopenia, poor response to antihistamines and to omalizumab, and a good response to cyclosporine. Novel targeted therapies for CSU are under development such as ligelizumab, an anti-IgE, fenebrutinib and remibrutinib, Bruton's tyrosine kinase inhibitors, and dupilumab, an anti–IL-4Rα. Further studies should investigate the overlap between autoallergic and type IIb autoimmune CSU, optimize the diagnosis of both autoimmune endotypes using easy-to-perform, noninvasive, and inexpensive markers, and assess differences in response to therapy. [ABSTRACT FROM AUTHOR]

Mast cells are highly granular tissue-resident cells and key drivers of inflammation, particularly in allergies as well as in other inflammatory diseases. Most mast cell research was initially conducted in rodents but has increasingly shifted to the human system, with the advancement of research technologies and methodologies. Today we can analyze primary human cells including rare subpopulations, we can produce and maintain mast cells isolated from human tissues, and there are several human mast cell lines. These tools have substantially facilitated our understanding of their role and function in different organs in both health and disease. We can now define more clearly where human mast cells originate from, how they develop, which mediators they store, produce de novo , and release, how they are activated and by which receptors, and which neighboring cells they interact with and by which mechanisms. Considerable progress has also been made regarding the potential contribution of mast cells to disease, which, in turn, has led to the development of novel approaches for preventing key pathogenic effects of mast cells, heralding the era of mast cell–targeted therapeutics. In this review, we present and discuss a selection of some of the most significant advancements and remaining gaps in our understanding of human mast cells during the last 25 years, with a focus on clinical relevance. [ABSTRACT FROM AUTHOR]

Hereditary angioedema (HAE) is a rare, life-threatening genetic disorder characterized by recurrent episodes of subcutaneous or submucosal angioedema. The ultimate goals of treatment for HAE remain ill-defined. The aim of this Delphi process was to define the goals of HAE treatment and to examine which factors should be considered when assessing disease control and normalization of the patient's life. The Delphi panel comprised 23 participants who were selected based on involvement with scientific research on HAE or coauthorship of the most recent update and revision of the World Allergy Organization/European Academy of Allergy and Clinical Immunology guideline on HAE. The process comprised 3 rounds of voting. The final round aimed to aggregate the opinions of the expert panel and to achieve consensus. Two direct consensus questions were posed in round 2, based on the responses received in round 1, and the panel agreed that the goals of treatment are to achieve total control of the disease and to normalize the patient's life. For the third round of voting, 21 statements were considered, with the participants reaching consensus on 18. It is clear from the wide-ranging consensus statements that the burdens of disease and treatment should be considered when assessing disease control and normalization of patients' lives. The ultimate goal for HAE treatment is to achieve no angioedema attacks. The availability of improved treatments and disease management over the last decade now makes complete control of HAE a realistic possibility for most patients. [ABSTRACT FROM AUTHOR]

Background: Sleep disturbance remains insufficiently characterized in many dermatoses.Objective: To investigate the prevalence, burden, and factors associated with sleep disturbance in dermatologic patients.Methods: We recruited 800 patients and recorded pruritus characteristics and sociodemographic and clinical parameters. Validated questionnaires were used to assess sleep disturbance, psychological distress, health-related quality of life, and work productivity.Results: Two thirds of patients met criteria of poor sleep, which was associated with psychological distress, diminished health-related quality of life, and lost work productivity. Patients with average and maximum pruritus on the visual analog scale exceeding 5 and 6.5 points, respectively, were at high risk of suffering pruritus-related sleep disturbance. Overall pruritus intensity and its nocturnal exacerbation contributed independently to sleep disturbance. Psychological distress was of even higher impact on sleep than pruritus and almost a third of the relationship between pruritus intensity and sleep was mediated by psychological distress.Conclusion: Sleep disturbance is prevalent in dermatologic patients and constitutes a considerable burden.Clinical Implication: Dermatologic patients with intense pruritus and psychological distress should be examined for sleep disorders. Adequate antipruritic therapy and complementary psychotherapy in affected patients may help them regain restorative sleep. [ABSTRACT FROM AUTHOR]

A C 57 BL-6 mouse model and functional and phenomenological in vivo assays facilitate the analysis of the granulation, localization and number of mast cells (MC) during murine hair cycle. Anagen growth in mice is activated by MC which function through their secretory products. MC plays a role in the process of physiological tissue remodeling such as those related with cycle loss and development of hair follicles.

Taking a novel approach, this narrative review collates knowledge about nasal polyposis and the biological functions of IgE in several diseases (allergic rhinitis, allergic asthma, nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease, and chronic spontaneous urticaria) to consider which IgE-mediated mechanisms are relevant to nasal polyposis pathology. A type 2 eosinophil-dominated inflammatory signature is typical in nasal polyp tissue of European patients with nasal polyposis, with a shift toward this endotype observed in Asian populations in recent years. Elevated polyclonal IgE is present in the nasal tissue of patients with and without allergy. It is derived from many different B-cell clones and, importantly, is functional (proinflammatory). Staphylococcus aureus enterotoxins are thought to act as superantigens, inducing production of polyclonal IgE via B-cell and T-cell activation, and triggering release of inflammatory mediators. In some patients, exposure to antigens/triggers leads to production of high levels of antigen-specific IgE, which mediates cross-linking of the high-affinity IgE receptor on various cells, causing release of inflammatory mediators. The efficacy of omalizumab confirms IgE as an important inflammatory mediator in nasal polyposis. By blocking IgE, omalizumab targets the T2 inflammation in nasal polyposis, reduces nasal polyp score and improves symptoms. [ABSTRACT FROM AUTHOR]

Background: Pruritus often accompanies chronic skin diseases, exerting considerable burden on many areas of patient functioning; this burden and the features of pruritus remain insufficiently characterized.Objective: To investigate characteristics, including localization patterns, and burden of pruritus in patients with chronic dermatoses.Methods: We recruited 800 patients with active chronic skin diseases. We assessed pruritus intensity, localization, and further characteristics. We used validated questionnaires to assess quality of life, work productivity and activity impairment, anxiety, depression, and sleep quality.Results: Nine out of every 10 patients had experienced pruritus throughout their disease and 73% in the last 7 days. Pruritus often affected the entire body and was not restricted to skin lesions. Patients with moderate to severe pruritus reported significantly more impairment to their sleep quality and work productivity, and they were more depressed and anxious than control individuals and patients with mild or no pruritus. Suicidal ideations were highly prevalent in patients with chronic pruritus (18.5%) and atopic dermatitis (11.8%).Conclusions: Pruritus prevalence and intensity are very high across all dermatoses studied; intensity is linked to impairment in many areas of daily functioning. Effective treatment strategies are urgently required to treat pruritus and the underlying skin disease. [ABSTRACT FROM AUTHOR]

The Mas-related G protein–coupled receptor X2 (MRGPRX2) is a multiligand receptor responding to various exogenous and endogenous stimuli. Being highly expressed on skin mast cells, MRGPRX2 triggers their degranulation and release of proinflammatory mediators, and it promotes multicellular signaling cascades, such as itch induction and transmission in sensory neurons. The expression of MRGPRX2 by skin mast cells and the levels of the MRGPRX2 agonists (eg, substance P, major basic protein, eosinophil peroxidase) are upregulated in the serum and/or skin of patients with inflammatory and pruritic skin diseases, such as chronic spontaneous urticaria or atopic dermatitis. Therefore, MRGPRX2 and its agonists might be potential biomarkers for the progression of cutaneous inflammatory diseases and the response to treatment. In addition, they may represent promising targets for prevention and treatment of signs and symptoms in patients with skin diseases or drug reactions. To assess this possibility, this review explores the role and relevance of MRGPRX2 and its activators in cutaneous inflammatory disorders and chronic pruritus. [ABSTRACT FROM AUTHOR]

Symptomatic dermographism (SD) is the most common form of chronic inducible urticaria. The criterion standard for diagnosing SD and disease activity assessment in SD is provocation testing. As of now, if and what cofactors have an impact on provocation test results is unknown. We sought to determine whether the induction of signs and symptoms of SD is affected by the intake of food. We performed standardized skin provocation testing with a dermographometer (FricTest) before and after the intake of food. Patients were off antihistamine treatment for at least 3 days before testing. In total, 17 patients were tested after not having eaten for at least 4 hours (preprandial) on one volar forearm and 60 minutes after a carbohydrate-rich meal (postprandial) on the other. FricTest responses (wheals, itch) at trigger thresholds were assessed at 5 and 30 seconds as well as at 1, 2, 5, and 10 minutes. We identified 7 patients with SD who showed faster onset of FricTest-induced whealing and/or lower trigger thresholds after the intake of food, that is, food-exacerbated SD. In 5 other patients, FricTest provocation testing resulted in a positive response only after the intake of food, but not before. Three of these 5 patients with food-dependent SD had comorbid chronic spontaneous urticaria and 1 had cholinergic urticaria. We describe 2 previously unknown subtypes of SD, food-exacerbated SD and food-dependent SD. The prevalence and underlying pathomechanisms of food-exacerbated SD and food-dependent SD need to be investigated, and the impact of food intake on other forms of chronic inducible urticaria should be explored. [ABSTRACT FROM AUTHOR]

Chronic spontaneous urticaria (CSU) is considered to be primarily a mast cell–driven disease. However, recent evidence suggests that eosinophils may also have an axial role in symptomology. Histologic studies have demonstrated the presence of both eosinophils and eosinophil granules, indicative of activation, in CSU lesions. Although many allergic and inflammatory conditions are associated with a peripheral blood eosinophilia, the converse appears to be the case in CSU, with a peripheral blood eosinopenia being observed in many patients. Possible mechanisms include the depletion of blood eosinophils by recruitment into the skin during active disease and immunologic destruction in the blood. We also address in some detail the interactions between eosinophils and mast cells, particularly the cytokine cross-talk of these cells and mediator release possibly leading to clinical symptoms. Also, activation by eosinophil proteins of the coagulation pathway leads to the generation of thrombin and increased mast cell degranulation. Finally, treatments aimed at reducing eosinophil accumulation and activation, such as the anti–IL-5 antibodies mepolizumab, reslizumab, and benralizumab, have been reported to reduce CSU symptoms. Clearly, a new picture of an important role of eosinophils in the pathogenesis of CSU is emerging. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are capable of executing powerful inflammatory response programs triggered by surface IgE cross-linking or through pattern recognition receptors. The question of how MCs contribute to human disease has been intensely investigated and stimulated much controversy. Correlative evidence comes from human studies, pointing to pathogenetic or protective MC functions in patients with atopic conditions, autoimmune disorders, type 2 diabetes, chronic urticaria, mastocytosis, and cancer. Experiments in MC-deficient mice underpinned key roles for MCs in patients with IgE-mediated allergic conditions. Important pathogenetic MC contributions to other inflammatory and neoplastic conditions were suggested by studies in traditional KIT mutant MC-deficient mouse strains. However, many of these findings were not reproduced in more recently developed improved mouse models of MC deficiency, largely ruling out roles for MCs in mouse models for autoimmune disease, diabetes, and cancer. We discuss limitations of studies in mice and human subjects and provide suggestions for how they can be overcome, such as through the development of specific and selective MC-targeted treatments. [ABSTRACT FROM AUTHOR]

Background Several treatment options for cold urticaria (ColdU) have been studied and reported, but systematic reviews and meta-analyses are limited. Objectives We sought to meta-analyze and review the efficacy and safety of ColdU treatments. Methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Suitable reports were identified by searching PubMed, Scopus, and Web of Science. Our systematic review included 16 studies, 9 of which met the eligibility criteria for the meta-analysis. We analyzed the effects of treatments on critical temperature thresholds (CTTs) and critical stimulation time thresholds (CSTTs), as well as on rates of complete response and adverse events. Results Our pooled meta-analyses showed that nonsedating second-generation H 1 -antihistamines (nsAHs) are effective in the treatment of ColdU and that updosing of nsAHs significantly reduced CTTs relative to their own standard doses and placebos. In 4 studies involving CSTTs, updosing of nsAHs also resulted in significantly better CSTTs than their own standard doses or placebos. Omalizumab resulted in a marked reduction of CTTs in H 1 -antihistamine–resistant patients. Of 118 adverse events in 8 studies, standard-dose nsAHs, updosed nsAHs, and omalizumab produced lower numbers of adverse events than first-generation antihistamines. Conclusions Our study showed that greater dosages of nsAHs were more effective than standard dosages in controlling ColdU symptoms. Increasing the dosages was not significantly associated with higher adverse event rates. Omalizumab at 150 and 300 mg every 4 weeks was shown to be effective for patients with ColdU refractory to antihistamines. [ABSTRACT FROM AUTHOR]

Urticarial vasculitis (UV) is a difficult-to-treat condition characterized by long-lasting urticarial rashes and histopathologic findings of leukocytoclastic vasculitis. Treatment is dictated by the severity of skin and systemic involvement and the underlying systemic disease. This is a comprehensive systematic review of the efficacy of current UV treatment options. We searched for relevant studies in 7 databases, including MEDLINE, Scopus, and Web of Science. In total, 261 eligible studies and 789 unique patients with UV were included in the systematic review. Most patients with UV are adult women with chronic (≥6 weeks) and systemic disease. UV is mostly idiopathic but can be associated with drugs, malignancy, autoimmunity, and infections. It usually resolves with their withdrawal or cure. Corticosteroids are effective for the treatment of skin symptoms in more than 80% of patients with UV. However, their long-term administration can lead to potentially serious adverse effects. The addition of immunomodulatory or immunosuppressive agents often allows corticosteroid tapering and improves the efficacy of therapy. Biologicals, including omalizumab, as well as corticosteroids, cyclophosphamide, dapsone, mycophenolate mofetil, plasmapheresis, colchicine, hydroxychloroquine, intravenous immunoglobulin, nonsteroidal anti-inflammatory drugs, and cyclosporine, can be effective for both skin and systemic symptoms in patients with UV. H 1 -antihistamines, montelukast, danazol, H 2 -antihistamines, pentoxifylline, doxepin, and tranexamic acid are not effective in most patients with UV. As of yet, no drugs have been approved for UV, and management recommendations are based mostly on case reports and retrospective studies. Prospective studies investigating the effects of treatment on the signs and symptoms of UV are needed. [ABSTRACT FROM AUTHOR]

The Urticaria Control Test (UCT) is a well-established, very easy to use and calculate 4-item patient-reported outcome measure to assess chronic urticaria disease control during the previous 4 weeks. Clinical trials and practice may benefit from the use of a UCT version with a shorter recall period, but this does not exist. We sought to develop and validate a UCT version with a 7-day recall period, the UCT7. The UCT7 was developed, based on the UCT, and tested, in 152 patients with chronic urticaria (spontaneous: n = 101, inducible: n = 51) for its reliability, validity and screening accuracy, and clinimetric properties, in other words, the cutoff for well-controlled disease and the minimal clinically important difference. The UCT7 showed excellent internal consistency reliability with a Cronbach αvalue of 0.91 and test-retest reliability with an intraclass correlation coefficient of 0.83. Convergent validity was high and strongly correlated with anchors of disease control, wheal and angioedema frequency, and urticaria-related quality of life impairment. The UCT7 showed excellent sensitivity to change; however, changes in angioedema activity and impact did not correlate well with changes in UCT7. Based on receiver-operating characteristic curve analysis, the proportion of correctly classified patients, and patients' assessment of treatment efficacy, we recommend a cutoff value of 12 points for identifying patients with well-controlled disease. The UCT7 minimal clinically important difference for improvement was estimated to be 2 points. The UCT7 is a validated 7-day recall period version of the UCT. It is ideal for the assessment of disease control at short intervals in patients with chronic urticaria in clinical studies and practice. [ABSTRACT FROM AUTHOR]

Background The efficacy of omalizumab (anti-IgE) and increased IgE levels in patients with chronic spontaneous urticaria (CSU) suggest autoallergic mechanisms. Objective We sought to identify autoallergic targets of IgE in patients with CSU. Methods Serum samples of patients with CSU together with those of patients with idiopathic anaphylaxis and healthy control subjects (7 of each) were screened for IgE autoantibodies by using an array of more than 9000 proteins. Sera of 1062 patients with CSU and 482 healthy control subjects were used in an IgE-anti–IL-24–specific ELISA to investigate the association of IgE-anti-IL-24 and CSU. Results By using array analyses, more than 200 IgE autoantigens were found in patients with CSU that were not found in control subjects. Of the 31 IgE autoantigens detected in more than 70% of patients, 8 were soluble or membrane bound and expressed in the skin. Of these, only IgE autoantibodies to IL-24 were found in all patients with CSU. In vitro studies showed IL-24 to release histamine from human mast cells sensitized with purified IgE of patients with CSU but not control subjects. By using ELISA, mean ± SD levels of IgE-anti–IL-24 were 0.52 ± 0.24 IU/mL in patients with CSU and 0.27 ± 0.08 IU/mL in control subjects, with 80% of patients with CSU but only 20% of control subjects having levels greater than 0.33 IU/mL ( P < .0001). IgE-anti–IL-24 showed acceptable predictive properties for CSU, with a likelihood ratio of 3.9. Clinically, IgE-anti–IL-24 levels showed an association with disease activity, as assessed by the urticaria activity score and with reduced basophil counts. Conclusion Our findings show that patients with CSU frequently exhibit IgE autoantibodies against many autoantigens and that IL-24 is a common, specific, and functional autoantigen of IgE antibodies in patients with CSU. [ABSTRACT FROM AUTHOR]

Background Chronic inducible urticaria (CindU) is a condition characterized by the appearance of recurrent wheals, angioedema, or both as a response to specific and reproducible triggers. Objective We sought to systematically assess evidence on the efficacy and safety of treatment options for CindU. Results were used to inform the 2017 update of “The EAACI/GA 2 LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria.” Methods Randomized controlled trials and controlled intervention studies were searched systematically in various databases. Included studies were evaluated with the Cochrane Risk of Bias tool. Where possible, results from single studies were meta-analyzed, applying the Mantel-Haenszel approach by using a random-effects model (Der Simonian–Laird). Results We identified 30 studies that included patients with cold urticaria, symptomatic dermographism, delayed-pressure urticaria, or cholinergic urticaria. No studies on other forms of CindU were eligible. Risk of bias was often rated as unclear or high. Overall, second-generation antihistamines were more effective than placebo, and available data indicate that updosing might be effective. Omalizumab proved effective in patients with symptomatic dermographism, who did not respond to antihistamines. Detailed results are given for each type of CindU. Conclusions The available evidence is limited by small samples, heterogeneous efficacy outcomes, and poor reporting quality in many of the included studies. The findings are congruent with the suggested stepwise approach to treating CindUs. However, the data do not allow for drawing specific conclusions for specific subtypes of CindU. [ABSTRACT FROM AUTHOR]

Background Omalizumab, a recombinant anti-IgE antibody, effectively treats chronic spontaneous urticaria. Evidence is lacking in patients with chronic inducible urticarias (CIndUs), which are frequently H 1 -antihistamine resistant. Objective From the current published literature, we aimed to determine the strength of evidence for omalizumab efficacy and safety in the treatment of CIndUs. Methods We performed a PubMed search to identify evidence on omalizumab use in the following 9 CIndU subtypes: symptomatic dermographism, cold urticaria, delayed-pressure urticaria, solar urticaria, heat urticaria, vibratory angioedema, cholinergic urticaria, contact urticaria, and aquagenic urticaria. Results Forty-three trials, case studies, case reports, and analyses were identified. Our review indicates that omalizumab has substantial benefits in patients with various CIndUs. The evidence is strongest for symptomatic dermographism, cold urticaria, and solar urticaria. Little/no evidence was available on vibratory angioedema and aquagenic and contact urticaria. Our review supports rapid onset of action demonstrated through early symptom control in most cases, sometimes within 24 hours. Many patients gained complete/partial symptom relief and substantially improved quality of life. Adverse events were generally low, with omalizumab being well tolerated by most patients, including children. Conclusions A strong body of evidence supports the use of omalizumab in the treatment of patients with therapy-refractory CIndU. More data from randomized controlled studies are warranted. [ABSTRACT FROM AUTHOR]