In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose–response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H₁-antihistamines at approved or increased doses, alone or in combination with H₂-antihistamines or leukotriene-receptor antagonists.

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one‐airway‐one‐disease,” coined over 20 years ago, is a simplistic approach of the links between upper‐ and lower‐airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper‐ and lower‐airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one‐airway‐one‐disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll‐Like Receptors and IL‐17 for rhinitis alone as a local disease; IL‐33 and IL‐5 for allergic and non‐allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono‐ or pauci‐sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Kolkhir P, et al. Allergy Asthma Immunol Res. 2021 Jul;13(4):545-559. https://doi.org/10.4168/aair.2021.13.4.545

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense pruritus, eczematous lesions, and relapsing course. It presents with great clinical heterogeneity, while underlying pathogenetic mechanisms involve a complex interplay between a dysfunctional skin barrier, immune dysregulation, microbiome dysbiosis, genetic and environmental factors. All these interactions are shaping the landscape of AD endotypes and phenotypes. In the “era of allergy epidemic”, the role of food allergy (FA) in the prevention and management of AD is a recently explored “era”. Increasing evidence supports that AD predisposes to FA and not vice versa, while food allergens are presumed as one of the triggers of AD exacerbations. AD management should focus on skin care combined with topical and/or systemic treatments; however, in the presence of suspected food allergy, a thorough allergy evaluation should be performed. Food-elimination diets in food-allergic cases may have a beneficial effect on AD morbidity; however, prolonged, unnecessary diets are highly discouraged since they can lead to loss of tolerance and potentially increase the risk of IgE-mediated food allergy. Preventive AD strategies with the use of topical emollients and anti-inflammatory agents as well as early introduction of food allergens in high-risk infants seem promising in managing and preventing food allergy in AD patients. The current review aims to overview data on the complex AD/FA relationship and provide the most recent developments on whether food allergy interventions change the AD course and vice versa.

Background: Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold‐induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU.Methods: An international, cross‐sectional study COLD‐CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest^® performed. ColdA was defined as an acute cold‐induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms.Results: Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold‐induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes.Conclusion: ColdA is common in typical ColdU. High‐risk patients require education about their condition and how to use an adrenaline autoinjector.