Eosinophilic esophagitis (EoE) is a multifaceted disease characterized by a wide heterogeneity of clinical manifestations, endoscopic and histopathologic patterns, and responsiveness to therapy. From the perspective of an effective approach to the patient, the different inflammatory mechanisms involved in the pathogenesis of EoE and biologics, in particular monoclonal antibodies (mAbs), targeting these pathways are needed. Currently, the most relevant is dupilumab, which interferes with both interleukin (IL)-4 and IL-13 pathways by binding IL-4 receptor α, and is the only mAb approved by the European Medicine Agency and US Food and Drug Administration for the treatment of EoE. Other mAbs investigated include mepolizumab, reslizumab, and benralizumab (interfering with IL-5 axis), cendakimab and dectrekumab (anti-IL-13s), tezepelumab (anti-TSLP), lirentelimab (anti-SIGLEG-8), and many others. Despite the undeniable economic impact of biologic therapies, in the near future, there will be room for further reflection about the opportunity to prescribe biologic agents, not only as a last-line therapy in selected cases such as patients with comorbidities involving common pathways. Although recent findings are very encouraging, the road to permanent success in the treatment of EoE is still long, and further studies are needed to determine the long-term effects of mAbs and to discover new potential targets.

Background. Allergen-specific immunotherapy (AIT) is the only disease-modifying therapy for allergic conditions, resulting in a long-lasting tolerance beyond the duration of the treatment. Due to the strong relationship between the effectiveness, its optimal duration (at least three years) and the observation of the correct administration protocol, appropriate adherence to the plan of treatment represents a critical factor for the therapeutical success of AIT. Methods. Analysis of studies about the rate of adherence in subcutaneous and sublingual immunotherapy, which are the main routes of administration of AIT. Results. There are different causes leading to a premature interruption of the therapy or to it being incorrectly carried out; the most reported include erroneous expectations of the effectiveness and the adverse effects, economic issues, inconvenience and unrelated clinical conditions. Conclusions. An attentive analysis of the main causes of dropouts may be useful to improve the management of these patients and to develop new strategies for a personalized approach. These strategies should be dynamic, involving attentive communication between the physician and the patient about all the possible criticalities, especially in the initial phase of the therapy, and facilitating, as much as possible, access to healthcare providers over the course of the maintenance phase, including by exploiting technological tools.

Allergen immunotherapy (AIT) is the only treatment which acts on the causes of allergic diseases by modifying their natural history. In the eighties subcutaneous immunotherapy (SCIT) with high biological power allergen extracts caused a number of severe systemic reactions and also fatalities in the UK and the US, resulting in its limitation and in the introduction of other routes of administration. A decisive advance for SCIT safety was understanding that the major cause of mortality was injecting the allergen extract to patients with uncontrolled asthma at the time of injection. This awareness resulted in a significant decrease in fatalities, but not in their abolition. In 2019, an increase in SCIT-related mortality was observed, suggesting to continue the research for still unidentified factors favoring severe reactions, such as the administration of a wrong extract or of allergen doses higher than listed, unintentional intravenous administration, and missed dose reduction after protracted interruption. Moreover, in the context of the improving of the safety, the role played in tolerance-promoting by adjuvants such as CpG oligodeoxynucleotides has to be taken into account, as well as the potential preventive effect performed by the monoclonal anti-IgE antibody omalizumab against the exacerbation of severe reactions during SCIT. The safety of SCIT is good, but the research to improve it further must continue. In particular, the pathophysiological mechanisms related to AIT for inhalants and for Hymenoptera venom should be studied, based on the evident diversity demonstrated by the complete absence of fatal reactions to Hymenoptera venom immunotherapy from its introduction in comparison with the history of serious and fatal offenses examined in this review.

Given their nutritional features and environmental sustainability, black soldier fly (Hermetia illucens) larvae are currently being considered in Europe for commercialization as human food. The primary goal of this study is the determination of in vitro IgE-cross-reactivity to recombinant tropomyosin (_HITPM) and arginine kinase (_HIAK) of H. illucens in subjects sensitized to crustaceans and/or mites. Dot blot assays for recombinant _HITPM were carried out with the sera of 48 subjects, 30 sensitized to crustaceans (Cr+) and/or house dust mites (HDM+) (STUDY group) and 18 non-sensitized (CTRL group). A higher rate of IgE-reactivity to recombinant _HITPM was found in the STUDY group compared to non-sensitized controls (73% vs. 44%; p 0.066). No significant relationship was achieved upon dot blot assays for _HIAK. No relevant association between a positive history of food reactions and immunoreactivity to _HITPM and to _HIAK was reported (15% in _HITPM+ vs. 6% in _HITPM-, p NS; 28% in _HIAK+ vs. 50% in _HIAK-, p NS), contrary to the _HITPM+Cr+HDM+ subset (50% vs. 0%, p 0.022). Considering the wide overlap of pan-allergens within the Arthropoda phylum, concerns about allergenic potential due to the eventual consumption of H. illucens-enriched foods might be valid. Therefore, targeted studies involving basophil activation tests, skin prick tests, and a double-blind placebo-controlled oral food challenge using H. illucens are needed.

Background/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) represents a common and debilitating inflammatory disorder primarily driven by type 2 immune mechanisms. Its frequent overlap with asthma, allergic rhinoconjunctivitis and atopic dermatitis highlights the need for therapeutic strategies able to address multimorbidity within the same pathogenic spectrum. The development of monoclonal antibodies targeting signaling pathways provides an effective and well-tolerated option that addresses common comorbidities. Targeting the IL-4 receptor alpha subunit, dupilumab is a completely human IgG4 monoclonal antibody that reduces type 2 inflammation in many organ systems by blocking IL-4 and IL-13 signaling. This study aimed to assess the long-term effectiveness and safety of dupilumab in a real-world cohort of patients with severe CRSwNP, stratified according to the presence of common type 2 comorbidities, over a 52-week treatment period. Methods: We conducted a prospective, multicenter, observational study across ten Italian secondary care centers for Allergy and Clinical Immunology and Otolaryngology. All participating centers were affiliated with the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). Enrolled adult subjects with severe CRSwNP received dupilumab treatment in the context of standard care for 52 weeks. Several efficacy parameters were used. Results: A significant improvement was detected for all the applied efficacy parameters, i.e., 22-item Sinonasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the first second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI), Atopic Dermatitis Control Toll (ADCT) and Dermatology Life Quality Index (DLQI) scores for AD. Dupilumab was well-tolerated, with no new safety signals. Conclusions: This multicenter real-world study demonstrates that dupilumab provides sustained, clinically meaningful, and safe benefits for patients with severe CRSwNP and coexisting type 2 comorbidities, supporting its role as an integrated therapeutic option in precision management of type 2 inflammatory diseases.

The demographic increase, environmental concerns, and heightened awareness about health has led Western countries to consider edible sources previously overlooked. The novelty of these sources implies a scarce knowledge about their allergenicity. This review has the purpose of offering an arranged view about the allergenicity of different categories of novel foods, such as edible insects, new plant-based foods and microalgae, by exploring cross-reactivity and common traits with other food allergies but also specific peculiarities. A particular regard is reserved to the framework in Western countries. Increasing efforts have been directed in the last years to identify dangerous cross-reactive allergens in novel foods, i.e. tropomyosin. On the other hand, eventual primary sensitizations should also be considered, especially for idiopathic anaphylaxis. In view of the partial knowledge about the allergenic potential of the novel sources, the education of the patient on this topic (particularly those with known food allergies), and an appropriate labeling of product's packages may reveal helpful to minimize the risk.