Summary:Background. Recent advancements in hereditary angioedema (HAE) management have focused mainly on long-term prophylaxis (LTP), aiming to achieve total disease control and normalize patients' lives. The latest international guidelines recommend as first-line options for LTP plasma-derived C1-INH, lanadelumab, and berotralstat. Berotralstat is a highly selective inhibitor of plasma kallikrein and the first licensed oral therapy for HAE, to be taken once daily. Given the limited clinical experience with berotralstat in Italy, members of the Italian Network for Hereditary and Acquired Angioedema (ITACA) here present and discuss some representative clinical cases treated with berotralstat in their institutions to provide practical guidance for the use of this medication. Methods. Three main topics were identified, (I) the switch from injectable medications to new oral therapies, with a focus on shared decision-making, (II) the switch from androgens to berotralstat, and (III) the management of comorbid patients, with a focus on polypharmacy. Results. The Italian experience to date indicates that (I) the decision on LTP should be always shared with patients and, given the importance for patients of administration route, berotralstat should always be considered and proposed; (II) an overlap period between androgens and berotralstat, with progressive tapering of androgens, is the more appropriate strategy when planning this shift; (III) potential drug-drug interactions must be evaluated in patients on multiple medications, with berotralstat showing a good safety profile in this perspective. Conclusions. Patient engagement, awareness of androgen risks, transition strategies and drug-interaction evaluation are essential to guide individualized LTP choices.
Summary:Background. Lipid transfer protein (LTP)-mediated food allergy represents one of the most severe and heterogeneous forms of IgE-mediated food allergy in Mediterranean populations. Although Pru p 3 is the main marker of LTP sensitization, the clinical relevance of pollen-derived LTPs such as Art v 3 remains incompletely defined. Methods. We conducted a retrospective observational study including 241 adult patients with LTP-mediated food allergy and confirmed sensitization to Pru p 3. Art v 3-specific IgE was determined using component-resolved diagnostics. Clinical severity was assessed using the Food Allergy Severity Score (FASS). Profilin sensitization was analyzed when available. Correlations were evaluated using Spearman's coefficient. Results. Art v 3 sensitization was detected in 124 patients (51.5%). A higher proportion of moderate-to-severe reactions (FASS ≥ 3) was observed in Art v 3-sensitized patients compared with non-sensitized patients (64.0% vs 56.3%), although this difference did not reach statistical significance (OR = 1.38; 95% CI: 0.82-2.31). A statistically significant but low positive correlation was observed between Art v 3- and Pru p 3-specific IgE levels (Spearman's ρ = 0.46). Profilin sensitization was not associated with clinical severity (p = 0.36). Conclusions. Art v 3 sensitization is associated with a more complex immunological profile rather than acting as an independent predictor of clinical severity. Its clinical value may lie in risk stratification. Prospective studies are needed.
Summary:Background. Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disorder that has been increasingly recognized over recent decades. It is characterized by a type 2 inflammatory response, shared with other type 2 inflammatory conditions such as allergic rhinitis (AR), food allergy (FA), atopic dermatitis (AD), bronchial asthma (BA), and chronic rhinosinusitis with nasal polyps (CRSwNP). Methods. A total of 295 patients with EoE, followed at seven Italian allergy centers with expertise in managing EoE, were included. We analyzed annual EoE diagnoses, diagnostic delay, and the presence of type 2 comorbidities - including AR, FA, BA, AD and CRSwNP - assessed via allergological evaluations at the participating centers. Statistical analyses included non-parametric trend tests, linear and logistic regressions, chi-square tests, and descriptive analyses. Results. Annual EoE diagnoses showed a significant upward trend from 2014 to 2024 (p = 0.002). However, the diagnostic delay remained consistently high, showing no corresponding reduction despite the rise in diagnoses. The burden of type 2 comorbidities was substantial, with 83.4% of patients presenting at least one comorbidity, and most patients exhibited multiple comorbidities. Conclusions. Our findings are consistent with previously reported increases in EoE diagnoses in Italy, alongside persistent diagnostic delays, and highlight the substantial burden of type 2 comorbidities in these patients, emphasizing the importance of systematic allergological evaluation and multidisciplinary managementin patients with EoE.
Summary:Background. Eosinophilia in hospitalized patients is associated with increased mortality. However, eosinophilia was poorly investigated in the intensive care unit (ICU). The aim of our study was to investigate the prevalence of eosinophilia and its association with clinical outcomes in critically ill patients. Methods. This retrospective cohort study analyzed data from the Russian Intensive Care Dataset. The primary endpoint was the prevalence of eosinophilia (>0.5 x 109/L) in ICU patients. The secondary endpoints included all-cause hospital mortality, mechanical ventilation and vasoactive drug use. Subgroup analysis was performed for patients with mild eosinophilia (0.5-1.5 x 109/L) and hypereosinophilia (>1.5 x 109/L). Results. Among the 2,082 patients included in the analysis, 406 (19%) developed eosinophilia during ICU stay, including 362 (17%) with mild eosinophilia and 44 (2%) with hypereosinophilia. Out of 2,082 patients, 1,676 (81%) did not develop eosinophilia, and 406 (19%) developed eosinophilia during ICU stay. Compared with patients without eosinophilia, patients in the eosinophilia group had longer hospital stay (41 [24-63] versus 32 [22-48] p < 0.001) and more frequently required mechanical ventilation (236 [58.1%] versus 722 [43.1%], p < 0.001) and vasoactive drugs (83 [24.6%] versus 226 [17.0%], p < 0.001). Mortality was higher in hypereosinophilia group compared with patients without eosinophilia (13 [29.5%] versus 201 [12%], p < 0.001). Conclusions. Patients with eosinophilia had longer hospital stays, increased requirement of mechanical ventilation and vasopressor support compared with patients without eosinophilia. Eosinophilia could represent a disease severity marker.
Summary:Background. Eosinophilia in hospitalized patients is associated with increased mortality. However, eosinophilia was poorly investigated in the intensive care unit (ICU). The aim of our study was to investigate the prevalence of eosinophilia and its association with clinical outcomes in critically ill patients. Methods. This retrospective cohort study analyzed data from the Russian Intensive Care Dataset. The primary endpoint was the prevalence of eosinophilia (>0.5 x 109/L) in ICU patients. The secondary endpoints included all-cause hospital mortality, mechanical ventilation and vasoactive drug use. Subgroup analysis was performed for patients with mild eosinophilia (0.5-1.5 x 109/L) and hypereosinophilia (>1.5 x 109/L). Results. Among the 2,082 patients included in the analysis, 406 (19%) developed eosinophilia during ICU stay, including 362 (17%) with mild eosinophilia and 44 (2%) with hypereosinophilia. Out of 2,082 patients, 1,676 (81%) did not develop eosinophilia, and 406 (19%) developed eosinophilia during ICU stay. Compared with patients without eosinophilia, patients in the eosinophilia group had longer hospital stay (41 [24-63] versus 32 [22-48] p < 0.001) and more frequently required mechanical ventilation (236 [58.1%] versus 722 [43.1%], p < 0.001) and vasoactive drugs (83 [24.6%] versus 226 [17.0%], p < 0.001). Mortality was higher in hypereosinophilia group compared with patients without eosinophilia (13 [29.5%] versus 201 [12%], p < 0.001). Conclusions. Patients with eosinophilia had longer hospital stays, increased requirement of mechanical ventilation and vasopressor support compared with patients without eosinophilia. Eosinophilia could represent a disease severity marker.
Summary:Background. Obesity is associated with worse asthma outcomes, partly due to inflammasome-mediated neutrophilic Type IVc immunity. However, the impact of adiposity on Type IVb airway inflammation remains poorly understood. This study aimed to evaluate the effect of body fat on Type 2 (T2) airway inflammation, measured using fractional exhaled nitric oxide (FeNO). Methods. This community-based cross-sectional study included 726 children aged 7-12 years (48.9% female) from 71 classrooms in 20 public schools. Anthropometry and bioelectrical impedance analysis assessed body mass index (BMI) category, total body fat (%), fat mass (kg), fat-free mass (kg) and trunk-predicted muscle mass (%). FeNO levels were measured to evaluate airway inflammation and converted into height- and sex-adjusted z-scores (zFeNO) using generalized additive models for location, scale and shape (GAMLSS). Linear regression models were applied to assess associations between BMI classifications and body composition measures with zFeNO. Children with asthma (n=45) were excluded. Results. Mean zFeNO was 0.78 (±2.64). After adjustment for sex, age, parental education, second-hand smoke exposure, caffeine intake, and allergic sensitisation, children classified as overweight according to the International Obesity Task Force had lower zFeNO than normal-weight peers (adjusted β [aβ] -0.63; 95% CI: -1.26 to -0.02). Similar findings were observed among overweight males classified by CDC (aβ -0.96; 95% CI: -1.88 to -0.03). Conclusions. Height- and sex-adjusted FeNO z-scores were established, and overweight was associated with lower zFeNO in school-aged children. BMI and body composition should be considered when interpreting FeNO as a biomarker of airway inflammation in children.
Summary:Background. Cross-reactivity among phylogenetically distant invertebrates-such as mites, crustaceans, and mollusks-is mainly driven by conserved panallergens including tropomyosin, arginine kinase, and troponin C. However, the clinical impact and molecular basis of these cross-reactivities remain incompletely defined. Methods. A multicenter observational study was conducted in 3,777 patients reactive to at least one arthropod or invertebrate allergen component. Serum IgE profiles were assessed using the ALEX²® multiplex platform, including allergens from mites, crustaceans, mollusks, and related taxa. Clinical data were analyzed according to molecular sensitization patterns. Results. Mite sensitization was detected in nearly 80% of patients, 80% of whom showed co-sensitization to other invertebrates. Sensitization to mollusks and/or crustaceans occurred in 31.9% (n = 1,207), with a marked predominance of concomitant mite sensitization (79.1% for crustaceans, 60.3% for mollusks). Clinically relevant shellfish reactions were reported in > 95% of patients co-sensitized to mites and shellfish allergens but were uncommon among those mono-sensitized to decapod or mollusk components. Tropomyosin-specific IgE was detected in > 95% of symptomatic individuals and was significantly associated with moderate-to-severe reactions (p < 0.001). Conclusions. Mite-shellfish co-sensitization defines the major molecular and clinical phenotype of shellfish allergy, supporting a model in which mite-derived tropomyosin acts as the primary sensitizer enabling cross-reactivity to homologous invertebrate proteins. In contrast, isolated shellfish sensitization rarely results in symptoms. Component-resolved diagnostics are crucial to identify at-risk patients and to avoid unnecessary dietary restrictions.
Summary:Background. The allergic asthma phenotype is the most extensively investigated. However, few studies have explored the association between sensitization to different aeroallergens, asthma severity and blood eosinophil counts, an important biomarker of Type 2 inflammation. This study aims to evaluate associations between sensitization to aeroallergens, severity of asthma, eosinophilic phenotypes and age of onset of symptoms. Methods. This was a cross-sectional study involving a tropical urban population sample. We included 450 individuals with mild asthma (MA) and 441 with moderate to severe asthma (MSA). Serum-specific IgE to nine aeroallergens was measured by the ImmunoCap™. We considered a cut-off point of 0.70 KU/L for mites and 0.35 KU/L for all other allergens. Blood eosinophilia was considered if the count was > 260 cells/mm3, and the age of onset was defined as early (EO < 12 years) and late (LO greater/equal 12 years). Results. Patients with asthma sensitive to dust mites, B. germanica and those with polysensitization are 1.6 to 1.8-fold more likely to have MSA, while in cases of sensitization to A. fumigatus this probability increases to 3-fold. Regarding the eosinophilic phenotype, individuals with MA sensitized to dust mites, B. germanica, dog epithelium and polysensitized individuals are more likely to present the eosinophilic phenotype (p < 0.05). However, we did not observe any association between sensitization to different aeroallergens and age of symptom onset (p > 0.05). Conclusions. We conclude that polysensitization or sensitization to mites, B. germanica, and mainly to A. fumigatus, are associated with the severity of asthma. Only in individuals with mild asthma, sensitization to dust mites, B. germanica, dog epithelium and polysensitization is associated with eosinophilic asthma. No sensitization profile was associated with the age of onset of asthma symptoms.
Summary:Background. Oral immunotherapy (OIT) is a promising strategy for severe and persistent cow's milk (CM) allergy. However, clinical experience concerning long-term follow-up is scarce. The objective is to assess long-term efficacy and safety of maintenance phase of OIT in real-life. Methods. Prospective study of children with severe IgE-mediated CM allergy that underwent CM-OIT, and were followed-up by the authors, up to 15 years. Complete desensitisation was defined when maintenance dose of 200 mL daily was achieved. Characterization (clinical and laboratory) was performed before and after OIT during follow-up. Results. Thirty-three patients enrolled: 58% male, 70% asthmatics and 67% with previous history of CM-anaphylaxis. Mean age at onset of CM-OIT was 7±2.8 years. Complete desensitisation was ensured in 94% (free diet with dairy 200mL of CM or equivalent). During maintenance phase 79% developed allergic reactions, with anaphylaxis in 33%, including exercise-induced anaphylaxis in 15% and with cheese intake in 15%. We stress that eosinophilic esophagitis appeared in 12%. Specific IgE levels and skin prick tests (SPT) to CM and casein have significantly decreased, and in most patients (61%) SPT became negative. When available, specific IgG4 levels have significantly increased. Conclusions. This real-life study supports long-term efficacy and safety of CM-OIT. CM-OIT had a high success rate, allowing diet without restrictions with persistence of the effect up to 15 years. However, one-third of patients experienced anaphylaxis during maintenance phase. CM-OIT should always be performed by allergy experts and only motivated families should be enrolled, since long-term follow-up is required, and daily intake of CM is needed to ensure desensitization.
Summary:Background.Soy allergy represents a diagnostic challenge, particularly when mediated by Gly m 4, a PR-10 protein known for its cross-reactivity with birch pollen allergens. Traditional diagnostic methods, including skin prick tests (SPTs) and specific IgE assays, often lack sensitivity or specificity, especially for Gly m 4-mediated allergies. Methods. In this study, the basophil activation test (BAT) was evaluated as a tool to distinguish true allergy from mere sensitization to Gly m 4. Results.A total of four patients sensitized to Gly m 4 and Bet v 1 (PR-10 of soy and birch) were included in this study. Two patients were confirmed allergic to soy based on positive BAT results with Gly m 4 and soy total extract, correlating with clinical symptoms of allergy. Conversely, two other patients were determined to be sensitized but clinically tolerant, as BAT results were negative, consistent with their symptom-free status during oral food challenges. Conclusions. The study highlights the limitations of traditional diagnostic methods, which often yielded false-negative or inconclusive results, and underscores the BAT's ability to provide functional evidence of allergen reactivity. We demonstrate the utility of BAT in identifying clinically relevant Gly m 4-mediated soy allergies. By enabling precise differentiation between allergy and sensitization, the BAT emerges as a valuable diagnostic tool, complementing molecular allergen-specific IgE assays and offering a safer and more specific alternative to oral food challenges.
Summary:Background.Combination therapy with montelukast and oral antihistamines is commonly used in allergic rhinitis (AR), but its comparative benefit over montelukast monotherapy remains unclear. This meta-analysis aimed to evaluate the efficacy of combination therapy compared to monotherapy, with a focus on symptom-specific outcomes. Methods. A comprehensive search of PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases was conducted through April 2025. We systematically reviewed randomized controlled trials comparing montelukast combined with oral antihistamines to montelukast monotherapy in patients with AR. Outcomes included total symptom scores, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores, and individual symptom domains. Pooled effects were analyzed using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results. Thirteen RCTs enrolling 2,950 patients were identified. Combination therapy significantly improved daytime symptoms (SMD = 0.25; 95%CI 0.15 to 0.35), with limited benefit for nighttime symptoms (SMD = 0.10; 95%CI -0.01 to 0.21) or RQLQ scores (SMD = 0.11; 95%CI -0.05 to 0.26). In subgroup analysis, all combinations with loratadine, desloratadine, or levocetirizine showed greater efficacy than monotherapy in improving daytime symptoms. However, only the levocetirizine-based combination demonstrated a significant benefit for nighttime symptoms. When analyzed by individual symptoms, the levocetirizine combination resulted in significantly better outcomes than monotherapy, improving sneezing, nasal itching, nasal obstruction, and rhinorrhea. Conclusions. Montelukast combined with antihistamines improves daytime and individual nasal symptoms more effectively than monotherapy. However, the effectiveness of each drug combination varied by symptom domain. These findings may assist clinicians in selecting appropriate combination regimens based on individual symptom patterns.
Background. Hen's egg allergy is one of the most common pediatric food allergies, requiring accurate diagnosis and management strategies. Oral food challenges (OFCs) are critical in evaluating food allergies; however, limited research has focused on the outcomes of challenges involving egg yolks. This retrospective study aims to assess the outcomes and characteristics of pediatric patients who underwent oral challenges with boiled egg yolk. Methods. We evaluated patients diagnosed with egg allergy who underwent an OFC with egg yolk between 2019 and 2022. Results. The study included 123 patients with a median age of 12 months. The first presentation of symptoms occurred at a mean age of 6 months. Initial symptoms included eczema flare-ups (70%), urticaria (13.8%), and anaphylaxis (8.9%). The median age of the first egg yolk OFC was 12 months. For the first egg white OFC to assess the tolerance, the median age was 16 months. Of the 123 egg yolk OFCs, 115 (93.4%) patients were tolerant and consumed egg yolk at home. In the egg yolk-tolerant group, the mean duration of egg white tolerance was 4 months post-OFC; for non-tolerant patients, this extended to 11 months. The egg yolk non-tolerant group had higher egg white-specific IgE levels than the tolerant group (28 kU/L [IQR: 2.4-85.9] vs. 4.2 kU/L [IQR: 0.9-8.8], p<0.01). Conclusions. Though mild symptoms may occur, most children with egg allergies can safely consume boiled egg yolk. Consuming hen's egg yolk after a negative OFC could expand dietary options and improve quality of life.
Summary:Chronic rhinosinusitis (CRS) is a complex heterogeneous disease of the nose and paranasal sinuses that presents different phenotypes and endotypes. CRS is a common health problem associated with significant morbidity, as well as with high health care expenditure. As our knowledge on inflammation, tissue remodeling and pathophysiological mechanisms develops, both diagnosis and therapeutic approaches to CRS improve. This review outlines key drivers in the pathogenesis of CRS with and without nasal polyps, current diagnostic tools clinicians can rely on in clinical practice, and current and future treatment options, while providing a general overview of up-to-date guidelines for CRS diagnosis and management. A better understanding of CRS can pave the way for the optimization and development of novel therapies, benefiting patients who suffer with more severe phenotypes and allowing a personalized approach to the disease.
Summary:Background. Children with milk and egg allergies have outcomes in which three-quarters are tolerant to baked forms of the allergenic food. Identifying predictors of tolerance to baked foods for IgE-mediated immediate-type reactions may guide the early introduction of baked allergens to diet and tolerance development. This study explores factors associated with early tolerance to baked foods. Methods. We retrospectively analyzed patients with IgE-mediated immediate-type food allergy in infancy who either became tolerant to the baked form before two years or remained reactive after two years. Results. We examined 143 patients solely with IgE-mediated immediate-type egg and/ or milk allergies excluding those with atopic dermatitis. 76 (42 egg-allergics; 34 milk-allergics) achieved tolerance, and 67 (38 egg-allergics; 29 milk-allergics) were reactive beyond the age of two. Receiver operating characteristic analysis determined cut-off values for specific-Immunoglobulin E (sIgE) levels (kU/L) predicting mild phenotype at first admission: egg white-sIgE ≤ 7.39, milk-sIgE ≤ 5.99, and casein-sIgE ≤ 4.99, with AUC values of 0.703, 0.716, and 0.749, respectively. Conclusions. This study identifies key prognostic factors for tolerance to baked allergen for IgE-mediated immediate-type reactions, providing valuable insights to determine the patients who need more intensive care versus the ones who don't need baked allergen avoidance early in their life from their initial admission at infancy.
