Search Results (436)

The rising prevalence of pediatric food allergies represents a growing public health concern, with hospitalizations for food-induced anaphylaxis on the rise. Early cutaneous manifestations, particularly in the setting of atopic dermatitis (AD), may indicate sensitization via the skin—a critical route for allergen exposure in early life. Pediatric food allergies can be IgE-mediated, non-IgE-mediated, or mixed, with each type presenting distinct pathophysiological and clinical features. IgE-mediated reactions often involve acute urticaria and angioedema, while non-IgE forms, such as food protein-induced enterocolitis syndrome (FPIES), manifest with delayed gastrointestinal symptoms and limited skin involvement. AD is closely linked with food allergies, both in pathogenesis and symptom exacerbation, with a high prevalence of co-occurrence. Diagnosis primarily relies on clinical evaluation, supported by testing such as skin prick testing, serum IgE, and oral food challenges, though limitations exist in sensitivity and specificity. Management emphasizes allergen avoidance, symptom control, and multidisciplinary care. While many pediatric food allergies resolve with age, others persist or present chronically, necessitating long-term strategies. Coordinated management between allergy and dermatology is key to minimizing complications and supporting better long-term outcomes for affected children. Full article

Orange allergy is estimated to account for up to 3–4% of food allergies. Major allergens identified in orange (Citrus sinensis) include Cit s 1 (germin-like protein) and Cit s 2 (profilin), while Cit s 3 (non-specific lipid transfer protein, nsLTP) and Cit s 7 (gibberellin-regulated protein) have also been described. The objective of this study was to investigate the presence and IgE-binding capacity of germin-like proteins in citrus fruits other than oranges. We describe five patients with immediate allergic reactions after orange ingestion. All patients underwent skin prick tests (SPT) to aeroallergens and common food allergens, prick-by-prick testing with orange, lemon, and mandarin (pulp, peel, seeds), total IgE, specific IgE (sIgE), anaphylaxis scoring (oFASS), and the Food Allergy Quality of Life Questionnaire (FAQLQ-AF). Protein extracts from peel and pulp of orange, lemon, and mandarin were analyzed by Bradford assay, SDS-PAGE, and IgE immunoblotting using patient sera. Selected bands were identified by peptide mass fingerprinting. A 23 kDa band was recognized by all five patients in orange (pulp and peel), lemon (peel), and mandarin (peel). This band was consistent with Cit s 1, a germin-like protein already annotated in the IUIS allergen database for orange but not for lemon or mandarin. Peptide fingerprinting confirmed the germin-like identity of the 23 kDa bands in all three citrus species. Germin-like proteins of approximately 23 kDa were identified as IgE-binding components in peel extracts of orange, lemon, and mandarin, and in orange pulp. These findings suggest a potential shared allergen across citrus species that may contribute to allergic reactions independent of LTP sensitization. Full article

Deoxynojirimycin (DNJ), the first isolated iminosugar, is a natural alkaloid acting as a potent inhibitor of α-glucosidase with high nutritional value. It naturally occurs in plants (especially Morus spp.), microbes, and insects or can be synthesized. Diverse biological activities, such as antihyperglycemic, lipid-lowering, antitumor, antiviral, and anti-inflammatory, have been recognized for this compound. However, DNJ has not been approved as a food supplement until now. Several studies, also in clinics, are carried out on Morus spp. containing DNJ. Among Morus spp., Morus alba L. (white mulberry), Morus nigra L. (black mulberry), and Morus rubra L. (red mulberry) are the three main species that grow all over the world. Some spurious studies have been conducted on Reducose^® and Glubloc™, two products that contain DNJ and Morus alba, respectively. However, mulberry allergy, including respiratory allergy, airborne contact urticaria, anaphylaxis, oral allergy syndrome, and food induced urticaria, may be observed. This review aims to explore a crucial and timely question: how DNJ exerts its biological effects and what role it may play in therapeutic applications. We provide a comprehensive summary of the current understanding of DNJ’s pharmacological potential and the methods used for its production. We also report recent developments in clinical studies on Morus alba, Reducose^® and Glubloc™. Full article

Background/Objectives: A food allergy (FA) is an immune-mediated hypersensitivity reaction to specific food. FA reactions vary from mild to life-threatening anaphylaxis. Despite the effectiveness of epinephrine auto-injectors (EAIs), barriers such as lack of knowledge, limited access, and fear of needles hinder their use. This study explores EAI possession among children with parent-reported food allergies in Saudi Arabia. Methods: A cross-sectional study conducted from October 2023 to February 2024 included 296 parents of children with reported food allergies under the age of 18. Data were collected through a validated self-administered questionnaire. Results: Among 2102 respondents, 296 (14.1%) reported having a child with a food allergy. Most respondents were female (70%), with asthma being the most common comorbidity (26%). Common allergens included eggs, tree nuts, peanuts, milk, and sesame. Only 23.3% of children had an EAI. Higher EAI possession was associated with parental education, maternal allergy history, and access to specialist care. Conclusions: EAI possession among Saudi children with food allergies is suboptimal. Targeted educational interventions, increased access to allergists, and comprehensive management plans are essential to improve preparedness for anaphylaxis. Full article

Background: Cow’s milk allergy (CMA) is the most common food allergy in children, typically resolving by adolescence. In contrast, the clinical spectrum of allergies to non-cow mammalian milk and their patterns of IgE cross-reactivity are less well documented. Nutritional differences between various mammalian milks may also impact dietary management in milk-allergic patients. Objectives: To characterize clinical features, onset age, and IgE cross-reactivity patterns of non-cow mammalian milk allergies in adult patients seen at a tertiary allergy center, and to compare these findings with published cases. Methods: A retrospective analysis of patients included in the “Extended Laboratory Investigation for Rare Causes of Anaphylaxis study” with mammalian milk allergy was performed using clinical history, skin testing, and serum-specific IgE measurements. Cross-reactivity patterns were assessed in selected cases using immunoblotting, specific IgE inhibition, and basophil activation testing, and compared with published reports of non-cow mammalian milk allergy. Results: In our case series of 22 patients with mammalian milk allergy and 10 healthy control subjects, 3 patients were identified with isolated adult-onset non-cow mammalian milk allergy (n = 1 buffalo milk; n = 2 mare milk), confirmed via immunoblotting and basophil activation testing. Streptavidin-based specific IgE measurement for buffalo cheese was positive in the buffalo milk allergic patient. The literature review identified 82 cases of non-cow mammalian milk allergy. These cases typically showed late onset (mean age 8.6 years; range 1–70 years), severe reactions (CoFAR (Consortium for Food Allergy Research) grade 3 or 4 in 66%, and one fatality), and selective sensitization (affecting sheep and/or goat, camel, mare, buffalo, donkey, or combinations thereof in 56, 10, 5, 5, 4, and 2 cases, respectively). Conclusions: Non-cow mammalian milk allergies are rare but generally present later in life with selective IgE cross-reactivity, differing from the broader cross-reactivity observed in CMA. This selectivity may allow for safe dietary alternatives. These findings underscore the need for improved diagnostics and personalized dietary management in this patient population. Full article

Background/Objectives: Food allergy (FA) is a growing concern in pediatric care, requiring effective avoidance strategies and timely emergency responses. The role of caregivers is central to the daily management of FA. This study aimed to assess parental knowledge, preparedness, and behaviors regarding pediatric FA management, focusing on both prevention and emergency readiness. Methods: A cross-sectional survey was conducted from December 2024 to April 2025 through the SurveyMonkey^® platform, promoted by the Italian Society of Pediatric Allergology and Immunology (SIAIP). The anonymous, structured questionnaire was distributed online and in two Italian university hospitals. A total of 129 fully completed responses from caregivers of children with FA were analyzed. The survey explored self-perceived knowledge, symptom recognition, preventive actions, emergency preparedness, and communication practices. Results: Only 9.3% of parents considered themselves “very informed,” while 54.3% reported limited or no knowledge. Just 16.0% recognized all symptoms of an allergic reaction, and only 24.0% could distinguish mild reactions from anaphylaxis. Notably, 67.4% reported not knowing how to respond to anaphylaxis, and 83.7% did not possess an epinephrine auto-injector. Preventive measures at home were inconsistently applied, and 41.1% took no precautions when eating out. Communication with external caregivers was often informal or absent. Only 33% updated physicians regularly. Conclusions: The findings reveal significant gaps in parental preparedness and highlight critical areas for educational intervention. Enhanced caregiver training, standardized communication protocols, and improved clinical follow-up are essential to strengthen pediatric FA management and safety. Full article

The diagnosis of allergic diseases and anaphylaxis is complex and encompasses a broad spectrum of in vitro and in vivo diagnostic tests. The choice of diagnostic tests is related to the presumed pathophysiological mechanism of the allergic reaction. In the past decade the implementation of component-resolved diagnostics (CRD) into clinical practice has significantly improved the depicting of sensitization profiles, which has aided in the assessment of clinically relevant allergen components that are associated with true allergy, as well as the levels of risk of severe anaphylactic reactions. Recently, multiplex-specific immunoglobulin E (IgE) platforms have emerged for better selection of patients at risk for anaphylaxis and have improved the selection criteria for patients undergoing allergen immunotherapy, including novel regimes such as oral immunotherapy. This review describes the advantages of the utilization of component-resolved diagnostics and multiplex assays in clinical settings, especially in cases of anaphylaxis when no clear trigger is recognized or where multiple culprits are suspected. As multiplex component-resolved diagnostics becomes more readily available globally and with the use of novel approaches, CRD will certainly be a crucial tool in personalized and individually tailored management plans and reduce the financial burden of anaphylaxis. Full article

The benefits of regular physical exercise, primarily moderate-intensity exercise, are widely known, recognized, and acclaimed. As an important lifestyle modification, regular training activities are gaining increasing popularity in the general population. Apart from the obvious benefits, physical exercise may carry the risk of trauma, cardiovascular events, and exercise-induced asthma and bronchoconstriction, to name just a few well-known clinical situations reported in athletes, both recreational and competitive. In susceptible individuals, acute bouts of exercise may lead to the appearance of urticaria, angioedema, and anaphylaxis. Among these three clinical phenomena, angioedema is the least addressed and recognized, often being considered an accompanying clinical feature of urticaria or a hallmark of imminent anaphylactic reaction. To fill this knowledge gap, in this review, we focus on exercise-associated angioedema symptoms and highlight their most important features, both as isolated phenomena and in association with urticaria or anaphylaxis. Full article

The incidence of fatal anaphylaxis is increasing, but there is still no recognized “golden standard” for forensic diagnosis. Due to its non-specific symptoms, especially cardiovascular symptoms without cutaneous changes, it can easily be misdiagnosed as acute myocardial infarction. Here, we established rat models (n = 12) of fatal anaphylaxis (FA), acute myocardial infarction (AMI), and coronary atherosclerosis with anaphylaxis (CAA). The untargeted metabolomics of plasma and 16S rRNA sequencing of fecal matter was performed, and a random forest was used to identify potential biomarkers. Three metabolites (tryptophan, trans-3-indole acrylic acid, and imidazole acetic acid) and three microbial genera (g_Prevotellaceae_Ga6A1_group, g_UCG_008, and g_Eubacterium_hallii_group) were identified as potential biomarkers for distinguishing anaphylaxis and non-anaphylaxis. The classification model of plasma metabolites showed a much better discriminatory performance than that of microbial genus, serum IgE, and tryptase. The performance of the microbial genera was superior to the serum IgE but inferior to the serum tryptase. Forensic samples of fatal anaphylaxis and non-anaphylaxis deaths (n = 12) were collected for untargeted metabolomics detection. The results showed that among the three identified metabolic biomarkers, tryptophan has better stability in cadaveric blood samples. Its diagnostic performance (AUC = 87.1528) was superior to serum IgE and tryptase, making it more suitable as a postmortem biomarker of fatal anaphylaxis. Full article

Kiwifruit allergy was first described over 40 years ago and is becoming increasingly common worldwide. This is most likely related to the fact that kiwifruit production and consumption increased by almost two orders of magnitude during the last 50 years. Currently, there are thirteen officially registered allergens belonging to the species Actinidia deliciosa (green kiwifruit), and three officially registered allergens belonging to the species Actinidia chinensis (golden kiwifruit). The molecular properties of the kiwifruit allergens are summarized, and their features are discussed, considering the protein families to which they belong. At present, kiwifruit allergens are found to belong to 13 protein families. Allergic reactions caused by these molecules can be local, for example, related to the oral cavity, but in some cases systemic responses, such as anaphylaxis, are also observed. Generally, kiwifruit allergy should not be considered as a homogenous disorder, as it was noted that there are distinct groups of patients with different sensitization profiles. Therefore, the diagnostic process may be challenging, as in many cases other food allergies must be considered. Frequently cross-reactivity between kiwifruit allergens and their homologs originating from other organisms has a significant impact on the wellbeing of the affected individuals. Full article

Background/Objectives: Allergens can trigger severe immune responses in hypersensitive individuals, with mast cells releasing inflammatory mediators via IgE-FcɛRI signaling. Spleen tyrosine kinase (Syk) is a key regulator in this pathway, making it a promising therapeutic target. Natural modulators of Syk-mediated mast cell activation remain underexplored. This study investigated the anti-allergic effects of a 70% ethanol extract of Salvia miltiorrhiza (SME) using in vitro and in vivo models. Methods: SME was evaluated using IgE-sensitized RBL-2H3 cells, a passive cutaneous anaphylaxis model, and a DNCB-induced atopic dermatitis-like mouse model. Allergic responses were assessed via degranulation assays, histopathology, serum IgE levels, and the spleen index. Results: SME significantly inhibited mast cell degranulation by 44.4 ± 1.6% in RBL-2H3 cells at 100 µg/mL following 30 min of treatment compared to the untreated control. Western blot analysis demonstrated dose-dependent suppression of protein kinase B (PKB, also known as AKT), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and spleen tyrosine kinase (Syk) phosphorylation, indicating inhibition of key allergic signaling pathways. In an IgE/Ag-induced passive cutaneous anaphylaxis model in ICR mice, SME (100 mg/kg, orally) significantly attenuated vascular permeability, as evidenced by a 20.6 ± 9.7% reduction in Evans blue extravasation relative to the Ag-treated group. In a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD)-like model, six treatments of SME significantly improved the skin condition, reduced spleen enlargement associated with allergic inflammation, and decreased serum IgE levels by 43.3 ± 11.2% compared to the DNCB group. Conclusions: These findings suggest that SME may help to alleviate allergic responses and AD by modulating key immune signaling pathways. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause hypersensitivity reactions and lead to anaphylactic shock. These drugs also act as cofactors in allergic reactions. Lipid transfer proteins (LTPs), found in plants, represent a unique group of allergens in which cofactors play a crucial role. This case report describes a 26-year-old female who developed anaphylactic symptoms after ingesting grapes and taking ketoprofen. The patient experienced swelling of the lips, tongue, and throat, as well as shortness of breath, dizziness, and loss of consciousness, after consuming grapes and taking ketoprofen. She had previously used ketoprofen and acetylsalicylic acid without issues but had developed urticaria on several occasions after consuming multi-ingredient dishes. Skin prick tests showed positive results for peanut and orange allergens. Further testing using the ALEX multiparametric test detected antibodies to several LTP allergens. Intradermal tests with ketoprofen yielded a positive result, although irritant reactions could not be ruled out. A provocation test with acetylsalicylic acid (ASA) showed no adverse reactions. Skin tests with ibuprofen were negative, and provocation tests confirmed its tolerance. A diagnosis of LTP allergy and selective ketoprofen allergy was made, with the recommendation to avoid ketoprofen and follow a diet excluding foods from the LTP group. Full article

The mRNA vaccine has protected humans from the Coronavirus disease 2019 (COVID-19) and has taken the lead in reversing the epidemic efficiently. However, the Centre of Disease Control (CDC) reported and raised the alarm of allergic or acute inflammatory adverse reactions after vaccination with mRNA-LNP vaccines. Meanwhile, the US Food and Drug Administration (FDA) has added four black-box warnings in the instructions for mRNA-LNP vaccines. Numerous studies have proven that the observance of side effects after vaccination is indeed positively correlated to the level of anti-PEG antibodies (IgM or IgG), which are enhanced by PEGylated preparations like LNP vaccine and environmental exposure. After literature research and review in the past two decades, it was found that the many clinical trial failures (BIND-014, RB006 fell in phase II) of PEG modified delivery system or PEGylated drug were related to the high expression of anti-PEG IgM and IgG. In the background of shooting multiple mRNA-LNP vaccines in billions of people around the world in the past three years, the level of anti-PEG antibodies in the population may have significantly increased, which brings potential risks for PEG-modified drug development and clinical safety. This review summarizes the experience of using mRNA-LNP vaccines from the mechanism of the anti-PEG antibodies generation, detection methods, clinical failure cases of PEG-containing products, harm analysis of abuse of PEGylation, and alternatives. In light of the increasing prevalence of anti-PEG antibodies in the population and the need to avoid secondary injuries, this review article holds greater significance by offering insights for drug developers. It suggests avoiding the use of PEG excipients when designing PEGylated drugs or PEG-modified nano-formulations and provides references for strategies such as utilizing PEG-free or alternative excipients. Full article

Background: Children, including the estimated 7% with food allergy, spend most of their waking hours in school. Variations in school-based food allergy (FA) practices exist. We aimed to examine differences in FA management practices across schools in Canada and the United States (US). Methods: Parents of children with Immunoglobulin E (IgE)-mediated FA were recruited through social media to complete a survey evaluating the schools’ stock epinephrine, epinephrine storage locations, school type, and location. Data were described, analyzed using logistic and linear regressions, and then reported as odds ratios (ORs) and standardized coefficients (b), respectively, with corresponding 95% confidence intervals (95%CIs) and p < 0.05. This study was approved by the University of Manitoba Health Research Ethics Board. Results: Overall, 177 participants (14% [26/177] Canada, 86% [151/177] US) were included. Children were, on average, 4.92 ± 3.12 years and were commonly but not mutually exclusively allergic to tree nuts (50% Canada; 40% US) and peanuts (33% Canada; 29% US). Compared to US parents, Canadian parents were more likely to report epinephrine self-carriage by their children (OR = 4.58; 95%CI = 1.67–12.59). Parents with children age > 5 years were more likely to report epinephrine self-carriage by their children (OR = 3.70; 95%CI = 1.38–9.93) but less likely to report that their children’s school had an allergen-friendly zone (OR = 0.25; 95%CI = 0.06–0.99). Compared to US parents, Canadian parents were more likely to report their child’s school had anaphylaxis management policies (OR = 8.98; 95%CI = 1.11–72.42). Conclusions: Significant in-school FA management differences exist between countries. These findings stress the need for consistent policies and practices to ensure effective care. Full article

Background/Objectives: The incidence of food allergies and other allergic diseases is rising. Emerging evidence links both antimicrobials and acid-suppressive therapy with gut dysbiosis, which is implicated in allergy development. We investigated the relationship between the use of acid-suppressive medications or antimicrobials in infancy and the risk of developing childhood allergic diseases. Methods: The US network in the TriNetX platform was used to identify patients prescribed proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H₂RAs), antimicrobials ≥1, or antimicrobials ≥3 times during their first year of life from October 2015 to January 2022. ICD-10 diagnoses were used to assess two-year outcomes of anaphylaxis, food allergy, and atopic dermatitis. A sub-analysis in gastroesophageal reflux (GERD) patients was also performed. Results: Risks of anaphylaxis and food allergy increased with the prescription of PPIs (risk ratio [95% CI], 2.49 [1.40–4.41], 5.33 [4.97–5.71]), H₂RAs (4.48 [3.43–5.86], 4.21 [4.01–4.41]), and antimicrobials ≥1 (2.41 [2.13–2.72], 1.90 [1.86–1.94]), or ≥3 times (3.69 [3.12–4.37], 2.79 [2.70–2.88]). Risk of atopic dermatitis was increased in both H₂RA (1.41 [1.35–1.48]) and antimicrobial groups (2.25 [2.22–2.28], 3.35 [3.29–3.41]), but not in the PPI group. In the GERD sub-analysis, anaphylaxis risk was not significantly different, food allergy risk was increased in both PPI (2.30 [2.08–2.53]) and H₂RA groups (1.77 [1.63–1.92]), and atopic dermatitis decreased in the PPI group (0.76 [0.67–0.85]) but slightly increased in the H₂RA group (1.11 [1.03–1.20]). Conclusions: Exposure to acid-suppressive or antimicrobial medications during infancy was associated with increased risk of food allergy and anaphylaxis in early childhood. In infants diagnosed with GERD, exposure to acid-suppressive medications was still associated with increased food allergy risk. Full article