Search Results (59)

Food allergy is an increasingly prevalent global health condition characterized by immune-mediated reactions to dietary antigens and a substantial clinical burden. Growing understanding of IgE-mediated mechanisms has highlighted the central role of type 2 inflammation, effector-cell activation, and impaired immune regulation. These advances have prompted the development of disease-modifying therapies beyond allergen avoidance. This narrative review summarizes recent advances in the therapeutic management of IgE-mediated food allergy. A structured PubMed search was performed to identify clinical trials, randomized studies, and meta-analyses published within the last five years. Both allergen-specific and non-allergen-specific interventions were evaluated. Current evidence supports oral immunotherapy as the most effective strategy for increasing reaction thresholds and inducing desensitization in peanut, milk, and egg allergies. However, safety concerns remain, and sustained unresponsiveness after treatment discontinuation is achieved inconsistently. Sublingual and epicutaneous immunotherapy show improved safety but lower efficacy. Modified allergen approaches, including baked milk and processed peanut products, may improve tolerability and facilitate immune modulation in selected patients. Biologic therapies, particularly anti-IgE agents, demonstrate efficacy both alone and when combined with immunotherapy. Emerging approaches include peptide vaccines, DNA immunization, microbiome-targeted interventions, and early dietary modulation. These strategies may improve durable immune tolerance through personalized, mechanism-based therapeutic approaches. Future progress will depend on optimizing safety, identifying predictive biomarkers, and integrating multimodal approaches to achieve durable immune tolerance. Full article

Background: Allergic rhinitis (AR) is commonly treated with intranasal and oral pharmacotherapy or allergen immunotherapy (AIT), each associated with distinct safety considerations. This study aimed to systematically evaluate and compare the safety profiles of these therapeutic approaches by analysing adverse events (AEs) reported in completed randomised controlled trials (RCTs). Methods: A meta-epidemiological analysis was conducted using completed RCTs registered in ClinicalTrials.gov up to 20 October 2023. Trials investigating intranasal drugs, oral medications, or AIT for AR were identified using predefined search terms. Adverse events were manually extracted and categorised according to treatment class and dosage. Other adverse events (OAEs) were classified using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) and Medical Dictionary for Regulatory Activities (MedDRA) terminology. Meta-analyses compared OAE incidence across treatment groups, including standard-dose, higher-dose, and placebo arms. Results: A total of 216 RCTs were included. Intranasal therapies accounted for 55.56% of trials, predominantly intranasal corticosteroids (INCS) and intranasal antihistamines (INAH). OAE incidence was 16.37% for INCS, 29.43% for INAH, and 8.71% for combination therapy. INAH was associated with higher rates of dysgeusia and nasal discomfort, while higher INCS doses were linked to an increased risk of urinary tract infections. AIT trials comprised 22.69% of studies and demonstrated higher OAE rates, particularly for sublingual immunotherapy (64.96%), followed by subcutaneous (53.98%) and intralymphatic immunotherapy (62.50%). Oropharyngeal AEs were most frequent with sublingual immunotherapy. Oral medications (18.06%) showed the lowest OAE incidence, with upper respiratory tract infections occurring more frequently with oral antihistamines. Conclusions: Among intranasal therapies, INCS demonstrated the most favourable safety profile. Sublingual immunotherapy was associated with a higher frequency of OAEs compared with other AIT modalities. Combination oral antihistamine and leukotriene receptor antagonist therapy appeared to be the safest oral treatment option. Further well-designed studies are needed to refine comparative safety assessments across AR treatments. Full article

Introduction: Peanut oral immunotherapy (P-OIT) is an emerging treatment strategy for peanut allergy (PA). Although a standardized pharmaceutical product, Peanut (Arachis hypogaea) Allergen Powder-dnfp, has been approved in several countries, it is not universally available. In such contexts, real-world protocols using readily utilizable peanut products may represent an alternative approach. This study aimed to describe the feasibility, safety, and clinical outcomes of P-OIT using toasted peanuts in a real-world effort in a pediatric population. Methods: This single-center retrospective cohort study enrolled children who initiated P-OIT at our tertiary pediatric hospital Allergy Unit between April 2015 and December 2024. Demographic and clinical features, allergy test results, and information about P-OIT were recorded. Desensitization was defined as tolerance of 630 mg of peanut protein (PP). Results: Sixty patients (51.7% male; median age 8.2 years) were included. 22/60 (36.7%) achieved desensitization within a median time of 22.7 months. 21/60 (35%) were still undergoing P-OIT at a median tolerated dose of 100 mg of PP, and 17/60 (28.3%) discontinued treatment, most commonly due to loss to follow-up (44%). At least one adverse reaction occurred in 43/60 (71.7%) patients, predominantly mild and self-limiting (68.3% resolved spontaneously, 39.5% occurred at home). However, 11/60 (18.3%) showed anaphylaxis, and 3/60 (5%) received adrenaline. A reduction in Ara h 2 serum-specific IgE levels compared to the baseline was observed in patients completing escalation (p = 0.03). Conclusions: In this real-world single-center cohort, P-OIT using toasted peanuts was feasible in a subset of patients and was associated predominantly with mild adverse reactions, although systemic reactions were also recorded. Treatment discontinuation and adherence remain relevant challenges. These findings highlight the need for prospective, controlled studies to better define the role, safety profile, and patient selection criteria for food-based P-OIT protocols in settings where standardized products are not available. Full article

Food allergies arise when environmental factors, lifestyle choices, and genetic predispositions affect the integrity of the gut epithelial barrier. Under healthy conditions, gut microbiota supports intestinal tight junction integrity and promotes immune tolerance to dietary allergens. Disruption of this microbiota increases susceptibility to epithelial barrier leakage, thereby enabling food allergens to penetrate the bloodstream from the gut and leading to allergic sensitization. Restoring gut homeostasis through allergen-specific immunotherapy (AIT), executed via oral termed as oral immunotherapy (OIT), skin as subcutaneous immunotherapy (SCIT), or under the tongue in the form of sublingual immunotherapy (SLIT), remains a promising yet complex and multifaceted approach. In parallel, probiotics offer a simpler alternative to reinforce epithelial barrier function, restore cellular homeostasis, mitigate allergy symptoms, and represent the probiotics-based OIT. Recently, several bioengineering strategies have been developed toward enriching gut microbiota, such as using additives such as carbohydrates, polyphenols, and probiotics. While generic probiotics have shown efficacy, their undefined dosages and administration protocols pose challenges for clinical standardization in the form of OIT. Emerging developments include recombinant probiotics engineered to express the specific allergen in a controlled manner inside the gut. However, safety concerns regarding their clinical application remain under active discussion. This review highlights various bioengineering strategies to enhance the probiotic capacity, address safety considerations, and explore future prospects for managing food allergies. Full article

Food allergies (FA) are a major public health concern in both children and adults. Immunoglobulin E (IgE)-mediated FA is characterized by allergic reactions driven by allergen-specific IgE and the subsequent degranulation of mast cells and basophils. Current FA management primarily involves avoidance of allergen-containing food, and more recently, therapies such as oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and the anti-IgE biologic omalizumab. However, these interventions are not curative. The gut microbiome has been implicated in the development and regulation of oral tolerance to food antigens. This narrative review explores the role of probiotics, fecal microbiota transplantation (FMT), dietary interventions, and the interaction between the microbiome and OIT as potential strategies to manage established FA. We also explore barriers to their proliferation as part of regular clinical care. We conclude that future research should (1) address how the microbiome interacts with immunotherapies other than OIT, (2) explore the role of novel microbiome-based treatments like FMT as potential adjuvants to existing food allergy therapeutics, and (3) focus on developing standardized protocols and endpoints for microbiome-based therapeutics. Full article

Background: Food allergy is a growing public health concern, and oral immunotherapy (OIT) has emerged as a promising approach to induce desensitization and potentially sustained unresponsiveness to allergenic foods. Changes in humoral immunity, particularly in allergen-specific immunoglobulin levels, play a central role in the immunological mechanisms underlying OIT. This review aims to summarize the current evidence on how OIT modulates allergen-specific immunoglobulin E (IgE), G (IgG) and A (IgA) responses in individuals with food allergy. Methods: We conducted a review of original research articles reporting longitudinal data on allergen-specific IgE, IgG, and/or IgA in patients undergoing OIT for common food allergens. Results: OIT was consistently associated with a transient increase in allergen-specific IgE levels during early phases, followed by a gradual decline. In contrast, Allergen-specific IgG4 levels showed a robust and sustained increase, correlating with desensitization and proposed to function as blocking antibodies. Several studies also reported an increase in allergen-specific IgA, particularly secretory IgA at mucosal sites, suggesting a potential role in enhancing mucosal tolerance and immune exclusion of allergens. Conclusions: Humoral immune responses during OIT are characterized by distinct and dynamic changes in immunoglobulin patterns. In particular, the rise in IgG4 and, in some cases, IgA suggests a role in promoting tolerance. Monitoring these biomarkers may offer insights into treatment efficacy and support individualized approaches to OIT. Full article

Shellfish allergy is among the most common food allergies (FAs) worldwide and represents a severe immunoglobulin E (IgE)-mediated FA with tropomyosin functioning as the predominant pan-allergen. Current management of shellfish allergies is strictly palliative with allergen avoidance, underscoring the critical need for disease-modifying therapies. While conventional allergen-specific immunotherapy (AIT) approaches, namely oral and sublingual immunotherapies, demonstrate capacity for desensitization, more clinical applications are needed in the potential safety concerns and prolonged treatment durations. Innovative treatments, such as the design of modified shellfish allergens, DNA vaccine technologies, and nanoparticle-based delivery platforms such as virus-like particles (VLP), show efficacy and potential in inducing protective antibodies while promoting antigen-specific immune tolerance with reduced allergenic risks. These innovative approaches hint at a promising pathway in achieving safe, effective, and long-lasting clinical tolerance for shellfish allergy. This review describes the current perspectives on allergen immunotherapy regarding shellfish allergy and analyzes emerging therapeutic strategies poised to overcome these limitations. Full article

Cow’s milk protein allergy (CMPA) is one of the most common food allergies in early childhood. Although a strict elimination diet effectively prevents allergic symptoms, it does not promote the development of tolerance to cow’s milk proteins (CMPs). The milk ladder is a stepwise approach to the reintroduction of CMPs, starting with extensively heated forms and gradually progressing to unheated cow’s milk, according to the individual tolerance levels. The rationale for this approach lies in the reduced allergenicity of heated forms, mainly due to the food matrix effect. The milk ladder was originally developed to gradually expand the diet in children with non-IgE-mediated CMPA. However, recent evidence suggests that it can also be applied in IgE-mediated CMPA to accelerate tolerance development. In children with high-risk IgE-mediated CMPA, this approach may be more challenging. Even minor recipe modifications, particularly those affecting composition or heating conditions, can alter the allergenicity of heated foods. Moreover, barriers to reintroducing food allergens, including parental anxiety or the child’s food aversion, may be more pronounced in this group. Although for high-risk patients, reintroduction is usually performed in hospital settings, increasing evidence indicates that, in selected cases, it may also be safely conducted at home. Several emerging strategies, including early low-dose exposure and oral immunotherapy, show promise in further enhancing tolerance development. Despite these challenges, early reintroduction of CMPs appears to play a crucial role in modulating the immune response and promoting tolerance. This review provides the summary of evidence and practical insights into the implementation of the milk ladder in children with IgE-mediated CMPA. Full article

Background/Objectives: School-age children with food allergies (FAs) face substantial psychosocial challenges. Herein, we aimed to synthesize the experiences of such children. Methods: A systematic review of qualitative studies was conducted using the Joanna Briggs Institute methodology. The protocol was registered in PROSPERO (CRD42022359854). A systematic search was conducted of eight databases. Thirteen studies met the inclusion criteria. The data were synthesized through meta-aggregation, and the confidence in the findings was assessed using the ConQual approach. Results: Seventy-three unequivocal findings were extracted and synthesized into three integrated findings. (1) Children with FAs live with daily fear, social restrictions, and emotional stress. To ensure their safety and foster self-management skills, the trusted adults in their lives must be well-informed about allergy management. (2) Children with FAs experience isolation, teasing, and exclusion from peers, whereas peer communication can foster understanding and acceptance. To address this, schools must promote peer empathy, provide allergy education, and build inclusive environments that empower children to express their needs safely. (3) Motivated by curiosity and personal goals, some children engage in oral immunotherapy or allergen reintroduction, leading to meaningful outcomes, such as increased food choices, social inclusion, and reduced anxiety. At the same time, they face emotional and physical burdens, highlighting the need for safety-focused, informed, supported care that considers both the benefits and burdens. Conclusions: This review highlights the need for child-centered, emotionally supportive, and inclusive care involving families, schools, and healthcare providers. However, the moderate ConQual score of the synthesized findings indicates that the recommendations should be considered with caution. 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

In the context of IgE-mediated food allergies in children, the use of hypoallergenic foods may offer an appropriate solution for enabling informed dietary choices and reducing reactivity to allergenic foods. It is well established that certain foods can alter their allergenicity depending on the method of processing. As such, processed foods may serve both as an alternative dietary option and as a useful tool in oral immunotherapy for children with IgE-mediated food allergies. Nevertheless, an oral food challenge is always recommended when a pediatric allergist considers incorporating processed foods into a child’s diet. This review aims to explore the potential use of processed forms of the nine major food allergens in IgE-mediated food allergies, supporting pediatric allergists in partially liberalizing children’s diets and facilitating the development of tolerance. Full article

Background: The degree of desensitization achieved through oral immunotherapy (OIT) varies widely. This study aimed to identify factors predictive of full desensitization—defined as daily, symptom-free consumption of allergenic foods—in children with food allergies under real-world conditions. Methods: A follow-up survey was conducted for all children who received OIT at Mie National Hospital, Japan, between 2008 and 2017, to assess long-term safety. Patients treated for hen’s egg, cow’s milk, or wheat allergy with at least five years of follow-up were included in the analysis. Data were collected from surveys and medical records, including treatment-emergent adverse events (TEAEs), baseline allergen-specific IgE (sIgE), and daily intake of allergenic foods. TEAEs were evaluated using the World Allergy Organization grading system. Full desensitization was defined as the ability to consume a typical daily portion of allergenic food without symptoms. Predictive factors were identified by multivariate logistic regression. Results: A total of 111 patients (142 OIT courses: egg n = 72, milk n = 47, wheat n = 23) met inclusion criteria. The median age at OIT initiation was 6 years (IQR: 5–8). No TEAEs of grade 4 or grade 5 were reported. Overall, 30% of them achieved full desensitization: 32% in the egg group, 24% in the milk group, and 39% in the wheat group. Low baseline sIgE and absence of mild oral symptoms during build-up were identified as significant predictors. Conclusions: Mild oral symptoms may signal lower likelihood of success. Monitoring them may support individualized OIT. Full article

Food allergies result from dysregulated immune responses to dietary antigens. IgE antibodies are key in triggering allergic reactions through binding to high-affinity receptors on mast cells and triggering mast cell activation when crosslinked by allergens. In contrast, IgG antibodies—particularly IgG4—are linked to immunomodulation and tolerance. Allergen-specific memory B cells, especially IgG1+ cells, undergo class-switching to IgE, and IgE plasma cells underlie allergy persistence. Although there is no cure, allergen-specific immunotherapy (AIT) aims to achieve sustained unresponsiveness by gradually increasing allergen exposure. Oral immunotherapy (OIT), a form of AIT, induces a shift from a TH2-skewed response to a more regulated immune profile, characterized by a switch from IgE to IgG4 and IgA isotypes. This review outlines current insights into AIT’s cellular and humoral mechanisms, with implications for improving long-term outcomes and developing predictive biomarkers. Full article

Food allergies are becoming more common globally. The strict elimination diet, as the main approach so far, has a negative impact on different areas of the lives of children suffering from food allergies, as well as on their caregivers. Oral immunotherapy (OIT), which consists of ingesting small, gradually increasing amounts of food allergens, is a promising approach. Although efficient, this approach is accompanied by frequent adverse reactions (AR), some of which are as severe as anaphylaxis. It seems that, generally, slow dose escalation, as well as low maintenance doses with longer durations, make OIT safer, especially in children with severe food allergies. Furthermore, less allergenic forms of allergens, such as baked milk or egg, also contribute to OIT safety. Adjuvant therapy in combination with OIT has the potential to improve OIT efficiency and safety. Treatment with monoclonal antibodies such as omalizumab and dupilumab in combination with OIT is promising. While both could improve efficiency, omalizumab seems to have a better effect on safety. Interferon γ shows promising results. In contrast, the effect of probiotics and vitamin D supplementation in combination with OIT is still controversial, and new trials about their synergistic effect are needed. Full article

Peanut allergy is a persistent and potentially life-threatening condition affecting millions worldwide, necessitating effective therapeutic strategies beyond strict avoidance. Oral immunotherapy (OIT) has emerged as a promising approach, with peanut (Arachis hypogaea) allergen powder dnfp (Palforzia Aimmune therapeutics Brisbane Calif]) being the first FDA-approved standardized OIT for peanut allergy. This review synthesizes current clinical evidence on PTAH (peanut-tolerant Arachis hypogea), focusing on its efficacy, safety, and long-term outcomes. A systematic literature search was conducted, analyzing key phase 3 trials, including PALISADE, ARTEMIS, and POSEIDON, as well as long-term extension studies such as ARC004 and ARC008. Findings indicate that PTAH significantly increases the peanut protein threshold tolerated by allergic individuals, reducing the risk of severe reactions upon accidental exposure. While adverse events such as gastrointestinal symptoms and anaphylaxis occur, they are generally manageable and decline over time with continued therapy. Notably, younger children in the POSEIDON trial exhibited higher desensitization rates, suggesting the potential benefits of early intervention. Long-term studies demonstrate sustained immune modulation, with reductions in peanut-specific IgE and an increase in IgG4, indicative of developing tolerance. Despite limitations such as adherence challenges and the need for ongoing maintenance dosing, PTAH represents a paradigm shift in peanut allergy management, offering improved safety and quality of life for patients and caregivers. Full article