Search Results (53)

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: Sublingual immunotherapy (SLIT) is an effective treatment for house dust mite (HDM)-induced allergic rhinitis (AR); however, the significance of qualitative changes in specific IgE (sIgE) remains unclear. This study evaluated post-treatment changes in sIgE reactivity and compared the performance of three immunoassays. Methods: In this prospective study, monosensitized patients with HDM-induced AR were identified using skin prick testing and followed for 12 months after SLIT. Serum sIgE levels were assessed at baseline and after treatment using immunoblot, chemiluminescent immunoassay (CLIA), and ImmunoCAP as the reference method. Qualitative changes in sIgE reactivity were analyzed. Clinical response was assessed using the total nasal symptom score (TNSS), and total IgE (tIgE) levels were measured. Results: At baseline, HDM-sIgE reactivity was detected in 85.7%, 82.1%, and 92.9% of patients by immunoblot, CLIA, and ImmunoCAP, respectively. Following SLIT, a significant qualitative conversion to non-reactive status was observed across all assays (p < 0.001). Conversion rates were 94.0% for immunoblot, 83.3% for CLIA, and 100.0% for ImmunoCAP. Significant improvements in TNSS and reductions in tIgE were also observed. Conclusions: SLIT induces a marked qualitative reduction in HDM-sIgE reactivity, with complete serological conversion detected by ImmunoCAP. Although the immunoassays showed comparable rates of HDM-sIgE detection, their agreement in classifying individual patients differed, indicating variability in assay performance. Qualitative assessment of sIgE may provide a clinically meaningful approach for monitoring immunotherapy response. 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

Background/Objectives: Allergen immunotherapy (AIT), involving subcutaneous (SCIT) or sublingual (SLIT) administration of the culprit allergen, is the only treatment capable of modifying the natural course of allergic diseases, and provides lasting benefits in terms of symptom reduction and medication use. AIT for allergic rhinitis is acknowledged as safe and effective in both adults and children; however, no studies have comprehensively evaluated the safety and efficacy of AIT in these populations, integrating results from randomized controlled trials (RCTs) and real-world evidence (RWE). Methods: We evaluated data in the literature including studies from RCTs and RWE in which the safety and efficacy of AIT in both children and adults have been analyzed. A narrative literature search was conducted in PubMed up to January 2026 using the following keywords for the search string: “allergen immunotherapy,” “AIT,” “safety,” “efficacy,” “clinical outcome,” and “clinical evaluation.” Results: RCTs and meta-analyses showed that both SCIT and SLIT significantly reduced allergic symptoms and medication use and improved quality of life (QoL). Large SLIT tablet trials have confirmed its efficacy in adults and children, whereas RWE supports its effectiveness in broader populations. Safety data indicated that SCIT carries a small but higher risk of systemic reactions than SLIT, which mainly causes mild local effects. Conclusions: AIT was effective and safe for treating allergic rhinitis across RCT and RWE studies. Integrating RWE with RCT findings is essential for guideline development, particularly for capturing long-term outcomes and real-world applications. 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/Objectives: Allergic asthma (AA) is a common chronic respiratory disease characterized by airway inflammation and bronchial hyperreactivity triggered by environmental allergens such as pollen and dust mites. Allergen-specific immunotherapy (AIT), particularly its sublingual formulation (SLIT), is the only treatment capable of modifying the disease’s natural course by targeting IgE-mediated sensitization mechanisms. Methods: We analyzed demographic, clinical, functional (FEV₁, FVC, FEV₁/FVC), and immunological data (specific IgE for Phl p1, Phl p5, Der p1, Der p2, Der p23), alongside asthma control parameters (ACT score), reliever use, and exacerbation frequency, in patients undergoing SLIT for grass pollen and dust mite allergens. Results: After at least twelve months of treatment, we observed significant reductions in exacerbation rate (p < 0.01) and reliever use (p = 0.0002). These improvements were particularly evident in the subgroup receiving grass pollen SLIT (p = 0.03 and p = 0.01, respectively). An increase in ACT score was observed but did not reach statistical significance (p = 0.07), likely due to already high baseline control. All patients reported improved rhinitis symptoms. Lung function parameters showed no significant changes. SLIT was well tolerated, with no serious adverse events or discontinuations. The subgroup of patients treated with dust mite SLIT was small, limiting the statistical power and generalizability of these findings. Consequently, the dust mite results should be interpreted cautiously and considered exploratory. The more robust and statistically supported findings pertain to the grass pollen SLIT group, reflecting a more consolidated evidence base for this allergen. Conclusions: SLIT for grass pollen demonstrated promising, statistically supported benefits in reducing exacerbations and improving disease control, supporting its role as an effective adjunct therapy in AA. While dust mite SLIT also showed positive trends, the limited sample size warrants further investigation to confirm these preliminary findings. Overall, SLIT appears to be a safe and potentially beneficial option for patients with AA and allergic rhinitis, but larger studies are needed to substantiate its efficacy across different allergens. 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

In this review, our intention was to shed some light on the history of sublingual and buccal delivery over the past 75 years. By searching the query sublingual and buccal, we noticed four steady growth periods in the number of publications between 1950 and 2025. The early phase of sublingual and buccal drug delivery (1950–1982) saw limited attempts to explore this delivery route. The exploratory growth phase (1983–1993) was marked by the use of nitroglycerin to treat angina, calcium channel blockers to treat hypertension, ACE inhibitors to treat heart conditions, the use of opioids in pain management therapy, and peptide and hormonal therapy. The diversification and discovery phase (1994–2009) was marked by the introduction of small molecules for the treatment of opioid use disorder and analgesia, the use of animal models to enhance the pharmacokinetic understanding of the sublingual and buccal route, the use of penetration enhancers, peptide and hormonal therapy, and few marked FDA drug approvals in this area. The innovation and integration phase (2010–2025) was marked by the use of nanoparticles, multilayered mucoadhesive systems, pediatric formulations (fast-dissolving films and tablets), immunotherapy and vaccine delivery, and a broad spectrum of therapeutic agents, such as steroids, antifungals, cannabinoids, antidepressants, antipsychotics, and narcotics (e.g., buprenorphine and apomorphine), novel formulations of fentanyl and diazepam for pain and seizure control, and the introduction of buccal vitamin D3 sprays. Understanding the history of sublingual and buccal delivery demonstrates a growing area of research focused on enhancing mucosal drug delivery for achieving local and systemic therapeutic benefits. Full article

Peanut allergy is a prevalent and potentially life-threatening condition affecting millions of people worldwide, necessitating strict dietary vigilance. Despite its widespread impact, current treatment options are predominantly limited to allergen avoidance and emergency management of allergic reactions. This review explores contemporary immunotherapeutic strategies aimed at achieving long-term relief for individuals with peanut allergy. We conducted a comprehensive literature review to discuss different treatment approaches, such as subcutaneous immunotherapy (SCIT), epicutaneous immunotherapy (EPIT), oral immunotherapy (OIT), and sublingual immunotherapy (SLIT), focusing on their mechanisms, efficacy, and safety profiles. Additionally, the review delves into novel approaches such as monoclonal antibodies targeting IgE and other critical immune pathways, adjuvanted therapies utilizing nanoparticles and gut microbiota, and advances in adoptive cell therapy including CAR-T cells and regulatory T cells. Furthermore, we highlight some clinical trials that test the efficacy and safety of these novel immunotherapeutic approaches in patients with peanut allergy. Collectively, we provide an overview of advancements in immunotherapeutic interventions for peanut allergy and recommendations for personalized immunotherapy regimens, ultimately paving the way for more effective treatment strategies. Full article

Peanut allergy, a significant public health issue, poses challenges due to its potential for life-threatening anaphylaxis and profound impact on quality of life. Traditional management approaches, including allergen avoidance and epinephrine administration, are effective in mitigating acute symptoms but do not address the underlying allergy or long-term disease burden. Recent advances in immunotherapy and biologics, as well as innovative technologies such as gene editing and microbiome modulation, have introduced promising pathways for desensitization and sustained unresponsiveness. This review provides a comprehensive exploration of emerging therapies for peanut allergy, including oral, sublingual, and epicutaneous immunotherapy, biologic agents, gene-editing techniques, and novel drug therapies. We discuss their mechanisms, clinical efficacy, and associated challenges, emphasizing the potential for these innovations to revolutionize peanut allergy treatment. Despite significant progress, barriers such as adverse reactions, cost, and limited access remain. Addressing these challenges through further research and standardization could transform the future of peanut allergy management. Full article

Background/Objectives: Urinary tract infections (UTIs) caused by multidrug-resistant (MDR) bacteria pose a considerable challenge due to high treatment failure rates and associated healthcare costs. This pioneering study evaluates the effectiveness of personalized autovaccine therapy in managing recurrent UTIs in patients with MDR bacteria, aiming to offer an innovative treatment that reduces antibiotic resistance and hospitalizations. Methods: In this prospective, single-center study, 40 patients with recurrent MDR UTIs received personalized sublingual autovaccines derived from their own bacterial isolates. The study assessed UTI recurrence rates, changes in antibiotic use, and hospitalization days over 12 months. Results: The autovaccine therapy significantly reduced UTI recurrence, with 67.5% of patients experiencing fewer infections. Antibiotic usage decreased by 74.4%, and total hospitalization days annually reduced from 400 to 216. A significant shift was observed from MDR to multi-susceptible bacterial profiles among participants. Conclusions: This study is the first to demonstrate that autovaccine therapy is a safe and effective approach for managing recurrent UTIs caused by MDR bacteria, significantly lowering infection frequency, antibiotic needs, and hospitalization. These findings support integrating autovaccine therapy into standard UTI management to combat antibiotic resistance and lessen healthcare burdens. Full article

Background: Sublingual immunotherapy (SLIT) has shown promise in mitigating allergic asthma symptoms; nevertheless, its high dose and prolonged duration of treatment raise safety concerns. This study explored the potential of Lactobacillus paracasei (L. paracasei) to enhance the effectiveness of SLIT in a mouse model of allergic asthma. Methods: Allergic asthma was induced in Balb/c mice following sensitization and challenge with a house dust mite (HDM) allergen. Subsequently, the mice were subjected to SLIT (66 and 132 µg) either alone or in combination with L. paracasei supplementation. Asthma-associated parameters, including rubbing frequency, IgE level, cytokine profiles, and histological changes, were evaluated to assess treatment efficacy. Results: mice that received SLIT 132 µg combined with the probiotic (combined 132) demonstrated a significant reduction in allergic symptoms (rubbing). This treatment strategy led to a marked IgE and eosinophil level decrease in serum; an increase in anti-inflammatory cytokines like IFN-γ and IL-10; and a reduction in pro-inflammatory cytokines IL-17 and TNF-α. The combination therapy also mitigated lung inflammation and supported the restoration of the structural integrity of the colon, promoting the recovery of goblet cells and mucus secretion. Probiotic treatment alone also effectively reduced IgE levels, increased IFN-γ, and decreased levels of IL-17 and TNF-α. Conclusions: The adjuvant effect of L. paracasei in enhancing SLIT represents a promising approach for improving asthma treatment efficacy. Full article

Food allergy represents a significant public health concern, with its prevalence increasing in recent decades. Tree nuts are among major allergenic foods, and allergies to them are frequently linked to severe and potentially life-threatening reactions. Data on the prevalence and natural history of tree nut allergy are limited. Primary nut allergy typically presents with rapid-onset IgE-mediated symptoms. Diagnosis can be confirmed by demonstrating a positive skin prick test (SPT), specific IgE (sIgE), or through an oral food challenge. Component-resolved diagnostics (CRD) can identify those with a high risk of anaphylaxis. The main management strategy involves avoiding the culprit allergen and treating symptoms after accidental exposure. New therapeutic options, such as sublingual immunotherapy, oral food immunotherapy, with or without omalizumab, and other monoclonal antibodies, are being investigated to modify tree nut allergy. Tree nut allergy is a lifelong disease with a low likelihood of resolution. The aim of this paper is to present the current data on the prevalence, diagnosis, natural history, and management options for tree nut allergy. Full article

Introduction: Lipid Transfer Proteins (LTPs) are plant-derived panallergens that have emerged as significant allergens in Mediterranean populations. Though less common in children, LTP allergies represent a critical consideration for physicians diagnosing plant food allergies in this demographic. Methodology: PRISMA-ScR guidelines were followed. A search with specific terms was performed in searchable databases. Two of the authors extracted and evaluated the data. Results: A total of 21 original studies and 6 case reports focusing on LTP allergies in the paediatric population met the inclusion criteria. Diagnostic tools, predictive markers and management options for LTP allergies were examined. Allergens, clinical presentation and history were the diagnostic tools investigated. The clinical and laboratory phenotypes of the patient were considered possible predictive markers for the evaluation and progression of LTP allergies. Lastly, dietary modifications and sublingual immunotherapy were identified as the main focus of LTP allergy management. Discussion: A summary of the results is presented, and at the same time, questions concerning the nature of LTP allergies and their management are raised. Conclusions: LTP allergy in children is something physicians should be aware of. Further research is needed to establish the differences in LTP allergies in children and adults and the effectiveness of immunotherapy in paediatric populations. Full article