Search Results (709)

Background/Objectives: Cow’s milk allergy (CMA) manifests with various clinical syndromes and has a wide range of symptoms in infants. This study aims to investigate the prevalence, clinical presentation, and outcome of clinical types and subtypes of CMA diagnosed in children within the first 12 months of life. Methods: Children with a CMA diagnosis were included in this mixed retrospective and prospective cohort study and were followed up for four years. Data recorded included clinical manifestations, feeding modes, and outcomes. Follow-up included oral cow’s milk (CM) challenge and/or elimination—reintroduction of CM, provided there was parental consent. Also, skin prick test and serum CM-specific IgE were assessed when needed. Results: A total of 93 infants (age: 3 days to 24 months) diagnosed with CMA were included. Prevalence was 28% for IgE-mediated CMA and 72%, 49.5%, 18.3%, and 3.7% for non-IgE-mediated CMA and its subtypes, Allergic Proctocolitis (AP), Food Protein induced Enteropathy (FPE), and Food Protein Induced Enterocolitis Syndrome (FPIES), respectively. Main manifestations were gastrointestinal (74%), skin rash (31%), failure to thrive (11.8%), feeding aversion (15.1%), respiratory symptoms (5.4%), and irritability/restlessness (9.7%). Follow-up revealed a high rate of AP and FPE tolerance within the first year, while FPIES and IgE-mediated CMA achieved tolerance at an older age. Conclusions: Our study demonstrated the predominance of AP and increased incidence of gastrointestinal involvement. Outcome was good for AP and FPE but less favorable for FPIES and IgE-mediated CMA. Our results, combined with published data, could increase our understanding of CMA-associated syndromes in infants and contribute to the guidance of effective management. Full article

Background and Clinical Significance: Otitis media with effusion (OME) is characterized by persistent middle ear effusion without acute infection. Type 2 inflammation, mediated by IL-4 and IL-13 signaling via the IL-4Rα receptor, has been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and possibly OME. Refractory OME in adults remains a therapeutic challenge, as conventional treatments often fail to achieve long-term resolution. Targeted biologic therapies that modulate type 2 inflammation may offer a novel treatment option. Case Presentation: We report the case of a 60-year-old man with a 15-year history of allergic rhinitis and CRSwNP, complicated by recurrent asthma exacerbations, who presented with bilateral aural fullness, hearing loss, and tinnitus. His symptoms persisted despite repeated tympanic punctures, Eustachian tube insufflation, and corticosteroid therapy. Otoscopy revealed dull tympanic membranes with effusion, and audiometry showed conductive hearing loss with a B-type tympanogram on the left. Laboratory findings demonstrated mild peripheral eosinophilia. The patient was diagnosed with OME, likely secondary to type 2 inflammation. After nine biweekly injections of Stapokibart (CM310)—a humanized monoclonal antibody targeting IL-4Rα—aural fullness completely resolved. Otoscopic findings and tympanograms normalized, and hearing thresholds improved significantly. Retrospective evaluation using Iino’s diagnostic framework suggested that the patient did not meet the full criteria for eosinophilic otitis media (EOM); nevertheless, marked symptomatic and functional improvement was achieved. No recurrence or adverse effects were observed during follow-up. Conclusions: This case suggests that IL-4Rα blockade with Stapokibart may be effective in treating refractory OME associated with type 2 inflammation, even in patients who do not fulfill the diagnostic criteria for EOM. These findings highlight the potential of anti-IL-4Rα biologics as a novel therapeutic option for middle ear diseases driven by type 2 inflammation. Full article

Background/Objectives: To investigate the relationship between patient age and the clinical efficacy of subcutaneous immunotherapy (SCIT) for allergic rhinitis (AR), aiming to provide a reference for patient selection and efficacy improvement in clinical practice. Methods: We conducted a retrospective statistical analysis of clinical data from 240 AR patients who underwent standardized house dust mite (HDM) SCIT for at least 6 months at our hospital between 2019 and 2025. Patients were stratified into four age groups (children, young adults, middle-aged adults, and the elderly) according to the World Health Organization (WHO) classification. The clinical efficacy, nasal symptom scores, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores, peripheral blood regulatory T cell (Treg) and regulatory B cell (Breg) levels, and adverse reactions were analyzed across these age strata. Additionally, to investigate the underlying mechanisms, we utilized a public single-cell transcriptomic dataset (GSE176269; n = 35, age 4 months-65 years) to assess the relationship between T cell senescence and age through data integration and senescence gene set scoring. For multiple comparisons, the significance level was adjusted using the Bonferroni method. This adjustment ensured the overall significance level (α) of the study was maintained at 0.05, and the final adjusted significance level (α′) for each age group was 0.0125. Results: The overall response rate for the entire cohort was 62.5%. Age-stratified analysis revealed a significantly higher response rate in children (83.3%) compared to middle-aged and elderly patients (48.5% and 20%, respectively), with the difference being statistically significant (p < 0.001). Following treatment, both total nasal symptom scores and RQLQ scores decreased significantly across all age groups compared to baseline (p < 0.001). Peripheral blood Treg and Breg levels increased post-treatment in all age groups; however, the increase was not statistically significant in the middle-aged and elderly groups (p > 0.0125). The incidence of systemic adverse reactions was 4.17% (all Grade I), occurring primarily in the child and young adult groups, but the difference among age groups was not statistically significant (p > 0.0125). Mechanistically, our single-cell analysis revealed that T cells within the nasal mucosa exhibit significant age-dependent senescence. Conclusions: SCIT is a safe and effective treatment for AR across all age groups. However, pediatric patients appear to derive greater benefit compared to middle-aged and elderly patients, a finding that corresponds with age-stratified immunological data. Therefore, different efficacy expectations should be considered when selecting SCIT for patients of varying ages, and future research should explore strategies targeting T cell senescence to enhance desensitization efficacy in elderly patients. Full article

The rising global prevalence of food allergy (FA) necessitates innovative therapeutic strategies. This study investigates the protective effects of three probiotic strains, Lacticaseibacillus rhamnosus HN001 (HN001), Bifidobacterium lactis HN019 (HN019), and Lactobacillus acidophilus NCFM (NCFM) against FA in a murine model. Probiotic administration significantly alleviated allergic symptoms and suppressed the Th2 response, reducing IgE, histamine, and cytokines (TNF-α, IL-2/5), while concurrently enhancing CD4+CD25+ regulatory T cell (Treg) activity and TGF-β1 expression. Treatment also restored intestinal integrity by upregulating tight junction proteins (ZO-1, claudin-1). 16S rRNA sequencing revealed that protection was underpinned by microbiota remodeling, marked by increased α-diversity and enrichment of SCFA-producing taxa (Lachnospiraceae and Muribaculaceae), which correlated with elevated acetate, butyrate, and propionate levels. Spearman analysis linked these microbial shifts to improved immune and barrier markers. Collectively, these findings demonstrate that probiotics mitigate FA through a convergent mechanism of immune rebalancing, barrier reinforcement, and SCFA-mediated microbiota-immune crosstalk, offering a promising microbiome-targeted therapy. Full article

Background/Objectives: Worldwide, an estimated 20–30% of infants suffer from infant colic (IC), with excessive crying and unsettled behavior, during the first three months of life. These infants are often referred for a medical evaluation, but the pathogenesis of IC remains poorly understood. The aim of this narrative review is to critically appraise the available literature regarding the relation between IC and cow’s milk allergy (CMA). Methods: A literature search using the search strings cow’s milk allergy [MeSH Terms] OR food allergy [MesH Terms] AND colic [MeSH Terms] OR crying [MeSH Terms], limited to the English language, from inception to 15 June 2025, resulted in the identification of 135 articles. Of these, 18 clinical trials assessed the effect of a cow’s milk elimination diet on IC. Results: The role of CMA in IC in the absence of other allergic manifestations remains uncertain. However, when standard treatment of infant colic has failed and when other allergic symptoms are present, CMA may be considered. A diagnostic elimination diet which includes a 2–4-week trial of maternal cow’s milk elimination in breastfed infants or an extensively hydrolyzed cow’s milk or hydrolyzed rice formula should be performed. If the elimination diet results in a significant decrease in symptoms, reintroduction of cow’s milk protein into the diet is mandatory to fulfill the diagnostic criteria of CMA. Conclusions: Considering the limited current evidence, future research should prioritize large well-designed clinical trials with a focus on investigating CMA in colicky breastfed and formula-fed infants. Full article

Background/Objectives: Headache attributed to rhinosinusitis (HRS) is uncommon in children but often misdiagnosed as migraine or tension-type headache (TTH). Overlapping phenotypes, incidental sinus findings on neuroimaging, and limited communication in younger patients complicate diagnosis and lead to inappropriate treatment. Methods: We retrospectively analyzed 3065 pediatric patients (<19 years) presenting with headache at two tertiary neurology clinics (2014–2023) with ≥1 year follow-up. Headaches were classified by ICHD-3 criteria. HRS diagnosis required radiologic sinus pathology and ≥50% improvement within 72 h of antibiotic or decongestant therapy. Demographic, clinical, neuroimaging, and family history data were collected. Symptom profiling used principal component analysis (PCA) and k-means clustering; multivariate logistic regression identified independent predictors. Results: Of 3065 patients, 32.7% had migraines, 15.5% TTH, and 4.5% HRS. Nearly one-third of HRS cases were initially misclassified. Compared with migraine and TTH, HRS patients were younger (median 9 years), more often male, and enriched in preschool age. Independent predictors included shorter duration (<1 h; OR 0.62), higher intensity (OR 2.165), nasal symptoms (OR 9.836), hearing impairment (OR 22.52), allergic rhinitis (OR 8.468), and family history of HRS (OR 32.602) (all p < 0.001). PCA showed overlap but distinct clustering: HRS was characterized by sinonasal and otologic features, whereas migraine clustered around sensory hypersensitivity. Conclusions: Pediatric HRS shows distinct predictors—young age, acute severe headache, nasal and auditory symptoms, allergic history, and family history—despite overlap with migraine and TTH. Structured use of these predictors with otolaryngologic assessment may improve diagnostic accuracy, reduce misclassification, and avoid unnecessary neuroimaging or inappropriate therapy. Full article

Allergic bronchopulmonary aspergillosis (ABPA) is mediated by hypersensitivity reactions to Aspergillus fumigatus, which is ubiquitous in the environment. People with Cystic Fibrosis (PwCF) are at an increased risk for developing ABPA, which can lead to frequent pulmonary exacerbations and progressive decline in lung function. In the age of highly effective modulator therapies (HEMT), PwCF have improved clinical outcomes and overall life expectancy, but they continue to suffer from comorbidities such as ABPA, which may be difficult to diagnose and treat. Establishing the diagnosis of ABPA in PwCF requires high clinical suspicion due to similarities in symptoms with the underlying disease. First-line treatment involves corticosteroids and anti-fungals, which have multiple side effects and drug interactions, especially with HEMT. Given this challenge, biologics have gained attention as potential agents directly targeting the Th-2 inflammatory pathway of ABPA with good tolerability and without significant drug interactions with HEMT. In this review, we discuss the diagnostic process and management of ABPA in PwCF, including a brief overview of the current literature on biologic agents. Full article

Background/Objectives: Machine learning is an extremely important issue, considering the potential to prevent the onset of long-term complications from coronavirus disease or to ensure timely detection and effective treatment. The aim of our study was to develop an algorithm and mathematical model to predict the risk of developing long COVID in children who have had acute SARS-CoV-2 viral infection, taking into account a wide range of demographic, clinical, and laboratory parameters. Methods: We conducted a cross-sectional study involving 305 pediatric patients aged from 1 month to 18 years who had recovered from acute SARS-CoV-2 infection. To perform a detailed analysis of the factors influencing the development of long-term consequences of coronavirus disease in children, two models were created. The first model included basic demographic and clinical characteristics of the acute SARS-CoV-2 infection, as well as serum levels of vitamin D and zinc for all patients from both groups. The second model, in addition to the aforementioned parameters, also incorporated laboratory test results and included only hospitalized patients. Results: Among 265 children, 138 patients (52.0%) developed long COVID, and the remaining 127 (48.0%) fully recovered. We included 36 risk factors of developing long COVID in children (DLCC) in model 1, including non-hospitalized patients, and 58 predictors in model 2, excluding them. These included demographic characteristics of the children, major comorbid conditions, main symptoms and course of acute SARS-CoV-2 infection, and main parameters of complete blood count and coagulation profile. In the first model, which accounted for non-hospitalized patients, multivariate regression analysis identified obesity, a history of allergic disorders, and serum vitamin D deficiency as significant predictors of long COVID development. In the second model, limited to hospitalized patients, significant risk factors for long-term sequelae of acute SARS-CoV-2 infection included fever and the presence of ≥3 symptoms during the acute phase, a history of allergic conditions, thrombocytosis, neutrophilia, and altered prothrombin time, as determined by multivariate regression analysis. To assess the acceptability of the model as a whole, an ANOVA analysis was performed. Based on this method, it can be concluded that the model for predicting the risk of developing long COVID in children is highly acceptable, since the significance level is p < 0.001, and the model itself will perform better than a simple prediction using average values. Conclusions: The results of multivariate regression analysis demonstrated that the presence of a burdened comorbid background—specifically obesity and allergic pathology—fever during the acute phase of the disease or the presence of three or more symptoms, as well as laboratory abnormalities including thrombocytosis, neutrophilia, alterations in prothrombin time (either shortened or prolonged), and reduced serum vitamin D levels, are predictors of long COVID development among pediatric patients. Full article

Background/Objectives: Allergic diseases are highly prevalent worldwide and represent a significant public health burden. Current therapies mainly alleviate symptoms without addressing underlying immune dysfunction, which has increased interest in nutritional bioactive compounds as preventive or modulatory agents. This review summarizes evidence on omega-3 polyunsaturated fatty acids, vitamin D, curcumin, ginger bioactives, quercetin, and epigallocatechin gallate (EGCG) in allergy prevention and management. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to July 2025, including preclinical and clinical studies reporting immunological, mechanistic, and clinical outcomes. Results: Omega-3 fatty acids modulate Th2 responses, promote regulatory T cells, and generate specialized pro-resolving mediators, with modest clinical benefits observed in pregnancy and early life. Vitamin D contributes to immune tolerance and epithelial integrity, although supplementation trials remain heterogeneous. Curcumin inhibits NF-κB/MAPK signaling, enhances barrier function, and improves allergic rhinitis and dermatitis despite limited bioavailability. Ginger constituents ([6]-gingerol, [6]-shogaol) modulate Th1/Th2 balance, mast-cell activity, and oxidative stress, with early clinical evidence in rhinitis and asthma. Quercetin stabilizes mast cells, inhibits Lyn/PLCγ pathways, and improves rhinitis symptoms in small randomized trials using bioavailable formulations. EGCG stabilizes mast cells, attenuates FcεRI signaling, and reduces airway inflammation in preclinical models, though clinical data are scarce. Conclusions: Overall, preclinical findings consistently support the immunomodulatory potential of these compounds, while clinical results are promising but heterogeneous. Standardized formulations, long-term trials, and exploration of synergistic effects are required to confirm efficacy and safety, providing future research directions in allergy prevention. Full article

Background/Objectives: Food protein-induced allergic proctocolitis (FPIAP) is a non-immunoglobulin-E-mediated allergic colitis. Most cases resolve after 1 year of age, but delayed resolution and growth retardation may occur in some refractory cases. We aimed to explore the clinical characteristics, treatment approaches, and outcomes of such pediatric patients. Methods: We retrospectively analyzed 35 patients with refractory FPIAP at our center between January 2015 and January 2025. Patients were categorized into early- and non-early-onset groups according to timing of symptom onset; various clinical data were collected and treatment regimens were monitored. Results: The proportion of patients with growth retardation was significantly higher in the non-early onset group than in the early-onset group (73.3% vs. 35.0%, p = 0.041), whereas hemoglobin levels were higher in the early-onset group (118.95 ± 11.26 g/L vs. 107.93 ± 14.61 g/L, p = 0.017).The proportion of corticosteroid use was significantly lower in the early-onset group (15.0% vs. 60.0%; p = 0.011). During follow-up, among 35 patients, 14 (40%) could not tolerate certain foods, including cow’s milk (100%), eggs (42.9%), and wheat (35.7%). Conclusions: Refractory FPIAP was protracted, with a higher incidence of growth retardation, lower hemoglobin levels, and higher corticosteroid use in the non-early onset group. The optimal treatment approach should be explored. Full article

Psoriasis and allergic contact dermatitis (ACD) are the most common chronic inflammatory diseases, which are accompanied by epithelial alterations and a T cell-mediated immunopathology. In this study, we investigated the anti-ACD and anti-psoriasis effects of sea anemone Heteractis magnifica peptide HCRG21, a blocker of the TRPV1 channel, in 2,4-dinitrofluorobenzene (DNFB)- and imiquimod (IMQ)-induced mouse models, respectively. We found that topical application of 0.005–0.1% HCRG21 gels normalized hematological and immunological blood parameters in mice, significantly reduced the severity of ACD- and psoriasiform-like skin lesions, and increased the rate of tissue repair. The use of 0.005 and 0.05% HCRG21 gels decreased the production of IL-23-A and macrophage-derived chemokine (MDC) proteins in blood plasma, reduced the expression of Tnf, Il1β, Il6, Il23a, and Il17a genes, but increased the levels of the Il10 gene in scabs and/or blood of IMQ-treated mice. On the other hand, topical application of 0.05 and 0.1% HCRG21 reduced the expression of Il6 and Il23a in the DNFB-treated mice’s blood and it had no significant effects on TNF-α and IL-1β production. Thus, HCRG21 has the potential to be a treatment for psoriasis and dermatitis due to its potent anti-inflammatory properties. This effect is achieved by reducing pro-inflammatory cytokines associated with TRPV1 and normalizing immune cell levels in the bloodstream. This, in turn, leads to a decrease in clinical symptoms and an improvement in skin healing. Full article

Introduction: Apart from the typical AR phenotype and its standard clinical manifestations—rhinorrhea, sneezing, nasal itching, and congestion—the so-called local allergic rhinitis (LAR) can be observed in a subset of subjects presenting rhinitis symptoms, a negative skin prick test (SPT), and serum-specific immunoglobulin E (sIgE) for the relevant allergens and confirmed with a positive nasal provocation test (NPT), which is the gold standard in LAR diagnosis. Our study aims to assess the clinical symptoms and local mucosal sIgE presence induced by NPT and natural exposure to HDM allergens in subjects with suspected LAR. Methods: In total, 25 suspected LAR subjects were included in the study. The total nasal symptom score (TNSS) and visual analog scale (VAS) were used for the subjective assessment. A nasal provocation test (NPT) was performed with house dust mite allergens. The nasal lavage technique was used for nasal secretion acquisition, in which the levels of sIgE were measured. Results: During the period of increased exposure vs. the off-exposure period, the TNSS and VAS were significantly higher (p = 0.0361 and p = 0.0031, respectively). Levels of IgE specific to Dermatophagoides pteronyssinus in nasal lavage were high (p = 0.0502). Similarly, high levels of sIgE to Dermatophagoides farinae were noted (p = 0.0164). Comparing pre-NPT and post-NPT results, LAR diagnosis was confirmed in 8 subjects. Only the VAS score was higher after a positive NPT. Both sIgE to Dermatophagoides pteronyssinus and Dermatophagoides farinae in nasal lavage were higher after a positive NPT; however, the change was not statistically significant. A higher fold change in the median relative value (sIgE/Total IgE) for both allergens was noted in the positive-NPT group compared to the negative-NPT group. Conclusions: Assessing the local nasal production of sIgE and other inflammatory mediators may contribute to expanding our knowledge of LAR pathogenesis. Further studies including a larger number of subjects are needed for a better understanding of the LAR entity in terms of diagnosis and treatment options. Full article

Allergic rhinitis (AR) is a common chronic respiratory disease that significantly impairs the life of children. While a combination intranasal spray of azelastine hydrochloride and fluticasone propionate (Aze-Flu) is an established effective treatment for adults with moderate-to-severe AR, the clinical evidence available in the pediatric population is limited. This review summarizes the current evidence on the efficacy, safety, and impact on Quality of Life (QoL) of Aze-Flu in children. Clinical trials have demonstrated that Aze-Flu provides faster and greater symptom relief in children with AR compared to fluticasone propionate (FP) monotherapy. One randomized controlled trial demonstrated that, although the overall change in the reflective Total Nasal Symptom Score (rTNSS) was not statistically different from the placebo, this was possibly due to rater assessment bias. Children’s symptoms self-assessment showed considerable ameliorations in both nasal and ocular scores. Furthermore, treatment with Aze-Flu has been shown to produce clinically relevant and statistically significant improvements in QoL compared to placebo in children with moderate-to-severe seasonal AR. The safety profile is favorable; a 3-month study confirmed that Aze-Flu is well-tolerated, with an incidence of treatment-related adverse events comparable to that of FP monotherapy. Beyond AR, emerging evidence suggests potential benefits of Aze-Flu in children with adenoid hypertrophy. The available evidence supports Aze-Flu as an effective and well-tolerated therapeutic option for children with moderate-to-severe AR, offering superior and faster symptom control than monotherapy and leading to meaningful improvements in quality of life. Future pediatric trials should incorporate validated, child-specific assessment tools to better capture treatment efficacy. Full article

LTP allergy and its accurate diagnosis remain a challenge in modern allergology. Patients sensitized to lipid transfer proteins (LTPs) present a wide range of symptoms, from mild manifestations—such as oral allergy syndrome, urticaria, and angioedema—to severe systemic reactions, including anaphylaxis. Oral food challenges (OFCs), the gold standard in food allergy diagnostics, are problematic in this group of patients due to the high risk of life-threatening reactions during the procedure. The basophil activation test (BAT), a functional assay based on flow cytometry, is a promising diagnostic tool that may benefit many food-allergic patients by reducing the need for OFCs. In 2023, BAT was incorporated into selected diagnostic pathways for food sensitization in the guidelines issued by the European Academy of Allergy and Clinical Immunology (EAACI). While many studies have investigated BAT in the context of peanut allergy, evidence regarding its application in LTP allergy remains limited. In this systematic review, we analyzed the currently available studies on the use of BAT in the diagnosis of LTP sensitization and evaluated its potential to supplement or even replace OFCs in specific clinical scenarios. Full article

Objective: Allergic rhinitis (AR) continues to adversely affect the life quality of a substantial patient population, highlighting the necessity for enhanced treatment modalities. Our research utilized licorice extract (LE) in nasal irrigation for managing this condition, with its therapeutic efficacy gauged against traditional saline nasal irrigation (SNI) through clinical trials. Additionally, the study incorporated traditional Chinese medicine (TCM) principles, measuring not just subjective symptom relief but also the objective shifts in lung meridian electrical conductance (MEC), to provide a comprehensive evaluation of the treatment’s effectiveness. Methods: Based on our previous laboratory and animal studies, we developed an LE solution and applied it through nasal irrigation to treat AR. In a one-month controlled trial, 60 patients with AR received either licorice nasal irrigation (LNI) or SNI daily. We assessed treatment efficacy by subjective questionnaire scores (Total Nasal Symptom Score [TNSS] and 22-item Sino-Nasal Outcome Test [SNOT-22]) and objective lung MEC analysis. Result: In the trial, 30 participants were randomly allocated to each group, and 28 individuals in the LNI group and 24 in the SNI group finished the study without any side effects. The LNI group had better improvements in sneezing, nasal itchiness, and rhinorrhea, along with a greater overall TNSS reduction. On the SNOT-22, the LNI group scored better across most nasal and extra-nasal symptoms, sleep, and physiological and psychosocial well-being. Participants were sorted into low, normal, and high lung MEC subgroups. After treatment, those in the LNI group normalized their lung MEC levels in both the low and high subgroups, which was not observed in the SNI group. Conclusions: LNI markedly improves symptoms in patients with AR, enhancing their quality of life. This treatment method, integrating Western and TCM practices, also normalizes abnormal lung MEC values following therapy. It offers a method of objectively validating the effectiveness of treatments based on TCM theories. Full article