Allergies

Atopic dermatitis is a chronic inflammatory skin disease increasingly recognized as part of a broader atopic and type 2 inflammatory spectrum rather than a condition confined to the skin alone. Although its dermatologic burden is well established, its relevance to otorhinolaryngology remains relatively underrecognized. This narrative review examines atopic dermatitis from an otorhinolaryngology-centered perspective, focusing on ear, nose and throat (ENT) associations, clinical overlaps, shared inflammatory pathways, and practical implications for clinical care. Particular emphasis is placed on allergic rhinitis, chronic rhinosinusitis, ear-related eczematous manifestations, and the head and neck phenotype of atopic dermatitis. Shared pathophysiologic mechanisms, including epithelial barrier dysfunction, allergen sensitization, immune dysregulation, type 2 inflammation, microbiome alterations, and allergic multimorbidity, provide a framework for understanding these overlaps. Upper airway and ear-related conditions should not be interpreted as direct manifestations of atopic dermatitis in all patients, but as disorders that may coexist within a shared atopic or type 2 inflammatory background. The review further considers the implications of this perspective for targeted history-taking, differential diagnosis, referral decisions, therapeutic awareness, and multidisciplinary care. Overall, atopic dermatitis may serve as a clinically useful marker of broader allergic and inflammatory multimorbidity, with relevant implications for selected patients encountered in otorhinolaryngology practice. Full article

Severe pediatric asthma remains a significant clinical challenge despite advances in conventional therapy. Some children continue to experience persistent symptoms, recurrent exacerbations, and substantial morbidity despite optimized treatment with inhaled corticosteroids and long-acting bronchodilators. Advances in the understanding of asthma immunopathology, particularly type 2 (T2) inflammation, have led to the development of targeted biologics that modulate key inflammatory pathways. Several monoclonal antibodies are now approved for pediatric use, including the anti-immunoglobulin E (IgE) agent omalizumab, anti-interleukin (IL)-5 therapies such as mepolizumab, and the IL-4 receptor antagonist dupilumab. These biologics significantly reduce exacerbation rates, improve lung function, and decrease dependence on systemic corticosteroids in selected pediatric populations. Their effective use, however, requires careful assessment of clinical phenotypes and biomarkers, including blood eosinophils, serum IgE, and fractional exhaled nitric oxide. Uncertainties remain regarding treatment sequencing, duration, long-term safety, and cost-effectiveness. Agents targeting upstream epithelial cytokines, including tezepelumab, are broadening the therapeutic landscape. Despite this progress, pediatric evidence remains fragmented across age groups, biologic agents, study designs, and real-world cohorts, while many reviews focus on individual therapies or partly extrapolate from adult data. This review synthesizes pediatric evidence on efficacy, safety, biomarker-guided selection, age-related indications, and implementation challenges across approved and emerging biologics. It aims to provide clinicians with a practical framework for treatment selection and monitoring while identifying priorities for future pediatric research. Full article

Allergic contact dermatitis (ACD) is an increasingly common condition among athletes due to repeated exposure to sport-specific equipment, environmental allergens, and topical products. Sweating and repetitive cutaneous trauma facilitate allergen penetration. Rubber accelerators, metals, textile dyes, adhesives, synthetic resins, and topical medications represent the principal allergen categories implicated in sports-related ACD. This narrative review synthesizes the current literature on the epidemiology, pathophysiology, allergen profiles, and sport-specific exposure patterns of ACD in athletes, while outlining the essential principles of clinical recognition and targeted allergen avoidance. Full article

Pediatric food allergy is an increasing public health challenge associated with severe allergic reactions, psychosocial burden, and healthcare inequalities. This study aimed to characterise molecular sensitisation patterns among Bulgarian children with suspected food allergy using component-resolved diagnostics and to evaluate family quality of life in a healthcare setting without access to epinephrine auto-injectors. A total of 1163 pediatric patients underwent molecular allergy testing using the ALEX² multiplex platform, while 90 caregivers completed structured quality-of-life questionnaires. A sensitisation threshold of >0.10 kUA/L was applied to maximise sensitivity for molecular profiling and co-sensitisation analyses. Tree nut allergens showed the highest sensitisation prevalence, predominantly involving Ana o 3, Pis v 1, Jug r 1, Cor a 9, and Cor a 14. Younger children showed a predominance of stable storage protein sensitisation, whereas older children more frequently demonstrated PR-10-associated cross-reactive profiles. Correlation analyses identified strong co-sensitisation clustering among phylogenetically related allergen families, particularly cashew-pistachio, walnut-hazelnut, mammalian milk, and fish allergens. Questionnaire responses revealed substantial psychosocial burden related to fear of anaphylaxis, chronic hypervigilance, restricted daily activities, and inadequate emergency preparedness. These findings highlight the importance of molecular risk stratification and underscore major unmet needs in pediatric food allergy management in Bulgaria. Full article

Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with severe ocular complications (SOCs) are devastating mucocutaneous disorders characterized by chronic ocular surface inflammation and epithelial damage. Although genome-wide association studies have identified IKZF1 as a susceptibility gene, its functional role in conjunctival epithelial cells remains unclear. Objective: This study aimed to characterize transcriptional changes and enrichment profiles associated with IKZF1 overexpression in primary human conjunctival epithelial cells. Methods: Primary human conjunctival epithelial cells (PHCjECs) were transfected with an IKZF1 expression plasmid or empty vector under matched transfection conditions, followed by microarray profiling, RT-qPCR validation, and Enrichr-based transcription factor enrichment analysis. Results: IKZF1 overexpression was associated with increased expression of CXCL8 and multiple stress-related transcripts, including DDIT3, and with enrichment of DDIT3-, ATF3-, and JUN-related transcriptional signatures. RT-qPCR confirmed significant induction of ER stress pathway genes, including ATF4, GRP78, and TRIB3. Furthermore, CHOP protein expression was markedly increased in conjunctival epithelium from patients with SJS/TEN compared with controls. Conclusions: IKZF1 overexpression is associated with inflammatory and stress-related transcriptional changes in conjunctival epithelial cells. These findings support a working hypothesis that epithelial IKZF1 upregulation may contribute to ocular surface pathology in SJS/TEN with severe ocular complications, but direct molecular mechanisms remain to be established. Full article

Biologic therapies have significantly improved outcomes for patients with moderate-to-severe atopic dermatitis (AD), yet access to these treatments remains uneven and frequently limited. This systematic review synthesizes evidence on insurance-related, financial, administrative, prescriber-level, and structural barriers that limit equitable access to biologic therapies for AD. In contrast to prior reviews that primarily focus on biologic efficacy, safety, or general disease management, this review evaluates access itself as the primary outcome. Across diverse study designs and populations, findings consistently demonstrate that high out-of-pocket costs, restrictive insurance policies, and administrative burdens disproportionately impact low-income, minority, and Medicaid-insured patients. However, racial and ethnic disparities should be interpreted cautiously, as factors like insurance type, Medicaid enrollment, socioeconomic status, geographic access, and other structural determinants may influence these associations. Pediatric patients and caregivers also face challenges such as insurance delays, financial burden, and long-term effects of poor disease control. These barriers contribute to delays in treatment initiation, reduced adherence, and poorer clinical outcomes. Persistent racial, socioeconomic, and geographic disparities further exacerbate inequities in care delivery. Variability in prescribing patterns and provider familiarity with biologics also influence treatment access. Collectively, these findings underscore the need for comprehensive policy reform, streamlined authorization processes, and targeted interventions to improve equitable access to biologic therapies in AD. Full article

Eosinophilia is a heterogeneous clinical finding ranging from benign reactive states to clonal hematologic disorders associated with significant morbidity. This narrative, practical clinical review provides a structured, mechanism-based approach to the evaluation and management of peripheral eosinophilia by integrating contemporary consensus definitions, epidemiologic data, and diagnostic frameworks. Eosinophilia is defined as an absolute eosinophil count of ≥500 cells/µL, with hypereosinophilia defined as ≥1500 cells/µL. Etiologies are broadly classified as primary (clonal) or secondary (reactive). Peripheral eosinophil counts do not reliably predict organ involvement. Evaluation requires systematic assessment, including clinical history, laboratory testing, and targeted investigations. Management is guided by etiology and the presence of organ damage, with corticosteroids as first-line therapy in many cases and targeted therapies for clonal disease. The objective of this narrative, practical clinical review is to provide a structured, mechanism-based approach to the evaluation and management of peripheral eosinophilia, with emphasis on common reactive causes, recognition of organ involvement, and identification of high-risk clonal or hypereosinophilic presentations. Full article

Background: Allergic respiratory diseases, primarily asthma and allergic rhinitis, affect hundreds of millions worldwide. Their rising prevalence reflects complex gene–environment interactions that the exposome framework organizes into external, internal, and social domains shaping the development and progression of respiratory allergic diseases. Methods: Narrative review based on structured searches in PubMed/MEDLINE and Scopus (2015–2025), supplemented with 11 key references; 42 publications were selected from 1015 records. Results: Air pollution showed consistent but modest associations with asthma (HR 1.04–1.12); household dampness and mold showed larger effect sizes on symptom severity (OR 1.48–1.52); and occupational exposures showed the largest effect sizes across studies (RR 3.2–4.3). Systemic inflammation, oxidative stress, and nasal microbiome alterations were identified as internal mediators linking exposures to allergic phenotypes, though mechanistic pathways remain incompletely defined. Social exposome studies suggested context-dependent patterns: socioeconomic advantage correlated with greater sensitization in some settings, while deprivation could amplify disease progression and mortality risk (HR 1.18–1.32). Conclusions: The exposome offers a valuable integrative framework, but clinical translation is limited by scarce longitudinal multi-exposure studies and underrepresentation of low- and middle-income regions. Priorities include life-course cohorts integrating all three domains and targeted interventions in housing and occupational settings. Full article

Background: Brazilian wasp venoms represent a clinically relevant yet underexplored source of bioactive molecules with important implications for allergy, toxicology, and neuropharmacology. This review discusses the biological and immunological activities of venoms from Neotropical wasp species prevalent in Brazil, particularly within the genera Polybia, Synoeca, Polistes, and Agelaia, with emphasis on venom composition, IgE-mediated hypersensitivity, and ion-channel modulation. Methods: A narrative literature review was conducted using studies focused on venom characterization, electrophysiological effects, immune responses, and clinical manifestations associated with Brazilian and other Hymenoptera species. Results: Brazilian wasp venoms contain a diverse repertoire of peptides, enzymes, and low-molecular-weight compounds that act synergistically on multiple cellular targets. Among these, mastoparan-like peptides exhibit antimicrobial, immunomodulatory, and membrane-disruptive activities, contributing to inflammation and cellular dysfunction. In addition, several venom components interact with ion channels and neuronal receptors, modulating neuronal excitability and synaptic signaling, which highlights their potential applications in neuropharmacology. Simultaneously, allergenic proteins can induce IgE sensitization and immediate hypersensitivity reactions ranging from localized manifestations to systemic anaphylaxis. The marked taxonomic and biochemical diversity of Brazilian wasps contributes to substantial variability in venom composition and clinical outcomes. Conclusions: Overall, these venoms constitute a valuable and still insufficiently explored source of biologically active compounds with potential applications in allergy diagnosis, venom immunotherapy, and drug development. Full article

Allergic diseases are increasing globally, particularly among children, who are highly vulnerable due to critical windows of immune development. This review examines climate change as a key environmental determinant driving the rising burden of pediatric allergic diseases, including asthma, allergic rhinitis (AR), atopic dermatitis (AD), and food allergy (FA). Climate change influences disease risk through interconnected pathways, such as increased air pollution, altered aeroallergen patterns, and more frequent extreme weather events. Elevated carbon dioxide (CO₂) levels and rising temperatures prolong pollen seasons and enhance allergenicity, while pollutants such as ozone (O₃) and particulate matter (PM) exacerbate airway inflammation and immune dysregulation. Emerging evidence emphasizes the role of early-life exposure, particularly during prenatal and early postnatal periods, when environmental insults can induce long-term effects via epigenetic modifications and immune reprogramming. These mechanisms may increase susceptibility to allergic sensitization and subsequent disease development. Epidemiological studies consistently link exposure to air pollution, including PM_2.5 (PM with aerodynamic diameter < 2.5 μm) and nitrogen dioxide (NO₂), with increased risk of allergic diseases in children. Additionally, climate change-related events such as wildfires, sand and dust storms, and thunderstorms further elevate exposure to allergens and pollutants, contributing to acute exacerbations and disease progression. Climate change may also contribute to allergic diseases through microbiome dysbiosis, as altered environmental microbial exposures, biodiversity loss, air pollution, and antibiotic-associated microbial disruption may impair immune tolerance and promote allergic sensitization in children. Addressing this growing public health challenge requires integrated mitigation strategies to reduce greenhouse gas (GHG) emissions and improve air quality, alongside adaptive interventions to enhance resilience and reduce exposure. Understanding these mechanisms is essential for developing targeted prevention strategies and protecting child health in a changing climate. Full article

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by diverse and evolving clinical manifestations, often resulting in delayed diagnosis and increased morbidity. Although traditionally viewed as distinct, allergic and autoimmune diseases share overlapping immunologic pathways and clinical features. Symptoms commonly encountered in allergy practice, including urticaria, angioedema, and pruritus, may represent early or coexisting manifestations of underlying lupus rather than primary allergic disease. This narrative review examines the clinical and pathophysiologic overlap between allergy and lupus, with a focus on presentations that may bring patients with undiagnosed SLE to the allergy setting. Shared mechanisms, including complement dysregulation, autoreactive IgE, and mast cell activation, are discussed as contributors to overlapping symptomatology. Key clinical features that distinguish lupus-associated presentations from primary allergic conditions are outlined, along with associated systemic findings that should prompt further evaluation. A practical approach to assessment is emphasized, including targeted history, judicious use of serologic testing, and indications for dermatologic and rheumatologic referral. Improved recognition of these patterns in allergy practice may facilitate earlier diagnosis, reduce unnecessary testing, and improve patient outcomes. Full article

Approximately 10% of the general population reports a penicillin allergy, making it one of the most commonly documented drug allergies in clinical practice. Yet formal evaluation confirms true hypersensitivity in fewer than 10% of these cases. This gap has practical consequences. Patients who carry an inaccurate allergy label are more likely to receive broader-spectrum alternative antibiotics, with downstream effects on cost, adverse drug events, and antimicrobial resistance. Although primary care physicians are often the first to record these labels and the ones who face their consequences most often in daily prescribing, they have remained peripheral to most systematic delabeling efforts. In this narrative review, we examine how antibiotic allergy labels arise, why they persist, and what they cost—clinically, economically, and from a stewardship perspective. We also discuss emerging approaches to reassessment in primary care, including risk stratification tools and international guideline recommendations, along with the possible role of digital health tools and patient education in improving the accuracy of allergy documentation. Full article

Food allergy (FA) and eosinophilic esophagitis (EoE) represent two of the most rapidly increasing allergen-driven conditions in pediatric medicine. Both diseases share key immunological features, including Th2 polarization and epithelial barrier dysfunction. Over the past two decades, compelling epidemiological and mechanistic evidence has established EoE as a late-manifesting component of the allergic march—the well-recognized sequential progression of atopic disease in childhood, which typically begins with atopic dermatitis, followed by IgE-mediated food allergy, allergic rhinitis, and asthma. Children with IgE-mediated food allergy carry a substantially elevated risk of developing EoE, and shared genetic susceptibility loci—including CAPN14, TSLP, and filaggrin (FLG)—underscore common pathogenic pathways. We conducted a narrative review of the literature by systematically searching PubMed/MEDLINE, EMBASE, and the Cochrane Library using the terms “eosinophilic esophagitis,” “food allergy,” “atopic march,” “IgE-mediated allergy,” and “pediatric” in combination; articles published from 2000 to March 2026 were considered, with priority given to systematic reviews, meta-analyses, randomized controlled trials, and guideline documents. This narrative review comprehensively examines the epidemiology, pathomechanisms, clinical presentation, diagnostic approach, and therapeutic landscape for pediatric FA and EoE, with particular emphasis on their immunological intersections and the evolving evidence positioning EoE within atopic disease trajectories. We highlight approval of dupilumab for children as young as 1 year with EoE—representing a paradigm shift toward biologic therapy for atopic multimorbidity—and discuss the pipeline of emerging agents including cendakimab, lirentelimab, and anti-IL-5 strategies. Identification of shared pathogenic mechanisms offers promising avenues for unified prevention, early diagnosis, and precision therapeutic approaches for children with multiple atopic diseases. Full article

The widespread use of proton pump inhibitors (PPIs) in clinical practice has increased the number of related hypersensitivity reactions (HSRs). The active ingredient is not always responsible for the reaction. In some cases, HSRs may be related to the excipients contained in the drug. The adverse reactions to anti-SARS-CoV-2 vaccines have drawn the scientific community’s attention to the potential roles of excipients such as polyethylene glycol (PEG) and polysorbate 80. We present a case of a patient with three anaphylactic reactions following the administration of the anti-SARS-CoV-2 vaccine and a history of HSR to omeprazole. Through an in-depth medical history and allergy testing, we found that the patient was sensitized to PEG contained in the vaccine and to the omeprazole formulation used. We also conducted a mini-review of the literature, reporting all cases of reactions to PPIs, both related to the active ingredient and to excipients. Adverse reactions to PPIs are rare but still increasing. To our knowledge, this is the first reported case of anaphylaxis to PPI-related PEG. Some excipients are widely used in commonly used products, including non-pharmaceuticals. Therefore, in patients with multiple episodes of anaphylaxis, it appears necessary to exclude a possible allergy to excipients. This could ensure a greater safety and a better quality of life. Full article

Type 2 inflammation is a central immunopathogenic driver of chronic immune-mediated disease, characterized by IgE polarization, eosinophilia, epithelial barrier disruption, and tissue remodeling. In veterinary medicine, especially in canine atopic and allergic disorders, the absence of validated functional endpoints hampers disease monitoring and therapeutic assessment. In humans, this endotype underlies a spectrum of linked conditions, including asthma, allergic rhinitis, atopic dermatitis, and chronic rhinosinusitis with nasal polyps (CRSwNP), where olfactory dysfunction is common, quantifiable, and clinically meaningful. In this narrative review, we examine the relationship between type 2 inflammation and olfactory outcomes in human disease and consider its translational relevance in dogs within a reverse translational One Health framework. Evidence from human studies, particularly in CRSwNP, shows a strong association between type 2 inflammatory burden and olfactory loss, while biologics targeting these pathways yield clinically meaningful gains in smell function. Comparable clinical evidence is still lacking in dogs. Olfactory function should therefore be regarded as a promising, yet unvalidated, translational endpoint in canine type 2 disease and a priority for prospective clinical investigation and methodological validation. Full article

Background: Gestational diabetes mellitus (GDM) is an increasingly prevalent metabolic disorder of pregnancy. Beyond its well-established metabolic consequences, growing evidence suggests that exposure to maternal hyperglycemia during fetal life may influence immune system development and increase the risk of allergic diseases in offspring. Objective: This study aimed to systematically review the available evidence on the association between gestational diabetes mellitus and the development of allergic diseases in children, with particular emphasis on immunological mechanisms and the role of early-life gut microbiota. Methods: A systematic review was conducted using the PubMed and Scopus databases. Original human and animal studies, including cohort, case–control, cross-sectional, and clinical studies, were eligible for inclusion. Study selection followed PRISMA guidelines and was performed independently by three reviewers. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS) and Joanna Briggs Institute (JBI) Critical Appraisal Tools. Results: The included studies suggest that children born to mothers with GDM may have an increased risk of developing allergic diseases, particularly atopic dermatitis, food allergy, allergic rhinitis, and urticaria. Associations with childhood asthma were less consistent and appeared to depend on maternal body mass index, glycemic control, and duration of follow-up. Evidence suggests that maternal hyperglycemia may disrupt fetal immune programming through chronic low-grade inflammation, oxidative stress, altered cytokine profiles, and impaired regulatory T-cell development. Additionally, GDM has been associated with early alterations in neonatal gut microbiota composition and metabolic pathways, which may further contribute to immune dysregulation and increased susceptibility to allergic diseases. Importantly, effective metabolic control during pregnancy was associated with a lower risk of adverse allergic outcomes in offspring. Conclusions: GDM may represent an important prenatal exposure associated with altered immune maturation and a higher risk of allergic diseases in offspring. Early metabolic disturbances, immune dysregulation, and alterations in gut microbiota appear to be key mechanisms underlying this association. Optimizing glycemic control during pregnancy and implementing early-life preventive strategies may reduce the long-term burden of allergic diseases. Further well-designed longitudinal and mechanistic studies are required to clarify causal pathways and identify effective preventive interventions. Full article

Bacterial and fungal airway communities play a critical role in allergic respiratory diseases, yet they are often studied independently despite evidence of cross-kingdom ecological interactions. We investigated bacterial–fungal interactions across allergic rhinitis (AR), asthma (AS), allergic rhinitis with asthma comorbidity (ARAS), and healthy controls (HC) in a cohort of 286 participants (531 samples) using network analysis. Buccal and nasal samples were sequenced for 16S rRNA and ITS amplicons and networks constructed using sparse inverse covariance estimation for ecological association and statistical inference. Inferred bacterial–fungal connections comprised approximately one-third of the network edges. Taxonomic analyses of cross-kingdom-associated ASVs from the bacterial genera Dolosigranulum, Gamella, Haemophilus, Lawsonella, and Moraxella and the fungal genus Cladosporium revealed significant (p < 0.05) differences in mean relative abundance between the disease groups and healthy controls. Network topology analysis further identified distinct high-weight and high-degree microbial hubs, predominantly comprising fungal ASVs (Aleurina, Cladosporium, Malassezia, and Vishniacozyma) acting as putative keystone taxa and with disease-specific patterns. Together, these findings demonstrate that allergic airway diseases in this cohort are characterized by altered cross-kingdom network structure and disease-specific reorganization of microbial interaction patterns; this highlights the importance of integrated bacteriome–mycobiome analyses in understanding airway dysbiosis. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory dermatosis characterized by pruritus, eczematous lesions, and a fluctuating course. It imposes substantial quality-of-life and economic burdens through sleep disturbance, pain, psychosocial distress, and frequent healthcare utilization. Recent global estimates suggest AD affects hundreds of millions worldwide, with meaningful prevalence in both children and adults. AD pathogenesis is multifactorial, reflecting the interaction of genetic predisposition, immune dysregulation dominated by type 2 inflammation, epidermal barrier impairment, neuroimmune itch pathways, and microbial dysbiosis. Clinical diagnosis remains primarily clinical, supported by classic criteria emphasizing pruritus, typical morphology, chronicity, and atopic history. Disease severity and treatment response are commonly quantified using validated measures such as EASI and SCORAD, enabling standardized monitoring and evidence-based escalation. Management has shifted from broad immunosuppression to a stepwise, endotype-aware approach integrating barrier repair, anti-inflammatory topical therapy, phototherapy, conventional systemic agents, and rapidly expanding targeted options. Recent guidelines and approvals highlight increasing roles for biologics and JAK pathway inhibition, alongside newer nonsteroidal topicals. This review summarizes current concepts and practical treatment integration, with emphasis on safety, monitoring, and future research directions. Full article