Allergies doi: 10.3390/allergies6020017

Authors: Edward Sung Yashan Wang Marcos Pérez-Losada

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.

Allergies doi: 10.3390/allergies6020016

Authors: Caijun Jin Zhiyuan Ding Pham Ngoc Chien Chan Yeong Heo

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.

Allergies doi: 10.3390/allergies6020015

Authors: Zainab Al Alawi Rabab Abbas Majzoub Ossama M. Zakaria

Background: Cow’s milk protein allergy (CMPA) is a common cause of gastrointestinal and dermatologic symptoms in infancy. In clinical practice, infants with atopic dermatitis (AD) and suspected non-IgE-mediated CMPA are frequently managed with formula modification, although real-world comparative data across different formula strategies remain limited. Aim: To evaluate gastrointestinal symptom resolution, improvement in AD, and growth outcomes following formula modification in infants with AD and suspected non-IgE-mediated CMPA. Methods: This retrospective comparative cohort study included 107 infants aged ≤12 months with documented AD and suspected non-IgE-mediated CMPA evaluated at a tertiary academic center between January 2024 and December 2025. Infants were categorized according to initial management strategy: switch to extensively hydrolyzed formula (eHF; n = 63), switch to amino acid formula (AAF; n = 29), or continued standard cow’s milk-based formula (n = 15). The primary outcome was resolution of gastrointestinal symptoms within 2–4 weeks. Secondary outcomes included improvement in AD, weight gain, and need for further formula escalation. Multivariable logistic regression was performed to adjust for potential confounders. Results: Overall, gastrointestinal symptom resolution occurred in 74 of 107 infants (69.2%). Resolution rates were 71.4% in the eHF group, 79.3% in the AAF group, and 40% in the standard formula group (p = 0.01). In adjusted analysis, switching to eHF (aOR 2.8; 95% CI 1.1–7.3; p = 0.03) and AAF (aOR 4.1; 95% CI 1.3–12.5; p = 0.01) was independently associated with higher odds of symptom resolution compared with continued standard formula. Improvement in AD was observed in 57.9% of infants overall and differed significantly across groups (p = 0.04). Mean weight gain during follow-up did not differ significantly between groups (p = 0.63). Subsequent formula escalation was more frequent in the standard formula group (46.7%) compared with eHF (17.5%) and AAF (13.8%) groups (p = 0.004). Conclusions: In infants with AD and suspected non-IgE-mediated CMPA, substitution with extensively hydrolyzed or amino acid formula was independently associated with greater gastrointestinal symptom resolution and improvement in dermatitis compared with continued standard formula, without evidence of compromised growth. These findings provide supportive real-world evidence consistent with current international guidelines; however, given the observational design and potential for residual confounding, they should be interpreted as hypothesis-generating rather than confirmatory evidence of causal treatment effects.

Allergies doi: 10.3390/allergies6020014

Authors: George N. Konstantinou Konstantinos Petalas

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory syndrome of the sinonasal mucosa that is imperfectly captured by phenotypes with or without nasal polyps. Since allergic rhinitis (AR) and atopy often occur alongside CRS, the term “allergic CRS” is commonly used. However, it is uncertain whether this term indicates a specific allergen-related, IgE-mediated endotype or merely represents a clinical overlap. We synthesize epidemiologic data, mucosal immunobiology, epithelial barrier dysfunction, and host–microbe interactions that can generate IgE-rich type 2 inflammation in CRS. We propose an operational entity test (objective CRS; clinically relevant allergy; evidence of IgE relevance in target tissue; exposure–response patterns; and differential response to allergy-directed interventions) to guide hypothesis testing rather than diagnosis. Using this framework, allergic fungal rhinosinusitis and central compartment atopic disease emerge as the clearest clinical prototypes where allergen contact patterns and IgE relevance plausibly contribute to disease expression. In contrast, microbial superantigens and other non-allergen stimuli can drive local IgE amplification, limiting the specificity of systemic sensitization as a causal marker. We discuss therapeutic implications, including biologics targeting type 2 pathways and epithelial alarmin blockade, and outline research priorities for endotype-resolved cohorts and mechanism-informed trials to test whether allergic CRS should evolve from a heuristic descriptor into a validated endotype.

Allergies doi: 10.3390/allergies6020013

Authors: Yukihiro Yoshimura Aya Fujii

Background: High dietary salt intake has been implicated in immune-mediated inflammatory diseases; however, its impact on allergic contact dermatitis (ACD) remains unclear. This study examined whether dietary salt exposure during the sensitization phase influences the severity of DNFB-induced ACD in mice. Methods: Female C57BL/6N mice were fed a normal diet (ND) or an 8% high-salt diet (HSD). In a subset, salt intake was normalized prior to sensitization (HSD → ND). ACD was induced using a DNFB sensitization and challenge protocol. Ear swelling was quantified using incremental area under the curve (iAUC). Histological analyses and measurements of plasma and skin sodium were performed. Results: HSD-fed mice showed greater ear swelling and higher iAUC than ND controls, accompanied by enhanced inflammatory cell infiltration. Skin sodium concentration differed among groups, with a higher concentration in HSD-fed mice compared that in the HSD → ND group. Normalization of salt intake prior to sensitization attenuated disease severity. Spearman analyses indicated that total sodium intake and plasma potassium concentration were associated with inflammatory severity. Conclusions: Dietary salt exposure during immune sensitization exacerbated experimental ACD and was associated with systemic electrolyte alterations. These findings suggest that sodium exposure during immune activation may influence allergic skin inflammation.

Allergies doi: 10.3390/allergies6020012

Authors: Anuj Tharakan Ankit Kumar Carmen Camarena Daniel H. Conrad Rebecca K. Martin

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Allergies doi: 10.3390/allergies6020011

Authors: Maykon Jhuly Martins de Paiva Livia Cavalcante de Araújo Maressa de Oliveira Marinho Renata Ferreira Diogo de Paiva Vitória Pires dos Santos Costa Gabriela Pires Santomé de Faria Guilherme Silva de Souza Sávia Denise Silva Carlotto Herrera Iangla Araújo de Melo Damasceno Taides Tavares dos Santos Juliane Farinelli Panontin Walmirton Bezerra D’Alessandro

Chronic urticaria (CU) is a mast cell-driven inflammatory skin disorder characterized by recurrent wheals, angioedema, or both lasting more than six weeks, often resulting in significant impairment of quality of life. Although CU has traditionally been regarded as a predominantly histamine-mediated condition, evidence accumulated over the past decade has redefined chronic spontaneous urticaria (CSU) as a complex immune-mediated disease with marked biological heterogeneity. Distinct pathogenic mechanisms involving autoimmune pathways, dysregulated mast cell activation, and chronic inflammatory networks have been identified, providing a mechanistic basis for disease persistence, variable severity, and therapeutic refractoriness. This review synthesizes current concepts in CSU pathophysiology, with emphasis on mast cell biology, autoimmune endotypes, and inflammatory amplification mechanisms. We further discuss emerging biomarkers with potential relevance for disease stratification and treatment prediction, as well as established and novel therapeutic strategies targeting key pathogenic pathways. By integrating mechanistic insights with clinical implications, this review highlights the transition toward endotype-driven and biomarker-guided management of chronic urticaria.

Allergies doi: 10.3390/allergies6010010

Authors: Giulia Laterra Federica Giammona Indaco Simone Bongiorno Antonino Maniaci Salvatore Maira Mariangela Lodato Carmelo Battaglia Marco Barbanti Cosimo Galletti

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease effectively treated with dupilumab, a monoclonal antibody that inhibits IL-4 and IL-13 signaling. Dupilumab is an effective treatment for type 2 inflammatory diseases such as CRSwNP. Although efficacy of dupilumab in controlling upper airway inflammation is well established, concerns have emerged regarding its potential cardiovascular effects. Emerging evidence suggests that IL-4/IL-13 signaling plays a protective role in post-myocardial infarction remodeling by promoting anti-inflammatory macrophage polarization, angiogenesis, and controlled fibrosis, especially during the early healing phase. Pharmacological blockade of the IL-4/IL-13 signaling pathway, such as that induced by dupilumab, may theoretically impair myocardial repair mechanisms, particularly in male patients who appear more responsive to these cytokines. Although rare, dupilumab-associated hypereosinophilia and myocarditis have been reported. In patients with pre-existing ischemic heart disease or heart failure, a multidisciplinary risk–benefit evaluation should be considered. Concomitant use of cardioprotective agents such as sacubitril/valsartan or SGLT2 inhibitors may help mitigate potential cardiac risks. Future studies are needed to clarify the safety and therapeutic implications of combining dupilumab with cardiovascular therapies in patients with coexisting CRSwNP and heart disease. This review critically evaluates emerging evidence of potential interference with post-infarction myocardial repair and highlights the importance of a multidisciplinary approach in managing patients with coexisting inflammatory and cardiovascular diseases. The aim of this review is to explore the available data on the cardiovascular impact of dupilumab and to provide possible future perspectives.

Allergies doi: 10.3390/allergies6010009

Authors: Lara Barros Diana Arantes Leonor Nora Inês Pádua

Background: Current recommendations for infant weaning suggest the early introduction of solid and diverse foods. Although homemade meals are advisable, there is a demand for commercially available complementary foods (CACFs), and the information present on their labeling influences caregivers’ choices. The aim of this study was to evaluate recommended-age-of-introduction labeling of CACFs in the Portuguese market, in light of current guidelines for complementary feeding. Methods: Between November and December 2025, labels of all CACFs found in infant feeding sections of 13 Portuguese grocery retailers were analyzed. Milk formulas, powders, products for children over 15 months, and those for children with food allergies or intolerances were excluded. Results: Of the 539 products analyzed, 458 showed a recommended age for introduction, ranging from 4 to 12 months, with significant variability being observed between food categories. Significant variability was also observed in the recommended age for introduction depending on whether major allergens were present. Conclusions: The results of our study identified an age-segmented approach to complementary feeding recommendations in CACF labeling, not reflecting current infant feeding guidelines that support complementary feeding. Our results reinforce the need for more support from scientific evidence and health guidelines in food availability and marketing.

Allergies doi: 10.3390/allergies6010008

Authors: Marine Delmas Manon D’Almeida Séverine Dameron-Puech Nicolas Macian Gisèle Pickering Rémi Shrivastava

(1) Allergic rhinitis (AR) is a chronic inflammatory condition of nasal mucosa that impairs quality of life (QOL). Beyond pharmacological treatments, some patients seek non-pharmacological options due to side effects or incomplete symptom control. Allerspray-G (AAG) is a barrier-forming Class IIa medical device (Medical Device Regulation (MDR) 2017/745) designed to reduce allergen contact and alleviate AR symptoms. This study evaluated the safety and efficacy of AAG in adults with AR in a real-life post-marketing setting through an open-label, single-center investigation using a two-stage Fleming design. (2) Tolerance was the primary outcome, assessed through the monitoring of adverse events. Secondary outcomes included efficacy measures, evaluated using the Total Nasal Symptom Score (TNSS) and patient-reported QOL outcomes. (3) In total, 20% reported a possible or probable event related to AAG, with all being mild. The TNSS decreased significantly from baseline (mean change: −1.94, p < 0.001), and 73.3% achieved a ≥30% reduction. Significant improvements were also observed across all QOL domains (p < 0.05). (4) AAG was safe, well tolerated, and improved nasal symptoms and QOL, supporting its use as a non-pharmacological option for symptom relief in allergic rhinitis. These findings are consistent with and further reinforce results from the initial 2017 clinical study.

Allergies doi: 10.3390/allergies6010007

Authors: Federica Trovato Antonio Di Guardo Maria Elisabetta Greco Giovanni Grossi Annunziata Dattola Steven Paul Nisticò Giovanni Pellacani

Urticaria is a mast cell-mediated disorder commonly encountered in women of reproductive age, making its interaction with pregnancy clinically relevant. Gestation induces profound hormonal and immunologic adaptations—including shifts between Th1/Th17 and Th2/Treg responses and sustained exposure to sex steroids and placental hormones—that can modulate mast cell reactivity. As a result, chronic urticaria (CU) shows heterogeneous behavior during pregnancy: approximately half of patients improve, one third worsen, and the remainder remain stable. Pregnancy also presents several urticaria-like dermatoses, notably polymorphic eruption of pregnancy (PEP/PUPPP), atopic eruption of pregnancy (AEP) and pemphigoid gestationis (PG), as well as rare hormone-induced hypersensitivity reactions. Additionally, systemic disorders such as intrahepatic cholestasis of pregnancy (ICP), chronic kidney disease–associated pruritus and urticarial vasculitis may mimic urticaria but differ markedly in prognosis, maternal–fetal risk and management. Given this complexity, accurate diagnosis requires integration of temporal pattern, lesion morphology and duration, distribution, systemic features and targeted investigations, as outlined in the diagnostic algorithm proposed. Most pregnancy-specific eruptions are benign, whereas PG, ICP and urticarial vasculitis warrant prompt recognition due to potential fetal implications. Management of CU in pregnancy generally follows standard guidelines, with second-generation H1-antihistamines as first-line therapy and omalizumab reserved for severe refractory cases.

Allergies doi: 10.3390/allergies6010006

Authors: Luigi Cofone Marise Sabato

Introduction: The potential role of food hypersensitivity in the insurgence of inflammatory activity in arthritis such as Rheumatoid Arthritis (RA) has received intermittent attention, also supported by theoretical links involving mucosal immunity, mast-cell activation, and microbiome–immune interactions. Despite biological plausibility, the clinical significance of dietary antigens in RA remains uncertain. Methods: A systematic review was conducted following the PRISMA guidelines. Searches using PubMed, Scopus, and Web of Science identified studies exploring dietary interventions or food hypersensitivity in RA. Eligible articles included clinical trials, case reports, and observational studies, in English or Italian, up to the 10 December 2025. Data extraction and quality assessment were performed using the Newcastle–Ottawa Scale. Results: Eight studies met the inclusion criteria. Findings indicate that elimination or elemental diets occasionally yielded subjective improvements—such as a reduction in pain, morning stiffness, and functional improvements—yet objective inflammatory markers rarely changed. Small, highly selected, cohorts demonstrated immuno-histological alterations, including reduced mast-cell density, while long-term diets (e.g., gluten-free or vegan) have reduced specific IgG levels without altering radiographic progression. Conclusions: Evidence suggests that dietary interventions may offer symptomatic relief only in a minority of RA patients. Due to methodological constraints, inconsistent outcomes, and limited applicability to contemporary treatments, dietary approaches need further exploration and investigation. Rigorous trials in modern cohorts are warranted to clarify whether food hypersensitivity meaningfully influences RA pathophysiology.

Allergies doi: 10.3390/allergies6010005

Authors: Claire Chitty Lerato Obadimeji Rafah Mahmood Amy Skett Catherine J. Hornung Rani Scott Farmer Sandra Vale Jennifer J. Koplin Michaela Lucas James Yun Sandra M. Salter

Penicillin allergy delabelling improves patient outcomes, reduces healthcare costs, and supports antimicrobial stewardship. While PADL protocols (PADL-P) are increasingly used in clinical practice, the consistency of Australian PADL-Ps and their alignment with established guidance remain unclear. A cross-sectional study (from June to August 2025) identified Australian PADL-Ps through organisational and professional outreach, the literature, and structured internet searches. Protocol features were extracted iteratively and deductively. Citation counts and overlap were determined using the Graphical Representation of Overlap for OVErviews (GROOVE) methodology. Protocols were applied to 20 validated penicillin allergy scenarios, and the Australasian Society for Clinical Immunology and Allergy (ASCIA) Consensus Statement for the Management of Suspected Penicillin Allergy and risk alignment were compared. Fifteen Australian PADL-Ps were identified. They shared similar features; however, differences were observed in the no/low-risk criteria and subsequent delabelling actions. Protocols cited a mean of nine references (mean of 4.7 (43.9%) unique), with one protocol citing no references. When applied to clinical scenarios, protocol-assigned risk did not consistently align with the ASCIA risk classification (54.6% of adult and 77.8% of paediatric protocols assigned scenarios to the same risk level). Adult protocol alignment was lowest for no-risk (31.9%) and low-risk (50.0%) scenarios and highest for moderate-risk scenarios (78.8%), whereas paediatric protocol alignment was 33.3% for moderate risk and 100% for low and high-risk scenarios. Although Australian PADL-Ps shared core structural features, incongruencies in risk criteria and alignment with established guidelines may result in different clinical outcomes for patients with similar penicillin allergy histories. These findings emphasise the complexity of clinical decision-making around penicillin allergy and suggest a need for standardisation of PADL-Ps to maximise delabelling benefits and safety across Australian healthcare settings.

Allergies doi: 10.3390/allergies6010004

Authors: Ramon Grimalt

Background: Dermatitis affecting the earlobe is a highly frequent clinical presentation, predominantly attributed to Allergic Contact Dermatitis (ACD) caused by metallic ions like nickel from earrings. However, a significant subset of patients presents with recurrent eczematous lesions highly suggestive of ACD but with inconclusive or negative patch test results, posing a profound diagnostic and therapeutic dilemma. Objective: This comprehensive review critically evaluates the differential diagnosis of earlobe eczema in the context of negative patch tests. Drawing from a representative case of a 30-year-old female with recurrent earlobe eczema and a strong family history of psoriasis, we explore alternative non-immunological and endogenous mechanisms, specifically Irritant Contact Dermatitis (ICD) and the Koebner Phenomenon on a background of Psoriatic Diathesis. Methods: We performed an extensive review of the current literature focusing on the epidemiology and pathogenesis of metal ACD, non-allergic mechanisms of jewelry-induced dermatitis (ICD), the molecular basis of the Koebner phenomenon, and the clinical overlap between eczema and psoriasis (Eczematous Psoriasis). Results: The localized nature of the inflammation, coupled with the absence of generalized nickel sensitivity, strongly suggests that the mechanical and occlusive trauma from earrings can induce a purely irritant reaction. Crucially, the presence of a familial psoriatic diathesis supports the hypothesis that this local irritation acts as a Koebner phenomenon trigger, leading to an eczematous manifestation of an underlying psoriatic tendency. Conclusions: Not all recurrent eczematous lesions at common contact sites are caused by ACD. Clinicians must adopt an integrated diagnostic approach, factoring in personal and family history alongside patch test results, to differentiate true allergy from ICD and the Koebner phenomenon. This nuanced perspective is vital for providing appropriate counseling (strict jewelry avoidance) and targeted, often steroid-sparing, management (e.g., topical calcineurin inhibitors) for a durable therapeutic outcome.

Allergies doi: 10.3390/allergies6010003

Authors: Katarzyna Napiorkowska-Baran Alicja Gruszka-Koselska Karolina Osinska Gary Andrew Margossian Carla Liana Margossian Aleksandra Wojtkiewicz Pawel Treichel Jozef Slawatycki

Food allergy diagnosis remains challenging due to the difficulty of distinguishing true clinical allergy from asymptomatic sensitization. Inaccurate diagnosis may result in unnecessary dietary restrictions, reduced quality of life, or, conversely, failure to identify individuals at risk of severe allergic reactions. This review critically analyzes the efficacy, limitations, and clinical utility of currently available diagnostic tests for food allergy, with particular emphasis on their ability to predict true clinical reactivity. A comprehensive literature review was conducted to evaluate the sensitivity, specificity, and predictive values of both traditional and emerging diagnostic modalities. English-language guidelines, systematic reviews, and key clinical studies published primarily within the past 15 years (up to 2025) were identified through PubMed and Google Scholar. Classic diagnostic tools, including skin prick testing (SPT) and serum-specific IgE (sIgE), were assessed alongside novel approaches such as component-resolved diagnostics (CRD), basophil activation test (BAT), mast cell activation test (MAT), atopy patch testing (APT), cytokine profiling, and omics-based diagnostics. Particular attention was given to how these tests compare with the oral food challenge (OFC), which remains the diagnostic gold standard. The findings demonstrate that while conventional tests offer high sensitivity and are valuable for initial risk assessment, their limited specificity often leads to overdiagnosis. Emerging molecular and cellular assays show improved specificity and functional relevance, especially in complex cases involving polysensitization or unclear clinical histories and may reduce reliance on OFCs in the future. However, accessibility, cost, and lack of standardization currently limit their widespread clinical application. Advances in artificial intelligence and data integration hold promise for improving diagnostic accuracy through enhanced interpretation of complex immunological data. Based on the synthesized evidence, this review proposes an evidence-based, stepwise, and individualized diagnostic algorithm for food allergy. Integrating clinical history, targeted testing, and selective use of OFCs can improve diagnostic certainty, enhance food safety, minimize unnecessary dietary avoidance, and optimize patient outcomes. The review underscores the need for continued research, standardization, and validation of novel diagnostic tools to support personalized and precise food allergy management.

Allergies doi: 10.3390/allergies6010002

Authors: Diana Mitkova Hristova Martin Vladimirov Bozhidar Karamishev Anatoli Kolev Daria Koleva Liliya Koleva Victoria Spasova Svetlana Shumarova Vesela Karamisheva

Background: Presence of milk, fruits, eggs, fish, nuts and wheat antigens in the amniotic fluid is described in the literature. Studies show a contradictory relationship between maternal exposure to allergens and early sensitization of the fetus to allergens. Hemochorionic type of the human placenta allows for easier transfer of nutrients and antibodies from the mother’s blood to the fetal circulation through the direct contact of maternal blood with the fetal chorion. During the third trimester of pregnancy, immunoglobulin G (IgG) is actively transferred through the placenta into the fetal via neonatal FcRN receptor (FcRN). In addition, monomeric immunoglobulin E (IgE) cannot cross the placenta Aim: The objective of our study is to track intrauterine sensitization to essential food proteins at birth in umbilical cord blood in mothers with established peripheral blood eosinophilia and in their infants using allergen-specific IgE and IgG. Methods: An observational study was carried out in a cohort of 22 mothers with eosinophilia and their babies. Differences in expression between groups were assessed. Blood samples were collected to determine serum IgE and IgG specific to a set of inhalant and food allergens. Results: We did not find a significant correlation between specific IgE to cow’s milk (p = 0.857), egg white (p = 0.926) and egg yolk (p = 0.096) in umbilical cord blood and maternal blood samples taken immediately before birth. Spearman’s correlation of the specific IgE and IgG in umbilical cord blood showed no dependence between the two variables. In contrast, statistical analysis showed that maternal eosinophilia in peripheral blood could be a risk factor for the development of allergy in the offspring (χ2, p = 0.0347). However, given the small number of patients, this claim needs to be confirmed with further studies. Conclusions: Due to the functional immaturity of the developing immune system of the fetus, the generation and maintenance of an independent immune response to allergens are incomplete. Maternal IgG (specific) passes to the baby and high maternal IG to a specific allergen reduces babies IgE production. In addition, low maternal specific IgG may promote IgE production in the baby under the influence of microenvironmental factors (cytokine background). The main limitation of our study is the small number of patients. Further research is needed in this direction to clarify the mechanisms and risk factors for early sensitization in newborns.

Allergies doi: 10.3390/allergies6010001

Authors: Marta Trujillo Beatriz Beroiz Carmen Cuadrado Rosario Linacero Isabel Ballesteros

Lupin (Lupinus spp.) is increasingly incorporated into processed foods as a gluten-free ingredient and alternative protein source, but it is also a regulated allergen in the European Union due to cross-reactivity with other legumes, especially peanut. Reliable methods for detecting undeclared lupin traces in complex food matrices are therefore essential for consumer protection. In this study, a loop-mediated isothermal amplification (LAMP) assay was developed for rapid and sensitive detection of lupin DNA. Several nuclear and chloroplast regions were evaluated for primer design, and gene encoding the Lup a 1 allergen was selected as the optimal target. Amplification was monitored by real-time fluorescence, agarose gel electrophoresis, and visual colorimetry. The selected primer set achieved a detection limit of 25 pg of lupin DNA and consistently detected lupin in binary mixtures down to 10 mg/kg, with no cross-reactivity against closely related legumes or tree nuts. Application to processed foods confirmed detection in products declaring lupin and revealed potential undeclared presence in some commercial samples. Colorimetric detection provided reliable results comparable to real-time monitoring, enabling simple readouts without specialized equipment. Overall, the developed LAMP assay represents a rapid, specific, and sensitive alternative to PCR-based methods for allergen monitoring and food safety management.

Allergies doi: 10.3390/allergies5040044

Authors: Lucio H. T. Fung Ho Lam Yeung Chun Wai Lim Shan Jiang Nicki Y. H. Leung Patrick S. C. Leung Ting Fan Leung Christine Y. Y. Wai

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.

Allergies doi: 10.3390/allergies5040043

Authors: Aleksandra Ossowska Adrian T. De Jager Kasith Abdul Cader Danusha Sanchez

Pediatric food allergies are an escalating public health concern, with nut allergies representing a primary cause of persistent hypersensitivity and anaphylaxis. New data suggests that pediatric populations with multiple nut allergies (MNA) may be at higher anaphylaxis risk than their counterparts with single nut allergies. Despite this, there is an absence of literature posing multiple nut allergies against singular nut allergy cases. The majority of the research in this topic is directed towards singular nut allergy, without any differentiation between children with one versus multiple sensitivities. Epidemiological evidence indicates that multiple nut allergies are associated with lifelong sensitization, high cross-reactivity potential and increased risk and severity of reactions. Compounding clinical risk factors reinforce the already high risk associated with MNA and indicate that these children require careful monitoring and individual management. Diagnostic tools, including component-resolved diagnostics and oral food challenges, enable differentiation between true multi-nut sensitization and cross-reactivity, guiding targeted interventions. Management strategies must therefore be multifaceted, encompassing selective allergen avoidance, emergency preparedness with epinephrine auto-injectors, asthma control, nutritional support, and psychosocial care. Recognizing MNA as a distinct, high-risk phenotype highlights the necessity of precision-based, biomarker-driven clinical approaches to optimize safety, reduce morbidity, and improve quality of life for affected pediatric populations.

Allergies doi: 10.3390/allergies5040042

Authors: Prashant Kaushik Faryal S. Bhatti Tanmay Bangale Creticus P. Marak

Alpha-gal syndrome (AGS) is an emerging, relatively newly recognized allergic disorder with clinical manifestations that occur as a result of hypersensitivity reactions to oligosaccharide galactose-α-1,3-galactose (α-gal), a carbohydrate present in lower-mammalian meat, dairy products, and some biopharmaceutical products. These reactions are delayed with oral ingestion of the antigen but can be immediate with intravascular or other parenteral antigenic exposure. Over the past 15 years, many revelations have occurred in the realm of AGS. However, there is still a huge unmet need related to its pathophysiology, diagnostics, timely recognition, and management. This article is geared towards providing a review of AGS for healthcare providers (HCPs) from all realms of medicine. It is a universal challenge, with cases being recognized from various parts of the world. Hence, it is critically important for HCPs planet-wide to pay heed to the prompt recognition of AGS and educate their patients. This can prevent morbidity as well as potentially fatal complications like severe anaphylaxis. It is a narrative clinical review. The PubMed database was searched from 2009 to 2025. Alpha-gal syndrome and related topics were included in the search engine.

Allergies doi: 10.3390/allergies5040041

Authors: Francois Rosset Valentina Pala Umberto Santaniello Valentina Celoria Luca Mastorino Federico Goso Andrea Pucciariello Eleonora Bongiovanni Simone Ribero Pietro Quaglino

Background: Pruritus is burdensome across dermatoses. Beyond Staphylococcus, broader components of the cutaneous microbiome—bacteria, fungi, and viruses—and their products shape itch via barrier disruption, immune polarization, and direct neurosensory activation. Methods: We conducted a narrative review of human and translational studies. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to 27 August 2025 using terms for itch, skin microbiome, bacteriotherapy, proteases, PAR, TRP channels, IL-31, Malassezia, and AHR ligands. English and Italian records were screened; randomized trials, systematic reviews, and mechanistic studies were prioritized; and unsupported single case reports were excluded. Results: Beyond Staphylococcus aureus, microbial drivers include secreted proteases activating PAR-2/4; pore-forming peptides and toxins engaging MRGPRs and sensitizing TRPV1/TRPA1; and metabolites, especially tryptophan-derived AHR ligands, that recalibrate barrier and neuro-immune circuits. Commensal taxa can restore epidermal lipids, tight junctions, and antimicrobial peptides. Early studies of topical live biotherapeutics—Roseomonas mucosa and Staphylococcus hominis A9—report reductions in disease severity and itch. Fungal communities, particularly Malassezia, contribute via lipases and bioactive metabolites with context-dependent effects. Across studies, heterogeneous itch metrics, small samples, and short follow-up limit certainty. Conclusions: The cutaneous microbiome actively contributes to itch and is targetable. Future studies should prioritize standardized itch endpoints, responder stratification, and robust safety for live biotherapeutics.

Allergies doi: 10.3390/allergies5040040

Authors: Ernestina B. Hansen-Sackey Stella Hartono

Atopic dermatitis (AD) is a chronic inflammatory skin disease marked by pruritus and eczematous lesions that significantly impacts patient quality of life. This review covers the intricate interplay of barrier dysfunction, immune dysregulation, and microbial dysbiosis in the complex pathophysiology of AD. The roles of epigenetic factors and environmental exposures are also examined. The evolving understanding of these factors has revolutionized AD treatment. Beyond foundational topical agents, the landscape for moderate-to-severe AD treatment is now dominated by highly targeted immunotherapies, such as biologics and Janus Kinase (JAK) inhibitors, that precisely block specific inflammatory pathways. Emerging strategies explore microbiome modulation and vitamin D supplementation. This paradigm shift from broad immunosuppression to precision medicine offers improved disease control and reduced systemic toxicities and enables more personalized AD management, significantly benefiting patients.

Allergies doi: 10.3390/allergies5040039

Authors: Lauren Trzcinski Suhas Bharadwaj Randall A. Bloch Joseph K. Han Kent K. Lam

Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) are common comorbid sinonasal conditions. CRS is classically divided into two distinct phenotypes: CRS with nasal polyposis (CRSwNP) and CRS without nasal polyposis (CRSsNP). The purpose of this retrospective observational study is to determine whether aeroallergen sensitization profiles in patients with comorbid CRS and AR can distinguish between CRSwNP and CRSsNP. A total of 241 patients diagnosed with comorbid CRS and AR who underwent skin prick testing or in vitro allergy testing in a single tertiary rhinology practice were included for evaluation. The rates of allergen-specific sensitizations in CRSwNP patients were compared with those in CRSsNP patients. Of the allergens tested in the routine panels, Dermatophagoides pteronyssinus (OR = 1.82, p = 0.03), Alternaria (OR = 2.55, p < 0.01), and animal dander (OR = 1.48 for cat and OR = 3.01 for dog, p < 0.01) were predictive of CRSwNP. Sensitization to any grass allergen was also predictive of CRSwNP (OR = 2.09, p < 0.01). Multiple perennial aeroallergens showed strong associations with CRSwNP; however, broad sensitization to perennial allergens as a whole group was not significantly predictive of CRSwNP (OR = 1.83, p = 0.22).

Allergies doi: 10.3390/allergies5040038

Authors: Emília Ma. Medeiros de Andrade Belitardo Paula C. Almeida Flávia A. Sena Eduardo S. Silva Danilo J. P. G. Rocha Juliana Mendonça Carina S. Pinheiro Peter Briza Fatima Ferreira Lúcio R. Queiroz Eric R. G. R. Aguiar Álvaro A. Cruz Luis G. C. Pacheco Neuza M. Alcantara-Neves

Severe asthma is a heterogeneous condition often resistant to conventional corticosteroid therapy, necessitating the identification of novel biomarkers and therapeutic targets. This study investigates immunological, transcriptional, and proteomic biomarkers in severe asthma patients from the Brazilian ProAR cohort. Cytokines were measured using a multiplex technology and the differential sputum cell count was performed by cytospin preparations. Sputum transcriptomics was performed by RNA-seq using Ion S5 next-generation sequencing platform. The proteomic study of sputum was performed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) using Q Exactive Orbitrap technology. Compared to mild-to-moderate asthma (MMA) and treatment-controlled severe asthma (SAC), the treatment-resistant severe asthma (SAR) group exhibited increased sputum neutrophilia, eosinophilia, and elevated IL-6 and TNF levels, correlating with impaired lung function. Transcriptomic and proteomic analyses revealed a Th2-independent molecular signature characterized by downregulation of the Hippo signaling pathway and upregulation of JAK–STAT inflammatory cascades. Distinctive microRNA profiles suggest regulatory involvement in inflammatory and proliferative processes. These findings align with prior studies, reinforcing the presence of an IL-6- and TNF-high severe asthma phenotype across diverse populations. Our results highlight key inflammatory pathways that may underlie corticosteroid resistance, offering potential targets for personalized therapeutic interventions in severe asthma.

Allergies doi: 10.3390/allergies5040037

Authors: Christos Kogias Elpis Hatziagorou

Atopic eczema is the most prevalent chronic dermatitis in childhood, characterised by relapsing pruritic lesions and significant heterogeneity in clinical expression and immunological profile. The disease impacts quality of life and healthcare systems, especially when persistent into adulthood. Epidemiological data from the International Study of Asthma and Allergies in Childhood (ISAAC) demonstrate significant geographic and temporal variability in the prevalence of atopic eczema, with an overall upward trend observed in paediatric populations across most regions. A systematic literature search was conducted in PubMed, ScienceDirect, and the Cochrane Library to identify relevant studies published between 1990 and 2025. Seven studies met the inclusion criteria—six cross-sectional and one prospective—conducted in the urban centres of Athens, Thessaloniki, and Patras. Sample sizes ranged from 517 to 3076 participants, encompassing children and adolescents aged 6 to 17. Prevalence rates ranged from 4.5% to 16.1% in children and 8.9% in adolescents, with notable geographic and temporal variability. Male sex, younger age, environmental exposures, and a family history of atopic diseases were identified as key risk factors. Comparative data from European studies reflect similar trends, with increasing atopic eczema prevalence and plateauing asthma rates suggesting distinct etiological pathways. The psychosocial and economic burden of atopic eczema remains substantial, highlighting the need for early recognition and effective management. Despite methodological variability and limitations in study design, findings indicate an underestimation of atopic eczema prevalence in Greece and underscore the importance of standardised epidemiologic surveillance.

Allergies doi: 10.3390/allergies5040036

Authors: Taeuk Kang

Background/Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disorder increasingly recognized for its association with psychiatric comorbidities. However, the extent of this association compared to dermatologic controls in Asian populations remains underexplored. We sought to evaluate the prevalence and risk of psychiatric comorbidities in adult patients with AD compared to those with melanocytic naevi using a nationwide population-based cohort. Methods: We conducted a retrospective cohort study utilizing the Korean National Health Insurance Service (NHIS) database, including individuals diagnosed with AD (ICD-10 code L20.0) or melanocytic naevi (ICD-10 code D22, excluding melanoma) between 1 January 2010 and 31 December 2023. Patients were required to have at least five years of diagnostic history and be 25 years or older at the end of the study. Psychiatric comorbidities were identified based on ICD-10 codes. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to compare psychiatric morbidity between groups. Results: Among 1,902,114 individuals (1,813,320 with AD and 88,794 with naevi), psychiatric comorbidities were more prevalent in the AD group (28.2%) compared to the naevi group (27.1%) (adjusted OR 1.04, 95% CI 1.02–1.05). While differences for major depression, bipolar disorder, and personality disorders were not statistically significant, other psychiatric categories suggested significantly higher prevalence in the AD group. Sex-stratified analysis revealed a higher overall psychiatric morbidity in women compared to men; however, the relative risk increase associated with AD was slightly greater in men than in women. Comparison with previous international studies suggests that Korea’s healthcare accessibility and nationwide mental health programs may contribute to the smaller observed difference. Conclusions: This large-scale cohort study highlights a modest but significant association between AD and psychiatric comorbidities in adults. Our findings underscore the importance of integrating mental health assessment into routine dermatologic care for AD patients to improve comprehensive disease management.

Allergies doi: 10.3390/allergies5040035

Authors: Bruno Marques Vieira

Glucocorticoids (GCs) remain the cornerstone of asthma treatment due to their potent anti-inflammatory and eosinophil-suppressive effects in the airways, including the induction of peripheral eosinophil apoptosis and downregulation of type 2 cytokine signaling. However, emerging evidence reveals a paradoxical role for GCs in the bone marrow, where they enhance eosinophil production (eosinopoiesis), especially under allergic, infectious, or surgical stress conditions. This duality reflects a complex immunoendocrine interplay involving GC-induced modulation of eosinophil progenitor survival, proliferation, and responsiveness to eosinopoietic cytokines such as interleukin-5 and granulocyte-macrophage colony-stimulating factor. Furthermore, GCs synergize with lipid mediators like cysteinyl-leukotrienes and prostaglandins, modulating both transcriptional and adhesion molecule profiles that prime eosinophil precursors for migration and differentiation. This review examines the molecular and cellular mechanisms underlying GC-induced eosinopoiesis, its functional link to airway inflammation, and its clinical implications for asthma management. We also explore potential therapeutic strategies aimed at selectively modulating bone marrow eosinophil output without compromising the peripheral anti-inflammatory benefits of GCs. Understanding this paradoxical duality holds significant translational potential for improving disease control and preventing asthma exacerbations.

Allergies doi: 10.3390/allergies5040034

Authors: Victor Alexandru Felicia Manole Alexia Manole

Both allergic rhinitis and chronic rhinosinusitis with or without nasal polyps have important factors in common with asthma. They are often present simultaneously, they have similar pathogenesis processes, and they have synergistic effects on the clinical manifestations. There are also important considerations regarding the common treatment of these pathologies. Taking all these into account, it is possible to place these diseases under the “united airway disease” umbrella. However, matters such as embryologic origins, anatomy and function of the upper and lower airways, as well as cases where the aforementioned pathologies can be observed independently and have different treatment responses, make up reasonable counterarguments for the “united airway disease”. This narrative review attempts to put all these factors into perspective for a slightly better understanding of the complexity of this topic. We will take into consideration factors such as epidemiological data, pathogenesis and pathology, clinical considerations, and the benefits of a common treatment.

Allergies doi: 10.3390/allergies5040033

Authors: Cintia Estefano Alves Tawany Gonçalves Santos Luana Beatriz Vitoretti Cinthya Cosme Gutierrez Gutierrez Duran Stella Zamuner Rodrigo Labat José Antonio Silva Maria Cristina Chavantes Flavio Aimbire Renata Kelly da da Palma Ana Paula Ligeiro de de Oliveira

This study aimed to evaluate the effects of different dosimetric parameters of photobiomodulation therapy (PBMT) in an experimental model of chronic obstructive pulmonary disease (COPD). C57BL/6 mice were assigned to the following groups: Baseline, COPD, and COPD treated with PBMT at doses of 1 J, 3 J, 5 J, and 7.5 J. Treatment was performed using a diode laser (660 nm, 100 mW) applied for 10 s, 30 s, 50 s, and 120 s, respectively, over 15 consecutive days. COPD was induced by orotracheal instillation of cigarette smoke extract twice weekly for 45 days. Analyses included total cell count, immune cell profiling by flow cytometry, pulmonary infiltration of inflammatory markers, necrosis, apoptosis, and reactive oxygen species (ROS) production. Data were analyzed using one-way ANOVA followed by the Newman–Keuls post hoc test, with statistical significance set at p < 0.05. PBMT significantly reduced inflammatory cell infiltration, with the most pronounced anti-inflammatory effects observed at doses of 1 J and 3 J, highlighting the importance of appropriate dosimetry in optimizing the therapeutic outcomes of PBMT for COPD.

Allergies doi: 10.3390/allergies5040032

Authors: Christian Messina Mariateresa Zuccarello

Pruritus (itching) is an underrecognized but often debilitating symptom in patients with central nervous system (CNS) demyelinating diseases, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). It is often considered a paroxysmal symptom. Although less studied than pain or spasticity, pruritus can significantly impair the quality of life. This review aims to provide a comprehensive overview of the pathophysiological mechanisms underlying pruritus in demyelinating CNS disorders, its clinical presentations, and the available treatment options. We explore the central origins of neuropathic itch, focusing on spinal cord, brainstem, and cerebral lesions, with particular emphasis on white matter involvement and spinothalamic tract dysfunction. In addition, we review pruritus triggered or exacerbated by disease-modifying therapies (DMTs) used in MS and NMOSD.

Allergies doi: 10.3390/allergies5030031

Authors: Alexandra Nicoleta Mureșan Ilinca Maria Țăpuc Daniela Mihaela Neagu

Insect bite hypersensitivity (IBH) is a seasonally recurrent allergic dermatitis representing one of the most prevalent dermatological conditions in horses worldwide. This condition, driven by hypersensitivity to salivary allergens of Culicoides spp., causes substantial discomfort, welfare impairment, and potentially economic loss in equine populations. The pathogenesis of IBH is complex, involving genetic predisposition, epithelial barrier dysfunction, and a skewed T-helper 2 (Th2)-mediated immune response with elevated IgE production and eosinophilic inflammation. Advances in immunogenetics and molecular immunology have improved the understanding of the disease’s multifactorial nature. Research on immunotherapy and cytokine-targeted treatments is contributing to the development of more effective therapeutic options. This review synthesizes current knowledge on the immunopathogenesis and genetic determinants of IBH and discusses both conventional and emerging strategies for its clinical management.

Allergies doi: 10.3390/allergies5030030

Authors: Seung Hoon Lee Gunhyuk Park Hye-Sun Lim Yoonseo Hong Huiyun Seo

Mast cells (MC) are key effector cells in allergic diseases and are increasingly recognized for their roles in the immunopathogenesis of tuberculosis (TB). In allergic conditions, MCs are hyperactivated, driving T-helper Type 2 (Th2)-skewed immune responses that may antagonize the T-helper Type 1 (Th1)-mediated immunity essential for controlling Mycobacterium tuberculosis (Mtb) infection. This immunological imbalance may contribute to increased TB susceptibility, altered granuloma dynamics, and accelerated fibrotic remodeling. Histopathological and in vivo studies have revealed that MCs are recruited to TB lesions, where they release a spectrum of mediators, including histamine, IL-17A, TNF-α, TGF-β, tryptase, and chymase. These mediators can either support initial immune defense or promote chronic inflammation and tissue damage, depending on context and regulation. Moreover, individuals with chronic allergic diseases such as asthma and allergic rhinitis may experience worse TB outcomes due to their baseline immune dysregulation. Environmental exposures (e.g., air pollution, smoking), genetic polymorphisms (e.g., IL-4 −589C/T, IL-13 R130Q), and gut-lung axis disturbances further modulate MC activity and TB pathogenesis. This review synthesizes current findings on MC involvement in TB, particularly in allergic settings, and highlights the need for epidemiological studies and mechanistic research. It also explores the promise of host-directed therapies (HDTs) that target MCs or their mediators, such as antihistamines, MC stabilizers, leukotriene inhibitors, and cytokine modulators, as novel adjuncts to standard TB treatment. Personalized approaches that consider immune profiles, genetic risk, and comorbid allergies may improve TB outcomes and inform future clinical guidelines.

Allergies doi: 10.3390/allergies5030029

Authors: Allison Bai Rachel Granovsky Courtney Chau Gabriela Cobos

Medium and variable vessel vasculitides are a heterogeneous group of rare, immune-mediated vascular disorders that are associated with significant morbidity and mortality. The standard treatment approach involves glucocorticoids and immunosuppressive agents. However, many patients exhibit poor tolerance or respond inadequately to these medications. Recent advances in biologic therapies and Janus Kinase inhibitors (JAKis) offer promising alternatives. This review consolidates current knowledge on the pathogenesis, immunology, and therapeutic efficacy of biologics and JAKis in the management of medium and variable vessel vasculitis. While further research is needed to establish long-term safety and optimize treatment protocols, biologics and JAKis represent emerging therapeutic strategies with the potential to improve outcomes.

Allergies doi: 10.3390/allergies5030028

Authors: Annabel Hou Joyce J. Zhu Pratiksha Patra Sharon Albers

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

Allergies doi: 10.3390/allergies5030027

Authors: Federica Trovato Antonio Di Guardo Alessandra Rallo Annunziata Dattola Elena Zappia Steven Paul Nisticò Giovanni Pellacani

Mount Etna, located on the eastern coast of Sicily, is Europe’s most active volcano. Over the past five years, it has experienced numerous significant eruptive episodes, with the most recent occurring in August 2024. During this event, substantial amounts of volcanic ash were dispersed over densely populated areas, particularly in the province of Catania. Environmental factors, such as volcanic eruptions, are known to influence inflammatory skin conditions, including atopic dermatitis. We analyzed a cohort of patients with atopic dermatitis who were exposed to volcanic ash during the Mount Etna eruption in August 2024, aiming to evaluate the impact of the eruption on respiratory and cutaneous symptoms, treatment response, use of protective equipment, and changes in EASI scores over an eight-week period. A total of 67 Caucasian atopic dermatitis patients (mean age 41.2) were assessed after a volcanic eruption. Symptom worsening occurred in 58.9% (respiratory) and 26.9% (skin) of patients. EASI scores significantly increased (p < 0.05). No clinical difference was found between treatment types or mask use, which did not prevent symptom exacerbation. Volcanic ash exposure significantly worsened respiratory and skin symptoms in atopic dermatitis patients, underscoring the need for improved protective measures and further research on environmental triggers of chronic inflammatory conditions.

Allergies doi: 10.3390/allergies5030026

Authors: Guillermo Cervera-Ygual Ana Delgado-Prada Francisco Gascon-Gimenez

Multiple sclerosis (MS) and allergic diseases, traditionally considered immunologically opposing entities, may share pathogenic mechanisms rooted in immune dysregulation. While MS is predominantly mediated by Th1 and Th17 responses and allergies by Th2 responses, emerging evidence suggests overlapping immunological pathways, including the involvement of histamine, regulatory T cells, and innate lymphoid cells. This review synthesizes current knowledge on the epidemiological and immunopathological associations between MS and allergies. Epidemiological studies have yielded inconsistent results, with some suggesting a protective role for respiratory and food allergies against MS onset, while others find no significant correlation. Clinical studies indicate that food allergies in adults may be associated with increased MS inflammatory activity, whereas childhood atopy might exert a protective effect. In addition, we review hypersensitivity reactions to disease-modifying treatments for MS, detailing their immunological mechanisms, clinical presentation, and management, including desensitization protocols where applicable. Finally, we explore how treatments for allergic diseases—such as clemastine, allergen immunotherapy, montelukast, and omalizumab—may modulate MS pathophysiology, offering potential therapeutic synergies. Understanding the interplay between allergic and autoimmune processes is critical for optimizing care and developing innovative treatment approaches in MS.

Allergies doi: 10.3390/allergies5030025

Authors: Ethan Schilling Stacey Neuharth-Pritchett Sofia H. Davie Yvette Q. Getch

Background/Objectives: This study assessed teacher self-efficacy in school-based asthma management in two southern states in the United States. Current literature focuses primarily on supporting school-based asthma management, but few studies have focused on teacher self-efficacy in the asthma management process. Methods: With data collected from a two-state survey of a randomly selected group of teachers in grades kindergarten to grade eight (n = 379), teachers’ demographic variables, general opinions about asthma management practices, and their self-perceptions on the Teacher Asthma Management and Information Seeking Scale, which assesses self-efficacy, were examined. Results: Teachers’ self-efficacy in managing asthma and seeking information was significantly higher among teachers who had completed in-service professional learning sessions and those who had access to community resources or links to community agencies. Additionally, teachers with personal experience of chronic illness, asthma, or allergies and those who had students with chronic illnesses in their classrooms reported higher self-efficacy scores. Conclusions: Findings suggest that providing professional learning about asthma for teachers, offering access to asthma action plans and community resources, and increasing awareness of chronic conditions and training for handling medical emergencies can enhance teachers’ self-efficacy and improve outcomes for students with chronic illnesses.

Allergies doi: 10.3390/allergies5030024

Authors: Raphael Chagas Silva Márcia Barbosa da Silva Alana Alcantara Galvão Jamile Souza Fernandes Gabriela Pimentel Pinheiro Álvaro A. Cruz Carina da Silva Pinheiro Neuza Maria Alcântara-Neves

Background/Objectives: Toxocara spp. infection has been associated with severe asthma and allergic manifestations due to the activation of eosinophils by the release of Th2 cell cytokines. The aim of this study was to investigate the association between Toxocara spp. infection and eosinophil levels in severe asthmatic patients. Methods: The socio-demographic, peripheral blood eosinophils counting total IgE, sIgE to aeroallergens and FEV1 results were acquired from the Program of Asthma and Rhinitis Control (ProAR) at the Salvador–Brazil databank; IgG anti-Toxocara spp. levels were measured in 176 severely asthmatic patients by indirect ELISA. Results: The Toxocara spp. seroprevalence was 50.6%. Eosinophilia was present in 54% of the population. The correlation between IgG anti-Toxocara spp. levels and eosinophils levels was positive. Eosinophilic individuals with SPT, sIgE for D. pteronyssinus, D. farinae and B. tropicalis showed positive results; IgE ≥ 160 UI/dL and uncontrolled asthma presented more positive results for IgG anti-Toxocara spp. Conclusions: Our findings suggest that eosinophil levels are influenced by the presence of IgG antibodies against Toxocara spp. Additionally, helminth infection may modulate immunological responses in allergies and uncontrolled asthma, which could help explain the exacerbation of asthma symptoms.

Allergies doi: 10.3390/allergies5030023

Authors: Oscar Manuel Calderón-Llosa César Alberto Galván María José Martínez Ruperto González-Pérez Eva Abel-Fernández Fernando Pineda

Allergic diseases, particularly respiratory allergies like asthma and allergic rhinitis, are a growing public health concern influenced by environmental factors such as climate change and air pollution. The exposome framework enables a comprehensive assessment of how lifelong environmental exposures shape immune responses and allergic sensitization. Peru’s diverse ecosystems and climates provide a unique setting to investigate regional variations in allergic sensitization. This study characterized these patterns in five Peruvian regions with distinct climatic, urbanization, and socioeconomic characteristics. A total of 268 individuals from Lima, Piura, Tarapoto, Arequipa, and Tacna were analysed for allergen-specific IgE responses using a multiplex IgE detection system. The results revealed significant geographical differences in sensitization frequencies and serodominance profiles, based on descriptive statistics and supported by Chi-square comparative analysis. House dust mites were predominant in humid regions, while Arequipa exhibited higher sensitization to cat allergens. In Tacna, olive pollen showed notable prevalence alongside house dust mites. Tarapoto’s high humidity correlated with increased fungal and cockroach allergen sensitization. Notably, some allergens traditionally considered minor, such as Der p 5 and Der p 21, reached sensitization prevalences close to or exceeding 50% in certain regions. These findings provide the most detailed molecular characterization of allergic sensitization in Peru to date, highlighting the importance of region-specific allergy management strategies. Understanding environmental influences on allergic diseases can support more effective diagnostic, therapeutic, and preventive approaches tailored to diverse geographical contexts.

Allergies doi: 10.3390/allergies5030022

Authors: Andreea D. Ona

Affecting around 30–40% of the population worldwide, allergic disorders including asthma, rhinitis, eczema, and food allergies, are relatively common. Environmental factors, such as air pollution and climate change, which aggravate allergic reactions, contribute to the growth of these diseases. Although conventional treatments such as antihistamines and immunotherapy remain the standard for symptom management, growing interest in natural remedies highlights the potential value of medicinal plants as complementary therapies. Commonly present in plants, vitamins and antioxidants have strong anti-inflammatory and antioxidant actions that can control immune responses, lower oxidative stress, and thus reduce inflammation, which is the main element in allergic reactions. By focusing on the fundamental causes of inflammation and immunological dysregulation, phytochemicals have shown encouraging effects in reducing allergic symptoms. This review investigates the role of plant flavonoids, polyphenols, and vitamins in lowering allergic symptoms and inflammation, and suggests their potential in allergy management. It also aims to provide a short review of various plant species that are used in folk medicine for allergy treatment. The inclusion of plant-based compounds in allergy therapy could provide more complete and environmentally friendly remedies to enhance patients’ quality of life.

Allergies doi: 10.3390/allergies5020021

Authors: Mariana de Gouveia-Pereira Pimentel Carolina Sanchez Aranda Rafaela Rola Guimarães Edson Kiyotaka Ishizuka Dirceu Solé Antônio Condino-Neto

Purpose: This study aimed to evaluate the immunological response to the 23-valent pneumococcal polysaccharide vaccine (PPV23) in patients investigated for immunodeficiencies due to recurrent infections at EPM-UNIFESP Clinical Immunology outpatient clinic. Methods: This is a longitudinal retrospective study. Data were collected from the medical records of patients between 2012 and 2020. The analyses were developed in two stages: before and after administration of the PPV23 vaccine. Results: A total of 390 patients who received the PPV23 vaccine were selected. Among those who demonstrated an adequate serological response (63.6%), there was a notable decrease in the risk of upper respiratory tract infections (URTI) by 66%, tonsillitis by 74%, otitis by 76%, sinusitis by 49%, and uncomplicated pneumonia (PNM) by 77%. For invasive infections, the risk reduction was 95% for pneumonia with parapneumonic effusion and 93% for meningitis. Conclusions: The study demonstrated a significant decrease in the risk of bacterial infections following the administration of the PPV23 vaccine in this population. Therefore, we recommend including PPV23 in the vaccination schedule following pneumococcal conjugated vaccines for patients with recurrent pneumococcal infections to enhance protection and avoid complications.

Allergies doi: 10.3390/allergies5020020

Authors: Rayad B. Shams Hiral S. Patel Christopher J. Sayed

Hidradenitis suppurativa (HS) and atopic dermatitis (AD) are both inflammatory dermatoses that can significantly impact patient quality of life, however, limited research exists regarding their association. The purpose of this comprehensive review is to compare the inflammatory pathogenesis of HS and AD, explore the associations between these diseases, and discuss standalone and concomitant disease treatment options. Although HS and AD are understood to be primarily driven by the Th1 and Th2 inflammation pathways, respectively, these conditions both utilize the Janus Kinase/Signal transducer and activator of transcription (JAK/STAT) pathway to promote inflammation. Newer research also suggests that IL-36 and IL-1 receptor-associated kinase 4 (IRAK4) may be two additional inflammatory signals shared between the HS and AD disease pathways. These shared mechanisms are reflected in patient presentations as HS and AD are often concomitantly present and demonstrate a bidirectional association in the current literature. Treatment options for concomitant disease are limited, but leverage the shared immune pathogenesis of both diseases. Dupilumab has been reported to improve both HS and AD symptoms in select patients. JAK inhibitors are currently FDA-approved for the treatment of AD, and early trials have suggested benefits from JAK inhibitors such as upadacitinib, povorcitinib, and topical ruxolitinib for HS. Possible future avenues for research on treating both HS and AD include IRAK-4 inhibitors such as zabedosertib and BAY1830839, and diet and gut microbiome modifications.

Allergies doi: 10.3390/allergies5020019

Authors: Mateusz Kamil Ożóg Alicja Derkacz Dawid Klimczak Sara Winkler Laura Wojciuch

Psoriasis is a chronic inflammatory autoimmune disease primarily affecting the skin and, in some cases, the joints, and is characterized by erythematous, scaling lesions. Building up the doses has been conventional, but many patients will not obtain good results and a new, more targeted therapeutic strategy is desired. In the past few years, immune checkpoint inhibitors have revolutionized moderate to severe psoriasis management by blocking crucial pro-inflammatory cytokines, introducing new avenues for biological therapies. This review summarizes recent developments in biological therapies, including their mechanisms of action and clinical efficacy. While bimekizumab, an IL-17A and IL-17F inhibitor, strongly suppresses inflammation, selective inhibition of the IL-12/23 pathways is targeted with the small molecule TYK2 inhibitor deucravacitinib. For example, spesolimab, an inhibitor of IL-36 signaling, is being investigated for generalized pustular psoriasis. In this respect, new therapies provide better efficacy and quality of life, target specific psoriasis subtypes, and are safer and more effective than anti-inflammatory treatments. Such therapies could radically inform the standards of care, and the long-term safety and patient-centered outcomes of these innovative strategies will be the subject of continued research.

Allergies doi: 10.3390/allergies5020018

Authors: Kamila Saramak

The interplay between allergic diseases and neurological disorders has gained increasing attention over the past decades, highlighting potential shared pathophysiological pathways. Allergic diseases, including asthma, eczema, and allergic rhinitis, are characterized by chronic inflammation and immune dysregulation, which may impact the pathogenesis of certain neurological conditions. Emerging evidence suggests that conditions such as multiple sclerosis (MS), migraine, epilepsy, neurodegenerative diseases, and neurodevelopmental disorders may be influenced by systemic inflammation and altered immune responses associated with allergies. The purpose of this paper is to provide an overview of current epidemiological evidence suggesting a relationship between allergic and neurological diseases. Understanding the complex interactions between allergic and neurological diseases could provide new insights into their aetiology and reveal novel therapeutic targets, paving the way for integrated approaches in managing comorbid allergic and neurological conditions, ultimately improving patient outcomes and quality of life.

Allergies doi: 10.3390/allergies5020017

Authors: Marco Michelon Edoardo Vincenzo Savarino Michele Montori Maria Eva Argenziano Pieter Jan Poortmans Pierfrancesco Visaggi Roberto Penagini David J. Tate Marina Coletta Andrea Sorge

Esophageal fibrotic remodeling is a major complication of chronic inflammation in eosinophilic esophagitis (EoE) and represents one of the main determinants of symptoms in adult patients with EoE, with a remarkable impact on patients’ quality of life and the healthcare system. Esophageal fibrotic remodeling is diagnosed through upper gastrointestinal endoscopy, radiological studies, and a functional luminal imaging probe. However, diagnostic underestimation of esophageal strictures and suboptimal adherence to EoE guidelines still represent limitations of current clinical practice. Combined with medical therapy and/or elimination diets, endoscopic dilation remains the cornerstone treatment for esophageal strictures and rings, offering a safe and effective option for managing obstructive symptoms. Different modalities are available for esophageal endoscopic dilation of EoE, including mechanical and balloon dilators. Mechanical dilators provide tactile feedback during the procedure and exert longitudinal and radial forces. In contrast, balloon dilators apply a purely radial force and enable direct visualization of the esophageal mucosa during the procedure. Both mechanical and balloon dilators are safe and effective, with no single modality demonstrating clear superiority. Consequently, the choice of dilation technique is guided by stricture characteristics, the expertise of the endoscopist, and considerations related to the financial and environmental sustainability of the devices. This review aims to summarize the most relevant evidence on the endoscopic evaluation and dilation of fibrostenotic complications in EoE, also providing practical guidance for clinicians to optimize the endoscopic management of these patients.

Allergies doi: 10.3390/allergies5020016

Authors: Marcos Pérez-Losada

Allergic rhinitis and asthma are significant public health concerns worldwide. While previous studies have explored how nasal and buccal bacteriotas influence these conditions, few have directly compared their bacteriomes within the same cohort. To bridge this gap, I analyzed 16S rRNA next-generation sequencing data from 347 individuals, including participants with allergic rhinitis, asthma and healthy controls. The nasal and buccal bacteriomes shared all dominant bacterial taxa but differed significantly in their phylum- and genus-level relative abundances. Alpha-diversity was significantly higher in the buccal cavity, while beta-diversity varied significantly across all indices and clinical groups. Over 80% of the predicted metabolic pathways were differentially regulated between the two cavities, yet these functional differences remained fairly consistent across clinical groups. Naso-buccal bacterial networks exhibited striking differences in structure, complexity and hub nodes. Notably, the network of healthy controls showed a clear segregation between nasal and buccal bacteria, with 93.5% of the interactions occurring within each respective cavity, and contained few pathogenic keystone taxa. In contrast, bacterial networks from diseased individuals exhibited reduced ecological specialization and more pathogenic keystone taxa linked to airway disease. These findings, thus, demonstrate that the naso-buccal bacteriome plays distinct yet interconnected roles in allergic rhinitis and asthma.

Allergies doi: 10.3390/allergies5020015

Authors: Alessandra de Cássia Romero

Population growth and the depletion of natural resources have driven the incorporation of edible insects into the human food matrix. Despite their high nutritional value and the environmental benefits of insect farming compared to conventional protein sources, their consumption poses potential risks, including food allergies. Sensitization to insect allergens can occur through various exposure routes, with cross-reactions involving other foods and environmental allergens being well-documented. Vulnerable groups such as children and the elderly may have increased susceptibility not only because of genetic predisposition but also because of age-related physiological factors. This review explores the emerging risks of edible insect consumption, with a focus on children and the elderly. Age-related alterations in the gut microbiota, digestion, immune function, and overall physiology can facilitate the absorption of intact allergenic proteins and impair immune responses. Furthermore, the allergenic potential of insect proteins and their associated microbiota remains poorly characterized. Limited research exists on the effects of processing methods on these proteins. Consequently, incorporating edible insects into food products could present an additional allergenic risk, particularly for these vulnerable populations. Understanding these risks is essential for ensuring the safety and acceptance of edible insects as sustainable food ingredients.

Allergies doi: 10.3390/allergies5020014

Authors: Marcos Pérez-Losada

Pediatric asthma is the most common chronic childhood disease in the US and a major public health concern. It is considered to comprise multiple clinical variants or phenotypes with different etiologies and pathophysiologies. Former research has shown that airway bacteriomes vary in composition and structure across pediatric asthma phenotypes, but their functional diversity and bacterial interactions have hardly been investigated. A previous study of 163 children from Washington DC identified three statistically different asthma phenotypes, each with a unique nasopharyngeal bacterial composition and diversity. Here, I reanalyze 16S rRNA high-throughput sequences from the same cohort to characterize their bacterial metabolism and interactions. I detect 61 to 102 metabolic pathways (PICRUSt2; q ≤ 0.05) differentially expressed across the three asthma phenotypes. Most of those pathways are related to biosynthesis and degradation processes and statistically (p ≤ 0.0012) separated the three clinical groups. Co-occurrence networks also differ in connectivity across phenotypes, suggesting unique bacterial interactions in each group. Five to eight keystone taxa are detected across phenotypes. Insights from this and previous studies, hence, confirm the airway bacteriome heterogeneity across pediatric asthma, increasing our understanding of its etiology and pathophysiology, and provide new taxonomic and functional biomarkers of disease for targeted interventions and therapies.

Allergies doi: 10.3390/allergies5020013

Authors: Anuj Tharakan Ankit Kumar Carmen Camarena Daniel H. Conrad Rebecca K. Martin

Introduction: Allergic rhinitis (AR) is largely driven by IgE-induced immune cell activation, which promotes allergen-induced upper airway inflammation. The regulatory mechanisms of IgE synthesis in AR are poorly understood. Several analyses associate single nucleotide polymorphisms (SNPs) which reduce the expression of the D2HGDH gene with AR. D2HGDH encodes an enzyme that converts D-2-hydroxyglutarate (D2HG) to α-ketoglutarate (α-KG). This study aims to clarify the relationship between AR and SNPs in D2HGDH. Methods: Mice were treated with vehicle control or octyl-D2HG prior to intranasal exposure to Alternaria alternata. Draining lymph nodes (dLNs) were then evaluated for IgE-producing cells and T-cell polarization. Next, mice were exposed to intranasal Alternaria on days 0, 10, 20, and 27–30 and were treated intranasally with octyl-D2HG or vehicle control on days 20 and 27. Nasal inflammation was analyzed in nasal lavage fluid (NLF) cellularity and antigen-specific IgE production. Results: The administration of D2HG prior to Alternaria exposure suppressed IgE synthesis (p < 0.01) and Th2 cell polarization (p < 0.01) in dLNs. In a murine model of AR, D2HG administration reduced overall cellular infiltrates and eosinophils in NLF. Further, antigen-specific IgE in NLF was significantly reduced in mice treated with D2HG (p < 0.05). Conclusions: An analysis of the regulatory landscape surrounding the rs34290285 SNP demonstrates that the downregulation of D2HGDH expression reduces the risk of AR. Downregulation of D2HGDH likely results in accumulation of D2HG intracellularly, suggesting that D2HG is protective against allergic rhinitis. We show that the administration of D2HG impairs IgE production, leading to the amelioration of allergic sinonasal inflammation in a murine model of AR. These findings suggest a causal relationship between D2HGDH expression, D2HG levels, and allergic rhinitis risk.

Allergies doi: 10.3390/allergies5020012

Authors: Ramin Beheshti Polly Huang Megan Le Rachel Peterson Jody R. Tversky

Worldwide, cat allergies affect 15% of the population. Cat allergens are ubiquitous and challenging to eliminate from homes, making it difficult to implement effective allergen reduction strategies. Developing strategies to reduce cat allergens in homes could alleviate the burden of allergic diseases, enhance symptom management, lower healthcare expenses, and improve patients’ quality of life. Studies have produced varied results concerning the effectiveness of specific environmental control measures in lowering cat allergen levels and improving clinical outcomes for allergic diseases. This review evaluates the existing evidence on the effectiveness of environmental control measures in reducing cat allergens and their potential clinical impact.

Allergies doi: 10.3390/allergies5020011

Authors: Mohamad Ammar Ayass Trivendra Tripathi Natalya Griko Ramya Ramankutty Nair Tutku Okyay Jin Zhang Kevin Zhu Victor Pashkov Lina Abi-Mosleh

Peanut allergies, driven by sensitization to key allergens Ara h1, Ara h2, and Ara h3, present significant health risks, particularly in food processing and consumer settings where accidental exposure is frequent. To mitigate this risk, we developed AYA22AR321, a novel aptamer with selective, high-affinity binding to these allergens (Kd values: 0.5 nM for Ara h1, 14.5 nM for Ara h2, and 6.6 nM for crude peanut extract). Functional assays using RBL-2H3 (rat basophilic leukemia cell line) cells showed that AYA22AR321 significantly reduces IgE-mediated degranulation, indicating its potential to attenuate allergic responses. To translate these findings into practical use, we formulated an allergen-neutralizing spray, FISTOQ, containing AYA22AR321, which effectively neutralized peanut allergens on peanut-butter-contaminated surfaces. Stability tests confirmed that FISTOQ, comprising eco-friendly surfactant and preservative, maintains its allergen-neutralizing efficacy over time. Comprehensive safety assessments, including immunogenicity, cytotoxicity in human PBMCs, and mutagenicity via the Ames test, demonstrated that AYA22AR321 is non-immunogenic, non-cytotoxic, and non-mutagenic. This study establishes AYA22AR321 as a promising, targeted strategy for allergen control, providing a significant advancement in allergen mitigation and food safety for high-risk environments.

Allergies doi: 10.3390/allergies5020010

Authors: Hee-Jae Jung Saja Mustafa Ali Reena Khianey Jamal Mikdashi

(1) Background: Allergic disorders and systemic lupus erythematosus (SLE) are immune dysregulation conditions that are increasingly prevalent, with growing evidence suggesting shared pathogenesis. (2) Results: Patients with SLE have a higher risk of allergic conditions, particularly allergic rhinitis and asthma; notably, children born to mothers with SLE show an increased asthma risk. This association appears linked to shared mechanisms involving T-helper 2 cells, IgE, human leukocyte antigen, genetic factors, and environmental triggers. Various medications used in allergic disorders and SLE have benefits in both diseases. Many SLE medications benefit allergic dermatitis. Meanwhile, omalizumab used for severe asthma may reduce SLE activity. (3) Conclusions: More research is essential to clarify the shared pathways and cross-benefits of treatments for allergic disorders and SLE. Novel treatment strategies are warranted to clarify the roles of biologic treatment in allergic disorders in the setting of SLE.

Allergies doi: 10.3390/allergies5020009

Authors: Alexandra Danielidi Spyridon Lygeros Alexandra Anastogianni Gerasimos Danielidis Sophia Georgiou Constantinos Stathopoulos Katerina Grafanaki

Background: Atopic dermatitis (AD), allergic rhinitis (AR), and chronic rhinosinusitis with nasal polyps (CRSwNP) represent interconnected conditions within the spectrum of type 2 inflammatory diseases. While these conditions share common genetic and epigenetic pathways, the precise molecular mechanisms remain underexplored. Methods: This review integrates the latest insights on the genetic and epigenetic factors linking AD, AR, and CRSwNP, focusing on genome-wide association studies, DNA methylation patterns, histone modifications, and microRNA regulation. Results: In all three conditions, epigenetic modifications, including DNA methylation (Me) and histone acetylation (Ac) and methylation, regulate inflammatory and barrier-related genes, influencing disease severity. Notably, miRNAs such as miR-146a and miR-155 play pivotal roles in modulating inflammation across all three diseases, while disease-specific miRNAs contribute to airway remodeling (miR-125b and miR-21 in AR and CRSwNP). Emerging evidence underscores the role of microbiome-driven inflammasome activation and matrix metalloproteinases (MMP-2, MMP-9, and MMP-12) in perpetuating chronic inflammation and remodeling. Conclusions: The interplay between genetic predispositions, epigenetic modifications, and exposomal factors underscores the systemic nature of type 2 inflammation. A deeper understanding of these interconnected mechanisms could lead to transformative, personalized diagnostic and therapeutic advancements.

Allergies doi: 10.3390/allergies5010008

Authors: Stephen A. Y. Gipson Jacqueline B. Nesbit Lauren T. Swientoniewski Stephen I. Rogers S. Shahzad Mustafa Stephen C. Dreskin Suzanne S. Teuber Hsiaopo Cheng Soheila J. Maleki

Background: Tree nut allergy affects approximately 1% of the U.S. population and the prevalence is increasing. Walnut allergy is the most commonly reported tree nut allergy in the United States. This study aimed to investigate the IgE cross-reactivity between walnut allergen Jug r 4 and peanut allergen Ara h 3 in individuals with dual walnut and peanut allergies. Methods: Jug r 4 was purified from whole walnut extract and analyzed via western blot using anti-Ara h 3 antibodies alongside serum IgE from walnut allergic patients. Sera from individuals allergic to both peanuts and walnuts were utilized to examine peptide microarrays comprising synthetic overlapping 15 mer peptides, offset by five amino acids, of Ara h 3 and Jug r 4. These results were compared against computationally predicted IgE epitopes using the Structural Database for Allergic Proteins (SDAP). Additionally, SWISS-MODEL protein modeling software was employed to map IgE epitopes onto Ara h 3 and Jug r 4. Results: Our findings revealed previously unreported IgE epitopes for dual-allergic sera within both allergens, highlighting the locations of empirically determined and SDAP-predicted IgE epitopes. Conclusions: While six epitopes were predicted as cross-reactive, only three were frequently recognized by IgE in dual-allergic individuals, underscoring their potential significance in clinically relevant cross-reactivity.

Allergies doi: 10.3390/allergies5010007

Authors: Arthur Helbling Mathilde Foglierini Victor Colin Yannick D. Muller Elisabeth Schuller Annika Stern Kaspar Strub

In Switzerland, only scarce data are available on the prevalence and treatment of allergic rhinitis. Although the presence of AR symptoms in temporal relation to the respective aeroallergen is indicative, still a substantial number of affected individuals are deemed underdiagnosed and potentially undertreated. A national online survey was conducted for consecutive participants with AR symptoms in medical practices irrespective of diagnosis, therapy, or the reason for the visit. Univariate and multivariate regression analyses were performed, as well as multiple correspondence analysis for participants with allergic rhinitis diagnosis (ARwD) and without diagnosis (ARwoD). A total of 392 of 637 participants with rhinitic symptoms self-reported an AR diagnosis with a symptom onset more than 5 years ago in 74%. Despite treatment, up to one-third of participants with ARwD had persistent severe symptoms. Asthma was reported more frequently in participants with ARwD (148/392) than with ARwoD (26/245), (42% vs. 12%, p < 0.001, q < 0.001). Allergologists were consulted more often by participants with ARwD (106/392; 30% vs. 3/245; 2%), while more participants with ARwoD visited pharmacies for treatment advice (40/392; 11% vs. 57/245; 40%). The coexistence of AR and asthma with severe symptoms is a specific phenotype with difficult to treat nasal symptoms, amongst others. Hence, appropriate diagnosis and treatment of suspected and diagnosed AR should be prioritized, especially, but not limited to, patients with AR and asthma.

Allergies doi: 10.3390/allergies5010006

Authors: Yohei Sato

Regulatory T cells (Tregs) play a central role in immune regulation and tolerance. The transcription factor FOXP3 is a master regulator of Tregs in both humans and mice. Mutations in FOXP3 lead to the development of IPEX syndrome in humans and the scurfy phenotype in mice, both of which are characterized by fatal systemic autoimmunity. Additionally, Treg dysfunction and FOXP3 expression instability have been implicated in nongenetic autoimmune diseases, including graft-versus-host disease, inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. Recent investigations have explored FOXP3 expression in allergic diseases, revealing Treg alterations in food allergies, asthma, and atopic dermatitis. This review examines the multifaceted roles of FOXP3 and Tregs in health and various pathological states, including autoimmune disorders, allergic diseases, and cancer. Additionally, this review focuses on the impact of recent technological advancements in facilitating Treg-mediated cell and gene therapy approaches, including CRISPR/Cas9-based gene editing. The critical function of FOXP3 in maintaining immune homeostasis and tolerance to both self-antigens and alloantigens is emphasized. Considering the potential involvement of Tregs in allergic diseases, pharmacological interventions and cell-based immunomodulatory strategies may offer promising avenues for developing novel therapeutic approaches in this field.

Allergies doi: 10.3390/allergies5010005

Authors: Travis Satnarine Alana Xavier de Almeida Malaika Woody Krisia Banegas Carballo Diana Chan Pytregay Thompson Gary Kleiner Melissa Gans

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.

Allergies doi: 10.3390/allergies5010004

Authors: Travis Satnarine Nadia Makkoukdji Valishti Pundit Alexia Vignau Pranav Sharma Duenna Warren Gary Kleiner Melissa Gans

Peanut allergy presents a significant and growing public health concern, marked by its increasing prevalence and potential for severe allergic reactions. Traditional diagnostic methods, such as skin prick testing and serum IgE assays, serve as cornerstone approaches but often fall short in specificity, sensitivity, and risk stratification. This has driven the development of innovative diagnostic technologies, including component-resolved diagnostics, basophil activation tests, bead-based epitope assays, molecular diagnostics, and artificial intelligence applications. These advancements promise greater diagnostic precision, improved patient stratification, and tailored management strategies. However, challenges such as high costs, accessibility issues, and the need for standardized protocols hinder their widespread clinical adoption. This review explores the evolution of peanut allergy diagnostics, comparing traditional and emerging methodologies, and discusses their clinical implications, limitations, and future directions. The integration of advanced technologies with established approaches holds the potential to revolutionize peanut allergy diagnosis and management, ultimately enhancing patient care and outcomes.

Allergies doi: 10.3390/allergies5010003

Authors: Inmaculada Sánchez-Machín Ruperto González-Pérez Elena Mederos-Luis Sara García-Gil Paloma Poza-Guedes

Background/Objectives: Hereditary angioedema (HAE) is a rare genetic condition marked by recurring episodes of intense swelling that affect the skin, gastrointestinal system, and airways. Lanadelumab, a monoclonal antibody that inhibits plasma kallikrein, is approved for long-term prophylaxis (LTP) in HAE patients, and has shown substantial efficacy in reducing disease symptoms. This single-center, retrospective study analyzed the real-world impact of lanadelumab on healthcare resource utilization, angioedema episode frequency, and quality of life (QoL) among adult HAE patients treated at the allergy department of Hospital Universitario de Canarias, Tenerife, Spain. Methods: This study included patients with a confirmed diagnosis of bradykinin-mediated HAE type 1 who were receiving lanadelumab 300 mg subcutaneously every two weeks, meeting specific inclusion criteria. A retrospective review of medical records from March 2021 to June 2024 assessed clinical outcomes under lanadelumab therapy, compared to prior clinical status. Key metrics included angioedema attack frequency, use of on-demand icatibant treatment, hospital visits, and QoL using the HAE-QoL questionnaire, alongside any adverse reactions associated with lanadelumab. Results: The investigation revealed a 75.3% reduction in hospital visits and a 94.1% decrease in angioedema episodes among HAE patients. Additionally, use of on-demand rescue medication (icatibant) was reduced by 61% (p < 0.05), while quality of life (QoL) scores improved from 62.2 to 99.5, with no significant adverse effects reported. Conclusions: Lanadelumab significantly reduced healthcare resource use and angioedema episodes, with marked improvements in quality of life. The reduced need for on-demand medication and hospital visits highlights lanadelumab’s value as an effective long-term prophylactic treatment with minimal adverse effects for HAE patients in real-world settings.

Allergies doi: 10.3390/allergies5010002

Authors: Elena Mederos-Luis Tania Galán María J. Martínez Ruperto González-Pérez Inmaculada Sánchez-Machín Fernando Pineda Paloma Poza-Guedes

Seafood is a crucial source of nutrients, with global consumption steadily increasing. Among seafood-related allergies, shellfish are a significant cause of food allergy and anaphylaxis worldwide, affecting approximately 0.5–2.5% of the general population. While the majority of existing research has focused on crustaceans, allergic reactions to mollusks, including their clinical characteristics, remain poorly understood. In the Canary Islands, limpets (a type of marine gastropod) are widely consumed as part of the traditional cuisine. Despite isolated reports of limpet allergy, no large-scale studies or comprehensive clinical analyses have been published on this topic. A cohort of patients sensitized to limpets was analyzed: 66 patients were monosensitized to limpets (Group A), while 64 patients demonstrated additional sensitization to other shellfish (Group B). Limpet ingestion was associated with delayed and severe symptoms, including anaphylaxis and severe asthma. Notably, only 11.5% of patients in Group A tested positive for shellfish allergens using ALEX testing compared to 67.9% in Group B. The identification of protein bands in the 25–40 and 50–200 kDa molecular weight ranges in monosensitized patients provides a novel finding that differentiates this study from prior research. Our study represents the largest reported series of patients with documented limpet allergy to date.

Allergies doi: 10.3390/allergies5010001

Authors: András Gyovai Gabriella Metzler Krisztián Papp József Prechl

In vitro tests of cellular activity form part of the diagnostic algorithm of drug hypersensitivity reactions. Because of the wide range of pharmacological mechanisms, clinical symptoms, genetic components, and laboratory tests involved, it is important to know how a particular test performs in the diagnostic procedure. We carried out a detailed retrospective analysis of more than 6000 measurements of numerous drug compounds tested in 738 serum samples over the past 6 years. Our cell viability-based lymphocyte transformation had a coefficient of variation of 10% and showed similar performance over the whole range of tested ages. With an adequate number of parallel measurements, the test can identify modest increases in stimulation indices with high confidence. Similar percentages of analytically positive responses (11.4%, 13.5%, and 9.7%) were observed for the three most frequently tested drug groups, namely, antibiotics, non-steroid anti-inflammatory agents, and anesthetics. These results confirm that cell viability tests are suitable alternatives for proliferation assays in drug allergy testing.

Allergies doi: 10.3390/allergies4040017

Authors: Yukihiro Yoshimura Momoka Takahashi

Background/Objectives: Allergic contact dermatitis (ACD), an inflammatory skin condition, is commonly treated with topical corticosteroids; however, long-term use of these drugs is associated with various risks, such as skin atrophy and steroid resistance. Triacetin (TA), a triglyceride metabolized to acetate, exerts anti-inflammatory affects by activating AMP-activated protein kinase (AMPK) and suppressing mast cell degranulation. Here, we aimed to assess the immediate and long-term effects of TA on ACD suppression, focusing on AMPK activation, using a 2,4-dinitrofluorobenzene-induced rodent model. Methods: Various concentrations of TA were topically applied to rats with 2,4-dinitrofluorobenzene-induced dermatitis. Ear thickness was measured, and histological analysis was performed to assess the inflammation, mast cell infiltration, and degranulation in the established models. AMPK activation was analyzed via Western blotting, and TA degradation was assessed via gas chromatography-mass spectrometry. Dorsomorphin (an AMPK inhibitor) was used to evaluate the effects of AMPK on ACD. Results: TA significantly inhibited inflammation and mast cell degranulation in a dose-dependent manner, with 0.25 mmol/L showing the most potent effects. It also activated AMPK activation. Notably, AMPK inhibition reversed the effects of TA. Conclusions: Overall, TA exerted immediate and long-term anti-inflammatory effects via AMPK activation and inhibition of mast cell degranulation, showing potential as a non-steroidal therapeutic for ACD.

Allergies doi: 10.3390/allergies4040016

Authors: Moslem Sabaghi Soheila J. Maleki

This review explores strategies for mitigating food allergies by treating foods with biopolymers, bioactive compounds, and food-grade enzymes. Biopolymers like chitosan, alginate, and pectin show potential in reducing the allergenic properties of food. Polyphenols such as quercetin, resveratrol, curcumin, and epigallocatechin gallate demonstrate promise as anti-inflammatory molecules that can lessen the symptoms and severity of allergic reactions. Enzymes, including proteases such as pepsin, papain, and bromelain, and transferases like transglutaminase, offer the potential to reduce the allergenic potency of proteins by various mechanisms, though more research is needed for the optimization and assessment of the safety and palatability of treated foods. Overall, this review offers insights into potential strategies to alleviate allergic reactions by reducing the allergenic properties of food proteins.

Allergies doi: 10.3390/allergies4040015

Authors: Nikos Priftis Dimitra Karaviti Kostas Douros

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.

Allergies doi: 10.3390/allergies4040014

Authors: Ahsanullah Unar Muqaddas Qureshi Hassan Imran Afridi Shafkatullah Wassan

Food allergies (FAs) represent a significant and growing global health issue, with increasing prevalence across different age groups. This review provides a comprehensive analysis of the epidemiology, mechanisms, and risk factors involved in FA development. Currently, FAs are estimated to affect 2% of the general population, with higher rates in children (~8%). However, these figures may be inaccurate because of the reliance on self-reported data and immunoglobulin E (IgE) testing, which may not reflect clinically confirmed cases. Environmental and genetic factors, including exposure to bacterial toxins, dietary habits, and the gut microbiota, play critical roles in FA development. Specifically, Staphylococcus aureus enterotoxins are implicated in disrupting intestinal barriers and enhancing immune sensitization to allergenic proteins. This immune dysregulation promotes Th2 responses and compromises regulatory T cell function, crucial elements in allergy pathogenesis. As the prevalence of FAs continues to rise, there is a pressing need for accurate diagnostic tools, heightened public awareness, and effective prevention strategies. Further research is needed to elucidate the specific role of bacterial toxins and other environmental factors in FA development to advance clinical management approaches.

Allergies doi: 10.3390/allergies4040013

Authors: Yvette Q. Getch Ethan Schilling Stacey M. Neuharth-Pritchett Sofia Hirt

Background/Objectives: This study assessed teacher comfort in supporting the medical management of children with asthma in elementary and middle schools in two southern states in the U.S. Teacher comfort in asthma management is a largely underexplored area yet holds promise to support medical management in schools. Methods: Using survey methods, data were gathered from a random sample of teachers in two southern U.S. states (n = 574). Data from the Teacher Capability and School Resource Scale for Asthma Management scale were used to assess teacher comfort and capability in managing stressful asthma management episodes. Results: Teachers expressed comfort in supporting children with asthma in their classrooms. On the Teacher Capability in Social and Emotional Aspects of Asthma Management (SEAM) factor, the mean rating was 3.89 (SD = 0.83) out of 5, and the mean rating for the School Resources/Institutional Capability for Asthma Management factor was 3.77 (SD = 0.99) out of 5. Conclusions: The findings demonstrate that access to school, community, and medical resources; coordinated school-based asthma care plans; and pre-service preparation improve teacher comfort. School nursing support is needed for teacher education.

Allergies doi: 10.3390/allergies4040012

Authors: Julian Ang Farshid Bayat Aoife Gallagher David O’Keeffe Melissa Isabella Meyer Roberto Velasco Zaheera Yusuf Juan Trujillo

Since the publication of the Adverse Childhood Experiences (ACEs) Study in 1998, there has been a dramatic increase in the number of studies exploring the immunoendocrinological sequelae of toxic stress. However, the literature exploring this in relation to paediatric atopy predominantly revolves around asthma. This review aims to (1) explore the association between ACEs and non-asthmatic, non-iatrogenic paediatric allergies (NANIPA) in the developed world and (2) further focus on the association between exposure to violence and NANIPA. Methods: PubMed and Scopus were searched for articles examining adversity and NANIPA before age 18. Non-English papers, publications before 1998, reviews, opinion pieces and case reports/series were excluded. Screening, data extraction, and risk-of-bias were independently reviewed by the first two authors. Results: Nine of the one thousand eighty-nine records identified were included. Four pertained to objective 1, four to objective 2, and one pertained to both. Regarding objective 1, all studies reported a positive dose-response relationship between ACEs and NANIPA, which was most significant among preschoolers and diminished with age. Studies relevant to objective 2 were too heterogenous to compare. However, two interesting associations emerged: (1) The types of violence significantly associated with NANIPA in adolescence differ in a sex-dependent manner, and (2) verbal abuse and bullying are the violence types most powerfully and significantly associated with NANIPA. Conclusion: Psychological stress is a probable IgE-independent driver of atopy in children exposed to adversity and/or violence. While the literature is too underdeveloped to allow for meaningful cross-comparison between studies, this review has identified many interesting areas for future research.

Allergies doi: 10.3390/allergies4040011

Authors: Georgina Jones Rachel House Sinthia Bosnic-Anticevich Lynn Cheong Biljana Cvetkovski

Allergic Rhinitis (AR) currently affects 27% of young adults (18–24 years old) in Australia. Although the nature of AR and its management are well-researched in adult and paediatric populations, little is known about young adults. Given the biopsychosocial developmental challenges faced by young adults, this study aims to investigate young adults’ AR management and the source of its influence. A total of 185 young adults with AR in Australia completed an online survey. Seventy-eight percent were female and had a mean age of 21.9 years old. The majority (99%) had moderate to severe symptoms and affected at least one aspect of their quality of life (97%). Despite this, only 11% of participants were using appropriate medications. Parents (50%) were the most common influencer in young adults’ medication use, and general practitioners were most commonly sought for information (63%) and advice (70%). Young adults do not manage their AR with appropriate medications despite consulting healthcare providers, and this was reflected in the heavy burden reported on their quality of life. This study bridges our gap in understanding and shows that young adults lack developmentally appropriate support to equip them with the health literacy skills required to transition into adult healthcare.

Allergies doi: 10.3390/allergies4030010

Authors: Russell J. Hopp

Although the small airway component of chronic asthma is becoming a more important topic, its impact in the daily assessment of pediatric asthma is limited. The intrinsic airway autonomic control in asthma suggests some potential mechanisms by which more distal obstruction may dominate in some situations. We suggest theoretical possibilities for small airway dominance and present clinical data supporting this possibility.

Allergies doi: 10.3390/allergies4030009

Authors: Raphael Chagas Silva Jaqueline Wang da Silva Antônio Márcio Santana Fernandes Camila Alexandrina Viana de Figueiredo Natália Gomes de Morais Coneglian Neuza Maria Alcântara Neves Carina da Silva Pinheiro

This study was conducted using data from the SCAALA (Social Change Asthma and Allergy in Latin America) cohort in Brazil from 2005 to 2013. We examined the seroprevalence and risk factors of toxocariasis, a parasitic infection leading to conditions such as visceral larva migrans, utilizing an indirect ELISA with T. canis antigens, alongside with data from questionnaires, eosinophil counts, sIgE to aeroallergens, IL-10 levels, and Skin Prick Test results; the research provided insights into the disease’s dynamics. The prevalence of anti-Toxocara spp. IgG increased from 48% to 53% over the studied period, with a 25% increase in new cases in 2013. The significant risk factors included age and pet exposure, while higher maternal education and living on paved streets were found to offer protection. The study uncovered a complex interaction between Toxocara spp. infection and the immune system, indicating that the infection could both trigger inflammation and modulate skin reactions. Based on these findings, the study proposed a roadmap for controlling toxocariasis, which includes strategies such as enhancing public education about the disease and preventive measures, improving environmental sanitation, strengthening veterinary control measures like pet deworming, increasing access to healthcare and screening, and implementing community-based interventions to address the identified risk factors. These measures aim to reduce the prevalence of toxocariasis and its impact on public health by addressing environmental and socioeconomic risk factors, providing a pathway to significantly reduce the burden of this parasitic infection.

Allergies doi: 10.3390/allergies4030008

Authors: Mohamad Ammar Ayass Trivendra Tripathi Natalya Griko Ramya Ramankutty Nair Tutku Okyay Jin Zhang Kevin Zhu Kristen Melendez Victor Pashkov Lina Abi-Mosleh

Food allergy, particularly peanut allergy (PA), is a growing health concern affecting millions globally. PA can lead to severe reactions, including fatal anaphylaxis. Despite the availability of FDA-approved therapies like Palforzia, a cure remains elusive. Current immunotherapies show promise but lack a definitive cure. This study applies an established computational biology tool to design aptamers targeting Ara h1 and Ara h2. The in silico design aims to streamline the selection process, enabling cost-effective and rapid identification of aptamer candidates. The developed aptamers (AYA22A, including AYA22AR321, AYA22AR211, and AYA22AR524), demonstrated efficacy in inhibiting degranulation of RBL-2H3 cells (rat basophilic leukemia cell line) in vitro. They showed promise in neutralizing peanut allergen-induced immune responses. The selected aptamers inhibited degranulation in RBL-2H3 cells, addressing concerns in raw peanuts. Moreover, these aptamers demonstrated stability and effectiveness in peanut plant seeds and commercial products. Our aptamers exhibited potential in modulating immune responses associated with peanut allergy. They influenced Th1/Th2 balance, indicating a role in cytokine regulation. In vitro studies also showed the aptamers’ impact on immune cell expression and cytokine production, resembling responses observed with established immunotherapies. The findings suggest AYA22A aptamers as a potential therapeutic option for peanut allergy, providing a basis for further in vivo investigations.

Allergies doi: 10.3390/allergies4030007

Authors: Caoimhe Cronin Hannah Keohane Eimear O’Rourke Ciobha O’Kelly Yukta Ramesh Laura Flores Aoife Gallagher Anda Dumitrescu Roberto Velasco Juan Trujillo

Background: Despite the importance of caregivers being trained in anaphylaxis management and the use of adrenaline auto-injectors (AAIs), studies have revealed inadequate caregiver knowledge. The caregiver anaphylaxis knowledge in an Irish population has not been previously assessed. This study aims to evaluate the anaphylaxis management knowledge and AAI administration proficiency among parents of children with food allergies. Methods: The parents of children with food allergies who were prescribed an AAI were invited to take part in a study involving online education. The participants completed an online questionnaire assessing anaphylaxis knowledge. They then took part in an online educational intervention where their AAI administration ability was assessed. Results: Out of a total score of 12, the mean anaphylaxis knowledge score was 9.76/12, SD 1.577, or 81.33%. Of the 152 participants, 26.7% (n = 40) performed all three critical AAI administration steps correctly. A household income under EUR 40,000 per annum reduced the likelihood of successful AAI administration (OR 0.33 95% CI 0.125–0.87, p = 0.025). Regarding the AAI devices, 46.4% claimed to have switched between devices at least once before. Conclusions: The parents demonstrated good knowledge of anaphylaxis management, but the prevalence of device switching underscores the importance of comprehensive AAI training. Future assessments should include evaluations of enhancements in knowledge, anxiety levels, and overall quality of life.

Allergies doi: 10.3390/allergies4020006

Authors: Ayrton Lisboa Neuza Alcantara-Neves Eric Aguiar Carina Pinheiro Luis Pacheco Eduardo da Silva

Updated notions about the so-called hygiene hypothesis consider now that helminths may have influence in the training of the immune system during childhood. Considering the similar type of immune response between helminth infections and allergic illnesses, the objective of this study was to evaluate how structural and functional conservation between house-dust mite allergens and their helminth orthologs might contribute to the cross-induction of IgE responses in allergies and helminthiasis. Amino acid sequences from group-1, -2, -5, -9, -10, -18, -21, and -23 allergens of the house dust mite Dermatophagoides pteronyssinus were retrieved from curated databases, and orthologs were identified in other mite species and different helminth parasites. We also assessed structural, conservational, functional, and immunologic relationships between these major mite allergens and their helminth counterparts. De novo 3D-modelling, B-cell epitopes prediction, structural conservation, and docking analyses were analyzed by Robetta platform, ElliPro and CBTope, RaptorX, and Z-Dock, respectively. Our results extend previous findings on structural conservations between major allergens and parasite proteins and show that these conservations go beyond the well-known conservations and may account for the observed immunological cross-reactions. This understanding can contribute in the near future to the development of more specific serological testing for mite-induced allergies and helminthiasis.

Allergies doi: 10.3390/allergies4020005

Authors: Margarita Dimitroglou Dafni Moriki Olympia Sardeli Elpiniki Kartsiouni Despoina Koumpagioti Angeliki Galani Vassiliki Papaevangelou Konstantinos Douros

According to parental reports, about 10% of children are believed to be allergic to at least one antibiotic, leading to the prescription of second line medications. This incurs higher costs, results in less effective treatments, and contributes to global concern of antibiotic resistance. De-labeling programs could mitigate these problems. The primary objectives of this study were to assess the proportion of children that tolerate the suspected antibiotic well through allergy testing and, secondly, to examine which information in their medical history correlates with a positive test result. Children with a history of antibiotic allergy were categorized into high- and low-risk groups for immediate allergic reaction. The latter underwent oral provocation testing (OPT), while the high-risk group underwent the test only after negative skin tests (STs). In total, 76.8% of children tolerated the tested antibiotic well. Among children with positive OPT, two (8.0%) had to receive adrenaline for symptom resolution. Children who had exhibited suspected symptoms within one hour after antibiotic administration, and those with a history of asthma or food allergy, had an increased risk of positive allergic testing (p < 0.05). In conclusion, the adoption of a standardized protocol for an antibiotic allergy de-labeling program is essential for every allergy department.

Allergies doi: 10.3390/allergies4020004

Authors: Jennifer L. P. Protudjer Melissa L. Engel

Background: Food allergy management requires avoidance of allergenic food. While the direct costs of food allergy management have been described, avoidance may also contribute to time and opportunity costs. We aimed to conduct a scoping review of the peer-reviewed literature on the indirect costs of food allergy, and to characterise these costs through a series of fictitious case studies. Methods: We performed a scoping review, guided by Arskey and O’Malley’s methodological framework, and reported using the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews. Eligible studies included original, peer-reviewed, English language literature with no lower limits to publication dates, which addressed the indirect costs of food allergy, including time and opportunity costs. A search strategy was developed by content experts with experience performing multi-database scoping reviews. The search was performed on 10 July 2023, managed using Rayyan (Cambridge, USA), and screened for eligibility. Results: Searches yielded 104 articles. After deduplication, 96 articles were screened at the title and abstract level; 12 articles were included following full-text screening. Of these, three studies were performed on adults with food allergy, eight studies were based on data collected from caregivers of children with food allergy, and one study made use of data reflecting adults and caregivers of children with food allergy. Collectively, indirect costs were identified as higher amongst those with vs. without food allergy. The few studies on age and food allergy differences (e.g., type and number of food allergies, history of reaction) are equivocal. Conclusions: The limited body of peer-reviewed literature supports that food allergy commonly carries substantial indirect costs across diverse measurement tools, albeit with age-group differences.

Allergies doi: 10.3390/allergies4020003

Authors: Hannah Crum Brandon Gagnon Alexis Thumann Abbey Sidebottom Marc Vacquier Krista Gens

Documented penicillin allergies are associated with an increased risk of surgical site infections (SSIs), and first-line antibiotics (e.g., cefazolin) are associated with a lower risk of SSIs. The goal of this study was to evaluate the effect of a pharmacist-driven penicillin allergy de-labeling pilot program on the use of preoperative cefazolin in selected surgery patients with documented penicillin allergies. This single-center, quasi-experimental study included adult patients with a charted penicillin allergy who underwent CT or spine surgery in 2021 (control group) or during the 6-month intervention pilot (October 2022–March 2023). In the intervention group, qualifying patients were interviewed via phone to assess allergy history. Qualified patients were de-labeled or referred to an allergist for outpatient skin testing and/or oral challenge. The primary outcome was the rate of cefazolin use preoperatively. Secondary outcomes included 30-day SSIs, Clostridioides difficile infection, acute kidney injury, readmission, and hospital length of stay. Of the intervention group, 57 (79.2%) patients completed the interview. Cefazolin was used preoperatively in 71.0% (152) of the control group versus 88.9% (64) of the intervention group (p < 0.002). There were no clinically significant differences in secondary outcomes. The pharmacist-driven penicillin allergy de-labeling pilot program in CT and spine surgery patients was associated with increased cefazolin use.

Allergies doi: 10.3390/allergies4010002

Authors: Roy Kennedy

The treatment of allergic conditions presents a challenge for both seasonal allergic rhinitis and perennial rhinitis sufferers. The increasing prevalence of both of these types of allergic responses requires the use of a range of treatments which can provide relief. The treatment of allergic rhinitis has been considered under the ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines. Current treatment options include medication and avoidance for those with reduced responses, but more expensive treatments include immunotherapy and the use of monoclonal antibodies (mAb). All treatments target specific parts of the inflammatory response which includes mast cells, eosinophils and basophils. Phototherapy can be a useful addition to these treatments, and combinations of UV-B (5%), UV-A (25%) and visible light (70%) in phototherapy treatments have been shown to reduce the severity of symptoms. Phototherapy consisting of visible wavelengths and infrared light (660 nm 940 nm) was shown to be particularly effective in treating perennial rhinitis. The use of a range of wavelengths in the control of allergic responses is described in this paper. Phototherapy can form part of an effective treatment regime for allergic rhinitis sufferers which can exploit synergies in the control of the condition elicited through several pathways.

Allergies doi: 10.3390/allergies4010001

Authors: Clarissa A. Seidler Ricarda Zeindl Monica L. Fernández-Quintero Martin Tollinger Klaus R. Liedl

Allergens are substances that cause abnormal immune responses and can originate from various sources. IgE-mediated allergies are one of the most common and severe types of allergies, affecting more than 20% of the population in Western countries. Allergens can be subdivided into a limited number of families based on their structure, but this does not necessarily indicate the origin or the route of administration of the allergen, nor is the molecular basis of allergenicity clearly understood. This review examines how understanding the allergenicity of proteins involves their structural characterization and elucidates the study of conformational diversity by nuclear magnetic resonance spectroscopy. This article also discusses allergen cross-reactivity and the mechanisms by which IgE antibodies recognize and bind to allergens based on their conformational and linear epitopes. In addition, we outline how the pH, the proteolytic susceptibility and the endosomal degradation affect the outcome of allergic reactions, and how this is correlated with conformational changes and secondary structure rearrangement events. We want to emphasize the importance of considering structural diversity and dynamics, proteolytic susceptibility and pH-dependent factors to fully comprehend allergenicity.

Allergies doi: 10.3390/allergies3040014

Authors: Christos Kogias Aikaterini Drylli Demosthenes Panagiotakos Konstantinos Douros George Antonogeorgos

Allergic rhinitis is the most common immune disorder worldwide, affecting approximately 10–40% of the general population. It is characterized by an inflammatory response of the nasal mucosa following exposure to non-infectious, inhaled, and airborne allergens that are defined based on the period of exposure to the allergen as annual, seasonal, or episodic. A variety of factors are found to relate to the prevalence of allergic rhinitis, i.e., sex, race, age, seasonality, personal and family-positive atopic history, as well as exposure to environmental and epigenetic factors. In addition to the local inflammation in the nasal mucosa, systemic inflammation is activated in the entire respiratory system, such as rhinoconjunctivitis, asthma, sinusitis, and otitis media with effusion. The aim of this study was to evaluate the trends in the prevalence of allergic rhinitis in the Greek pediatric and adolescent population since 1990. Research was performed in electronic databases (PubMed, ScienceDirect, and Cochrane Library) using appropriate MeSH terms for related studies from 1990 to 2023. We found 12 studies, 11 prospective and 1 cross-sectional, conducted in the cities of Athens, Thessaloniki, Patras and Evros prefecture, with sample sizes varying from 517 to 3076 subjects aged 6–17 years old. The prevalence of allergic rhinitis showed geographic and temporal variability, ranging between 2.1 and 32.5% in children and 25.3 and 30.8% in adolescents, with increasing trends. Factors such as gender (male), age (8–10 years), environmental exposures (moisture, mites, and fungi), positive atopic profile, and family history (asthma and eczema) were related to the manifestation of the disease. The need for systematic research in the Greek child and adolescent population is vital to recognize, prognosis, and control allergic rhinitis manifestations.

Allergies doi: 10.3390/allergies3040013

Authors: Masumi Nagae Maki Nagata Masako Matsumoto Naomichi Takemoto Yhiya Amen Dongmei Wang Yuri Yoshimitsu Kuniyoshi Shimizu

Eriobotrya japonica (E. japonica) leaves have been used as an herbal traditional medicine in China and Japan owing to their anti-inflammatory and protective effects against skin conditions and allergy symptoms. These beneficial effects are likely mediated by the various triterpenoids present in E. japonica leaves. However, the efficacy of E. japonica leaves in the treatment of allergic rhinitis has not been evaluated in humans. Therefore, in the present study, a randomized, controlled, double-blind trial was performed on healthy adults of age >20 (n = 27) who were randomly assigned to receive either 2.5 g of placebo or E. japonica leaf supplements once daily for 4 weeks. The Japanese Allergic Rhinitis Quality of Life Standard Questionnaire (JRQLQ), dermatological allergy symptoms, Dermatology Life Quality Index, and skin condition parameters were assessed at baseline and after 4 weeks. Significant differences were observed in the variability of the itchy nose, itchy eyes, and eye symptoms between the E. japonica supplementation and placebo groups after 4 weeks. Arm skin transepidermal water loss was improved only in the E. japonica supplementation group. This study suggests that E. japonica leaves can be used as a functional food ingredient to relieve allergic symptoms.

Allergies doi: 10.3390/allergies3030012

Authors: Camilo Vieira Raphael Silva Elisânia Silveira Antônio Fernandes Dumar Jaramillo-Hernández Luis Garcés Larissa Fonseca Bruna Machado Jamille Fernandes Gabriela Pinheiro Álvaro Cruz Fatima Ferreira Philip Cooper Luis Pacheco Neuza Alcantara-Neves Carina Pinheiro Eduardo da Silva

(1) Background: Modification of the structural elements of allergens is widely used in the field of allergies. The goal of the present research was to express, purify, and characterize the shortened recombinant group 5 allergen of Dermatophagoides pteronyssinus (rDer p 5). (2) Methods: rDer p 5 storage stability and aggregation capacity were explored through in silico analysis, dynamic light scattering (DLS), and SDS-PAGE. Serum IgE reactivity and cytokine amount were investigated in sera or cell culture supernatants through ELISA, MULTIPLEX®, and Western blot analysis using sera from sensitized humans from Brazil, Colombia, and Ecuador. (3) Results: Dimeric rDer p 5 was detected through native PAGE, and this result was confirmed by data from DLS. The protein was thermically stable, as it did not degrade at 4 °C for 21 days. The shortened rDer p 5 was classified as a major IgE allergen in Brazil and Colombia, but minor in Ecuador. IL-13, IL-10, IL-1β, and IL-6 were significantly elevated in the sera of rDer p 5-reactive patients. The same cytokines plus IL-5 were more secreted by human cells upon rDer p 5 stimulation. (4) Conclusions: N-terminal peptide deletion led to a higher rDer p 5 folding stability, which, even though dimeric, was an IgE-reactive protein. Therefore, rDer p 5 could be used for molecular diagnostic applications or as backbone for hypoallergen design.

Allergies doi: 10.3390/allergies3030011

Authors: Marco Spalletti Valentina Lasala Paolo Cameli Laura Bergantini Marco Saletti Valerio Beltrami Elena Bargagli Miriana d’Alessandro

Pollen food allergy syndrome (PFAS) is an allergic reaction to specific foods in persons previously sensitised to pollen. The diagnosis of PFAS is made after taking a patient’s medical history and, in some cases, conducting skin tests and oral food tests with raw fruit or vegetables. The aim of the present study was to evaluate the role of Pru p 7 in patients suspected of having PFAS, who show clinical symptoms, positivity for Cup a 1 and negativity for Pru p 1 and Pru p 3. A total of 51 patients (mean age ± standard deviation, 33 ± 15 years; 20 men and 31 women), referred to the respiratory diseases and allergology units of Siena University Hospital, were enrolled retrospectively. All of them underwent allergy consultation and IgE evaluation for Cup a 1, Pru p 1 and Pru p 3 by immuno solid-phase allergen chip (ISAC). Pru p 7 assay was performed by the ImmunoCAP Phadia method in patients who tested positive for Cup a 1 and simultaneously negative for Pru p 1 and Pru p 3 by ISAC. The serum of 51 patients was tested for sensitisation to Pru p 7 by the ImmunoCAP Phadia method, and nine patients (17.65%) were found positive. An area under the receiver operating characteristic (AUROC) curve of 99.51% made it possible to distinguish PFAS and non-PFAS patients on the basis of Pru p 7 values. The best cut-off value was 0.16 kUA/l, which gave a 85.7% sensitivity and 97.73% specificity. This study helps define the role of Pru p 7 in PFAS patients sensitised to cypress pollen and testing negative to Pru p 1 and Pru p 3. A fast, easy and non-invasive diagnostic method is proposed to detect IgE specific for Pru p 7. Inclusion of Pru p 7 in the ISAC assay panel would facilitate the diagnosis of PFAS.

Allergies doi: 10.3390/allergies3030010

Authors: Annick Barre Hervé Benoist Pierre Rougé

Most of the allergenic proteins from fruits identified so far belong to different families of pathogenesis-related (PR) proteins. These PR proteins have been classified in different families of structurally and functionally unrelated proteins, but the majority of all fruit allergens belong to three groups, in particular PR-5 thaumatin-like proteins (TLP), PR-10 Bet v 1-like proteins, and PR-14 non-specific lipid transfer proteins (nsTLP). Some allergenic proteins from fruits can also be found among PR-protein families of PR-2 β1,3-glucanase proteins, PR-3 chitinases I, II, IV–VII, and PR-8 chitinases III. In addition, other important fruit allergens occur in protein families unrelated to the PR-protein families, such as the profilins and the newly emerging group of gibberellin-regulated proteins (GBRP). Finally, proteins that belong to seed storage proteins from higher plants, including 2S albumins, 7S globulins (vicilin), and 11S globulins (legumin), must be retained as possible potential fruit allergens resulting from the unintended consumption of the seeds. Here, we present an overview of the structural organization, functional properties, and phylogenetical relationships among these different groups of fruit allergens, supporting the occurrence of cross-reactivity and cross-allergenicity often described between fruit allergens, and the corresponding allergens from vegetables and pollens.

Allergies doi: 10.3390/allergies3020009

Authors: Dimitrina Miteva Snezhina Lazova Tsvetelina Velikova

Asthma is a common respiratory disease that affects people of all ages, characterized by considerable heterogeneity in age, clinical presentation, genetics, epigenetics, environmental factors, treatment response, and prognostic outcomes. Asthma affects more than 330 million people worldwide, of which 33% are children under 14 years, and 27% are adults whose first symptoms occurred in childhood. However, the genetic and epigenetic mechanisms of childhood allergic diseases and asthma are still not fully understood. Here, we conducted a biomedical narrative review of genes associated with the risk, severity, and susceptibility of childhood asthma since it differs from asthma in adults regarding their pathophysiology, development, and outcomes. We also systematized the available information on epigenetic changes associated with childhood asthma.

Allergies doi: 10.3390/allergies3020008

Authors: Caoimhe Cronin Ciobha O’Kelly Hannah Keohane Laura Flores Villarta Ciara Tobin Roberto Velasco Juan Trujillo Wurttele

Adrenaline auto injectors (AAI) are the mainstay of treatment in anaphylaxis. However, many caregivers of children with food allergies are unable to administer an AAI when assessed. One proposed factor for this finding is the lack of training and familiarity of the different AAI devices. The aim of this study is to explore the usage of different brands of adrenaline auto-injectors among caregivers of children with food allergies in Ireland. A cross-sectional study method was employed using an online questionnaire. An amount of 121 (75.58%) caregivers reported that their child carried an Epipen®, 25 (15.82%) carried Jext®, and 12 (7.59%) carried Anapen®. An amount of 48.73% (n = 77) of caregivers had switched brands of AAI at least once before, with lack of availability of their usual device at their pharmacy being the most common reason for this. Factors associated with change were a household income >100,000 € (70% vs. 44.9% of those with less income; p = 0.04) and parents ≥40 years old (59.6% vs. 32.8% of patients whose parents younger; p < 0.01). When asked what they preferred about a particular AAI brand, caregivers appreciated a simple design with minimal steps involved in administration, clear colour coding, online resources, formal training from a healthcare professional, and first-hand experience in using the AAI. These findings show, for the first time, that switching brands is a common occurrence among caregivers of children with food allergies. These findings support the EAACI recommendation to train parents regularly in all available brands of AAI and to retrain parents when switching to different devices.

Allergies doi: 10.3390/allergies3020007

Authors: Henry C. Ezechukwu Oyelola A. Adegboye Wahab O. Okunowo Theophilus I. Emeto

The search for an effective treatment of allergic conditions is an ongoing global health challenge due to the high prevalence of allergies. Epinephrine and glucocorticosteroids remain the oldest and most widely used treatment regimen for allergy, and these medications are for short relief. In extreme allergy manifestations, the current treatment options aim to use monoclonal antibody (mAb) to target pathological pathways of inflammation involving mast cells, eosinophils, and basophils. These cells have the propensity to induce an allergic-inflammatory response. Studies have shown that they are responsible for several allergic diseases, such as allergic asthma, atopic dermatitis, rhinitis, and conjunctivitis. Studies evaluating monoclonal antibodies against serum IgE (Omalizumab), Th-2 cytokines, such as IL-4, IL-13 (dupilumab), and IL-5 suggest an attenuation of allergic symptoms and improvement in patients’ overall well-being. However, several factors such as cost of production (i.e., antibody purification), host immunogenicity, safety, and efficacy have hindered the availability of purified mAb in developing countries. Gene therapy is a promising tool for treating allergy, and emerging studies have suggested that antibody gene therapy may be the future for treating extreme cases of allergy manifestations. This paper describes the use of purified monoclonal antibodies for treating severe allergic responses and the associated limitations. It explores the prospects of antibody gene therapy for modulating allergy episodes.

Allergies doi: 10.3390/allergies3010006

Authors: Angela Klain Giulio Dinardo Cristiana Indolfi Marcella Contieri Alessandra Salvatori Sossio Vitale Fabio Decimo Giorgio Ciprandi Michele Miraglia del Giudice

The prevalence of allergic rhinitis is rising, and it is impacting children’s growth and quality of life. To uncover unconventional treatment modalities, research was carried out to clarify the significance of novel components in the pathophysiology of allergic rhinitis. One of these elements was gut microbiota, which plays a crucial role in the development and evolution of allergic disorders. Specifically, dysbiosis, defined as impaired microbiota composition, characterizes allergic disorders. In light of this concept, probiotics (beneficial bacteria) may restore gut dysbiosis, rebalance the immune response, and indirectly influence the clinical course of allergic diseases. In this article, we discussed the role of the gut–lung axis in children and reported on new findings. We also reviewed the most relevant studies about probiotics in patients with allergic rhinitis.

Allergies doi: 10.3390/allergies3010005

Authors: Youssouf Sereme Moïse Michel Soraya Mezouar Nicolas Orain Renaud Cezar Tran Tu Anh Pierre Corbeau Anne Filleron Joana Vitte

Background: The natural history of immunoglobulin (Ig) E-mediated diseases in preterm infants is still elusive. We aimed at developing a non-invasive tool for detecting specific IgE (sIgE) and eosinophil-derived neurotoxin (EDN) in neonatal fecal samples and evaluating its predictive value for the development of IgE-mediated diseases during the first year of life. Methods: We developed a stool extraction protocol, followed by freeze-drying and solubilization. The sIgEs were investigated in neonatal fecal samples from 21 preterm infants with a 300-allergen multiplex and confirmed by a capillary Western blot with a nano-immunoassay. EDN concentration was used to investigate the local eosinophilic component. Results: The multiplexed allergen assay detected sIgE in all of the samples. A Western blot was used to confirm the results. The frequency and levels of sIgE in the neonatal fecal samples differed between the infants who developed IgE-mediated diseases and the controls. Allergen specificity was associated with the development of cow’s milk allergy (CMA) and asthma. The development of CMA was predicted by the sIgE response to milk proteins (sensitivity was 88%; specificity was 78%). The EDN levels predicted the development of IgE-mediated diseases (sensitivity was 100%; specificity was 75%). Conclusion: The non-invasive investigation of neonatal fecal sIgE is a promising tool for predicting the subsequent development of IgE-mediated diseases. Clinical Implications: The non-invasive sIgE and EDN profiling of neonatal fecal samples from preterm infants can predict the development of IgE-mediated diseases.

Allergies doi: 10.3390/allergies3010004

Authors: Annick Barre Hervé Benoist Pierre Rougé

Celiac peptide-generating α- and γ-gliadins consist of a disordered N-terminal domain extended by an α-helical-folded C-terminal domain. Celiac peptides, primarily located along the disordered part of α- and γ-gliadin molecules, are nicely exposed and directly accessible to proteolytic enzymes occurring in the gastric (pepsin) and intestinal (trypsin, chymotrypsin) fluids. More than half of the potential celiac peptides identified so far in gliadins exhibit cleavage sites for pepsin. However, celiac peptides proteolytically truncated by one or two amino acid residues could apparently retain some activity toward HLA-DQ2 and HLA-DQ8 receptors in docking experiments. Together with the uncleaved peptides, these still active partially degraded CD peptides account for the incapacity of the digestion process to inactivate CD peptides from gluten proteins. In contrast, sourdough fermentation processes involve other proteolytic enzymes susceptible to the deep degradation of celiac peptides. In particular, sourdough supplemented by fungal prolyl endoproteases enhances the degrading capacities of the sourdough fermentation process toward celiac peptides. Nevertheless, since tiny amounts of celiac peptides sufficient to trigger deleterious effects on CD people can persist in sourdough-treated bread and food products, it is advisable to avoid consumption of sourdough-treated food products for people suffering from celiac disease. As an alternative, applying the supplemented sourdough process to genetically modified low gluten or celiac-safe wheat lines should result in food products that are safer for susceptible and CD people.

Allergies doi: 10.3390/allergies3010003

Authors: Abha Jain

Plants are essential for humans as they serve as a source of food, fuel, medicine, oils, and more. The major elements that are utilized for our needs exist in storage organs, such as seeds. These seeds are rich in proteins, show a broad spectrum of physiological roles, and are classified based on their sequence, structure, and conserved motifs. With the improvements to our knowledge of the basic sequence and our structural understanding, we have acquired better insights into seed proteins and their role. However, we still lack a systematic analysis towards understanding the functional diversity associated within each family and their associations with allergy. This review puts together the information about seed proteins, their classification, and diverse functional roles along with their associations with allergy.

Allergies doi: 10.3390/allergies3010002

Authors: Annick Barre Hélène Sénéchal Christophe Nguyen Claude Granier Pascal Poncet Pierre Rougé

The present work was aimed at identifying the IgE-binding epitopic regions on the surface of the Cup s 3 allergen from the common cypress Cupressus sempervirens, that are possibly involved in the IgE-binding cross-reactivity reported between Cupressaceae species. Three main IgE-binding epitopic regions were mapped on the molecular surface of Cup s 3, the PR-5 thaumatin-like allergen of common cypress Cupressus sempervirens. They correspond to exposed areas containing either electropositive (R, K) or electronegative (D, E) residues. A coalescence occurs between epitopes #1 and #2, that creates an extended IgE-binding regions on the surface of the allergen. Epitope #3 contains a putative N-glycosylation site which is actually glycosylated and could therefore comprise a glycotope. However, most of the allergenic potency of Cup s 3 depends on non-glycosylated epitopic peptides. The corresponding regions of thaumatin-like allergens from other closely related Cupressaceae (Cryptomeria, Juniperus, Thuja) exhibit a very similar conformation that should account for the IgE-binding cross-reactivity observed among the Cupressaceae allergens.

Allergies doi: 10.3390/allergies3010001

Authors: Rosalinda Monroy Del Toro Ryan Incrocci Olivia Negris Shaina McGrath Julie A. Swartzendruber

Probiotics are an attractive target for reducing the incidence of allergic disease. Bacillus subtilis is a gut-associated probiotic bacteria that can suppress allergic lung disease; however, it is not clear for how long this protection lasts. We exposed C57Bl/6 mice to B. subtilis via oral gavage and challenged them with intranasal house-dust mite for up to 8 weeks. We found that B. subtilis treatment was able to provide protection from eosinophil infiltration of the airways for 3 weeks. This loss of protection correlated with an increase in the eosinophil chemoattractant CCL24. Additionally, we demonstrate that B. subtilis treatment altered the bacterial composition by increasing the phylum Bacteroidetes and Verrucomicorbiota. The phylum Verrucomicorbiota was reduced in B. subtilis-treated mice at 8 weeks when protection was lost. These results support B. subtilis as a prophylactic for preventing the production of allergic lung disease and highlights that protection can last up to 3 weeks. This work also expands our understanding of how B. subtilis mediates protection and that in addition to modifying the immune system it is also altering the host microbiota.

Allergies doi: 10.3390/allergies2040014

Authors: Hiroshi Kumanomidou Mitsuhiro Okano

Allergic rhinitis (AR) is a type I allergic disease characterized by immunoglobulin E (IgE) -mediated hypersensitivity of the nasal mucosa. Here, we focused on a commercial test kit named Allerwatch® (AW) for the diagnosis of allergic conjunctivitis (AC) in which total tear IgE is qualitatively detected based on immunochromatography. We evaluated the usefulness of the AW test for detecting total IgE in the nasal discharge of AR and non-allergic rhinitis (non-AR) patients in comparison and combination with the conventional nasal smear examination for eosinophils. Using the AW test, total IgE in nasal fluid was detected in 64.76% of the AR patients and 11.11% of the non-AR patients, with a significant difference between the groups (p < 0.001). As compared to non-AR, the sensitivity and specificity of the detection of total IgE in nasal fluid for detecting AR were 64.76% and 88.89%, respectively. In the AR patients, house dust mites (57.1% of patients) and Japanese cedar pollen (93.3% of patients) were the major sensitizing antigens. When we considered a positive result in either of the two examinations to indicate a positive result, the rate of positivity in AR patients increased to 78.10%. As compared to non-AR, the sensitivity and specificity of the combination of both examinations for detecting AR were 78.10% and 83.33%, respectively. The AW test in the nasal cavity and the qualitative measurement of total IgE in nasal fluid may enable the detection of allergic elements in patients who present to a medical institution with nasal symptoms. In addition, the detection rate is increased when combined with the nasal smear examination for eosinophils.

Allergies doi: 10.3390/allergies2040013

Authors: Giorgio Ciprandi Valerio Damiani Vittorio Cordara Maria Angela Tosca

Recurrent respiratory infections (RRIs) account for relevant economic and social implications and significantly affect family life. Local Bacteriotherapy (LB) represents an innovative option in preventing RRIs. Local bacteriotherapy consists of administering “good” and safe bacteria (probiotics) by nasal or oral route. In particular, two strains (Streptococcus salivarius 24SMB and Streptococcus oralis 89a) are commonly used. The present article presents and discusses the literature concerning LB. Infections of airways include the upper and lower respiratory tract. A series of clinical trials investigated the preventive role of LB in preventing upper and lower RIs. These studies demonstrated that LB safely reduced the prevalence and severity of RIs, the use of antibiotics, and absences from school. Therefore, Local Bacteriotherapy may be considered an interesting therapeutic option in RRI prevention.

Allergies doi: 10.3390/allergies2040012

Authors: Stephan Vlaminck Emmanuel Prokopakis Hideyuki Kawauchi Marc Haspeslagh Jacques Van Huysse João Simões Frederic Acke Philippe Gevaert

Background: The EPOS guidelines promote cellular analysis as a primary goal in endotyping chronic rhinosinusitis (CRS). Current analysis is mainly based on biopsy or operative tissue collection, whereas the use of sinonasal secretions for inflammatory endotyping is not advocated in clinical practice. Early endotyping is crucial though, especially regarding the increasing evidence of patient-tailored therapy. We aimed to investigate the diagnostic value and reproducibility of sinonasal secretions sampling. Methods: First, preoperative secretion analysis of 53 Caucasian CRS patients was compared to subsequent operative tissue analysis. Second, secretion analysis at two different time points was compared for 10 postoperative Caucasian CRS patients with type 2 (T2) inflammation and 10 control participants. Secretions were collected by both endoscopic aspiration and nasal blown secretions in all participants. Results: The sensitivity to detect T2 inflammation was higher in nasal aspiration samples (85%) compared to nasal blow secretions (32%). A specificity of 100% for both techniques was obtained. A 90% reproducibility for T2 eosinophil detection was found by sampling at different time points regardless of the technique. Of the T2 patients, 60% showed no T2 inflammatory pattern more than one year after endoscopic sinus surgery. Conclusions: Nasal secretion sampling, especially aspiration of nasal secretions, is useful in the detection of T2 inflammation in CRS pathology. We proposed a structured histopathology analysis to be useful in daily clinical practice, which includes Congo red staining sensitive for eosinophilic cells and free eosinophil granules. Analysis of nasal secretions enables endotyping in an early stage, allowing more directed therapy.

Allergies doi: 10.3390/allergies2030011

Authors: Giorgio Ciprandi Maria Angela Tosca

Allergic rhinitis (AR) is a widespread medical condition affecting up to 40% of the general population. Type 2 inflammation determines typical nasal symptoms. In addition, gut and respiratory dysbiosis are present in AR patients. Probiotics have several beneficial effects on immunity, inflammatory pathways, and anti-infective properties. Namely, probiotic supplementation could restore immune response, promote eubiosis, and switch off inflammation. Thus, probiotics have also been investigated in AR. In addition, there is accumulating evidence that some specific strains of probiotics may improve AR. Five meta-analyses on probiotics in AR management were consistently published in the first half of 2022. The conclusions, although not definitive, argue for the possible use of probiotics as part of an add-on strategy in managing patients with allergic rhinitis.

Allergies doi: 10.3390/allergies2030010

Authors: Annick Barre Hélène Sénéchal Christophe Nguyen Claude Granier Pierre Rougé Pascal Poncet

Pectate-lyase allergens, the group 1 of allergens from Cupressaceae pollen, consist of glycoproteins exhibiting an extremely well-conserved three-dimensional structure and sequential IgE-binding epitopes. Up to 10 IgE-binding epitopic regions were identified on the molecular surface, which essentially cluster at both extremities of the long, curved β-prism-shaped allergens. Most of these IgE-binding epitopes possess very similar conformations that provide insight into the IgE-binding cross-reactivity and cross-allergenicity commonly observed among Cupressaceae pollen allergens. Some of these epitopic regions coincide with putative N-glycosylation sites that most probably consist of glycotopes or cross-reactive carbohydrate determinants, recognized by the corresponding IgE antibodies from allergic patients. Pectate-lyase allergens of Cupressaceae pollen offer a nice example of structurally conserved allergens that are widely distributed in closely-related plants (Chamæcyparis, Cryptomeria, Cupressus, Hesperocyparis, Juniperus, Thuja) and responsible for frequent cross-allergenicity.

Allergies doi: 10.3390/allergies2030009

Authors: Claire C. Y. Wang Henry H. L. Wu Arvind Ponnusamy Isobel Pye Alexander Woywodt

Chronic kidney disease-associated pruritus (CKDaP) is an often under-diagnosed and under-recognized condition, despite its considerable prevalence within the chronic kidney disease (CKD) population. Universally accepted guidelines are also lacking. The true prevalence of CKDaP worldwide therefore remains unknown, although its negative impact on mortality and health-related quality of life outcomes is very clear. The pathophysiological mechanisms leading to the onset of CKDaP are only partly understood. CKDaP is currently believed to be caused by a multifactorial process, from local skin changes, metabolic alterations, the development of neuropathy and dysregulation of opioid pathways, and psychological factors. Much work has been carried out towards a more systematic and structured approach to clinical diagnosis. Various tools are now available to assess the severity of CKDaP. Many of these tools require greater validation before they can be incorporated into the guidelines and into routine clinical practice. Further efforts are also needed in order to increase the awareness of clinicians and patients so that they can identify the CKDaP signs and symptoms in a timely manner. Currently established treatment options for CKDaP focus on the prevention of xerosis via topical emollients, the optimization of dialysis management, early referral to kidney transplantation if appropriate, oral antihistamine, and a variety of neuropathic agents. Other novel treatment options include the following: topical analgesics, topical tacrolimus, cannabinoid-containing compounds, antidepressants, oral leukotrienes, opioids, and non-pharmacological alternative therapies (i.e., phototherapy, dietary supplements, acupuncture/acupressure). We provide an updated review on the evidence relating to the epidemiology, the pathophysiology, the clinical assessment and diagnosis, and the management of CKDaP.

Allergies doi: 10.3390/allergies2030008

Authors: Sayantani B. Sindher Vanitha Sampath Andrew R. Chin Kari Nadeau Rebecca Sharon Chinthrajah

The prevalence of allergic diseases is rising globally, inducing heavy quality of life and economic burdens. Allergic reactions are mediated by the complex bi-directional cross-talk between immune and nervous systems that we are only beginning to understand. Here, we discuss our current understanding of the molecular mechanisms of how this cross-talk occurs in the skin, gut, and lungs. An improved understanding of the communication between the immune and nervous system may lead to the development of novel therapies for allergic diseases.

Allergies doi: 10.3390/allergies2030007

Authors: Antonella Tammaro Camilla Chello Francesca Romana Parisella Ganiyat Adenike Ralitsa Adebanjo

Occupational allergic contact dermatitis is an occupational skin condition which is characterized by a delayed cell-mediated hypersensitivity reaction triggered by one or more work-related substances. In this article, we describe a hairdresser who presented with occupational allergic contact dermatitis and was treated with alitretinoin. It is important to emphasize the value of early diagnosis and treatment of occupational contact dermatitis as this allows us to tackle the physical, psychosocial and cost-related burdens that this disorder brings.