BackgroundMustard allergy is uncommon but can cause severe reactions, while mustard-specific oral immunotherapy (OIT) data are almost absent.MethodsWe retrospectively described four children managed with mustard-directed OIT or structured oral exposure at two French centers and updated a focused PubMed search through 17 October 2026. Pretreatment diagnostic certainty varied. Continued maintenance was defined pragmatically as ingestion according to the documented home regimen at latest follow-up and was not equated with desensitization.ResultsAges at treatment initiation ranged from 4 to 12 years. Two younger children progressed to 3 g of prepared commercial mustard condiment daily without a documented treatment-requiring maintenance reaction, although baseline challenges did not establish unequivocal systemic thresholds. An 11-year-old boy with previous systemic reactions and mustard-specific IgE >100 kUA/L developed pruritus, paroxysmal cough, and conjunctivitis during escalation to 420 mg mustard ingredient in mayonnaise; symptoms resolved with desloratadine and inhaled salbutamol. He later discontinued because of recurrent dosing-related symptoms despite dose reduction. A 12-year-old boy progressed to 5 g mustard daily and subsequently once or twice weekly. Products, dose units, diagnostic certainty, and maintenance schedules were heterogeneous, and mustard-protein doses were not analytically quantified.ConclusionThis series describes heterogeneous real-world pathways of mustard-directed OIT and structured oral exposure, including treatment-limiting intolerance, but does not establish an efficacy or desensitization rate. Future studies require prespecified diagnostic criteria, explicit product characterization and dose units, prospective safety and adherence capture, defined maintenance schedules, patient-centered outcomes, and standardized outcome challenges.
BackgroundAtopic dermatitis (AD) is a prevalent chronic inflammatory skin disease of childhood. Omega-3 fatty acids have been investigated for their potential role in modulating allergic inflammation; however, evidence regarding their effectiveness in preventing or treating AD remains inconsistent.ObjectiveTo systematically review and narratively synthesize randomized controlled trial evidence on prenatal and postnatal omega-3 fatty acid supplementation for the prevention and treatment of AD in infants and children.MethodsPubMed and Web of Science were searched in October 2025, with an updated PubMed search in October 2026, to identify randomized controlled trials of omega-3 supplementation given during pregnancy or after birth that reported AD outcomes. Data were extracted, and risk of bias was assessed using RoB 2. Trials were grouped by clinical indication (prevention or treatment) and timing of supplementation, and a narrative synthesis was performed because of substantial heterogeneity.ResultsEleven randomized controlled trials were included: nine prevention trials (six prenatal and three postnatal) and two treatment trials in children with established AD. Prenatal supplementation did not show a consistent preventive effect. Lower IgE-associated eczema was reported in two trials in high-risk families, but the effect was not always significant after adjustment and did not persist at longer follow-up; the two most recent trials found no overall effect, and one trial reported more eczema with omega-3. In one trial, the effect differed by maternal PTGS1 (COX-1) genotype. None of the three postnatal prevention trials found a significant effect. Both treatment trials reported improvement in AD severity, but they were small and short, and one used a multi-component product. Risk of bias was low in one trial, raised some concerns in seven, and was high in three.ConclusionsRandomized controlled trial evidence does not support omega-3 supplementation for the prevention of AD, whether given prenatally or postnatally. Limited evidence suggests a possible benefit in children with established AD, which should be tested in larger trials. Any role of fatty acid composition or maternal genotype remains hypothesis-generating.Systematic Review RegistrationPROSPERO CRD420251161453.
BackgroundVenom Immunotherapy (VIT) safety remains a key consideration in daily clinical practice. Currently, there is considerable variation in the reported frequency of adverse events (AE) during VIT, and risk factors have not been fully elucidated. Furthermore, no previous study has used Latent Class Analysis (LCA) to assess the real-life safety of VIT across different patient profiles.MethodsLCA was performed on data from 212 adults and 165 children undergoing 398 VIT treatments using different protocols and products across 8 European countries, retrieved from the Adverse Events Registry (ADER). Associations between identified profiles and the frequency of local and systemic AE were evaluated using logistic regression.ResultsThree latent classes were identified; each class encompassed different characteristics of patients’ demographics, treatment protocols and products. Class 1: 135 patients undergoing premedicated VIT treatment without adjuvants, through ultrarush up-dosing regimens associated with a “moderate-risk” regarding AE frequency but with more severe systemic AE recorded in this class; Class 2: 138 younger patients (median age: 13.6 years old) receiving premedicated VIT, without adjuvants, using rush up-dosing associated with a “higher-risk” profile for experiencing frequent AEs [OR = 6.523, 95% CI = (3.211 –13.253); p < 0.001] and systemic AEs [OR = 4.149, 95% CI = (1.765–9.754); p = 0.001]. Honeybee (HB) venom and female sex were associated with SAE and AE, respectively, in this class, whereas each one-year increase in age was associated with 3.6% reduction in odds for AE [OR = 0.964, 95% CI (0.931–0.999), p = 0.045]. Class 3: the oldest group of patients (n = 104), receiving mostly HB-VIT with adjuvants, through conventional and cluster up-dosing protocols without premedication, associated with a “low-risk” of AE. In the overall study population, VIT with HBV, female sex and rush updosing protocol were associated with higher odds for AE.ConclusionVIT is generally well-tolerated in real-life clinical practice both in children and adults, although systemic AEs were recorded in 17.2% of cases. A high-risk profile for frequent AEs was identified in our study, with younger age, honeybee venom and female sex independently associated with higher odds of AE. These associations, together with rush updosing, were also confirmed in the overall population.
Type 2 inflammation contributes to host defense and tissue repair but, when dysregulated, can cause a broad spectrum of allergic diseases. Although atopy has traditionally been considered the result of interactions between environmental factors and polygenic susceptibility, the identification of primary atopic disorders (PADs) has revealed that single-gene defects can drive severe allergic phenotypes. In this review, we discuss selected paradigmatic disorders to illustrate how distinct molecular defects can converge on type 2 inflammation and a shared atopic phenotype, including impaired antigen-receptor signaling in CARD11-associated atopy, enhanced cytokine signaling in STAT6 gain-of-function disease, loss of immune tolerance in FOXP3 deficiency, cytoskeletal and immune-synapse dysfunction in DOCK8 deficiency, and epithelial barrier and signaling abnormalities in Netherton syndrome. We also highlight the clinical features that should raise suspicion of an underlying monogenic disorder in patients with severe atopy and discuss how molecular diagnosis may inform targeted therapeutic strategies. Collectively, insights from rare PADs provide a framework for understanding the molecular heterogeneity of type 2 inflammation and may reveal mechanisms and therapeutic targets relevant to more common allergic diseases.
Wood smoke particulate matter (WSP) is an important public health hazard. The objective of this study was to establish a mouse model of WSP-induced airway inflammation and hyperreactivity. WSP has been linked to a genetic risk variant that regulates the expression of the ERK1/2 regulator Sprouty2 (Spry2). We examined the importance of Spry2 in WSP-induced airway pathology and activation of critical immune cells in mice with inducible Spry2 gene deletion. A short-term airway exposure of naïve B6 mice to WSP induced airway hyperreactivity to methacholine and eosinophilic, and, to a lower extent, modest neutrophilic inflammation, mucus production and airway remodeling. The induction of the foregoing pathologic abnormalities was associated with number of ILC2s and CD4 T cells, increased ERK1/2 phosphorylation, and increased production of IL5, IL13 and IL17A. Inducible deletion of Spry2 prevented the induction airway hyperreactivity, airway inflammation, mucus production, Collagen deposition, and phosphorylation of ERK1/2. Spry2-/- inhibited the increase in ILC2 but not CD4 T cell frequency. ERK1/2 phosphorylation was inhibited in both ILC2s and Th2 cells in the absence of Spry2. Spry2 deletion reduced IL5, IL13 and IL17A expressing ILC2s. Similarly, Spry2 deletion reduced production of IL17A and IL13 but not IL5 in CD4 T cells. We conclude that WSP induces eosinophilic and modestly neutrophilic airway inflammation and other features of asthma. Spry2 plays a non-redundant role in WSP-induced airway pathologies, in part, by facilitating ERK1/2 activation.
