Background: Asthma and obesity frequently coexist in childhood, yet whether asthma predisposes to later adiposity remains underexplored, particularly using measures beyond body mass index (BMI). Considering this, we aimed to examine the association between asthma in early childhood and subsequent adiposity through adolescence, assessed using BMI and body fat percentage, and to evaluate sex-specific effects. Methods: This prospective study included 4717 participants from the Portuguese population-based Generation XXI birth cohort. Physician-diagnosed asthma at age 4 years was the exposure. Incident obesity and overweight/obesity were assessed at ages 7-, 10-, and 13-years using BMI and body fat percentage estimated by bioelectrical impedance analysis and classified according to age- and sex-specific percentiles. Children who were already overweight or obese at age 4 were excluded from the respective analysis. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for confounders. Effect modification by sex was tested, and sex-stratified analyses were performed. Results: Asthma was associated with a higher risk of incident obesity defined by body fat percentage in adjusted analyses (aHR=1.91, 95%CI:1.16-3.16), whereas associations with BMI-defined obesity were not statistically significant. Sex-stratified analyses showed that these associations were confined to girls, who had increased risk of obesity (aHR=1.97, 95%CI:1.19-3.26) and overweight/obesity (aHR=1.75, 95%CI:1.02-3.01) defined by body fat percentage. No significant associations were observed among boys. Conclusions: Asthma in early childhood was associated with increased adiposity in adolescence assessed by body fat percentage, particularly among girls. These findings suggest that children with asthma may develop excess fat accumulation not fully captured by BMI and support the integration of body composition and metabolic risk assessment into paediatric asthma care.

Background: The evolution of mite sensitisation profiles from childhood to adulthood is associated with distinct clinical outcomes. Longitudinal sensitisation trajectories have never been addressed across two generations over an extended time frame. Using molecular diagnosis, we aimed to investigate how the evolution of mite sensitisation relates to the expression of rhinitis and asthma in adult versus paediatric patients over a 20-year period. Methods: Specific IgE (sIgE) to mite molecular allergens was determined using MeDALL allergen chip (Der p 1, 2, 4, 5, 7, 10, 11, 14, 15, clone 16, 18, 21 and 23; Der f 1, Der f 2, Lep d 2, Blot t 5). Assessment was made in adult (n=21), adolescent (n=11) and paediatric patients (n=19) with rhinitis and/or asthma, in T1 (20-years-ago) and in T2 (current time). Results: After the 20-year-period, the adult cohort significantly decreased the number of sIgE responses to mite components - T1: 7 [3-9] versus T2: 4 [2-6], median [IQR], p=0.0040. A strong negative correlation was observed between age and the 20-year variation of sensitisation count (r = - 0.5305; p<0.0001). In adults, the reduction in mite molecular IgE responses was associated with improvement in rhinitis (p=0.0010) and asthma (p=0.0020), reflecting disease progression patterns not observed in the paediatric cohort. Conclusions: This is the first analysis to show that molecular mite sensitisation declines with ageing, and this reduction may relate to decreased asthma and rhinitis symptoms and severity. This age-associated decline highlights the importance of careful clinical interpretation in older adults to avoid overtreatment and missed diagnoses.

Allergic rhinitis (AR) is the most common chronic condition from childhood to adulthood and remains a major, often underestimated, contributor to impaired quality of life, school performance, and healthcare use. Although symptoms frequently begin early in life, pediatric AR is still underdiagnosed and inadequately treated, with important consequences for physical, emotional, and cognitive development. In this narrative review, we summarise recent evidence on the treatment of AR in children, highlighting age-specific challenges and evolving treatment concepts. International recommendations, particularly those from ARIA, support a stepwise, patient-centred approach focused on symptom control, safety, and long-term outcomes. Intranasal corticosteroids remain the cornerstone of therapy for moderate-to-severe disease, while second-generation antihistamines and intranasal antihistamines provide effective options for milder or intermittent symptoms. Fixed-dose intranasal steroid-antihistamine combinations are highly effective, providing options for children with more severe or uncontrolled AR. Allergen immunotherapy is the only disease-modifying intervention. Emerging strategies, including biologics and novel immunotherapy approaches, are promising but currently limited to specific contexts. Alongside pharmacological treatment, education, adherence support, and pragmatic environmental measures are essential to achieve sustained disease control. Ongoing gaps in the pediatric evidence-base highlight the need for age-adapted algorithms and long-term studies focusing on early intervention and disease modification.

Single Dose Amoxicillin Challenge for Suspected Serum Sickness-Like ReactionsAuthors : Nikhil A. Crain, MD1, Kirstin D. Carel, MD2, Sean T. O’Leary, MD, MPH3, Laura A. Wang, MD, MPH21 Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA2 Department of Pediatrics, Section of Allergy & Immunology, University of Colorado School of Medicine, Aurora, CO, USA3 Department of Pediatrics, Section of Infectious Disease, University of Colorado School of Medicine, Aurora, CO, USARunning Title: Single Dose Amoxicillin Challenge SSLRCorrespondence : Laura Ann Wang, MD, Children’s Hospital Colorado Anschutz Medical Campus, 13123 East 16th Ave, Aurora, CO, USA 80045, T: 720-777-1234, F: 720-848-1947Word Count: 844Tables : 1Figures : noneConflicts of Interest: noneFunding source: noneKey Words: Serum sickness-like reactions, amoxicillin, penicillin allergy, single dose drug challenge, drug allergy labelsTo the Editor:Serum sickness–like reactions (SSLRs) are delayed adverse reactions triggered by viral infections and medications.1 SSLRs associated with penicillin-based antibiotics are generally uncommon and mild, and a prior study suggests that graded oral challenges may be used to differentiate between beta-lactam-induced SSLRs and viral exanthems.2 Nevertheless, tolerance of a challenge does not preclude SSLR recurrence with future antibiotic exposure.1 While allergy practice parameters endorse direct drug challenges for low-risk benign cutaneous reactions, there is no consensus regarding SSLR challenge protocols—namely, whether to use single-dose, multi-dose, or graded approaches.3 In this retrospective study, we share outcomes of children who underwent direct single-dose amoxicillin challenges after being referred for symptoms concerning for SSLR by primary care providers.We reviewed electronic medical records (EMR) of patients who completed a direct single dose amoxicillin challenge in the outpatient allergy clinic at Children’s Hospital Colorado between 2020 and 2025. Patients received a single dose of oral amoxicillin (45 mg/kg, up to 1 g) followed by a one-hour observation period. Children were classified as having SSLR if they met the following criteria: 1) rash or hives with swelling, arthritis, or arthralgia, or 2) clinical suspicion for SSLR (e.g., swollen hands). Due to its variability in presentation, fever was not a requirement for inclusion, although its presence or absence was noted. Data were collected on patient demographics, index reaction characteristics, and labeling outcomes at the time of chart review. Summary statistics were generated to describe the demographic and clinical outcomes of patients. Our institution investigational research board (IRB) approved this study for exemption and determined consent was not required (IRB #23-1190).A total of 867 children underwent single-dose amoxicillin challenge. Seventy-four (9%) patients had index reaction symptoms consistent with SSLR (Table 1 ). Half of patients were male (50%), 32% were 2 to <6 years, 31% were 6 to <11 years, and 37% were either <2 years or ≥11 years. Index reaction was on average 4.2 years prior to allergist visit. Over half (54%) had no atopic history. Fifty-six (76%) patients had reports of swelling (e.g., “swelling”, “edema”, “puffiness”), 13 (18%) had fever, and 11 (15%) had arthritis/arthralgia (e.g., “joint pain”, “pain with walking”); nearly all (92%) presented with concurrent rash or hives. Amoxicillin was the index reaction antibiotic for most patients (91%). Most symptoms occurred after the second day of antibiotic course (57%). All patients (100%) passed a single dose amoxicillin challenge with a 1-hour observation period and were sent home following the challenge. Two patients developed late symptoms after the initial challenge (rash and joint swelling, ranging from 7 hours to 3 days after the challenge dose).There was documentation that 11 (16%) patients had exposure to a penicillin-based antibiotic course after passing the challenge. Of these, one had a documented reaction (diffuse rash with some swelling on hands, ears and face approximately three days into amoxicillin course) that occurred five years after the initial challenge. There was no documented reaction among the other patients with penicillin-based antibiotic exposure. The remaining 62 (84%) patients did not have documentation of subsequent penicillin class exposure or reaction.This retrospective study is among the first to describe children with clinical presentations concerning for SSLR who underwent a single dose amoxicillin challenge. Of note, all patients passed the direct oral challenge without immediate symptoms concerning for anaphylaxis or requiring emergency care. Among the 867 total patients in our overall cohort, about 10% had symptoms (e.g., swelling, fever, arthralgia/arthritis) consistent with SSLR, warranting closer assessment by an allergist. Amoxicillin has been reported as the most common antibiotic associated with serum sickness or SSLR reactions, which was the primary index reaction drug among penicillin-based antibiotics in our study.4 The prevalence of amoxicillin-induced SSLRs is challenging to discern due to symptom overlap and diagnostic uncertainty, with reports of the prevalence of amoxicillin-related SSLR ranging from 4 to 87%.5,6Fernandez et al. recently reported findings that children may unpredictably develop SSLR symptoms upon subsequent exposure to culprit antibiotics – often in the setting of concurrent illness – despite passing drug challenges.7 Their research highlights the difficulty of predicting SSLR and the complex immune interplay between antibiotics and infection.8,9 Average length of follow up from drug challenge to chart review in our cohort was 1.6 years (range 0.5-5.1 years). Research that incorporates longitudinal follow-up and identifies patient, drug, or illness factors associated with SSLR recurrence is warranted.This study has several limitations. First, the smaller sample size, coupled with a predominantly white cohort, may limit generalizability to populations outside our state. Second, as a retrospective review, findings were reliant on information available in our institution’s electronic medical record, and events occurring outside the system may not be captured. Third, our broad inclusion criteria may have included patients that did not truly have an SSLR. Diagnostic clarity and consensus criteria around SSLR would enhance future surveillance of outcomes.8In conclusion, this study supports the feasibility and safety of single dose amoxicillin challenges for children with suspected SSLR. Future collaboration among allergists and researchers should focus on defining optimal challenge protocols and developing approaches to potentially risk-stratify patients for future SSLR reactions.Nikhil A. Crain, MD, Kirstin D. Carel, MD, Sean T. O’Leary, MD, MPH, Laura A. Wang, MD, MPH, University of Colorado School of Medicine, Aurora, CO, USAAcknowledgements : NoneKey Message: This research supports the feasibility of single-dose amoxicillin challenges in children who were referred for symptoms concerning for SSLR by primary care providers.

Cross-reactivity among cacao and tree nuts in a paediatric allergic patientTo the Editor:Chocolate is produced from cacao beans from the Theobroma cacao tree, through a multistep process involving fermentation, drying, roasting, nib grinding and refining, and tempering, to ensure its stability and flavour [1].Most studies have reported beneficial effects of polyphenols from cacao consumption on health, specially on the cardiovascular system [2] and cognitive functions [3], among others. According the International Cocoa Organization (ICCO), the total estimated world production of cacao beans in 2023–24 was 4.368 tons, principally from Africa [4], being Europe the largest regional market, accounting for a significant share of cocoa consumption.Even though chocolate is widely consumed in the world, food allergy to cacao is unfrequent and reports on true allergy are scarce.We present the case of a 9-year old boy who for the last year, presented with oral pruritus every time he ingested almonds, cashew nuts, walnuts and hazelnuts. He also developed oral itchiness as well as vomiting and lethargy, minutes after ingesting cacao containing foods. He tolerated peanuts and sunflower and sesame seeds.Regarding his atopic background, he suffered from exercise induced asthma and mild rhinitis, being sensitised to dust mites.Skin prick test with tree nuts, peanut and cacao extracts (Diater and Leti Laboratories, Madrid, Spain) yielded positive for almond (15x8mm), hazelnut (17x10mm), walnut (7x8mm), pecan nut (20x10mm), macadamia nut (10x5mm), pistachio nut (25x10mm), cashew nut (20x15mm), pine nut (5x2mm), peanut (5x2,5mm), sesame seeds (3x5mm).Prick by prick with pure cacao powder 100% (Valor Cacao®) was positive (5x5mm). Serum specific IgE determination to cacao by ImmunoCAP (ThermoFisher Scientific, Madrid, Spain) was 0.36kU/L. Total serum IgE was 702kU/L.ALEX® assay showed patient’s specific IgE recognition of Ana o 2 (11S globuline) and Ana o 3 (2S albumin), from cashew nut; Cor a 9 (11S globuline) and Cor a 11 (7/8 globuline), from hazelnut; Jug r 1 (2S albumin), Jug r 2 (7/8 globulin), Jug r 4 (11S globulin) and Jug r 6 (7/8 globuline), from walnut; Pis v 1 (2S albumin), Pis v 2 (11S globuline), and Pis v 3 (7/8 globuline), from pistachio nut; Pru du from almond; Ses I from sesame seeds; Hel a from sunflower seeds; Pap a 2S albumin from poppy seeds.SDS-PAGE-Immunoblotting was performed according to the Laemmli method [5] to estimate de molecular mass of the IgE-reactive proteins from samples from two different and popular cacao brands in Spain: Valor® Cacao (pure cacao bean powder with no tree nut traces as reported by manufacturer) and Cola Cao® (sugar, defatted cocoa, and a cola-malted cereal cream, made from wheat flour, barley malt extract, and kola nut extract, with no tree nut traces as indicated in label), under reducing and non-reducing conditions. Cacao proteins were previously isolated: protein extraction from Cola-Cao® yielded a concentration of 453mcg/ml and from Valor® Cacao, 426 mcg/ml. A diffuse protein profile was obtained by SDS-PAGE without clearly defined bands from both extracts (Figure 1). This result is likely due to the complex composition of cacao, which contains a relatively low number of soluble proteins mixed with polyphenols, lipids, and carbohydrates. Even so, a ~16 kDa band from the Valor Cacao® extract was recognised by patient’s specific IgE (Figure 2).For Western Blot inhibition, pure cacao extract (Valor Cacao®) was used. Total inhibition of the 16 kDa band was shown after incubating patient’s serum with cashew nut and walnut extracts, respectively. Hazelnut caused only partial inhibition (Figure 2).Perfetti et al [6], reported the case of a confectionery worker suffering from occupational asthma due to cacao. They identified six different bands from cacao powder by SDS-PAGE: three between 10 and 20kDa, two of 30kDa and one of 50kDa. Although this patient showed IgE-mediated sensitisation to cacao by SPT and RAST, there was no IgE binding to any of those bands detected most probably due to the low levels of specific IgE, as suggested by them.In another recent case report, Nin Valencia et al [7] presented a cacao allergic patient, previously sensitised to walnut and almond, who recognised a 17, 5kDa and a 17,5-21kDa bands from cacao by SDS-immunoblotting. Partial cross-reactivity among those tree nuts and cacao was demonstrated by blotting inhibiton.We hypothesize that the 16kDa band found by us and the 17,5kDa band described by Nin Valencia et al [7] could correspond to same protein, being specifically a fragment of a vicilin-like globulin storage protein. This vicilin consists of three subunits with apparent molecular masses of 47 kDa, 31 kDa, and 15 kDa, respectively, which are derived from fragmentation of a 66- kDa precursor. These subunits have been shown to retain IgE-binding epitopes [8], which could explain their recognition by both patients’ specific IgE.In the case we present, total inhibition of IgE binding to cacao by cashew nut and walnut suggested primary sensitisation to these nuts. Moreover, partial inhibition by hazelnut sugests cross-reactivity between hazelnut and cacao. On the other hand, we did not find cross-reactivity between cacao and almond, contrary to that reported by Nin Valencia et al [7].Although rare, few clinical cases of food allergy to cacao [7, 9] as well as cacao as a cause of occupational asthma in confectionery workers, have been reported [7, 10].Lopes et al [9] reported three paediatric patients sensitised to cacao as demonstrated by SPT and serum cacao specific IgE who developed anaphylactic reactions during food challenge. Two of them were allergic to tree nuts as well. In the case we present, we did not perform food challenge with cacao because the patient’s mother had tried several brands of pure cacao at home, that the patient did not tolerate, developing oral pruritus and vomiting after its ingestion. At the present time they agreed to start oral tolerance induction with cacao.In summary, although chocolate allergy is commonly attributed to the presence of other allergens included in its composition, as nuts, peanuts or milk, true allergy to cacao should be considered.In the present report, we could demonstrate cross-reactivity among cacao and tree nuts as cashew, walnut and hazelnut, suggesting that primary tree nut allergy might predispose to the development of cacao allergy.Written consent for permission to publish was obtained from patient’s parents, following recommendation of the Ethics Committee of A Coruña-Ferrol (Spain).Key words: chocolate, cacao, allergy, tree nuts, cross-reactivity, SDS-Page, immunoblotting.Word count: 1031.

Background: Food allergy algorithms provide a systematic approach to assigning food allergy outcomes in research studies when oral food challenges (OFC) are not performed. Currently no such algorithms, validated for infants, exist. We aimed to develop and validate a research algorithm for classifying infant food allergies. Methods: An algorithm incorporating skin prick test (SPT), allergen ingestion, and reaction data, was developed and validated by comparing peanut, cashew, egg and cow’s milk algorithm outcomes to OFC outcomes, in infants from the Vitality (n=285) (NCT02112734), EarlyNuts (n=111) (ACTRN12618001990213), and HealthNuts (n=191) studies. Results: Validation included 740 OFCs from 587 infants (191 SPT-negative [0mm] and 396 SPT-positive [≥ 1mm] infants; first-OFC median age: 14.4 months). The algorithm assigned all SPT-negative infants as tolerant, achieving 99.5% agreement with OFCs (peanut 100% [n=135/135]; egg 98.2% [n=55/56]). The algorithm assigned an allergic or tolerant outcome to 57% (82/144) of peanut SPT-positive, 28% (30/108) cashew SPT-positive, 76% (n=196/258) egg SPT-positive, and 88% (n=35/39) milk SPT-positive, infants. Agreement with OFC was 81% (n=66/82) for peanut, 83% (n=25/30) for cashew, 90% (n=176/196) for egg and 97% (n=34/35) for milk. Accuracy and areas under the curve (AUCs) were fair-to-excellent: peanut (AUC=0.79 [95% confidence interval [CI]: 0.70-0.90]; sensitivity=88% [95%CI: 75-96]; specificity=70% [95%CI: 51-84]), cashew (AUC=0.83 [95%CI: 0.69-0.97]; sensitivity=83% [95%CI: 59-96]; specificity=83% [95%CI: 52-98]); egg (AUC=0.85 [95%CI: 0.77-0.93]; sensitivity=92% [95%CI: 86-95]; specificity=79% [95%CI: 59-92]); milk (AUC=0.98 [95%CI: 0.94-1]; sensitivity=96% [95%CI: 80-100]; specificity=100% [95%CI: 69-100]). Conclusion: Using routinely collected data, this validated infant-focused food allergy algorithm performed well in classifying peanut, cashew, egg and cow’s milk allergies, offering applicability in research settings.

Background: The role of partially hydrolyzed formulas (pHF) as a nutritional intervention for the prevention of Allergic Manifestations (AM) remains debatable, and the effectiveness of each specific pHF should be longitudinally examined. Objective: To investigate whether the risk-reduction effect of a specific pHF compared to a standard formula (SF) on Atopic Dermatitis (AD) within the first 6 months of life observed in the Allergy Reduction Trial (A.R.T.) persists at the age of 5 years and, if it applies to other AM. Methods: Parents/legal guardians of the A.R.T. participants who constituted the Intention-to-Treat population set (N=551) were invited to answer an enriched validated questionnaire regarding doctor diagnosis of AM between 1-5 years of age, including AD, Food Allergy (FA), Asthma, and Allergic Rhinitis. Results: Four hundred and fifty-five subjects (83%) completed the 5-year follow-up (pHF: 131/160, SF: 145/171 and EBF: 179/220). Infant feeding with the pHF resulted in 87% risk-reduction of FA [1,5% vs 12.4%, RR 0.13 (0.03-0.58), p=0.007] between the ages of 1-5 years compared to SF. The RR from birth to 5 years was significantly lower in the pHF group, for the development of any AM [32.7% vs 51.7%, RR 0.73 (0.57-0.94), p=0.02], AD [22.1% vs 38.5%, RR 0.58 (0.41-0.83), p=0.003] and, FA [10.5% vs 20.4%, RR 0.53 (0.29-0.95), p=0.03] compared to the SF group. Conclusion: In non-exclusively breastfed infants at high-risk for allergy, mixed-feeding with a specific whey-based pHF may reduce the risk of atopic dermatitis and food allergy from birth up to the age of 5 years.

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Associations between bathing and skin care routines and severity of atopic dermatitis (AD)To the editor,Atopic dermatitis (AD) is one of the most common inflammatory skin disorders and is often diagnosed throughout infancy and childhood (1–3). AD is a heterogenous skin condition, but is usually characterised by xerantic and pruritic lesions, which hamper the quality of life of the individual with AD, as well as their caregivers (3,4). The mainstay of treatment is the frequent use of emollients, especially following bathing (3). Presently, mixed messaging regarding the optimal bathing and skincare routine is being provided to people with AD and their caregivers (5–7). One recent review compared six evidence-based guidelines from organizations in North America, Europe and Asia (7). Three of the six guidelines suggest short bath duration (<10 minutes), while two are unspecified and one suggests longer baths (>10 minutes). As for bathing frequency, five of six guidelines note no specific recommendations, while one indicates a maximum of one bath daily. Though all guidelines were evidence-based, a lack of consistency between guidelines remains, and some organizations admit that the evidence was largely grounded in personal experience and consensus of professionals in the field, rather than studies (8,9). The present study aimed to determine associations between the use of topical medications, frequency of bathing and duration of bathing and severity of AD, in hopes of guiding resources regarding skincare regimens given to individuals with AD and their caregivers.This was an observational cross-sectional study that made use of questionnaire data collected from October 2021 to May of 2022. The study received approval from the University of Manitoba Research Ethics Board, ethics file number H2020:426 (HS24294). Thirty-one mother-infant dyads were recruited from social media and clinics in Winnipeg, Manitoba, Canada. To be included in the study, mothers had to be age under 19 months with diagnosed AD. The Patient-Oriented SCORing Atopic Dermatitis index (PO-SCORAD) was utilized to determine severity of AD. Regarding AD severity, the PO-SCORAD tool is a validated scoring system utilizing visual aids to allow mothers to indicate the severity of objective symptoms such as dryness, redness, swelling, etc., while subjective symptoms such as itching and sleeplessness are ranked on a 10-point scale. Higher scoring indicates more severe AD. The two groups analyzed for this study include mild (scored <25), and moderate-severe (≥25) AD. In addition to the PO-SCORAD, participants completed several questions pertaining to their child’s AD, including age of onset, symptoms experienced, and allergic comorbidities (10).Questionnaires regarding bathing and skincare routines, including use of topical medication (i.e., yes vs. no[reference]), were also utilized. Given the small sample size, bathing duration and frequency were collapsed into binary variables. Duration was characterized as ≤15 minutes vs. >15 minutes, with ≤15 minutes forming the reference category. Frequency, was analyzed as “daily” (reference) and “less than daily” categories. Demographic surveys were also completed to create two models adjusting for possible confounding variables: Model 1, adjusting for household income and ethnicity, and Model 2, adjusting for household income, ethnicity, maternal age and additional children in the home. Participant demographics can be found in Table 1.Statistical analyses were performed using Stata BE Version 17.0 (College Station, Texas, United States of America). Demographic data was described using descriptive statistics. Of the 31 mother-infant dyads, the average age of mothers and infants was 30.0 years and 7.6 months, respectively. The average age of the infants at diagnosis of AD was 3.1 months. Eight infants (25.8%) had other allergic diseases beyond AD. PO-SCORAD scores were calculated as continuous scores (presented as mean ± standard deviation [SD]) and categorical scores (presented as counts and percentages). Linear regression was used to assess the association between bathing duration, bathing frequency and use of topical medication and continuous PO-SCORAD scores. Logistic regression was used to assess the associations between the categorical PO-SCORAD scores and the same skincare variables. Statistical significance was set at p <0.05. Associations were reported using beta coefficients (b ) and odds ratios (OR), in combination with 95% confidence intervals (CI).The mean overall score for the PO-SCORAD was 26.3 ± 18.1, with 18 (58.1%) participants classified as having mild AD and 13 (41.9%) as moderate-severe. As shown in Table 2, when utilizing PO-SCORAD as a continuous variable, no significant associations were found when comparing daily vs. less than daily bathing (b =8.07, 95% CI=-5.75-21.89, p =0.24), or bathing duration >15 mins vs. ≤15 mins (b =4.86, 95% CI = -12.18-21.90, p =0.56). Similarly, when utilizing PO-SCORAD as a categorical variable, no significant associations were found when comparing bathing less than daily vs. daily (OR=1.43, 95% CI =0.32-6.49, p=0.64), or bathing duration >15 mins vs. ≤15 mins (OR=0.64, 95% CI= 0.10-4.14, p=0.64). The two models adjusting for potential confounding variables also resulted in no significant associations between bathing routine and severity of AD.The use of topical medication was significantly associated with AD severity, both in continuous PO-SCORAD models (unadjusted:b =13.47, 95% CI=0.86-26.08, p =0.04; fully adjusted:b =21.49, 95% CI=8.92-34.06,p <0.01) and categorical PO-SCORAD models (unadjusted: OR=5.24, 95% CI=1.06-25.97,p =0.04; fully adjusted: OR=5.11, 95% CI=1.03-25.49,p =0.03). This is likely due to those with more severe symptoms being prescribed topical medications.Based on the findings of this study, along with the literature (7), the contradictory messaging regarding best practices when it comes to bathing routines for people with AD is understandable. With no clear relationship between bathing and AD severity, it is challenging to make evidence-informed recommendations on the optimal duration and frequency. It could be that, since each case of AD is unique to the individual, a series of trial and error is required to find the best personal routine. However, this study has a relatively small sample size, and if conducted on a larger scale, associations may in fact be found. Further research into bathing routines and use of soaps and bleach is warranted in order to provide the best possible advice for those with AD.Sincerely,Kaitlyn A. Merrill, B.Sc.(Hons.)1,2, Ory Edlunden3, Michael A. Golding, MA1,2, Sandra Ekström3,4,5, PhD, Jennifer L. P. Protudjer, PhD1, 2,6-81Department of Pediatrics and Child Health, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada2Children’s Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada3Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden4Department of Clinical Research and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden5Center for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden6Department of Food and Human Nutritional Sciences, Faculty of Agricultural and Food Sciences, University of Manitoba, Winnipeg, Manitoba, Canada7George and Fay Yee Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada8Centre for Allergy Research, Karolinska Institutet, Stockholm, SwedenKey words:Atopic dermatitis, bathing routine, skincare routine, eczema, SCORAD, allergy, pediatricsDisclosure statement KM declares no competing interests. OE declares no competing interests. MG declares no competing interests. SE declares no competing interests. JP is Section Head for Allied Health, and Co-Lead, Research Pillar, for the Canadian Society of Allergy and Clinical Immunology; sits on the steering committee for Canada’s National Food Allergy Action Plan, and reports consultancy for Novartis, ALK Abelló and FOODiversity.Funding Funding for this study was provided by Research Manitoba. The funding body had no influence on the study design, data collection, analysis and interpretation, or manuscript writing.References1. Gupta R, Sheikh A, Strachan DP, Anderson HR. Burden of allergic disease in the UK: secondary analyses of national databases. Clinical & Experimental Allergy. 2004 Apr 1;34(4):520–6. 2. Kay J, Gawkrodger DJ, Mortimer MJ, Jaron AG. The prevalence of childhood atopic eczema in a general population. Journal of the American Academy of Dermatology. 1994 Jan 1;30(1):35–9. 3. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. The Lancet. 2020 Aug 1;396(10247):345–60. 4. Ali F, Vyas J, Y. Finlay A. Counting the Burden: Atopic Dermatitis and Health-related Quality of Life. Acta Derm Venereol. 2020 Jun 9;100(12):330–40. 5. Winfred Frazier, Bhardwaj N. Atopic Dermatitis: Diagnosis and Treatment. American Family Physician. 2020 May 15;101(10):590–8. 6. Chu DK, Schneider L, Asiniwasis RN, Boguniewicz M, De Benedetto A, Ellison K, et al. Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE– and Institute of Medicine–based recommendations. Annals of Allergy, Asthma & Immunology. 2024 Mar 1;132(3):274–312. 7. Pagliaro M, Pecoraro L, Stefani C, Pieropan S, Piacentini G, Pietrobelli A. Bathing in Atopic Dermatitis in Pediatric Age: Why, How and When. Pediatr Rep. 2024 Jan 8;16(1):57–68. 8. Wollenberg A, Kinberger M, Arents B, Aszodi N, Avila Valle G, Barbarot S, et al. European guideline (EuroGuiDerm) on atopic eczema – part II: non-systemic treatments and treatment recommendations for special AE patient populations. Journal of the European Academy of Dermatology and Venereology. 2022 Nov 1;36(11):1904–26. 9. Eichenfield LF MD, Ahluwalia J MD, Waldman A MD, Borok J BS, Udkoff J MA, Boguniewicz M MD. Current guidelines for the evaluation and management of atopic dermatitis: A comparison of the Joint Task Force Practice Parameter and American Academy of Dermatology guidelines. Journal of allergy and clinical immunology. 2017;139(4):S49–57. 10. Stalder JF, Barbarot S, Wollenberg A, Holm EA, De Raeve L, Seidenari S, et al. Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe: PO-SCORAD self-assessment scale validation. Allergy (Copenhagen). 2011;66(8):1114–21.

Background Maternal body mass index (BMI) before pregnancy and gestational weight gain (GWG) have been implicated in offspring health, yet their specific impact on the development of allergic diseases remains unclear. We aimed to evaluate associations between pre-pregnancy BMI and GWG with asthma, rhinitis, eczema, food allergy, anaphylaxis, and allergic sensitization during childhood and adolescence. Methods We analyzed 7280 mother-child pairs from Generation XXI, a Portuguese population-based birth cohort. Maternal BMI was categorized per World Health Organization criteria and grouped into underweight/normalweight vs.overweight/obesity. GWG was considered using Institute of Medicine (IOM) guidelines and GWG z-scores. Allergic outcomes were assessed via parent-reported physician diagnosis at 4, 7, 10, and 13 years, and allergic sensitization was determined at 10 years using ImmunoCAP. Associations were analyzed using logistic regression models adjusted for confounders. Results Children of mothers with excessive GWG had increased odds of asthma at ages 7 and 13 (aOR=1.30; 95%CI 1.01-1.66 and aOR=1.29; 95%CI 1.01-1.65, respectively), and rhinitis at 4 (OR=1.48; 95%CI 1.10-1.98). Higher GWG z-scores were associated with increased odds of asthma (aOR=1.33; 95%CI 1.03-1.72), rhinitis (aOR=1.54; 95%CI 1.13-2.09), and sensitization (aOR=1.44; 95%CI 1.05-1.97). Lower GWG z-score was associated to higher eczema odds at 13, while higher GWG z-score reduced eczema odds at age 4. Maternal overweight/obesity was associated with lower odds of eczema at age 13 (aOR=0.73; 95%CI 0.60-0.88). Conclusion Higher GWG is associated with increased odds of childhood asthma, rhinitis, and sensitization. In contrast, maternal overweight/obesity is linked to lower odds of eczema, suggesting condition-specific effects of maternal weight on childhood allergy risk.

Background De-labeling suspected adverse drug reactions (ADRs) is a critical goal in clinical practice, as misdiagnosed allergies lead to unnecessary medicalization and unwarranted restrictions on available medications. In children, high-risk factors for ADR, such as immediate urticaria, often overlap with common viral rashes, complicating risk stratification. This challenge is compounded by caregiver-reported histories, which can distort symptom timing and severity. This case-control study evaluated the reliability of caregivers and the influence of non-clinical factors in predicting the risk. Methods Patients and caregivers referred to the Allergy Units of two tertiary care hospitals for suspected hypersensitivity reactions (HSRs) were included. Questionnaires were offered to caregivers and patients aged 7-17. Participants were divided into two groups: patients with suspected HSRs and controls without a history of HSR. Enrolled subjects were asked to recognize pictures of maculopapular, micropapular, and urticaria via a multiple-choice questionnaire. Results Data from 405 participants were collected between September 2023 and August 2024. Statistical analysis showed that a higher caregiver education and a positive personal or familiar history of HSR and/or urticaria significantly improved recognition accuracy. Nevertheless, over 50% of participants with suspected HSR history misidentified urticaria with micropapular rash, underscoring the low reliability of caregiver reports. In addition, rash recognition skills did not differ significantly between healthcare and non-healthcare caregivers. Conclusions These findings highlight the need for systematic approaches beyond descriptive histories. Integrating non-clinical factors into diagnostic frameworks could enhance risk stratification and support safer and more effective allergy workup for de-labeling suspected HSR in pediatric patients.

A document by Caitlin Ying Ming Louey. Click on the document to view its contents.

Specialist teaching to school pupils can increase knowledge and confidence surrounding anaphylaxis

Background Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV-bronchiolitis requiring admission. In 2023-2024, Catalonia and Andorra adopted immunization strategies for children < 6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis. Methods In the epidemic season of 2023-2024, a test-negative case-control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV-bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non-immunized and non-eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables. Results 234 patients were included. RSV was detected in 141/234(60.2%), being less common in the immunized group (37% vs 75%, p<0.001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV-associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9-90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7-96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral co-infections, the need for NIV/CMV or length of hospital stay. Conclusions This study provides real-world evidence of the effectiveness of nirsevimab in preventing RSV-LRTI hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral co-infections nor differences in clinical severity once admitted.

THE IMPORTANCE OF FOLLOW-UP OF ESOPHAGEAL EOSINOPHILIA IN CHILDREN WITH SEVERE COW’S MILK ALLERGYTo the Editor:The current understanding of the intricate interplay between food allergy (FA) and eosinophilic esophagitis (EoE) remains incomplete, particularly in patients with severe manifestations of FA or those undergoing oral immunotherapy (OIT). EoE has been recognized as part of the atopic march1, as it shares type 2 inflammation and poses a risk of progression to other atopic diseases, including IgE-mediated food allergy (IgE-FA). However, the incidence of EoE even before food reintroduction2 raises doubts about whether this group represents a subtype of FA and how esophageal changes develop. In clinical practice, there are concerns about underdiagnosing EoE and its potential long-term complications, especially in children whose symptoms are often nonspecific and may be masked by adaptive behaviors3. The proposed longitudinal study aims to characterize esophageal eosinophilia (EE) in children with IgE-mediated cow’s milk allergy (IgE-CMA) and compare clinical and endoscopic findings between patients with and without esophageal symptoms over one year of follow-up.Patients aged 6 to 18 years were recruited from a Brazilian IgE-CMA reference center between 2019-2022. They underwent a standard routine, which included inquiries about esophageal symptoms, laboratory tests, and esophagogastroduodenoscopy (EGD) with biopsy. With the assistance of caregivers, patients verbally reported the frequency and intensity of esophageal symptoms over the last month. Adaptive eating behaviors were assessed using the IMPACT acronym4. Patients who confirmed the persistence of at least one esophageal symptom were classified as symptomatic. Caregivers completed the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) v2.05during the same visit. The specific IgEs for CM, α-lactalbumin, β-lactoglobulin, casein, egg, soy, wheat, peanut, Brazil nut, codfish, and shrimp were measured using the ImmunoCAP® method. Serum levels of eosinophils and total IgE were also collected.Subsequently, all patients underwent EGD, with at least 4-6 esophageal biopsies (proximal/mid and distal esophagus), along with gastric and duodenal biopsies. Macroscopic characteristics were described using the Endoscopic Reference Score (EREFS)6, completed by the same endoscopist. The histological evaluation included eosinophil count per high-power field (hpf) in each region. Biopsies were evaluated by a single pathologist trained in the EoE Histologic Scoring System (EoEHSS)7 for both proximal/mid and distal regions. The presence of ≥ 15 eos/hpf in the esophageal mucosa was designated as EE. After excluding other causes of EE, symptomatic patients were classified as EoE, while asymptomatic patients were classified as asymptomatic esophageal eosinophilia (aEE). EGD was repeated after at least 8 weeks of treatment for EoE or 1-year follow-up without intervention for aEE. See supplemental data for the detailed methodology.Thirty-three patients with IgE-CMA were assessed. Most were male (57.6%) with a median age of 8.75 years. 84.8% had other atopic conditions, with nearly all reporting prior CM anaphylaxis (87.8%), and 75.7% still reacted to baked milk. The frequency of EE was 45.4%, with 21.2% diagnosed with EoE and 24.2% with aEE. Regarding clinical data, statistically significant differences were not observed between the groups with and without EE (see Table 1). Laboratory tests showed higher results in the EE group but without statistical significance. The percentage of patients sensitized to other food allergens besides CM was similar between the two groups.Comparing patients with EoE and aEE, most of the clinical data did not differ statistically between the groups. A higher median age was found in those with EoE (10.3 vs 8.2 years, p=0.03), along with higher specific IgE values for CM and casein (p=0.02 and p=0.008, respectively). The percentage of patients sensitized to another food allergen was higher in the EoE group (85.7% vs 50%), but this difference did not reach statistical significance. The eosinophil count in the esophagus was statistically similar between the groups, with a predominance of non-diffuse distribution in both. None of the patients exhibited eosinophilia in the stomach or duodenum suggestive of other eosinophilic gastrointestinal diseases8.Table 2 illustrates the comparison of scores between the EoE and aEE groups. EoE patients had significantly higher median PEESS v2.0 total scores (p=0.01), particularly in domains associated with pain and dysphagia (p=0.02). Specifically, four questions were able to distinguish patients with EoE (1, 9, 11, and 12). EREFS scores were similar between the groups, although the frequency of abnormal macroscopy was higher in EoE patients (100% vs 37.5%, p=0.02). EoEHSS also showed no significant differences between the groups. During the follow-up period (see Table 3), most EoE patients achieved clinical and histological remission with omeprazole treatment, including the resolution of fibrosis. Among the 8 patients with aEE, 6 (75%) remained asymptomatic after one year. Of the 6 repeated EGDs, 3 revealed normal histology. The remaining 3 exhibited persistent fibrosis, involving 2 patients who maintained aEE and one who developed EoE.This is the first follow-up study in patients with IgE-CMA that evaluated EE beyond eosinophil counts, utilizing standardized EoE scores in childhood. A high frequency of EE was observed, particularly associated with severe cases of IgE-CMA, highlighting the importance of EoE screening among FA-IgE patients. Given the absence of reliable clinical markers for predicting EE, the challenge persists in identifying symptomatic patients who require EGD. While the use of PEESS contributed to EoE diagnosis in this study, we acknowledge the practical limitations of understanding sporadic complaints or oligosymptomatic patients. To grade PEESS questions or to assess the social impacts of symptoms could provide deeper insights into esophageal involvement. Another noteworthy finding of this study is the possibility of disease activity even before symptom onset, as endoscopic and histological features related to EE were similar between symptomatic and asymptomatic patients. However, since we still lack markers to define active EoE aside from clinical symptoms, debates continue regarding whether aEE should be considered a precursor to EoE or merely a transient phenomenon9.Diagnosing EoE is a relevant concern in IgE-FA patients, especially for those eligible for OIT. In this study, patients with EoE were distinguished from those with aEE by older age and higher levels of CM-specific IgE. However, due to the low incidence of EoE during this follow-up, predicting which aEE patients should be treated over time remains challenging. The phenotype definition could also contribute to understanding this progression. In both EE groups, our results suggest the predominance of a non-fibrostenotic phenotype with favorable outcomes over a period without changes in CM intake: (1) EREFS and EoESS features were mainly inflammatory, regardless of symptom presence, with most showing reversal of fibrosis during follow-up. (2) Histologic remission occurred spontaneously in asymptomatic patients or after omeprazole treatment in the majority of patients with EoE. As this is a small sample of pediatric patients followed for a short period, further follow-up studies will be necessary to confirm whether other IgE-FA groups exhibit a similar disease course.In line with previous research involving FA patients2,10, this study suggests that EoE originates from the sustained activity of inflammatory mediators, regardless of the presence of a food antigen in the esophagus. Especially in atopic individuals, characterized by type 2 immune dysregulation, further investigation is warranted to determine whether eosinophils play a protective or harmful role over time. Consequently, conducting additional research to elucidate the natural progression of EoE, including its underlying mechanisms and factors influencing its course, is essential. This deeper understanding not only promises to facilitate the development of more effective diagnostic and prognostic tools but also to pave the way for timely therapeutic interventions.Word count: 1999Keywords: eosinophilic esophagitis, esophageal eosinophilia, cow’s milk allergy, children, PEESS, EREFS, EoEHSS

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization and natural history review. Numerous factors that may affect disease activity and patient wellbeing need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even ‘real-time’, monitoring between visits. Following an approach that included needs assessment, evidence appraisal and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

This review summarises recent advances in characterising the transcriptional pathways associated with outcomes following Oral Immunotherapy. Recent technological advances including single-cell sequencing are transforming the ways in which the transcriptional landscape is understood. The application of these technologies is still in its infancy in food allergy but here we summarise current understanding of gene expression changes following oral immunotherapy for food allergy and specific signatures underpinning the different clinical outcomes of desensitisation and remission (sustained unresponsiveness). T helper 2A cells have been identified as a cell type which correlates with disease activity and is modified by treatment. Molecular features at study entry may differentiate individuals who achieve more positive outcomes during OIT. Recent findings point to T cell anergy and Type 1 interferon pathways as potential mechanisms supporting redirection of the allergen-specific immune response away from allergy towards remission. Despite these developments in our understanding of immune mechanisms following OIT, there are still significant gaps. Additional studies examining immune signatures associated with long term and well-defined clinical outcomes are required to gain a more complete understanding of the pathways leading to remission of allergy, in order to optimise treatments and gain improved outcomes for patients.

Background: Accidental allergic reactions (AAR) in children are under-studied, especially with precise pediatrician-based exact diagnoses and follow-ups. This study aimed to assess the prevalence and risk factors for AAR in Japanese children with immediate-type food allergies. Methods: This single-center study included children with immediate-type hen’s egg (HE), cow’s milk (CM), wheat, or peanut allergy who had been followed-up regularly at a national center specialized for allergy in Japan. Low-dose reactivity was defined as allergic reactions to a low dose of ≤250, ≤102, ≤53, or ≤133 mg HE, CM, wheat, or peanut protein, respectively. From January to December 2020, pediatricians followed the AAR experience every 2–4 months. Risk factors for AAR were analyzed using multiple logistic regression. Results: Of the 1096 participants, 609, 457, 138, and 90 had HE, CM, wheat, and peanut allergies, respectively. In this cohort, the median age was 5.0 years, 39% had completely eliminated allergenic food, and 24% had low-dose reactivity. The annual AAR rate was 0.130 in all sub-cohorts. Moderate and severe symptoms occurred in 50% and 0.7%, respectively, of children who experienced AAR. Multiple logistic regression revealed that low-dose reactivity was a significant risk factor for AAR in the overall, HE, and CM cohorts, respectively ( p <0.001, p = 0.029 and 0.036). Conclusion: In Japanese children with immediate-type food allergies, the annualized rate of AAR was relatively low; however, half of the participants with AAR had moderate to severe symptoms. Children, especially those with low-dose reactivity, would require careful risk management of AAR.