A systematic review and meta-analysis of nutritional and dietary interventions in randomized controlled trials for skin symptoms in children with atopic dermatitis and without food allergy: An EAACI task force report.

This systematic review and meta-analysis aimed to consolidate evidence on dietary interventions for atopic eczema/dermatitis (AD) skin symptoms in children without food allergies, following PRISMA 2020 guidelines. Systematic review updates were conducted in May 2022 and June 2023, focusing on randomized placebo-controlled trials (RCTs) involving children with AD but without food allergies. Specific diets or supplements, such as vitamins, minerals, probiotics, prebiotics, symbiotics, or postbiotics, were explored in these trials. Exclusions comprised descriptive studies, systematic reviews, meta-analyses, letters, case reports, studies involving elimination diets, and those reporting on food allergens in children and adolescents. Additionally, studies assessing exacerbation of AD due to food allergy/sensitization and those evaluating elimination diets' effects on AD were excluded. Nutritional supplementation studies were eligible regardless of sensitization profile. Evaluation of their impact on AD clinical expression was performed using SCORAD scores, and a meta-analysis of SCORAD outcomes was conducted using random-effect models (CRD42022328702). The review encompassed 27 RCTs examining prebiotics, Vitamin D, evening primrose oil, and substituting cow's milk formula with partially hydrolyzed whey milk formula. A meta-analysis of 20 RCTs assessing probiotics, alone or combined with prebiotics, revealed a significant reduction in SCORAD scores, suggesting a consistent trend in alleviating AD symptoms in children without food allergies. Nonetheless, evidence for other dietary interventions remains limited, underscoring the necessity for well-designed intervention studies targeting multiple factors to understand etiological interactions and propose reliable manipulation strategies.

Levels of IgE sensitization drive symptom thresholds in allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a common respiratory disease encompassing a variety of phenotypes. Patients can be sensitized to 1 or more allergens. There are indications that polysensitization is associated with more severe disease. However, the extent to which the level of sensitization is associated with clinical disease variability, underlying the distinct nature of AR from AR+ conjunctivitis or AR+ asthma, is not known. OBJECTIVE: To evaluate phenotypical differences between monosensitized and polysensitized patients with AR and to quantify their symptomatic variability. METHODS: A total of 565 patients with a confirmed diagnosis of AR were included in this cross-sectional study. Of those, 155 were monosensitized and 410 were polysensitized. Interactions between sensitization levels and the reporting of different symptoms of AR and co-morbidities, disease duration, and impact were assessed. Furthermore, patients were stratified into monosensitized, oligosensitized, and polysensitized to assess whether the effect of sensitization on the phenotype was ranked. RESULTS: Polysensitized patients reported itchy eyes significantly more often (P = .001) and had a higher number of ocular (P = .005), itch-related (P = .036), and total symptoms (P = .007) than monosensitized patients. In addition, polysensitized adults and children more often reported wheeze (P = .015) and throat-clearing (P = .04), respectively. Polysensitization was associated with more burdensome AR based on a visual analog scale (P = .005). Increased sensitization level was reflected in more itchy eyes, a higher number of ocular, itch-related, and total number of symptoms, and disease burden. CONCLUSION: With an increasing number of sensitizations, patients with AR experience an increased diversity of symptoms. Multimorbidity-related symptoms increase with sensitization rank, suggesting organ-specific thresholds.

EAACI Molecular Allergology User's Guide 2.0.

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.

A randomized, observer-blind, vehicle-control, multi-center clinical investigation for assessing the efficacy and tolerability of a 1% ectoine and hyaluronic acid 0.1%-containing medical device in pediatric patients with mild-to-moderate atopic dermatitis.

BACKGROUND: Ectoine is a widespread osmolyte enabling halophilic bacteria to withstand high osmotic stress that has many potential applications ranging from cosmetics to its use as a therapeutic agent. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of ectoine 1% and hyaluronic acid 0.1% containing (EHA) cream with a vehicle cream in children with mild-to-moderate atopic dermatitis (AD). METHODS: A randomized, controlled, observer-blind, multicenter clinical trial was conducted in children aged 2-18 years, diagnosed with mild-to-moderate AD (SCORAD ≤20). Patients were randomized to either receiving EHA cream or vehicle cream twice daily for 4 weeks. The primary outcome measure was the mean change in objective SCORAD from baseline to the final visit. The secondary outcome measures included the mean change in Investigator's Global Assessment score, patient's judgment of efficacy and patient's assessment of pruritus. Safety of EHA cream was also assessed. RESULTS: A total of 70 patients (35 in each group) were randomized and 57 were included in the final analysis set. Based on SCORAD measurements, patients using EHA cream achieved superior clinical improvement compared to the control group at 28 days (p < .001). EHA cream was also superior to the vehicle cream regarding all secondary outcome measures. Eight (23.5%) patients receiving EHA cream and two (5.7%) patients receiving vehicle cream experienced mild cutaneous adverse events (AEs). CONCLUSIONS: In children 2-18 years old with mild-to-moderate AD, EHA cream was superior to vehicle cream, with minor AEs.

Remission Patterns of Food Protein-Induced Enterocolitis Syndrome in a Greek Pediatric Population.

BACKGROUND: Data on the prevalence and clinical course of food protein-induced enterocolitis syndrome (FPIES) vary between populations and according to the culprit food. OBJECTIVE: To evaluate the incidence, clinical characteristics, and remission patterns of FPIES among children in a Greek pediatric allergy referral center. METHODS: We retrospectively studied children with acute FPIES. Data on age, sex, type of reaction, the implicated food, and oral food challenge (OFC) outcomes at baseline and upon reevaluation were analyzed. RESULTS: Between October 2010 and March 2017, 72 (38 males) out of 15,114 subjects who had been referred to our department due to any reported allergic symptoms were diagnosed with acute FPIES. The most commonly implicated foods were cow's milk (CM) (45.8%), fish (34.7%), rice (9.7%), egg (6.9%), and chicken (2.8%). The mean age at diagnosis was 7.1/19.3/9.1/18.7/8.7 months for those with CM/fish/rice/egg/chicken FPIES, respectively. Sixty-nine OFCs were performed, of which 8 were diagnostic and 61 for tolerance evaluation. The type of culprit food was significantly associated with the outcome of the tolerance OFCs. OFCs to fish resulted positive at a significantly higher rate (12/22; 54.5%) than OFCs to CM (4/29; 13.7%), rice (1/5; 20%), egg (0/3; 0%), and chicken (0/2; 0%) (p = 0.01). The time period between diagnosis and tolerance acquisition was prolonged in the fish FPIES cases (74.8 months; 95% CI: 57.9-91.6) compared to that with other foods such as CM (20.7 months; 95% CI: 17.3-24.1), rice (31.8 months; 95% CI: 21.9-41.7), and egg (24.3 months; 95% CI: 10.7-37.9), as shown in a Kaplan-Meier analysis (log-rank, p < 0.001). When the fish FPIES children were assessed for tolerance, OFCs were significantly more often positive than in CM FPIES children (52 vs. 18.1%; p = 0.03), despite the fact that the children were challenged at an older age (fish: 70.4 months, 95% CI: 58.3-82.5, vs. CM: 26.57 months, 95% CI: 21.1-32, p < 0.001). CONCLUSIONS: Acute FPIES had a low incidence in our population. CM and fish were the two most frequent elicitors. Significantly delayed presentation and prolonged remission was noted for FPIES caused by fish.

Detection of genuine grass pollen sensitization in children by skin testing with a recombinant grass pollen hybrid.

BACKGROUND: Skin testing represents a commonly used first diagnostic method in clinical practice, but allergen extracts may vary in composition and often contain cross-reactive allergens and therefore do not always allow the precise identification of the sensitizing allergen source. Our aim was to investigate the suitability of a single recombinant hybrid molecule, consisting of the four major timothy grass pollen allergens (Phl p 1, Phl p 2, Phl p 5, and Phl p 6) for in vivo diagnosis of genuine grass pollen allergy in children suffering from pollinosis. METHODS: Sixty-four children aged from 6 to 17 years with a positive skin reaction and/or specific IgE to grass pollen extract and respiratory symptoms of pollinosis as well as 9 control children with allergy to other allergen sources were studied. SPT was performed with the recombinant hybrid, the four recombinant timothy grass pollen allergens, and grass pollen extract. Specific IgE reactivity to 176 micro-arrayed allergen molecules was determined using ImmunoCAP ISAC technology. IgE reactivity to the hybrid was detected by non-denaturing RAST-based dot blot assay. RESULTS: Genuine grass pollen sensitization was confirmed in 94% of the children with positive SPT to grass pollen extract by SPT and IgE reactivity to the hybrid. The four hybrid-negative children showed IgE reactivity to cross-reactive allergens such as Phl p 4, Phl p 11, and Phl p 12 and had also sensitizations to pollen allergens from unrelated plants. CONCLUSIONS: The recombinant hybrid molecule represents a useful tool for in vivo diagnosis of genuine grass pollen sensitization.

Detection of local allergic rhinitis in children with chronic, difficult-to-treat, non-allergic rhinitis using multiple nasal provocation tests.

BACKGROUND: There is little evidence on the incidence and characteristics of local allergic rhinitis (LAR) in children. Most studies have included subjects with perennial rhinitis only, and results are based on the investigation of no more than three allergens per study. Our aim was to determine the proportion of children with LAR amongst children with chronic, difficult-to-treat, perennial or seasonal, rhinitis but no evidence of sensitization to aeroallergens, or other alternative diagnosis. METHODS: We performed multiple nasal provocation tests (M-NPTs) with four locally relevant aeroallergens (Phleum pratense, Olea europea, Alternaria alternata, and Dermatophagoides pteronyssinus) in children with absence of aeroallergen sensitization, seen during a calendar year in a specialized rhinitis clinic. We additionally performed single NPT to children with allergic rhinitis (AR; positive control group). The result of the NPT was based on symptoms and acoustic rhinometry. Identification of nasal hyper-reactivity (NHR) triggers was through a questionnaire. RESULTS: Local allergic rhinitis was confirmed in 29.2% (7/24) of the negative SPT/blood testing population. All but one of the children reacted to one allergen and one to two. All AR children had positive single NPT with results similar to the LAR. There were no differences in age at examination and rhinitis onset, gender distribution, family atopy, and past or current environment of residency, while the prevalence of reported NHR triggers was comparable amongst the three groups. CONCLUSION: This is the first pediatric study where the seasonal or perennial rhinitis population was thoroughly tested for LAR against four aeroallergens. LAR is present in a considerable proportion of children with chronic, difficult-to-treat rhinitis and no sensitization to aeroallergens, and therefore, the performance of NPT should be strongly considered in these cases. There were no distinct clinical characteristics between LAR, AR, and non-allergic rhinitis in children.

Assessment of atopic dermatitis as a risk factor for chronic spontaneous urticaria in a pediatric population.

Background: Atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) represent two of the most common chronic inflammatory pruritic skin diseases. Any relationship between atopic skin disorders and CSU is controversial, mostly due to the paucity of relevant epidemiologic and pathogenetic data. Objective: To evaluate whether a history of AD in early childhood represents a risk factor for the subsequent occurrence of CSU in a pediatric population. Methods: Retrospective data of new cases of patients who visited the outpatient allergy unit of a tertiary pediatric hospital in Athens, Greece, between June 2014 and August 2016, were analyzed. Diagnoses of CSU and AD were based on diagnostic criteria proposed by the European Academy of Allergy and Clinical Immunology and the Hanifin and Rajka criteria, respectively. The data analyzed included CSU and AD diagnoses and the association with gender and season of birth as well as a personal and family history of allergy-related diseases (e.g., asthma, allergic rhinitis, AD, and food and drug allergies). Results: Records from 2261 children were included in the analysis (1365 boys; mean ± standard deviation [SD] age, 8.7 ± 5.8 years). Fifty-one children (31 boys; mean ± SD age, 9.1 ± 4.6 years) were diagnosed with CSU, whereas AD was reported in 761 children (466 boys; mean ± SD age, 5.2 ± 3.8 years). Multivariate data analysis showed that the children with a history of an early diagnosis of AD were at increased risk for later CSU occurrence (odds ratio 2.923 [95% confidence interval, 1.647-5.189], p < 0.001). No significant associations were observed with respect to other demographic and atopy-associated characteristics of the patients. Conclusion: Results of our study indicated that AD may constitute an important risk factor to the subsequent occurrence of CSU. This notion warrants further study with well-designed prospective cohorts.

Complementary Feeding Practices: Recommendations of Pediatricians for Infants with and without Allergy Risk.

AIM: To investigate the routine guidance provided by pediatricians concerning the timing of complementary feeding (CF) for both healthy infants and those at a heightened risk of allergies. METHODS: A total of 233 pediatricians participated in an anonymous online survey that included questions about demographics and recommendations for CF. Specifically, they provided guidance on the types of foods, preparation methods, supplements, time intervals for introducing new foods to infants at low and high allergy risk, and delayed food introductions for high-risk cases. RESULTS: The respondents advised introducing certain foods at specific ages: fruits, starchy non-gluten grains, vegetables, olive oil, and meat were appropriate at 6 months; gluten-rich grains at 7 months; yogurt, hard-boiled eggs, and legumes at 8 months; fish at 8.5 months; and nuts at 9 months. Pediatricians, especially those with less than 15 years of practice, often introduced egg, seafood, gluten-rich grains, legumes, and nuts earlier for high-risk infants. Parenthood and male gender were associated with the earlier introduction of eggs and grains. CONCLUSIONS: Greek pediatricians follow a structured food introduction schedule for CF in infants. Interestingly, they tend to delay the introduction of common food allergens and recommend longer intervals between introducing new foods, particularly for high-risk infants. Key Notes: Despite recent evidence-based indications on healthy complementary feeding strategies for infants, discrepancies persist among pediatricians regarding food choices and the order and timing of food introduction, both for healthy infants and those at risk of allergy. Guidance on complementary feeding by pediatricians is influenced by their individual characteristics. Pediatricians tend to delay the introduction of common food allergens and recommend longer intervals between introducing new foods, particularly for high-risk infants.