Impaired bone mineral density and microarchitecture in female adolescents with IgE-mediated cow's milk allergy.

This study compared the bone parameters of adolescents with persistent cow's milk allergy (CMA) with those of healthy adolescents. Adolescents with CMA had compromised bone parameters (lower bone mineral density, impaired trabecular microarchitecture, and lower bone strength). Partial exclusion diet was associated with better bone parameters than total exclusion diet. BACKGROUND: Persistent immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) may impair bone parameters and increase the risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a novel methodology that not only assesses trabecular and cortical bone compartments and volumetric density measurements, but also evaluates bone microarchitecture and estimates biomechanical properties through finite element analysis (FEA). Both HR-pQCT and bone strength parameters derived from FEA have shown a strong correlation with fracture risk. PURPOSE: To assess the bone density, microarchitecture, and bone strength of adolescents with persistent IgE-mediated CMA (IgE-CMA). METHODS: This was an observational, cross-sectional study with female adolescents with persistent IgE-CMA and healthy control participants matched by female sex and sexual maturation. Bone parameters were assessed by areal bone mineral density (aBMD) through dual-energy X-ray absorptiometry (DXA), bone microarchitecture by HR-pQCT at the radius and tibia, and laboratory markers related to bone metabolism. RESULTS: The median age of adolescents with persistent IgE-CMA (n = 26) was 13.0 years (interquartile range (IQR) 11.4-14.7) and of healthy control participants (n = 28) was 13.6 years (IQR 11.9-14.9). Adolescents with IgE-CMA ingested 27.4% less calcium (p = 0.012) and 28.8% less phosphorus (p = 0.009) than controls. Adolescents with IgE-CMA had lower bone mineral content (BMC) (38.83 g vs. 44.50 g) and aBMD (0.796 g/cm2 vs. 0.872 g/cm2) at lumbar spine, and lower BMC (1.11 kg vs. 1.27 kg) and aBMD (0.823 g/cm2 vs. 0.877 g/cm2) at total body less head (TBLH) (p < 0.05). However, Z-scores BMC and Z-scores aBMD at lumbar spine and TBLH, when adjusted for Z-score height/age, were not significantly different between the groups. Moreover, CMA adolescents had lower bone strength at the distal tibia (S 169 kN/mm vs. 194 kN/mm; F Load 8030 N vs. 9223 N) (p < 0.05). Pairing of groups by the presence of menarche showed compromised parameters at the tibia-lower total volumetric BMD (Tt.vBMD) (293.9 mg HA/cm3 vs. 325.9 mg HA/cm3) and trabecular vBMD (Tb.vBMD) (170.8 mg HA/cm3 vs. 192.2 mg HA/cm3), along with lower cortical thickness (Ct.th) (1.02 mm vs. 1.16 mm) and bone strength (S 174 kN vs. 210 kN; F Load 8301 N vs. 9950 N)-and at the radius (S 61 kN/mm vs. 71 kN/mm; F Load 2920 N vs. 3398 N) (p < 0.05) among adolescents with IgE-CMA. Adolescents with IgE-CMA on a total exclusion diet (n = 12) showed greater impairment of bone features than those on a partial exclusion diet (n = 14), with lower lumbar spine Z-score BMC (- 0.65 vs. 0.18; p = 0.013), lumbar spine trabecular bone score (TBS) (1.268 vs. 1.383; p = 0.005), Z-score TBS (0.03 vs. 1.14; p = 0.020), TBLH Z-score BMC (- 1.17 vs. - 0.35; p = 0.012), TBLH Z-score aBMD (- 1.13 vs. - 0.33; p = 0.027), Tt.vBMD at the tibia (259.0 mg HA/cm3 vs. 298.7 mg HA/cm3; p = 0.021), Ct.th at the tibia (0.77 mm vs. 1.04 mm; p = 0.015) and Ct.th at the radius (0.16 mm vs. 0.56 mm; p = 0.033). CONCLUSION: Adolescents with persistent IgE-CMA had lower aBMD and compromised microarchitecture (impaired trabecular microarchitecture and lower bone strength). Adolescents on a partial exclusion diet had better bone parameters than those on a total exclusion diet.

A real-world cross-sectional study evaluating the role of an oral amino acid-based supplement in nutrient intake by preschoolers on a cow's milk elimination diet.

INTRODUCTION AND OBJECTIVES: Food allergy has several negative nutritional consequences and may persist beyond the first year of lives. This study aimed to assess the role of a complete oral amino acid-based supplement in the diet of children on cow's milk protein elimination diet because of food allergy. MATERIALS AND METHODS: This study included two groups of children aged 1-5 years paired by age and socioeconomic status: (1) study group, on cow's milk protein elimination diet plus an oral amino acid-based supplement, and (2) control group, on cow's milk protein elimination diet. Sociodemographic, clinical, anthropometric, and dietary data were obtained through online interviews. Two 24-h dietary recalls were collected on nonconsecutive days. Both groups comprised mostly boys. RESULTS: The study group presented lower values of body mass index. The frequency of feeding difficulties was similar between groups. The study group had a higher intake of energy, protein, carbohydrates, calcium, iron, zinc, phosphorus, magnesium, copper, selenium, vitamins D, E, B1, B2, B6, and B12, niacin, and folic acid compared to the control group. A higher proportion of children in the study group had adequate intake according to the recommendations made for energy, carbohydrates, iron, phosphorus, selenium, vitamins A, D, E, B1, B2, and B6, and folic acid. CONCLUSIONS: The use of a complete oral amino acid-based supplement has a positive effect on the diet quality of preschoolers on cow's milk elimination diet because of food allergy, promoting higher intake of energy, calcium, vitamin D, and other essential nutrients.

Predicting the Outcome of Pediatric Oral Food Challenges for Determining Tolerance Development.

PURPOSE: Despite the risk of anaphylaxis, oral food challenges (OFCs) are performed clinically for various indications, particularly to confirm tolerance development. This study aimed to assess OFCs by relevant indications and build an outcome prediction model to help determine when to perform OFCs in children who are likely to have developed immune tolerance. METHODS: In total, 432 pediatric OFCs were retrospectively analyzed according to indications. Clinical characteristics, serum total immunoglobulin (Ig) E, blood eosinophils, and specific IgE and IgG4 levels for food allergens were noted and compared. Machine learning was utilized to select the most important variables in determining the passage of the OFCs, and prediction models were constructed using the selected variables. RESULTS: OFCs were most commonly performed to confirm tolerance development (number, %; 267, 61.8%). The most common food allergens tested were egg (191, 44.2%) and milk (135, 31.3%). Children who passed the egg challenges for confirming tolerance acquisition had significantly lower egg white-specific IgE level (P = 0.008). Similarly, those who passed milk challenges had significantly lower cow's milk-specific IgE (P = 0.002) and casein-specific IgE levels (P = 0.005). We developed a nomogram to predict the outcome of OFCs to determine the tolerance acquisition with the selected variables; lower food-specific IgE, higher total IgE, and younger age indicated a higher probability of passage. The area under the curve (95% confidence interval) was 0.623 (0.503-0.743) for egg and 0.734 (0.628-0.840) for milk. CONCLUSIONS: Serum total IgE and food-specific IgE combined with age showed trends toward passing OFCs for confirming tolerance development. The constructed model may be used by clinicians as a practical guide for minimizing the risks of OFCs and a timely reintroduction for children with food allergies.

Nutritional status and feeding difficulties in children up to 2 years of age with cow's milk allergy.

BACKGROUND/OBJECTIVES: To assess the nutritional status and incidence of feeding difficulties in Polish children up to 2 years of age with cow's milk allergy (CMA) on cow's milk proteins-free diet. METHODS: A cross-sectional, multi-center study included children aged 6 months to 2 years with confirmed or suspected (without oral food challenge) diagnosis of CMA on the elimination diet for at least 1 month. The primary outcomes were an assessment of proportion of children with impaired nutritional status (with the weight for length and body mass index (BMI) z-score > 1 and <-1), and feeding difficulties according to the Montreal Children's Hospital Feeding Scale. Children with confirmed and suspected CMA were assessed separately. RESULTS: A 144 children with confirmed CMA and 88 with suspected CMA were included (57 and 78% with multiple food allergies, respectively). Among children with confirmed CMA, one-third (35.5%) of participants had any nutritional status impairment regardless of definition. Among those, most of children had mild malnutrition (10.4 vs. 9%) and possible risk of overweight (11.1 vs. 9.7%; following respectively BMI for age and weight for length z-scores). Only 16.0% of children had feeding difficulties. Feeding difficulties was identified to be a risk factor for moderate malnutrition compared to children without feeding difficulties (odds ratio 10, 95% confidence interval: 4-27). CONCLUSIONS: Mild malnutrition and possible risk of overweight are concern in children up to 2 years of age on cow's milk proteins-free diet. Feeding difficulties are less common, however, may affect the nutritional status.

Clinician Experience with Using Hypoallergenic Formulas to Treat Infants with Suspected Cow's Milk Protein Allergy: A Secondary Analysis of a Prospective Survey Cohort.

Purpose: Cow's milk protein allergy (CMPA) is a common condition in infants, but little is known about healthcare providers' clinical experience treating infants with CMPA. To address this gap, we analyzed prospectively collected data from healthcare providers (HCPs) who treated infants under six months old with suspected CMPA using hypoallergenic formulas. The study focused on a commercial extensively hydrolyzed formula containing Lactobacillus rhamnosus GG (ATCC53103) (eHF-LGG) or a commercial amino acid formula (AAF). Methods: In this secondary analysis of prospectively collected survey data, 52 HCPs treated 329 infants under six months old with suspected CMPA using hypoallergenic formulas. A series of two de-identified surveys per patient were collected by HCPs to assess short-term symptom relief in the patients and HCP's satisfaction with the management strategies. The initial survey was completed at the initiation of treatment of CMPA, and the second survey was completed at a follow-up visit. Results: The majority of HCPs (87%) in the study were general pediatricians, and most saw 2 to 10 CMPA patients weekly. Results showed that clinicians reported satisfaction with treatment in 95% of patients in the EHF cohort and 97% of patients in the AAF cohort and achieved expected clinical results in 93% and 97% of patients using eHF and AAF, respectively. Furthermore, few patients were switched from the hypoallergenic formula once initiated. Conclusion: The study provides new insights into HCP perspectives on treating infants with CMPA and supports using hypoallergenic formulas to manage this condition. However, additional prospective controlled studies are needed to confirm these initial findings.

Short-term symptom improvement in infants with suspected cow's milk protein allergy using amino acid formula: a prospective cohort analysis.

Background: Cow's milk protein allergy (CMPA) occurs commonly in infants. While the long-term efficacy of amino acid formulas for managing CMPA is well-established, there is limited data on the short-term symptom improvement of using amino acid formula (AAF). Objective: This study aimed to determine the short-term effects of managing suspected CMPA in infants aged 6 months and under using a commercial AAF. Methods: Healthcare providers who treated infants with suspected CMPA aged 6 months or younger (n = 104) provided de-identified survey data in this prospective study. Healthcare providers scored symptoms for severity from 0 to 3 (none, low, moderate, severe) before using a commercial AAF at Visit 1 and at Visit 2 (3-6 weeks later). Results: Gastrointestinal (94%), skin (87%), respiratory (86%), and uncategorized symptoms (89%) improved from AAF initiation, and these findings were consistent across different follow-up visit durations. Conclusion: This study is the most extensive prospective analysis conducted in the United States examining the short-term change in suspected CMPA symptoms using an AAF. These findings suggest that AAF may decrease the severity of suspected CMPA symptoms in infants 6 months or younger, often by the next follow-up visit. Further randomized controlled trials are required to confirm these initial findings.

The Effectiveness of Probiotics in Treating Food and Cow's Milk Allergies among Pediatric Age Group: A Meta-analysis of Randomized Controlled Trials.

The global prevalence of allergies is on the rise. Food allergies are of special concern among children under 5 years of age, leading to morbidity and mortality. Though the standard management is avoidance, probiotics are being used widely to prevent and treat food allergies. We aimed to determine the effect of probiotics as a therapeutic option for controlling food and cow's milk allergy among children under 5 years of age. A systematic search of electronic medical literature databases was conducted. We included all eligible randomized controlled trials available from inception until May 2021. The primary outcome of interest was the relief of allergic symptoms, while the secondary outcome was the induction of tolerance. Two investigators undertook the literature search, screening, data extraction, and quality appraisal independently. Data analysis and synthesis were performed using STATA 14 software. Subgroup analysis was performed for the duration of use and follow-up, and the age category of children included in the outcome were done. Twenty trials involving 4043 pediatric patients with food allergies were included in the review. Subgroup analysis also revealed that probiotics were effective in treating food allergies across the various subgroups included in the model. Around 15 trials reported our primary outcome, relief of symptoms, as a binary variable, which was pooled to obtain a risk ratio of 0.86 (95% confidence interval [CI], 0.77-0.95), with very low heterogeneity (I2 7.7%). Six trials were included for the secondary outcome of interest, which gave an imprecise pooled estimate of 1.29 (95% CI, 0.98-1.70) with significant heterogeneity (I2 7). Thus, we conclude that probiotics can serve as a vital therapeutic option in tackling food allergies among children less than 5 years of age. Further larger studies exploring the effectiveness of individual strains and their safety pattern are essential.

Cow's milk alternatives for children with cow's milk allergy and beyond.

Cow's milk allergy (CMA) is one of the most common food allergies in the first years of life, with worldwide prevalence estimated to range from 2% to 5%. While the majority of children with CMA will eventually develop tolerance to cow's milk proteins (it is estimated that >75% of children with CMA develop tolerance to cow's milk proteins by the age of 3 years, and >90% develop tolerance by the age of 6 years), the selection of an appropriate cow's milk (CM) alternative for those with CMA is vital to ensure adequate growth and development during childhood. The increasing number of CM alternative products on the commercial market with markedly different nutritional content and micronutrient fortification adds a layer of complexity that can be challenging for both families and clinicians to navigate. This article aims to provide guidance and clarity to Canadian paediatricians and primary care clinicians on recommending the most appropriate, safe, and nutritionally optimal CM alternatives for individuals with CMA, and beyond.

Conhecer antes de incorporar: um retrato dos programas para alergia ao leite implementados no Brasil / Understanding before incorporating: a portrait of milk allergy programs implemented in Brazil

Este trabalho objetiva caracterizar a assistência ofertada às crianças com alergia ao leite em programas públicos, e os desafios enfrentados na sua implantação, no contexto da pré-incorporação no Sistema Único de Saúde, de três fórmulas infantis para alergia ao leite. Estudo exploratório, transversal e abordagem quantitativa. Foram avaliados 21 programas/serviços de todas as regiões brasileiras. O principal indutor da criação destes programas foi a judicialização (80,9%), e o fornecimento destas fórmulas especiais foi realizado para crianças com até 2 anos de idade. Os principais desafios para a criação e execução destes programas foram a falta de recursos humanos e financeiros, a falta da contrapartida da União, protocolo unificado para o diagnóstico (Teste de Provocação Oral), e a escolha dos tipos das fórmulas. A estratégia mais adotada para redução dos custos foi a adequação das normas e protocolos (61,9%). Não houve diferença significativa entre os programas estaduais e municipais. Este estudo apresenta uma avaliação inédita e detalhada sobre os programas, trazendo discussões que corroboram a tomada de decisões, o uso racional de recursos públicos, a melhor assistência às crianças e o fortalecimento do sistema de saúde nacional.

This paper aims to characterize the assistance offered to children with cow's milk allergy in public programs and challenges to their implementation, specifically assessing the pre-incorporation phase in the Brazilian Unified Health System of 3 formulas for infants with milk allergy. This exploratory, cross-sectional study with a quantitative approach assessed 21 programs/services from all regions of the country. The main motivation for the creation of these programs was judicialization (80.9%), and these special formulas were provided for children up to 2 years of age. The main challenges to creating and implementing these programs were a lack of human and financial resources, no counterpart federal program, no unified protocol for diagnosis (oral provocation test), and the selection of formula types. The most common strategy for reducing costs was updating norms and protocols (61.9%), which did not differ significantly between state and municipal programs. This study presents an unprecedented and detailed evaluation of the programs, raising discussion about decision-making, the rational use of public resources, better care for children, and means of strengthening of the national health system.

Getting to know before incorporating: a picture of milk allergy programmes implemented in Brazil / Conhecer antes de incorporar: um retrato dos programas para alergia ao leite implementados no Brasil

The objective of this article is to characterize the assistance offered to children with milk allergies in public programs and the challenges faced in its implementation, in the context of the pre-incorporation in the Unified Health System of three infant formulas for milk allergy. Exploratory, cross-sectional study and quantitative approach. Twenty-one programs and/or services were evaluated (15 municipal and 6 states) from all Brazilian regions. The main driver of the creation of these programs was judicialization (80.9%) and the provision of these special formulas was carried out to children up to 2 years of age. Among the main difficulties in creating and executing these programs, the lack of human and financial resources was the most common reason, representing 71.4% and 61.9%, respectively. The most adopted strategy to reduce costs was the adequacy of norms and protocols (61.9%). There was no significant difference between state and municipal programs. This study presents an unprecedented and detailed evaluation of the programs, bringing discussions that support decision-making, rational use of public resources, better care for children and strengthening of the national health system. Key words: Unified Health System. Program Evaluation. Continuity of Patient Care. Milk Hypersensitivity. Health Manager.

Objetiva-se neste artigo caracterizar a assistência ofertada às crianças com alergia ao leite em programas públicos e os desafios enfrentados na sua implantação, no contexto da pré-incorporação no Sistema Único de Saúde de três fórmulas infantis para alergia ao leite. Estudo exploratório, transversal e abordagem quantitativa. Foram avaliados 21 programas e/ou serviços (15 municipais e 6 estaduais) de todas as regiões brasileiras. O principal indutor da criação destes programas foi a judicialização (80,9%) e o fornecimento destas fórmulas especiais era realizado às crianças com até 2 anos de idade. Dentre as principais dificuldades para criação e execução destes programas, a falta de recursos humanos e financeiros foram as razões mais presentes, representando 71,4% e 61,9%, respectivamente. A estratégia mais adotada para redução dos custos foi a adequação das normas e protocolos (61,9%). Não houve diferença significativa entre os programas estaduais e municipais. Este estudo apresenta uma avaliação inédita e detalhada sobre os programas trazendo discussões que corroboram na tomada de decisões, uso racional de recursos públicos, melhor assistência às crianças e fortalecimento do sistema de saúde nacional. Palavras-Chave: Sistema Único de Saúde. Avaliação de Programas e Projetos de Saúde. Continuidade da Assistência ao Paciente. Hipersensibilidade a Leite. Gestor de Saúde.

Correlation between cow's milk protein allergy and otitis media: a systematic review / Correlação entre alergia à proteína do leite de vaca e otite média: uma revisão sistemática

Abstract Objectives To review the evidence pertaining to the association between cow's milk protein allergy and recurrent acute otitis media and otitis media with effusion. Methods The CENTRAL, Web of Science, EMBASE, MEDLINE, LILACS databases, and gray literature were searched. Results Four studies were included, identifying the prevalence rates: 0.2% of delayed speech due to chronic otitis media with effusion in 382 children with cow's milk protein allergy, 10.7% of cow's milk protein allergy in 242 children who underwent ENT procedures, 40% of cow's milk protein allergy in 25 children with recurrent otitis media with effusion and higher tendency to otitis media in children with cow's milk protein allergy of 186 children (1.5 + 0.6 vs. 0.4 + 0.1; p< 0.1). Conclusion Considering the characteristics and methodological variations of the identified studies, it is not possible to state that there is reliable evidence of an association between cow's milk protein allergy and otitis media.

Resumo Objetivo Revisar as evidências sobre a correlação entre alergia à proteína do leite de vaca e otite média aguda recorrente e otite média com efusão. Métodos As buscas foram feitas nas bases de dados Central, Web of Science, Embase, Medline, Lilacs e na literatura cinzenta. Resultados Quatro estudos foram incluídos, identificaram‐se as prevalências: 0,2% de fala atrasada devido a otite média com efusão crônica entre 382 crianças com alergia à proteína do leite de vaca, 10,7% de alergia à proteína do leite de vaca entre 242 crianças submetidas a procedimentos otorrinolaringológicos, 40% de alergia à proteína do leite de vaca entre 25 crianças com otite média com efusão recorrente e maior tendência à otite média em alérgicos à proteína do leite de vaca entre 186 crianças (1,5 + 0,6vs.0,4 + 0,1; p < 0,1). Conclusão Se considerarmos as características e variações metodológicas dos estudos identificados, não é possível afirmar a existência de evidência confiável sobre a correlação entre alergia à proteína do leite de vaca e otite média.

Anafilaxia durante o primeiro ano de vida em pacientes com alergia à proteína do leite de vaca / Anaphylaxis during the first year of life of infants with cow's milk protein allergy

Objetivo: Descrever as manifestações de anafilaxia precoce em lactentes com alergia à proteína do leite de vaca (APLV) e descrever as condutas terapêuticas utilizadas. Método: Estudo observacional transversal retrospectivo que analisou pacientes com APLV atendidos no Instituto da Criança e do Adolescente do Hospital das Clínicas da FMUSP, entre 1990-2015, que apresentaram sintomas de alergia no primeiro ano de vida, com diagnóstico de anafilaxia, comparados a pacientes alérgicos sem anafilaxia desencadeada por ingestão de leite de vaca. Os pacientes foram caracterizados de maneira epidemiológica, tipo de sintoma apresentado e tratamento realizado. Os dados foram analisados no programa estatístico GraphPad Software Inc. Para avaliar a associação entre categorias, foi utilizado o Teste Exato de Fisher, e para comparações entre grupos, o Teste de Mann Whitney. Os resultados de p < 0,05 foram considerados significativos. Resultados: De um total de 120 crianças avaliadas (68 M:52 F), 85 (70,83%) lactentes preencheram os critérios da World Allergy Organization (WAO) para anafilaxia. As manifestações de alergia IgE mediada foram prioritariamente cutâneas [102 (85%)]. Nos pacientes com diagnóstico de anafilaxia, as principais manifestações foram urticária [39 (45,8%)], vômito [36 (42,3%)] e dispneia [19 (22,3%)]. A recorrência do episódio de anafilaxia ocorreu em 41 (34,16%) pacientes. A adrenalina (45%) e o anti-histamínico (63,3%) foram os medicamentos mais utilizados. Observa-se também que 6 (7%) pacientes com diagnóstico de anafilaxia não receberam nenhum tratamento. Conclusão: Anafilaxia no primeiro ano de idade apresenta quadro clínico semelhante aos pacientes mais velhos, mas ainda há elevada taxa de recorrência de episódios e subtratamento. Mais estratégias de educação precisam ser desenvolvidas.

Objective: To describe the early manifestations of anaphylaxis in infants with cow's milk protein allergy (CMPA) and the therapeutic approach. Method: In this cross-sectional observational study, we retrospectively reviewed the medical records of patients with CMPA treated at the Institute for Children and Adolescents of Hospital das Clínicas, University of São Paulo Medical School, from 1990 to 2015. Patients who developed allergic symptoms during the first year of life and had a diagnosis of anaphylaxis were compared with allergic patients without anaphylaxis triggered by cow's milk. Patients were characterized according to epidemiological features, type of symptoms, and treatment received. Data were analyzed using GraphPad software. Associations between categories were assessed by Fisher's exact test, and groups were compared by the Mann-Whitney test. Results with p<0.05 were considered statistically significant. Results: Of 120 infants evaluated (68 male: 52 female), 85 (70.83%) met the World Allergy Organization criteria for anaphylaxis. Most infants had cutaneous manifestations of immunoglobulin E (IgE)-mediated allergy (n=102, 85%). In those with a diagnosis of anaphylaxis, the main manifestations were urticaria (n=39, 45.8%), vomiting (n=36, 42.3%), and dyspnea (n=19, 22.3%). Anaphylaxis recurred in 41 patients (34.16%). Epinephrine (45%) and antihistamines (63.3%) were the most used drugs. Six patients (7%) with a diagnosis of anaphylaxis received no treatment. Conclusion: Anaphylaxis during the first year of life showed clinical features similar to those of older pediatric patients, but the rates of episode recurrence and undertreatment are still high. More education strategies need to be developed.

Tolerance to sterilised cow's milk in patients with eosinophilic oesophagitis triggered by milk.

BACKGROUND: Cow's milk protein is the main food trigger for eosinophilic oesophagitis (EoE) in children and adults and should be continuously avoided once identified as such. AIMS: To evaluate tolerance of sterilised cow's milk (boiled instead of UHT processing) with regard to maintenance of EoE remission, health-related quality of life (HRQoL), nutritional intake and allergic sensitisation in patients of all ages with milk-triggered EoE METHODS: We prospectively recruited patients in whom cow's milk was demonstrated to trigger EoE after an empirical food elimination diet-based study. They were given 200 ml of sterilised cow's milk twice daily for 8 weeks. Endoscopic assessment, peak eosinophil counts, oesophageal-related symptoms, HRQoL, blood eosinophils, eosinophil cationic protein (ECP), skin prick test and serum total and specific immunoglobulin E (IgE) to major milk proteins were monitored before and after sterilised milk intake. RESULTS: Eighteen patients (13 male) in EoE remission underwent a sterilised milk challenge. Twelve maintained EoE remission (<15 eos/hpf) while EoE recurred in the remainder. Endoscopic appearances deteriorated in non-tolerant patients. HRQoL scored well at baseline and was maintained among patients tolerant to sterilised milk, but deteriorated in reactive ones. No significant changes in blood eosinophil count, ECP, tryptase or total and milk-specific IgE serum levels were observed from baseline. However, cow's milk-specific IgE increased slightly in non-tolerant patients. Clinical and histological remission were maintained in patients who regularly consumed sterilised milk for 1 year. CONCLUSION: Sterilised milk did not trigger EoE in two-thirds of patients with documented milk-induced EoE, in either the short or long term.

Hypoallergenicity assessment of an extensively hydrolyzed whey-protein formula in cow's milk allergic infants.

BACKGROUND: Extensively hydrolyzed formulas are recommended for the dietary management of infants with cow's milk allergy (CMA). OBJECTIVES: Hypoallergenicity, growth, and gastrointestinal (GI) tolerability of a new extensively hydrolyzed whey-protein formula (eHWF) in CMA children were assessed. METHODS: In this prospective, randomized, international, multi-center study (Trial NL3889), 34 children with confirmed CMA (74% IgE-mediated) underwent a double-blind, placebo-controlled food challenge (DBPCFC) with an eHWF developed with non-porcine enzymes, supplemented with prebiotic short-chain galacto- and long-chain fructo-oligosaccharides (0.8 g/L, ratio 9:1), arachidonic acid (0.35/100 g), and docosahexaenoic acid (0.35/100 g). If tolerant to the eHWF, children participated in a 7-day open food challenge with this eHWF. Anthropometrics and GI tolerability were assessed in an optional 16-weeks follow-up. RESULTS: Of the 34 children who started the DBPCFC with the eHWF, 25 subjects (19 boys, mean age: 61 weeks, 18 with IgE-mediated CMA) completed the DBPCFC and 7-day open challenge without major protocol deviations and tested negative at both challenges. One child experienced a late moderate eczematous allergic reaction in the optional follow-up period, indicating the need for close monitoring of subjects starting new formula. Weight and length gain followed the World Health Organization growth curves. Changes in frequency and consistency of stools upon test formula intake were transient. CONCLUSIONS: The newly developed eHWF is a suitable option in CMA treatment as all subjects tolerated the product. This result is in line with the international criteria for hypoallergenicity (American Academy of Pediatrics) that state that more than 90% of CMA children must tolerate the formula. Use of the formula is also associated with normal growth curves and GI tolerability. TRIAL REGISTRATION: Trial NL3889, https://www.trialregister.nl/trial/3889.

Alergia alimentar não IgE mediada: proctocolite induzida por proteínas alimentares ­ Atualização / Non-IgE mediated food allergy: food protein-induced allergic proctocolitis ­ An update

Nas últimas décadas observa-se aumento na prevalência mundial de alergia alimentar, que já acomete aproximadamente 6% das crianças, atribuído à interação entre fatores genéticos, ambientais e alterações na resposta imunológica e pode envolver reações mediadas por IgE, não mediadas e mistas. As formas não IgE mediadas decorrem de reação de hipersensibilidade tardia, mediada por linfócitos T e afetam prioritariamente o trato gastrointestinal, como a Síndrome da enterocolite induzida por proteína alimentar (FPIES), Síndrome da proctocolite alérgica induzida por proteína alimentar (FPIAP), Síndrome da enteropatia induzida por proteína alimentar (FPE) e doença celíaca. As características destas reações podem ser diferenciadas por sua apresentação clínica, gravidade, idade de início e história natural. Entre as reações alérgicas aos alimentos não IgE mediadas, a proctocolite alérgica é a mais frequente. Geralmente ocorre no primeiro ano de vida e apresenta excelente prognóstico. Embora costume ter um curso benigno, traz grande preocupação aos cuidadores por frequentemente cursar com quadro de hematoquezia exigindo diagnóstico diferencial adequado. O conhecimento e manejo da proctocolite alérgica é de suma importância para a prática médica em Alergia e Imunologia. Seu diagnóstico é baseado na história clínica seguindo-se dieta de exclusão, especialmente do leite de vaca, com subsequente provocação oral, que geralmente pode ser realizada no domicílio. O diagnóstico preciso é importante, para se evitar dietas de exclusão desnecessárias. Nesta revisão foram utilizados artigos publicados nos últimos anos, com busca realizada através da base PubMed envolvendo revisões, diagnóstico e tratamento de alergias não IgE mediadas, com foco em proctocolite alérgica.

An increase in the worldwide prevalence of food allergies has been observed in the past decades, currently affecting 6% of children. This increase has been associated with the interaction between genetic, environmental, and immune response factors and can be observed in IgE, non-IgE, and mixed mediated reactions. Non-IgE mediated food allergies result from delayed-type hypersensitivity and mostly affect the gastrointestinal tract, such as food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), food protein-induced enteropathy (FPE), and celiac disease. These reactions can be differentiated by their clinical presentation, severity, age at onset, and natural history. Among non-IgE-mediated allergic reactions to food, allergic proctocolitis is the most frequent. It usually develops in the first year of life and has excellent prognosis. Although it has a benign course, allergic proctocolitis is challenging for health care professionals because it often presents with hematochezia, requiring an accurate differential diagnosis. Knowledge and management of allergic proctocolitis is of paramount importance for medical practice in allergy and immunology. Its diagnosis is based on clinical history followed by elimination diet, especially cow's milk, with subsequent oral food challenge, which may usually be performed at home. Accurate diagnosis is important to avoid unnecessary elimination diets. For this review, PubMed database was searched for recently published literature reviews and studies on the diagnosis and treatment of non- IgE mediated allergies, with a focus on allergic proctocolitis.

Evaluation of the complementary feeding practices, dietary intake, and nutritional status of infants on a cow's milk protein elimination diet

Abstract Objective: To evaluate the complementary feeding practices, food intake, and nutritional status of infants on a cow's milk protein elimination diet. Methods: A cross-sectional and observational study was conducted to compare infants aged 4-18 months who were on a cow's milk protein elimination diet with a control group of healthy infants without any dietary restrictions. General information on the child's health, demographic data, and food consumption were collected. Results: The study included 96 infants in the elimination diet group and 99 in the control group. In the elimination diet group, the median age (in months) of introduction of solid foods (5.0 × 4.0; p < 0.001) and water (5.5 × 4.0; p < 0.05) was later, consumption of soft drinks and industrialized cookies was less frequent (p < 0.05), and a lower index of complementary feeding inadequacies (2.75 × 3.50; p < 0.001) was observed. The elimination diet group presented lower individual values of Z scores for weight/age, weight/height, and body mass index/age, although they were fed with higher amounts of energy (117.4 × 81.3 kcal/kg of weight; p < 0.001) and macro-and micronutrients, except for vitamin A. In the elimination diet group, breast milk and its substitutes contributed to more than 67% of energy intake. Although calcium consumption was a deficit in 31.5% of the infants, none received supplementation. Conclusion: Infants on an elimination diet presented more adequate complementary feeding practices and higher nutritional intake, despite lower body weight values.

International Cross-Sectional Survey among Healthcare Professionals on the Management of Cow's Milk Protein Allergy and Lactose Intolerance in Infants and Children.

Purpose: The present international survey among healthcare providers aimed to collect data on theoretical knowledge and clinical practices in the diagnosis and management of cow's milk protein allergy (CMPA) and lactose intolerance (LI) in infants. Methods: A global survey was conducted in several countries with diverse health care settings. The survey consisted of multiple-choice questions in 3 main domains: (1) understanding and clinical practices around CMPA and LI; (2) case scenarios; and (3) disease-specific knowledge and potential educational needs. Results: Responses were available from 1,663 participants. About 62% of respondents were general practitioners or general pediatricians, and the remainder were pediatric allergists/gastroenterologists (18%) or other health practitioners (20%). The survey identified knowledge gaps regarding the types of CMPA (IgE-mediated vs. non-IgE-mediated) and the clinical overlap with LI. The survey suggested diverse clinical practices regarding the use of hypoallergenic formulas, as well as misconceptions about the prebiotic benefits of lactose in extensively hydrolyzed formulas in non-breastfed infants with CMPA. Responses to the two case scenarios highlighted varying levels of awareness of the relevant clinical practice guidelines. While respondents generally felt confident in managing infants with CMPA and LI, about 80% expressed an interest for further training in this area. Conclusion: The current survey identified some knowledge gaps and regional differences in the management of infants with CMPA or LI. Local educational activities among general and pediatric healthcare providers may increase the awareness of clinical practice guidelines for the diagnosis and treatment of both conditions and help improve clinical outcomes.

Fatores preditores do desfecho do Teste de Provocação Oral na Alergia à Proteína do Leite de Vaca: in natura vs. alimentos processados / Predictors of the outcome of the Oral Food Challenge for Cow's Milk Protein Allergy: raw vs. processed foods

Objetivos: Descrever uma população de crianças com alergia à proteína do leite de vaca (APLV) IgE mediada, submetidas ao teste de provocação oral (TPO) com alimentos processados vs. in natura, e comparar características clínico-epidemiológicas e laboratoriais, avaliando preditores de desfecho ao uso dessas diferentes apresentações de proteína. Métodos: Estudo transversal realizado em ambulatório de alergia de um hospital terciário em Fortaleza, Ceará. A coleta dos dados foi realizada entre outubro de 2018 a setembro de 2019. O questionário foi preenchido com os dados epidemiológicos, clínicos e laboratoriais encontrados no prontuário; amostra total de 49 crianças, com APLV IgE mediada tolerantes ao TPO com alimentos processados ou in natura. Resultados: Na comparação das características clinico-epidemiológicas das populações tolerantes a alimentos in natura vs. processados (respectivamente), a maioria apresentou dados semelhantes, como sexo masculino (60% vs. 57,9%), etnia parda (73,3% vs. 68,4%), idade gestacional a termo (80% vs. 77,8%), sem intercorrências durante a gestação (58,3% vs. 80,0%) ou parto (70% vs. 78,9), média de idade materna (32 anos vs. 35 anos), escolaridade materna (ensino médio completo - 43,3% vs. 47,4%), idade de início dos sintomas de APLV entre 1 e 6 meses (76,7% vs. 68,4%), aleitamento materno exclusivo entre 4 e 6 meses (60% vs. 68,45%), histórico de alergia familiar alimentar (73% vs. 68,4%), sendo as principais comorbidades alérgicas as respiratórias (38,9% vs. 35,7%) e alimentares (38,9% vs. 35,7%). Em relação aos dados laboratoriais, a maioria das frações de proteína no grupo tolerante a alimentos in natura e a alimentos processados apresentou valores ≤ 10 kU/L. Foi constatado que a idade materna (p = 0,006) e a idade de introdução de fórmula complementar (p = 0.020) se correlacionam de forma estatisticamente significante no grupo de pacientes tolerantes a alimentos processados. Conclusões: Foi observado que a idade materna (p = 0,006) e a idade de introdução de fórmula complementar (p=0.020) se correlacionam de forma estatisticamente significante no grupo de pacientes tolerantes alimentos processados. Os dados laboratoriais seguiram distribuição proporcionais entre os dois grupos, com maior frequência de valores ≤ 10 kU/L para todas as frações de proteína do leite de vaca, sem significância estatística. Estudos populacionais semelhantes em populações APLV IgE mediada são importantes para caracterizar melhor esse fenótipo e otimizar ferramentas diagnósticas e protocolos de tratamento. Destaca-se também o papel da terapia baked, que auxilia na aquisição de tolerância a diferentes apresentações da PLV de forma mais breve, melhorando, portanto, a qualidade de vida desses pacientes (AU)

Objectives: To describe the population of children with IgE-mediated CMPA tolerant to processed or raw CMP in the OFC, comparing their clinical, epidemiological and laboratory characteristics and evaluating the possible predictors of outcomes associated with these different presentations of CMP. Methods: Cross-sectional study carried out in an allergy clinic of a tertiary hospital in Fortaleza, Ceará. Data collection was carried out between October 2018 and September 2019. The questionnaire was filled out with epidemiological, clinical and laboratory data found in the medical records. The total sample was composed of 49 children with IgE-mediated CMPA tolerant to processed or raw foods in the OFC. Results: The comparison of the clinical and epidemiological characteristics of populations tolerant to raw foods vs. processed (respectively) showed similarities, such as the predominance of the male gender (60% vs. 57.9%); mixed ethnicity (73.3% vs. 68.4%); delivery at term (80% vs. 77 .8%); no complications during pregnancy (58.3% vs. 80.0%) or childbirth (70% vs. 78.9); mean maternal age (32 years vs. 35 years); level of education of the mothers (complete high school - 43.3% vs. 47.4%); age of onset of CMPA symptoms between 1 and 6 months (76.7% vs. 68.4%); exclusive breastfeeding for 4 to 6 months (60% vs. 68.45%); family history of food allergy (73% vs. 68.4%); and respiratory (38.9% vs. 35.7%) and food allergies (38.9% vs. 35.7%) as the main allergic comorbidities. Regarding laboratory data, most protein fractions had values ≤ 10 kU/L in both groups. It was found that maternal age (p = 0.006) and age of introduction of formula (p = 0.020) were statistically significant in the group of patients tolerant to processed foods. Conclusions: It was observed that maternal age (p = 0.006) and age of introduction of formula (p = 0.020) were statistically significant in the group of patients tolerant to processed foods. Laboratory data were proportionally distributed across the two groups, with a higher frequency of values lower than or equal to 10 kU/L for all CMP fractions, with no statistical significance between the groups. Similar population studies in IgE-mediated CMPA populations are important to better characterize this phenotype and optimize diagnostic tools and treatment protocols. The role of baked therapy is also noteworthy, as it helps patients to develop tolerance to different presentations of CMP more quickly, improving their quality of life (AU)

Discrepancy between Guidelines and Clinical Practice in the Management of Cow's Milk Allergy in Children: An Online Cross-Sectional Survey of Polish Physicians.

The aim of this study was to assess the compliance between current guidelines on the diagnosis and management of children with cow's milk allergy (CMA) and clinical practice by a survey of Polish physicians. An online cross-sectional survey involving a convenience series of participants was performed from January 15 to March 20, 2020. Data provided by 605 physicians (74.2% of them pediatricians working in general practice) were analyzed. Contrary to the current recommendations, only a minority of respondents (27.4%) reported performing oral food challenge (OFC) to confirm the diagnosis of CMA. Among those who reported performing OFC (n = 160 respondents), the majority performed an open challenge (82.5%). Most respondents (79.2%) correctly recommended as the first-line treatment extensively hydrolyzed cow's milk formula for a child with mild-to-moderate CMA. Less than half of participants (43.8%) recommended amino acid-based formula for a child with severe CMA (anaphylaxis). Only half of respondents (50.8%) reassessed tolerance to cow's milk proteins. For assessing tolerance acquisition, more respondents recommended challenge to baked milk compared with fresh cow's milk (60.5% vs. 39.5%, respectively). This survey study found that only a minority of responding physicians follow current guidelines for diagnosis and management of children with CMA in Poland.