Advances in butyrates and intestinal immune tolerance in children with cow′s milk protein allergy / 国际儿科学杂志

Cow′s milk protein allergy is common in infants, which is an abnormal immune reaction caused by the imbalance of intestinal immune tolerance system.Butyrates, the fermentation product of intestinal anaerobic bacteria, can be used as a histone deacetylase inhibitors and a ligand of G protein-coupled receptors to regulate intestinal innate immunity and adaptive immune function, thereby inducing intestinal immune tolerance in children with cow′s milk protein allergy, which has potential clinical therapeutic value for cow′s milk protein allergy.However, this theory is still only based on the exploration of mechanisms at the cellular and animal levels and has not been applied in the clinic.This article reviews the intestinal immune mechanism of cow′s milk protein allergy, the anabolism of butyrates and the important role of butyrates in intestinal immune tolerance of cow′s milk protein allergy, aiming to lay a theoretical foundation for further clinical application of butyrate-induced intestinal immune tolerance of cow′s milk protein allergy.

Growth of infants with gastrointestinal manifestations of cow's milk protein allergy / Crescimento de lactentes com manifestações gastrointestinais de alergia à proteína do leite de vaca

ABSTRACT Objective To assess linear growth and weight gain in infants with suspected cow's milk protein allergy with gastrointestinal manifestations, seen at a gastropediatrics clinic. Methods A retrospective cohort study conducted with demographic, clinical, anthropometric and dietary information on 84 infants first seen between 2015 and 2018 and followed-up for six months. Stature-for-age, weight-for-age, and body mass index-for-age in z-scores were evaluated according to the cut off points established by the World Health Organization in 2006. Accelerated growth or catch-up was considered a gain ?0.67 in the z-score of the referred indices, evaluated at 3 and 6 months. Results Median age at baseline was 4.0 months and 88.1% of the infants were already in diet exclusion. Regarding the anthropometric evaluation short stature frequency was 15.5% and the underweight frequency was 8.3% and 3.6% respectively based on the weight-for-age and body mass index-for-age indices. High recovery growth was observed during the follow-up period but was not considered catch up. In boys, the gains in weight-for-age and body mass index-for-age were significant (p=0.02 and p=0.01 respectively) and close to the threshold that characterizes the catch up, 0.58 and 0.59, respectively. In girls, significant gains in stature-for-age and weight-for-age (0.38 and 0.37 respectively, p=0.02 for both) were observed. Conclusion Infants with suspected cow's milk protein allergy with gastrointestinal manifestations should have early access to specialized nutritional counseling to avoid exposure to allergenic food and control allergy symptoms, thereby avoiding malnutrition and ensuring adequate nutritional recovery.

RESUMO Objetivo Avaliar o crescimento linear e o ganho de peso de lactentes com suspeita de alergia à proteína do leite de vaca, com manifestações gastrointestinais, atendidos em um ambulatório de gastropediatria. Métodos Estudo de coorte retrospectivo, com informações demográficas, clínicas, antropométricas e dietéticas de 84 lactentes que iniciaram atendimento entre 2015 e 2018 e foram acompanhados durante seis meses. Foram avaliados os índices estatura/idade, peso/idade e índice de massa corporal/idade em escore-z, segundo os pontos de corte da Organização Mundial de Saúde de 2006. Considerou-se crescimento acelerado (ou catch-up growth) um ganho ?0,67 escore-z nos referidos índices, avaliados em três e seis meses. Resultados No baseline, a mediana de idade foi 4,0 meses e 88,1% dos lactentes já estavam em dieta de exclusão. A frequência de baixa estatura foi de 15,5% e a de baixo peso foi de 8,3% e de 3,6% segundo os índices peso/idade e índice de massa corporal/idade, respectivamente. Houve elevado crescimento de recuperação durante o período de acompanhamento, mas que não configurou catch up. Nos meninos, ganhos no peso/idade e índice de massa corporal/idade foram significantes (p=0,02 e p=0,01) e próximos do limiar que caracteriza catch up: 0,58 e 0,59, respectivamente. Nas meninas, foram observados ganhos significantes na estatura/idade e peso/idade, de 0,38 e 0,37 (p=0,02 para ambos). Conclusão Demonstrou-se que lactentes com suspeita de alergia à proteína do leite de vaca, com manifestações gastrointestinais, deveriam ter acesso precoce ao aconselhamento nutricional para evitar exposição ao alimento alergênico, controlar sintomas e, assim, evitar a desnutrição ou garantir recuperação nutricional adequada.

Guidelines for diagnosis and nutritional intervention of mild to moderate non-IgE mediated cow′s milk protein allergy in Chinese infants / 中华实用儿科临床杂志

Cow′s milk protein allergy (CMPA) is one of the most common presentations of food allergy seen in early childhood.It is an abnormal immune response caused by cow′s milk protein.CMPA can be clinically subdivided into either immediate-onset IgE mediated or delayed onset non-IgE mediated, or both.At present, concerns regarding the early and timely diagnosis of CMPA have been high-lighted over the years and there are many expert consensus on CMPA in China, but these consensus did not distinguish IgE mediated or non-IgE mediated CMPA.In view of the obvious clinical differences between the two type of CMPA and non-IgE mediated CMPA is more common in infancy, experts focus on pediatric gastroenterology, allergy/immunology, dermatology, nutrition and child healthcare convened by the Allergy Prevention and Control Professional Committee of Chinese Preventive Medicine Association present this guideline to help practitioners in primary care settings to early recognize and make suitable management of non-IgE mediated CMPA in China.The guideline incorporates the cutting-edge international guidance and the actual situation of Chinese children describing in detail the types, clinical features, diagnosis and nutritional intervention of non-IgE mediated CMPA.There are 42 recommendations in 7 categories in total referring to the common questions related to non-IgE mediated CMPA.

Effect of food avoidance therapy on gut microbiota in infants with cow′s milk protein allergy / 中国小儿急救医学

Objective:To investigate the effect of dietary avoidance therapy on gut microbiota in infants who were diagnosed as cow′s milk protein allergy by comparing the gut microbiota changes before and after the treatment.Methods:The infants with artificial feeding and clinical diagnosis of cow′s milk protein allergy were collected from the outpatient of Gastroenterology departement in our hospital.They were fed with amino acid formula instead of ordinary formula for 4 weeks.Among them, 23 cases of successful intervention were selected.The fecal samples before and after treatment were collected, and the fecal genomes were extracted respectively.The PCR products of specific segments of 16S rDNA were sequenced by high-throughput sequencing.The results were analyzed by bioinformatics, and the differences of flora composition before and after the intervention were compared to find the different species between groups.Results:No obvious difference was found between before and after treatment of gut microbiota diversity( P>0.05). The compose of gut microbiota of the cow′s milk protein allergy was changed after feeding with amino acid milk.At the level of phylum, proteobacteria decreased significantly after treatment.At the level of class, alphaproteobacteria and gammaproteobacteria decreased significantly.Enterobacteriaceae, enterobacteriaceae and streptococcus granulosus decreased significantly.At the family level, the number of peptostridium, peptostridium and clostridium decreased significantly compared with that before treatment.Lactobacillus eubacteriaceae and eubacterium, ruminococcaceae, limosum, pasteurella, pasteurellaceae, haemophilus parainfluenzae T3T1, infantis ATCC15697/JCM1222/DSM2008 and Pseudocatenulatum-DSM20438/JCM1200/LMG10505 were higher than that before treatment with statistically different( P<0.05). Conclusion:For children with cow′s milk protein allergy, the harmful bacteria in intestinal flora decreased and the beneficial bacteria increased after dietary avoidance treatment.

Research progress of cow′s milk protein allergy and intestinal flora characteristics in premature infants / 中华实用儿科临床杂志

Cow′s milk protein allergy (CMPA) is the most common food allergy in infancy.Since the early symptoms of CMPA in premature infants lack specificity and are prone to misdiagnosis or missed diagnosis, which would induce inappropriate fasting and unreasonable application of antibiotics, more attention should be paid to CMPA in premature infants.It has been proved in accumulating studies that the establishment and improvement of intestinal flora is the basic factor for the maturation of the immune system and the induction of immune response balance after birth.There are differences in the type and amount of intestinal flora between food allergic infants and non-allergic infants.Compared with term infants, preterm infants have significantly lower diversity and abundance of intestinal flora, immature gastrointestinal tract and immune system development, and are at greater risk for allergies.The use of probiotics can enhance intestinal barrier function and improve immune tolerance.The clinical diagnosis and treatment of preterm CMPA, the characteristics of intestinal flora and the use of probiotics in preterm infants would be reviewed in this paper.

Recomendaciones sobre el diagnóstico y el tratamiento de la alergia a la proteína de la leche de vaca en población pediátrica colombiana - Posición de expertos / Expert recommendations for diagnosis and treatment of cow's milk protein allergy in the Colombian pediatric population

Resumen Objetivo: generar recomendaciones sobre el diagnóstico y el tratamiento de la alergia a la proteína de la leche de vaca (APLV), que sirvan de referencia y consulta para los médicos pediatras y de cuidado primario. Materiales y métodos: el presente documento de posición de expertos fue desarrollado por un grupo de médicos, especialistas en diferentes áreas terapéuticas y con experiencia en APLV. Se definieron los temas más relevantes y se realizó una revisión de la literatura científica disponible, a fin de elaborar una propuesta de recomendaciones que fue discutida por los autores. Resultados: se elaboró un documento de posición que propone un enfoque práctico sobre la definición, el diagnóstico y el tratamiento de la APLV en el paciente pediátrico. Conclusiones: el diagnóstico temprano y el manejo adecuado de la APLV pueden contribuir a una disminución de la carga de esta enfermedad y sus complicaciones.

Abstract Objective: The objective of this paper is to develop and present recommendations for diagnosis and treatment of Cow's Milk Protein Allergy (CMPA) which can serve as a reference for pediatric and primary care physicians to consult. Materials and methods: This expert position document was developed by a group of doctors who are specialists in several therapeutic areas who have experience in CMPA. The most relevant topics were defined and a review of the available scientific literature was carried out to prepare a proposal for recommendations that was then discussed by the authors. Results: A position paper was developed that proposes a practical approach to definition, diagnosis and treatment of CMPA in pediatric patients. Conclusions: Early diagnosis and proper management of CMPA can help decrease the burden of this disease and its complications.

Alergia a la proteína de la leche de vaca: enfoque diagnóstico y terapéutico / Diagnostic and therapeutic approach to cow's milk protein allergy

Resumen La prevalencia de la alergia a las proteínas de la leche de vaca (APLV) en el ámbito mundial es, aproximadamente, de 1,9 a 4,9 %. En Colombia, esta cifra se desconoce. En un alto porcentaje de los casos, no existe la sospecha por parte del personal de salud, y, por lo tanto, el diagnóstico y el tratamiento se retrasan. Esto acarrea un aumento en el tiempo y en los recursos que emplean los profesionales de la salud y los padres en procura de establecer la etiología del padecimiento de los niños que presentan esta enfermedad. Dentro de este contexto, la historia clínica es fundamental en la sospecha de la APLV, y es especialmente relevante la evaluación de antecedentes, en los cuales se destacan la presencia de la exposición temprana a la proteína, así como la atopia en familiares en primer grado de consanguinidad. La presentación de la APLV puede manifestarse con reacciones inmediatas a nivel digestivo (vómitos, diarrea aguda), cutáneo (urticaria, dermatitis, angioedema) y, con menos frecuencia, a partir de signos respiratorias y sistémicos. Sin embargo, la amplia variedad de manifestaciones clínicas y signos puede ser un reto para el profesional que no se encuentre sensibilizado con la patología, e incluso soslayar este diagnóstico retrasa la suspensión de la proteína de la leche de vaca de la dieta y demora el acceso a un tratamiento eficaz. El tratamiento ideal reconocido es la dieta de exclusión, la cual requiere un estricto cumplimiento. En los niños alimentados con lactancia materna exclusiva, será necesaria la dieta restrictiva de leche y sus derivados en la madre. En quienes no reciben lactancia, se deberá tratar mediante fórmulas de proteínas lácteas extensamente hidrolizadas (FEH) o a base de aminoácidos (FAA). Así bien, el pronóstico es favorable y la mayoría de niños tolerarán las proteínas de la leche de vaca a los 2 años, mientras que en pacientes con polisensibilización el proceso puede prolongarse. En el caso de no alcanzar la tolerancia, la inmunoterapia oral es una opción disponible.

Abstract The worldwide prevalence of cow's milk protein allergy (CMPA) is approximately 1.9% to 4.9%. Its prevalence in Colombia is unknown. A high percentage of cases are unsuspected by medical personnel resulting in delayed diagnosis and treatment which increase the time and resources used to establish the etiology of this condition in children. The clinical history is fundamental for diagnosis of CMPA, especially the background evaluation. Of special importance are early exposure to the protein and atopy in first degree relatives. CMPA's initial presentation may be digestive, cutaneous or respiratory. Digestive symptoms can include vomiting and acute diarrhea, and cutaneous symptoms include hives, dermatitis and angioedema. Respiratory and systemic manifestations occur less frequently. The wide variety of clinical manifestations and signs can challenge health care professionals who are not alert to this pathology to the point that the diagnosis is not even considered event though delaying the suspension of cow's milk protein from the diet delays access to an effective treatment. The well-recognized ideal treatment is an exclusion diet which requires strict compliance. For children who are exclusively breastfed, the mother's diet must restrict milk and its derivatives. Children who are not breastfed, should be fed formulas of extensively hydrolyzed milk proteins based on amino acids. The prognosis is favorable, and most children will tolerate cow's milk proteins at two years. The process may take more years for polysensitive patients. Oral immunotherapy is an option that is available for patients who do not achieve toleration.

Research advances in animal models of cow's milk protein allergy / 国际儿科学杂志

Cow's milk protein allergy (CMPA) is the most common food allergy among infants and young children,which has an increasing incidence in recent years.Performing suitable animal experiments is a key to study CMPA,but currently there aren't proper models consistent with human physiological sensitization process.Ideal animal models can serve as critical tools to reveal the mechanisms of CMPA and develop preventive and therapeutic approaches.Animal species and strains,different types of the models,biological detection methods and evaluation are reviewed in this paper.It also summarizes characteristics of animal models,which will provide a reference for basic and applied researches of CMPA.

A perspective on partially hydrolyzed protein infant formula in nonexclusively breastfed infants / 소아과

The World Health Organization recommends that infants should be exclusively breastfed for the first 6 months of life to provide optimal nutrition in this critical period of life. After this, infants should receive nutritionally adequate and safe complementary foods while breastfeeding continues for up to 2 years of age or beyond. For nonbreastfed infants, infant formula is an available option to provide the nutrition needed. Infant formula is usually prepared from industrially modified cow's milk and processed to adjust for the nutritional needs of infants. However, cow's milk is one of the most common causes of food allergy, affecting 2%–5% of all formula-fed infants during their first year of life. One strategy to prevent cow's milk allergy in nonbreastfed infants is the use of partially hydrolyzed formula (pHF) in high-risk infants, which are infants born in families with atopic disease. However, based on an epidemiological study, approximately half of the infants who develop allergy are not part of the at-risk group. This is because the non-at-risk group is significantly larger than the at-risk group and the non-at-risk infants have approximately 15% risk of developing allergies. This study aimed to evaluate the effects of partially hydrolyzed whey formula (pHF-W) in nonbreastfed infants and determine whether pHF-W can prevent atopic disease in high-risk infants and can be used as routine starter formula regardless of the allergy risk status.

The association between polymorphisms of Eotaxin gene and the allergy to cow's milk protein in infants / 中华实用儿科临床杂志

Objective To assess the association between-426C＞T,-384A＞G,+ 67G＞A polymorphisms in Eotaxin gene and cow's milk protein allergy (CMPA) in infants.Methods One hundred and six patients with CMPA who were hospitalized at Children's Hospital Affiliated to Nanjing Medical University from July 2014 to July 2015 were selected as CMPA group,and 124 healthy infants chosen from Ninghai Road Community Health Service Centers at the same time were selected as healthy control group,and the serum levels of Eotaxin in 2 groups were measured by enzyme-linked immunosorbent assay (ELISA),polymerase chain reaction (PCR) and DNA direct sequencing technology were used to detect the genotypes for single nucleotide polymorphisms (SNPs) of-426C ＞ T,-384A ＞ G,and + 67G ＞ A in Eotaxin gene.The association between the SNPs of-426C ＞ T,-384A ＞ G,and + 67G ＞ A in Eotaxin gene and CMPA,the peripheral blood eosinophil counts,serum Eotaxin levels,and serum total immunoglobulin E levels were analyzed.Results For-426C ＞ T,the frequency of each genotype of the CMPA group was CC,CT,TF (79.25％,19.81％,0.94％),while the frequency of each genotype of the healthy control group was CC,CT,TT(88.71％,8.06％,3.23％).There was a significant difference in the genotype frequency in-426C ＞ T between the CMPA group and the healthy control group (x2 =7.83,P ＜ 0.05).The individuals with heterozygous genotype(CT) had a 1.75-fold increased risk of developing CMPA compared with the individuals with wild-type genotype (CC) [odds ratio (OR) =2.75,95％ confidence interval(CI):1.23-6.15,P ＜ 0.05].For position + 67G ＞ A,CMPA patients with a genotype including variant nucleotide had lower peripheral blood eosinophil counts [(0.48 ± 0.06) × 109/L] and serum Eotaxin levels [(157.67 ± 12.72) ng/L] than those with wild-type genotype [(0.85 ± 0.09) × 109/L,(286.96 ± 33.23) ng/L] (F =10.30,5.75,all P ＜ 0.05).Conclusions Polymorphism of the Eotaxin gene (-426C ＞ T) was associated with the susceptibility to CMPA.Polymorphism of the Eotaxin gene(+ 67G ＞ A) was related to the blood eosinophil counts and the serum Eotaxin levels in children with CMPA.

Analysis of positive rate of sIgE for common allergens in infants with cow's milk protein allergy / 吉林大学学报(医学版)

Objective:To explore the differences in the positive rates of specific-IgE(sIgE)of the common allergens between the cow's milk protein allergy(CMPA)and healthy infants and the distribution characteristics of positive sIgE of common allergens in the CMPA infants,and to provide basis for comprehensive intervention of the CMPA infants.Methods:A total of 156 cases of CMPA and 318 cases of healthy infants were selected as the subjects.The serum sIgE and total IgE levels of common allergens of the infants in two groups were detected by enzyme-linked immunosorbent assay.The differences in the positive rates of serum sIgE of common allergens and total IgE of the infants in two groups were compared.Results:There were no statistical differences in the positive rates of serum sIgE and total IgE for common allergens of the infants between CMPA group and healthy group(P>0.05).The major food allergens with high positive rates of sIgE in CMPA group were cow's milk(44.2%),egg white(10.3%)and cashew nut(5.1%),and the inhale allergens with high positive rates of sIgE were cat hair (21.2%),dog hair(9.6%)and house dust mite(4.5%).While for the healthy infants,the major food allergens with high positive rates of sIgE were cow's milk(45%),egg white(14.2%)and cashew nut(6.0%),and the inhale allergens with high positive rates of sIgE were cat hair(25.8%),dog hair(14.5%)and fungus combinations(4.5%).The analysis in different age groups(<1 year old and 1-2 years old)showed that there were no statistical differences in the positive rates of serum sIgE and total IgE for common allergens of the infants between CMPA group and healthy group(P>0.05).Conclusion:There are no significant differences in the serum sIgE and total IgE positive rates between the CMPA and healthy infants.The detection of serum sIgE and total IgE of common allergens is of little clinical significance for the CMPA infants.

Analysis of positive rate of sIgE for common allergens in infants with cow's milk protein allergy / 吉林大学学报(医学版)

Objective: To explore the differences in the positive rates of specific-IgE (sIgE) of the common allergens between the cow's milk protein allergy (CMPA) and healthy infants and the distribution characteristics of positive sIgE of common allergens in the CMPA infants, and to provide basis for comprehensive intervention of the CMPA infants. Methods: A total of 156 cases of CMPA and 318 cases of healthy infants were selected as the subjects. The serum sIgE and total IgE levels of common allergens of the infants in two groups were detected by enzyme-lmked immunosorbent assay. The differences in the positive rates of serum sIgE of common allergens and total IgE of the infants in two groups were compared. Results: There were no statistical differences in the positive rates of serum sIgE and total IgE for common allergens of the infants between CMPA group and healthy group (P> 0.05). The major food allergens with high positive rates of sIgE in CMPA group were cow's milk 44.2%), egg white (10.3%) and cashew nut (5.1%), and the inhale allergens with high positive rates of sIgE were cat hair 21.2%), dog hair (9.6%) and house dust mite 4.5%). While for the healthy infants, the major food allergens with high positive rates of sIgE were cow's milk 45%), egg white (14.2%) and cashew nut (6.0%), and the inhale allergens with high positive rates of sIgE were cat hair (25.8%), dog hair (14.5%) and fungus combinations 4.5%). The analysis in different age groups (0.05). Conclusion: There are no significant differences in the serum sIgE and total IgE positive rates between the CMPA and healthy infants. The detection of serum sIgE and total IgE of common allergens is of little clinical significance for the CMPA infants.

Cow's Milk-related Symptom Score as a predictive tool for cow's milk allergy in Indian children aged 0–24 months

BACKGROUND: Cow's milk protein causes an unfavorable and unwanted reaction in some individuals called cow's milk protein allergy (CMPA). It is more often imprecise and easily missed in primary care settings. Cow's Milk-related Symptom Score (CoMiSS) was developed as a screening and awareness tool to suggest the presence of CMPA using general, dermatological, gastrointestinal, and respiratory symptoms. OBJECTIVE: Assess the utility of CoMiSS in the diagnosis of CMPA in Indian children aged between 0 and 24 months. METHODS: A pilot multicentric, observational, longitudinal study was conducted over a period of 4 months among infants aged 0–24 months with symptoms suggestive of CMPA to measure the positive and negative predictive value of CoMiSS. A predesigned questionnaire was used to record the information via CoMiSS. The patients were confirmed of having CMPA via oral food challenge/skin prick test or ImmunoCAP test. RESULTS: A total of 83 children were enrolled in the study and majority of them had gastrointestinal complaints (61%, 51 of 83) followed by respiratory (41%, 34 of 83) and skin complaints (33%, 27 of 83). CoMiSS was >12 in 72.3% of the infants and amongst them 84.3% were confirmed via oral food challenge/ImmunoCAP test. The positive and negative predictive values for CoMiSS were 93% and 33% respectively. CONCLUSION: CoMiSS can help predict CMPA in children aged less than 2 years in the Indian primary care setting, aiding in early diagnosis. Prospective randomized studies are needed to evaluate the use of CoMiSS further.

Relationship between infants cow's milk protein allergy and gastroesophageal reflux disease / 中华实用儿科临床杂志

Objective To investigate the relationship between cow's milk protein allergy(CMPA)and gastroesophageal reflux disease(GERD)and the prognosis of GERD combined with CMPA.Methods Fifty patients(24 boys and 26 girls)with GERD were enrolled in this study from January 2015 to June 2016 at Department of Pediatrics,Tangdu Hospital of the Fourth Military Medical University.All children were treated with serum milk protein soluble IgE(sIgE)and milk protein avoidance test,and those with positive results of children's milk protein by provocation test and those with milk serum protein sIgE negative by milk protein provocation tests were diagnosed as CMPA children with GERD according to the CMPA diagnostic criteria and received diet therapy for 1 month and then their blood eosinophil ratio and 24-hour esophageal pH were monitored.Results Twenty-three cases(46％)of 50 children with GERD were diagnosed as CMPA.There was significant difference in clinical symptoms between GERD group and GERD combined with CMPA group(x2=22.78,P0.05).For children with GERD combined with CMPA,the patients received dietary treatment for 1 month.There was significant improvement in vomiting,runny nose/wheezing/cough and diarrhea(P0.05).The proportions of blood eosinophils were decreased after treatment compared with those before treatment [(2.7±1.8)％vs.(8.2±2.7)％,t=10.006,P<0.01].The results of 5 children's 24-hour esophageal pH monitoring showed that the reflux index and the number of acid GERD episodes were lower than before,and the difference was all statistically significant before and after(all P<0.05).Conclusions The occurrence of GERD in infants is partly related to CMPA,and the treatment of CMPA can relieve the clinical symptoms of GERD.

The clinical, endoscopic and pathologic characteristics of eosinophilic gastroenteritis of 24 cases infants resulted from milk protein allergy / 中国内镜杂志

Objective By studying clinical features, treatment and prognosis of eosinophilic gastroenteritis of infants resulted from milk protein allergy an, to improve the diagnosis and treatment level of eosinophilic gastroenteritis. Methods 24 cases of infants which diagnosed eosinophilic gastroenteritis were chosen from June of 2010 to January of 2014 in children’s Hospital of XX province and By retrospective analysis clinical manifestations, endoscopic features, histopathology, treatment and prognosis of the 24 cases. Results The 24 cases who were vomiting, paroxysmal crying, abdominal distension (100.00%), which accompanied by haematemesis 23 cases (95.83%), 1case (4.17%) hematochezia, 17cases (70.83%) eczema, 21 cases (87.50%) mild to moderate anemia, 1 cases (4.17%) severe anemia, 19 cases (79.17%) the increasing of peripheral blood eosinophil cells, 8 cases (33.33%)the increasing of IgE of the serum and 4 cases (16.67%) the test of antibody of the Helicobacter pylori in Serum was positive; 3 cases (12.50%) were milk protein allergy by the detecting of food allergen-speciifc IgE antibodies, the endoscopic characteristics were hyperemia, edema, erosion, ulcer of gastric and duodenal mucosa. Among them, 24 cases (100.00%) were gastritis, 5 cases (20.83%) duodenitis and 1 cases (4.17%) duodenal ulcer. The histopathology of the 24 cases revealed that there were gastric or duodenal eosinophils infiltration (> 20/HPF) and were all associated with mast cell infiltration; By antisecretory, protection of the gastrointestinal mucosa and the obviating of milk protein had a satisfactory treatment effect, 24 cases of children with oral general formula milk test conifrmed that the milk protein allergy, The 3 cases of the patients were reviewed by 8~12 weeks after gastroscope, and the mucosa of the duodenum was smooth, Eosinophils were/HPF<8, mast cells were/HPF<5. Conclusion There are no speciifc clinical and endoscopic manifestations in eosinophilic gastroenteritis of infants resulted from milk protein allergy, gastrointestinal mucosa eosinophil inifltration and simultaneously are accompanied by abnormal mast cell inifltration;Mucosal type without the use of corticosteroids, through milk protein avoidance treatment can achieve satisfactory results, But definite diagnosis must rely on biopsy and eosinophils, combined with avoidance stimulation test of milk protein can further confirmed, But the excitation test should be at least 10 days of observation of children, and carefully recorded symptoms, so as not to delay the missed diagnosis of CMPA.

Pooled Analysis of the Cow's Milk-related-Symptom-Score (CoMiSS™) as a Predictor for Cow's Milk Related Symptoms / 대한소아소화기영양학회지

PURPOSE: The diagnosis of cow's milk (CM) allergy is a challenge. The Cow's Milk-related-Symptom-Score (CoMiSS™) was developed to offer primary health care providers a reliable diagnostic tool for CM related symptoms. The predictive prospective value of the CoMiSS™ was evaluated in three clinical trials. METHODS: Pooled analyses of the three studies were conducted based on regressing the results of the month-1 challenge test on the month-1 CoMiSS™, adjusting for baseline CoMiSS™ using a logistic regression model. In addition a logistic regression model was also fitted to the month-1 challenge test result with the change in CoMiSS™ from baseline as a predictor. RESULTS: Results suggest that infants having a low CoMiSS™ (median, 5) after 1 month dietary treatment free from intact CM protein have a significant risk of having a positive challenge test (odds ratio, 0.83; 95% confidence interval, 0.75-0.93; p=0.002). Pooled data suggest that the change in CoMiSS™ from baseline to month-1 can predict CM related symptoms as a confirmed diagnosis according to the challenge test at month-1. However, in order to validate such a tool, infants without CM related symptoms would also need to be enrolled in a validation trial. A concern is that it may not be ethical to expose healthy infants to a therapeutic formula and a challenge test. CONCLUSION: Pooled data analysis emphasizes that the CoMiSS™ has the potential to be of interest in infants suspected to have CM-related-symptoms. A prospective validation trial is needed.

The clinical characteristics and related factors of cow's milk protein allergy in infants less than 3 months old in Guangxi District / 中国小儿急救医学

Objective To study the clinical characteristics and risk factors of cow's milk protein allergy(CMPA)in infants less than 3 months old in Guangxi District.Methods From July 1 ,2012,to December 30,2014,infants less than 3 months old suspected of CMPA visiting the pediatric outpatient depart-ment of Maternal and Children Hospital of Guangxi Zhuang Autonomous Region were recruited,which included initial diagnosis and being transported from peripheral hospitals.Observation scale was formulated, attending physician screened patients and their senior made a definite diagnosis.All the infants underwent diagnostic algorithms and were followed up constantly.Results A total of 137 cases were divided into aller-gy group(n =51 )and control group(n =86).Two groups shared some common symptoms such as diarrhea, constipation,bloody stool,stomachache,gastroesophageal reflux(GER),indigestion,anorexia,feeding diffi-culties.Between the allergy group and control group the parameters such as feeding patterns (including breast feeding,mix feeding,formula feeding),improper deeding of food supplement,long-term use of antibiotics in neonatal period and parental atopy showed no significant differences(P ﹥0.05).The parameters in neonatal period including GER [20 cases (39.2%)vs.7 cases (8.1 %)],intake of cow's milk formula [51 cases (100%)vs.71 cases (82.6%)],feeding intolerance (including GER)[17 cases (33.3%)vs.1 1 cases (12.8%)],gut infection[8 cases(15.7%)vs.4 cases(4.7%)],transfusion of blood or/and bloody prod-ucts[12 cases(23.5%)vs.1 1 cases(12.8%)]showed statistically significant differences between the aller-gy group and control group(χ2 =19.538,P =0.000;χ2 =9.989,P =0.002;χ2 =8.308,P =0.004;χ2 =4.691 ,P =0.030;χ2 =5.198,P =0.023 ).Conclusion Symptoms of CMPA in infants no more than 3 months old involve mainly digestive system such as diarrhea,bloody stool,GER.Intake of cow milk formula in neonatal period play an important role in triggering CMPA.

Diagnostic and therapeutic value of open food challenge in children of cow′s milk protein allergy / 中国免疫学杂志

Objective:To study the diagnostic and therapeutic value of open food challenge in children with cow ′s milk protein allergy.Methods:It is a retrospective analysis of 55 children with suspected cow′s milk protein allergy ( CMPA ) who attended the clinic of the pediatric gastroenterology department ,the First Hospital of Jilin University from March 2014 to March 2015.These children were fed by a mino acid based formulae ( AAF) for 2-4 weeks and then open food challenge ( OFC) test was performed.Those children who tested positive , were diagnosed as having CMPA.They were then fed with AAF for further 3 months and OFC was performed again.Then discusse the diagnostic and therapeutic value of open food challenge in children with cow ′s milk protein allergy.Results:Out of 55 CMPA suspected children ,52 tested positive with OFC yielding a positive rate of 94.55%.These 52 children were fed with AAF for further 3 months and then tested with OFC ,9 children tested positive yielding a positive rate of 17.30%.These 9 children were again fed with AAF for 3 months and then tested with OFC.This time 2 children tested positive yielding a positive rate of 3.85%.Con-clusion:Open food challenge teats are of great significance in the diagnosis of CMPA ,and evaluation of tolerance to cow′s milk protein ( CMP).

Neonatal Cow’s Milk Protein Allergy with Sepsis Like Initial Symptom / 天津医药

Objective To summarize the diagnosis and treatment in neonatal cow’s milk protein allergy (CMPA) with sepsis like initial symptom. Methods CMPA patients with the sepsis like initial symptom (n=10) were selected in our hospital from July 2009 to December 2013. History data, clinical manifestation, laboratory results and the treatment outcome of them were retrospectively analyzed. Results Among these 10 cases, 6 have family history of allergy. Main clinical mani-festations include skin, gastrointestinal symptoms and 1 case of anaphylactic shock. IgE mediated 6 cases with acidophilic cells count of (1.40±0.17)×109/L (5%); The rest 4 cases were not mediated by IgE, with acidophilic cells count of (0.71± 0.08)×109/L (0.02-0.03). Blood cultures were all negative;Blood leukocyte count is (24.5±3.3)×109/L;Rod nucleus granulo-cyte/neutrophils count is (0.161±0.035) ×109/L;The platelet count is (655±39)×109/L;Blood interleukin (IL)-6 is 0.31-0.93μg/L;C reactive protein (CRP) is 85-144 mg/L. All 10 cases were with extensively hydrolyzed formular or amino acid formu-lar feeding. Then their clinical symptoms improved or disappeared significantly and the inflammatory indexes returned to nor-mal. Conclusion It is necessary to make the differential diagnosis between sepsis and neonatal CMPA,which is accompa-nied by increased platelet and acidophil. The most effective treatment of neonatal CMPA is hypoallergenic formular replace-ment therapy.

Food protein-induced enterocolitis syndrome caused by cow's milk protein allergy in an infant：case report and review of literature / 临床儿科杂志

To discuss clinical diagnosis and treatment of cow’s milk protein allergy and cow’s milk protein-induced FPIES (food protein induced enterocolitis syndrome). Methods We retrospectively analyzed clinical data of one infant with milk protein allergy-induced FPIES. Results A 67 days old female on mixed breast and formula feeding developed recurrent diarrhea, abdominal distension, vomiting, mucousy and bloody stools, feeding dififculty, anemia, and failure to thrive since 2 weeks after birth. Laboratory studies showed anemia, increased CRP level and elevation of peripheral white blood count and eosinophil proportion. Milk-speciifc IgE was negative. She was previously hospitalized 4 times, all with admitting diagnosis of“necrotizing enterocolitis”. We treated her with milk protein elimination for 4 weeks and all symptoms were resolved. Milk protein re-challenge test was positive, consistent with clinical features of cow’s milk protein allergy-induced infant FPIES. Conclusions Cow’s milk protein allergy and cow’s milk protein-induced FPIES can present with non-speciifc and variable clinical symptoms and signs, and should be considered in the differential diagnosis.