Alergia a la leche de vaca: ¿se pueden evitar las pruebas de provocación oral? Un análisis probabilístico basado en datos clínicos / Cow's milk allergy: Can oral food challenges be avoided? A probabilistic analysis based on clinical data

Introducción. La prueba de provocación oral (PPO) para el diagnóstico de alergia a las proteínas de la leche de la vaca (APLV) presenta riesgos y requiere de recursos. Nuestro objetivo fue evaluar condiciones y pruebas complementarias para identificar una alta probabilidad de APLV. Población y métodos. Análisis secundario sobre estudio de pacientes atendidos en una unidad de alergia entre 2015 y 2018. Se determinaron las probabilidades prepruebas asociadas a los síntomas y sus combinaciones, y las probabilidades pospruebas luego de realizadas pruebas cutáneas y determinación de inmunoglobulina E (IgE) sérica. Resultados. Se evaluó la información de 239 pacientes. Se observaron probabilidades mayores al 95 % en pacientes con angioedema y combinación de urticaria y vómitos. Usando puntos de corte propuestos por Calvani et al., la combinación de vómitos con rinitis, sin angioedema, también superó el 95 %. Conclusión. Se ofrece una metodología para identificar pacientes en los que puede diagnosticarse APLV sin realización de PPO.

Introduction. The oral food challenge (OFC) for the diagnosis of cow's milk protein allergy (CMPA) poses risks and requires resources. Our objective was to assess conditions and complementary tests used to identify a high probability of CMPA. Population and methods. Secondary analysis of a study of patients seen at a unit of allergy between 2015 and 2018. Pre-testing probabilities associated with symptoms and their combinations and post-testing probabilities after skin prick testing and serum immunoglobulin E (IgE) levels were determined. Results. The data from 239 patients were assessed. A probability greater than 95% was observed for angioedema and a combination of urticaria and vomiting. Based on the cut-off points proposed by Calvani et al., the combination of vomiting with rhinitis, without angioedema, also exceeded 95%. Conclusion. A methodology is provided to identify patients in whom CMPA may be diagnosed without an OFC.

Very early onset perinatal constipation: Can it be cow's milk protein allergy?

Delayed passage of meconium or constipation during the perinatal period is traditionally regarded as a signal to initiate further work up to evaluate for serious diagnoses such as Hirschsprung's disease (HD), meconium ileus due to Cystic Fibrosis, etc. The diagnosis of HD particularly warrants invasive testing to confirm the diagnosis, such as anorectal manometry or rectal suction biopsy. What if there was another etiology of perinatal constipation, that is far lesser known? Cow's milk protein allergy (CMPA) is often diagnosed in infants within the first few weeks of life, however, there are studies that show that the CMPA allergen can be passed from mother to an infant in-utero, therefore allowing symptoms to show as early as day one of life. The presentation is more atypical, with perinatal constipation rather than with bloody stools, diarrhea, and vomiting. The diagnosis and management would be avoidance of cow's milk protein within the diet, with results and symptom improvement in patients immediately. Therefore, we discuss whether an alternative pathway to address perinatal constipation should be further discussed and implemented to potentially avoid invasive techniques in patients. This entails first ruling out CMPA with safe, noninvasive techniques with diet modification, and if unsuccessful, then moving forward with further diagnostic modalities.

Case report: Pneumatosis in a neonate with thrombocytopenia absent radius syndrome.

BACKGROUND: Thrombocytopenia absent radius (TAR) syndrome is a rare disease with an estimated prevalence of one in 200,000 live births. TAR is associated with cardiac and renal anomalies as well as gastrointestinal problems such as cow's milk protein allergy (CMPA). Typically neonates with CMPA present with mild intolerance, with few reports in the literature of more severe intolerance resulting in pneumatosis. We present a case of a male infant with TAR syndrome who developed gastric and colonic pneumatosis intestinalis. CASE DESCRIPTION: An eight-day-old male infant born at 36 weeks gestation with a diagnosis of TAR, presented with bright red blood in his stool. At this time he was on full formula feeds. Given continued bright red blood within his stool, an abdominal radiograph was obtained which was consistent with colonic and gastric pneumatosis. A complete blood count (CBC) was notable for worsening thrombocytopenia, anemia and eosinophilia. Once enteral feeds were held there was rapid resolution of the radiographic findings and resolution of his bloody stool. He was ultimately diagnosed with a CMPA. CONCLUSION: Though there are reports of CMPA in patients with TAR, the severity of this patient's presentation with both colonic and gastric pneumatosis is unique. Without the knowledge of the association of CMPA with TAR, this case could have been misdiagnosed and led to reintroduction of cow's milk containing formula, resulting in further complications. This case highlights the importance of a timely diagnosis and severity of CMPA in this population.

The long-term clinical course of protein-losing enteropathy combined with iron deficiency anemia in Korean toddlers: Possible association with cow's milk protein.

BACKGROUND: Protein-losing enteropathy (PLE), a rare condition with excessive gastrointestinal protein loss, presents with hypoalbuminemia, edema, or ascites. Several cases of PLE combined with severe iron deficiency anemia (IDA) have been reported in infants and toddlers that were considered to result from excessive cow's milk consumption, although the mechanism has not been clearly established. METHODS: We retrospectively reviewed the clinical, laboratory, endoscopic, and radiologic characteristics of patients diagnosed and treated for PLE with IDA between 2015 and 2021. Long-term outcomes were analyzed according to dietary intervention during the follow-up period. RESULTS: A total of 10 patients aged 7.0-26.7 months were enrolled in the study and the median follow-up duration of them was 9.4 months (range, 1.3-18.0). Six of them were fed powdered formula, while two were fed whole cow's milk, and their median daily intake was 700 mL (range, 300-900). The times to normalization of hemoglobin, albumin, and eosinophil count were shorter in patients with dietary elimination of cow's milk protein immediately after diagnosis compared to those with reduced intake or no dietary change. CONCLUSION: Early complete elimination of cow's milk protein should be considered, especially if the laboratory parameters are not normalized with adequate iron supplementation even though the clinical symptoms show improvement. We would like to draw attention to the possibility of the cow's milk protein in the pathogenesis of the condition through the non-IgE-mediated immune reactions.

Utilidad de las pruebas analíticas en el diagnóstico de alergia a las proteínas de la leche de vaca / Usefulness of analytic tests for the diagnosis of cow's milk protein allergy

Introducción. La alergia a las proteínas de la leche de vaca es la alergia alimentaria más frecuente en los niños y para su diagnóstico se emplean historia clínica dirigida y prueba de provocación oral (PPO), el dosaje sérico de inmunoglobulina E específica (sIgE) y pruebas cutáneas de puntura (SPT, por su sigla en inglés). Sin embargo, su utilidad diagnóstica es difícil de establecer en la población local. El objetivo fue evaluar la utilidad de las pruebas para el diagnóstico de alergia a las proteínas de la leche de vaca (PLV) en la población estudiada. Población y métodos. Análisis retrospectivo de datos de pacientes atendidos en la Unidad de Alergia del Hospital Elizalde entre 2015 y 2018. Se evaluaron SPT y sIgE para leche, alfa-lactoalbúmina, beta-lactoglobulina y caseína, seguidos de PPO y se determinó la utilidad diagnóstica para cada prueba, y sus combinaciones. Resultados. Se evaluaron las pruebas de 239 pacientes. La PPO fue hospitalaria en el 54,8 % de los casos, por reexposición domiciliara en el 35,5 % y en el 9,6 % por incorporación de PLV a la madre. La mayor especificidad fue la de SPT con caseína (96,7 %; intervalo de confianza [IC95%]: 90,8-99,3) y la mayor sensibilidad, la de la combinación de SPT y sIgE con los 4 alérgenos (55,3 %; IC95%: 45,7-64,6). Conclusiones. El trabajo estableció la utilidad diagnóstica de las SPT y el sIgE en la población estudiada.

Introduction. Cow's milk protein allergy is the most common food allergy among children. It can be diagnosed based on a guided history taking and using an oral food challenge (OFC), serum specific immunoglobulin E levels (sIgE), and skin prick tests (SPT). However, it is difficult to establish their diagnostic performance in the local population. Our objective was to assess the usefulness of tests used to diagnose cow's milk protein (CMP) allergy in the studied population. Population and methods. Retrospective analysis of data from patients seen at the Unit of Allergy of a tertiary care pediatric hospital between 2015 and 2018. SPT and sIgE tests were done for milk, alpha-lactalbumin, beta-lactoglobulin, and casein, followed by an OFC, and the diagnostic usefulness of each test, as well as their combination, was established. Results. The tests of 239 patients were assessed. OFC was performed at the hospital in 54.8 % of cases, via a rechallenge test at home in 35.5 %, and through CMP intake by the mother in 9.6 %. The highest specificity was observed with the casein SPT (96.7 %; 95 % confidence interval [CI]: 90.8-99.3) and the highest sensitivity, with the 4-allergen SPT and sIgE combination (55.3 %; 95 % CI: 45.7-64.6). Conclusions. The study established the diagnostic usefulness of SPT and sIgE in the studied population.

Single-dose oral challenges to validate eliciting doses in children with cow's milk allergy.

BACKGROUND: There is increasing interest in the use of eliciting doses (EDs) to inform allergen risk management. The ED can be estimated from the distribution of threshold doses for allergic subjects undergoing food challenges within a specified population. Estimated ED05 values for cow's milk (the dose expected to cause objective allergic symptoms in 5% of the milk-allergic population) range from 0.5 mg to 13.9 mg cow's milk protein. We undertook a single-dose challenge study to validate a predicted ED05 for cow's milk of 0.5 mg protein. METHODS: Participants were recruited from 4 clinical centres. Predetermined criteria were used to identify patients reacting to 0.5 mg cow's milk protein (approximately 0.015 mL of fresh cow's milk). Children over 1 year underwent formal challenge to cow's milk to confirm clinical reactivity. RESULTS: 172 children (median age 6.0 (IQR 0.7-11) years, 57% male) were included in this analysis. Twelve (7.0%, 95% CI 3.7%-11.9%) children experienced objective symptoms that met the predetermined criteria. One participant had mild anaphylaxis that responded to a single dose of adrenaline, the remainder experienced only mild symptoms with no treatment required. We did not identify any baseline predictors of sensitization that were associated with objective reactivity to the single-dose challenge using 0.5 mg cow's milk protein. CONCLUSIONS: These data support an estimated ED05 for cow's milk of 0.5 mg protein. Values for ED05 above 0.5 mg for cow's milk protein proposed for allergen risk management need to be reviewed.

DL-propargylglycine administration inhibits TET2 and FOXP3 expression and alleviates symptoms of neonatal Cows' milk allergy in mouse model.

BACKGROUND: Cows' milk allergy (CMA) is a hypersensitivity immune reaction brought on by specific immunologic mechanisms to cow's milk proteins. As one of the most common food allergies in infants, the incidence of CMA during the first year of life is estimated to be nearly 7.5%. Due to the limitation in the knowledge of the pathological mechanism underlying CMA, however, the clinical interventions and therapies remain very unsatisfactory. AIM OF THE STUDY: The transcriptional factor FOXP3 possesses crucial roles in CMA, and increased FOXP3 mRNA expression has a predictive function in faster acquisition of tolerance in infants with CMA. But the exact mechanism remains not fully elucidated. METHODS: For PAG treatment, PAG (dissolved in saline 30 mg/mL, 0, 5, 10, 20 mg/kg BW) was administered daily intraperitoneally (ip) for one week at the time that 6 weeks after the CMP sensitisation. RESULTS: In the present study, we revealed that the expression of FOXP3 is significantly up-regulated in PBMCs from CMA patients and CMA mice on mRNA and protein level. Furthermore, a dramatic reduction in the FOXP3 TSDR methylation and a significant increase in the expression of TET2 are observed in CMA patients and CMA mice. More importantly, we found that propargylglycine (PAG) significantly alleviates symptoms of CMA in mice by suppressing the expression of FOXP3 through restoring TET2 expression. CONCLUSIONS: Our work revealed a novel function of PAG on CMA, which may provide a deeper insight into the pathomechanism of CMA and a novel therapy target for CMA clinical interventions.

Guidelines on Diagnosis and Management of Cow's Milk Protein Allergy.

JUSTIFICATION: Cow's milk protein allergy (CMPA) is increasingly being diagnosed in the West, while there is scant data on the subject from India. There is low awareness among pediatricians about its diagnosis and management; leading to improper diagnosis. PROCESS: A group of experts from the pediatric gastroenterology sub-specialty chapter of Indian Academy of Pediatrics (Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition) met at Mumbai on 26 October, 2018 and discussed various issues relating to the subject. A broad consensus was reached and a writing committee was formed. They met again on 11 August, 2019 at Chennai for a detailed discussion. The statement was sent to the entire group by e-mail and their approval obtained. OBJECTIVE: To formulate a consensus statement enable proper diagnosis and management of Cow's milk protein allergy. RECOMMENDATIONS: Cow's milk protein allergy is most common in the first year of life. Gastrointestinal manifestations are usually non-IgE mediated and therefore skin prick test and specific IgE levels are not useful in diagnosis. Clinical response to elimination diet followed by a positive oral food challenge is diagnostic. In patients with only gastrointestinal manifestations, sigmoidoscopy and rectal biopsy may be considered as an alternative. Management involves strict avoidance of all forms of bovine milk protein. For infants who are artificially fed, an extensively hydrolyzed formula is the first choice. Soy formula is an alternative in those above six months of age. Since most infants outgrow the allergy, elimination diet is only for a limited period and re-evaluation should be done periodically.

A novel electrochemical mast cell-based paper biosensor for the rapid detection of milk allergen casein.

Developing low-cost, portable and simple analysis tools is of vital importance for food safety point-of-care testing. Therefore, herein, a new low-cost, simple to fabricate, disposable, electrochemical mast cell-based paper sensor is proposed and developed to sensitively determine the major milk allergen casein. Then, a graphene (GN)/carbon nanofiber (CN)/ Gelatin methacryloyl (GelMA) composite material with high conductivity and good biocompatibility was modified on the cell-based paper sensor to improve the electrical conductivity and provide a sensing recognition interface for the immobilization of rat basophilic leukemia (RBL-2H3) mast cells. The cyclic voltammetry and differential pulse voltammetry measurement of the mast cells in the paper sensor revealed an irreversible anodic peak, whose peak current is proportional to the number of cells in the range from 1 × 102 to 1 × 108 cells/mL. For the milk allergen detection tests, mast cells exposed to the casein caused a significant reduction in the current signal, displaying an inverse dose-dependent relationship. The developed cell sensor exhibited a range of linearity between 1 × 10-7 and 1 × 10-6 g/mL of casein with a detection limit of 3.2 × 10-8 g/mL and a great reproducibility and selectivity. The electrochemical responses obtained using the cell-based paper sensor were well consistent with the conventional detection assay, with good stability and reproducibility. Therefore, a simple and novel electrochemical method for food allergens detection was developed, demonstrating its potential application in the food safety determination and evaluation.

A new Luminex-based peptide assay to identify reactivity to baked, fermented, and whole milk.

BACKGROUND: The majority of children with cow's milk allergy (CMA) tolerate baked milk. However, reactivity to fermented milk products such as yogurt/cheese has not been previously evaluated. We sought to determine whether children with CMA could tolerate yogurt/cheese and whether a patient's IgE and IgG4-binding pattern to milk protein epitopes could distinguish clinical reactivity. METHODS: Four groups of reactivity were identified by Oral food challenge: baked milk reactive, fermented milk reactive, whole milk reactive, and outgrown. sIgE and sIgG4 binding to milk protein epitopes were assessed with a novel Luminex-based peptide assay (LPA). Using machine learning techniques, a model was developed to predict different degrees of CMA. RESULTS: The baked milk reactive patients demonstrated the highest degree of IgE epitope binding, which was followed sequentially by fermented milk reactive, whole milk reactive, and outgrown. Data were randomly divided into two groups with 75% of the data utilized for model development (n = 68) and 25% for testing (n = 21). All 68 children used for training were correctly classified with models using IgE and IgG4 epitopes. The average cross-validation accuracy was much higher for models using IgE plus IgG4 epitopes by LPA (84.8%), twice the performance of the serum component proteins assayed by UniCAP (41.9%). The performance of the model on "unseen data" was tested using the 21 withheld patients, and the accuracy of IgE was 86% (AUC = 0.89) while of IgE+IgG4 model was 81% (AUC = 0.94). CONCLUSION: Using a novel high-throughput LPA, we were able to distinguish the diversity of IgE/IgG4 binding to epitopes in the varying CMA phenotypes. LPA is a promising tool to predict correctly different degrees of CMA.

Early Onset Allergic Proctitis in a Preterm Neonate-A Case Report and Review of the Literature.

Cow's milk protein allergy/intolerance (CMPA/CMPI) is a common entity in the pediatric population with a nonspecific presentation ranging from gastrointestinal symptoms to systemic manifestations. Most infants with CMPI are term, and symptoms often appear in the week following the introduction of cow's milk-based formula. There is typically a significant delay in the onset of milk allergy in premature infants compared to full term. We report a rare case of a premature neonate who presented with symptoms of CMPA within the first 2 days of life.

Risk prediction of severe reaction to oral challenge test of cow's milk.

Cow's milk is one of the most common food allergens among children. Oral food challenge tests determine the threshold dose of allergens, but have not been standardized. To reduce the severe reactions, we developed a practical model of the test. We studied 111 high-risk patients who underwent a first milk oral food challenge on the risk-stratified dose between 2011 and 2017 for predicting the severe reaction risk. Severe reactions were defined as showing > 3 of Sampson's classification grade. Twenty-eight patients (25%) showed severe reactions without death. Prior to oral food challenge, severe reaction patients experienced milk avoidance (71% vs. 45%, p = 0.02) or bronchial asthma (61% vs. 28%, p = 0.003) more frequently and showed higher milk-specific IgE levels (median 28.3 vs. 7.7 UA/mL, p < 0.0001) than non-severe reaction patients. Multivariate logistic regression analyses established a formula including severe reaction-associated factors; increased levels of milk-specific IgE (odds ratio 11.61, p = 0.001), milk avoidance (odds ratio 3.88, p = 0.02), and bronchial asthma (odds ratio 3.75, p = 0.02). This model had 86% sensitivity and 56% specificity (cut-off 0.25) for risk. Five patients with < 25% probability developed severe reactions, which started in > 3 grade dyspnea up to 20 mL of challenge.Conclusion: This model could effectively reduce the severe reaction development on the first milk oral food challenge test according to the individual needs. What is Known: •Higher levels of milk-specific IgE values, bronchial asthma, and complete milk avoidance are independent risk factors of severe reactions during the cow's milk oral food challenge. What is New: •Statistical analyses of our milk oral food challenge records for 111 patients helped us develop a model formula predicting severe reactions at the first test with high specificity and sensitivity. •This simple risk-stratified protocol is useful for minimizing the adverse events in the first milk challenge.

Positivity rates of in vitro inhalant/respiratory and food allergy tests in the northern midwestern United States.

Rates of allergy-test positivity vary by country and by regions within countries. Several studies have looked at allergy test results to determine the most common allergens. Many of these studies have been based on surveys or on studies of small numbers of tests. Positivity rates for allergy tests are poorly defined in the northern midwestern region of the United States. We conducted a study to identify the rates of positive allergy tests for both inhalant/respiratory allergens and food allergens in the upper Midwest. We extracted from our laboratory database the results of all test samples sent for one of eight allergen panels that had been analyzed between Sept. 1, 2014, and Sept. 1, 2015. All testing was performed at The Cleveland Clinic with the Phadia ImmunoCAP system. The percentage of positive tests, the distribution of the most frequently positive tests, and the class of in vitro responses were identified. A total of 148,628 test results for 63 different allergens were identified. Of the 125,190 tests for inhalant/respiratory allergens, the most frequently positive were dog dander (24% of tests), cat dander (23%), dust mites (23% for both Dermatophagoides pteronyssinus and Dermatophagoides farinae), and June grass (21%). Of the 23,438 food tests, the most frequently positive test results were for milk (18%), peanut (17%), wheat (16%), and egg white (15%). Most of the results fell into classes 1 through 3, although there was still a notable number of very high responses (class 5 and 6). These findings suggest that there is wide variability in the positivity of in vitro allergy tests and that the likelihood of a positive result in screening panels can be estimated. Evaluating such rates will help identify the most and least common allergens and will help to cost-effectively refine allergy screening panels.

Accuracy of serum IgE concentrations and papule diameter in the diagnosis of cow's milk allergy / Acurácia de concentrações de IgE séricas e de diâmetros de pápulas no diagnóstico de alergia ao leite de vaca

Abstract Objective To compare serum concentrations of specific IgE and mean papule diameters induced in the immediate skin reactivity test with cow's milk and its fractions with results of the oral challenge test, and to establish cutoff points capable of predicting clinical reactivity to cow's milk in patients treated at a referral service. Methods One hundred and twenty-two children (median of 17 months) with a history of immediate reactions to cow's milk and presence of specific IgE for cow's milk and/or its fractions (positive skin and/or IgE serum tests) were submitted to open oral challenge test with cow's milk. Results The oral challenge test was positive in 59.8% of the children, 49% of whom were males. Serum levels of specific IgE, as well as mean cow's milk papule diameters, were significantly higher in allergic patients (medians: 3.39 kUA/L vs. 1.16 kUA/L, 2.5 mm vs. 0 mm). The optimal cutoff points (Youden's index) of serum IgE specific for cow's milk and its fractions capable of predicting cow's milk reactivity (positive oral challenge test) were: 5.17 kUA/L for cow's milk, 0.95 kUA/L for α-lactalbumin, 0.82 kUA/L for β-lactoglobulin, and 0.72 kUA/L for casein, whereas for papule diameters the cutoff points were 3.5 mm for cow's milk and 6.5 mm, 9.0 mm, and 3.0 mm for the α-lactalbumin, β-lactoglobulin, and casein fractions, respectively. Conclusions The cutoff points capable of predicting clinical reactivity to cow's milk were: 5.17 kUA/L for serum-specific IgE and 3.5 mm for papule diameter measurement, values considered discriminatory for the diagnosis of cow's milk allergy.

Resumo Objetivo Comparar concentrações séricas de IgE específica e diâmetros médios das pápulas induzidas no teste cutâneo de leitura imediata com leite de vaca e suas frações com resultados do teste de provocação oral e estabelecer pontos de corte, capazes de predizer reatividade clínica ao leite de vaca em pacientes atendidos em um serviço de referência. Métodos Cento e vinte e duas crianças (mediana 17 meses), com história de reações imediatas ao leite de vaca e presença de IgE específicas para leite de vaca e/ou frações (testes cutâneos e/ou IgE sérica positivos) foram submetidas ao teste de provocação oral aberto com leite de vaca. Resultados O teste de provocação oral foi positivo em 59,8% das crianças, 49% eram do sexo masculino. Os níveis séricos de IgE específica, assim como os diâmetros médios das pápulas para leite de vaca, foram significantemente maiores nos alérgicos (medianas: 3,39kUA/L vs. 1,16 kUA/L; 2,5 mm vs. 0 mm). Os "pontos de corte ótimos" (Índice de Youden) das IgE séricas específicas para o leite de vaca e suas frações capazes de predizer a reatividade ao leite de vaca (teste de provocação oral positivo) foram: 5,17kUA/L para o leite de vaca, 0,95 kUA/L para α-lactoalbumina, 0,82kUA/L para β-lactoglobulina e 0,72kUA/L para caseína e para os diâmetros de pápulas foram 3,5 mm para leite de vaca e 6,5 mm, 9,0 mm e 3,0 mm para as frações α-lactoalbumina, β-lactoglobulina e caseína, respectivamente. Conclusões Os níveis de corte capazes de predizer reatividade clínica ao leite de vaca foram: 5,17kUA/L para IgE sérica específica e 3,5 mm para a medida do diâmetro da pápula, valores considerados discriminatórios para o diagnóstico da alergia ao leite de vaca.

Actualización en manejo de alergia a la proteína de leche de vaca: fórmulas lácteas disponibles y otros brebajes / Update on management of cow's milk protein allergy: available milk formulas and other juices

La alergia a la proteína de leche de vaca (APLV) es una enfermedad frecuente, con una prevalencia entre 2-7%, cifras que van en aumento. Se caracteriza por una reacción alérgica a una o más pro teínas de la leche de vaca. No existen manifestaciones clínicas patognomónicas, y éstas dependerán del tipo de reacción inmunológica involucrada. Una buena aproximación diagnóstica evita el sub y sobre diagnóstico y por lo tanto, sub y sobre tratamiento. El tratamiento de la APLV es la eliminación de la proteína de leche de vaca de la dieta. Una dieta de restricción en un niño que no la requiere o que ha desarrollado tolerancia, puede alterar el crecimiento, la calidad de vida y producir costos innecesarios. El objetivo de esta actualización es presentar las diferentes fórmulas y brebajes usados en Chile para tratar la APLV en aquellos casos en que no sea posible la lactancia materna con dieta de exclusión. Para ello se revisó la composición nutricional, ingredientes y otras características relevan tes de todas aquellas fórmulas o brebajes que se comercializan en Chile como tratamiento de APLV. La información se obtuvo desde los distribuidores o vendedores oficiales, o en su defecto, desde las páginas web oficiales. Se puede concluir que existen y se usan múltiples fórmulas y brebajes para el tratamiento de APLV, no todas ellas del todo adecuadas desde el punto de vista nutricional y de seguridad. Conocerlas en detalle ayudará al pediatra a indicarlas de manera más informada de acuerdo a sus beneficios y sus carencias para el manejo adecuado de esta patología.

Cow's milk protein allergy (CMPA) is a common disease with a prevalence of 2-7%, increasingly so. It is characterized by an allergic reaction to one or more cow's milk proteins. There are not pathog nomonic clinical symptoms, and these will depend on the type of immune reaction involved. A good diagnostic approach avoids under and over diagnosis and, therefore, under and over treatment. The CMPA treatment is the elimination of cow's milk protein from the diet. A restricted diet in a child does not require it or who has developed tolerance can alter growth, quality of life, including unne cessary costs. The objective of this review is to present the different milk formulas available in Chile to treat CMPA in those cases where breastfeeding with exclusion diet is not possible. For this purpose, nutritional composition, ingredients and other relevant characteristics of all the milk formulas and juices marketed in Chile as CMPA treatment were reviewed. The information was obtained from the official distributors or sellers or failing that, from the official websites. There are multiple milk formulas and beverages used for the treatment of CMPA, and not all of them are nutritionally or immunologically secure. Knowing them in detail will help the pediatrician to indicate them in a more informed way according to their benefits and their deficiencies for the proper management of this pathology.

Celiac Disease and Other Causes of Duodenitis.

CONTEXT: - Patients who receive an upper gastrointestinal endoscopic examination frequently have biopsies taken from the duodenum. Accurate interpretation of duodenal biopsies is essential for patient care. Celiac disease is a common clinical concern, but pathologists need to be aware of other conditions of the duodenum that mimic celiac disease. OBJECTIVE: - To review the normal histologic features of duodenal mucosa and describe the clinical and histologic findings in celiac disease and its mimics, listing the differentiating features of biopsies with villous atrophy and epithelial lymphocytosis. DATA SOURCES: - The study comprises a literature review of pertinent publications as of November 30, 2016. CONCLUSIONS: - Celiac disease is a common cause of abnormal duodenal histology. However, many of the histologic features found in the duodenal biopsy of patients with celiac disease are also present in other conditions that affect the small bowel. Diagnostic precision may be enhanced by obtaining a careful patient history and by ancillary laboratory testing, particularly for the presence of antitissue transglutaminase antibodies.

The prevalence and characteristics of cow's milk protein allergy in infants and young children with iron deficiency anemia.

BACKGROUND: The clinical presentation of cow's milk protein allergy (CMPA) in children varies. This retrospective study aimed to investigate the prevalence and clinical manifestations of CMPA in young children who visited for evaluation of iron deficiency anemia (IDA). METHODS: Patients aged <4 years who were diagnosed as having IDA (serum ferritin <12 ng/mL) at the National Cheng Kung University Hospital, Taiwan in the period 2005-2015 were reviewed. Their clinical presentations, laboratory data, endoscopy findings, and prognosis were analyzed. RESULTS: Seven of 51 IDA patients (13.7%) had CMPA. The pallor (100%), failure to thrive (43%), and general edema (43%) were the common features. Six (86%) had hypoalbuminemia and four (57%) had positive occult blood in the stool. Of the five patients who underwent skin prick test, four (80%) had positive results. Most of the colonoscopies revealed erosive and hemorrhagic colitis and lymphoid hyperplasia, but none of the biopsies demonstrated eosinophilia in the lamina propria. All of the patients recovered from their IDA within seven months of cow's milk protein elimination and iron supplementation. CONCLUSION: CMPA should be considered in young children with undetermined IDA. Cow's milk protein elimination and iron supplementation help in the recovery.

Avoidance of Cow's Milk-Based Formula for At-Risk Infants Does Not Reduce Development of Celiac Disease: A Randomized Controlled Trial.

BACKGROUND & AIMS: Feeding during the first months of life might affect risk for celiac disease. Individuals with celiac disease or type 1 diabetes have been reported to have high titers of antibodies against cow's milk proteins. Avoidance of cow's milk-based formula for infants with genetic susceptibility for type 1 diabetes reduced the cumulative incidence of diabetes-associated autoantibodies. We performed a randomized controlled trial in the same population to study whether weaning to an extensively hydrolyzed formula reduced the risk of celiac disease autoimmunity or celiac disease. METHODS: We performed a double-blind controlled trial of 230 infants with HLA-defined predisposition to type 1 diabetes and at least 1 family member with type 1 diabetes. The infants were randomly assigned to groups fed a casein hydrolysate formula (n = 113) or a conventional formula (control, n = 117) whenever breast milk was not available during the first 6-8 months of life. Serum samples were collected over a median time period of 10 years and analyzed for antibodies to tissue transglutaminase (anti-TG2A) using a radiobinding assay, to endomysium using an immunofluorescence assay, and antibodies to a deamidated gliadine peptide using an immunofluorometry assay. Duodenal biopsies were collected if levels of anti-TG2A exceeded 20 relative units. Cow's milk antibodies were measured during the first 2 years of life. RESULTS: Of the 189 participants analyzed for anti-TG2A, 25 (13.2%) tested positive. Of the 230 study participants observed, 10 (4.3%) were diagnosed with celiac disease. We did not find any significant differences at the cumulative incidence of anti-TG2A positivity (hazard ratio, 1.14; 95% confidence interval, 0.51-2.54) or celiac disease (hazard ratio, 4.13; 95% confidence interval, 0.81-21.02) between the casein hydrolysate and cow's milk groups. Children who developed celiac disease had increased titers of cow's milk antibodies before the appearance of anti-TG2A or celiac disease. CONCLUSIONS: In a randomized controlled trial of 230 infants with genetic risk factors for celiac disease, we did not find evidence that weaning to a diet of extensively hydrolyzed formula compared with cow's milk-based formula would decrease the risk for celiac disease later in life. Increased titers of cow's milk antibody before anti-TG2A and celiac disease indicates that subjects with celiac disease might have increased intestinal permeability in early life. ClinicalTrials.gov Number: NCT00570102.