Tratamiento de la alergia a la proteína de la leche de vaca. Consenso interdisciplinario de expertos / Cow's milk allergy treatment. An expert consensus

El tratamiento de la alergia a las proteínas de la leche de vaca se basa en la eliminación completa de las proteínas de leche de vaca de la dieta del niño y de la madre en los que reciben leche materna. Para lograr la remisión de los síntomas y la tolerancia futura, la exclusión debe ser total. En los niños que reciben fórmula, esta deberá tener hidrolizado extenso de proteínas en las formas leves o moderadas, mientras que aquellas a base de aminoácidos se reservan para los casos más graves. El tiempo de tratamiento, la adquisición de tolerancia y el momento para la prueba de provocación oral van a variar según el cuadro clínico, el mecanismo inmunológico implicado y la edad del paciente. El objetivo de este consenso ha sido reflejar el conocimiento actualizado junto con la experiencia de neonatólogos, pediatras, especialistas en alergia, nutrición y gastroenterología.

The treatment of cow's milk protein allergy is based on the complete elimination of cow's milk protein from the diet. To achieve remission of symptoms and future tolerance, exclusion must be total. In formula fed infants the extensively hydrolysed formula is the most appropriate option in mild or moderate forms, while those based on amino acids are reserved for the most severe cases. The treatment time, the acquisition of tolerance and the moment for the oral provocation test will vary according to the clinical picture, the immunological mechanism involved and the age of the patient. The aim of this consensus has been to reflect the updated knowledge together with the experience of neonatologists, pediatricians, experts in allergy, nutrition and gastroenterology

Alergia a las proteínas de la leche de vaca: proceso diagnóstico. Consenso interdisciplinario de expertos / Cow's milk allergy: diagnostic process. Expert consensus

Las proteínas de la leche de vaca pueden causar alergia alimentaria. Los distintos mecanismos de acción involucrados y la variabilidad clínica según la etapa de la vida pediátrica en la que se manifieste ocasionan dificultades en su abordaje, con riesgo de sub- o sobrediagnóstico. En este proceso, intervienen profesionales de diversas áreas y es recomendable su interacción. Es por ello que el objetivo de este consenso ha sido reflejar el conocimiento actualizado desde la interdisciplina, generando recomendaciones para su correcto diagnóstico. Hemos trabajado con el método de Delphi para sumarle a la evidencia científica, la experiencia proveniente de neonatólogos, pediatras, especialistas en alergia, nutrición y gastroenterología. Pensamos que este enfoque interdisciplinario de trabajo va a resultar de utilidad práctica y promoverá una atención más integral de estos pacientes.

Cow's milk protein can cause food allergy. The different mechanisms of action involved, the clinical variability depending on the stage of pediatric life in which it manifests, leads to difficulties in its approach, with the risk of under- or over-diagnosis. Professionals from various areas intervene in this process and their interaction is recommended. That is why the objective of this consensus has been to reflect the updated knowledge in an interdisciplinary mode, generating recommendations for its correct diagnosis. We have worked with the Delphi method to add to the scientific evidence, the experience from neonatologists, pediatricians, experts in allergy, nutrition and gastroenterology. We think that this interdisciplinary approach will be of practical use and will promote more comprehensive care for these patients.

Inmunomodulación con bióticos y alergia alimentaria en pediatría / Immunomodulation properties of biotics and food allergy in pediatrics

El parto prematuro, la cesárea, el uso de antibióticos y la lactancia materna limitada son señalados como responsables en parte del aumento de enfermedades crónicas no transmisibles en niños, como las alergias, principalmente la alergia a la proteína de la leche de vaca (APLV). Quienes desarrollan enfermedades alérgicas muestran diferencias en la composición de su microbiota intestinal durante los primeros meses de vida, en comparación con los que no lo hacen. Las intervenciones tempranas para modular la microbiota intestinal y el sistema inmunológico pueden ser herramientas claves para el abordaje y tratamiento de la APLV. El criterio clínico y el trabajo interdisciplinario de alergólogos, gastroenterólogos, inmunólogos, microbiólogos y nutricionistas le permitirá al pediatra lograr un adecuado diagnóstico y un tratamiento oportuno. En este contexto, el empleo de bióticos (prebióticos, probióticos, sinbióticos y posbióticos) como herramientas nutricionales complementarias tiene un presente con sustento científico y un futuro promisorio para la prevención y tratamiento de estas patologías.

Preterm birth, C-section, antibiotic use, and limited breastfeeding are blamed in part for the increasing incidence of chronic noncommunicable diseases among children, such as allergies, mainly cow's milk protein allergy (CMPA). Those who develop allergic diseases, against those who do not, show differences in the composition of their gut microbiota during the first months of life. Early interventions to modulate the intestinal microbiota and the immune system may be the key tools for the management of CMPA. Clinical judgment and the interdisciplinary work of allergists, gastroenterologists, immunologists, microbiologists, and nutritionists will allow pediatricians to achieve an adequate diagnosis and a timely treatment. In this setting, the use of biotics (prebiotics, probiotics, synbiotics, and postbiotics) as supplementary dietary tools is scientifically supported at present and seems to be very promising for the prevention and treatment of these conditions.

Consensus on the diagnosis and treatment of cow's milk protein allergy of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Cow's milk protein allergy (CMPA) is the most frequent cause of food allergy in the first months of life. Despite the fact that there are different guidelines and recommendations on the management of children with CMPA, there continues to be great variability in diagnostic and therapeutic criteria in Latin America. The Food Allergy Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition summoned a group of Latin American experts to reach a consensus and formulate a document to unify diagnostic and therapeutic criteria for CMPA. Three teams were formed, each with a coordinator, and the members of each team developed a series of statements for their corresponding module: a) clinical manifestations and diagnosis; b) diagnostic tools, and c) treatment. A search of the medical literature was carried out to support the information presented in each module and 28 statements were then selected. The statements were discussed, after which they were evaluated by all the experts, utilizing the Delphi method. Their opinions on statement agreement or disagreement were anonymously issued. The final statements selected were those with above 75% agreement and their corresponding recommendations were formulated, resulting in the document presented herein.

Estructura, propiedades y genética de las caseínas de la leche: una revisión / Structure, properties and genetic of milk caseins: a review / Estrutura, propriedades e genética das caseínas do leite: uma revisão

Resumen La leche es un alimento esencial para los humanos y una de sus importancias radica en el contenido de proteínas lácteas. Las proteínas más frecuentes en este preciado líquido son las caseínas (αS1-caseína, αS2-caseína, β-caseína y κ-caseína), las cuales son fuente de aminoácidos para la dieta de los mamíferos en sus primeros días de vida. En la leche, las caseínas, están formadas por agregados moleculares de proteínas de tamaños variables denominados micelas. El objetivo de esta revisión es presentar un panorama general de la estructura, propiedades y genética de las caseínas lácteas y su relación con la salud humana. A partir de esta revisión, se pudo establecer, que las αs1 y αs2 caseínas se encuentran en conjunto con la β-caseína, formando el núcleo micelar, interactuando con los iones de calcio, para formar y mantener la micela estable. Animales caracterizados genéticamente con algunas variantes de estas proteínas, se asocian con un rendimiento en el volumen de leche. La κ-caseína, por su parte, está asociada con un aumento en el rendimiento y calidad de los quesos, de ahí su importancia económica, mientras que las formas más comunes de β-caseína en razas de ganado lechero son A1 y A2. La β-caseína A2 no presenta efectos negativos a la salud humana, por el contrario, ha sido asociada con propiedades reductoras de colesterol y triacilglicéridos. Sin embargo, la variante A1 de la β-caseína produce un péptido bioactivo denominado β-casomorfina-7 (BCM-7), que puede desempeñar un papel etiológico poco claro en el desarrollo de algunas enfermedades en humanos, tales como: enfermedad isquémica del corazón, diabetes mellitus tipo 1, síndrome de muerte súbita infantil (SIDS), desórdenes neurológicos, como autismo y esquizofrenia.

Abstract Milk is an essential food for humans and one of the reasons of its importance lies in the content of milk proteins. The most frequent proteins in this precious liquid are caseins (αS1-casein, αS2-casein, β-casein and κ-casein), which are a source of amino acids for the diet of mammals in their first days of life. In milk, caseins are made up of molecular aggregates of proteins of varying sizes called micelles. The objective of this review is to present an overview of the structure, properties and genetics of dairy caseins and their relation with human health. From this review, it was established that αs1 and αs2 caseins are found together with β-casein, forming the micellar nucleus and interacting with calcium ions, to form and maintain stable the micelle. Animals genetically characterized with some variants of these proteins are associated with a yield in milk volume. For its part, κ-casein is associated with an increase in the yield and quality of cheeses, hence its economic importance, while the most common forms of β-casein in dairy cattle are A1 and A2. β-casein A2 does not have negative effects on human health; on the contrary, it has been associated with lowering properties of cholesterol and triacylglycerides. However, the A1 variant of β-casein produces a bioactive peptide called β-casomorphin-7 (BCM-7), which may play an unclear etiological role in the development of some diseases in humans, such as: ischemic heart disease, type 1 diabetes mellitus, sudden infant death syndrome (SIDS), neurological disorders, such as autism and schizophrenia.

Resumo O leite é um alimento essencial para o ser humano e uma de suas principais característica é o teor de proteínas do leite. As proteínas mais frequentes neste líquido são as caseínas (αS1-caseína, αS2-caseína, β-caseína e κ-caseína), que são uma fonte de aminoácidos para a dieta dos mamíferos nos primeiros dias de vida. As caseínas no leite são constituídas por agregados moleculares de proteínas de variados tamanhos, chamados micelas. O objetivo desta revisão é apresentar uma visão geral da estrutura, propriedades e genética das caseínas lácteas e sua relação com a saúde humana. A partir desta revisão, foi estabelecido que as caseínas αs1 e αs2 são encontradas em conjunto com a β-caseína, formando o núcleo micelar, interagindo com os íons cálcio, para formar e manter a micela estável. Animais geneticamente caracterizados com algumas variantes dessas proteínas estão associados com o rendimento da produção de leite. Por sua vez, a κ-caseína está associada ao aumento do rendimento da produção e da qualidade dos queijos, por isso sua importância econômica, enquanto as formas mais comuns de β-caseína em bovinos leiteiros são A1 e A2. A Β-caseína A2 não tem efeitos negativos na saúde humana, pelo contrário, tem sido associada a propriedades redutoras do colesterol e dos triacilglicéridos. No entanto, a variante A1 da β-caseína produz um peptídeo bioativo denominado β-casomorfina-7 (BCM-7), que pode desempenhar uma função etiológico ainda desconhecida no desenvolvimento de algumas doenças em humanos, tais como: doença isquêmica do coração, diabetes mellitus tipo 1, síndrome da morte súbita infantil (SMSL), distúrbios neurológicos, como autismo e esquizofrenia.

Alergia a la proteína de la leche de vaca: reporte de un caso infrecuente en el período neonatal / Cow's milk protein allergy, a rare case report in the neonatal period

La alergia alimentaria se define como una reacción adversa que resulta de una respuesta inmunológica específica y reproducible desencadenada por la exposición al alimento. La respuesta inmune puede ser mediada por inmunoglobulina E, no mediada por inmunoglobulina E o mixta. Durante el primer año de vida, la proteína de la leche de vaca es la primera proteína a la cual se enfrentan los niños alimentados mediante lactancia materna o artificial, motivo por el cual constituye la forma de alergia alimentaria más frecuente en los primeros meses de la vida. El objetivo de este trabajo es presentar un caso clínico grave y poco frecuente de alergia a la proteína de la leche de vaca en el período neonatal.

Food allergy is defined as a reproducible adverse reaction that results from a specific and reproducible immune response triggered by exposure to food. The immune response can be mediated by immunoglobulin E, not mediated by immunoglobulin E or both. During the first year, cow´s milk protein is the first protein faced by children fed with breast milk or artificial milk. For that reason, it constitutes the form of food allergy most frequent in the first months of life. The objective of this paper is to describe a serious and rare clinical case of milk hypersensitivity in the neonatal period.

A Latin American and Spanish pediatric gastroenterology group's understanding of cow's milk protein allergy diagnosis and treatment: Results of a survey by the Food Allergy Working Group of the Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica. / Conocimiento sobre el diagnóstico y el tratamiento de la alergia a las proteínas de la leche de vaca por un grupo de gastroenterólogos pediatras en Iberolatinoamérica: resultado de la encuesta del Grupo de Trabajo de Alergia Alimentaria de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica.

INTRODUCTION: There are discrepancies in the diagnosis and management of cow's milk protein allergy (CMPA) in Spain and Latin America. The aim of the present study was to find out how Spanish and Latin American pediatric gastroenterologists diagnose and treat CMPA. MATERIAL AND METHODS: Pediatric gastroenterologists, members of the Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición, were invited to fill out a structured survey, the results of which were then compared with the 2012 and 2014 diagnosis and treatment guidelines, respectively. RESULTS: The survey results showed that 17% of the participants follow the diagnostic recommendations based on the published consensus and guidelines. To diagnose non-IgE-mediated CMPA, 15% of the participants utilize IgE-specific skin prick tests, 22% use IgE-specific blood tests, and 45% employ oral food challenges. To diagnose IgE-mediated CMPA the percentages for the same diagnostic methods were 57, 83 and 22%, respectively. Once diagnosis is confirmed, 98% of the participants provide dietary recommendations. In children that are not breastfed, 89% of the participants prescribe an initial extensively hydrolyzed formula, 9% an amino acid formula, 1% a soy formula, and 1% a hydrolyzed rice formula. In patients with IgE-mediated CMPA, 34% of the participants carry out an oral challenge once treatment is completed, 39% according to symptom severity, and 27% in relation to IgE-specific testing. CONCLUSION: CMPA management is diverse and there is poor adherence to the clinical practice guidelines.

Perinatal factors associated with the development of cow's milk protein allergy.

UNLABELLED: The prevalence of cow's milk protein allergy (CMPA) has increased in recent years, and is associated with antimicrobial use during the perinatal period, prematurity, the type of childbirth, and the decrease in breastfeeding. The aim of this study was to analyze whether there is any association between these factors and the development of CMPA. MATERIAL AND METHODS: A retrospective, comparative, cross-sectional, observational study was conducted by reviewing the case records of 101 children diagnosed with CMPA and seen at the Department of Gastroenterology and Nutrition of the Instituto Nacional de Pediatría within the time frame of January 2012 and August 2013. The following variables were included: age, sex, weeks of gestation, history of maternal infection and antimicrobial use during the pregnancy, type of delivery, and feeding with human milk, and its duration. Likewise, the case records of 90 children were reviewed as a control group on not having CMPA or any other allergy. The chi-square test was used for proportions, and the Mann-Whitney U test was used for comparing means in the statistical analysis. RESULTS: The factors associated with CMPA were the use of antimicrobials during gestation and breastfeeding duration in months. Both factors were statistically significant (P<.001). No association was found between CMPA and gestational age or type of delivery. CONCLUSIONS: The statistically significant associated factors were breastfeeding duration and the use of antimicrobials during the gestational stage. These results underline the necessity for prospective studies.

[24-h intraesophageal pH determination in children allergic to cow's milk protein at a tertiary care hospital]. / Determinación de pH intraesofágico de 24 h en niños con alergia a las proteínas de la leche de vaca en un hospital de tercer nivel.

BACKGROUND: Cow's milk protein allergy (CMPA) is being seen more frequently on a daily basis in pediatric consultations. It shares symptoms with gastroesophageal reflux (GER), which can complicate the differential diagnosis. AIMS: To attempt to corroborate the presence of acid GER in children with CMPA, as well as to find a characteristic profile through the 24-hour pH monitoring study in children with GER and CMPA METHODS: The intraesophageal pH monitoring studies performed on 47 children with CMPA were reviewed. The measurements in all the studies were carried out within a 24-hour period using Digitrapper® equipment with a multi-use GeroFlex® catheter, after calibration with pH 7 and pH 1 buffer solutions. RESULTS: Of the 47 children, 23 were boys (32.4%) and 24 were girls (33.8%) and the mean age was 5±3.7 years. Fourteen of the 47 children (29%) presented with GER, according to the result of the 24-hour intraesophageal measurement. Only 2 of the 47 patients studied fit the phasic profile. CONCLUSIONS: The findings show the existing relation between the two pathologies. Nevertheless, it is important to determine the presence of non-acid or weak acid reflux, because their existence can increase this association.

Kappa caseína de la leche: aspectos bioquímicos, moleculares, productivos y nutricionales / Kappa casein of milk: productive, molecular, biochemical and nutritional aspects

La caseína hace parte de las proteínas secretadas en la leche de la mayoría de los mamíferos, es una fosfoproteína producida por cuatro genes que codifican para las caseínas a s1, a s2, β y κ, las cuales se organizan en forma de micelas o unidades solubles. Las caseínas tienen un alto contenido de aminoácidos esenciales que se separan de la parte acuosa por acción de enzimas como la quimosina, la cual precipita la proteína en la elaboración quesos. Dentro de la caseínas de la leche, la kappa-caseína tiene gran influencia en la composición de la leche en relación con su capacidad de coagulación, tiempo de formación del cuajo, tasa de formación de la cuajada, y vigor del coágulo en la producción de queso para consumo humano. El conocimiento de los factores que definen el nivel de kappa caseína en la leche es de relevancia para los productores y procesadores, puesto que la elevación de su contenido puede derivar en un mayor rendimiento del producto para la elaboración de derivados lácteos y, a su vez, en un mayor beneficio económico.

Casein is a phosphoprotein secreted in the milk of most mammal species. It belongs to a group of proteins coded by four genes, namely a s1, a s2, β and κ, which are organized in micelles or soluble units. Proteins from this group have a high content of essential amino acids. These molecules are separated by precipitation from the aqueous part by enzymes, such as chymosin, during the production of cheese. Moreover, the caseins, kappa-casein plays a major role on milk coagulation, thus, influencing the rennet formation time, the curd production rate and the consistency of cheese made for human consumption. Knowledge on the factors involved in regulating kappa-casein levels in milk, is of the most relevant aspects to milk producers and dairy product manufacturers given that an increase in its content, may improve milk yield and finally, economic profit.