Outcomes and factors associated with tolerance in infants with non-IgE-mediated cow's milk allergy with gastrointestinal manifestations

Abstract Objectives To evaluate outcomes of oral food challenge (OFC) test to assess tolerance in infants with non-IgE-mediated cow's milk allergy (CMA) with gastrointestinal manifestations and explore clinical data predictive of these outcomes. Methods Single-center retrospective study including infants (age < 12 months) who were referred for CMA between 2000 and 2018 and underwent OFC on follow-up. A univariate logistic regression test was performed to evaluate variables associated with the outcomes of the follow-up OFC test. Results Eighty-two patients were included, 50% were male. Eighteen patients had a positive OFC test (22%). Most patients had presented with hematochezia (77%). The median age of symptom onset was 30 days. Two-thirds of the patients were on appropriate infant formula (extensively hydrolyzed or amino acid-based formula), exclusively or in association with breastfeeding. The median time on an elimination diet before the OFC test was 8 months (Q1 6 - Q3 11 months). All cases with positive follow-up OFC tests (n= 18) had been exposed to cow's milk-based formula before the first clinical manifestation of CMA. Five out of eight cases with Food Protein-Induced Enterocolitis Syndrome (FPIES) had positive OFC tests. Exposure to cow's milk-based formula before diagnosis, a history of other food allergies, hematochezia and diarrhea were predictors of a positive OFC test. Conclusions In infants with non-IgE-mediated CMPA with gastrointestinal manifestations, the use of cow's milk-based formula, a history of other food allergies, and hematochezia and diarrhea upon initial presentation were associated factors for the later achievement of tolerance.

Proctocolite induzida por proteína alimentar - teste de provocação oral deve ser realizado para confirmar o diagnóstico de alergia ao leite de vaca em neonatos? / Induced proctocolitis - oral food challenge should be done to confirm the diagnosis of cow's milk allergy in neonates?

ABSTRACT Background: Suspicion of food protein-induced proctocolitis based on empirical understanding of rectal bleeding can lead to misdiagnosis. Objective: to verify clinical and evaluative characteristics of patients who presented neonatal rectal bleeding and were on a restricted cow's milk diet. Methods: A cross-sectional retrospective study included patients followed up in a tertiary care center, who presented rectal bleeding in the neonatal period. The analyzed data included gender, gestational age, type of delivery, use of antibiotics during the last trimester of pregnancy, use of parenteral nutrition before the first manifestation, use of mechanical ventilation, initial clinical manifestations associated with rectal bleeding, diet before the first manifestation, period of elimination diet, oral food challenge (OFC) results and symptoms presented in cases of positive OFC. Fisher's exact test and Mann-Whitney test were used to analyze the data. The level of significance was set to 5%. Results: Forty-two patients were selected: 30 preterm infants, 34 cesarean deliveries, 10 exclusively breastfed patients before rectal bleeding. Median age at OFC was 6.3 months old. Median of length of the elimination period before OFC was 5.9 months. OFC was negative in 33/42 (79%) patients and positive in 9/42 (21%). There was no association between OFC results and the evaluated data. The main symptom observed in patients with positive OFC was blood in stools. Conclusion: OFC was negative in most cases of suspected cow's milk allergy due to rectal bleeding in neonates, most of them with a history of prematurity.

RESUMO Contexto: A suspeita de proctocolite induzida por proteína alimentar (PCIPA) com base na compreensão empírica de sangramento retal pode levar a diagnósticos equivocados. Objetivo Verificar as características clínicas e evolutivas de pacientes que apresentavam sangramento retal neonatal e faziam uso de dieta restrita com leite de vaca. Métodos: Estudo transversal retrospectivo com pacientes acompanhados em um centro terciário, que apresentaram sangramento retal no período neonatal. Os dados analisados incluíram: sexo, idade gestacional, tipo de parto, uso de antibióticos no último trimestre da gravidez, uso de nutrição parenteral antes da primeira manifestação, uso de ventilação mecânica, manifestações clínicas iniciais associadas ao sangramento retal, dieta antes da primeira manifestação, período de dieta de eliminação, resultados do teste de provocação oral (TPO) e sintomas apresentados em casos de TPO positivo. O teste exato de Fisher e o teste de Mann-Whitney foram usados para analisar os dados. O nível de significância adotado foi de 5%. Resultados: Quarenta e dois pacientes foram selecionados: 30 prematuros, 34 partos cesáreos, 10 pacientes amamentadas exclusivamente antes do sangramento retal. A idade média na ocasião do TPO foi de 6,3 meses. A mediana da duração do período da dieta de eliminação antes do TPO foi de 5,9 meses. O TPO foi negativo em 33/42 (79%) pacientes e positivo em 9/42 (21%). Não houve associação entre os resultados do TPO e os dados avaliados. O principal sintoma observado em pacientes com TPO positivo foi sangue nas fezes. Conclusão: O TPO foi negativo na maioria dos casos de suspeita de alergia ao leite de vaca devido a sangramento retal em neonatos, a maioria deles com história de prematuridade.

Cow's milk allergy immunoglobulin E-mediated: intake of proteins and amino acids

SUMMARY OBJECTIVE: Children with cow's milk allergy may be at nutritional risk due to the lower intake of nutrients, such as protein, calcium, and vitamin A, which are present in cow's milk. The objective was to evaluate children's diets with Children with cow's milk allergy compared with healthy controls as well as to compare the intake of proteins and amino acids from the diet followed by Children with cow's milk allergy who consume special infant formula or plant-based dairy alternatives with Children with cow's milk allergy who do not consume special infant formula or plant-based dairy alternatives. METHODS: Through a cross-sectional controlled study, the dietary intake of 57 children (27 with immunoglobulin E-mediated Children with cow's milk allergy and 30 healthy controls) was evaluated. Using 24-h nutritional recalls, the total energy intake value, macronutrients, and amino acids were calculated. RESULTS: No statistically significant difference was found between the Children with cow's milk allergy group and healthy controls for the intake of proteins and amino acids. However, the Children with cow's milk allergy do not consume special infant formula or plant-based dairy alternatives group had a lower protein (g/kg) and branched-chain amino acid (mg/kg) intake than the Children with cow's milk allergy consume special infant formula or plant-based dairy alternatives group. CONCLUSIONS: The Children with cow's milk allergy group achieved the recommendations for the intake of proteins and amino acids compared to the healthy control group. However, the Children with cow's milk allergy do not consume special infant formula or plant-based dairy alternatives group had a lower intake of protein (g/kg) and branched-chain amino acid (mg/kg) than the Children with cow's milk allergy consume special infant formula or plant-based dairy alternatives group.

Knowledge and practice of pediatricians and nutritionists regarding treatment of cow's milk protein allergy in infants / Conhecimento e prática de pediatras e nutricionistas sobre o tratamento da alergia às proteínas do leite de vaca em lactentes

ABSTRACT Objective This study evaluated the knowledge and practices of pediatricians and nutritionists about cow's milk protein allergy in infants, with an emphasis on issues related to the exclusion diet and nutritional status. Methods A cross-sectional, descriptive study was performed with a convenience sample of 204 pediatricians and 202 nutritionists randomly invited in scientific events in the city of São Paulo, from November 2014 to March 2016. Results Between 1.5% and 21.0% of respondents indicated inadequate products for the treatment of cow's milk protein allergy, including goat's milk, beverages or juices based on soy extract, lactose-free milk formula and partially hydrolyzed formula. The daily calcium recommendation for children between zero and 36 months of age was correctly indicated by 27.0% of pediatricians and 46.0% of nutritionists (p=0.001). Additionally, 96.1% of pediatricians and 82.7% of dietitians (p<0.001) provided guidance on about labels of industrialized products. Conclusion Pediatricians and nutritionists present gaps in knowledge about cow's milk protein allergy treatment in infants and educational strategies that increase the knowledge of the professionals are important for the management of cow's milk protein allergy.

RESUMO Objetivo Este estudo avaliou o conhecimento e práticas de pediatras e nutricionistas sobre alergia às proteínas do leite de vaca em lactentes, com ênfase em questões relacionadas à dieta de exclusão e ao estado nutricional. Métodos Estudo transversal, descritivo, realizado com uma amostra de conveniência de 204 pediatras e 202 nutricionistas, convidados aleatoriamente em eventos científicos na cidade de São Paulo, de novembro de 2014 a março de 2016. Resultados Entre 1,5% e 21,0% dos entrevistados indicaram produtos inadequados para o tratamento da alergia às proteínas do leite de vaca, incluindo leite de cabra, bebidas ou sucos à base de extrato de soja, fórmula de leite sem lactose e fórmula parcialmente hidrolisada. A recomendação diária de cálcio para crianças entre zero e 36 meses de idade foi corretamente indicada por 27,0% de pediatras e 46,0% de nutricionistas (p=0,001). Além disso, 96,1% dos pediatras e 82,7% dos nutricionistas (p<0,001) forneceram orientação sobre os rótulos dos produtos industrializados. Conclusão Pediatras e nutricionistas apresentam lacunas no conhecimento sobre o tratamento da alergia às proteínas do leite de vaca em lactentes. Estratégias educacionais que aumentam o conhecimento dos profissionais são importantes para o gerenciamento da alergia às proteínas do leite de vaca.

Ksheeralasaka Vis-à-vis Cow’s Milk Allergy: A Critical Review

Ksheeralasaka is a multi-system disease of the breast-fed child caused by Sannipataja-stanya-dushti (breast milk vitiated by all the Tridoshas). A proper understanding of the condition is not available and it is confused with lactose intolerance and cow’s milk allergy. Hence a thorough review of Ksheeralasaka and its management in the light of Ayurvedic and modern principles is intended in this paper so that suitable therapies can be selected. Ksheera denotes breast milk and Alasaka is a type of Ajeerna (indigestion), a condition called Ama caused by Agnimandya or weak digestive/metabolic power. Thus Ksheeralasaka is Ajeerna or indigestion in the infant caused by intake of vitiated breast milk. Ksheeralasaka is most similar to non-IgE-mediated cow’s milk protein allergy and is also comparable with food allergies caused by egg, peanuts, etc. Lactose intolerance and lactose overload can also co-occur with cow’s milk protein allergy or food allergies. Being a disease of Ama and Stanyadushti, Apatarpana (depletion) in the form of Sodhana (purification) and Stanyasodhana (purification of breast milk) are the treatments to be adopted. Langhana or fasting is sufficient if Ama is mild, Langhana and Pachana (digestives) are needed if it is moderate and Sodhana (purification) is needed if severe. Vamana for mother and child purifies the gut and expels the allergens ingested. Breast milk purifiers and anti-diarrhoeals are judiciously advised for the mother and the child respectively. Advice regarding feeding practices can help reduce symptoms of lactose overload that may co-occur.

Uso de leite processado em altas temperaturas por paciente com alergia ao leite de vaca - relato de caso / Use of milk processed at high temperatures by a patient with cow's milk allergy: case report

Objetivo: Relatar a evolução clínica de um escolar com alergia ao leite de vaca (ALV) que fez uso de leite de vaca processado em altas temperaturas (LVPAT). Descrição: H.B.M., sexo masculino, 7 anos, com ALV IgE mediada diagnosticada com 1 ano e 3 meses. Aos 2 anos foi submetido a teste de provocação oral (TPO) aberto para leite de vaca (LV) in natura, evoluindo com urticária, congestão nasal e vômito após a primeira dose (1 mL). Mãe relatou alguns episódios de exposição acidental ao LV acompanhados de sintomas. As Imunoglobulinas E para LV e frações mantiveram-se elevadas (IgE leite total: 4,69 KU/L) até os 6 anos, quando a criança realizou TPO com LVPAT, sob a forma de bolo, evoluindo sem intercorrências. Passou a consumir diariamente uma porção do bolo contendo leite processado durante 6 meses. Aos 7 anos e com IgEs específicas mais baixas (IgE específica leite total: 2,2 KU/L), realizou TPO com LV in natura sem sintomas, sendo liberado na dieta. Comentários: O uso do leite de vaca processado em altas temperaturas em pacientes com ALV IgE mediada é uma estratégia promissora com impacto na tolerância futura ao alimento, tendo resultados favoráveis com ênfase na qualidade de vida e inclusão social. No entanto, vale ressaltar a importância da avaliação individualizada dos pacientes e a segurança da equipe na aplicação desses protocolos, além de levar em consideração que a alergia pode ser transitória, mesmo sem o uso do leite processado.

Objective: To report the clinical evolution of a school-age boy with cow's milk allergy CMA) who made use of cow's milk processed at high temperatures (CMPHT). Description: H.B.M., male, 7 years old, was diagnosed with IgE-mediated CMA at 1 year and 3 months of age. At 2 years of age, the patient underwent an open oral food challenge for raw cow's milk (CM) and developed urticaria, nasal congestion and vomiting after the first dose (1 mL). The mother reported some episodes of accidental exposure to CM, accompanied by symptoms. Specific IgEs against CM and its fractions remained elevated (total cow's milk: 4.69 KU/L) until 6 years of age, when the patient underwent a new oral food challenge for CMPHT, in the form of a cake, without symptoms. He then began to consume a portion of cake containing baked milk daily, for 6 months. At the age of 7 and with lower levels of specific IgEs (total cow's milk: 2.2 KU/L), he underwent another oral food challenge for raw CM, without symptoms. An unrestricted diet was then authorized. Comments: The use of cow's milk processed at high temperatures in patients with IgE-mediated cow's milk allergy is a promising strategy, with impact on future food tolerance, favorable results, with emphasis on quality of life and social inclusion. However, an individualized assessment of each patient is extremely important, as is the confidence of the team while applying these protocols. It should be taken into consideration that the allergy may be transient even without the use of processed milk.

Cow's milk oral immunotherapy in real life: 8-year long-term follow-up study

BACKGROUND: Oral immunotherapy (OIT) has been recognized as a promising treatment for severe and long-lasting cow's milk (CM) allergy. Once maintenance has been achieved, patients should maintain daily intake of CM to ensure desensitization. Clinical experience concerning long-term follow-up is scarce. OBJECTIVE: The authors aimed to assess long-term efficacy and safety of a maintenance phase of OIT in real life. METHODS: Prospective study of all children and adolescents, who underwent CM-OIT and were subsequently followed at our allergy center on maintenance dose (200 mL daily) for at least 36 months after reaching the maintenance phase (from 2009 to 2016). RESULTS: Forty-two patients were enrolled: 60% male, 36% with history of anaphylaxis and 57% with asthma. The median time of follow-up was 69 months (range, 39–105 months) and the median age at the last clinical evaluation was 13 years (range, 6–23 years). Regarding adherence to the protocol: 92% are on free diet (at least 200 mL of CM daily; 7-g protein); 14% had transient interruptions and 7% definitely withdrawn with loss of tolerance. During maintenance, 45% developed mild to severe allergic reactions, and 7% had more than 3 episodes. A positive correlation between the occurrence of allergic reactions and history of anaphylaxis (p < 0.001) was found. The coexistence of asthma was risk factor for the occurrence of allergic reactions during maintenance. CONCLUSION: This real-life study supports long-term efficacy and safety of CM-OIT. Despite daily intake, 41% had symptoms at some moment during the complete follow-up period; a total of 33 symptomatic days in patients with mean follow-up time of 67.5 months. Clinical tolerance depends on daily intake. The protective effect reached can be lost after CM withdrawal. History of anaphylaxis was a risk factor for the occurrence of allergic reactions during the maintenance phase.

Oral Food Desensitization in Children With IgE-Mediated Cow's Milk Allergy: Immunological Changes Underlying Desensitization

PURPOSE: This study aimed to evaluate the safety and efficacy to induce clinical desensitization to cow's milk (CM) of an oral immunotherapy (OIT) protocol in a pediatric population with cow's milk allergy (CMA). In addition, the immune responses against β-casein, of peripheral blood mononuclear cells (PBMCs) from CMA patients, before and after the protocol were evaluated and compared to a nonallergic population. METHODS: A group of 20 children with IgE-mediated CMA and 15 nonallergic children were recruited. Allergic subjects underwent an OIT protocol based on weekly doses of commercial semi-skimmed ultra-high temperature treated (UHT) CM, followed by a maintenance phase. Immune profiles and changes in all subjects were investigated by measuring Th1, Th2, and Treg cytokines, transcription factors, and specific IgE and IgG4 levels. RESULTS: The CM-OIT protocol enabled to desensitize 70% of the allergic patients. Successful OIT was accompanied by significant increases in casein-specific IgG4 levels, together with a reduction in the concentration of antigen-specific IgE and in IL-5, IL-13, and IL-10 production by β-casein-stimulated PBMCs. Baseline significant differences observed between allergic and nonallergic children in IL-13 and IL-5 levels were no longer found once the protocol had finished. CONCLUSIONS: The OIT protocol was safe and effective in inducing milk desensitization in 70% of the children with CMA, leading to alterations in their immune profiles toward a nonallergic phenotype.

Características clínicas y manejo de lactantes menores de 1 año con sospecha de alergia a proteína de leche de vaca / Clinical characteristics and management of infants less than 1-year-old suspected with allergy to cow's milk protein

Introducción: La alergia a proteína de leche de vaca (APLV) es frecuente en lactantes (2-5% en < 1 año). Tiene múltiples formas de presentación y un amplio diagnóstico diferencial, por lo que es relevante confirmar el diagnóstico. El estándar de oro del diagnóstico es el test de provocación oral (TPO), que en la práctica no siempre se realiza. En Chile hay escasa literatura respecto a esta entidad. Objetivo: Describir características demográficas, clínicas y manejo de lactantes < 1 año con sospecha de APLV. Pacientes y Método: Estudio retrospectivo en menores de 1 año atendidos por sospecha de APLV entre 2009-2011. Se registraron datos demográficos, historia perinatal, antecedentes de atopia, alimentación al momento del diagnóstico, síntomas de sospecha de APLV, estudios realizados para su confirmación, y respuesta a tratamiento. Se consideró como estándar de diagnóstico la respuesta a la dieta y la contraprueba. Se definió como respuesta a la dieta la ausencia de los síntomas atribuidos a la APLV al menos 4 semanas desde el cambio de leche. Se realizó estadística descriptiva mediante programa Epiinfo™. Resultados: Se incluyeron 106 lactantes, 51% varones, 80% recién nacidos de término, 74% con al menos un progenitor atópico, 34% con alguno de los padres o algún hermano con alergia alimentaria. La mediana de edad al inicio fue 1,5 meses (rango: 1,5-2 m). El 15% recibió fórmula desde el período neonatal y el 50% antes del tercer mes. Los síntomas más frecuentes fueron: vómitos (63%), cólicos (50%) y rectorragia (40%); el 61% presentó ≥ 2 síntomas al comienzo. Solo en el 34% se hizo TPO, en el resto se evaluó la respuesta a la dieta de exclusión y se realizaron exámenes. La realización de exámenes no cambió la conducta. Tratamiento: 43% lactancia materna con dieta de exclusión, 24% solo fórmula extensamente hidrolizada, 26% solo fórmula aminoacídica y 7% otros. Conclusión: Las características demográficas y antecedentes de los pacientes concuerdan con lo descrito en la literatura extranjera. El inicio clínico fue precoz, predominando los síntomas digestivos. Se realizaron exámenes en una proporción alta de pacientes, sin contribuir a un cambio de conducta; el TPO fue subutilizado como herramienta diagnóstica.

Introduction: Cow's milk protein allergy (CMPA) is highly prevalent in infants (2-5%). It has a wide clinical spectrum, and confirmation through an oral food challenge (OFC) is relevant for its differential diagnosis. Information on this topic is scarce in Chile. Objective: To describe the demographic and clinical features of infants with suspected CMPA. Patients and Method: A retrospective study of patients < 1 year-old, treated for suspected CMPA between 2009 and 2011. Demographic data, symptoms of atopy, nutrition at the time of diagnosis, CMPA symptoms, diagnostic studies, and response to treatment were recorded. Diet response at least 4 weeks after milk modification, and clinical behavior when suspected foods were added back to the diet were considered standard diagnostic criteria. Descriptive statistics were performed using Epiinfo ™ software. Results: The study included 106 infants, of whom, 51% male, 80% term newborns, 74% with ≥ 1 atopic parent, and 34% with ≥ 1 parent/sibling with food allergy. The median age at onset of symptoms was 1.5 months (range 1.5-2 m). Almost half (46%) were breast-feeding ≥ 6 m, with 15% receiving formula milk since the neonatal period, and 49% before the third month. Common symptoms were: vomiting (63%), colic (49%), and bleeding on passing stools (41%). No anaphylaxis was identified, and 61% had ≥ 2 symptoms at debut. Only 34% were subjected to OFC. The most frequently requested tests were, test patch (43%), prick test (40%), and blood in stools (37%). Treatment: 43% breast feeding with exclusion diet, 24% extensively hydrolysed formula, 26% amino acid formula, and 7% others. Conclusion: Demographic characteristics and risk factors were similar to those previously described in international literature. Clinical presentation was early in life, and digestive symptoms predominated. OFC was underused for diagnosis, and most of the tests requested did not change management.

INFLUENCIA DEL TIPO DE ALIMENTACIÓN EN EL DESARROLLO DE LA ALERGIA A LA LECHE DE VACA. FACTORES INVOLUCRADOS EN EL PROCESO POR EL CUAL SE ADQUIERE LA ENFERMEDAD / Infl uence of the type of feeding in the development of cow's milk allergy. Factors involved in the process by which the disease is acquired

Antecedentes. Los resultados de las investigaciones sobre la historia natural de la alergia a la leche de vaca (ALV) no han provisto aún, de un cuadro claro y consistente que ayude en la práctica al médico tratante. Objetivo. Identifi car los factores involucrados en el desarrollo de la enfermedad en lactantes pequeños, con el fi n de determinar perfi les específi cos e índices predictivos. Lugar de realización: Río Cuarto, Córdoba, Argentina. Diseño. Análisis observacional y retrospectivo. Población. 91 niños con diagnóstico de ALV y 91 controles, de ambos sexos, menores de 6 años. Método. Análisis de factores seleccionados de las historias clínicas, su relación individual con el diagnóstico (prueba X2, Odds Ratios, diferencias de medias) y su incidencia conjunta en la probabilidad de ser ALV para determinar perfi les (análisis de correspondencias múltiple y regresión logística). Elaboración de 3 índices predictivos basados en: odds ratios individuales, los correspondientes a la regresión logística y la identifi cación de criterios mayores y menores, con su respectiva evaluación de efectividad diagnóstica (sensibilidad, especifi cidad, valores predictivos y curva ROC). Resultados. Se encontró que la edad de inicio de los síntomas, el tipo de alimentación recibida hasta el 3er mes de vida, la exposición al humo de cigarrillo, los antecedentes alérgicos maternos y el tipo de manifestaciones clínicas con que comienza la ALV son factores que con mayor probabilidad inciden en su desarrollo. Conclusión. La utilidad de estos perfi les e índices predictivos radica en una temprana identifi cación de pacientes con riesgo de padecer ALV(AU)

Background: The results of the research on the natural history of allergy to cow's milk allergy (CMA) still have not provided a clear picture and consistent that in practice helps the attending physician. Objective: to identify the factors involved in the development of the disease in young infants, in order to determine specifi c profi les and predictive clinical indexes. Setting: Río Cuarto, Córdoba, Argentina. Design: observacional and retrospective analysis. Population: 91 children with a diagnosis of CMA and 91 controls, of both sexes, under the age of 6 years. Methods: analysis of selected factors of the clinical histories, their relationship with the individual diagnosis (test X2, Odds Ratios, differences in average) and their combined impact on the probability of being CMA to determine profi les (multiple correspondence analysis and logistic regression). Elaboration of 3 predictive indices based on: individual Odds Ratios, corresponding to the logistic regression and the identifi cation of greater and smaller criteria, with its respective evaluation of effectiveness diagnoses (predictive sensitivity, specifi city, values and ROC curve). Results: we found that the age of onset of symptoms, the type of feeding received until the 3rd month of life, exposure to cigarette smoke, the maternal allergy history and the type of clinical manifestations with that begins the CMA, are factors that most likely have an impact on its development. Conclusion: the utility of these profi les and predictive clinics indexes lies in an early identifi cation of patients at risk of CMA.(AU)

ALERGIA A LA PROTEíNA DE LA LECHE DE VACA. EVALUACIóN DE SU RESOLUCIóN ESPONTáNEA POR MEDIO DE DESAFíOS DOBLE CIEGO PLACEBO CONTROLADOS / cows milk allergy. an assesment of its spontaneous resolution through double blind placebo controlled challenges.

Introducción. la alergia a la leche de vaca (aplv) es un problema sanitario global. Su diagnóstico adecuado y su seguimiento son esenciales ya que la leche de vaca es un alimento importante en la dieta de muchos lactantes. los desafíos orales doble ciego controlados por placebo (ddcpc) son la herramienta ideal para el diagnóstico y seguimiento de las alergias alimentarias. este estudio describe las características evolutivas de pacientes con aplv y las posibles variables que la pudieran modificar. material y métodos. Se estudiaron pacientes con diagnóstico de aplv previo con desafíos abiertos. Se catalogaron las reacciones de acuerdo a la normativa dracma. positivas fueron las pruebas en las que se presentaron alteraciones clínicas o variaciones hemodinámicas. negativas fueron aquellas en las que el paciente toleró la leche. Se consideraron edades de inicio y de realización del ddcpc, sexo y patología de aplv. resultados. Se estudiaron 106 pacientes (50 masculinos, 56 femeninos), promedio edad de inicio de síntomas 5,31 m (rango: 1-48 meses) y al procedimiento 23,14 m (5 meses - 5 años), y 13 pruebas positivas. un conjunto se refirió al mecanismo fisiopatológico y se dividió en ige mediadas (n=55) con 8 pruebas positivas y mixtas/celulares (n=51) con 5 pruebas positivas. otro conjunto fueron no gastrointestinales (n=61) con 7 pruebas positivas y gastrointestinales (n=45) con 6 pruebas positivas. todos los grupos fueron similares en cuanto a las variables demográficas. el sexo masculino y el diagnóstico de anafilaxia fueron factores de riesgo para no resolver su aplv (p=0,0125 y p=0,002 respectivamente). conclusiones. el momento de resolución de la aplv es independiente del mecanismo fisiopatológico subyacente o la edad de inicio de los síntomas. en general resuelven el problema de manera espontánea hacia los dos años de vida en más de un 87% de los casos. el sexo masculino (en ige mediadas) y el antecedente de anafilaxia podrían ser factores de riesgo para tener menos probabilidades de resolver la APLV. (AU)

Introduction: cow´s milk allergy (cma) is a global health issue. a proper diagnosis and follow up become essential. double blind placebo controlled challenges (dbpcc) is the gold standard for this purpose. this paper describes clinical evolution and characteristics of cma, as well as variables that may modify the affection course. methods & material: a group of patients, with a previous diagnosis of cma by open challenges, has been studied and its results cataloged according to dracma guidelines. tests with hemodynamic changes or clinical symptoms were considered as positives, while those with no clinical reaction were considered as negatives. variables involved were: age of symptoms starting, age of dbpcc performing, gender and cma clinical manifestations. results: 106 patients has been studied (50 male, 56 female), with a median age of 5,31 mo (range 5 ­ 48 mo) at the starting symptoms, and a median age of 23,14 mo (range 5 mo ­ 5 y) at the performing of dbpcc. 13 tests were negative. as regards to the different immune mechanisms, 55 were ige dependent (8 negative), and 51 were mediated by mixed/cellular (5 negative). patients were divided into two groups: with gastrointestinal symptoms (n=45) and with no gastrointestinal symptoms (n=61). they showed 6 and 7 negative results, respectively. all groups were similar. male gender, and anaphylaxis diagnosis turned out to be risk factors not to resolve cma (p=0,0125 and p=0,002 respectively). conclusions: cma resolution is independent of the immune mechanisms involved or the age of its symptoms starting. cma is solved spontaneously towards the age of two in 87% of the cases. male gender, and anaphylaxis may become risk factors not to resolve cma.(AU)

Alergia ao leite de vaca: achados do ultrassom com Doppler colorido em neonatos com hematoquezia / Cow's milk allergy: color Doppler ultrasound findings in infants with hematochezia

OBJETIVO: o ultrassom (US) tem sido uma importante ferramenta de diagnóstico para identificar várias causas de hemorragia gastrointestinal. Neonatos com alergia ao leite de vaca (ALV) podem apresentar hematoquezia, e a confirmação do diagnóstico pode ser difícil. O objetivo deste estudo é descrever achados com ultrassom em escala de cinza e com Doppler colorido em pacientes com ALV. MÉTODOS: estudamos, retrospectivamente, 13 neonatos com ALV. Todos eles apresentaram hematoquezia severa e dor abdominal e foram submetidos a um estudo com US, com o diagnóstico de colite alérgica. O diagnóstico teve como base os achados clínicos, a recuperação após a dieta de exclusão do neonato ou da mãe, no caso de amamentação exclusiva, e o teste de provocação oral positivo. RESULTADOS: a idade média variou de um a seis meses (média = 3,53). Sete dos 13 neonatos (53,8%) passaram novamente por ultrassonografia em escala de cinza e com Doppler colorido após a dieta de exclusão. Dentre eles, 12 dos 13 (92,3%) mostraram anormalidades no US e no ultrassom com Doppler colorido (USDC) no início. Os achados positivos que sugeriram colite foram paredes intestinais espessas e aumento na vascularização, principalmente no cólon descendente e sigmoide. Os resultados da colonoscopia e histopatológicos foram compatíveis com colite alérgica. Após uma mudança na dieta, os 13 neonatos se recuperaram e seus testes de provocação oral foram positivos. CONCLUSÃO: o US com Doppler pode ser muito útil para diagnosticar a colite secundária, como a ALV, e para excluir várias outras doenças abdominais que podem imitar essa doença.

OBJECTIVE: ultrasound (US) has been an important diagnostic tool to identify several causes of gastrointestinal bleeding. Infants with cow's milk allergy (CMA) may present hematochezia and the confirmation of the diagnosis can be difficult. The aim of this study is to describe grayscale and color Doppler ultrasound findings in patients with CMA. METHODS: we retrospectively studied 13 infants with CMA. All infants presented severe hematochezia and abdominal pain. All underwent an US study with the diagnosis of allergic colitis. This diagnosis was based on clinical findings, recovery after infant or mother exclusion diets in the case of exclusive breastfeeding and positive oral challenge test. RESULTS: the mean age ranged from 1 to 6 months (mean = 3.53). Seven out of 13 infants (53.8%) had grayscale and color Doppler sonographic repeated after exclusion diet. Twelve out of 13 (92,3%) showed abnormalities at US and CDUS at beginning. The positive findings suggesting colitis were thickened bowel walls and increased vascularity, especially in the descending and sigmoid colon. Colonoscopy and histopathological findings were compatible with allergic colitis. After a diet change the 13 infants recovered and their oral challenge tests were positive. CONCLUSION: Doppler US may be very useful in diagnosing secondary colitis, such as CMA, and to exclude several other abdominal diseases that can emulate this disease.

Interleukin 10 (IL10) and transforming growth factor 1 (TGF1) gene polymorphisms in persistent IgE-mediated cow's milk allergy

OBJECTIVES: The aim of this cross-sectional study was to evaluate whether interleukin 10 (IL10) and transforming growth factor β1 (TGFβ1) gene polymorphisms were associated with persistent IgE-mediated cow's milk allergy in 50 Brazilian children. The diagnostic criteria were anaphylaxis triggered by cow's milk or a positive double-blind, placebo-controlled food challenge. Tolerance was defined as the absence of a clinical response to a double-blind, placebo-controlled food challenge or cow's milk exposure. METHOD: The genomic DNA of the 50 patients and 224 healthy controls (HCs) was used to investigate five IL10 gene polymorphisms (-3575A/T, -2849A/G, -2763A/C, -1082G/A, -592C/A) and one TGFβ1 polymorphism (-509C/T). RESULTS: Among the five IL10 polymorphisms analyzed, homozygosis for the G allele at the -1082 position was significantly higher in the patients compared with the healthy controls (p = 0.027) and in the persistent cow's milk allergy group compared with the healthy controls (p = 0.001). CONCLUSIONS: Homozygosis for the G allele at the IL10 -1082G/A polymorphism is associated with the persistent form of cow's milk allergy. .

The management of food allergy in Indonesia

Prevalence of allergic diseases is increasing worldwide, including food allergy. It is different between countries because food allergy can vary by culture and population. Prevalence of food allergy in Indonesia is unknown; therefore it is not known yet the burden and impact of food allergy in our population. However, we already start to formulate guidelines for diagnosis and management of food allergy, especially cow's milk allergy.

Cow's Milk Allergy among Children with Gastroesophageal Reflux Disease

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) and cow's milk allergy (CMA) are two common conditions that occur in infancy. This study was performed to investigate the frequency of CMA in a group of patients with GERD. METHODS: Eighty-one children with signs and symptoms of GERD were enrolled in this study. All subjects received omeprazole for 4 weeks after the initial evaluation. Empirical elimination of cow's milk from the diet was started for the patients who did not respond to the omeprazole treatment. RESULTS: Seventy-two cases presented with gastrointestinal signs and symptoms, whereas the remaining nine cases presented with respiratory complaints. After the initial treatment with omeprazole, two thirds of the cases (54 patients, 66.7%) responded well, and all of their symptoms were resolved. Cow's milk was eliminated from the diets of the remaining 27 patients. All signs and symptoms of GERD were resolved in this group after a 4 week elimination of cow's milk from the diet. CONCLUSIONS: A diagnosis of CMA was considered in one third of the pediatric cases with signs and symptoms of GERD. This finding shows that CMA can mimic or aggravate all signs and symptoms of severe GERD during infancy.

A Follow-Up Study of Hematochezia in Neonates and During Early Infancy

PURPOSE: There are many causes of hematochezia in neonates and during early infancy. Cow`s milk allergy is considered to be the most common cause of bloody stools in infants; however, cow`s milk allergy is diagnosed in relatively few patients. In a significant proportion of case investigations, the etiology of hematochezia is not determined. The objectives of this study were to evaluate the clinical course and prognosis of patients with hematochezia of unknown etiology. METHODS: The patients were <4-month-old infants with hematochezia in whom infectious and surgical etiologies had been excluded. We investigate retrospectively the clinical course and laboratory finding. We also perform 2-years follow-up study and evaluate prognosis of the patients. RESULTS: In all study patients, RAST milk was negative. All patients had self-limited hematochezia. In 2-years of follow-up, the prognosis of patients was good. There were no differences at 2-year regarding allergic tendencies of the patients, as determined by the increase in total eosinophil count. CONCLUSION: Hematochezia in neonates and during early infancy is generally a benign and self-limiting symptom. Based on 2-years of follow-up, the prognosis of the patients is good.

Desempenho de pais de crianças em dieta de exclusão do leite de vaca na identificação de alimentos industrializados com e sem leite vaca / The performance of parents of children receiving cow's milk free diets at indentification of commercial food products with and without cows's milk

OBJETIVO: Investigar o desempenho de pais de crianças em dieta isenta da proteína do leite de vaca no reconhecimento de expressões e alimentos que contenham ou não proteínas do leite de vaca. MÉTODOS: Foram entrevistados 24 pais de crianças em dieta de exclusão do leite de vaca e derivados e 23 sem necessidade de nenhum tipo de dieta de exclusão. Foi questionado se reconheciam 12 expressões relacionadas ao leite de vaca. A seguir, foi solicitado que classificassem 10 produtos industrializados quanto ao conteúdo ou não de proteínas do leite de vaca. RESULTADOS:Termos iniciados com a palavra leite foram os mais reconhecidos pelos dois grupos. Os responsáveis por crianças em dieta de exclusão reconheceram mais freqüentemente as palavras proteína do leite de vaca, traços do leite e formulação ou preparação láctea (p < 0,05). Caseína, caseinato, lactoalbumina e lactoglobulina foram reconhecidas por menos de 25,0 por cento dos entrevistados. O número de identificação correta dos 10 produtos industrializados foi maior para os produtos com leite de vaca nos dois grupos. A mediana de acertos dos produtos com leite de vaca (n = 5) pelos pais em dieta de exclusão (4,0) foi maior que a do grupo controle (3,0; p = 0,005). Leitura de pelo menos um rótulo associou-se com maior chance de identificação correta de mais de cinco dos 10 produtos (razão de chance = 8,0). CONCLUSÃO:Apesar de orientados, os pais de crianças em dieta de exclusão não estão plenamente preparados para sua correta realização, indicando a necessidade de aprimoramento das orientações para essa dieta de exclusão.

OBJECTIVE: To investigate how well the parents of children on cow's milk free diets perform at recognizing whether or not expressions describe and foods contain cow's milk proteins. METHODS: Interviews were conducted with 24 parents of children on cow's milk and by-products exclusion diets and 23 parents of children with no need for any type of exclusion diet. They were asked if they recognized 12 expressions relating to cow's milk. They were then asked to classify 10 commercial food products in terms of whether or not they contained cow's milk proteins. RESULTS: Terms that included the word milk were more often recognized by both groups of parents. The parents of children on exclusion diets recognized the terms cow's milk protein, traces of milk and milk formulation or preparation most frequently (p < 0.05). Less than 25.0 percent of those interviewed recognized casein, caseinate, lactalbumin and lactoglobulin. Both groups correctly identified more of the commercial products containing cow's milk than those free from milk. The median number of products containing cow's milk (total = 5) correctly identified by the parents of children on exclusion diets (4.0) was greater than for the control group (3.0; p = 0.005). Reading at least one label was associated with a greater chance of correctly identifying more than five of the 10 products (odds ratio = 8.0). CONCLUSIONS: Despite having received guidance, the parents of children on exclusion diets were not fully prepared to manage these diets, indicating a need for improvements to the instruction provided when indicating exclusion diets.

A Case of Hemorrhagic Gastritis due to Cow's Milk Allergy / 대한소아소화기영양학회지

Hematemesis is a rare condition in infants and can be a symptom of cow's milk-induced hemorrhagic gastritis. Other clinical manifestations of cow's milk allergy are vomiting, malnutrition and anemia. The criteria for the diagnosis of cow's milk allergy includes elimination of cow milk formula resulting in improvement of symptoms, specific endoscopic and histologic findings as well as exclusion of other causes. Cow's milk allergy should be considered in the etiologic differential diagnosis of hematemesis and gastritis in infancy. We have experienced a 1-month-old female infant with hematemesis due to cow's milk-induced hemorrhagic gastritis, and report the case with a review of previously published cases.

Clinical Observations of Gastrointestinal Cow Milk Allergy in Children According to a New Classification / 대한소아소화기영양학회지

PURPOSE: A new classification of gastrointestinal food allergy was published, but the changes of terminology between previously reported terms and the new ones were in a state of disorder. This has resulted in confusion between medical communication and diagnostic and therapeutic approaches. The clinical observations of infants presenting with gastrointestinal cow milk allergy (GI-CMA) were performed, and the changes in the terminology reviewed through the published Korean literature. METHODS: Between March 2003 and July 2003, data from 37 consecutive infants with GI-CMA, aged 2 weeks to 15 months, were reviewed. The challenge and elimination test of cow milk, and the endoscopic and histologic findings, were used for the seven subdivisions of GI-CMA according to a new classification on the basis of patients' ages, clinical manifestations and location of gastrointestinal lesions. RESULTS: The 37 patients had a mean age of 5.4+/-4.8 months, with those observed in 26 (70.3%) of patients being below 6 months of age. The seven final diagnoses were; cow milk protein-induced enterocolitis (CMPIE) in 12 (32.4%), cow milk protein proctitis (PROC) in 12 (32.4%), IgE-mediated (IGE) in 6 (16.2%), gastroesophageal reflux-associated cow milk allergy (GERA) in 5 (13.5%) and eosinophilic gastroenterocolitis in 2 (5.4%). CMPIE was revealed as the typical type in 7 (18.9%) and the atypical type in 5 (13.5%), and all of typical CMPIE revealed cow milk protein-induced enteropathy. The mean age at symptom onset was 4.3+/-0.8 months, and for those with typical and atypical CMPIE, and PROC and GERA were 3.8+/-4.6, 10.4+/-3.8, 3.4+/-3.9 and 7.8+/-5.7 months, respectively (p<0.05). The period from onset of symptom to diagnosis was 2.4+/-3.3 (0.5~12) months, with those observed in atypical CMPIE and GERA being over 3months. Although the birth weights in all patients were within the 10~90 percentile range, the body weights on diagnoses were below the 3 percentile in 48.6%; IGE 16.7%, EOS 0%, typical CMPIE 85.7%, atypical CMPIE 60.0%, PROC 25.0% and GERA 100% (p<0.05). Through the review of the Korean literature, 8 case reports and 14 original articles for GI-CMA were found. CONCLUSION: GI-CMA is not a rare clinical disorder and is subdivided into seven categories on the basis of the patient's age, clinical manifestations and location of the gastrointestinal lesions. The terms for GI-CMA are changing with new classifications, and careful approaches are necessary for medical communications.