A.K.F. Gushken

Establishing a cut-off for the serum levels of specific IgE to milk and its components for cow's milk allergy: Results from a specific population

BACKGROUND Cows milk allergy diagnosis many times requires double-blind placebo-controlled food challenge (DBPCFC), which presents high accuracy but involves risks, specifically in infants and anaphylactic patients. The identification of the cut-off values for specific IgE to milk or its components would contribute to cows milk allergy (CMA) diagnosis. The aim of this study was to compare discriminating concentration of a cows milk specific IgE and its fractions (α-lactoalbumin, β-lactoglobulin, casein) in children for the CMA diagnosis. METHODS this study included 123 patients (M:F=1.3:1) median age at diagnosis=1.91 years, (3.5m to 13.21y) with CMA diagnosis via DBPCFC (n=26), proven anaphylaxis due to cows milk (n=46) or a suggestive clinical history associated with a positive skin prick test (n=51) and open oral food challenge. The control group included 61 patients (1 male:1.1 female) ages ranging from 0.66 to 16.7 years (median=6.83 years). Receiver operator characteristics (ROC) curves were constructed to determine the best cut-offs that guarantees high specificity (>95%) for cows milk and its components. RESULTS considering 98% specificity, cut-off points were: 3.06 kU/L for cows milk, 2.06 kU/L for α-lactalbumin, 1.85 kU/L for β-lactoglobulin and 1.47kU/L for casein. The best ROC curve (area under the curve=0.929) was obtained evaluating cows milk. CONCLUSION this study showed that the cut-off point detected for whole cows milk revealed a better discriminatory capacity for CMA diagnosis without the necessity of the milk components testing.

Double-blind, placebo-controlled food challenges in Brazilian children: Adaptation to clinical practice

BACKGROUND A double-blind, placebo-controlled food challenge (DBPCFC) is considered the gold standard for diagnosing food allergy, but because of methodological difficulties it is rarely conducted in clinical practice, especially in paediatric patients. The purpose of the study was to propose a DBPCFC protocol that is adapted to our conditions for the diagnosis of an IgE-mediated cows milk allergy (CMA) in a Brazilian reference centre for paediatric allergies. METHODS This study includes the experimental phase (choice of materials, adjustments made to protocols described in the literature) and the test execution phase. DBPCFCs were performed in 58 patients aged 1-15 years who were separated into two groups: Group 1 (n=39), sex 1.6 M:F, 5.3 years median age, suggestive history of IgE-mediated CMA; and Group 2 (n=19), sex 1.4 M:F, 8.3 years median age with symptoms not associated with milk ingestion and laboratory data not compatible with IgE-mediated CMA. RESULTS The materials were standardised for testing: containers and disposable products, low-lactose cows milk (CM) and vehicles, such as natural fruit juice, vegetable soup and soybean-based beverages. Each DBPCFC was performed in a single day with two blind, randomised phases with a 2-h interval between them. The milk doses were gradually increased and offered in regular intervals of 15-30 min. Following negative or inconclusive results, patients underwent an open oral challenge test with 200 mL of low-lactose CM. CONCLUSIONS The proposed adaptation for the DBPCFC allowed to implement this important test for the diagnosis of IgE-mediated CMA in a reference centre for paediatric allergies. It was considered feasible and safe if performed in an appropriate setting with physician supervision.

Interleukin 10 (IL10) and transforming growth factor β1 (TGFβ1) 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 cows milk allergy in 50 Brazilian children. The diagnostic criteria were anaphylaxis triggered by cows 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 cows 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 cows 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 cows milk allergy.

Conhecimento da rotulagem de produtos industrializados por familiares de pacientes com alergia a leite de vaca

OBJETIVO: Avaliar a capacidade de identificacao dos termos relacionados ao leite de vaca em rotulos de produtos industrializados por familiares de pacientes com alergia a bebida. METODOS: Estudo transversal, descritivo, baseado em entrevista com familiares de pacientes. Inicialmente, aplicou-se um questionario sobre o habito de leitura de rotulos e identificacao de termos relacionados ao leite e, posteriormente, apresentaram-se rotulos de 12 produtos industrializados para que os familiares decidissem sobre a sua exclusao da dieta do paciente. RESULTADOS: Dos 52 entrevistados, 80,8% eram maes e 79,0% apresentavam nivel medio ou superior de escolaridade. A mediana do tempo em seguimento ja com orientacao para dieta de exclusao era de dois anos e sete meses (tres meses a 17 anos e seis meses). A leitura habitual de rotulos de alimentos, medicamentos e cosmeticos foi relatada por 57,7%, 59,6% e 46,2% dos familiares, respectivamente. Entre as reacoes alergicas ocorridas no seguimento, 39,5% foram relacionadas a erros na leitura de rotulos. Lactose, caseina e caseinato foram os termos identificados por 92,3%, 38,5% e 23,1% dos familiares, respectivamente. Lactato foi interpretado como presenca de leite de vaca por 51,9% dos entrevistados. Na segunda etapa, os familiares identificaram a lactose (55,8%), a caseina (26,9%) e o caseinato (5,8%) como substâncias relacionadas ao leite. CONCLUSOES: Constatou-se deficiente compreensao e identificacao, por parte dos pais, dos termos relacionados ao leite apesar das orientacoes recebidas. E fundamental a adequacao da rotulagem e a adocao de novas estrategias para orientacao da leitura de rotulos, possibilitando a busca e a identificacao de produtos que contenham leite de vaca.OBJECTIVE: To evaluate the ability of relatives of patients with cows milk allergy to identify terms related to cows milk on labels of manufactured products. METHODS: Cross-sectional descriptive study based on interviews with relatives of patients with cows milk allergy. Initially, a questionnaire about the habit of reading labels and the identification of terms related to cows milk was applied. Next, 12 original labels of manufactured products were shown to the interviewees so that they could decide whether to exclude or not those products from the patients diet. RESULTS: Of the 52 interviewees, 80.8% were mothers and 79.0% had at least 8 years of schooling. The median time of follow-up after receiving information about exclusion diet was 2 years and 7 months (from 3 months to 17 years and 6 months). The habit of reading labels of foods, drugs and cosmetics was reported by 57.7, 59.6, and 46.2% of the relatives, respectively. Among the allergic reactions during follow-up, 39.5% were related to mistakes when reading labels. Lactose, casein, and caseinate were the terms identified by 92.3, 38.5, and 23.1% of the family members, respectively. Lactate was interpreted as presence of cows milk by 51.9% of the interviewees. During the second phase of the study, family members identified lactose (55.8%), casein (26.9%) and caseinate (5.8%) as related to cows milk. CONCLUSION: There was a deficient understanding and identification of cows milk-related terms in spite of previous counseling. It is important to improve labels and to establish new strategies that allow lay people to identify labels of products containing cows milk.

Baked milk tolerant patient: Is there any special feature?

BACKGROUND Determining whether patients with cows milk allergy (CMA) can tolerate foods produced with baked milk could provide a better quality of life, a better prognosis, and an option for desensitization. OBJECTIVES The aim of this study was to identify which patients over four years of age with persistent CMA could tolerate baked milk, to compare the clinical and laboratory characteristics of reactive and non-reactive groups and to describe their clinical evolution. MATERIALS AND METHODS A cross-sectional study was conducted (January/13 to November/14) that included all the patients followed at a food allergy center who met the inclusion criteria. The patients underwent an oral food challenge (OFC) with a muffin (2.8g of cows milk protein). To exclude cows milk (CM) tolerance, the patients were subsequently challenged with unheated CM. RESULTS Thirty patients met all the inclusion criteria. Fourteen patients (46.7%) were considered non-reactive to baked milk and reactive to unheated CM. When the groups that were reactive and non-reactive to baked milk were compared, no statistically significant differences in clinical features were found. The prick test for α-lactalbumin (p=0.01) and casein (p=0.004) and the serum specific IgE for casein (p=0.05) presented statistical differences. After one year, none of the patients who were reactive to baked milk were ingesting CM, while 28% of the tolerant patients were consuming fresh CM (p=0.037). CONCLUSIONS Baked milk can be tolerated by patients with CMA, especially those with lower levels of casein and α-lactalbumin. This option can improve quality of life and accelerate tolerance.

Cow's milk allergy: Evaluating tolerance through skin-prick test.

Objective: To evaluate the wheal diameter in allergy skin-prick tests (SPT) with cows milk extract (CM) comparing tolerant and persistent patients. Method: A retrospective cohort study involving database analysis of children with diagnosis of cows milk protein allergy (CMPA) mediated by immunoglobulin E in a specialized outpatient clinic that regularly performed SPT between January 2000 and July 2015. Patients were allocated into two groups: tolerant or persistent. Comparisons were made at diagnosis and over time between tolerant and persistent patients using Fishers, Mann-Whitney or Wilcoxon tests and significance level at 5%. Results: After applying inclusion and exclusion criteria, the sample includes 44 patients (29 tolerant and 15 who persisted with CMPA). In the tolerant group, the medians of SPT were: 6 mm at diagnosis and 2 mm at the development of tolerance; a significant difference (p<0.0001) was found. In the persistent group, the median SPT at diagnosis was 7 mm, while in the last SPT it was 5 mm, with no statistical difference (p=0.173). The comparison of medians in the last SPT between groups was significant (p=0.001), with a reduction greater than 50% in SPT in the tolerant group. Conclusion: Serial SPTs were useful for diagnosis, and a decrease higher than 50% in diameter can indicate the moment to perform oral food challenge (OFC) tests, helping to detect tolerance in CMPA.

Difficulties of caregivers of cow's milk allergy patients in understanding the labeling of processed products

Methods Cross-sectional and descriptive study was carried out with CMA patient’s caregivers in follow-up at a pediatric reference center for FA. All of them were previously instructed about labels. This study included a questionnaire about the knowledge regarding the labels reading. Caregivers evaluated 20 labels (15 of foods, 3 of medicines and 2 of cosmetics) and should decide if the product was safe and the reason it can or not be offered to the patients. 15/20 contained words meaning milk protein. Results were expressed in number of labels reading (20 labels/caregivers)

Evaluating the role of clinical history and laboratorial tests in IgE mediated cow's milk allergy diagnosis

Background IgE mediated cow’s milk allergy (CMA) is a frequent disease in pediatric population, and challenge tests are considered gold standard in its diagnosis, although its use is limited in clinical practice. An appropriated anamnesis and laboratorial analysis are the most frequent and feasible used tools. The aim of this study was to evaluate the role of these practices in IgE mediated CMA diagnosis.

Tolerance to baked milk in Brazilian children with persistent cow’s milk allergy

Methods Patients with cow s milk allergy, over 4 years-old, were submitted to oral challenge with baked milk, from January to November, 2013, at Universidade de Sao Paulo, Brazil. The tested product was a muffin that contained 2,8 g milk protein and was baked at 350° F in an oven for 30 minutes. The challenge was made under physician supervision and at the first sign of allergy reaction it was discontinued, and the patient received the proper medical assistance.

Oral food desensitisation: are the patients safe after the end of protocol?

Desensitization protocols are increasing in food allergy centers and a higher number of patients submitted to these protocols have been showing a higher number of adverse events even after well succeed procedure. The aim of this study is to describe adverse reactions after cows milk desensitization.