Padronização de protocolos de provocação oral em crianças com reações de hipersensibilidades alimentares em um hospital público infantil do Brasil

Abstract

Introduction: In both IgE-mediated and non-IgE-mediated food allergy (FA), an oral food challenge (OFC) is required to assess immune tolerance to the food. Objectives: To evaluate the development of immune tolerance in children from southeastern Brazil with IgE-mediated and non-IgE-mediated FA (chronic food protein-induced enterocolitis syndrome – FPIES) to milk or egg, and to investigate tolerance to extensively heated (baked) milk or egg in children with IgE-mediated FA, using standardized OFC protocols. Methods: This thesis comprises a mixed-design investigation involving a convenience sample of children followed at a food allergy outpatient clinic in a Brazilian state capital. Three articles were developed, including children with IgE-mediated FA (Articles 1 and 3; descriptive studies) and non-IgE-mediated FA (Article 2; randomized cross-over clinical trial). In IgE-mediated FA, freeze-dried or baked food protein was administered in increasing doses in the hospital setting, whereas in non-IgE-mediated FA the calculated protein dose (0.3 g/kg) or placebo was added to the child’s usual food vehicle for home consumption. OFCs were based on international consensus guidelines. On the day of the OFC, clinical and anthropometric data were collected, followed by calculation and classification of weight-for-age, height-for-age, and BMI-for-age indices according to the 2006/2007 World Health Organization (WHO) growth standards. Descriptive analyses were performed, and the Shapiro–Wilk and chi-square tests were applied in all three articles. Receiver operating characteristic (ROC) curves were constructed for Articles 1 and 3 to identify the IgE cut-off point with the highest sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Results: Article 1: Seventy OFCs were performed (39 to milk, 31 to egg), with median ages at challenge of 27 (16–51) and 22 (15–43) months, and age at first symptoms of 5 (3–7) and 6 (68) months of life, respectively. OFCs were negative in 89.7% for milk at an IgE level of 1.4 KUA/L (sensitivity 75%, specificity 28.6%, PPV 10.7%, NPV 90.9%) and in 64.5% for egg at an IgE level of 1.1 KUA/L (sensitivity 90.9%, specificity 80.0%, PPV 71.4%, NPV 94.1%). From a nutritional standpoint, low height-for-age was observed in 15.4% and 3.2%, low weight-for-age in 7.7% and 6.5%, and risk of overweight in 10.3% and 9.7%, respectively. Nutritional status classification did not differ by sex, age at first symptom, or OFC outcome (p > 0.05). Article 2: Sixty-one OFCs to milk were performed; 63.9% of participants were male, with a median age of 19 months (13.0–28.0). First symptoms occurred at a mean age of 3 months (1.09.0). OFCs were negative in 83.6% of cases. Among positive challenges, none of the children required medical or hospital care. From a nutritional perspective, 18% had low height-for-age, 16.4% low weight-for-age, and 8.2% excess weight. Article 3: Forty-five OFCs were performed (25 to milk, 20 to egg), with median ages of 71 (50131) and 68 (42–92) months, and a significant difference in age at first symptoms of 4 (2–5) and 7 (6–9) months of life, respectively. OFCs were negative in 68% for milk at an IgE level of 13.9 KUA/L (sensitivity 75%, specificity 35.3%, PPV 35.3%, NPV 75%) and in 65% for egg at an IgE level of 16.8 KUA/L (sensitivity 85.7%, specificity 69.2%, PPV 60%, NPV 90%). From a nutritional standpoint, low height-for-age and low weight-for-age were found in 8% and 5%, thinness in 12% and 5%, and excess weight in 4% and 5%, respectively. In positive challenges, the most frequent symptoms—vomiting, urticaria, anaphylaxis, pruritus, rash, and wheezing—were controlled with immediate medical intervention. Conclusion: Standardization of OFCs made it possible to identify children who had developed immunological tolerance and could consume milk or egg, including in baked form, thereby allowing expansion of the diet and potential recovery of identified nutritional deficits. Future studies should prioritize, in addition to the clinical approach, the development of tests or biomarkers to determine the optimal timing for reintroducing foods into children’s diets.