Non-IgE-Mediated Gastrointestinal Food Protein-Induced Allergic Disorders. Clinical Perspectives and Analytical Approaches

Non-IgE-mediated gastrointestinal food allergy (non-IgE-GI-FA) is the name given to a series of pathologies whose main entities are food protein-induced allergic proctocolitis (FPIAP), food protein-induced enteropathy (FPE), and food protein-induced enterocolitis syndrome (FPIES). These are more uncommon than IgE-mediated food allergies, their mechanisms remain largely unknown, and their diagnosis is mainly done by clinical history, due to the lack of specific biomarkers. In this review, we present the latest advances found in the literature about clinical aspects, the current diagnosis, and treatment options of non-IgE-GI-FAs. We discuss the use of animal models, the analysis of gut microbiota, omics techniques, and fecal proteins with a focus on understanding the pathophysiological mechanisms of these pathologies and obtaining possible diagnostic and/or prognostic biomarkers. Finally, we discuss the unmet needs that researchers should tackle to advance in the knowledge of these barely explored pathologies.

The Challenge of Home Allergen Re-introductions Using the Ladder Approach in Children With Non-IgE Mediated Gastrointestinal Food Allergy

Background: Oral food challenges remain the most reliable method for allergy confirmation. Although consensus guidelines have been published to unify Immunoglobulin E (IgE)-mediated challenges, this does not exist for non-IgE mediated gastrointestinal allergies outside of Food Protein Induced Enterocolitis Syndrome. We therefore set out to establish the use of home introduction protocols (HIP) for confirmation of food allergy for milk, soya, egg and wheat using a ladder approach in children with non-IgE mediated allergy.Materials and Methods: Patients with suspected non-IgE mediated gastrointestinal allergies (0–16 years) were recruited following symptom improvement on an elimination diet. All children had skin prick or specific IgE tests to rule out IgE-mediated allergies prior to suggestion the HIP. Number of trials and outcome was documented. HIPs were developed using a published ladder approach for cow's milk as baseline and final dose was calculated based on guidelines for food protein induced enterocolitis syndrome and portions for age from the National Diet and Nutrition Survey. First foods were baked/highly processed and every 4th day patients moved to a more unprocessed/unheated food.Results: From 131 recruited patients, 117 (89.3%) followed the HIP for food allergens. No adverse events were documented. In more than 50% of cases one attempt at the HIP was sufficient to establish allergy status, but many required 2–5 attempts before the outcome was clear. About half of the children were fully tolerant to foods they initially eliminated: 36, 26 and 30% were partially tolerant to milk, soya, and egg and only 15% achieved partial tolerance to wheat. Wheat was the allergen introduced earliest, followed by soya, cow's milk and egg.Conclusions: This study indicates that home HIPs are safe in non-IgE mediated gastrointestinal food allergy and that the ladder approach may be useful in re-introducing allergens in children at home with non-IgE mediated gastrointestinal allergies. From this study we can also conclude that tolerance to processed/baked allergens was observed in many children. Further studies should be performed on the HIP and ideally reintroduction should occur pre-defined time intervals.

Analysis of the content of I-FABP in urine and blood serum in children with gastrointestinal food allergy

Introduction. Protein-induced enteropathy is one of the common manifestations of gastrointestinal food allergy in young children. The search of non-invasive methods for intestine estimation is especially relevant for early diagnosis and timely prevention of exacerbation.The aim of the study was to determine the serum and urinal levels of the intestinal fraction of the protein binding fatty acids in children with protein-induced enteropathy and to evaluate their clinical and diagnostic significance.Materials and methods. It was examined 36 children with protein-induced enteropathy aged 1.5 months to 1 year and 20 healthy children (control group). All patients underwent esophagogastroenteroscopy with morphological examination of biopsy specimens for differential diagnosis with congenital gastrointestinal diseases. The Cow’s Milk-related Symptom Score (CoMMiS) was used to evaluate clinical symptoms. The intestinal fraction of a fatty acid binding protein was determined for all children in blood serum, urine by enzyme- linked immunosorbent analysis.Results. It was found the increase its serum level (125.20 ± 23.79 pg / ml), and urinal level (0.164 ± 0.031 pkg / ml) compared with the control group (19.21 ± 4.94 pg / ml, 00.039 ± 4.62 pkg / ml, respectively, p < 0.05). There were found direct strong correlations between the severity of gastrointestinal manifestations and its serum and urine level (p < 0.05).Discussion. Epithelial barrier damage provides an increased penetration of intact food allergens. It plays a key role in allergic sensitization, and it is the first pathogenetic link of allergic inflammation in most cases. A statistically significant I-FABP increased level in all studied biological fluids correlates with morphological changes in the children with protein-induced enteropathy, as well as with clinical symptoms of gastrointestinal tract lesions. That confirms its high informational value for an indirect assessment of the state of the intestinal barrier.Conclusions. Thus, an increase in serum and urinal I-FABP levels in children with protein-induced enteropathy confirms the clinical and diagnostic significance of determining this biomarker in all biological fluids. Its high sensitivity and specificity of determination in urine are promising for use in pediatric practice.

Vitamin D Status in Young Children with Gastrointestinal Manifestations of Food Allergy

Aim is to investigate vitamin D status in young children with gastrointestinal manifestations of food allergy. Materials and methods. 30 children aged 4 months to 3 years with enterocolitis syndrome induced by dietary proteins were examined. General clinical examination included assessment of physical and somatic status (body weight, height, sleep, appetite), condition of the skin and mucous membranes, skeletal system, internal organs, nature and frequency of bowel movements. To assess vitamin D status in children with gastrointestinal allergy, we used quantitative determination of the concentration of 25 (OH) D (25-hydroxycalciferol) in blood serum using the Architect 2000sr I «ABBOT» immunochemical assay (USA). Complex treatment of the underlying disease involved correction of vitamin D deficiency using the drug «Aquadetrim» containing aqueous solution of colecalciferol for oral administration at a dose of 2000 U/day for 1 month. The comparison group included 20 children aged 12–24 months with non$aggravated individual and family history of allergies, who had functional diseases of the gastrointestinal tract (functional constipation, functional diarrhea, flatulence syndrome) and did not take vitamin D preparations. The data of clinical and laboratory trials were processed by the methods of mathematical statistics adopted in biology and medicine. The reliability of differences in comparative indicators was determined using the Student's t-test and nominal data using Fisher's exact test. Results and conclusions. Based on the results of assessing the vitamin D status in young children with gastrointestinal food allergy by determining serum concentrations of 25-hydroxycalciferol, vitamin D deficiency was established in 86.7% of patients — with average of 26.39 (21.08–29.98) ng/ml. Administration of aqueous solution of colecalciferol (Aquadetrim) at a dose of 2000 IU per day for 1 month to children with gastrointestinal food allergy helped to normalize the concentration of 25-hydroxycalciferol in blood serum of 92.3% of children. Against the background of the use of the vitamin D preparation (Aquadetrim), there were no cases of deterioration of gastrointestinal and skin manifestations of the disease; «Akvadetrim» preparation was well tolerated, without side reactions. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of these Institutes. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: gastrointestinal manifestations of food allergy, young children, vitamin D.

Obstructive Fecalomas in an Infant Treated with Successful Endoscopic Disimpaction

A fecaloma is a mass of accumulated feces with a consistency much harder than that of a fecal impaction. It is most frequently observed in the rectum and sigmoid area, and associated complications include colonic obstruction, ulceration, bleeding, and perforation. A one-year-old, previously healthy boy with no history of chronic constipation was admitted because of vomiting and abdominal distension. An abdominal computed tomography scan showed small and large bowel distension due to multiple obstructive fecalomas in the transverse colon. As the fecalomas could not be resolved by laxatives, enemas, or colonic lavage, endoscopic disimpaction under general anesthesia was attempted. Repeatedly shaving the fecalomas with biopsy forceps finally resulted in gradual fragmentation with subsequent passage. Gastrointestinal food allergy was later suggested as the cause because eosinophilic infiltration was found in a biopsy specimen of the colon wall. Endoscopic disimpaction is an effective treatment approach for addressing fecalomas to avoid more invasive surgical intervention.