Food protein-induced allergic proctocolitis may have distinct phenotypes.

BACKGROUND: Food protein-induced allergic proctocolitis (FPIAP) is a non-immunoglobulin E (IgE)-mediated food allergy, which presents with bloody mucoid stool in infants. Although IgE-mediated allergy and sensitizations to offending foods have been described in other non-IgE-mediated food allergies, it has not been investigated in FPIAP. OBJECTIVE: To investigate IgE-mediated allergy and sensitization to offending foods in FPIAP. METHODS: Patients (n = 204) were retrospectively recruited and grouped as FPIAP (n = 180; FPIAP with or without the symptoms of IgE-mediated food hypersensitivity to offending and nonoffending foods at initial consultation), FPIAP-IgE sensitization to offending foods (n = 17), and FPIAP-transition to IgE-mediated allergy to offending foods (n = 7). The study was performed in accordance with the protocol approved by the local ethical committee of the Hacettepe University. RESULTS: The median age of onset of symptoms and the development of tolerance was 2 months (interquartile range [IQR], 1.0-3.0) and 12 months (IQR, 10.0-14.0), respectively, and of the patients with skin prick test or serum specific IgE tests (n = 196), 38 (19.4%) had evidence of IgE sensitization to offending foods at the initial consultation or during follow-up; 17 (8.6%) had IgE sensitization, 7 (3.6%) indicated a transition to IgE-mediated allergy to FPIAP-induced foods. The median age of tolerance development of the FPIAP-transition group (19 months, IQR, 18.0-29.0) was significantly later than that of the FPIAP group (11 months, IQR, 10.0-14.0; P < .001) and the FPIAP-IgE sensitization group (11.0 months, IQR, 9.5-12.0; P < .001). Tolerance was observed within the study period in almost all the patients. CONCLUSION: Children with FPIAP may have sensitization or develop IgE-mediated allergy over time to offending foods. In addition, IgE sensitization in FPIAP does not have an unfavorable effect on tolerance development; however, the transition to an IgE-mediated phenotype may delay tolerance for a brief time.

Tolerance development in food protein-induced allergic proctocolitis: Single centre experience.

BACKGROUND: Food protein-induced allergic proctocolitis (FPIAP) is characterised by inflammation of the distal colon in response to one or more food proteins. It is a benign condition of bloody stools in a well-appearing infant, with usual onset between one and four weeks of age. OBJECTIVE: Our objective was to examine the clinical properties of patients with FPIAP, tolerance development time as well as the risk factors that affect tolerance development. METHODS: The clinical symptoms, offending factors, laboratory findings, methods used in the diagnosis and tolerance development for 77 patients followed in the Paediatric Allergy and Gastroenterology Clinics with the diagnosis of FPIAP during January 2010-January 2015 were examined in our retrospective cross-sectional study. RESULTS: The starting age of the symptoms was 3.3±4.7 months (0-36). Milk was found as the offending substance for 78% of the patients, milk and egg for 13% and egg for 5%. Mean tolerance development time of the patients was 14.7±11.9 months (3-66 months). Tolerance developed before the age of one year in 40% of the patients. Tolerance developed between the age of 1-2 years in 27%, between the age of 2-3 years in 9% and after the age of 3 years in 5% of the patients. CONCLUSIONS: Smaller onset age and onset of symptoms during breastfeeding were found associated with early tolerance development. In the majority of the patients, FPIAP resolves before the age of one year, however in some of the patients this duration may be much longer.

Food Protein-Induced Enterocolitis Syndrome, Allergic Proctocolitis, and Enteropathy.

Food protein-induced enterocolitis (FPIES), allergic proctocolitis (FPIAP), and enteropathy (FPE) are among a number of immune-mediated reactions to food that are thought to occur primarily via non-IgE-mediated pathways. All three are typically present in infancy and are triggered most commonly by cow's milk protein. The usual presenting features are vomiting with lethargy and dehydration in FPIES; bloody and mucous stools in FPIAP; and diarrhea with malabsorption and failure to thrive in FPE. Diagnosis is based on convincing history and resolution of symptoms with food avoidance; confirmatory diagnostic testing other than food challenge is lacking. The mainstay of management is avoidance of the suspected inciting food, with interval challenge to assess for resolution, which usually occurs in the first years of life. Studies published in the past few years clarify common presenting features, report additional culprit foods, address potential biomarkers, and suggest new management strategies.

Characteristics and Prognosis of Allergic Proctocolitis in Infants.

OBJECTIVES: The dietary protein proctocolitis, also known as allergic proctocolitis (AP), is characterized by the presence of mucoid, frothy, and bloody stools in an otherwise healthy infant. The aim of this study was to describe a group of children with AP, diagnosed according to the criterion-standard method, food challenge to provide clinicians with more information on typical presentation, and an overview on nutritional management strategies and prognosis. METHODS: We collected data on infants with AP in our allergy and gastroenterology outpatient clinics. Any other conditions that may cause bloody diarrhea were ruled out. Skin prick tests and atopy patch tests were performed for diagnosis, and patients were studied for resolution. To the patients whose rectal bleeding did not recover with oligoantigenic maternal diet in addition to amino acid-based formula, endoscopic evaluation was performed to confirm the diagnosis and to exclude other reasons of rectal bleeding. RESULTS: Sixty patients were diagnosed as having AP. The age of onset was 1.7 ±â€Š1.32 months. All of the patients were triggered by milk, 6.6% with milk and egg, 3.3% with milk and chicken, 1.7% with milk and wheat, 1.7% with milk and potato, and 3.3% had multiple food allergy. 53.3% (n = 32) acquired tolerance by age 1, 25.0% (n = 15) by 2 years, 5% (n = 3) by 3, and 1.7% (n = 1) by 4 years. CONCLUSIONS: Milk was a triggering factor for all of the patients. Resolution of AP is usually within 1 year but symptoms of some patients may continue even longer. An extension of the follow-up period is required according to our study.

Food protein-induced enterocolitis syndrome and allergic proctocolitis.

Non-IgE-mediated food allergic disorders account for up to 40% of milk protein allergy in infants and young children. We aim to review the recent literature and to provide an update on diagnosis and management of food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP). The peer-reviewed articles indexed in PubMed have been reviewed. FPIES manifests in infants as profuse, repetitive vomiting and lethargy, often with diarrhea, leading to acute dehydration, or weight loss and failure to thrive, in chronic form. FPIES is caused most commonly by cow's milk (CM) and soy proteins; rice, oat, and other solid foods may also trigger FPIES. FPIES rarely occurs in the exclusively breastfed infants. FPIES is underrecognized; children are often mismanaged as having acute viral gastrointestinal illness, sepsis, or surgical disease, delaying diagnosis of FPIES for many months. Approximately 25% of children with FPIES develop food-specific IgE antibodies and some transition to immediate food allergy; IgE positivity is associated with a more protracted course. FPIES is a self-limiting condition, with most cases resolving by age three to five years. Ondansetron may be helpful in managing acute FPIES. FPIAP is a benign condition of bloody stools in a well-appearing infant, with usual onset between one and four weeks of age. Up to 60% of cases occur in exclusively breastfed infants and resolve with maternal elimination of CM and soy proteins. The majority of cases resolve by age 12 months. FPIES may transition to IgE-mediated food allergy in some patients; IgE positivity to the FPIES food is a marker of a more persistent disease. FPIAP is benign and resolves by age 12 months in most patients.

Gastrointestinal food allergy in infants.

Food allergies are classified into three types, "IgE-mediated," "combined IgE- and cell-mediated" and "cell-mediated/non-IgE-mediated," depending on the involvement of IgE in their pathogenesis. Patients who develop predominantly cutaneous and/or respiratory symptoms belong to the IgE-mediated food allergy type. On the other hand, patients with gastrointestinal food allergy (GI allergy) usually develop gastrointestinal symptoms several hours after ingestion of offending foods; they belong to the cell-mediated/non-IgE-mediated or combined IgE- and cell-mediated food allergy types. GI allergies are also classified into a number of different clinical entities: food protein-induced enterocolitis syndrome (FPIES), food protein-induced proctocolitis (FPIP), food protein-induced enteropathy (Enteropathy) and eosinophilic gastrointestinal disorders (EGID). In the case of IgE-mediated food allergy, the diagnostic approaches and pathogenic mechanisms are well characterized. In contrast, the diagnostic approaches and pathogenic mechanisms of GI allergy remain mostly unclear. In this review, we summarized each type of GI allergy in regard to its historical background and updated clinical features, offending foods, etiology, diagnosis, examinations, treatment and pathogenesis. There are still many problems, especially in regard to the diagnostic approaches for GI allergy, that are closely associated with the definition of each disease. In addition, there are a number of unresolved issues regarding the pathogenic mechanisms of GI allergy that need further study and elucidation. Therefore, we discussed some of the diagnostic and research issues for GI allergy that need further investigation.

Intestinal microbiota and secretory immunoglobulin A in feces of exclusively breast-fed infants with blood-streaked stools.

Episodes of blood-streaked stools are not uncommon in exclusively breast-fed infants under 6 months of age. Such bleeding is thought to be associated with food protein-induced proctocolitis, however the pathomechanism remains unclear. The aim of this study was to investigate intestinal microbiota and secretory immunoglobulin A in the feces of exclusively breast-fed infants with blood-streaked stools. Fecal specimens from 15 full-term infants with blood-streaked stools and 15 breast-fed healthy infants were studied and the results compared. All infants had been delivered vaginally and exclusively breast-fed. The fecal microbiota were investigated by phylogenetic analysis combined with culture methods for some bacterial species, and feces were assessed for the presence of fecal secretory immunoglobulin A by enzyme-linked immunosorbent assay. Phylogenetic cluster analysis revealed four major clusters of fecal bacteria, cluster A being found only in healthy infants. The Bacteroides fragilis group was observed more frequently in controls than in patients (P < 0.05). In the controls, the predominant species belonging to the Enterobacteriaceae group was Escherichia coli, whereas in the patients it was Klebsiella (P < 0.05). Concentrations of secretory immunoglobulin A were high in one third of the healthy controls. In conclusion, the pathomechanism of rectal bleeding in exclusively breast-fed infants may be related to differences in the composition of their intestinal flora.

Allergic proctocolitis refractory to maternal hypoallergenic diet in exclusively breast-fed infants: a clinical observation.

BACKGROUND: Allergic proctocolitis (APC) in exclusively breast-fed infants is caused by food proteins, deriving from maternal diet, transferred through lactation. In most cases a maternal cow milk-free diet leads to a prompt resolution of rectal bleeding, while in some patients a multiple food allergy can occur. The aim of this study was to assess whether the atopy patch test (APT) could be helpful to identify this subgroup of patients requiring to discontinue breast-feeding due to polisensitization. Additionally, we assessed the efficacy of an amino acid-based formula (AAF) when multiple food allergy is suspected. amino acid-based formula METHODS: We have prospectively enrolled 14 exclusively breast-fed infants with APC refractory to maternal allergen avoidance. The diagnosis was confirmed by endoscopy with biopsies. Skin prick tests and serum specific IgE for common foods, together with APTs for common foods plus breast milk, were performed. After a 1 month therapy of an AAF all patients underwent a follow-up rectosigmoidoscopy. RESULTS: Prick tests and serum specific IgE were negative. APTs were positive in 100% infants, with a multiple positivity in 50%. Sensitization was found for breast milk in 100%, cow's milk (50%), soy (28%), egg (21%), rice (14%), wheat (7%). Follow-up rectosigmoidoscopy confirmed the remission of APC in all infants. CONCLUSIONS: These data suggest that APT might become a useful tool to identify subgroups of infants with multiple gastrointestinal food allergy involving a delayed immunogenic mechanism, with the aim to avoid unnecessary maternal dietary restrictions before discontinuing breast-feeding.

Atopy Patch Test in the Diagnosis of Food Allergens in Infants with Allergic Proctocolitis Compared with Elimination/Introduction C.

Allergic proctocolitis is a cell-dependent food allergy that is present in both breast and formula-fed infants. The presence of blood with different amounts in the stool is the main manifestation of the disease. Different results have been published on the accuracy and specificity of the atopic patch test (APT). The purpose of this study was to evaluate the results of the APT and compare them with those obtained in the food elimination/introduction (E/I) challenge, as the gold standard of confirming the allergy. Twenty-eight patients (18 boys, 10 girls, <1 year) with allergic proctocolitis were recruited in this study. The mean age of the disease onset and enrolling the study were 2.23±1.7 and 5.25±2.19 months, respectively. After performing APT with fresh foods, an E/I challenge was done in a patient with positive tests, and results were analyzed. APT was positive in 14/28 (50%) individuals. The most common foods detected by APT in all of the individuals were: milk (10/28), rice (5/28), soy (4/28), and egg white (4/28), while in E/I challenge in the APT-positive individuals were: milk (8/10), rice (3/5), egg white (1/4), and soy (0/4). APT was positive in half of the infants<1 year with allergic proctocolitis and there was no significant correlation between the APT results and the E/I challenge test for all foods. Comparing the results of APT and E/I challenge methods showed a convergence between the milk and rice sensitivity, thus we suppose APT to be a useful tool in identifying these two allergens in cell-mediated food allergies like allergic proctocolitis.

Non-IgE-Mediated Gastrointestinal Food Allergies in Children: An Update.

Non-immunoglobulin E-mediated gastrointestinal food allergic disorders (non-IgE-GI-FA) include food protein-induced enterocolitis syndrome (FPIES), food protein-induced enteropathy (FPE) and food protein-induced allergic proctocolitis (FPIAP), which present with symptoms of variable severity, affecting the gastrointestinal tract in response to specific dietary antigens. The diagnosis of non-IgE-GI-FA is made clinically, and relies on a constellation of typical symptoms that improve upon removal of the culprit food. When possible, food reintroduction should be attempted, with the documentation of symptoms relapse to establish a conclusive diagnosis. Management includes dietary avoidance, nutritional counselling, and supportive measures in the case of accidental exposure. The prognosis is generally favorable, with the majority of cases resolved before school age. Serial follow-up to establish whether the acquisition of tolerance has occurred is therefore essential in order to avoid unnecessary food restriction and potential consequent nutritional deficiencies. The purpose of this review is to delineate the distinctive clinical features of non-IgE-mediated food allergies presenting with gastrointestinal symptomatology, to summarize our current understanding of the pathogenesis driving these diseases, to discuss recent findings, and to address currents gaps in the knowledge, to guide future management opportunities.

Unique features of non-IgE-mediated gastrointestinal food allergy during infancy in Japan.

PURPOSE OF REVIEW: An increase in incidence of unique phenotypic non-IgE-mediated gastrointestinal food allergies (non-IgE GIFAs) has occurred in Japan ahead of Western countries. There are differences in clinical features of non-IgE GIFAs in Western and Japanese patients. As this phenotype has now come to be recognized internationally, we describe it in this review. RECENT FINDINGS: A large number of Japanese patients with non-IgE GIFAs present with vomiting accompanied by bloody stool, putting them between food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis. Some neonates and early infants with non-IgE GIFAs who present with fever and elevated C-reactive protein have symptoms consistent with severe systemic bacterial infections (e.g., sepsis). Some of these cases have now been defined in international guidelines as chronic FPIES. Eosinophils might be involved in the inflammatory process observed. The incidence of FPIES and food protein-induced allergic proctocolitis is increasing in Western countries and likely worldwide, after it has increased in Japan. SUMMARY: The phenotype observed in Japan shows distinct clinical features compared with the classical phenotype, that is, increased levels of eosinophils, suggestive of 'eosinophilic shift' alongside symptomatic differences, making it difficult to categorize.

Microbiota in non-IgE-mediated food allergy.

PURPOSE OF REVIEW: To perform a nonsystematic review of the literature on the microbiota in the different types of non-IgE-mediated food allergy. RECENT FINDINGS: The commonest non-IgE-mediated disorders managed by allergists include: eosinophilic esophagitis, food protein-induced enteropathy, food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis. The review of the literature describes how at phylum level we observe an increase of Proteobacteria in eosinophilic esophagitis esophageal microbiota and in food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis gut microbiota, while we observe an increase of Bacteroidetes in healthy controls. Several studies endorse the concept that a bloom of Proteobacteria in the gut reflects dysbiosis or an unstable gut microbial community structure. In several studies, the type of diet, the use of probiotics and in a single experience the use of fecal microbiota transplantation has produced significant variations of the microbiota. SUMMARY: Genetic factors alone cannot account for the rapid rise in food allergy prevalence and the microbiome might be contributing to allergy risk. Our review showed that common features of the pathological microbiota among different types of non-IgE-mediated food allergy can be identified. These evidences suggest a possible role of the microbiota in the pathogenesis and non-IgE-mediated food allergies and the need to understand the effects of its modulation on the disorders themselves.

Markers of inflammation and tolerance development in allergic proctocolitis. / Marcadores de inflamación y desarrollo de tolerancia en la proctocolitis alérgica.

BACKGROUND: Today, as a result of an increase in the frequency of food protein-induced allergic proctocolitis (FPIAP), there is a need for studies not only to enlighten the pathophysiology of the disease but also to determine simple, non-invasive markers in both diagnosis, and evaluation of the development of tolerance. No study has been found in the literature about the place of neutrophil/lymphocyte ratio (NLR) and mean platelet volume (MPV), which are easy to calculate and non-invasive markers. OBJECTIVES: The purpose is to determine the relation between NLR and MPV with the diagnosis and development of tolerance in children with FPIAP. METHODS: In this retrospective cross-sectional study, clinical, demographic symptoms and laboratory findings of patients, monitored with FPIAP diagnosis in allergy and gastroenterology clinics, were acquired from the patient record system. Hemogram values at the time of diagnosis were compared with the values of healthy children of the same age and gender. RESULTS: Among 59 patients diagnosed with FPIAP, males constitute 47.4% and females constitute 52.6%. MPV and platelet crit (PCT) values were significantly high when compared to the control group (n: 67) in FPIAP cases (p < 0.001). Also, MPV and PCT values were significantly high in non-tolerance developing cases when compared to developing ones (p= 0.01). CONCLUSIONS: Contrary to NLR, MPV and PCT values have been considered to be good markers in predicting prognosis in cases with FPIAP since they are quick, cost effective and easy to calculate.

ANTECEDENTES: Con el incremento de la proctocolitis alérgica inducida por proteínas de la dieta (PAIPD), son necesarios estudios que aclaren su fisiopatología y determinar marcadores no invasivos y sencillos para el diagnóstico y la evaluación del desarrollo de tolerancia. No hallamos estudios publicados sobre la función del índice de neutrófilos/linfocitos (INL) y el volumen plaquetario medio (VPM), que son marcadores no invasivos fácilmente medibles, en pacientes con PAIPD. OBJETIVOS: Determinar la relación entre el INL y el VPM con el diagnóstico y desarrollo de tolerancia en niños con PAIPD. MÉTODOS: Estudio transversal retrospectivo, los datos se obtuvieron del sistema de registros médicos, los síntomas y los resultados de laboratorio de los pacientes con diagnóstico de PAIPD fueron controlados en los consultorios de alergia y gastroenterología. Se compararon valores del hemograma al momento del diagnóstico con el grupo de niños sanos de edad y sexo similares. RESULTADOS: Entre los 59 pacientes con diagnóstico de PAIPD, los varones representaron el 47,4% y las niñas, el 52,6%. El VPM y el volumen plaquetario relativo (VPR) eran significativamente más altos entre los pacientes con PAIPD en comparación con el grupo de referencia (n: 67) (p < 0,001). Asimismo, VPM y el VPR fueron significativamente elevados en pacientes que no desarrollaron tolerancia comparados con los que la desarrollaron (p= 0,01). Con el INL no hubo diferencias entre los grupos. CONCLUSIONES: El VPM y el VPR se consideraron marcadores adecuados para predecir el pronóstico de los pacientes con PAIPD dado que son rápidos, costo-efectivos y fáciles de medir.

Food Protein Induced Proctocolitis: A Benign Condition with an Obscure Immunologic Mechanism.

Food protein-induced proctocolitis (FPIP) is the most common colonic manifestation of food allergy in infants, accounting for up to 60% of exclusively breast-fed children. The causative foods derived from the mother's diet, which are then excreted in her milk. The suggested risk factors for the development of FPIP are an immature immune system, altered intestinal permeability and other factors that activate local immune function, such as genetic susceptibility in combination with particularly sensitizing foods. FPIP is an enhanced immune responsiveness of some infants to very small amounts of food antigens, inducing an inflammatory mucosal response, mediated by T cells.

Gastrointestinal food allergy in Ghanaian children: a case series.

BACKGROUND: Food allergy is an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food. Food allergies are classified into three types: Ig(immunoglobulin)E mediated, mixed IgE and cell mediated and cell-mediated non IgE mediated. Gastrointestinal (GIT) food allergy has classically encompassed a number of different clinical entities: food protein-induced enterocolitis syndrome (FPIES), food protein-induced proctocolitis (FPIP), food protein-induced enteropathy and eosinophilic gastrointestinal disorders (EGID). CASE PRESENTATIONS: These are 5 cases of infants and toddlers who presented with various features of gastrointestinal food allergies, the commonest of which is lower gastrointestinal bleed. Two infants on exclusive breast feeding, presented with lower gastrointestinal bleeding and these resolved with maternal dietary milk and all dairy elimination. The third infant had rectal bleeding at age 6 months after the introduction of infant formula. The bleeding and eczema resolved with the introduction of hydrolyzed formula. One of the toddlers presented with severe eczema and malnutrition which improved with 6 food elimination. The last case had massive lower gastrointestinal bleed which resulted in hemicolectomy with no improvement until dietary elimination was instituted. CONCLUSION: Gastrointestinal food allergy is not uncommon in children in Ghana. A high index of suspicion is required to make the right diagnosis, to minimize morbidity and unnecessary therapy. SOURCE OF FUNDING: None.

Paediatric non-IgE mediated food allergy: guide for practitioners.

AIM: Food avoidance in children is increasingly common due to concerns about allergy. We aim to review the current literature on paediatric non-IgE mediated food allergy including what is known about pathophysiology, diagnosis, management and prognosis of common and severe presentations. Considerations regarding appropriate formula selection are also presented. METHODS: Common non-IgE mediated conditions were searched through common medical databases. Thorough review of available literature was then synthesised and critically appraised. RESULTS: Current understanding of immunological mechanisms of most non-IgE mediated conditions remains elusive. Most conditions are outgrown in childhood and have a good prognosis. Dietary modification for some conditions is important to ensure safety. They are not recommended in all situations due to potentially harmful consequences. CONCLUSION: Assessment of children with concerns regarding non-IgE mediated conditions requires a thorough history and is generally not supported by reliable diagnostic tests. Caution is warranted when advising families to undertake dietary exclusions unless well supported by the evidence and ensuring benefits outweigh any potential harm.