Food Protein-induced Allergic Proctocolitis Research Articles

Pediatric Eosinophilic Gastrointestinal Disease: Perspectives and Pearls from the Allergy Clinic

Eosinophilic Gastrointestinal Diseases (EGID) are uncommon to rare gastrointestinal eosinophilic infiltrated clinicopathological conditions, ranging from the esophagus to the sigmoid colon. Outside of the near immediate newborn period, associated with milk or soy protein colitis ( Food protein-induced allergic proctocolitis) 1 the presence of exaggerated gastrointestinal eosinophilia is clinically relevant and has long-term concerns. In this review the separate clinical EGID conditions will be briefly reviewed, with added clinical pearls, based on an extensive Pediatric Allergy-Immunology experience.

Challenges and Pitfalls in the Diagnosis and Management of Non-IgE Cow’s Milk Protein Allergy: Two Cases

As the incidence of cow ’s milk protein allergy (CMPA) has increased in the last decades in both breastfed and formula fed infants, possible pitfalls in its diagnosis and management are also increasing. This is especially evident in non-IgE milk allergy due to the considerable delay between the appearance of clinical symptoms after ingestion of the allergen, and the non-specific gastrointestinal symptoms that characterize it. The misdiagnosis could often be combined with inappropriate use of either partially hydrolyzed or amino acid-based infant formula for the management of symptoms. The aim of the paper is to present two cases to illustrate common pitfalls in diagnosis and management of CMPA with divergent gastrointestinal syndrome manifestations: food protein-induced allergic proctocolitis and food protein-induced enterocolitis syndrome, in an effort to increase awareness of these conditions and to guide clinicians in day-to-day practice when facing suspected cases of CMPA. Int J Clin Pediatr. 2020;9(3):98-102 doi: https://doi.org/10.14740/ijcp375

Food Protein–Induced Enterocolitis Syndrome Food Challenges: Experience From a Large Referral Center

To describe experience with oral food challenges (OFCs) for food protein-induced enterocolitis syndrome (FPIES), using a protocol that includes ingestion of one-third of the goal food serving size with 4 hours of observation, followed by home titration to goal dose.A total of 119 subjects underwent 169 OFCs at Children’s Hospital of Philadelphia to 19 different foods between 2014 and 2017. Patients with food protein-induced allergic proctocolitis were excluded. Patients with intermittent food exposures and delayed emesis within 1 to 4 hours and/or diarrhea within 5 to 10 hours were classified as having acute FPIES. Patients with daily ingestion of the food with intermittent emesis, chronic diarrhea, poor weight gain, or malnutrition were classified as having chronic FPIES.This was a retrospective chart review. Data regarding age, sex, implicated foods, age of onset, and symptoms prompting food challenge were collected. OFC data were also collected, including age at the time of challenge, cumulative dose of food, outcome of challenge, timing to reaction, treatment of positive challenge results, disposition, and presence of a late reaction.Thirty OFCs (18%) resulted positive, with 17 (10%) resulting positive during the initial challenge and 13 (7.7%) during home dosing. Most reactions during initial OFC required intravenous fluids (IVFs). Two patients developed hypotension. In 139 OFCs (82%), patients tolerated both initial OFC and home dose titration. One hundred twenty six OFCs (75%) were performed in patients with a previous history of FPIES reaction to the index food, and 43 OFCs (25%) were performed to foods avoided as a precaution. In all positive OFC results, symptoms of acute FPIES reaction occurred at least 85 minutes after dosing. Of all OFCs performed, IVF was administered to 14 patients (7.1%), and ondansetron was administered to 12 patients (6.1%). The mean age of passing an OFC to milk, soy, and grain was lower than that of other solid foods. The mean age of passing an OFC to milk was 35 months, soy was 38.4 months, and grains were 35.7 months.This FPIES OFC protocol is safe. Early administration of IVFs may prevent the development of hypotension. It is difficult to stratify the risk of a severe or delayed reaction on the basis of patient characteristics. More data are needed to identify patients appropriate for home food introduction.Risk stratification based on patient histories is challenging. In the studied population, there was overlap of clinical features between patients who required IVFs and those who were able to orally rehydrate in the context of a positive OFC result. Data from this single-center referral center for FPIES are encouraging and suggest potential for home food reintroduction in older patients. Data regarding the mean age of successful reintroduction for various foods in this study may help to inform future studies.

Diagnosis and management of Non-IgE gastrointestinal allergies in breastfed infants-An EAACI Position Paper.

It is well-established that food proteins, such as egg, soya, cow's milk and wheat, are detectable in breastmilk for many hours or days after ingestion. Exposure to these proteins is important to the process of developing tolerance but can also sometimes elicit IgE-mediated and non-IgE-mediated allergic symptoms in breastfed infants. Non-IgE-mediated allergy, outside of food protein-induced allergic proctocolitis and eosinophilic oesophagitis, is not well understood, leading to variations in the diagnosis and management thereof. A primary objective of the European Academy for Allergy and Clinical Immunology is to support breastfeeding in all infants, including those with food allergies. A Task Force was established, to explore the clinical spectrum of non-IgE-mediated allergies, and part of its objectives was to establish diagnosis and management of non-IgE-mediated allergies in breastfed infants. Eight questions were formulated using the Patient, Intervention, Comparison, Outcome (PICO) system and Scottish Intercollegiate Guideline Network (SIGN) criteria for data inclusion, and consensus was achieved on practice points through the Delphi method. This publication aims to provide a comprehensive overview on this topic with practice points for healthcare professionals.

A Prospective Assessment of Food Protein-Induced Allergic Proctocolitis from the GMAP Healthy Infant Cohort

A Prospective Assessment of Food Protein-Induced Allergic Proctocolitis from the GMAP Healthy Infant Cohort

Markers of inflammation and tolerance development in allergic proctocolitis.

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. The purpose is to determine the relation between NLR and MPV with the diagnosis and development of tolerance in children with FPIAP. 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. 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). 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.

Estudio de validez diagnóstica de la prueba de hemorragia oculta fecal en lactantes con proctocolitis alérgica inducida por proteína alimentaria

Food protein-induced allergic proctocolitis (FPIAP) is the most frequent presenta tion of non-IgE mediated food allergy (FA). The diagnosis is made by oral food challenge, however, non-invasive diagnostic tests are not available. In Chile, the fecal occult blood test (FOBT) is fre quently used to confirm FPIAP, however, there are no studies that support this practice. To establish the diagnostic validity of FOBT in the evaluation of infants with FPIAP. Case-control study with prospective recruitment of infants with rectal bleeding and suspicion of FPIAP, and controls were healthy infants, in whom the FOBT was conducted. All cases underwent an elimination diet, after which the diagnosis of FPIAP was confirmed by oral food cha llenge. 25 cases and 29 controls were included without significant differences in age, gen der, type of delivery, feeding, and maternal age. The cases had higher rates of allergic comorbidities, medication use, and family history of allergy. The FOBT was positive in 84% of cases and in 34% of controls (p < 0.001). The sensitivity of the FOBT for the diagnosis of FPIAP was 84%, specificity was 66%, positive predictive value 68%, and the negative predictive value 83%. The area under the ROC curve was 0.75 (CI 95% 0.61-0.88). Although the FOBT has an adequate sensitivity to diagnose FPIAP in infants with rectal bleeding, this test had abnormal results in more than a third of healthy infants. Therefore, the routine use of FOBT is not recommended for the diagnosis of FPIAP.

Non-IgE-mediated Adverse Food Reactions.

The purpose of this review is to update what is currently known about the major non-IgE-mediated food allergies: food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy (FPE). These conditions are similar in that symptoms are regulated to the gastrointestinal tract; therefore understanding their specific features is important for diagnosis and management. The most progress has been made in understanding FPIES with several recent large cohorts being described. The first international consensus guidelines for FPIES were published in 2017 and propose specific diagnostic criteria for acute FPIES as well as guidance for diagnosing chronic FPIES. Recent studies in FPIAP have challenged our thinking about the recommended duration of food avoidance and that cow's milk avoidance is the primary management with reports of self-resolution without dietary management. FPE continues to appear to be on the decline. FPIES, FPIAP, and FPE are distinguished from one another by their main clinical features: delayed repetitive vomiting in FPIES, benign blood in stool in FPIAP, and chronic diarrhea in FPE. Due to the risk of nutritional deficiencies with food avoidance in both infant and maternal diets if breastfeeding, confirmation of diagnosis with challenges is encouraged. Additional studies are needed for these conditions to elucidate pathophysiology, search for diagnostic markers, and understand natural history.

Hematochezia caused by eosinophilic proctocolitis in a newborn before oral feeding: a case report

BackgroundHematochezia is a frequent symptom in early infancy. However, it occurs very rarely within the immediate neonatal period, and its occurrence before any oral intake is particularly rare. Because of the “congenital” presentation of hematochezia in our patient, we initially considered our case to be a non-classical, potentially severe type of food protein-induced allergic proctocolitis. This diagnosis needs to be confirmed by an abnormal oral challenge test once the hematochezia has disappeared. If such a challenge cannot demonstrate an allergic origin, then the etiology of the hematochezia could be a neonatal transient eosinophilic colitis. Only two similar cases have been described so far.Case presentationWe report the case of a black baby boy of African origin born at 36 weeks 5 days of gestational age who presented with massive hematochezia immediately after birth. A rectosigmoidoscopy revealed a severe inflammation associated with diffuse eosinophilic infiltration on biopsy. His clinical outcome was favorable after introduction of an amino acid formula diet. We initially considered our case to be a non-classical, potentially severe type of food protein-induced allergic proctocolitis but reintroduction of standard formula milk at the age of 3 months was successful. So, our patient is the first newborn in Europe who fits the diagnosis of “neonatal transient eosinophilic colitis.”ConclusionsWe discuss the possible etiology of “congenital” eosinophilic inflammation of the distal colon and conclude that hematochezia in well-looking neonates, in the absence of negative challenge tests later on, is more likely to be a neonatal transient eosinophilic colitis than an allergic proctocolitis. This new entity could be more frequent than previously thought, changing our medical care strategies for this kind of neonatal symptom.

Trends in Provider Management of Patients with Food Protein–Induced Enterocolitis Syndrome

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy. To better understand provider-level variation in FPIES knowledge and management. A 23-question online survey was administered to AAAAI members during the spring and summer of2014. Among 470 respondents, 64% reported "full understanding" of FPIES diagnosis/management; 78.8% reported managing 1 or more patient with FPIES; and 80.4% correctly identified an FPIES case vignette. FPIES was correctly differentiated from infantile colic or food protein-induced allergic proctocolitis by 82.5% and 71.3%, respectively. Among providers currently managing patients with FPIES, 47.5% indicated soy formula, 73.8% breast milk, and 94.5% elemental formula as appropriate substitutes in cow milk (CM)-FPIES. Skin testing is performed by 73.4%; 62.2% obtain serum food-specific IgE testing, 12.7% patch testing, 36.8% oral challenge,and 28% perform no tests. Eighty-four percent provide patients with FPIES with allergy action plans, 72.8% provide a personalized action plan, and 21% prescribe epinephrine autoinjectors. Odds of prescribing epinephrine were lower among those reporting "full understanding" of FPIES (odds ratio [OR], 0.41; 95% CI, 0.21-0.79). Academic providers had higher odds of providing an action plan (OR, 2.4; 95% CI, 1.17-4.98) and performing diagnostic oral food challenge (OR, 1.99; 95% CI, 1.99-3.25), but not of correct vignette differentiation of FPIES from other conditions, correct identification of appropriate CM-FPIES substitutes, or timing for food reintroduction. More years in practice wereassociated with lower odds of reporting full understanding of FPIES diagnosis/management (OR, 0.96; 95% CI, 0.94-0.99). Nearly one-third of respondents reported poor familiarity with FPIES. Considerable variation exists in the use of diagnostic tests, management, and choice of "safe" nutrition, indicating a strong need for FPIES practice guidelines.

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

BackgroundFood 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. ObjectiveOur objective was to examine the clinical properties of patients with FPIAP, tolerance development time as well as the risk factors that affect tolerance development. MethodsThe 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. ResultsThe 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. ConclusionsSmaller 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.

Characteristics of children with food protein-induced enterocolitis and allergic proctocolitis.

The aim of this study was to determine and compare the clinical and laboratory features of food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP), and to provide information about the short-term prognoses. Children diagnosed with FPIES or FPIAP between 2010 and 2015 were enrolled in this study. Overall, 64 infants (37 FPIAP, 27 FPIES) were evaluated, with the average age at the onset of symptoms being significantly lower in the patients with FPIAP than in the patients with FPIES (2 months [1-3 months] versus 4 months [1.5-6 months]; p = 0.043). Fifteen of the patients with FPIAP (40.5%) and six of the patients with FPIES (22.2%) were exclusively breast-fed at the time of the onset of symptoms. Cow's milk was the most frequent trigger (100% FPIAP, 74% FPIES); solid foods caused FPIES more frequently. Forty-eight of the 64 patients were followed up until at least 2 years of age, with the resolution rates being 91.3% for FPIAP and 60% for FPIES. The solid food-induced cases of FPIES (27.3%) had a significantly lower rate of resolution than the liquid food-induced FPIES (83.3%) (p = 0.003). Cow's milk is the most common trigger of both FPIAP and FPIES. The symptom onset age seemed to be earlier in FPIAP. The resolution age was similar, however, the recovery in FPIES may be later if the trigger food is solid. To our knowledge, this was the first clinical study to compare the clinical and laboratory characteristics of patients with FPIAP and FPIES.

Non-IgE-mediated gastrointestinal food allergies in children.

Non-IgE-mediated gastrointestinal food allergic disorders (non-IgE-GI-FA) including food protein-induced enterocolitis syndrome (FPIES), food protein-induced enteropathy (FPE), and food protein-induced allergic proctocolitis (FPIAP) are relatively uncommon in infants and young children, but are likely under-diagnosed. Non-IgE-GI-FA have a favorable prognosis, with majority resolving by age 3-5 years. Diagnosis relies on the recognition of symptoms pattern in FPIAP and FPIES and biopsy in FPE. Further studies are needed for a better understanding of the pathomechanism, which will lead eventually to the development of diagnostic tests and treatments. Limited evidence supports the role of food allergens in subsets of constipation, gastroesophageal reflux disease, irritable bowel syndrome, and colic. The immunologic pathomechanism is not fully understood and empiric prolonged avoidance of food allergens should be limited to minimize nutrient deficiency and feeding disorders/food aversions in infants.

Food Protein-Induced Non-Immunoglobulin E-Mediated Allergic Colitis in Infants and Older Children: What Cytokines Are Involved?

Background: Food protein-induced allergic proctocolitis (FPIAP) is mostly a non-immunoglobulin E-mediated disease where a T-cell-mediated reaction to cow's milk protein has been suggested. We determined the expression of transforming growth factor (TGF)-β, TGF-β receptor-1, tumor necrosis factor (TNF)-α, CD86, and CD23 on the colon mucosa to investigate their roles in the pathogenesis of the two subtypes of FPIAP, i.e. infantile FPIAP and FPIAP in older children. Methods: Group 1 comprised children with infantile FPIAP (age <6 months, n = 21), group 2 referred to FPIAP in older children (age >1.5 years, n = 7), and group 3 included children with juvenile hyperplastic polyps (n = 22). Immunohistochemical staining of colonic biopsy specimens was performed. Results: The expression of TNF-α was significantly higher in groups 1 and 2 compared to group 3. Group 2 patients had a significantly lower TGF-β expression compared to the other groups. The expression of CD86 was higher in group 1 than in group 3 (p = 0.012). Eosinophil counts per high-power field in the lamina propria were significantly correlated with CD86 expression (p = 0.026, r = 0.388). Conclusion: Our results suggest that TNF-α is implicated in the pathogenesis of both types of FPIAP. The decreased activity of TGF-β receptor-1 accompanied by the increased expression of CD86 in infants and the decreased activity of TGF-β in older children appear to play a role in the development of FPIAP.

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.

Non–IgE-mediated gastrointestinal food allergy

Non-IgE-mediated gastrointestinal food-induced allergic disorders (non-IgE-GI-FAs) account for an unknown proportion of food allergies and include food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy (FPE). Non-IgE-GI-FAs are separate clinical entities but have many overlapping clinical and histologic features among themselves and with eosinophilic gastroenteropathies. Over the past decade, FPIES has emerged as the most actively studied non-IgE-GI-FA, potentially because of acute and distinct clinical features. FPIAP remains among the common causes of rectal bleeding in infants, while classic infantile FPE is rarely diagnosed. The overall most common allergens are cow's milk and soy; in patients with FPIES, rice and oat are also common. The most prominent clinical features of FPIES are repetitive emesis, pallor, and lethargy; chronic FPIES can lead to failure to thrive. FPIAP manifests with bloody stools in well-appearing young breast-fed or formula-fed infants. Features of FPE are nonbloody diarrhea, malabsorption, protein-losing enteropathy, hypoalbuminemia, and failure to thrive. Non-IgE-GI-FAs have a favorable prognosis; the majority resolve by 1 year in patients with FPIAP, 1 to 3 years in patients with FPE, and 1 to 5 years in patients with FPIES, with significant differences regarding specific foods. There is an urgent need to better define the natural history of FPIES and the pathophysiology of non-IgE-GI-FAs to develop biomarkers and novel therapies.

Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report

Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report