non-IgE Mediated Food Allergy Research Articles

A Second Slice of FPIES: A Single-Center Reappraisal of Pediatric FPIES

BackgroundFood protein-induced enterocolitis syndrome (FPIES) is being increasingly recognized as a non-IgE mediated food allergy; however, it remains unclear if and how the presentation, diagnosis and management of this disease has changed in recent years. ObjectiveTo reappraise the FPIES cohort at a large United States pediatric tertiary referral center. MethodsWe performed a retrospective chart review of pediatric FPIES patients (ICD-10: K52.21) diagnosed in our allergy/immunology clinics between 2018-2022. ResultsThere were 210 children diagnosed with FPIES. Most were White (73.8%), non-Hispanic (71.4%) and male (54.3%) with private insurance (77.6%). Cow’s milk was the most common food trigger (35.2%) with the earliest median age of onset of 5 months. The atypical FPIES rate was 13.8%. FPIES was accurately diagnosed in 54.3% at the first medical contact. The oral food challenge pass rate was 73.5%. The rate of trigger resolution at 36 months was 77%. ConclusionBy comparing trends from a previous and current FPIES cohort, we were able to assess the potential impact of various guidelines and practice changes on the diagnosis and management of FPIES at our center. Milk and oat surpassed rice as the most common FPIES triggers; peanut and egg emerged as new FPIES triggers; there was a shorter time to diagnosis and an increased rate of atypical FPIES. Our findings reflect earlier recognition of FPIES and prompt allergy/immunology referral from community physicians, implementation of recent medical society guidelines for infant feeding practices and growing clinical expertise of allergists at our center.

Tolerance development in non-IgE mediated food allergies: lessons from Brazil

Tolerance development in non-IgE mediated food allergies: lessons from Brazil

Diagnostic and Management Strategies of Food Protein-Induced Enterocolitis Syndrome: Current Perspectives.

Food protein-induced enterocolitis syndrome (FPIES) is a form of non-IgE mediated food allergy that presents with delayed gastrointestinal symptoms after ingestion of the trigger food. The data regarding FPIES are sparse, despite being recognized as a distinct clinical entity. This narrative review presents the characteristics of this disorder in the pediatric population, as well-standard diagnostic and management protocols. FPIES can be classified into acute and chronic subtypes, and some cases may develop into an IgE-mediated allergy. Given that skin prick tests and specific IgE levels are negative in the majority of cases, diagnosis relies on clinical history and oral food challenges. Management involves elimination diets, assessment of tolerance through oral food challenges, and rehydration in the event of a reaction. Future research should focus on improving diagnostic methods, illustrating underlying pathogenesis and biomarkers, and assessing long-term natural history. Increased knowledge and awareness for FPIES are required.

A clinical case of secondary eosinophilia in a child

A couple of decades ago, the diagnostic search for the cause of blood eosinophilia concerned, mainly, the three major allergic diseases (bronchial asthma, allergic rhinitis, atopic dermatitis), or parasitic invasion. In recent years, more and more complex clinical syndromes, from reactive (secondary) eosinophilia to eosinophilic leukemia are increasingly considered by the doctors of different specialties. The aim of our work was to present a clinical case of secondary eosinophilia in a child with minimal clinical manifestations. Highlights: Sometimes blood eosinophilia in a patient is an “unexpected finding” for a physician, especially if the complaints are scanty, nonspecific, and objective examination does not reveal any significant health abnormalities. In the presented case, secondary (reactive) peripheral blood eosinophilia was diagnosed due to intestinal damage induced by food allergens. This clinical case is of practical interest to physicians, presenting a diagnostic search for the cause of blood eosinophilia, which eventually proved to be a mixed IgE/ non-IgE mediated food allergy manifesting as allergic enterocolitis. The IgE-mediated mechanism of food allergy is evidenced by a high level of IgE and its decrease with administered elimination diet; delayed-type response and low severity of clinical manifestations of food allergy, as well as blood eosinophilia suggest a non-IgE mediated food allergy. In this particular case, the severity of laboratory changes (blood eosinophilia, a significant increase in the levels of specific IgE) was associated with scarce intestinal symptoms. An opposite situation is observed, especially, in young children where the disease manifests with a pronounced clinical pattern of enterocolitis in the absence of laboratory changes.

Food protein-induced enterocolitis syndrome in an infant triggered by prunes

BackgroundFood protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy that has a cumulative incidence of 0.015 to 0.7% in infants [1]. The most common allergens causing FPIES reactions include cow’s milk, followed by soy, grains, and rice [1, 3]. Increasing clinical awareness of FPIES has resulted in the expansion of emerging triggers of FPIES, including fruit antigens.Case presentationWe describe an infant diagnosed with FPIES to prune.ConclusionFruit allergens are an emerging group of triggers for FPIES, both in their fresh and dried forms. To our knowledge, this case is the first presentation of FPIES to prunes (dehydrated plum). This case highlights that careful history taking can avoid unnecessary investigations and delay in diagnosing FPIES.

Bloody Stool in Infants: A Pediatric Allergy View

Objective: The prevalence of food allergy (FA) has gradually increased. Bloody stool is among the symptoms associated with non-immunoglobulin E (IgE) mediated FA in infants. In our study, we shared the clinical characteristics of the patients who applied to our clinic with bloody stool. Material and Methods: The data of the patients with bloody stool were reviewed. Patients’ characteristics and the time of onset of tolerance in patients with FA were recorded, retrospectively. Results: The 110 patient files were reviewed. 68% of the patients were diagnosed with FA (63 proctocolitis/12 enterocolitis), 22% with an anal fissure, and 9% with nonspecific colitis. The most common causative food was cow milk (57%), the second was the combination of egg and milk (24.2%), and the third was egg (18.2%). The presence of atopic dermatitis (AD) and eosinophil count at the time of admission did not affect tolerance development time but it was shown that skin prick test (SPT) positivity and the high level of total IgE at the time of admission delayed the development of tolerance [(p=0.02), (r=0.510, p=0.009)]. Conclusion: Bloody stool is one of the common complaints in infants. It does not always indicate a FA. The clinic is mild when the underlying disease is non-IgE mediated FA. However, accompanying IgE-type sensitivities negatively affect the prognosis. Elevated total IgE and SPT positivity at the time of diagnosis may give an impression that tolerance of baked products could be delayed in this type of allergy.

Food protein-induced enterocolitis syndrome: Healthcare utilization and referral patterns among a pediatric cohort.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy characterized by delayed, repetitive vomiting. FPIES is improving in recognition; however, there remains a lag in diagnosis. This study aimed to further explore this lag, as well as referral patterns and healthcare utilization, to help determine areas for earlier recognition. A retrospective chart review of pediatric FPIES patients at two hospital systems in New York was completed. Charts were reviewed for FPIES episodes and healthcare visits prior to diagnosis, and reason/source of referral to an allergist. A cohort of patients with IgE-mediated food allergy was reviewed for comparison of demographics and the time to the diagnosis. In total, 110 patients with FPIES were identified. The median time to diagnosis was 3 months, vs. 2 months in IgE-mediated food allergy (p < 0.05). Most referrals were from the pediatrician (68%) or gastroenterology (28%), none were from the ED. The most common reason for referral was concern of IgE-mediated allergy (51%), followed by FPIES (35%). There was a statistically significant difference in race/ethnicity between the FPIES cohort and IgE-mediated food allergy group (p < 0.0001), with a greater proportion of Caucasian patients in FPIES vs. IgE-mediated food allergy cohort. This study demonstrates a lag in the diagnosis of FPIES and a lack of recognition outside of the allergy community, as only one-third of patients were considered to have FPIES prior to an allergy evaluation.

Food Protein Induced Enterocolitis Syndrome: A Culprit Food Analysis

Food protein induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy. We investigated trigger foods and clinical presentation of patients with FPIES, before and after the 2015 early food introduction initiative, and hypothesized there would be a change in culprit foods.

The clinical and immunological basis of early food introduction in food allergy prevention.

IgE-mediated food allergy has an estimated prevalence of 6%-10% in developed countries. Allergen avoidance has long been the main focus in the prevention of food allergy and late solid food introduction after 6-12 months of age was recommended in high-risk infants. However, the rising prevalence of food allergy despite delayed exposure to allergens and the observations that IgE-mediated sensitization to food products could even occur before the introduction of solid foods resulted in a shift towards early solid food introduction as an attempt to prevent IgE-mediated food allergy. Since then, many trials focused on the clinical outcome of early allergen introduction and overall seem to point to a protective effect on the development of IgE-mediated food allergies. For non-IgE-mediated diseases of food allergy, evidence of early food introduction seems less clear. Moreover, data on the underlying immunological processes in early food introduction is lacking. The goal of this review is to summarize the available data of immunological changes in early food introduction to prevent IgE and non-IgE mediated food allergy.

ATYPICAL FOOD PROTEIN-INDUCED ENTEROCOLITIS SYNDROME (FPIES) TO SHELLFISH IN A PEDIATRIC PATIENT

<h3>Introduction</h3> Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy syndrome. Ingestion of food protein causes delayed onset of repetitive projectile vomiting, pallor, diarrhea, lethargy 1-4 hours after intake. Diagnosis is clinical. Pathophysiology involves antigen presentation and TNFα alteration of the intestinal tight junction barrier resulting in fluid shifts and symptoms. Atypical FPIES is rare and includes concomitant IgE sensitization to the food trigger, potentially from ‘Th2-skewing'. The majority of FPIES to seafood are published for adolescents/adults. Our case describes a rare presentation of atypical FPIES to shrimp in infancy. <h3>Case Description</h3> Patient is an 8-year-old male with PMH eczema who presented for evaluation. As a 12-month-old, the patient developed 3 episodes of projectile vomiting and mild lethargy 3 hours after shrimp ingestion. No associated IgE-mediated symptoms. He went to the urgent care and improved with zofran. Family history included atopic conditions of allergic rhinitis and eczema. Testing demonstrated positive skin prick testing (SPT) to shrimp (3 mm wheal) and positive shrimp-IgE (1.49 kU/L). Most recently, he had a repeat reaction to shellfish at age 8 with 4 episodes of vomiting and paleness 2-3 hours after ingestion. <h3>Discussion</h3> Up to 20% of FPIES cases may transform over time to an IgE-mediated phenotype. These atypical FPIES cases have been shown to have longer persistence, as seen in our patient (average tolerance to solid food triggers is age 4). Epinephrine should be prescribed in atypical FPIES due to the risk of anaphylaxis. Treatment includes food avoidance. Further work is essential to determine a disease biomarker.

A CASE OF ACUTE FOOD PROTEIN-INDUCED ENTEROCOLITIS (FPIES) TO FISH, TURKEY, AND DUCK

<h3>Introduction</h3> FPIES is a non-IgE mediated food allergy characterized by delayed vomiting after ingestion of a causal food. We present a case of FPIES to fish, turkey, and duck, suggesting cross-reactivity. <h3>Case Description</h3> The patient had two episodes of delayed vomiting following cod ingestion. The first occurred at age 2.5 yrs resulting in severe vomiting 2 hours after, requiring IV fluids. A second cod reaction occurred months later, with vomiting 3-4 hours following ingestion. He had previously tolerated various types of fish, including cod, but stopped ingestion of all fish after these reactions. At age 4 yrs the patient experienced abdominal pain, diarrhea, and repetitive vomiting 4 hours after eating turkey. He had previously tolerated turkey with his last exposure being 6 months prior. When 6 years old, the patient had severe, repetitive vomiting 4 hours after duck ingestion on 2 occasions. He continues to tolerate chicken. Skin prick testing was negative to cod, turkey, and duck, consistent with a diagnosis of FPIES. The patient was instructed to avoid all types of fish, and turkey/duck. <h3>Discussion</h3> There is limited information on the cross-reactivity of allergens in FPIES. Fish-chicken syndrome is described in IgE-mediated food allergies, attributed to homologous proteins parvalbumin, aldolase, and enolase. We hypothesize that these proteins may have a similar role in the pathogenesis of FPIES via an activation of T lymphocytes in our patient. Duck is an uncommon poultry meat and it is possible that those with FPIES to turkey may have an increased risk of reacting to duck.

Analysis of Serum Th2 Cytokines in Infants with Non-IgE Mediated Food Allergy Compared to Healthy Infants.

Background: The aim of this study is to assess the serum values of IL-4, IL-5, IL-10, and IL-13 in a group of infants with non-IgE mediated food allergies treated with a hydrolyzed formula and compare them with a group of healthy peers. Methods: A total of 53 infants aged 1 to 4 months, of which 34 with non-IgE mediated food allergies and 19 healthy infants were enrolled in this study. Infants were eligible if they had gastrointestinal symptoms of food allergy and needed to switch from their initial formula to hydrolyzed formulas with an improvement of symptoms. Controls were fed with either breastmilk or standard formula. Blood samples were taken within one week of a special diet for cases. Interleukinsin in peripheral blood was detected and analyzed using the real-time PCR MAMA method. Fecal calprotectin was evaluated using a quantitative assay. Results: Values of IL-4 and IL-13 were significantly higher in the non-IgE food allergy group compared to the control group (p < 0.05), while IL-5 and IL-10 were significantly lower than the control group (p < 0.05). Fecal calprotectin in the non-IgE food allergy group was significantly higher compared to the control group (p < 0.05). Conclusion: This study provides a theoretical basis that Th2 cytokine expression in infants with a non-IgE mediated food allergy is significantly different than in healthy infants; this finding supports the use of early dietetic treatment with hydrolyzed formulas.

Fad Foods & FPIES – Is Avocado Really a Low Risk FPIES Food?

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy with vomiting 1-4 hours after trigger ingestion and diarrhea within 24 hours. Our center appreciated an increase in avocado triggered FPIES and desired to stratify frequency compared to traditional classification schemes.

Modified oral food challenge protocol approach in the diagnosis of Food Protein-Induced Enterocolitis Syndrome

BackgroundFood Protein-Induced Enterocolitis Syndrome (FPIES) is a non-IgE mediated food allergy most commonly presenting in infants. The most common food triggers include soy, cow’s milk and grains. Symptoms may include intractable vomiting, diarrhea, lethargy, pallor, abdominal distention, hypotension and/or shock. Oral food challenges (OFCs) given at food protein dose of 0.06–0.6 g/kg in 3 equivalent doses administered over a few hours are recommended in guidelines to confirm a diagnosis.Case presentationThe patient is a 6-month-old girl with a history of severe FPIES symptoms to egg. In our clinic, we perform OFC with 1/100 serving dose on visit 1 and then increase the dose monthly. The patient takes the tolerated dose daily at home between visits. An OFC to baked egg at 1/100 of a serving was performed and was well-tolerated on her initial visit. The patient remained on the same dose upon returning home. Within 1-week, she developed FPIES symptoms including watery diarrhea and severe emesis requiring ondansetron. She required an Emergency Department visit for one of the reactions.ConclusionsOur patient had severe FPIES symptoms with a small amount of egg. We believe that administration of three large food challenge doses on one clinic visit, as guidelines currently suggest, does not allow adequate time for symptoms to appear. Our patient likely would have suffered a severe reaction. Also, this guidelines protocol does not allow for monitoring of more delayed or chronic FPIES. We propose a modified protocol to OFCs with cautious up-dosing to allow for safer OFCs and monitoring of chronic FPIES. We have implemented an OFC approach where only one food challenge dose (starting with 1/100 of final dose) is given at each visit. The up-titration of the dose is completed every 4-weeks with one dose only. When the serving sized dose is reached and tolerated, the food can be maintained in the diet.

Non-IgE mediated food allergies in breastfed children: A clinical challenge.

The prevalence of non-immunoglobulin E (IgE) mediated food allergy is poorly established outside of cow's milk allergy, with a challenge-proven adjusted incidence ranging between 0.13 and 0.72%. The presence and presentation of non-IgE mediated allergy in exclusively breastfed infants is highly debated. The dilemma this poses for healthcare professionals and parents, is on the one hand the unwarranted elimination and therefore health risk to the breastfeeding mother and on the other hand under-recognition of a food allergen being a culprit in the non-IgE mediated symptoms of breastfed infants. Current international guidelines recommend exclusive breastfeeding ideally until ~6months of age and the German guidelines 4-6 months. It is also acknowledged that breastfeeding should be promoted also within the population of food-allergic infants. This review paper aims to assess non-IgE mediated food allergies in breastfed infants using an evidence-based approach and provides clinicians working with these patients with practical guidance.

Non-IgE mediated food allergy: food protein-induced allergic proctocolitis - An update

Non-IgE mediated food allergy: food protein-induced allergic proctocolitis - An update

Pathophysiology of Non-IgE-Mediated Food Allergy.

Non-IgE-mediated food allergies are a group of disorders characterized by subacute or chronic inflammatory processes in the gut. Unlike IgE mediated food allergies that may result in multi-organ system anaphylaxis, the non-IgE mediated food allergies primarily affect the gastrointestinal tract. This review outlines the clinical manifestations, epidemiology, pathophysiology, and management of non-IgE-mediated food allergies. An updated literature search of selected non-IgE-mediated food allergies was conducted for this review using PubMed database to the current year (2021). Reviewed disorders include food protein-induced enterocolitis syndrome (FPIES), food-protein enteropathy (FPE), food protein-induced allergic proctocolitis (FPIAP), and eosinophilic gastrointestinal disorders (EGIDs) such as eosinophilic esophagitis (EoE). While extensive gains have been made in understanding FPIES, FPIAP, FPE, and EoE, more information is needed on the pathophysiology of these food allergies. Similarities among them include involvement of innate immunity, T-lymphocyte processes, alteration of the intestinal lumen at the cellular level with the appearance of inflammatory cells and associated histologic changes, and specific cytokine profiles suggesting food-specific, T-cell, and immune-mediated responses. While FPIES and FPIAP typically resolve in early childhood, EGIDs typically do not. Emerging new therapies for EoE offer promise of additional treatment options. Further studies identifying the immunopathogenesis, associated biomarkers, and mechanisms of tolerance are needed to inform prevention, diagnosis and management.

Intrinsic Atopic Dermatitis: Titration of Precipitins in the Screening of Food Allergens for Prescription of Elimination Diets and Desensitization Strategies

Background: The diagnosis of non-IgE mediated food allergies may be a complex puzzle when there is no start point to establish an elimination diet to allow a clear clinical field to initiate diagnostic Oral Food Challenges tests.&#x0D; Objective: To evaluate the opportunity of the tube titration of precipitins to select food allergens to proceed with elimination diets to assist the diagnosis and management of adult patients with Food Allergy manifested as Intrinsic Atopic Dermatitis (IAD).&#x0D; Methods: The tube titration of specific precipitins against anamnesis-chosen food allergens were performed in 64 IAD patients and their titers were associated with an Improvement Verbal Scale Rate (IVSR) of the patient’s perception of the benefits of the Precipitins-based Elimination Diet (PED) performed with these specific food allergens, as well correlated with their positive or negative perception of the impairment of symptoms after the reintroduction of the Symptom-Related Food Allergen (SRFA).&#x0D; Results: In most cases, the PED contributed to a significant clinical improvement that allowed the patients to evaluate the individual effect of the reintroduction of each food allergen on their diets. There was a significant positive correlation coefficient between the titers of the food-specific titration of precipitins and the percentage of positive SRFA (Pearson r = 0.91; p-value = 0.0004). &#x0D; Conclusion: The semiquantitative titration of specific precipitins against food allergens is a promising triage test to select food allergens to proceed with elimination diets to support the diagnosis and management of non-IgE mediated Food Allergy in patients with Intrinsic Atopic Dermatitis.

Association of Antibiotic Usage with Food Protein-Induced Enterocolitis Syndrome Development from a Caregiver's Survey.

Food protein-induced enterocolitis syndrome (FPIES) is a frequently misdiagnosed, serious, non-IgE mediated food allergy, and the precise mechanism of disease is unknown. Acute FPIES typically presents with repetitive, profuse vomiting approximately 1-4 hours post ingestion of a food trigger. Chronic FPIES is considered less common and less well characterized. We aimed to better describe FPIES and identify factors that may influence FPIES development through use of a self-reported, caregiver's survey. FPIES and allergy-free infant caregivers completed a survey regarding lifestyle factors that may influence allergy acquisition such as: antibiotic usage and delivery mode. FPIES caregivers reported symptoms, number of food triggers, type of FPIES, and symptoms from breastmilk ingestion. FPIES infants were compared to allergy-free infants to identify factors potentially associated with FPIES. Infant and prenatal maternal antibiotic usage was higher in FPIES infants compared to allergy-free infants (43.8% vs 20.6% and 48.8% vs 23.57%, respectively, p< 0.05). When compared to infants with ACUTE FPIES alone, infants described as BOTH acute and chronic FPIES reported earlier onset of symptoms, more non-specific symptoms and symptoms triggered by breast milk, more antibiotic exposure, and more food triggers (p< 0.05). Antibiotic usage was significantly higher in FPIES infants when compared to allergy-free infants. Work is needed to elucidate the role of antibiotic usage in the etiology of FPIES. Infants reported to have BOTH acute and chronic FPIES were significantly different from infants with ACUTE FPIES alone highlighting the need to more closely examine these different subtypes of FPIES.

M245 FOOD PROTEIN-INDUCED EOSINOPHILIC GASTROINTESTINAL INFLAMMATION IN AN EXCLUSIVELY BREASTFED INFANT

Non-IgE mediated food allergies generally occur during the first year of life after introduction to formula and/or solid foods. There are limited examples of this in exclusively breastfed infants, although food antigens can potentially be transferred through breast milk.