Food Protein-induced Allergic Proctocolitis Research Articles

The Effect of Lactobacillus rhamnosus GG in Infants with Food Protein-Induced Allergic Proctocolitis

The Effect of Lactobacillus rhamnosus GG in Infants with Food Protein-Induced Allergic Proctocolitis

The multiple facets of cow’s milk allergy

Cow’s milk allergy (CMA) is one of the most common food allergies in early childhood. CMA has varied presentations and multiple facets. A detailed clinical history is key for classification. In IgE-mediated CMA skin prick testing and serum specific IgE testing are useful in the diagnosis, but an oral food challenge (OFC) may still be necessary if there is doubt or to assess tolerance. Non-IgE-mediated CMA presentations include food protein-induced allergic proctocolitis (FPIAP), food protein-induced enterocolitis syndrome (FPIES), and eosinophilic esophagitis (EoE). The diagnosis of FPIAP and FPIES is based on the clinical history. An esophageal biopsy is required for the diagnosis of EoE. Atopy patch testing, IgG or IgG4 testing are not helpful in any CMA evaluation. Children with CMA (except those with FPIAP) are at risk for poor growth and a nutritional evaluation should be part of routine care. Extensively hydrolyzed formulas are the recommended first choice alternative formula for CMA. For IgE-mediated CMA, alternative approaches to traditional strict avoidance include oral immunotherapy (OIT) and omalizumab (both as monotherapy and as an adjunct to OIT). Multiple international guidelines have addressed evaluation and management of CMA providing key information, support and guidance for clinicians in daily practice.

Gut microbiome features in pediatric food allergy: a scoping review.

Increasing evidence suggests that alterations in the gut microbiome (GM) play a pivotal role in the pathogenesis of pediatric food allergy (FA). This scoping review analyzes the current evidence on GM features associated with pediatric FAs and highlights the importance of the GM as a potential target of intervention for preventing and treating this common condition in the pediatric age. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we searched PubMed and Embase using the keywords (gut microbiome OR dysbiosis OR gut microbiota OR microbiome signatures) AND (food allergy OR IgE-mediated food allergy OR food protein-induced allergic proctocolitis OR food protein-induced enterocolitis OR non-IgE food allergy OR cow milk allergy OR hen egg allergy OR peanut allergy OR fish allergy OR shellfish allergy OR tree nut allergy OR soy allergy OR wheat allergy OR rice allergy OR food sensitization). We included 34 studies reporting alterations in the GM in children affected by FA compared with healthy controls. The GM in pediatric FAs is characterized by a higher abundance of harmful microorganisms (e.g., Enterobacteriaceae, Clostridium sensu stricto, Ruminococcus gnavus, and Blautia spp.) and lower abundance of beneficial bacteria (e.g., Bifidobacteriaceae, Lactobacillaceae, some Bacteroides species). Moreover, we provide an overview of the mechanisms of action elicited by these bacterial species in regulating immune tolerance and of the main environmental factors that can modulate the composition and function of the GM in early life. Altogether, these data improve our knowledge of the pathogenesis of FA and can open the way to innovative diagnostic, preventive, and therapeutic strategies for managing these conditions.

Food-Protein-Induced Proctocolitis in Pre-Term Newborns with Bloody Stools in a Neonatal Intensive Care Unit.

The bloody stools of newborns may be a clue for several clinical entities of varying severity, ranging from idiopathic neonatal transient colitis to food-protein-induced allergic proctocolitis (FPIAP) or necrotizing enterocolitis (NEC). Distinguishing among them at an early stage is challenging but crucial, as the treatments and prognoses are different. We conducted a monocentric retrospective study including all pre-term infants with bloody stools admitted to the Neonatal Intensive Care Unit (NICU) of the Vittore Buzzi Children's Hospital (Milan) from December 2022 to May 2024. Patients diagnosed with NEC exhibited significantly lower eosinophil counts and higher procalcitonin levels than both patients with FPIAP and patients with idiopathic neonatal transient colitis, as well as a statistically significant increase in pathological features from abdomen ultrasounds and abdominal X-rays. In contrast, no lab markers or imaging techniques have been demonstrated to be useful in distinguishing between idiopathic neonatal transient colitis and FPIAP. Thus, after excluding a diagnosis of NEC, the only way to confirm FPIAP is through the oral food challenge, which can be performed in premature newborns presenting with bloody stools who are otherwise healthy and under medical supervision, in order to identify infants who may benefit from a cow's-milk-free diet.

The need for standardization in the diagnosis and management of food protein-induced allergic proctocolitis (FPIAP): the time has come to act

The need for standardization in the diagnosis and management of food protein-induced allergic proctocolitis (FPIAP): the time has come to act

IgE and non-IgE food allergy: A review of immunological mechanisms.

Food allergic (FA) conditions have been classified as immunoglobulin E (IgE) and non-IgE-mediated reactions that affect as many as 8% of young children and 2% of adults in Western countries, and their prevalence seems to be rising. Although the immunologic basis of IgE-mediated FA is well established, the mechanisms that govern non-IgE-mediated FA are not well understood and are marked by a paucity of comprehensive insights. The purpose of the present report is to examine the current classification and epidemiology of non-IgE-mediated FA, the latest immunologic mechanisms that underlie the three most commonly cited non-IgE FA conditions, viz., eosinophilic esophagitis, food protein-induced enterocolitis, and food protein-induced allergic proctocolitis, and explore what allergist/immunologists in practice should be aware of with regard to the condition. An extensive research was conducted in medical literature data bases by applying terms such as FA, non-IgE allergy, tolerance, unresponsiveness, cytokines, CD4+ T helper cell pathways, and key cytokine pathways involved in FA. Current evidence now supports the view that immune dysregulation and cytokine-induced inflammation are the fundamental bases for both IgE- and non-IgE-mediated FA. The existing non-IgE-related FA literature is mostly characterized by a relative dearth of mechanistic information in contrast to IgE-mediated FA, in which the immunologic underpinnings as a T helper type 2 directed entity are well established. Although the need for future methodologic research and adherence to rigorous scientific protocols is essential, it is also necessary to acknowledge past contributions that have given much to our understanding of the condition. In the present report, a novel signature cytokine-based classification of IgE-mediated and non-IgE-mediated allergy is proposed that may offer a novel template for future research in the field of non-IgE-mediated FA. The present report provides an overview of the current classification and frequency of IgE- and non-IgE-mediated FAs, and offers insights and potential solutions to address lingering questions, particularly when concerning the latest immunologic mechanisms that underlie the pathogenesis of non-IgE-mediated FA. Although some progress has been made in recent years toward making diagnostic and treatment options available for these conditions, there still remain many lingering questions and concerns to be addressed, which can be fully understood by future research.

Development of IgE-mediated food allergies in children with history of food protein-induced allergic proctocolitis: a series of five cases.

Food protein-induced allergic proctocolitis (FPIAP) is a non-IgE-mediated allergic condition that presents with hematochezia in otherwise healthy infants. It is most commonly induced by cow's milk protein via breast milk or formula. The prognosis for FPIAP is generally considered favorable with most infants achieving symptomatic resolution after diet modification. Most infants go on to tolerate the offending foods by 1-3 years of age. Over 8 years at our institution, five patients were identified and noted to have FPIAP to cow's milk during infancy with subsequent development of IgE-mediated allergic reaction to cow's milk and other foods. All five cases developed other atopic disorders (atopic dermatitis in four cases). IgE-mediated cow's milk allergy has persisted beyond the preschool years in at least two patients (currently 8 and 16 years old). For three of the patients, the IgE-mediated reaction to cow's milk was severe with development of anaphylaxis or angioedema. In addition, three patients experienced anaphylaxis or angioedema to allergens other than milk. While FPIAP is a non-IgE-mediated process traditionally thought not to progress past the first year of life, some infants with FPIAP develop severe, persistent IgE-mediated cow's milk allergy. To our knowledge, this is the first detailed clinical description of such patients.

NON – IgE – MEDIATED GASTROINTESTINAL FOOD ALLERGY IN CHILDREN

Nutrition allergy is unfavorable immune response to food proteins. Non-IgE-mediated gastrointestinal food allergy includes spectrum of disorders which are more uncommon that IgE- mediated food allergies. Their diagnosis is mainly done by clinical features cause the absence of specific biomarkers. Non-IgE-mediated food allergies include: food protein-induced enterocolitis sydrome (FPIES), food-protein induced allergic proctocolitis (FPIAP), food-protein induced allergic enteropathy (FPE), food protein induced dysmotility disorders (GERD) and mixed type diseases for examp. Eosinophilic esophagitis (EoE). In most cases non-IgE-mediated food allergy have a good prognosis and resolving during childhood.

Management of food protein-induced allergic proctocolitis in Italy: A nationwide survey by SIGENP.

Management of food protein-induced allergic proctocolitis in Italy: A nationwide survey by SIGENP.

To Diet or Not to Diet This Is the Question in Food-Protein-Induced Allergic Proctocolitis (FPIAP)-A Comprehensive Review of Current Recommendations.

Food-protein-induced allergic proctocolitis (FPIAP) is an increasingly reported transient and benign form of colitis that occurs commonly in the first weeks of life in healthy breastfed or formula-fed infants. Distal colon mucosal inflammation is caused by a non-IgE immune reaction to food allergens, more commonly to cow's milk protein. Rectal bleeding possibly associated with mucus and loose stools is the clinical hallmark of FPIAP. To date, no specific biomarker is available, and investigations are reserved for severe cases. Disappearance of blood in the stool may occur within days or weeks from starting the maternal or infant elimination diet, and tolerance to the food allergen is typically acquired before one year of life in most patients. In some infants, no relapse of bleeding occurs when the presumed offending food is reassumed after a few weeks of the elimination diet. Many guidelines and expert consensus on cow's milk allergy have recently been published. However, the role of diet is still debated, and recommendations on the appropriateness and duration of allergen elimination in FPIAP are heterogeneous. This review summarizes and compares the different proposed nutritional management of infants suffering from FPIAP, highlighting the pros and cons according to the most recent literature data.

Non-IgE-mediated food allergy

Food allergy is an immune response to proteins in food. It usually affects 8% of children and 2% of adults in Western countries. Non-IgE-mediated food allergy mainly affects the gastrointestinal tract. Gastrointestinal food allergies are classified, by their underlying pathogenesis, as: IgE-mediated, non-IgE-mediated, or mixed. The symptoms of patients with food protein-induced allergic proctocolitis originate from local inflammation of the distal colon, which causes hematochezia in neonates. It can affect the entire gastrointestinal tract and cause symptoms of intractable emesis, with subsequent metabolic disorders and hypovolemic shock. Food protein-induced enterocolitis syndrome is a non-IgE-mediated allergy that usually appears in childhood, with prolonged repetitive vomiting, starting 1 to 4 hours after ingestion of food. The manifestation in adults is usually triggered by the consumption of shellfish. Atopic diseases affect 40-60% of patients with food protein- induced enterocolitis syndrome, including 40-50% of those with food protein-induced enteropathy and proctocolitis. Probiotics (Lactobacillus GG) can alleviate the symptoms of allergic proctocolitis induced by food proteins, by altering the composition of the intestinal microbiota. Fecal microbiota transplantation (FMT) can change intestinal microecology efficiently compared to food or probiotics.

Shellfish allergy – diagnostic approach

Shellfish allergy is one of the most common food allergies, with an estimated prevalence of 3% in the general population. Crustaceans and mollusks are part of this food category, being capable of immunologic hypersensitivity reactions (IgE-mediated, as well as non-IgE-mediated), but also non-immunologic reactions, based on intoxication with certain neurotoxins from contaminated seafood, in which neurological but also gastrointestinal symptoms predominate. The clinical picture in IgE-mediated hypersensitivity reactions can vary in severity, from mild reactions such as oral allergy syndrome to severe reactions such as anaphylaxis. Among the delayed, non-IgE mediated reactions, we can identify food protein-induced enterocolitis syndrome, food protein-induced enteropathy and food protein-induced allergic proctocolitis, which mainly involve gastrointestinal symptoms. Over the past decades, the knowledge gained regarding the characteristics of different allergens has improved the diagnostic approach. Thus, for an accurate diagnosis of seafood-induced allergy, a thorough history, along with skin prick testing and specific IgE dosing are essential, and when these are insufficient, an oral challenge test can disentangle causality.

A nationwide survey of non-IgE-mediated gastrointestinal food allergies in neonates and infants

BackgroundNon-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) seem to be increasing rapidly worldwide. However, nationwide studies have been limited to food-protein-induced enterocolitis (FPIES) and food-protein-induced allergic proctocolitis (FPIAP), with little attention to other non-IgE-GIFA subgroups. The aim of this study was to elucidate the clinical features of all patients with non-IgE-GIFAs, not just certain subgroups. MethodsWe conducted a nationwide cross-sectional survey of non-IgE-GIFAs in Japan from April 2015 through March 2016. A questionnaire was sent to hospitals and clinics throughout Japan. The questionnaire asked about the number of physician-diagnosed non-IgE-GIFA patients, the status of fulfillment of the diagnostic criteria, tentative classification into 4 clusters based on the initial symptoms, the day of onset after birth, complications, and the suspected offending food(s). ResultsThe response rate to that questionnaire was 67.6% from hospitals and 47.4% from clinics. Analyses were conducted about “diagnosis-probable” patient cohort (n = 402) and the “diagnosis-confirmed” patients (n = 80). In half of the reported non-IgE-GIFA patients, onset occurred in the neonatal period. The patients were evenly distributed among 4 non-IgE-GIFA clusters. In Cluster 1, with symptoms of vomiting and bloody stool, the onset showed a median of 7 days after birth, which was the earliest among the clusters. Cow's milk was the most common causative food. ConclusionsIn half of the patients, the onset of non-IgE-GIFAs was in the neonatal period. This highlights the importance of studying the pathogenesis in the fetal and neonatal periods.

Allarme rosso: il sanguinamento rettale

A 6-week-old, exclusively breastfed and well-appearing infant presented with blood in her stools. A diagnosis of food protein-induced allergic proctocolitis was promptly made by the presence of the high number of eosinophils in her blood and the prompt clinical response to the elimination of cow milk proteins from her mother's diet.

Allarme rosso: il sanguinamento rettale

A 6-week-old, exclusively breastfed and well-appearing infant presented with blood in her stools. A diagnosis of food protein-induced allergic proctocolitis was promptly made by the presence of the high number of eosinophils in her blood and the prompt clinical response to the elimination of cow milk proteins from her mother's diet.

A different starting line for allergic march: food protein-induced allergic proctocolitis.

The aim of this study is to investigate the long-term prognosis of food protein--induced allergic proctocolitis (FPIAP) patients, the risk of developing both allergic and gastrointestinal diseases, and to evaluate whether it leads to allergic march. A total of 149 children who were diagnosed with FPIAP and developed tolerance at least 5 years prior to the study and 41 children (with no history of food allergy) as a control group were enrolled. Both groups were re-evaluated for allergic diseases as well as gastrointestinal disorders. The mean age of diagnosis for the FPIAP group was 4.2 ± 3.0 months, while the mean age of tolerance was 13.9 ± 7.7 months. The mean age of both FPIAP and control groups at the last visit was 101.6 ± 24.4 and 96.3 ± 24.1 months, respectively (P = 0.213). At the final evaluation of both groups, the comorbid allergic disease was significantly higher in the FPIAP group (P < 0.001). There was no significant difference between the two groups in terms of functional gastrointestinal disorders (FGIDs), eosinophilic gastrointestinal diseases, and inflammatory bowel disease (P = 0.198, 0.579, and 0.579, respectively).In the FPIAP group, the allergic disease was significantly higher at the final visit in patients with comorbid allergic disease at diagnosis (P < 0.001). In the FPIAP group, FGID was significantly higher in the group that developed allergic diseases in the future, compared to the group that did not develop allergic diseases in the future (P = 0.034). The proportion of both FGID and allergic diseases was significantly higher in subjects that developed tolerance at >18 months, compared to subjects that developed tolerance at >18 months (P < 0.001 and <0.001, respectively). Patients with FPIAP may develop allergic diseases as well as FGID in the long term.

Evaluation of Eosinophil Count in Infants with Food Protein-Induced Allergic Proctocolitis

Evaluation of Eosinophil Count in Infants with Food Protein-Induced Allergic Proctocolitis

Longitudinal assessment of early growth in children with IgE- and non–IgE-mediated food allergy in a healthy infant cohort

BackgroundThere are conflicting associations reported between food allergies (FAs) and poor growth, with some indication that children with multiple FAs are at highest risk. ObjectiveWe analyzed longitudinal weight-for-length (WFL) trajectories from our healthy cohort to evaluate growth in children with IgE-mediated FAs and food protein-induced allergic proctocolitis (FPIAP), a non–IgE-mediated FA. MethodsOur observational cohort of 903 healthy newborn infants was prospectively enrolled to evaluate the development of FAs. Longitudinal mixed effects modeling was used to compare differences in WFL among children with IgE-FA and FPIAP, compared with unaffected children, through age 2. ResultsAmong the 804 participants who met inclusion criteria, FPIAP cases had significantly lower WFL than unaffected controls during active disease, which resolved by 1 year of age. In contrast, children with IgE-FA had significantly lower WFL than unaffected controls after 1 year. We also found that children with IgE-FA to cow's milk had significantly lower WFL over the first 2 years of age. Children with multiple IgE-FAs had markedly lower WFL over the first 2 years of age. ConclusionChildren with FPIAP have impaired growth during active disease in the first year of age which resolves, whereas children with IgE-FA, particularly those with multiple IgE-FA, have impaired growth more prominently after the first year of age. It may be appropriate to focus nutritional assessment and interventions accordingly during these higher risk periods in these patient populations.

Perspectives on Non-IgE-Mediated Gastrointestinal Food Allergy in Pediatrics: A Review of Current Evidence and Guidelines.

Food allergy is an immune-mediated disease that can result in considerable morbidity and even mortality, with a significant negative impact on patients' quality of life. It is characterized by allergic symptoms that can occur shortly after a relevant food allergen ingestion, or can be delayed or chronic, which make it more difficult for diagnosis. The symptoms of this disease can range from mild to severe, and rarely can cause anaphylaxis, a life-threatening allergic reaction. The prevalence of non-immunoglobulin E (IgE)-mediated food allergy is poorly established outside of cow's milk allergy, with an adjusted incidence ranging between 0.13% and 0.72%. Several disorders are classified as non-immunoglobulin E (IgE)-mediated food allergies that predominantly affect the gastrointestinal tract including food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), food protein-induced allergic enteropathy (FPE), and food protein-induced dysmotility disorders (GORD and constipation). Eosinophilic esophagitis (EoE) is listed in this group, even though it considered by some authorities to be mixed reaction with both IgE and cell-mediated immune response to be involved in the reaction. The most common types of non-IgE-mediated food allergy are food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP). These disorders typically present in infancy and are often triggered by cow's milk protein. Patients with FPIES present with profuse emesis and dehydration, while FPIAP patients present with hematochezia in otherwise healthy infants. Since there are no specific confirmatory non-invasive diagnostic laboratory tests, the diagnosis is usually made clinically when typical symptoms improve upon the removal of the culprit food. Food reintroduction should be attempted, when possible, with documentation of symptoms of relapse to confirm the diagnosis. The management includes dietary avoidance, supportive treatment in the case of accidental exposure, and nutritional counseling. This review focuses on the clinical manifestations, epidemiology, management, and recent guidelines of the most common non-IgE-mediated food hypersensitivity disorders (FPIES, FPIAP, and FPE).

Recent topics on gastrointestinal allergic disorders.

Gastrointestinal (GI) allergies are broadly associated with food allergies and divided into groups based on the degree of allergen-specific immunoglobulin E (IgE) involvement: IgE-mediated, non-IgE-mediated, and mixed. Non-IgE-mediated GI food allergies are mostly observed in neonates and infants and include food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy (FPE). In addition to the classical phenotype, unique phenotypes such as vomiting and bloody stool, suspected sepsis, and overlapping eosinophilic GI disorders (EGIDs) have increased in Japan over the past 2 decades. Some of these cases were defined as having chronic FPIES. More recently, cases of hen's-egg FPIES in Japan have increased dramatically since 2018, albeit for unknown reasons. Typical mixed-type food allergies are EGIDs, characterized by prominent eosinophil infiltration in the GI tract leading to GI symptoms. EGIDs are broadly classified into eosinophilic esophagitis (EoE) and non-EoE EGIDs that involve the GI tract with the exception of the esophagus. Of the EGIDs, EoE is the best known, as the number of cases has increased dramatically in Western countries, whereas pediatric EoE remains rare in Asia and non-EoE EGIDs may be more prevalent in Japan. A recent Japanese national survey showed that pediatric non-EoE EGIDs were persistent and severe compared to those in adults, possibly requiring further effective therapeutic options. Among the EGIDs, FPIAP is pathologically diagnosed as an infantile form of eosinophilic colitis. In addition, recent FPIES and FPE cases also involved eosinophilic inflammation. Recent cases of GI allergies may be associated with type 2 inflammation. A better understanding of the interactions between GI allergies and type 2 inflammation may clarify the pathogenesis of the recent increase in GI allergies.