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

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Assessing Feeding Difficulties in Children Presenting with Non-IgE-Mediated Gastrointestinal Food Allergies-A Commonly Reported Problem.

Many guidelines have been published to help diagnose food allergies, which have included feeding difficulties as a presenting symptom (particularly for non-IgE-mediated gastrointestinal allergies). This study aimed to investigate the prevalence of feeding difficulties in children with non-IgE-mediated gastrointestinal allergies and the association of such difficulties with symptoms and food elimination. An observational study was performed at Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. Children aged 4 weeks to 16 years without non-allergic co-morbidities who improved on an elimination diet using a previously published Likert scale symptom score were included. This study recruited 131 children, and 114 (87%) parents completed the questionnaire on feeding difficulties. Feeding difficulties were present in 61 (53.5%) of the 114 children. The most common feeding difficulties were regular meal refusals (26.9%), extended mealtimes (26.7%), and problems with gagging on textured foods (26.5%). Most children (40/61) had ≥2 reported feeding difficulties, and eight had ≥4. Children with feeding difficulties had higher rates of constipation and vomiting: 60.7% (37/61) vs. 35.8% (19/53), p = 0.008 and 63.9% (39/61) vs. 41.5% (22/53), p = 0.017, respectively. Logistic regression analysis demonstrated an association between having feeding difficulties, the age of the child, and the initial symptom score. Gender and the number of foods excluded in the elimination diet were not significantly associated with feeding difficulties. This study found that feeding difficulties are common in children with non-IgE-mediated gastrointestinal allergies, but there is a paucity of food allergy specific tools for establishing feeding difficulties, which requires further research in the long-term and consensus in the short term amongst healthcare professions as to which tool is the best for food allergic children.

Differences in the Course, Diagnosis, and Treatment of Food Allergies Depending on Age-Comparison of Children and Adults.

Food allergy (FA) has become a common global public health issue, with a growing prevalence in the modern world and a significant impact on the lives of patients, their families, and caregivers. It affects every area of life and is associated with elevated costs. Food allergy is an adverse immune reaction that occurs in response to a given food. The symptoms vary from mild to severe and can lead to anaphylaxis. This is why it is important to focus on the factors influencing the occurrence of food allergies, specific diagnostic methods, effective therapies, and especially prevention. Recently, many guidelines have emphasized the impact of introducing specific foods into a child's diet at an early age in order to prevent food allergies. Childhood allergies vary with age. In infants, the most common allergy is to cow's milk. Later in life, peanut allergy is more frequently diagnosed. Numerous common childhood allergies can be outgrown by adulthood. Adults can also develop new IgE-mediated FA. The gold standard for diagnosis is the oral provocation test. Skin prick tests, specific IgE measurements, and component-resolved diagnostic techniques are helpful in the diagnosis. Multiple different approaches are being tried as possible treatments, such as immunotherapy or monoclonal antibodies. This article focuses on the prevention and quality of life of allergic patients. This article aims to systematize the latest knowledge and highlight the differences between food allergies in pediatric and adult populations.

Resolution of Food Protein-Induced Enterocolitis Syndrome-A Long-Term Follow-Up Study of 113 Swedish Children.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES), a non-IgE-mediated allergy, primarily affects infants and young children. Whether and when tolerance develops seems to vary among populations and trigger foods. OBJECTIVE: This study aimed to evaluate tolerance development and its assessment in a Swedish cohort. METHODS: This was a prospective follow-up study of a Swedish cohort of 113 children, followed at 25 pediatric departments, with acute FPIES. Data on oral food challenges and FPIES resolution were collected through chart reviews and, if incomplete, supplemental caregiver interviews. RESULTS: The median age at last follow-up was 5.6 years (range: 8.7 months to 16.5 years). Eighty-three children (73%) developed tolerance to 96 of 137 (70%) foods: 93% for cow's milk, 92% for oat, and 46% for fish. The median age when tolerance was developed was 36.0 months (interquartile range: 23.7-48.2 months): 24.4 months for cow's milk, 30.1 months for oat, and 49.4 months for fish. Tolerance was determined in hospital in 45% of cases. Five percent demonstrated allergic sensitization to their FPIES trigger food. Age at tolerance development did not differ between sensitized and nonsensitized patients. CONCLUSIONS: Most of the children in this Swedish cohort with FPIES achieved tolerance before age 4 years. Cow's milk- and oat-induced FPIES had similar remission patterns, with early resolution. Development of tolerance to fish occurred significantly later compared with all other FPIES-inducing foods.

Heterogeneity of food protein-induced enterocolitis syndrome (FPIES).

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with gastrointestinal symptoms such as vomiting and diarrhea. The development of international consensus guidelines for the diagnosis and management of FPIES in 2017 enabled us to compare patients worldwide, regardless of geographic variation in disease features. As a result, it has become clear that there is heterogeneity among patients with FPIES or that there are cases that partly fit the diagnostic criteria for FPIES but have different characteristics. This review highlights the heterogeneity in FPIES characteristics in terms of trigger foods, the age of onset, differences in geographic regions, and symptoms; it further proposes four disease entities, including acute FPIES in children, acute FPIES in adults, chronic FPIES, and early-onset neonatal FPIES, depending on the age of onset and presumed pathophysiology. The major symptoms at onset and trigger foods differ in acute FPIES in children, acute FPIES in adults, and chronic FPIES, whereas the disease entities may share a similar pathophysiology. Early-onset neonatal FPIES may have a different pathophysiology than acute or chronic FPIES, and may not necessarily fulfil the full diagnostic criteria for acute or chronic FPIES described in the international consensus guidelines. Due to the similarity in symptoms, early-onset neonatal FPIES may sometimes be misdiagnosed as necrotizing enterocolitis. We aim to increase awareness of FPIES among medical staff in pediatrics, neonatology, and internal medicine and promote research, to gain a better understanding of the heterogeneity and pathophysiology of FPIES.

Effectiveness of continuous allergenic food intake for acute food protein-induced enterocolitis syndrome.

Continuous intake of allergenic food is a safe and efficient treatment strategy for patients with a prolonged course of acute food protein-induced enterocolitis syndrome. The initial dose, dose escalation rate, and starting age for continuous allergenic food intake need further clarification.

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.

The role of the atopy patch test in the diagnostic work-up of non-IgE gastrointestinal food allergy in children: a systematic review.

The "Atopy Patch Test" (APT) has been proposed as a diagnostic tool for food allergies (FA), especially in children with FA-related gastrointestinal symptoms. However, its diagnostic accuracy is debated, and its usefulness is controversial. The aim of this systematic review was to evaluate the APT diagnostic accuracy compared with the diagnostic gold standard, i.e., the oral food challenge (OFC), in children affected by non-IgE mediated gastrointestinal food allergies, including the evaluation in milk allergic subgroup. Both classical non-IgE mediated clinical pictures and food induced motility disorders (FPIMD) were considered. The search was conducted in PubMed and Scopus from January 2000 to June 2022 by two independent researchers. The patient, intervention, comparators, outcome, and study design approach (PICOS) format was used for developing key questions, to address the APT diagnostic accuracy compared with the oral food challenge (OFC). The quality of the studies was assessed by the QUADAS-2 system. The meta-analysis was performed to calculate the pooled sensitivity, specificity, DOR (diagnostic odds ratio), PLR (positive likelihood ratio), and NLR (negative likelihood ratio) with their 95% confidence intervals (CI). Out of the 457 citations initially identified via the search (196 on PubMed and 261 on Scopus), 37 advanced to full-text screening, and 16 studies were identified to be included in the systematic review. Reference lists from relevant retrievals were searched, and one additional article was added. Finally, 17 studies were included in the systematic review. The analysis showed that APT has a high specificity of 94% (95%CI: 0.88-0.97) in the group of patients affected by FPIMD. Data showed a high pooled specificity of 96% (95% CI: 0.89-0.98) and the highest accuracy of APT in patients affected by cow's milk allergy (AUC = 0.93).      Conclusion: APT is effective in identifying causative food in children with food-induced motility disorders.  What is Known: • Atopy patch test could be a useful diagnostic test for diagnosing food allergy, especially in children with food allergy-related gastrointestinal symptoms. What is New: • Atopy patch test may be a useful tool in diagnosing non IgE food allergy, especially in children with food-induced gastrointestinal motility disorders and cow's milk allergy.

Emerging Role of Alarmins in Food Allergy: An Update on Pathophysiological Insights, Potential Use as Disease Biomarkers, and Therapeutic Implications.

Food allergies are immuno-mediated adverse reactions to ingestion or contact with foods, representing a widespread health problem. The immune response can be IgE-mediated, non-IgE-mediated, or with a mixed mechanism. The role of innate immunity and alarmins in the pathogenesis of diseases such as asthma and atopic dermatitis is well known. Some authors have investigated the correlation between alarmins and food allergies, often obtaining interesting results. We analyzed articles published in English from the last 22 years present on PubMed concerning the role of alarmins in the pathogenesis of food allergies and their potential use as disease biomarkers, response biomarkers to therapy, or potential therapeutic targets. Nuclear alarmins (TSLP, IL-33, IL-25) appear to have a critical role in IgE-mediated allergies but are also implicated in entities such as eosinophilic esophagitis. Calprotectin and defensins may play a role as disease biomarkers and could help predict response to therapy, although results in the literature are often conflicting. Despite the promising results, more studies on humans still need to be conducted. Deepening our knowledge regarding alarmins and their involvement in food allergies could lead to the development of new biological therapies, significantly impacting patients' quality of life.

Outcomes reported in randomized controlled trials for mixed and non-IgE-mediated food allergy: Systematic review.

BACKGROUND: Mixed and non-IgE-mediated food allergy is a subset of immune-mediated adverse food reactions that can impose a major burden on the quality of life of affected patients and their families. Clinical trials to study these diseases are reliant upon consistent and valid outcome measures that are relevant to both patients and clinicians, but the degree to which such stringent outcome reporting takes place is poorly studied. OBJECTIVE: As part of the Core Outcome Measures for Food Allergy (COMFA) project, we identified outcomes reported in randomized clinical trials (RCT) of treatments for mixed or non-IgE-mediated food allergy. DESIGN: In this systematic review, we searched the Ovid, MEDLINE and Embase databases for RCTs in children or adults investigating treatments for food protein-induced enterocolitis syndrome, food protein-induced allergic proctocolitis, food protein-induced enteropathy and eosinophilic gastrointestinal disorders including eosinophilic esophagitis [EoE], eosinophilic gastritis and eosinophilic colitis published until 14 October 2022. RESULTS: Twenty-six eligible studies were identified, with 23 focused on EoE (88%). Most interventions were corticosteroids or monoclonal antibodies. All EoE studies assessed patient-reported dysphagia, usually using a non-validated questionnaire. Twenty-two of 23 EoE studies used peak tissue eosinophil count as the primary outcome, usually using a non-validated assessment method, and other immunological markers were only exploratory. Thirteen (57%) EoE studies reported endoscopic outcomes of which six used a validated scoring tool recently recommended as a core outcome for EoE trials. Funding source was not obviously associated with likelihood of an RCT reporting mechanistic versus patient-reported outcomes. Only 3 (12%) RCTs concerned forms of food allergy other than EoE, and they reported on fecal immunological markers and patient-reported outcomes. CONCLUSIONS: Outcomes measured in clinical trials of EoE and non-IgE-mediated food allergy are heterogeneous and largely non-validated. Core outcomes for EoE have been developed and need to be used in future trials. For other forms of mixed or non-IgE-mediated food allergies, core outcome development is needed to support the development of effective treatments. SYSTEMATIC REVIEW REGISTRATION: OSF public registry DOI:10.17605/OSF.IO/AZX8S.

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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

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.

[Non-IgE-mediated food allergy]. / Alergia alimentaria no mediada por IgE.

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.

La alergia alimentaria es una respuesta inmunitaria a las proteínas de los alimentos. Suele afectar al 8% de los niños y al 2% de los adultos en países occidentales. La alergia alimentaria no mediada por IgE afecta, principalmente, el aparato gastrointestinal. Las alergias alimentarias gastrointestinales se clasifican, por su patogenia subyacente, en: mediadas por IgE, no mediadas por IgE, o mixtas. Los síntomas de pacientes con proctocolitis alérgica inducida por proteínas alimentarias se originan por la inflamación local del colon distal, que causa hematoquecia en neonatos. Puede afectar todo el conducto gastrointestinal y provocar síntomas de emesis intratable, con subsiguientes trastornos metabólicos y choque hipovolémico. El síndrome de enterocolitis inducida por proteínas alimentarias es una alergia no mediada por IgE que suele aparecer en la infancia, con vómito prolongado repetitivo, que inicia entre 1 a 4 horas después de la ingestión de alimentos. La manifestación en adultos suele desencadenarse por el consumo de mariscos. Las enfermedades atópicas afectan del 40-60% de los pacientes con síndrome de enterocolitis inducida por proteínas alimentarias, incluso al 40-50% de quienes padecen enteropatía y proctocolitis inducidas por proteínas alimentarias. Los probióticos (Lactobacillus GG) pueden aliviar los síntomas de proctocolitis alérgica inducida por proteínas alimentarias, al alterar la composición de la microbiota intestinal. El trasplante de microbiota fecal (TMF) puede cambiar la microecología intestinal de manera eficiente comparada con los alimentos o probióticos.

Food protein-induced enterocolitis syndrome (FPIES): Beyond the guidelines.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE) cell mediated food allergy that can cause severe symptoms and is considered an allergic emergency. Objective: To describe FPIES epidemiology and appraise the approach to diagnosis and management. Methods: A review of the relevant articles published in the peer-reviewed journals since the publication of the First International FPIES Consensus Guidelines in 2017. Results: FPIES is estimated to affect 0.51-0.9% of children and 0.22% of adults in the United States. It typically presents with protracted, projectile vomiting, which occurs within 1-4 hours of ingesting culprit foods, sometimes followed by diarrhea within 24 hours of ingestion. In ∼15-20% of severe cases, patients go into hypovolemic or distributive shock. In chronic FPIES, infants may have failure to thrive and weight loss. The most common triggers include cow's milk, oat, rice, and avocado, with egg and peanut being more frequently reported. Examples of other common fruit and vegetable triggers include banana, apple, and sweet potato. FPIES can be classified into acute, chronic, adult-onset, or atypical subtypes. FPIES is associated with comorbid atopic conditions of IgE-mediated food allergy, atopic dermatitis, asthma, allergic rhinitis, and eosinophilic esophagitis. The natural history of infantile FPIES is generally favorable, with the exception of fish FPIES. Seafood FPIES in adults has low rates of resolution over 3-5 years. Correctly identifying FPIES can be challenging because there are no specific biomarkers for diagnosis and the constellation of symptoms may mimic those of infectious enteritis or sepsis. Management relies on dietary food avoidance, periodic re-evaluations for tolerance with oral food challenges, and management of acute reactions with rehydration and antiemetic ondansetron. Although the pathophysiology of FPIES remains poorly understood, underlying mechanisms such as cytokine release, leukocyte activation, and impaired gastrointestinal mucosal barrier function may act as cornerstones for further research. Conclusion: Prevention, laboratory diagnostic testing, and strategies to accelerate tolerance development are urgent unmet needs in FPIES.

FPIES: Data for Germany in international comparison.

Food protein-induced enterocolitis syndrome (FPIES) is a rare, non-IgE-mediated food allergy. The triggering foods differ significantly from the typical triggers of an IgE-mediated food allergy. Until recently, there were no data on triggers of FPIES in Germany. In order to create an advisory basis for the care of German patients, a large multicenter study was initiated and published at the end of 2021. This revealed clear differences in international comparisons. The most frequent triggers for FPIES in Germany are cow's milk, fish, vegetables, and meat. Most children (84%) react to only one food. The prognosis is usually good, depending on the trigger. Regional data should be used for counseling patients with FPIES. Specific recommendations for this are given in this article.

Diagnosis and management of food allergy-associated gastroesophageal reflux disease in young children-EAACI position paper.

Gastro-oesophageal reflux (GOR) and food allergy (FA) are common conditions, especially during the first 12 months of life. When GOR leads to troublesome symptoms, that affect the daily functioning of the infant and family, it is referred to as GOR disease (GORD). The role of food allergens as a cause of GORD remains controversial. This European Academy of Allergy and Clinical Immunology (EAACI) position paper aims to review the evidence for FA-associated GORD in young children and translate this into clinical practice that guides healthcare professionals through the diagnosis of suspected FA-associated GORD and medical and dietary management. The task force (TF) on non-IgE mediated allergy consists of EAACI experts in paediatric gastroenterology, allergy, dietetics and psychology from Europe, United Kingdom, United States, Turkey and Brazil. Six clinical questions were formulated, amended and approved by the TF to guide this publication. A systematic literature search using PubMed, Cochrane and EMBASE databases (until June 2021) using predefined inclusion criteria based on the 6 questions was used. The TF also gained access to the database from the European Society of Paediatric Gastroenterology and Hepatology working group, who published guidelines on GORD and ensured that all publications used within that position paper were included. For each of the 6 questions, practice points were formulated, followed by a modified Delphi method consisting of anonymous web-based voting that was repeated with modified practice points where required, until at least 80% consensus for each practice point was achieved. This TF position paper shares the process, the discussion and consensus on all practice points on FA-associated GORD.

The Natural Course of Adult-Onset Food Protein-Induced Enterocolitis Syndrome.

BACKGROUND: Adult-onset food protein-induced enterocolitis syndrome (FPIES) has been increasingly recognized in recent years. Adult FPIES differs from pediatric FPIES in terms of dietary triggers and symptoms, thus further broadening the clinical phenotypes of the disease. The natural history of FPIES in adulthood is poorly characterized. OBJECTIVE: To evaluate the natural course of FPIES in adults. METHODS: We performed an ambispective study of adults diagnosed with acute FPIES during 2016-2021. Data on age, sex, symptoms, implicated food, and oral food challenge (OFC) outcomes at baseline and during follow-up were analyzed. RESULTS: Forty-two adults were included (83.3% female; median age at diagnosis, 40 years). The predominant symptoms were diarrhea (92.9%) and abdominal cramps (71.4%); vomiting was reported by 59% of patients. The most common triggers were shellfish (n = 19, 45.2%) and fish (n = 19, 45.2%). The mean number of reactions before diagnosis was 6.3 (2-15). Twenty-one OFCs were carried out with the offending food in 15 patients. Six patients achieved tolerance (40%) after a mean of 17.8 months (range, 6-36 months). Twelve of all OFCs performed were positive (57.1%). The absolute leukocyte and neutrophil counts measured before and 1 to 2 hours after the positive challenge showed a mean increase of 3045 and 2736 cells/µL, respectively. Serum tryptase, C-reactive protein, and eosinophil and platelet values did not change significantly after the OFC. CONCLUSION: Some patients may outgrow adult-onset FPIES.

Food allergy and hypersensitivity reactions in children and adults-A review.

Adverse reactions after food intake are commonly reported and a cause of concern and anxiety that can lead to a very strict diet. The severity of the reaction can vary depending on the type of food and mechanism, and it is not always easy to disentangle different hypersensitivity diagnoses, which sometimes can exist simultaneously. After a carefully taken medical history, hypersensitivity to food can often be ruled out or suspected. The most common type of allergic reaction is immunoglobulin E (IgE)-mediated food allergy (prevalence 5-10%). Symptoms vary from mild itching, stomach pain, and rash to severe anaphylaxis. The definition of IgE-mediated food allergy is allergic symptoms combined with specific IgE-antibodies, and therefore only IgE-antibodies to suspected allergens should be analyzed. Nowadays, methods of molecular allergology can help with the diagnostic process. The most common allergens are milk and egg in infants, peanut and tree nuts in children, and fish and shellfish in adults. In young children, milk/egg allergy has a good chance to remit, making it important to follow up and reintroduce the food when possible. Other diseases triggered by food are non-IgE-mediated food allergy, for example, eosinophilic esophagitis, celiac disease, food protein-induced enterocolitis syndrome, and hypersensitivity to milk and biogenic amines. Some of the food hypersensitivities dominate in childhood, others are more common in adults. Interesting studies are ongoing regarding the possibilities of treating food hypersensitivity, such as through oral immunotherapy. The purpose of this review was to provide an overview of the most common types of food hypersensitivity reactions.