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

Background: Food Protein-Induced Enterocolitis Syndrome (FPIES) is a clinically well-characterised, non-Immunoglobulin E (IgE)-mediated food allergy syndrome, yet its rare atypical presen-tation remains poorly understood.Objective: Aim of this study was to present the 10-year experience of a referral centre high-lighting the atypical FPIES cases and their long-term outcome.Methods: FPIES cases were prospectively evaluated longitudinally in respect of food outgrowth and developing other allergic diseases with or without concomitant IgE sensitisation.Results: One hundred subjects out of a total of 14,188 referrals (0.7%) were identified. At pre-sentation, 15 patients were found sensitised to the offending food. Fish was the most frequent eliciting food, followed by cow’s milk and egg. Tolerance acquisition was earlier for cow’s milk, followed by egg and fish, while found not to be protracted in atypical cases. Resolution was not achieved in half of the fish subjects during the 10-year follow-up time. Sensitisation to food was not related to infantile eczema or culprit food, but was related to sensitisation to aeroallergens. In the long-term evaluation, persistence of the FPIES or aeroallergen sensitisation was significantly associated with an increased hazard risk of developing early asthma symptoms. Conclusion: Sensitisation to food was related neither to eczema or culprit food nor to tolerance acquisition but rather to the development of allergic asthma through aeroallergen sen-sitisation. In addition to an IgE profile at an early age, FPIES persistence may also trigger mechanisms switching FPIES cases to a T-helper 2 cells immune response later in life, predis-posing to atopic respiratory symptoms; albeit further research is required.

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Adults with possible food protein-induced enterocolitis syndrome with crustacean ingestion

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-020-00497-z ◽

2020 ◽

Vol 16 (1) ◽

Author(s):

Daniel H. Li ◽

Andrew Wong-Pack ◽

Andrea Leilani Macikunas ◽

Harold Kim

Keyword(s):

Time Course ◽

Immunoglobulin E ◽

Gastrointestinal Symptoms ◽

Case Series ◽

Retrospective Chart Review ◽

Food Protein ◽

Female Predominance ◽

Adolescents And Adults ◽

History Of ◽

Ige Mediated

Abstract Background Food protein-induced enterocolitis (FPIES), an entity previously thought to only affect children, has been increasingly described in adults. In this study, we report a Canadian cohort of 19 adolescents and adults with recurrent non-immunoglobulin E (IgE)-mediated gastrointestinal symptoms after crustacean ingestion, consistent with FPIES. Methods We conducted a retrospective chart review of patients in an outpatient allergy clinic from January 2005 to May 2020. Electronic records were searched using keywords for crustaceans and for symptoms consistent with FPIES. We included patients with gastrointestinal symptoms specifically to crustaceans on more than one occasion, who were 14 years or older at the time of index reaction. Exclusion criteria included symptoms suggestive of an IgE-mediated anaphylactic reaction or a likely alternative diagnosis. We identified 19 patients for our cohort who met the criteria. Results Our cohort was 68.4% female (13) and 32.6% (6) male. The average age at first reaction to crustaceans was 34 years old with a range of 14–68 years (median = 28 years; IQR = 32 years). Time from ingestion to beginning of symptoms ranged from 3 min to 6.5 h, with an average of 2.8 h (median = 2 h; IQR = 3.25 h). Duration of reaction ranged from less than a minute to over 48 h, with a mean of 9.4 h (median = 4 h; IQR = 7.75 h). Patients had 4.8 reactions on average; however, number of reactions ranged from 2 to 12.5 (median = 3, IQR = 3). All patients identified a “trigger” food in the crustacean group, and 12 subjects identified additional reactions to other seafood. Conclusions This case series will better characterize and advance our understanding of this disease entity in adults. There are key differences in the presentation of FPIES in adults compared to children, namely female predominance, difference in solid food trigger, and unpredictable time course. Future studies are needed to examine the pathophysiology and natural history of adult FPIES. Specific guidelines should be developed for the diagnosis and management in adults. Trial registration: retrospectively registered.

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Una FPIES in una neonata

Medico e Bambino pagine elettr ◽

10.53126/mebxxiv025 ◽

2021 ◽

Vol 40 (1) ◽

pp. 25-25

Author(s):

Francesco Maria Risso ◽

Sara Romano

Keyword(s):

Food Allergy ◽

Immunoglobulin E ◽

Food Protein ◽

Neonatal Onset ◽

Gastrointestinal Food Allergy

Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E cell-mediated gastrointestinal food allergy that usually occurs in infancy. The paper presents and discusses a case of FPIES with neonatal onset.

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Learning early about peanut-triggered food protein‐induced enterocolitis syndrome

Journal of Food Allergy ◽

10.2500/jfa.2021.3.210003 ◽

2021 ◽

Vol 3 (1) ◽

pp. 32-36 ◽

Cited By ~ 1

Author(s):

Catherine M. Freeman ◽

Juan Carlos Murillo ◽

Brittany T. Hines ◽

Benjamin L. Wright ◽

Shauna R. Schroeder ◽

...

Keyword(s):

Immunoglobulin E ◽

Pediatric Population ◽

Retrospective Chart Review ◽

Feeding Practice ◽

Food Protein ◽

Test Results ◽

Prick Test ◽

Infant Diet ◽

Peanut Skin ◽

Triggered Reactions

Background: Food protein‐induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E mediated food allergy that typically presents with repetitive emesis and may be associated with lethargy, marked pallor, hypotension, hypothermia, and/or diarrhea. Although many foods are known to cause FPIES, peanut-triggered FPIES is emerging due to changes in the feeding practice guidelines, which recommends early peanut introduction in infants. Objective: We aimed to characterize peanut-triggered acute FPIES cases in our pediatric population and to describe their attributes, treatment, and outcomes. We hypothesized that increases in the incidence of peanut-triggered FPIES coincided with implementation of the guidelines for early peanut introduction. Methods: A retrospective chart review was conducted of pediatric patients who presented to Phoenix Children’s Hospital Emergency Department and subspecialty clinics during a 6-year period (January 2013 to September 2019). Results: Thirty-three cases of patients with acute FPIES were identified, five of which were peanut triggered. In those patients with peanut-triggered FPIES, the median age for peanut introduction was 7 months (range, 5‐24 months). Two patients had positive peanut skin-prick test results. All five cases were identified in the past 2 years (2018 to 2019). No peanut-triggered reactions were documented in the preceding 4-year period (2013 to 2017). Conclusion: Peanut may be an emerging trigger of acute FPIES, coinciding with an earlier introduction of peanut in the infant diet after implementation of the new addendum guidelines for the prevention of peanut allergy. Oats and rice were the most common triggers of acute FPIES in our cohort. Further study will help clarify the significance and reproducibility of these findings.

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Food protein‐induced proctocolitis and enteropathy

Journal of Food Allergy ◽

10.2500/jfa.2020.2.200017 ◽

2020 ◽

Vol 2 (1) ◽

pp. 55-58

Author(s):

Jonathan S. Tam

Keyword(s):

Early Childhood ◽

Gastrointestinal Tract ◽

Immunoglobulin E ◽

Chronic Diarrhea ◽

Signs And Symptoms ◽

Food Allergies ◽

Food Protein ◽

Healthy Infants ◽

Allergic Proctocolitis ◽

Bloody Stools

Non-IgE (immunoglobulin E) mediated gastrointestinal food allergies include several separate clinical entities, including food protein‐induced allergic proctocolitis (FPIAP) and food protein‐induced enteropathy (FPE). Although FPIAP and FPE both primarily affect the gastrointestinal tract, their presentations are vastly different. FPIAP presents with bloody stools in otherwise healthy infants, whereas FPE presents with chronic diarrhea, vomiting, malabsorption, and hypoproteinemia. These both typically present in infancy and resolve by early childhood. Although the presenting signs and symptoms may be different, management is similar in that both require avoidance of the suspected causal food.

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Updates on Food Allergy, Increasingly Prevalent Challenge

JURNAL BIOMEDIK (JBM) ◽

10.35790/jbm.10.3.2018.21980 ◽

2018 ◽

Vol 10 (3) ◽

pp. 152

Author(s):

Tonny Tanus ◽

Sunny Wangko

Keyword(s):

Atopic Dermatitis ◽

Food Allergy ◽

Eosinophilic Esophagitis ◽

Immunoglobulin E ◽

Pediatric Population ◽

Food Allergies ◽

Food Protein ◽

Safety Issues ◽

Ige Mediated ◽

Allergic Disorders

Abstrak: Prevalensi alergi makanan makin meningkat di seluruh dunia dan mengenai semua usia. Keparahan dan kompleksitas penyakit juga meningkat terlebih pada populasi anak. Terdapat beberapa jenis reaksi alergi yang dibahas: immunoglobulin E (IgE) mediated allergies and anaphylaxis, food triggered atopic dermatitis, eosinophilic esophagitis, dan non IgE mediated gastrointestinal food allergic disorders seperti food protein induced enterocolitis syndrome (FPIEs). Tes alergi, baik melalui kulit maupun IgE yang telah dikerjakan sekian lama masih dibebani dengan hasil positif palsu dan negatif palsu yang bermakna dengan manfaat terbatas pada beberapa alergi makanan. Selain menghindari, tidak terdapat terapi yang ampuh untuk alergi makanan. Berbagai imunoterapi telah dipelajari melalui jalur, subkutan, epikutan, oral dan sublingual yang hanya menghasilkan desensitisasi sementara dan dibebani dengan berbagai isu mengenai keamanannya. Agen biologik yang menghambat sitokin/interleukin (IL) dan molekul pada reaksi alergi makanan tampaknya merupakan pilihan yang menjanjikan. Anti IgE telah dipergunakan pada asma dan urtikaria kronis. Anti IL-4 dan IL-13 yang menghambat produksi IgE diindikasikan untuk dermatitis atopik. Anti eosinofil anti IL-5 berhasil menurunkan eksaserbasi asma. Berbagai agen biologik telah dipelajari untuk berbagai kondisi alergik dan imunologik, tetapi efektivitas dan kepraktisan terapi yang mahal ini untuk alergi makanan masih menjadi tanda tanya.Kata kunci: alergi makanan, reaksi alergi, terapi alergi makananAbstract: Food allergies have been increasing in prevalence for years affecting all ages. Disease severity and complexity have also increased, especially in the pediatric population. There are several types of reactions including: immunoglobulin-E (IgE) mediated allergies and anaphylaxis, food-triggered atopic dermatitis, eosinophilic esophagitis, and non IgE mediated gastrointestinal food allergic disorders such as FPIEs. Though allergy testing has been around for years, both skin and IgE testing are burdened by significant false positives and negatives, and are only useful in some food allergies. Avoidance is the sole therapy for food allergy. A variety of immunotherapies have been studied; subcutaneous, epicutaneous, oral, and sublingual. At best they only produce a temporary state of desensitization and have many safety issues. Examples of biologicals which block critical cytokines/interleukins (IL) in allergic conditions are Anti IgE, anti IL-4 and IL-13, and Anti eosinophils, Anti IL-5. Other biologicals are being studied for allergic conditions, but whether these expensive future treatments will be proven effective and practical in food allergy is unknown.Keywords: food allergy, allergic reaction, food allergy therapy

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Development of food protein–induced enterocolitis syndrome (FPIES) to egg after immunoglobulin E–mediated egg allergy

Annals of Allergy Asthma & Immunology ◽

10.1016/j.anai.2018.05.028 ◽

2018 ◽

Vol 121 (3) ◽

pp. 379-380 ◽

Cited By ~ 5

Author(s):

Hannah Duffey ◽

Maureen Egan

Keyword(s):

Immunoglobulin E ◽

Food Protein ◽

Egg Allergy

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Intestinal anaphylaxis: mediation of the response of colonic longitudinal muscle in rat

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1995.268.5.g764 ◽

1995 ◽

Vol 268 (5) ◽

pp. G764-G771

Author(s):

M. R. Oliver ◽

D. T. Tan ◽

R. B. Scott

Keyword(s):

Mast Cell ◽

Smooth Muscle ◽

Cell Activation ◽

Contractile Response ◽

Immunoglobulin E ◽

Mast Cell Activation ◽

Induced Response ◽

Food Protein ◽

Leukotriene D4 ◽

Functional Changes

Colonic smooth muscle function may be altered in food protein hypersensitivity reactions and could contribute to the clinical manifestation of diarrhea. To characterize such functional changes and elucidate the mediators and mechanisms involved. Hooded-Lister rats were sensitized by intraperitoneal injection of egg albumin (10 micrograms), and controls were sham sensitized with saline. Fourteen days later the contractility of longitudinally oriented distal colonic segments (mucosa intact) were studied in standard tissue baths in response to antigen (Ag) or other agents. After Ag exposure, a contractile response was documented in animals that were sensitized [specific immunoglobulin E (IgE) antibody levels > or = 1:64] and was specific for the sensitizing Ag. Mast cell involvement was suggested by a significant reduction in the number of granulated mucosal mast cells in sensitized tissues after Ag challenge and in the magnitude of the Ag-induced contractile response in the presence of mast cell stabilizers. The antigen-induced response was significantly and independently inhibited by both cyclooxygenase and lipoxygenase enzyme inhibitors and by leukotriene D4 and platelet activating factor receptor antagonists. The Ag-induced response was resistant to histamine and the 5-hydroxytryptamine antagonists, atropine and tetrodotoxin. These results suggest that the food protein-induced contraction of colonic longitudinal smooth muscle in the sensitized rat is due to IgE-mediated mast cell activation with the subsequent production and release of membrane-derived mediators that, in vitro, act directly on the smooth muscle.

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Intestinal anaphylaxis: in vivo and in vitro studies of the rat proximal colon

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1988.255.2.g201 ◽

1988 ◽

Vol 255 (2) ◽

pp. G201-G205 ◽

Cited By ~ 1

Author(s):

D. Forbes ◽

M. Patrick ◽

M. Perdue ◽

A. Buret ◽

D. G. Gall

Keyword(s):

Mast Cell ◽

Immunoglobulin E ◽

Short Circuit ◽

Proximal Colon ◽

Antigen Challenge ◽

Food Protein ◽

Ussing Chambers ◽

Cl Secretion ◽

Ige Mediated

The response of the rat proximal colon to an immunoglobulin E (IgE)-mediated hypersensitivity reaction was examined. Rats were sensitized to egg albumin (EA) by intraperitoneal injection, and serum titers of specific anti-EA IgE were measured at 14 days. Sensitized animals had titers of greater than or equal to 1:64, whereas no anti-EA IgE antibodies were detected in controls. Water and electrolyte absorption in the proximal colon, before and during antigen challenge, was measured by in vivo marker perfusion. Antigen challenge resulted in significant inhibition of water, Na+, Cl-, and K+ absorption in vivo. Proximal colonic tissue from sensitized and control animals was studied in Ussing chambers under short-circuited conditions. Antigen challenge of sensitized tissue resulted in significant increases in short-circuit current due to the induction of active Cl- secretion. No such changes were seen in control tissue. The abnormalities induced by antigen challenge in tissue from sensitized animals was blocked by doxantrazole (10(-3) M), a mast cell stabilizer. The findings indicate that IgE-mediated reactions in rat proximal colon to a food protein cause pertubations in water and electrolyte transport secondary to active Cl- secretion and these abnormalities appear to be due to mast cell degranulation.

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Motility effects of intestinal anaphylaxis in the rat

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1988.255.4.g505 ◽

1988 ◽

Vol 255 (4) ◽

pp. G505-G511 ◽

Cited By ~ 6

Author(s):

R. B. Scott ◽

S. C. Diamant ◽

D. G. Gall

Keyword(s):

Animal Model ◽

Motor Activity ◽

Immunoglobulin E ◽

Food Protein ◽

Jejunostomy Tube ◽

Egg Albumin ◽

Immune Mediated ◽

Specific Immunoglobulin E ◽

Specific Immunoglobulin ◽

Before And After

Intestinal motility was examined in an animal model of intestinal anaphylaxis. Hooded-Lister rats were sensitized (S) by intraperitoneal injection of 10 micrograms egg albumin (Ag) and compared with sham-sensitized controls (C). Seven days later three bipolar jejunal electrodes and a jejunostomy tube for motility recording and Ag administration were implanted. On day 14 intestinal myoelectric and motor activity were measured in fasted animals before and after intraluminal administration of either 10 mg egg albumin in 0.5 ml saline, 10 mg bovine serum albumin (BSA) in 0.5 ml saline, or placebo (P) challenge with 0.5 ml saline. Specific immunoglobulin E serum titers were greater than or equal to 1:64 in S animals, whereas C animals showed no response. None of the C animals challenged with P or Ag and none of the S animals challenged with P or BSA defecated after challenge, but all the S animals challenged with Ag developed diarrhea (P less than 0.001). In S animals challenged with Ag, the fasting motility pattern was disrupted, the migrating motor complex was abolished (P = 0.002), and the frequency of aborally propagating clustered contractions was increased (P less than 0.01). In this animal model an immune-mediated reaction to food protein was associated with diarrhea and altered intestinal myoelectric and motor activity.

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