A Multicentre French Prospective Study of Children With Food Protein Induced Enterocolitis Syndrome in Its Acute Form (SEIPA-FPIES)

Pathways of Children With Food Protein Induced Enterocolitis Syndrome in Its Acute Form : a Multicentre Prospective Study - National FPIES Observatory

Food protein induced enterocolitis syndrome (FPIES), is a non-IgE mediated food allergy (FA) which seems to expand, and occurring in infancy. This disease is usually unknown by clinicians. In 2017, an international workgroup of American Academy of Allergy, Asthma and Immunology published clinical criteria to specify the diagnosis. However, there is a lack of information in literature for describe the evolution and atypical phenotypes. In addition, no prospective French series has been published to date. The aim of the study is to collect clinical features and allergy testing of children who have acute form of FPIES at diagnosis and during evolution during three years

Study Overview

• Status: Recruiting
• Conditions: Food Protein Induced Enterocolitis Syndrome (FPIES)
• Intervention / Treatment: Diagnostic test: allergy test

Detailed Description

Food protein induced enterocolitis syndrome (FPIES), is a non-IgE mediated food allergy (FA) which seems to expand, and occurring in infancy. Prevalence of FPIES is unknown. In 2011, Katz published cumulative incidence of cow 'milk FPIES of 3 per 1000 new-borns, from prospective birth cohort in Israel.

The offending food depend on the country, probably in relation to eating habits.

Cow's milk (CM) is most commonly incriminated and can lead to a chronic digestive disease or in its acute form with potentially life-threatening vomiting/diarrhoea/dehydration, confusing with anaphylaxis. Rice and oat in US, or fish and egg in France are the solid food most often implicated.

This disease is usually unknown by clinicians. Its diagnostic is based on clinical history, and differential diagnosis elimination.

In 2017, an international workgroup of American Academy of Allergy, Asthma and Immunology published clinical criteria to specify the diagnosis and management. According to this last definition (JACI 2017), patient have to meet the major criterion and at least 3 minor criteria. Major criterion is vomiting in the 1- to 4-h period after ingestion of the suspect food and absence of classic IgE-mediated allergic skin or respiratory symptoms. Minor criteria are :

1. A second (or more) episode of repetitive vomiting after eating the same suspect food,
2. Repetitive vomiting episode 1-4 h after eating a different food
3. Extreme lethargy with any suspected reaction
4. Marked pallor with any suspected reaction
5. Need for emergency department visit with any suspected reaction
6. Need for intravenous fluid support with any suspected reaction
7. Diarrhea in 24 h (usually 5-10 h)
8. Hypotension
9. Hypothermia Skin prick test et IgE antibody are negative except atypical FPIES. Acute management begins with clinical evaluation, then administer normal saline bolus quickly. Parenteral ondansetron can be used to stop vomiting. Nutritional management implicate elimination of the offending foods. Only the oral food challenge in hospital can be done to determine resolution of FPIES after a long time of no symptom.

The age of tolerance, depend of the food. The average age of acquiring tolerance for cow's milk changes in the literature, around 8-10 months in Korea, around 1 year in Israel, around 5 years in the United States. There is no data in France on the recovery age of CM-FPIES.

However, there is a lack of information in literature for describe the evolution and atypical phenotypes. In addition, no prospective French series has been published to date.

Our work is a national prospective study, which will collect news cases of acute FPIES diagnosis in sixteen French centres.

Main objective: To determine the rate of acquisition of tolerance by food at 1 year, 2 years, 3 years post inclusion.

Secondary objectives:

• Description of a population of children with newly diagnosed FPIES. 2. Describe the rate of patients with FPIES progressing to IgE sensitization whatever the food at 1 year, 2 years, 3 years post inclusion.

  3. Determine per food the rate of FPIES patients evolving towards IgE sensitization at 1 year, 2 years, 3 years post inclusion.

  4. Describe the rate of patients with FPIES progressing to clinical symptoms of IgE-mediated allergy, whatever the food, at 1 year, 2 years, 3 years post inclusion.

  5. Determine, by food, the rate of FPIES evolving towards clinical symptoms of IgE-mediated allergy at 1 year, 2 years, 3 years post inclusion.

  6. Describe the rate of patients with multiple FPIES at each time point of the study.

  7. Describe at each time the rates of patients with personal atopic comorbidities.

The inclusion period will last three years, and the follow up of each patient will last three years.

Allergologist will see the patient at inclusion visit, then one time a year. If the patient does not acquire tolerance, an oral food challenge (OFC) in hospital will lead to answer.

The aim of our work will help allergologist to manage FPIES children, with French specificities in offending food, and tolerance.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dominique Donzeau; Phone Number: 0492034560; Email: donzeau.d@chu-nice.fr
• Study Contact Backup: Name: Sibylle BLANC, MD; Phone Number: 0492030841; Email: blanc.si@pediatrie-chulenval-nice.fr

Study Locations

• France
  • Angers, France
    • Recruiting
    • Chu Angers
    • Contact: ANNE HOPPE, MD
  • Aulnay-sous-Bois, France
    • Recruiting
    • Chi Robert Ballanger
    • Contact: ARIANNE NEMNI
  • Clermont-Ferrand, France
    • Recruiting
    • Chu Clermont-Ferrand
    • Contact: ELODIE MICHAUD
  • Colmar, France
    • Recruiting
    • Hopital Civils de Colmar
    • Contact: JESSICA LOGLI
  • Grenoble, France
    • Not yet recruiting
    • CHU Grenoble
    • Contact: VIRGINIE JUBIN
  • Haguenau, France
    • Recruiting
    • CH Haguenau
    • Contact: CARINE FAVRE-METZ
  • Lille, France
    • Recruiting
    • Chr Lille Hopital Jeanne de Flandre
    • Contact: ANTOINE DESCHILDRE
  • Lille, France
    • Not yet recruiting
    • Hopital Saint Vincent de Paul Ghicl
    • Contact: NICOLAS KALACH
  • Lyon, France
    • Recruiting
    • Hopital Civil de Lyon
    • Contact: PRISCILLE BIERME
  • Montpellier, France
    • Recruiting
    • CHU Montpellier
    • Contact: DAVIDE CAIMMI
  • Nancy, France
    • Recruiting
    • Chu Nancy
    • Contact: AMANDINE DIVARET-CHAUVEAU
  • Nice, France
    • Recruiting
    • Hôpitaux Pédiatriques de Nice CHU-Lenval
    • Contact: Sibylle BLANC, MD; Phone Number: 0492030841; Email: blanc.si@pediatrie-chulenval-nice.fr
  • Nice, France
    • Not yet recruiting
    • Cabinet Berlioz
    • Contact: MICHELE BERLIOZ
  • Paris, France
    • Not yet recruiting
    • Aphp Armand Trousseau
    • Contact: ANAIS LEMOINE
  • Paris, France
    • Recruiting
    • Hopital Ambroise Pare Aphp
    • Contact: GREGOIRE BENOIST
  • Paris, France
    • Not yet recruiting
    • Hopital Necker Enfants Malades Aphp
    • Contact: GUILLAUME LEZMI
  • Paris, France
    • Not yet recruiting
    • Hopital Robert Debre Aphp
    • Contact: FLORE AMAT
  • Rouen, France
    • Recruiting
    • CHU Rouen
    • Contact: LAURE COUDERC
  • Toulouse, France
    • Not yet recruiting
    • Cabinet Chabbert
    • Contact: ANNE CHABBERT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age from 0 to 17 years old,
• seen in allergologist visit for acute FPIES, due to history of suggestive clinical symptoms, confirmed by the criteria published in 2017 in the JACI (Nowak-Wegrzyn et al, JACI 2017), or by an oral food challenge for diagnosis in the absence of the requested clinical criteria,
• affiliated to social security (public healthcare system)
• signed consent of one of the parents or the holder of parental authority

Exclusion Criteria:

• Associated pathology that may contraindicate OFC at the discretion of the investigating physician. In particular justifying permanent treatment with a beta-blocker or an angiotensin-converting enzyme inhibitor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FPEIS children	Diagnostic test: allergy test; allergy test are oral food challenge , prick test and IgE blood rate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tolerance acquisition	The acquisition of tolerance will be defined by negative OFC or accidental intake of the food at home tolerated according to parents discussion	through study completion, an average of 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
population description	The description of the population included will be made according to the clinical, the demographic data, the allergy tests, the history of the disease	through study completion, an average of 6 years
IgE sensitization	IgE sensitization is defined by the positivity of an immediate-read skin test (wheal of the prick test greater than half of the positive histamine control) and/or the presence of specific IgE antibody on a blood sample (≥0.35 kU/L).	at 1 year, 2 years, 3 years post inclusion
food sensitization	food sensitization is defined by the positivity of an immediate-read skin test (wheal of the prick test greater than half of the positive histamine control)	at 1 year, 2 years, 3 years post inclusion
IgE-mediated allergy	IgE-mediated allergy is defined by the demonstration of clinical symptoms related to the presence of these specific IgEs.	at 1 year, 2 years, 3 years post inclusion
IgE-dependent allergy	IgE-dependent allergy will be defined by the appearance of symptoms a few minutes to 2 hours after ingestion of the food, with skin signs (urticaria, angioedema) and/or respiratory symptoms (dyspnea, laryngospasm, cough, bronchospasm ); digestive and neurological signs being potentially common with the diagnosis of FPIES	at 1 year, 2 years, 3 years post inclusion
multiple FPIES	A multiple FPIES will be defined by the presence of clinical symptoms of FPIES for at least two different foods	at 1 year, 2 years, 3 years post inclusion
Atopic comorbidities	Atopic comorbidities will be defined by asthma, allergic rhinitis, atopic dermatitis, and eosinophilic esophagitis	at 1 year, 2 years, 3 years post inclusion

Collaborators and Investigators

• Sponsor: Fondation Lenval

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: July 29, 2022
• First Submitted That Met QC Criteria: September 2, 2022
• First Posted (Actual): September 6, 2022

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: children; Non IgE mediated food allergy; FPIES,
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Syndrome; Enterocolitis
• Other Study ID Numbers: 21-HPNCL-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No