Position paper
International consensus guidelines for the
diagnosis and management of food protein–induced
enterocolitis syndrome: Executive
summary—Workgroup Report of the Adverse
Reactions to Foods Committee, American Academy
of Allergy, Asthma & Immunology
Anna Nowak-We
˛
grzyn, MD, Mirna Chehade, MD, Marion E. Groetch, MS, RDN, Jonathan M. Spergel, MD, PhD,
Robert A. Wood, MD, Katrina Allen, MD, PhD, Dan Atkins, MD, Sami Bahna, MD, PhD, Ashis V. Barad, MD,
Cecilia Berin, PhD, Terri Brown Whitehorn, MD, A. Wesley Burks, MD, Jean-Christoph Caubet, MD,
Antonella Cianferoni, MD, PhD, Marisa Conte, MLIS, Carla Davis, MD, Alessandro Fiocchi, MD,
Kate Grimshaw, PhD, RD, RNutr, Ruchi Gupta, MD, Brittany Hofmeister, RD, J. B. Hwang, MD, Yitzhak Katz, MD,
George N. Konstantinou, MD, PhD, MSc, Stephanie A. Leonard, MD, Jennifer Lightdale, MD, Sean McGhee, MD,
Sami Mehr, MD, FRACP, Stefano Miceli Sopo, MD, Giovanno Monti, MD, PhD, Antonella Muraro, MD, PhD,
Stacey Katherine Noel, MD, Ichiro Nomura, MD, Sally Noone, RN, MSN, Hugh A. Sampson, MD,
Fallon Schultz, MSW, LCSW, CAM, Scott H. Sicherer, MD, Cecilia C. Thompson, MD, Paul J. Turner, MD,
Carina Venter, RD, PhD, A. Amity Westcott-Chavez, MA, MFA, and Matthew Greenhawt, MD, MBA, MSc
Food protein–induced enterocolitis (FPIES) is a non-IgE cell-
mediated food allergy that can be severe and lead to shock.
Despite the potential seriousness of reactions, awareness of
FPIES is low; high-quality studies providing insight into the
pathophysiology, diagnosis, and management are lacking; and
clinical outcomes are poorly established. This consensus
document is the result of work done by an international
workgroup convened through the Adverse Reactions to Foods
Committee of the American Academy of Allergy, Asthma &
Immunology and the International FPIES Association advocacy
group. These are the first international evidence-based
guidelines to improve the diagnosis and management of patients
with FPIES. Research on prevalence, pathophysiology,
diagnostic markers, and future treatments is necessary to
improve the care of patients with FPIES. These guidelines will be
updated periodically as more evidence becomes available. (J
Allergy Clin Immunol 2017;139:1111-26.)
Key words: Food protein–induced enterocolitis syndrome, guide-
lines, non–IgE-mediated food allergy
WORKGROUP MEMBERS
Anna Nowak-We
˛
grzyn, MD, PhD
Associate Professor of Pediatrics
Division of Allergy and Immunology
Icahn School of Medicine at Mount Sinai
New York, NY
Mirna Chehade, MD, MPH
Associate Professor of Pediatrics and Medicine
Director, Eosinophilic Disorders Center
Division of Allergy and Immunology
Icahn School of Medicine at Mount Sinai
New York, NY
Marion E. Groetch, MS, RDN
Director of Nutrition Service, Jaffe Food Allergy Institute
Division of Allergy and Immunology
Icahn School of Medicine at Mount Sinai
New York, NY
Jonathan M. Spergel, MD, PhD
Professor of Pediatrics
Division of Allergy and Immunology
The Children’s Hospital of Philadelphia
Perelman School of Medicine at University of Pennsylvania
Philadelphia, Pa
Robert A. Wood, MD
Professor of Pediatrics and International Health
Director, Division of Pediatric Allergy and Immunology
Johns Hopkins University School of Medicine
Baltimore, Md
Abbreviations used
AAF: Amino acid–based formula
CBC: Complete blood cell count
CM: Cow’s milk
FPIES: Food protein–induced enterocolitis syndrome
FTT: Failure to thrive
OFC: Oral food challenge
sIgE: Specific IgE
SPT: Skin prick test
TD: Threshold dose
1111
Katrina J. Allen, MD, PhD
University of Melbourne Department of Paediatrics
Murdoch Children’s Research Institute
Royal Children’s Hospital Melbourne, Australia
Institute of Inflammation and Repair
University of Manchester
Manchester, United Kingdom
Dan Atkins, MD
Chief, Allergy and Immunology Section
Co-Director, Gastrointestinal Eosinophilic Diseases Program
Children’s Hospital Colorado
Associate Professor of Pediatrics
University of Colorado School of Medicine
Aurora, Colo
Sami Bahna, MD, DrPH
Professor of Pediatrics & Medicine
Chief of Allergy & Immunology Section
Louisiana State University Health Sciences Center
Shreveport, La
Ashis Barad, MD
Section Chief, Division of Pediatric Gastroenterology,
Hepatology and Nutrition Baylor Scott & White McLane
Children’s Medical Center
Assistant Professor of Pediatrics Texas A&M Health Sciences
Center College of Medicine
Temple, Tex
Cecilia Berin, PhD
Associate Professor of Pediatrics
Division of Allergy and Immunology
Icahn School of Medicine at Mount Sinai
New York, NY
Terri Brown Whitehorn, MD
Division of Allergy and Immunology
The Children’s Hospital of Philadelphia
Associate Professor of Clinical Pediatrics
Perelman School of Medicine, University of Pennsylvania
Philadelphia, Pa
A. Wesley Burks, MD
Curnen Distinguished Professor of Pediatrics
Executive Dean and Chair Pediatrics
University of North Carolina
Chapel Hill, NC
Jean-Christoph Caubet
University Hospitals of Geneva
Pediatric Allergy Unit, Department of Child and Adolescent
Geneva, Switzerland
This project has been sponsored by The International FPIES Association.
Disclosure of potential conflict of interest: A. Nowak-We˛grzyn has a board membership
with Merck; has consultant arrangements with Aimmune and Nestle; is employed by
the Icahn School of Medicine; has received grants from DBV, Food Allergy Research
and Education (FARE), the National Institutes of Health (NIH), and Thermo Fisher;
has received payment for lectures from Nestle; has received payment for manuscript
preparation from Nestle; has received royalties from UpToDate; has received payment
for development of educational presentations from Annenberg Center; and is the chair
of the Medical Advisory Board for the International FPIES Organization. M. Chehade
is a member of the Medical Advisory Board for the International FPIES Association; is
a member of the Medical Advisory Panel for the American Partnership for
Eosinophilic Disorders; has consultant arrangements with Actelion, Receptos, and
Shire; and has received grants from Nutricia and Regeneron. M. Groetch has received
payment for lectures from Nutricia North American and has received royalties from
UpToDate. J. M. Spergel is on the Scientific Advisory Boards for DBV Technology and
Danone Nutricia; has consultant arrangements with GLG; has received grants from the
NIH, Aimmune Therapeutics, and DBV Technology; has received payment for
lectures from MEI; has received royalties from UpToDate; and has received stock/
stock options from DBV Technology. R. A. Wood is employed by Johns Hopkins
University; has received grants from the NIH, Astellas, DBV, and Aimmune; and has
received royalties from UpToDate. K. Allen has consultant arrangements with Nestle,
Thermo Fisher, Aspencare, and Nutricia. D. Atkins is on the Medical Advisory Board
for the American Partnership for Eosinophilic Disorders, is on the Data Monitoring
Safety Board for MILES study for DBV Technologies, has received payment for
lectures from Regeneron, and has received travel support from Monsanto. A. Barad has
received payment for lectures from Abbott Nutrition. C. Berin has received grants from
the NIH. A. W. Burks has received grants from the Food Allergy & Anaphylaxis
Network, the NIH, and the Wallace Research Foundation; has received personal fees
from FARE, the NIH AITC Review Panel, the NIH HAI Study Section, World Allergy
Organization, Aimmune Therapeutics, Epiva Biosciences, Genentech, Merck, Stal-
lergenes, Valeant Pharmaceuticals North America, PPD Development, Allertein, and
Sanofi US Services; and has received nonfinancial support from Regeneron
Pharmaceuticals. J.-C. Caubet is employed by Geneva University Hospitals and has
received payment for lectures from Thermo Fisher. A. Fiocchi has received a grant
from the International FPIES Association, has a board membership with Ferrero, and is
employed by Ospedale Pediatrico Bambino Ges
u. K. Grimshaw has consultant
arrangements with Reacta Biotech, has received payment for lectures from Danone and
Abbott, and has received travel support from Abbott. R. Gupta has consultant
arrangements with Kaleo and BEFORE Brands and has received grants from Mylan
Specialty, Aimmune, and United Healthcare Group. S. A. Leonard is on the Medical
Advisory Board for FARE, has received a grant from the FARE Clinical Network, has
received payment for lectures from Allergy and Asthma Medical Group and Research
Center, and has received travel support from the American Academy of Allergy,
Asthma & Immunology. J. Lightdale has consultant arrangements with Perrigo
Nutritionals, Norgine, and Medtronic; has received grants from Abbvie; has received
payment for lectures from Mead-Johnson; has received royalties from 5-Min Pediatric
Consult; and has received payment for development of educational presentations from
Mead-Johnson and Perrigo Nutritionals. S. Mehr has received grants from the Allergy
and Immu nology Foundation of Australasia and has received payment for lectures
from the Immune Deficiency Lecture Series. A. Muraro has consultant arrangements
with MEDA, Novartis, and Menarini; is employed by Padua University Hospital; and
has received payment for lectures from MEDA and Menarini. S. Noone has consultant
arrangements with Aimmune, is employed by Icahn School of Medicine at Mount
Sinai, and has received royalties from Up To Date. H. A. Sampson has received
royalties from UpToDate and was employed 60% of his time as a Professor of
Pediatrics and Director of the Jaffe Food Allergy Institute by the Icahn School of
Medicine at Mount Sinai and 40% of his time as the Chief Scientific Officer at DBV
Technologies. S. H. Sicherer has received grants from the National Institute of Allergy
and Infectious Diseases and Food Allergy Research and Education and has received
royalties from UpToDate. P. J. Turner has consultant arrangements with Reacta
Biotech and the UK Food Standards Agency; is employed by Public Health England
and Imperial College London; has received grants from the Medical Research Council,
NIHR/Imperial BRC, EU FP7 Programme, and UK Department of Health; and has
received travel support from the National Institute for Health and Care Excellence. C.
Venter has consultant arrangements with Danone and Mead Johnson and has received
payment for lectures from Nestle. A. Westcott-C havez is a board member for the
International FPIES Association. M. Greenhawt has received a grant from the Agency
for Healthcare Research and Quality (1K08HS024599-01, Career Development
Award); has received travel support from the National Institute of Allergy and
Infectious Diseases and the Joint Taskforce on Allergy Practice Parameters; is on the
scientific advisory council for the National Peanut Board; has consultant arrangements
with the Canadian Transportation Agency, Nutricia, Nestle, Aimmune, Kaleo
Pharmaceutical, Monsanto, and Intrommune Pharmaceutical; is an Associate Editor
for the Annals of Allergy, Asthma, and Immunology for the American College of Al-
lergy, Asthma & Immunology; and has received payment for lectures from Reach
MD, Thermo Fisher Scientific, New York Allergy and Asthma Society, UCLA/Harbor
Heiner Lectureship, Medscape, the Aspen Allergy Society, the European Academy of
Allergy and Clinical Immunology, the Canadi an Society of Allergy and Clinical
Immunology, the Pennsylvania Society for Allergy and Immunology, and American
College of Allergy, Asthma & Immunology. The rest of the authors declare that they
have no relevant conflicts of interest.
Received for publication September 2, 2016; revised December 7, 2016; accepted for
publication December 21, 2016.
Available online February 4, 2017.
Corresponding author: Anna Nowak-We˛grzyn, MD, Icahn School of Medicine at Mount
Sinai, Jaffe Food Allergy Institute One Gustave Levy Place, Box 1198, New York, NY
10029. E-mail: anna.nowak-wegrzyn@mssm.edu.
The CrossMark symbol notifies online readers when updates have been made to the
article such as errata or minor corrections
0091-6749
Ó 2017 The Authors. Published by Elsevier Inc. on behalf of the American Academy of
Allergy, Asthma & Immunology. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
http://dx.doi.org/10.1016/j.jaci.2016.12.966
J ALLERGY CLIN IMMUNOL
APRIL 2017
1112 NOWAK-WE˛ GRZYN ET AL
Antonella Cianferoni, MD, PhD
Assistant Professor of Pediatrics
Allergy and Immunology Division, Children’s Hospital of
Philadelphia
Perelman School of Medicine, University of Pennsylvania
Philadelphia, Pa
Marisa L. Conte, MLIS
Taubman Health Services Library
The University of Michigan Medical School
Ann Arbor, Mich
Carla Davis, MD
Associate Professor of Pediatrics
Baylor College of Medicine
Houston, Tex
Alessandro Fiocchi, MD
Director, Division of Allergy
Pediatric Hospital Bambino Gesu
Rome, Vatican City, Italy
Matthew Greenhawt, MD, MBA, MSc
Assistant Professor of Pediatrics
Pediatric Allergy Section
Children’s Hospital Colorado
University of Colorado Denver School of Medicine
Denver, Colo
Kate Grimshaw, PhD, RD, RNutr
Clinical and Experimental Sciences and Human Development
in Health Academic Unit
University of Southampton Faculty of Medicine
Department of Nutrition & Dietetics, Southampton’s
Children’s Hospital
Southampton, United Kingdom
Ruchi S. Gupta, MD, MPH
Northwestern Medicine, Chicago, IL
Ann & Robert H. Lurie Children’s Hospital of Chicago
Chicago, Ill
Brittany Hofmeister, RD
Medical Advisory Board
International FPIES Association (I-FPIES)
Point Pleasant Beach, NJ
Jin-Bok Hwang, MD
Department of Pediatrics
Keimyung University Dongsan Medical Center
Daegu, Korea
Yitzhak Katz, MD
Professor of Pediatrics
Sackler School of Medicine
Tel-Aviv University, Tel-Aviv, Israel
Director, Institute of Allergy Asthma and Immunology and
Food Allergy Center
‘‘Assaf Harofeh’’ Medical Center
Zerifin, Israel
George N. Konstantinou, MD, PhD, MSc
Department of Allergy and Clinical Immunology
424 General Military Training Hospital
Thessaloniki, Greece
Division of Allergy and Immunology
Jaffe Food Allergy Institute
Icahn School of Medicine at Mount Sinai
New York, NY
Stephanie A. Leonard, MD
Division of Pediatric Allergy & Immunology
Rady Children’s Hospital San Diego
University of California
San Diego, Calif
Jenifer R. Lightdale, MD, MPH, FAAP, AGAF
Chief of Pediatric Gastroenterology and Nutrition
UMass Memorial Children’s Medical Center
Professor of Pediatrics
University of Massachusetts Medical School
Worcester, Mass
Sean McGhee, MD
Clinical Associate Professor of Pediatrics
Division of Immunology and Allergy
Stanford University School of Medicine
Palo Alto, Calif
Sam Mehr, MD, FRACP
Department of Allergy and Immunology
Children’s Hospital at Westmead
Sydney, Australia
Stefano Miceli Sopo, MD
Pediatric Allergy Unit
Department of Women and Child Health
Catholic University of Sacred Hearth
Agostino Gemelli Hospital
Rome, Italy
Monti Giovanna, MD, PhD
Department of Paediatric and Adolescence Science
Regina Margherita Children’s Hospital A.O.U.
Citt
a della Salute e della Scienza
Turin, Italy
Antonella Muraro, MD, PhD
Food Allergy Referral Centre Veneto Region
Department of Women and Child Health Padua General
University Hospital
Padua, Italy
Stacey Katherine Noel, MD
Assistant Professor, Emergency Medicine
University of Michigan School of Medicine
Ann Arbor, Mich
Ichiro Nomura, MD, PhD
Department of Allergy and Clinical Immunology
National Center for Child Health and Development
Tokyo, Japan
Sally A. Noone, RN, MSN
Clinical Research Manager
Pediatric Allergy and Immunology
Jaffe Food Allergy Institute
New York, NY
Hugh A. Sampson, MD
Kurt Hirschhorn Professor of Pediatrics
Director, Jaffe Food Allergy Institute
Department of Pediatric
Icahn School of Medicine at Mount Sinai
New York, NY
Fallon Schultz, MSW, LCSW, CAM
President and Founder
International FPIES Association (I-FPIES)
Point Pleasant Beach, NJ
Scott H. Sicherer, MD
Clinical Professor of Pediatrics
Division Chief, Pediatric Allergy and Immunology
Icahn School of Medicine at Mount Sinai
J ALLERGY CLIN IMMUNOL
VOLUME 139, NUMBER 4
NOWAK-WE˛ GRZYN ET AL 1113
Jaffe Food Allergy Institute
New York, NY
Cecilia C. Thompson, MD
Division of Critical Care Medicine
Department of Pediatrics
Icahn School of Medicine at Mount Sinai
New York, NY
Paul J. Turner, MD
MRC Clinician Scientist and Clinical Senior Lecturer, Imperial
College London
Honorary Consultant in Paediatric Allergy & Immunology
Imperial College Healthcare NHS Trust
London, United Kingdom
Clinical Associate Professor in Paediatrics
University of Sydney
Sydney, Australia
Carina Venter, RD, PhD
Research Associate/Dietitian, Division of Allergy &
Immunology
Cincinnati Children’s Hospital Medical Center
Cincinnati, Ohio
Amity Westcott-Chavez, MA, MFA
International FPIES Association (I-FPIES)
Point Pleasant Beach, NJ
Food protein–induced enterocolitis (FPIES) is a non-IgE cell-
mediated food allergy that can be severe and lead to shock.
1
Despite the potential seriousness of reactions, awareness of
FPIES is low; high-quality studies providing insight into
pathophysiology, diagnosis, and management are lacking; and
clinical outcomes are poorly established. Unmet needs in the field
include identification of noninvasive biomarkers, understanding
of the pathophysiology and prevalence, and having uniform
approaches to diagnosis and management. This document
presents an executive summary of the first international consensus
based on available evidence and aims to assist practitioners in
their care of patients with FPIES. The full report is available
online as open access in this article’s Online Repository at
www.jacionline.org.
An international workgroup was convened through the Adverse
Reactions to Foods Committee of the American Academy of
Allergy, Asthma & Immunology and the International FPIES
Association advocacy group.
A comprehensive literature review was performed with the
assistance of a research librarian, with searches run in PubMed/
Medline, Web of Science, and Embase. Excluding abstracts, a
total of 879 citations were identified through February 2014; of
these, 110 were included. Individual sections were written by
using subgroup teams, critiqued, and revised based on feedback
from all authors until consensus was achieved. Evidence was
graded according to the previously established grading system for
clinical practice guidelines used by the Joint Task Force on
Allergy Practice Parameters.
2
SECTION I: DEFINITION AND CLINICAL
MANIFESTATIONS
Summary Statement 1: Recognize FPIES as a potential
medical emergency, which presents as delayed onset of pro-
tracted emesis and/or watery/bloody diarrhea, culminating
in hemodynamic instability and hypotension in at least 15%
of reactions. [Strength of recommendation: Strong; Evidence
strength: IIa/IIb; Evidence grade: B]
FPIES is a non–IgE-mediated food allergy that typically
presents in infancy, with repetitive protracted vomiting that
begins approximately 1 to 4 hours after food ingestion. Vomiting
is often accompanied by lethargy and pallor and can be followed
by diarrhea. Delayed onset and absence of cutaneous and
respiratory symptoms suggest a systemic reaction different
from anaphylaxis.
1,3
Severe cases can progress to hypothermia,
methemoglobinemia, acidemia, and hypotension, mimicking
sepsis.
3-5
The FPIES clinical phenotype is influenced by the age
of onset, nationality, timing, and duration of symptoms and
associated IgE-mediated food allergy (Table I).
Summary Statement 2: Recognize that the symptom pheno-
type in patients with FPIES is determined by the frequency of
food ingestion. [Strength of recommendation: Strong; Evi-
dence strength: IIa; Evidence grade: B]
The manifestations and severity of FPIES depend on the
frequency and dose of the trigger food, as well as the phenotype
and age of an individual patient.
6-9
The distinct pattern of emesis
starting within 1 to 4 hours after food ingestion (acute FPIES) oc-
curs when the food is ingested intermittently or after a period of
avoidance (Tables I and II). Watery diarrhea (occasionally with
blood and mucous) develops in some cases within 5 to 10 hours
of ingestion and can be present for up to 24 hours.
4,9-13
Symptoms
of acute FPIES usually resolve within 24 hours after food inges-
tion. In most children with acute FPIES, they are well between ep-
isodes with normal growth.
Chronic FPIES is less well characterized compared with acute
FPIES and only reported in infants younger than 4 months of age
fed with cow’s milk (CM) or soy infant formula. Chronic FPIES
develops on regular/repeated ingestion of the triggering food,
presenting as chronic/intermittent emesis, watery diarrhea, and
failure to thrive (FTT; Table I) Severe chronic FPIES can lead to
dehydration and shock.
6,14
Hypoalbuminemia and poor weight
gain can predict chronic CM-induced FPIES in young infants
with chronic gastrointestinal symptoms.
10
With elimination of
the chronic FPIES food trigger or triggers, symptoms resolve,
but subsequent feeding (accidental exposure or oral food chal-
lenge [OFC]) induces an acute FPIES reaction within 1 to 4 hours
of food ingestion (Table I). The acute symptomatology after food
avoidance distinguishes chronic FPIES from food protein–
induced enteropathy, eosinophilic gastroenteritis, or celiac dis-
ease. Chronic FPIES is uncommon but appears to be diagnosed
more frequently in Japan and Korea.
10,13,15
SECTION II: EPIDEMIOLOGY
There is limited, wide-scale epidemiologic information
regarding FPIES.
16
FPIES was recognized and formally defined
in the mid-1970s.
6
A 10th revision of the International Statistical
Classification of Diseases and Related Health Problems code for
FPIES (K52.2) was implemented in October 2015. Before this, no
uniform International Classification of Diseases code existed.
FPIES prevalence estimates vary greatly. Katz et al
12
presented
the only published prospective birth cohort noting a cumulative
incidence of infants with CM-induced FPIES of 3 per 1000 new-
borns born at a single hospital over 2 years (0.34%).
Summary Statement 3: Recognize that onset of FPIES to
CM and soy can occur at younger ages compared with FPIES
J ALLERGY CLIN IMMUNOL
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1114 NOWAK-WE˛ GRZYN ET AL
to solid foods. Patients can have a single trigger or multiple
triggers. [Strength of recommendation: Strong; Evidence
strength: IIb-III; Evidence grade: C]
The most commonly reported FPIES triggers are CM, soy, and
grains.
11,12,17
Soy-induced FPIES and combined soy/CM-
induced FPIES are common in the United States (approximately
25% to 50% in reported case series) but uncommon in Australia,
Italy, and Israel. Most reported solid food–induced FPIES is
attributable to rice and oat. Rice is the most commonly reported
grain trigger, except in Italy.
18
Combined rice/oat-induced FPIES
has been reported in almost a third of cases of rice-induced FPIES
in both the United States and Australia.
4,5,9
In contrast, fish-
induced FPIES is common in Italy and Spain but less common
elsewhere.
18,19
Multiple factors can be involved to explain this
geographic variation, including differences in the populations
studied in the case series, presence of atopic disease, breast-
feeding and dietary practices, and yet-to-be-discovered genetic
factors.
11,12,17,20
FPIES occurs once CM or soy-based formulas, solid foods,
or both are introduced into the infant’s diet, usually between 2
and 7 months of age.
4,8,9,12,16,18,21
Infants with CM- and soy-
induced FPIES typically present at a younger age
(<6 months) compared with those with solid food–induced
FPIES (6-12 months) reflecting earlier introduction of CM
and soy. The median age of solid food–induced FPIES onset
is similar between most series (5-7 months), with grain-
TABLE I. Proposed defining features for clinical phenotyping of FPIES
FPIES subtypes Defining features
Age of onset
Early Younger than age 9 mo
Late Older than age 9 mo
Severity
Mild-to-moderate Repetitive emesis with or without diarrhea, pallor, mild lethargy
Severe Repetitive projectile emesis with or without diarrhea, pallor, lethargy, dehydration, hypotension, shock,
methemoglobinemia, metabolic acidosis
Timing and duration of symptoms
Acute Occurs with intermittent food exposures, emesis starts usually within 1-4 h, accompanied by lethargy and pallor;
diarrhea can follow within 24 hours, with usual onset of 5-10 h. Usual resolution of symptoms within 24 h after
elimination of the food from the diet. Growth is normal, and child is asymptomatic during food trigger elimination.
Chronic Occurs with daily ingestion of the food (eg, feeding with CM- or soy-based formula in an infant); symptoms include
intermittent emesis, chronic diarrhea, poor weight gain, or FTT. Infants with chronic FPIES usually return to their
usual state of health within 3-10 d of switching to a hypoallergenic formula, although in severe cases temporary
bowel rest and intravenous fluids might be necessary. Subsequent feeding of the offending food after a period of
avoidance results in acute symptoms.
IgE positivity
Classic Food specific, IgE negative
Atypical Food specific, IgE positive
TABLE II. Proposed defining features of mild and severe acute FPIES
Mild-to-moderate acute FPIES Severe acute FPIES
Clinical features Required
d Vomiting (onset usually 1-4 h, can range from 30 min
to 6 h): few episodes of intermittent vomiting (1-3),
can be bilious
d Decreased activity level
d Pallor
d Self-resolving; the child is able to tolerate oral rehy-
dration at home
Optional
d Mild watery diarrhea, onset usually within 24 hours,
can be bloody (occasionally)
Required
d Vomiting (onset usually at 1-4 h, can range from
30 min to 6 h): projectile (forceful), repetitive (
>_
4),
bilious and dry heaving
d Altered behavior ranging from decreased activity to
lethargy
d Pallor
d Dehydration
d Requires intravenous hydration
Optional
d Hypotension
d Abdominal distention
d Hypothermia
d Diarrhea, onset usually within 24 hours, can be bloody
d Hospitalization
Laboratory features (optional,
when available)
d Increased white blood cell count with neutrophilia
d Thrombocytosis
d Stool might be positive for leukocytes, eosinophils, or
increased carbohydrate content
d Increased white blood cell count with neutrophilia
d Thrombocytosis
d Metabolic acidosis
d Methemoglobinemia
d Stool might be positive for leukocytes, eosinophils, or
increased carbohydrate content
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