FPIES

FPIES - Food Protein-Induced Enterocolitis Syndrome

Definition

Food Protein-Induced Enterocolitis Syndrome is a non-IgE mediated food allergy which presents as delayed onset of protracted emesis and/or watery/bloody diarrhea which can be severe and lead to shock (hemodynamic instability and hypotension)

Background

Typical onset in infancy
Protracted repetitive vomiting that begins 1-4hrs after food ingestion
Often accompanied by lethargy and pallor which can be followed by diarrhea
Severe cases can have hypothermia, methemaglobinemia, acidemia, hypotension
(note: no cutaneous or respiratory symptoms - unlike anaphylaxis)

Acute FPIES:

Emesis starting 1-4hrs after ingestion
Diarrhea (if they have it) starts 5-10hrs after ingestion
Symptoms resolve within 24hrs after ingestion
Well between episodes, normal growth

Patients can present with hypotensive shock, lethargy, acidosis, hypothermia, and increased neutrophil count.

Chronic FPIES:

Infants <4mo on cows milk or soy infant formula
Chronic or intermittent emesis
Watery diarrhea
Failure to thrive

Severe chronic FPIES can lead to:

Dehydration and shock
Hypoalbuminemia
Poor weight gain

Symptoms resolve with elimination of the chronic FPIES food trigger(s)
Subsequent feeding (accidental exposure or oral food challenge [OFC]) induces an acute FPIES reaction within 1 to 4 hours of food ingestion

The acute symptomatology after food avoidance distinguishes chronic FPIES from food protein–induced enteropathy, eosinophilic gastroenteritis, or celiac disease

Chronic FPIES is uncommon but appears to be diagnosed more frequently in Japan and Korea

Triggers:

Can be multiple
CM and Soy typically develop earlier than other triggers
Most common triggers are: Milk, Soy, Grains (Rice and Oat)

Consider specific IgE testing for FPIES triggers

Immunologically distinct from FPIES but 12% can have overlap
Do not routinely perform testing for food sIgE to identify food triggers of FPIES because FPIES is not an IgE-mediated process

Diagnosis:

Diagnose FPIES primarily based on a clinical history of typical characteristic signs and symptoms with improvement after withdrawal of the suspected trigger food. Exclude other potential causes and use in-office OFCs (oral food challenge) to help confirm the diagnosis if the history is unclear and there is a favorable risk/benefit ratio

Gold Standard: Conduct OFCs in patients with suspected FPIES in medically supervised settings in which access to rapid fluid resuscitation is available and prolonged observation can be provided, if necessary. (aka allergy clinic)

Differential diagnosis: Infectious gastroenteritis, sepsis, necrotizing enterocolitis, anaphylaxis, food aversion, inborn errors of metabolism, lactose intolerance, neurologic disorder, gastrointestinal reflux disease, Hirschsprung's disease, eosinophilic gastroenteropathy's (e.g. eosinophilic esophagitis or eosinophilic gastroenteritis), celiac disease, immune enteropathies (IBD, immunodeficiency), anatomic obstruction, coagulation defects, alpha-1 antitrypsin deficiency

Consider a work-up to rule out other gastrointestinal diseases resulting in symptoms that overlap with FPIES.

Management:

Treat acute FPIES as a medical emergency and be prepared to provide aggressive fluid resuscitation because approximately 15% of patients can have hypovolemic shock
Ondansetron PRN
Use dietary elimination of the trigger food or foods for the primary management of FPIES and educate caregivers and other care providers regarding avoidance strategies
Do not recommend routine maternal dietary elimination of offending triggers while breast-feeding if the infant is thriving and remains asymptomatic
Recognize that infants with CM or soy-induced FPIES might be at increased risk of having FPIES to other foods.
Children typically outgrow FPIES after toddlerhood, Reintroduce the foods triggering FPIES under a physician’s supervision
Use hypoallergenic formula in formula-fed infants or infants who can no longer breast-feed and are given a diagnosis of FPIES caused by CM

Letter for patients to take to the Emergency Room

Prognosis

In US studies: Resolution of FPIES to CM or soy: 35% by age 2 years, 70% by age 3 years, and 85% by age 5 years

Summary:
Breastfeeding may reduce the risk of developing FPIES, but data are mixed and it is not fully protective; established risk factors include male sex, delivery by cesarean section, and a family history of atopy or food allergy. FPIES classically presents in infancy (most cases begin in the first year of life, with a median onset around 5–6 months and many presenting before 9 months), with acute FPIES causing profuse vomiting 1–4 hours after ingestion of the trigger food, often followed by lethargy, pallor, diarrhea, and in severe cases hypovolemia and hypotension; chronic FPIES from repeated exposure produces intermittent vomiting, watery diarrhea, and failure to thrive. Management is strict avoidance of the offending protein, which is particularly challenging for formula‑dependent infants (specialist input to select hypoallergenic or amino‑acid formulas is frequently required). Acute management of severe reactions requires immediate supportive care in a monitored setting with intravenous access for rapid fluid resuscitation, ondansetron for vomiting control, and adjunctive corticosteroids at the clinician’s discretion; epinephrine is not routinely effective for FPIES unless there are concomitant IgE‑mediated features. Most children outgrow FPIES in early childhood, but timing varies by trigger (many cow’s‑milk and soy cases resolve by age 3, while some solid‑food FPIES resolve later, often by school age). Follow‑up with food allergy specialists is recommended to coordinate timing and performance of medically supervised oral food challenges to document resolution (commonly considered about 12–24 months after the last reaction, individualized by food and clinical course).

Reference:
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

https://www.jacionline.org/article/S0091-6749(17)30153-7/fulltext