Food protein-induced enterocolitis syndrome – a review of the literature with focus on clinical management

Figures & data

Table 1 Summary of our current understanding of the pathophysiology of FPIES

• A central role of T cells in the local intestinal inflammation has been suggested, but still need to be confirmed

• A deficit in TGF-β1 response and overzealous TNF-α response may be important factors in FPIES

• IL-10 might play a key role in acquisition of tolerance in patients with FPIES

• Increased serum IL-8 levels in patients with active FPIES suggest neutrophils involvement

• A potential role of IL-9 in the pathogenesis of FPIES has been recently suggested, potentially through its influence on intestinal permeability

• Elevated baseline serum tryptase levels have been found in patients with active FPIES suggest low-grade intestinal

• Mast cell activation or increased mast cell load

• Paucity of humoral response in FPIES has been suggested in several studies

Although several immune changes have been shown in FPIES patients, the pathophysiology of the disease remains not well defined and requires further characterization

Abbreviation: FPIES, food protein-induced enterocolitis syndrome.

Table 2 Distribution of offending food for FPIES in different countries

Year	Country	Total no of cases	Cow milk	Soy	Grains	Fish	Poultry	Vegetables	Fruits	Other	Comment	References
1998	USA	16	11	11	0	0	1				7 patients to both	^Citation1
2003	USA	14	5	8	9 O, 10 R, 2 B	0	1			3	11 (78%) > 1 food 9 (64%) also soy + CM	^Citation12
2003	Israel	6	3	2	0	0	4			2		^Citation39
2005	Spain	14				14					1 patient with IgE	^Citation40
2009	Korea	23	11	12	1 R	1	0			1		^Citation8
2009	Australia	31	7	10	14 R, 1 O	1	1			1	36% avec R-FPIES reaction to other foods	^Citation15
2011	Israel	44	44									^Citation7
2012	Italy	66	44	3	3 R 1 C	8	2			5	56 (85%) react to only 1 food	^Citation6
2013	USA	462	309	189	88 R, 74 O, 46 W, 18 B, 37 C	4	21	50	45	81	70% react to 1–2 foods	^Citation14
2013	Australia	4			Egg	None						^Citation41

Abbreviations: B, barley; C, corn; CM, cow milk; FPIES, food protein-induced enterocolitis syndrome; O, oat; R, rice; W, wheat.

Table 3 Diagnostic criteria FPIES

Powell^Citation18	Powell^Citation54	Leonard and Nowak-Wegrzyn^Citation53	Miceli Sopo et al^Citation74
Onset of symptoms at <2 months of age Infants <9 months of age at study time	Disappearance of symptoms (vomiting and diarrhea) and of diagnostic findings in the stool (blood and leukocytes) after all Ag are removed from the diet	Less than 9 months of age at initial diagnosis	Less than 2 years of age at first presentation (frequent feature but not mandatory)
While receiving the offending food (formula) the infant has watery stools with mucus, blood and leukocytes, and a peripheral PNL	No other cause for colitis detectable	Repeated exposure to causative food elicits gastrointestinal symptoms without alternative cause	Exposure to the incriminated food elicits repetitive and projectile vomiting, pallor, lethargy within 2–4 hours. Diarrhea may be present, much less frequently and later. The symptoms last a few hours, usually resolve within 6 hours
Diarrhea ceases and normal growth resumes when the offending food Ag is eliminated	Symptoms do not recur and weight gain is normal for 1 month on a low Ag formula as the only dietary source	Absence of symptoms that may suggest an IgE-mediated reaction	Absence of symptoms that may suggest an IgE-mediated reaction
The response to challenge meets the criteria of OFC	Challenge with CM or soy formula or other offending food Ag reproduces symptoms of vomiting within 1–3 hours and or diarrhea within 4–10 hours	Removal of causative food results in resolution of symptoms	Avoidance of the offending protein from the diet results in resolution of symptoms
		Reexposure or OFC elicits typical symptoms within 4 hours	Reexposure or OFC elicits typical symptoms within 2–4 hours Two typical episodes are needed to establish the diagnosis without the need to perform OFC

Note: Reproduced from Serafini S, Bergmann MM, Nowak-Węgrzyn A, Eigenmann PA, Caubet JC. A case of food protein–induced enterocolitis syndrome to mushrooms challenging currently used diagnostic criteria. J Allergy Clin Immunol Pract. 2015;3(1):135–137.⁷⁵

Abbreviations: Ag, antigen; CM, cow milk; FPIES; food protein-induced enterocolitis syndrome; PNL, polymorphonuclear leukocytosis; OFC, oral food challenge.

Table 4 Clinical features of FPIES and its differential diagnosis

Clinical features	Differential diagnosis
Signs and symptoms	Infections
Repetitive vomiting every 10 to 15 minutes, onset 1–3 hours after ingestion (>90%)	Viral gastroenteritis Sepsis
Diarrhea, onset 5 hours after ingestion (<50%)	Bacterial enteritis (Salmonella, Shigella, Campylobacter, Yersinia)
Lethargy (70%)	Parasites
Pallor (70%)
Dehydration	Allergic disorders
Hypotension (15%) Hypothermia (25%) Abdominal distension	Other gastrointestinal non-IgE mediated food allergy disorders (food protein-induced enteropathy and eosinophilic gastrointestinal disorders) Acute IgE mediated allergy (anaphylaxis)
Laboratory findings	Gastrointestinal disorders
Elevated neutrophil count	Gastroesophageal reflux disease
Thrombocytosis	Hirschsprung disease
Metabolic acidosis	Intussusception
Methemoglobinemia	Volvulus
Fecal leukocytes and eosinophils	Pyloric stenosis
Frank or occult fecal blood	Celiac disease
Increased carbohydrate content in stool
Elevated gastric juice leukocytes	Other
Negative IgE test to the trigger food in most cases	Neurologic disorders (i.e., seizure, encephalopathy, or bleeding) Heart defects (i.e., congenital heart disease, cardiomyopathy, or arrhythmia)
Radiologic features	Necrotizing enterocolitis
Intramural gas	Congenital methemoglobinemia
Air-fluid levels	Intoxication
	Metabolic disorders, that is, hypoglycemia, MCAD deficit, biotinidase deficit or anomalies of urea cycle

Note: Reproduced from Barasche J, Stollar F, Bergmann MM, Caubet JC. Severely altered-consciousness status and profuse vomiting in infants: Food Protein-Induced Enterocolitis Syndrome (FPIES) a challenging diagnosis. Pediatr Emerg Care. Epub 2016 Oct 6.⁷⁶ http://journals.lww.com/pec-online/pages/default.aspx. Promotional and commercial use of the material in print, digital or mobile device format is prohibited without the permission from the publisher Wolters Kluwer. Please contact [e-mail] for further information.

Abbreviations: FPIES, food protein-induced enterocolitis syndrome; MCAD, medium-chain-Acyl-CoA-dehydrogenase.

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