Basics
Description
- A non-IgE-mediated reaction to a food protein that involves the gastrointestinal (GI) tract
- Previously referred to as milk protein intolerance
- Includes the following:
- Food protein-induced proctocolitis
- Food protein-induced enteropathy
- Food protein-induced enterocolitis syndrome (FPIES)
Epidemiology
- Proctocolitis: Over 60% of infants with rectal bleeding have proctocolitis.
- Enteropathy: may occur after infectious gastritis
- FPIES
- Slight male predominance (60%)
- 30% of infants with FPIES have atopic disease(s).
- Family history of atopy present in 40-80%.
Risk Factors
- Proctocolitis
- 40% react to both milk and soy.
- 50-60% of infants are breastfed and react to milk and/or soy in mom's diet.
- Enteropathy: usually formula-fed and given intact cow's milk prior to 9 months of age
- FPIES: Exclusive breastfeeding appears to protect against FPIES, but a few cases have been reported.
- Currently, no reports that non-IgE-mediated GI food hypersensitivities are inherited.
Pathophysiology
- Unclear
- Assumed to be a cell-mediated reaction due to delayed onset
Etiology
- Cow's milk is number 1 cause of proctocolitis, enteropathy, and FPIES, followed by soy, egg and wheat.
- FPIES: can also react to solid foods thought to be hypoallergenic (rice, oat, barley, chicken, turkey, peanut, potato, corn, fruit protein, fish, and mollusks)
Diagnosis
History
- Proctocolitis
- Occurs between 1 and 6 months of age (usually between 2 and 8 weeks)
- Specks or streaks of blood ( � mucus) in the stool of an otherwise healthy infant
- Absence of vomiting and diarrhea
- Blood-tinged stools resolve with elimination of offending food protein.
- Rare in older children
- Enteropathy
- Persistent diarrhea (rarely bloody)
- Vomiting
- Abdominal pain
- FTT with hypoproteinemia and anemia
- Usually formula-fed
- Do not experience an acute reaction with reexposure
- FPIES
- Can begin anytime from within a few days of life through 12 months of age
- FPIES due to solid food usually begins when solids are first introduced (rice cereal).
- Profuse protracted emesis 1-3 hours after exposure to offending food protein
- Profuse diarrhea 4-8 hours after food ingestion in 25% of cases
- May appear acutely ill with 15% of cases presenting with dehydration and shock
- All non-IgE-mediated GI food hypersensitivities resolve when offending food protein removed from diet.
Physical Exam
- Proctocolitis: usually healthy-appearing child with normal physical exam
- Enteropathy
- Diffuse abdominal pain with distention
- Weight loss
- FPIES
- Profuse vomiting and watery diarrhea with signs of dehydration
- Lethargy, may appear septic
Diagnostic Tests & Interpretation
Diagnostic Procedures/Other
- All non-IgE-mediated GI food hypersensitivities are as follows:
- Diagnosed clinically
- No laboratory test available to diagnose hypersensitivity
- Serum-specific IgE testing and skin testing often negative
- Proctocolitis
- No endoscopy unless prolonged rectal bleeding, anemia, and/or FTT
- Eosinophils and lymphoid nodular hyperplasia may be present in the colon.
- Enteropathy
- Endoscopy shows villous injury with increase in crypt length and villous atrophy.
- FPIES
- Labs may also show anemia, leukocytosis, eosinophilia, neutrophilia, thrombocytosis, and hypoalbuminemia.
- If reaction to food is severe, patient may have metabolic acidosis.
- May see methemoglobinemia in up to 35% of cases that require hospitalization
- Stool may contain blood, mucus, leukocytes, eosinophils, and/or increased carbohydrate content due to malabsorption.
- Abdominal x-ray may show intramural gas (may be confused with necrotizing enterocolitis [NEC] or ileus).
- With FPIES, if the offending food is discontinued and restarted, the patient will experience vomiting and diarrhea within a few hours (not recommended to be performed at home).
Differential Diagnosis
- Proctocolitis
- Anal fissures
- Vascular malformations
- Intussusception
- Meckel diverticulum
- Enteropathy
- Lactose intolerance
- Celiac disease
- Inflammatory bowel disease (IBD)
- FPIES
- Anaphylaxis
- Sepsis
- NEC
- GI infection
- Reflux
- Metabolic disorder
- Surgical abdomen
Treatment
Additional Treatment
General Measures
- Proctocolitis
- Exclusively breastfed infant: Continue breastfeeding with mom eliminating all forms of dairy including casein and whey in packaged food.
- Symptoms should improve within 72 hours, but it may take up to 2 weeks to completely resolve.
- If no improvement, eliminate soy in mom's diet, followed by egg.
- If the infant is formula-fed, consider changing formula to a hydrolysate formula (e.g., Pregestimil, Nutramigen, Alimentum) because many patients are sensitive to both milk and soy protein.
- If bleeding continues, consider changing formula to an amino acid-based formula (e.g., Neocate, PurAmino, EleCare).
- Enteropathy
- Eliminate milk from diet.
- Symptoms should improve in 1-3 weeks.
- FPIES
- Acute episodes should be treated with IV fluids, methylprednisolone (1 mg/kg) to decrease possible cell-mediated intestinal inflammation, plus vasopressors, epinephrine, and/or bicarbonate for shock and possible metabolic acidosis.
- Long-term management involves strict avoidance of trigger food(s).
- Stop cow's milk or soy formula and start hydrolysate formula due to possible intolerance to both milk and soy protein.
- For solid food FPIES:
- Eliminate trigger food and allow the patient to continue eating foods previously tolerated.
- Consult allergist for future solid food introduction.
Alert
If suspect FPIES (patient with vomiting, acute dehydration, lethargy and acidosis), fluid resuscitation and refeeding should be performed in the hospital. �
Ongoing Care
Follow-up Recommendations
- Proctocolitis
- 95% tolerate reintroduction of food(s) at 9 months of age. Patient can reintroduce offending food at home 4-6 months after beginning protein elimination diet.
- Prognosis: excellent. Nearly all infants tolerate cow's milk and soy products by 12 months of age.
- Proctocolitis is not inherited; therefore, subsequent children should not be started on hydrolysate or amino acid formula.
- Enteropathy
- Most cases resolve spontaneously by 2 years of age.
- Food can be reintroduced at home 1-2 years after beginning protein elimination diet.
- FPIES
- The trigger food may be reintroduced 12-18 months after the last reaction, preferably under the supervision of a physician.
- Cow's milk and soy FPIES resolve in most patients by 3 years of age.
- Patients with solid food FPIES may experience protracted courses.
- Nutritional counseling may be helpful for children with multiple non-IgE-mediated reactions to food.
- Because close follow-up is needed to determine if tolerance has developed and if an oral food challenge can be performed, an allergy consult is warranted when FPIES is suspected.
Additional Reading
- Boyce �JA, Assa'ad �AH, Burks �AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-sponsored expert panel report. J Allergy Clin Immunol. 2010;126(6):1105-1118. �[View Abstract]
- Elizur �A, Cohen �M, Goldberg �MR, et al. Cow's milk associated rectal bleeding: a population based prospective study. Pediatr Allergy Immunol. 2012;23(8):766-770. �[View Abstract]
- J �rvinen �KM, Nowak-Węgrzyn �A. Food protein-induced enterocolitis syndrome (FPIES): current management strategies and review of the literature. J Allergy Clin Immunol Pract. 2013;1(4):317-322.
- Lake �AM. Food-induced eosinophilic proctocolitis. J Pediatr Gastroenterol Nutr. 2000;30(Suppl):S58-S60.
- Mehr �S, Kakakios �A, Frith �K, et al. Food protein-induced enterocolitis syndrome: 16-year experience. Pediatrics. 2009;123(3):e459-e464.
- Sampson �HA, Anderson �JA. Summary and recommendations: classification of gastrointestinal manifestations due to immunologic reactions to foods in infants and young children. J Pediatr Gastroenterol Nutr. 2000;30(Suppl):S87-S94. �[View Abstract]
- Sicherer �SH, Eigenmann �PA, Sampson �HA. Clinical features of food protein-induced enterocolitis syndrome. J Pediatr. 1998;133(2):214-219.
- Walker-Smith �JA. Cow's milk-sensitive enteropathy: predisposing factors and treatment. J Pediatr. 1992;121(5, Pt 2):S111-S115.
- Xanthakos �SA, Schwimmer �JB, Melin-Aldana �H, et al. Prevalence and outcome of allergic colitis in healthy infants with rectal bleeding: a prospective cohort study. J Pediatr Gastroenterol Nutr. 2005;41(1):16-22.
Codes
ICD09
- 558.3 Allergic gastroenteritis and colitis
- 579.8 Other specified intestinal malabsorption
- 271.3 Intestinal disaccharidase deficiencies and disaccharide malabsorption
ICD10
- Z91.011 Allergy to milk products
- E73.9 Lactose intolerance, unspecified
- K90.4 Malabsorption due to intolerance, not elsewhere classified
- K52.2 Allergic and dietetic gastroenteritis and colitis
SNOMED
- 15911003 Cow's milk protein sensitivity (disorder)
- 267425008 lactose intolerance (disorder)
- 302921006 Malabsorption due to intolerance to protein (disorder)
- 25868003 soy protein sensitivity (disorder)
FAQ
- Q: Will my child outgrow this?
- A: For proctocolitis, most children outgrow milk and/or soy intolerance by 12 months of age. For enterocolitis, symptoms resolve within 1-2 years. For FPIES, symptoms may resolve within 1-2 years, however, they may persist which is why food challenges are important to determine if symptoms have improved and the food can be safely reintroduced into the diet.
- Q: Should I refer the patient to an allergist?
- A: Infants with suspected FPIES should be referred to an allergist for both evaluation and future food challenges. A patient with proctocolitis or enteropathy that resolves with formula change does not need to be seen by a specialist unless symptoms persist despite a strict elimination diet.
- Q: Can my child have FPIES and an IgE-mediated food allergy?
- A: Although not as common as FPIES alone, there are reports of children with FPIES and elevated food-specific IgE levels. These children tend to have a more protracted course of FPIES and are at increased risk of developing IgE-mediated immediate-type symptoms when challenged. This supports the recommendation to refer children with suspected FPIES to an allergist for further evaluation.