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Food Hypersensitivity (Non–IgE-Mediated, Gastrointestinal), Pediatric

Basics

Description

- Proctocolitis - Occurs between 1 and 6 months of age (usually between 2 and 8 weeks) - Specks or streaks of blood ( пїЅ 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

- Proctocolitis: usually healthy-appearing child with normal physical exam - Enteropathy - Diffuse abdominal pain with distention - Weight loss

- 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

- 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).

- Proctocolitis - Anal fissures - Vascular malformations - Intussusception - Meckel diverticulum

- Enteropathy - Lactose intolerance - Celiac disease - Inflammatory bowel disease (IBD)

  • 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 proctocolitisFood protein-induced enteropathyFood protein-induced enterocolitis syndrome (FPIES)

Epidemiology

  • Proctocolitis: Over 60% of infants with rectal bleeding have proctocolitis.
  • Enteropathy: may occur after infectious gastritis
  • FPIESSlight male predominance (60%)30% of infants with FPIES have atopic disease(s).Family history of atopy present in 40-80%.

Risk Factors

  • Proctocolitis40% 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

  • ProctocolitisOccurs between 1 and 6 months of age (usually between 2 and 8 weeks)Specks or streaks of blood ( пїЅ mucus) in the stool of an otherwise healthy infantAbsence of vomiting and diarrheaBlood-tinged stools resolve with elimination of offending food protein.Rare in older children
  • EnteropathyPersistent diarrhea (rarely bloody)VomitingAbdominal painFTT with hypoproteinemia and anemiaUsually formula-fedDo not experience an acute reaction with reexposure
  • FPIESCan begin anytime from within a few days of life through 12 months of ageFPIES due to solid food usually begins when solids are first introduced (rice cereal).Profuse protracted emesis 1-3 hours after exposure to offending food proteinProfuse diarrhea 4-8 hours after food ingestion in 25% of casesMay 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
  • EnteropathyDiffuse abdominal pain with distentionWeight loss
  • FPIESProfuse vomiting and watery diarrhea with signs of dehydrationLethargy, may appear septic

Diagnostic Tests & Interpretation

Diagnostic Procedures/Other

  • All non-IgE-mediated GI food hypersensitivities are as follows:Diagnosed clinicallyNo laboratory test available to diagnose hypersensitivitySerum-specific IgE testing and skin testing often negative
  • ProctocolitisNo endoscopy unless prolonged rectal bleeding, anemia, and/or FTTEosinophils and lymphoid nodular hyperplasia may be present in the colon.
  • EnteropathyEndoscopy shows villous injury with increase in crypt length and villous atrophy.
  • FPIESLabs 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 hospitalizationStool 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

  • ProctocolitisAnal fissuresVascular malformationsIntussusceptionMeckel diverticulum
  • EnteropathyLactose intoleranceCeliac diseaseInflammatory bowel disease (IBD)
  • FPIESAnaphylaxisSepsisNECGI infectionRefluxMetabolic disorderSurgical abdomen

Treatment

Additional Treatment

General Measures

  • ProctocolitisExclusively 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).
  • EnteropathyEliminate milk from diet.Symptoms should improve in 1-3 weeks.
  • FPIESAcute 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. пїЅ

Ongoing Care

Follow-up Recommendations

  • Proctocolitis95% 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.
  • EnteropathyMost cases resolve spontaneously by 2 years of age.Food can be reintroduced at home 1-2 years after beginning protein elimination diet.
  • FPIESThe 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 пїЅJA, Assa'ad пїЅAH, Burks пїЅAW, 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. пїЅ[View Abstract]
  • Elizur пїЅA, Cohen пїЅM, Goldberg пїЅMR, et al. Cow's milk associated rectal bleeding: a population based prospective study. Pediatr Allergy Immunol. 2012;23(8):766-770. пїЅ[View Abstract]
  • J пїЅrvinen пїЅKM, Nowak-WД™grzyn пїЅA. 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 пїЅAM. Food-induced eosinophilic proctocolitis. J Pediatr Gastroenterol Nutr. 2000;30(Suppl):S58-S60.
  • Mehr пїЅS, Kakakios пїЅA, Frith пїЅK, et al. Food protein-induced enterocolitis syndrome: 16-year experience. Pediatrics. 2009;123(3):e459-e464.
  • Sampson пїЅHA, Anderson пїЅJA. 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. пїЅ[View Abstract]
  • Sicherer пїЅSH, Eigenmann пїЅPA, Sampson пїЅHA. Clinical features of food protein-induced enterocolitis syndrome. J Pediatr. 1998;133(2):214-219.
  • Walker-Smith пїЅJA. Cow's milk-sensitive enteropathy: predisposing factors and treatment. J Pediatr. 1992;121(5, Pt 2):S111-S115.
  • Xanthakos пїЅSA, Schwimmer пїЅJB, Melin-Aldana пїЅH, 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.