Food Hypersensitivity (Non–IgE-Mediated, Gastrointestinal)



  • 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)


  • Proctocolitis: >60% of infants with rectal bleeding have proctocolitis.
  • Enteropathy: may occur after infectious gastritis
    • 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.


  • Unclear
  • Assumed to be a cell-mediated reaction due to delayed onset


  • Cow’s milk is the most common 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)

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