What are non-IgE-mediated food allergies, like FPIES and FPIAP?

Do you know what non-IgE-mediated food allergies are? If not, you're not alone. Many people have never heard of food allergies that are not mediated by IgE, such as FPIES, FPE, and FPIAP. These types of food allergies are different from IgE-mediated food allergies, which are more common. In this post, we will describe non-IgE-mediated food allergies in detail and explain the difference between them and IgE-mediated food allergies.

What is IgE?

Immunoglobulin E (IgE) is a type of antibody. Normally, antibodies are produced by the immune system to protect the body from foreign substances, such as bacteria and viruses. IgE is thought to play a role in protecting us from parasite infections. It is different from other types of antibodies because it is involved in allergic reactions.

IgE-mediated allergic reactions occur when someone has allergen-specific IgE on their mast cells and ingests their allergen. For example, if Sweet Pea has peanut IgE on her mast cells and ingests peanut butter, then she will have an allergic reaction. What prevents someone with peanut IgE from having an allergic reaction to peanut is what's called tolerance. Read about tolerance here.

Not all allergic reactions involve IgE. These are called non-IgE-mediated food allergies, such as:

  1. Food protein-induced enterocolitis syndrome (FPIES),
  2. Food protein-induced allergic proctocolitis (FPIAP),
  3. Food-protein enteropathy (FPE), and
  4. Eosinophilic gastrointestinal disorders (EGIDs), such as eosinophilic esophagitis (EoE) – however, since there seems to be some role of IgE in EOE, we will discuss EOE and EGIDs in a different post.

Non-IgE-mediated food allergies are caused by a reaction in the gastrointestinal tract. The symptoms can vary depending on the person, but they may include vomiting, diarrhea, abdominal pain, and blood in the stool.

Non-IgE-mediated food allergies can be severe and even life-threatening. In rare cases, they chronically involve the lungs, such as in Heiner's Syndrome. Read more on this cow's milk-induced pulmonary disorder here.

Food Protein-Induced Enterocolitis Syndrome (FPIES)

FPIES is a non-IgE-mediated food allergy that affects the gastrointestinal tract. It typically presents in infancy or early childhood, but can occur in adults. The most common triggers are cow's milk and soy, but it can be caused by any food protein, including grains, legumes, meat, and fish.

Oats are a common trigger food of FPIES.
Oats are a common trigger food of FPIES.

Symptoms of “acute” FPIES reaction can include vomiting, diarrhea, dehydration, low blood pressure, and even shock. These acute symptoms occur within a few hours. Some patients have “chronic” FPIES. This presents more often in the first weeks to months of life. Chronic FPIES can cause severe failure-to-thrive associated with its gastrointestinal symptoms.

FPIES is diagnosed clinically, meaning there is not a test for it. The allergist will talk with the patient's family to help determine the trigger food.

FPIES is treated by avoiding the trigger food(s). It typically resolves within a year.

Don’t miss this fantastic FPIES discussion between Dr. Hoyt and world-renown FPIES expert Dr. Anna Nowak-Wegrzyn.

Food Protein-Induced Allergic Proctocolitis (FPIAP)

FPIAP is a self-limiting food allergy of infancy. It presents with blood-streaked and/or mucus-containing stools. FPIAP occurs in breast-fed babies more so than formula-fed babies. This means that sometimes mom may be eating a food that is triggering this condition.

FPIAP is diagnosed clinically. Like FPIES, there is no test for it. Also like FPIES, the allergist will talk with mom about potential trigger foods, such as cow's milk products.

FPIAP is a non-IgE-mediated food allergy. The symptoms in baby are sometimes helped by mom avoiding cow's milk products in her diet.
FPIAP is a non-IgE-mediated food allergy. The symptoms in baby are sometimes helped by mom avoiding cow's milk products in her diet.

FPIAP is treated a few ways. The mom can try avoiding trigger foods in her own diet. Also, a trial of extensively hydrolyzed formula may be tried. This condition typically resolves before the baby's first birthday.

Food-Protein Enteropathy (FPE)

FPE is a very rare non-IgE-mediated disorder. Symptoms include non-bloody, protracted diarrhea. This occurs within the first nine months of life, but symptoms often begin within the first eight weeks of life. Onset of symptoms may coincide with the introduction of cow's milk products. Soy, wheat, and egg may also be triggers. This disorder can cause abdominal pain, malabsorption, and failure to thrive.

FPE is diagnosed with a biopsy of the small intestine. Fortunately, this condition is incredibly rare these days.

It is treated with avoidance of the trigger food. When It typically resolves within 24-36 months.

FPE is a very rare non-IgE-mediated food allergy. When it is present, it typically resolves by age 3 years.
FPE is a very rare non-IgE-mediated food allergy. When it is present, it typically resolves by age 3 years.

Non-IgE-Mediated Food Allergies are Important!

Non-IgE-mediated food allergies are important to be aware of because they can present differently than IgE-mediated allergies. They can cause severe reactions and even be life-threatening. If you think your child may have a non-IgE-mediated allergy, speak with your allergist.


Thanks for reading this post “What are non-IgE-mediated food allergies, like FPIES?” Do you have any questions about food allergies? Reach out to me! And be sure to check out my other blog posts and podcast episodes about all things food allergy. Thanks for reading!
– Dr. Hoyt

P.S. Food allergy testing can be super confusing, so I've created this awesome ebook to clarify the facts from the fiction! Get your copy today!


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AAAAI Allergist Finder: https://allergist.aaaai.org/find/
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A note from Dr. Hoyt

I have talked about a non-profit…

Pam and I volunteer with the non-profit The Teal Schoolhouse. Its primary program is Code Ana. Code Ana equips schools for medical emergencies like anaphylaxis.

Code Ana’s Online Epinephrine Training Program helps support that goal. Through this program, you will educate yourself while you support this important mission!

A medical emergency response plan is important for everyone at any school. Code Ana's program Med-E Ready is a comprehensive approach to school-focused medical preparedness. This program guides schools through the process of creating a medical emergency response plan. A response team is also developed! This is one of the most important components of a school's food allergy policy!

Does your kiddo’s school have Code Ana?


You've just read Dr. Hoyt's post “What are non-IgE-mediated food allergies, like FPIES?” Remember, she's an allergist, but she isn't your allergist, so talk with your allergist about what you've just learned!

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