Is FPIES an Autoimmune Disease?

Food protein-induced enterocolitis (FPIES) is a rare food allergy that causes vomiting and diarrhea. Because some of the symptoms of FPIES look similar to other autoimmune diseases, like Chron’s disease or Celiac disease, people often ask if FPIES is an autoimmune disease as well. Research does not show that FPIES is an autoimmune disease at this time, but more research is being done on this relatively new condition.

How Serious Is FPIES?

People with FPIES experience a variety of symptoms, which most commonly include vomiting and diarrhea. It can be fatal in rare cases for young children who vomit so much that they go into shock. The disease can be managed by avoiding foods that trigger this immune response. You can see a list of the most common foods that trigger FPIES reactions here.

For most children and the adults that have it, FPIES isn’t fatal, but it can severely impact the quality of their daily lives. Some kids have so many foods to avoid that they are on allergy friendly formulas for the first few years of their lives, way longer than most babies. This helps them get all of the nutrients that they need when they are unable to get them from solid food.  

Even if the number of trigger foods isn’t that big, FPIES reactions can start after eating just a tiny piece of a trigger food. This means that families with FPIES have to constantly be on alert to keep themselves or their loved one safe. 

Is FPIES an Autoimmune Disease?

There are some similarities between FPIES and Celiac Disease, which is an autoimmune disease, but at this time, there is not enough evidence to show that FPIES is an autoimmune disease as well. 

Autoimmune diseases cause the body to start attacking itself. Celiac disease causes an immune response that activates T-cells which start to attack the lining of the small intestine.

Studies suggest that FPIES is caused by either an innate or an adaptive immune response. Innate immunity is something you are born with, and it allows your body to defend itself from birth against viruses and bacteria. It’s the trigger happy part of your immune system that senses there’s an invader and starts the process of vomiting and diarrhea to get rid of the germs. 

Adaptive immunity is developed over time. It’s your body’s ability to fight off a virus once and then remember what that virus looked like and how to kill it next time. This is a very simple explanation, but this happens because your body’s cells remember what those pathogens look like. 

Initially, studies were focused on figuring out which of the adaptive immune cells could be responsible for FPIES reactions, because of the way the reactions start. Many kids have reactions that begin the second time they try a food, even if the first exposure to that food is ok. This could point to an adaptive immune response, but researchers were unable to find the exact cells that would cause the reaction. 

A more recent study (Goswami et al., 2017) found that food reactions in FPIES are actually a function of the innate immune response. They found, “profound activation of cells of the innate immune system after food challenge, including monocytes, neutrophils, natural killer cells, and eosinophils”. This response wasn’t seen in the kids in the challenge that had outgrown FPIES.

They were then able to do RNA sequencing on a larger group of kids with FPIES and they found the same pattern; activated innate immune cells and T-cell activation. They concluded that the systemic innate immune response could be what causes the shock symptoms in babies (and adults) with acute FPIES.

Blood vials on medical table

FPIES and Celiac Look Similar

In order to diagnose Celiac disease, doctors will usually do a blood test, looking for elevated levels of certain antibodies in their blood. They will also usually do a biopsy of the small intestine to look for damage to the villi, which are tiny hair-like structures that absorb nutrients in the small intestine, or changes to the intestinal wall. If a patient has Celiac disease, the villi can be blunted or worn down by exposure to gluten over time.  

Similar intestinal changes were noticed in biopsies of babies with FPIES in the 1970’s (Fontaine & Navarro, 19775; Savilahti, 1973; & Kuitunen et al., 1973). There was a more recent study that also showed villi blunting being caused by FPIES (Ozdemir, 2018) and increased intestinal permeability as a result. 

This has led to the comparisons between FPIES and Celiac disease; both conditions can cause blunting of the villi in the small intestine. It’s also confusing because both diseases can cause similar symptoms; diarrhea, vomiting, skin rash, etc. 

FPIES and Celiac Work Differently in the Body

However, the way that these two diseases cause symptoms appears to be different, based on research from Berin (2015). One obvious difference is that Celiac symptoms are triggered by exposure to one specific food type; gluten, which is found in a handful of foods.

FPIES symptoms can be triggered in the same child by foods in vastly different food groups. The same baby can have an FPIES reaction to shellfish and banana or peas and chicken, which makes it harder to narrow down the cause of the reactions. 

Plate of pasta with shrimp and scallops

One issue with this comparison between FPIES and Celiac is the evidence of the villi blunting. Patients with Celiac often get biopsies done to look for damage in the small intestine, and that is a well-documented diagnostic criteria. Patients with FPIES aren’t usually given biopsies though, because it’s not part of the diagnostic criteria. 

If an FPIES patient does have a biopsy and villi blunting is seen, it could even be diagnosed as Celiac disease (in addition to their FPIES diagnosis) because there isn’t a precedent for villi blunting as a confirmed symptom of FPIES. 

Additionally, the i-FPIES website notes that there is a component of Celiac disease called a Celiac crisis, which can lead to the same explosive diarrhea and shock-like symptoms that FPIES causes. This definitely explains some of the confusion between the symptoms, especially since both diseases cause gastrointestinal upset and pain. The main difference between a Celiac crisis and Food Protein-Induced Enterocolitis is that FPIES usually causes blood in the baby’s stool as well, and Celiac reactions do not usually. 

More FPIES Research is Needed

There are some things that make FPIES tricky. It’s relatively new and unknown, so it’s harder to get consistent information to and from doctors. There also is no diagnostic test for FPIES, so it’s hard to get consistent information about patients. Currently, FPIES is diagnosed based on a combination of a description of the patient’s symptoms in the past, and oral food challenges

Even with the increase in studies, researchers are still having trouble identifying what immune mechanism is causing these symptoms. They know that FPIES causes other reactions in the gut, including increased numbers of inflammatory cells such as intraepithelial lymphocytes, CD4 T-cells, and IgM and IgA and eosinophils (Ozdemir, 2018). 
Researchers know what levels of inflammation rise during a reaction, and they know what types of cells seem to be less active. But, they aren’t sure yet exactly why food reactions happen or how people develop or outgrow FPIES yet.

The good news is that research is being done at a rapid rate. When my daughter first got her diagnosis six years ago, the allergist handed me a small stack of 4 research articles. I remember him telling me that she probably had a condition called FPIES, and that he was giving me all of the current research articles that were available at the time. He told me to read up on it, and then told me that unfortunately, I would probably know more about it than he did in the next few years, just because we were building personal experience managing this disease, and he was waiting on more research to come out.

Now, when I search for medical journal articles about FPIES, I can find pages and pages of relevant, current research. My younger brother learned about FPIES in one of his rare disease classes in medical school. There is hope. We are learning more about allergies and how they work all the time.


  2. Berin M. C. (2015). Immunopathophysiology of food protein-induced enterocolitis syndrome. The Journal of allergy and clinical immunology, 135(5), 1108–1113.
  3. Goswami, R., Blazquez, A. B., Kosoy, R., Rahman, A., Nowak-Węgrzyn, A., & Berin, M. C. (2017). Systemic innate immune activation in food protein-induced enterocolitis syndrome. The Journal of allergy and clinical immunology, 139(6), 1885–1896.e9.
  4. Özdemir Ö. Immuno pathogenesis of food protein induced enterocolitis syndrome (FPIES). MOJ Immunol. 2018;6(3):86-88. DOI: 10.15406/moji.2018.06.00199