What Is the Main Idea?

Food protein-induced enterocolitis syndrome (FPIES) is a rare type of food allergy that is not well understood and is thought to be underdiagnosed. In the open-access research article “Discrepancy between Caregivers’ Reports and Physicians’ Evaluation of Causative Foods in Food Protein-Induced Enterocolitis Syndrome in Japan: The Japan Environment and Children’s Study”, published in the journal International Archives of Allergy and Immunology, the authors investigate factors that may contribute to FPIES underdiagnosis.

What Else Can You Learn?

Different types of food allergy and their symptoms are described. The difficulties in accurately diagnosing FPIES and the food that triggers the reaction are also discussed.

Take-Home Message

Parents and healthcare practitioners should be aware that a child may have FPIES if they begin vomiting repeatedly once they begin weaning, particularly if they quickly improve after being sick. Taking notes whenever this happens, including what the child ate up to 3 days before the vomiting started, can help healthcare practitioners to make an accurate diagnosis.

What Is a Food Allergy?

A person is described as having a “food allergy” if their immune system has an unusual, and usually unpleasant, reaction to a specific food. Reactions to foods that are not classed as food allergies include food intolerances (where a food irritates the digestive system or the body cannot digest a particular food properly), reactions to food that has become contaminated, or something being in the food that can have drug-like effects on the body (like caffeine in coffee).

The body’s immune system protects your body from things that could make you ill, like harmful substances and infections. Key components are inflammation (which traps things that might be harmful and begins to heal injured tissue) and white blood cells (which identify and eliminate things that might cause infection). Some white blood cells make antibodies that, together with other specialized immune cells, enable the body to recognize and fight specific germs that it has previously come into contact with, sometimes providing lifelong protection. Antibodies are divided into five different classes – IgD, IgG, IgM, IgA, and IgE – based on their characteristics and roles.

Are There Different Types of Food Allergy?

Food allergies are divided into two types: IgE-mediated and non-IgE-mediated (NIM).

  • If a food allergy is IgE-mediated, it is caused by IgE antibodies wrongly recognizing the food as a threat. Within minutes of the food being ingested, hives (a raised and itchy rash, also called “urticaria”) and redness of the skin can appear. The person may also start to vomit and, if the reaction is serious, anaphylaxis can occur. Anaphylaxis is life-threatening and symptoms can include difficulty breathing, swelling of the throat and tongue, feeling faint or dizzy, wheezing or coughing, and tightness in the throat.
  • NIM food allergies are caused by components of the immune system other than IgE. They are not as well understood as IgE-mediated food allergies, but a key difference is that allergic reactions do not develop as quickly. Whereas IgE-mediated allergic reactions appear almost immediately after the trigger food is eaten, the appearance of symptoms of NIM reactions is delayed, sometimes appearing as long as several days later. This can make it more difficult to identify the food that is causing the reaction.

What Are the Symptoms of NIM Allergic Reactions?

NIM allergic reactions can affect any part of the gastrointestinal tract. This refers to the route that food and drink takes as it enters the body at the mouth, travels through the stomach and intestines, before waste is passed out of the body. Symptoms can include diarrhea, vomiting, discomfort in the stomach area, and constipation. Babies can also have “colic”, which is when a baby cries a lot without there seeming to be an obvious reason for it.

What Is FPIES?

FPIES is a rare type of NIM food allergy that is usually diagnosed in infants and that is likely to have been present from birth. It affects the small intestine, which is the part of the digestive tract that receives partially digested food from the stomach before it moves on to the colon (large intestine). In most cases, symptoms include repeated vomiting between 1 and 4 hours of the trigger food being eaten, often not long after the infant has first eaten it (for example, during weaning), and diarrhea within 24 hours. However, in some cases symptoms appear several days later. If the vomiting is severe the infant may become pale and floppy.

Common trigger foods include cow’s milk, hen’s eggs, and soy, but FPIES can also be caused by rice, meats, and other foods that are not often associated with food allergies. Although the reactions can be severe, some children “grow out of” the allergy and become able to tolerate the trigger food by the age of 2 years.

What Did the Study Investigate?

Unlike with IgE-mediated food allergies, there are currently no skin or blood allergy tests for NIM food allergies like FPIES. Instead, FPIES is diagnosed through a process of removing foods from the diet one at a time and then reintroducing them if the symptoms start to get better. As a result, it is thought that some cases of FPIES are not diagnosed, which is not helped by the fact that the symptoms are non-specific (in other words, they are common symptoms of illness that could be caused by several different things). Better understanding of the characteristics of FPIES that is not diagnosed by healthcare professionals may help to prevent underdiagnosis or someone being wrongly diagnosed with something else.

The authors of the study used information collected by the Japan Environment and Children’s Study to investigate how commonly FPIES is diagnosed in Japan, and to look for differences in parent- and healthcare professional-diagnosed FPIES. The Japan Environment and Children’s Study involved more than 100,000 pregnant Japanese women. Each woman was asked to complete questionnaires about their child and family at regular intervals until their child was aged 3 years, and were asked if their child had ever had any of the symptoms that suggest FPIES, particularly repeated vomiting. The authors of the study were then able to analyze the results collected at age 1.5 years and look for differences and trends.

What Did the Study Show?

The number of children diagnosed with FPIES was low, which was expected because FPIES is relatively rare, with less than 1% (0.69%) of parents reporting that their child had shown symptoms of FPIES. However, only 0.06% of children had been diagnosed as having FPIES by a healthcare practitioner, only around 10% of children whose parents had reported FPIES symptoms. This suggests that FPIES has been underdiagnosed in Japan.

In addition, there was a discrepancy between the trigger foods that the parents reported as causing the symptoms and the ones that healthcare professionals identified as being the cause of allergic reaction when making their diagnoses. Parents were more likely to report hen’s eggs as being the trigger food, while healthcare practitioners were more likely to diagnose an allergy to cow’s milk. These results suggest that, as well as more research being needed, healthcare practitioners need to have more accurate information about a child having episodes of similar symptoms in the past to be able to make an accurate diagnosis.

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