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Related Conditions

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Related Conditions

Adults with FPIES have significantly higher rates of atopic diseases. Allergic rhinitis, asthma, atopic dermatitis are conditions that occur more frequently in patients with FPIES.

Increased rates of classic food allergy (IgE mediated), compared with adults without FPIES have also been reported. Besides eosinophilic esophagitis is also a common condition associated with FPIES. These observations suggest a common predisposition and/or shared disease mechanism.

Urticaria has been observed more commonly than in the general population..

A slight major incidence of gastrointestinal diseases has also been observed in adults with FPIES, in addition to eosinophilic esophagitis, diseases such as inflammatory bowel disease, irritable bowel syndrome or celiac disease have a higher prevalence than in the general population.

Otherwise many conditions can mimic acute episodes of FPIES. In most patients, the first episodes of FPIES are misdiagnosed as viral gastroenteritis or food poisoning, but subsequent recurrent episodes confirm a relationship to specific foods.

In the case of patients that have FPIES symptoms triggered by fish,  anisakiasis must be ruled out. Anisakis simplex is a worm that infects humans after eating the raw or undercooked fish.  Symptoms include acute epigastric or severe abdominal pain, nausea, vomiting and abdominal distension. Diarrhea may also develop. These symptoms usually overlap with the manifestations of acute FPIES, however allergic reactions ranging from mild urticaria to bronchoconstriction, angioedema, and anaphylactic shock usually occur in anisakiasis, but not in FPIES. The recurrence of episodes in subsequent fish ingestion and the absence of specific IgE to anisakis in serum or skin test, rules out the diagnosis of anisakiasis and support the diagnosis of FPIES.

In classic food allergies, digestive symptoms may be present such as abdominal pain, vomiting, diarrhea but they are associated to skin symptoms such as hives or angioedema (rapid swelling of deep layers of the skin) or asthma. These symptoms are absent in FPIES.

Celiac disease is an immunologic disorder caused by the ingestion of gluten, that may debut both in children and in adults. Symptoms include abdominal pain, diarrhea and poor weight gain. Patients with Fpies triggered by cereals may have similar symptoms, but serologic test and biopsy will confirm or rule out celiac disease.

In adults with symptoms of FPIES induced by milk, differential diagnosis with lactose intolerance may be challenging, as they also share common clinical features. A normal hydrogen breath test and frequent presence of vomiting supports the diagnosis of FPIES.

Irritable bowel syndrome (IBS) is a common chronic condition of the digestive system. Its primary symptoms are abdominal pain and changes in bowel habits (constipation and/or diarrhea). In some uncommon cases of multiple-food FPIES, triggered by foods  that are consumed regularly like milk, egg or meat, differential diagnosis with IBS is difficult. A diet diary and oral food challenge are required for diagnosis. However collaboration with gastroenterology service is essential  in these cases to rule out other processes.

Inflammatory bowel disease includes conditions that cause inflammation of the digestive tract, including Crohn’s disease and ulcerative colitis (UC) in which  the immune system is implicated. Symptoms can be mild or severe and consist of diarrhea, abdominal pain, rectal bleeding, weight loss… No relationship with  foods is observed, however some patients complain that certain foods seem to worse symptoms such as milk, or other dairy foods. In patients with multiple-food FPIES suspicion, these conditions must be ruled out previously by gastroenterologists that will perform a colonoscopy and biopsy.

Related Conditions

There are a multitude of conditions that can mimic an acute episode of Food Protein-Induced Enterocolitis Syndrome (FPIES). In many cases, this often leads an initial misdiagnosis. Further, there is no specific testing for FPIES, it is currently diagnosed based on clinical symptoms and timing. As most families that have a child with FPIES are aware, the condition is often misdiagnosed as a viral or bacterial infection. This is due to two factors: 1. the nature of FPIES, in which the most common symptoms are repetitive vomiting, diarrhea, and dehydration, and 2. the perception of FPIES as rare amongst the medical community as a whole.

More severe FPIES symptoms of lethargy, low blood pressure, and pale or blue skin can be easily mistaken for sepsis (blood infection) or a surgical emergency. The most often mimics from a surgical perspective are:

  • Necrotizing enterocolitis: Inflammation and death of intestinal tissue typically in premature infants,
  • Intussusception:Telescoping of the intestine into each other, and
  • Hirschsprung’s disease enterocolitis:Inflammation from a bowel obstruction due to being born with no nerve cells in the end of the colon.

These are all life-threatening conditions, and as such, do not resolve within a few hours with intravenous fluids. In contrast, symptoms of acute FPIES will subside within a few hours of fluid resuscitation, and this difference will assist in recognizing FPIES from these conditions.

As discussed below, there are still numerous other conditions that can imitate the symptoms of acute FPIES:

  • Classic food allergiescan be distinguished from FPIES by the presence of common, additional symptoms including skin disease (e.g., hives), asthma, and rapid swelling of the deep layers of the skin (angioedema).
  • Eosinophilic gastroenteritisis a condition in which eosinophils, a type of white blood cell, invades the intestine in reaction to an allergen, typically food. This condition can involve any part of the intestinal tract (esophagus, stomach, small intestine, and/or colon). These conditions usually start later in childhood (age 3 and up), whereas FPIES typically starts in infancy. They can cause anywhere from vomiting to weight loss and swelling to bloody diarrhea. An endoscopy would confirm this diagnosis, whereas it would not be of much assistance in FPIES. Additionally, a reaction to a food in an eosinophilic gastrointestinal condition may not show itself for days.
  • Allergic proctocolitisis a food allergy condition that causes inflammation in the colon. It is also seen during infancy and usually presents in the first three months. Cow and soymilk protein are also major culprits for the reaction. However, allergic proctocolitis is usually marked by daily, low-grade symptoms. These infants may be fussy but are otherwise healthy and growing well. There is usually no vomiting and no life-threatening “attacks.” They often have blood in their stools, but it is seen with most bowel movements and the infants are not anemic (low blood count) from it. Infants with FPIES normally have much more violent reactions than infants with allergic proctocolitis. In addition, when children with allergic proctocolitis are reintroduced to the offending food, they do not have severe symptoms unlike infants with FPIES.
  • Inborn errors of metabolismare rare genetic disorders in which the body cannot properly turn food into energy. They lead to the accumulation of toxic products, and most present with a very ill newborn after an initial normal period of 24 to 48 hours: the infant stops feeding well, begins vomiting, and becomes lethargic (difficult to arouse). Abnormal labs, such as low blood sugar and high toxin levels, are usually present. However, some infants may survive this newborn period and present later when dietary changes add more protein to the diet (such as changing from breast milk to formula or adding protein solids) or when they become ill. The most common symptoms in these children will be vomiting and lethargy. Again, in contrast to FPIES, there are usually lab abnormalities seen in a metabolic disorder.
  • Celiac diseaseis an adverse, immune reaction to gluten, which is found in wheat, barley and rye. Children with Celiac disease can present during infancy, but many do not until much later in their childhood or even into adulthood. It can start when gluten is introduced in solid foods. It can commonly cause vomiting, poor appetite, poor weight gain and diarrhea in infants. Rarely, Celiac disease can cause what is called a Celiac crisis, in which an infant or child can have explosive watery diarrhea, abdominal swelling, low blood pressure, dehydration and lethargy. The difference between this and acute FPIES is that FPIES infants will often have blood in the stools and will be vomiting.

Provided by the I-FPIES Medical Advisory Board

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