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 allergies can 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 gastroenteritis is 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 proctocolitis is 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 metabolism are 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 disease is 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, September 2014. 

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