Food Allergies and Intolerances

Food Intolerance

• Is a nonimmune-mediated process
• Can occur because of
  • An underlying congenital or acquired enzyme deficiency in which a specific nutrient cannot be property metabolized. Examples include
    • Lactose intolerance
    • Galactosemia
    • Hereditary fructose intolerance
  • Ingestion of a toxin in food (eg, Staphylococcus, shellfish, mushrooms)
  • Ingestion of a pharmacological agent (eg, caffeine, which may cause arrythmia) 
  • Signs and symptoms of food intolerance
    • Abdominal pain
    • Diarrhea
    • Gas and bloating
    • Headaches or migraine
    • Heartburn
    • Nausea
    • Upset stomach 

Food Allergy

Cow Milk Protein Allergy 

• Breastfed newborns and infants who are highly sensitive to a cow milk protein may react to foods in the maternal diet, in which case maternal avoidance may be required.
• Most formula-fed newborns and infants who have evidence of protein milk allergy when standard cow milk formulas are given tolerate a formula labeled “hypoallergenic” (hydrolyzed casein-based formula).
• If a newborn or infant reacts to hypoallergenic cow milk–derived formulas, an amino acid formula may be tolerated.  

Up to 3% of newborns and infants have an allergy to cow milk protein. Milk allergies can be immunoglobulin E (IgE) or non-IgE mediated. 

• Approximately 60% of newborns and infants with cow milk protein allergy (CMPA) have the IgE-mediated form.
• The non-IgE–mediated CMPA may cause a variety of conditions, depending on where the allergy is located. These include 
  • Cow milk enteropathy
  • Food protein–induced proctitis/proctocolitis
  • Food protein–induced enterocolitis syndrome
  • Heiner syndrome

Immunoglobulin E–Mediated Cow Milk Protein Allergy  

Cow milk is among the most common causes of food-induced anaphylaxis, along with peanuts and tree nuts. 

• CMPA is more common in males and in those with atopic diseases.  

IgE-mediated CMPA symptoms occur within a few minutes and up to 2 hours after ingestion of cow milk. Symptoms include  

• Urticaria
• Angioedema
• Throat tightness
• Respiratory symptoms, including difficulty breathing, coughing, and wheezing
• Gastrointestinal symptoms, including abdominal pain, vomiting, and diarrhea
• Cardiovascular symptoms, including dizziness, confusion, and hypotension 

Diagnosis of IgE-mediated CMPA is not straightforward. The criterion standard is the double-blind food challenge. However, this is difficult to implement and carries risk for the infant or young child. 

• Laboratory testing must be interpreted in light of the clinical picture.
  • Skin prick tests are not themselves diagnostic.
  • Serum testing may show sensitization, but this does not, alone, have clinical significance. 

By age 5 years, 50% of those who develop IgE-mediated CMPA (which often begins in infancy) developed tolerance.  

• Physician-observed food challenges may be important to prevent lifelong avoidance of milk, which has been shown to lead to
  • Reduced linear growth
  • Vitamin D deficiency 

Non–Immunoglobulin E–Mediated Cow Milk Protein Allergy  

The symptoms of non–IgE-mediated CMPA (whey/casein) may be misinterpreted as lactose intolerance.  

• Symptoms generally include
  • Pain 
  • Flatulence
  • Diarrhea
  • Bloody stools 

Non–IgE-mediated CMPA can involve the gastrointestinal tract and the skin and may lead to respiratory symptoms.  

• Restriction of all milk protein leads to a resolution of symptoms within 4 to 6 weeks. 

For more information on diagnosis and treatment, see Food Protein–Induced Enterocolitis Syndrome. 

Food Protein-Induced Enterocolitis Syndrome (FPIES)

Food protein–induced enterocolitis syndrome (FPIES) is a type of allergic reaction in the gastrointestinal tract that usually begins in the first 6 months after birth in formula-fed infants. 

• Population prevalence in US infants is 0.51%. (ref)
• Symptoms begin 1 to 5 hours after eating a triggering food and include
  • Profuse vomiting and diarrhea leading to dehydration
  • Lethargy, hypotonia, hypothermia
  • Hypovolemic shock (20% of cases)
• Reported triggers are
  • Most commonly cow milk, followed by soy and then rice.
  • Other reported triggers include oats, barley, chicken, turkey, egg white, green pea, sweet potato, white potato, fruit protein, fish, and mollusks. 

FPIES diagnosis involves a standard skin prick testing; blood testing results for specific IgE are routinely negative. A careful history and physical examination are key in diagnosis. 

During an acute episode, laboratory findings may include 

• Elevated white blood cell count (increased neutrophils and eosinophils)
• Elevated platelet count
• Low red blood cell count or low albumin (particularly in chronic cases) 

Therapy consists of strict avoidance of the offending food.  

• A hypoallergenic diet can be an amino acid elemental formula or an extensively hydrolyzed casein or whey formula. 

Between 60% and 90% of children outgrow FPIES by the time they are 3 years old.  

Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is the most well-known member of a family of allergic enteropathies characterized by infiltration of the gastrointestinal tract with eosinophils. Related conditions are  

• Eosinophilic gastroenteritis
• Eosinophilic colitis

The incidence and prevalence of EoE is increasing, although figures are difficult to ascertain because of changes in diagnostic criteria and awareness. 

• Most estimates in the United States range from 40 to 90 cases per 100,000 persons.
• The prevalence of EoE in children with dysphagia and food impaction is high (63%–88%). Children with this presentation should be considered for timely endoscopic assessment.
• EoE occurs in approximately 4% of children with celiac disease.

More than 50% of patients with eosinophilic allergic enteropathies have a personal history of allergy, such as eczema, asthma, allergic rhinitis, or multiple food sensitivities. 

Symptoms may include 

• Vomiting
• Reflux
• Nausea
• Food aversion or refusal
• Failure to progress with food introduction
• Dysphagia
• Food impaction
• Growth failure
• Chest or abdominal pain 

Diagnosis  

Newborns and infants with symptoms of esophageal dysfunction should be considered for esophagogastroduodenoscopy. 

• Where EoE is a clinical possibility (even when normal mucosa is visualized), esophageal biopsy specimens should be obtained.

Criteria for the diagnosis of EoE 

1. Symptoms of esophageal dysfunction
   • Co-occurring atopic conditions should increase suspicion for EoE.
   • Endoscopic findings of rings, furrows, exudates, edema, stricture, narrowing, and crepe-paper mucosa should increase suspicion for EoE.
2. Eosinophils ≥15/HPF (~60/mm2) on esophageal biopsy
   • Eosinophilic infiltration should be isolated to the esophagus.
3. Assessment of non-EoE disorders that cause or potentially contribute to esophageal eosinophilia  

Note: The presence of eosinophils at ≥15/HPF is not diagnostic of EoE. For a diagnosis of EoE, patients cannot have another cause of eosinophil infiltration.  

A diagnosis of EoE is complicated by its relationship with gastroesophageal reflux disease (GERD). EoE and GERD are not necessarily mutually exclusive. 

• EoE can lead to secondary reflux because of dysmotility.
• GERD can lead to decreased epithelial integrity allowing eosinophilia. 

Due to the interrelatedness of EoE and GERD, and because no single test can exclude the presence of GERD, a proton pump inhibitor test is not part of the diagnostic criteria for EoE.  

Treatment 

Dietary restriction using elemental formula is the most effective treatment for EoE. However, the utility of elemental diets for infants and toddlers is low because 

• Infants often require feeding via a nasogastric tube to ensure nutritional adequacy.
• Long-term avoidance of solid food in children younger than 2 years or with known feeding dysfunction may lead to delayed oral-motor skill development.
• Reintroducing foods is a lengthy process, requiring multiple endoscopies with biopsies and several months of continued nutritional support, while a typical diet is gradually instituted.
• The high cost of elemental formula may not be covered by insurance. 

Because an elemental diet is difficult to implement and sustain and may have adverse developmental effects in infants, proton pump inhibitors, elimination diets, or topical steroids may be considered.  

Long-standing untreated EoE often leads to esophageal strictures.  

• Children typically do not have strictures because of a lack of disease progression. They tend to have esophageal narrowing, which often responds to antiinflammatory treatment.
• An infant or child with EoE should be referred to the nearest EoE center.