Basics
Description
Food allergy has recently been defined as "an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food." Most commonly, the protein component of the food is responsible for the adverse immunologic response.
- Classifications of food allergies:
- IgE mediated, including
- Anaphylaxis
- Acute urticaria
- Oral allergy syndrome
- Non-IgE mediated (cell mediated), including
- Food protein-induced enterocolitis syndrome (FPIES)
- Food protein-induced allergic proctocolitis
- Celiac disease
- Mixed IgE and non-IgE mediated, including
- Atopic dermatitis
- Eosinophilic gastroenteropathies (eosinophilic esophagitis, eosinophilic gastroenteritis)
- Most common IgE-mediated food allergies:
- Children
- Milk
- Egg
- Soy
- Peanut
- Wheat
- Fish
- Adults
- Peanuts
- Tree nuts
- Fish
- Shellfish
- Most common non-IgE-mediated food allergies associated with food protein enterocolitis and proctocolitis:
- Milk
- Soy
- Rice
- Oat
- Barley
- Chicken
Epidemiology
Food-induced anaphylaxis is the most common cause of anaphylactic reactions treated in emergency departments in the United States. The prevalence of food allergy has increased over the past 10-20 years.
Prevalence
- 5% of children <5 years of age, 4% of teens and adults
- Nearly 2.5% of infants have hypersensitivity reactions to cow's milk during 1st year ( ½ of these cases are thought to actually represent GI diseases); outgrown by most (80%) by 5 years of age.
- 1.6% have egg allergy by 2.5 years (based on population-based studies); 66% of children outgrow egg allergy by 7 years of age.
- 0.6% of U.S. population have peanut allergy.
- 37% of children < 5 years of age with moderate to severe atopic dermatitis have a food allergy.
- 34-49% of children with food allergy have asthma.
- 33-40% of children with food allergy have allergic rhinitis.
- Fatal and near-fatal reactions are associated with uncontrolled asthma.
Risk Factors
- Genetic
- Family history
- Presence of atopic dermatitis
- Other unknown factors suspected
Etiology
- Oral tolerance to food proteins believed to develop through T-cell anergy or induction of regulatory T cells. Food hypersensitivity develops when oral tolerance fails to develop or breaks down.
- IgE mediated: T cells induce B cells to produce IgE antibodies that initially bind on the surface of mast cells and basophils; when reexposed, the food protein binds to IgE antibodies, leading to degranulation of those cells and release of histamine and other chemical mediators.
- Non-IgE mediated (cell mediated): T cells react to protein-inducing proinflammatory cytokines, leading to inflammatory cell infiltrates and increased vascular permeability. These factors lead to subacute and chronic responses primarily affecting the GI tract.
- Mixed IgE and non-IgE mediated: Eosinophilic esophagitis and eosinophilic gastroenteropathy are characterized by eosinophilic infiltration of intestinal wall, occasionally reaching to serosa.
Commonly Associated Conditions
- Asthma (4-fold more likely)
- Allergic rhinitis (2.4-fold more likely)
- Other atopic diseases
- Dermatitis herpetiformis (celiac)
Diagnosis
Varies depending on the individual and the type of food hypersensitivity (see Table for symptoms of specific illnesses)
- IgE mediated
- Urticaria
- Angioedema
- Immediate GI reactions (emesis, cramping, etc.)
- Oral allergy syndrome
- Rhinitis
- Anaphylaxis (hypotension, dyspnea, dysphonia, wheezing, coughing, angioedema)
- Nausea, abdominal pain, colic, and vomiting develop within 2 hours of ingesting offending foods.
- Diarrhea: develops within 2-6 hours
- Mixed IgE and non-IgE (cell mediated)
- Eosinophilic gastroenteropathy
- Weight loss (key feature), pain, emesis, failure to thrive (FTT), anorexia
- Some infants have a large protein-losing enteropathy component causing low serum albumin and hypogammaglobulinemia.
- Eosinophilic esophagitis
- Dysphagia
- Food impaction
- Intermittent vomiting
- Food refusal
- Abdominal pain
- Irritability
- Failure to respond to reflux medication
- FTT
- Gastroesophageal reflux
- Non-IgE mediated
- Food protein enterocolitis
- Severe vomiting 2 hours after ingestion; profuse diarrhea
- Shock due to fluid/electrolyte loss
- Very ill appearing
- Food protein proctocolitis
- Food protein-induced enteropathy
- Diarrhea, bloating, FTT, anemia
Physical Exam
- IgE mediated
- Hives/angioedema (however, in 12% of patients with anaphylaxis, there are no skin findings and often these are most severe cases)
- Wheezing/dyspnea
- Hypotension/tachycardia
- Vomiting, abdominal tenderness
- Ill-appearing
- Mixed IgE mediated, non-IgE mediated:
- Eosinophilic esophagitis: abdominal tenderness (variable), growth concerns (in some)
- Eosinophilic gastroenteropathy
- Abdominal tenderness
- Weight loss
- Cell mediated
- Food protein-induced enterocolitis
- Abdominal distention
- FTT
- Severe dehydration (may present in shock)
- Celiac disease
Diagnostic Tests & Interpretation
Lab
Initial Lab Tests
Depends on clinical presentation and patient symptoms, may include
- CBC with differential
- Anemia in patients with enteropathy
- Eosinophilia may be seen in patients with eosinophilic gastroenteritis, enteropathy, and, on occasion, eosinophilic esophagitis (but cannot be used to monitor therapy).
- Serum IgE: may be elevated in
- IgE-mediated hypersensitivities
- Eosinophilic esophagitis, eosinophilic gastroenteritis
- Albumin: low in
- Protein-losing enteropathies
- Non-IgE-mediated protein enterocolitis (chronic version)
- Eosinophilic gastroenteritis
- Serologic tests: may aid in diagnosis of celiac disease
- Tryptase: may be elevated in anaphylaxis; obtain within 4 hours of initial reaction.
- ImmunoCAP assay may be helpful in IgE-mediated illness.
- ImmunoCAP has many false positives (do not send food allergy panels).
Diagnostic Procedures/Other
- Skin prick testing
- Used in conjunction with clinical history for IgE-mediated food allergies
- 50% positive predictive value; 95% negative predictive value
- Performed upon evaluation of patients with eosinophilic esophagitis
- Food challenges
- Gold standard for diagnosis of food allergy is double-blind placebo-controlled challenge but impractical in many clinical settings.
- Most sites use single-blind or open food challenge.
- Used to confirm food allergy in patients when unsure of diagnosis or to assess whether someone has outgrown food allergy (either IgE-mediated or food protein-induced enterocolitis)
- Challenge must be performed in setting equipped to treat severe allergic reactions.
- Endoscopy with biopsies of esophagus, stomach, and small bowel
- Patients should be on proton pump inhibitor prior to endoscopy if there are concerns for eosinophilic esophagitis, as GERD may also lead to eosinophils in esophagus.
- Colonoscopy
- If lower GI symptoms are present
- Patch skin testing
- May be used to evaluate for mixed (IgE/non-IgE mediated) or cell-mediated sensitivities
- Standards for interpretation and methods for reliability are under development.
- Elimination diets
- Should be conducted with care
- May lack critical nutrients
- Oral rechallenge should be carefully planned because a more severe reaction may ensue after a food has been temporarily removed.
Food Allergy/HypersensitivityView LargeFood Allergy/HypersensitivityClassificationIllnessSymptomsDiagnosisIgE mediatedAnaphylaxisRapid onset; nausea, vomiting; abdominal pain; hives, coughing, wheezing; involvement of other organ systems-skin, respiratory systemHistory + skin prick or ImmunoCAP test; oral challenge only in monitored setting with emergency access and anaphylaxis therapyIgE mediatedOral allergy syndrome (children and adults); due to cross-reactivity between food protein and pollenMild pruritus, angioedema of lips and oropharynx, sense of tightness in throat, rare systemic symptomsHistory + skin prick tests; oral challenge positive with fresh foods and negative with cooked foodsIgE and cell mediatedAllergic eosinophilic gastroenteritisFailure to thrive, weight loss, abdominal pain, irritability, early satiety, vomiting, protein-losing enteropathy, edema, ascitesHistory + skin prick, endoscopy and colonoscopy with biopsy, elimination diet; monitor closely, may need immunosuppressantsIgE and cell mediatedEosinophilic esophagitisGERD with failure to respond to proton pump inhibitor, vomiting, FTT, dysphagia, intermittent abdominal pain, irritabilityHistory, endoscopy with biopsy, elimination diet based on testing or history, elemental diet, or "swallowed" steroidsCell mediatedAllergic proctocolitis "breast milk colitis" (infants)Bloody stool, melena in first few months of life; no diarrhea or failure to thriveElimination of food (cow's milk or soy most commonly) clears bleeding in 72 hours, reexposure causes recurrencep; RAST/skin prick not helpful; typically outgrown by 12-18 months of ageCell mediatedFood protein-induced enterocolitis syndrome (FPIES)Severe symptoms; vomiting 2 hours after meal; severe vomiting; 6-8 hours later, diarrhea ħ blood, abdominal distention, failure to thrive, dehydration, hypotensionElimination of protein clears symptoms in 1-3 days. ImmunoCAP/skin prick not helpful; patch testing may be helpfulCell mediatedFood protein enteropathy (infants)Diarrhea, steatorrhea, abdominal distention, flatulence, failure to thrive or weight loss, nausea/vomiting, oral ulcersEndoscopy with biopsy; elimination diet resolves symptoms. Similar symptoms to celiac but resolves by 2 years of age.Cell mediatedCeliac disease (infants to adults)Diarrhea, steatorrhea, failure to thrive, abdominal distention, flatulence, weight loss, nausea/vomiting, oral ulcersEndoscopic biopsy when patient is on gluten; gluten-free diet resolves symptoms. Anti-gliadin and TTG antibodies; HLA-DQ2 and DQ8 are often found.
Pathologic Findings
- Increased eosinophils in eosinophilic gastroenteropathy
- Presence of intraepithelial lymphocytes and variable villous damage in celiac disease
Treatment
Medication
First Line
- Anaphylaxis
- Epinephrine for severe allergic reaction or anaphylaxis
- H1 antihistamines (diphenhydramine) may be given for milder symptoms.
- H2 antihistamines may be given in conjunction with H1 antihistamines.
- Systemic steroids
- Eosinophilic gastroenteritis
- Systemic steroids (briefly)
- "Swallowed" steroids
- Refers to having the patient use a corticosteroid inhaler
- However, the patient swallows after spraying rather than inhaling.
- Elemental formulas
- Dietary restrictions
Additional Therapies
General Measures
- Avoidance of food allergen
- Anaphylaxis
- Full monitoring of vital signs
- Epinephrine for severe allergic reaction or anaphylaxis given intramuscularly: may be repeated
- IV fluid bolus
- Antihistamines may be given for hives or mild skin swelling.
- Antihistamines (H1 and H2 blockers) and bronchodilators may be used as adjunct to epinephrine for severe reactions.
- Glucocorticoids may prevent biphasic reaction.
- Trendelenburg positioning: helps decrease risk of empty ventricle syndrome
- Nonanaphylactic food allergies: eosinophilic esophagitis
- Systemic steroids for a brief course
- Swallowed steroids (NPO for 30 minutes after use)
- Hydrolyzed or elemental formulas: Patients may respond to hypoallergenic formulas.
Issues for Referral
Allergy/immunology and/or gastroenterology and/or nutrition follow-up needed for most patients for diagnosis and long-term management.
Ongoing Care
Diet
Nonanaphylactic and anaphylactic food allergies: removal of the offending food agent from diet
Patient Education
- Epinephrine self-administration, if anaphylaxis
- Anaphylaxis plan for families to know which medication to use and when, along with education regarding when to go to the emergency department
- Education regarding specific food avoidance and label reading
Prognosis
- Generally good after offending food antigens are removed from diet and adequate nutrients are ensured
- Tolerance to food allergens may develop over time. Current research trials to help induce tolerance are underway.
- IgE-mediated disease may persist longer than non-IgE mediated.
- Eosinophilic esophagitis and eosinophilic gastroenteritis are considered chronic illnesses.
Complications
- Food protein allergy can be associated with
- Poor growth
- Feeding disorder
- Protein-losing enteropathy
- Anemia
- Eosinophilic esophagitis
- Strictures
- Hiatal hernia concerns
- Poor growth
- Feeding disorder
- Respiratory food-hypersensitivity reactions
- Heiner syndrome: rare food-induced pulmonary hemosiderosis
Additional Reading
- Bock SA. Diagnostic evaluation. Pediatrics. 2003;111(6, Pt 3):1638-1644. [View Abstract]
- Burks W. Skin manifestations of food allergy. Pediatrics. 2003;111(6, Pt 3):1617-1624. [View Abstract]
- Cianferoni A, Spergel JM. Food allergy: review, classification and diagnosis. Allergol Int. 2009;58(4):457-466. [View Abstract]
- James JM. Respiratory manifestations of food allergy. Pediatrics. 2003;111(6, Pt 3):1625-1630. [View Abstract]
- J ¤rvinen KM, Nowak-WÄgrzyn A. Food protein induced enterocolitis syndrome (FPIES): current management strategies and review of the literature. J Allergy Clin Immunol Prac. 2013;1(4):317-322. [View Abstract]
- NIAID-Sponsored Expert Panel. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol. 2010;126(6)(Suppl):S1-S58. [View Abstract]
- Sampson HA. Update on food allergy. J Allergy Clin Immunol. 2004;113(5):805-819. [View Abstract]
- Sicherer SH, Sampson HA. Food allergy: recent advances in pathophysiology and treatment. Annu Rev Med. 2009;60:261-277. [View Abstract]
Codes
ICD09
- 995.7 Other adverse food reactions, not elsewhere classified, init
- 995.6 Anaphylactic reaction due to unspecified food
- 693.1 Dermatitis due to food taken internally
- 708 Allergic urticaria
- 692.5 Contact dermatitis and other eczema due to food in contact with skin
ICD10
- L27.2 Dermatitis due to ingested food
- T78.1XXA Other adverse food reactions, not elsewhere classified, initial encounter
- Z91.018 Allergy to other foods
- T78.00XA Anaphylactic reaction due to unspecified food, init encntr
- L50.0 Allergic urticaria
- T78.03XA Anaphylactic reaction due to other fish, initial encounter
- T78.07XA Anaphylactic reaction due to milk and dairy products, init
- T78.05XA Anaphylactic reaction due to tree nuts and seeds, init
- T78.01XA Anaphylactic reaction due to peanuts, initial encounter
- T78.09XA Anaphylactic reaction due to oth food products, init encntr
- T78.02XA Anaphylactic reaction due to shellfish (crustaceans), init
- T78.04XA Anaphylactic reaction due to fruits and vegetables, init
- T78.08XA Anaphylactic reaction due to eggs, initial encounter
SNOMED
- 414285001 food allergy (disorder)
- 91941002 Food anaphylaxis (disorder)
- 200895000 Ingestion dermatitis due to food
- 402384009 Allergic urticaria due to ingested food
FAQ
- Q: What are the most common food allergens leading to IgE-mediated allergic reactions in childhood?
- A: The most common allergens to which children are sensitive are milk, egg, soy, wheat, fish, peanuts, and nuts.
- Q: Do you recommend elimination diets?
- A: Elimination diets are recommended when necessary to treat underlying disease. Nutrition evaluation is often necessary to avoid nutrient-deficient diets and malnutrition. Elimination diets are used only in extreme circumstances because they can result in nutrient deficiency and malnutrition without identifying the offending allergen. Double-blinded food challenges are a better method for identifying the offending agent.