BASICS
DESCRIPTION
- Hypersensitivity reaction caused by certain foods
- System(s) affected: gastrointestinal, hemic/lymphatic/immunologic, pulmonary, skin/exocrine
- Synonym(s): allergic bowel disease; dietary protein sensitivity syndrome
EPIDEMIOLOGY
- Predominant age: all ages but more common in infants and children
- Predominant sex: male > female (2:1)
Incidence
Prospective studies indicate ~2.5% of infants experience hypersensitivity reactions to cow's milk in their 1st year of life (1)[B].
Prevalence
- The true prevalence of IgE-mediated food allergy when assessed by double-blind, placebo-controlled food challenge is 3% (2)[B].
- The self-reported prevalence of food allergy is 12% in children and 13% in adults (2)[B].
- In young children, the most common food allergies are cow's milk (2.5%), egg (1.3%), peanut (0.8%), and wheat (0.4%) (3)[B].
- Adults tend to have allergies to shellfish (2%), peanut (0.6%), tree nuts (0.5%), and fish (0.4%).
- In general, only 3-4% of children >4 years of age have persisting food allergy; food allergy is frequently a transient phenomenon (4)[B].
- 20% of children with peanut protein allergy may outgrow their sensitivity by school age.
ETIOLOGY AND PATHOPHYSIOLOGY
Allergic response triggered by immunologic mechanisms, such as the classic IgE-allergic response or nonimmunologic-mediated mechanisms
- Any food or ingested substance can cause allergic reactions:
- Most commonly implicated foods include cow's milk, egg whites, wheat, soy, peanuts, fish, tree nuts (walnut and pecan), and shellfish.
- Several food dyes and additives may elicit non-IgE-mediated allergic-like reactions.
Genetics
In family members with a history of food hypersensitivity, the probability of food allergy in subsequent siblings may be as high as 50%.
RISK FACTORS
- Persons with allergic or atopic predisposition have increased risk of hypersensitivity reaction to food.
- Family history of food hypersensitivity
GENERAL PREVENTION
- Avoidance of offending food
- In patients at risk for anaphylaxis, epinephrine autoinjectors should be readily available.
DIAGNOSIS
PHYSICAL EXAM
- GI (system usually affected)
- More common: nausea, vomiting, diarrhea, abdominal pain, occult bleeding, flatulence, and bloating
- Less common: malabsorption, protein-losing enteropathy, eosinophilic-enteritis, colitis
- Dermatologic
- More common: urticaria/angioedema, atopic dermatitis, pallor, or flushing
- Less common: contact rashes
- Respiratory
- More common: allergic rhinitis, asthma and bronchospasm, cough, serous otitis media
- Less common: pulmonary infiltrates (Heiner syndrome), pulmonary hemosiderosis
- Neurologic
- Less common: migraine headaches
- Other symptoms
- Systemic anaphylaxis, vasculitis
DIFFERENTIAL DIAGNOSIS
- A careful history is necessary to document a temporal relationship with the manifestations of suspected food hypersensitivity.
- True food allergy or hypersensitivity should be differentiated from food intolerance which may present with similar symptoms.
- GI (irritable bowel syndrome, celiac sprue, dumping syndrome, inflammatory bowel diseases, etc.), dermatologic, respiratory, neurologic, psychiatric (generalized anxiety disorder, personality disorders, etc.), or other systemic manifestations may mimic a variety of clinical entities.
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- CBC with differential: Eosinophilia in blood or tissue suggests atopy.
- Serum IgA antitissue transglutaminase (IgA-anti-TTG)
- Epicutaneous (prick or puncture) allergy skin tests are used to document IgE-mediated immunologic hypersensitivity and can be done using commercially available extracts (variable sensitivities) or fresh-food skin testing.
- Skin testing using the suspect food is helpful. If positive on skin test, an oral challenge may aid in diagnosis. The overall correlation between commercially available allergy skin testing and oral food challenge is 60% but increases to 90% when fresh food skin testing is done (i.e., a positive skin test correlates with a positive challenge to a particular food)
- Skin testing has a high sensitivity (low false-negative rate) but a low specificity (high false-positive rate) so only skin test against antigens found on history (5)[C].
- Food-specific IgE assays (radioallergosorbent [RAST] and fluorescent enzyme immunoassay [FEI]) detect specific IgE antibodies to offending foods and are less sensitive to skin testing.
- In certain laboratories, the ImmunoCap food-specific IgE was almost as accurate as a skin test in predicting positive oral challenges.
- Using a serum assay alone to diagnose food allergy has been shown to result in misdiagnosis of true clinical food allergic sensitivity, particularly in children with atopic dermatitis. Do not test using a panel but rather for specific IgE to foods based on patient history.
- Periodic monitoring of the peanut-specific IgE levels every 2 years may be helpful. If the level of peanut-specific IgE falls to <0.5 kU/L, then a cautious oral challenge under the supervision of an allergist may be considered. A fresh food skin test with peanut protein should be considered prior to the oral challenge (6)[B].
- Patch testing for foods for determining delayed-sensitivity immunologic reactions, in patients with eosinophilic esophagitis and atopic dermatitis, is considered of marginal benefit (7)[B].
- Widespread allergy skin testing or serum IgE tests are not recommended because of their poor predictive value without a clinical correlating history (3)[B].
- Leukocyte histamine release and assays for circulating immune complexes are predominantly research procedures and are of limited use in clinical practices:
- Assays for IgG and IgG 4 subclass antibodies are commercially available.
- No convincing data suggest that these tests are reliable for the diagnosis of food allergy (4)[B].
- The provocative injection and sublingual provocative tests are highly controversial and have been proven useless for diagnosis of food allergy.
- The leukocytotoxic assay is an unproven diagnostic procedure and is not useful for the diagnosis of allergy (7)[B].
- Other unproven diagnostic procedures that are not recommended include provocative neutralization, lymphocyte stimulation, hair analysis, and applied kinesiology (3)[B].
Diagnostic Procedures/Other
Elimination and challenge test is the best procedure for confirming food allergy:
- The suspected food is eliminated from the diet for 1 to 2 weeks.
- The patient's symptoms are monitored. If they disappear or substantially improve, an oral challenge with the suspected food should be performed under medical supervision.
- Optimally, this challenge should be performed in a double-blind, placebo-controlled manner.
- Patients with history of anaphylaxis should not have an oral challenge unless lack of IgE sensitivity can be documented.
- Most allergic reactions will occur within 30 minutes to 2 hours after challenge, although late reactions have also been described that may occur from 12 to 24 hours.
- Consider referral to gastroenterology for endoscopy and/or psychiatry if history and testing are inconclusive.
Test Interpretation
Pathologic findings are not common in food allergies; however, inflammatory changes can sometimes be seen in the GI tract. The diagnosis of eosinophilic esophagitis is defined by the finding of >15 to 20 eosinophils per high-power field on esophageal biopsy (8)[C].
TREATMENT
GENERAL MEASURES
- Avoiding the offending food is the most effective mode of treatment for patients with food allergies.
- Those patients with exquisite and severe allergy hypersensitivity to a food should be more cautious in their avoidance of that food. They should carry epinephrine for self-administration in the event that the offending food is ingested unknowingly and a subsequent immediate reaction develops.
- Immunotherapy or hyposensitization with food extracts by various routes, including SC immunotherapy or sublingual neutralization, are not recommended. Research studies are in progress, but immunotherapy is considered experimental at this time.
MEDICATION
- Patients with significant type 1, IgE-mediated hypersensitivity should have epinephrine for autoinjection available in case of accidental ingestion and resulting severe anaphylactic reaction.
- After receiving epinephrine for a systemic anaphylactic reaction to a food, the patient should be monitored in a medical facility because 15-25% of patients may require >1 dose of epinephrine.
- Symptomatic treatment for milder reactions (e.g., antihistamine)
- The use of cromolyn has been suggested but is not recommended for use in most patients with food allergy.
COMPLEMENTARY & ALTERNATIVE MEDICINE
There are reports of benefit using various Chinese herbal medicines in laboratory animals with induced food allergy. Benefits have not been reported in humans at this time.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
As needed
DIET
- As determined by tests and clinical evaluation
- Strict avoidance of offending food
PATIENT EDUCATION
- Patients should be counseled by a dietitian to maintain a nutritionally sound diet despite avoiding those foods to which the patient is sensitive.
- Patient support: Food Allergy Research & Education, Inc.: 7925 Jones Branch Drive Suite 1100 McLean, VA 22102 Toll-Free: 800-929-4040; Web site www.foodallergy.org
- Other information available at: www.allergyasthmanetwork.org, www.acaai.org, and www.aaaai.org
PROGNOSIS
- Most infants will outgrow their food hypersensitivity by 2 to 4 years:
- It may be possible to reintroduce the offending food cautiously into the diet (particularly helpful when the food is one that is difficult to avoid). It is critical that a specific IgE to the offending food is checked, optimally by fresh food allergy skin test, and is negative prior to an oral challenge.
- 20% of young children with peanut allergy experience resolution by the age of 5 years.
- 42% of children with egg allergy and 48% of children with milk allergy develop clinical tolerance and lose their sensitivity over time (1)[C].
- Adults with food hypersensitivity (particularly to milk, fish, shellfish, or nuts) tend to maintain their allergy for many years (3)[B].
COMPLICATIONS
- Anaphylaxis
- Angioedema
- Bronchial asthma
- Enterocolitis
- Eosinophilic esophagitis
- Eczematoid lesions
REFERENCES
11 Sicherer SH, Sampson HA. Food allergy: epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014;133(2):291-307.22 Rona RJ, Keil T, Summers C, et al. The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol. 2007;120(3):638-646.33 Boyce JA, Assa'ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-sponsored expert panel report. J Allergy Clin Immunol. 2010;126(6):1105-1118.44 Burks AW, Tang M, Sicherer S, et al. ICON: food allergy. J Allergy Clin Immunol. 2012;129(4):906-920.55 Sicherer SH, Wood RA. Advances in diagnosing peanut allergy. J Allergy Clin Immunol Pract. 2013;1(1):1-13.66 Fleischer DM, Bock SA, Spears GC, et al. Oral food challenges in children with a diagnosis of food allergy. J Pediatr. 2011;158(4):578.e1-583.e1.77 Spergel JM, Brown-Whitehorn T, Beausoleil JL, et al. Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis. J Allergy Clin Immunol. 2007;119(2):509-511.88 Spergel JM, Brown-Whitehorn TF, Cianferoni A, et al. Identification of causative foods in children with eosinophilic esophagitis treated with an elimination diet. J Allergy Clin Immunol. 2012;130(2):461.e5-467.e5.99 Greer FR, Sicherer SH, Burks AW, et al. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics. 2008;121(1):183-191.1010 Du Toit G, Roberts G, Sayre PH, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372(9):803-813.
ADDITIONAL READING
- American College of Allergy, Asthma, & Immunology. Food allergy: a practice parameter. Ann Allergy Asthma Immunol. 2006;96(3)(Suppl 2):S1-S68.
- H ¸st A, Halken S. A prospective study of cow milk allergy in Danish infants during the first 3 years of life. Clinical course in relation to clinical and immunological type of hypersensitivity reaction. Allergy. 1990;45(8):587-596.
- Maloney JM, Rudengren M, Ahlstedt S, et al. The use of serum-specific IgE measurements for the diagnosis of peanut, tree nut, and seed allergy. J Allergy Clin Immunol. 2008;122(1):145-151.
SEE ALSO
Anaphylaxis; Celiac Disease; Irritable Bowel Syndrome
CODES
ICD10
- T78.1XXA Oth adverse food reactions, not elsewhere classified, init
- T78.00XA Anaphylactic reaction due to unspecified food, init encntr
- L27.2 Dermatitis due to ingested food
- L50.0 Allergic urticaria
- T78.04XA Anaphylactic reaction due to fruits and vegetables, init
- T78.09XA Anaphylactic reaction due to oth food products, init encntr
- T78.08XA Anaphylactic reaction due to eggs, initial encounter
- T78.03XA Anaphylactic reaction due to other fish, initial encounter
- T78.02XA Anaphylactic reaction due to shellfish (crustaceans), init
- T78.01XA Anaphylactic reaction due to peanuts, initial encounter
- T78.07XA Anaphylactic reaction due to milk and dairy products, init
- T78.05XA Anaphylactic reaction due to tree nuts and seeds, init
ICD9
- 995.7 Other adverse food reactions, not elsewhere classified
- 995.60 Anaphylactic reaction due to unspecified food
- 693.1 Dermatitis due to food taken internally
- 708.0 Allergic urticaria
- 995.63 Anaphylactic reaction due to fruits and vegetables
- 995.69 Anaphylactic reaction due to other specified food
- 995.68 Anaphylactic reaction due to eggs
- 995.67 Anaphylactic reaction due to milk products
- 995.66 Anaphylactic reaction due to food additives
- 995.64 Anaphylactic reaction due to tree nuts and seeds
- 995.62 Anaphylactic reaction due to crustaceans
- 995.61 Anaphylactic reaction due to peanuts
- 692.5 Contact dermatitis and other eczema due to food in contact with skin
- 995.65 Anaphylactic reaction due to fish
SNOMED
- 414285001 food allergy (disorder)
- 91941002 Food anaphylaxis (disorder)
- 200895000 Ingestion dermatitis due to food
- 402384009 Allergic urticaria due to ingested food
- 91937001 allergy to seafood (disorder)
- 91930004 Allergy to eggs (disorder)
- 15911003 Cow's milk protein sensitivity (disorder)
- 91934008 Allergy to nuts (disorder)
CLINICAL PEARLS
- Recent studies suggest that up to 20% of children with peanut allergy may outgrow their sensitivity:
- Periodic monitoring of the peanut-specific IgE levels every 2 years may be helpful. If the level of peanut-specific IgE falls to <0.5 kU/L, then a cautious oral challenge under the supervision of an allergist may be considered. A FRESH FOOD skin test with peanut protein should be considered prior to the oral challenge (1)[B].
- Oral itching following ingestion of fresh fruit may be a warning of risk for anaphylaxis but may also represent oral allergy syndrome.
- This syndrome is the result of cross-reacting proteins in pollens (e.g., patients sensitive to birch tree pollen frequently have cross-reactivity to fresh apples and pears. Cooked fruits are usually tolerated) (1)[B].
- Current evidence does not support a major role for maternal dietary restrictions during pregnancy or lactation in the prevention of atopic disease in infants. It is generally recommended to exclusively breastfeed for the first 6 months of life, particularly when there is a family history of atopy and food allergy. Although solid foods should not be introduced before 4 to 6 months of age, there is no convincing evidence that delaying their introduction beyond this period has a significant protective effect on the development of allergies (9)[C].
- There is a recent evidence suggesting that children 4 to 11 months of age who have eczema or other food allergy may benefit from early introduction of peanut protein. Allergy skin testing should be a consideration prior to introducing peanut protein (10).