The initial task in assessment of a patient with suspected food allergy is to separate atopic from nonatopic disease, and to distinguish symptoms and signs of minor adverse immune reactions from more severe concerns of anaphylactic response. It should also aim to identify, if possible, a culprit food. Testing for food allergens should be based on and interpreted in the context of the historical and physical findings.[36]American Academy of Allergy, Asthma & Immunology. Ten things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 [internet publication].
https://web.archive.org/web/20230402083712/https://www.choosingwisely.org/societies/american-academy-of-allergy-asthma-immunology
[37]American Academy of Pediatrics. Ten things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2022 [internet publication].
https://web.archive.org/web/20230325225612/https://www.choosingwisely.org/societies/american-academy-of-pediatrics
History and examination
Evaluation should begin with detailing the specific signs and symptoms reported by patient or parent, with particular focus on dermatologic, respiratory, gastrointestinal, ophthalmic, and severe cardiac or systemic manifestations. Findings that support the diagnosis of a food allergy include:
Pruritus, flushing, urticaria, and angioedema of the skin[Figure caption and citation for the preceding image starts]: Typical cutaneous findings in food allergy at 30 minutes after ingestion of peanutsFrom the collection of Duke University Medical Center; used with permission [Citation ends].
Sneezing, rhinorrhea, nasal congestion, metallic taste, hoarseness, stridor, a sense of choking, laryngeal edema, dyspnea, tachypnea, wheezing, coughing, or cyanosis
Nausea, vomiting, abdominal cramping, bloating, and diarrhea
Conjunctival injection, lacrimation, periorbital edema
In severe cases, conduction disturbances, tachycardia, bradycardia, arrhythmias, hypotension, and cardiac arrest.
Pertinent clues that support the clinical impression of atopic disease include a family member with food allergy, presence of other allergic disease (e.g., atopic dermatitis, allergic rhinitis, asthma), perinatal transdermal food exposure (e.g., peanut oil), dietary excess or diminished vitamin D, omega-3 polyunsaturated fatty acids or antioxidants, and a paucity of exposure to bacteria and infection. Studies in the UK have shown that if a first-degree family member has peanut allergy, the risk of peanut allergy increases 7 times.[15]Hourihane JO, Dean TP, Warner JO. Peanut allergy in relation to heredity, maternal diet, and other atopic diseases: results of a questionnaire survey, skin prick testing, and food challenges. BMJ. 1996 Aug 31;313(7056):518-21.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2351952/pdf/bmj00557-0020.pdf
http://www.ncbi.nlm.nih.gov/pubmed/8789975?tool=bestpractice.com
Monozygotic twins have been reported to have a 64% concordance rate for food allergy compared with 6.8% among dizygotic twins.[20]Sicherer SH, Furlong TJ, Maes HH, et al. Genetics of peanut allergy: a twin study. J Allergy Clin Immunol. 2000 Jul;106(1 Pt 1):53-6.
https://www.jacionline.org/article/S0091-6749(00)71311-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/10887305?tool=bestpractice.com
Patients with atopic dermatitis, asthma, and allergic rhinitis are more likely to have a food allergy. The presence of asthma is a risk factor for a fatal reaction.[38]Bock SA, Muñoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol. 2001 Jan;107(1):191-3.
http://www.ncbi.nlm.nih.gov/pubmed/11150011?tool=bestpractice.com
Two-thirds of children with atopic dermatitis and food allergy are reactive to egg.[39]Sampson HA. Food sensitivity and the pathogenesis of atopic dermatitis. J R Soc Med. 1997;90(suppl 30):2-8.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296079/pdf/jrsocmed00032-0005.pdf
http://www.ncbi.nlm.nih.gov/pubmed/9176122?tool=bestpractice.com
Ninety percent of reactions are caused by milk, egg, peanut, tree nuts, wheat, soy, fish, and shellfish in children, and by peanut, tree nuts, shellfish, fish, and vegetables in adults.[1]Sicherer SH, Sampson HA. 9. Food allergy. J Allergy Clin Immunol. 2006 Feb;117(2 suppl Mini-Primer):S470-5.
https://www.jacionline.org/article/S0091-6749(05)01921-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/16455349?tool=bestpractice.com
[40]Moneret-Vautrin DA, Morisset M. Adult food allergy. Curr Allergy Asthma Rep. 2005 Jan;5(1):80-5.
http://www.ncbi.nlm.nih.gov/pubmed/15659269?tool=bestpractice.com
[41]Osterballe M, Hansen TK, Mortz CG, et al. The prevalence of food hypersensitivity in an unselected population of children and adults. Pediatr Allergy Immunol. 2005 Nov;16(7):567-73.
http://www.ncbi.nlm.nih.gov/pubmed/16238581?tool=bestpractice.com
The causative food may often be revealed with careful questioning and consideration of the patient's response.
Has the suspected food allergen been ingested, inhaled, or touched? A specific suspect food should produce symptoms reproducibly nearly every time it is ingested.
How much of the food was ingested at the time of the reaction? IgE-mediated reactions may be triggered by minute amounts, whereas other disorders may require larger amounts.
How soon after exposure to the suspected food allergen did the symptoms occur? IgE-mediated reactions usually occur within 20 minutes of exposure and almost always within 2 hours.
How long did it take for the symptoms to resolve in the past and how was the reaction treated? IgE-mediated symptoms typically resolve within 4 to 12 hours. Reactions may resolve spontaneously or may respond to medical interventions.
Has exercise been associated with the development of symptoms? Food-dependent, exercise-induced anaphylaxis may occur if the food is eaten within 2 to 4 hours before or after exercise.[39]Sampson HA. Food sensitivity and the pathogenesis of atopic dermatitis. J R Soc Med. 1997;90(suppl 30):2-8.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296079/pdf/jrsocmed00032-0005.pdf
http://www.ncbi.nlm.nih.gov/pubmed/9176122?tool=bestpractice.com
Were any medications or alcohol ingested in proximity to the reaction? Medications and alcohol are believed to increase the rate of allergen absorption.[42]Sampson HA. Food allergy. J Allergy Clin Immunol. 1989 Dec;84(6 Pt 2):1062-7.
http://www.ncbi.nlm.nih.gov/pubmed/2600342?tool=bestpractice.com
[43]Burks AW, Sampson HA. Diagnostic approaches to the patient with suspected food allergies. J Pediatr. 1992 Nov;121(5 Pt 2):S64-71.
http://www.ncbi.nlm.nih.gov/pubmed/1280298?tool=bestpractice.com
[44]Lack G. Clinical practice. Food allergy. New Engl J Med. 2008 Sep 18;359(12):1252-60.
http://www.ncbi.nlm.nih.gov/pubmed/18799559?tool=bestpractice.com
Testing modalities for food allergy
If the initial evaluation is suggestive of food allergy, diagnostic testing should be performed. Testing may begin with either in vitro immunoglobulin (Ig) E immunoassays or skin prick testing. If the assessment is negative (e.g., the patient tolerates the food regularly and has no related symptoms), then diagnostic testing does not need to be performed and food allergy may be ruled out as a cause of the symptoms.[45]Singh AM, Anvari S, Hauk P, et al. Atopic dermatitis and food allergy: best practices and knowledge gaps - a work group report from the AAAAI Allergic Skin Diseases Committee and Leadership Institute Project. J Allergy Clin Immunol Pract. 2022 Mar;10(3):697-706.
http://www.ncbi.nlm.nih.gov/pubmed/35101439?tool=bestpractice.com
If a food has been tolerated in large quantities many times before, it is not likely a relevant allergen, even with a positive test. Commercially prepared extracts of fruits and vegetables are not as predictive because of the lability of the protein. Fresh fruits and vegetables should be used for skin testing.[46]Ortolani C, Ispano M, Pastorello EA, et al. Comparison of results of skin prick tests (with fresh foods and commercial food extracts) and RAST in 100 patients with oral allergy syndrome. J Allergy Clin Immunol. 1989 Mar;83(3):683-90.
http://www.ncbi.nlm.nih.gov/pubmed/2926087?tool=bestpractice.com
High sensitivity and low specificity of skin prick and IgE testing for food allergy can yield false positive results, which may lead to elimination diets that are potentially harmful to patients.[45]Singh AM, Anvari S, Hauk P, et al. Atopic dermatitis and food allergy: best practices and knowledge gaps - a work group report from the AAAAI Allergic Skin Diseases Committee and Leadership Institute Project. J Allergy Clin Immunol Pract. 2022 Mar;10(3):697-706.
http://www.ncbi.nlm.nih.gov/pubmed/35101439?tool=bestpractice.com
Therefore, do not perform an indiscriminate battery of IgE tests.[36]American Academy of Allergy, Asthma & Immunology. Ten things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 [internet publication].
https://web.archive.org/web/20230402083712/https://www.choosingwisely.org/societies/american-academy-of-allergy-asthma-immunology
In particular, do not perform food IgE testing in patients without a relevant medical history consistent with potential IgE-mediated food allergy.[36]American Academy of Allergy, Asthma & Immunology. Ten things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 [internet publication].
https://web.archive.org/web/20230402083712/https://www.choosingwisely.org/societies/american-academy-of-allergy-asthma-immunology
[37]American Academy of Pediatrics. Ten things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2022 [internet publication].
https://web.archive.org/web/20230325225612/https://www.choosingwisely.org/societies/american-academy-of-pediatrics
Effects such as progression to immediate-type allergy, including anaphylactic reactions have been reported.[45]Singh AM, Anvari S, Hauk P, et al. Atopic dermatitis and food allergy: best practices and knowledge gaps - a work group report from the AAAAI Allergic Skin Diseases Committee and Leadership Institute Project. J Allergy Clin Immunol Pract. 2022 Mar;10(3):697-706.
http://www.ncbi.nlm.nih.gov/pubmed/35101439?tool=bestpractice.com
[47]Chang A, Robison R, Cai M, et al. Natural history of food-triggered atopic dermatitis and development of immediate reactions in children. J Allergy Clin Immunol Pract. 2016 Mar-Apr;4(2):229-36;e1.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789144
http://www.ncbi.nlm.nih.gov/pubmed/26597013?tool=bestpractice.com
[48]David TJ. Anaphylactic shock during elimination diets for severe atopic eczema. Arch Dis Child. 1984 Oct;59(10):983-6.
https://www.doi.org/10.1136/adc.59.10.983
http://www.ncbi.nlm.nih.gov/pubmed/6541895?tool=bestpractice.com
[49]Eigenmann PA, Beyer K, Lack G, et al. Are avoidance diets still warranted in children with atopic dermatitis? Pediatr Allergy Immunol. 2020 Jan;31(1):19-26.
http://www.ncbi.nlm.nih.gov/pubmed/31273833?tool=bestpractice.com
Testing should be performed by an allergy specialist trained in the treatment of rare but potentially life-threatening events. If specific testing falls below values predictive of a reaction by immunoassay testing and by skin testing, or the diagnosis is in question, then a food challenge may be performed. Negative skin tests to foods early in life do not preclude the subsequent development of specific IgE hypersensitivity in later childhood.[22]Hill DJ, Hosking CS, de Benedictis FM, et al; EPAAC Study Group. Confirmation of the association between high levels of immunoglobulin E food sensitization and eczema in infancy: an international study. Clin Exp Allergy. 2008 Jan;38(1):161-8.
http://www.ncbi.nlm.nih.gov/pubmed/18028467?tool=bestpractice.com
Double-blind placebo-controlled food challenges are considered the key test in diagnosing food allergy.[50]Sampson HA, Gerth van Wijk R, Bindslev-Jensen C, et al. Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report. J Allergy Clin Immunol. 2012 Dec;130(6):1260-74.
http://www.jacionline.org/article/S0091-6749%2812%2901663-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23195525?tool=bestpractice.com
These challenges are graded, and there should be an equivalent number of placebo and food steps. If the patient passes this challenge, then an open feeding is performed. If this is tolerated, then food allergy has been excluded.
Do not perform any unproven diagnostic tests, such as immunoglobulin G (lgG) testing, in the evaluation of food allergy. IgG testing can lead to inappropriate diagnosis and treatment.[3]Sampson HA, Aceves S, Bock SA, et al. Food allergy: a practice parameter update - 2014. J Allergy Clin Immunol. 2014 Nov;134(5):1016-25;e43.
https://www.jacionline.org/article/S0091-6749(14)00672-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25174862?tool=bestpractice.com
[36]American Academy of Allergy, Asthma & Immunology. Ten things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 [internet publication].
https://web.archive.org/web/20230402083712/https://www.choosingwisely.org/societies/american-academy-of-allergy-asthma-immunology
[45]Singh AM, Anvari S, Hauk P, et al. Atopic dermatitis and food allergy: best practices and knowledge gaps - a work group report from the AAAAI Allergic Skin Diseases Committee and Leadership Institute Project. J Allergy Clin Immunol Pract. 2022 Mar;10(3):697-706.
http://www.ncbi.nlm.nih.gov/pubmed/35101439?tool=bestpractice.com
[51]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 Dec;126(6):1105-18.
http://www.jacionline.org/article/S0091-6749(10)01569-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/21134568?tool=bestpractice.com
Investigational studies
Purified or recombinant allergens are used to identify specific IgE sensitization to proteins within an individual food allergen in component-resolved diagnostics. Some studies have shown an increased ability to predict the likelihood of having a severe allergic reaction to foods like peanut, soy, or hazelnut; however, geographic pollen sensitization patterns may affect results, and further studies are needed to generalize interpretability.[52]Flores Kim J, McCleary N, Nwaru BI, et al. Diagnostic accuracy, risk assessment, and cost-effectiveness of component-resolved diagnostics for food allergy: a systematic review. Allergy. 2018 Aug;73(8):1609-21.
https://www.doi.org/10.1111/all.13399
http://www.ncbi.nlm.nih.gov/pubmed/29319184?tool=bestpractice.com
[53]Datema MR, van Ree R, Asero R, et al. Component-resolved diagnosis and beyond: Multivariable regression models to predict severity of hazelnut allergy. Allergy. 2018 Mar;73(3):549-59.
http://www.ncbi.nlm.nih.gov/pubmed/28986984?tool=bestpractice.com
The role of component testing continues to evolve.[54]Greenhawt M, Shaker M, Wang J, et al. Peanut allergy diagnosis: a 2020 practice parameter update, systematic review, and GRADE analysis. J Allergy Clin Immunol. 2020 Dec;146(6):1302-34.
https://www.jacionline.org/article/S0091-6749(20)31137-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32810515?tool=bestpractice.com
Atopy patch testing is typically used to identify allergens that cause reactions through delayed contact hypersensitivity where T cells play a major role. Allergenic extract is occluded against intact skin for 48 hours; it is available for investigational use only.[55]Nowak-Wegrzyn A. Future approaches to food allergy. Pediatrics. 2003 Jun;111(6 Pt 3):1672-80.
http://www.ncbi.nlm.nih.gov/pubmed/12777608?tool=bestpractice.com
Patch testing is well validated for contact dermatitis but not food allergy in general.