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Is there a gold-standard test for adverse food reactions?

Not all the specific AFR tests on the market have been directly evaluated

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The recommended process for diagnosing AFRs requires feeding a novel-protein diet or a hydrolyzed protein diet for an extended period, followed by challenge trials involving single-food proteins.

Some of the most common conditions seen in small-animal practice are gastrointestinal complaints, such as vomiting and diarrhea, and skin problems, including pruritis.1 Among the many differential diagnoses for these symptoms are adverse food reactions (AFRs). Such reactions are often called food allergies, though this term is more appropriately reserved for the subset of AFR that are directly mediated by the immune system, such as the immunoglobulin E- (IgE-) mediated acute hypersensitivity reactions seen in children with peanut allergies.

In humans, the gold-standard test for AFRs is the double-blinded, placebo-controlled food trial.2–4 The recommended process for diagnosing food allergies and other AFRs in dogs and cats is similar, and it involves feeding a limited ingredient novel-protein diet or a hydrolyzed protein diet for an extended period, followed by challenge trials involving single-food proteins.5–8 Because such testing is time-consuming and difficult, and it is often not possible for pet owners, there is great interest in alternative methods to diagnose AFR. Unfortunately, the evidence in humans and in veterinary patients suggests most of these tests are unreliable. They not only waste money and effort, they can easily create inaccurate beliefs in pet owners about food ingredients, making appropriate nutritional management of patients more difficult.

Testing for adverse food reactions

Given that food allergies and some other negative food reactions are immune-mediated responses, measurement of immunoglobulins has been suggested as a useful test for these AFRs. Measurement of food-specific IgE has some utility in people, though there are many limitations to these tests, and they can be unreliable and difficult to interpret in some cases.3,9,10 Measurement of total IgE, total immunoglobulin G (IgG), and various subsets of IgG has been shown not to be reliable in humans.3,11,12 Though there is less evidence in veterinary species, a number of studies have found that tests of serum immunoglobulins in dogs and cats are highly variable and not a reliable guide for diagnosis or clinical management.8,13–16

Skin prick testing is sometimes a useful alternative to diet trials in humans, though as with IgE testing, there are many limitations and caveats.3,9,10 Unfortunately, the limited research in dogs and cats has so far not found skin testing to be very useful in diagnosing food allergies in these species.7,14

In addition to skin testing and immunoglobulin serology, there are many other methods for food-allergy testing that are aggressively marketed to clinicians and patients in human medicine and to veterinarians and pet owners. Some of these are unequivocally nonsense and without any real scientific basis, such as applied kinesiology17–21 and iridology.21,22 Others may seem plausible, but have so far failed to prove their value. For example, the use of hair analysis and saliva testing to identify AFRs in humans have not been shown to be reliable, and both expert consensus and institutional clinical practice guidelines recommend against using these tests.21,23–25

A few studies have investigated specific commercial tests available to veterinarians and pet owners, and the results illustrate starkly the danger of using such unvalidated approaches to guide diagnosis and treatment of our patients.

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In one study,16 samples from 30 healthy dogs with no history of gastrointestinal or dermatologic symptoms were submitted to two companies for serum IgE testingA,B and one company for salivary IgM/IgA testing.C All the dogs tested positive for a purported AFR on at least one test. The different tests reported 60 to 100 percent of the samples as positive for AFR. Some dogs tested positive for all the specific foods tested. These tests demonstrated extremely high rates of false positive results, and they would mistakenly classify many normal dogs as having AFR.

The authors of this study collected diet histories from the owners of the dogs prior to submitting samples, and they were able to evaluate any potential relationship between food exposure and the test results. They found no correlation at all between what the dogs were reported to have eaten in the past and what the tests reported as foods to which these dogs should have an AFR. It is difficult to argue these tests are measuring anything real at all when they produce results that seem more consistent with chance than with known dietary exposures in dogs with no evidence of having any actual AFR.

Another study26 submitted samples to a different company offering an AFR test directly to pet ownersD (this test is no longer available). In this study, the samples were fur and saliva from two dogs, one known to have food allergies and the other with no evidence of AFR. The authors also submitted synthetic fake fur from a costume and tap water for testing. Positive results for AFR and environmental allergies were obtained for samples from both dogs and the fake samples. The distribution of positive and negative test results was not statistically different from random chance. This dramatically illustrates the unreliability of this particular test, and supports evidence from other studies in humans21,23–25 and veterinary patients27 showing hair and saliva testing in general to be unreliable. Again, a test that cannot distinguish dogs with known AFR from unaffected dogs, or even dog hair and saliva from fake fur and tap water, should not be used to diagnose or manage AFR.

Bottom line

Adverse food reactions are an important cause of common clinical problems in small-animal veterinary medicine. The only reliable methods for identifying specific foods triggering such reactions in an individual patient are novel-protein or hydrolyzed protein diet trials. These should last at least four weeks and possibly as long as four months, and they require strict owner compliance and careful recording of symptom patterns. Following this elimination phase, challenge trials with specific foods should be conducted to identify the likely cause of an AFR. This gold-standard testing procedure is not always possible, but unfortunately none of the proposed alternatives have proven as reliable.

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Specific methods for AFR testing that are unreliable and should not be used include skin testing, immunoglobulin serology, and hair and saliva testing. It is possible some variant of these methods may prove useful in the future, but none of the specific assays currently available have been convincingly shown to be useful, and several have been clearly shown to be misleading. Such tests can easily do more harm than good by convincing owners their pets’ symptoms are caused by an AFR and they have identified specific foods that are safe or problematic for their pets. Such misconceptions based on faulty tests can delay appropriate diagnosis and therapy, creating unnecessary suffering for patients and encouraging unproductive and useless dietary manipulations.

While not all the specific AFR tests on the market have been directly evaluated, all such tests should be viewed skeptically until they can provide controlled clinical research evidence that they accurately and usefully identify AFR and important dietary triggers. If food allergy or other AFR is suspected in a given patient, diet trial testing should be used if possible, and alternative AFR tests should be avoided.

References 
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2 Ballmer-Weber BK. Value of Allergy Tests for the Diagnosis of Food Allergy. Dig Dis. 2014;32:84-88. doi:10.1159/000357077
3 Lock RJ, Unsworth DJ. Food allergy: which tests are worth doing and which are not? Ann Clin Biochem. 2011;48(4):300-309. doi:10.1258/acb.2011.011011
4 J Pediatr Gastroenterol Nutr. 2007;45(4):399-404. doi:10.1097/MPG.0b013e318054b0c3
5 Kennis RA. Food Allergies: Update of Pathogenesis, Diagnoses, and Management. Vet Clin North Am Small Anim Pract. 2006;36(1):175-184. doi:10.1016/j.cvsm.2005.09.012

6 Rosser EJ. Diagnosis of food allergy in dogs. J Am Vet Med Assoc. 1993;203(2):259-262. http://www.ncbi.nlm.nih.gov/pubmed/8407485. Accessed November 23, 2018.
7 Kunkle G, Horner S. Validity of skin testing for diagnosis of food allergy in dogs. J Am Vet Med Assoc. 1992;200(5):677-680. http://www.ncbi.nlm.nih.gov/pubmed/1568911. Accessed November 19, 2018.
8 Jeffers JG, Shanley KJ, Meyer EK. Diagnostic testing of dogs for food hypersensitivity. J Am Vet Med Assoc. 1991;198(2):245-250. http://www.ncbi.nlm.nih.gov/pubmed/2004984. Accessed November 23, 2018.
9 Gupta M, Cox A, Nowak-Węgrzyn A, Wang J. Diagnosis of Food Allergy. Immunol Allergy Clin North Am. 2018;38(1):39-52. doi:10.1016/j.iac.2017.09.004
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11 Stapel SO, Asero R, Ballmer-Weber BK, et al. Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report*. Allergy. 2008;63(7):793-796. doi:10.1111/j.1398-9995.2008.01705.x
12 Carr S, Chan E, Lavine E, Moote W. CSACI Position statement on the testing of food-specific IgG. Allergy Asthma Clin Immunol. 2012;8(1):12. doi:10.1186/1710-1492-8-12
13 Mueller, Tsohalis. Evaluation of serum allergen-specific IgE for the diagnosis of food adverse reactions in the dog. Vet Dermatol. 1998;9(3):167-171. doi:10.1046/j.1365-3164.1998.00107.x
14 Mueller RS, Olivry T. Critically appraised topic on adverse food reactions of companion animals (4): can we diagnose adverse food reactions in dogs and cats with in vivo or in vitro tests? BMC Vet Res. 2017;13(1):275. doi:10.1186/s12917-017-1142-0
15 Jackson HA, Jackson MW, Coblentz L, Hammerberg B. Evaluation of the clinical and allergen specific serum immunoglobulin E responses to oral challenge with cornstarch, corn, soy and a soy hydrolysate diet in dogs with spontaneous food allergy. Vet Dermatol. 2003;14(4):181-187. http://www.ncbi.nlm.nih.gov/pubmed/12895222. Accessed November 19, 2018.
16 Lam ATH, Johnson LM, Heinze CR. Evaluation of clinical accuracy of serological and salivary testing for food allergens in asymptomatic dogs. In: Abstracts of the North Americal Veterinary Dermatology Forum. Orlando Fla.; 2017.
17 Garrow JS. Kinesiology and food allergy. Br Med J (Clin Res Ed). 1988;296(6636):1573-1574. http://www.ncbi.nlm.nih.gov/pubmed/3135014. Accessed November 23, 2018.
18 Schmitt WH, Leisman G. Correlation of applied kinesiology muscle testing findings with serum immunoglobulin levels for food allergies. Int J Neurosci. 1998;96(3-4):237-244. http://www.ncbi.nlm.nih.gov/pubmed/10069623. Accessed November 23, 2018.
19 Schwartz SA, Utts J, Spottiswoode SJP, et al. A Double-Blind, Randomized Study to Assess the Validity of Applied Kinesiology (AK) as a Diagnostic Tool and as a Nonlocal Proximity Effect. EXPLORE. 2014;10(2):99-108. doi:10.1016/j.explore.2013.12.002
20 Lüdtke R, Kunz B, Seeber N, Ring J. Test-Retest-Reliability and Validity of the Kinesiology Muscle Test. Complement Ther Med. 2001;9(3):141-145. doi:10.1054/ctim.2001.0455

21 Niggemann B, Gruber C. Unproven diagnostic procedures in IgE-mediated allergic diseases. Allergy. 2004;59(8):806-808. doi:10.1111/j.1398-9995.2004.00495.x
22 Ernst E. Iridology: A Systematic Review. Complement Med Res. 1999;6(1):7-9. doi:10.1159/000021201
23 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. Nutr Res. 2011;31(1):61-75. doi:10.1016/j.nutres.2011.01.001
24 National Institute for Health and Clinical Excellence. Diagnosis and Assessment of Food Allergy in Children and Young People in Primary Care and Community Settings.; 2011.
25 Kelso JM. Unproven Diagnostic Tests for Adverse Reactions to Foods. J allergy Clin Immunol Pract. 2018;6(2):362-365. doi:10.1016/j.jaip.2017.08.021
26 Coyner K, Schick A. Hair and saliva test fails to identify allergies in dogs. J Small Anim Pract. October 2018. doi:10.1111/jsap.12952
27 Udraite Vovka L, Watson A, Dodds WJ, Klinger CJ, Classen J, Mueller RS. Testing for food-specific antibodies in the saliva and blood of atopic and normal dogs (abstract). Vet Dermatol. 2017;28:552.

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Footnotes
A Food Allergen Panel, IDEXX Laboratories, Inc., Westbrook, Maine
B Allercept Serum IgE Assay, Heska Veterinary Diagnostic Laboratories, Loveland, Colo.
C Nutriscan Food Sensitivity & Intolerance Test, Hemopet, Garden Grove, Calif.
D ImmuneIQ, VetDVM LLC, Boulder, Colo.

Brennen McKenzie, MA, MSc, VMD, cVMA, discovered evidence-based veterinary medicine after attending the University of Pennsylvania School of Veterinary Medicine and working as a small animal general practice veterinarian. He has served as president of the Evidence-Based Veterinary Medicine Association and reaches out to the public through his SkeptVet blog, the Science-Based Medicine blog, and more. He is certified in medical acupuncture for veterinarians. Columnists’ opinions do not necessarily reflect those of Veterinary Practice News.

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