Assessment of food allergies and sensitivities

Total IgA is often routinely requested to assess for IgA deficiency, since the presence of IgA deficiency renders IgA-tTG insensitive.[77]Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2005 Jan;40(1):1-19. https://journals.lww.com/jpgn/Fulltext/2005/01000/Guideline_for_the_Diagnosis_and_Treatment_of.1.aspx http://www.ncbi.nlm.nih.gov/pubmed/15625418?tool=bestpractice.com ​ IgA deficiency is more common in people with coeliac disease than in the general population.[78]Kumar V, Jarzabek-Chorzelska M, Sulej J, et al. Celiac disease and immunoglobulin a deficiency: how effective are the serological methods of diagnosis? Clin Diagn Lab Immunol. 2002 Nov;9(6):1295-300. https://journals.asm.org/doi/10.1128/cdli.9.6.1295-1300.2002 http://www.ncbi.nlm.nih.gov/pubmed/12414763?tool=bestpractice.com All diagnostic serological testing should be done with patients on a gluten-containing diet.[58]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com

Immunoglobulin A tissue transglutaminase (IgA-tTG) test is the preferred single test for detection of coeliac disease, including in individuals less than 2 years who are not IgA deficient.[58]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com ​ The test should be ordered in any case of suspected coeliac disease. Higher titres have increased positive predictive value. All diagnostic serological testing should be done with patients on a gluten-containing diet.[58]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com

Small bowel histology is the most specific and sensitive test. If the suspicion of coeliac disease is high, small bowel biopsy should be pursued even if serology tests are negative.[58]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com

EMA is an alternative to IgA-tTG, with greater specificity but lower sensitivity.[81]Sheppard AL, Elwenspoek MMC, Scott LJ, et al. Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease. Aliment Pharmacol Ther. 2022 Mar;55(5):514-27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305515 http://www.ncbi.nlm.nih.gov/pubmed/35043426?tool=bestpractice.com ​ A combination of high-level IgA-tTG (>10 times upper limit of normal) with a positive EMA in a second blood sample can be used to diagnose coeliac disease in children. In symptomatic adults unwilling or unable to undergo upper gastrointestinal endoscopy, the same criteria may be considered as a diagnosis of likely coeliac disease.[58]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com ​ All diagnostic serological testing should be done with patients on a gluten-containing diet.[58]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com

IgA-tTG and EMA-IgA may be less sensitive in children aged <2 years, therefore guidelines recommend that testing for coeliac disease in children younger than 2 years include both IgA-tTG and DGP-IgG. Testing for coeliac disease in children with IgA deficiency should be performed using IgG-based antibodies (DGP-IgG or IgG-tTG).[58]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com ​ All diagnostic serological testing should be done with patients on a gluten-containing diet.[58]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com

About 95% of coeliac patients are positive for HLA-DQ2.[36]Sciurti M, Fornaroli F, Gaiani F, et al. Genetic susceptibilty and celiac disease: what role do HLA haplotypes play? Acta Biomed. 2018 Dec 17;89(9-s):17-21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502200 http://www.ncbi.nlm.nih.gov/pubmed/30561391?tool=bestpractice.com

Milk and milk products are excluded from diet for 2 weeks and then re-introduced while patient keeps symptom diary.

In general, the greater the wheal diameter, the more likely the individual is to have an immediate reaction to the food following ingestion.[65]Peters RL, Gurrin LC, Allen KJ. The predictive value of skin prick testing for challenge-proven food allergy: a systematic review. Pediatr Allergy Immunol. 2012 Jun;23(4):347-52. http://www.ncbi.nlm.nih.gov/pubmed/22136629?tool=bestpractice.com

In general, the greater the wheal diameter, the more likely the individual is to have an immediate reaction to the food following ingestion.[65]Peters RL, Gurrin LC, Allen KJ. The predictive value of skin prick testing for challenge-proven food allergy: a systematic review. Pediatr Allergy Immunol. 2012 Jun;23(4):347-52. http://www.ncbi.nlm.nih.gov/pubmed/22136629?tool=bestpractice.com

Only to be performed when the patient does not respond to adequate treatment for gastroesophageal reflux disease.

May be falsely negative in patients with the disease.

The association between MSG and sensitivity reactions has not been demonstrated in clinical trials.[7]Heyman MB; Committee on Nutrition. Lactose intolerance in infants, children, and adolescents. Pediatrics. 2006 Sep;118(3):1279-86. https://pediatrics.aappublications.org/content/118/3/1279.full http://www.ncbi.nlm.nih.gov/pubmed/16951027?tool=bestpractice.com [40]Stevenson DD. Monosodium glutamate and asthma. J Nutr. 2000 Apr;130(4S Suppl):1067S-73S. https://academic.oup.com/jn/article/130/4/1067S/4686674 http://www.ncbi.nlm.nih.gov/pubmed/10736384?tool=bestpractice.com  The challenge may need to be repeated several times to demonstrate a true reaction.

Studies involving tyramine challenges in patients with food-induced migraines have failed to find an association between tyramine ingestion and the development of migraines.[8]Jansen SC, van Dusseldorp M, Bottema KC, et al. Intolerance to dietary biogenic amines: a review. Ann Allergy Asthma Immunol. 2003 Sep;91(3):233-40. http://www.ncbi.nlm.nih.gov/pubmed/14533654?tool=bestpractice.com  The challenge may need to be repeated several times to demonstrate a true reaction.

Should be performed by an allergist experienced with conducting oral food challenges and treating anaphylaxis.[54]McGill SK, Hashash JG, Platts-Mills TA. AGA clinical practice update on alpha-gal syndrome for the GI clinician: commentary. Clin Gastroenterol Hepatol. 2023 Apr;21(4):891-6. https://www.cghjournal.org/article/S1542-3565(23)00040-X/fulltext http://www.ncbi.nlm.nih.gov/pubmed/36958889?tool=bestpractice.com ​ May be considered if other testing is inconclusive.