- Open Access
Debates in allergy medicine: food intolerance does exist
© Vandenplas. 2015
- Received: 30 July 2015
- Accepted: 25 November 2015
- Published: 14 December 2015
Health care professionals and patients mix and mingle (hyper)sensitivity, allergy and intolerance. The consequences are discrepancies which result in confusion. The following is a very personal point of view, intended to start a debate to come to consensus.
We aimed to clarify the proposed terminology for the primary health care professional from the point of view of the pediatric gastroenterologist.
Many patients present with symptoms “related to food ingestion”. We propose to use this wording if no underlying mechanism can be identified. Intolerance should be restricted to carbohydrate malabsorption causing symptoms. Allergy is restricted to IgE mediated allergy and non-IgE manifestations that can only be explained through an immune mediated mechanism, such as food induced atopic dermatitis and allergic colitis with blood in the stools. Unfortunately, primary heath care physicians have no diagnostic tools for non-IgE mediated allergy. A positive challenge test is a proof of a food-induced symptom, but does not proof that the immune system is involved. (Hyper)sensitivity suggests immune mediated mechanisms and should therefore not be used. The pathophysiologic mechanism of many food-related symptoms is unclear. The same symptom can be caused by allergy or be considered functional, such as infantile colic, gastro-esophageal reflux and constipation related to cow’s milk ingestion in infants. In fact, “functional” is used if the pathophysiologic mechanism causing the symptom cannot be explained. Since the long term outcome of “allergy” differs substantially from “functional symptom”, allergy should not be used inappropriate.
“Food related symptom” should be used in each patient in which the pathophysiologic mechanism is not clear. Intolerance means a carbohydrate malabsorption that causes symptoms. Allergy should be used when the immune system is involved.
- Atopic Dermatitis
- Celiac Disease
- Food Allergy
- Eosinophilic Esophagitis
- Lactose Intolerance
• Hypersensitivity: a reaction to an ingested food, whatever the mechanism causing the symptoms
• Food allergy: a reaction to a food that can be explained by an immune mediated mechanisms, IgE-mediated or non-IgE mediated
• Intolerance: a reaction to a food that is caused by a deficiency of a disaccharidase
• Food related symptom: any symptom that is/seems caused by a food but for which no causing mechanism can be indicated
It is important to not mix “CMA” with “functional GI CM-related symptoms” because the middle to long term outcome of CMA versus functional GI disorders differs substantially. The onset of allergic disease at a young age (as is the case with CMA) will predispose the child to a two times increased risk of developing asthma and allergic rhinitis later in life [2, 6]. Once the diagnosis of CMA is made after a positive challenge test, it is recommendation to put the child on an exclusion diet for 6 to 9 months, or up to the age of year if that is reached first . (The higher the IgE levels, the longer CMA allergy will persist.) Although up to 90 % of the CMA children are CM tolerant by the age of three years, this is only the case in 50 % at the age of one year. Functional GI symptoms tend to improve much faster. Infantile colic and crying starts to decrease by the age of three to four months . The frequency of regurgitation drops sharp from the age of six months onwards . Functional constipation, on the contrary, does not tend to disappear spontaneously over time . Thus, prognosis and long-term outcome differ for allergy or a functional GI disorder. One should not overlook that any of these manifestations can as well be caused by organic disease, different from allergy. This is the area where “CMA” versus “symptoms related to CM” becomes relevant. In function of the presenting symptoms, interpretation and therapeutic attitude may differ, influenced by the presenting symptom. A score, the Cow’s Milk related Symptom Score (CoMiSS), was recently developed to raise awareness of health care professionals for this entity .
Focussing on gluten, the situation is even more complex. The diagnostic criteria for celiac disease are well established. Other individuals may suffer from IgE mediated gluten allergy. But, there are patients claiming to develop symptoms when ingesting gluten and to feel much better on a gluten free diet. Whether this is non-IgE mediated allergy or more psychological related as may occur in aversion is debated. A casein-free and gluten-free diet is very popular in autistic children, but we showed recently in a double-blind placebo controlled trial that a short challenge during seven days was not accompanied by an increase of the behavioural symptoms . IgG4 antibodies are often measured and increased in these individuals. According to most opinion leaders the presence of these antibodies means that the immune system has been in contact with these food antigens, but not that there is an abnormal immunological reaction. The fact that patients report disappearance of symptoms is often supposed to be placebo-induced. Also for IgG4, CMA was well studied. IgG4 anti-betalactoglobulin levels failed to show a relation with CMA . Nevertheless, patients do spend hundreds of Euro to obtain “pages” of IgG4 levels to several foods and food components, to which –at least according to the interpretation of these labs- the patient is allergic or reacting.
Perception plays a major role in many adverse reactions to foods. Many Western individuals will reaction with aversion by the idea to have to eat insects or dog. Thus, once we move outside the classic adverse reactions to food that can easily be explained as occurs in diseases like IgE mediated allergy and celiac disease, cultural background does have an important role, and the “pro and con debates” start. Non-IgE mediated allergy is an accepted entity. If the patient develops objective symptoms such as blood in the stools, a non-IgE mediated allergic colitis is an accepted diagnosis. However, the same diagnosis is not (well) accepted in case the symptoms are more subjective such as nausea, itching, fatigue, feeling unwell,… Although the patch-test may play a role in these situations, its diagnostic accuracy has been insufficiently validated to be recommended . Unfortunately, data from double-blind placebo controlled challenges are very limited in these situations; this is mainly due to the fact that patients refuse these. However, a positive challenge is not a proof of involvement of the immune system.
Some patients develop symptoms related to ingestion of food that are “easy to classify” such as anaphylaxis, IgE mediated allergic symptoms, immune mediated disease such as in celiac disease. Lactose intolerance is another example. However, there are patients in who all standard diagnostic tests are within normal ranges. In order to avoid confusion, we prefer to designate these as “food ingestion related symptoms”.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Fiocchi A, Brozek J, Schünemann H. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guidelines. World Allergy Organ J. 2010;3:157–61.View ArticleGoogle Scholar
- Koletzko S, Niggemann B, Arato A, Dias JA, Heuschkel R, Husby S, et al. Diagnostic approach and management of cow’s-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines. J Pediatr Gastroenterol Nutr. 2012;55:221–9.View ArticlePubMedGoogle Scholar
- Nwaru BI, Hickstein L, Panesar SS, Roberts G, Muraro A, Sheikh A, et al. Prevalence of common food allergies in Europe: a systematic review and meta-analysis. Allergy. 2014;69:992–1007.View ArticlePubMedGoogle Scholar
- van den Hoogen SC, van de Pol AC, Meijer Y, Toet J, van Klei C, de Wit NJ. Suspected cow’s milk allergy in every day general practice: a retrospective cohort study on health care burden and guideline adherence. BMC Res Notes. 2014;7:507.View ArticlePubMedPubMed CentralGoogle Scholar
- Merras-Salmio L, Aronen ET, Kuitunen M, Pelkonen AS, Mäkelä MJ, Kolho KL. How mothers perceive infants with unspecific gastrointestinal symptoms suggestive of cow’s milk allergy? Acta Paediatr. 2014;103:524–8.View ArticlePubMedGoogle Scholar
- Vandenplas Y, Abkari A, Bellaiche M, Benninga M, Chouraqui JP, Çokura F, et al. Prevalence and Health Outcomes of Functional Gastrointestinal Symptoms in Infants From Birth to 12 Months of Age. J Pediatr Gastroenterol Nutr. 2015;61:531-7.Google Scholar
- Vandenplas Y, Benninga M, Broekaert I, Falconer J, Gottrand F, Guarino A, et al. Functional gastro-intestinal disorder algorithms focus on early recognition, parental reassurance and nutritional strategies. Acta Paediatr. 2015 [Epub ahead of print].Google Scholar
- Tabbers MM, DiLorenzo C, Berger MY, Faure C, Langendam MW, Nurko S, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition; North American Society for Pediatric Gastroenterology. Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr. 2014;58:258-74.Google Scholar
- Vandenplas Y, Dupont C, Eigenmann P, Host A, Kuitunen M, Ribes-Koninckx C, et al. A workshop report on the development of the Cow's Milk-related Symptom Score awareness tool for young children. Acta Paediatr. 2015;104:334-9Google Scholar
- Pusponegoro HD, Ismael S, Sastroasmoro S, Firmansyah A, Vandenplas Y. An observation cross-sectional study on the association between maladaptive behavior and gastrointestinal disorders in children with autism spectrum disorder. Acta Paediatr. (In press)Google Scholar
- Iacono G, Carroccio A, Cavataio F, Montalto G, Lorello D, Kazmierska I, et al. IgG anti-betalactoglobulin (betalactotest): its usefulness in the diagnosis of cow’s milk allergy. Ital J Gastroenterol. 1995;27:355–60.PubMedGoogle Scholar
- Caglayan Sozmen S, Povesi Dascola C, Gioia E, Mastrorilli C, Rizzuti L, Caffarelli C. Diagnostic accuracy of patch test in children with food allergy. Pediatr Allergy Immunol. 2015 [Epub ahead of print].Google Scholar