Gluten challenge test

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Gluten challenge test
Synonyms Gluten challenge
PurposeDiagnose gluten-related disorders

The gluten challenge test is a medical test in which gluten-containing foods are consumed and (re-)occurrence of symptoms is observed afterwards to determine whether and how much a person reacts to these foods. The test may be performed in people with suspected gluten-related disorders in very specific occasions and under medical supervision, for example in people who had started a gluten-free diet without performing duodenal biopsy. [1] [2] [3]

Contents

Gluten challenge is discouraged before the age of 5 years and during pubertal growth. [4]

Gluten challenge protocols have significant limitations because a symptomatic relapse generally precedes the onset of a serological and histological relapse, and therefore becomes unacceptable for most patients. [1] [3] [4] [5]

History

Before serological and biopsy-based diagnosis of coeliac disease was available, a gluten challenge test was a prerequisite for diagnosis of coeliac disease. [6]

Today, with serological testing (determination of coeliac disease-specific antibodies in the blood) and duodenal biopsy with histological testing being available for diagnosing coeliac disease, patients with suspected coeliac disease are strongly advised to undergo both serological and biopsy testing before undertaking a gluten-free diet. [7] People who present minor damage of the small intestine often have negative blood antibodies titers and many patients with coeliac disease are missed when a duodenal biopsy is not performed. [8] Serologic tests have a high capacity to detect coeliac disease only in patients with total villous atrophy and have very low capacity to detect cases with partial villous atrophy or minor intestinal lesions with normal villi. [2] Currently, gluten challenge is no longer required to confirm the diagnosis in patients with intestinal lesions compatible with coeliac disease and a positive response to a gluten-free diet. [2] Nevertheless, in some cases, a gluten challenge with a subsequent biopsy may be useful to support the diagnosis, for example in people with a high suspicion for coeliac disease, without a biopsy confirmation, who have negative blood antibodies and are already on a gluten-free diet. [2] Gluten challenge is discouraged before the age of 5 years and during pubertal growth. [4] European guidelines suggest that in children and adolescents with symptoms which are compatible with coeliac disease, the diagnosis can be made without the need for an intestinal biopsy if anti-tTG antibodies titres are very high (10 times the upper limit of normal). [9]

A recently proposed criterion to non-coeliac gluten sensitivity diagnosis concludes that an improvement of gastrointestinal symptoms and extra-intestinal manifestations higher than 50% with a gluten-free diet, assessed through a rating scale, may confirm the clinical diagnosis of non-coeliac gluten sensitivity. Nevertheless, this rating scale, is not yet applied worldwide. To exclude a placebo effect, a double-blind placebo-controlled gluten challenge is a useful tool, although it is expensive and complicated in routine clinical ground, and therefore, is only performed in research studies. [1] [10]

Testing

The test is also frequently used in clinical trials, for example for assessing the efficacy of novel drugs for patients with coeliac disease. [6]

Medical guidelines for performing a gluten challenge vary in terms of the recommended dose and duration of the test.

Preparation

In order to be able to assess the results of the gluten challenge, the patient needs to have been on a gluten-free diet beforehand, with symptoms having disappeared sufficiently for allowing for a subsequent re-appearance of symptoms under gluten challenge to be observed.

Procedure

It remains unclear what daily intake of gluten is adequate and how long the gluten challenge should last. [3] Some protocols recommend eating a maximum of 10 g of gluten per day for 6 weeks. Nevertheless, recent studies have shown that 2-week challenge of 3 g of gluten per day may induce histological and serological abnormalities in most adults with proven coeliac disease. [3] [5] This newly proposed protocol has shown higher tolerability and compliance, and it has been calculated that its application in secondary-care gastrointestinal practice would identify celiac disease in 7% patients referred for suspected non-coeliac gluten sensitivity, while in the remaining 93% would confirm non-coeliac gluten sensitivity, [3] but is not yet universally adopted. [5] A double-blind placebo-controlled gluten challenge can be performed by means of capsules containing gluten powder (or wheat powder) or a placebo, respectively, [11] although it is expensive and complicated in routine clinical ground, and therefore, is only performed in research studies. [1] [10] Longer challenges might be necessary in some people especially in adults. [12]

There are indications that patients with non-coeliac gluten sensitivity show a reappearance of symptoms in far shorter time than is the case for coeliac disease: in non-coeliac gluten sensitivity, symptoms usually relapse in a few hours or days of gluten challenge. [13] [14]

In cases of suspected coeliac disease, a gastrointestinal biopsy is performed at the end of the gluten challenge. [2] For an alternative diagnosis of non-coeliac gluten sensitivity, the reappearance of symptoms is assessed. However, there is no agreement so far as to how to perform a non-coeliac gluten sensitivity symptom evaluation after a gluten challenge. [11]

For people eating a gluten-free diet who are unable to perform an oral gluten challenge, an alternative to identify a possible celiac disease is an in vitro gliadin challenge of small bowel biopsies, but this test is available only at selected specialized tertiary-care centers. [5]

Variations

For determining whether certain foods such as oats can be tolerated by certain patients, a gradual challenge may be performed. [15]

Related Research Articles

<span class="mw-page-title-main">Gluten</span> Group of cereal grain proteins

Gluten is a structural protein naturally found in certain cereal grains. The term gluten usually refers to the combination of prolamin and glutelin proteins that naturally occur in many cereal grains, and which can trigger celiac disease in some people. The types of grains that contain gluten include all species of wheat, and barley, rye, and some cultivars of oat; moreover, cross hybrids of any of these cereal grains also contain gluten, e.g. triticale. Gluten makes up 75–85% of the total protein in bread wheat.

<span class="mw-page-title-main">Coeliac disease</span> Autoimmune disorder that results in a reaction to gluten

Coeliac disease or celiac disease is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barley. Classic symptoms include gastrointestinal problems such as chronic diarrhoea, abdominal distention, malabsorption, loss of appetite, and among children failure to grow normally. Non-classic symptoms are more common, especially in people older than two years. There may be mild or absent gastrointestinal symptoms, a wide number of symptoms involving any part of the body, or no obvious symptoms. Coeliac disease was first described in childhood; however, it may develop at any age. It is associated with other autoimmune diseases, such as Type 1 diabetes mellitus and Hashimoto's thyroiditis, among others.

<span class="mw-page-title-main">Irritable bowel syndrome</span> Functional gastrointestinal disorder

Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain, abdominal bloating and changes in the consistency of bowel movements. These symptoms may occur over a long time, sometimes for years. IBS can negatively affect quality of life and may result in missed school or work or reduced productivity at work. Disorders such as anxiety, major depression, and chronic fatigue syndrome are common among people with IBS.

<span class="mw-page-title-main">Gluten-free diet</span> Diet excluding proteins found in wheat, barley, and rye

A gluten-free diet (GFD) is a nutritional plan that strictly excludes gluten, which is a mixture of prolamin proteins found in wheat, as well as barley, rye, and oats. The inclusion of oats in a gluten-free diet remains controversial, and may depend on the oat cultivar and the frequent cross-contamination with other gluten-containing cereals.

<span class="mw-page-title-main">Malabsorption</span> Medical condition

Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety of anaemias.

Food intolerance is a detrimental reaction, often delayed, to a food, beverage, food additive, or compound found in foods that produces symptoms in one or more body organs and systems, but generally refers to reactions other than food allergy. Food hypersensitivity is used to refer broadly to both food intolerances and food allergies.

<span class="mw-page-title-main">Gliadin</span> Protein in wheat & other cereals

Gliadin is a class of proteins present in wheat and several other cereals within the grass genus Triticum. Gliadins, which are a component of gluten, are essential for giving bread the ability to rise properly during baking. Gliadins and glutenins are the two main components of the gluten fraction of the wheat seed. This gluten is found in products such as wheat flour. Gluten is split about evenly between the gliadins and glutenins, although there are variations found in different sources.

<span class="mw-page-title-main">Eosinophilic esophagitis</span> Allergic inflammatory condition of the esophagus

Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus that involves eosinophils, a type of white blood cell. In healthy individuals, the esophagus is typically devoid of eosinophils. In EoE, eosinophils migrate to the esophagus in large numbers. When a trigger food is eaten, the eosinophils contribute to tissue damage and inflammation. Symptoms include swallowing difficulty, food impaction, vomiting, and heartburn.

<span class="mw-page-title-main">Gluten-related disorders</span> Set of diseases caused by gluten exposure

Gluten-related disorders is the term for the diseases triggered by gluten, including celiac disease (CD), non-celiac gluten sensitivity (NCGS), gluten ataxia, dermatitis herpetiformis (DH) and wheat allergy. The umbrella category has also been referred to as gluten intolerance, though a multi-disciplinary physician-led study, based in part on the 2011 International Coeliac Disease Symposium, concluded that the use of this term should be avoided due to a lack of specificity.

Gluten-sensitive enteropathy–associated conditions are comorbidities or complications of gluten-related gastrointestinal distress. GSE has key symptoms typically restricted to the bowel and associated tissues; however, there are a wide variety of associated conditions. These include bowel disorders, eosinophilic gastroenteritis and increase with coeliac disease (CD) severity. With some early onset and a large percentage of late onset disease, other disorders appear prior to the coeliac diagnosis or allergic-like responses markedly increased in GSE. Many of these disorders persist on a strict gluten-free diet, and are thus independent of coeliac disease after triggering. For example, autoimmune thyroiditis is a common finding with GSE.

Anti-gliadin antibodies are produced in response to gliadin, a prolamin found in wheat. In bread wheat it is encoded by three different alleles, AA, BB, and DD. These alleles can produce slightly different gliadins, which can cause the body to produce different antibodies. Some of these antibodies can detect proteins in specific grass taxa such as Triticeae, while others react sporadically with certain species in those taxa, or over many taxonomically defined grass tribes.

Anti-transglutaminase antibodies (ATA) are autoantibodies against the transglutaminase protein. Detection is considered abnormal, and may indicate one of several conditions.

<span class="mw-page-title-main">Enteropathy-associated T-cell lymphoma</span> Complication of coeliac disease

Enteropathy-associated T-cell lymphoma (EATL), previously termed enteropathy-associated T-cell lymphoma, type I and at one time termed enteropathy-type T-cell lymphoma (ETTL), is a complication of coeliac disease in which a malignant T-cell lymphoma develops in areas of the small intestine affected by the disease's intense inflammation. While a relatively rare disease, it is the most common type of primary gastrointestinal T-cell lymphoma.

Oat sensitivity represents a sensitivity to the proteins found in oats, Avena sativa. Sensitivity to oats can manifest as a result of allergy to oat seed storage proteins either inhaled or ingested. A more complex condition affects individuals who have gluten-sensitive enteropathy in which there is an autoimmune response to avenin, the glutinous protein in oats similar to the gluten within wheat. Sensitivity to oat foods can also result from their frequent contamination by wheat, barley, or rye particles.

The immunochemistry of Triticeae glutens is important in several inflammatory diseases. It can be subdivided into innate responses, class II mediated presentation, class I mediated stimulation of killer cells, and antibody recognition. The responses to gluten proteins and polypeptide regions differs according to the type of gluten sensitivity. The response is also dependent on the genetic makeup of the human leukocyte antigen genes. In gluten sensitive enteropathy, there are four types of recognition, innate immunity, HLA-DQ, and antibody recognition of gliadin and transglutaminase. With idiopathic gluten sensitivity only antibody recognition to gliadin has been resolved. In wheat allergy, the response pathways are mediated through IgE against other wheat proteins and other forms of gliadin.

<span class="mw-page-title-main">Dermatitis herpetiformis</span> Chronic autoimmune disorder leading to blistering skin

Dermatitis herpetiformis (DH) is a chronic autoimmune blistering skin condition, characterised by intensely itchy blisters filled with a watery fluid. DH is a cutaneous manifestation of coeliac disease, although the exact causal mechanism is not known. DH is neither related to nor caused by herpes virus; the name means that it is a skin inflammation having an appearance similar to herpes.

FODMAPs or fermentable oligosaccharides, disaccharides, monosaccharides, and polyols are short-chain carbohydrates that are poorly absorbed in the small intestine and ferment in the colon. They include short-chain oligosaccharide polymers of fructose (fructans) and galactooligosaccharides, disaccharides (lactose), monosaccharides (fructose), and sugar alcohols (polyols), such as sorbitol, mannitol, xylitol, and maltitol. Most FODMAPs are naturally present in food and the human diet, but the polyols may be added artificially in commercially prepared foods and beverages.

Non-celiac gluten sensitivity (NCGS) or gluten sensitivity is a controversial disorder which can cause both gastrointestinal and other problems.

Duodenal lymphocytosis, sometimes called lymphocytic duodenitis, lymphocytic duodenosis, or duodenal intraepithelial lymphocytosis, is a condition where an increased number of intra-epithelial lymphocytes is seen in biopsies of the duodenal mucosa when these are examined microscopically. This form of lymphocytosis is often a feature of coeliac disease but may be found in other disorders.

<span class="mw-page-title-main">Carlo Catassi</span> Italian gastroenterologist, epidemiologist, and researcher

Carlo Catassi is an Italian gastroenterologist, epidemiologist, and researcher. He is known for international studies on the epidemiology of celiac disease. Currently, he is Head of the Department of Pediatrics at the Università Politecnica delle Marche, Ancona, Italy, and Visiting Scientist at Massachusetts General Hospital in Boston, Massachusetts, United States. From 2013 to 2016, he served as President of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP). His research had included contributions to understanding the clinical spectrum of celiac disease and other gluten-related disorders.

References

  1. 1 2 3 4 Volta U, Caio G, De Giorgio R, Henriksen C, Skodje G, Lundin KE (Jun 2015). "Non-celiac gluten sensitivity: a work-in-progress entity in the spectrum of wheat-related disorders". Best Pract Res Clin Gastroenterol. 29 (3): 477–91. doi:10.1016/j.bpg.2015.04.006. PMID   26060112.
  2. 1 2 3 4 5 Rostom A, Murray JA, Kagnoff MF (Dec 2006). "American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease". Gastroenterology (Review). 131 (6): 1981–2002. doi: 10.1053/j.gastro.2006.10.004 . PMID   17087937.
  3. 1 2 3 4 5 Elli L, Branchi F, Tomba C, Villalta D, Norsa L, Ferretti F, Roncoroni L, Bardella MT (Jun 2015). "Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity". World J Gastroenterol (Review). 21 (23): 7110–9. doi: 10.3748/wjg.v21.i23.7110 . PMC   4476872 . PMID   26109797.
  4. 1 2 3 Ontiveros N, Hardy MY, Cabrera-Chavez F (2015). "Assessing of Celiac Disease and Nonceliac Gluten Sensitivity". Gastroenterology Research and Practice (Review). 2015: 1–13. doi: 10.1155/2015/723954 . PMC   4429206 . PMID   26064097.
  5. 1 2 3 4 Aziz I, Hadjivassiliou M, Sanders DS (Sep 2015). "The spectrum of noncoeliac gluten sensitivity". Nat Rev Gastroenterol Hepatol (Review). 12 (9): 516–26. doi:10.1038/nrgastro.2015.107. PMID   26122473. S2CID   2867448.
  6. 1 2 Denise Faustman (13 March 2014). The Value of BCG and TNF in Autoimmunity. Elsevier Science. p. 130. ISBN   978-0-12-800461-6.
  7. ↑ Green PH, Lebwohl B, Greywoode R (May 2015). "Celiac disease". J Allergy Clin Immunol (Review). 135 (5): 1099–106. doi:10.1016/j.jaci.2015.01.044. PMID   25956012. S2CID   21552589.
  8. ↑ van der Windt DA, Jellema P, Mulder CJ, Kneepkens CM, van der Horst HE (2010). "Diagnostic testing for celiac disease among patients with abdominal symptoms: a systematic review". JAMA . 303 (17): 1738–46. doi:10.1001/jama.2010.549. PMID   20442390. Most studies used similar histological criteria for diagnosing celiac disease (Marsh grade ≥III), but the level of damage may vary across populations. Only 4 studies presented the proportion of patients in whom only partial villous atrophy was found (Marsh grade of IIIA), which ranged from 4% to 100%. The presence of positive serum antibodies has been shown to correlate with the degree of villous atrophy, and patients with celiac disease who have less severe histological damage may have seronegative findings. This could be important, especially in primary care, in which levels of mucosal damage may be lower, and consequently, more patients with celiac disease may be missed.
  9. ↑ Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, Shamir R, Troncone R, Giersiepen K, Branski D, Catassi C, Lelgeman M, Mäki M, Ribes-Koninckx C, Ventura A, Zimmer KP, ESPGHAN Working Group on Coeliac Disease Diagnosis, ESPGHAN Gastroenterology Committee, European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (Jan 2012). "European Society for Pediatric Gastroenterology, Hepatology, and Nutrition Guidelines for the Diagnosis of Coeliac Disease". Journal of Pediatric Gastroenterology and Nutrition (Practice Guideline). 54 (1): 136–160. doi: 10.1097/MPG.0b013e31821a23d0 . PMID   22197856. S2CID   15029283.
  10. 1 2 Vriezinga SL, Schweizer JJ, Koning F, Mearin ML (Sep 2015). "Coeliac disease and gluten-related disorders in childhood". Nature Reviews. Gastroenterology & Hepatology (Review). 12 (9): 527–36. doi:10.1038/nrgastro.2015.98. PMID   26100369. S2CID   2023530.
  11. 1 2 Lundin KEA, Alaedini A, Non-celiac Gluten Sensitivity. In: Benjamin Lebwohl; Peter H. R. Green (1 November 2012). Celiac Disease, An Issue of Gastrointestinal Endoscopy Clinics. Elsevier Health Sciences. ISBN   978-1-4557-4735-1.
  12. ↑ Maglione, Margaret A.; Okunogbe, Adeyemi; Ewing, Brett; Grant, Sean; Newberry, Sydne J.; Motala, Aneesa; Shanman, Roberta; Mejia, Nelly; Arifkhanova, Aziza (January 2016). "Table 16, Length of gluten challenge". www.ncbi.nlm.nih.gov. Retrieved 2024-02-19.
  13. ↑ Volta, Umberto; Caio, Giacomo; Tovoli, Francesco; De Giorgio, Roberto (2013). "Non-celiac gluten sensitivity: an emerging syndrome with many unsettled issues". Italian Journal of Medicine. 8 (4): 225. doi: 10.4081/itjm.2013.461 . ISSN   1877-9352.
  14. ↑ Caio, Giacomo; Volta, Umberto; Tovoli, Francesco; De Giorgio, Roberto (2014). "Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity". BMC Gastroenterology. 14 (1): 26. doi: 10.1186/1471-230X-14-26 . ISSN   1471-230X. PMC   3926852 . PMID   24524388.
  15. ↑ H. A. Harfi; F. B. Stapleton; William Oh; H. Nazer; R. J. Whitley (10 January 2012). Textbook of Clinical Pediatrics. Springer Science & Business Media. p. 1899. ISBN   978-3-642-02202-9.
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