Tuesday 10 th April 2018 Dr Rukhsana Hussain. Disclaimers apply:

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1 Tuesday 10 th April 2018 Dr Rukhsana Hussain

2 What is Non-Coeliac Gluten Sensitivity (NCGS)? Symptoms Pathophysiology Diagnosis Treatment Summary

3 NCGS is a condition in which consumption of gluten leads to symptoms similar to those of Coeliac disease. NCGS has been increasingly recognized over the past decade as a medical condition. The prevalence of NCGS has been variably reported, with certain studies reporting it as high as 13%. 3 Indirect evidence suggests that NCGS is more common than Coeliac Disease. 2 It is non-allergic and non-autoimmune in nature. It is termed "sensitivity" because symptoms are relieved by gluten withdrawal and reappear with reintroduction of gluten to the diet. Gluten in the diet triggers a constellation of gastrointestinal and extra-intestinal symptoms. 4

4 Typical GI symptoms of NCGS include postprandial abdominal pain, bloating, diarrhoea, and/or constipation. Extra-intestinal symptoms can be diverse and include peripheral neuropathy, eczema, joint and muscle aches, anxiety, and headaches. A prominent feature is the feeling of a "foggy brain," which manifests as slowed thinking and memory issues. These extraintestinal features are in major contrast with irritable bowel syndrome (IBS) symptoms, which are primarily GI symptoms.

5 Unlike in Coeliac disease, other systemic features are absent, including iron deficiency anemia, weight loss, and dermatitis herpetiformis rash. Because NCGS does not cause malabsorption, no nutrient deficiencies (eg, folic acid, fat-soluble vitamins) are noted. Whereas in Coeliac disease, symptoms may take weeks to manifest and subside, the associated symptoms in NCGS generally increase and diminish within hours to days of gluten exposure. Many patients often notice the association of gluten-containing foods with their symptoms. 3

6 Frequency Intestinal Extraintestinal VERY COMMON Bloating Lack of wellbeing Abdominal pain Tiredness COMMON Diarrhoea Headache Epigastric pain Anxiety Nausea Foggy mind Aerophagia Numbness GORD Joint/muscle pain Aphthous stomatitis Skin rash/dermatitis Alternating bowel habits Constipation

7 UNDETERMINED Haematochezia Weight loss Anal fissure Anaemia Loss of balance Depression Rhinitis /asthma Weight gain Interstitial cystitis Sensory symptoms Menstrual disturbance Disturbed sleep Mood swings Autism Schizophrenia

8 The pathophysiology of NCGS is still under investigation. The main antigen present in gluten is a protein called "gliadin." When gluten is partially digested, gliadin binds to gut wall receptors, leading to increased intestinal permeability. This allows gluten to be mistakenly recognized as a pathogen by the immune system. In Coeliac disease, the adaptive immune response leads to gluten molecules being cross-linked by tissue transglutaminase. This then binds to human leukocyte antigen (HLA) DQ2 or DQ8 on antigen-presenting cells. This interacts with CD+ T cells in the lamina propria and activates a proinflammatory cascade, which leads to the systemic response to gluten and secretory diarrhoea due to increased gut permeability. 3,4

9 In NCGS, unlike in Coeliac disease, the innate immune response is thought to play a larger role, with local cytokine release leading to recruitment of intraepithelial lymphocytes. The reaction is expressed by decreased gut permeability and an increased epithelial barrier, causing osmotic diarrhoea. Although a systemic effect is observed, it is much less robust compared with the adaptive immune system cascade.

Diagnosis is based on clinical symptoms after Coeliac disease and other potential causes have been ruled out and with resolution of symptoms when a gluten/wheat-free diet is adhered to for at least 3

10 Diagnosis is based on clinical symptoms after Coeliac disease and other potential causes have been ruled out and with resolution of symptoms when a gluten/wheat-free diet is adhered to for at least 3 weeks. 3 In 2015, a group of experts met in Salerno, Italy, to describe a standard way of testing for NCGS. Their consensus statement describes a double-blind, placebo-controlled gluten challenge. (due to the lack of validated biomarkers). The first step is to rule out Coeliac disease while a patient is consuming a glutenrich diet. The patient is given a questionnaire to assess their baseline symptoms while consuming gluten.

11 The patient is then placed on a 6-week gluten-free diet, and the questionnaire is repeated. If symptoms improvement is less than 30%, NCGS is ruled out. If a larger improvement is noted, the patient is then moved to phase 2, where they are introduced to either a placebo or gluten-containing pill. The gluten dose is standardized to 8 g, which is equivalent to about two pieces of bread. This is given over the course of a week, followed by a 1-week washout period with a gluten-free diet. The other pill is then given for another week. Symptoms are reassessed at each step. The goal is to determine whether gluten is associated with at least a 30% change in symptoms. 4 In clinical practice, where standardized gluten and placebo pills may be hard to come by, this can be done with gluten-containing or glutenfree bread.

12 In the age of food fads and needless gluten avoidance, clinicians still need to recognize NCGS. A high degree of suspicion should be present in patients who are believed to have IBS but who demonstrate extraintestinal symptoms, as well as patients who have features of Coeliac disease but negative serologic testing results.

13 Treatment is by adhering to a gluten-free diet but it is unknown if long-term strict avoidance of all gluten related products is necessary. 2 It has been suggested that NCGS may be a transient condition, therefore experts recommend that the gluten-free diet should be followed for a given period eg, months before testing gluten tolerance again. 3

14 Non-Coeliac Gluten Sensitivity is a recognized medical condition that is assumed to be more prevalent than Coeliac disease. Symptoms in NCGS occur with a much short latency period after gluten ingestion compared to in Coeliac disease. Clinicians should maintain a high degree of suspicion for NCGS in patients with IBS symptoms combined with extraintestinal features as well as in those with symptoms of Coeliac disease but negative serology results. Diagnosis is via a trial of a gluten free diet which results in resolution of symptoms. The condition is still poorly understood and it is not clear whether long term strict gluten avoidance (as in Coeliac disease) is necessary.

15 1.Alexander Potashinsky, John W. Birk. A 36-Year-Old Woman With Cramping and Diarrhea - Medscape - Mar 20, Catassi C, Elli L, Bonaz B, et al, Diagnosis of non-celiac gluten sensitivity (NCGS): the Salerno experts' criteria. Nutrients. 2015;7: Leonard MM, Sapone A, Catassi C, Fasano A. Celiac disease and nonceliac gluten sensitivity: a review. JAMA. 2017;318: Igbinedion SO, Ansari J, Vasikaran A, et al. Non-celiac gluten sensitivity: all wheat attack is not celiac. World J Gastroenterol. 2017;23:

The ImmuneCare Guide to. Gluten Sensitivity

The ImmuneCare Guide to. Gluten Sensitivity The ImmuneCare Guide to Gluten Sensitivity Gluten Sensitivity Introduction Gluten sensitivity, also called non-coeliac gluten sensitivity (NCGS), is a condition related to gluten ingestion that can cause