Non-Celiac Gluten Sensitivity: How to Diagnose and Differentiate it from Celiac Disease
- Non-Celiac Gluten Sensitivity can present with intestinal and extra-intestinal symptoms
- There are no biomarkers for diagnosis
- Autoantibodies (TTG, EMA, DGP) are absent
- There is no villous atrophy
- Diagnosis requires excluding celiac disease by serological tests
- A gluten-free diet should not be started before ruling out celiac disease
- The gluten-free diet is complicated and expensive
- Patients should be referred to a dietitian with expertise in the gluten-free diet.
The spectrum of gluten-related disorders includes celiac disease, dermatitis herpetiformis, gluten ataxia, wheat allergy and non-celiac gluten sensitivity. The term non-celiac gluten sensitivity (NCGS) is used to describe the clinical state of individuals who develop symptoms when they consume gluten-containing foods and feel better on a gluten-free (GF) diet but do NOT have celiac disease.
Celiac disease is a multi-system autoimmune disorder that is triggered by ingestion of gluten (a protein in wheat, rye and barley) in genetically susceptible individuals. A common disorder, affecting about 1% of the population, patients can present with a variety of intestinal and non-intestinal symptoms. Autoantibodies such as tissue transglutaminase antibody (TTG), endomysial antibody (EMA) and deamidated gliadin peptide (DGP) are produced in the body and form the basis of serological tests used for screening. The diagnosis of celiac disease is confirmed by a small intestinal biopsy and treatment consists of a strict GF diet for life. Adherence to the GF diet results in the resolution of symptoms and intestinal inflammation, with the autoantibodies becoming negative over time. Celiac disease is a serious disorder with patients being at risk for nutritional deficiencies and development of other autoimmune disorders and rarely malignancies such as small intestinal lymphoma.
Non-Celiac Gluten Sensitivity
Non-celiac gluten sensitivity (NCGS) is frequently a self-diagnosis; hence the true prevalence is difficult to establish. There are currently no biomarkers for this disorder. In a survey of 1,002 people from the United Kingdom, 13% reported having gluten sensitivity, with 3.7% claiming to be on a GF diet. In a large study from Italy of 12,255 individuals, NCGS was found to be only slightly more common than celiac disease. Data from the National Health and Nutrition Examination Survey in the United States found that 0.55 to 0.63% of people followed a GF diet in the absence of celiac disease. This prevalence is similar to that of combined diagnosed and undiagnosed cases of celiac disease.
The symptoms of NCGS are highly variable. These include bloating, abdominal pain and diarrhea; symptoms mimicking irritable bowel syndrome. Other intestinal manifestations include nausea, acid reflux, mouth ulcers and constipation. Individuals may have non-intestinal symptoms such as feeling generally unwell, fatigue, headaches, foggy mind, numbness, joint pains, or skin rash. An individual may have one or more symptoms.
The clinical symptoms of NCGS and celiac disease overlap making it difficult to distinguish the two disorders on the basis of symptoms alone. In one study of adults, patients with celiac disease were more likely to have a positive family history, personal history of other autoimmune disorders and nutrient deficiencies compared to those with NCGS. It is important to note that in NCGS, the TTG, EMA and DGP antibodies are absent and there is no villous atrophy (damage to small intestine) on biopsy. Therefore, the diagnosis of NCGS can only be established by excluding celiac disease.
Non-celiac gluten sensitivity was first reported in the 1970’s. However, over the last decade an increasing number of people are following a GF diet for perceived health benefits. This has renewed both interest and concern whether these individuals have a true gluten-related disorder. There is a real possibility that some of those who go on a GF diet on their own could, in fact, have celiac disease. These individuals may not get diagnosed or receive adequate nutritional counseling from a dietitian and appropriate follow-up from their physicians. As a result, this may put them at risk for long-term complications of celiac disease. Since the small intestinal damage resolves and the TTG (and other antibodies) normalize after starting a GF diet, the true diagnosis of celiac disease becomes difficult to establish.
Most clinical trials investigating the phenomenon of gluten sensitivity gave study subjects gluten-containing grains such as wheat, rye and barley in their diet rather than pure gluten. Therefore, it has been postulated that individuals with NCGS may be reacting to other components in wheat rather than gluten. FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) are types of carbohydrates that some people cannot digest very well. The bacteria in the colon ferment these carbohydrates resulting in gas, bloating, abdominal pain and diarrhea. Wheat, barley and rye are high in FODMAP, which may be a contributing factor to these symptoms. Furthermore, wheat contains other proteins called amylase/trypsin inhibitors (ATI) that in laboratory studies have shown to cause intestinal inflammation.
The GF diet can be very challenging to follow, as it is complicated and expensive. In addition, there are concerns about the nutritional adequacy of GF products as they can be high in fat and sugar, and often low in fiber, iron and B vitamins. For these reasons, patients requiring a GF diet should be referred to a registered dietitian with expertise in this diet.
Currently, a lot remains unknown about NCGS. What is its exact pathophysiology? Is the sensitivity/intolerance to gluten a dose-related phenomenon? Is it a transient or a permanent problem? Do some individuals outgrow this condition over time? Are there specific diagnostic tests that can confirm the diagnosis? Clearly, more research is needed to clarify these issues.
Take Home Message
What is most important for the public and health care professionals to know is that the diagnosis of non-celiac gluten sensitivity should not be made without excluding celiac disease. A gluten-free diet should NOT be initiated without a proper clinical assessment that includes serological testing with IgA-tissue transglutaminase antibody while the individual is on a regular gluten-containing diet.
Primary author: Dr. Mohsin Rashid
- Lebwohl B, Ludvigsson JF, Green PHR. Celiac disease and non-celiac gluten sensitivity. BMJ 2015;351;h4347
- Volta U, Bardella MT, Calabro A et al. An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity. BMC Medicine. 2014;12:85.
- Kabbani TA, Vanga RR, Leffler DA et al. Celiac disease or non-celiac gluten sensitivity? An approach to clinical differential diagnosis. Am J Gastroenterol. 2014;109;(5);741-6