Non-celiac gluten sensitivity, also called gluten sensitivity or gluten intolerance, is a clinical disorder that occurs in response to consuming gluten, a protein found in wheat, rye, and barley. The ingestion of gluten causes intestinal and extra-intestinal symptoms that improve readily if gluten is removed from the diet. Celiac disease and wheat allergy must be ruled out before an individual can be diagnosed as having nonceliac gluten sensitivity.
To understand non-celiac gluten sensitivity, it is important to differentiate it from celiac disease, a more serious disease with long-term consequences. Celiac disease, also called gluten sensitive enteropathy, is a hereditary autoimmune disease in which the ingestion of gluten causes attacks that damage finger-like projections (villi) of tissue lining the small intestine. Once the small intestine has become damaged, the intestinal walls become increasingly permeable (a condition called increased gut permeability) and nutrients can no longer be absorbed properly. Individuals with celiac disease are at risk for long-term complications and require lifelong treatment.
Studies of gluten sensitivity estimate that 18 million Americans are affected by the condition, which is six times greater than the number of Americans who have celiac disease. Many more cases are self-reported, but without a medical diagnosis of a specific gluten-related disorder, the exact number of cases cannot be estimated. Anyone of any age, gender, or race/ethnicity can develop gluten sensitivity. The worldwide prevalence is estimated to be between 6% and 10%, based on results of international studies. Many more individuals in Western countries are found to avoid gluten-containing foods but this is believed due to high awareness of the gluten-free diet and not due to an actual medical diagnosis of gluten sensitivity.
Gluten-sensitive individuals cannot tolerate gluten. Consuming gluten-containing foods will bring on gastrointestinal symptoms similar to those experienced in celiac disease, but substantially less severe. Non-celiac gluten sensitivity also is not accompanied by antibodies found in tissues of the small intestine (transglutaminase autoantibodies) or the development of diabetes and other autoimmune diseases as in celiac disease. Although celiac disease is associated with increased permeability of the intestinal walls, this characteristic is not found in non-celiac gluten sensitivity. Studies of both diseases show that the two gluten-associated disorders are different clinical entities with their own type of immune response.
The latest research on gluten sensitivity disorders places all such disorders except celiac disease under the concept of non-celiac gluten sensitivity. Studies have been done on the prevalence, immune mechanisms, similarities to symptoms of irritable bowel syndrome (IBS), and associations with immunoglobulin E-based wheat allergy (an adverse immune response with similar symptoms). The consensus is that gluten sensitivity is marked by a unique immune response and an increase in an adaptive immune marker not found in celiac disease. Researchers have suggested that not only gluten proteins (glutenin, gliadin, prolamin, hordein, glutenin) are the source of non-celiac gluten sensitivity but that components of other gluten-containing cereal grains (e.g., amylase-trypsin inhibitors found in wheat) may be involved. FODMAPs, a group of compounds (Fermentable Oligosaccharides, Disaccharides [which include lactose], Monosaccharides and Polyols) that contribute to irritable bowel syndrome, have also been suggested as a possible trigger for gluten sensitivity because a FODMAP-free diet improves symptoms of non-celiac gluten sensitivity. FODMAPS are shortchain carbohydrates in certain foods that are poorly absorbed in the small intestine (e.g., wheat, rye, barley, yogurt, apples, apricots, pears, and cauliflower). A study of 100 adults in the United Kingdom also found that individuals with non-celiac gluten sensitivity had an increased prevalence for irritable bowel syndrome than those without gluten sensitivity.
Although heredity (having a first-degree relative with celiac disease) is a risk factor for celiac disease, no known risk factors have been identified for non-celiac gluten sensitivity. Anyone of any age, gender, or race/ethnicity can develop gluten sensitivity, with or without a relative with the disorder. Individuals who have exhibited other allergic reactions may be more susceptible to non-celiac gluten sensitivity but this has not been confirmed with sufficient study data.
Non-celiac gluten sensitivity is a reaction in the digestive tract to foods containing gluten. It is associated with an immune response but not like the response seen in celiac disease patients. Although it may be caused by an immune process, it is not associated with specific genes (HLA-DQ2 or HLA-DQ8) as is celiac disease. It is also not associated with the presence of the same antibodies as found in celiac disease. No specific mechanism has been found to explain the adverse effects of consuming gluten-containing foods. “Gluten-related disorders” and “gluten intolerance” both describe any disorder involving ingestion of gluten, but only celiac disease has a known genetic cause. Research is ongoing to find a cause underlying food-induced adverse reactions to gluten. Some researchers have suggested that non-celiac gluten sensitivity could be a non-IgE mediated wheat allergy. Other researchers found an immune marker that is present in non-celiac gluten sensitivity and not in celiac disease, but more must be learned about this marker and about non-celiac gluten sensitivity before it can be used in screening tests.
The symptoms of non-celiac gluten sensitivity occur only when gluten is consumed and are quite similar to those of celiac disease. The main difference is that individuals who are non-celiac gluten sensitive do not test positive for celiac disease. The symptoms resolve in both diseases when gluten is removed from the diet. When gluten is consumed, the symptoms found in celiac disease may also occur among some individuals with non-celiac gluten sensitivity, including mental symptoms such as depression, foggy thinking (called “brain fog”), behavior similar to attention-deficit/hyperactivity disorder (ADHD); and gastrointestinal symptoms similar to irritable bowel syndrome (IBS), including bloating, diarrhea, and constipation. Some individuals may also have headaches, bone or joint pain, chronic fatigue, and sometimes numbness in the legs, arms or fingers.
Diagnosis of non-celiac gluten sensitivity can be confusing to the doctor and the patient. Making a correct diagnosis of non-celiac gluten sensitivity is essential, mainly to distinguish it from celiac disease or any other gastrointestinal illness with similar intestinal symptoms. Although available tests promoted as diagnostic for gluten sensitivity may provide clues for diagnosis, specific and sensitive diagnostic tests are not yet widely available to detect non-celiac gluten sensitivity definitively. Even performing an intestinal biopsy would have normal results in someone with gluten sensitivity. Researchers are actively searching for a biological marker that would confirm a diagnosis of non-celiac gluten sensitivity when tests for celiac disease are negative. Tests on blood serum (serological tests) have shown that more than half of individuals diagnosed with non-celiac gluten sensitivity are positive for IgG antigliadin antibodies, but are negative for other antibodies specific to celiac disease. Although this does not make IgG antigliadin antibody a strong marker for non-celiac gluten sensitivity, it does assist somewhat in diagnosis.
Because no antibodies in the blood or stool are specific or sensitive enough to positively identify nonceliac gluten sensitivity, this condition is diagnosed by ruling out celiac disease and wheat sensitivity. In other words, when symptoms common to celiac disease and non-celiac gluten sensitivity are present, the tests for celiac disease are performed. If these tests turn out to be negative and the individual still feels the symptoms, the diagnosis is most likely non-celiac gluten sensitivity.
Wheat allergies or sensitivities must also be ruled out when gluten sensitivity is suspected. Diagnosis of IgE or non-IgE wheat sensitivity requires that the individual has reproducible gastrointestinal or skin symptoms after eating wheat. Physicians may order tests to detect whether IgE or non-IgE antibodies are present in blood serum. Pediatricians often find reactions similar to gluten sensitivity or wheat sensitivity in children attributed to cow's milk protein hypersensitivity, consumption of soy-based food products, or a condition called food protein-induced enteropathy. Skin tests are reported to be neither specific nor sensitive enough to differentiate these food-sensitivity disorders.
After collecting personal and family medical history, including a list of symptoms, a thorough physical examination will be performed. In addition, the doctor may ask the individual to keep a detailed food diary, recording foods consumed and noting which foods cause symptoms to develop. An elimination diet may be recommended in which certain foods are removed from the diet and added back one at a time while noting the return of symptoms. If eliminating all gluten-containing foods relieves all symptoms, the diagnosis is typically considered to be non-celiac gluten sensitivity. A food challenge also may be done in which any foods suspected to be a cause of symptoms are gradually reintroduced into the diet in increasing amounts while observing for symptoms.
Tests for wheat allergy may include a skin test in which allergen extracts for wheat proteins are pricked into the skin surface and observed for allergic reaction. Blood testing may involve screening for allergy-causing antibodies to common allergens, including wheat proteins. Identifying a wheat allergy does not mean conclusively that the disorder is not non-celiac gluten sensitivity, but the information will assist in the overall diagnosis.
Accurate testing for celiac disease involves remaining on a gluten-containing diet. Screening is done using a simple blood test that identifies the transgluta-minase IgA antibody (tTG-IgA antibody test), which will be positive in the blood serum of anyone with celiac disease. Children will also be tested for deamidated gliadin IgA and IgG antibodies (DGP IgA and IgG). Biopsy of tissue from the small intestine, however, is the most accurate way to diagnose celiac disease.
Genetic testing for celiac disease is done by identifying the human leukocyte antigen (HLA) genes HLA-DQ2 and HLA-DQ8, which are present in about 25% to 30% of the general population and in a greater percentage of celiac patients (celiac 3%, general population 1%). If the genes are present, the individual is at greater risk of having celiac disease than the general population, but it is not a definitive diagnosis of celiac disease. A positive test for these genes along with a family history of celiac disease increases risk to 40%.
Endoscopic examination (endoscopy) may be done to visualize the small intestines and take a sample of tissue for biopsy. The Celiac Disease Foundation recommends endoscopy and biopsy for anyone who has positive antibody screening or genetic screening for celiac disease. The stained biopsy sample is examined microscopically by a pathologist, and a Marsh classification is assigned (Modified March Type), indicating either symptomatic celiac disease (Marsh Type 3), or Marsh Types 1 and 2, which also suggest potential celiac disease. In addition, density of white blood cells called intra-epithelial lymphocytes in the intestinal tissue and grooves in the intestinal lining may show signs of damage characteristic of celiac disease. Although the biopsy provides the most accurate diagnosis of celiac disease, it will be negative in non-celiac gluten sensitivity.
The only treatment for non-celiac gluten sensitivity is adhering to a gluten-free diet, at least while symptoms still appear with the ingestion of gluten-containing foods. Many individuals with non-celiac gluten sensitivity are able to tolerate small amounts of gluten without developing symptoms and after one or two years, some individuals successfully reintroduce small amounts of gluten. Proper nutritional counseling is important, and individuals will need to follow a healthful, balanced dietary plan.
In contrast, the gluten-free diet for celiac disease must be followed more strictly—absolutely no gluten for the individual's lifetime to prevent more intestinal damage and the development of chronic diseases such as diabetes and other autoimmune diseases.
The individual with non-celiac gluten sensitivity may be able to follow a low-gluten rather than gluten-free diet, but this should be determined after consultation with the doctor. Food labels can be especially helpful in avoiding gluten-containing ingredients. Nevertheless, choosing foods on a gluten-free diet can sometimes be difficult. To help clarify food choices, two lists of foods are available: foods to avoid with gluten sensitivity and foods to include on a gluten-free diet.
The prognosis for non-celiac gluten sensitivity is excellent if the individual follows a gluten-free dietary plan. Some individuals may even be able to eventually include some gluten-containing foods in their diet as long as foods are introduced gradually and with a doctor's guidance.
No specific preventive measures are known to help individuals avoid developing gluten sensitivity. Careful observance for any gastrointestinal reactions to food, and noting the particular foods, may be the only way to identify early signs of gluten sensitivity.
Suspected food allergies can then be discussed with a doctor, and the diet can be modified if necessary. A gluten-free diet is not of benefit to individuals who have not been diagnosed as non-celiac gluten sensitive.
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