Understanding celiac disease, wheat allergy, non-celiac gluten sensitivity, and other gluten-related disorders
It used to be quite rare to meet somebody who avoids gluten – the protein found in wheat, rye, spelt, semolina, and triticale. Nowadays, however, gluten free dieting is all the rage. In 2016, 8% of North Americans followed a wheat- or gluten-free diet; as of 2020 it jumped to 30%. The market for GF (gluten free) food more than doubled in the two years between 2013 and 2015, reaching a global market of $5.6 billion as of 2020.1,2
Some folks avoid gluten to save their lives. Others feel better and healthier on a GF diet. And others are just being fashionable.
While eating GF is indeed en vogue in some circles, the trend is, in fact, informed by the epidemiology of diseases exacerbated by gluten. Conditions on the rise that are directly aggravated by gluten include celiac disease (CD), gluten ataxia, dermatitis herpetiformis, wheat allergy, and non-celiac gluten sensitivity (NCGS). We are also seeing an increase in the rates of other conditions that are also often exacerbated by gluten, such as intestinal permeability (aka “leaky gut”), irritable bowel syndrome (IBS), and Hashimoto’s thyroiditis and other autoimmune diseases. People afflicted with one or more of these ailments are not just being trendy when they eat the burger but not the bun.
Let’s take a closer look at what differentiates these conditions.
Celiac disease (CD) is a genetically- and environmentally-mediated autoimmune condition in which gluten causes significant damage to the small intestine. The small intestine is the place where the body absorbs nutrients from food. Damage to the small intestine thus reduces the body’s ability to take in vitamins, in turn causing a host of health problems.
The only known treatment for CD is to follow to a strict, life-long, gluten-free diet. Folks with CD must also restrict their exposure to gluten in its non-food forms: Folks with CD need to use cosmetics free of wheat germ and other gluten products, choose medications and supplements that do not use gluten as a binder or filler, and even avoid spending time in bakeries, pizzerias, and other settings in which gluten is in the air and can be inhaled. If a person with CD goes undiagnosed and continues to be exposed to gluten, their risk of death increases by 400%.3 The consumption of gluten in those with CD also significantly increases their risk of developing gastrointestinal cancers.4
Although gluten causes small intestine damage in those with CD, it’s worth mentioning that many celiacs (people with CD) have no digestive ailments. The old medical stereotype of the celiac patient being underweight with a bellyache is misleading: Individuals with CD come in all shapes and sizes. Some have digestive trouble and others do not, suggesting that CD is not merely a digestive ailment, but a systemic disease. That’s because gluten consumption triggers the production of tissue transglutaminase antibodies, which can attack and injure various sites throughout the body.5
A genetic test (for HLA-DQ2/DQ8) determines if somebody is at risk of developing CD. (You can’t get the disease without the gene.) Folks with the gene won’t necessarily go on to develop CD, though they might if they’re exposed to certain environmental triggers like viral infections and microbial dysbiosis.4
CD can occur at any age, which is why I typically screen HLA-positive patients (and their blood relatives) for the disease every three years. While an endoscopy with biopsy is considered the gold standard for diagnosis, highly sensitive and specific blood tests can also be used.4 There is no single blood test for CD – a panel of tests must be ordered.
Another type of autoimmune disease related to wheat consumption is gluten ataxia. In this condition, the consumption of gluten triggers the body to create antibodies that attack and destroy brain cells. Specifically, the cells under attack are the Purkinje cells, which affect coordination and movement. The symptoms of gluten ataxia include difficulty in walking, trouble with speech, nystagmus (involuntary movement of the eyes), uncontrollable jerking movements, and other issues with coordination. 6,7
Another chronic, autoimmune disease triggered by gluten consumption in susceptible individuals is dermatitis herpetiformis. This skin disease is often associated with CD, as transglutaminase antibodies are implicated in both conditions. In the case of dermatitis herpetiformis, the body produces epidermal transglutaminase antibodies upon exposure to gluten. These antibodies then attack the skin, causing itchy blisters, rashes, and other skin lesions on the knees, elbows, buttocks, scalp, and/or other body parts.8,7 As with CD and gluten ataxia, people with dermatitis herpetiformis must follow a strict GF lifestyle for the long haul.
Another way that folks can react to gluten-containing grains is via the “good old fashioned” allergic response. Like other food allergies, wheat allergy can affect both children and adults, and typically causes symptoms within minutes to hours after an affected individual eats, breathes, or touches wheat. These symptoms can include swelling or itching of the mouth or throat, hives, nasal congestion, headache, breathing challenges, nausea, vomiting, diarrhea, and/or anaphylaxis (a life-threatening allergic reaction.)9
A subset of folks with wheat allergy is also afflicted with wheat-dependent exercise-induced anaphylaxis (WDEIA). WDEIA is a serious (but thankfully rare) food allergy in which anaphylactic reactions occur after a person with the disease eats wheat and then exercises.10
While most food allergies are mediated by a type of antibody response known as IgE (or immunoglobulin E), the immune response in wheat allergy can be both IgE and non-IgE mediated.11 Many people with wheat allergy are just allergic to wheat, but others have cross-reactivity with other gluten-containing grains and must avoid them entirely.11
While people with active reactions to wheat need to avoid eating, breathing, or touching the grain for a while, the good news is that it is possible to “outgrow” a wheat allergy. It has been observed that almost half of young children with the disease become tolerant to wheat by the time they’re eight years old.12 The findings of a 2019 study further confirm that wheat allergy can go away on its own – even in adults. In this study, ten adults (mean age 40 years) with IgE-mediated wheat allergy followed a strict wheat-free diet for over four years. By the end of the five-year study, nine out of the ten patients were wheat-tolerant, with an observed reduction in their blood IgE levels.13
The data suggest that before an individual can outgrow wheat allergy, however, they have to first follow a strict gluten-free diet for several years.
Non-celiac gluten sensitivity (gluten intolerance)
Yet another condition related to gluten exposure is non-celiac gluten sensitivity (NCGS, also known as gluten sensitivity or gluten intolerance). NCGS is more common than CD: it’s estimated that 18 million people in the US report having gluten sensitivity – six times the number of people who have celiac disease.14
Symptom-wise, NCGS can look a lot like CD and other gluten-related diseases, irritable bowel syndrome (IBS), and Crohn’s disease.15 The key difference, however, is that folks with NCGS will test negative for all of these other conditions.16
Thankfully, the intestinal damage seen in NCGS is much milder than that associated with CD. Like CD, however, NCGS can cause symptoms outside of the digestive system. Unlike wheat allergy, which typically triggers allergic symptoms within hours of eating wheat, NCGS can be more slow and subtle. People with NCGS tend to have vague symptoms like headache, brain fog, joint pain, and altered skin sensation, and these reactions to gluten might not appear until several days after gluten is eaten. (This delayed response is typical for innate immune conditions like NCGS.)18 This delayed reaction can also make it very tricky for a person (or their healthcare provider) to connect the dots and realize that gluten may be the culprit.
NCGS may also be implicated in other conditions like irritable bowel syndrome (IBS), chronic fatigue, and autoimmunity.17 New research has also illuminated an overlap over non-IgE wheat allergy, NCGS, and IBS symptoms.19
Unlike CD, wheat allergy, and many other diseases, however, NCGS lacks a diagnostic blood test. This creates significant limitations in our understanding of the disease and even our ability to study it.20 Nevertheless, people can be diagnosed with the condition if they have symptoms (whether digestive or non-digestive symptoms) related to eating gluten that improve when gluten is removed from the diet, and if CD and wheat allergy have been ruled out via testing.5
Another challenge is that many medical professionals do not know about NCGS.
For these reasons, under-informed healthcare providers may erroneously dismiss NCGS patients as hypochondriacs. One study explains: “Although there is clearly a fad component to the popularity of the GFD [gluten free diet], there is also undisputable and increasing evidence for NCGS.”17
Which condition do I have? Does it really matter?
It is difficult – if not downright impossible – for a provider or patient to diagnose a gluten-related disease without the proper diagnostic tests. Even in the case of non-celiac gluten sensitivity (NCGS), celiac disease and wheat allergy must first be ruled out via testing.5
It is important to know what disease a person does (or does not) have, as a diagnosis will significantly determine the treatment. For example, people with wheat allergy may just need to eat GF for a few years, whereas those with celiac disease will not only need to follow a strict gluten free diet for life, but also avoid cosmetics, medications, and other products that contain even traces of gluten. Folks with celiac disease will also require more frequent health checks (eg: to assess their nutritional status and bone density) and special screening tests (like cancer screens) than people with non-celiac gluten sensitivity – extra care that their health insurance is obligated to cover.5
It’s also important to note that testing for these conditions is only accurate if a person is still regularly eating gluten: It is important to get tested for celiac disease before going GF. As tempting as it may be to just go gluten free and skip the testing, I highly encourage all of my patients to first identify what it is that they’re treating.
Gluten free diets are more than a fad – for many people, they are a life-saving, medically necessary treatment.
- Statista. U.S. Gluten-free Foods Market – Statistics & Facts [Internet}. Hamburg (Germany): Statista; 2020 [cited 2021 Sep 22]. Available from: https://www.statista.com/topics/2067/gluten-free-foods-market/
- Livingston M. Top 3 reasons why so many people go gluten-free: celiac disease is only one. San Francisco (CA): CNET; 2020 [ccited 2021 Sep 22]. Available from: https://www.cnet.com/health/nutrition/reasons-for-eating-a-gluten-free-diet/
- Rubio-Tapia A, et al. Increased prevalence and mortality in undiagnosed celiac disease. Gastroenterology. 2009;137(1):88-93. doi:10.1053/j.gastro.2009.03.059
- Caio G, et al. Celiac disease: a comprehensive current review. BMC Med. 2019;17(1). doi:10.1186/s12916-019-1380-z
- Leonard MM, et al. Celiac disease and nonceliac gluten sensitivity: a review. JAMA – J Am Med Assoc. 2017;318(7):647-56. doi:10.1001/jama.2017.9730
- Hadjivassiliou M, et al. Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain. 2003;126(3):685-91. doi:10.1093/brain/awg050
- Sabença C, et al. Wheat/gluten-related disorders and gluten-free diet misconceptions: a review. Foods. 2021;10(8). doi:10.3390/foods10081765
- Clarindo MV, et al. Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and treatment. An Bras Dermatol. 2014;89(6):865-77. doi:10.1590/abd1806-4841.20142966
- Mayo Clinic. Wheat allergy – symptoms and causes [Internet]. Rochester (MN): Mayo Clinic; 2020 [cited 2021 Sep 24]. Available from: https://www.mayoclinic.org/diseases-conditions/wheat-allergy/symptoms-causes/syc-20378897
- Scherf KA, et al. Wheat-dependent exercise-induced anaphylaxis. Clin Exp Allergy. 2016;46(1):10-20. doi:10.1111/cea.12640
- Czaja-Bulsa G, Bulsa M. What do we know now about IgE-mediated wheat allergy in children? Nutrients. 2017;9(1). doi:10.3390/nu9010035
- Keet CA, et al. The natural history of wheat allergy. Ann Allergy, Asthma Immunol. 2009;102(5):410-5. doi:10.1016/S1081-1206(10)60513-3
- Scibilia J, et al. Favorable prognosis of wheat allergy in adults. J Investig Allergol Clin Immunol. 2019;29(2):118-123. doi:10.18176/jiaci.0296
- Beyond Celiac. Non-celiac gluten sensitivity [Internet]. Ambler (PA): Beyond Celiac; 2020 [cited 2021 Sep 24]. Available from: https://www.beyondceliac.org/celiac-disease/non-celiac-gluten-sensitivity/
- Roszkowska A, et al. Non-celiac gluten sensitivity: a review. Med. 2019;55(6). doi:10.3390/medicina55060222
- Hollon J, et al. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients. 2015;7(3):1565-1576. doi:10.3390/nu7031565
- Fasano A, et al. Nonceliac gluten sensitivity. Gastroenterology. 2015;148(6):1195-204. doi:10.1053/j.gastro.2014.12.049
- Sapone A, et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med. 2012;10:13. doi:10.1186/1741-7015-10-13
- Catassi C, et al. The overlapping area of non-celiac gluten sensitivity (NCGS) and wheat-sensitive irritable bowel syndrome (IBS): an update. Nutrients. 2017;9(11). doi:10.3390/nu9111268
- Caio G, et al. Pathophysiology of non-celiac gluten sensitivity: where are we now? Minerva Gastroenterol Dietol. 2017;63(1):16-21. doi:10.23736/S1121-421X.16.02346-1
[This article by Dr. Erica Zelfand first appeared at Allergy Research Group, and is reposted here with permission.]