Understanding Celiac Disease
Celiac disease is a genetic immune-mediated disorder. This means that it is a condition that is passed down in families where the immune system attacks a healthy part of the body by mistake. Grains, such as wheat, rye and barley, contain specific storage proteins that are sticky and elastic and allow dough and bread to rise. These proteins are specifically known as gliadin when found in wheat, secalin in rye, and hordein in barley. In celiac disease, the storage proteins in these grains trigger the body to cause damage to the small intestine. All forms of these grains must be avoided. The only treatment for celiac disease is to follow a gluten-free diet for life.1 Visit the Simple Start to the Gluten-Free Diet section to learn which grains to choose and which to avoid.
Prevalence of Celiac Disease
Celiac disease (CD) may affect as many as 1.4% of North America’s population. An accurate number is unknown because many cases remain undiagnosed.2 It is most commonly diagnosed in people with North American or European descent. It is also found in people from the Middle East, North Africa, Turkey, India and around the world. Women are slightly more likely to be affected by CD.2 Although the most common age at diagnosis in the US is about 40 years, CD may be diagnosed at any age and most people probably develop CD at a younger age.3,4
Common Questions About Celiac Disease
Whether you suspect having a gluten intolerance or have been recently diagnosed with celiac disease, it is important to understand how celiac disease can affect your health. The following questions and answers provide valuable information about celiac disease symptoms and diagnosis.
How do symptoms and associated conditions of celiac disease respond to a gluten-free diet?
Symptoms and Associated Conditions That Usually Respond to a Gluten-Free Diet6,7
- Fecal urgency or incontinence (soiling (stool) accidents)
- Abdominal bloating
- Abdominal discomfort/pain
- Excess gas
- Fatty stools
- Nutritional deficiencies, such as protein, calories, iron, calcium, vitamin D, B vitamins, vitamins A, E, and K, zinc and other minerals
- Dermatitis herpetiformis
- Canker sores (aphthous ulcers)
- Angular cheilitis (cracks at the corners of the mouth)
- Abnormally high liver enzymes on blood testing
- Anemia from deficiency of iron, B12, and/or folic acid (in the absence of other GI manifestations)
These conditions should respond to the gluten-free diet (GFD) when they are caused by celiac disease. CD may coexist with other conditions, such as small intestinal bacterial overgrowth, other food intolerances or irritable bowel syndrome. Symptoms such as diarrhea, abdominal bloating, gas, and constipation can persist despite a GFD.5 These other diagnoses should be reviewed by your gastroenterologist if your symptoms persist after one year on the GFD.
Symptoms and Associated Conditions That Sometimes Respond to a Gluten-Free Diet
- Lactose intolerance
- Fructose malabsorption
- Microscopic colitis
- Reduced function of the spleen
- Depressed mood
- Poor concentration
- Alopecia (hair loss)
- Follicular keratosis
- Dental enamel loss
- Short stature
- Thinning of the bones (osteoporosis and osteopenia)
- Joint pains
- Reduced fertility (men and women)
- Recurrent miscarriages
Symptoms and Associated Conditions That Are Not Expected To Respond to a Gluten-Free Diet
- Small intestinal bacterial overgrowth
- IgA deficiency
- Lupus (SLE)
- Poor coordination (cerebellar ataxia)
- Tingling and numbness of hands and feet (peripheral neuropathy)
- Seizure disorder
- Patches of depigmentation (vitiligo)
- Primary biliary cirrhosis
- Autoimmune hepatitis
- Rheumatoid arthritis
- Type 1 diabetes
- Thyroid disease
- Addison’s disease
- IgA nephropathy (inflammation in the kidneys)
- Fibrosing alveolitis (fine scarring in the air sacs of the lungs)
- Pulmonary hemosiderosis (bleeding in the lungs)
- Lung cavities
- Inflammatory bowel disease (IBD)
Inflammatory bowel diseases (Crohn’s, Ulcerative Colitis) are more often found among individuals with celiac disease; it may be because celiac disease testing at diagnosis and follow-up may help to uncover a more rapid diagnosis of concurrent IBD.
What is the difference between celiac disease, non-celiac gluten sensitivity, and a wheat or gluten allergy?
Celiac disease is a genetic, immune-mediated disease triggered by the ingestion of gluten. The individual makes antibodies called auto-antibodies and has an inflammatory reaction that attacks and damages the lining of the small intestine.
Non-celiac gluten sensitivity (NCGS) is a recently described condition with symptoms like those in celiac disease. Unlike CD, there is no genetic susceptibility to NCGS and there is no direct damage of the lining of the small intestine. It is also less associated with other autoimmune diseases.5-8 Even though the small intestine is normal, an immune reaction triggered by gluten may be the cause of NCGS.9,10 Extra-intestinal manifestations such as fatigue, neurological and psychiatric symptoms, joint pain and “foggy mind” may be seen in both NCGS and CD.11 Symptoms improve or even disappear after withdrawing gluten from their diet.12 As a result, many patients with NCGS will try a GFD on their own.
NCGS is a diagnosis of exclusion. This means that your doctor will only give you a diagnosis of NCGS if both CD and a gluten or wheat allergy have been ruled out. However, whether this is a life-long condition and to what degree gluten should be avoided is currently being studied. Until new data arrives, people with NCGS should do whatever they feel offers them the best quality of life overall.
A gluten or wheat allergy involves an adverse immune response to the gluten or other wheat (cereal) proteins that leads to symptoms such as swelling around the mouth, hives, sneezing and stomach discomfort. Damage to the small intestine, however, is mild and usually short-lived.13 Some symptoms are the same as in celiac disease, but an allergy can, at times, result in immediate and life-threatening symptoms.
What are the different forms of celiac disease?
There are four main categories of celiac disease1,14:
Classical Celiac Disease
Classical celiac disease is characterized primarily by gastrointestinal problems such as diarrhea, weight loss and abdominal pain or nutritional problems due to malabsorption. A biopsy of the small intestine will show villous atrophy (damage). Improvement of this damage will usually be seen on the gluten-free diet. Symptoms should also improve on a gluten-free diet.
Non-Classical Celiac Disease
There are few or no gastrointestinal symptoms presented in non-classical celiac disease. Non-gastrointestinal features, such as Dermatitis Herpetiformis (a very itchy skin rash), iron deficiency anemia, or osteoporosis are more common. Other examples include fertility issues, unexplained high liver enzymes, unexplained headaches, movement disorders (ataxia), and tingling in the hands and feet (polyneuropathy). Like classical celiac disease, the diagnosis is made by blood testing for antibodies commonly found in CD. Damage is seen in the small intestinal biopsy and symptoms improve on a GFD. The 'atypical' presentation of celiac disease is currently the most common one.
Subclinical Celiac Disease
Similar terms are silent celiac disease and asymptomatic celiac disease. Subclinical celiac disease is celiac disease but does not have any of the symptoms or other abnormal lab values, except for positive circulating antibodies.14 As such, there are no related gastrointestinal or non-gastrointestinal symptoms or nutritional deficiencies seen. Damage still occurs to the small intestine, however. Individuals with subclinical CD are usually found through screenings of high-risk individuals. Examples include a person with a family history of CD or type 1 diabetes, or someone diagnosed on routine endoscopy that was done for other reasons. A gluten-free diet is still recommended among asymptomatic individuals who have intestinal damage to prevent future problems (from malabsorption, osteoporosis, and infertility).
Potential Celiac Disease
People with a normal small intestinal mucosa who are at increased risk of developing celiac disease as indicated by positive celiac disease serology.14 Blood tests are positive for celiac antibodies (either endomysial antibody or tissue transglutaminase antibody). The small intestinal biopsy is normal with no evidence of villous atrophy. Individuals with potential CD may develop active CD later in life, either with symptoms or changes in their small intestinal biopsies. When asymptomatic and without nutritional deficiencies, the values of treating potential CD with a GFD is unproven. Most doctors recommend to stay on a normal diet but with increased awareness that active CD may develop over time.14
What causes celiac disease to develop?
Celiac disease tends to run in families because people who have celiac disease inherited the genes and may be exposed to similar environmental risks. CD can begin at any time, or not at all, during a person's life because of certain environmental factors.
To develop celiac disease, you must have genetic markers of either HLA DQ2, HLA DQ8 or both of these genes. For this reason, we screen for CD among your family members since they may have inherited the genes and have one of the many forms of CD. However, having the genes alone is not enough to develop the disease.
Other required conditions are:
- The person must have been exposed to gluten (such as when a baby is given wheat cereal as infant food).
- Environmental or physiological (having to do with the body) factors may also contribute to the onset of celiac disease.
Environmental or physiological (bodily) factors include surgery, pregnancy, childbirth, and gastrointestinal infections, especially viral or severe emotional stress.14 Researchers are also looking into other factors that may influence the symptoms of CD including cow's milk formulas, breastfeeding, age at gluten introduction, quantity of gluten, quality of cereals, and use of probiotics.16,17
What happens when a person eats gluten?
In all humans, gluten is not completely digested. If someone has celiac disease, eating gluten results in an increase in intestinal permeability (leaky gut) and the immune system damages the villi (fingerlike hairs) which line the small intestine.1 These villi take in nutrients from food and move them into the bloodstream where the body can use them. Without enough healthy villi, a person will not get enough of the nutrients he/she needs.18 Most of the time, antibodies (anti-deamidated gliadin peptides [DGP]) are also made against gluten. Other antibodies are made against tissue transglutaminase, a common enzyme in the intestinal lining. These antibodies are detected with blood tests.
If I suspect celiac disease, should I start a gluten-free diet before I see a gastroenterologist?
We do not recommend making changes to your diet before consulting a physician. Always speak to your doctor if you have any symptoms that concern you.
It is important to have a medical evaluation of celiac disease before starting a gluten-free diet. Once on the diet, the common tests including biopsy of the intestine will start to heal and this will make it difficult to make a diagnosis.3
Does it matter how quickly I get an official diagnosis?
The longer a person goes without a diagnosis and untreated, the greater the chance of developing long-term medical problems.19
Once a diagnosis of celiac disease is made, screening for silent manifestations can take place and thus detect conditions related to the disease, such as osteoporosis and vitamin and mineral deficiencies such as iron, folate and vitamin D deficiency. The duration of gluten exposure does correlate with the risk of developing associated autoimmune diseases. Therefore, early diagnosis is preferable.20
The symptoms listed above are not unique to celiac disease and can occur with other disorders and diseases.
With more widespread use of antibody testing and small intestinal biopsies to diagnose CD, several categories of CD have now emerged. These include classical disease, non-classical presentations, subclinical and potential forms of the disease. Knowing which form of CD you have is important information for you and your doctor.
The non-classical form of CD is currently the most common or typical presentation of CD. For this reason, both patients and doctors need to be on the close look-out for the wide variety of symptoms and to screen for CD so that it can be found as early as possible.
If you or your doctor recognizes your symptoms in the list above, consider getting tested for CD.
If you suspect CD, do not start a gluten-free diet on your own until you have met with a gastroenterologist and have been evaluated.
Early diagnosis and effective treatment of celiac disease greatly improves your health outcomes and reduces the risks of complications from untreated disease.
Non-celiac gluten sensitivity (NCGS) is an increasingly seen clinical condition with gastrointestinal symptoms like those found in CD. It is important to screen for CD and/or a wheat or gluten allergy before starting a gluten-free diet, as NCGS is a diagnosis of exclusion.
- Green PH, Cellier C. Celiac Disease. N Eng J Med. 2007;357(17):1731-43.
- Singh P, Arora A, Strand TA et al. Global prevalence of celiac disease: systematic review and meta-analysis. Clin Gastronterol Hepatol. 2018; 16(6):823-836.
- Green PH. The many faces of celiac disease: clinical presentation of celiac disease in the adult population. Gastroenterol. 2005; 128 (4 Suppl 1):S74-8.
- Green PH, Stavropoulos SN, Panagi SG, et al. Characteristics of adult celiac disease in the USA: results of a national survey. Am J Gastroenterol. 2001;96(1):126-31.
- Leffler DA, Dennis M, Hyett B, et al. Etiologies and predictors of diagnosis in nonresponsive celiac disease. Clin Gastroenterol Hepatol. 2007;5(4):445-450.
- Therrien A., Kelly C.P., Silvester J.A. Extraintestinal manifestations of celiac disease. J Clin Gastroenterol. 2020;54(1):8-21.
- Kelly, CP. Common and Uncommon Presentations of Celiac Disease. In Real Life with Celiac Disease: Troubleshooting and Thriving Gluten-Free. Eds. Dennis M, Leffler D. AGA Press. Bethesda, MD, 2010.
- Catassi C, Elli L, Bonaz B, et al. Diagnosis of non-celiac gluten sensitivity (NCGS): The Salerno experts’ criteria. Nutrients. 2015;7(6):4966-4977.
- Leffler DA. Gluten Intolerance: You Mean I Don't Have Celiac Disease? In Real Life with Celiac Disease: Troubleshooting and Thriving Gluten-Free. Eds. Dennis M, Leffler D. AGA Press. Bethesda, MD, 2010.
- Uhde M, Ajamian M, Caio G et al. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of celiac disease. Gut. 2016; 65 (12): 1930-37.
- Casella G, Villanacci V, Di Bella C, et al. Non celiac gluten sensitivity and diagnostic challenges. Gastroenterol Hepatol Bed Bench. 2018; 11(3): 197-202.
- Biesiekierski JR, Newnham ED, Irving PM, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blinded randomized placebo-controlled trial. Am J Gastroenterol. 2010; 106(3):508-14.
- Up to Date. www.uptodate.com. May 21, 2019. Accessed March 26, 2021
- Ludvigsson JF, Leffler DA, Bai JC et al. The Oslo definitions for coeliac disease and related terms. Gut. 2013; 62(1):43-52.
- Lebwohl B,Sanders DS, Green PHR, Coeliac disease. Lancet. 2018;391(10115):70-81.
- Popp A, Mäki M.Front Pediatr. Changing pattern of childhood celiac disease epidemiology: contributing factors. Front Pediatr. 2019 Aug 29;7:357.
- Caio G, Volta U, Sapone A, Leffler DA, De Giorgio R, Catassi C, Fasano A. Celiac disease: a comprehensive current review. BMC Med. 2019 Jul 23;17(1):142.
- National Institute of Diabetes and Digestive and Kidney Diseases. June 2016. www.niddk.nih.gov. Accessed February 26, 2021.
- Rubio-Tapia A, Kyle RA, Kaplan EL, et al. Increased prevalence and mortality in undiagnosed celiac disease. Gastroenterol. 2009;137(1):88–93.
- Ventura A, Magazzu G, Greco L. Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for Autoimmune Disorders in Celiac Disease. Gastroenterol. 1999;117:297-303.
Revision Date: March 1, 2022
Author: Amelie Therrien MD
Editors: Melinda Dennis, MS, RDN, LD, and Daniel Leffler, MD, MS