Definition
Celiac disease (CD) is an inflammatory disease that affects the small intestine. It is caused by the consumption of gluten in genetically predisposed individuals. Gluten is a protein found in various cereals, notably rye, wheat, and barley, as well as in products containing them. Chronic inflammation of the small intestine alters the structure of the intestinal mucosa and leads to malabsorption of nutrients.
Epidemiology
The prevalence of CD is estimated at 1% among the global population. The disease is mainly observed in people of Caucasian origin and affects about twice as many women as men. Some people are at higher risk of developing CD. This notably includes first-degree relatives (mother, father, brother, sister, child) and individuals with another disease such as Down syndrome or type 1 diabetes.
Etiology
The development of CD requires the ingestion of gluten as well as a genetic predisposition. In people with CD, gluten ingestion triggers the production of antibodies by the immune system. These antibodies damage the inner wall of the small intestine by causing atrophy (shortening) of the villi, the small hairs responsible for nutrient absorption. The absence of villi reduces the absorption surface of the intestine and leads to malabsorption of nutrients. Since CD is a hereditary disease, affected individuals must carry certain genes, HLA-DQ2 and/or HLA-DQ8. However, people carrying these genes do not always develop the disease.
Symptoms
Symptoms of CD can appear at any age and can be very variable. The severity of symptoms depends on the proportion of the small intestine affected by the disease. In children, symptoms generally include abdominal bloating, growth delay, and diarrhea. Other symptoms may include anorexia, vomiting, and anemia. In adults, many people are asymptomatic and show no digestive symptoms. Otherwise, symptoms may include diarrhea, malnutrition, and weight loss. There may also be anemia, osteoporosis, abdominal pain, abdominal bloating, and reduced fertility. Additionally, about 10% of individuals with CD have dermatitis herpetiformis, a painful skin rash.
Diagnosis
The diagnosis of CD is based on the presence of the aforementioned symptoms, blood tests, small intestine biopsies, and response to a gluten-free diet. Doctors may also use genetic tests to make their diagnosis.
Blood tests
Blood tests allow for the measurement of antibodies directed against gluten. They must be performed on individuals who consume gluten. The antibody level is proportional to the degree of villous atrophy. If the tests are positive, the individual must undergo an intestinal biopsy to establish the diagnosis. If the tests are negative, CD is unlikely.
Small intestine biopsy
The small intestine biopsy involves taking a small piece of tissue from the intestinal mucosa to observe its structure under a microscope. It must be performed on individuals whose diet contains gluten. In the majority of people with CD, the intestinal mucosa biopsy shows villous atrophy. However, the absence of villi is not specific to CD, which is why blood tests are also necessary to establish the diagnosis.
Response to a gluten-free diet
A positive response to a gluten-free diet also supports the diagnosis of CD. A response is positive if symptoms disappear, antibody levels directed against gluten decrease, and the surface of the small intestine normalizes following the introduction of a gluten-free diet.
Genetic tests
In some cases, diagnosis may also include genetic tests, especially when blood tests and biopsy do not agree. Genetic tests check if the person carries genes associated with CD. If the genes are absent, CD is excluded. However, their presence is not diagnostic of CD, as carriers may never develop the disease.
Nutritional consequences
CD affects nutrient absorption in the small intestine. The severity of malabsorption and its consequences depend on the extent of villous atrophy. The larger the region of the intestine affected by the disease, the greater the malabsorption and its consequences. The nature of the malabsorbed nutrients may also vary depending on the portion affected by the disease. For example, if the affected portion is the duodenum and proximal jejunum, malabsorption mainly concerns iron, folate, and calcium, which are primarily absorbed in this part of the intestine. Consequences include macrocytic anemia and bone mass loss. If the entire small intestine is affected, then all macronutrients (carbohydrates, lipids, and proteins) and micronutrients (vitamins and minerals) may be malabsorbed. Carbohydrate malabsorption can cause diarrhea, gas, and bloating. Protein malabsorption can cause edema and muscle mass loss. There may also be signs of vitamin and mineral deficiencies such as iron-deficiency anemia and bone mass loss. Many adults with CD have low bone mass (osteopenia, osteoporosis) and are at higher risk of fractures than the general population.
Treatment
Currently, the only treatment for CD is to follow a lifelong gluten-free diet. Total exclusion of gluten from the diet is required, as even small amounts can cause symptoms. The gluten-free diet excludes rye, oats (pure uncontaminated oats are allowed), wheat (including kamut and spelt), barley, and triticale (a hybrid between rye and wheat). Due to the omnipresence of gluten in North American diets, such a diet can be complex to follow. It is therefore recommended to consult a dietitian for a nutritional assessment, education on the gluten-free diet, and follow-up. In more severe forms of the disease, doctors may also prescribe vitamin and mineral supplements. It is important to remember that the diagnosis of CD must be made before starting the gluten-free diet.
The gluten-free diet helps improve symptoms, antibody levels, and villous atrophy. Generally, symptom improvement occurs about 2 weeks after starting the gluten-free diet. Then, blood tests show a decrease in antibody levels between 6 to 12 months after starting the diet. Finally, a few months to two years after gluten removal from the diet, the small intestine usually regains its normal structure (presence of villi) and resumes its normal absorption functions.
If there is no improvement after starting the diet, the diagnosis should be rechecked and diet adherence verified. If the diagnosis is correct and the diet is well followed, other causes such as small intestine cancer, lactose or fructose intolerance, or other food allergies should be ruled out. It is also possible that CD has reached the refractory stage. In this case, individuals continue to have gastrointestinal symptoms and villous atrophy despite adherence to a gluten-free diet. For refractory CD, doctors may prescribe corticosteroids to control symptoms.
Complications
Individuals with undiagnosed CD and those with poor adherence to the gluten-free diet have higher mortality than the general population. However, fatal outcomes are rare and most individuals live normally with a gluten-free diet. People with CD are also at higher risk of developing certain digestive tract cancers, notably small intestine lymphoma. Adherence to a gluten-free diet significantly reduces the risk of cancer.
Future treatments
Today, the only available treatment for CD is a lifelong gluten-free diet. However, this diet can be difficult to follow and some individuals continue to have symptoms despite adherence. There is therefore a need to develop non-dietary treatments. Various mechanisms involved in CD functioning have been identified during clinical trials as potential avenues for developing non-dietary treatments. Potential treatments include enzymatic degradation of gluten, sequestration of gliadin (the toxic fraction of gluten), protection of intestinal cells against gliadin with a probiotic, gluten tolerance with a vaccine, and treatments targeting immune cells. Currently, no non-dietary treatment is approved and more studies are needed to develop an alternative treatment for CD.
References
- https://www.celiac.ca/en/
- https://www.fqmc.org/
- https://www.merckmanuals.com/professional/gastrointestinal-disorders/malabsorption-syndromes/celiac-disease#
- https://www.merckmanuals.com/home/digestive-disorders/malabsorption/celiac-disease
- https://www.merckmanuals.com/home/quick-facts/digestive-disorders/malabsorption/celiac-disease
- Semrad, C. E. “Celiac Disease.” Modern Nutrition in Health and Disease, by A. Catharine Ross, Wolters Kluwer/Lippincott Williams & Wilkins, 2014, pp. 1089–1095.
- Oxentenko, A. S., & Rubio-Tapia, A. (2019). Celiac Disease. Mayo Clinic proceedings, 94(12), 2556–2571. https://doi.org/10.1016/j.mayocp.2019.02.019
- Rubin, J. E., & Crowe, S. E. (2020). Celiac Disease. Annals of internal medicine, 172(1), ITC1–ITC16. https://doi.org/10.7326/AITC202001070