Celiac Disease/Coeliac disease is also known as celiac sprue is a unique autoimmune, genetic element (human leukocyte antigen (HLA)-DQ2 and HLA-DQ8), based gluten-sensitive immune-mediated enteropathic with the auto-antigen involved (tissue transglutaminase (tTG)), and the environmental trigger (gluten) are all well-defined condition where the immune system mistakes healthy cells for harmful ones and produces antibodies which result in the small intestine becoming inflamed and less able to absorb nutrients, maldigestion, and malabsorption of most nutrients and vitamins. It can cause a range of symptoms including diarrhea.
Celiac disease (CD) is an autoimmune condition characterized by a specific serological and histological profile triggered by gluten ingestion in genetically predisposed individuals [rx]. Gluten is the general term for alcohol-soluble proteins present in various cereals, including wheat, rye, barley, spelled, and Kamut [rx].
Celiac disease is a chronic digestive and immune disorder that damages the small intestine. The disease is triggered by eating foods containing gluten. Gluten is a protein found naturally in wheat, barley, and rye, and is common in foods such as bread, pasta, cookies, and cakes. Many products contain gluten, such as prepackaged foods, lip balms and lipsticks, toothpaste, vitamin and nutrient supplements, and, rarely, medicines.
Types of Celiac Disease
Recently a consensus paper redefined the types of celiac disease.
- Classic celiac disease – refers to the presence of symptoms of malabsorption such as diarrhea, failure to thrive, and weight loss and may occur in adults and children.
- Non-classic celiac disease – refers to celiac disease without prominent gastrointestinal symptoms or malabsorption; however, individuals with atypical celiac disease can also have gastrointestinal symptoms such as reflux, abdominal pain, bloating, vomiting, constipation, and dyspepsia. Approximately 70% of individuals are diagnosed based on extraintestinal manifestations associated with celiac disease. This group includes monosymptomatic and subclinical forms.
Marsh classification of histologic findings in celiac disease
| Marsh 0 | Normal mucosal architecture without significant intraepithelial lymphocytic infiltration. |
| Marsh I | Lymphocytic enteritis: Normal mucosal architecture with a marked infiltration of villous epithelium by lymphocytes; arbitrarily defined marked as more than 30 lymphocytes per 100 enterocytes |
| Marsh II | Lymphocytic enteritis with crypt hyperplasia: intraepithelial lymphocytosis and elongation and branching of crypts in which there is an increased proliferation of epithelial cells |
| Marsh III | Intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy. There are 3 distinct stages of villous atrophy |
| Marsh IIIA | Partial villous atrophy, the villi are blunt and shortened. Arbitrarily, samples are classified as partial villous atrophy if the villus-crypt ratio was less than 1:1 |
| Marsh IIIB | Subtotal villous atrophy, villi are clearly atrophic but still recognizable |
| Marsh IIIC | Total villous atrophy, villi are rudimentary or absent, and the mucosa resembles colonic mucosa. |
Causes of Celiac Disease
The symptoms of celiac disease are due to the damage of enterocytes in the small intestine. In the full-blown clinical picture, the typical features of the small intestine are chronic inflammation and villi atrophy. [rx][rx][rx]
- An individual has to have HLA-dominant DQ2 or DQ8 genes. The disease is a result of the immune system reacting adversely to gluten, and one of the important proteins involved is an antibody to tissue transglutaminase. There are however other pathways proposed that contribute to the disease. The glycoprotein gliadin (present in gluten) has a direct toxic effect on enterocytes by the up-regulating production of IL-15.
- Celiac disease is also called celiac sprue, nontropical sprue, and gluten-sensitive enteropathy.
- Celiac disease can only occur in people who have certain genes. You are more likely to develop the celiac disease if someone in your family has the disease.
- Celiac disease affects children and adults in all parts of the world. In the United States, celiac disease is more common among white Americans than among other racial or ethnic groups. A celiac disease diagnosis is more common in females than in males.
- Celiac disease is also more common in people who have certain chromosomal disorders, such as Down syndrome, Turner syndrome, and Williams syndrome.
Experts have found that some people have both celiac disease and other disorders related to the immune system. These disorders include
- type 1 diabetes
- thyroid diseases, such as Hashimoto’s disease, Graves’ disease, Addison’s disease, and primary hyperparathyroidism
- selective immunoglobulin A (IgA) deficiency, a condition in which your body makes little or no IgA, an antibody that fights infections
- rheumatic diseases, such as Sjögren’s syndrome NIH external link
- liver diseases, such as autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cholangitis
- Potential celiac disease
- Non-celiac gluten sensitivity
- Food allergies (cereals, milk proteins, soy derivatives, fish, rice, chicken)
- Infectious (viral enteritis, Giardia, Cryptosporidium, Helicobacter pylori)
- Bacterial contamination of the small intestine
- Drugs (e.g., non-steroidal anti-inflammatory drugs)
- Immune system diseases (Hashimoto’s thyroiditis, rheumatoid arthritis, systemic erythematosus lupus, type 1 diabetes mellitus, autoimmune enteropathy)
- Common variable immune deficiency
- Chronic inflammatory intestinal diseases (Crohn’s disease, ulcerative colitis)
- Lymphocytic colitis
Research suggests that celiac disease only occurs in people who have certain genes and eat food that contains gluten. Experts are studying other factors that may play a role in causing the disease.
Genes
The celiac disease almost always occurs in people who have one of two groups of normal gene variants, called DQ2 and DQ8. People who do not have these gene variants are very unlikely to develop celiac disease. About 30 percent of people have DQ2 or DQ8. However, only about 3 percent of people with DQ2 or DQ8 develop celiac disease.4
Researchers are studying other genes that may increase the chance of developing celiac disease in people who have DQ2 or DQ8.
Gluten
Consuming gluten triggers the abnormal immune system response that causes celiac disease. However, not all people who have the gene variants DQ2 or DQ8 and eat gluten develop the disease. Research suggests that among children with a genetic predisposition for celiac disease, those who eat more gluten in early childhood may have a greater risk for celiac disease.
Other factors
Researchers are studying other factors that may increase a person’s chances of developing celiac disease. For example, research suggests that a higher number of infections in early life and certain digestive tract infections may increase the risk. Experts also think changes in the microbiome—the bacteria in the digestive tract that help with digestion—could play a role in the development of celiac disease.
Symptoms of Celiac Disease
Symptoms of celiac disease vary widely, and a person may have multiple symptoms that come and go. If you have celiac disease, you may have digestive problems or other symptoms. Digestive symptoms are more common in children than in adults. Digestive symptoms of celiac disease may include
- The main symptoms are stomach pain, gas, and bloating, diarrhea, weight loss, anemia, edema, bone or joint pain.
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Anemia due to defective absorption of vitamin B12, folate, or iron
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Coagulopathy due to impaired absorption of vitamin K
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Osteoporosis
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Neurological symptoms like muscle weakness, paresthesias, seizures, and ataxia
- bloating
- chronic diarrhea
- constipation
- gas
- lactose intolerance due to damage to the small intestine
- loose, greasy, bulky, and bad-smelling stools
- nausea or vomiting
- pain in the abdomen
- frequent bouts of diarrhea or loose stools
- nausea, feeling sick, and vomiting
- stomach pain and cramping
- lots of gas and bloating
- feeling tired all the time, ongoing fatigue
- anemia (you would be told if you’re anemic following a blood test)
- weight loss (although not in all cases)
- regular mouth ulcers
- constipation or hard stools
For children with celiac disease, being unable to absorb nutrients at a time when they are so important to normal growth and development can lead to
- damage to the permanent teeth’s enamel
- delayed puberty
- failure to thrive, meaning that an infant or a child weighs less or is gaining less weight than expected for his or her age
- mood changes or feeling annoyed or impatient
- slowed growth and short height
- weight loss
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Anemia due to defective absorption of vitamin B12, folate or iron
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Coagulopathy due to impaired absorption of vitamin K
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Osteoporosis
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Neurological symptoms like muscle weakness, paresthesias, seizures and ataxia
Some people with celiac disease have symptoms that affect other parts of the body. These symptoms may include
- dermatitis herpetiformis
- fatigue, or feeling tired
- joint or bone pain
- mental health problems, such as depression or anxiety
- nervous system symptoms, such as headaches, balance problems, seizures, or peripheral neuropathy
- reproductive problems in women and girls—which may include infertility, delayed start of menstrual periods, missed menstrual periods, or repeated miscarriages and male infertility
- symptoms involving the mouth, such as canker sores; a dry mouth; or a red, smooth, shiny tongue
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Anemia due to defective absorption of vitamin B12, folate or iron
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Coagulopathy due to impaired absorption of vitamin K
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Osteoporosis
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Neurological symptoms like muscle weakness, paresthesias, seizures and ataxia
Most people with celiac disease have one or more symptoms before they are diagnosed and begin treatment. Symptoms typically improve and may go away after a person begins eating a gluten-free diet. Symptoms may return if a person consumes small amounts of gluten.
Depending on how old you are when a doctor diagnoses your celiac disease, some symptoms, such as short height and tooth defects, may not improve. People with celiac disease who have no symptoms can still develop complications over time if they do not get treatment.
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Gastrointestinal signs/symptoms (e.g., diarrhea, malabsorption, abdominal pain, distention, bloating, vomiting, weight loss)
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Dermatitis herpetiformis
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Chronic fatigue
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Joint pain/inflammation
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Neurologic symptoms (e.g., peripheral neuropathy, ataxia, seizures, migraines, attention-deficit disorder, poor school performance)
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Osteoporosis/osteopenia
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Infertility and/or recurrent fetal loss
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Short stature and/or failure to thrive
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Delayed puberty
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Dental enamel defects
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Autoimmune disorders
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Individuals with disorders associated with celiac disease (e.g., Down syndrome, Turner syndrome, Williams syndrome, selective IgA deficiency, insulin-dependent diabetes mellitus, Sjögren syndrome, thyroiditis)
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Absence of history of self-limited enteritis and/or tropical sprue
According to NCBI.NLM.NIH symptoms are
The following extraintestinal symptoms are secondary to malabsorption [rx,rx]
- Peripheral neuropathy (vitamin B12 and B1 deficiency)
- Anemia (iron, vitamin B12 and folate deficiency)
- Growth failure in children
- Bone pain (osteoporosis and osteopenia, vitamin D and calcium deficiency)
- Muscle cramps (magnesium and calcium deficiency)
- Night blindness (vitamin A deficiency)
- Weight loss (impaired absorption of most nutrients)
- Edema (protein and albumin loss)
- Weakness (hypokalemia and electrolyte depletion)
- Bleeding and hematoma (vitamin K deficiency)
The following extraintestinal symptoms/manifestations are probably not secondary to malabsorption (atypical CD) [rx]
- Neurological disorders such as depression, epilepsy, migraine, ataxia
- Dermatitis herpetiformis
- Elevated liver enzymes, liver failure
- Infertility
- Stomatitis
- IgA nephritis
- Myocarditis
- Idiopathic pulmonary hemosiderosis
- Arthritis
The following diseases/conditions are associated with celiac disease [rx–rx]
- Autoimmune diseases such as type 1 diabetes, Sjögren syndrome, thyroid diseases (Hashimoto’s thyroiditis and Graves’s disease), autoimmune hepatitis and primary biliary cirrhosis
- Selective IgA deficiency
Turner’s syndrome - Down’s syndrome
Dermatitis herpetiformis
Dermatitis herpetiformis is an itchy, blistering skin rash that usually appears on the elbows, knees, buttocks, back, or scalp. Among people with untreated celiac disease, about 2 to 3 percent of children and 10 to 20 percent of adults have dermatitis herpetiformis.3 Some people with celiac disease may have the rash and no other symptoms. After a person starts a gluten-free diet, the rash may take some time to heal and may return if a person consumes small amounts of gluten.
Children
Children with celiac disease are more likely than adults to have digestive problems, including:
- Nausea and vomiting
- Chronic diarrhea
- Swollen belly
- Constipation
- Gas
- Pale, foul-smelling stools
The inability to absorb nutrients might result in:
- Failure to thrive for infants
- Damage to tooth enamel
- Weight loss
- Anemia
- Irritability
- Short stature
- Delayed puberty
- Neurological symptoms, including attention-deficit/hyperactivity disorder (ADHD), learning disabilities, headaches, lack of muscle coordination and seizures
Diagnosis of Celiac Disease
Doctors use information from your medical and family history, a physical exam, a dental exam, and medical test results to look for signs that you might have celiac disease and should be tested. Doctors typically diagnose celiac disease with blood tests and biopsies of the small intestine.
Medical and family history
Your doctor will ask about your symptoms.
- Celiac disease isn’t diagnosed based on symptoms alone because some of the symptoms are like the symptoms of other digestive disorders, such as irritable bowel syndrome (IBS) or lactose intolerance. Some people with celiac disease have symptoms that affect parts of the body outside the digestive tract.
- The doctor will review your medical history, including your history of conditions that are more common in people who have celiac disease. Your doctor will also ask about your family’s medical history and whether anyone in your family has been diagnosed with celiac disease.
Physical exam
During a physical exam, a doctor may
- check for signs of weight loss or growth problems
- examine your skin for rashes, such as dermatitis herpetiformis
- listen to sounds in the abdomen using a stethoscope
- tap on the abdomen to check for pain or swelling
In some cases, a dentist may notice signs of celiac disease during an exam. Celiac disease may cause problems with the teeth and mouth, such as defects in tooth enamel or canker sores.
Doctors most often use blood tests and biopsies of the small intestine to diagnose or rule out celiac disease. Doctors don’t recommend starting a gluten-free diet before diagnostic testing because a gluten-free diet can affect test results.
In some cases, doctors may order additional tests, such as skin biopsies and genetic tests, to help diagnose or rule out celiac disease.
Lab Test
- Blood tests – A health care professional will take a blood sample from you and send the sample to a lab. Blood tests can show levels of certain antibodies that are often higher than normal in people who have untreated celiac disease. Blood tests may also show signs of health problems that could be related to celiac disease, such as anemia.
- Biopsies of the small intestine – A doctor obtains biopsies of the small intestine during an upper GI endoscopy. For an upper GI endoscopy, a doctor uses an endoscope—a flexible tube with a camera—to see the lining of your upper GI tract, including the first part of your small intestine. The doctor passes an instrument through the endoscope to take small pieces of tissue from your small intestine. A pathologist will examine the tissue under a microscope to look for signs of celiac disease.
- Skin biopsies – A doctor may order skin biopsies if you have a rash that could be dermatitis herpetiformis. For skin biopsies, a doctor removes small pieces of skin tissue on and next to the rash. A pathologist will examine the tissue under a microscope to look for signs of dermatitis herpetiformis.
- Genetic testing – In some cases, a health care professional may take a blood sample or use a swab to collect cells from the inside of your cheek. The sample will be tested for groups of gene variants called DQ2 and DQ8. If you do not have these gene variants, you are very unlikely to have celiac disease. Having DQ2 or DQ8 alone does not mean you have celiac disease. Most people with these gene variants do not develop celiac disease. If you do have DQ2 or DQ8, your doctor may recommend additional tests to check for or rule out celiac disease.
- HLA tests – Based on studies for which sensitivity could be calculated, the ACG estimated the negative predictive value of the HLA-DQ2/HLA-DQ8 combination test at more than 99 percent in diagnosing celiac disease.
- Screening is testing – for diseases when you have no symptoms. Doctors in the United States do not routinely screen people for celiac disease. However, blood relatives of people with celiac disease and those with type 1 diabetes should talk with their doctor about their chances of getting the disease to see if they should be tested.
- Endoscopy – This test uses a long tube with a tiny camera that’s put into your mouth and passed down your throat (upper endoscopy). The camera enables your doctor to view your small intestine and take a small tissue sample (biopsy) to analyze for damage to the villi.
- Capsule endoscopy – This test uses a tiny wireless camera to take pictures of your entire small intestine. The camera sits inside a vitamin-sized capsule, which you swallow. As the capsule travels through your digestive tract, the camera takes thousands of pictures that are transmitted to a recorder.
Serological tests
- Anti-tissue transglutaminase antibodies – the best strategy for serological diagnosis is the blood detection of IgA anti-tissue transglutaminase antibodies (tTGA) by enzyme-linked immunosorbent assay (ELISA). These antibodies show a sensitivity up to 97%, a specificity around 96%, and an accuracy of 98%, whereas IgA anti-endomysial (IgA EMA) antibodies are employed as a confirmatory test in tTGA positive cases due to their higher specificity (about 100% vs 91% of tTGA). In concomitance of IgA deficiency and celiac disease, found in around 2%-10% of the patients, it is recommended to detect celiac disease testing tTG-IgG. “False-negative” occurs, as previously reported, in the case of IgA deficiency. The IgA EMA represents the most specific test (approximately 100%), with a sensitivity around 94% and a diagnostic accuracy of 97%[rx]. However, EMA is routinely detected by indirect subjective immunofluorescence[rx]. These antibodies can also result falsely negative in case of IgA deficiency and in children aged > 2 years.
- anti-gliadin antibodies – The antigliadin (AGA) antibodies (IgG and IgA) are today no longer recommended because of their low sensitivity and specificity and inferior accuracy, except in younger children[rx].
- Deamidated gliadin peptides – Actually detection of antigliadin antibodies has been replaced by the more recently developed immunoassays employing antibodies to deamidated gliadin peptides, IgA and IgG. To increase the diagnostic accuracy, in the last years the clinicians tend to prescribe serial testing.
- Blood tests check other parts of your immune system.
- Intestinal fatty acid-binding protein tests show if there’s damage to the intestine.
- A complete blood count looks for anemia (low red blood cells).
- C-reactive protein tests show if there’s inflammation.
- Metabolic panels test liver and kidney function.
- Vitamin D, B12, and folate tests look for vitamin deficiencies.
- Iron and ferritin tests look for iron deficiency.
- Swallowing a small camera can show problems in your digestive tract.
- Imaging tests show signs in the intestine, like wall thickening or changes to blood vessels.
- Genetic testing looks for human leukocyte antigens to rule out celiac disease.
Laboratory findings
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Iron deficiency anemia
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Vitamin and/or mineral deficiencies (e.g., calcium, vitamin D, vitamin B12, folic acid)
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Electrolytes may reveal hypocalcemia, hypokalemia, metabolic acidosis
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Anemia due to deficiency of folate, iron or Vit B12
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Prothrombin time may be prolonged
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Stool are greasy and have a rancid odor
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In individuals on a gluten-containing diet:
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Elevated serum tissue transglutaminase (tTG) IgA
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Elevated serum anti-deamidated gliadin-related peptide (a-DGP) IgA and IgG
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Elevated serum endomysial antibody (EMA) IgA; highest specificity (~99%) but sensitivity subject to observer variability
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Treatment for Celiac Disease
Gluten-free diet
Doctors treat celiac disease by helping people to follow a gluten-free diet. Gluten is a protein found naturally in certain grains, including wheat, barley, and rye. Gluten is also added to many other foods and products. In people who have celiac disease, consuming gluten triggers an abnormal immune system reaction that damages the small intestine.
Symptoms greatly improve for most people with celiac disease who stick to a gluten-free diet. For most people, following a gluten-free diet will heal damage in the small intestine and prevent more damage. Many people see symptoms improve within days to weeks of starting the diet.
Your doctor will explain the gluten-free diet and may refer you to a registered dietitian who specializes in treating people who have celiac disease. The dietitian will teach you how to avoid gluten while following a healthy diet and recommend substitutes for foods that contain gluten. He or she will help you
- check food and product labels for gluten
- design everyday meal plans
- make healthy choices about foods and drinks
Avoiding medicines and other products that may contain gluten
In addition to prescribing a gluten-free diet, your doctor will want you to avoid all hidden sources of gluten. If you have celiac disease, ask a pharmacist about ingredients in
- herbal and nutritional supplements
- prescription and over-the-counter medicines
- vitamin and mineral supplements
Medicines are rare sources of gluten. Even if gluten is present in a medicine, it is likely to be in such small quantities that it would not cause any symptoms.
Other products can be hidden sources of gluten. You may take in small amounts of gluten if you consume these products, use them around your mouth, or transfer them from your hands to your mouth by accident. Products that may contain gluten include
- children’s modeling dough, such as Play-Doh
- cosmetics
- lipstick, lip gloss, and lip balm
- skin and hair products
- toothpaste and mouthwash
- communion wafers
Reading product labels can sometimes help you avoid gluten. Some companies label their products as being gluten-free. In the United States, products labeled gluten-free must have less than 20 parts per million of gluten, which should not be a problem for the vast majority of people. If a label doesn’t tell you what is in a product, ask the company that makes the product for an ingredients list. You cannot assume that the product is gluten-free.
Gluten-degrading enzymes
Enzyme supplement therapy with bacterial prolyl-endopeptidases expressed by various microorganisms has been proposed to accelerate gluten digestion in the gastrointestinal tract and thus to destroy T cell epitopes[rx]. Prolyl-endopeptidases are proline-specific enzymes capable to cleave gluten peptides. Actually, there are introduced into clinical trials two drug candidates, ALV003 and AN-PEP (Aspergillus niger prolyl-endoprotease). Recent data on results of two phases 1 clinical trials have revealed that pre-treating gluten with ALV003 eliminates the peripheral blood T cell response in celiac disease patients, suggesting the potential therapeutic utility of gluten-specific enzymes to treat celiac disease[rx]. Currently is undergoing clinical phase IIa testing showing significantly reduce gluten-related T-cell responses compared with placebo but without a significant reduction of symptoms typically induced by the gluten[rx].
AN-PEP is an enzyme that degrades gluten peptides efficiently in a pH compatible with that found in the stomach. Therefore this enzyme might be suitable for oral supplementation but further studies are necessary[rx].
Modified grains
Can be developed either through selective breeding of early wheat species or using small interfering RNA (siRNA) technology to mutate or silence immunostimulatory sequence[tx].
Blocking gluten entry across the intestinal epithelium
Zonulin inhibitor larazotide (AT-1001) corrects intestinal barrier defects. It has been explored in an animal model[rx]. AT-1001 is currently the best-studied pharmacologic agent to treat patients with celiac disease, actually undergone in phase II clinical trials[rx]. It has been shown that patients treated with AT-1001 had an improved symptom score, a less pronounced autoantibody response and pro-inflammatory production, and lower urinary nitrate excretion when compared with the placebo controls[rx].
Rho/Rho-kinase inhibition
It has been clarified that the increase in intestinal permeability is dependent on Rho kinase (ROCK) activity[rx]. In addition to regulating tight junction structure and function, ROCK is known to regulate axon growth[rx,rx]. The drug could be used to establish whether ROCK inhibition can reverse the gluten-dependent increase in intestinal permeability in these patients[rx].
Immunotherapy
The first observation of the occurrence of celiac disease following allogeneic bone marrow transplantation performed in a patient with acute leukemia, made evident the involvement of T-lymphocyte in the pathogenesis of this condition[rx]. Since then, a lot of acknowledgments have been acquired such that many efforts are being made to develop immunologic therapeutic tools. Cytokine therapies based either on amplification of regulatory cytokines or on blockage of inflammatory cytokines expression are largely diffused for management of severe autoimmune disorders. Also for celiac disease resistant to dietary approach and especially for refractory celiac disease, the use of immunomodulators is developing. IL-15 blocking antibodies have shown the capability to induce intra-epithelial lymphocytes apoptosis in the intestinal epithelium of human IL-15 transgenic mouse models[rx].
Continues RX
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Treatment with a gluten-free diet should be started only after the diagnosis has been established by intestinal biopsy.
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A dietitian experienced in treating celiac disease should be involved.
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Symptoms may improve rapidly while serologic tests may take up to 12 months to normalize on the gluten-free diet.
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For some individuals, even a small amount of gluten (i.e., 100 mg) can damage the small intestine. Note that a slice of bread contains approximately 2.5 grams of gluten.
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It can be difficult to adhere to the gluten-free diet, as gluten is found in many foods and other ingested products. Some hidden sources of gluten:
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Non-starchy foods such as soy sauce and beer
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Non-food items such as some medications and cosmetics (e.g., lipstick)
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Nutritional deficiencies and metabolic bone disease should be treated in the usual manner.
Therapies Under Investigation
Several novel therapeutic approaches that potentially could be used as alternatives for or additives to a gluten-free diet are being investigated (reviewed in Castillo et al [2015] and Rashtak & Murray [2012]):
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Larazotide, a tight junction regulatory peptide that is considered to prevent the passage of gliadin peptides into the mucosa. This drug is in clinical trials.
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Peptides that block the binding groove of DQ2 and DQ8 to prevent activation of gluten-sensitive T cells. The viability of this approach is currently uncertain.
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Transglutaminase (tTG) inhibitors
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Cytokine blockers, particularly for refractory celiac disease. Of particular interest is an anti-IL15 antibody.
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Drugs that selectively inhibit leukocyte adhesion and migration of lymphocytes into inflamed tissues
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Detoxifying gluten, using oral proteases. Latiglutenase, a glutenous, is currently in clinical trials.
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Gluten-sequestering polymers. An oral polymeric resin, P(HEMA-co-SS), binds to gluten and is under study.
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Gluten tolerization. A peptide-based vaccine could desensitize or induce tolerance in individuals with celiac disease. A prototype vaccine, Nexvax2, involving a set of gluten peptides recognized by HLA-DQ2, is in clinical trials.
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Rho/Rho-kinase inhibition to theoretically reverse the gluten-dependent increase in intestinal permeability [Sollid & Khosla 2011]
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Antibodies to proteins involved in autoimmune pathologies, including anti-IFN-γ, anti-CD3, anti-CD20 therapy, and anti-IL-15. [Sollid & Khosla 2011]
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Another approach: interfering with the homing of gluten-specific T cells to the gut mucosa by using CCR9 antagonists. A Phase II clinical trial is listed in Sollid & Khosla [2011].
Follow-up
Your doctor may recommend regular follow-up visits to make sure symptoms and health problems related to celiac disease are improving on a gluten-free diet. Follow-up may include blood tests to check levels of certain antibodies, which are higher in untreated celiac disease but typically return to normal after treatment. In some cases, doctors may recommend additional biopsies to find out if the small intestine has healed.
What if a gluten-free diet isn’t working?
If you continue to have celiac disease symptoms while you are following a gluten-free diet, talk with your doctor or a registered dietitian, who can help you find the cause. In about 20 percent of people with celiac disease, symptoms continue or come back even while they are following a gluten-free diet.7 Symptoms may be caused by consuming small amounts of gluten, other health problems, or refractory celiac disease.
Consuming small amounts of gluten
If your symptoms continue or come back after you start a gluten-free diet, you may still be eating or drinking a small amount of gluten. Keep a food journal and talk with your doctor and a registered dietitian about your diet and products you use that might contain gluten. Finding and avoiding all sources of gluten may help your symptoms improve. Hidden sources of gluten include additives made with wheat, such as
- modified food starch
- malt flavoring
- preservatives
- stabilizer
Other health problems
Your doctor may order tests to confirm the diagnosis of celiac disease and check for other health problems. Health problems that cause symptoms similar to those of celiac disease and may occur along with celiac disease include irritable bowel syndrome, lactose intolerance, microscopic colitis, problems with the pancreas, or small intestinal bacterial overgrowth.
Refractory celiac disease
Refractory celiac disease is a rare condition in which symptoms and damage to the small intestine continue or come back, even while a person is following a strict gluten-free diet. Refractory celiac disease may lead to complications, such as malnutrition or a type of cancer called enteropathy-associated T-cell lymphoma.
Therapies Under Investigation
Other tests include looking at the impact of malabsorption (due to celiac disease). The following can be monitored: full blood count, iron stores, folate, ferritin, levels of vitamin D and other fat-soluble vitamins, and bone mineral density.
Several novel therapeutic approaches that potentially could be used as alternatives for or additives to a gluten-free diet are being investigated (reviewed in Castillo et al [2015] and Rashtak & Murray [2012]):
-
Larazotide, a tight junction regulatory peptide that is considered to prevent the passage of gliadin peptides into the mucosa. This drug is in clinical trials.
-
Peptides that block the binding groove of DQ2 and DQ8 prevent activation of gluten-sensitive T cells. The viability of this approach is currently uncertain.
-
Transglutaminase (tTG) inhibitors
-
Cytokine blockers, particularly for refractory celiac disease. Of particular interest is an anti-IL15 antibody.
-
Drugs that selectively inhibit leukocyte adhesion and migration of lymphocytes into inflamed tissues
-
Detoxifying gluten, using oral proteases. Latiglutenase, a glutenous, is currently in clinical trials.
-
Gluten-sequestering polymers. An oral polymeric resin, P(HEMA-co-SS), binds to gluten and is under study.
-
Gluten tolerization. A peptide-based vaccine could desensitize or induce tolerance in individuals with celiac disease. A prototype vaccine, Nexvax2, involving a set of gluten peptides recognized by HLA-DQ2, is in clinical trials.
-
Rho/Rho-kinase inhibition to theoretically reverse the gluten-dependent increase in intestinal permeability [Sollid & Khosla 2011]
-
Antibodies to proteins involved in autoimmune pathologies, including anti-IFN-γ, anti-CD3, anti-CD20 therapy, and anti-IL-15. [Sollid & Khosla 2011]
-
Another approach: interfering with the homing of gluten-specific T cells to the gut mucosa by using CCR9 antagonists. A Phase II clinical trial is listed in Sollid & Khosla [2011].
Search ClinicalTrials.gov in the US and www.ClinicalTrialsRegister.eu in Europe for information on clinical studies for a wide range of diseases and conditions.
What are the complications of celiac disease?
Long-term complications of celiac disease include
- accelerated osteoporosis NIH external link or bone softening, known as osteomalacia
- anemia
- malnutrition, a condition in which you don’t get enough vitamins, minerals, and other nutrients you need to be healthy
- nervous system problems
- problems related to the reproductive system
Rare complications can include
- adenocarcinoma, a type of cancer of the small intestine
- liver damage, which may lead to cirrhosis or liver failure
- non-Hodgkin lymphoma
In rare cases, you may continue to have trouble absorbing nutrients even though you have been following a strict gluten-free diet. If you have this condition, called refractory celiac disease, your small intestine is severely damaged and can’t heal. You may need to receive intravenous (IV) nutrients and specialized treatment.
It’s a common misconception that eating a little gluten will not harm you. Eating even tiny amounts can trigger symptoms of coeliac disease and increase your risk of developing the complications outlined below.
Malabsorption
Malabsorption (where your body does not fully absorb nutrients) can lead to a deficiency of certain vitamins and minerals. This can cause conditions such as:
- iron deficiency anaemia
- vitamin B12 and folate deficiency anaemia
- osteoporosis – a condition where your bones become brittle and weak
Malnutrition
As coeliac disease causes your digestive system to work less effectively, severe cases can sometimes lead to a critical lack of nutrients in your body. This is known as malnutrition, and can result in your body being unable to function normally or recover from wounds and infections.
If you have severe malnutrition, you may become fatigued, dizzy and confused. Your muscles may begin to waste away and you may find it difficult to keep warm. In children, malnutrition can cause stunted growth and delayed development.
Treatment for malnutrition usually involves increasing the number of calories in your diet and taking supplements.
Lactose intolerance
If you have coeliac disease, you’re more likely to also develop lactose intolerance, where your body lacks the enzyme to digest the milk sugar (lactose) found in dairy products. Lactose intolerance causes symptoms such as bloating, diarrhoea and abdominal discomfort.
Unlike gluten in coeliac disease, lactose does not damage your body. But you may get some gut-related symptoms when you eat foods containing lactose because you can’t digest it properly.
Lactose intolerance can be effectively treated by not eating and drinking dairy products that contain lactose. You may also need to take calcium supplements – dairy products are an important source of calcium, so you’ll need to compensate for not eating them.
Cancer
Cancer is a very rare but serious complication of coeliac disease.
Someone with coeliac disease has a slightly increased risk of developing certain cancers. Recent research shows that this increased risk is less than previously thought.
Cancers associated with coeliac disease are small bowel cancer, small bowel lymphoma and Hodgkin lymphoma. However, most people with coeliac disease will not develop any of these.
If you’ve been following a gluten-free diet for 3 to 5 years, your risk of developing these types of cancer is the same as that of the general population.
Coeliac disease in pregnancy
Poorly controlled coeliac disease in pregnancy can increase the risk of developing pregnancy-related complications, such as giving birth to a baby with a low birthweight.
How will I need to change my diet if I have celiac disease?
If you have celiac disease, you will need to remove foods and drinks that contain gluten from your diet. Following a gluten-free diet can relieve celiac disease symptoms and heal damage to the small intestine. People with celiac disease need to follow a gluten-free diet for life to prevent symptoms and intestinal damage from coming back. Your doctor or a registered dietitian can guide you on what to eat and drink to maintain a balanced diet.
If you or your child has been diagnosed with celiac disease, you may find support groups helpful as you learn about and adjust to a gluten-free lifestyle. Your doctor or a registered dietitian may be able to recommend support groups and other reliable sources of information.
What foods and drinks contain gluten?
Gluten occurs naturally in certain grains, including
- wheat and types of wheat, such as durum, emmer, semolina, and spelled
- barley, which may be found in malt, malt extract, malt vinegar, and brewer’s yeast
- rye
- triticale, a cross between wheat and rye
Gluten is found in foods that contain ingredients made from these grains, including baked goods, baking mixes, bread, cereals, and pasta. Drinks such as beer, lagers, ale, flavored liquors, and malt beverages may also contain gluten.
Many foods such as colorings, flavorings, starches, and thickeners—are made from grains that contain gluten. These ingredients are added to many processed foods, including foods that are boxed, canned, frozen, packaged, or prepared. Therefore, gluten may be found in a variety of foods, including candy, condiments, hot dogs and sausages, ice cream, salad dressing, and soups.
Cross-contact
Cross-contact occurs when foods or products that contain gluten come into contact with gluten-free foods. Cross-contact can spread gluten to gluten-free foods, making the gluten-free foods unsafe for people with celiac disease to consume. Cross-contact can occur at any time, including when foods are grown, processed, stored, prepared, or served.
How can I identify and avoid foods and drinks that contain gluten?
A registered dietitian can help you learn to identify and avoid foods and drinks that contain gluten when you shop, prepare foods at home, or eat out.
For example, when you shop and eat at home
- carefully read food labels to check for grains that contain gluten—such as wheat, barley, and rye—and ingredients or additives made from those grains.
- check for gluten-free food labeling.
- don’t eat foods if you aren’t sure whether they contain gluten. If possible, contact the company that makes the food or visit the company’s website for more information.
- store and prepare your gluten-free foods separately from other family members’ foods that contain gluten to prevent cross-contact.
When you eat out at restaurants or social gatherings
- before you go out to eat, search online for restaurants that offer a gluten-free menu.
- review restaurant menus online or call ahead to make sure a restaurant can accommodate you safely.
- at the restaurant, let the server know that you have celiac disease. Ask about food ingredients, how food is prepared, and whether a gluten-free menu is available. Ask to talk with the chef if you would like more details about the menu.
- when attending social gatherings, let the host know you have celiac disease and find out if gluten-free foods will be available. If not, or if you are unsure, bring gluten-free foods that are safe for you to eat.
What should I eat if I have celiac disease?
If you have celiac disease, you will need to follow a gluten-free diet. Your doctor and a registered dietitian can help you plan a healthy, balanced diet to make sure that you get the nutrients you need.
Gluten-free foods
Many foods, such as meat, fish, fruits, vegetables, rice, and potatoes, without additives or some seasonings, are naturally gluten-free. Flour made from gluten-free foods, such as potatoes, rice, corn, soy, nuts, cassava, amaranth, quinoa, buckwheat, or beans are safe to eat.
You can also buy packaged gluten-free foods, such as gluten-free types of baked goods, bread, and pasta. These foods are available from many grocery stores, restaurants, and at specialty food companies. Packaged gluten-free foods tend to cost more than the same foods that have gluten, and restaurants may charge more for gluten-free types of foods.
Talk with your doctor or a registered dietitian about whether you should include oats in your diet and how much. Research suggests that most people with celiac disease can safely eat moderate amounts of oats. If you do eat oats, make sure they are gluten-free. Cross-contact between oats and grains that contain gluten is common and can make oats unsafe for people with celiac disease.
Gluten-free labeling
The U.S. Food and Drug Administration (FDA) requires that foods labeled gluten-free meet specific standards. One requirement is that foods with the terms gluten-free, no gluten, free of gluten, or without gluten on the label must contain less than 20 parts per million of gluten. This amount of gluten is too small to cause problems in most people with celiac disease.
The FDA rule does not apply to foods regulated by the U.S. Department of Agriculture, including meat, poultry, and some egg products. The rule also does not apply to most alcoholic beverages, which are regulated by the U.S. Department of the Treasury.
Should I start a gluten-free diet before I talk with my doctor?
No. If you think you might have celiac disease, you should talk with your doctor about testing to diagnose celiac disease before you begin a gluten-free diet. If you avoid gluten before you have tested, the test results may not be accurate.
Also, if you start avoiding gluten without advice from a doctor or a registered dietitian, your diet may not provide enough of the nutrients you need, such as fiber, iron, and calcium. Some packaged gluten-free foods may be higher in fat and sugar than the same foods that contain gluten. If you are diagnosed with celiac disease, your doctor and dietitian can help you plan a healthy gluten-free diet.
If you don’t have celiac disease or another health problem related to gluten, your doctor may not recommend a gluten-free diet. In recent years, more people without celiac disease have begun avoiding gluten, believing that a gluten-free diet is healthier or could help them lose weight. However, researchers have found no evidence that a gluten-free diet promotes better health or weight loss for the general population.
Screening of persons at risk for celiac disease
Asymptomatic/atypical manifestations
- first-degree relatives 10 – 20%
- Down syndrome 5 – 12%
- Ullrich–Turner syndrome 2 – 5%
- Williams–Beuren syndrome 9%
- selective IgA deficiency 2 – 8%
- autoimmune thyroiditis 3 – 7%
- autoimmune hepatitis (children) 12 – 13%
- type 1 diabetes 2 – 12%
- juvenile chronic arthritis 1.5 – 2.5%
Oligosymptomatic manifestations
- failure to thrive
- weight loss
- short stature / growth retardation
- delayed puberty (amenorrhea)
- iron-deficiency anemia
- anorexia
- dyspeptic symptoms (nausea/vomiting)
- chronic, recurrent abdominal pain (bloating)
- chronic constipation
- chronic fatigue/diminished performance
- recurrent aphthous sores
- chronic/intermittent diarrhea
- difficulty concentrating
- depressed mood
- chronic headache
- elevated transaminases
- tooth-enamel defects
- osteoporosis/osteopenia
Complications of classic celiac disease
- acute global/selective malabsorption (anemia and other consequences)
- somatic and psychosocial retardation
- impairment of quality of life
- infertility, miscarriage, preterm birth, low birth weight (rx)
- osteoporosis (rx)
- extraintestinal manifestations, e.g., neurological (cerebellar ataxia, peripheral neuropathy), renal (IgA nephropathy), pulmonary (pulmonary hemosiderosis)
- autoimmune diseases (type 1 diabetes, autoimmune thyroiditis) (rx)
- cancer, particularly enteropathy-associated T-cell lymphoma (EATL) (rx)
- increased mortality (39, 40)
FUTURE TREATMENT APPROACHES
Hydrolysis of toxic gliadin peptide
Prolyl endopeptidases – Prolyl endopeptidases (PEPs) are endoproteolytic enzymes expressed in micro-organisms and plants. These enzymes cleave proline-rich gluten to smaller peptides that are ready for digestion by intestinal brush-border enzymes (aminopeptidases and carboxypeptidases). Limited efficiency was found, since PEP required 3 h preincubation with gluten containing foods to achieve full detoxification of peptides and to prevent intestinal transport of active gluten fragments[rx]. This is unlikely to be achieved by co-administration of PEP and gluten-containing diet.
A two-stages cross-over phase II clinical trial was performed using asymptomatic CD patients eating, a slice of bread daily and a slice of bread pre-treated with PEP daily[rx]. After 2 wk of PEP-treated gluten challenge, the majority of patients did not develop malabsorption, measured by fecal fat excretion and D-xylose malabsorption tests. The tests likely lacked the necessary sensitivity to assess minor malabsorption resulting from active CD, since no histological confirmation was performed to determine deterioration in the Marsh grading[rx]. When PEPs were consumed as jam spread on a slice of gluten-containing bread by CD patients, villous blunting was seen in small bowel biopsy histological evaluation in most patients[rx]. Further studies are needed to determine the appropriate dose of enzyme and time of administration relative to the quantity of ingested gluten.
ALV003 – ALV003, a mixture of two glutenases, an endoprotease from germinating barley and PEP, was pretreated with wheat flour and tested in CD patients[rx]. Symptoms typically associated with gluten ingestion were not significantly reduced by ALV003 pre-treatment, but ALV003 abolished immune responses induced by gluten in CD patients. A randomized controlled phase IIa clinical trial has been performed where CD patients received either ALV003 or placebo daily for 6 wk at the time of 2 g gluten contained bread. This proof-of-concept study demonstrated that ALV003 can attenuate gluten-induced small intestinal mucosal injury in CD patients[rx]. After six weeks period, biopsies proved lower small intestinal mucosal injury in patients treated with ALV003 than placebo-treated patients despite of persistent intestinal inflammation in many patients on a strict GFD. Placebo-treated patients were found to have suffered more adverse events, most commonly including abdominal distention, flatulence, eructation, abdominal pain and diarrhea[rx].
Lactobacilli – Lactobacilli added to sourdough for fermentation are able to lyse the proline-/glutamine-rich gluten peptides and thus decrease immunotoxicity[rx–rx]. A mixture of fermented wheat flour with oat, millet and buckwheat allows sourdough bread to retain its baking characteristics. A pilot study in patients with CD suggested that this bread was well tolerated[rx]. However, these patients were challenged for only 2 d, which is clearly not sufficient to draw any firm conclusions. Hence, another 60-d diet of fully hydrolyzed wheat flour with sourdough lactobacilli and fungal proteases (8 ppm residual gluten; n = 5) was further studied. The pretreated flour was rendered non-toxic by serological, morphometrical, and immunohistochemical analysis[rx]. A larger group of subjects in the trial and palatability of digested flour baked products needs to be taken into consideration.
VSL3 – VSL3 is a probiotic containing lyophilised bacteria, including bifidobacteria (Bifidobacterium longum, Bifidobacterium infantis and Bifidobacterium breve), lactobacilli (Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus delbrueckii subsp., Lactobacillus bulgaricus and Lactobacillus plantarum) and Streptococcus salivarius subsp., Thermophiles. It is used to hydrolyse gliadin peptides in pre-treated flour and tested for efficacy in rat intestinal cell line and celiac jejunal biopsies[rx]. VSL3 pre-digested gliadins did not show an increase of the infiltration of CD3+ intraepithelial lymphocytes and caused a less pronounced effect on intestinal mucosa permeability (determined by lower F-actin rearrangement and zonulin release). Hence, VSL#3 may have importance during food processing to produce pre-digested gluten-free products.
Prevention of toxic gliadin peptide absorption
Larazotide – Larazotide (AT-1001, Alba Therapeutics, Baltimore, MA), is a synthetic hexapeptide derived from Zonula Occludens toxin of Vibrio cholera[rx]. It is used to inhibit the opening of tight junctions of the small intestine epithelial cells. Clinical trial phase I in CD patients suggested that Larazotide therapy is well tolerated by patients and reduces intestinal barrier dysfunction, proinflammatory cytokine production, and gastrointestinal symptoms in CD individuals after gluten exposure[rx]. Encouraging results were obtained from a 6-wk phase IIb trial in terms of symptoms and antibody titers[rx], showing larazotide acetate a promising drug candidate. This drug inhibits the paracellular route of gliadin absorption through tight junctions, which is not the only mechanism of gliadin absorption. Indeed, gliadin may gain access to the mucosa through transcellular pathways in addition to paracellular route[rx,rx]. Hence, this strategy might be best exploited in combination with other treatments.
Synthetic polymer poly (hydroxyethylmethacrylate-co-styrene sulfonate) – Poly (hydroxyethylmethacrylate-co-styrene sulfonate) [P (HEMA-co-SS)] forms supra-molecular particles upon gliadin complexation in gastric and intestinal conditions[rx,rx], and deteriorates gliadin’s effect on epithelial cells[rx]. This complexation decreases the effect of gastrointestinal (GI) digestive enzymes on gliadin absorption, and thus the formation of immunogenic peptides is reduced. Gluten-sensitive HLA-HCD4/DQ8 mice co-administered with P (HEMA-co-SS) showed attenuated gliadin-induced changes in permeability and inflammation[217]. Low side effect, cost and possibility to be taken, occasionally with gluten-containing food, makes it an attractive option. Further investigation of the mechanisms of action and its interaction with human tissues is required before its efficacy is investigated in human trials[rx].
Anti-gliadin egg yolk antibody – Oral antibody passive immunotherapy may be of value due to the advantages of reduced cost, ease of administration, and potential to treat localized conditions in the gastrointestinal tract[rx]. Among antibodies, chicken egg yolk immunoglobulin (IgY), is ideal for passive immunotherapy, as it may be readily obtained in large quantities from egg yolk, presenting a more cost-effective, convenient, and hygienic alternative to mammalian antibodies. Oral immunotherapeutic IgY is a promising alternative to neutralize gliadin in the GI tract and prevention it from absorption[rx]. Mannitol contained antibody preparation is highly resistant against GI enzymes and proved to effectively neutralized gliadin under simulated GI conditions in the presence of food. In vivo study; BALB/c mice fed with IgY formulation and gliadin ratio of 1:5 (w/w), demonstrated that gliadin absorption in the gastrointestinal tract was minimal at < 1%[rx]. Further investigations in CD patients is requires to prove its efficacy and determine dosing regimen of antibody relative to the amount of gliadin ingestion.
Blockage of selective deamidation of specific glutamine residues by tissue transglutaminase 2 inhibitor
Transglutaminases (a family of eight enzymes) have diverse functions in human and are involved in several biological and pathological processes[rx]. tTG2 is an enzyme that has a pro-inflammatory effect and increases the immunostimulatory epitopes present in the lamina propria of the small intestine. Blockage of tTG2 may be a promising approach to inhibit the inflammatory process upon gluten ingestion. There are two essential classes of tTG2 inhibitors; irreversible and reversible inhibitors[rx]. Irreversible inhibitors form a stable covalent bond with this enzyme, and thus prevent deamidation of gliadin peptides[rx,rx]. Reversible inhibitors are more desirable to minimize possible side effects. These include aldehyde-bearing tTG modulators[rx], cinnamoyl triazole derivatives[rx], and the highly specific modified peptide targeting the active cysteine site of tTG2[rx]. Since a few gluten T-cell epitopes can be recognized without being deamidated by tTG2[rx,rx], this approach will not inhibit the innate response[rx], or the immune response induced by non-deamidated peptides[rx]. To be able to use tTG2 inhibitors clinically, it is critical to design highly specific inhibitors, since all human tTG share high sequence homology.
Vaccine application to restore immune tolerance towards gluten
Autoimmune enteropathy in CD has been proposed to be due to impairment of immunoregulatory mechanisms that controls oral tolerance. Systematic peptide mapping of T-cell was performed to determine gliadin reactive epitopes recognized by approximately 90% of CD patients. A clinical trial phase I study has been initiated as Nexvax2 (Nexpep Pty, Ltd., Australia) peptide vaccine-containing mixture of immunotoxic α- and ω-gliadins and B-hordein[rx].
Engineered Lactococcus lactis secreting a DQ8-re-stricted gliadin peptide administered orally[rx], or recombinant α-gliadin in HLA-DQ8 administered intranasally in transgenic mouse model[rx], have been studied to modulate immune response to gluten. However, it is difficult to appreciate how the vaccine or the intranasal peptide administration can modulate the Tr1 response. More work is needed to assess the effect of these therapies on the spectrum of gluten peptides presented to the gut.
Dermal inoculation of human hookworm (Necator americanus) has also been used to modulate the immune response to gluten[rx]. A phase II trial with CD patients suggested that hookworm infection on its own may not obviate the necessity for a restricted diet in CD, but appears to be safe and might impact on immune pathology[rx]. Here in, hookworm infection is expected to reduce gluten sensitivity and immune reactivity.
Modulation of immune response to dietary gliadin
HLA-DQ blocker: HLA-DQ blocker is used to block the binding sites of HLA-DQ2 or DQ8 for it to be unrecognized by T cells as well to block the presentation of the antigen. This is not a new concept that was developed without much success to treat type 1 diabetes mellitus and rheumatoid arthritis, due to difficulties in effective drug delivery[rx,rx]. By amino-acid substitution of gliadin T-cell stimulatory sequence, the epitope can be converted to an agonist or antagonist, abolishing the inflammatory cascade[rx]. IFN-γ production by peripheral blood lymphocytes was prevented when either an alanine or lysine amino acid was substituted through the immunodominant α-gliadin peptide, corresponding to the peptide’s anchor to the HLA-DQ cleft[rx]. To develop this as a new therapeutic agent, more studies need to be performed, looking at the mass T-cell action of the gut towards these modified peptides.
Interleukin blocker – Modulation of cytokine production has been evaluated for the treatment of several autoimmune diseases, although their side effects may be severe. Modulation of proinflammatory IL-15 and anti-inflammatory IL-10 cytokines has been suggested to influence the immune balance between tolerance and autoimmunity[rx,rx–rx]. Blocking IL-15 may promote maintenance of epithelial integrity, limit epithelial destruction, leading to decreased passage of dietary gliadin.
NKG2D antagonists – MICA molecules, strongly expressed on active CD epithelial cell surface upon gliadin challenge[rx], interact with the NKG2D-activating receptor on human natural killer cells and CD8 T cells, leading to villous atrophy due to an IEL-mediated damage to enterocytes[rx,rx]. Thus, NKG2D antagonists[rx] and anti-NKG2D antibodies[rx], have been proposed as therapeutics in CD.
Restoration of intestinal architecture by R-spondin-1
R-spondin-1 is an intestinal mitogen, shown to stimulate crypt cell growth, accelerate mucosal regeneration and restore intestinal architecture in mouse models of colitis[rx]. This agent has yet to be tested in human to be considered as a therapeutic agent in CD.
Lifestyle and home remedies
If you’ve been diagnosed with celiac disease, you’ll need to avoid all foods that contain gluten. Ask your doctor for a referral to a dietitian, who can help you plan a healthy gluten-free diet.
Read labels
Avoid packaged foods unless they’re labeled as gluten-free or have no gluten-containing ingredients, including emulsifiers and stabilizers that can contain gluten. In addition to cereals, pastas and baked goods, other packaged foods that can contain gluten include:
- Beers, lagers, ales and malt vinegars
- Candies
- Gravies
- Imitation meats or seafood
- Processed luncheon meats
- Rice mixes
- Salad dressings and sauces, including soy sauce
- Seasoned snack foods, such as tortilla and potato chips
- Seitan
- Self-basting poultry
- Soups
Pure oats aren’t harmful for most people with celiac disease, but oats can be contaminated by wheat during growing and processing. Ask your doctor if you can try eating small amounts of pure oat products.
Allowed foods
Many basic foods are allowed in a gluten-free diet, including:
- Eggs
- Fresh meats, fish and poultry that aren’t breaded, batter-coated or marinated
- Fruits
- Lentils
- Most dairy products, unless they make your symptoms worse
- Nuts
- Potatoes
- Vegetables
- Wine and distilled liquors, ciders and spirits
Grains and starches allowed in a gluten-free diet include:
- Amaranth
- Buckwheat
- Corn
- Cornmeal
- Gluten-free flours (rice, soy, corn, potato, bean)
- Pure corn tortillas
- Quinoa
- Rice
- Tapioca
- Wild rice
Complications of Coeliac disease
Untreated, celiac disease can cause
- Malnutrition – This occurs if your small intestine can’t absorb enough nutrients. Malnutrition can lead to anemia and weight loss. In children, malnutrition can cause slow growth and short stature.
- Bone weakening – Malabsorption of calcium and vitamin D can lead to a softening of the bone (osteomalacia or rickets) in children and a loss of bone density (osteopenia or osteoporosis) in adults.
- Infertility and miscarriage – Malabsorption of calcium and vitamin D can contribute to reproductive issues.
- Lactose intolerance – Damage to your small intestine might cause you abdominal pain and diarrhea after eating or drinking dairy products that contain lactose. Once your intestine has healed, you might be able to tolerate dairy products again.
- Cancer – People with celiac disease who don’t maintain a gluten-free diet have a greater risk of developing several forms of cancer, including intestinal lymphoma and small bowel cancer.
- Nervous system problems – Some people with celiac disease can develop problems such as seizures or a disease of the nerves to the hands and feet (peripheral neuropathy).
References
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