Definition of celiac disease
Celiac (pronounced ‘seel-ee-ak’) disease, also sometimes called celiac sprue, non-tropical sprue or gluten-sensitive enteropathy, is an autoimmune disease that causes genetically susceptible individuals to negatively respond to gluten. Gluten is a protein found naturally in grains like wheat, rye, barley and oats and is common in foods such as bread, pasta, cookies and cakes. Gluten is also used in some vitamins, nutritional supplements, medicines and lip balms.
When people with celiac disease eat foods or use products containing gluten their immune system produces certain antibodies. These antibodies destroy or damage the inner lining of the small intestine. The small, finger-like projections along the lining of the small intestine that absorb nutrients, called villi, become inflamed and flattened. This is referred to as villous atrophy. Villous atrophy reduces the surface area of the bowel available for nutrient absorption, which can lead to various gastrointestinal and malabsorptive symptoms.
Celiac disease affects each person differently. Symptoms may occur in the digestive system, or in other parts of the body. One person might have diarrhoea and abdominal pain, while another person may be irritable or depressed. A number of serious health consequences can result if the condition is not diagnosed and treated properly.
Difference between celiac, non-celiac gluten sensitivity and wheat allergy
Celiac disease is not a food allergy or intolerance, it is an autoimmune disease where the body’s immune system attacks itself when gluten is eaten. This causes damage to the linings of the gut and means that the body cannot properly absorb nutrients from food.
Non-celiac gluten sensitivity, also known as gluten intolerance, also cause the body to have a negative response to gluten and the symptoms are similar to celiac disease. But it is not clear how the immune system might be involved because no antibodies are produced and the gut lining does not appear to be damaged.
Wheat allergy is a reaction to a number of food proteins found in wheat, including gluten, triggered by the immune system and usually occurs within seconds or minutes of eating. Unlike celiac disease, this immune response is most often temporary and does not cause on going harm to the small intestine unless the reaction causes anaphylaxis, the most serious type of allergic reaction.
Unlike celiac, gluten intolerance and wheat allergy doesn’t usually cause long-term harm to the body.
Causes and risks of developing celiac disease
Celiac disease can develop at any age after people start eating foods or medications that contain gluten and it affects both men and women. Genetic factors, autoimmunity and environmental factors like gluten exposure play an important role. Almost all people who develop celiac disease are born with a genetic predisposition for this disease. The two genes most closely linked to celiac disease are HLA DQ2 and HLA DQ8. Nearly everyone who is diagnosed with celiac disease carries at least one of these two genes. But not everyone who carries HLA DQ2 and HLA DQ8 develops celiac disease and in very rare cases, a person will not have these genes but might develop celiac disease anyway. Celiac disease runs in families that means a first-degree relative with celiac disease (parent, child, sibling) has a about a 10% chance of developing celiac disease as well. I addition people with autoimmune diseases such as type 1 diabetes and autoimmune thyroid disease are at increased risk for celiac disease. There are also a number of other autoimmune disorders linked to celiac disease.
How celiac disease affects the digestive system
The normal process of digestion is to take in food, then grind and digest this food to absorb nutrients and eliminate the resulting waste. This works because digestion breaks the nutrients into simple compounds. These compounds are then absorbed and used for energy and building new tissue. Much of the small intestine is covered in projections called villi that increase the surface area of the tissue available to absorb nutrients from the gut contents, so the majority of nutrient and energy absorption happens in the small intestine.
When someone eats something with gluten (i.e. wheat, barley, rye, etc.), it goes through this normal digestion process and the gut breaks down the gluten, which is made up of many different proteins. The two main types of proteins formed by breaking down gluten are gliadin and glutenin. This is normally not a problem and is further broken down by the immune system into amino acids and then absorbed by the body to be used to make own proteins. In individuals with celiac disease the presence of gliadin, which appears to be the primary cause of celiac disease, does something different. It initiates a hyperactive immune response where the body not only attacks the molecule that’s seen as a “foreign body”, it also attacks the mucosa (lining) of the small intestine and this causes inflammation of the villi (little finger-like projections lining the wall of the intestines), referred to as villous atrophy. As a result of this inflammation, the surface area of the small intestine, which enables the absorption of nutrients and minerals, is seriously reduced. And as the small intestine is primarily involved in absorbing those nutrients received from breaking down the food, this process will be compromised. Individual won’t be getting as many nutrients from the food as they should be getting. This is called malabsorption.
The result of celiac disease on general health
The body requires a steady supply of nutrients to build, repair, and maintain itself, to produce energy, enzymes, hormones, proteins, cells, tissues and bone, and to fight infections. Nutrients come from the diet and include many essential vitamins and minerals (micronutrients). If the intestines, like in celiac disease, are unable to or prevented from absorbing nutrients, then the nutrients are eliminated from the body in the stool resulting in malabsorption. Because of that people with untreated celiac disease often are deficient in iron, calcium, zinc, copper, magnesium, folic acid, vitamin B3, vitamin B6, vitamin B-12 and vitamin D.
It’s also quite common that blood tests in those with celiac show iron deficiency. The body needs iron to make red blood cells, which carry oxygen around the body. If the body doesn’t have enough haemoglobin, the tissues and muscles won’t get enough oxygen to be able to work effectively. This leads to a condition called anaemia, causing a feeling of tiredness, shortness of breath and affected persons may also complain of fatigue and weakness.
In newly diagnosed celiac disease patients, secondary lactose intolerance is also quite common due to the loss of lactase, an enzyme that digests milk sugar along the lining of the small intestine. The damage that gluten causes in the small intestine is the main factor in the lack of lactase for people with celiac disease. While following a strict gluten-free diet, the gut is able to heal, making lactose intolerance temporary in most celiac disease patients.
Unexplained weight loss is also a common side effect of undiagnosed or untreated celiac disease and many people with this condition also have trouble maintaining a healthy weight.
Celiac disease is a systemic long-term autoimmune disorder that primarily affects the small intestine but also other body systems and organs. Long-standing and untreated this condition may lead, because of the intestinal damage, to other serious complications.
Structures and pathways involved in this disease
Digestive system and Excretory system
Next to the damage that gluten causes in the small intestine and the common gastrointestinal problems, such as bloating, chronic diarrhea, pale, foul-smelling stools, abdominal pain and stomach ulcers, individuals with diagnosed celiac could also have irritable bowel syndrome (IBS) and a slightly increased risk of developing small bowel cancer.
But celiac disease not only affects the intestine, it can also cause aphthous ulcers (canker sores) in the mouth, dental enamel defects, delayed dental development and more cavities in children. It is also not unusual for people who just got diagnosed with celiac disease that they have mildly elevated liver enzymes, which sometimes but not always, indicates a problem with the liver. But as soon as gluten is eliminated from the diet these enzymes typically return to normal levels. Celiac is also associated with a higher risk of more serious liver conditions, ranging from fatty liver disease to severe liver failure. Many who suffer from celiac disease also experience issues with their gallbladder. For those of them who don’t stick to a gluten-free diet have shown that gallbladders don’t empty properly following a fatty meal, potentially resulting in the development of cholesterol gallstones. Although having celiac disease can have an impact on how the gallbladder functions, it does not mean that they are at a higher risk of developing gallbladder disease. Furthermore it also has been shown that patients with celiac disease have an increased risk of developing pancreatitis.
Circulatory system / Cardiovascular system
The condition of celiac disease can also have and effect on the cardiovascular system. Research has shows that people with celiac disease may have a higher risk of coronary artery disease (narrowing or blockage of the coronary arteries) and celiac disease has also been linked to irregular heartbeats and possible heart failure.
Endocrine system
Patients with celiac disease are also at a greater risk of developing endocrine disorders, such as Typ1 diabetes mellitus (a chronic condition in which the pancreas produces little or no insulin) and thyroid diseases such as Hashimoto’s thyroiditis (a autoimmune disorder that can cause hypothyroidism or underactive thyroid).
Integumentary system / Exocrine system
Also the skin can be affected for those with celiac, causing an itchy, blistering rash known as dermatitis herpetiformis. Lesions can sting and burn as well and appear anywhere but occur most often on the elbows, knees, buttocks, lower back and the back of the neck and head. Besides dermatitis herpetiformis people with celiac disease may also have psoriasis, an autoimmune condition that causes thick, scaly red skin patches and discomfort on the skin. People with psoriasis often have high levels of antibodies to gluten circulating in their bloodstreams, which indicates that they are reacting to gluten in their diets even if they haven’t been diagnosed with celiac disease. Eczema, another itchy rash, occurs most often in children with celiac disease, but adults also can have this skin condition. Alopecia areata, an autoimmune condition in which the body attacks the hair follicles and causes the hair to fall out, also has been linked in research studies to celiac disease. Celiac patients have also a higher risk in developing chronic hives and often suffer from very dry skin and acne.
Immune system and lymphatic system
In celiac disease the immune system mistakes substances found inside gluten as a threat to the body and attacks the own tissues. People with one autoimmune disorder are prone to getting other autoimmune disorders. For people with celiac disease, the later the age of diagnosis the greater the chance of developing another autoimmune disorder.
The most common autoimmune disorders associated with celiac disease are Type 1 diabetes and thyroid diseases such as Hashimoto’s thyroiditis.
But there are also a number of other autoimmune disorders and other serious conditions linked to celiac disease, such as Addison’s disease (a disorder of the adrenal glands, causing them to produce insufficient amounts of cortisol and aldosterone), Arthritis (Arthritis is a general term for conditions that affect the joint or tissues around the joints, most types of arthritis cause pain and stiffness in and around the affected joint or joints), Idiopathic Dilated Cardiomyopathy (a condition in which the heart muscle becomes weakened and enlarged), Berger’s disease (is a disorder that forms clumps inside the kidneys tiny filters), Multiple Sclerosis (MS) and Sjogren’s Syndrome (an autoimmune disorder that affects the moisture-producing glands) and people who have Down Syndrome, a common genetic disorder, tend to develop celiac disease at rates far above those in the general population.
Celiac disease is an immune system condition and lymphocytes are part of the immune system, so it’s possible that a condition like celiac could cause cancer in those cells. Not everyone with celiac disease will get lymphoma. It’s more likely to get this cancer if someone gets celiac disease later in life and has more damage to the intestines.
Muscular system
Muscle weakness is common in celiac disease. It may stem from one or more nutrient deficiencies, associated disorders or complications
Nervous system
Celiac disease may initially present as one or more neurological signs and / or symptoms. On the other hand, it may be associated with or complicated by neurological manifestations. Neurological presentations are rare in children but many adults with celiac disease show neurological abnormalities. The most common neurological symptoms in people with celiac disease are ataxia and neuropathy. Ataxia includes clumsiness, loss of balance and uncoordinated movements leading to a tendency to fall and slurred speech. Neuropathy is damage or dysfunction of one or more nerves that typically results in numbness, tingling, muscle weakness and pain in the affected area. Other nervous system complications that can occur are epilepsy, dementia, cognitive disorders, depression, migraines and myopathy.
Renal system and Urinary system
Celiac disease furthermore has been implicated in a secondary cause of IgA nephropathy, also known as Berger’s disease, is a disorder that forms clumps inside the kidney’s filters.
Reproductive system
There is evidence that women with celiac disease may have a significantly increased risk of infertility and miscarriage or may have issues with late menarche or early menopause. But sticking to a gluten-free diet may be able to reduce the risk of reproductive problems in people with this disease.
Respiratory system
For some people with celiac disease eating gluten can cause the tonsils to enlarge and throat muscles to swell, which can lead to difficulty breathing.
Skeletal System
The small intestine is responsible for absorbing important nutrients, such as calcium. Calcium is essential for building and maintaining healthy bones. If the small intestine doesn’t heal because gluten is still consumed then some people with celiac disease, even if they consume enough calcium, are often deficient in this nutrient and might develop low bone density and then osteoporosis.
Fortunately, timely diagnosis of celiac disease and treatment with a gluten free diet can prevent or reverse many of the associated health conditions.
Possible symptoms of celiac disease
Celiac disease affects people differently and there are more then 300 known symptoms. Sign and symptoms may begin from early childhood to adulthood. While many with celiac disease may present these classic GI-tract symptoms such as abdominal pain, bloating, steatorrhea, constipation and diarrhoea, many others may not experience any of them at all. Instead they may complain of atypical symptoms such as joint pain, rashes or anaemia or experience psychological symptoms like having big moods swings, feeling easily irritated, angry or anxious or neurological symptoms such as headaches, foggy brain, slow thinking and cognitive difficulties. If symptoms of celiac are present they also can range from mild to severe and often come and go.
Physical symptoms
In classical celiac disease patients can experience gastrointestinal symptoms such as chronic or recurrent diarrhoea, steatorrhea (pale, foul-smelling, fatty stools), bloating, gas, feeling of fullness, constipation, nausea and vomiting, abdominal distension, abdominal pain, cramping as well as malabsorption and unexplained weight loss. They may also suffer from prolonged fatigue, weakness and lethargy, heartburn, anaemia usually from iron deficiency, vitamin and mineral deficiencies, loss of bone density or softening of bone, dental enamel defects, itchy and blistery skin rashes (dermatitis herpetiformis) and severe or recurrent mouth ulcers.
Neurological symptoms
Neurological manifestations of celiac disease relate to symptoms affecting the nervous system. The most common neurological symptoms reported by those suffering from celiac disease are brain fog (the feeling that the processes of thinking, understanding and remembering are not working as they should) and difficulty concentrating. Secondly most common reported are headaches and migraines. Also quite common celiac affected people experience is joint pain, tingling or numbness in the hands and / or feet. Less usual are problems with coordination (also called ataxia) and difficulty or pain when swallowing.
Psychological symptoms
Also a wide range of psychological symptoms can arise for patients with untreated celiac disease. These can include difficulties adjusting to the new diagnosis of chronic illness as well as dealing with adherence to a gluten-free diet and other aspects of disease management. Most people feel tired and fatigue after exposure to gluten. This is also the most common of non-GI symptoms. Other psychological symptoms can include feeling easily irritated, anxious or angry, panic attacks, lack of interest in eating or in food, feeling of sadness or depression, finding little or no pleasure in life, having big mood swings, having very low energy or experiencing a change in sleeping patterns.
Common symptoms in Children
Symptoms of celiac disease vary from child to child and can begin at any age. Infants and toddlers often tend to have more obvious symptoms, which usually manifest in the GI-tract. Symptoms include vomiting, bloating, irritability, poor growth, swollen belly, diarrhoea with very pale and foul-smelling stools and malnutrition. They can also be picky eaters and in addition not wanting to eat certain foods, because of the discomfort due to their inability to digest gluten. Vomiting is less common in school-age children than in infants and toddlers. School-age children may experience symptoms like constipation, trouble gaining weight or weight loss, abdominal distension, stomach cramps or abdominal pain and diarrhoea. Older children and teens may also have symptoms or concerning signs that are not obviously related to the intestinal tract, which are called atypical symptoms such as stunted growth, weight loss, delayed puberty, achy pain in the bones or joints, chronic fatigue, recurrent headaches or migraines, itchy skin rash (dermatitis herpetiformis), recurring mouth sores. Adolescents with celiac disease may also have mood disorders, including anxiety and depression, as well as panic attacks.
How celiac disease is diagnosed
In adults, the age at diagnosis is usually between 30 and 50. On average, the time between the first symptoms and diagnosis is about 11 years due to the wide range of non-specific symptoms and lack of symptoms in some people. Typically, celiac disease testing starts with antibody serology test. If positive, they are often followed up with an upper endoscopy to confirm the diagnosis. Genetic testing can also help rule out celiac disease.
It is important to not start a gluten-free diet prior being tested for coeliac disease. If gluten has been removed from the diet, a normal diet must be resumed for at least six weeks prior to testing. It is important the gluten challenge is carried out properly to ensure reliable testing results.
Blood tests (celiac serology)
Antibody serology test looks for certain antibodies in the blood. Elevated levels of certain antibody proteins indicate an immune reaction to gluten. Positive antibody tests alone are insufficient to diagnose coeliac disease and confirmation of the diagnosis by gastroscopy and small intestinal biopsy is needed. It might be also possible to have a positive blood test and not actually have celiac disease.
A small bowel biopsy
The only way to confirm a celiac disease diagnosis is to have an endoscopic biopsy (small tissue sample) of the small intestine that shows the damage to the villi, called villous atrophy. In the majority of cases, the bowel damage present in those with untreated coeliac disease is not visible to the naked eye. The biopsies are examined under a microscope to confirm the presence of villous atrophy. It is also possible to do a video capsule endoscopy (VCE), which is more sensitive at detecting macroscopic atrophies in comparison with regular upper endoscopy.
Gene testing (HLA genes)
Genetic testing is useful when the diagnosis is unclear. People with celiac carry one or both of the HLA DQ2 and HLA-DQ8 genes, but carrying these genes is not a diagnosis of celiac disease nor does it mean you will ever develop celiac disease. Just one in 40 people who carry one or both the HLA DQ2 and HLA DQ8 genes will develop this condition, so most people who are gene positive will never get coeliac disease. If the gene test is negative then coeliac disease can be excluded.
The problem of how celiac disease alters nutritional intake in a person
Anyone diagnosed with celiac disease must avoid foods containing gluten. Consuming even trace amounts of gluten can cause adverse reactions and damage to the lining of the gut. A gluten-free diet means to eliminate all foods that contain wheat, varieties and derivatives of wheat like durum, wheat berries, spelt, emmer, farina, graham, kamut, farro, semolina and einkorn wheat as well as other gluten containing grains like rye, barley, triticale, malt and possibly oats. Pure oats are gluten-free and safe for most people with gluten intolerance. However, oats are often contaminated with gluten because they may be processed in the same facilities as gluten-containing grains like wheat, rye, and barley. Some individuals with celiac disease do not tolerate even gluten-free oats. Common foods that contain gluten are pasta, noodles, breads and pastries, crackers, baked goods, cereal and granola, breakfast foods, breading and coating mixes, croutons and stuffings, sauces and gravies (many use wheat flour as a thickener), traditional soy sauce, flour tortillas, beer and malt beverages and also brewer’s yeast often contains gluten traces from barley. But also medications and non-food products like vitamin and mineral supplements, herbal and nutritional supplements, lip balms, toothpaste, mouthwash, play dough, envelope and stamp glue that contain gluten must be avoided.
Adhering a truly gluten-free diet is nearly impossible. For a food labeled as gluten-free, the FDA stated that it must contain no more then 20 parts per million (ppm) of gluten. The choice of 20 ppm rather than zero ppm is because current technology cannot reliably measure gluten presence below 20 ppm. Any product that has less than 20 ppm of gluten can carry the labels gluten-free, free of gluten, without gluten, no gluten. Also an ingredient that has been derived from a gluten-containing grain can be labeled as gluten-free if it has been processed to remove gluten and use of that ingredient results in the presence of less than 20 ppm of gluten in the food. If people with celiac wish to avoid all traces of gluten, it’s better for them to eat naturally gluten-free foods.
Many flours that contain gluten and most conventional (gluten-containing) pastas, cereals and breads made from flour are enriched with iron and B Vitamins. Unlike wheat flour, gluten-free flours typically made from rice flour, tapioca starch, sorghum flour or potato starch are not usually enriched or fortified. That means that these flours may contain much smaller amounts of B Vitamins and iron then whole grain or even highly processed white flour products. Therefore people with celiac disease, following a strict gluten-free diet, often miss out on some important nutrients like fiber, folic acid and iron.
Gluten-free versions of bread, pasta and cereal are notoriously low in fiber. Those with celiac should increase their intake of naturally gluten-free high fiber foods like vegetables, fruits, beans, sweet potatoes, nuts, chia, ground flax seeds and gluten-free grains such as quinoa, wild rice, amaranth and millet. Fiber helps the body to slow the absorption of sugar into the blood and improves digestion by maintaining regular bowel movements.
Celiac disease can damage the part of the small intestine where iron, folic acid and Vitamin B12 are absorbed and very few gluten-free flour, breads, cereals or pasta products are enriched with folic acid, iron or B12. The damage to the small intestine can lead to reduced nutrient absorption and in combination with the strict gluten-free diet people with celiac may not get enough of these nutrients. They need to consume more gluten-free foods rich in folic acid, such as dark green vegetables, legumes, asparagus, broccoli, beets lean beef and eggs. They also should increase foods high in iron like red meats, liver, egg yolk, shellfish, nuts, legumes, molasses, dried fruits and make sure that they eat enough Vitamin-B12-rich foods like liver, fish, meat, poultry and eggs.
Calcium and vitamin D are necessary for healthy bone mineralization and the prevention of osteopenia or osteoporosis in people with celiac disease. They need to make sure to get adequate calcium and vitamin D and avoid excessive use of alcohol. Good food sources of Vitamin D are oily fish, liver, eggs and cod liver oil and foods rich in calcium are leafy vegetables, egg yolk, shellfish, nuts, seeds and milk products.
When people are first diagnosed with coeliac disease, the lining of the gut still has the damage caused by eating gluten, which can mean that the body does not make enough lactase or people may not be able to digest lactose. Most people have different levels of tolerance to lactose, some can tolerate a little bit of milk or cheese and others have reactions that are so bad that they can’t eat any diary products at all. But once following a gluten free diet, the gut is able to heal and they will be able to digest lactose again. Therefore, lactose intolerance is usually temporary.
To avoid nutritional deficiencies, a person with celiac should be sure to consume a variety of nutritious and naturally gluten-free plant-based foods and consider taking supplements. Lowering fat intake by baking or broiling the foods whenever possible, rather then frying and decreasing sugar intake. Those with celiac should always carefully read food labels to check for grains that contain gluten. When eating packaged food they should choose the items with the least number of ingredients and check for gluten-free food labeling. It is also better to rely less on gluten-free processed foods and instead eat more whole foods. If it’s not sure whether a product contains gluten, then it might be a good idea to contact the company that makes the food or visit the company’s website for more information. It is also recommendable to store and prepare the gluten-free foods separately from other family member’s foods that contain gluten to prevent cross contact. Before going out in restaurants it can help to review the restaurants menus online or call ahead to make sure they can accommodate someone safely with celiac disease. When attending social gatherings people with celiac should let the host know they have celiac disease and find out if gluten-free foods will be available or just bring their own gluten-free foods. Planning ahead and preparing food in advance can also help to avoid drawbacks.
Possible outcomes of this condition
People with celiac disease remain sensitive to gluten throughout their life, so in this sense they are never cured. The long-term outlook having this disease can vary because some people have no symptoms, while others have severe malabsorption features. When patients diagnosed with celiac disease continue to have frequent symptoms and damage to the absorbing lining of the intestine despite following a gluten-free diet for more than a year, they are considered to have refractory celiac disease.
Overall, people with untreated or unresponsive celiac disease have increased early morality compared to the general population. Without diagnosis and treatment, celiac disease is ultimately fatal in 10 to 30 % of people. Currently this outcome is rare, as most people do well if they avoid gluten.
Even though celiac disease has no cure it can be managed by avoiding all sources of gluten. Once the gluten is eliminated form the diet, it reduces inflammation in the small intestine and the small intestine can begin to heal. The earlier the disease is found, the less time healing takes. Improvements begin within weeks of starting the diet and the small intestine is usually completely healed, meaning the villi are intact and working, in about 6 to 18 month. But studies also have shown that even after two years on gluten-free diet, 30-60 % of adults with celiac disease still have persistent gut damage. In rare cases there can be long-term damage to the lining of the intestines before the diagnosis is made.
A repeat biopsy should occur approximately 18 – 24 months after commencing treatment with a gluten free diet to confirm small bowel healing. A healthy looking biopsy is good and means the gluten free diet is being followed adequately, but it does not mean coeliac disease has been cured. Relapse will occur if gluten is reintroduced to the diet. Coeliac disease is for life, and a gluten free diet needs to be followed lifelong to maintain health.
Possible treatments for celiac disease
It seems that the only recognised medical treatment for celiac disease is to follow a strict, lifelong gluten-free diet.
As the damage to the small intestine can lead to poor absorption of vitamins and minerals, people with celiac disease need to be careful to eat nutritious food and if the nutritional deficiencies are severe then they might need to take supplements for the common deficiencies of iron, vitamin B12, folic acid, Vitamin B6, calcium, vitamin D, zinc and copper.
For people who have refractory celiac disease the doctor might recommend some steroids to control inflammation and for those with itchy, blistering skin rashes (dermatitis herpetiformis) caused by celiac disease the doctor might recommend the medication Dapsone to offer short-term relief.
There are several treatments for celiac disease currently under study. For e.g. a product from ImmuogenX, called Latiglutenase, which is made up of a combination of two enzymes that degrade gluten and could relieve symptoms and prevent intestinal damage in those who have celiac disease. Promising studies also suggest that probiotics might play a role in treatment of celiac disease in the future. Another new approach to treating celiac disease by using nanoparticles to program the immune system to tolerate gluten also showed promise in early results.
