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Facts on Coeliac Disease

Coeliac disease (also called celiac disease, non-tropical sprue, celiac sprue, gluten enteropathy and gluten intolerance) is a digestive disorder in genetically-predisposed individuals. The only susceptibility locus established is the HLA-DQ. It is characterized by damage or flattening to all or part of the villi lining the small intestine, causing scar tissue that cannot absorb nutrients. This damage is caused by exposure to gluten (gliadin) and related proteins found in wheat, rye, malt, barley and oats.

Signs and symptoms
Damage to the villi reduces the ability of the intestines to absorb nutrients, and it is believed that the resulting nutritional deficiencies likely cause the wide spectrum of symptoms associated with the disorder. Celiac disease may lead to digestive problems, such as indigestion, heartburn and irritable bowel syndrome, unexplained weight loss or other signs of nutritional deficiency due to malabsorption, and a wide range of other problems in different bodily systems, including the nervous system, the heart, and the teeth and bones.

Other symptoms can include dermatitis (an itchy rash), diarrhea, excessive tiredness or fatigue, aching in joints and a general feeling of being unwell.
Celiacs (people with celiac disease) may also be symptom-free, but they are still doing damage to their small intestines. Regardless of the presence or absence of symptoms, the disorder is associated with an increased risk of osteoporosis and MALT lymphoma, a form of intestinal cancer.

Strict adherence to a gluten-free diet typically resolves all symptoms and conditions caused by celiac disease. In celiacs who are not on a gluten-free diet, the disease may present through one or more of the following symptoms. The presence of these symptoms does not mean the individual is celiac. These symptoms are also associated with other diseases, some of which are life-threatening; therefore, patients with these symptoms should promptly consult a doctor for differential diagnosis.

Dietary deficiencies, which may manifest as symptoms in particular body systems (e.g., digestive or nervous system) or may be noticed on routine blood tests, are common in celiacs. Up to 50% of celiac disease patients have malabsorption-related diarrhea (with bulky, pale, offensive-smelling stools which may float in the toilet bowl). This symptom is known as steatorrhea. However, some celiacs suffer from constipation. Excess flatulence is common, and some celiacs also experience infrequent, minor rectal bleeding. Unexplained weight loss (or even obesity occasioned by overeating due to cravings for nutrients), indigestion, acid reflux, excessive tiredness (celiacs have reported falling asleep while driving) and an itchy rash (dermatitis) may also be a sign of the disorder. Delayed puberty (or short stature prior to adolescence) might also be a symptom. Rarely, celiacs may experience symptoms similar to those of sinus infections and/or the formation of thick, choking plugs or ropes of mucus that require considerable effort to expel. A low-grade, persistent pain may be present, possibly lessened by eating, which may all too easily be taken for the presence of ulcers.

In young children, the most common symptoms are steatorrhoea, weight loss, abdominal distension, and slow growth/failure to thrive, but irritability, vomiting and tiredness are common. It has been suggested that some cases of autism may be caused by celiac disease.

In adults, the symptoms of celiac disease may be mistaken for irritable bowel syndrome (IBS) or an inflammatory bowel disease such as Crohn's disease. However, celiac disease is also associated with anemia, cardiomyopathy, depression, fatigue and "mental fog," dental problems (see below), adverse pregnancy outcome (particularly miscarriage), peripheral neuropathy, and according to some studies, schizophrenia. A very high proportion of patients diagnosed with dermatitis herpetiformis are celiacs.

Selective dietary deficiencies such as dietary iron deficiency, vitamin B12 deficiency, osteoporosis (due to Vitamin D and calcium malabsorption), poor thyroid function, or other secondary dietary deficiencies may be the sole symptom (predominantly in older patients), or found in addition to diarrhea or weight loss. Some celiacs experience dental problems as a result of malabsorption of nutrients essential for dental health. Celiacs who have dental symptoms typically have tooth enamel problems, which manifest primarily as discoloration and/or severe tooth decay. A pattern of symmetrical decay is particularly associated with celiac disease.

Diagnosis
The condition is frequently misdiagnosed or overlooked as it can exhibit multiple symptoms and often the patient or medical staff may not link seemingly unconnected conditions. It is most frequently misdiagnosed when the sufferer complains of diarrhea, persistent indigestion, a rash or irritable bowel syndrome.

Tests
The gold standard test for celiac disease is still upper endoscopy with biopsy of the distal duodenum or jejunum. To avoid false negative results, the first endoscopy must be done while the patient is on a normal, gluten-containing diet or very shortly after going on a gluten-free diet. Sometimes the endoscopy is repeated after the patient has been on a gluten-free diet, in order to ensure that the bowel has healed. However, upper endoscopy always carries a risk of false negative results. This is because celiac disease may or may not damage villi throughout the entire small intestine, and upper endoscopy only examines the upper part of the intestine. In a patient whose intestinal damage is located further down, the biopsy may come back negative. If the endoscopy is positive the diagnosis is confirmed, but if it is negative, the diagnosis is not necessarily excluded.

Serology has been proposed as a screening measure, because the presence in the blood of IgA antibodies reactive against gliaden and tissue transglutaminase is indicative of celiac disease. Like the endoscopy, these tests are not accurate in patients who have been on a gluten-free diet for some time; they must be performed while the person is on a normal diet or within a few months after eliminating gluten from the diet. A thorough workup includes four tests:

  • Anti-tissue transglutaminase Antibody (tTG), IgA. This test is sometimes used alone. If this test is positive it is highly likely that the patient has celiac disease. tTG test is not reliable in children before the age of 2.
  • Anti-gliadin antibodies (AGA), IgG and IgA. These tests are often useful when testing young symptomatic children, but they are found in fewer celiacs than Anti-tTG, and their presence does not automatically indicate celiac disease because they are found in some other disorders. Some people have an IgA deficiency. They are unable to mount an IgA response to any antigen and will have false negative tests for the IgA type celiac tests.
  • Anti-endomysial antibodies (EMA), IgA. This test is being replaced by the Anti-tTG test because both tests measure the autoantibodies that cause the tissue damage associated with celiac disease. Many physicians still order this test. This test as tTG test is also not reliable in children before the age of 2.
  • An older test, the Anti-reticulin antibodies (ARA), IgA. IgA Anti-ARA is not ordered as frequently as it once was, because it is less sensitive and less specific than the other tests. It is found in about 60% of people with celiac disease and 25% of those with dermatitis herpetiformis.

Many doctors will not consider positive blood tests as definitive proof of celiac disease, but will still require biopsy confirmation. A growing minority consider celiac disease to be diagnosed where the patient has positive blood tests and shows improved symptoms after the adoption of a gluten-free diet. Because upper endoscopies are expensive and may produce false negative results, this group of doctors considers serology tests and a positive response to eliminating gluten from the diet to be sufficient for diagnosis. The problem with this approach is that patients later commonly want to know if they really have Celiac disease and need to be gluten restricted. A diagnosis with biopsy confirmation at the time of initial diagnosis eliminates this common clinical problem. A small minority of doctors advocate gluten-free diets even for symptom-free patients who have not had an endoscopy but have had a positive blood test, because some confirmed celiacs are completely symptom-free throughout their lives; in symptom-free patients, the purpose of the diet is to avoid nutritional deficiencies, osteoporosis, and intestinal lymphoma.

Other tests that may assist in the diagnosis are a full blood count, electrolytes, renal function and liver enzymes. Coagulation testing may be useful to identify deficiency of vitamin K, which predisposes patients to hemorrhage.

Biopsy appearance
The standard changes seen under dissecting microscope are loss of villous height and hypertrophy of the crypts. There is often some degree of inflammation with inflammatory cells (plasma cells and lymphocytes) seen in the lamina propria.

Causes
The cause is presently presumed to be: Partly a genetic susceptibility to the illness. Together with an environmental agent, probably a virus or other infection, but stress and pregnancy have also been invoked as possible triggers. It is associated with other autoimmune diseases; these diseases are also probably a combination of susceptibility and infection. Possible exposure to gluten as a young baby before the gut barrier has developed fully (although this is still subject to further research). Autoantigens are probably of major importance in the pathogenesis of celiac disease (transglutaminase), a trait it shares with many other autoimmune diseases; thyroiditis: thyroglobulin, thyroid peroxidase; multiple sclerosis: myelic basic protein, etc.). To some extent infectious agents may increase the risk of certain autoimmune diseases (e.g. Coxsackie B in type 1 diabetes). However, in the case of celiac disease, there are few proofs of infections triggering celiac disease. Some researchers have suggested that smoking is protective against celiac disease. Results on this topic are however inconsistent, and smoking cannot be recommended as a means to avoid developing celiac disease.

The timing of the first exposure to gluten is also thought to be important. Children who were exposed to gluten between the ages of four and six months were less likely to exhibit celiac disease later in life.

In July 2005, University of Colorado scientists published information on their studies, which indicated that exposure to gluten in the first three months of a baby's life increased the risk of celiac disease five-fold. This is believed to be a result of gluten crossing the baby's relatively undeveloped gut barrier. However, after the baby is six months old, the risk appears to be less. There is ongoing research in this area.

Celiac disease has been identified in some diabetics or people suffering from milk allergies; there is some debate in medical circles as to whether these conditions are linked to gut damage caused by the disease.

Pathophysiology
Antibodies to the enzyme tissue transglutaminase (tTG) are found in an overwhelming majority of cases, and cross-react to gluten2. This has led to the theory that they cause the autoimmune attack on the bowel lining (which is high in tTG), prompted by the continuous stimulation by gluten. This reaction happens almost exclusively in patients with human leukocyte antigen types DQ2 and DQ8, which is inherited in families. Over 95% of patients carry one or both of these genes. About 20% of normal people carry HLA-DQ2, which raises the question of what other factors cause a subgroup of those patients to develop celiac disease.

The inflammatory process leads to disruption of the structure and function of the small bowel's mucosa, and causes malabsorption (it impairs the body's ability to absorb nutrients and fat-soluble vitamins A, D, E and K from food).
The targets of the immunologic response are gliadin, hordein, and secalin, proteins contained in the gluten component of wheat, barley, and rye respectively. Traditionally, oats have been included in the list as well, but some recent studies have brought into question whether this is necessary. Maize (corn), sorghum, and rice are safe for a patient to consume. They do not contain gluten and do not trigger the disease.

Treatment
The only treatment is a life-long gluten-free diet. No medications are required, and none have proven useful; trials with immunosuppressive medicines (to control the bowel inflammation) have been largely unsuccessful. Therefore, celiacs do not need any medication; the disease can be controlled by strict adherence to a gluten-free diet, which allows the intestines to heal and resolves all symptoms in the vast majority of cases and, depending on how soon the diet is begun, can also eliminate the heightened risk of osteoporosis and intestinal cancer.

In the vast majority of patients, a strict gluten-free diet will relieve the symptoms. A tiny minority of patients suffer from refractory sprue, which means they do not improve on a gluten-free diet. This may be because the disease has been present for so long that the intestines are no longer able to heal. In other patients, the intestinal damage of celiac disease may have been aggravated by other problems, such as intolerance to the dietary proteins found in eggs, milk, or soy. Just as a person who is allergic to cats may also happen to be allergic to pollen, a patient with celiac disease may also happen to have other food intolerances that cause similar symptoms. In rare cases only the complete removal of members of the Gramineae family of plants from the diet will bring about recovery from symptoms.

Epidemiology
Susceptibility to celiac disease is genetic and many cases are diagnosed in childhood, but the disease can be triggered by environmental factors at any point in life. It is probably most common in the UK, with the average incidence there being 1 in 100 people [1]. With 1 in 250 people diagnosed, Italy also has one of the highest rates of celiac disease. Those in other countries with British or Italian ancestory are likely to be at risk, owing to the genetic component of the disease. People of African, Japanese, and Chinese descent are rarely diagnosed. It is estimated that 1 in every 133 to 500 persons (up to 3 million) in the United States and Europe are affected by celiac disease. The disease is not limited to those of European origin; it is found in other races, but the prevalence is not known. Celiac disease is more common in women than in men. In symptomatic adults, the average delay between onset of symptoms and diagnosis is estimated at 11 years. This lengthy delay appears to be caused by the variety of symptoms associated with the disease, the fact that some celiacs have no digestive-tract symptoms at all, and lack of widespread, up-to-date information among doctors. Epidemiologically, the disease predominates in Northern European populations. Estimates of its frequency among people of European origin range from 1 in 300 to 1 in 500. Some studies indicate that among the Irish, the frequency may be as high as 1 in 133, whilst in the UK the average incidence is 1 in 100. Because it is partly genetic, doctors commonly recommend that the first-degree relatives of diagnosed celiacs should be tested for the disorder even if they are symptom-free. There is an increased risk of intestinal T-cell lymphoma and osteoporosis in untreated cases. In recent years it has also become more evident that celiac disease in the pregnant mother could have an adverse effect on the fetus. Offspring to mothers with undiagnosed (and untreated) celiac disease are more often preterm and low birth weight (weigh less than 2500 grams/5 pounds at birth) than offspring to mothers without celiac disease. This may be due to the mother's inability to absorb all the nutrients she eats. In children of women with celiac disease and a gluten-free treatment there seems to be no such risk increase. Women with celiac disease have fertility similar to that of the general female population, but they often have their babies at an older age. A number of patients with other diseases are often screened for celiac disease, including patients with type 1 diabetes, Down's syndrome, Turner's syndrome, irritable bowel syndrome, lupus, and autoimmune thyroid disease.

Social Impact and Lifelong diet
The lifelong diet can be difficult and socially troublesome, especially in young patients, but it is crucial in order to avoid serious health consequences. Teenagers in particular occasionally rebel against the dietary strictures and suffer relapses or complications as a result. The widespread use of wheat byproducts in prepared food, soups and sauces can make dining out problematic. This is especially true in the United States, where celiac disease is less widely-known among the wider population than it is in Europe. However, certain types of restaurant (e.g., Japanese, Thai, Indian, and Latin American) already offer a wide range of gluten-free menu options, and many major restaurant chains have responded to growing awareness of celiac disease by posting information about the gluten content of their menu items on their websites.

It is important for celiacs to understand that one does not "get over" celiac disease; it is present for life. As celiac disease has become better understood, the availability of gluten-free replacements for everyday treats such as muffins, bagels, pasta and the like has continually improved, as has their quality. This positive trend shows no sign of slowing, so it will become easier and easier to manage a gluten-free diet.

 

  Copyright © 2006 Andy's Market. This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Coeliac Disease".


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