Coeliac disease in Europe

Coeliac disease is a condition predominantly of the small bowel, resulting from sensitivity to ingested gluten, a protein found in wheat, barley and rye. Coeliac disease may be present in approximately 1 in 150–300 Europeans, yet it remains underdiagnosed in most countries. Coeliac disease as a clinical entity has been recognized for many years. As far back as the second century AD, Aretaeus from Cappadocia described what is believed to be the first report of a gastrointestinal condition resembling coeliac disease when he outlined a chronic wasting illness associated with diarrhoea. The first detailed description of the ‘coeliac affection’ was in 1888 by Samuel Gee, a paediatrician in St Bartholomew's Hospital, London, who was also the first to propose dietary manipulation as the mainstay of treatment. However, his diets were quite restrictive, and although patients improved, few could be prevailed upon to endure the regimen for long. During World War II, food shortages, in particular of cereal, led Dicke, a Dutch paediatrician, to the conclusion that a ‘wheat factor’ led to coeliac disease. Affected children thrived when cereal was in short supply and deteriorated once the products became widely available again. The classical picture of coeliac disease consists of malabsorption with diarrhoea and weight loss in children. Children are irritable, fail to thrive, are pale with a distended abdomen and wasted buttocks, and have pale bulky foul-smelling stools. This presentation has been declining in European countries over the last few decades. Changes in feeding practices, with more mothers breast-feeding and a delay in the introduction of gluten in the diet, are thought to account for this change. More coeliac patients are presenting in adulthood; up to one-third of coeliac patients are now diagnosed when over 65 years of age. Unlike children, adults do not usually present with malabsorption. Adults often have vague symptoms of tiredness, upper abdominal pain, diarrhoea or constipation. Consequently, coeliac disease may often be overlooked. Both the diversity of symptoms and disease severity has led to the concept of a ‘coeliac iceberg’ (Figure 1). Patients with typical symptoms are easily recognized as having coeliac disease and are ‘floating above the surface’. Patients with vague or atypical symptoms are not as easily recognized and make up the majority of patients ‘below the surface’. It is important to increase awareness of the varied presentations possible with coeliac disease, so as to increase the number of cases diagnosed (Table 1). Coeliac iceberg. Coeliac disease screening employs a simple blood test. Antibodies to gliadin, the particular protein in gluten, which is toxic to coeliac patients, are elevated in people with the disorder. With the introduction of a gluten-free diet, these antibodies return to normal. Other antibodies produced in coeliac disease include antiendomysial antibodies and tissue transglutaminase antibodies. These are autoantibodies, or antibodies produced by the body against itself, and are responsible for the damage induced by gluten in the small bowel. They appear to be more sensitive than antigliadin antibodies. Like antigliadin antibodies, they return to normal when gluten is removed from the diet. A positive blood test requires tissue confirmation. A tissue biopsy also allows the degree of damage present to be assessed. When a gluten-free diet is initiated, the damage to the small bowel returns to normal over a period of a few months to 1–2 years in the majority of patients. Failure of the bowel to recover is nearly always due to gluten slipping into the diet. Dietary manipulation is central to coeliac disease management. This involves the avoidance of foods containing wheat, rye and barley. Complete avoidance is not easy. Along with bread, cakes, and pasta, the obvious sources of gluten, gluten can be found in sauces, soups, and in the flavourings and preservatives of processed foods such as sliced ham, yogurt, ice cream and crisps. It takes motivation, time and patience to become accustomed to a gluten-free diet. It also takes a multidisciplinary team approach from the doctors, dieticians and support groups for coeliac disease. The diet is for life, and ongoing involvement of doctors and dieticians is essential. As stated previously, it has been estimated in recent studies that 1 : 150–1 : 300 Europeans may have coeliac disease, although the majority remain undiagnosed throughout their lifetime (Table 2). Coeliac disease is more prevalent in families of affected individuals. Previous work has estimated that as many as 10% of first-degree relatives of patients have coeliac disease.1 These findings are consistent with previous data, which revealed a strong association between coeliac disease and the human leucocyte antigen DQ2/DQ8. Recent confirmatory work has been performed in both high- and low-risk populations.2 This group reported prevalences of 1 : 22 in first degree relatives, 1 : 56 for symptomatic subjects and 1 : 133 for asymptomatic low-risk individuals. Similar figures have been reported in Europe.3–9 Definitive diagnosis of coeliac disease requires an endoscopy and tissue biopsy. To confirm improvement with the introduction of a gluten free-diet, a repeat oesophagogastro-duodenoscopy (OGD) and biopsy is advised after a year of treatment. The average cost of this is €1000 per patient. Obviously, as coeliac disease is a lifelong condition, costs accumulate over time. Based on supermarket prices a gluten-free diet is €4 more expensive per day than a normal diet. Over a year, this amounts to nearly €1500. In addition, vitamin and mineral supplements including iron, folic acid, B12, calcium and vitamin D are required. Review in clinics by doctors and dieticians, blood tests and dual energy X-ray absorptiometry (DEXA) scans all add to the cost (Table 3). Additional hidden costs are difficult to calculate. Many suffering with this condition are not diagnosed, therefore their plight goes unnoticed. Coeliac disease results in a significant reduction in energy levels, and is associated with myriad uncomfortable chronic symptoms, all of which can have a significant negative impact on a person's quality of life. This effect appears to persist despite improvement in disease parameters, possibly as a result of the limitations of treatment.10 Coeliac disease represents a major public health issue, as osteoporosis and anaemia are common consequences of untreated coeliac disease. In untreated coeliac patients, the incidence of lymphoma is increased 4–100-fold, and other conditions such as diabetes, thyroid disease, and epilepsy are also increased. Untreated coeliac patients have an increased incidence of infertility, miscarriages and neonatal defects. The mortality of coeliac patients is double that of the rest of the population. The treatment of coeliac disease by a gluten-free diet removes or substantially reduces the risk of disease complications. Many forms of cancer are increased in coeliac disease, and strict adherence to a gluten-free diet can reduce the risk. The most frequent cancer is a lymphoma, which affects the small bowel. This is up to 40 times more common in coeliac disease. Patients present with weight loss, abdominal pain and diarrhoea. It can be insidious and difficult to diagnose, often requiring multiple investigations such as repeated camera tests, X-ray screening with computed tomography scans or barium studies and may ultimately require surgery to make a definitive diagnosis. Patients with coeliac disease are also at increased risk of oesophageal cancer, pharyngeal cancer and cancer of the large intestine. The risk has been estimated to be up to 10 times higher with coeliac disease. Nutritional deficiencies are common in coeliac disease and should be sought out and prevented if possible. Weight loss, osteoporosis and iron and folic acid anaemia are the most frequent problems. On commencement of the appropriate diet, the majority of patients will gain weight. Iron and folic acid supplementation may still be necessary and regular monitoring of this is advised. Dietary calcium and vitamin D intake require attention and DEXA scanning, a radiological test for osteoporosis is recommended at diagnosis and at regular intervals thereafter in an attempt to reduce the development of pathalogical fractures in later life. Deficiencies of many other minerals and vitamins may occur, including magnesium, zinc, copper, selenium, and vitamins A, B12, D, E, and K. As previously mentioned, autoimmune diseases are more common in coeliac disease, as are thyroid disease, diabetes, primary biliary cirrhosis affecting the liver, and dermatitis herpetiformis, an extremely itchy rash affecting the elbows, buttocks and knees. Some patients fail to improve after starting a gluten-free diet, and are said to have refractory coeliac disease. The fear is that these patients may have an underlying malignancy and this needs to be assessed diligently. Many treatments are used to try to improve response to the diet in these patients, and all involve trying to suppress the immune system. Coeliac disease is a common underdiagnosed disease with significant preventable complications. Its treatment is effective and simple. This disorder is extremely prevalent in most European countries and as such represents one of the most important digestive disorders managed by most gastroenterologists. The diet, although effective, is difficult to comply with and adds to a household's monthly expenditure. Recent developments in public awareness have led to improvements in diagnosis and to an expansion in the variety of foods available for inclusion in the dietm as well as better advertising on food packaging of either gluten inclusion or absence. Further investment both in medical research of coeliac disease and in promoting public awareness could substantially improve the quality of life of sufferers.