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Coeliac disease (also termed non-tropical sprue, celiac disease and gluten intolerance) is an autoimmune disease characterised by chronic inflammation of the proximal portion of the small intestine caused by exposure to certain dietary gluten proteins. Coeliac disease may lead to weight loss, malabsorption and various other problems. The only treatment is a gluten-free diet. Trials with immunsuppressive medicines (to control the bowel inflammation) have been largely unsuccessful.
Signs and symptoms
Up to 50% of coeliac disease patients have malabsorption-related diarrhea (with bulky, pale, offensive-smelling stools which may float in the toilet bowl).
Some people are diagnosed after a period of marked weight loss, especially small children. In young children, the most common symptoms are probably diarrhoea, weight loss, abdominal distension, and thin extremities but also irritability, vomiting and tiredness are common.
Selective dietary deficiencies such as dietary iron deficiency, vitamin B12 deficiency, osteoporosis (due to Vitamin D and calcium malabsorption), or other secondary dietary deficiencies may be the sole symptom (predominantly in older patients), or found in addition to diarrhea or weight loss.
Epidemiologically, the disease predominates in Northern European populations. It is partly hereditary.
There is an increased risk of intestinal T-cell lymphoma in untreated cases. In recent years it has also become more evident that coeliac disease in the pregnant mother could have an adverse effect on the foetus. Offspring to mothers with coeliac disease are more often preterm and low birth weight (weigh less than 2500 grams at birth) that offspring to mothers without coeliac disease.
A number of patients with other diseases are usually screened for coeliac disease; among them patients with type 1 diabetes, Turner's syndrome and autoimmune thyroid disease.
Diagnosis
Tests
The gold standard is still upper endoscopy with biopsy of the distal duodenum or jejunum. Biopsy is obtained while the patient is sick and on a gluten-containing food. Sometimes the biopsy is repeated when the patient is on a gluten-free diet to ensure that the bowel has healed.
Serology has been proposed as a screening measure, as IgA antibodies reactive against gluten and tissue transglutaminase may be indicative of coeliac disease. A positive test does not fully confirm coeliac disease, and will still require biopsy confirmation. Conversely, IgA deficiency may cause a false negative test and therefore IgA levels are commonly determined at the same time to allow for this problem. Avoidance of gluten may occasionally lead to negative results.
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, predisposing 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 (identical twins do not have 100% concordance however).
- Together with an environmental agent, probably a virus or other infection.
- It is associated with other autoimmune diseases; these diseases are also probably a combination of susceptibility and infection.
Autoantigens are probably of major importance in the pathogenesis of coeliac 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. rheumatoid arthritis: Mycobacteria; multiple sclerosis: Papillomavirus; and diabetes mellitus type 1: Coxsackie B). However, in the case of coeliac disease, there are few proofs of infections triggering coeliac disease.
Some researchers have suggested that smoking is protective against coeliac disease. Results on this topic are however inconsistent, and smoking cannot be recommended as a means to avoid developing coeliac disease.
Pathophysiology
Antibodies to the enzyme tissue transglutaminase (tTG) are found in an overwhelming majority of cases, and cross-react to gluten (Dieterich et al 1997). 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. The exact cause for this predisposition is still uncertain, but some 95% of patients carry these genes (although they are also common in the general population in Western countries).
The inflammatory process leads to disruption of the structure and function of the small bowel's mucosa, and impairs the body's ability to digest or absorb nutrients 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. Corn (maize), sorghum, and rice are considered safe for a patient to consume. They contain types of gluten that do not trigger the disease.
Treatment
In most patients, a strict wheat- and gluten-free diet will relieve the symptoms. Some patients suffer from refractory sprue. Many cases of refractory sprue are in patients exquisitely sensitive to even trace amount of the problematic glutens; thus, dietary restriction fails due to trace contamination of products with wheat proteins. In other patients, a sprue-like condition may be due to intolerance to other dietary proteins such as those found in egg, milk, or soy.
Epidemiology
It is estimated that 1 in every 133 to 250 persons (up to 3 million) in the United States and 1 percent of people in the world are affected by coeliac disease. These figures may however vary according to ethnicity and geographic area. Coeliac disease is more common in women than in men.
Social impact
Lifelong diet
The lifelong diet, especially in young patients, can be difficult and socially troublesome. Teenagers, in particular, occasionally rebel against the dietary strictures and suffer relapses or complications as a result. A re-challenge to gluten with repeat endoscopy is occasionally used to assess whether a patient is still at risk, or the dietary regimen may be alleviated. It is important to emphasize to patients that oats are now considered safe to eat for coeliac patients.
Catholic Church
The Catholic Church teaches that Communion hosts must contain some unleavened wheat, as it believes that the bread served at the Last Supper did. Sufferers of celiac disease who are Catholic cannot safely consume wheat gluten, and this causes conflict if the attendee's church refuses to make an exception. However, gluten-free communion wafers are now widely available. Several bishops and parishoners have also petitioned for a change in church teaching.
Reference
- Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, Schuppan D. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997;3:797-801. PMID 9212111.
See also
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