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Coeliac Disease
Essentials
- The clinical picture of coeliac disease has changed: classic malabsorption is nowadays rare, and the disease is often diagnosed based on mild gastrointestinal symptoms or associated conditions.
- High levels (> 10 times the upper limit of normal range) of transglutaminase antibodies together with positive endomysial antibodies are diagnostic for coeliac disease. A small bowel biopsy is needed to confirm the diagnosis only if the aforementioned conditions are not met.
- The patient should be encouraged to adhere to a strictly gluten-free diet.
Definition
- In coeliac disease, dietary gluten causes inflammation of the small bowel mucosa, leading to villous atrophy and crypt hyperplasia in genetically susceptible persons. The damage can be reversed by a gluten-free diet but will recur if the patient resumes a normal diet.
- Coeliac disease can also manifest as a skin disease (dermatitis herpetiformis) Chronic Bullous Diseases (Dermatitis Herpetiformis, Pemphigoid) in which an itching, blistering rash erupts especially in the area of the elbows (picture 1), knees (picture 2) and buttocks. In dermatitis herpetiformis, similar damage to the bowel as seen in coeliac disease is present, but it is often milder. Granular IgA deposits found in biopsies from uninvolved skin are diagnostic.
Symptoms
- The most typical symptoms are chronic diarrhoea or loose stools, flatulence, weight loss, and, in children, retarded growth.
- The symptoms are often quite mild and may resemble those of irritable bowel syndrome.
- The most common sign of malabsorption is anaemia, which may be caused by iron deficiency (hypochromic, microcytic), folic acid deficiency (macrocytic) or both. Vitamin B12 deficiency is less common.
- Calcium malabsorption may occur and it may lead to osteoporosis.
- Atypical symptoms include enamel defects in permanent teeth, ulcers on oral mucous membranes (aphthae), and joint symptoms.
- Neurological symptoms (ataxia, polyneuropathy, memory impairment) or recurring spontaneous abortions may also be due to coeliac disease.
- Liver enzymes (aminotransferases) may be elevated in untreated coeliac disease Assessing a Patient with an Abnormal Liver Function Test Result.
- Asymptomatic coeliac disease may be found either incidentally in routine biopsies from small intestinal mucosa taken during gastroscopy or by antibody screening of risk groups.
Prevalence
- The prevalence of diagnosed coeliac disease in the Finnish adult population is 0.7% but, according to screening studies, 1% of children, 2% of adults and as many as 2.7% of the elderly have the disease.
- 60-75% of coeliac disease patients are women; dermatitis herpetiformis is more common in men than in women.
- Today, coeliac disease is most often diagnosed at the age of 30 to 50 years or in children.
- Dermatitis herpetiformis is diagnosed in about 10% of patients with coeliac disease.
Diagnosis
- People with few symptoms or belonging to risk groups should be screened by antibody testing http://www.dynamed.com/condition/celiac-disease#RECOMMENDATIONS_FOR_ANTIBODY_TESTING.
- The primary investigation is the determination of serum IgA class tissue transglutaminase antibodies.
- Determination of endomysial antibodies, which are highly specific for coeliac disease, increases diagnostic sensitivity and specificity.
- The specificity of deamidated gliadin peptide antibodies (DPGAbA) is similar to that of transglutaminase antibodies, but their role in the diagnostics of coeliac disease is not yet established.
- In patients with IgA deficiency, IgG antibody test should be used.
- If the diagnosis cannot be made on the basis of high antibody levels, it should be based on a small bowel or skin biopsy.
- Small bowel biopsy should be taken during gastroscopy as distally in the small bowel as possible.
- When dermatitis herpetiformis is suspected, a dermatologist takes the biopsy from uninvolved skin.
Principles of diagnostics
- If a patient has high levels (more than 10 times the upper limit of normal range) of transglutaminase antibodies together with positive endomysial antibodies, the diagnosis of coeliac disease can be made without small bowel biopsy.
- If transglutaminase antibodies are less than 10 times the upper limit of normal range or endomysial antibodies are negative, a small bowel biopsy is required to confirm the diagnosis.
- If there is strong suspicion of the disease, a small bowel biopsy (in dermatitis herpetiformis, skin biopsy) should always be taken. Seronegative coeliac disease may occur in up to 10% of adults with coeliac disease, and in one out of three persons with dermatitis herpetiformis no coeliac antibodies can be detected in the serum. Antibody screening can be used to verify the diagnosis but negative antibodies do not completely rule out coeliac disease.
- Antibody tests and small intestinal biopsy should be performed during a normal diet. If the patient has started a gluten-free diet, he/she should return to a gluten-containing diet for at least three months before the samples are taken.
- Most patients with coeliac disease are found to have the HLA DR3-DQ2 or DR18-DQ8 haplotype; their absence excludes coeliac disease in practice. However, these genotypes are common in the population and the genetic test can therefore only be used to rule out coeliac disease; positive results do not have any additional diagnostic value http://www.dynamed.com/condition/celiac-disease#HLA-DQ_SEROTYPING. The test should not be performed routinely in primary health care.
- Care should be taken to obtain high-quality biopsies: samples cut obliquely may give a false impression of normal intestinal villi or, on the other hand, lead to a false positive diagnosis. An experienced pathologist may be asked to reassess the sample if contradictory findings are obtained.
Treatment
- Treatment consists of a life-long gluten-free diet http://www.dynamed.com/condition/celiac-disease#DIET, with wheat, rye and barley and any products containing these cereals eliminated.
- Patients should be provided with initial guidance by a therapeutic dietitian after diagnosis and also later on, if this is considered necessary.
- Gluten-free oats http://www.dynamed.com/condition/celiac-disease#OATS are suitable for most patients with coeliac disease or dermatitis herpetiformis, but the most sensitive patients may develop symptoms even if no damage to the small intestinal villi occurs.
- The initial treatment of dermatitis herpetiformis includes dapsone http://www.dynamed.com/condition/dermatitis-herpetiformis#MEDICATIONS. Treatment should be placed in the hands of a dermatologist.
- On a gluten-free diet, the symptoms usually disappear within a few weeks or months. Skin symptoms, however, subside more slowly: despite adherence to a gluten-free diet dapsone therapy is often required for 1-2 years.
- The intestinal villi have been found to become normal again in patients using gluten-free wheat starch products.
- The new EU Commission Regulation changed the terminology for a gluten-free diet and the safety thresholds for foodstuffs suitable for people with coeliac disease http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:016:0003:0005:FI:PDF.
- If the content of gluten does not exceed 20 mg/kg the foodstuff is labelled gluten-free. If the content of gluten exceeds 20 mg/kg but not 100 mg/kg the foodstuff is labelled very low gluten.
Follow-up
- After the diagnosis is made, in an adult patient antibody levels should be determined within a clinical follow-up visit http://www.dynamed.com/condition/celiac-disease#FOLLOW_UP, the latest, after one year. If a good treament response can be observed, the interval of the follow-up visits may be increased to 2-3 years.
- A follow-up small bowel biopsy is not required routinely, since by following a strict diet therapy the villous atrophy is repaired in almost all patients over time. A follow-up biopsy is required only if treatment response remains inadequate. This may be caused by the patient letting the diet slide or by refractory coeliac disease where the intestinal villi are not repaired and symptoms not resolved despite gluten-free diet. Also in seronegative coeliac disease a follow-up biopsy is recommended to ensure the efficacy of diet therapy.
- In dermatitis herpetiformis, the disappearance of the rash and normalization of transglutaminase antibodies are sufficient signs of the success of the treatment.
- Also in children, disappearance of antibodies and improvement of clinical condition suffice; follow-up biopsies are taken very rarely.
- Bone densitometry one year after diagnosis is recommended for an adult patient with coeliac disease with severe clinical picture or when diet is not realized.
Refractory coeliac disease
- The most common reason for poor response to treatment is a faulty diet. Patients may fail to observe the gluten-free diet intentionally but even slight unintentional contamination with gluten may result in antibody levels not decreasing and the small intestinal mucosa not recovering as expected.
- In rare cases, poor efficacy of a gluten-free diet may turn out to be due to misdiagnosis. Other diseases of the small intestine may also cause villous atrophy; if problems arise, specialized care should be consulted.
- If symptoms continue despite the recovery of the small intestinal mucosa, the patient may have some other disease of the gastrointestinal tract, such as microscopic colitis Microscopic Colitis or irritable bowel syndrome Functional Bowel Disorders and the Irritable Bowel Syndrome (Ibs).
- If villous atrophy in the small intestine and the symptoms of malabsorption are not corrected despite a strictly gluten-free diet observed for 1 to 2 years, or if they recur after a good response, the patient is said to have refractory coeliac disease. The risk of refractory disease is particularly high in patients with coeliac disease diagnosed only at an advanced age, with severe intestinal symptoms and clear signs of malabsorption.
- There are two subtypes of refractory disease.
- In type 2, an abnormal inflammatory cell population is found in the small intestine, and about a half of the patients develop small intestinal lymphoma (EATL or enteropathy-associated T-cell lymphoma) within 4 to 6 years.
- In type 1, small intestinal inflammatory cells are similar to those found in uncomplicated coeliac disease, and the prognosis is clearly better.
- Refractory coeliac disease and small intestinal lymphoma should be diagnosed and treated in specialized care.
Diagnosis and chain of treatment of coeliac disease
- Concerning adult patients, the diagnosis of coeliac disease may usually be made in primary health care, and also follow-up is organized in the unit that made the diagnosis.
- Screening of risk groups http://www.dynamed.com/condition/celiac-disease#SCREENING is performed in primary health care.
- A unit with the capacity to perform gastroscopy and to take biopsy samples from the small intestine is consulted as required.
- Coeliac disease in children and dermatitis herpetiformis are diagnosed by specialists in the respective fields.
- Patients with dermatitis herpetiformis receiving dapsone treatment should be followed up by a dermatologist. When the rash can be controlled simply by a gluten-free diet, the follow-up may be transferred to primary health care.
- A therapeutic dietitian should provide guidance at least when coeliac disease is diagnosed and after 1 to 6 months of observing a gluten-free diet, as necessary.
- Any complications should be examined and treated in specialized care.
Social security
- Children with coeliac disease are given a disability allowance until the age of 16 years.
- The dietary grant previously paid for adults was abolished on 1.1.2016.
References
- Rubio-Tapia A, Van Dyke CT, Lahr BD et al. Predictors of family risk for celiac disease: a population-based study. Clin Gastroenterol Hepatol 2008;6(9):983-7. [PubMed].
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- Virta LJ, Kaukinen K, Collin P. Incidence and prevalence of diagnosed coeliac disease in Finland: results of effective case finding in adults. Scand J Gastroenterol 2009;44(8):933-8. [PubMed]
- Mäki M, Mustalahti K, Kokkonen J et al. Prevalence of Celiac disease among children in Finland. N Engl J Med 2003;348(25):2517-24. [PubMed]
- Lohi S, Mustalahti K, Kaukinen K et al. Increasing prevalence of coeliac disease over time. Aliment Pharmacol Ther 2007;26(9):1217-25. [PubMed]
- Vilppula A, Kaukinen K, Luostarinen L et al. Increasing prevalence and high incidence of celiac disease in elderly people: a population-based study. BMC Gastroenterol 2009;9():49. [PubMed]
- Hill ID. What are the sensitivity and specificity of serologic tests for celiac disease? Do sensitivity and specificity vary in different populations? Gastroenterology 2005;128(4 Suppl 1):S25-32. [PubMed]
- Lewis NR, Scott BB. Meta-analysis: deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac disease. Aliment Pharmacol Ther 2010;31(1):73-81. [PubMed]
- Peräaho M, Kaukinen K, Mustalahti K et al. Effect of an oats-containing gluten-free diet on symptoms and quality of life in coeliac disease. A randomized study. Scand J Gastroenterol 2004;39(1):27-31. [PubMed]
- Peräaho M, Kaukinen K, Paasikivi K et al. Wheat-starch-based gluten-free products in the treatment of newly detected coeliac disease: prospective and randomized study. Aliment Pharmacol Ther 2003;17(4):587-94. [PubMed]
- Al-Toma A, Verbeek WH, Hadithi M et al. Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience. Gut 2007;56(10):1373-8. [PubMed]