Coeliac Disease

Synonyms: gluten sensitive enteropathy, celiac disease, celiac sprue

This is a genetically-determined chronic inflammatory intestinal disorder of the proximal bowel induced by gluten, a protein found in wheat, rye and barley. Oats are normally OK for most patients with coeliac disease (CD), although it may cause damage in a very small number of people with severe sensitivity to gluten.

Prevalence is approximately 1 in 100 people in the UK.^1,2 Prospective birth cohort studies suggest 1% of children have IgA endomysial antibodies by 7 years of age,^3,4 although only 1:2,500 will have been diagnosed as having CD at that time.^5,6 This demonstrates that there must be a large number of undiagnosed coeliac patients in the community, which presents a large diagnostic challenge to Primary Care. Delayed diagnosis of CD may result in continuing ill health, osteoporosis, miscarriage and a modest, increased risk of intestinal malignancy (in adults); also, growth failure, delayed puberty and dental problems (in children).⁴

It is a multigenetic disorder, associated with HLA types HLA-DQ2 (90%) or HLA-DQ8, plus other genetic or environmental factors. There is a familial tendency (10-15% of first degree relatives will also be affected), identical twins concordance is 70%. It is theoretically possible by HLA testing to provide more accurate information to parents with a child with CD about the real risk for another child having the disease, including an antenatal assessment.⁷

2-8% of patients with type 1 diabetes mellitus also have CD,⁸ and it also occurs with increased frequency in patients with Down's Syndrome, Hashimoto's thyroiditis,⁹ irritable bowel syndrome (IBS), and in the Irish, Punjabis and other South Asians.

May present at any age - presentation in childhood now less common, and increasingly being recognised in adults (may present with non-specific bowel or abdominal symptoms).

• Babies and young children present any time after weaning (peak 9 months to 3 years). Malabsorption generally presents with diarrhoea (frequent paler stools), weight loss and failure to thrive. Vomiting, anorexia, irritability, and constipation are also common. The abdomen may protrude, with eversion of the umbilicus.
• Older children and adults may present with anaemia (folate or iron deficiency) non-specific symptoms of abdominal discomfort, arthralgia, anaemia, fatigue and malaise, as well as diarrhoea, steatorrhoea and malabsorption. Mouth ulcers and angular stomatitis are common (85% have asymptomatic iron/folate deficiency, 15-30% have vitamin D deficiency and 10% vitamin K deficiency). Some are identified at infertility clinics.

Dermatitis herpetiformis is the classic skin manifestation of CD - almost all of patients with the rash have either detectable villous atrophy (~75%) or minor mucosal changes. Acquired ichthyosis has been reported.¹²

Because CD is considerably under-diagnosed in Primary Care,¹¹ consider the diagnosis and perform serological testing in all patients who present with:⁴

• chronic or intermittent diarrhoea
• failure to thrive or faltering growth in children
• persistent or unexplained gastrointestinal symptoms including nausea and vomiting
• prolonged fatigue ('tired all the time')
• recurrent abdominal pain, cramping or distension
• sudden or unexpected weight loss
• unexplained iron-deficiency anaemia, or other unspecified anaemia

Also offer testing to patients with:⁴

• autoimmune thyroid disease
• dermatitis herpetiformis
• irritable bowel syndrome¹³
• type 1 diabetes
• first-degree relative (parents, siblings or children) with CD

NICE also suggests considering serological testing in patients with:⁴ Addison's disease, amenorrhoea, aphthous stomatitis (mouth ulcers), autoimmune liver conditions, autoimmune myocarditis, chronic thrombocytopenia purpura, dental enamel defects, depression or bipolar disorder, Down's syndrome, epilepsy, lymphoma, metabolic bone disease (such as rickets or osteomalacia), microscopic colitis, persistent or unexplained constipation, persistently raised liver enzymes with unknown cause, polyneuropathy, recurrent miscarriage, reduced bone mineral density and/or low-trauma fracture, sarcoidosis, Sjögren's syndrome, Turner's syndrome, unexplained alopecia, unexplained subfertility.

Serological testing

• IgA anti-tissue transglutaminase antibodies (tTGAs) is the preferred investigation. Endomysial antibodies (EMAs) are used if tTGA) test is not available or equivocal. The tTGA is a newer test (tTGA is the autoantigen of EMA) and is gradually replacing the latter, but both are highly specific and sensitive for untreated CD provided patient is still on gluten.¹⁰
• False negatives occur if the patient has selective IgA deficiency, as occurs in ~0.4% of the general population¹⁴ and in 2.6% of patients with CD (laboratories should test for IgA deficiency on negative samples). Use IgG tTGA and/or IgG EMA serological tests for people with confirmed IgA deficiency.
• Antibodies frequently become undetectable after 6-12 months of a GFD and thus can be used to monitor the disease.

Antigliadin antibodies are no longer recommended - they are less specific, but can be either IgA (AGA) or IgG (AGG). They can be positive in other gastrointestinal conditions such as Crohn's disease.

Biopsy confirmation

Patients with positive serological tests should be offered referral to local gastroenterologist for endoscopic or enteroscopic distal duodenal or jejunal biopsy to confirm diagnosis.^4,14,15 They need to stay on gluten until after the biopsy. Referral should also be made where the serology is negative but there is still clinical suspicion of CD.

• The diagnosis of CD is made when biopsy shows villous atrophy while the patient is eating adequate amounts of gluten, followed by full clinical remission on excluding gluten.
• Under these circumstances, tTGA or EMA antibodies found at the time of diagnosis and their disappearance after gluten exclusion, means that it is only necessary to perform a further biopsy (and even a further gluten challenge and more biopsies) if there are still doubts. The further gluten challenge should always be performed if CD is diagnosed in children less than 2 yrs because of a high incidence of other causes of flat mucosa.¹⁶

Other investigations

• FBC shows anaemia in 50%; iron and folate deficiency are both common (microcytes and macrocytes), hypersegmented leucocytes and Howell-Jolly bodies (splenic atrophy). Also check B12, folate, ferritin, LFT, calcium and albumin.
• Small bowel barium studies are occasionally needed to exclude other causes of malabsorption and diarrhoea, and diagnose rare complications such as obstruction or lymphoma.

Histological examination of the mucosa which has been exposed to gluten classically shows "subtotal villous atrophy" and results in malabsorption - however mucosa is of normal thickness, villous atrophy is compensated by crypt hyperplasia. There may be a range of abnormality, from a normal villous architecture with epithelial lymphocytosis, to total villous atrophy.¹⁰

IBS,¹⁷ lactose or other food intolerances, colitis (including inflammatory bowel disease), other causes of malabsorption.

The following occurring with increased frequency in CD include osteoporosis, subfertility, Down's Syndrome and various autoimmune diseases (especially Hashimoto's thyroiditis and type 1 diabetes mellitus; however, it is probably also true of Sjögren's syndrome and primary biliary cirrhosis), and IgA deficiency. Always consider CD in patients thought to have IBS.¹⁷

Starting a GFD rapidly induces clinical improvement, which is mirrored by the mucosa. The diet consists of no wheat, barley, rye, or any food containing them (e.g. bread, cake, pies). Moderate quantities of oats (free from other contaminating cereals) can be consumed as recent studies suggest that they do not damage the intestinal mucosa.¹⁹ Rice, maize, soya, potatoes, sugar jam, syrup and treacle are all allowed. Gluten-free biscuits, flour, bread and pasta are NHS prescribable. Coeliac UK produces a prescribing guide.²⁰

Arrange dietitian appointment (with regular reviews). Even minor dietary lapses may cause recurrence. GFD should be lifelong, as relaxation of diet generally brings a return of symptoms and increased incidence of complications. Add supplements as necessary (e.g. folic acid, iron, calcium and vitamin D).
Serial tTGA or EMA antibodies can be used to monitor response to diet.

Oats - there was originally some concern about including oats in a GFD, but recent research has emphasised that oats can be given to almost all patients with coeliac disease.^21,22

Oral proteases are being developed (which digest gluten) and these may offer therapeutic options in the future.²³

Why follow up patients with coeliac disease?¹⁵

• Patient compliance with a GFD is poor, ranging from 45-87%. The long-term health risks for patients who comply poorly with a GFD include nutritional deficiency and reduced bone mineral density.
  About a quarter of patients with CD have osteoporosis of the lumbar spine compared to 5% of matched controls. Bone mineral density improves significantly with a GFD.
• Dietary compliance positively correlates with regular follow-up and knowledge of the condition.
• Half of all coeliac patients have an inadequate energy intake, and 10% have inadequate intake of calcium and vitamin B6. 80% of elderly patients have inadequate intake of vitamin D.
• GPs are responsible for the appropriate prescription of gluten-free products.²⁰
• Regular follow-up is an opportunity to provide patient-centred care that is sensitive to the individual's life circumstances.

How often should patients be reviewed?

• Patients should be followed up throughout their lifetime.
• After diagnosis, the patient should be reviewed at the gastroenterology clinic after 3 months and 6 months to ensure they are making satisfactory progress and managing the diet.
• If well, they should be reviewed annually or sooner if problems arise - follow-up assessments are currently being carried out by dietitians, nurses, general practitioners and gastroenterologists in primary and secondary care.

When should the patient be under specialist care?

You should consider specialist referral if there is:

• Poor response to GFD
• Weight loss on GFD
• Blood in stools
• Onset of unexplained abdominal pain
• Other clinical concerns

CD appears to be underdiagnosed in primary care.⁵

• In order to uncover the "iceberg" GPs need to screen for CD - especially patients with autoimmune disease, unexplained anaemia,²⁴ unexplained osteoporosis,¹⁶ chronic abdominal pain or other bowel symptoms (e.g. IBS), or family history of CD.²⁵
• Patients having upper GI endoscopy for iron deficiency or macrocytic anaemia may be suitable for screening with distal duodenal biopsies (but it may be better to perform CD serology first and follow algorithm).¹⁴ The case for childhood screening is currently being considered. NICE recommends screening children with type 1 diabetes for CD every 3 years until adulthood, and subsequently if adults have a low body mass index or develop unexplained weight loss.¹⁵

• Osteoporosis see box above.²⁶
• Cancer risk - there is conflicting research on this subject. Some research fails to show any increased risk,²⁷ whilst other papers have shown a very modest increase in overall risks of developing malignancy, e.g. gastrointestinal cancers and several types of lymphoma (risk greatest in first year after CD diagnosis).^28,29 Interestingly, CD patients may have a reduced incidence of breast and lung cancers (reasons unclear).
  Intestinal lymphoma usually presents with return of bowel symptoms, although usually responds poorly to treatment.