Coeliac Disease (CD)

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, although it may cause damage in a very small number of people with severe sensitivity to gluten.

1 in 100-200 people in the UK.^1,2 Prevalence (prospective birth cohort) studies suggest 1% of children have IgA endomysial antibodies by 7 years of age;³ although only 1:2500 will have been diagnosed as having coeliac disease at that time.^4,5 There must be a large number of undiagnosed coeliac patients in the community which presents a large diagnostic challenge to Primary Care.

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.⁶

2-8% of patients with type 1 diabetes mellitus also have coeliac disease,⁷ and it also occurs with increased frequency in patients with Down's Syndrome, Hashimoto's thyroiditis,⁸ 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) nonspecific 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 Vit D deficiency, 10% Vit K deficiency). Some are identified at infertility clinics.

Dermatitis herpetiformis is the classic skin manifestation of coeliac disease - almost all of patients with the rash have either detectable villous atrophy (~75%) or minor mucosal changes. Acquired ichthyosis has been reported.¹¹

Because Coeliac Disease is considerably under-diagnosed in Primary Care,¹⁰ consider the diagnosis and perform serological testing in all patients who present with either anaemia, "tired all the time", chronic abdominal pain or any chronic bowel symptoms (including patients labelled as having IBS).¹²

• Serological testing - the preferred investigations are IgA Anti-tissue transglutaminase (tTG) or IgA Endomysial (EMA) antibodies. The former is a newer test (tTG is the autoantigen of EMA) and is gradually replacing the latter, but both are highly specific and sensitive for untreated coeliac disease provided patient is still on gluten⁹ (and the patient doesn't have selective IgA deficiency, as occurs in ~0.4% of the general population and in 2.6% of patients with coeliac disease - in which case IgG antibody tests should be used). Antibodies frequently become undetectable after 6-12 months of a gluten free diet and thus can be used to monitor the disease.
  Antigliadin antibodies are less specific, but can be either IgA (AGA) or IgG (AGG). They can be positive in other gastrointestinal conditions such as Crohn's.
  A very small number of patients with coeliac disease are tissue transglutaminase antibody negative (0.4% in one series).¹³
  

  Serological testing for identifying coeliac disease should only be done when a patient is on a diet containing gluten (check patients have not already been on a gluten free diet prior to test). Arrange serology test if a patient has been on a gluten containing diet for at least six weeks. A suitable challenge is a diet including four slices of normal bread per day for a minimum of two weeks - test 6 weeks later. If the result is positive then intestinal biopsy should be offered.14

  
  Serological testing can be used to decide who needs subsequent endoscopic or enteroscopic distal duodenal or jejunal biopsy.¹³
• The diagnosis of coeliac disease 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, with tTG 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 coeliac disease is diagnosed in children less than 2 yrs because of a high incidence of other causes of flat mucosa.¹⁵
• 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.⁹

Irritable bowel syndrome (IBS),¹⁶ lactose or other food intolerances, colitis (including inflammatory bowel disease), other causes of malabsorption.

The following occur with increased frequency in coeliac disease include osteoporosis, subfertility, Down's Syndrome, and various autoimmune diseases (especially Hashimoto's thyroiditis and type 1 diabetes mellitus; but is probably also true of Sjogren's Syndrome and Primary biliary cirrhosis); and IgA deficiency. Always consider coeliac disease in patients thought to have IBS.¹⁶

Starting a gluten-free diet (GFD) rapidly induces clinical improvement, which is mirrored by the mucosa. The diet consists of no wheat, barley, rye, or any food containing them (eg 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.¹⁸ Rice, maize, soya, potatoes, sugar jam, syrup and treacle are all allowed. Gluten-free biscuits, flour, bread and pasta are NHS prescribable. Coeliac UK produce a prescribing guide.¹⁹

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 (eg folic acid, iron, calcium and Vitamin D).
Serial tTG or EMA antibodies can be used to monitor response to diet.

Oats - there was originally some concern about including oats in a gluten-free diet, but recent research has emphasised that oats can be given to almost all patients with coeliac disease.^20,21

Oral proteases are being developed (which digest gluten) and these may offer therapeutic options in the future.²²

Why follow-up patients with coeliac disease?¹⁴

• Patient compliance with a gluten-free diet is poor, ranging from 45-87%. The long-term health risks for patients who comply poorly with a gluten-free diet include nutritional deficiency and reduced bone mineral density.
  About a quarter of patients with coeliac disease have osteoporosis of the lumbar spine compared to 5% of matched controls. Bone mineral density improves significantly with a gluten-free diet.
• 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.¹⁹
• 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 gluten-free diet.
• Weight loss on gluten-free diet.
• Blood in stools.
• Onset of unexplained abdominal pain.
• Other clinical concerns.

Coeliac disease appears to be underdiagnosed in primary care.⁴

• In order to uncover the "iceberg" GP's need to screen for coeliac disease - especially patients with autoimmune disease, unexplained anaemia,²³ unexplained osteoporosis,¹⁵ chronic abdominal pain or other bowel symptoms (eg IBS); or family history of coeliac disease.²⁴
• 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).¹³ The case for childhood screening is currently being considered. NICE recommend screening children with type 1 diabetes for coeliac disease every 3 years until adulthood, and subsequently if adults have a low body mass index or develop unexplained weight loss.¹⁴

• Osteoporosis see above.
• Cancer Risk - There is conflicting research on this subject. Some research fails to show any increased risk,²⁵ 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).^26,27 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.