Adult coeliac disease

What is coeliac disease and why is it more common now?

Coeliac disease (or gluten sensitive enteropathy) is defined as a state of heightened immunological responsiveness to ingested gluten (from wheat, barley, or rye) in genetically susceptible individuals. Coeliac disease has historically been considered to be an uncommon gastrointestinal condition. In addition, most clinicians expect to recognise infant or childhood presentations with overt symptoms of malabsorption (or failure to thrive).

A paradigm shift has occurred, however, in our conceptual understanding of coeliac disease. Recent international studies assessing the prevalence of coeliac disease in the general population have consistently reported that coeliac disease affects 0.5-1% of all adults.^w1 Adult presentations are now more frequent than paediatric (a ratio of 9:1, according to the 2005 membership data of the Coeliac UK charity). Patients most commonly present during their 40s.^w2

Patients with adult coeliac disease rarely present with symptoms suggestive of malabsorption (low body mass index accounts for 5% of all cases diagnosed, with most having either a normal or overweight body mass index^w3). Far more commonly they describe non-specific or subtle gastrointestinal symptoms (for example, non-specific abdominal pain, symptoms similar to those of irritable bowel syndrome, or even upper gastrointestinal symptoms5 6). Any gastrointestinal presentation of coeliac disease is now broadly described as the typical (classic) form. However, a substantial proportion of patients have no gastrointestinal symptoms but present with extraintestinal manifestations (box) and/or recognised associated conditions (table⇓). This manner of presentation is now called the atypical or silent form (figure⇓). Patients who present in this way may initially be overlooked because of the lack of gastrointestinal symptoms.7 8 Finally, some individuals may have the potential to develop coeliac disease (figure⇓).

Iceberg model, showing the hidden forms of coeliac disease lying below the waterline.

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The increasing recognition of coeliac disease is attributed to several factors: new serological assays; advances in flexible endoscopy, allowing clinicians to take duodenal biopsies easily at the time of gastroscopy; and the realisation that patients often do not have gastrointestinal symptoms.

Diagnosis

What are the risks for people with coeliac disease?

Recent population based studies suggest that patients with coeliac disease have only a modestly increased risk of malignancy and mortality. This risk seems to fall as time from diagnosis increases (in those patients who comply with a gluten-free diet).^w6-w8 Although small bowel lymphoma may be 50 times more common in someone with coeliac disease, the annual incidence is low (0.5-1 per million people), so the absolute risk for patients with coeliac disease is modest.

At the time of diagnosis reduced bone mineral density (osteoporosis or osteopenia) has been shown in 40% of patients with coeliac disease. ^w9 The reduced bone mineral density also translates to an increased risk of fracture16, but this risk is modest, with recent studies describing a rate ratio of 1.9 for hip fractures (compared with healthy controls).17 Current recommendations suggest that all patients with coeliac disease should have dual energy x ray absorptiometry either at presentation or follow-up.18

Infertility, reduced fertility, and an increased risk of an adverse outcome during pregnancy (miscarriage, low birth weight, and intrauterine growth retardation) have all been attributed to undiagnosed coeliac disease. However, these risks may be lower than historically described.^w10

Functional hyposplenism has been shown to occur in 30% of patients with coeliac disease—for this reason, Haemophilus influenzae, pneumococcal, and annual influenza vaccination should be offered to the patient if there is evidence of hyposplenism on a blood film.19

In general, all the potential complications described are either reversible or avoidable by complying with a gluten-free diet. With specific regard to reduced bone mineral density, following a gluten-free diet may either maintain or improve the density.^w11

The initial improvement in quality of life after one year of starting a gluten-free diet may not be sustained at the same level in the long term. However, although patients with coeliac disease may have a poorer quality of life than controls, it is still an improvement compared with their life before diagnosis, particularly for the patients who presented with typical symptoms.^w12

Who should be tested and what are the unresolved controversies?

Coeliac disease should be considered and tested for when several symptoms and/or disease associations are identified (see box and table⇑). The prevalence of coeliac disease among first degree relatives is reported as 4-22.5%,^w13 so they too should receive counselling and be offered testing.

Some might argue that coeliac disease fulfils the tenets of any screening programme, but when would we decide to screen? At what age and how often thereafter? Serological markers may be highly sensitive and specific, but the value of these tests decreases when they are used in the general population. Although the investigational process for population screening and case finding may be the same, there is an important ethical difference between them. If a patient seeks medical help, then the physician is trying to diagnose the underlying condition. This would be classified as case finding and clearly it is the patient who has initiated the consultation and in some sense is giving consent for investigation. However, individuals who were not patients but have been found to have coeliac disease through a screening programme may have considered themselves to be “well,” and it is the physician or healthcare system that is identifying them as potentially ill.20 Despite some evidence showing that overall quality of life is improved in screen detected patients, this benefit seems to be short lived, with subsequent poor compliance with a gluten-free diet.^w14

Management

Patients who have a positive antibody or in whom coeliac disease is strongly suspected should be referred to a gastroenterologist. A biopsy before starting a gluten-free diet is mandatory. Histological confirmation ensures validity of the diagnosis, allows an assessment of the degree of histological severity as a baseline (should symptoms not improve), and influences any advice about family screening. Confirmation of the diagnosis based on resolution of symptoms with gluten exclusion alone may ultimately result in confusion for the patient. This point can be illustrated in patients with irritable bowel syndrome who have had a normal duodenal biopsy but who may benefit from a gluten-free diet.^w15

A gluten-free diet can be a major and initially overwhelming undertaking. However, it is the cornerstone of treatment in coeliac disease. For this reason, expert dietetic advice is essential. A dietitian's role enables improvement of symptoms and avoidance of nutritional deficiencies related to both the coeliac disease and a subsequent gluten-free diet. The dietitian's role encompasses education about iron, folate, vitamin B-12, fibre, calcium, and vitamin D.21 The role increases further when advice is required for the weight gain that can occur when the small bowel recovers. Compliance with a gluten-free diet may be compromised by a lack of education, limited medical support (from doctors and dietitians), or the absence of symptoms at the time of diagnosis (or in screen detected patients).22 Compliance can be assessed by repeating the duodenal biopsy, antibody testing (levels should normalise on a gluten-free diet), dietary history, and symptom resolution.

Patients are recommended to have a yearly follow-up with a dietitian or doctor to help compliance, as the best evidence to date is that regular specialist follow-up improves compliance.23 Patient surveys show that the optimal follow-up is an appointment with a dietitian in a dedicated clinic but with specialist medical expertise available (concurrently) should they require it.^w16 Reasons for lapses in a gluten-free diet include poor palatability, the absence of a recurrence of symptoms after lapses, high cost of gluten-free products, and the unspecified presence of gluten in food and medications.24 Patients who are established on a gluten-free diet may be able to reintroduce oats. Oats have been shown to be safe in several long term studies,^w17 although cross contamination with wheat flour has been shown (and occasionally “molecular mimicry”), which may result in a recurrence of symptoms.^{w17 w18}

If symptoms persist despite a gluten-free diet, the most common reason is inadvertent non-compliance. However, several other conditions are linked to coeliac disease and can cause persisting symptoms, so a gastroenterological opinion should be sought.^w19

Conclusion

Many alternatives to a gluten-free diet are being evaluated (see “Ongoing research” box). However, an important aspect of the new therapies is that they could have as yet unreported side effects or complications, whereas a gluten-free diet is safe.25

In conclusion, adult coeliac disease is common with many undetected cases still present in the community. We and others have shown a delay in diagnosis in patients with coeliac disease—perhaps the important change in our clinical practice (both in primary and secondary care) is to have a low threshold for case finding and serological testing.