Coeliac Disease

(This page covers adult presentation, testing and monitoring. For paediatric-specific non-biopsy diagnostic criteria, see coeliac disease in paediatrics.)

Condition

An immune illness triggered by dietary gluten that damages the small intestinal mucosa in genetically susceptible people, causing a broad range of gastrointestinal and extra-intestinal manifestations. As 1.5% of Australians have coeliac disease, it is one of the most common autoimmune illnesses that general practitioners will encounter. 80% of Australians with coeliac disease remain undetected because of its often subtle presentation. Untreated disease increases healthcare use, reduces quality of life, and increases mortality because of lymphoproliferative malignancy, sepsis and refractory disease. Associated with Down syndrome, T1DM, autoimmune thyroid disease, and other autoimmune disease.

Diagnosis rests on the combination of positive serology and characteristic small intestinal histology (raised intraepithelial lymphocytes, crypt hyperplasia, villous atrophy). Disease remission is confirmed by symptom resolution, normalised coeliac disease serology and, most reliably, mucosal healing following treatment with a GFD. Coeliac disease can be present despite negative serology, though this is uncommon.

Classification:

• Classical coeliac disease — signs and symptoms of GI malabsorption (e.g. diarrhoea).
• Non-classical coeliac disease — the most common presentation; extra-intestinal symptoms such as fatigue or dermatitis herpetiformis.
• Sub-clinical coeliac disease — no overt symptoms.
• Potential coeliac disease — positive antibodies but negative biopsies; uncertain prognosis, some go on to develop coeliac disease.

Not the same as non-coeliac gluten/wheat sensitivity: many people who self-report gluten sensitivity are not actually sensitive to gluten — they may instead be reacting to other wheat components such as FODMAPs. An empirical trial of a gluten-free diet has no role in the diagnosis of coeliac disease, so anyone who has already self-started a GFD needs a formal diagnostic pathway (below), not just symptom response, before committing to lifelong dietary restriction.

Who to test

Test: chronic/intermittent diarrhoea; failure to thrive; IBS; unexplained nausea/vomiting/abdominal pain; unexplained weight loss; unexplained iron, B12, or folate deficiency; severe/persistent mouth ulcers; autoimmune thyroid disease (at diagnosis); T1DM (at diagnosis); dermatitis herpetiformis; first-degree relative with coeliac disease; persistent unexplained abdominal/GI symptoms; prolonged fatigue.

Consider testing: Down syndrome; Turner syndrome; gynaecological — amenorrhoea, recurrent miscarriage, subfertility; depression/bipolar disorder; constipation; elevated LFTs without another known cause; metabolic bone disorder (reduced BMD, osteomalacia); unexplained neurological symptoms (particularly peripheral neuropathy or ataxia); dental enamel defects.

An active case-finding approach can improve detection of coeliac disease by more than 40-fold. Population screening isn’t recommended — around 30 at-risk people need to be tested to find one positive case. Coeliac disease can develop at any age (median age of diagnosis is 40) and should not be excluded on the basis of ethnicity; a third of patients are overweight or obese at diagnosis.

Family screening: the risk of coeliac disease in a first-degree relative of an affected patient is around 10%, rising to 20% if multiple family members are affected — screen all first-degree relatives regardless of symptoms (many “asymptomatic” relatives turn out to have nutrient deficiencies, reduced bone density, or improve on a GFD once tested). Combining HLA-DQ2/8 genotyping with serology is more informative for relatives than serology alone: a relative without HLA susceptibility needs no further monitoring, while a relative with the susceptibility genotype but normal serology should have serology repeated if suggestive symptoms develop. Screening can be delayed to age 4 in a well, symptom-free child with an affected relative.

Testing pathway

If consuming gluten: blood tests for tissue transglutaminase IgA (tTG-IgA), total IgA, ± deamidated gliadin peptide IgG (DGP-IgG); add IgA EMA (endomysial antibodies) if tTG is weakly positive. If IgA deficiency is present, use IgG EMA, IgG DGP, or IgG tTG instead. There is a 10–15% false-negative rate, so repeat testing may be indicated if symptoms are highly suspicious. If serology is positive, refer for endoscopy and histological sampling.

If not consuming gluten: eat gluten (2 slices of bread or 2 Weet-Bix/day) for 2–6 weeks, then re-test. Ideally 3–6 g or more of gluten should be consumed each day for six or more weeks (2–4 slices of wheat bread, 2–4 Weet-Bix, or 0.5–1 cup cooked pasta daily), started gradually and in divided doses over the day to improve tolerability. If this is intolerable, do genetic testing first — HLA-DQ2/8 genotyping. A negative result makes coeliac disease very unlikely. A positive result (found in 40–50% of the general population) doesn’t confirm the diagnosis — serology still needs to be done after the patient resumes eating gluten. Specialists may consider HLA-DQ2/8 testing directly in patients unable or unwilling to do a gluten challenge who have a high suspicion of coeliac disease. A symptomatic response to gluten challenge or withdrawal is not by itself diagnostic — it’s only informative when accompanied by objective serology/histology testing.

Patients with normal antibody concentrations but a high clinical suspicion of coeliac disease should also be referred for endoscopic evaluation — a negative serology result doesn’t rule out the diagnosis on its own if the pre-test suspicion is high.

Management

Avoid gluten; refer to a dietitian at diagnosis.

Review for complications at diagnosis: micronutrient deficiencies (iron, B12, folate, vitamin D, calcium); other autoimmune disorders (T1DM, thyroid disease); consider bone mineral density testing, especially if delayed diagnosis, previous fractures, post-menopausal, or men aged >55. Immunisation status should be reviewed, particularly pneumococcal vaccination, as infection risk with this organism is higher in patients with coeliac disease, probably secondary to functional hyposplenism.

At 3–6 months: re-check that tTG levels are falling; re-check that symptoms are resolving (if present at diagnosis).

Annually: review gluten-free diet adherence and complications. Symptoms, serology, liver function and thyroid function tests should be reviewed annually, and bone mineral density tested in all patients every two years. Persistently elevated antibodies or ongoing GI symptoms should prompt referral to a dietitian to reassess adherence, rather than automatic repeat biopsy — routine re-biopsy after treatment isn’t recommended, but is reasonable if symptoms persist despite good adherence (raising the possibility of refractory coeliac disease or an alternative diagnosis).

Complications of untreated coeliac disease: nutrient deficiencies; other autoimmune diseases; small bowel lymphoma, as well as peripheral neuropathy, ataxia, and psychiatric conditions such as depression and anxiety.