Presents up-to-date information on coeliac disease, with recommendations on whom to test and how to test them, and how to manage patients once they are diagnosed.

Summary

Background
Coeliac disease (CD) is an autoimmune condition affecting at least 1% of the population, many of whom remain undiagnosed. It is characterised by chronic inflammation of the small-intestinal mucosa and triggered by eating gluten. It is challenging to diagnose because of the many and varied ways in which it may present.

Discussion
Primary care practitioners have a crucial role in improving rates of CD diagnosis, and in the ongoing care of patients with CD. A blood test for coeliac-specific antibodies will identify most patients who need to undergo duodenal biopsy to make the diagnosis. Management encompasses supporting patients with adherence to the gluten-free diet and conducting a CD-focused clinical review every 1–2 years

Andrew S. Day

Kristin Kenrick

English

Analysis and Policy Observatory (APO)

674  REPRINTED FROM AUSTRALIAN FAMILY PHYSICIAN VOL. 43, NO. 10, OCTOBER 2014
Coeliac disease: 
where are we in 2014?
Background
Coeliac disease (CD) is an autoimmune condition affecting 
at least 1% of the population, many of whom remain 
undiagnosed. It is characterised by chronic inflammation of 
the small-intestinal mucosa and triggered by eating gluten. 
It is challenging to diagnose because of the many and varied 
ways in which it may present.
Objective
To present up-to-date information on CD as we now 
understand it, with recommendations on whom to test and 
how to test them, and how to manage patients once they are 
diagnosed.
Discussion
Primary care practitioners have a crucial role in improving 
rates of CD diagnosis, and in the ongoing care of patients with 
CD. 
A blood test for coeliac-specific antibodies will identify most 
patients who need to undergo duodenal biopsy to make the 
diagnosis. Management encompasses supporting patients 
with adherence to the gluten-free diet and conducting a 
CD-focused clinical review every 1–2 years.
Keywords
Coeliac disease
Previously understood to be a disease of the gastrointestinal 
tract, coeliac disease (CD) is now recognised as the most 
common of the autoimmune conditions. The target organ 
is the small intestine and the condition is characterised 
by chronic inflammation of the intestinal mucosa, 
leading to a wide range of clinical manifestations. These 
include malabsorption and abdominal symptoms, and 
extraintestinal symptoms such as fatigue and skin rashes. 
CD is unique among the autoimmune conditions because 
the environmental trigger of the destructive immune 
response (gluten ingestion) is well known and, for the 
majority of patients, removal of that trigger by commencing 
a gluten-free diet (GFD) brings about resolution of the 
mucosal damage and prevents complications.1 
Defining coeliac disease
There have been many attempts to define the various patterns of CD 
over time, but the 2013 Oslo definitions provide the clearest taxonomy 
of the types of CD to date.2 A summary of the key definitions is given 
in Table 1. 
The role of gluten
Gluten, the principal storage protein in wheat, consists of a number 
of proline- and glutamine-rich proteins. These amino acids are highly 
resistant to digestion and in genetically predisposed individuals their 
contact with the intestinal mucosa triggers the immune response seen 
in CD.3 This response to gluten is initiated by tissue transglutaminase 
(tTG), an enzyme that deamidates gluten peptides present in the 
small bowel mucosa. The deamidated gliadin peptides (DGPs) are 
then detected by antigen-presenting cells, which activate and lead to 
the proliferation of gluten-specific activated cytotoxic T cells.4 This 
immune response leads to the mucosal destruction in the small bowel, 
characteristic of CD. Because of the close similarity of their storage 
proteins to those in wheat, barley and rye also provoke this response.
Prevalence of coeliac disease
Although CD has been around for centuries, it is only in recent decades 
that we have begun to appreciate its complexities and impact on our 
Kristin Kenrick
Andrew S Day 
Immumology
REPRINTED FROM AUSTRALIAN FAMILY PHYSICIAN VOL. 43, NO. 10, OCTOBER 2014  675
population. Prior to this it was believed that CD was a rare disease, 
mostly affecting children, particularly those of Celtic or Northern 
European descent.
It is now clear that CD affects adults and children alike, and its 
presence has been confirmed in every continent.5 A population-based 
study in New Zealand determined a prevalence of biopsy-proven CD 
of 1.2%.6  A more recent Australian study estimated a prevalence 
of CD of 1.2% in men and 1.9% in women.7 There is also evidence 
that the prevalence of CD has increased over recent years in some 
countries.8–10
Recognising coeliac disease
CD presents in many different ways, which makes it challenging 
to recognise. Consequently, the number of people diagnosed 
remains well short of the number predicted to have CD, including 
in Australia.11 In addition to this, the average time to diagnosis can 
extend to several years.12,13
Classical CD is characterised by malabsorption and symptoms 
or signs associated with the gastrointestinal tract (Table 1). The 
more commonly occurring non-classical CD may manifest in a 
wide range of complaints. In addition to symptomatic patients, 
many individuals have subclinical CD. These patients may have 
underlying conditions associated with increased risk of CD (such as 
Down syndrome or type 1 diabetes mellitus) or have a first-degree 
relative with CD. Correct diagnosis of CD in these individuals 
relies on clinicians recognising their risk of CD and investigating 
accordingly. The significance of potential CD remains uncertain. A 
recent study following 175 children with this diagnosis found that 
67% continued to have normal duodenal histology after 9 years of 
follow-up.14
The 2009 NICE guidelines, Recognition and assessment of coeliac 
disease,15 provide recommendations to guide clinicians on when to 
investigate patients for possible CD, as summarised in Table 2.
Table 1. A summary of the Oslo definitions for coeliac disease2
Definition* Features
Classical CD Dominated by symptoms, signs and sequelae of gastrointestinal malabsorption. Patients have 
positive coeliac antibodies and villous atrophy on duodenal biopsy.
Non-classical CD The most commonly presenting variant of CD in which extraintestinal symptoms (such as fatigue) 
are predominant. There are no overt symptoms of malabsorption. Patients have positive coeliac 
antibodies and villous atrophy on duodenal biopsy.
Subclinical CD Patients have no overt symptoms or signs so are below the threshold of clinical detection. They do 
test positive for coeliac antibodies (usually found on screening at-risk individuals) and evidence of 
intestinal damage on biopsy.
Potential CD Previously known as latent CD. The diagnosis in patients with positive coeliac antibodies but no 
histological evidence of intestinal damage.
*Additional definitions were developed but are beyond the scope of this article. These include a definition for non-coeliac 
gluten sensitivity (NCGS), which is the Oslo panel’s preferred term for conditions labelled as gluten-sensitivity or gluten-
intolerance. For a recent discussion that summarises the current understanding of NCGS, refer to work by Biesiekierski 
et al.21
Table 2. NICE recommendations on who to test 
for coeliac disease15
Offer testing to patients (adults and children) with any of 
the following:
• Diarrhoea – chronic or intermittent
• Failure to thrive 
• Irritable bowel syndrome
• Persistent, recurrent or unexplained nausea, vomiting, 
abdominal pain or bloating
• Sudden or unexpected weight loss
• Unexplained iron-deficiency  (or other) anaemia
• Autoimmune thyroid disease
• Type 1 diabetes
• Dermatitis herpetiformis
• First-degree relative with CD
Consider testing patients with any of the following:
• Addison’s disease
• Autoimmune conditions – especially autoimmune liver 
disease, myocarditis, Sjögren’s syndrome, ITP
• Bone disease – osteomalacia, osteopaenia, osteoporosis, 
rickets, fragility fractures
• Down syndrome
• Gynaecological conditions – amenorrhoea, recurrent 
miscarriage, unexplained subfertility
• Lymphoma
• Mood disorders – depression or bipolar disease
• Neurological conditions – epilepsy, polyneuropathy
• Oral health problems – recurrent aphthous stomatitis, 
dental enamel defects
• Other gastrointestinal presentations – persistent 
or unexplained constipation, microscopic colitis, 
unexplained elevated liver enzymes
• Sarcoidosis
• Turner syndrome
• Unexplained alopecia
FOCUS Coeliac disease: where are we in 2014?
676  REPRINTED FROM AUSTRALIAN FAMILY PHYSICIAN VOL. 43, NO. 10, OCTOBER 2014
to identify false-positive antibody tests, leading to a reduction 
in unnecessary biopsies. However, this approach has yet to be 
confirmed by other investigators and is not yet endorsed for routine 
practice. 
In addition to the above, other tests are important to assess the 
impact of CD on intestinal function. These include full blood count, iron 
studies, vitamin B12, folate, vitamin D and liver chemistry. 
Managing coeliac disease
At present the only treatment for CD is a lifelong GFD. The diet should 
be commenced following confirmation of the diagnosis, with input from 
a dietitian with expertise in the area. As well as leading to resolution 
of symptoms and inducing mucosal healing, strict adherence to the 
GFD also reduces the subsequent risk of the potential sequelae of CD 
such as osteoporosis, other autoimmune diseases and small bowel 
lymphoma.16,17
Although a GFD has benefits, it can also lead to adverse effects. 
Patients on a GFD need to ensure that their diet contains enough fibre 
and the B-goup vitamins normally derived from gluten-containing 
grains. Constipation and overweight can occur, and the diet can also be 
high in saturated fats and sugars.18
The inclusion of oats in the GFD remains contentious. In the 
past it was believed that oats were harmful to patients with CD 
but this may not always be the case. The storage protein in oats 
is sufficiently different from wheat gluten that for the majority 
of patients it will not cause harm. However, oats are frequently 
contaminated with wheat or other cereals, compromising their 
inclusion in a GFD. The inclusion of uncontaminated oats in an 
individual’s GFD should be considered only after consultation with 
their gastroenterologist and dietitian, and when a comprehensive 
plan for follow-up is in place.16
Primary care practitioners have important roles to play in the 
ongoing care of patients with CD, as outlined in Table 4. Current 
guidelines recommend that all patients with CD should have an 
annual focused review. Primary care would be an appropriate place 
Diagnosing coeliac disease
Testing for CD in older children and adults is usually straightforward, 
providing the patient is eating a gluten-containing diet, as outlined 
in Table 3. Blood tests can detect the presence of specific IgA 
antibodies, such as those directed towards tTG and DGP as well 
as anti-endomysial antibodies (EMA), and can be used to identify 
individuals with possible CD. In patients with specific IgA-deficiency 
(2% of patients with CD) these tests will be falsely negative and  
IgG-based tests are then required. In addition, DGP antibodies 
have been shown to be more reliable than tTG in younger children 
(especially those less than 2 years of age).16
For patients already on a GFD, the situation is more complicated 
as the standard antibody tests may be falsely negative. These 
patients should therefore be advised to undertake a gluten challenge 
before being tested. The most recent recommendation for an 
adequate gluten challenge is that patients should consume at least 
two slices of wheat-bread per day for a minimum of 2 weeks and up 
to 8 weeks.17 
Although the antibody tests have high sensitivity and specificity 
for CD, definitive diagnosis relies on histological examination of 
biopsies from the duodenum and duodenal cap. Therefore, in the 
setting of a positive antibody test, or if an individual has significant 
symptoms and there is high clinical suspicion of CD, referral should 
be made for endoscopy. The characteristic features of CD (villous 
atrophy, crypt hyperplasia, intraepithelial lymphocytosis and 
mucosal inflammation) are seen under light microscopy of mucosal 
biopsies.1,16,17
Genetic testing with the HLA DQ2/DQ8 test can be helpful in 
certain circumstances. Given that >99% of patients with CD carry 
one or other of these markers, a negative test effectively excludes 
CD. A positive test is less helpful and cannot be used to diagnose 
CD because either HLA DQ2 or HLA DQ8 is present in at least 50% of 
the population,7 the majority of whom do not have CD. A recent study 
by Anderson et al7 suggests that when a patient returns a positive 
tTG or DGP test, the addition of HLA testing will enable clinicians 
Table 3. An approach to testing for coeliac disease
Patient eating gluten?
YES 
NO  gluten challenge: 2 slices bread/day for 2–8 weeks then coeliac serology 
If serology negative at 2 weeks then continue with challenge and repeat serology at 8 weeks
Coeliac serology IgA-tTG +/– IgA-EMA +/– IgA-DGP; total IgA levels
Negative serology IgA low +/– IgG test if available
IgA normal and low index of suspicion  NOT CD
IgA normal and high index of suspicion  refer for specialist review
Consider HLA DQ2 and DQ8 testing  negative test rules out CD
Positive serology Refer for duodenal biopsy*
*Duodenal biopsy (with multiple biopsies from the proximal duodenum) is required to confirm the diagnosis of CD. Other 
conditions that can give an elevated tTG include type 1 diabetes, inflammatory bowel disease, liver disease and other 
autoimmune diseases
tTG, tissue transglutaminase; EMA, endomysial antibody; DGP, deamidated gliadin peptide; IgA, immunoglobulin A
FOCUSCoeliac disease: where are we in 2014?
REPRINTED FROM AUSTRALIAN FAMILY PHYSICIAN VOL. 43, NO. 10, OCTOBER 2014  677
Authors
Kristin Kenrick BMedSci, MB ChB, Dip Obs, FRNZCGP, senior lecturer 
and PhD candidate, Department of General Practice and Rural Health, 
Dunedin School of Medicine, University of Otago, Dunedin, NZ.
Andrew S Day MB, ChB, MD, FRACP, Professor of Paediatrics, 
Department of Paediatrics, University of Otago, Christchurch, NZ
Competing interests: Andrew S Day is on the advisory board of 
Janssen and receives payment for this.
Provenance and peer review: Commissioned, externally peer reviewed.
References
1. Green PH, Cellier C. Celiac disease. N Eng J Med 2007;357:1731–43.
2. Ludvigsson JF, Leffler DA, Bai JC, et al. The Oslo definitions for coeliac 
disease and related terms. Gut 2013;62:43–52.
3. Kaukinen K, Lindfors K, Mäki M. Advances in the treatment of coeliac 
disease: an immunopathogenic perspective. Nat Rev Gastroenterol Hepatol 
2014;11:36–44.
4. Schuppan D, Zimmer KP. The diagnosis and treatment of celiac disease. 
Dtsch Arztebl Int 2013;110:835–46.
5. Kang JY, Kang AH, Green A, et al. Systematic review: worldwide varia-
tion in the frequency of coeliac disease and changes over time. Aliment 
Pharmacol Ther 2013;38:226–45.
6. Cook HB, Burt MJ, Collett JA, et al. Adult coeliac disease: prevalence and 
significance. J Gastroenterol Hepatol 2000;15:1032–36. 
7. Anderson RP, Henry MJ, Taylor R, et al. A novel serological approach deter-
mines the community prevalence of celiac disease and informs improved 
diagnostic pathways. BMC Med 2013;11:188–201.
8. Lohi S, Mustalahti K, Kaukinen K, et al. Increasing prevalence of coeliac 
disease over time. Aliment Pharmacol Ther 2007;26:1217–25.
9. Catassi C, Kryszak D, Bhatti B, et al. Natural history of celiac disease auto-
immunity in a USA cohort followed since 1974. Ann Med 2010;42:530–38.
10. White LE, Merrick VM, Bannerman E, et al. The rising incidence of celiac 
disease in Scotland. Pediatrics 2013;132:e924–31.
11. Anderson RP. Coeliac disease: current approach and future prospects. Int 
Med J 2008;38:790–99.
12. Cranney A, Zarkadas M, Graham I, et al. The Canadian celiac health survey. 
Dig Dis Sci 2007;52:1087–95.
for that to occur.16,17,19 In addition to enquiring about adherence to the 
GFD, an evaluation of symptoms should be undertaken (especially new 
symptoms suggestive of complications), and nutritional state should be 
assessed (especially in children). Primary care practitioners also have a 
role in ensuring that individuals with CD are fully vaccinated, including 
against encapsulated bacteria (eg Streptococcus pneumoniae), and 
receive annual influenza immunisations.16 
Although not currently relevant to the management of CD, a number 
of new therapies are undergoing evaluation. They include a therapeutic 
vaccine targeting T-lymphocyte activation, gluten-specific proteases 
(derived from bacteria, fungi or cereals) to degrade gluten proteins, 
probiotics, and immune modulation with hookworm infection.3,20 These 
therapies raise the future prospect that not all patients will require a GFD.
Key points
• CD affects at least 1% of the population; evidence suggests its 
prevalence is increasing.
• The diagnosis of CD depends on primary care practitioners being 
alert to its myriad presentations and those situations in which 
patients are at higher risk of the disease. 
• Testing for possible CD is simple: a blood test for tTG and/or DGP 
antibodies. The gold standard for diagnosing coeliac disease 
remains duodenal biopsy.
• The HLA DQ2/ DQ8 test is useful for excluding CD. 
• Treatment is a lifelong, strict GFD but a range of new treatments are 
under investigation.
• Patients with CD should be reviewed regularly, with attention to 
symptoms, adherence to the GFD, growth (in children), monitoring 
for complications and provision of preventive health initiatives.
Table 4. Management of patients with coeliac disease15,16
At diagnosis • Ensure referral to dietitian with expertise in CD
• Investigate for and treat micronutrient deficiencies (eg iron, vitamin B12, folate, vitamin D, 
calcium)
• Review for presence of complications or associated conditions (eg other autoimmune disorders)
• Consider evaluating bone mineral density (important for those with delayed diagnosis; past 
fragility fractures; post-menopausal women; men aged over 55 years)
• Review immunisation status
• Encourage to join coeliac support group (www.coeliac.org.au)
At 3–6 months • Assess response to diet: 
 – symptoms: should be resolving/have resolved
 – antibodies levels (especially tTG) should be falling 
 – micronutrient deficiencies should be resolving/have resolved
• Consider specialist dietetic review if recovery inadequate
• Recommend screening of first-degree relatives 
At 12 months and 
annually thereafter
• Review symptoms, GFD adherence, complications, associated diseases 
• Consider specialist gastroenterology review if recovery inadequate or new concerns
CD, coeliac disease; GFD, gluten-free diet; tTG, tissue transglutaminase 
FOCUS Coeliac disease: where are we in 2014?
678  REPRINTED FROM AUSTRALIAN FAMILY PHYSICIAN VOL. 43, NO. 10, OCTOBER 2014
13. Taylor E, Dickson-Swift V, Anderson K. Coeliac disease: the path to 
diagnosis and the reality of living with the disease. J Hum Nutr Diet 
2013;26:340–48.
14. Auricchio R, Tosco A, Piccolo E, et al. Potential celiac children: 9-year fol-
low-up on a gluten-containing diet. Am J Gastroenterol 2014;109:913–21.
15. National Institute for Health and Clinical Excellence. Coeliac disease: rec-
ognition and assessment of coeliac disease. 2009. Available at www.nice.
org.uk/guidance/CG86 [Accessed 30 June 2014].
16. Rubio-Tapia A, Hill ID, Kelly CP, et al. ACG clinical guidelines: diagnosis 
and management of celiac disease. Am J Gastroenterol 2013;108:656–76.
17. Ludvigsson JF, Bai JC, Biagi F, et al. Diagnosis and  management of adult 
coeliac disease: guidelines from the British Society of Gastroenterology. 
Gut 2014;63:1210–28.
18. Shepherd SJ, Gibson PR. Nutritional inadequacies of the gluten-free diet 
in both recently-diagnosed and long-term patients with coeliac disease. J 
Hum Nutr Diet 2013;26:349–58.
19. Haines ML, Anderson RP, Gibson PR. Systematic review: The evidence 
base for long-term management of coeliac disease. Aliment Pharmacol 
Ther 2008;28:1042–66.
20. Lähdeaho M-L, Kaukinen K, Laurila K, et al. Glutenase ALV003 Attenuates 
Gluten-Induced Mucosal Injury in Patients with Celiac Disease. 
Gastroenterology 2014;146:1649–58.
21. Biesiekierski JR, Muir JG, Gibson PR. Is Gluten a Cause of Gastrointestinal 
Symptoms in People Without Coeliac Disease? Curr Allergy Asthma Rep 
2013;13:631–38.


ACG clinical guidelines: diagnosis and management of celiac disease.

Coeliac disease: current approach and future prospects.

Coeliac disease: the path to diagnosis and the reality of living with the disease.

Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology.

for Health and Clinical Excellence. Coeliac disease: recognition and assessment of coeliac disease.

Increasing prevalence of coeliac disease over time. Aliment Pharmacol Ther

Is Gluten a Cause of Gastrointestinal Symptoms in People Without Coeliac Disease? Curr Allergy Asthma Rep 2013;13:631–38.

Natural history of celiac disease autoimmunity in a USA cohort followed since 1974. Ann Med 2010;42:530–38.

Nutritional inadequacies of the gluten-free diet in both recently-diagnosed and long-term patients with coeliac disease.

Potential celiac children: 9-year follow-up on a gluten-containing diet.

Systematic review: The evidence base for long-term management of coeliac disease. Aliment Pharmacol Ther

The Canadian celiac health survey. Dig Dis Sci 2007;52:1087–95. CD, coeliac disease; GFD, gluten-free diet; tTG, tissue transglutaminase FOCUS Coeliac disease: where are we in 2014? 678

The rising incidence of celiac disease in Scotland. Pediatrics

Coeliac disease: where are we in 2014?

http://apo.org.au/sites/all/modules/pubdlcnt/pubdlcnt.php?nid=41584&file=http://www.racgp.org.au/download/Documents/AFP/2014/October/201410Focus-Day.pdf

Coeliac disease: where are we in 2014?

Abstract

Similar works

Full text

Available Versions

Analysis and Policy Observatory (APO)