– HOW TO INCREASE COELIAC DISEASE DETECTION OF A COMMON DISORDER

Transcription

– HOW TO INCREASE COELIAC DISEASE DETECTION OF A COMMON DISORDER
COELIAC DISEASE – HOW TO INCREASE
DETECTION OF A COMMON DISORDER
THAT IS COMMONLY MISSED.
Coeliac disease is a common disease with effective treatment, however the vast
majority of cases are detected late and many cases remain undetected. Raised
awareness by the primary care physician can play a vital role in increasing
detection.
The aim of this article is to increase physician awareness by answering the
question: “Who should be tested for coeliac disease?” Readers will then be
presented with a simple and effective way to deal with patients who have
suspected coeliac disease.
DEFINITION
Coeliac disease is an immune disorder characterised by an intolerance to gluten,
a term used broadly to describe the storage proteins in wheat, rye, and barley.
Gluten triggers chronic small bowel inflammation in genetically predisposed
individuals, which can lead to the classic features of villous atrophy and
malabsorption.
EPIDEMIOLOGY
Approximately 1% of Australians have coeliac disease. Increasing use of
serological screening tests over the last 10 years has revolutionized coeliac
disease - it is clearly a common disease that manifests a diverse range of
pathology.
In the USA the prevalence of coeliac disease was reported to be 1 in 5000 in
Olmsted County in 1994, but in the landmark 2003 study based on serological
screening verified by small bowel histology, 1 in 133 Americans had coeliac
disease - fewer than 5% had been diagnosed through standard medical care.
INCREASING MEDICAL AWARENESS
Clinical awareness of coeliac disease is now relatively high in Australia. The
monthly figures for Medicare claims for ‘coeliac serology’ rose 60% between
January 2004 and October 2007; during this period 824 965 claims were lodged,
being roughly 4% of Australia’s population. Typically, 1 in 30-50 patients tested
for coeliac disease by GPs is confirmed by small bowel biopsy.
Even though improved technology and medical awareness have significantly
increased detection rates, coeliac disease remains substantially underdiagnosed. In most developed countries with sophisticated health care, only 10%
of people with coeliac disease are diagnosed.
INCREASING DETECTION OF COELIAC DISEASE
Detection of coeliac disease can be increased when the primary care physician is
familiar with both the classic presentation and is also aware of the nonspecific
nature of coeliac disease.
CLASSIC PRESENTATION
The classic presentation of coeliac disease is of malabsorption, with diarrhoea or
steatorrhoea, weight loss and nutritional deficiencies.
HIGH-RISK POPULATIONS
The most cost effective way to increase detection of coeliac disease is by
identifying high-risk populations.
RELATIVES
First-degree relatives of patients with coeliac disease are at higher risk, with a
prevalence of at least 10%. The highest prevalence of coeliac disease occurs in
first-degree relatives from families with more than one index case, while the
prevalence in second-degree relatives is lower (2.6-5.5%).
IRON DEFICIENCY ANAEMIA
Coeliac disease should be considered in any adult with unexplained iron
deficiency anemia (FDA), including menstruating women.
The prevalence of coeliac disease in symptomatic patients with FDA is 10-15%.
OSTEOPOROSIS
The prevalence of coeliac disease may be increased in patients with
osteoporosis (1.5-3%), especially in those with premature osteoporosis.
TYPE 1 DIABETES MELLITUS
The prevalence of coeliac disease in patients with type 1 diabetes mellitus
ranges from 2% to 5% in adults and from 3% to 8% in children.
PATIENTS WITH LIVER DISEASE
There is an association between coeliac disease and liver disease. Primary care
physicians should be aware of these associations and test for coexistent coeliac
disease in patients with unexplained elevated transaminase levels, autoimmune
hepatitis, and primary biliary cirrhosis.
GENETIC DISORDERS
The prevalence of coeliac disease in patients with Down syndrome ranges from
3%-12%, and for patients with Turner’s syndrome the range is 2%-10%.
REPRODUCTIVE DISORDERS
Coeliac disease is associated with reproductive complications, including delayed
menarche, fewer live births, and higher rates of miscarriage. The prevalence of
coeliac disease ranges between 2.1% and 4.1% in women with unexplained
infertility.
OTHER DISEASES
Coeliac disease has also been associated with Addison’s disease, IgA
nephropathy, idiopathic epilepsy, occipital calcifications, and ataxia.
There is also an increased prevalence of coeliac disease in several autoimmune
disorders, such as Sjogren’s syndrome.
NONSPECIFIC PRESENTATION
However, many cases of coeliac disease present with subtle, nonspecific GI
symptoms. There are numerous extra-gastrointestinal manifestations of coeliac
disease, and there are many cases which are completely asymptomatic.
LOCAL EXPERIENCE
A retrospective study of 2000 consecutive patients undergoing upper endoscopy
in South Western Sydney highlighted the atypical presentation of coeliac
disease.
Constipation occurred as commonly as diarrhoea in patients with coeliac disease
(34%). Weight loss was the least common clinical feature (18%), and weight gain
was also seen in some patients.
Abdominal pain, bloating and irritable bowel symptoms occur commonly in
coeliac disease, as do fatigue and recurrent headaches. The astute physician will
consider coeliac disease when vague, nonspecific symptoms are unexplained by
other causes.
SCREENING TESTS
The following tests are available in the screening and diagnosis of coeliac
disease:
Serology (IgA/IgG)
Tissue transglutaminase (tTG)
Antiendomyseal antibody (EMA)
Antigliadin antibody
HLA genotyping (HLA DQ2/DQ8)
Small Bowel Histology
WHAT IS THE BEST TEST FOR SCREENING?
In the primary care setting, the IgA tTG is the most efficient single serologic test
for the detection of coeliac disease. In low-risk adults, this is the only test that
needs to be ordered, and a negative test effectively excludes coeliac disease.
WHAT ARE THE EXCEPTIONS?
IgA tTG is an excellent tool for exclusion of coeliac disease in low-risk adult
patients, but in groups at high risk of coeliac disease the negative predictive
value of tTG deteriorates. Adding additional serological tests (e.g. antigliadin)
and HLA DQ genotyping will increase the sensitivity of testing for high-risk
patients.
In addition, almost 10% of coeliac disease is seronegative and serological
testing is unreliable in the very young, in people already on a low gluten diet, and
those using immunosuppressive medications These patients require further
testing with HLA genotyping &/or small bowel biopsy.
HLA DQ GENOTYPING
HLA genotyping can be a useful test, particularly when a diagnosis of coeliac
disease remains unclear. Almost all patients with coeliac disease have either
HLA DQ2 or DQ8. This means that the absence of these alleles in a patient
virtually excludes coeliac disease.
However, since these alleles are present in 40% of the general population,
genotyping is only useful as a test of exclusion (sensitivity 99%, specificity <5%).
In other words, a negative test excludes coeliac disease, whereas a positive test
does not provide additional information.
HLA genotyping is the only diagnostic test that does not depend on gluten
exposure. This makes it a particularly useful test for patients who are already on
a GFD and who are unable to tolerate a gluten challenge.
DIAGNOSIS
The diagnosis of coeliac disease requires both positive small bowel histology
(gold standard), as well as clinical improvement on strict GFD. Serology and
gene tests are supportive but alone, are not sufficient to diagnose coeliac
disease.
It is crucial that the dietary status of the patient at the time of biopsy be taken
into account. Patients should undergo biopsy promptly after a positive serological
test and should be told not to avoid gluten until after biopsies are taken.
Unfortunately, many people who believe they are ‘gluten sensitive’ and follow a
gluten-free diet have not been adequately assessed to exclude coeliac disease.
A gluten-reduced diet may reduce the severity of histological changes and cause
patients to become seronegative, making a definitive diagnosis difficult.
If gluten has not been regularly consumed for more than a month ‘gluten
challenge’ is necessary to ensure that small bowel histology is interpretable.
GLUTEN CHALLENGE
Gluten challenge should consist of at least 2-4 slices of wheat or rye bread daily
for more than 1 month, preferably 3-6 months. The duration of gluten challenge is
generally determined by symptoms - rye is often tolerated better than wheat
bread.
TREATMENT
Treatment of coeliac disease requires a strict, lifelong adherence to a gluten free
diet (GFD). Consultation with an experienced dietician, referral to the Coeliac
Society, and clinical follow-ups for compliance are recommended.
Treatment of nutritional deficiency states (iron, folate, B12) is essential, and BMD
to assess for osteoporosis is recommended.
PROMOTING ADHERENCE TO A GLUTEN-FREE DIET
Perhaps the strongest motivation for adherence to a GFD is that symptoms
typically improve with weeks of gluten exclusion. Patients should also have an
understanding that compliance with GFD can significantly improve nutritional
parameters and bone mineral density, and is likely protective against the
development of non-Hodgkin’s lymphoma.
MONITORING ADHERENCE
Repeat small bowel histology 3-6 months after commencing GFD is helpful in
confirming remission and optimal dietary compliance. Serology is less reliable in
monitoring remission, and is only sensitive for major but not minor dietary
indiscretions.
A NOTE ON OATS
GFD with exclusion of foods derived from wheat, rye and barley is mandatory for
coeliac disease. In some countries, such as Australia, oats are also excluded in
GFD, however this is controversial.
It should be assumed that unless clearly stated they are ‘free of gluten
contamination’, all oats should be considered contaminated with gluten and not
suitable for coeliac disease. There is also evidence that a gluten-like avenin
protein in oats can cause mucosal damage. However, if patients are monitored
with small bowel biopsy, an oats challenge may be trialed.
CONCLUSIONS
Coeliac disease is a common and curable disorder which is often missed. The
key to increased detection is better clinician awareness of both the classical
presentation as well as the nonspecific presentations. IgA tTG is the best
screening test in the primary care setting. High-risk populations require additional
screening tests. HLA genotyping is useful as a test of exclusion, and is the only
test which does not depend on gluten exposure.
Small bowel histology is mandatory in making a diagnosis of coeliac disease
(gold standard), although dietary status at the time of biopsy needs to be taken
into account - a gluten challenge may be required.
Currently the only effective treatment of coeliac disease is strict lifelong
adherence to a gluten free diet (GFD), however pharmaceuticals to target various
steps in the pathogenesis of coeliac disease are under development.
WHO SHOULD BE TESTED FOR COELIAC DISEASE?
The clinician needs to be familiar with the classic presentation of coeliac disease
and target high-risk populations, such as those with diarrhoea, weight loss, iron
deficiency anaemia, and positive family history. The clinician should also be
aware of the nonspecific nature of coeliac disease and should consider screening
those with unexplained GI or constitutional symptoms, such as abdominal pain,
bloating, fatigue and recurrent headaches.
HIGH-RISK POPULATIONS
Table 1 The prevalence of coeliac disease in certain high-risk populations.
Relatives
10%
Iron deficiency anaemia
10-15%
Osteoporosis
1.5-3%
Type 1 diabetes mellitus
2-5%
Liver disease
1.5-9%
Genetic disorders
3-12%
Autoimmune thyroid disease
1.5-6.7%
Reproductive disorders
2.1-4.1%
Other diseases
ENDOSCOPY
Figure 1 The typical findings on endoscopic examination of the small bowel include
scalloping of the duodenal folds, a mosaic and nodular mucosal pattern, and loss of
duodenal folds. These changes are only apparent to the endoscopist in 50 to 87.5% of
cases, and coeliac disease can be missed unless a routine small bowel biopsy is taken
SMALL BOWEL HISTOLOGY
Figure 2 The slide on the left demonstrates normal villi, whereas the slide on the right
shows the typical features of coeliac disease, which include increased intraepithelial
lymphocytes, crypt hyperplasia, and villous atrophy.
REFERENCES
1. Anderson RP. Coeliac disease: current approach and future prospects. Int
Med J 2008; 38: 790-9.
2. AGA Institute Medical Position Statement on the Diagnosis and Management
of Celiac Disease. Gastroenterology 2006; 131: 1977-80.
3. Simring AA, Eslick GD, Kalantar JS. Routine duodenal biopsy is a costeffective way to increase the yield of diagnosing coeliac disease in patients
undergoing upper gastrointestinal endoscopy. Gastroenterology 2008; 134(4):
A364.