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Wheat is the most important cereal crop worldwide. Approximately 8% of people suffer from gluten-related disorders.
Coeliac disease (CD) is an immune-mediated systemic disease triggered by the intake of gluten and related prolamins in genetically susceptible individuals. It is characterised by the presence of various combinations of:
- Small intestinal damage
- Coeliac-specific antibodies
- Genetics (HLA DQ2 or HLA DQ8)
- Gluten-dependent clinical manifestations.
Elimination of gluten leads to complete resolution of the disease and there is a permanent sensitivity to gluten. It occurs in 1% of the world population and can develop across the lifespan.
Why is it important?
If untreated, it poses long-term adverse health consequences including:
- Poor growth
- Nutritional deficiencies in iron, zinc, calcium, Vitamin A, D, E, K, B12
- Intestinal lymphoma.
CD occurs in 1% of the population. Prevalence differs depending on the geographical and ethnical variation, but it can occur at any age from early childhood to the elderly. It has two peaks: shortly after weaning in the first two years and between 40-50 years. Less than 36% of cases are diagnosed in childhood. The average age of diagnosis is 44-52 years of age. It has female predominance at a ratio of 2:1.
The prevalence increases to 3% in those seropositive for HLA-DQ2 or HLA-DQ8. The incidence has increased rapidly over the past four decades.
Why is the prevalence of CD increasing?
The reason for the rapid increase in CD is unknown and hypotheses include viral infections in childhood and gut microbiota dysbiosis. Quality of gluten in the production of new grain variants produced for technological rather than nutritional reasons might also play a role. Another reason could be the consumption of very high quantities of gluten (up to 20g per day) in some diets, eg extreme versions of the Mediterranean diet.
There is now widespread use of highly sensitive and specific diagnostic tests for CD and there is an increase in knowledge and awareness among physicians. However, despite increased awareness around CD, the majority of CD patients remain undiagnosed.
Sero-epidemiological studies suggest that for every CD case, there are five to seven undiagnosed CD cases.
Wheat proteins, the gliadins and glutenin form rubbery aggregate gluten that is responsible for the baking properties of wheat flour. Gliadins, key components of gluten, are complex proteins unusually rich in prolines and glutamines and are not completely digestible by intestinal enzymes.
Gluten is a general term for alcohol-soluble proteins present in various cereals eg. wheat, rye and barley. These proteins are naturally present in:
- Wheat as gliadin, barley as hordein, rye as secalin and oats as avenins
- 100g wheat contains ~ 11g gluten
- 100g barley contains ~ 4g hordein
- 100g rye contains ~ 8g secalin
- 100g oats contains ~ 1g avenin
- Avenins are present at a lower concentration (10%–15% of total protein content) in oats as compared to gluten in wheat (80%–85%).
Environmental factors include gluten in the diet. Certain infections result in an increased risk of CD, such as gastrointestinal infections, frequent rotavirus infections, reovirus can be associated with increased risk of CD. The rotavirus vaccine has a protective effect.
Certain medications are associated with an increased risk of CD, such as proton pump inhibitors.
A higher socioeconomic status and hygiene vs more health-seeking behaviour has increased associations of CD.
There is no clear association in Caesarean section births and conflicting data regarding maternal iron supplementation/iron overload. There is no association in maternal gluten consumption.
In terms of seasonality, there is a slightly higher risk if born in summer. Breastfeeding is probably not protective.
The microbiome and CD
There is an environmental-dependent dysbiosis between host and environment causing a change in the microbiome and leading to CD.
Neonates with family risk factors for CD had:
- Increased bacteroidetes
- Increased Firmicutes
- Decreased lactobacillus species.
Associated risks for CD (estimated lifetime prevalence )
- First degree relatives of those with CD (10%)
- Twins: monozygotic 50 %; dizygotic 10%
- IgA deficiency (1.7-7.7%)
- Type 1 diabetes (>8%)
- Autoimmune thyroid disease (15%)
- Autoimmune liver disease (12%)
- Trisomy 21 (5-12%)
- Williams syndrome (>8.2%)
- Turner syndrome (4.1-8.1%)
- Juvenile chronic arthritis
- Dermatitis herpetiformis (75%).
Patients with these associated risks must all be screened for CD.
Diagnosis of CD can be challenging as symptoms vary significantly between patients. Many conditions can be mistaken for CD.
- Clinical: Typical signs and symptoms ( diarrhoea and malabsorption)
- Serological: Antibody positivity
- Genetic: HLA-DQ2 and /or HLA-DQ8 positivity
- Histological: Intestinal damage (villous atrophy)
- Clinical response to gluten-free diet
- Person must be on a gluten-containing diet.
A diagnostic delay ranges from 4-13 years. Patients with associated risks and those with clinical manifestations of CD should all be screened (tissue transglutaminase [TTG]-IgA) for CD.
The role of serology in CD diagnosis
Serology is useful in:
- Screening patients for CD
- The diagnosis of CD
- Identifying patient who don’t need an intestinal biopsy
- Monitoring adherence to a gluten-free diet.
- TTG and endomysial antibodies (EmA) antibodies are very specific
- IgA class antigliadin anti-gliadin antibodies (AGA) is now obsolete with levels of sensitivity and sensitivity lower than TTG and EMA
- However, antibodies against deaminated gliadin (DGP) perform as well as TTG. They are useful in children <2 years as they are the first antibodies to appear
- IgG antibody tests should only be used in patients with selective IgA deficiency. IgA deficiency is defined as total serum IgA <0.2g/l
- Blood tests are recommended
- Saliva: encouraging but not sufficient evidence to recommend
- Faeces: sensitivity very low at 10%, therefore not suitable.
Coeliac-specific serology is very reliable for the diagnosis of CD. The most accurate initial testing is IgA and TTG-IgA antibodies. HLA DQ-2 and HLA DQ-8 are useful to exclude CD, not to diagnose it.
The no biopsy approach for CD diagnosis is safe in children with symptoms suggestive of CD with: TTG-IgA >10x normal, positive EMA –IgA in a second sample. Serological and histological normalisation can take years.
If TTG-IgA is greater than 10 times the upper limit of normal then a duodenal biopsy on a gluten diet is necessary. Currently, the only treatment is a lifelong gluten-free diet (easy in theory, difficult and costly to follow).
A dietician is essential to educate the patient about what a gluten-free diet entails. Guide patients to CD resources. New treatments (as adjuvants to a gluten-free diet) are in the pipeline.
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