Coeliac Disease

Epidemiology

Prevalence differs a lot among different parts of the world and it is considered to be underestimated – it is approximately 1%. It is seen more often in diabetes, autoimmune disorders and relatives of Coeliac disease individuals (1).

The average prevalence is about 1% in USA and Europe, but higher in Africa: 5.6% in West Sahara (2).

Pathophysiology

Coeliac disease has a complex pathogenesis that is not yet fully understood. It results from a combination of immunological responses to an environmental factor (gliadin) and genetic factors (HLA-DQ2/DQ8). Infant feeding practices, viral infections and gut bacteria may also play a role in developing coeliac disease.

Immune mechanisms

In simple words, when the body’s immune system overreacts to gluten in food, the reaction damages the villi that line the small intestine. Villi help to absorb vitamins, minerals and nutrients. When villi are damaged malabsorption occurs.

Coeliac disease is considered a T cell-mediated immune disorder. The main characteristics are development of inflammatory anti-gluten CD4 T cell response, anti-gluten antibodies, autoantibodies against tissue transglutaminase, endomysium (connective tissue surrounding intestinal muscle) and the activation of intraepithelial lymphocytes. All of these result in epithelial cell destruction and villous atrophy (3).

Risk factors

The main risk factor is gluten included in the diet of a genetically predisposed child.

Gluten is a protein found in three types of cereal (4):

• Wheat
• Barley
• Rye

Food that contains the above cereals (4):

• bread
• beers, lagers, stouts and ales
• barley water drinks (e.g. fruit and barley squash)
• biscuits or crackers
• breakfast cereals
• cakes and pastries
• packet and jar gravies and sauces
• pasta
• pies
• some types of ready meals

Conditions related with coeliac disease (5):

• Type 1 diabetes
• Down syndrome
• Turner syndrome
• Other autoimmune diseases, such as thyroid disease, rheumatoid arthritis & Addison’s disease.

Clinical Presentation

The clinical picture of coeliac disease varies a lot. Younger children tend to develop the classic form with gastrointestinal symptoms, whereas older children and adults may manifest extra-intestinal symptoms more commonly.

The following clinical forms have been recognised (6):

1. Classical form: Most common presentation at 9-24 months of age with features of malabsorption, such as failure to thrive/ weight loss, loose stool, steatorrhea, anorexia, abdominal pain, abdominal distention, muscle waste. Child is often miserable with behavioral changes. Histology reveals crypt hyperplasia and villous atrophy.
2. Atypical form: Usually no intestinal symptoms, but associated extra intestinal conditions such as osteoporosis, peripheral neuropathy, anaemia and infertility. There is usually positive coeliac serology, limited abnormalities of the small intestinal mucosa.
3. Latent form: presence of predisposing gene HLADQ2 and/or HLADQ8, normal intestinal mucosa and possible positive serology
4. Silent form: Damaged small intestinal mucosa, positive serology but no clinical symptoms
5. Potential: normal mucosal morphology, positive autoimmune serology and patients may not be symptomatic. This group is genetically predisposed to develop at some point coeliac disease.

Apart from the classical gastrointestinal symptoms there are a variety of extra-intestinal symptoms such as (7):

• Dermatitis herpetiformis
• Dental enamel hypoplasia
• Osteoporosis
• Delayed puberty
• Short stature
• Iron- deficient anaemia- resistant to oral Fe
• Liver and biliary tract disease
• Arthritis
• Peripheral neuropathy, epilepsy, ataxia

Differential Diagnoses

Among the conditions to consider are the following (8):

• Tropical sprue
• Cystic fibrosis
• Inflammatory bowel disease
• Post – gastroenteritis
• Autoimmune enteropathy
• Eosinophilic enteritis

Investigations

1. Serology:

Offer serological testing for coeliac disease to (9):

• children with any of the following:
  • persistent unexplained abdominal or gastrointestinal symptoms
  • faltering growth
  • prolonged fatigue
  • unexpected weight loss
  • severe or persistent mouth ulcers
  • unexplained iron, vitamin B12 or folate deficiency
  • type 1 diabetes, at diagnosis
  • autoimmune thyroid disease, at diagnosis
  • irritable bowel syndrome (in adults)
• First‑degree relatives of people with coeliac disease

Investigations for coeliac disease will be accurate only if the patient is having gluten in the diet at the period of the testing and for at least 6 weeks before testing.

• Test for total immunoglobulin A (IgA) and IgA tissue transglutaminase (tTG) as the first choice
• If IgA tTG is weakly positive, then use IgA endomysial antibodies (EMA)
• If  total IgA is deficient, then consider using IgG EMA, IgG deamidated gliadin peptide (DGP) or IgG tTG

• Only consider using HLA DQ2 (DQ2.2 and DQ2.5)/DQ8 testing in the diagnosis of coeliac disease in specialist settings (for example, in children who are not having a biopsy, or in people who already have limited gluten ingestion and choose not to have a gluten challenge).

• Endoscopic intestinal biopsy is necessary when the serology is positive
• Referral to specialists is required if serology is positive or ongoing clinical concerns despite negative serology

2. Biopsy:

Duodenal biopsy is considered the gold standard to diagnose if a child has coeliac disease, to ensure findings are improved on a gluten-free diet or diagnose a different gastrointestinal disorder.

Classification by Marsh

Management

The only treatment for coeliac disease is lifelong diet free of gluten. In cases where children had obvious malabsorption at time of diagnosis, it is appropriate to treat with diet supplements, such as iron.

Patients with coeliac disease should have annual follow up to check for symptoms, diet compliance, development, growth and long term complications.

Gluten free diet:

• most dairy products, cheese, butter and milk
• fruit and vegetables
• meat and fish
• potatoes
• rice
• gluten-free flours, including rice, corn, soy and potato (10)

Prognosis

Prognosis is good for children when they strictly follow a gluten free diet.

Complications may include:

• anaemia
• osteopenia/ osteoporosis
• refractory coeliac disease( symptoms persist despite diet, my need treatment with steroids)
• malignancy
• fertility problems/ adverse events during pregnancy
• depression/ anxiety (11, 12)

References

Authors:

1st Author: Paediatric ST1 Dr Natalia Georgara

Senior reviewer: Dr Hema Kannappa, Paediatric ST8