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Coeliac disease
Coeliac disease

Coeliac disease

Coeliac disease is an autoimmune condition where one reacts to gluten peptides in the small bowel. It affects about 1% of the population, usually developing in early childhood but can develop at any age

Pathophysiology

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Auto-antibodies to gluten are created and these target the epithelial cells of the small bowel → inflammation. The jejunum in particular is most commonly affected.

We lose immune tolerance to peptide antigens in wheat (gluten and gliadin), rye (secalin) and barley (hordein). These peptides are resistant to protease breakdown and as a result they persist in our lumen. When they enter the lamina propria (through unknown mechanisms) they trigger an innate and adaptive immune response.

Gluten peptides are de-amidated in the submucosa through tissue transglutaminase (tTG) which then allows binding to coeliac-associated HLA molecules, those being HLA-DQ2 (95%) or HLA-DQ8 (5%), which are found on APCs and T-helper cells. Th2 cells trigger anti-deamidated gliadin peptide antibodies (anti-DGP) and anti-tTG antibody production.

The activation of these cells results in tissue remodelling and villous atrophy. We then get crypt hyperplasia as well.

🧬 Genetic associations

  1. HLA-DQ2
  2. HLA-DQ8

🧬 Auto-antibodies

  1. Anti-tTG
  2. Anti-DGP
  3. Anti-endomysial antibodies (EMAs)

😷 Presentation

About 20% of patients are asymptomatic.

  • Chronic or intermittent diarrhoea
  • Failure to thrive in children (failure to gain weight as they should be)
  • Bloating and abdominal discomfort/pain
  • Prolonged fatigue - feeling constantly tired. Anaemia is a common complication of coeliac disease (iron, folate, B12)
  • Persistent/unexplained nausea and vomiting
  • Weight loss
  • Dermatitis herpetiformis - an itchy, blistering skin rash that is typically on the abdomen and is associated with coeliac disease.
  • Osteopenia/osteoporosis - or history of bone fractures. This is due to vitamin D deficiency and hypocalcaemia.
  • IgA deficiency - it is important to remember that anti-tTG and anti-EMA are also IgA, so when testing for coeliac antibodies we need to exclude IgA deficiency first. If there is deficiency the as can check the IgG version of these antibodies or do an endoscopy with biopsy
🧠
Neurological symptoms:

Sometimes, rarely, coeliac disease may present with neurological symptoms such as:

  1. Peripheral neuropathy
  2. Cerebellar ataxia
  3. Epilepsy
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🔍 Investigations

🧬
IgA levels:

The patient must remain on a normal diet that they were on (containing gluten) or else antibodies may not be detected.

  1. Check total IgA first to ensure there is no IgA deficiency that will render a tTG test insensitive. This is also important as IgA deficiency is more common in coeliac patients than the general population.
  2. 🥇 IgA-tTG - elevated.
  3. 🥇 IgG-DGP - if the patient has IgA deficiency, this is the test of choice.
  4. 🥇 IgA-EMA - elevated.
  • FBC is also done to look for signs of anaemia:
    • Low Hb
    • Low MCV
    • Hypochromic cells
    • High MCV if there is folate (and sometimes B12) deficiency.
🏆
Endoscopic biopsy:

Gold-standard investigation is biopsy. It is normally done in the duodenum. The endoscopic appearance is not sensitive, but biopsy is essential and sensitive.

Findings that can support a diagnosis include:

  1. Villous atrophy
  2. Crypt hyperplasia
  3. Increase in intraepithelial lymphocytes
  4. Lamina propria lymphocyte infiltration

If the patient has any skin lesion such as dermatitis herpetiformis then it should be biopsied too.

🔢 Classification

We can use the Modified Marsh Classification of histologic findings for coeliac disease. It grades the disease from 0-3c based on intraepithelial enterocytes in the duodenum and jejunum, the presence of crypt hyperplasia, and the degree of atrophy of the villi. It is not essential to know this classification (in my opinion) as there has been a bit of controversy whether it is useful and reliable.

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🧰 Management

  • 🥇 Gluten-free diet - the first-line and most valuable treatment is a gluten-free diet. This is “curative” in most cases. However, patients will relapse when eating gluten. Anti-tTGs may be checked to assess compliance with the diet. Rice, potatoes and corn are gluten-free and are often to be mistaken for containing gluten.
  • 🥇 Vitamin supplementation
    • Ferrous sulfate - for iron deficiency.
    • Calcium carbonate - for hypocalcaemia.
    • Ergocalciferol - for Vitamin D deficiency.
    • Folic acid - for folate deficiency.
    • Cyanocobalamin - for B12 deficiency.

If refractory to dietary changes, one should be referred to a dietician or gastroenterologist.

⏰
Coeliac crisis:

This is rare but presents with hypovolaemia, watery diarrhoea, acidosis, hypocalcaemia and hypoalbuminaemia. It may follow a major medical event prior such as abdominal surgery.

  1. Rehydration and electrolyte correction
  2. Short course of glucocorticoids
    1. Budesonide (9mg orally OD)
    2. OR prednisolone (40-60mg orally OD initially)

🚨 Complications

  • Anaemia
  • Osteoporosis
  • Ulcerative jejunitis
  • Vitamin deficiency
  • Non-Hodgkin Lymphoma
  • Enteropathy-associated T-cell Lymphoma (EATL)
  • Functional hyposplenism
    • As a result, Coeliac UK recommends that everyone with coeliac disease has a pneumococcal vaccine and booster every 5 years as well as the annual influenza vaccine.

Some associations that we may find with coeliac disease are:

  1. Thyroid disease
  2. Type 1 diabetes mellitus - therefore, we test all coeliac patients for T1DM even if they have no symptoms as the conditions are often linked.
  3. Autoimmune hepatitis
  4. Primary biliary cirrhosis
  5. Primary sclerosing cholangitis