Coeliac Disease

 

• Background

  Pathophysiology

  • Gliadin – part of the protein composite which forms gluten along with glutenin – is modified during digestion by the enzyme tissue transglutaminase (tTG). This leads to the formation of a covalently bonded complex, comprising tTG and gliadin.
  • Coeliac disease involves an autoimmune response to this complex, resulting in intestinal damage.
  • The anti-tTG antibodies that form also bind to tTG in the endomysium, part of the connective tissue sheath of muscles. While used in diagnosis, this plays no role in coeliac pathology or symptoms.
  • The HLA-DQ variants DQ2 and DQ8 – part of the MHC II antigen-presentation molecule – are present in nearly all patients, as these bind more strongly to gliadin peptides.

  Epidemiology

  • Prevalence: 1/100 in the UK.
  • Presents at any age, but small peak in kids age 1-3 years, when first exposed to gluten.

• Signs and symptoms

  GI:

  • Diarrhoea and steatorrhea.
  • Abdominal pain.
  • Bloating
  • Weight loss.

  Other:

  • Anaemia leading to fatigue.
  • Osteoporosis due to Ca2+ and vitamin D malabsorption, leading to bone fractures.
  • Mouth ulcers and angular stomatitis.
  • Dermatitis herpetiformis.

  Infants and young children:

  • Diarrhoea and/or constipation.
  • Failure to thrive.
  • Vomiting and anorexia.
  • Abdominal protrusion and wasted buttocks.

• Risk factors

  • Family history of coeliac.
  • Other autoimmune disease: T1 diabetes, autoimmune thyroid disease.
  • IgA deficiency.

• Investigations

  Diagnosis:

  • Anti-tTG IgA. Check total IgA too, and if deficient (1/25), use tTG IgG or DGP IgG instead.
  • Endomysial antibody is more specific but less sensitive. Use if anti-tTG is equivocal.
  • Biopsy via upper endoscopy to confirm the diagnosis. Shows villous atrophy and crypt hyperplasia.
  • HLA-DQ2/8 typing if diagnosis unclear. Coeliac is very unlikely if negative.
  • Patients should stay on gluten while under investigation to ensure test accuracy.

  Other tests:

  • FBC and blood smear: anaemia, which is usually iron-deficiency (check ferritin), but can also be B12 or folate deficiency.
  • LFT: may show raised transaminases.
  • Ca2+ and albumin.
  • Skin biopsy in dermatitis herpetiformis.
  • TFT and glucose for other autoimmune diseases.
  • Bone check: DEXA.

  Screening for coeliac:

  • 1st degree relatives of anyone with coeliac.
  • Patients with autoimmune thyroid disease or T1 diabetes.

• Management

  Dietary:

  • Life-long gluten free diet. Arrange regular follow up with a dietician. Common gluten sources are wheat (inc. bread and pasta), rye, and barley. 'Hidden' sources include oats (if harvested with wheat), sauces, shared kitchen equipment, and processed meats.
  • Replace micronutrients if deficient: Ca2+, vitamin D, iron, folate, B12.

  Monitoring:

  • Annual review: at minimum, check BMI and review diet and symptoms. Consider checking FBC, LFTs, Ca2+, albumin, ferritin, folate, B12, TFT, and glucose.
  • DEXA 1-3 years after diagnosis, and at menopause (or age 55 in men).

• Complications

  • Osteoporosis
  • Small increase in risk of small bowel adenocarcinoma and enteropathy-associated T cell lymphoma.