Coeliac Disease (Gluten-Sensitive Enteropathy)

Tuesday, June 16, 2026
Coeliac Disease (Gluten-Sensitive Enteropathy)
Aetiology & Pathophysiology
  • Definition: A systemic, T-lymphocyte mediated autoimmune disorder triggered by the ingestion of gluten in genetically predisposed individuals.
  • Genetic Susceptibility:
  • Strongly associated with specific HLA class II genes.
  • The majority of patients possess the DQ2 heterodimer (encoded by HLA-DQA105 and HLA-DQB102 alleles) or the DQ8 heterodimer (encoded by HLA-DQA103 and HLA-DQB10302 alleles).
  • A negative HLA DQ2/DQ8 test effectively excludes the diagnosis, but a positive test is not diagnostic (found in > 50% of the general population, whereas only 3% of those develop the disease).
  • Trigger Proteins (Prolamins):
  • Gliadin (in wheat), hordeins (in barley), and secalins (in rye).
  • Avenin (in oats) is generally tolerated, but oats are often cross-contaminated during processing with wheat, barley, or rye, and are therefore avoided.
  • Pathogenic Pathway: Gluten ingestion → Deamidation of peptides by tissue transglutaminase (tTG) → Presentation by HLA-DQ2/DQ8 to intestinal T-lymphocytes → Activation of Th1 T-cells → Pro-inflammatory cytokine release → Mucosal inflammation & villous damage.
Associated Conditions
  • Endocrine:
  • Type 1 Diabetes Mellitus (T1DM): Coeliac disease occurs in 4–9% of children with T1DM.
  • Addison disease.
  • Autoimmune thyroid disorders.
  • Chromosomal Syndromes:
  • Down Syndrome (Trisomy 21): 5–7% prevalence; routine screening is recommended at 24 months of age.
  • Turner Syndrome: ~5% prevalence; screening is recommended every 2 years from mid-childhood regardless of symptoms.
  • 22q11.2 Deletion syndrome.
  • Immunological: Selective IgA deficiency (occurs in 1 in 50 patients with coeliac disease).
Clinical Features
  • Gastrointestinal Signs & Symptoms:
  • Severe diarrhoea presenting between 3 and 9 months of age, or moderate diarrhoea presenting from 9 months to late childhood.
  • Abdominal distension ("pot belly") accompanied by weak abdominal musculature.
  • Steatorrhoea or offensive stools.
  • Extraintestinal / Systemic Signs:
  • Growth failure: Falling weight percentiles characteristically timed with the introduction of gluten-containing cereals into the diet.
  • Short stature / failure to thrive.
  • Irritability (frequently associated with concomitant iron deficiency).
  • Anaemia (due to mucosal malabsorption of folate, vitamin B12, or iron).
  • Dermatitis herpetiformis (a characteristic skin manifestation).
  • Pubertal delay.
⚠️ Red Flags in Comorbidities:
  • In T1DM, coeliac disease is asymptomatic in 2/3 of patients but can present dangerously as frequent unexplained hypoglycaemia or poor metabolic control.
Investigations
  • Serology (First-Line Screening):
  • Total Serum IgA: Must be measured concurrently to evaluate for selective IgA deficiency, ensuring accurate interpretation of IgA-based serology.
  • Anti-tissue transglutaminase (tTG) IgA: High sensitivity (95%) and specificity (90%).
  • Endomysial antibody (EMA) IgA: Sensitivity 90%, specificity approaches 100%.
  • If IgA Deficient: Test for tTG IgG or anti-deamidated gliadin-related peptide (a-DGP) IgG (both isotypes of a-DGP are highly sensitive and specific for active disease).
  • Age < 2 years: Antigliadin IgG antibodies may be used as children under 2 have a limited ability to produce IgA antibodies.
  • Gluten Challenge: Serology may be falsely negative if the patient is already on a gluten-free diet. A challenge (2 slices of wheat-based bread per day for 2–8 weeks) may be required before testing.
  • Endoscopy and Small Bowel Biopsy (Gold Standard):
  • Obtained endoscopically from the post-bulbar duodenum.
  • Classical Histological Triad:
  1. Partial or complete villous atrophy.
  1. Crypt hyperplasia.
  1. Increased intraepithelial lymphocytes.
  • Stool Analysis (Adjunct):
  • Fatty acid crystals (confirms mucosal malabsorption).
  • Elevated faecal alpha-1-antitrypsin (FA1AT) excretion test (identifies protein-losing enteropathy caused by transudation of serum proteins across the inflamed mucosa).
Management
  • Dietary Modification:
  • Lifelong strict Gluten-Free Diet (GFD).
  • Avoid the BROW grains + cross-breeds: Barley, Rye, Oats, Wheat, malt, and triticale.
  • Encourage well-tolerated grains: Rice, corn, and sorghum.
  • Prognosis on Treatment: Removal of the gluten trigger resolves both the mucosal damage and the systemic complications.
Resources: Weyne & Harris 5E | Prepared by Dr Rasika Kulasinghe
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