Key Facts

Coeliac disease is a systemic autoimmune disorder triggered by ingestion of gluten (found in wheat, barley, rye) in genetically susceptible individuals. It causes inflammation and villous atrophy in the small intestine, leading to malabsorption.

Epidemiology

Prevalence is approximately 1% in the UK (1 in 100), but up to 75% remain undiagnosed ("coeliac iceberg"). Female:male ratio is 2:1. Can present at any age — bimodal distribution with peaks in childhood (after weaning) and 40-60 years. First-degree relatives have 10% prevalence. More common in Northern European populations.

Aetiology

• Genetic: HLA-DQ2 (present in ~95% of coeliac patients) and HLA-DQ8 (~5%). These are necessary but not sufficient — 30-40% of the general population carry HLA-DQ2/DQ8 but only 1% develop coeliac disease
• Environmental trigger: gluten (gliadin peptides from wheat, secalins from rye, hordeins from barley). Oats are tolerated by most coeliacs unless contaminated
• Other factors: early childhood infections, timing of gluten introduction, gut microbiome

Pathophysiology

Gliadin peptides resist complete enzymatic digestion. Deamidated gliadin peptides are presented by HLA-DQ2/DQ8 on antigen-presenting cells to CD4+ T cells. This triggers a Th1-mediated immune response causing:

1. Intraepithelial lymphocyte (IEL) infiltration: CD8+ T cells causing epithelial damage
2. Crypt hyperplasia: compensatory proliferation
3. Villous atrophy: progressive destruction of villi → reduced absorptive surface area
4. Autoantibody production: anti-tTG and anti-endomysial antibodies (markers used for diagnosis)

The resulting malabsorption affects multiple nutrients: iron (duodenum), folate (jejunum), fat-soluble vitamins (A, D, E, K), calcium, and B12 (terminal ileum if extensive disease).

Classical Presentation

• Chronic diarrhoea (pale, bulky, malodorous — steatorrhoea)
• Bloating and abdominal distension
• Weight loss/failure to thrive (children)
• Fatigue

Non-classical/Atypical Presentation (increasingly recognised)

• Iron deficiency anaemia (most common presenting feature in adults)
• Unexplained fatigue
• Osteoporosis/osteomalacia (vitamin D/calcium malabsorption)
• Mouth ulcers (aphthous stomatitis)
• Elevated liver enzymes (unexplained transaminitis)
• Infertility/recurrent miscarriage
• Peripheral neuropathy
• Depression

Dermatitis Herpetiformis

• Intensely itchy vesicular rash on extensor surfaces (elbows, knees, buttocks)
• "Skin manifestation" of coeliac disease
• Granular IgA deposits on skin biopsy (dermal papillae)

Red Flags

• Unintentional weight loss despite GFD (non-responsive coeliac — consider lymphoma)
• New abdominal pain/obstruction in known coeliac (EATL)
• Persistent symptoms despite strict GFD >12 months (refractory coeliac disease)
• Severe malnutrition or hypoalbuminaemia

Bedside

• Ensure patient is eating gluten: must have consumed gluten-containing food for ≥6 weeks before testing (ideally ≥1 portion/day)

Bloods

• tTG-IgA: first-line serological test — sensitivity/specificity >95%
• Total IgA: 2-3% of coeliacs have IgA deficiency (false-negative tTG-IgA)
• If IgA deficient: request IgG-based tests (tTG-IgG, deamidated gliadin peptide IgG — DGP-IgG)
• Endomysial antibodies (EMA-IgA): confirmatory test — very high specificity (~99%)
• FBC: iron deficiency anaemia, folate deficiency (macrocytosis), mixed picture
• Ferritin, folate, B12: nutritional deficiency assessment
• Calcium, vitamin D, PTH: bone metabolism
• LFTs: unexplained transaminitis (resolves with GFD)
• Thyroid function: associated autoimmune thyroiditis
• HLA-DQ2/DQ8: negative result virtually excludes coeliac disease (useful in diagnostic uncertainty, patients already on GFD)

Imaging

• Not routinely required for diagnosis
• DEXA scan: baseline bone density at diagnosis (osteoporosis screening)

Special Tests

• OGD with duodenal biopsies: gold standard — ≥4 biopsies from D2 + ≥1 from D1 (bulb)
  • Marsh classification: 0 (normal) → 1 (IELs only) → 2 (IELs + crypt hyperplasia) → 3a/3b/3c (partial/subtotal/total villous atrophy)
• Coeliac UK serology pathway: in adults with strongly positive tTG-IgA (≥10x ULN) + positive EMA, diagnosis may be made without biopsy (ESPGHAN criteria increasingly adopted in adults)

Non-pharmacological

• Lifelong strict gluten-free diet (GFD): exclude wheat, barley, rye; oats tolerated by most if uncontaminated. Expert dietitian essential
• Coeliac UK membership: food labelling guidance, GF prescription products
• Gluten-free prescriptions: available on NHS for staple items (bread, pasta, flour)
• Nutritional supplementation: iron, folate, calcium, vitamin D as needed
• Pneumococcal vaccination: functional hyposplenism in coeliac disease
• Annual review: symptoms, adherence, tTG-IgA (should normalise), FBC, ferritin, folate, B12, calcium, vitamin D, LFTs, thyroid function

Pharmacological

• Correct nutritional deficiencies: ferrous sulphate 200 mg BD/TDS, folic acid 5 mg OD, calcium/vitamin D, B12 injections if deficient
• Dapsone 50-100 mg OD: for dermatitis herpetiformis (with GFD)
• Refractory coeliac disease (RCD): type I — budesonide 9 mg OD, azathioprine; type II — consider cladribine or autologous stem cell transplant (specialist centres)

Surgical/Interventional

• Not routinely indicated
• Surgery may be needed for EATL or small bowel lymphoma complicating coeliac disease

Referral Criteria

• Gastroenterology referral for all new diagnoses for biopsy confirmation and GFD education
• Specialist dietitian referral at diagnosis (essential)
• DEXA scan: at diagnosis and repeat if abnormal
• Suspect refractory coeliac disease if persistent symptoms despite strict GFD >12 months → specialist centre referral

Most patients achieve complete symptomatic and histological remission on a strict GFD. Villous atrophy typically resolves within 6-24 months. Serological markers normalise within 6-12 months. Untreated coeliac disease increases risk of: enteropathy-associated T-cell lymphoma (EATL — 6-10x risk, but absolute risk still low), small bowel adenocarcinoma, osteoporotic fractures, and adverse pregnancy outcomes. Strict GFD adherence reduces cancer risk to near-population levels. Refractory coeliac disease type II has a 50% 5-year risk of progression to EATL.

Marsh Classification

Conditions Warranting Coeliac Screening (NICE NG20)