Coeliac Disease
Summary
Coeliac disease is a chronic immune-mediated enteropathy triggered by dietary gluten in genetically predisposed individuals (HLA-DQ2/DQ8 positive). Gluten exposure causes villous atrophy and crypt hyperplasia in the small intestine, leading to malabsorption. Presentation ranges from classic gastrointestinal symptoms (diarrhoea, bloating, weight loss) to non-classic manifestations (iron deficiency anaemia, osteoporosis, fatigue) or silent disease. Diagnosis requires positive serology (IgA-TTG) WHILE ON A GLUTEN-CONTAINING DIET, confirmed by duodenal biopsy showing villous atrophy. Treatment is a strict lifelong gluten-free diet. Untreated coeliac disease increases the risk of osteoporosis, anaemia, infertility, and enteropathy-associated T-cell lymphoma (EATL).
Key Facts
- Definition: Immune-mediated enteropathy triggered by dietary gluten
- Incidence: 1% prevalence worldwide (largely underdiagnosed)
- Demographics: Any age; peak diagnosis bimodal (childhood, 40-60 years)
- Pathognomonic: Villous atrophy + positive serology + clinical response to GFD
- Gold Standard Investigation: IgA-TTG + duodenal biopsy (while on gluten)
- First-line Treatment: Strict lifelong gluten-free diet
- Prognosis: Excellent with GFD adherence; increased lymphoma risk if untreated
Clinical Pearls
IgA Deficiency Pearl: 2-3% of coeliac patients are IgA deficient - always check total IgA. If deficient, use IgG-based testing (IgG-TTG or IgG-DGP).
Gluten Challenge Pearl: Serology and histology require gluten exposure. Patients must be on gluten-containing diet for accurate testing.
DH Pearl: Dermatitis herpetiformis is the skin manifestation of coeliac disease. Diagnose with skin biopsy showing IgA in dermal papillae.
Family Screening Pearl: First-degree relatives have 10% risk. Screen with serology if willing to have gluten in diet.
Bone Pearl: All newly diagnosed coeliac adults should have a DEXA scan - osteoporosis is common.
Why This Matters Clinically
Coeliac disease is common (1%) but underdiagnosed. It causes preventable complications including anaemia, osteoporosis, infertility, and malignancy. A high index of suspicion and appropriate testing transforms outcomes.
Prevalence
| Population | Prevalence |
|---|---|
| General population | 1% (0.7-1.4%) |
| First-degree relatives | 10% |
| Type 1 diabetes | 3-8% |
| Down syndrome | 5-12% |
| Autoimmune thyroid disease | 2-5% |
| Turner syndrome | 4-8% |
| IgA deficiency | 10-15% |
Demographics
- Any age: Can present from infancy to elderly
- Sex: Slight female predominance (1.5:1)
- Ethnicity: Higher in European descent, but occurs globally
- Iceberg phenomenon: For every diagnosed case, 3-5 undiagnosed
Risk Factors
| Factor | Risk |
|---|---|
| HLA-DQ2 | Present in 90-95% of coeliacs |
| HLA-DQ8 | Present in 5-10% of coeliacs |
| First-degree relative with coeliac | 10% risk |
| Type 1 diabetes | 3-8% |
| Autoimmune thyroid disease | 2-5% |
| Down syndrome | 5-12% |
Mechanism Overview
Step 1: Genetic Predisposition
- HLA-DQ2 (95%) or HLA-DQ8 (5%) essential but not sufficient
- Non-HLA genes also contribute
- HLA-DQ2/DQ8 present in 30-40% of population but only 1% develop coeliac
Step 2: Environmental Trigger
- Gluten ingestion (wheat, barley, rye)
- Gliadin is the immunogenic component of gluten
- Other factors: infections, gut microbiome
Step 3: Tissue Transglutaminase Modification
- Tissue transglutaminase (tTG) deamidates gliadin peptides
- Deamidated gliadin peptides bind HLA-DQ2/DQ8 with high affinity
- Presented to CD4+ T cells in lamina propria
Step 4: Adaptive Immune Response
- Gliadin-specific CD4+ T cells activated
- Th1 cytokine release (IFN-γ)
- B cell activation → anti-tTG and anti-DGP antibodies
- Intraepithelial lymphocyte (IEL) infiltration (CD8+ cytotoxic)
Step 5: Intestinal Damage
- Villous atrophy (flattened villi)
- Crypt hyperplasia (compensatory)
- Intraepithelial lymphocytosis
- Malabsorption of nutrients
Step 6: Consequences
- Iron, folate, B12 deficiency
- Calcium/vitamin D malabsorption → osteoporosis
- Fat malabsorption → steatorrhoea
- Systemic manifestations
Histological Changes (Marsh Classification)
| Stage | Histology | Clinical |
|---|---|---|
| Marsh 0 | Normal | Pre-infiltrative |
| Marsh 1 | Increased IELs (greater than 25/100 enterocytes) | Latent |
| Marsh 2 | IELs + crypt hyperplasia | |
| Marsh 3a | Partial villous atrophy | Classic coeliac |
| Marsh 3b | Subtotal villous atrophy | |
| Marsh 3c | Total villous atrophy | Severe |
Classic Gastrointestinal Symptoms
| Symptom | Frequency |
|---|---|
| Chronic diarrhoea | 50-70% |
| Abdominal bloating | 50-60% |
| Abdominal pain | 40-50% |
| Weight loss | 30-40% |
| Steatorrhoea | 20-30% |
| Nausea/vomiting | 20% |
Non-Classic (Atypical) Manifestations
| System | Manifestation |
|---|---|
| Haematological | Iron deficiency anaemia (most common presentation in adults), folate/B12 deficiency |
| Bone | Osteoporosis, osteopenia, fractures |
| Neurological | Peripheral neuropathy, ataxia, epilepsy |
| Reproductive | Infertility, recurrent miscarriage, delayed puberty |
| Dermatological | Dermatitis herpetiformis |
| Hepatic | Elevated transaminases |
| Dental | Enamel defects |
| Psychiatric | Depression, anxiety |
Associated Conditions
| Condition | Association |
|---|---|
| Type 1 diabetes | 3-8% have coeliac |
| Autoimmune thyroid | 2-5% |
| Dermatitis herpetiformis | 100% have coeliac on biopsy |
| IgA nephropathy | Increased |
| Primary biliary cholangitis | Increased |
| Sjögren's syndrome | Increased |
Red Flags
[!CAUTION]
- Severe weight loss and malnutrition
- Failure to respond to strict GFD (refractory coeliac)
- New lymphadenopathy or abdominal mass (EATL)
- Severe dermatitis herpetiformis
- Neurological deterioration
General Inspection
- Pallor (anaemia)
- Cachexia (severe malabsorption)
- Short stature (if childhood onset)
- Dermatitis herpetiformis (extensor surfaces, buttocks)
Abdominal Examination
- Abdominal distension
- Hyperactive bowel sounds
- Generally non-tender
- May have hepatomegaly (fatty liver)
Systemic Examination
- Skin: Dermatitis herpetiformis (vesicular, pruritic eruption)
- Mouth: Aphthous ulcers, glossitis, angular stomatitis
- Nails: Koilonychia (iron deficiency)
- Musculoskeletal: Bone tenderness (osteomalacia)
- Neurological: Peripheral neuropathy, ataxia
Serological Testing
First-Line: IgA Tissue Transglutaminase (IgA-TTG)
- Sensitivity: 95-98%
- Specificity: 95-98%
- MUST check total IgA level simultaneously
| Scenario | Action |
|---|---|
| IgA-TTG positive | Refer for duodenal biopsy |
| IgA-TTG negative, clinical suspicion high | Check total IgA; if deficient, use IgG-TTG or IgG-DGP |
| IgA deficient | Use IgG-based testing |
Confirmatory/Additional Serology:
- Anti-endomysial antibodies (EMA): Highly specific
- Anti-deamidated gliadin peptide (DGP): Useful in IgA deficiency and children
HLA Typing
- HLA-DQ2 and/or HLA-DQ8
- Negative HLA-DQ2/DQ8 essentially excludes coeliac disease
- Positive result does not confirm (30-40% of population positive)
- Useful for: excluding coeliac in uncertain cases, family screening
Duodenal Biopsy
Gold standard for diagnosis
- At least 4 biopsies from D2, 1-2 from duodenal bulb
- Must be on gluten-containing diet (at least 6 weeks, ideally 3+ months)
- Histology: Villous atrophy, crypt hyperplasia, increased IELs
Additional Investigations
| Test | Purpose |
|---|---|
| FBC | Anaemia (iron, B12, folate) |
| Iron studies | Iron deficiency |
| Folate, B12 | Deficiency |
| Calcium, vitamin D | Bone health |
| LFTs | Elevated transaminases |
| TFTs | Associated thyroid disease |
| DEXA scan | Bone mineral density |
| Glucose/HbA1c | Associated diabetes |
Diagnostic Criteria
Diagnosis confirmed by:
- Positive serology (IgA-TTG) WHILE ON GLUTEN
- Duodenal biopsy showing villous atrophy (Marsh 3)
- Clinical and histological response to GFD
Alternative (no biopsy, ESPGHAN paediatric criteria adapted for adults):
- IgA-TTG greater than 10x upper limit of normal
- Positive EMA
- Positive HLA-DQ2/DQ8
- Symptomatic
Management Algorithm
SUSPECTED COELIAC DISEASE
↓
┌──────────────────────────────────────────────┐
│ CHECK IgA-TTG + TOTAL IgA │
│ (Patient must be on gluten-containing diet)│
└──────────────────────────────────────────────┘
↓
IgA-TTG Positive?
↓ Yes ↓ No
┌───────────────┐ ┌─────────────────────────────┐
│ Refer for │ │ Check total IgA level │
│ duodenal │ │ If deficient: IgG-TTG/DGP │
│ biopsy │ │ If high suspicion: consider │
│ │ │ biopsy anyway │
└───────────────┘ └─────────────────────────────┘
↓
┌──────────────────────────────────────────────┐
│ DUODENAL BIOPSY (4+ samples) │
│ Villous atrophy (Marsh 3) confirms │
└──────────────────────────────────────────────┘
↓
┌──────────────────────────────────────────────┐
│ CONFIRMED COELIAC DISEASE │
│ 1. Strict lifelong GFD │
│ 2. Dietitian referral (essential) │
│ 3. Baseline investigations │
│ 4. Screen for complications │
│ 5. Family screening discussion │
└──────────────────────────────────────────────┘
↓
┌──────────────────────────────────────────────┐
│ FOLLOW-UP │
│ - Symptoms and dietary adherence │
│ - Serology at 6-12 months (should fall) │
│ - Annual review │
│ - Repeat biopsy if non-responsive │
└──────────────────────────────────────────────┘
Gluten-Free Diet
Must avoid (contain gluten):
- Wheat (bread, pasta, cereals, baked goods)
- Barley (beer, malt)
- Rye
- Contaminated oats (pure oats often tolerated)
Safe foods:
- Rice, corn, potato
- Pure oats (if tolerated, less than 50g/day)
- Naturally GF grains: quinoa, buckwheat, millet
- Meat, fish, eggs, dairy, fruits, vegetables
Dietitian referral is ESSENTIAL.
Nutritional Supplementation
| Deficiency | Treatment |
|---|---|
| Iron | Iron replacement until replete |
| Folate | Folic acid 5mg daily |
| B12 | IM hydroxocobalamin if malabsorption |
| Vitamin D | Colecalciferol 800-4000 IU daily |
| Calcium | 1000-1200mg daily |
Bone Health
- DEXA scan at diagnosis in adults
- Calcium and vitamin D supplementation
- Repeat DEXA after 1-2 years on GFD
- Consider bisphosphonates if osteoporosis
Vaccinations
- Pneumococcal vaccine (hyposplenism occurs in coeliac)
- Influenza annually
Monitoring
| Timepoint | Assessment |
|---|---|
| Diagnosis | Baseline bloods, DEXA, dietitian |
| 6-12 months | Symptoms, serology (TTG should fall), dietary adherence |
| Annually | Clinical review, serology if needed |
| Non-response | Repeat biopsy, assess for refractory coeliac or other causes |
| Complication | Incidence | Prevention/Management |
|---|---|---|
| Osteoporosis | 30-40% at diagnosis | DEXA, calcium, vitamin D, bisphosphonates |
| Anaemia | 30-50% | Iron, B12, folate replacement |
| Refractory coeliac disease | 1-2% | Type 1 (polyclonal IELs): steroids; Type 2 (clonal): poor prognosis |
| EATL (lymphoma) | Less than 1% | Strict GFD reduces risk; suspect if weight loss, pain, obstruction |
| Small bowel adenocarcinoma | Rare | Surveillance if refractory |
| Infertility/miscarriage | Increased | GFD improves fertility |
| Hyposplenism | 30-50% | Vaccination (pneumococcal) |
Response to GFD
- Symptoms improve: days to weeks
- Serology normalises: 6-12 months
- Histology normalises: 1-2 years (may take longer in adults)
Long-Term Outcomes
- Excellent prognosis with strict GFD adherence
- Mortality returns to near-normal after 3-5 years GFD
- 5-10% have persistent symptoms despite GFD (non-responsive)
Non-Responsive Coeliac Disease
Causes:
- Ongoing gluten exposure (most common)
- Wrong diagnosis
- Lactose intolerance or other food intolerance
- Microscopic colitis
- Bacterial overgrowth
- Refractory coeliac disease
Key Guidelines
-
NICE Guideline NG20. Coeliac Disease: Recognition, Assessment and Management — 2015 (updated 2022)
-
BSG Guidelines for Diagnosis and Management of Coeliac Disease — 2021
-
ACG Clinical Guideline: Diagnosis and Management of Celiac Disease — Rubio-Tapia A et al. Am J Gastroenterol. 2013;108(5):656-676. PMID: 23609613
-
ESGE/ESGENA Guidelines on Duodenal Biopsies — Al-Toma A et al. United European Gastroenterol J. 2019;7(5):583-613. PMID: 31210940
Key Evidence
Screening in At-Risk Groups
- First-degree relatives: 10% prevalence
- Type 1 diabetes: 3-8%
- Cost-effective to screen these groups
GFD and Mortality
- Strict GFD adherence reduces mortality to near-normal
- Non-adherence associated with 2-6x increased mortality
What is Coeliac Disease?
Coeliac disease is a condition where your immune system reacts to gluten, a protein found in wheat, barley, and rye. This reaction damages the lining of your small intestine and stops you absorbing nutrients properly.
Is it an allergy?
No, it's an autoimmune condition, not an allergy. Your immune system mistakenly attacks your own gut lining when you eat gluten.
What is the treatment?
A strict gluten-free diet for life. This means avoiding all wheat, barley, and rye. Even small amounts of gluten can cause damage.
Will I feel better?
Yes! Most people feel much better within weeks of starting a gluten-free diet. Your gut will heal, and your blood tests will improve.
What foods can I eat?
- Rice, potatoes, corn, quinoa
- Meat, fish, eggs
- Fruits and vegetables
- Dairy products
- Many products are now labelled "gluten-free"
What about my family?
Your first-degree relatives (parents, siblings, children) have a 10% risk. They should be offered testing.
-
Al-Toma A et al. European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European Gastroenterol J. 2019;7(5):583-613. PMID: 31210940
-
Rubio-Tapia A et al. ACG Clinical Guideline: Diagnosis and Management of Celiac Disease. Am J Gastroenterol. 2013;108(5):656-676. PMID: 23609613
-
NICE Guideline NG20. Coeliac disease: recognition, assessment and management. 2015.
-
Ludvigsson JF et al. The Oslo definitions for coeliac disease and related terms. Gut. 2013;62(1):43-52. PMID: 22345659
-
Lebwohl B et al. Coeliac disease. Lancet. 2018;391(10115):70-81. PMID: 28760445
-
Husby S et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. J Pediatr Gastroenterol Nutr. 2020;70(1):141-156. PMID: 31568151
-
Catassi C et al. Diagnosis of non-celiac gluten sensitivity (NCGS). Nutrients. 2015;7(6):4966-4977. PMID: 26096570
-
Ludvigsson JF et al. Mortality and malignancy in celiac disease. Ann Intern Med. 2009;151(4):W71. PMID: 19652116
Viva Points
"Coeliac disease is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals (HLA-DQ2/DQ8). Diagnosis requires positive IgA-TTG while on gluten, PLUS duodenal biopsy showing villous atrophy. Always check total IgA (2-3% are IgA deficient). Treatment is strict lifelong GFD. Screen for osteoporosis (DEXA) and nutrient deficiencies. Complications include refractory coeliac and EATL."
Key Examination Points
- Signs of malabsorption (pallor, cachexia, glossitis)
- Dermatitis herpetiformis (vesicular rash on extensors, buttocks)
- Abdominal distension
- Dental enamel defects
Common Mistakes
- ❌ Testing serology when patient already on GFD (false negative)
- ❌ Not checking total IgA level (miss IgA-deficient patients)
- ❌ Not referring to dietitian
- ❌ Forgetting to screen for osteoporosis (DEXA)
- ❌ Missing hidden gluten sources causing non-response
Differentials
- Irritable bowel syndrome
- Inflammatory bowel disease
- Lactose intolerance
- Small intestinal bacterial overgrowth
- Microscopic colitis
- Non-coeliac gluten sensitivity
Last Reviewed: 2026-01-01 | MedVellum Editorial Team