Overview
Coeliac Disease
1. Topic Overview (Clinical Overview)
Summary
Coeliac Disease is a chronic, immune-mediated enteropathy triggered by ingestion of gluten (proteins found in Wheat, Barley, Rye) in genetically susceptible individuals (HLA-DQ2/DQ8 positive). The immune response to Gliadin (a component of gluten) and Tissue Transglutaminase (tTG) causes villous atrophy in the small bowel, leading to malabsorption. Clinical features range from classic GI symptoms (diarrhoea, bloating, weight loss) to extra-intestinal manifestations (iron deficiency anaemia, osteoporosis, dermatitis herpetiformis). Diagnosis requires serological testing (tTG-IgA) while on a gluten-containing diet, followed by duodenal biopsy showing villous atrophy (Marsh classification). Treatment is a lifelong strict Gluten-Free Diet (GFD).
Key Facts
- Prevalence: ~1% worldwide. Often underdiagnosed.
- Genetics: HLA-DQ2 (>90%) or HLA-DQ8. Necessary but not sufficient.
- Trigger: Gluten (Wheat, Barley, Rye). Gliadin specifically.
- Serology: Tissue Transglutaminase IgA (tTG-IgA) – Most sensitive. (Must be on gluten diet for test!).
- Histology: Villous Atrophy, Crypt Hyperplasia, Intraepithelial Lymphocytosis (Marsh Criteria).
- Treatment: Lifelong Gluten-Free Diet (GFD).
- Complications: EATL (Lymphoma), Hyposplenism, Osteoporosis.
Clinical Pearls
"Don't Test Off Gluten": tTG-IgA and biopsy will be falsely negative if the patient is already on a gluten-free diet. They need ≥6 weeks of gluten ingestion before testing.
"Check IgA Level": ~2% of coeliac patients have IgA deficiency. If total IgA is low, use IgG-based tests (tTG-IgG, DGP-IgG).
"Iron Deficiency in Young Women – Consider Coeliac": Unexplained iron deficiency anaemia is a common presentation. Always consider coeliac.
"Dermatitis Herpetiformis IS Coeliac": The itchy blistering rash (Dermatitis Herpetiformis) is pathognomonic for coeliac. Diagnosis can be made on skin biopsy.
Why This Matters Clinically
Coeliac disease is common but underdiagnosed. Early diagnosis and strict GFD prevent complications including osteoporosis and small bowel lymphoma.
2. Epidemiology
Prevalence
- Global Prevalence: ~1% (Higher in Europe, North America, Australasia).
- Underdiagnosis: For every diagnosed case, ~3-5 are undiagnosed.
- Sex: Slight female predominance (2:1).
- Age: Can present at any age. Peak in childhood and 30-40s.
Associations
| Condition | Association |
|---|---|
| Type 1 Diabetes | ~5-10% have coeliac. |
| Autoimmune Thyroiditis | Increased risk. |
| Down Syndrome | ~5-10% have coeliac. |
| Turner Syndrome | Increased risk. |
| IgA Deficiency | ~2% of coeliac. Affects IgA-based testing. |
| First-Degree Relatives | ~10% risk. |
3. Pathophysiology
Mechanism
| Step | Detail |
|---|---|
| 1. Gluten Ingestion | Gliadin (Gluten protein) ingested. |
| 2. Deamidation by tTG | Tissue Transglutaminase deamidates Gliadin, increasing immunogenicity. |
| 3. Antigen Presentation | Modified Gliadin presented by HLA-DQ2/DQ8 on APCs. |
| 4. T-Cell Activation | CD4+ T-cells activate in lamina propria. |
| 5. Mucosal Damage | Cytokine release -> Intraepithelial Lymphocytosis, Crypt Hyperplasia, Villous Atrophy. |
| 6. Malabsorption | Loss of brush border -> Reduced absorption of Iron, Folate, Fat-soluble vitamins, Calcium. |
Genetics
| Gene | Frequency |
|---|---|
| HLA-DQ2 | >0% of coeliac patients. |
| HLA-DQ8 | ~5-10%. |
| Both Negative | Coeliac essentially excluded. (High Negative Predictive Value). |
4. Clinical Presentation
Classic (GI) Symptoms
| Symptom | Notes |
|---|---|
| Diarrhoea | Steatorrhoea (Fatty, Foul-smelling, Floating stools). |
| Bloating / Abdominal Distension | Common. Wind. |
| Weight Loss | Malabsorption. |
| Failure to Thrive (Children) | Short stature. |
| Aphthous Ulcers | Mouth ulcers (Recurrent). |
Non-Classic (Extra-Intestinal) Symptoms
| Symptom | Notes |
|---|---|
| Iron Deficiency Anaemia | Often presenting feature. Jejunum (Iron absorption) affected. |
| Fatigue | Anaemia, Malabsorption. |
| Osteoporosis / Osteopenia | Calcium/Vitamin D malabsorption. |
| Dermatitis Herpetiformis | Intensely itchy, grouped vesicles on extensor surfaces (Elbows, Knees, Buttocks). Pathognomonic. |
| Neurological | Peripheral neuropathy, Ataxia. |
| Infertility / Recurrent Miscarriage | Subfertility common. |
| Elevated Transaminases | Unexplained LFTs. |
"Iceberg" Model
Many patients are asymptomatic or have mild symptoms ("Silent Coeliac").
Common presentation.
Classic symptomatic cases are the "Tip of the Iceberg".
Common presentation.
5. Clinical Examination
GI Examination
- Abdominal distension.
- May be entirely normal.
Extra-Intestinal Signs
| Sign | Notes |
|---|---|
| Pallor | Anaemia. |
| Angular Stomatitis | Iron deficiency. |
| Koilonychia | Iron deficiency. |
| Dermatitis Herpetiformis | Grouped vesicles, Elbows, Knees, Buttocks. Very itchy. |
| Short Stature (Children) | Growth failure. |
6. Investigations
Step 1: Serology (On Gluten Diet!)
| Test | Notes |
|---|---|
| tTG-IgA (Tissue Transglutaminase IgA) | First-line. High sensitivity (>5%) and specificity. |
| Total IgA | Check concurrently. IgA deficiency causes false negative tTG-IgA. |
| If IgA Deficient | Use tTG-IgG or DGP-IgG (Deamidated Gliadin Peptide IgG). |
| EMA (Endomysial Antibody) | Very specific (~99%), but more expensive. Confirmatory. |
Step 2: Duodenal Biopsy (Gold Standard)
| Finding | Notes |
|---|---|
| Villous Atrophy | Blunted/Absent villi. |
| Crypt Hyperplasia | Compensatory proliferation. |
| Intraepithelial Lymphocytosis (IELs) | >5 IELs per 100 enterocytes. |
Take ≥4 biopsies from D2 (Duodenum) and at least 1 from D1 (Duodenal Bulb).
Marsh Classification
| Stage | Histology |
|---|---|
| Marsh 0 | Normal. |
| Marsh 1 | Increased IELs only. |
| Marsh 2 | IELs + Crypt Hyperplasia. |
| Marsh 3a | Partial Villous Atrophy. |
| Marsh 3b | Subtotal Villous Atrophy. |
| Marsh 3c | Total Villous Atrophy. |
HLA Typing
| Indication | Notes |
|---|---|
| To Exclude Coeliac | If HLA-DQ2/DQ8 negative, coeliac is essentially excluded (~99% NPV). |
| Equivocal Serology/Biopsy | Helpful in uncertain cases. |
| Screening High-Risk Groups | First-degree relatives. |
Other Investigations
| Test | Purpose |
|---|---|
| FBC | Anaemia? |
| Iron Studies, Ferritin, B12, Folate | Deficiencies? |
| Calcium, Vitamin D, PTH | Metabolic bone disease? |
| LFTs | Unexplained transaminitis? |
| DEXA Scan | Osteoporosis screening. |
7. Management
Principles
- Lifelong Strict Gluten-Free Diet (GFD).
- Dietitian Input.
- Monitor for Compliance and Complications.
- Address Nutritional Deficiencies.
- Vaccinations (Hyposplenism).
Gluten-Free Diet
| Allowed | Avoid |
|---|---|
| Rice, Corn, Potato, Quinoa | Wheat, Barley, Rye |
| Oats (Uncontaminated pure oats OK for most) | Bread, Pasta, Cakes (unless GF versions) |
| Fresh Meat, Fish, Eggs | Beer, Lager (unless GF) |
| Fruits, Vegetables | Many processed foods (Check labels) |
Dietitian Role
- Education on GFD.
- Label reading.
- Preventing nutritional deficiencies.
- Coeliac UK membership (Prescribable GF food list).
Monitoring
| Assessment | Frequency |
|---|---|
| tTG-IgA | 6-12 months after diagnosis. Should normalise on GFD. |
| Dietary Review | Annual (Dietitian). |
| DEXA Scan | At diagnosis (Adults). Repeat if low at baseline. |
| FBC, Iron, Folate, B12, LFTs | Annual. |
Vaccinations
| Vaccine | Rationale |
|---|---|
| Pneumococcal Vaccine (Pneumovax) | Hyposplenism risk. |
| Annual Influenza | Recommended. |
8. Complications
| Complication | Notes |
|---|---|
| EATL (Enteropathy-Associated T-cell Lymphoma) | Rare but serious. Risk reduced by strict GFD. |
| Refractory Coeliac Disease | Persistent symptoms despite strict GFD. May need immunosuppression. |
| Osteoporosis | From malabsorption. |
| Hyposplenism | Increased infection risk (Encapsulated organisms). Vaccinate. |
| Infertility / Miscarriage | Risk reduced with GFD. |
| Small Bowel Adenocarcinoma | Slightly increased risk. |
9. Prognosis & Outcomes
- On Strict GFD: Mucosal healing. Symptoms resolve. Reduced complication risk.
- Poor Compliance: Persistent mucosal damage. Increased lymphoma risk.
- Life Expectancy: Normal with strict adherence to GFD.
10. Evidence & Guidelines
Key Guidelines
| Guideline | Organisation | Notes |
|---|---|---|
| BSG Guidelines on Coeliac Disease | British Society of Gastroenterology | UK Standard. Serology, Biopsy, GFD. |
| NICE NG20 | NICE | Diagnosis and Management in Adults. |
| ACG Guidelines | American College of Gastroenterology | US Standard. |
11. Exam Scenarios
Scenario 1:
- Stem: A 30-year-old woman presents with fatigue and iron deficiency anaemia that has not responded to oral iron. What diagnosis should you consider?
- Answer: Coeliac Disease. Test tTG-IgA (Ensure she is eating gluten).
Scenario 2:
- Stem: A patient's tTG-IgA is negative, but their total IgA is very low. What should you do?
- Answer: The patient may have IgA deficiency. Use IgG-based tests (tTG-IgG, DGP-IgG).
Scenario 3:
- Stem: What is the definitive treatment for Coeliac Disease?
- Answer: Lifelong Strict Gluten-Free Diet (Avoid Wheat, Barley, Rye).
Scenario 4:
- Stem: A patient with coeliac disease asks about vaccinations. What should you recommend?
- Answer: Pneumococcal Vaccine (Hyposplenism risk). Annual Influenza vaccine.
12. Triage: When to Refer
| Scenario | Urgency | Action |
|---|---|---|
| Positive tTG-IgA | Routine | Gastroenterology for OGD + Duodenal Biopsy. |
| Confirmed Coeliac Disease | Routine | Dietitian referral. Annual gastro review. |
| Refractory Coeliac Disease | Urgent | Gastroenterology. Biopsy. Exclude EATL. |
| Dermatitis Herpetiformis | Routine | Dermatology. Skin biopsy confirms diagnosis. |
14. Patient/Layperson Explanation
What is Coeliac Disease?
Coeliac disease is a condition where your immune system reacts to gluten (a protein in wheat, barley, and rye). This reaction damages the lining of your gut and stops you absorbing food properly.
What are the symptoms?
- Diarrhoea, bloating, wind.
- Tiredness (from anaemia).
- Weight loss.
- An itchy blistering rash (Dermatitis Herpetiformis).
How is it treated?
- A strict, lifelong gluten-free diet. This means avoiding all wheat, barley, and rye.
- A dietitian will help you understand what you can and cannot eat.
Key Counselling Points
- Gluten-Free for Life: "This is a lifelong condition. Sticking to the diet prevents complications."
- Read Labels: "Many processed foods contain hidden gluten. Always read the ingredients."
- Oats: "Most people with coeliac can eat uncontaminated pure oats, but check with your dietitian."
- Vaccinations: "You may need a Pneumonia vaccine because coeliac can affect your spleen."
- Prescription Foods: "You may be entitled to gluten-free foods on prescription – ask your GP."
15. Quality Markers: Audit Standards
| Standard | Target |
|---|---|
| tTG-IgA test performed on gluten-containing diet | 100% |
| OGD with duodenal biopsies for positive serology | >5% |
| Dietitian referral after diagnosis | 100% |
| DEXA scan at diagnosis (Adults) | >0% |
| Pneumococcal vaccination offered | 100% |
16. Historical Context
- Samuel Gee (1888): British physician who gave the first modern description of coeliac disease in children.
- Willem Dicke (1940s): Dutch paediatrician who linked the condition to wheat ingestion (Observed during WWII bread shortages in the Netherlands).
- tTG Identified (1997): Tissue Transglutaminase identified as the autoantigen.
17. References
- BSG Guidelines: Coeliac Disease. Gut. 2021. gut.bmj.com
- NICE NG20. Coeliac disease: recognition, assessment and management. 2015. nice.org.uk
- Coeliac UK: coeliac.org.uk
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. If you suspect you have coeliac disease, please consult a healthcare professional.