- A multisystem autoimmune disorder triggered by an aberrant adaptive immune response to gluten
- Causes villous atrophy and malabsorption
Epidemiology
- Prevalence is around 1% – and has increased significantly (bread and other foodstuffs contains much more gluten than in the past)
- Around 75% is undiagnosed in UK. Delay in diagnosis often 10 years
- Probably only more prevalent in Caucasians because of the diet, not necessarily genetics
- Also high rates in India, Mexico, North Africa, Finland
- More common in women
- About 13% of the UK population think they have symptoms when they eat gluten (some of these have IBS)
- If someone says they get symptoms after eating gluten – chance of Coeliac disease is 10%
Clinical features
- Persistent / unexplained GI symptoms (test anyone with IBS)
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- Diarrhoea, steatorrhea, occasionally constipation
- Abdominal pain
- Bloating, flatulence
- Dyspepsia
- Nausea
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- Reduced growth in kids
- Prolonged fatigue
- Weight loss
- Mouth ulcers
- Unexplained iron, Vitamin B12 or folate deficiency
- Dermatitis herpetiformis (itchy blistering rash often on elbows, knees, buttocks, back, and scalp)
- Hyposplenism common (higher risk of pneumococcal sepsis)
- Unexplained deranged LFTs
- Metabolic bone disease
- Unexplained neurological symptoms (ataxia, peripheral neuropathy)
- Infertility or recurrent miscarriage
- Dental enamel defects
- Mild cognitive defects
- Increased risk of GI malignancies
- Mortality hazard ratio 1.4 x general population
Associations
- T1 DM – prevalence of Coeliac is 4%
- Autoimmune thyroid disease – if patients require high doses of levothyroxine, suspect Coeliac
- Downs syndrome
- Turners syndrome
- IgA deficiency – in which case antibody tests can be falsely negative
Diagnosis
- Screen for Coeliac if
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- Clinical features
- A recognised associated disease
- Family history
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- Bloods – also check TFTs, B12 and folate, haematinics, vitamin D, calcium, LFTs
- Antibodies
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- Ensure patient not already on gluten free diet before testing. Otherwise false negatives can occur
- Transglutaminase antibodies are the most useful screening test – Some tests are still positive if patient IgA deficient, others not – so consider checking immunoglobulins /total IgA too
- Antibodies at 10 x upper limit of normal has a positive predictive value of 98% for villous atrophy on biopsy
- Patients can spontaneously lose the antibody however without starting a gluten free diet
- Result can be confirmed with IgA endomysium
- Anti-endomysial antibodies are 95% sensitive and specific
- Persistence of anti-endomysial antibodies 6/52 after starting a gluten free diet usually suggest poor compliance (but not always)
- Gliadin antibodies not as good and no longer used
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- Elevated in 10% of normal people, and higher in those with GI symptoms but no Coeliac
- Also associated with cerebellar ataxia of unclear cause which is occasionally treated successfully by a gluten free diet
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- Scope and biopsy
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- Gold standard for diagnosis is jejunal biopsy
- If antibodies > 10x upper limit of normal (ULN), might be no need for biopsy / scope (although some still advise biopsy for all)
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- Positive predictive value of antibodies 10x ULN is 98% and specificity is 100%
- Around 30% of those with Coeliac have antibody levels >10x ULN
- Take patient views into account – some don’t want scopes
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- Biopsy advised if
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- Antibodies <10x ULN
- Seronegative but there is clinical suspicion (eg signs and symptoms of malabsorption, or symptoms and a family history)
- History of IgA deficiency
- There is another reason for a scope
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- Look for macroscopic signs of villous atrophy
- Can be diagnosed incidentally when scoping for something else
- Around 12% of those with Coeliac’s will have had an OGD for GI symptoms in the 5 years before diagnosis, but no biopsy was taken
- Patients are under-referred for scopes when serology is positive
- Usually take 6 biopsies in total – can double diagnostic yield (many don’t get enough). 4 from D2 and 2 from the bulb (some patients only have atrophy in the bulb)
- There is some variation in histopathologial assessment of biopsies
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- Piecing it together
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- Antibodies + villous atrophy = Coeliac Disease
- Antibodies + normal bowel
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- Could be
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- Early coeliacs
- False positive serology
- Transient coeliac autoimmunity
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- Consider sending HLA DQ2 and DQ8
- Could be
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- No antibodies + villous atrophy = seronegative enteropathy
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- A differential is non-Coeliac gluten sensitivity
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- Does exist, but unclear at present what’s going on
- Most people however in RCTs who self-report gluten sensitivity don’t feel better without gluten if they don’t have Coeliac
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Management
- The aim to achieve symptom resolution and mucosal healing
- Essentially one treatment – A gluten free diet (discovered in 1953!)
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- No wheat, rye or barley
- Some people will find it difficult and restrictive. Some will be hypervigilant
- It can sometimes trigger disordered eating
- Gluten free foods can be more expensive
- Dietician input helps
- ‘Safe’ foods include rice, corn, buckwheat and potatoes
- 80% of those exposed to gluten will get an acute response (nausea and vomiting, abdominal discomfort, diarrhoea) but symptoms might change with repeated exposure. 20% get no symptoms
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- Check bone health
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- DEXA scan for most newly diagnosed patients (do at one year, as a gluten free diet will help bones initially)
- Probably only do DEXA if aged >30 (unless other risk factors)
- Repeat DEXA after 3 years if persistent villous atrophy
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- Advise testing relatives – prevalence of coeliacs is 10% in first degree relatives
- Can signpost to online resources or give written information
- Pneumococcal vaccine to all newly diagnosed patients (as hyposplenic)
- Surveillance
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- Usually review in 3-6 months after diagnosis – consider bloods at this stage, assess adherence (there is no test that will confirm this) and symptoms
- How to ask about diet – The Biagi Questionnaire
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- Do you eat gluten voluntarily? (if yes: a normal portion or just a taste?)
- When you eat out, do you tell the cook/waiter about your disease?
- Do you check labels on food?
- Do you only ever eat packaged food guaranteed by the coeliac association?
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- Repeat TTG levels
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- High levels don’t necessarily mean poor adherence to diet, and persistent high levels also don’t tell you about likelihood of persistent villous atrophy
- Can send them, but don’t review result in isolation – make it part of a bigger clinical picture
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- Might not be practical to follow up all patients throughout their lives (and especially not if well controlled)
- Routine re-biopsy not recommended
- Patient who do need regular follow up
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- Persistent symptoms or signs
- Poor adherence to diet (or those at risk of poor adherence)
- Those with complications
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- If persistent symptoms
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- Check for persistent villous atrophy (although mucosal healing can take 1-2 years)
- Rule out refractory coeliac (see below)
- Consider non-coeliac causes – dysmotility, IBS, microscopic colitis, cancer (IBS and microscopic colitis are more prevalent in Coeliacs)
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Persistent symptoms
- Probably around 20% continue of have symptoms on a gluten free diet, and many of those have persistent villous atrophy (some do not)
- Revisit initial diagnosis
- Ensure up to date OGD and biopsies taken from duodenum
- If duodenal inflammation, consider
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- Slow healing
- Super-sensitivity
- Gluten exposure (commonest cause) – get a dietetic review
- Refractory Coeliac
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- If no inflammation
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- Dietician review and consider FODMAP trial
- Consider CT, bloods, breath test, SeHCAT scan, colonoscopy, faecal elastase or calprotectin – all depends on symptoms
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- Refractory Coeliac’s (types 1 and 2)
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- Maybe occurs in 2% (depending on definition and study)
- Type 1 has a better prognosis. Looks like active Coeliacs.
- Type 2
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- Can have low albumin, weight loss, anaemia, extensive enteropathy (and more distal SB disease) and a high mortality (50% in 5 years)
- Often Coeliacs was diagnosed at an older age
- Can transform into enteropathy associated T cell lymphoma
- Managed by specialists
- Flow cytometry can help diagnosis
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- Can try budesonide (open capsule) for type 1 – histology improves in nearly 60%. Symptoms resolve in 50% and improve in 30%
- Oral prednisolone occasionally used
- Other therapies used in type 2 include cladribine, stem cell transplant, JAK inhibitors
- Lots of others under investigation including endopeptidases, intestinal barrier modulation, TG2 inhibition, tolerance induction
- Consider associated T cell lymphoma – survival rate is 10% at 5 years
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