Coeliac disease
Description
- Immune-mediated enteropathy triggered by gluten (wheat, rye, barley) in HLA-DQ2/DQ8-positive individuals
- Proximal small bowel disease -> villous atrophy -> malabsorption of iron, folate, calcium, fat-soluble vitamins
- Oats are tolerated by most, but are commonly contaminated during processing
Presentations
| Classical | Diarrhoea, steatorrhoea, weight loss, failure to thrive |
| Non-classical (most adults) | Iron deficiency anaemia, osteoporosis, fatigue, abnormal LFTs, infertility, neurological symptoms, dyspepsia, IBS-like |
| Subclinical | Detected on screening in a risk group |
| Potential | Positive serology + HLA, normal biopsy |
| Refractory | Persistent symptoms and villous atrophy despite >12 months of strict gluten-free diet |
- *Most Australian adults with coeliac disease do not have diarrhoea* - waiting for it delays the diagnosis by years
Epidemiology
- ~1% of Australians; ~80% remain undiagnosed
- F:M ~2:1 for diagnosed disease
- Bimodal: early childhood after gluten introduction, and 4th-5th decade
- First-degree relatives ~10%
- HLA-DQ2 in ~90%, HLA-DQ8 in most of the rest
- ~30-40% of the general population carry DQ2/DQ8, so the test is only useful to exclude**
Aetiopathogenesis
- Gluten -> gliadin peptides cross the epithelium
- Tissue transglutaminase (tTG) deamidates gliadin -> inc affinity for HLA-DQ2/DQ8 on antigen-presenting cells
- -> CD4 T-cell activation -> IFN-gamma, IL-15
- -> intraepithelial lymphocyte expansion + enterocyte apoptosis
- -> crypt hyperplasia and villous atrophy
- IgA anti-tTG antibodies are produced - the basis of the serological test
- *Anti-tTG titre falls on a gluten-free diet* - which is why the patient must still be eating gluten when tested
Risk modifiers
- HLA-DQ2 homozygosity - highest risk, most severe
- Enteric infection, rotavirus; timing of gluten introduction in infancy does NOT affect risk (contrary to older teaching)
Diagnosis
Step 1 - serology, while still eating gluten
- IgA tissue transglutaminase (tTG-IgA) + total IgA - first-line
- Sensitivity and specificity >95%
- *IgA deficiency (2-3% of coeliac patients, 10-15x population rate) causes a false negative -> if IgA deficient, use IgG deamidated gliadin peptide (DGP) or IgG-tTG*
- Anti-endomysial antibody (EMA) - near 100% specific, used as a confirmatory test
- Anti-gliadin antibodies are obsolete
- Gluten challenge if already gluten-free: >=4 slices of bread/day (or ~10 g gluten) for 6 weeks before testing
Step 2 - duodenal biopsy is required in adults
- Gastroscopy with >=4 biopsies from D2/D3 plus >=1-2 from the duodenal bulb
- Patchy disease - a single biopsy misses it
- Endoscopic appearance: scalloping, mosaic pattern, loss of folds - often normal, so biopsy regardless
- Marsh classification:
- Marsh 1 - intraepithelial lymphocytosis (>25 per 100 enterocytes) alone
- Marsh 2 - + crypt hyperplasia
- Marsh 3a/b/c - + partial / subtotal / total villous atrophy
- In children with tTG >10x ULN, positive EMA and HLA-DQ2/DQ8, biopsy may be omitted (ESPGHAN). This does not apply to adults in Australia - biopsy is needed for PBS/Medicare-supported management and to exclude alternatives
HLA-DQ2/DQ8 typing
- Only useful for its NEGATIVE predictive value - a negative result essentially excludes coeliac disease
- Use when: already gluten-free and unwilling to challenge, equivocal results, Down syndrome, screening relatives
At diagnosis
- FBE, iron studies, B12, folate, vitamin D, calcium, LFT, TSH, zinc
- DEXA bone density
- Pneumococcal vaccination - functional hyposplenism
- Dietitian referral; family screening
Differentials for villous atrophy
- Olmesartan (and other sartan) enteropathy, giardiasis, tropical sprue, small bowel bacterial overgrowth, common variable immunodeficiency, autoimmune enteropathy, Crohn, HIV enteropathy, EATL
Management
The only treatment is a strict, lifelong gluten-free diet
- Dietitian-led education is essential - hidden gluten in sauces, medications, beer, cross-contamination
- Coeliac Australia membership and food-labelling support
- Response: symptoms improve in weeks; serology normalises over 6-12 months; histology takes 1-2 years in adults (and never fully normalises in some)
Monitor
- tTG-IgA at 6 and 12 months, then annually - a rising titre means gluten exposure
- Weight, symptoms, FBE, iron, B12, folate, vitamin D, calcium, LFT, TSH
- Repeat DEXA per bone density result and risk
- Repeat biopsy if symptoms persist or serology fails to normalise
Replace deficiencies
- Iron, folate, B12, vitamin D and calcium; zinc
- Secondary lactose intolerance is common early and usually resolves as villi recover
Non-responsive coeliac disease - work through it in order
1. Ongoing gluten exposure - by far the commonest cause (dietitian re-review, serology)
2. Wrong diagnosis - re-examine the original biopsy and serology
3. Coexisting: microscopic colitis, lactose or fructose intolerance, SIBO, pancreatic insufficiency, IBS
4. Refractory coeliac disease (persistent symptoms and villous atrophy >12 months on a strict diet)
- Type I - normal intraepithelial lymphocyte phenotype -> corticosteroids (budesonide), azathioprine
- Type II - clonal aberrant intraepithelial lymphocyte population = pre-lymphoma. Poor prognosis; ~50% progress to EATL
Other
- Pneumococcal vaccine (and consider influenza) - hyposplenism
- Screen for type 1 diabetes and thyroid disease
- Screen first-degree relatives
- Dermatitis herpetiformis: gluten-free diet plus dapsone for rapid rash control (check G6PD first)
Associations
Dermatitis herpetiformis - the cutaneous manifestation
- Intensely pruritic, symmetrical vesicular/papular rash on EXTENSOR surfaces - elbows, knees, shoulders, buttocks
- Caused by granular IgA deposition at the dermal papillary tips (direct immunofluorescence of perilesional skin is diagnostic)
- Responds to a gluten-free diet; dapsone gives faster symptom control
- Almost all patients have enteropathy on biopsy even without GI symptoms
Autoimmune
- Type 1 diabetes (~5-10%), autoimmune thyroid disease
- IgA deficiency (10-15x)
- Autoimmune hepatitis, PBC; Sjogren; Addison disease; ITP; alopecia areata, vitiligo
Genetic
- Down syndrome, Turner syndrome, Williams syndrome
- First-degree relatives ~10%
Consequences
- Iron deficiency anaemia (the commonest adult presentation)
- Osteoporosis and osteomalacia
- Functional hyposplenism -> Howell-Jolly bodies -> vaccinate
- Infertility, recurrent miscarriage, delayed puberty
- Neurological: gluten ataxia, peripheral neuropathy, epilepsy with occipital calcification
- Abnormal LFTs ("coeliac hepatitis") - resolves on diet
- Recurrent aphthous ulceration, dental enamel defects
Natural history & complications
- Excellent prognosis on a strict gluten-free diet - mortality approaches background
- Poor adherence -> persistent villous atrophy, osteoporosis and continued malignancy risk
Malignancy
- Enteropathy-associated T-cell lymphoma (EATL) - rare but the characteristic complication
- Suspect on new weight loss, abdominal pain, fever, obstruction or bleeding in an established, previously well-controlled patient
- Preceded by refractory coeliac disease type II
- Small bowel adenocarcinoma
- Oesophageal and oropharyngeal SCC
- Overall lymphoma risk is much lower than older literature suggested, and falls with dietary adherence
Other complications
- Refractory coeliac disease (type I and II)
- Ulcerative jejunitis
- Coeliac crisis - rare, severe diarrhoea with dehydration and electrolyte derangement
- Osteoporotic fracture; hyposplenism-related sepsis
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