Coeliac disease

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Coeliac disease is caused by adaptive immune response to wheat, barley and rye gluten in people carrying permissive HLA. Villous injury reduces absorption and can produce diarrhoea, steatorrhoea, weight loss, bloating, aphthous ulcers, iron or folate deficiency and low bone density. Extra-intestinal presentations include dermatitis herpetiformis, transaminitis, fatigue, neuropathy, ataxia, infertility and enamel change. Type 1 diabetes, autoimmune thyroid disease, selective IgA deficiency, Down syndrome and a first-degree relative increase pre-test probability.

Accurate diagnosis is a sequence. Gluten restriction lowers antibodies and heals mucosa, so the diet must remain gluten-containing during testing unless the patient is too unwell or declines after informed discussion. Total IgA identifies a common reason for false-negative IgA tTG. HLA-DQ2 or DQ8 has value mainly for exclusion when absent, especially after self-restriction or equivocal histology; its presence is common and does not establish disease.

The 2026 BSG adult guideline updates older biopsy assumptions. A pragmatic no-biopsy route exists for a carefully selected subgroup in secondary care after expert review of serology, symptoms and alternative diagnoses. Others still require high-quality duodenal histology. Management begins only after diagnosis is secure. Follow-up should be tailored: early dietetic support and biochemical recovery are important, while stable patients need an accessible review pathway rather than uncritical repeated endoscopy.

Key points

Coeliac disease is an immune-mediated enteropathy triggered by gluten in genetically susceptible people; presentation ranges from diarrhoea and weight loss to isolated iron deficiency, osteoporosis, neuropathy or abnormal liver tests.
Test while the person eats gluten in more than one meal daily for at least six weeks where possible, and advise against starting a gluten-free diet before specialist diagnosis.
First-line adult serology is total IgA plus IgA tissue transglutaminase; use EMA for appropriate equivocal results and IgG-based testing when IgA deficient.
Positive serology warrants gastroenterology assessment. The 2026 BSG guideline permits a no-biopsy diagnosis only in a selected secondary-care subgroup, not as a universal shortcut.
If biopsy is required, obtain sufficient samples from duodenal bulb and distal duodenum because changes are patchy and orientation affects interpretation.
Treatment is a lifelong strict gluten-free diet taught by a specialist dietitian, with practical attention to cross-contact, labels, eating out and adequate fibre and micronutrients.
Assess iron, folate, B12, vitamin D, calcium, weight and bone risk at diagnosis; correct measured deficits and consider hyposplenism and vaccination through the current pathway.
Persistent symptoms demand diagnostic review: inadvertent gluten, IBS, lactose intolerance, microscopic colitis, pancreatic insufficiency and rare refractory coeliac disease are not interchangeable.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Genetic susceptibility

Almost all affected people carry permissive HLA-DQ variants, but these are common in the population and are not diagnostic alone.

Dietary gluten exposure

Gluten proteins from wheat, barley and rye provide the antigenic trigger; reducing exposure before testing can normalise serology and histology.

Autoimmune association

Type 1 diabetes, autoimmune thyroid disease, IgA deficiency and a family history increase pre-test probability and justify a lower threshold for testing.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Gluten peptide modification
Tissue transglutaminase modifies gluten peptides, increasing their binding to susceptible HLA molecules in the small-intestinal mucosa.
2
Adaptive immune injury
Gluten-specific T-cell activation drives cytokine release, intraepithelial lymphocytosis and autoantibody production against tissue transglutaminase in genetically susceptible people.
3
Villous atrophy and malabsorption
Crypt hyperplasia and villous shortening reduce absorptive surface, producing diarrhoea, iron deficiency, weight loss or extra-intestinal manifestations.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Classical malabsorption

Chronic diarrhoea, bulky stool, weight loss, distension, oedema or broad nutrient deficiency suggests extensive enteropathy and requires nutrition and refeeding assessment.

Non-classical presentation

Unexplained iron-deficiency anaemia, osteoporosis, recurrent aphthae, raised transaminases, infertility, fatigue or peripheral neuropathy may be the only clue.

Dermatitis herpetiformis

Intensely itchy grouped vesicles or excoriations on extensor surfaces strongly associates with gluten-sensitive enteropathy; dermatology biopsy and treatment pathways are specialised.

Coeliac crisis or severe depletionRed flag

Profuse diarrhoea, dehydration, major electrolyte disturbance, hypoalbuminaemia or rapid wasting is rare but needs admission, nutrition support and specialist exclusion of infection or refractory disease.

Refractory or complicated diseaseRed flag

Persistent malabsorption and villous atrophy despite verified strict diet raises ongoing gluten, wrong diagnosis, refractory coeliac disease, ulcerative jejunitis or lymphoma and warrants an expert centre.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Total IgA and IgA tTGFirst step
Why
Screen symptomatic or at-risk adults while consuming gluten and identify IgA deficiency that changes assay choice.
Interpretation and limitations
A positive result increases probability but enters a specialist pathway; a negative result is less reliable with gluten restriction, IgA deficiency or high pre-test probability.
02
EMA or IgG-based coeliac serology
Why
Use EMA for weakly positive tTG as the local algorithm specifies, and IgG tTG or deamidated gliadin peptide when IgA deficient.
Interpretation and limitations
Assay thresholds and calibration differ. Avoid translating one laboratory's multiple-of-normal rule directly to another.
03
Upper endoscopy with duodenal biopsies
Why
Sample bulb and distal duodenum in patients outside the selected no-biopsy route or when alternative mucosal pathology matters.
Interpretation and limitations
Villous atrophy, crypt hyperplasia and lymphocytosis support coeliac disease but can arise from medicines, infection and immune disorders; pathologist orientation and clinical data matter.
04
HLA-DQ2 and DQ8 typing
Why
Clarify selected equivocal cases, particularly after gluten restriction, uncertain prior diagnosis or discordant serology and histology.
Interpretation and limitations
Absence makes coeliac disease very unlikely; presence has low positive specificity and cannot prove the diagnosis.
05
Baseline deficiency and bone assessment
Why
Check FBC, ferritin and iron indices, B12, folate, vitamin D, calcium, liver profile and weight, and assess DXA need from age, fracture and severity risk.
Interpretation and limitations
Combined deficiency can mask MCV changes. Biochemical recovery supports response but antibody normalisation does not prove complete mucosal healing.
06
Non-response work-up
Why
Review diet with an expert, repeat serology and consider repeat histology, stool studies, faecal calprotectin, pancreatic tests, colon biopsies or small-bowel imaging according to symptoms.
Interpretation and limitations
Ongoing gluten is common, while refractory coeliac is rare and requires persistent villous atrophy plus specialist phenotyping.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Irritable bowel syndrome

A compatible pain-stool pattern without deficiencies or objective enteropathy supports IBS, but coeliac serology should precede that diagnosis in appropriate adults.

Non-coeliac wheat sensitivity

Symptoms linked to wheat with negative coeliac evaluation and no wheat allergy may support this diagnosis; improvement off gluten does not prove coeliac disease.

Crohn disease or pancreatic insufficiency

Inflammatory markers, ulceration or transmural imaging favour Crohn disease, while low faecal elastase and pancreatic structural disease suggest maldigestion.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01DiagnoseSerology to confirmed diseaseFirst stepCoeliac disease is suspected from symptoms, deficiency or risk group.

1AlternativeConfirm adequate gluten exposure and order total IgA with IgA tTG, using alternative assays when IgA deficient.
2Refer positive or strongly suspected cases to gastroenterology without advising gluten exclusion; address severe dehydration or malnutrition immediately.
3Apply the live 2026 BSG secondary-care criteria for selected no-biopsy diagnosis or undertake correctly sampled duodenal histology.
4Document the evidence supporting diagnosis before prescribing a lifelong restrictive diet.

02TreatNewly diagnosed coeliac diseaseCoeliac disease is confirmed through the current specialist pathway.

1Provide specialist dietetic education on strict lifelong exclusion of wheat, barley and rye, cross-contact, labels, oats and balanced substitute foods.
2Measure and replace deficiencies, assess bone and vaccination needs, and screen associated autoimmune disease when clinically indicated.
3Arrange early review for symptom, weight and biochemical recovery and ensure practical access to local prescribing or food-support policy.
4Give urgent refeeding or electrolyte support when severe malnutrition makes rapid normal eating unsafe.

03ReviewPersistent symptoms on gluten-free dietSymptoms, anaemia, weight loss or serology do not improve as expected.

1Reconfirm the original diagnosis and conduct detailed dietetic assessment for hidden gluten, cross-contact and adherence barriers.
2Evaluate common alternatives including IBS, lactose intolerance, microscopic colitis, bile acid diarrhoea and pancreatic insufficiency.
3Repeat endoscopy or small-bowel assessment when persistent villous injury, weight loss, pain, anaemia or systemic alarm suggests complication.
4Refer suspected refractory coeliac disease to an expert centre for histological and lymphocyte phenotyping before immunosuppression.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Restores iron and haemoglobin while gluten exclusion permits mucosal recovery.

Oral or intravenous iron

Select a current BNF regimen based on anaemia severity, inflammation, absorption, ongoing loss and tolerance; use intravenous treatment through local governance when oral therapy fails.

Iron replacement must not substitute for investigation of bleeding. Oral products cause gastrointestinal effects; intravenous formulations can cause reactions and product-specific hypophosphataemia.

Corrects deficiency and supports bone health during intestinal recovery.

Colecalciferol and calcium

Use a local loading and maintenance plan based on vitamin D, calcium intake, renal function and bone disease, then reassess.

Avoid indiscriminate calcium in hypercalcaemia or stone risk. Severe symptomatic hypocalcaemia requires monitored emergency therapy and magnesium assessment.

Corrects haematinic deficiencies resulting from malabsorption or restricted intake.

Hydroxocobalamin or folic acid

Use current BNF cause- and severity-specific replacement; treat neurological B12 deficiency urgently and check B12 before folic acid alone.

Folate can improve anaemia while neurological B12 injury progresses. Persistent deficiency despite diet requires another cause or adherence review.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Anaemia and micronutrient deficiency

Iron, folate, vitamin B12 and other deficits cause fatigue, neuropathy or mucosal symptoms and require replacement alongside mucosal healing.

Low bone density

Calcium and vitamin D malabsorption, inflammation and low weight increase osteopenia, osteoporosis and fracture risk, particularly after delayed diagnosis.

Refractory disease and malignancy

Persistent villous atrophy despite verified gluten exclusion warrants specialist review for hidden exposure, alternative enteropathy, refractory coeliac disease or lymphoma.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Review symptoms, stool, weight and functional recovery after diet initiation, avoiding a single universal schedule for every stable patient.
Repeat FBC, ferritin, folate, B12, vitamin D, calcium and liver tests according to baseline deficits and treatment response.
Use coeliac serology as an adherence and recovery aid, not as a perfect measure of mucosal healing.
Assess diet quality, fibre, cross-contact and social or financial burden with a coeliac-experienced dietitian.
Revisit bone health, fractures, menstrual or reproductive issues and associated autoimmune disease when clinically indicated.
Escalate persistent weight loss, pain, fever, night sweats, obstruction, hypoalbuminaemia or anaemia for complication assessment.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

No-biopsy is not no-specialist

The 2026 pathway narrows biopsy use in a selected adult subgroup but still requires rigorous secondary-care confirmation and assay-aware criteria.

HLA is an exclusion tool

Many healthy people carry DQ2 or DQ8. Absence is powerful; presence adds little proof without compatible serology or histology.

Oats are a separate conversation

Pure uncontaminated oats are tolerated by many, but contamination and a minority with oat sensitivity require dietetic guidance and symptom review.

IgA deficiency changes the test

Total IgA prevents false reassurance from a negative IgA tTG and flags a group with higher coeliac probability.

Non-response is usually not refractory

Hidden gluten and common overlapping disorders far outnumber true refractory coeliac disease, which requires expert histological confirmation.

11Common pitfallsFrequent interpretation and management errors.

01
Starting gluten exclusion before serology and specialist diagnosis.
02
Calling positive HLA typing diagnostic.
03
Using a paediatric no-biopsy rule or remembered antibody threshold in every adult.
04
Taking only one poorly oriented distal duodenal biopsy.
05
Assuming normalised tTG proves mucosal healing.
06
Labelling persistent symptoms refractory disease before dietary and alternative-cause review.