Celiac Disease

Overview.

Celiac disease is an immune-mediated enteropathy triggered by dietary gluten in genetically susceptible individuals. It affects approximately 1% of the global population, yet up to 70% remain undiagnosed. While classic symptoms include chronic diarrhoea and malabsorption, over half of adults present with extraintestinal features — iron deficiency anaemia, osteoporosis, unexplained liver enzyme elevation, or infertility — making blood test screening essential.

Gluten peptides (gliadin) interact with tissue transglutaminase 2 (tTG2) to form complexes that trigger an adaptive immune response in the duodenal mucosa. HLA-DQ2 (present in ~90% of cases) and HLA-DQ8 (~5-10%) are necessary but not sufficient genetic co-factors. The result is villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis — graded by the Marsh classification (Marsh 1-3c). The only treatment is a strict, lifelong gluten-free diet.

Prevalence: Approximately 1% globally (1 in 100 people). Up to 70% are undiagnosed. Higher prevalence in first-degree relatives (~10%). Roughly equal in men and women, but symptomatic presentation is more common in women.

Medical name: Coeliac Disease

Symptoms.

Early warnings

• Iron deficiency anaemia refractory to oral iron supplementation
• Unexplained elevated liver transaminases
• Recurrent mouth ulcers (aphthous stomatitis)
• Chronic bloating and flatulence
• Unexplained osteoporosis or osteopenia, especially in younger adults
• Infertility or recurrent miscarriage

Classic symptoms

• Chronic diarrhoea with steatorrhoea
• Abdominal bloating, distension, and flatulence
• Weight loss and malabsorption
• Fatigue and lethargy
• Iron deficiency anaemia (most common extraintestinal finding)
• Dermatitis herpetiformis (intensely pruritic blistering rash)
• Osteoporosis from calcium and vitamin D malabsorption
• Peripheral neuropathy
• Short stature and failure to thrive (children)
• Dental enamel defects (children)

Progression

Untreated celiac disease causes progressive villous atrophy, worsening malabsorption, and increased risk of complications: refractory celiac disease, enteropathy-associated T-cell lymphoma (rare), and small bowel adenocarcinoma. Strict gluten-free diet reverses mucosal damage in most patients. tTG-IgA typically normalises within 6-12 months of dietary adherence.

Risk factors.

• First-degree relative with celiac disease (~10% prevalence)
• Type 1 diabetes mellitus (~5-10% have celiac disease)
• Autoimmune thyroid disease (Hashimoto's, Graves') — ~4x general population risk
• HLA-DQ2 or HLA-DQ8 positivity (necessary but not sufficient)
• Down syndrome, Turner syndrome, Williams syndrome
• IgA nephropathy
• Selective IgA deficiency (2-3% of celiac patients)

Lab interpretation.

Key biomarkers

• tTG-IgA — Elevated (>10 U/mL); strongly positive values (>10x ULN) have >95% specificity (primary)
• Total IgA — Must be normal to trust tTG-IgA; if low, use IgG-based tests instead (primary)
• Ferritin — Low; iron deficiency anaemia is the most common extraintestinal presentation (secondary)
• ALT — May be mildly elevated (cryptogenic hypertransaminasemia that resolves on GFD) (supportive)
• Vitamin D — Often low due to malabsorption; monitor for osteoporosis (supportive)

Diagnostic criteria

• Adults: positive tTG-IgA while on gluten-containing diet → endoscopic duodenal biopsy (≥4 biopsies) for confirmation (ACG 2023)
• Children: tTG-IgA >10x ULN + positive EMA + HLA-DQ2/DQ8 → no-biopsy diagnosis acceptable (ESPGHAN 2020)
• If IgA deficient: use tTG-IgG or DGP-IgG instead; biopsy still recommended
• HLA-DQ2/DQ8 negative → celiac disease effectively ruled out (99% NPV)
• Must be consuming gluten at time of testing — gluten-free diet causes false negatives

Recommended panels

• Cmp

When & next steps.

When to test

• Unexplained iron deficiency anaemia, especially if refractory to oral iron
• Chronic diarrhoea or bloating without clear cause
• First-degree relative with celiac disease
• Type 1 diabetes or autoimmune thyroid disease
• Unexplained elevated liver transaminases
• Unexplained osteoporosis in younger adults
• Infertility or recurrent pregnancy loss
• Dermatitis herpetiformis (skin biopsy confirms)
• Children with growth failure or delayed puberty

If suspected

• Order tTG-IgA AND total IgA simultaneously
• Patient must be on a gluten-containing diet at time of testing
• If tTG-IgA positive → referral to gastroenterologist for duodenal biopsy
• If IgA deficient → order DGP-IgG or tTG-IgG
• HLA-DQ2/DQ8 testing to exclude diagnosis if serology is equivocal

If confirmed

• Strict lifelong gluten-free diet (GFD) — sole proven treatment
• Dietitian referral essential for education and support
• Repeat tTG-IgA at 6 and 12 months to confirm serological remission
• Check CBC, iron studies, folate, B12, vitamin D, calcium annually
• DXA scan at diagnosis for osteoporosis assessment
• Consider follow-up biopsy if tTG-IgA fails to normalise at 12-24 months

FAQs.

Important note.