Coeliac disease
Celiac Disease (Coeliac Disease)
Introduction
Celiac disease (CeD) is a chronic, immune-mediated enteropathy precipitated by dietary gluten in genetically susceptible individuals carrying the HLA-DQ2 or HLA-DQ8 haplotypes. Recent American College of Gastroenterology (ACG) guidelines classify CeD as an autoimmune disorder rather than a mere malabsorption syndrome, underscoring its systemic impact . Global meta-analyses estimate a seroprevalence of ~1 %–1.4 % and a biopsy-confirmed prevalence of ~0.7 %, with regional variation and steadily rising detection rates owing to wider screening and improved assays .
Pathogenesis: “When Gluten Meets Genetics”
- Gluten ingestion (wheat, barley, rye) → generation of immunogenic gliadin peptides.
- Tissue transglutaminase-2 (TG2) deamidates gliadin, increasing its affinity for HLA-DQ2/8 on antigen-presenting cells.
- Adaptive immunity: Gliadin-specific CD4⁺ T cells secrete IFN-γ, driving villous atrophy and crypt hyperplasia.
- Autoantibody production: Anti-TG2 IgA/IgG, endomysial antibodies (EMA), and deamidated gliadin peptide (DGP) antibodies.
- Intestinal and systemic sequelae: Disrupted barrier, micronutrient malabsorption, and extra-intestinal manifestations (dermatitis herpetiformis, neurologic syndromes, osteoporosis). Multifactorial triggers—viral infections, microbiome shifts, and early-life gluten load—are active research areas .
Clinical Spectrum
| Presentation | Common Features | Extra-intestinal Clues |
|---|---|---|
| Classical | Chronic diarrhea, steatorrhea, weight loss, failure to thrive (children) | Iron-deficiency anemia, osteopenia, infertility |
| Non-classical | Bloating, functional dyspepsia, isolated anemia, elevated liver enzymes | Peripheral neuropathy, ataxia, dermatitis herpetiformis |
| Silent/Screen-detected | Positive serology without symptoms | Often first-degree relatives or type 1 diabetes patients |
| Early recognition is vital because a gluten-free diet (GFD) normalizes mortality to that of the general population and mitigates long-term risks such as enteropathy-associated T-cell lymphoma. |
Diagnosis
ACG 2023 algorithm (adults) 1. High-quality serology on a gluten-containing diet: - TG2-IgA (≥ ULN × 10 suggests high probability) - Reflex total IgA to exclude selective IgA deficiency; if deficient, use TG2-IgG or DGP-IgG. 2. Confirmatory duodenal biopsy (≥ 4 distal + 1 bulb sample) demonstrating Marsh 2–3 lesions. 3. HLA typing to rule out CeD when diagnosis uncertain (negative DQ2/DQ8 virtually excludes).
Emerging non-biopsy pathways
- Pediatrics: ESPGHAN permits no-biopsy diagnosis when TG2-IgA ≥ 10 × ULN + positive EMA + compatible symptoms .
- Adults: Multicenter U.S. data show > 90 % positive predictive value for TG2-IgA ≥ 10–15 × ULN, fueling debate over extending the no-biopsy approach .
- Ongoing studies aim to refine cutoffs and incorporate machine-learning algorithms combining serology with HLA status and clinical metadata.
Management
| Strategy | Key Components | Practical Tips |
|---|---|---|
| Strict gluten-free diet | Eliminate wheat, barley, rye; < 20 ppm gluten tolerated | Smartphone barcode scanners & Indian FSSAI gluten-free logo help patients identify safe foods. |
| Nutritional repletion | Monitor iron, B₁₂, folate, vitamin D, calcium, zinc; DEXA at baseline & 2 years | Use Excel/Google Sheets to track labs and flag deficiencies. |
| Vaccinations | Pneumococcus, hepatitis B (if non-immune), ensure routine adult schedule | |
| Follow-up | TG2-IgA at 6 & 12 months, then annually; repeat biopsy if antibodies persist or symptoms recur | Create EHR reminders; ChatGPT prompts can auto-draft follow-up letters. |
| Manage complications | Refractory CeD, hyposplenism, small-bowel adenocarcinoma surveillance in high-risk cases | Early referral to celiac center for refractory disease. |
| #### Pipeline therapies – “Beyond the GFD” | ||
| - Enzymatic detoxifiers (latiglutenase), tight-junction modulators (larazotide), and peptide vaccines are in phase 2–3 trials . | ||
| - TPM502 nanoparticle therapy showed early success in modulating gluten-specific T-cells without systemic immunosuppression . | ||
| - Inverse vaccines are advancing toward phase 2 trials, aiming to induce antigen-specific tolerance—a potential “holy grail” for CeD and other autoimmune diseases . | ||
| --- | ||
| ### Prognosis & Long-Term Outcomes | ||
| With sustained dietary adherence, mucosal healing occurs in > 80 % of children and ~ 60 % of adults within 2 years, restoring quality of life and normalizing fracture and malignancy risks. Persistently elevated TG2-IgA or ongoing villous atrophy correlates with increased all-cause mortality and lymphoma incidence; thus, structured follow-up is essential . |
Future Directions
- Non-invasive diagnostics integrating serology, HLA, and stool/urine gluten-immunogenic peptide assays.
- Artificial-intelligence tools for automated dietary label scanning and symptom tracking.
- Precision immunotherapies (nanoparticle inverse vaccines, neo-antigen-specific T-cell modulation) aiming for gluten tolerance rather than gluten avoidance.
- Population screening strategies in high-prevalence regions (e.g., South Asia) to capture asymptomatic cases early.
Conclusion
Celiac disease is a highly prevalent, systemic autoimmune disorder whose only proven therapy remains lifelong gluten exclusion. Advances in serologic accuracy, evolving no-biopsy criteria, and novel immunomodulatory treatments promise to reshape the diagnostic and therapeutic landscape. Clinicians must balance rigorous dietary counseling with vigilant monitoring for nutritional deficits and long-term complications while staying abreast of emerging disease-modifying therapies.
References
- Rubio-Tapia A, et al. ACG Clinical Guidelines for Celiac Disease. Am J Gastroenterol. 2023.
- Husby S, et al. ESPGHAN 2020 Paediatric CeD Diagnostic Guidelines. J Pediatr Gastroenterol Nutr. 2020.
- Singh P, et al. Global CeD Prevalence Meta-analysis. Clin Gastroenterol Hepatol. 2024.
- Lebwohl B, et al. Non-biopsy Diagnosis in Adults – Multicenter Study. DDW Presentation. 2025.
- TPM502: Novel Nanoparticle Therapy for CeD. Celiac Disease Foundation Blog. 2025.
- Chey WD. Emerging Therapies for Celiac Disease. BioSpace Opinion. 2025.
- Devlin S. Inverse Vaccines for Autoimmunity. The Guardian. 2025.