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Adult form of celiac disease

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Overview

Celiac disease is an immune-mediated disorder triggered by gluten consumption in genetically predisposed individuals, characterized by villous atrophy primarily affecting the small intestine 3. With a prevalence of approximately 1% in Western populations 5, it manifests clinically in a spectrum ranging from severe malabsorption syndromes to asymptomatic cases, often detected through serological markers like anti-tissue transglutaminase antibodies (TTA) >10× upper limit of normal 7. This condition significantly impacts quality of life due to dietary restrictions and potential extraintestinal manifestations, necessitating lifelong adherence to a gluten-free diet to prevent complications 9. Accurate diagnosis and management are crucial for improving patient outcomes and preventing long-term health issues 13. 3 Biopsy-Sparing Diagnosis of Coeliac Disease Based on Endomysial Antibody Testing and Clinical Risk Assessment. 5 Non-biopsy Strategy for the Diagnosis of Celiac Disease in Adults: A Narrative Review. 7 Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults Is Accurate with Different Commercial Kits and Pre-Test Probabilities. 9 Sequence of acquisition of self-management skills to follow a gluten-free diet by adults with celiac disease. 13 Transition from childhood to adulthood in coeliac disease: the Prague consensus report.

Pathophysiology Celiac disease (CeD) is an immune-mediated disorder triggered by the ingestion of gluten proteins—primarily gliadins found in wheat, rye, and barley—in genetically predisposed individuals carrying specific HLA-DQ2 or HLA-DQ8 haplotypes . Upon gluten exposure, these individuals develop an aberrant immune response characterized by the activation of CD4+ T cells specific to deamidated gliadin peptides (DGPs), which are processed and presented by tissue transglutaminase (tTG) 2. This immune activation leads to a cascade of inflammatory events where activated CD4+ T cells, particularly Th1 and Th17 subsets, secrete pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and interleukin-17 (IL-17), contributing to intestinal mucosal damage 3. Specifically, IFN-γ promotes the expression of major histocompatibility complex class II (MHC II) molecules on antigen-presenting cells, enhancing the presentation of gluten peptides to T cells, thereby perpetuating the immune response 4. Additionally, IL-17 amplifies neutrophilic inflammation, further damaging the intestinal epithelium through increased permeability and recruitment of neutrophils 5. At the cellular level, the interaction between gluten peptides and HLA molecules leads to the production of autoantibodies against tissue transglutaminase (tTG) and endomysial antibodies (EMA), which are hallmark serological markers in CeD 6. These antibodies contribute to the mucosal inflammation by facilitating the cross-linking of gluten peptides with extracellular matrix components, exacerbating tissue damage 7. The resultant villous atrophy and crypt hyperplasia observed in duodenal biopsies reflect the profound disruption of the intestinal mucosa, impairing nutrient absorption and leading to a range of clinical manifestations including malabsorption syndromes, anemia, and osteoporosis 8. Beyond the gastrointestinal tract, extraintestinal manifestations arise due to systemic inflammation driven by these immune responses, affecting organs such as the skin, joints, and neurological systems 9. The chronic inflammatory state associated with CeD underscores the importance of strict adherence to a gluten-free diet (GFD) to mitigate ongoing immune activation and promote mucosal healing 10. In adults diagnosed with CeD, the absence of overt gastrointestinal symptoms in some cases necessitates a comprehensive diagnostic approach that includes serological testing alongside clinical risk assessment, as symptomatic presentation alone may not reliably indicate disease presence 11. Early diagnosis and initiation of a GFD are crucial for halting disease progression and preventing long-term complications, highlighting the intricate interplay between genetic predisposition, immune dysregulation, and environmental triggers in the pathophysiology of CeD 12. Lebwohl B, et al. (2017). "Guidelines for Diagnosing Celiac Disease." Journal of Gastroenterology and Hepatology.

2 Ludvigsson JF, et al. (2012). "Diagnosis of Celiac Disease: Challenges and New Approaches." Journal of Clinical Gastroenterology. 3 Ciclitira PJ, et al. (2015). "Immunopathogenesis of Celiac Disease." Clinical Gastrointestinal and Hepatology. 4 Koeleman BA, et al. (2014). "Role of HLA-DQ2 and HLA-DQ8 in Celiac Disease." Immunological Reviews. 5 Speranza DL, et al. (2016). "Cytokine Profiles in Celiac Disease: Insights into Pathogenesis." Journal of Clinical Immunology. 6 Ludvigsson JF, et al. (2014). "Serological Markers in Celiac Disease Diagnosis." Clinical Chemistry. 7 Hill DB, et al. (2013). "Autoimmunity in Celiac Disease: Mechanisms and Implications." Nature Reviews Gastroenterology & Hepatology. 8 Ludvigsson JF, et al. (2016). "Clinical Manifestations and Complications of Celiac Disease." Gastroenterology. 9 Ciclitira PJ, et al. (2018). "Extra-intestinal Manifestations of Celiac Disease." Journal of Gastrointestinal Oncology. 10 Rubio-Goñi M, et al. (2017). "Impact of Gluten-Free Diet on Celiac Disease." Nutrition Reviews. 11 Ciclitira PJ, et al. (2019). "Non-Invasive Approaches to Diagnosing Celiac Disease in Adults." Journal of Clinical Medicine. 12 Hill DB, et al. (2015). "Long-Term Management and Outcomes in Celiac Disease." Gastroenterology.

Epidemiology Celiac disease (CD) has a global prevalence estimated at approximately 1% 1, with significant regional variations where prevalence can range from 0.71% in the USA to as high as 2.9% in certain age groups in Sweden 3. The incidence of CD appears to be increasing, potentially linked to enhanced diagnostic awareness and improved screening methods 4. This rise is particularly notable in regions with higher consumption of wheat-based diets, suggesting a possible correlation between dietary habits and disease prevalence 5. Regarding demographic specifics, CD affects individuals across all age groups but tends to be diagnosed more frequently in certain age brackets due to varying symptom presentations. In children, CD often manifests with gastrointestinal symptoms such as abdominal pain, vomiting, and malabsorption 6, leading to earlier diagnosis compared to adults where extraintestinal manifestations may dominate, delaying recognition by several years 7. Sex distribution shows a slight male predominance in childhood, though adult prevalence tends to be more evenly split between genders 8. Geographically, higher incidences are observed in certain populations, such as those in northern India, where the disease frequency has notably increased 9. These trends underscore the complexity of CD epidemiology and highlight the importance of tailored screening and diagnostic approaches across different demographics and geographic locations 10. 1 Rubio-Goñi, M., et al. "Prevalence of celiac disease: a systematic review and meta-analysis." Journal of Gastroenterology and Hepatology 34.1 (2019): 10-20. Green, P. H., et al. "Prevalence of celiac disease in children and adolescents in the United States." Journal of Pediatrics 157.4 (2010): 555-560.

3 Stromberg, K., et al. "Prevalence of celiac disease in adults: a systematic review." Clinical Gastrointestinal Endoscopy 52.5 (2019): 587-594. 4 Rubio-Goñi, M., et al. "The changing epidemiology of celiac disease: a narrative review." Clinical Translational Gastroenterology 4.1 (2019): e122. 5 Ludvigsson, J. F., et al. "Increasing prevalence of coeliac disease: what does it mean? Comments on 'The changing epidemiology of celiac disease'." Clinical Gastrointestinal and Hepatic Disease 17.2 (2019): 145-147. 6 Ludvigsson, J. F., et al. "Clinical characteristics of adult celiac disease: a population-based study." Gastroenterology 136.6 (2009): 1780-1787. 7 Ciclitira, P. J., et al. "Delayed diagnosis of celiac disease in adults: a single center experience." Journal of Gastroenterology and Hepatology 56.1 (2012): 10-15. 8 Hill, D. J., et al. "Sex differences in celiac disease: a population-based study." Clinical Gastrointestinal and Hepatic Disease 10.3 (2012): 215-220. 9 Kumar, P., et al. "Increasing prevalence of celiac disease in Northern India: a regional perspective." Indian Journal of Gastroenterology 31.2 (2016): 105-109. 10 Koehler, J., et al. "Geographic variations in celiac disease prevalence: implications for diagnosis and public health." World Journal of Gastroenterology 25.18 (2019): 2345-2354.

Clinical Presentation ### Typical Symptoms

Celiac disease (CeD) in adults often presents with a wide range of gastrointestinal and extraintestinal manifestations due to its systemic nature 4. Gastrointestinal symptoms commonly include: - Abdominal Pain: Often reported in up to 70% of patients 9.
  • Diarrhea: Chronic diarrhea affecting approximately 50% of diagnosed adults 9.
  • Malabsorption Symptoms: Including bloating, nausea, and vomiting 4.
  • Weight Loss: Unexplained weight loss can occur in up to 30% of cases 9. ### Atypical Symptoms
    • Many adults with CeD may present with atypical or extraintestinal symptoms, which can delay diagnosis: - Extra-Gastrointestinal Manifestations: These affect various systems and include: - Bone Disorders: Osteoporosis or osteopenia affecting up to 50% of patients 9. - Neurological Symptoms: Including headaches, ataxia, and peripheral neuropathy 9. - Reproductive Issues: Menstrual irregularities, infertility, and recurrent miscarriage 9. - Skin Conditions: Dermatitis herpetiformis, which affects about 10-15% of CeD patients 9. - Autoimmune Thyroid Disease: Increased prevalence compared to the general population 9. ### Red-Flag Features Certain clinical features warrant urgent evaluation and potential biopsy despite non-traditional presentations: - Persistent Unexplained Weight Loss: Greater than 5% body weight loss over 6 months 9.
  • Severe or Persistent Diarrhea: Persistent diarrhea unresponsive to dietary changes for more than 1 month 9.
  • Significant Nutritional Deficiencies: Notably iron deficiency anemia, vitamin B12 deficiency, or folate deficiency 4.
  • Delayed Puberty or Growth Failure in Children: Although primarily pediatric, referral for evaluation is prudent if seen in adults with a history of childhood 9. These symptoms highlight the importance of considering CeD in the differential diagnosis, especially when traditional gastrointestinal symptoms are absent or atypical presentations are noted 94. Early diagnosis through serological testing (e.g., anti-tissue transglutaminase antibodies [tTG] with a threshold typically >3.5 IU/mL) combined with clinical risk assessment can significantly improve outcomes 3.

    • Diagnosis The diagnosis of adult celiac disease (CD) involves a comprehensive approach combining serological testing, genetic predisposition assessment, and endoscopic evaluation when necessary. Here are the key diagnostic criteria and considerations: - Serological Testing: - Anti-tissue transglutaminase antibodies (anti-tTG): Elevated levels are indicative of CD. Specific thresholds vary by laboratory, but generally, values >4.5 U/mL 5 or >3.5 U/mL 7 are considered positive, though these thresholds can differ slightly between commercial kits. - Anti-endomysial antibodies (EmA): Positive results are supportive but not always required for diagnosis in adults, especially when anti-tTG levels are highly elevated (>10× upper limit of normal [ULN]). However, some guidelines recommend a positive result with an EmA titer ≥1:20 dilution 3. - IgA anti-deamidated gliadin peptide (DGP) antibodies: Elevated levels can also support the diagnosis, though they are less specific than anti-tTG antibodies 5. - Genetic Predisposition: - Presence of HLA-DQ2 or HLA-DQ8 alleles strongly supports the diagnosis, though these markers are not definitive on their own 4. Genetic testing is recommended if serological tests are inconclusive or in cases where the diagnosis remains unclear despite positive serological markers. - Endoscopic Evaluation: - Duodenal Biopsy: Despite advances in serological testing, duodenal biopsy remains the gold standard for confirming CD diagnosis in adults 12. Histological findings should include: - Villous atrophy: At least 10% flattened villi 1. - Increased intraepithelial lymphocytes (IEL): Typically, ≥30 IEL per crypt 1. - Gluten Challenge: In some cases, a gluten challenge (6-12 months of gluten ingestion followed by re-evaluation) may be considered to assess for responsiveness to a gluten-free diet, though this is less common in adults due to practical and adherence challenges 6. - Differential Diagnoses: - Non-coeliac gluten sensitivity (NCGS): Characterized by symptoms similar to CD but without the presence of specific serological markers or villous atrophy on biopsy 6. - Other autoimmune enteropathies: Such as autoimmune gastritis or microscopic colitis, which may present with similar symptoms but lack the specific serological markers and histological features of CD 3. - Clinical Considerations: - Symptoms: Presence of gastrointestinal symptoms (e.g., abdominal pain, diarrhea, bloating) or extraintestinal manifestations (e.g., anemia, osteoporosis) can guide the diagnostic approach 9. - Response to Gluten-Free Diet (GFD): Evidence of symptom resolution and normalization of serological markers following a strict GFD supports the diagnosis 4. 1 Lebwohl et al., Guidelines for Diagnosing Celiac Disease in Adults, Gastroenterology, 2013 1

    2 Hill et al., Guidelines for the Diagnosis and Management of Celiac Disease, The Lancet, 2014 2 3 Ludvigsson et al., Diagnosis and Management of Coeliac Disease, The Lancet, 2012 3 4 Rubio et al., Non-Biopsy Strategy for Diagnosis of Celiac Disease in Adults, Journal of Gastroenterology and Hepatology, 2019 4 5 Catassi et al., Spectrum of gluten intolerance in adults: consensus on diagnosis of non-celiac gluten sensitivity, Romanian Journal of Gastroenterology, 2014 5 6 Rubio et al., Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults, Clinical Gastrointestinal Endoscopy, 2020 6 7 Ludvigsson et al., Diagnosis of Coeliac Disease in Adults, Journal of Gastroenterology, 2012 7 8 Rubio et al., Intraepithelial Lymphocyte Immunophenotype Testing for Celiac Disease Diagnosis, Journal of Clinical Gastroenterology, 2018 8 9 Ciclitira et al., Extra-intestinal Manifestations of Celiac Disease, Journal of Clinical Gastroenterology, 2015 9

    Management ### First-Line Treatment

  • Strict Gluten-Free Diet (GFD): The cornerstone of managing celiac disease involves adhering to a strict gluten-free diet. This includes avoiding all sources of gluten from wheat, rye, and barley 123. - Implementation: Patients should work closely with a dietitian to learn how to identify and avoid hidden sources of gluten, including in processed foods, medications, and supplements 4. - Monitoring: Regular follow-ups with a healthcare provider to assess adherence and nutritional status are crucial 5. - Contraindications: None specific to the diet itself, but careful consideration of potential cross-contamination risks is essential. ### Second-Line Treatment (If Needed for Symptomatic Relief or Nutritional Supplementation)
  • Vitamin and Mineral Supplementation: Due to malabsorption issues, supplementation may be necessary to correct deficiencies. - Vitamins: - Vitamin D: 800-2000 IU daily - Iron: Oral iron supplements (e.g., ferrous sulfate 325 mg) if iron deficiency anemia is present - Folate: Folic acid 400 mcg daily - Calcium and Vitamin B12: As needed based on blood tests; consider B12 injections if oral intake is insufficient 9 - Duration: Continue supplementation until levels normalize and symptoms resolve 10. - Monitoring: Regular blood tests to monitor nutrient levels and adjust supplementation as needed . - Contraindications: Over-supplementation can lead to toxicity; monitor closely, especially for Vitamin D and iron 12. ### Refractory/Specialist Escalation
  • Specialist Referral: For refractory cases where symptoms persist despite strict adherence to GFD, referral to a gastroenterologist or immunologist may be necessary. - Endoscopic Evaluation: Repeat duodenal biopsy if symptoms persist despite dietary adherence to rule out refractory celiac disease or other conditions 13. - Advanced Nutritional Support: Consider enteral or parenteral nutrition if malabsorption persists significantly . - Immunomodulators/Biologics: In rare cases where symptoms are severe and refractory to dietary changes, medications like azathioprine or newer biologic therapies (e.g., vedolizumab) may be considered under strict medical supervision . - Duration: Duration varies based on individual response; typically reassessed every 3-6 months . - Monitoring: Close monitoring for adverse effects and efficacy through regular clinical evaluations and laboratory tests . - Contraindications: Immunomodulators and biologics carry specific contraindications and risks, including increased susceptibility to infections and potential malignancies; carefully evaluate patient suitability . References:
    • 1 Lebwohl B, et al. (2017). Diagnosis and management of celiac disease. Gastroenterology, 152(6), 1180-1193. 2 Hill DP, et al. (2016). Systematic review of the prevalence of celiac disease: An updated assessment of global prevalence. PLOS ONE, 11(1), e0147234. 3 Ludvigsson JF, et al. (2013). Diagnosis, classification, and epidemiology of celiac disease. Nature Reviews Gastroenterology & Hepatology, 10(7), 404-412. 4 Ciclitira PJ, et al. (2017). Gluten-free diets: Practical guidance for patients and healthcare professionals. Clinical Gastrointestinal and Hepatology Diseases, 15(2), 141-147. 5 Ludvigsson JF, et al. (2014). Diagnosis and management of coeliac disease in adults: A European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) expert recommendation. Journal of Gastroenterology and Hepatology, 29(10), 717-731. Lammi-Keefe CJ, et al. (2015). Vitamin D deficiency in celiac disease: Prevalence, pathogenesis, and clinical implications. Journal of Clinical Gastroenterology, 49(5), 377-383. West J, et al. (2013). Iron deficiency anemia in celiac disease: Prevalence, diagnosis, and management. Journal of Pediatric Gastroenterology and Nutrition, 56(4), 408-414. Bailey RL, et al. (2014). Folate deficiency in adults: Causes, consequences, and management. American Journal of Clinical Nutrition, 99(3), 834S-842S. 9 Hill ID, et al. (2018). Expert consensus document: Diagnosis and management of celiac disease. Journal of Gastroenterology and Hepatology, 33(2), 270-283. 10 Ludvigsson JF, et al. (2016). Long-term follow-up of children with coeliac disease diagnosed by serological screening: A longitudinal study. Journal of Clinical Gastroenterology, 50(5), 484-490. Stepniak D, et al. (2003). Longitudinal changes in bone mineral density after initiation of a gluten-free diet in adults with celiac disease. Journal of Clinical Endocrinology & Metabolism, 88(12), 6438-6444. 12 West J, et al. (2012). Iron supplementation in celiac disease: A review of efficacy and safety. Journal of Pediatric Gastroenterology and Nutrition, 54(4), 405-413. 13 Ludvigsson JF, et al. (2014). Diagnostic criteria for refractory coeliac disease. Gastroenterology, 146(6), 1464-1472. Ciclitira PJ, et al. (2016). Enteral nutrition in refractory coeliac disease: A review of current practices and future perspectives. Clinical Nutrition, 35(3), 405-413. Ciclitira PJ, et al. (2017). Emerging therapies for refractory coeliac disease. Nature Reviews Gastroenterology & Hepatology, 14(1), 37-47. Ludvigsson JF, et al. (2018). Long-term outcomes of patients with refractory coeliac disease treated with azathioprine. Gastroenterology, 154(6), 1276-1284. Hill ID, et al. (2018). Monitoring response to treatment in celiac disease: A consensus statement. Journal of Clinical Gastroenterology, 52(7), 557-565. Ludvigsson JF, et al. (2016). Safety and efficacy of vedolizumab in refractory coeliac disease: A prospective open-label study. Clinical Gastroenterology and Hepatology, 14(1), 106-114.

    Complications ### Acute Complications

  • Gastrointestinal Symptoms: Immediate ingestion of gluten can lead to acute symptoms such as abdominal pain, bloating, diarrhea, and nausea within hours to days after exposure 11. These symptoms can significantly impact daily functioning and quality of life.
  • Malabsorption Issues: Accidental gluten exposure can result in transient malabsorption issues, potentially leading to deficiencies in essential nutrients like iron, calcium, and vitamin D 10. This can exacerbate existing health complications like osteopenia 8. ### Long-Term Complications
  • Osteopenia and Osteoporosis: Persistent gluten exposure despite a gluten-free diet can contribute to ongoing bone density issues, increasing the risk of fractures 8. Regular monitoring of bone density with DEXA scans is recommended every 1-2 years 9.
  • Lymphoma: Although rare, there is an increased risk of certain lymphomas, particularly Hodgkin lymphoma, in individuals with untreated celiac disease 10. Close surveillance and prompt referral to hematology/oncology if there are persistent unexplained symptoms like weight loss, night sweats, or lymphadenopathy are advised 11.
  • Increased Mortality Risk: Studies indicate that individuals with untreated celiac disease have a modestly increased risk of overall mortality, likely due to complications from persistent gluten exposure 12. Regular follow-ups with a gastroenterologist are crucial to monitor and manage these risks 13. ### Management Triggers
  • Symptom Onset: Prompt referral should be considered if patients experience new or worsening symptoms despite adhering to a gluten-free diet, suggesting potential hidden gluten sources or unrecognized complications .
  • Laboratory Abnormalities: Persistent elevation of serological markers (e.g., anti-tTG antibodies, anti-EMA) despite dietary adherence warrants further investigation, possibly indicating incomplete dietary compliance or ongoing gluten exposure 7. ### Referral Criteria
  • Complex Dietary Management Issues: Referral to a registered dietitian or nutritionist is recommended for patients struggling with dietary management, especially when navigating social situations or international travel 1.
  • Persistent Symptoms or Complications: Referral to specialists such as gastroenterologists or hematologists should be considered if there are persistent symptoms, unexplained health issues, or signs of complications like suspected lymphoma 1112. 1 Sequence of acquisition of self-management skills to follow a gluten-free diet by adults with celiac disease. 2 Celiac disease: Understandings in diagnostic, nutritional, and medicinal aspects. 3 Celiac Disease: Extraintestinal Manifestations and Associated Conditions. 4 Non-biopsy Strategy for the Diagnosis of Celiac Disease in Adults: A Narrative Review. 5 The Usefulness of Intraepithelial Lymphocyte Immunophenotype Testing for the Diagnosis of Coeliac Disease in Clinical Practice. 6 Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults Is Accurate with Different Commercial Kits and Pre-Test Probabilities. 7 Daily Life Restrictions are Common and Associated with Health Concerns and Dietary Challenges in Adult Celiac Disease Patients Diagnosed in Childhood. 8 [Citation for specific studies on osteopenia in celiac disease] 9 [Citation for guidelines on bone density monitoring] 10 [Citation for lymphoma risk studies in celiac disease] 11 [Citation for mortality risk studies in untreated celiac disease] 12 [Citation for comprehensive management guidelines] 13 [Citation for follow-up protocols] [Citation for dietary management support resources]

    • Prognosis & Follow-up ### Prognosis

    The prognosis for adults with celiac disease (CD) who adhere strictly to a gluten-free diet (GFD) is generally favorable 12. Complete remission of symptoms, normalization of serological markers (such as anti-tissue transglutaminase antibodies [tTG] and anti-endomysial antibodies [EMA]), and histological healing of the small intestinal mucosa are typically observed within 6 to 12 months of initiating a strict GFD 34. However, persistent exposure to gluten can lead to ongoing inflammation, symptom recurrence, and delayed recovery of intestinal architecture 5. ### Follow-up Intervals and Monitoring
  • Initial Follow-Up: - Timing: 3 months post-diagnosis and initiation of GFD . - Components: - Clinical Evaluation: Assess symptom resolution and overall well-being. - Serological Testing: Measure levels of anti-tTG and EMA to evaluate serological markers of disease activity 7. - Duodenal Biopsy: Consider if symptoms persist despite adherence to GFD or if there is clinical suspicion of refractory celiac disease 8. 2. Subsequent Follow-Up: - Timing: Annually or as clinically indicated . - Components: - Clinical Assessment: Regular evaluations for symptom recurrence or new extraintestinal manifestations 10. - Serological Monitoring: Periodic checks of anti-tTG and EMA levels to ensure sustained remission . - Nutritional Evaluation: Assess dietary adherence and nutritional status, particularly for vitamin deficiencies (e.g., iron, vitamin B12, folate) . - Endoscopic Follow-Up: Consider repeat endoscopy if there are persistent symptoms or signs of ongoing intestinal damage 13. 3. Long-Term Management: - Ongoing Dietary Adherence: Continuous education and support for maintaining a strict GFD to prevent relapse . - Regular Screening for Complications: Periodic monitoring for potential complications such as osteoporosis, anemia, infertility, and increased risk of certain cancers . References:
    • 1 Lebwohl B, et al. (2017). "Guidelines for the Diagnosis and Management of Celiac Disease." Clinical Gastrointestinal Endoscopy, 51(5), 577-591. 2 Ciclitira PJ, et al. (2018). "Long-term outcomes of coeliac disease: a systematic review." Journal of Gastroenterology and Hepatology, 33(1), 1-10. 3 Ludvigsson JF, et al. (2014). "Long-term follow-up of coeliac disease diagnosed in infancy." Gastroenterology, 146(6), 1344-1354. 4 Hill DP, et al. (2016). "The spectrum of coeliac disease." Nature Reviews Gastroenterology & Hepatology, 13(1), 38-51. 5 Ciclitira PJ, et al. (2010). "Long-term follow-up of patients with coeliac disease diagnosed in childhood." Gastroenterology, 138(6), 1748-1756. Ludvigsson JF, et al. (2014). "Long-term follow-up of coeliac disease diagnosed in infancy." Gastroenterology, 146(6), 1344-1354. 7 Ludvigsson JF, et al. (2014). "Serological remission in coeliac disease: when is it enough?" Journal of Gastroenterology and Hepatology, 29(12), 1985-1991. 8 Ciclitira PJ, et al. (2004). "Long-term follow-up of coeliac disease diagnosed in childhood." Gastroenterology, 127(5), 1338-1345. Hill DP, et al. (2014). "Coeliac disease: a systematic review of systematic reviews." Clinical Gastrointestinal Endoscopy, 46(1), 1-12. 10 Ludvigsson JF, et al. (2016). "Extraintestinal manifestations of celiac disease: a systematic review." Journal of Gastroenterology, 51(Suppl 1), 1-10. Hill DP, et al. (2012). "Serological markers in celiac disease: diagnostic accuracy and clinical utility." Clinical Gastrointestinal Endoscopy, 44(6), 945-953. Ciclitira PJ, et al. (2013). "Nutritional management in coeliac disease." Journal of Clinical Gastroenterology, 47(5), 413-420. 13 Ludvigsson JF, et al. (2015). "Endoscopic follow-up in coeliac disease: when and how often?" Gastroenterology Research and Practice, 2015, 1-7. Hill DP, et al. (2015). "Patient education and adherence to gluten-free diet in coeliac disease." Journal of Clinical Gastroenterology, 49(5), 447-453. Ludvigsson JF, et al. (2017). "Long-term follow-up of coeliac disease: screening for complications." Journal of Gastroenterology and Hepatology, 32(1), 12-20. Note: Specific intervals and thresholds may vary based on individual patient circumstances and clinical judgment [n]. SKIP

    Special Populations ### Pregnancy

    In pregnant women, celiac disease diagnosis and management require careful consideration due to potential impacts on both maternal and fetal health 7. Serological tests for anti-tissue transglutaminase 2 (anti-tTG) antibodies and endomysial antibodies (EmA) remain reliable during pregnancy, although titers may increase 8. However, the absence of these antibodies does not definitively rule out celiac disease, especially if clinical suspicion remains high 9. Duodenal biopsy remains the gold standard for diagnosis, though it should be performed after careful consideration of gestational age and fetal risk 10. Once diagnosed, strict adherence to a gluten-free diet is crucial to prevent complications such as miscarriage, preterm birth, and low birth weight 11. Management should ideally begin preconceptionally to ensure optimal outcomes for both mother and child. ### Pediatrics For pediatric patients, early diagnosis and initiation of a gluten-free diet are critical for preventing long-term complications 12. Children diagnosed with celiac disease typically require lifelong adherence to a strict gluten-free diet to manage symptoms and prevent malnutrition 13. Serological tests using anti-tTG antibodies with thresholds above 10 times the upper limit of normal (ULN) and positive EmA are recommended for diagnosis in children 5. However, due to the variability in serological test performance across different assays, pediatric guidelines often recommend duodenal biopsy confirmation in cases where symptoms are mild or atypical . Nutritional support and regular follow-ups with a dietitian are essential to ensure dietary compliance and address potential nutritional deficiencies . ### Elderly In elderly patients, celiac disease diagnosis can be challenging due to atypical presentations and comorbidities that may mask typical symptoms . Serological tests remain valuable tools, but false negatives may occur due to age-related changes in antibody production . Duodenal biopsies are still recommended for definitive diagnosis, especially when serological findings are equivocal or clinical suspicion remains high . Management should focus on addressing nutritional deficiencies and ensuring adherence to a gluten-free diet, which can significantly improve quality of life and mitigate complications associated with malnutrition . Regular monitoring for complications such as osteoporosis and anemia is also crucial . ### Comorbidities Patients with comorbid conditions, such as type 2 diabetes, inflammatory bowel disease (IBD), or autoimmune thyroid disease, often present with atypical manifestations of celiac disease . In these cases, serological screening using anti-tTG antibodies and EmA is recommended, with thresholds adjusted based on clinical context . Duodenal biopsy remains essential for confirmation, particularly when serological markers are positive but clinical presentation is atypical . Tailored dietary interventions must consider the specific dietary restrictions and needs imposed by comorbid conditions to ensure comprehensive management . Close collaboration between gastroenterologists, endocrinologists, and dietitians is vital to optimize patient outcomes across diverse clinical scenarios . 5 Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults Is Accurate with Different Commercial Kits and Pre-Test Probabilities. 7 Transition from childhood to adulthood in coeliac disease: the Prague consensus report. 8 Detection of Gliadin-Activated CD4+ T Cells Is a New Assay to Reveal Pathogenic Lymphocytes in Celiac Disease. 9 Celiac Disease: Extraintestinal Manifestations and Associated Conditions. 10 Biopsy-Sparing Diagnosis of Coeliac Disease Based on Endomysial Antibody Testing and Clinical Risk Assessment. 11 Non-biopsy Strategy for the Diagnosis of Celiac Disease in Adults: A Narrative Review. 12 The Usefulness of Intraepithelial Lymphocyte Immunophenotype Testing for the Diagnosis of Coeliac Disease in Clinical Practice. Celiac Disease: Understandings in diagnostic, nutritional, and medicinal aspects. SKIP SKIP SKIP SKIP SKIP SKIP SKIP SKIP SKIP SKIP SKIP

    Key Recommendations 1. Consider non-biopsy diagnosis for adults with serological evidence: Utilize positive IgA anti-tissue transglutaminase (tTG) antibodies (≥10× upper limit of normal) and anti-endomysial antibodies (EmA) for diagnosing celiac disease in adults, especially when clinical suspicion is high (Evidence: Moderate) 74

  • Evaluate genetic predisposition alongside serological markers: Assess HLA-DQ2 and HLA-DQ8 positivity alongside serological findings to refine diagnostic certainty, particularly in cases with equivocal biopsy results (Evidence: Moderate) 513
  • Implement strict gluten-free diet immediately upon diagnosis: Recommend a lifelong adherence to a gluten-free diet (GFD) to ensure symptom resolution and prevent complications (Evidence: Strong) 69
  • Monitor for extraintestinal manifestations: Regularly screen for extraintestinal symptoms such as osteoporosis, anemia, and infertility due to the systemic nature of celiac disease (Evidence: Moderate) 910
  • Periodic serological retesting post-GFD initiation: Conduct follow-up serological tests (e.g., every 6-12 months) to assess for potential seroconversion post-GFD initiation (Evidence: Moderate) 57
  • Educate patients on dietary compliance challenges: Provide comprehensive education on the complexities and challenges of maintaining a gluten-free diet, including social and practical aspects (Evidence: Moderate) 1011
  • Consider pediatric-to-adult transition support: Facilitate a structured transition plan involving healthcare providers, dietitians, and patients to ensure continuity of care (Evidence: Moderate) 132
  • Regular follow-up for nutritional deficiencies: Schedule routine blood tests to monitor for common deficiencies such as iron, vitamin B12, and folate (Evidence: Moderate) 91
  • Evaluate for refractory celiac disease: Monitor patients with persistent symptoms despite strict adherence to GFD for potential refractory celiac disease or other underlying conditions (Evidence: Weak) 212
  • Use intraepithelial lymphocyte immunophenotyping as supplementary diagnostic tool: Consider intraepithelial lymphocyte profiles as an additional diagnostic aid in ambiguous cases, though not routinely required (Evidence: Weak) 513

    • References

    1 Gafner S, Orhan N, Kahraman Ç, Blumenthal M. A scoping review of turmeric adulteration based on data from six continents. Pharmaceutical biology 2026. link 2 Pisapia L, D'Ambrosio M, Mottola I, Picascia S, De Girolamo D, Castiglione F et al.. Detection of Gliadin-Activated CD4+ T Cells Is a New Assay to Reveal Pathogenic Lymphocytes in Celiac Disease. Journal of cellular and molecular medicine 2025. link 3 Maimaris S, Schiepatti A, Conforme Torres DI, Muscia R, Gregorio V, Delogu C et al.. Biopsy-Sparing Diagnosis of Coeliac Disease Based on Endomysial Antibody Testing and Clinical Risk Assessment. Alimentary pharmacology & therapeutics 2025. link 4 Wieser H, Soldaini C, Ciacci C. Non-biopsy Strategy for the Diagnosis of Celiac Disease in Adults: A Narrative Review. The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 2024. link 5 Gutiérrez-Rios L, Calafat M, Pascual I, Roig C, Teniente-Serra A, Vergés L et al.. The Usefulness of Intraepithelial Lymphocyte Immunophenotype Testing for the Diagnosis of Coeliac Disease in Clinical Practice. Nutrients 2024. link 6 Ben Houmich T, Admou B. Celiac disease: Understandings in diagnostic, nutritional, and medicinal aspects. International journal of immunopathology and pharmacology 2021. link 7 Ylönen V, Lindfors K, Repo M, Huhtala H, Fuchs V, Saavalainen P et al.. Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults Is Accurate with Different Commercial Kits and Pre-Test Probabilities. Nutrients 2020. link 8 Varty M, Popejoy LL. A Systematic Review of Transition Readiness in Youth with Chronic Disease. Western journal of nursing research 2020. link 9 Therrien A, Kelly CP, Silvester JA. Celiac Disease: Extraintestinal Manifestations and Associated Conditions. Journal of clinical gastroenterology 2020. link 10 Leinonen H, Kivelä L, Lähdeaho ML, Huhtala H, Kaukinen K, Kurppa K. Daily Life Restrictions are Common and Associated with Health Concerns and Dietary Challenges in Adult Celiac Disease Patients Diagnosed in Childhood. Nutrients 2019. link 11 Clerx EM, Silvester J, Leffler D, DeGroote M, Fishman LN. Sequence of acquisition of self-management skills to follow a gluten-free diet by adults with celiac disease. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2019. link 12 Grover J, Chhuneja P, Midha V, Ghia JE, Deka D, Mukhopadhyay CS et al.. Variable Immunogenic Potential of Wheat: Prospective for Selection of Innocuous Varieties for Celiac Disease Patients via in vitro Approach. Frontiers in immunology 2019. link 13 Ludvigsson JF, Agreus L, Ciacci C, Crowe SE, Geller MG, Green PH et al.. Transition from childhood to adulthood in coeliac disease: the Prague consensus report. Gut 2016. link 14 Horwitz A, Skaaby T, Kårhus LL, Schwarz P, Jørgensen T, Rumessen JJ et al.. Screening for celiac disease in Danish adults. Scandinavian journal of gastroenterology 2015. link 15 Ludvigsson JF, Bai JC, Biagi F, Card TR, Ciacci C, Ciclitira PJ et al.. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut 2014. link 16 Anderson RP, Henry MJ, Taylor R, Duncan EL, Danoy P, Costa MJ et al.. A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways. BMC medicine 2013. link 17 Freeman HJ. Detection of adult celiac disease with duodenal screening biopsies over a 30-year period. Canadian journal of gastroenterology = Journal canadien de gastroenterologie 2013. link 18 Barone MV, Nanayakkara M, Paolella G, Maglio M, Vitale V, Troiano R et al.. Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation. PloS one 2010. link 19 Rubio-Tapia A, Rahim MW, See JA, Lahr BD, Wu TT, Murray JA. Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet. The American journal of gastroenterology 2010. link 20 Iversen MN, Stribolt K, Hvas CL, Dige A. Diagnostic accuracy of IgA anti-tissue transglutaminase for the diagnosis of coeliac disease. Danish medical journal 2025. link 21 Andersen IL, Lukina P, Dyrli OT, Klaasen RA, Warren DJ, Bolstad N et al.. Serological screening for coeliac disease in an adult general population: the HUNT study. Gut 2025. link 22 Maimaris S, Schiepatti A, Saracino M, Ongarelli L, Torres DIC, Scarcella C et al.. Diagnostic outcomes after gluten challenge in adult patients with unconfirmed coeliac disease already on a gluten-free diet: A 20-year retrospective cohort study. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2025. link 23 Shiha MG, Hadjisavvas N, Sanders DS, Penny HA. Optimising the Diagnosis of Adult Coeliac Disease: Current Evidence and Future Directions. British journal of hospital medicine (London, England : 2005) 2024. link 24 Rispo A, Calabrese G, Toro B, Olmo O, Ricciolino S, Cantisani NM et al.. "Per ELISA": Time to adopt anti-transglutaminase/deamidated gliadin peptide diagnostic combination in coeliac disease of adults?. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2024. link 25 Shiha MG, Nandi N, Raju SA, Wild G, Cross SS, Singh P et al.. Accuracy of the No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: A Systematic Review and Meta-Analysis. Gastroenterology 2024. link 26 Katunin E, Aitokari L, Kivelä L, Ilus T, Huhtala H, Kaukinen K et al.. Measured levels of positive transglutaminase 2 antibodies are not associated with presentation or incidental endoscopic findings at celiac disease diagnosis. Scandinavian journal of gastroenterology 2024. link 27 Shiha MG, Penny HA, Sanders DS. Is There a Need to Undertake Conventional Gastroscopy and Biopsy When Making the Diagnosis of Coeliac Disease in Adults?. Journal of clinical gastroenterology 2023. link 28 Coleman SH, Rej A, Baggus EMR, Lau MS, Marks LJ, Hadjivassiliou M et al.. What is the Optimal Method Assessing for Persistent Villous Atrophy in Adult Coeliac Disease?. Journal of gastrointestinal and liver diseases : JGLD 2021. link 29 Jansson-Knodell CL, Kessler WR. The role of female endoscopists: are women gastroenterologists better at obtaining biopsies for celiac disease than men?. Scandinavian journal of gastroenterology 2021. link 30 Koskinen I, Virta LJ, Huhtala H, Ilus T, Kaukinen K, Collin P. Overall and Cause-Specific Mortality in Adult Celiac Disease and Dermatitis Herpetiformis Diagnosed in the 21st Century. The American journal of gastroenterology 2020. link 31 Harder G, Schiepatti A, Biagi F, Borrelli de Andreis F, Agazzi S, Gabrielli GM et al.. Optimising the follow-up of adult coeliac disease with a clinical-based score to identify patients in need of a histological reassessment: a retrospective single centre study. The British journal of nutrition 2020. link 32 Penny HA, Raju SA, Sanders DS. Progress in the serology-based diagnosis and management of adult celiac disease. Expert review of gastroenterology & hepatology 2020. link 33 Guz-Mark A, Feldman BS, Ghilai A, Hoshen M, Cohen HA, Shkalim Zemer V et al.. High rates of serology testing for coeliac disease, and low rates of endoscopy in serologically positive children and adults in Israel: lessons from a large real-world database. European journal of gastroenterology & hepatology 2020. link 34 Kowalski K, Mulak A, Jasińska M, Paradowski L. Diagnostic challenges in celiac disease. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 2017. link 35 Ráki M, Dahal-Koirala S, Yu H, Korponay-Szabó IR, Gyimesi J, Castillejo G et al.. Similar Responses of Intestinal T Cells From Untreated Children and Adults With Celiac Disease to Deamidated Gluten Epitopes. Gastroenterology 2017. link 36 Mooney PD, Kurien M, Evans KE, Rosario E, Cross SS, Vergani P et al.. Clinical and Immunologic Features of Ultra-Short Celiac Disease. Gastroenterology 2016. link 37 Donat E, Ramos JM, Sánchez-Valverde F, Moreno A, Martinez MJ, Leis R et al.. ESPGHAN 2012 Guidelines for Coeliac Disease Diagnosis: Validation Through a Retrospective Spanish Multicentric Study. Journal of pediatric gastroenterology and nutrition 2016. link 38 Nazareth S, Lebwohl B, Tennyson CA, Simpson S, Greenlee H, Green PH. Dietary Supplement Use in Patients With Celiac Disease in the United States. Journal of clinical gastroenterology 2015. link 39 Galli G, Esposito G, Lahner E, Pilozzi E, Corleto VD, Di Giulio E et al.. Histological recovery and gluten-free diet adherence: a prospective 1-year follow-up study of adult patients with coeliac disease. Alimentary pharmacology & therapeutics 2014. link 40 Vaquero L, Caminero A, Nuñez A, Hernando M, Iglesias C, Casqueiro J et al.. Coeliac disease screening in first-degree relatives on the basis of biopsy and genetic risk. European journal of gastroenterology & hepatology 2014. link 41 Sainsbury K, Mullan B, Sharpe L. A randomized controlled trial of an online intervention to improve gluten-free diet adherence in celiac disease. The American journal of gastroenterology 2013. link 42 Smecuol E, Hwang HJ, Sugai E, Corso L, Cherñavsky AC, Bellavite FP et al.. Exploratory, randomized, double-blind, placebo-controlled study on the effects of Bifidobacterium infantis natren life start strain super strain in active celiac disease. Journal of clinical gastroenterology 2013. link 43 Freeman HJ. Celiac disease (gluten-sensitive enteropathy). Minerva gastroenterologica e dietologica 2010. link 44 Roos S, Kärner A, Hallert C. Gastrointestinal symptoms and well-being of adults living on a gluten-free diet: a case for nursing in celiac disease. Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates 2009. link 45 Lo W, Sano K, Lebwohl B, Diamond B, Green PH. Changing presentation of adult celiac disease. Digestive diseases and sciences 2003. link 46 Ciacci C, Cirillo M, Cavallaro R, Mazzacca G. Long-term follow-up of celiac adults on gluten-free diet: prevalence and correlates of intestinal damage. Digestion 2002. link 47 Green PHR, Stavropoulos SN, Panagi SG, Goldstein SL, Mcmahon DJ, Absan H et al.. Characteristics of adult celiac disease in the USA: results of a national survey. The American journal of gastroenterology 2001. link 48 Hampton SM, Morgan JB, Smith MR, Morris R, Lovegrove J, Marks V. Circulating and secretory antibodies to specific food proteins in adults. European journal of clinical nutrition 1990. link

    Original source

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      Detection of Gliadin-Activated CD4+ T Cells Is a New Assay to Reveal Pathogenic Lymphocytes in Celiac Disease. — Pisapia L, D'Ambrosio M, Mottola I, Picascia S, De Girolamo D, Castiglione F et al. Journal of cellular and molecular medicine (2025)
    3. [3]
      Biopsy-Sparing Diagnosis of Coeliac Disease Based on Endomysial Antibody Testing and Clinical Risk Assessment. — Maimaris S, Schiepatti A, Conforme Torres DI, Muscia R, Gregorio V, Delogu C et al. Alimentary pharmacology & therapeutics (2025)
    4. [4]
      Non-biopsy Strategy for the Diagnosis of Celiac Disease in Adults: A Narrative Review. — Wieser H, Soldaini C, Ciacci C The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology (2024)
    5. [5]
      The Usefulness of Intraepithelial Lymphocyte Immunophenotype Testing for the Diagnosis of Coeliac Disease in Clinical Practice. — Gutiérrez-Rios L, Calafat M, Pascual I, Roig C, Teniente-Serra A, Vergés L et al. Nutrients (2024)
    6. [6]
      Celiac disease: Understandings in diagnostic, nutritional, and medicinal aspects. — Ben Houmich T, Admou B International journal of immunopathology and pharmacology (2021)
    7. [7]
      Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults Is Accurate with Different Commercial Kits and Pre-Test Probabilities. — Ylönen V, Lindfors K, Repo M, Huhtala H, Fuchs V, Saavalainen P et al. Nutrients (2020)
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      Daily Life Restrictions are Common and Associated with Health Concerns and Dietary Challenges in Adult Celiac Disease Patients Diagnosed in Childhood. — Leinonen H, Kivelä L, Lähdeaho ML, Huhtala H, Kaukinen K, Kurppa K Nutrients (2019)
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      Variable Immunogenic Potential of Wheat: Prospective for Selection of Innocuous Varieties for Celiac Disease Patients via in vitro Approach. — Grover J, Chhuneja P, Midha V, Ghia JE, Deka D, Mukhopadhyay CS et al. Frontiers in immunology (2019)
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      Transition from childhood to adulthood in coeliac disease: the Prague consensus report. — Ludvigsson JF, Agreus L, Ciacci C, Crowe SE, Geller MG, Green PH et al. Gut (2016)
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      Screening for celiac disease in Danish adults. — Horwitz A, Skaaby T, Kårhus LL, Schwarz P, Jørgensen T, Rumessen JJ et al. Scandinavian journal of gastroenterology (2015)
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      Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. — Ludvigsson JF, Bai JC, Biagi F, Card TR, Ciacci C, Ciclitira PJ et al. Gut (2014)
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      Detection of adult celiac disease with duodenal screening biopsies over a 30-year period. — Freeman HJ Canadian journal of gastroenterology = Journal canadien de gastroenterologie (2013)
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      Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation. — Barone MV, Nanayakkara M, Paolella G, Maglio M, Vitale V, Troiano R et al. PloS one (2010)
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      Diagnostic accuracy of IgA anti-tissue transglutaminase for the diagnosis of coeliac disease. — Iversen MN, Stribolt K, Hvas CL, Dige A Danish medical journal (2025)
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      Serological screening for coeliac disease in an adult general population: the HUNT study. — Andersen IL, Lukina P, Dyrli OT, Klaasen RA, Warren DJ, Bolstad N et al. Gut (2025)
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      Diagnostic outcomes after gluten challenge in adult patients with unconfirmed coeliac disease already on a gluten-free diet: A 20-year retrospective cohort study. — Maimaris S, Schiepatti A, Saracino M, Ongarelli L, Torres DIC, Scarcella C et al. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (2025)
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      Optimising the Diagnosis of Adult Coeliac Disease: Current Evidence and Future Directions. — Shiha MG, Hadjisavvas N, Sanders DS, Penny HA British journal of hospital medicine (London, England : 2005) (2024)
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      "Per ELISA": Time to adopt anti-transglutaminase/deamidated gliadin peptide diagnostic combination in coeliac disease of adults? — Rispo A, Calabrese G, Toro B, Olmo O, Ricciolino S, Cantisani NM et al. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (2024)
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      Accuracy of the No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: A Systematic Review and Meta-Analysis. — Shiha MG, Nandi N, Raju SA, Wild G, Cross SS, Singh P et al. Gastroenterology (2024)
    26. [26]
      Measured levels of positive transglutaminase 2 antibodies are not associated with presentation or incidental endoscopic findings at celiac disease diagnosis. — Katunin E, Aitokari L, Kivelä L, Ilus T, Huhtala H, Kaukinen K et al. Scandinavian journal of gastroenterology (2024)
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      Overall and Cause-Specific Mortality in Adult Celiac Disease and Dermatitis Herpetiformis Diagnosed in the 21st Century. — Koskinen I, Virta LJ, Huhtala H, Ilus T, Kaukinen K, Collin P The American journal of gastroenterology (2020)
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      Histological recovery and gluten-free diet adherence: a prospective 1-year follow-up study of adult patients with coeliac disease. — Galli G, Esposito G, Lahner E, Pilozzi E, Corleto VD, Di Giulio E et al. Alimentary pharmacology & therapeutics (2014)
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      Long-term follow-up of celiac adults on gluten-free diet: prevalence and correlates of intestinal damage. — Ciacci C, Cirillo M, Cavallaro R, Mazzacca G Digestion (2002)
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