Diagnostic Gaps in the Endoscopic Recognition of Autoimmune Atrophic Gastritis
Keywords:
Autoimmune atrophic gastritis, autoimmune gastritis, endoscopy, diagnostic delay, gastric atrophy, biopsy protocol, image-enhanced endoscopy, artificial intelligence, gastric neuroendocrine tumor, gastric precancerous conditionsAbstract
Introduction: Autoimmune atrophic gastritis (AAG) is a chronic immune-mediated gastric disorder characterized by corpus-predominant oxyntic atrophy, parietal cell loss, hypochlorhydria, and impaired absorption of iron and vitamin B12. Although upper gastrointestinal endoscopy is routinely performed in clinical practice, AAG is frequently recognized late, often after hematological, neurological, or neoplastic complications have already developed. This structured narrative review examines why endoscopic recognition of AAG continues to lag behind histological diagnosis. Methods: Evidence from clinical studies, systematic reviews, meta-analyses, and international guidelines was synthesized to identify disease-related, endoscopist-related, procedure-related, and guideline-related contributors to missed diagnosis. Results: The review shows that early AAG may produce subtle or nonspecific mucosal changes, while advanced disease may overlap endoscopically with *Helicobacter pylori*-associated atrophic gastritis. Limited endoscopist awareness, inadequate inspection, non-systematic biopsy strategies, interobserver variability, and inconsistent guideline recommendations further contribute to delayed recognition. Image-enhanced endoscopy and artificial intelligence-assisted systems offer promising opportunities to improve mucosal assessment and reduce diagnostic variability, but they should be regarded as adjuncts to careful inspection, clinical suspicion, and systematic biopsy protocols. Conclusions: The findings suggest that AAG should be understood not only as an autoimmune gastric disease but also as a quality-of-endoscopy challenge. Earlier recognition requires targeted endoscopic training, standardized reporting, risk-based mapping biopsies, clearer guideline integration, and validation of emerging technologies in real-world clinical settings.
References
Angerilli, V., Vanoli, A., Celin, G., Ceccon, C., Gasparello, J., Sabbadin, M., De Lisi, G., Paudice, M., Lenti, M. V., Rovedatti, L., Di Sabatino, A., Bazzocchi, F., Lonardi, S., Savarino, E., Luchini, C., Parente, P., Grillo, F., Mastracci, L., & Fassan, M. (2024). Gastric carcinoma in autoimmune gastritis: A histopathologic and molecular study. *Modern Pathology, 37*(6), Article 100491. https://doi.org/10.1016/j.modpat.2024.100491
Carabotti, M., Lahner, E., Esposito, G., Sacchi, M. C., Severi, C., & Annibale, B. (2017). Upper gastrointestinal symptoms in autoimmune gastritis: A cross-sectional study. *Medicine, 96*(1), Article e5784. https://doi.org/10.1097/MD.0000000000005784
Castellana, C., Eusebi, L. H., Dajti, E., Iascone, V., Vestito, A., Fusaroli, P., Fuccio, L., D’Errico, A., & Zagari, R. M. (2024). Autoimmune atrophic gastritis: A clinical review. *Cancers, 16*(7), Article 1310. https://doi.org/10.3390/cancers16071310
Cellini, M., Santaguida, M. G., Virili, C., Capriello, S., Brusca, N., Gargano, L., & Centanni, M. (2017). Hashimoto’s thyroiditis and autoimmune gastritis. *Frontiers in Endocrinology, 8*, Article 92. https://doi.org/10.3389/fendo.2017.00092
Chen, S., Xu, L., Yan, L., Li, T., Zheng, Q., Chen, Y., Qian, J., Jiang, X., Hu, Y., Shen, H., Shen, J., Zhu, Z., Hu, G., Rao, B., Chen, Y., & Chen, Y. (2024). A novel endoscopic artificial intelligence system to assist in the diagnosis of autoimmune gastritis: A multicenter study. *Endoscopy, 57*(4), 299–309. https://doi.org/10.1055/a-2451-3071
Chen, Y., Ji, X., Zhao, W., Lin, J., Xie, S., Xu, J., & Mao, J. (2025). A real-world study on the characteristics of autoimmune gastritis: A single-center retrospective cohort in China. *Clinics and Research in Hepatology and Gastroenterology, 49*(3), Article 102556. https://doi.org/10.1016/j.clinre.2025.102556
Chen, Z., Wei, D., Guan, W., Zhang, Y., Ren, Y., & Tao, Y. (2023). Incidence and risk factors for gastric cancer in patients with autoimmune gastritis: A systematic review and meta-analysis. *Frontiers in Oncology, 13*, Article 1090349. https://doi.org/10.3389/fonc.2023.1090349
Conti, L., Lenti, M. V., Di Sabatino, A., Miceli, E., Galli, G., Cazzato, M., Rondonotti, E., Neri, M., Vanoli, A., & Lahner, E. (2020). Seronegative autoimmune atrophic gastritis is less severe than seropositive autoimmune atrophic gastritis. *Digestive and Liver Disease, 52*(5), 510–515. https://doi.org/10.1016/j.dld.2020.01.007
De Block, C. E. M., De Leeuw, I. H., & Van Gaal, L. F. (2008). Autoimmune gastritis in type 1 diabetes: A clinically oriented review. *Journal of Clinical Endocrinology & Metabolism, 93*(2), 363–371. https://doi.org/10.1210/jc.2007-2134
Dinis-Ribeiro, M., Libanio, D., Buxbaum, J., Dariusz, N., Esposito, G., Foley, K., Hassan, C., Ihara, Z., Repici, A., Sipponen, P., & Pimentel-Nunes, P. (2025). Management of epithelial precancerous conditions and lesions in the stomach (MAPS III): European Society of Gastrointestinal Endoscopy guideline update 2025. *Endoscopy, 57*(3), 284–321. https://doi.org/10.1055/a-2530-6352
Dottori, L., Bricca, L., Cingolani, S., Agostini, D., Schiavone, F. P., Palumbo, C., Lahner, E., & Annibale, B. (2024). Antral atrophy regression after *Helicobacter pylori* eradication and its impact on endoscopic diagnosis of autoimmune gastritis. *Digestive and Liver Disease, 56*(5), 801–808. https://doi.org/10.1016/j.dld.2023.11.029
Eshmuratov, A., Nah, J. C., Kim, N., Lee, H. S., Lee, H. E., Chang, H., Kim, J. M., Kim, J. S., Jung, H. C., & Song, I. S. (2019). The correlation of endoscopic and histological diagnoses of gastric atrophy. *Digestive Diseases and Sciences, 55*(5), 1364–1375. https://doi.org/10.1007/s10620-009-0906-7
Hershko, C., & Camaschella, C. (2014). How I treat unexplained refractory iron deficiency anemia. *Blood, 123*(3), 326–333. https://doi.org/10.1182/blood-2013-10-512624
Kalkan, C., & Soykan, I. (2016). Polyautoimmunity in autoimmune gastritis. *European Journal of Internal Medicine, 31*, 79–83. https://doi.org/10.1016/j.ejim.2016.01.004
Kamada, T., Maruyama, Y., Monobe, Y., & Haruma, K. (2023). Endoscopic features and clinical importance of autoimmune gastritis. *Digestive Endoscopy, 35*(3), 273–286. https://doi.org/10.1111/den.14459
Kawamura, M., Sekine, H., Ito, M., Kotachi, T., Yoshida, T., Arihiro, K., & Haruma, K. (2015). Reliability of Kimura–Takemoto classification system for endoscopic assessment of gastric mucosal atrophy: A prospective multicenter study. *Digestive Endoscopy, 27*(2), 200–207. https://doi.org/10.1111/den.12331
Kishino, T., & Nonaka, K. (2022). Endoscopic diagnosis of autoimmune gastritis: Current status, challenges, and perspectives. *Digestive Endoscopy, 34*(7), 1308–1317. https://doi.org/10.1111/den.14263
Lahner, E., Esposito, G., Zullo, A., Hassan, C., Carabotti, M., Annibale, B., & Dinis-Ribeiro, M. (2022). Differences in sex and age in autoimmune atrophic gastritis: A cross-sectional study. *Digestive and Liver Disease, 54*(3), 330–336. https://doi.org/10.1016/j.dld.2021.07.026
Lenti, M. V., Di Sabatino, A., Rugge, M., Annibale, B., & Corazza, G. R. (2020). Autoimmune gastritis. *Nature Reviews Disease Primers, 6*(1), Article 56. https://doi.org/10.1038/s41572-020-0187-8
Lenti, M. V., Miceli, E., Cococcia, S., Klersy, C., Staiani, M., Guglielmi, F., Cantu, P., Ciccocioppo, R., Ardizzone, S., Massari, A., Vecchi, M., Ferretti, F., & Di Sabatino, A. (2019). Determinants of diagnostic delay in autoimmune atrophic gastritis. *Alimentary Pharmacology & Therapeutics, 50*(2), 167–175. https://doi.org/10.1111/apt.15290
Li, H., Liang, Y., Li, J., & Xu, C. (2025). Global prevalence of autoimmune gastritis: A systematic review and meta-analysis. *Journal of Gastroenterology and Hepatology*. Advance online publication. https://doi.org/10.1111/jgh.16870
Nishizawa, T., Yoshida, S., Toyoshima, A., Ushiku, T., Akahane, T., Hamamoto, Y., Saito, Y., Fujishiro, M., & Toyoshima, O. (2021). Endoscopic detection of autoimmune gastritis after successful *Helicobacter pylori* eradication. *Digestive Endoscopy, 33*(7), 1054–1061. https://doi.org/10.1111/den.13898
Rugge, M., Genta, R. M., Di Mario, F., El-Omar, E. M., El-Serag, H. B., Fassan, M., Hunt, R. H., Kuipers, E. J., Malfertheiner, P., Sugano, K., & Graham, D. Y. (2022). Gastric cancer as preventable disease. *Clinical Gastroenterology and Hepatology, 21*(12), 3257–3274. https://doi.org/10.1016/j.cgh.2022.10.012
Rokkas, T., & Ekmektzoglou, K. (2023). Current role of narrow band imaging in diagnosing gastric intestinal metaplasia: A systematic review and meta-analysis of its diagnostic accuracy. *Annals of Gastroenterology, 36*(2), 149–156. https://doi.org/10.20524/aog.2023.0784
Rustgi, S. D., Bijlani, P., & Shah, S. C. (2021). Autoimmune gastritis, with or without pernicious anemia: Epidemiology, risk factors, and clinical management. *Therapeutic Advances in Gastroenterology, 14*, 1–14. https://doi.org/10.1177/17562848211038192
Shah, S. C., Piazuelo, M. B., Kuipers, E. J., & Li, D. (2021). AGA clinical practice update on the diagnosis and management of atrophic gastritis: Expert review. *Gastroenterology, 161*(4), 1325–1332.e7. https://doi.org/10.1053/j.gastro.2021.06.078
Shi, Y., Wei, N., Wang, K., Tao, T., Yu, F., & Lv, B. (2023). Diagnostic value of artificial intelligence-assisted endoscopy for chronic atrophic gastritis: A systematic review and meta-analysis. *Frontiers in Medicine, 10*, Article 1134980. https://doi.org/10.3389/fmed.2023.1134980
Soykan, I., Er, R. E., Baykara, Y., & Kalkan, C. (2025). Unraveling the mysteries of autoimmune gastritis: Clinical presentation, endoscopic and histological findings, and associated autoimmune conditions. *Turkish Journal of Gastroenterology, 36*(2), 135–144. https://doi.org/10.5152/tjg.2025.24492
Tenca, A., Massironi, S., Pugliese, D., Consonni, D., Cavalcoli, F., Cantu, P., Penagini, R., Vecchi, M., & Invernizzi, P. (2016). Proton pump inhibitors and gastro-esophageal reflux in autoimmune gastritis. *World Journal of Gastroenterology, 22*(22), 5213–5221. https://doi.org/10.3748/wjg.v22.i22.5213
Yagi, K., Nakamura, A., & Sekine, A. (2012). Characteristic endoscopic and magnified endoscopic findings in the normal stomach without *Helicobacter pylori* infection. *Journal of Gastroenterology and Hepatology, 17*(1), 39–45. https://doi.org/10.1046/j.1440-1746.2002.02665.x
Zhao, Z., Yin, Z., Wang, S., Pang, B., Chen, Q., Chen, J., & Wang, P. (2020). Meta-analysis: The diagnostic yield and safety of capsule endoscopy for *Helicobacter pylori* infection. *Journal of Gastroenterology and Hepatology, 35*(4), 537–545. https://doi.org/10.1111/jgh.14869
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