{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:56:12Z","timestamp":1781279772036,"version":"3.54.1"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Autoimmune gastritis (AIG) is an uncommon and often underestimated condition in children, characterized by chronic stomach inflammation leading to the destruction of oxyntic glands with subsequent atrophic and metaplastic changes. This condition is associated with hypo-\/achlorhydria, impairing iron and vitamin B12 absorption. The pathogenesis involves the activation of helper type 1 CD4+\/CD25-T-cells against parietal cells. Clinical manifestations in children are not specific and include abdominal pain, bloating, nausea, vomiting, and iron deficiency anemia (IDA). The disease is also linked to an increased risk of pernicious anemia, intestinal-type gastric cancer, and type I neuroendocrine tumors. AIG is often diagnosed through the presence of autoantibodies in the serum, such as parietal cell (APCA) and intrinsic factor (IF) antibodies. However, therapeutic recommendations for pediatric AIG are currently lacking. We aim to present two clinical cases of pediatric-onset AIG, highlighting the heterogeneous clinical manifestations and the challenges in diagnosis with the support of an updated literature review. A 9-year-old girl presented with refractory IDA, initial hypogammaglobulinemia, and a 12-year-old boy was initially diagnosed with eosinophilic esophagitis. Both cases underline the importance of considering AIG in children with chronic gastrointestinal symptoms and gastric atrophy. Diagnostic workup, including endoscopy and serological tests, is crucial for accurate identification. A better understanding of this condition is imperative for timely intervention and regular monitoring, given the potential long-term complications, including the risk of malignancy. These cases contribute to expanding the clinical spectrum of pediatric AIG and highlight the necessity for comprehensive evaluation and management in affected children.<\/jats:p>","DOI":"10.3390\/diseases13050133","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T08:02:57Z","timestamp":1745568177000},"page":"133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical Heterogeneity of Early-Onset Autoimmune Gastritis: From the Evidence to a Pediatric Tailored Algorithm"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0372-523X","authenticated-orcid":false,"given":"Ivan","family":"Taietti","sequence":"first","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4271-8649","authenticated-orcid":false,"given":"Martina","family":"Votto","sequence":"additional","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0029-9383","authenticated-orcid":false,"given":"Riccardo","family":"Castagnoli","sequence":"additional","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8669-8291","authenticated-orcid":false,"given":"Mirko","family":"Bertozzi","sequence":"additional","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Pediatric Surgery Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"De Filippo","sequence":"additional","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Di Sabatino","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy"},{"name":"First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ombretta","family":"Luinetti","sequence":"additional","affiliation":[{"name":"Unit of Anatomic Pathology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5146-1486","authenticated-orcid":false,"given":"Alessandro","family":"Raffaele","sequence":"additional","affiliation":[{"name":"Pediatric Surgery Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2976-7032","authenticated-orcid":false,"given":"Alessandro","family":"Vanoli","sequence":"additional","affiliation":[{"name":"Unit of Anatomic Pathology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"},{"name":"Department of Molecular Medicine, Unit of Anatomic Pathology, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Vincenzo","family":"Lenti","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy"},{"name":"First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Luigi","family":"Marseglia","sequence":"additional","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1773-6482","authenticated-orcid":false,"given":"Amelia","family":"Licari","sequence":"additional","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s10654-010-9482-0","article-title":"Incidence of chronic atrophic gastritis: Systematic review and meta-analysis of follow-up studies","volume":"25","author":"Adamu","year":"2010","journal-title":"Eur. J. Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Saglietti, C., Sciarra, A., Abdelrahman, K., Schneider, V., Karpate, A., Nydegger, A., and Sempoux, C. (2018). Autoimmune Gastritis in the Pediatric Age: An Underestimated Condition Report of Two Cases and Review. Front. Pediatr., 6.","DOI":"10.3389\/fped.2018.00123"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/nrgastro.2013.101","article-title":"Autoimmune atrophic gastritis\u2014Pathogenesis, pathology, and management","volume":"10","author":"Neumann","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e00510","DOI":"10.14309\/ctg.0000000000000510","article-title":"Mucosal Overexpression of Thymic Stromal Lymphopoietin and Proinflammatory Cytokines in Patients with Autoimmune Atrophic Gastritis","volume":"13","author":"Lenti","year":"2022","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103143","DOI":"10.1016\/j.autrev.2022.103143","article-title":"Seronegative autoimmune diseases: A challenging diagnosis","volume":"21","author":"Lenti","year":"2022","journal-title":"Autoimmun. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1056\/NEJM199711133372007","article-title":"Pernicious Anemia","volume":"337","author":"Toh","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1136\/bmj.2.5316.1347","article-title":"Autoimmune Phenomena in Pernicious Anaemia: Gastric Antibodies","volume":"2","author":"Taylor","year":"1962","journal-title":"Br. Med. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S0140-6736(59)92216-0","article-title":"Inhibition of intrinsic factor by pernicious an\u00e6mia sera","volume":"2","author":"Taylor","year":"1959","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00428-004-1157-3","article-title":"Immunological and morphogenic basis of gastric mucosa atrophy and metaplasia","volume":"446","author":"Faller","year":"2005","journal-title":"Virchows Arch."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jaut.2008.04.007","article-title":"Extrathymic mechanisms of T cell tolerance: Lessons from autoimmune gastritis","volume":"31","author":"Hogan","year":"2008","journal-title":"J. Autoimmun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/(SICI)1097-0029(20000315)48:6<327::AID-JEMT3>3.0.CO;2-L","article-title":"Histomorphological characteristics of gastric mucosa in patients with Zollinger-Ellison syndrome or autoimmune gastric atrophy: Role of gastrin and atrophying gastritis","volume":"48","author":"Lehy","year":"2000","journal-title":"Microsc. Res. Tech."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15780","DOI":"10.3748\/wjg.v20.i42.15780","article-title":"Autoimmune gastritis presenting as iron deficiency anemia in childhood","volume":"20","author":"Oliveira","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1097\/MPG.0000000000002547","article-title":"Autoimmune Gastritis in Pediatrics: A Review of 3 Cases","volume":"70","author":"Mitsinikos","year":"2020","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4944","DOI":"10.1210\/jc.2003-031597","article-title":"Early manifestations of gastric autoimmunity in patients with juvenile autoimmune thyroid diseases","volume":"89","author":"Segni","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1016\/j.dld.2019.09.016","article-title":"Chronic atrophic gastritis: Natural history, diagnosis and therapeutic management. A position paper by the Italian Society of Hospital Gastroenterologists and Digestive Endoscopists [AIGO], the Italian Society of Digestive Endoscopy [SIED], the Italian Society of Gastroenterology [SIGE], and the Italian Society of Internal Medicine [SIMI]","volume":"51","author":"Lahner","year":"2019","journal-title":"Dig. Liver Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1097\/MPH.0000000000000069","article-title":"Refractory iron-deficiency anemia and autoimmune atrophic gastritis in pediatric age group: Analysis of 8 clinical cases","volume":"36","author":"Miguel","year":"2014","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_17","first-page":"e99","article-title":"Insights into Pediatric Autoimmune Gastritis: Is There a Role for Helicobacter pylori Infection?","volume":"68","author":"Silva","year":"2019","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.3109\/00365521.2014.953574","article-title":"Gastric carcinoid tumor in a 14-year-old girl","volume":"49","author":"Kirsaclioglu","year":"2014","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1016\/S0022-3468(97)90330-4","article-title":"Pernicious anemia and adenocarcinoma of the stomach in an adolescent: Clinical presentation and histopathology","volume":"32","author":"Katz","year":"1997","journal-title":"J. Pediatr. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1007\/s00431-007-0664-z","article-title":"Autoimmune gastritis and parietal cell reactivity in two children with abnormal intestinal permeability","volume":"167","author":"Greenwood","year":"2008","journal-title":"Eur. J. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1097\/MPG.0b013e3181fedb2a","article-title":"Do children and adolescents with type 1 diabetes mellitus have a higher frequency of parietal cell antibodies than healthy controls?","volume":"52","author":"Huber","year":"2011","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e148","DOI":"10.1097\/MPG.0b013e318242da36","article-title":"15-year-old Girl with Metaplastic Atrophic Gastritis and Enterochromaffin-like Cell Hyperplasia","volume":"55","author":"Russell","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1097\/PAS.0000000000000378","article-title":"Pediatric non-Helicobacter pylori atrophic gastritis: A case series","volume":"39","author":"Pogoriler","year":"2015","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_24","first-page":"70","article-title":"Gastrointestinal Neuroendocrine Tumors in Two Children","volume":"53","author":"Koca","year":"2016","journal-title":"Indian. Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1111\/pedi.12482","article-title":"Revisiting autoimmune gastritis in children and adolescents with type 1 diabetes","volume":"18","author":"Michaud","year":"2017","journal-title":"Pediatr. Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s40618-019-01081-y","article-title":"Anti-gastric parietal cell antibodies for autoimmune gastritis screening in juvenile autoimmune thyroid disease","volume":"43","author":"Calcaterra","year":"2020","journal-title":"J. Endocrinol. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.humpath.2021.07.002","article-title":"Pediatric autoimmune gastritis: Clinical correlates and histologic features","volume":"116","author":"Kulak","year":"2021","journal-title":"Hum. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/jpn3.12318","article-title":"Clinical characteristics and outcomes of pediatric patients with autoimmune gastritis","volume":"79","author":"Granot","year":"2024","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e12716","DOI":"10.1111\/hel.12716","article-title":"Autoimmune atrophic gastritis: The role of Helicobacter pylori infection in children","volume":"25","author":"Demir","year":"2020","journal-title":"Helicobacter"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/j.dld.2020.04.015","article-title":"Seronegative autoimmune atrophic gastritis is more common in elderly patients","volume":"52","author":"Conti","year":"2020","journal-title":"Dig. Liver Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1097\/PAS.0b013e3180cab60c","article-title":"Gastrointestinal Tract Pathology in Patients with Common Variable Immunodeficiency (CVID): A Clinicopathologic Study and Review","volume":"31","author":"Daniels","year":"2007","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_32","first-page":"407","article-title":"RE.GA.IN.: The Real-world Gastritis Initiative-updating the updates","volume":"73","author":"Rugge","year":"2024","journal-title":"Gut"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s00125-024-06086-8","article-title":"Autoimmune comorbidity in type 1 diabetes and its association with metabolic control and mortality risk in young people: A population-based study","volume":"67","author":"Samuelsson","year":"2024","journal-title":"Diabetologia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1007\/s12328-020-01333-y","article-title":"A case of eosinophilic esophagitis with autoimmune polyendocrine syndrome type 2, including autoimmune gastritis","volume":"14","author":"Ayaki","year":"2021","journal-title":"Clin. J. Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1365-2559.2006.02553.x","article-title":"Pathology of non-infective gastritis","volume":"50","author":"Srivastava","year":"2007","journal-title":"Histopathology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"837","DOI":"10.14309\/ajg.0000000000002619","article-title":"Long-Term Natural History of Autoimmune Gastritis: Results from a Prospective Monocentric Series","volume":"119","author":"Miceli","year":"2024","journal-title":"Am. J. Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1111\/apt.12239","article-title":"Letter: Gastric cancer and pernicious anaemia--often Helicobacter pylori in disguise","volume":"37","author":"Rugge","year":"2013","journal-title":"Aliment. Pharmacol. Ther."}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/13\/5\/133\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:21:29Z","timestamp":1760030489000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/13\/5\/133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,25]]},"references-count":37,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["diseases13050133"],"URL":"https:\/\/doi.org\/10.3390\/diseases13050133","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,25]]}}}