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©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
Diagnostic clues in patients with clinical malabsorption and pathological small intestinal villous atrophy: Immune-mediated type and beyond
Mu-Han Li, Qi-Pu Wang, Cheng-Zhu Ou, Tian-Ming Xu, Yang Chen, Hao Tang, Yan Zhang, Yan-Jun Lai, Xu-Zhen Qin, Ji Li, Wei-Xun Zhou, Jing-Nan Li
Mu-Han Li, Qi-Pu Wang, Cheng-Zhu Ou, Tian-Ming Xu, Yang Chen, Hao Tang, Ji Li, Jing-Nan Li, Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100730, China
Yan Zhang, Department of Haematology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100730, China
Yan-Jun Lai, Department of Gastroenterology, Zhangzhou Municipal Hospital of Fujian Province, Zhangzhou 363000, Fujian Province, China
Xu-Zhen Qin, Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100730, China
Wei-Xun Zhou, Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100730, China
Co-first authors: Mu-Han Li and Qi-Pu Wang.
Co-corresponding authors: Ji Li and Wei-Xun Zhou.
Author contributions: Li MH, Wang QP, and Ou CZ reviewed the literature and drafted the manuscript. Xu TM, Chen Y, Tang H, and Lai YJ verified the accuracy of the gastroenterological descriptions in this review. Zhou WX ensured the accuracy of the pathological information. Zhang Y and Qin XZ supplemented the draft and verified the accuracy of the descriptions related to other specialties, including hematology and laboratory medicine. Li JN, Zhou WX, and Li J contributed to outlining the manuscript, providing financial support, and refining the final version. All the authors read and approved the final manuscript. Li MH and Wang QP collaboratively conducted a comprehensive literature review and systematically organized the figures and tables. Li MH and Ou CZ jointly drafted the initial manuscript, integrating critical insights from other authors and revising the review accordingly. Wang QP critically reviewed the manuscript and performed language editing to enhance clarity and coherence. These authors have made crucial and indispensable contributions toward the completion of the review and thus qualify as co-first authors of the paper. As co-corresponding authors, Li J and Zhou WX defined the framework of this review and meticulously reviewed the manuscript to ensure the accuracy of its clinical content. Li J and Li JN provided essential financial support, contributed to manuscript revisions, and oversaw the finalization of the manuscript.
Supported by National High-Level Hospital Clinical Research Funding, No. 2022-PUMCH-B-022, and No. 2022-PUMCH-D-002; CAMS Innovation Fund for Medical Sciences, No. CIFMS 2021-1-I2M-003; and Undergraduate Innovation Program, No. 2024dcxm025.
Conflict-of-interest statement: Authors had nothing to disclose.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Ji Li, MD, Professor, Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, No. 1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing 100730, China.
liji0235@pumch.cn
Received: July 21, 2025
Revised: August 18, 2025
Accepted: December 2, 2025
Published online: January 14, 2026
Processing time: 175 Days and 20.8 Hours
Small intestinal villi are essential for nutrient absorption, and their impairment can lead to malabsorption. Small intestinal villous atrophy (VA) encompasses a heterogeneous group of disorders, including immune-mediated conditions (e.g., celiac disease, autoimmune enteropathy, inborn errors of immunity), lymphoproliferative disorders (e.g., enteropathy-associated T-cell lymphoma), infectious causes (e.g., tropical sprue, Whipple’s disease), iatrogenic factors (e.g., Olmesartan-associated enteropathy, graft-vs-host disease), as well as inflammatory and idiopathic types. These disorders are often rare and challenging to distinguish due to overlapping clinical, serological, endoscopic, and histopathological features. Through a systematic literature search using keywords such as small intestinal VA, malabsorption, and specific enteropathies, this review provides a comprehensive overview of diagnostic clues for VA and malabsorption. We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies. Current studies still have many limitations and lack broader and deeper investigations into these diseases. Therefore, future research should focus on the development of novel diagnostic tools, predictive models, therapeutic targets, and mechanistic molecular studies to refine both diagnosis and management strategies.
Core Tip: Small intestinal villous atrophy is a key pathological feature of various rare and heterogeneous disorders associated with malabsorption. Owing to overlapping clinical, serological, and histological features among immune-mediated, lymphoproliferative, infectious, iatrogenic, inflammatory, and idiopathic causes, timely and accurate diagnosis remains challenging. This review highlights distinctive diagnostic clues and proposes a structured approach to help differentiate these entities, with the aim of improving diagnostic precision and guiding appropriate therapeutic strategies.
