Napiórkowska-Baran Katarzyna, Treichel Paweł, Wawrzeńczyk Adam, Alska Ewa, Zacniewski Robert, Szota Maciej, Przybyszewska Justyna, Zoń Amanda, Bartuzi Zbigniew
Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Torun, 85-067 Bydgoszcz, Poland.
Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Torun, 85-067 Bydgoszcz, Poland.
Life (Basel). 2025 Jul 13;15(7):1098. doi: 10.3390/life15071098.
Non-celiac villous atrophy (NCVA) is a multifaceted and under-recognized clinical entity with an etiology beyond celiac disease. This review critically examines the diverse pathophysiological mechanisms underlying NCVA, including autoimmune enteropathies, immune deficiency-related disorders, infectious processes, drug-induced trauma, and metabolic or environmental influences. A comprehensive synthesis of peer-reviewed literature, clinical studies, and case reports was conducted, adopting a multidisciplinary perspective that integrates immunologic, infectious, metabolic, and pharmacologic insights. The literature search was performed in three phases: identification of relevant studies, critical assessment of selected publications, and synthesis of key findings. Searches were carried out in PubMed, Scopus, Web of Science, and Google Scholar databases. The final search, completed in June 2025, included international, English-language articles, electronic books, and online reports. Studies were included if they addressed NCVA in the context of pathophysiology, clinical manifestations, or management strategies, with priority given to publications from the last ten years (2015-2025). The search strategy used the primary term "" combined with supplementary keywords such as , , , , , , , , , and . Histopathological evaluations reveal that NCVA often manifests with varying degrees of villous blunting, crypt hypertrophy, and intraepithelial lymphocytosis, albeit without the gliadin-specific immune response seen in celiac disease. Various immune pathways are involved, such as autoimmune deregulation and chronic inflammatory responses, while drug-induced and environmental factors further complicate its clinical picture. These findings highlight significant diagnostic challenges and underscore the need to adapt diagnostic algorithms that combine clinical history, serologic evaluations, and histopathologic analysis. In conclusion, an in-depth understanding of the heterogeneous etiology of NCVA is critical to improving diagnostic accuracy and optimizing therapeutic strategies. Future research should prioritize the identification of specific biomarkers and the development of targeted interventions to address the unique mechanisms underlying NCVA, thereby improving patient management and outcomes.
非乳糜泻性绒毛萎缩（NCVA）是一种多方面且未得到充分认识的临床实体，其病因超出了乳糜泻的范畴。本综述批判性地审视了NCVA潜在的多种病理生理机制，包括自身免疫性肠病、免疫缺陷相关疾病、感染过程、药物性损伤以及代谢或环境影响。采用多学科视角，综合免疫、感染、代谢和药理学见解，对同行评议文献、临床研究和病例报告进行了全面综合。文献检索分三个阶段进行：确定相关研究、对选定出版物进行批判性评估以及综合关键发现。检索在PubMed、Scopus、Web of Science和谷歌学术数据库中进行。最终检索于2025年6月完成，包括国际英文文章、电子书和在线报告。如果研究涉及NCVA的病理生理学、临床表现或管理策略，则纳入研究范围，优先考虑过去十年（2015 - 2025年）的出版物。检索策略使用主要术语“ ”并结合诸如 、 、 、 、 、 、 、 、 和 等补充关键词。组织病理学评估显示，NCVA通常表现为不同程度的绒毛变钝、隐窝肥大和上皮内淋巴细胞增多，尽管没有乳糜泻中所见的麦醇溶蛋白特异性免疫反应。涉及多种免疫途径，如自身免疫失调和慢性炎症反应，而药物性和环境因素进一步使临床情况复杂化。这些发现凸显了重大的诊断挑战，并强调需要调整结合临床病史、血清学评估和组织病理学分析的诊断算法。总之，深入了解NCVA的异质性病因对于提高诊断准确性和优化治疗策略至关重要。未来研究应优先确定特定生物标志物并开发针对性干预措施，以应对NCVA潜在的独特机制，从而改善患者管理和治疗结果。
