Non-Celiac Villous Atrophy—A Problem Still Underestimated

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, infecti...

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Main Authors: Katarzyna Napiórkowska-Baran, Paweł Treichel, Adam Wawrzeńczyk, Ewa Alska, Robert Zacniewski, Maciej Szota, Justyna Przybyszewska, Amanda Zoń, Zbigniew Bartuzi
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Language:English
Published: MDPI AG 2025-07-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/15/7/1098
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author Katarzyna Napiórkowska-Baran
Paweł Treichel
Adam Wawrzeńczyk
Ewa Alska
Robert Zacniewski
Maciej Szota
Justyna Przybyszewska
Amanda Zoń
Zbigniew Bartuzi
author_facet Katarzyna Napiórkowska-Baran
Paweł Treichel
Adam Wawrzeńczyk
Ewa Alska
Robert Zacniewski
Maciej Szota
Justyna Przybyszewska
Amanda Zoń
Zbigniew Bartuzi
author_sort Katarzyna Napiórkowska-Baran
collection DOAJ
description 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 “<i>non-celiac villous atrophy</i>” combined with supplementary keywords such as <i>autoimmune enteropathy</i>, <i>common variable immunodeficiency</i>, <i>tropical sprue</i>, <i>drug-related enteropathy</i>, <i>pathophysiology</i>, <i>immunological mechanisms</i>, <i>chronic inflammation</i>, <i>genetic factors</i>, <i>environmental influences</i>, and <i>clinical management</i>. 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.
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spelling doaj-art-8190553aacde4564b6fb5f9d407d25012025-08-20T03:58:26ZengMDPI AGLife2075-17292025-07-01157109810.3390/life15071098Non-Celiac Villous Atrophy—A Problem Still UnderestimatedKatarzyna Napiórkowska-Baran0Paweł Treichel1Adam Wawrzeńczyk2Ewa Alska3Robert Zacniewski4Maciej Szota5Justyna Przybyszewska6Amanda Zoń7Zbigniew Bartuzi8Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Torun, 85-067 Bydgoszcz, PolandStudent Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Torun, 85-067 Bydgoszcz, PolandDepartment of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Torun, 85-067 Bydgoszcz, PolandDepartment of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Torun, 85-067 Bydgoszcz, PolandDepartment of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Torun, 85-067 Bydgoszcz, PolandDepartment of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Torun, 85-067 Bydgoszcz, PolandDepartment of Nutrition and Dietetics, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Torun, 85-067 Bydgoszcz, PolandUniversity Hospital No. 2 in Bydgoszcz, 85-168 Bydgoszcz, PolandDepartment of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Torun, 85-067 Bydgoszcz, PolandNon-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 “<i>non-celiac villous atrophy</i>” combined with supplementary keywords such as <i>autoimmune enteropathy</i>, <i>common variable immunodeficiency</i>, <i>tropical sprue</i>, <i>drug-related enteropathy</i>, <i>pathophysiology</i>, <i>immunological mechanisms</i>, <i>chronic inflammation</i>, <i>genetic factors</i>, <i>environmental influences</i>, and <i>clinical management</i>. 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.https://www.mdpi.com/2075-1729/15/7/1098non-celiac villous atrophyvillous atrophyenteropathyimmune defects
spellingShingle Katarzyna Napiórkowska-Baran
Paweł Treichel
Adam Wawrzeńczyk
Ewa Alska
Robert Zacniewski
Maciej Szota
Justyna Przybyszewska
Amanda Zoń
Zbigniew Bartuzi
Non-Celiac Villous Atrophy—A Problem Still Underestimated
Life
non-celiac villous atrophy
villous atrophy
enteropathy
immune defects
title Non-Celiac Villous Atrophy—A Problem Still Underestimated
title_full Non-Celiac Villous Atrophy—A Problem Still Underestimated
title_fullStr Non-Celiac Villous Atrophy—A Problem Still Underestimated
title_full_unstemmed Non-Celiac Villous Atrophy—A Problem Still Underestimated
title_short Non-Celiac Villous Atrophy—A Problem Still Underestimated
title_sort non celiac villous atrophy a problem still underestimated
topic non-celiac villous atrophy
villous atrophy
enteropathy
immune defects
url https://www.mdpi.com/2075-1729/15/7/1098
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