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ORIGINAL RESEARCH ARTICLE

Systemic and gastrointestinal amyloid A amyloidosis in rheumatoid arthritis: A post-mortem clinicopathologic study of 161 cases

Miklós Bély1* ,  Ágnes Apáthy2
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1 Department of Pathology, Hospital of the Order of the Brothers of Saint John of God, Budapest, Hungary
2 Department of Rheumatology, St. Margaret Clinic, Budapest, Hungary
Global Translational Medicine 2025, 4(1), 104–125; https://doi.org/10.36922/gtm.5325
Submitted: 21 October 2024 | Revised: 12 January 2025 | Accepted: 20 January 2025 | Published: 7 March 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Amyloidosis syndromes are characterized by the extracellular deposition of fibrillar proteins, with 22 systemic and 27 localized forms identified. Among these, amyloid A (AA) amyloidosis is a complication of chronic inflammatory diseases, particularly rheumatoid arthritis (RA), and can affect multiple organs, including the gastrointestinal (GI) tract. The study aimed to determine the prevalence and severity of systemic AA amyloidosis (sAAa) and GI AA amyloidosis (giAAa) in RA, evaluate their role in mortality, and clarify the diagnostic value of GI biopsy. A total of 161 randomly selected autopsy patients with RA were studied. In this study, the GI tract refers specifically to the stomach, small intestine, and large intestine. The presence and extent of sAAa and giAAa were assessed histologically; with AA deposition quantified using a semi-quantitative visual estimation scale ranging from 0 to 3. Demographic differences between patient cohorts were analyzed using the Student’s (Welch) t-test. sAAa was identified in 34 (23.13%) of the 161 patients. Among these cases, tissue blocks containing one or more sections of the GI tract were available in 31 patients. In 29 of these cases, AA deposits were detected in branches of blood vessels and various tissue structures of the GI tract, while giAAa was histologically excluded in two patients with sAAa. sAAa and giAAa may develop in both sexes and can occur at any stage in the course of RA. These conditions represent progressive and cumulative processes, initially affecting only a few structures within various organs and expanding in the later stages of the disease. Although giAAa does not appear to be a life-threatening complication of RA, it emerges as an early pathological feature of significant clinical and diagnostic importance, particularly as an optimal biopsy site.

Keywords
Rheumatoid arthritis
Systemic amyloid A amyloidosis
Amyloid A amyloidosis of the gastrointestinal tract
Funding
None.
Conflict of interest
The authors declare no conflicts of interest.
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