EC Pulmonology and Respiratory Medicine

Introduction: Systemic AA amyloidosis (sAAa) is one of the main and most insidious complications of rheumatoid arthritis (RA) characterized by amyloid A (AA) deposition in various organs.
Aim of the Study: The aim of this study was to determine the relationship between demographics of RA patients and the amount of amyloid A deposits in various organs at death in association with clinical laboratory parameters, respectively in association with the mortality
Patients: One hundred sixty-one (161) random autopsy patients with RA were studied. The patients had clinically diagnosed RA which fulfilled the criteria of the American College of Rheumatology (ACR). The patients’ clinical histories and protocols were reviewed by the co-author, Ágnes Apáthy, rheumatologist, neurologist; the autopsies and histopathologic reports were by Miklós Bély.
Introduction:The presence and amount of sAAa was confirmed histologically. AA deposition was diagnosed histologically by a modified, more sensitive Congo red staining according to Romhányi. The amount of AA deposition was evaluated by semi-quantitative, visual estimation on a 0 to 3 plus scale. Based on the amount of deposited amyloid A (AA), early, advanced and terminal stages of sAAa were distinguished as minimal, abundant or massive AA deposits. Demographics and classic clinical laboratory parameters of different patient cohorts were compared with the Student (Welch) T-test. The correlation existing between the sAAa and the amount of AA deposits at early, advanced and terminal stages of amyloidosis was calculated with Pearson’s chi-squared (χ2 ) test.
Results: RA was complicated by sAAa in 34 (23,12 %) of 161 patients. AA deposits in 5 patients were classified as “early stage” with minimal (< 0,2), 22 patients had “advanced stage” with abundant (0,2-1,0), and 7 patients were “terminal stage” with massive (> 1,0) AA deposits.
Discussion and Conclusion: Amyloidosis developed in both sexes and at any time of the disease. The diagnostic values of the discussed laboratory parameters were limited, and none of them were specific for amyloidosis. The more or less significant differences between RA patients with and without sAAa at early, advanced and terminal stage during the progressively cumulative AA deposition showed an impaired renal function or were connected to the basic inflammatory disease only. Comparing the classic laboratory parameters there was no significant difference between the groups of patients with minimal, abundant and massive AA deposits at early, advanced and terminal stages of sAAa, respectively the differences had no diagnostic value for amyloidosis. For the diagnosis of amyloidosis, a biopsy is needed using a specific staining procedure.
Keywords: Rheumatoid Arthritis; Systemic AA Amyloidosis; Classic Laboratory Parameters

1. Bély M and Apáthy Á. “Clinical pathology of rheumatoid arthritis: Cause of death, lethal complications and associated diseases in rheumatoid arthritis”. Akadémiai Kiadó, Budapest, Hungary (2012): 1-440.
2. Buxbaum JN., et al. “Amyloid nomenclature 2024: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee”. Amyloid 31.4 (2024): 249-256.
3. Romhányi G. “Selective differentiation between amyloid and connective tissue structures based on the collagen specific topo-optical staining reaction with Congo red”. Virchows Archiv 354.3 (1971): 209-222.
4. Bély M and Makovitzky J. “Sensitivity and Specificity of Congo red Staining According to Romhányi - Comparison with Puchtler’s or Bennhold’s Methods”. Acta Histochemica 108.3 (2006): 175-180.
5. Bratthauer GL. “The avidin-biotin complex (ABC) method and other avidin-biotin binding methods”. Methods in Molecular Biology (Clifton N.J.) 588 (2010): 257-270.
6. Romhányi G. “Selektive darstellung sowie methodologische möglichkeiten der analyse ultrastruktureller unterschiede von amyloidablagerungen”. Zentralblatt für Allgemeine Pathologie und Pathologische Anatomie 123 (1979): 9-16.
7. Bély M. “Histochemical differential diagnosis and polarization optical analysis of amyloid and amyloidosis”. The Scientific World Journal 6 (2006): 154-168.
8. Bély M and Apáthy Á. “Differential diagnosis of amyloid deposits by light, polarization and electron microscopy”. In: Bély M, Apáthy Á, editors. BP International, UK London, India West Bangalia, Tarakeswar (2021): 1-253.
9. Lentner C. “Statistical methods” Volume 2. In: Geigy scientific tables. Ciba-Geigy Limited, Basle, Switzerland, Editor: Lentner C, Compiled by: Diem K, Seldrup J (1982): 227.
10. Szentágothai J and Réthelyi M. “Verőerek, Visszerek”. In: Funkcionális anatómia II. Medicina, Budapest, Editor: Szentágothai J (2002): 770-786 and 786-788.
11. Bely M and Apathy A. “Progression of AA amyloidosis (Sequence of AA deposition) in the pancreas - A postmortem clinicopathologic study of 161 patients”. Gastroenterology and Hepatology International Journal 3.2 (2018): 000143.
12. Bély M and Apáthy A. “A comparative postmortem clinicopathologic study of renal and cardiac AA amyloidosis in rheumatoid arthritis”. Journal of Clinical Trials in Cardiology 6.1 (2019): 1-20.
13. Bély M and Apáthy Á. “AA amyloidosis of the liver in rheumatoid arthritis - a postmortem clinicopathologic study of 152 autopsy patients”. Archives of Gastroenterology and Hepatology 3.2 (2020): 26.
14. Kuroda T., et al. “Diagnosis and treatment of AA amyloidosis with rheumatoid arthritis: state of the art”. Chapter 9 In Amyloidosis, (Ed: Feng D) Educational Technology Research and Development 47 (1999): 43-62.
15. Sasatomi Y., et al. “Prognosis of renal amyloidosis: A clinicopathological study using cluster analysis”. Nephron 87.1 (2001): 42-49.
16. Husby G. “Amyloidosis and rheumatoid arthritis”. Clinical and Experimental Rheumatology 3.2 (1985): 173-180.
17. Gertz MA and Kyle RA. “Secondary systemic amyloidosis: response and survival in 64 patients”. Medicine 70.4 (1991): 246-254.
18. Schneider F. “Die AA-Amyloidose bei entzündlich-rheumatischen Erkrankungen”. Zeitschrift für Rheumatologie 51 (1992): 177-182.
19. Goldwasser P and Feldman J. “Association of serum albumin and mortality risk”. Journal of Clinical Epidemiology 50.6 (1997): 693-703.
20. Shcherbinina MB. “Low blood bilirubin level: possible diagnostic and prognostic importance”. Klinicheskaia Meditsina (Mosk) 85.10 (2007): 10-14.
21. Dhawan R., et al. “AA (inflammatory) amyloidosis workup”. Medscape reference (2022).
22. Yamada T. “Serum amyloid A (SAA): a concise review of biology, assay methods and clinical usefulness”. Clinical Chemistry and Laboratory Medicine 37.4 (1999): 381-388.
23. Uhlar CM and Whitehead AS. “Serum amyloid A, the major vertebrate acute-phase reactant”. European Journal of Biochemistry 265.2 (1999): 501-523.
24. Zhang N., et al. “Serum amyloid A-luciferase transgenic mice: response to sepsis, acute arthritis, and contact hypersensitivity and the effects of proteasome inhibition”. Journal of Immunology 174.12 (2005): 8125-8134.
25. Hawkins PN. “10 years’ experience with serum amyloid P component scintigraphy”. Book of Abstracts, The IX. International Symposium on Amyloidosis, Budapest Hungary, July 15-21, 2001. Amyloid: The Journal of Protein Folding Disorders (Guest Editor: M Bély), 8.2: 166-168.
26. Spitz J and Freudenberg LS. “The impact of nuclear medicine procedures on the diagnosis and follow-up of amyloidosis”. Book of Abstracts, The IXth International Symposium on Amyloidosis, Budapest Hungary, July 15-21, 2001. Amyloid: The Journal of Protein Folding Disorders. (Guest Editor: M Bély), 8.2: 170-174.
27. Linke RP. “Diagnosis of the various amyloid diseases and new developments”. Book of Abstracts, The IX. International Symposium on Amyloidosis, Budapest Hungary, July 15-21, 2001. Amyloid: The Journal of Protein Folding Disorders (Guest Editor: M Bély) 8.2 (2001): 153-155.
28. Cohen AS. “Amyloidosis associated with rheumatoid arthritis”. The Medical Clinics of North America 52.3 (1968): 643-653.