AB0327 Clinical significance of hormone-related (ISOLATED) amyloidosis of the islets of langerhans – a postmortem clinicopathologic statistical study of 234 rheumatoid arthritis patients

Abstract

Background“All forms of amyloidosis related to the circulation of blood are systemic, and all forms of amyloidosis not connected to the circulation are isolated (localised)”.1 Systemic AA amyloidosis (AAa) – characterised by amyloid A deposition – is one of the major chronic complication of rheumatoid arthritis (RA), in most of the cases leading to renal and less frequently to cardiac insufficiency and death.2 Islet amyloidosis (IA) (islet amyloid polypeptide – IAPP – prohormone fragment deposition localised to islets of Langerhans) is an isolated (localised) form of amyloidosis of clinical (diagnostic) significance in adult type II diabetes mellitus (DM).ObjectivesThe aim of this study was to determine the prevalence of AAa and IA in RA, to analyse the relationship between them, furthermore to evaluate the possible role of IA in DM in RA patients.MethodsAt the National Institute of Rheumatology 11 558 patients died between 1969 and 1998; among them 234 with RA, and all of them were autopsied. RA was confirmed clinically according to the criteria of the ACR.3 The diagnosis of DM based on clinical data. Tissue samples of pancreas were available for histologic evaluation in 150 of 234 patients. AAa and IA was diagnosed histologically, amyloid A and IAPP deposits were confirmed histochemically.4 The relationships between AAa and IA further more between IA and DM were analysed by Pearson’s chi-squared (χ2) test.ResultsAAa complicated RA in 32 (21.33%) of 150 patients. Hormone-related IAlocalised to the islets of Langerhans was observed in 15 (10.0%) of 150pancreases:Clinically diagnosed DM was associated with RA in 31 (20.66%) of 150 patients. AAa was associated with LA in 2 (6.45%) of 31 cases. The relationship between AAa and IA was not significant, even the association’s coefficient was negative: −0.2381, χ2;=0.0785, p<0.77). IA associated with clinically diagnosed DM in 8 (53.3%) of 15 patients. There was a positive and significant correlation between clinically diagnosed IA and DM (association’s coefficient: 0.6953, χ2;=10.8475, p<0.0009). IA was present without the clinical diagnosis of DM in 7 (46.7%) of 15 patients. The relationship between IA and clinically not diagnosed DM was also positive and significant (association’s coefficient: 0.6037, χ2;=6.8717, p<0.008).ConclusionsSystemic or localised types of amyloidosis may exist simultaneously side by side or may be present independently from each other. AAa and IA are independent phenomena based on the negative association’s coefficient and not significant relationship between them, and may coexist in RA. According to our interpretation the early stage of IA (involving only a few islets with minimal IAPP deposits) represents a clinically latent DM and the advanced stage of it is clinically manifest DM. The strong positive and significant correlation between IA and clinically manifest DM suggest close relationship between them. Based on the positive and significant correlation between IA and clinically not diagnosed DM, the IA may be a good indicator of potentia...

β-cell Related Amyloidosis Localized to the Islets of Langerhans, Type II Diabetes Mellitus and Liponecrotic Pancreatitis in Rheumatoid Arthritis: A Postmortem Clinicopathologic Statistical Study of 234 Autopsy Patients

“…Islet amyloidosis (IA) characterized by islet amyloid polypeptide (IAPP, also called amylin) prohormone fragment deposition localized to the islets of Langerhans is an isolated (localized) form of amyloidosis [35][36][37][38][39][40]. IA also represents a chronic progressive process [1,2,38,39], which may accompany RA as an associated disease independently from AAa, and may have clinical (diagnostic) significance in adult, non-insulin dependent, type II diabetes mellitus (DM) [1,2]. There is an agreement in the literature that the fibrillar amyloid IAPP (AIAPP) deposition is toxic to insulin-producing β-cells, induces apoptosis and islet cell dysfunction resulting in type 2 DM [39,41].…”

“…Prevalence of AAa was specified histologically based on the presence of amyloid A in blood vessels of different calibers or in different tissue structures of five organs (heart, lung, liver, kidney and pancreas) in each patient [50]. Prevalence of IA concerns the presence of islet amyloid polypeptide (IAPP) prohormone fragment deposition localized to the islets of Langerhans [2].…”

“…Systemic AA amyloidosis (AAa) is one of the main chronic and progressive complications of rheumatoid arthritis (RA) -characterized by amyloid A deposition in various organs leading in most cases to renal and less frequently to cardiac insufficiency and death [1,2]. Systemic (secondary, reactive) amyloid A deposition (AA amyloidosis -AAa) occurs in a wide spectrum of chronic inflammatory diseases [3][4][5], such as Chronic microbial infections: Tuberculosis [6,7], leprosy [8,9], fibrocystic lung diseases [10,11], bronchiectasis [7,12,13], lung abscess [6], chronic osteomyelitis [6,13], chronic xanthogranulomatous pyelonephritis [14][15][16], chronic mesenteric lymphadenitis [17], decubitus [7], etc.…”