AB0327 Clinical significance of hormone-related (ISOLATED) amyloidosis of the islets of langerhans – a postmortem clinicopathologic statistical study of 234 rheumatoid arthritis patients
Authors: Á. Apáthy, M. Bély
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> "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)".<sup>1</sup> Systemic AA amyloidosis (<b>AAa</b>) – characterised by amyloid A deposition – is one of the major chronic complication of rheumatoid arthritis (<b>RA</b>), in most of the cases leading to renal and less frequently to cardiac insufficiency and death.<sup>2</sup> Islet amyloidosis (<b>IA</b>) (<i>islet amyloid polypeptide</i> – <b>IAPP</b> – <i>prohormone fragment deposition localised to islets of Langerhans</i>) is an isolated (localised) form of amyloidosis of clinical (diagnostic) significance in <i>adult type II diabetes mellitus</i> (<b>DM</b>). <h3>Objectives</h3> The <b>aim</b> of this study was to determine the <b><i>prevalence</i></b> of <b>AAa</b> and <b>IA</b> in <b>RA</b>, to analyse the relationship between them, furthermore to evaluate the possible role of <b>IA</b> in <b>DM</b> in <b>RA</b> patients. <h3>Methods</h3> At the National Institute of Rheumatology 11 558 patients died between 1969 and 1998; among them <b>234</b> with <b>RA</b>, and all of them were autopsied. <b>RA</b> was confirmed clinically according to the criteria of the <b>ACR</b>.<sup>3</sup> The diagnosis of <b>DM</b> based on clinical data. Tissue samples of pancreas were available for histologic evaluation in <b>150</b> of 234 patients. <b>AAa</b> and <b>IA</b> was diagnosed histologically, <b>amyloid A</b> and <b>IAPP</b> deposits were confirmed histochemically.<sup>4</sup> The relationships between <b>AAa</b> and <b>IA</b> further more between <b>IA</b> and <b>DM</b> were analysed by Pearson's chi-squared (χ<sup>2</sup>) test. <h3>Results</h3> <b>AAa</b> complicated <b>RA</b> in <b>32</b> (<b>21.33</b>%) of 150 patients. <b>Hormone-related IA</b>localised to the islets of Langerhans was observed in <b>15</b> (<b>10.0</b>%) of <b>150</b>pancreases: Clinically diagnosed <b>DM</b> was associated with <b>RA</b> in <b>31</b> (<b>20.66</b>%) of 150 patients. <b>AAa</b> was associated with <b>LA</b> in <b>2</b> (<b>6.45</b>%) of 31 cases. The relationship between <b>AAa</b> and <b>IA</b> was <b>not significant</b>, even the association's coefficient was negative: −0.2381, χ<sup>2</sup>;=0.0785, p&lt;0.77). <b>IA</b> associated with clinically diagnosed <b>DM</b> in <b>8</b> (<b>53.3</b>%) of <b>15</b> patients. There was a <b>positive</b> and <b>significant correlation</b> between clinically diagnosed <b>IA</b> and <b>DM</b> (association's coefficient: 0.6953, χ<sup>2</sup>;=10.8475, p&lt;0.0009). <b>IA</b> was present without the clinical diagnosis of <b>DM</b> in <b>7</b> (<b>46.7</b>%) of <b>15</b> patients. The relationship between <b>IA</b> and clinically <b>not</b> diagnosed <b>DM</b> was also <b>positive</b> and <b>significant</b> (association's coefficient: 0.6037, χ<sup>2</sup>;=6.8717, p&lt;0.008). <h3>Conclusions</h3> Systemic or localised types of amyloidosis may exist simultaneously side by side or may be present independently from each other. <b>AA</b>a and <b>IA</b> are <b><i>independent phenomena</i></b> based on the negative association's coefficient and not significant relationship between them, and may coexist in <b>RA</b>. According to our interpretation the early stage of <b>IA</b> (involving only a few islets with minimal <b>IAPP</b> deposits) represents a clinically latent <b>DM</b> and the advanced stage of it is clinically manifest <b>DM</b>. The strong positive and significant correlation between <b>IA</b> and clinically manifest <b>DM</b> suggest close relationship between them. Based on the positive and significant correlation between <b>IA</b> and clinically <b>not</b> diagnosed <b>DM</b>, the <b>IA</b> may be a good indicator of potential <b>DM</b> in the latent stage of disease. This correlation may help recognise <b>DM</b> in its early stage. For this reason we recommend that all biopsy material and surgical specimens of pancreas to be tested for <b>IA</b> or <b>IAPP</b> deposition. <h3>References</h3> [1] Bély M, Apáthy Á. Amyloid2000;7:212–217. [2] Apáthy Á, Bély M. Ann Rheum Dis, 2010;69(Suppl 3):348. [3] Arnett FC, et al. Arthritis Rheum1988;31:315–324. doi:10.1002/art.1780310302 [4] Bély M. The Scientific World Journal2006;6:154–168. doi:10.1100/tsw.2006.35 [PMID: 16493520] <h3>Disclosure of Interest</h3> None declared