ObjectivesThe aim of this study was to describe the prevalence and formal pathogenesis of multi (micro) focal liponecrotic pancreatitis (LnP) caused by systemic secondary AA amyloidosis (AAa) in rheumatoid arthritis (RA).MethodsA randomized autopsy population of 161 in-patients with RA was studied. RA was confirmed clinically according to the criteria of the ACR. Tissue samples of pancreas were available for histologic evaluation in 111 of 161 patients. Pancreatitis and AAa were diagnosed histologically [1]. The possible role of AAa in the pathogenesis of LnP was analyzed by Pearson's chi-squared (χ2) test.Results:AAa complicated RA in 29 (26.12%) of 111 patients. Amyloid A deposition on different tissue structures of pancreas was detected in 25 (86.2 %) of 29 cases. Marked amyloid A deposition was found in the walls of arterioles, small and medium size arteries, and on different tissue structures of the pancreas.Acute or chronic LnP with or without AAa was present in different stages of the pathological process (necrotic foci with or without inflammatory reaction, and/or consecutive focal accentuated fibrosis) in 15 (13.51%) of 111 patients. Seven (46.66 %) of these 15 were associated with massive AAa. The correlation between LnP and prevalence of AAa was significant (c²=5.7939, p<0.016). Two (33.33%) of 15 LnP showed a special scattered multifocal appearance throughout the pancreas, characterized by necrotic foci of different size and stage of necrobiosis, without or with inflammation, and in association with severe AAa. The pancreatitis was basically not hemorrhagic, differing from hemorrhagic pancreatitis due to arterial erosions. Ductal changes were not present. The histological picture was dominated by more or less pronounced atrophy of pancreatic glands. The link between this special type of LnP and AAa very strong and significant (c²=16.2658, p<0.0005).ConclusionsThe close relationship between AAa and LnP suggests a relationship between amyloidosis and the prevalence of pancreatitis, that even may lead to a special multi (mico) focal pancreatitis. Amyloid A deposition in the walls of the pancreatic arterioles, small and medium size arteries (branches of splenic artery, upper and lower gastroduodenal arteries) can lead to local ischemia and to regressive changes in the pancreatic gland. This process is more or less widespread and multifocal, depending on the number of involved vessels. The size of necrobiotic areas is determined by the size of involved bood vessels. Multi (micro) focal necrosis of the pancreas caused by diminished blood supply is followed by reactive inflammation, and later fibrosis, depending on the stages of the pathological process.AAa is a progressive cumulative process involving more and more blood vessels of different sizes, thus the regressive changes accumulate in the pancreas with time, and exist in different stages at death. Different size and stage of focal necrosis, and the co-existent marked AAa may identify this type of pancreatitis. The progressive and cumulative process of A...

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...

BackgroundSystemic sclerosis (SSc), like all chronic autoimmune disorders, may be complicated by AA amyloidosis (AAa). An associated B-cell lymphoma my cause amyloid λ or κ light-chain deposition and AL amyloidosis (ALa) in SSc as well.ObjectivesThe aim of this study was to determine the prevalence and type of amyloidosis in SSc patients, appraise the extent of amyloid deposits in various organs.Methods12 patients (females 11, age: 54.82 years, range 66–32, onset of SSc: 48.86, disease duration: 6.43 years; one male, age: 65.0 years at death, onset of SSc and disease duration not known) were studied. All patients were autopsied. SSc was diagnosed clinically according to the criteria of the ACR [1].Amyloid deposits on different tissue structures [arteriole, small artery, medium size artery, venule, small vein, medium size vein, interstitial collagen fiber, reticulin fiber (collagen IV), basal lamina, nerve, renal glomerulus] of 6 organs [heart, lungs, kidney, gastrointestinal tract, skin and brain] were determined histologically. The extent of amyloid A deposits was evaluated by semi-quantitative, visual estimation on a 0 to 3 plus scale, based on the number of involved tissue structures per light microscopic field [2] (“0”: no amyloid deposits, “1”: Sporadic, minimal amyloid deposits on different tissue structures, “2”: less than five, “3”: five or more involved tissue structures per microscopic field at objective magnification of x20)The prevalence and extent of amyloid deposits in various organs were compared by Student (Welch) t-probe.ResultsSystemic AL-l light-chain amyloidosis was diagnosed in 1 (8.0%) 67 year old female patient (onset of SSc: 66 years, disease duration 1 year), and systemic AAa in 1 (8.0%) 53 year old female patient (onset of SSc: 41 years, disease duration 12 years).The prevalence (in %) and the average extent of AL-l light-chain and amyloid A deposits (absolute value) in various organs of SSc patients are summarized in Table 1.Tab;e 1OrgansSSc-λSSc-AAap

Background Amyloidosis is a progressive, cumulative process, involving in its early stage only a few structures in some organs, and increasingly more in the later stages of the disease [1]. Objectives The aim of this study was to study amyloid A deposits in the kidneys of rheumatoid arthritis (RA) patients at death. Methods A randomized autopsy population of 161 in-patients with RA was studied. AA amyloidosis (AAa) complicated RA in 34 (21.1%) cases. Tissue samples of both kidneys were available for histologic evaluation in 33 of these 34 patients. The existence of amyloid A deposits in various structures was determined histologically. The extent of amyloid A deposition was evaluated by semi-quantitative, visual estimation on a 0 to 3 plus scale, based on the number of involved blood vessels per light microscopic field (x40 objective of an Olympus BX51). Results Amyloid deposition is increasing simultaneously in all structures of kidney, but deposition in various structures does not begin at the same time. Conclusions In manifest amyloidosis the amount of deposited amyloid A protein increases simultaneously in blood vessels and in other renal structures, but deposition does not start at the same time in different structures. Amyloid A deposition starts in the most frequently involved structures of the most frequently involved organ (1). In the kidneys amyloid A starts depositing in the wall of arterioles and small arteries. Later interstitial collagen fibers, glomeruli, and peripelvic fat tissue are involved. The involvement of peripelvic nerves and cortical basement membranes of the convoluted tubules indicates advanced stages of amyloid deposition in the kidney. This chronology of amyloid A deposition allows an indirect assessment of the stage of amyloidosis. Based on the involved structures in renal biopsy specimens the pathologist may estimate the involvement of other structures. Involvement of arterioles alone (without involvement of small arteries) indicates an early stage of amyloidosis, whereas and vica versa amyloid A deposits in peripheral nerves suggests an advanced stage with massive involvement of numerous glomeruli. References Bély M, Apáthy Άgnes: Clinical Pathology of rheumatoid arthritis: Cause of death, lethal complications and associated diseases in rheumatoid arthritis. First English edition. Published by Akadémiai Kiadό, Member of Wolters Kluwer Group. Budapest 2012 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1230

Background:Psoriasis (P) may be complicated by psoriatic arthritis (psoriatic arthropathy (PsA), in 15 % of psoriatic patients [1]. The risk of mortality is increased in PsA outpatients compared to the general population [2].Objectives:The aim of this study was to determine the mortality of PsA or associated diseases in an in-patient autopsy population.Methods:At the National Institute of Rheumatology 11860 patients died between 1968 and 1998; among them 12 patients with PsA (females 6. mean age of 68.17 years, range 86 – 52, onset of PsA 53.60, average duration of PsA 15.40 years; males 6, mean age of 62.83 years, range 82 – 33, onset of PsA 46.67, average duration of PsA 3.67 years). All patients were autopsied.The basic disease, complication(s), and cause of death were determined by a detailed review of extensive histological material, all the available clinical and pathological reports retrospectively. From each patient a total of 50-100 tissue blocks of 16 organs were studied microscopically.PsA was confirmed clinically according to the criteria of the ACR updated by Sukfa (2019) [1].Results:The cause of death was related to PsA only in one (8.33 %) of 12 patients; a 33 year old man who died of pulmonary embolism after synovectomy.In 11 (91.66 %) of 12 PsA patients the cause of death was related to allied diseases namely atherosclerosis (Ath) in 9 (75 %), tuberculosis complicated by miliary dissemination (TB- mTB) in 1(8.33 %), and alcoholic cirrhosis (AC) in 1 (8.33 %). Ath was complicated by hypertension (HT) and adult type diabetes mellitus (DM) in 4, was associated with TB in 1 and with AC in 1 of 9 patients; HT and DM were present in one PsA patient without Ath (Table 1).AA amyloidosis (AAa) complicated PsA in 2 (16.66 %) of 12 PsA patients; in one case due to the long standing and severe inflammation of PsA, and in the other case the AAa was associated with TB and mTB.Table 1.P-PsABasic disease (leading to death)Complication(s)Cause of death1P-PsAAth, TBAdhesive pericarditis and pleuritisCirculatory failure2P-PsAAth-HT-DM Hyperplasic prostatePostoperative complicationPulmonary embolism3P-PsAAth-HT-DMBrain necrosis, Pulmonary embolismCirculatory failure4P-PsAAthPurulent bronchitis-BronchopneumoniaCirculatory failure5P-PsATB-mTBAAa, Arosion bronchial arteryMassive bronchial bleeding6P-PsAAthAAa, Coronary artery thrombosisMyocardial infarction7P-PsASynovectomyPulmonary embolism8P-PsAAth-HT-DMCoronary artery thrombosisMyocardial infarction9P-PsAAthMyocardial fibrosisCirculatory failure10P-PsAAth, Alcoholic cirrhosisAscites, Purulent bronchitisCirculatory failure11P-PsAAlcoholic cirrhosis, HT-DMAscitesHepatorenal syndrome12P-PsAAth-HT-DMMyocardial fibrosisCirculatory failureConclusion:In our autopsy population Ath (with or without HT and DM) was the most important basic disease leading to circulatory failure and death of PsA patients.Diseases of the circulatory system were also the most common cause of death in Wong’s outpatient PsA population as well [2].PsA is not a mild disease, but is not a life-threatening complication of P, however in association with Ath, HT, DM or TB it may increase mortality, as was also found by Arumugam and McHugh (2012): ‘the mortality of PsA may be increased in a more severe disease’ [3].References:[1]Sukfa P (2019) https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Psoriatic-Arthritis#sthash.kN0iC8N7.dpu[2]Wong K, et al: Arth Rheum 1997; 40(10):1868-1872 PMID: 9336423[3]Arumugam R, McHugh NJ: J Rheumatol Suppl, 2012; 89:32-5. doi: 10.3899/jrheum.120239Disclosure of Interests:None declared.