Secondary Amyloidosis Research Articles

S2411 Secondary Amyloidosis Presenting as a Rare Complication of IBD

Introduction: 35% of patients with Inflammatory Bowel Disease (IBD) experience extraintestinal manifestations. However, amyloidosis is a rare complication of IBD;the incidence in the US is <1% for both Crohn's disease (CD) and Ulcerative Colitis (UC). We hope to shed some light in this underdiagnosed consequence with a clinical vignette. Case description/methods: A 75 year old man with recently diagnosed UC 6 weeks prior and history of thoracic laminectomy presented with bilateral lower extremity weakness that resulted in a fall in the shower and complaints of bloody diarrhea. Prior to his admission he was ambulating with a walker, he then developed loss of motor function of his lower extremities. He had been having several episodes of bloody diarrhea a day along with tenesmus and fecal incontinence for almost a year. He delayed getting medical aid until recently due to the COVID-19 pandemic. He had a colonoscopy which revealed pancolitis and he was started on aggressive steroids and mesalamine. CT and MRI imaging of the spine were inconclusive, but revealed swelling of the iliopsoas muscle with concern for polymyositis. However EMG, muscle enzymes and Immunological studies were all unremarkable. Muscle biopsy of the gastrocnemius revealed interstitial amyloid deposition. Mass spectrometry was indeterminate and could not isolate the type of amyloid protein. The patient's UC flare slowly improved after several weeks and he was transferred to acute rehab and later to a tertiary care center for further evaluation. Discussion: Primary amyloidosis is AL amyloid deposition associated with plasma cell dyscrasias such as multiple myeloma (MM). AA Amyloid can also build up as an acute phase reactant from chronic inflammatory conditions such as IBD and be deposited in extracellular tissue. Amyloidosis is more associated with CD than UC, more found in men and is often associated with renal involvement. One study found that only 15 out of 1709 (0.9%) patients with CD and 1 in 1341 (0.7%) patients with UC had amyloidosis. Our patient's long standing uncontrolled UC likely resulted in amyloid protein production and deposition. Although it is important to rule out MM in cases of amyloidosis, the timing of our patient's lower extremity weakness and diagnosis of amyloidosis in the setting of uncontrolled UC flare strongly suggests secondary amyloidosis. We hope this diagnostic walk through can guide clinicians to approach similar situations in the future.

A Case of Secondary Renal Amyloidosis Associated with HIV

A Case of Secondary Renal Amyloidosis Associated with HIV

Amyloidosis in a Renal Transplant Recipient

Amyloidosis is an infiltrative disease where amyloid fibrils get deposited in the extracellular space. Inflammatory arthritis, chronic infections, and malignancies are some known etiologies. Liver is commonly involved in amyloidosis, more common in primary (AL) than secondary (AA) amyloidosis. It is a perplexing diagnosis as it usually presents with nonspecific symptoms and minimal laboratory derangements. In this study, the patient had ankylosing spondylitis as an existing risk factor, but renal cell carcinoma detected in the native kidneys after transplantation accelerated the liver decompensation. This case highlights the importance of excluding liver amyloidosis in patients of systemic amyloidosis as liver amyloidosis can be clinically silent pretransplantation.

Amyloidosis and Glomerular Diseases in Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. It may also involve the cardiovascular system, the gastrointestinal tract and the central nervous system. Other glomerulonephritis may equally affect FMF patients, including vasculitis such as IgA vasculitis and polyarteritis nodosa. A differential diagnosis among different primary and secondary causes of nephrotic syndrome is mandatory to determine the right therapeutic choice for the patients. Early detection of microalbuminuria is the first signal of kidney impairment in FMF, but new markers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) may radically change renal outcomes. Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy. According to new evidence, SAA may also have an active pathogenic role in the regulation of NALP3 inflammasome activity as well as being a predictor of the clinical course of AA amyloidosis. Beyond colchicine, new monoclonal antibodies such as IL-1 inhibitors anakinra and canakinumab, and anti-IL-6 tocilizumab may represent a key in optimizing FMF treatment and prevention or control of AA amyloidosis.

Association of ulcerative colitis and IgA nephropathy: A case report

The extradigestive manifestations of chronic inflammatory bowel disease most often affect the articulations, skin, eyes, liver and bile ducts. Renal involvement is rare, and manifests as kidney stones, glomerulonephritis, tubulointerstitial nephritis, and secondary amyloidosis. In this context of chronic inflammatory bowel disease, in particular ulcerative colitis, renal involvement is very often secondary to nephrotoxicity of the basic treatment of digestive pathology, and very rarely an authentic extradigestive manifestation of intestinal disease. We report a case of IgA nephropathy as an extra-digestive manifestation of ulcerative colitis. The objective of this study is not to neglect the IgA nephtopathy as an extradigestive manifestation of IBD which, even though rare, remains a condition to be looked for by clinicians during the follow-up of IBD.

К вопросу о вторичном амилоидозе почек при ювенильном ревматоидном артрите у детей

В обзоре литературы изложены современные данные о частоте, механизмах развития, клинических проявлениях, диагностике и лечении вторичного амилоидоза (АА-амилоидоза) почек у детей с ювенильным ревматоидным артритом (ЮРА). Частота встречаемости АА-амилоидоза почек при ЮРА у детей составляет от 0,8 до 2 %, у взрослых с длительностью ЮРА 28,3 года — 8,9 %. В последние годы на фоне иммунобиологической терапии частота АА-амилоидоза почек у взрослых уменьшилась до 2 %. На сегодняшний день установлен основной механизм развития АА-амилоидоза, который заключается в постоянном или периодическом повышении концентрации сывороточного амилоида А (SAA). Установлено, что на синтез SAA влияют провоспалительные цитокины: интерлейкин-1 (ИЛ-1), ИЛ-6, фактор некроза опухоли альфа (ФНО-α), ИЛ-2, ИЛ-11 и другие. Для реализации амилоидогенного потенциала SAA необходимо не только воздействие воспалительного процесса в организме, но и его продолжительность. Обсуждается роль генетических факторов в развитии АА-амилоидоза почек при ЮРА. АА-амилоидоз почек чаще всего развивается у детей при системной форме, у взрослых — при системной и полиартикулярной формах ЮРА. Первым симптомом АА-амилоидоза почек является изолированная протеинурия, которая трансформируется в нефротический синдром. Особенности нефротического синдрома заключаются в отсутствии в большинстве случаев гиперхолестеринемии, сочетании у некоторых больных с артериальной гипертензией, гематурией, нарушением функции почек. Основным методом, подтверждающим диагноз АА-амилоидоза почек, является прижизненное морфологическое исследование почек с окраской биоптатов конго красным. Повышение уровня SAA в крови у детей с ЮРА отражает степень воспалительного процесса и рассматривается как фактор риска развития АА-амилоидоза почек. Применение иммунобиологических препаратов (тоцилизумаб, анакинра) при АА-амилоидозе почек у детей с ЮРА имеет терапевтическую эффективность.

Случай вторичного AA-амилоидоза при болезни Бехтерева: успешная 3-летняя терапия адалимумабом

Описано клиническое наблюдение пациента, страдающего более 20 лет ревматологическим процессом, который идентифицирован как болезнь Бехтерева в последние 5 лет. Прогрессирование анкилозирующего спондилита осложнилось развитием нефротического синдрома и прогрессирующим снижением функции почек до уровня хронической болезни почек 4-й стадии (расчетная скорость клубочковой фильтрации (рСКФ) — 19,8 мл/мин), анемии и кахексии. Биопсия десны не выявила амилоида, биопсия почки подтвердила наличие АА-амилоидоза. Была начата терапия адалимумабом в дозе 40 мг 1 раз в неделю, через 2 месяца — 1 раз в 2 недели. Одновременно пациент получал олмесартан, симптоматическую терапию. Трехлетнее введение адалимумаба привело к стойкому контролю активности анкилозирующего спондилита и постепенному восстановлению функции почек до рСКФ 62 мл/мин. На фоне лечения у пациента родились дети. Приведена детальная характеристика нефробиоптата. Лечение адалимумабом и олмесартаном продолжается.

Gastrointestinal AA amyloidosis secondary to chronic pyelonephritis presenting with refractory diarrhea and severe hypoalbuminemia

Secondary amyloidosis is a rare complication of chronic inflammatory diseases, such as collagen diseases, and is often difficult to treat. In addition, the gastrointestinal tract is frequently involved in amyloid deposition that often results in various disorders and symptoms. A 70-year-old woman was admitted to our hospital with refractory diarrhea and hypoalbuminemia. Abdominal computed tomography demonstrated extensive edematous wall thickening of the small intestine and colon. Video capsule endoscopy revealed multiple ulcerations with a white mossy appearance of the ileum. Double-balloon endoscopy showed severe circumferential ulcers in the entire ileum. Histological examination of ileum biopsy samples revealed severe amyloid deposition in the lamina propria and perivascular areas of the submucosa. The patient was diagnosed with gastrointestinal AA amyloidosis. The cause of AA amyloid deposition was presumed to be chronic pyelonephritis due to ureteral stones that had been left untreated for 35years. After treatment with ureteral drainage and antibiotics, the patient's symptoms and serological abnormalities improved dramatically. Here, we describe a case of severe gastrointestinal AA amyloidosis secondary to chronic pyelonephritis. Clinicians should thoroughly investigate the entire gastrointestinal tract in patients with refractory diarrhea and severe hypoalbuminemia considering the possibility of gastrointestinal amyloidosis.

A case of effective use of interleukin 6 inhibitors in patients with ankylosing spondylitis with secondary amyloidosis

Ineffectiveness of interleukin 6 inhibitors (iIL6), tocilizumab (TCZ) and sarilimumab in ankylosing spondylitis (AS) was shown in randomized clinical trials. However, there is ample evidence that IL6 is actively involved in the pathogenesis of this disease. In addition, the efficacy of iIL6 in patients with secondary AA-amyloidosis was established.Objective: to analyze the results of TCZ administration in AS, complicated by secondary AA-amyloidosis.Patients and methods. The analysis included 6 patients with AS with secondary AA-amyloidosis. All patients were HLA-B27 positive male. The average age of patients was 44±9.2 years, the average age of the disease onset was 16.3±7.9 years, the average duration of AS was 26.0±7.5 years. All 6 patients had pathomorphologic confirmed secondary AA-amyloidosis: all had kidney affection, 5 patients also had gastrointestinal tract affection and 2 had heart affection. As a first biological drug TCZ was prescribed in 2 patients, and 4 patients had previously received one or more inhibitors of tumor necrosis factor α. The average duration of TCZ treatment was 27.6 [3.0; 36.0] months.Results and discussion. During TCZ therapy, the level of CRP (M±σ) significantly decreased: from 81.1±74.5 to 1.2±0.8 mg/L (p&lt;0.05), as well as daily proteinuria (Me [25th ; 75th percentile]): from 1.8 [1.0; 2.1] to 0.2 [0.1; 0.3] g/day (p&lt;0.05) and AS activity indices – BASDAI (M±σ): from 6.2±1.6 to 3.3±0.9 (p&lt;0.05 ); ASDAS-CRP (M±σ) from 4.6±1.1 to 2.04±0.7 (p&lt;0.05). Positive dynamics was also noted in relation to a decrease in the number of patients with inflammatory back pain, arthritis and coxitis. A case of clinical and laboratory remission of AS on TCZ treatment is described. Conclusion. The presented data show that in certain clinical situations iIL6 can be highly effective in AS.

Diagnostic delay and characterization of the clinical prodrome in AL amyloidosis among 1523 US adults diagnosed between 2001 and 2019.

Light-chain (AL) amyloidosis is a multisystem disorder with a high early mortality and diagnostic delays of >1year from symptom onset. This retrospective observational study sought to characterize the clinical prodrome and diagnostic delay to inform early detection. We identified 1523 adults with newly diagnosed AL amyloidosis in the Optum de-identified Clinformatics® Datamart US healthcare claims database as those with ≥2 new diagnosis codes for AL or other amyloidosis in 90days with ≥1 multiple myeloma treatment within 730days, excluding patients with prior hereditary or secondary amyloidosis and Familial Mediterranean Fever. We considered 34 signs/symptoms using diagnosis codes in all observable time on or before AL amyloidosis diagnosis. Sign/symptom prevalence was compared to that of 1:4 matched population controls. The overlap and sequence of signs/symptoms and the median time from first sign/symptom to AL amyloidosis diagnosis were explored. Healthcare utilization was summarized. The most common individual AL amyloidosis signs/symptoms were malaise/fatigue (61%) and dyspnea (59%). Cardiac signs/symptoms were observed in 77% of patients, followed by renal (62%) and neurologic (59%) signs/symptoms. Multisystem involvement (≥3 systems) was present in 54%. Monoclonal gammopathy was detected in 29% before diagnosis. Median time from symptom onset to AL amyloidosis diagnosis was 2.7years. Healthcare utilization was high between first AL amyloidosis signs/symptoms and diagnosis, with 50% visiting ≥5 physician types. AL amyloidosis patients have a lengthy and complex clinical prodrome. Novel approaches to early diagnosis are needed to improve outcomes.

Epidemiology of Amyloidosis and Genetic Pathways to Diagnosis and Typing

We reviewed our studies on epidemiology and germline genetics of amyloidosis. In epidemiology, we considered both hereditary and non-hereditary amyloidosis. As the source of data, we used the nationwide Swedish hospital discharge register. We estimated the incidence of hereditary ATTR amyloidosis, for which Sweden is a global endemic area, at 2/million. Surprisingly, the disease was also endemic within Sweden; the incidence in the province with the highest incidence was 100 times higher than in the rest of Sweden. Risk of non-Hodgkin lymphoma increased five-fold in the affected individuals. Among non-hereditary amyloidosis, the incidence for AL amyloidosis (abbreviated as AL) was estimated at 3.2/million, with a median survival time of 3 years. Secondary systemic amyloidosis (most likely AA amyloidosis) showed an incidence of 1.15/million for combined sexes. The female rate was two times higher than the male rate, probably relating to the higher female prevalence of rheumatoid arthritis. The median survival time was 4 years. We also identified patients who likely had familial autoinflammatory disease, characterized by early onset and immigrant background from the Eastern Mediterranean area. Young Syrian descendants had the highest incidence rate, which was over 500 times higher than that in individuals with Swedish parents. Germline genetics focused on AL on which we carried out a genome-wide association study (GWAS) in three AL cohorts (N = 1129) from Germany, UK, and Italy. Single nucleotide polymorphisms (SNPs) at 10 loci showed evidence of an association at p &lt; 10−5; some of these were previously documented to influence multiple myeloma (MM) risk, including the SNP at the IRF4 binding site. In AL, SNP rs9344 at the splice site of cyclin D1, influencing translocation (11;14), reached the highest significance, p = 7.80 × 10−11; the SNP was only marginally significant in MM. The locus close to gene SMARCD3, involved in chromatin remodeling, was also significant. These data provide evidence for common genetic susceptibility to AL and MM. We continued by analyzing genetic associations in nine clinical profiles, characterized by organ involvement or Ig profiles. The light chain only (LCO) profile associated with the SNP at the splice site of cyclin D1 with p = 1.99 × 10−12. Even for the other profiles, distinct genetic associations were found. It was concluded that the strong association of rs9344 with LCO and t(11;14) amyloidosis offer attractive mechanistic clues to AL causation. Mendelian randomization analysis identified associations of AL with increased blood monocyte counts and the tumor necrosis factor receptor superfamily member 17 (TNFRSF17 alias BCMA) protein. Two other associations with the TNFRSF members were found. We discuss the corollaries of the findings with the recent success of treating t(11;14) AL with a novel drug venetoclax, and the application of BCMA as the common target of plasma cell immunotherapies.

Association of Ulcerative Colitis and IgA Nephropathy: A Case Report

The extra-digestive manifestations of chronic inflammatory bowel disease most often affect the joints, skin, eyes, liver and bile ducts. Renal involvement is rare, and manifests as kidney stones, glomerulonephritis, tubulointerstitial nephritis, and AA-type secondary amyloidosis. In this context of chronic inflammatory bowel disease, in particular ulcerative colitis, renal involvement is very often secondary to nephrotoxicity of the basic treatment of digestive pathology, and very rarely an authentic extra-digestive manifestation of intestinal disease. We report a case of IgA nephropathy as an extra-digestive manifestation of ulcerative colitis.

Atypical Corneal Phenotype in Patients With Trachoma and Secondary Amyloidosis.

Purpose:To report clinical presentation, in vivo confocal microscopic features, and corneal phenotype in patients with trachomatous keratopathy (TK) and secondary amyloidosis.Methods:Histopathological records of all patients undergoing keratoplasty at the Dr. Rajendra Prasad Centre for Ophthalmic Sciences over a 3-year period were scanned retrospectively for a diagnosis of TK and amyloidosis. Demographic profile and details of preoperative comprehensive ophthalmic assessment were extracted. The histopathology was freshly reviewed.Results:Fifteen patients (29 eyes) with TK and atypical corneal involvement due to amyloid deposition were identified. Herbert's pits and upper palpebral conjunctival scarring were present in all cases. Central or total diffuse corneal scarring was present involving the anterior stroma in 5 (31%) and the full thickness of the cornea in 11 (69%) of the eyes. Eight (73%) of 11 patients with deep stromal amyloid deposits revealed bilateral, discrete, blue-white opacities at the level of deep stroma and Descemet membrane (DM). Endothelial cells were atrophic and flattened with gutta formation. Confoscans revealed hyperreflective, needle-shaped crystalline deposits of extracellular amyloid at various depths of the corneal stroma up to DM. All host corneal buttons demonstrated Congo red–positive amyloid deposits on histopathological examination.Conclusions:We describe a distinct form of TK unlike the usual presentation of dense, leucomatous, vascularized corneal scarring in trachoma. We believe that amyloid deposits in DM and the corneal endothelium have not previously been reported in patients with trachoma.

La inhibición de la interleucina-6 como posible diana terapéutica en la amiloidosis AA

IntroductionAA (secondary) amyloidosis is a severe complication of chronic inflammatory disorders. It is characterized by the systemic deposition of an abnormal protein called amyloid, affecting mainly renal function. IL-6 is a cytokine with a relevant role in this disease development. Interleukin-receptor antagonists, like Tocilizumab (TCZ), have become possible treatment choice for AA amyloidosis. In published reports, TCZ has shown good efficacy for AA amyloidosis, being associated with regression of renal amyloid deposits. MethodsRetrospective review that included patients with histological diagnosis of AA renal amyloidosis under treatment with TCZ during the years 2018-2019 in our center. We have registered clinical and demographic variables. Renal function was measured by means of CKD-EPI equation to estimate the glomerular filtration rate (FG) and protein/creatinine ratio (IPC) at 3, 6 and 12 months. We define renal response as a decrease by at least 30% of proteinuria and/or stabilization or improvement of FG. We consider that an anti-inflammatory response is a decrease of more than 50% in serum amyloid protein (PSA) and/or C-reactive protein (CRP). ResultsWe collected 3 cases of patients with histologically proven AA amyloidosis treated with TCZ (2 men; 1 woman; aged 55, 74 and 75 years). The follow-up was 13, 14 and 75 months. FG was stabilized in two patients. The third patient remained on hemodialysis during follow-up, although with excellent control of her underlying inflammatory disease. In all three cases, reduced PSA and CRP were observed. There have been no adverse events. ConclusionsThe TCZ may be an effective and safe option in treatment of AA amyloidosis with renal involvement. Our results position it as an interesting therapeutic option to consider in these cases, although prospective studies would be necessary to evaluate the global role of TCZ in AA amyloidosis.

Difficulties of biological therapy in the patient with active rheumatoid arthritis and secondary renal amyloidosis: A report of clinical case

A clinical case of a patient with active rheumatoid arthritis (RA) resistant to standard basic therapy is presented, which served as the reason for the appointment of the target drug – Janus kinase, tofacitinib (Jaquinus) and then biological therapy using anti-IL6 receptor antibody tocilizumab (Actemra). This clinical example demonstrates the patient with the presence of several complications, both the course of the disease – amyloid nephropathy with the development of nephrotic syndrome (NS) as a manifestation of secondary amyloidosis with kidney damage, as well as basic therapy – the presence of comorbid infections with hospital pneumonia and infectious (septic) knee arthritis.An additional contribution of NS to the development of infectious complications in patients with RA receiving immunosuppressive therapy is supposed. Current treatment options for resistant RA and the feasibility of early use of biologics before the development of irreversible complications, as well as the difficulties of therapy and the complications associated with immunosuppression are discussed. Preventive measures for immunization with the anti-pneumococcal vaccine and the need to correct hemostatic disorders in patients with RA and NS are important.

Nephrotic Syndrome Following Resection of an Adrenal Incidentaloma:A Case Report

A 69 year old man had a 5 cm right adrenal lesion discovered incidentally while being investigated for a deterioration in previously well-controlled hypertension. Routine investigations including serum albumin were normal. Further investigation confirmed a non-functioning adrenal lesion. MRI revealed a ‘non-fat-containing T1 hyperintense indeterminate adrenal lesion with speckling of T2 hyperintensity, not typical for adenoma, hyperplasia, myelolipoma, haemangioma or pheochromocytoma’. An uncomplicated laparoscopic adrenalectomy was performed. Histology revealed a 118 g adrenal neoplasm, modified Weiss score 0, with abundant hyaline deposits.3 months later the patient complained of peripheral oedema. Investigations revealed a serum albumin of 24 g/L and 14 g of proteinuria in 24 hours. Serum protein electrophoresis revealed a monoclonal IgA type lambda band. Renal biopsy revealed amorphous material displaying apple green birefringence on staining with Congo Red, which stained with antibodies to lambda light chains, confirming AL amyloid. Therefore the patient’s resected adrenal specimen was retrieved and stained with Congo Red, revealing apple green birefringence in the walls of the blood vessels, confirming the presence of amyloidosis. Although adrenal gland involvement in secondary amyloidosis is common, adrenal involvement in primary amyloidosis is less well described. This case illustrates the indolent nature of primary amyloidosis, prior to the development of often catastrophic symptoms. Consideration should be given to Congo Red staining of resected pathologic specimens containing hyaline deposition, to potentially allow for earlier recognition of this devastating disease. A pathophysiologic link between the patient’s incidentaloma, adrenalectomy, and onset of nephrotic syndrome remains a matter for conjecture.

Successful Treatment of AA Amyloidosis in Ankylosing Spondylitis Using Tocilizumab: Report of Two Cases and Review of the Literature.

Historically, secondary amyloidosis has been a feared complication of chronic inflammatory conditions. The fibril protein AA derives from the acute phase reactant serum amyloid A (SAA). Long-term elevation of SAA levels remains a major risk factor for the development of AA amyloidosis in rheumatic diseases, and the prognosis may be unpredictable. Nowadays, with increased availability of effective biological agents, the incidence of AA amyloidosis seems to be declining. Still, genetically predisposed subjects with slowly progressive disease and mild symptoms combined with ongoing systemic inflammation may be at risk. Interleukin-6 (IL-6) is one of the drivers of SAA release and effectiveness of the humanized anti-IL-6 receptor antibody tocilizumab (TCZ) for the treatment of AA amyloidosis has been observed in some rheumatic conditions. Herein, we report two male subjects with longstanding ankylosing spondylitis (AS) complicated by renal amyloidosis who received TCZ with rapid and beneficial effects regarding inflammation and proteinuria. To the best of our knowledge, the use of TCZ in AS patients with this extra-articular manifestation has not previously been described. The paper includes histopathology, clinical follow-up, and longitudinal data of the two cases along with a comprehensive review of relevant literature. Mechanisms behind amyloid-mediated tissue damage and organ dysfunction are discussed. Altogether, our data highlight that blocking IL-6 signaling may represent a promising therapeutic option in patients with renal AA amyloidosis.

Difficulties in diagnosing multiple myeloma with lung damage

Multiple myeloma occupies a leading position among malignant blood diseases. There is clinical evidence that multiple myeloma can be complicated by secondary amyloidosis. The article presents a clinical case for the diagnosis of multiple myeloma complicated by secondary pulmonary amyloidosis. The participation of doctors of various specialties (pulmonologist, hematologist, pathologist), the use of high-tech diagnostic methods (histological examination of a biopsy of lung tissue, trepanobiopsy, immunohistochemical examination of histological preparations of lungs and bone marrow), made it possible to establish a clinical diagnosis.

Serum Amyloid A in Inflammatory Rheumatic Diseases: A Compendious Review of a Renowned Biomarker.

Serum amyloid A (SAA) is an acute phase protein with a significant importance for patients with inflammatory rheumatic diseases (IRD). The central role of SAA in pathogenesis of IRD has been confirmed by recent discoveries, including its involvement in the activation of the inflammasome cascade and recruitment of interleukin 17 producing T helper cells. Clinical utility of SAA in IRD was originally evaluated nearly half a century ago. From the first findings, it was clear that SAA could be used for evaluating disease severity and monitoring disease activity in patients with rheumatoid arthritis and secondary amyloidosis. However, cost-effective and more easily applicable markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), overwhelmed its use in clinical practice. In the light of emerging evidences, SAA has been discerned as a more sensitive biomarker in a wide spectrum of IRD, especially in case of subclinical inflammation. Furthermore, a growing number of studies are confirming the advantages of SAA over many other biomarkers in predicting and monitoring response to biological immunotherapy in IRD patients. Arising scientific discoveries regarding the role of SAA, as well as delineating SAA and its isoforms as the most sensitive biomarkers in various IRD by recently developing proteomic techniques are encouraging the revival of its clinical use. Finally, the most recent findings have shown that SAA is a biomarker of severe Coronavirus disease 2019 (COVID-19). The aim of this review is to discuss the SAA-involving immune system network with emphasis on mechanisms relevant for IRD, as well as usefulness of SAA as a biomarker in various IRD. Therefore, over a hundred original papers were collected through an extensive PubMed and Scopus databases search. These recently arising insights will hopefully lead to a better management of IRD patients and might even inspire the development of new therapeutic strategies with SAA as a target.

Review of current recommendations for diagnosis and treatment of familial Mediterranean fever (periodic disease)

In the presented article contemporary conceptions of genetics and clinical aspects of familial Mediterranean fever (FMF) used to termed ‘Periodic disease’ and being the commonest form of autoinflammatory syndrome have been discussed. Great attention is paid to gen MEFVpathogenic mutations, which are associated with sever FMF clinical manifestation. FMF characteristic clinical picture, criteria for diagnosis in children and adults as well as classification criteria Eurofever / PRINTO (2019) for FMF, considering genetic marker as major criterion, have been presented. Management of FMF according to EULAR recommendations (2016) based on traditional use of colchicine and alternative treatment with IL-1 inhibitors is analyzed. Brief review of clinical data and results of randomized trials have demonstrated high efficacy and safety of canakinumab in resistant FMF as well as in secondary amyloidosis treatment.