scholarly journals Rituximab Therapy in Renal Amyloidosis Secondary to Rheumatoid Arthritis

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 136 ◽  
Author(s):  
Levent Kilic ◽  
Abdulsamet Erden ◽  
Yusuf Sener ◽  
Berkan Armagan ◽  
Alper Sari ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Improvement ◽  
Inflammatory Diseases ◽  
Case Series ◽  
New Drugs ◽  
Renal Amyloidosis ◽  
Secondary Amyloidosis ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Significant Clinical Improvement

Secondary amyloid A (AA) amyloidosis is a late and serious complication of poorly controlled, chronic inflammatory diseases. Rheumatoid arthritis (RA) patients with poorly controlled, longstanding disease and those with extra-articular manifestations are under risk for the development of AA amyloidosis. Although new drugs have proven to be significantly effective in the treatment of secondary AA amyloidosis, no treatment modality has proven to be ideal. To date, only in small case series preliminary clinical improvement have been shown with rituximab therapy for AA amyloidosis secondary to RA that is refractory to TNF-α inhibitors (TNF-i) therapy. In these case series, we assessed the efficacy and safety of rituximab therapy for patients with RA and secondary amyloidosis. Hacettepe University Biologic Registry was developed at 2005. The data of the RA patients who were prescribed a biological drug were recorded regularly. Patients with biopsy proven AA amyloidosis patients were screened. Of 1022 RA patients under biologic therapy, 0.7% patients had clinically apparent histologically confirmed amyloidosis. Four of seven patients who were prescribed rituximab at least one infusion enrolled to those case series. Two of four patients showed significant clinical improvement and one of them also had decrease in proteinuria and the other one had stable renal function and proteinuria. The main goal for the treatment of AA amyloidosis is to control the activity of the underlying disorder. In this study, we showed that rituximab may be an effective treatment in RA patients with amyloidosis who were unresponsive to conventional disease modifying anti-rheumatic drugs (DMARDs) and/or TNFi.

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

2021 ◽  
Vol 8 ◽  
Author(s):  
Per Eriksson ◽  
Johan Mölne ◽  
Lina Wirestam ◽  
Christopher Sjöwall
Keyword(s):  
Ankylosing Spondylitis ◽  
Therapeutic Option ◽  
Relevant Literature ◽  
Acute Phase Reactant ◽  
Renal Amyloidosis ◽  
Secondary Amyloidosis ◽  
Aa Amyloidosis ◽  
Beneficial Effects ◽  
Amyloid A ◽  
Inflammatory Conditions

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.

scholarly journals Is renal amyloidosis uncommon in Egypt? A-25-year study

2018 ◽  
Vol 8 (1) ◽  
pp. 5-5
Author(s):  
Amal Labib ◽  
Marwa M Shakweer ◽  
Manal I Salman ◽  
Elham I Seif
Keyword(s):  
Inflammatory Diseases ◽  
Renal Involvement ◽  
Underlying Disease ◽  
Renal Amyloidosis ◽  
Al Amyloidosis ◽  
Positive Staining ◽  
Aa Amyloidosis ◽  
University Hospitals ◽  
Amyloid A ◽  
Renal Biopsies

Background: Renal amyloidosis is a well-known disease. The forms of amyloidosis that are frequently associated with renal involvement are AL and AA amyloidosis. In Theodor Bilharz Institute, in Egypt, 2.5% of the total number of renal biopsies examined showed amyloidosis including secondary type in 80% and primary type in 20% of cases. Objectives: To investigate the prevalence of amyloidosis among Egyptian renal patients within 25 years and to screen the amyloid type whether AA or AL. Materials and Methods: Demographic and pathological data of archived renal biopsies presented to Ain Shams University hospitals in 25 years (1990-2015) were the material of this study. The diagnosis of all renal biopsies included in the study was confirmed by electron microscopy (EM). Immunohistochemical (IHC) staining of paraffin blocks for amyloid typing was carried out on archived material from (2010-2015). Results: Of a total number of 3962 biopsies examined; 118 were renal amyloidosis (2.97%). IHC typing of the screened samples revealed positive staining for amyloid A protein in 14 cases (73.68%). Light chain AL amyloidosis was found in 5 cases (26.3%). Conclusions: Renal amyloidosis is not uncommon in Egypt. AA amyloidosis represents the commonest type of renal amyloidosis in this study. The most common underlying disease was systemic inflammatory diseases, on top of familial Mediterranean fever (FMF).

scholarly journals Sexual Dimorphisms of Adrenal Steroids, Sex Hormones, and Immunological Biomarkers and Possible Risk Factors for Developing Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Alfonse T. Masi ◽  
Azeem A. Rehman ◽  
Laura C. Jorgenson ◽  
Jennifer M. Smith ◽  
Jean C. Aldag
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Sexual Dimorphism ◽  
Sex Hormones ◽  
Inflammatory Diseases ◽  
Interleukin 2 ◽  
Tumor Necrosis Factor Receptor ◽  
Serum Levels ◽  
Amyloid A ◽  
Neuroendocrine Factors

Innate immunity and immunological biomarkers are believed to be interrelated with sex hormones and other neuroendocrine factors. Sexual dimorphism mechanisms may be operating in certain rheumatic and inflammatory diseases which occur more frequently in women than men, as rheumatoid arthritis (RA). Less data have been available on altered interrelations of the combined neuroendocrine and immune (NEI) systems as risk factors for development of certain diseases. In this study, serological interrelations of NEI biomarkers are analyzed before symptomatic onset of RA (pre-RA) versus control (CN) subjects, stratified by sex. Sexual dimorphism was found in serum levels of acute serum amyloid A (ASAA), soluble interleukin-2 receptor alpha (sIL-2Rα), and soluble tumor necrosis factor receptor 1 (sTNF-R1). Multiple steroidal and hormonal (neuroendocrine) factors also showed highly(p<0.001)significant sexual dimorphism in their assayed values, but less for cortisol(p=0.012), and not for 17-hydroxyprogesterone(p=0.176). After stratification by sex and risk of developing RA, differential NEI correlational patterns were observed in the interplay of the NEI systems between the pre-RA and CN groups, which deserve further investigation.

Effective Anti-TNF-α Therapy Can Induce Rapid Resolution and Sustained Decrease of Gastroduodenal Mucosal Amyloid Deposits in Reactive Amyloidosis Associated with Rheumatoid Arthritis

2009 ◽  
Vol 36 (11) ◽  
pp. 2409-2415 ◽  
Author(s):  
TAKESHI KURODA ◽  
YOKO WADA ◽  
DAISUKE KOBAYASHI ◽  
SHUICHI MURAKAMI ◽  
TAKEHITO SAKAI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Aa Amyloidosis ◽  
Laboratory Findings ◽  
Protein Levels ◽  
Amyloid A ◽  
Biopsy Specimens ◽  
Amyloid Deposits ◽  
Reactive Amyloidosis ◽  
Serum Amyloid A Protein ◽  
Before And After

Objective.To examine the effect of anti-tumor necrosis factor-α (anti-TNF) therapy in patients with reactive AA amyloidosis associated with rheumatoid arthritis (RA).Methods.Fourteen patients with reactive AA amyloidosis associated with RA were prospectively evaluated. Four patients were treated with infliximab and 10 with etanercept. The mean period of anti-TNF therapy was 20.1 ± 13.8 months. Laboratory findings and renal function were examined before and after initiation of anti-TNF therapy. In 9 patients the area of amyloid deposits in serial gastroduodenal mucosal biopsy specimens was examined and image analysis was performed.Results.C-reactive protein and serum amyloid A protein levels were significantly reduced after initiation of anti-TNF therapy. Twenty-four hour creatinine clearance improved in 4 patients, did not change in 5, and deteriorated in 3. Twenty-four hour urinary protein excretion was significantly decreased in 3 patients, not exacerbated in 6, and increased in 3 after initiation of anti-TNF therapy. The biopsy specimens from the 9 patients who underwent serial gastroduodenal biopsies showed significant decreases in the area of amyloid deposits, from 8.8% ± 6.4% to 1.6% ± 0.6% (p = 0.003) after initiation of anti-TNF therapy. Four patients showed a sustained decrease in the areas of amyloid deposits in their third biopsy specimens, and amyloid deposits were not detectable in 2.Conclusion.Our results indicate a striking effect of anti-TNF therapy for rapid removal and sustained disappearance of amyloid deposits in gastric mucosal tissue with amelioration of renal functions in patients with reactive amyloidosis due to RA.

Treatment with Biologic Agents Improves the Prognosis of Patients with Rheumatoid Arthritis and Amyloidosis

2012 ◽  
Vol 39 (7) ◽  
pp. 1348-1354 ◽  
Author(s):  
TAKESHI KURODA ◽  
NAOHITO TANABE ◽  
DAISUKE KOBAYASHI ◽  
HIROE SATO ◽  
YOKO WADA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Survival Rate ◽  
Biologic Therapy ◽  
Statistical Significance ◽  
Biologic Agents ◽  
Aa Amyloidosis ◽  
Free Survival ◽  
Risk Of Death ◽  
Amyloid A ◽  
Systemic Complication

Objective.Reactive amyloid A (AA) amyloidosis is a serious and life-threatening systemic complication of rheumatoid arthritis (RA). We evaluated the safety of therapy with anti-tumor necrosis factor and anti-interleukin 6 biologic agents in RA patients with reactive AA amyloidosis, together with prognosis and hemodialysis (HD)-free survival, in comparison with patients with AA amyloidosis without such therapy.Methods.One hundred thirty-three patients with an established diagnosis of reactive AA amyloidosis participated in the study. Clinical data were assessed from patient records at the time of amyloid detection and administration of biologics. Survival was calculated from the date when amyloid was first demonstrated histologically or the date when biologic therapy was started until the time of death or to the end of 2010 for surviving patients. Patients who had started HD were selected for inclusion only after the presence of amyloid was demonstrated.Results.Fifty-three patients were treated with biologic agents (biologic group) and 80 were not (nonbiologic group). Survival rate was significantly higher in the biologic group than in the nonbiologic group. Nine patients in the biologics group and 33 in the nonbiologic group started HD. Biologic therapy had a tendency for reduced risk of initiation of HD without any statistical significance.Conclusion.Patients with amyloidosis have a higher mortality rate, but the use of biologic agents can reduce risk of death. The use of biologics may not significantly influence the HD-free survival rate.

scholarly journals THERAPEUTIC APPROACH OF A CASE OF RHEUMATOID ARTHRITIS COMPLICATED WITH RENAL AMYLOIDOSIS IN A YOUNG WOMAN

2017 ◽  
Vol 26 (1) ◽  
pp. 41-44
Author(s):  
Alexandra Burlui ◽  
◽  
Anca Cardoneanu ◽  
Luana Macovei ◽  
Claudia Banu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Acute Phase Proteins ◽  
Certolizumab Pegol ◽  
Renal Involvement ◽  
Active Form ◽  
Scientific Data ◽  
Renal Amyloidosis ◽  
Secondary Amyloidosis ◽  
Inflammatory Biomarker ◽  
Nephrotic Range Proteinuria

Systemic AA amyloidosis is an uncommon complication of rheumatoid arthritis (RA), especially in poorly controlled RA. Renal involvement caused by deposits of amyloid fibrils derived from acute-phase proteins is represented by nephrotic-range proteinuria ultimately leading to renal failure. We report the case of 27-year-old woman diagnosed with RA, with a history of musculoskeletal involvement since the age of 16, manifested by arthritis involving the wrists, knees and ankles; accompanied by severe and persistent inflammatory syndrome. She presented with an active form of RA complicated with secondary amyloidosis manifested by nephrotic-range proteinuria at the time of admission. Renal biopsy confirmed the presence of amyloid deposits. Anti-TNFα therapy with Certolizumab pegol proved effective in reducing proteinuria and inflammatory biomarker levels in our patient. The efficacy of anti TNF-α therapy in RA complicated with renal amyloidosis is demonstrated by recent scientific data.

scholarly journals Renal amyloidosis: validation of a proposed histological scoring system in an independent cohort

2020 ◽  
Author(s):  
Joris J Hoelbeek ◽  
Jesper Kers ◽  
Eric J Steenbergen ◽  
Joris J T H Roelofs ◽  
Sandrine Florquin
Keyword(s):  
The Netherlands ◽  
Light Chain ◽  
Scoring System ◽  
Renal Involvement ◽  
Case Series ◽  
Original Study ◽  
Renal Outcome ◽  
Renal Amyloidosis ◽  
Amyloid A ◽  
Amyloid Deposits

Abstract Background In systemic amyloidosis, the kidney is frequently affected and renal involvement has a major impact on survival. Renal involvement is clinically characterized by decreased estimated glomerular filtration rate (eGFR) and proteinuria. The two most common renal amyloidosis types are light chain-related amyloidosis (AL) and serum amyloid A (AA) amyloidosis. Standardized histopathological scoring of amyloid deposits is crucial to assess disease progression. Therefore, we aimed to validate the proposed scoring system from Rubinstein et al. (Novel pathologic scoring tools predict end-stage kidney disease in light chain (AL) amyloidosis. Amyloid 2017; 24: 205–211) in an independent patient cohort. Methods We attempt to reproduce the scoring system, consisting of an amyloid score (AS) and a composite scarring injury score (CSIS), in a multicentre AL and AA case series. Additionally, we analysed all renal amyloidosis kidney biopsies performed in the Netherlands between 1993 and 2012. Results Similar to the original study, AS and CSIS correlated to eGFR (r = −0.45, P = 0.0061 and r = −0.60, P &lt; 0.0001, respectively) but not to proteinuria at diagnosis. Furthermore, AS, but not CSIS, was associated with renal outcome. The scoring system was not reproducible in AA patients. The median incidence rate for renal amyloidosis in the Netherlands was 2.3 per million population per year, and increased during the study period. Conclusions In our AL case series and the original study, AS and CSIS were correlated to eGFR but not to proteinuria, and AS correlated with renal outcome. Overall, we regard this scoring system as competent for standardized histopathological assessment of amyloid deposits burden and thereby disease advancement in renal biopsies.

scholarly journals Abdominal Fat Aspiration Biopsy and Genotyping of Serum Amyloid A Contribute to Early Diagnosis of Reactive AA Amyloidosis Secondary to Rheumatoid Arthritis

2003 ◽  
Vol 42 (9) ◽  
pp. 800-805 ◽  
Author(s):  
Watara ISHII ◽  
Masayuki MATSUDA ◽  
Akinori NAKAMURA ◽  
Naoshi NAKAMURA ◽  
Akio SUZUKI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Diagnosis ◽  
Serum Amyloid A ◽  
Abdominal Fat ◽  
Serum Amyloid ◽  
Aspiration Biopsy ◽  
Aa Amyloidosis ◽  
Amyloid A

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

2021 ◽  
Vol 59 (2) ◽  
pp. 225-228
Author(s):  
R. A. Osipyants ◽  
M. Z. Kanevskaya ◽  
N. L. Kozlovskaya ◽  
K. A. Demyanova ◽  
M. M. Saidova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Case ◽  
Active Rheumatoid Arthritis ◽  
Biological Therapy ◽  
Treatment Options ◽  
Janus Kinase ◽  
Renal Amyloidosis ◽  
Secondary Amyloidosis ◽  
Additional Contribution ◽  
Basic Therapy

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.

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