scholarly journals Secondary Amyloidosis Presenting as Ischemic Proctitis

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Saad Hashmi ◽  
Assad Munis ◽  
Ryan T. Hoff ◽  
Hymie Kavin ◽  
Eli D. Ehrenpreis
Keyword(s):  
Low Voltage ◽  
Rectal Wall ◽  
Amyloid Deposition ◽  
Wall Thickening ◽  
Secondary Amyloidosis ◽  
Gastrointestinal Involvement ◽  
Aa Amyloidosis ◽  
Mediterranean Fever ◽  
Electrocardiogram Ecg ◽  
Ischemic Proctitis

A 49-year-old man presented with abdominal pain and rectal bleeding for two days associated with a 50-pound unintentional weight loss. History was notable for hypertension, chronic kidney disease, obesity, gout, and acute cholecystitis status post cholecystectomy. Computed tomography (CT) of the abdomen and pelvis showed rectal wall thickening. Colonoscopy showed proctitis with superficial ulcerations. In the setting of renal insufficiency, malabsorption, and low-voltage QRS complexes on electrocardiogram (ECG), amyloidosis was considered in the differential diagnosis. Rectal and renal biopsies with subsequent retrospective staining of gallbladder tissue confirmed amyloid deposition. Gastrointestinal involvement of amyloidosis is relatively uncommon. Particularly, amyloid deposition in the gallbladder and rectum is very rare. The development of AA amyloidosis in our patient may have been related to gout, obesity, and the presence of a heterozygous complex variant for the MEFV (familial Mediterranean fever) gene. Awareness of this atypical presentation of amyloidosis is important, as additional staining of biopsy samples is necessary, and diagnosis allows for directed treatment.

scholarly journals Treatment of experimental amyloidosis with antirheumatic drugs

2010 ◽  
Vol 17 (1-2) ◽  
pp. 17-29
Author(s):  
Laima LEONAVIČIENĖ ◽  
Danutė POVILĖNAITĖ ◽  
Rūta BRADŪNAITĖ ◽  
Dalia VAITKIENĖ ◽  
Algirdas VENALIS
Keyword(s):  
Prophylactic Treatment ◽  
Combined Treatment ◽  
Amyloid Deposition ◽  
Secondary Amyloidosis ◽  
Amyloid Formation ◽  
Aa Amyloidosis ◽  
Therapeutic Treatment ◽  
Antirheumatic Drugs ◽  
Experimental Amyloidosis ◽  
Amyloid Deposits

Background. Because at present there is no known specific effective therapy for secondary amyloidosis, the aim of this study was to determine whether antirheumatic drugs inhibit the development of experimental AA amyloidosis induced in C57BL/6 mice by casein and fibrin injections. Materials and methods. Monotherapy with sulfasalazine (SSL) and diclofenac (D) and a combined treatment with diclofenac and prednisolone (D/P) according to prophylactic and therapeutic treatment protocols were investigated. The drugs were administered through intragastric gavage 5 times a week for 5 or 4 weeks in the following doses: D – 1 mg/kg, P – 10 mg/kg, and SSL – 100 mg/kg. A histopathological examination of splenic, kidney and hepatic tissues of mice was performed. The amount of amyloid was assessed semi-quantitatively by polarizing microscopy after Congo red staining. Results. Our study indicated that no positive effect of the prophylactic treatment with D could be seen on amyloid deposition in the target organs. Prophylactic combined treatment with D/P resulted in a significant improvement of disease symptoms and markedly reduced amyloid deposits in the spleen, kidneys and liver (p < 0.02–0.001). SSL therapy alone was more successful in the prophylactic treatment of experimental amyloidosis: the decrease of amyloid deposits was statistically significant in all examined organs (p < 0.04–0.001), and the suppression of amyloid formation was most significant in the kidneys and liver (p < 0.004–0.001). In the therapeutic treatment of experimental amyloidosis, combined treatment with D/P showed the most pronounced inhibition of amyloid formation in the internal organs (p < 0.006–0.001). The suppression (by 86.7%; p < 0.001) of amyloid deposits was most notable in the liver. Treatment of mice with D alone produced a significant reduction in amyloid deposition only in the liver (p < 0.03) and with SSL only in the spleen (p < 0.03). Conclusions. These findings suggest that D/P and SSL at relevant doses suppress amyloidogenesis, and this suppression is possibly related to the anti-inflammatory effect of antirheumatic drugs. Although these drugs cannot completely inhibit the disease in this model, a possibility remains that they may be clinically useful in rheumatic diseases associated with the formation of amyloidogenic derivatives. Keywords: mice, experimental AA amyloidosis, antirheumatic drugs

scholarly journals Amyloidosis and Glomerular Diseases in Familial Mediterranean Fever

Medicina ◽  
2021 ◽  
Vol 57 (10) ◽  
pp. 1049
Author(s):  
Rossella Siligato ◽  
Guido Gembillo ◽  
Vincenzo Calabrese ◽  
Giovanni Conti ◽  
Domenico Santoro
Keyword(s):  
Nephrotic Syndrome ◽  
Familial Mediterranean Fever ◽  
Periodic Fever ◽  
Rapid Progression ◽  
Secondary Amyloidosis ◽  
Aa Amyloidosis ◽  
Glomerular Diseases ◽  
Amyloid A ◽  
Serum Amyloid A Protein ◽  
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.

scholarly journals A temporal and ultrastructural relationship between heparan sulfate proteoglycans and AA amyloid in experimental amyloidosis.

1991 ◽  
Vol 39 (10) ◽  
pp. 1321-1330 ◽  
Author(s):  
A D Snow ◽  
R Bramson ◽  
H Mar ◽  
T N Wight ◽  
R Kisilevsky
Keyword(s):  
Heparan Sulfate ◽  
Amyloid Fibrils ◽  
Dermatan Sulfate ◽  
Polyclonal Antibodies ◽  
Amyloid Deposition ◽  
Sulfate Proteoglycan ◽  
Aa Amyloidosis ◽  
Experimental Amyloidosis ◽  
Protein Core ◽  
Dermatan Sulfate Proteoglycan

Previous histochemical studies have suggested a close temporal relationship between the deposition of highly sulfated glycosaminoglycans (GAGs) and amyloid during experimental AA amyloidosis. In the present investigation, we extended these initial observations by using specific immunocytochemical probes to analyze the temporal and ultrastructural relationship between heparan sulfate proteoglycan (HSPG) accumulation and amyloid deposition in a mouse model of AA amyloidosis. Antibodies against the basement membrane-derived HSPG (either protein core or GAG chains) demonstrated a virtually concurrent deposition of HSPGs and amyloid in specific tissue sites regardless of the organ involved (spleen or liver) or the induction protocol used (amyloid enhancing factor + silver nitrate, or daily azocasein injections). Polyclonal antibodies to AA amyloid protein and amyloid P component also demonstrated co-localization to sites of HSPG deposition in amyloid sites, whereas no positive immunostaining was observed in these locales with a polyclonal antibody to the protein core of a dermatan sulfate proteoglycan (known as "decorin"). Immunogold labeling of HSPGs (either protein core or GAG chains) in amyloidotic mouse spleen or liver revealed specific localization of HSPGs to amyloid fibrils. In the liver, heparan sulfate GAGs were also immunolocalized to the lysosomal compartment of hepatocytes and/or Kupffer cells adjacent to sites of amyloid deposition, suggesting that these cells are involved in HSPG production and/or degradation. The close temporal and ultrastructural relationship between HSPGs and AA amyloid further implies an important role for HSPGs during the initial stages of AA amyloidosis.

Thyroid disorders in familial Mediterranean fever: think about AA amyloidosis!

2021 ◽  
Author(s):  
Hélène Vergneault ◽  
Rim Bourguiba ◽  
Samuel Ardois ◽  
Anael Dumont ◽  
Léa Savey ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Thyroid Disorders ◽  
Aa Amyloidosis ◽  
Mediterranean Fever

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 Deposition, Clearance, and Reinduction of Amyloid A Amyloid in Interleukin 1 Receptor Antagonist Knockout Mice

2016 ◽  
Vol 54 (1) ◽  
pp. 99-110 ◽  
Author(s):  
K. Watanabe ◽  
K. Uchida ◽  
J. K. Chambers ◽  
N. Ushio ◽  
H. Nakayama
Keyword(s):  
Receptor Antagonist ◽  
Knockout Mice ◽  
Interleukin 1 ◽  
Recovery Process ◽  
Amyloid Deposition ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Enhancing Factor ◽  
Amyloid Deposits ◽  
Amyloid Enhancing Factor

Amyloid A (AA) amyloidosis is characterized by the extracellular deposition of AA amyloid and results in the irreversible dysfunction of parenchymal organs. In experimental models, AA amyloid deposits are cleared following a decrease in circulating serum amyloid A (SAA) concentrations. Additional inflammatory stimuli during this recovery process may induce more severe amyloid redeposition. In the present study, we confirmed the deposition, clearance, and reinduction of AA amyloid deposits in interleukin 1 receptor antagonist knockout mice (IL-1raKO) and studied the SAA levels and amyloid-enhancing factor activity based on the time-dependent changes of amyloid deposition. Histopathologically, following initial (day 0) injection of amyloid-enhancing factor in combination with an inflammatory stimulus (silver nitrate [AgNO3]), amyloid deposition peaked by day 20, and its deposition gradually decreased after day 35. SAA concentrations in serum were precipitously elevated on day 1 but returned to normal levels by day 10, whereas the SAA dimer was detected in serum after day 45. An additional AgNO3 injection was administered to mice with amyloidosis on day 5, 10, 35, or 50, and all mice developed large amyloid deposits. Amyloid deposition was most severe in mice treated with AgNO3 on day 35. The inoculation of sera from mice with AA amyloidosis, combined with AgNO3, induced AA amyloidosis. Serum samples collected on days 35 and 50, which contained high concentrations of the SAA dimer, induced amyloidosis in a high proportion (83%) of mice. Therefore, increased SAA and/or its dimer in serum during the recovery process may markedly exacerbate the development of AA amyloidosis.

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 Amyloid deposition in granuloma of tuberculosis patients: A pilot study

2021 ◽  
Author(s):  
Shreya Ghosh ◽  
Akansha Garg ◽  
Chayanika Kala ◽  
Ashwani Kumar Thakur
Keyword(s):  
Serum Amyloid A ◽  
Amyloid Deposition ◽  
Serum Amyloid ◽  
Secondary Amyloidosis ◽  
Amyloid Formation ◽  
Tuberculosis Patients ◽  
Amyloid A ◽  
Inflammatory Conditions ◽  
Amyloid Deposits ◽  
Serum Amyloid A Protein

AbstractThe formation of granuloma is one of the characteristic feature of tuberculosis. Besides, rise in the concentration of acute phase response proteins mainly serum amyloid A is the indicator for chronic inflammation associated with tuberculosis. Serum amyloid A drives secondary amyloidosis in tuberculosis and other chronic inflammatory conditions. The linkage between serum amyloid A (SAA) protein and amyloid deposition site is not well understood in tuberculosis and other chronic inflammatory conditions. We hypothesized that granuloma could be a potential site for amyloid deposition because of the presence of serum amyloid A protein and proteases that cleave SAA and trigger amyloid formation. Based on this hypothesis, for the first time we have shown the presence of amyloid deposits in the granuloma of tuberculosis patients using the gold standard, Congo red dye staining.

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