Incidence Of AA Amyloidosis Research Articles

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.

Small Bowel Amyloidosis.

The goal of this paper is to review the literature on small bowel amyloidosis. Our review focuses on the underlying etiology, histopathology, clinical features, endoscopic and radiologic findings, and the mainstay of management. The latest research shows changing epidemiological trends of different types of amyloidosis. It also reveals a better understanding of its pathophysiology and shows improvement in treatment outcomes. Amyloidosis is a group of diseases of multiple etiologies and clinical presentations. It is characterized by pathological deposition of insoluble fibrillar proteins within various organs leading to disruption of their structure and function. The classification of amyloidosis includes primary, secondary, dialysis-related, senile, and hereditary. Amyloidosis can be systemic or localized. The incidence of AA amyloidosis is declining in frequency. If the gastrointestinal (GI) tract is involved, the small intestine is the most commonly affected site. Overall, outcomes among patients with newly diagnosed amyloidosis have improved. This article focuses on small bowel amyloidosis.

Autosomal dominant familial Mediterranean fever in Northern European Caucasians associated with deletion of p.M694 residue-a case series and genetic exploration.

This study was undertaken to characterize the phenotype and response to treatment in patients with autosomal dominant FMF caused by MEFV p.M694del mutation and to use haplotype reconstruction to investigate the possibility of common ancestry. MEFV gene was analysed in 3500 subjects with suspected FMF referred to a single UK centre between 2002 and 2014. Patients with p.M694del underwent additional screening of the SAA1 gene as well as haplotype reconstruction of the MEFV locus. The p.M694del variant was identified in 21 patients, sharing an identical disease haplotype that appears to have arisen about 550 years ago. The SAA1.1 allele was found in four patients, including two with AA amyloidosis. The clinical features comprised typical FMF symptoms with median age at onset of 18 years; three patients presented with AA amyloidosis, of whom two had had symptoms of FMF in retrospect. Fifteen patients had received colchicine treatment, all with excellent responses. The p.M694del variant is associated with autosomal dominantly inherited FMF in Northern European Caucasians. Symptoms may develop later in life than in classical recessive FMF but are otherwise similar, as is the response to colchicine treatment. The 14% incidence of AA amyloidosis may reflect delay in diagnosis associated with extreme rarity of FMF in this population. The common haplotype suggests a single founder living in about 1460.

Experimental transmission of AA amyloidosis by injecting the AA amyloid protein into interleukin-1 receptor antagonist knockout (IL-1raKO) mice.

The incidence of AA amyloidosis is high in humans with rheumatoid arthritis and several animal species, including cats and cattle with prolonged inflammation. AA amyloidosis can be experimentally induced in mice using severe inflammatory stimuli and a coinjection of AA amyloid; however, difficulties have been associated with transmitting AA amyloidosis to a different animal species, and this has been attributed to the "species barrier." The interleukin-1 receptor antagonist knockout (IL-1raKO) mouse, a rodent model of human rheumatoid arthritis, has been used in the transmission of AA amyloid. When IL-1raKO and BALB/c mice were intraperitoneally injected with mouse AA amyloid together with a subcutaneous pretreatment of 2% AgNO3, all mice from both strains that were injected with crude or purified murine AA amyloid developed AA amyloidosis. However, the amyloid index, which was determined by the intensity of AA amyloid deposition, was significantly higher in IL-1raKO mice than in BALB/c mice. When IL-1raKO and BALB/c mice were injected with crude or purified bovine AA amyloid together with the pretreatment, 83% (5/6 cases) and 38% (3/8 cases) of IL-1raKO mice and 17% (1/6 cases) and 0% (0/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. Similarly, when IL-1raKO and BALB/c mice were injected with crude or purified feline AA amyloid, 33% (2/6 cases) and 88% (7/8 cases) of IL-1raKO mice and 0% (0/6 cases) and 29% (2/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. These results indicated that IL-1raKO mice are a useful animal model for investigating AA amyloidogenesis.

PW02-024-B - First report of AA amyloidosis in Blau syndrome

Systemic AA amyloidosis is a life-threatening complication of different chronic infectious and inflammatory diseases. The deposition of amyloid fibrils derived from the serum amyloid A (SAA) protein represents its pathological hallmark. A long lasting and increased serum level of SAA is a prerequisite to its development. The group of inherited autoinflammatory diseases includes different disorders consequence of a genetically-determined dysregulation of innate immune system. All these diseases are associated with a marked acute phase response. The incidence of AA amyloidosis varies widely among them, with the higher incidence in Muckle-Wells syndrome and in TNF receptor-associated periodic syndrome. Inversely, no cases of AA amyloidosis have been reported in some few inherited autoinflammatory diseases, including Blau syndrome, a dominantly-inherited disease caused by NOD2 mutations.

Turkish experience in rheumatoid arthritis patients with clinical apparent amyloid deposition

Objectives: We evaluated the frequency of clinical apparent amyloid deposition, clinical features and outcome in our rheumatoid arthritis (RA) patients.Methods: Medical records of 1415 RA patients were examined. During routine follow-up, RA patients with proteinuria on urinalysis, underwent rectal biopsy.Results: Eleven patients (0.78%) were diagnosed with clinical apparent amyloid deposition. While the mean annual incidence of AA amyloidosis between 2001 and 2005 was 0.2%, it was 0.13% between 2006 and 2011. At initial presentation, three RA-related AA amyloidosis patients had nephrotic-range proteinuria and renal insufficiency, four had only nephrotic-range proteinuria, three had non-nephrotic-range proteinuria, and one had non-nephrotic-range proteinuria and renal insufficiency. The mean age in RA patients with AA amyloidosis was 60.8 years and disease duration was 12 years. Ten of 11 cases had positive rheumatoid factor. Two RA patients with AA amyloidosis who had been diagnosed in the pre-anti-TNF era died. Of the rest nine patients with AA amyloidosis, eight were administered anti-TNF therapy and one was given rituximab. In four patients, anti-TNF therapy led to disappearance of clinical features, decrement in proteinuria and resulted in improvement of or at least stabilization of renal functions. One patient using anti-TNF therapy died because of tuberculosis. One patient discontinued anti-TNF therapy and developed end-stage renal disease. Two patients have been started to be given anti-TNF therapy recently. In one patient who was given rituximab, there was regression of proteinuria and improvement in renal functions.Conclusions: We diagnosed a 0.78% frequency of AA amyloidosis in RA. It seems that – other than the risks of infection, tuberculosis – anti-TNF drugs seem to be effective on RA disease activity and also have renoprotective effects in RA patients with AA amyloidosis.

Decreasing incidence of AA amyloidosis in Spain

Decreasing incidence of <scp>AA</scp> amyloidosis in <scp>S</scp>pain

THU0379 A 20 year single centre experience of aa amyloidosis demonstrating changes in its epidemiology

BackgroundAA amyloidosis is the most serious potential complication of chronic inflammation and can result in renal failure and death. It is seen much less often in the USA than in...

Causes of Death in Autopsied Patients with Rheumatoid Arthritis in Japan

Objective: To investigate causes of death in Japanese patients with Rheumatoid Arthritis (RA) and whether recent RA treatment has been associated with a decrease in AA-amyloidosis among RA patients. Methods: Data from records of RA patients autopsied in Japan during 2000-2004 and 1985-1989 were analyzed. Cause of death, age at death, gender, and incidence of amyloidosis were assessed. Results: The average age at death in the recent RA group was 69.1 years in 817 females and 70.1 years in 408 males. Unlike the general population, RA females died earlier than males. In the past 15 years, a survival rate of RA patients has improved. The leading cause of death of recently diagnosed RA patients was infection (32.8%), respiratory diseases (20.2%), and AA-amyloidosis (11.3%). In comparison with patients surveyed in 1985-1989 this represents an increase in deaths from infection and respiratory diseases, a decrease in deaths from RA itself and renal diseases, and no change in deaths from AA-amyloidosis. In RA, more males died of interstitial lung disease (odds 2.94) and more females died from AA-amyloidosis (odds 3.52). Conclusion: Cause of death is significantly different in RA patients compared to the general population. Although outcomes of RA patients have been improving, the incidence of AA-amyloidosis remains high in Japan.

Renal Amyloidosis in Cattle with Inflammatory Diseases

The association of inflammatory diseases such as traumatic reticuloperitonitis (TRP), mastitis, metritis, and pododermatitis with renal amyloidosis in cattle is poorly described. Serum amyloid A (SAA) levels are elevated during inflammatory diseases, and renal amyloidosis is formed as a complication. This study was conducted with 82 crossbred cattle with mastitis (n = 18 cows), metritis (n = 11 cows), TRP (n = 30 cows), and pododermatitis (n = 23 : 15 cows and 8 beef cattle). Ten clinically healthy cows served as controls. Hematological, urinary, and blood parameters, including SAA, were measured by an automated procedure provided with trade kits. Determination of amyloidal structures was made by histopathological examination of renal biopsy specimens. At the end of this trial, amyloidosis was detected in 5 cows displaying typical nephrotic syndrome, with hypoproteinemia and proteinuria in combination with polyuria and weight loss. Furthermore, it was observed that cows with renal amyloidosis had significantly higher (P < .01) total leukocyte counts, serum and urine enzyme activities, and urea and creatinine concentrations, with lower serum total protein concentrations, when compared with animals without renal amyloidosis. The incidence of AA amyloidosis in cattle in this study suggests that cattle with mastitis, metritis, and pododermatitis have a high prevalence of systemic amyloidosis in response to inflammation.

Analysis of SAA1 gene polymorphisms in the Greek population: rheumatoid arthritis and FMF patients relative to normal controls. Homogeneous distribution and low incidence of AA amyloidosis

Objective. To address whether or not the rarity of amyloidosis in Greek patients with rheumatoid arthritis (RA) is related to specific alleles of single nucleotide polymorphisms (SNPs) in the 5′-flanking region and the exon 3 of the SSA1 gene.Methods. The genotypes of the −13T/C SNP in the 5′-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined in 88 Greek patients with RA, 14 patients with familial Mediterranean fever (FMF) and 110 healthy controls. Linkage disequilibrium and haplotype frequencies involving −13T/C, 2995C/T and 3010C/T in these populations were tested and estimated, respectively.Results. The genotypic distribution and allelic frequencies were similar in all groups tested. SNPs 2995 and 3010 were in linkage disequilibrium for all study populations (p < 0.05), whereas SNP −13 was not in linkage disequilibrium with either 2995 or 3010 (p ≥ 0.05). Two major haplotypes presented in all patients with RA and FMF and controls: −13C; 2995T; 3010C (−13C; α) and −13C; 2995C; 3010T (−13C; β). The −13T allele was linked with the γ haplotype in Greek patients with RA and controls. The frequency of the −13T allele was found to be very rare in all groups tested.Conclusions. In conclusion, the rarity of the putative amyloidogenic −13T allele in Greek populations may be related to low prevalence of AA amyloidosis development in Greek RA patients.

Renal type AA amyloidosis associated with rheumatoid arthritis: a cohort study showing improved survival on treatment with pulse cyclophosphamide.

To determine the incidence of renal AA amyloidosis and its association with rheumatoid arthritis (RA) in a cohort of all renal biopsies at one referral hospital and to measure the effect of a monthly pulse of cyclophosphamide on renal function and survival in these RA patients. All renal biopsies with proven AA amyloidosis from a single pathology unit linked to a major nephrology referral unit in a university hospital were selected retrospectively and RA patients were identified. We studied 6931 renal biopsies. The effect of treatment with and without pulse cyclophosphamide on renal function and survival was studied in these patients. From March 1977 to February 1999, the incidence of AA amyloidosis was 2.4 cases/yr. The incidence and prevalence of the association of AA amyloidosis with RA were 0.68 cases/yr and 0.22% (15/6931) respectively. RA patients treated with cyclophosphamide (n=6) had a lower rate of renal function loss (P=0.013) and a higher median survival (P=0.026) than untreated patients (n=9). During the follow-up period, two out of six treated patients (33%) and all nine untreated patients (100%) died. AA amyloidosis is a rare complication of RA and complicates the evaluation of treatment. This retrospective study suggests that treatment with cyclophosphamide is able to reduce the incidence of end-stage renal failure and to increase survival. Prospective studies are needed to clarify this issue.

Amyloid A amyloidosis in non-infected and avian leukosis virus-C persistently infected inbred ducks

The breeding history of the first inbred strain of Khaki Campbell ducks is presented. The genetic homogeneity of this strain was tested on the basis of serum amyloid A (SAA) polymorphism and it was established that it harbours only the SAA allele A, which is expressed in liver, lung and bursa of Fabricius tissues. Pathogenic changes in control and avian leukosis virus-C (ALV-C) persistently infected ducks were evaluated during the period spanning 1 to 10 months after hatching. In both groups, AA amyloidosis was revealed and characterized. In spite of the inbred nature of animals, the incidence of amyloid A deposition varied among experiments, suggesting that additional non-genetic factors are involved. Similar variation was found in ALV-C persistently infected ducks, where only in one out of three experiments was the incidence ofAA amyloidosis significantly higher than in controls.