The Prevalence and Management of Systemic Amyloidosis in Western Countries

Abstract

Background: Amyloidosis has been a mystery for centuries, but research of the last decennia has clarified many of the secrets of this group of diseases. A protein-based classification of amyloidosis helps to understand problems that were part of the obsolete clinical classification in primary, secondary, and familial amyloidosis. All types of amyloid are secondary to some underlying precursor-producing process: each type is caused by a misfolded soluble precursor protein that becomes deposited as insoluble amyloid fibrils. Summary: The incidence of amyloidosis is not well documented, but probably falls between 5 and 13 per million per year. Prevalence data are scarce, but one UK study indicates about 20 per million inhabitants. Amyloidosis can be localized (amyloid deposited in the organ or tissue of precursor production) or systemic (amyloid at one or more sites distant from the site of precursor production). The major systemic types of amyloidosis are AL (associated with a light chain-producing plasma cell dyscrasia), AA (associated with longstanding inflammation), wild-type ATTR (associated with normal transthyretin and old age), and hereditary ATTR (associated with a transthyretin mutation) amyloidosis. Imaging techniques, such as cardiac ultrasound, magnetic resonance imaging, bone scintigraphy, and serum amyloid P component scintigraphy, are useful both for diagnosing amyloidosis and for assessing disease severity. Serologic markers are useful for detecting organ disease and disease monitoring during follow-up. Current treatment modalities are directed against the ongoing supply of precursor proteins and thereby aim to stop further accumulation of amyloid. Novel treatment modalities, such as interference with amyloid formation and even removal of amyloid, are being studied. A well-thought and planned monitoring during follow-up helps to assess the effect of treatment and to early detect possible progression of amyloidosis. Key Messages: Clinical management comprises histologic proof of amyloid, evidence of systemic deposition, reliable typing, precursor assessment, severity of organ disease, risk assessment and prognosis, choice of treatment, and planned monitoring during follow-up. Facts from East and West: (1) AL amyloidosis is the most prevalent type of amyloidosis accounting for 65% of the amyloidosis-diagnosed patients in the UK and for 93% of the amyloidosis-diagnosed patients in China. The predisposition of men over women to develop AL amyloidosis might be higher in China than in Western countries (2:1 vs. 1.3:1). Both in the East and West, incidence increases with age. At the time of diagnosis, edema is twice as frequent and the proportion of renal involvement is higher in Chinese compared to Western patients. (2) Melphalan followed by autologous stem cell transplantation (ASCT) is the current standard therapy but is restricted to eligible patients. The efficacy and safety of bortezomib combined with dexamethasone were proven in Western patients and recently confirmed in a Chinese cohort. Recent stu...

Epidemiology of AL amyloidosis: a real-world study using US claims data

“…1,4,5,7,15,19 For example, in a study by Weiss et al, 59% of the 1,430 AL amyloidosis patients identified in Sweden between 1995 and 2013 were men. 4 In another Swedish study by Hemminiki et al with 813 AL amyloidosis patients identified between 2001 and 2008, men were found to have a 1.3 times higher incidence of the disease than women.…”

“…Awareness is essential for timely detection and treatment of amyloidosis. 19 We further call for widespread education about the disease, as many institutions lack the training and resources to support these educational efforts.…”

“…As there is no diagnosis code specific to AL amyloidosis, the following algorithm, which was used in a previously published study, 16 was used to identify patients in each calendar year during the study period ( [17][18][19][20][21] for AL amyloidosis (bendamustine, bortezomib, carfilzomib, cyclophosphamide, dexamethasone, prednisone, doxycycline, lenalidomide, melphalan, pomalidomide, thalidomide, or hematopoietic stem cell transplant [HSCT]) on or after the first amyloidosis diagnosis in the study period. A similar population-identification algorithm was used in a recent publication and confirmed with clinical input.…”

Serum, salivary, and tissue levels of plasminogen in familial Mediterranean fever, amyloidosis, and chronic periodontitis

“…Amyloidosis is one of the most serious potential complications of FMF, which is characterized by extracellular deposition of pathological insoluble fibrillar proteins in organs and tissues that is localized or systemic . Amyloid deposition detected in the gingiva is called ligneous periodontitis (LP) which is also an inflammatory destructive membranous disease characterized by a plasminogen (PLG) deficiency …”

Automatic identification of crossovers in cryo‐EM images of murine amyloid protein A fibrils with machine learning

“…These diseases are characterized by the formation of abnormal protein filaments, termed amyloid fibrils, which deposit inside the tissue (Chiti & Dobson, 2017). Examples hereof are Alzheimer's or Parkinson's diseases (Chiti & Dobson, 2017) or the various forms of systemic amyloidosis (Nienhuis et al, 2016). Examples hereof are Alzheimer's or Parkinson's diseases (Chiti & Dobson, 2017) or the various forms of systemic amyloidosis (Nienhuis et al, 2016).…”