Current approaches to the diagnosis and management of amyloidosis

Abstract

Amyloidosis is a collection of diseases caused by the misfolding of proteins that aggregate into insoluble amyloid fibrils and deposit in tissues. While these fibrils may aggregate to form insignificant localised deposits, they can also accumulate in multiple organs to the extent that amyloidosis can be an immediately life‐threatening disease, requiring urgent treatment. Recent advances in diagnostic techniques and therapies are dramatically changing the disease landscape and patient prognosis. Delays in diagnosis and treatment remain the greatest challenge, necessitating physician awareness of the common clinical presentations that suggest amyloidosis. The most common types are transthyretin (ATTR) amyloidosis followed by immunoglobulin light‐chain (AL) amyloidosis. While systemic AL amyloidosis was previously considered a death sentence with no effective therapies, significant improvement in patient survival has occurred over the past 2 decades, driven by greater understanding of the disease process, risk‐adapted adoption of myeloma therapies such as proteosome inhibitors (bortezomib) and monoclonal antibodies (daratumumab) and improved supportive care. ATTR amyloidosis is an underdiagnosed cause of heart failure. Technetium scintigraphy has made noninvasive diagnosis much easier, and ATTR is now recognised as the most common type of amyloidosis because of the increased identification of age‐related ATTR. There are emerging ATTR treatments that slow disease progression, decrease patient hospitalisations and improve patient quality of life and survival. This review aims to update physicians on recent developments in amyloidosis diagnosis and management and to provide a diagnostic and treatment framework to improve the management of patients with all forms of amyloidosis.

AA Amyloidosis: A Contemporary View

“…In systemic amyloidosis, the amyloid precursor protein must be specified to guide the patient management [ 56 ]. Immunohistochemical analysis for SAA protein is the most commonly used method to detect AA amyloidosis [ 56 ].…”

“…In systemic amyloidosis, the amyloid precursor protein must be specified to guide the patient management [ 56 ]. Immunohistochemical analysis for SAA protein is the most commonly used method to detect AA amyloidosis [ 56 ]. Alternatively, direct immunofluorescence for kappa and lambda light chains on fresh frozen tissue is a reliable method to detect amyloid deposits and rule out AL amyloidosis in kidney biopsies [ 56 ].…”

“…Immunohistochemical analysis for SAA protein is the most commonly used method to detect AA amyloidosis [ 56 ]. Alternatively, direct immunofluorescence for kappa and lambda light chains on fresh frozen tissue is a reliable method to detect amyloid deposits and rule out AL amyloidosis in kidney biopsies [ 56 ]. Since various amyloid subtypes may involve different glomerular parts, these features are not entirely specific, and subtyping still requires immunohistochemical methods with specific antibodies against precursor proteins [ 50 ].…”

Renale Amyloidosen

“…Obwohl eine gründliche Anamnese beziehungsweise laborchemische Umfelddiagnostik ( Tab. 1 ) den Verdacht auf eine Amyloidose aufbringen können, sind es doch häufig Zufallsdiagnosen, die dann einer gründlichen Aufarbeitung bedürfen 20 . Je nach Vorläuferprotein kann das Amyloid in der Niere in unterschiedlichen Kompartimenten liegen und damit den renalen Phänotyp des Patienten prägen.…”

Towards a Diagnosis of Cardiac Amyloidosis: Single Center Experience with 99m Technetium Pyrophosphate Planar Imaging and Opportunities for Standardization of Diagnostic Workflow

“…It is a systemic disease that can involve any organs in the body. Amyloidosis usually presents with a wide range of clinical signs and symptoms including but not limited to poor appetite, early satiety, abdominal distension, hepatomegaly, nephrotic syndrome, peripheral neuropathy, carpel tunnel syndrome and others [ 1 ]. Involvement of the heart, cardiac amyloidosis (CA), is recognized as one of the most common causes of restrictive cardiomyopathy and heart failure [ 2 , 3 , 4 ].…”