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Systemic Amyloidosis

  • Tamer Rezk
  • Philip N. HawkinsEmail author
Chapter

Abstract

Amyloidosis describes a group of rare diseases caused by abnormal fibrillar protein aggregation within the interstitium of tissues and organs throughout the body. This chapter focuses upon the pathogenesis, epidemiology, diagnosis and management of these heterogeneous disorders. AA amyloidosis is one of the most feared complications of autoinflammatory syndromes but it is becoming increasingly rare with the advent of effective anti-inflammatory therapy. The most common of the systemic amyloidoses are immunoglobulin light chain (AL) type and wildtype transthyretin (wtATTR) amyloidosis, the latter a probably much underdiagnosed cause of heart failure in the elderly. Precise diagnosis, confirmation of amyloid type, evaluation of amyloidotic organ involvement and associated underlying disorders are imperative for optimal patient care. Although histology has long been the diagnostic gold standard, new technologies including mass spectrometry of tiny tissue samples and highly specific imaging comprising; I123 labelled serum amyloid P (SAP) component scintigraphy, 99mTc-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy and cardiac MRI (CMR), have lately transformed the evaluation of patients. A multidisciplinary approach to management is key. Treatment comprises support of failing amyloidotic organs, measures to reduce production of the respective amyloid fibril protein such as suppression of serum amyloid A (SAA) in systemic AA amyloidosis, and recently, novel therapies aimed at enhancing clearing of existing amyloid deposits.

Keywords

Amyloidosis Autoinflammatory Systemic Suppression Nephrotic syndrome Heart failure Chemotherapy Neuropathy 

Abbreviations

ACE

Angiotensin-converting enzyme

AEF

Amyloid-enhancing factor

ARB

Angiotensin receptor blockers

ASCT

Autologous stem cell transplantation

BJP

Bence Jones proteinuria

CAPS

Cryopyrin-associated autoinflammatory syndrome

CINCA

Chronic inflammatory neurological cutaneous articular

CKD

Chronic kidney disease

CMR

Cardiac MRI

CPHPC

((R)-1-(6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexa-noyl) pyrrolidine-2 carboxylic acid), a novel bis (D-proline)

DPD

99mTc-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD)

eGFR

Estimated glomerular filtration rate

ESRD

End stage renal disease

ESRF

End stage renal failure

FAP

Familial amyloid polyneuropathy

FCAS

Familial cold autoinflammatory syndrome

FLC

Free light chains

FMF

Familial Mediterranean fever

GAG

Glycosaminoglycans

IHC

Immunohistochemical

IVSD

Interventricular septal diameter

MGUS

Monoclonal gammopathy of unknown significance

MKD

Mevalonate kinase deficiency

MM

Multiple myeloma

MWS

Muckle-Wells syndrome

NAC

National Amyloidosis Centre

NOMID

Neonatal onset multisystem inflammatory disease

NT-proBNP

N terminal pro brain natriuretic peptide

SAA

Serum amyloid A

SAP

Serum amyloid P

TNF

Tumor necrosis factor

TRAPS

TNF receptor-associated periodic syndrome

TTR

Transthyretin

UK

United Kingdom

USA

United States of America

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.National Amyloidosis Centre, UCL Division of Medicine, Royal Free CampusLondonUK
  2. 2.UCL Centre for Nephrology, Division of MedicineUniversity College London, Royal Free CampusLondonUK

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