Skip to main content
SpringerLink
Log in

Systemic Amyloidosis

  • Chapter
  • First Online:
Textbook of Autoinflammation

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

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

References

  1. Lachmann HJ, Hawkins PN. Systemic amyloidosis. Curr Opin Pharmacol. 2006;6:214–20.

    Article  CAS  PubMed  Google Scholar 

  2. Pepys MB. Amyloidosis. In: Frank MM, Austen KF, Claman HN, Unanue ER, editors. Samter’s immunologic diseases. 5th ed. Boston: Little, Brown and Company; 1994. p. 637–55.

    Google Scholar 

  3. Sipe JD, Benson MD, Buxbaum JN, et al. Nomenclature 2014: Amyloid fibril proteins and clinical classification of the amyloidosis. Amyloid. 2014;21:221–4.

    Article  PubMed  Google Scholar 

  4. Pepys MB. Amyloidosis. Annu Rev Med. 2006;57:223–41.

    Article  CAS  PubMed  Google Scholar 

  5. Bonar L, Cohen AS, Skinner MM. Characterization of the amyloid fibril as a cross-beta protein. Proc Soc Exp Biol Med. 1969;131:1373–5.

    Article  CAS  PubMed  Google Scholar 

  6. Glenner GG, Eanes ED, Bladen HA, Linke RP, Termine JD. β-pleated sheet fibrils. A comparison of native amyloid with synthetic protein fibrils. Prog Histochem Cytochem. 1974;22:1141–58.

    Article  CAS  Google Scholar 

  7. Jaroniec CP, MacPhee CE, Bajaj VS, McMahon MT, Dobson CM, Griffin RG. High-resolution molecular structure of a peptide in an amyloid fibril determined by magic angle spinning NMR spectroscopy. Proc Natl Acad Sci U S A. 2004;101:711–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Pepys MB, Rademacher TW, Amatayakul-Chantler S, et al. Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure. Proc Natl Acad Sci U S A. 1994;91:5602–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Botto M, Hawkins PN, Bickerstaff MCM, et al. Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene. Nat Med. 1997;3:855–9.

    Article  CAS  PubMed  Google Scholar 

  10. Reixach N, Deechongkit S, Jiang X, Kelly JW, Buxbaum JN. Tissue damage in the amyloidoses: transthyretin monomers and nonnative oligomers are the major cytotoxic species in tissue culture. Proc Natl Acad Sci U S A. 2004;101:2817–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lundmark K, Westermark GT, Nystrom S, Murphy CL, Solomon A, Westermark P. Transmissibility of systemic amyloidosis by a prion-like mechanism. Proc Natl Acad Sci U S A. 2002;99:6979–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lachmann HJ, Goodman HJB, Gilbertson JA, et al. Natural history and outcome in systemic AA amyloidosis. N Engl J Med. 2007;356:2361–71.

    Article  CAS  PubMed  Google Scholar 

  13. Stangou AJ, Hawkins PN, Heaton ND, et al. Progressive cardiac amyloidosis following liver transplantation for familial amyloid polyneuropathy: implications for amyloid fibrillogenesis. Transplantation. 1998;66:229–33.

    Article  CAS  PubMed  Google Scholar 

  14. Hawkins PN. Studies with radiolabelled serum amyloid P component provide evidence for turnover and regression of amyloid deposits in vivo. Clin Sci. 1994;87:289–95.

    Article  CAS  Google Scholar 

  15. Van Rooijen N, Sanders A. Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods. 1994;174:83–93.

    Article  PubMed  Google Scholar 

  16. Pepys MB. Pathogenesis, diagnosis and treatment of systemic amyloidosis. Philos Trans R Soc Lond Ser B Biol Sci. 2001;356:203–10; discussion 10–1.

    Article  CAS  Google Scholar 

  17. Pinney JH, Smith CJ, Taube JB, et al. Systemic amyloidosis in England: an epidemiological study. Br J Haematol. 2013;161:525–32.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Tanskanen M, Peuralinna T, Polvikoski T, et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study. Ann Med. 2008;40:232–9.

    Article  CAS  PubMed  Google Scholar 

  19. Hawkins PN. Systemic amyloidosis. In: Weinsten WM, Hawkey CJ, Bosch J, editors. Clinical gastroenterology and hepatology. 1st ed. London: Elseiver Health Sciences; 2005. p. 853–8.

    Google Scholar 

  20. Livneh A, Langevitz P, Zemer D, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum. 1997;40:1879–85.

    Article  CAS  PubMed  Google Scholar 

  21. Sipe J. Revised nomenclature for serum amyloid A (SAA). Nomenclature Committee of the International Society of Amyloidosis. Part 2. Amyloid. 1999;6:67–70.

    Article  CAS  PubMed  Google Scholar 

  22. Sun L, Ye RD. Serum amyloid A1: structure, function and gene polymorphism. Gene. 2016;583:48–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nakamura T, Higashi S, Tomoda K, Tsukano M, Baba S, Shono M. Significance of SAA1.3 allele genotype in Japanese patients with amyloidosis secondary to rheumatoid arthritis. Rheumatology (Oxford). 2006;45:43–9.

    Article  CAS  Google Scholar 

  24. Akar N, Hasipek M, Akar E, Ekim M, Yalcinkaya F, Cakar N. Serum amyloid A1 and tumor necrosis factor-alpha alleles in Turkish familial Mediterranean fever patients with and without amyloidosis. Amyloid. 2003;10:12–6.

    Article  CAS  PubMed  Google Scholar 

  25. Touitou I. The spectrum of familial Mediterranean fever (FMF) mutations. Eur J Hum Genet. 2001;9:473–83.

    Article  CAS  PubMed  Google Scholar 

  26. Mukhin NA, Kozlovskaya LV, Bogdanova MV, Rameev VV, Moiseev SV, Simonyan A. Predictors of AA amyloidosis in familial Mediterranean fever. Rheumatol Int. 2015;35:1257–61.

    Article  CAS  PubMed  Google Scholar 

  27. Touitou I, Sarkisian T, Medlej-Hashim M, et al. Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever. Arthritis Rheum. 2007;56:1706–12.

    Article  PubMed  Google Scholar 

  28. Lachmann HJ, Papa R, Gerhold K, et al. The phenotype of TNF receptor-associated autoinflammatory syndrome (TRAPS) at presentation: a series of 158 cases from the Eurofever/EUROTRAPS international registry. Ann Rheum Dis. 2014;73:2160–7.

    Article  CAS  PubMed  Google Scholar 

  29. Georgin-Lavialle S, Stankovic Stojanovic K, Buob D, et al. French Amyloidosis CAPS study: AA Amyloidosis complicating cryopyrin-associated periodic syndrome: a study on 14 cases and review of 53 cases from literature. Pediatr Rheumatol Online J. 2015;13(Suppl 1):P32.

    Article  PubMed Central  Google Scholar 

  30. Lovat LB, Persey MR, Madhoo S, Pepys MB, Hawkins PN. The liver in systemic amyloidosis: insights from 123I serum amyloid P component scintigraphy in 484 patients. Gut. 1998;42:727–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kyle RA, Linos A, Beard CM, et al. Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood. 1992;79:1817–22.

    CAS  PubMed  Google Scholar 

  32. Kyle RA, Bayrd ED. Amyloidosis: review of 236 cases. Medicine. 1975;54:271–99.

    Article  CAS  PubMed  Google Scholar 

  33. Sattianayagam PT, Hawkins PN, Gillmore JD. Systemic amyloidosis and the gastrointestinal tract. Nat Rev Gastroenterol Hepatol. 2009;6:608–17.

    Article  CAS  PubMed  Google Scholar 

  34. Dwulet FE, Benson MD. Primary structure of an amyloid prealbumin and its plasma precursor in a heredofamilial polyneuropathy of Swedish origin. Proc Natl Acad Sci U S A. 1984;81:694–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Suhr O, Danielsson A, Holmgren G, Steen L. Malnutrition and gastrointestinal dysfunction as prognostic factors for survival in familial amyloidotic polyneuropathy. J Intern Med. 1994;235:479–85.

    Article  CAS  PubMed  Google Scholar 

  36. Marcoux J, Mangione PP, Porcari R, et al. A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis. EMBO Mol Med. 2015;7:1337–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gillmore JD, Lachmann HJ, Rowczenio D, et al. Diagnosis, pathogenesis, treatment, and prognosis of hereditary fibrinogen A alpha-chain amyloidosis. J Am Soc Nephrol. 2009;20:444–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Westermark P, Sletten K, Johansson B, Cornwell GG. Fibril in senile systemic amyloidosis is derived from normal transthyretin. Proc Natl Acad Sci U S A. 1990;87:2843–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Westermark P, Bergstrom J, Solomon A, Murphy C, Sletten K. Transthyretin-derived senile systemic amyloidosis: clinicopathologic and structural considerations. Amyloid. 2003;10(Suppl 1):48–54.

    CAS  PubMed  Google Scholar 

  40. Youngstein T, Gilbertson JA, Hutt DF, et al. Carpal Tunnel biopsy identifying transthyretin amyloidosis. Arthritis Rheumatol (Hoboken, NJ). 2017;69:2051.

    Article  Google Scholar 

  41. Puchtler H, Sweat F, Levine M. On the binding of Congo red by amyloid. J Histochem Cytochem. 1962;10:355–64.

    Article  CAS  Google Scholar 

  42. van Gameren II, Hazenberg BP, Bijzet J, van Rijswijk MH. Diagnostic accuracy of subcutaneous abdominal fat tissue aspiration for detecting systemic amyloidosis and its utility in clinical practice. Arthritis Rheum. 2006;54:2015–21.

    Article  PubMed  Google Scholar 

  43. Guy CD, Jones CK. Abdominal fat pad aspiration biopsy for tissue confirmation of systemic amyloidosis: specificity, positive predictive value, and diagnostic pitfalls. Diagn Cytopathol. 2001;24:181–5.

    Article  CAS  PubMed  Google Scholar 

  44. Ebert EC, Nagar M. Gastrointestinal manifestations of amyloidosis. Am J Gastroenterol. 2008;103:776–87.

    Article  PubMed  Google Scholar 

  45. Quarta CC, Gonzalez-Lopez E, Gilbertson JA, et al. Diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis. Eur Heart J. 2017;38:1905–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Silver MM, Hearn SA, Walton JC, Lines LA, Walley VM. Immunogold quantitation of immunoglobulin light chains in renal amyloidosis and kappa light chain nephropathy. Am J Pathol. 1990;136:997–1007.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Gilbertson JA, Theis JD, Vrana JA, et al. A comparison of immunohistochemistry and mass spectrometry for determining the amyloid fibril protein from formalin-fixed biopsy tissue. J Clin Pathol. 2015;68:314–7.

    Article  PubMed  Google Scholar 

  48. Vrana JA, Gamez JD, Madden BJ, Theis JD, Bergen HR 3rd, Dogan A. Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood. 2009;114:4957–9.

    Article  CAS  PubMed  Google Scholar 

  49. Vrana JA, Theis JD, Dasari S, et al. Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics. Haematologica. 2014;99:1239–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Mangione PP, Mazza G, Gilbertson JA, et al. Increasing the accuracy of proteomic typing by decellularisation of amyloid tissue biopsies. J Proteome. 2017;165:113–8.

    Article  CAS  Google Scholar 

  51. Lachmann HJ, Booth DR, Booth SE, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med. 2002;346:1786–91.

    Article  CAS  PubMed  Google Scholar 

  52. Landau HJ, Comenzo RL, Zhou P, et al. Al amyloidosis in a patient with a T60A TTR mutation. XIth International Symposium on Amyloidosis 2008:160–2.

    Google Scholar 

  53. Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354:1362–9.

    Article  CAS  PubMed  Google Scholar 

  54. Hawkins PN, Lavender JP, Pepys MB. Evaluation of systemic amyloidosis by scintigraphy with 123I-labeled serum amyloid P component. N Engl J Med. 1990;323:508–13.

    Article  CAS  PubMed  Google Scholar 

  55. Richards DB, Cookson LM, Berges AC, et al. Therapeutic clearance of amyloid by antibodies to serum amyloid P component. N Engl J Med. 2015;373:1106–14.

    Article  CAS  PubMed  Google Scholar 

  56. Wechalekar AD, Schonland SO, Kastritis E, et al. A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood. 2013;121:3420–7.

    Article  CAS  PubMed  Google Scholar 

  57. Gertz MA, Comenzo R, Falk RH, et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis. Am J Hematol. 2005;79:319–28.

    Article  PubMed  Google Scholar 

  58. Falk RH. Diagnosis and management of the cardiac amyloidoses. Circulation. 2005;112:2047–60.

    Article  PubMed  Google Scholar 

  59. Perugini E, Rapezzi C, Piva T, et al. Non-invasive evaluation of the myocardial substrate of cardiac amyloidosis by gadolinium cardiac magnetic resonance. Heart. 2006;92:343–9.

    Article  CAS  PubMed  Google Scholar 

  60. Martinez-Naharro A, Treibel TA, Abdel-Gadir A, et al. Magnetic resonance in transthyretin cardiac amyloidosis. J Am Coll Cardiol. 2017;70:466–77.

    Article  CAS  PubMed  Google Scholar 

  61. Murtagh B, Hammill SC, Gertz MA, Kyle RA, Tajik AJ, Grogan M. Electrocardiographic findings in primary systemic amyloidosis and biopsy-proven cardiac involvement. Am J Cardiol. 2005;95:535–7.

    Article  PubMed  Google Scholar 

  62. Dubrey SW, Cha K, Anderson J, et al. The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement. QJM. 1998;91:141–57.

    Article  CAS  PubMed  Google Scholar 

  63. Sayed RH, Rogers D, Khan F, et al. A study of implanted cardiac rhythm recorders in advanced cardiac AL amyloidosis. Eur Heart J. 2015;36:1098–105.

    Article  PubMed  Google Scholar 

  64. Rapezzi C, Merlini G, Quarta CC, et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation. 2009;120:1203–12.

    Article  CAS  PubMed  Google Scholar 

  65. Gillmore JD, Damy T, Fontana M, et al. A new staging system for cardiac transthyretin amyloidosis. Eur Heart J. 2018;39:2799–806.

    Article  PubMed  Google Scholar 

  66. Lachmann HJ, Gallimore R, Gillmore JD, et al. Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br J Haematol. 2003;122:78–84.

    Article  CAS  PubMed  Google Scholar 

  67. Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133:2404–12.

    Article  CAS  PubMed  Google Scholar 

  68. Bochtler T, Hegenbart U, Kunz C, et al. Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study. Blood. 2016;128:594–602.

    Article  CAS  PubMed  Google Scholar 

  69. Bahlis NJ, Lazarus HM. Multiple myeloma-associated AL amyloidosis: is a distinctive therapeutic approach warranted? Bone Marrow Transplant. 2006;38:7–15.

    Article  CAS  PubMed  Google Scholar 

  70. Derlin T, Bannas P. Imaging of multiple myeloma: current concepts. World J Orthop. 2014;5:272–82.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Dispenzieri A, Gertz M, Kyle R, et al. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol. 2004;22:3751–7.

    Article  CAS  PubMed  Google Scholar 

  72. Mannu GS. The non-cardiac use and significance of cardiac troponins. Scott Med J. 2014;59:172–8.

    Article  PubMed  Google Scholar 

  73. Palladini G, Foli A, Milani P, et al. Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure. Am J Hematol. 2012;87:465–71.

    Article  CAS  PubMed  Google Scholar 

  74. Sanders PW. Mechanisms of light chain injury along the tubular nephron. J Am Soc Nephrol. 2012;23:1777–81.

    Article  CAS  PubMed  Google Scholar 

  75. Sattianayagam PT. The pathogenesis, investigation and management of systemic amyloidosis. London: UCL Medical School; 2012.

    Google Scholar 

  76. Brater DC. Diuretic therapy. N Engl J Med. 1998;339:387–95.

    Article  CAS  PubMed  Google Scholar 

  77. Ruggenenti P, Mosconi L, Vendramin G, et al. ACE inhibition improves glomerular size selectivity in patients with idiopathic membranous nephropathy and persistent nephrotic syndrome. Am J Kidney Dis. 2000;35:381–91.

    Article  CAS  PubMed  Google Scholar 

  78. Odabas AR, Cetinkaya R, Selcuk Y, Bilen H. Effect of losartan treatment on the proteinuria in normotensive patients having proteinuria due to secondary amyloidosis. Ups J Med Sci. 2001;106:183–8.

    Article  CAS  PubMed  Google Scholar 

  79. Rezk T, Whelan CJ, Lachmann HJ, et al. Role of implantable intracardiac defibrillators in patients with cardiac immunoglobulin light chain amyloidosis. Br J Haematol. 2018;182:145–8.

    Article  PubMed  Google Scholar 

  80. Gillmore JD, Lachmann HJ, Wechalekar A, Hawkins PN. Hereditary fibrinogen A alpha-chain amyloidosis: clinical phenotype and role of liver transplantation. Blood. 2010;115:4313; author reply 4–5.

    Article  CAS  PubMed  Google Scholar 

  81. Lane T, Loeffler JM, Rowczenio DM, et al. AA amyloidosis complicating the hereditary periodic fever syndromes. Arthritis Rheum 2013;65(4):1116–1121.

    Google Scholar 

  82. Ugurlu S, Ergezen B, Hacioglu A, Ozdogan H. Anti-interleukin 1 therapy in FMF amyloidosis: a single center experience (Case Series). Ann Rheum Dis. 2017;76:412.

    Google Scholar 

  83. Lane T, Gillmore JD, Wechalekar AD, Hawkins PN, Lachmann HJ. Therapeutic blockade of interleukin-6 by tocilizumab in the management of AA amyloidosis and chronic inflammatory disorders: a case series and review of the literature. Clin Exp Rheumatol. 2015;33(Suppl 94):46–53.

    Google Scholar 

  84. Ugurlu S, Hacioglu A, Adibnia Y, Hamuryudan V, Ozdogan H. Tocilizumab in the treatment of twelve cases with aa amyloidosis secondary to familial Mediterranean fever. Orphanet J Rare Dis. 2017;12:105.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Pinney JH, Lachmann HJ, Sattianayagam PT, et al. Renal transplantation in systemic amyloidosis-importance of amyloid fibril type and precursor protein abundance. Am J Transplant. 2013;13:433–41.

    Article  CAS  PubMed  Google Scholar 

  86. Moser C, Pohl G, Haslinger I, et al. Successful treatment of familial Mediterranean fever with anakinra and outcome after renal transplantation. Nephrol Dial Transplant. 2009;24:676–8.

    Article  CAS  PubMed  Google Scholar 

  87. Kisilevsky R, Ancsin JB, Szarek WA, Petanceska S. Heparan sulfate as a therapeutic target in amyloidogenesis: prospects and possible complications. Amyloid. 2007;14:21–32.

    Article  CAS  PubMed  Google Scholar 

  88. Dember LM, Hawkins PN, Hazenberg BPC, et al. Eprodisate for the treatment of renal disease in AA amyloidosis. N Engl J Med. 2007;356:2349–60.

    Article  CAS  PubMed  Google Scholar 

  89. Comenzo RL, Reece D, Palladini G, et al. Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain (AL) amyloidosis. Leukemia. 2012;26:2317–25.

    Article  CAS  PubMed  Google Scholar 

  90. Palladini G, Dispenzieri A, Gertz MA, et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012;30:4541–9.

    Article  CAS  PubMed  Google Scholar 

  91. Dimopoulos MA, Kastritis E. Bortezomib for AL amyloidosis: moving forward. Blood. 2011;118:827–8.

    Article  CAS  PubMed  Google Scholar 

  92. Venner CP, Lane T, Foard D, et al. Cyclophosphamide, bortezomib and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression free survival. Blood. 2012;119:4387–90.

    Article  CAS  PubMed  Google Scholar 

  93. Venner CP, Lane T, Foard D, et al. Stringent patient selection improves outcomes in patients with AL amyloidosis undergoing autologous stem cell transplantation. International Society of Amyloidosis; XIIIth International Symposium on Amyloidosis from misfolded proteins to well-designed treatment. 2012;PC58(May):211.

    Google Scholar 

  94. Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet. 2016;387:2641–54.

    Article  CAS  PubMed  Google Scholar 

  95. Coelho T, Maia LF, Martins da Silva A, et al. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology. 2012;79:785–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Sekijima Y, Dendle MA, Kelly JW. Orally administered diflunisal stabilizes transthyretin against dissociation required for amyloidogenesis. Amyloid. 2006;13:236–49.

    Article  CAS  PubMed  Google Scholar 

  97. Berk JL, Suhr OB, Obici L, et al. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA. 2013;310:2658–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Coelho T, Adams D, Silva A, et al. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med. 2013;369:819–29.

    Article  CAS  PubMed  Google Scholar 

  99. Adams D, Suhr OB, Dyck PJ, et al. Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy. BMC Neurol. 2017;17:181.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Edwards CV, Gould J, Langer AL, et al. Interim analysis of the phase 1a/b study of chimeric fibril-reactive monoclonal antibody 11-1F4 in patients with AL amyloidosis. Amyloid. 2017;24(suppl 1):58–9.

    Article  PubMed  Google Scholar 

  101. Edwards CV, Gould J, Langer AL, et al. Final analysis of the phase 1a/b study of chimeric fibril-reactive monoclonal antibody 11-1f4 in patients with relapsed or refractory AL amyloidosis. Blood. 2017;130:509.

    Google Scholar 

  102. Tennent GA, Lovat LB, Pepys MB. Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer’s disease and systemic amyloidosis. Proc Natl Acad Sci U S A. 1995;92:4299–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Amyloidosis Centre, UCL Division of Medicine, Royal Free Campus, London, UK

    Tamer Rezk & Philip N. Hawkins

  2. UCL Centre for Nephrology, Division of Medicine, University College London, Royal Free Campus, London, UK

    Tamer Rezk

Authors
  1. Tamer Rezk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philip N. Hawkins
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philip N. Hawkins .

Editor information

Editors and Affiliations

  1. Pediatric Rheumatology Unit, Shaare Zedek Medical Center and Hebrew University, Jerusalem, Israel

    Philip J. Hashkes

  2. Department Paediatrics, Division of Rheumatology, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada

    Ronald M. Laxer

  3. Department of Internal Medicine, Radboudumc Expertisecenter for Immunodeficiency and Autoinflammation, Radboud University Medical Center, Nijmegen, The Netherlands

    Anna Simon

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Rezk, T., Hawkins, P.N. (2019). Systemic Amyloidosis. In: Hashkes, P., Laxer, R., Simon, A. (eds) Textbook of Autoinflammation. Springer, Cham. https://doi.org/10.1007/978-3-319-98605-0_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-98605-0_15

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-98604-3

  • Online ISBN: 978-3-319-98605-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation