Amyloidosis

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Amyloidosis Main page

Overview

Historical Perspective

Classification

AL amyloidosis
AA amyloidosis
Heritable amyloidosis
Age-related (senile) systemic amyloidosis
Dialysis-related amyloidosis

Pathophysiology

Systemic Amyloidosis
Organ-specific Amyloidosis
Microscopic Pathology

Causes

Differentiating Amyloidosis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

For patient information, click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2]

Overview

In 1639, Nicolaus Fontanus autopsied a young man who had ascitis, jaundice, liver abscess and splenomegaly and his report has been the first description of amyloidosis. and in 1959, Cohen and Calkins assessed an ultra-thin sections of amyloidotic tissues by electron microscopic examination. Amyloidosis may be classified based on precursor of amyloidogenic protein into different subtypes, include AL amyloidosis (Light chains of immunoglobulines), AA amyloidosis (Serum amyloid A protein), AF amyloidosis (Mutant transthyretin, A1-apolipoprotein, gelsolin, fibrinogen, etc.), ATTRwt amyloidosis (Wild-type transthyretin), and AH amyloidosis (ß2-microglobulin). Amyloidosis also may classified by their extension of organ involvement as systemic amyloidosis (primary amyloidosis, secondary amyloidosis, hereditary amyloidosis) and Organ-specific amyloidosis (cardiac amyloidosis, hepatic amyloidosis, renal amyloidosis, etc.). Amyloid is an abnormal insoluble extracellular protein that deposits in the different tissues and causes organic dysfunction. These abnormal amyloids derived from misfolding and aggregation of normally soluble proteins. In systemic amyloidosis, amyloid gradually accumulate and amyloid deposition is widespread in the viscera, blood vessel walls, and in the different connective tissues. In organ-specific amyloidoses, amyloid deposition occurs only in the origin organ or tissue of precursor protein. In microscopy pathology of amyloidosis, amyloid is detectable as typical green birefringence under polarized light after Congo red staining, linear non-branching fibrils, distinct X-ray diffraction pattern consistent with Pauling's model of a cross-beta fibril.

Historical Perspective

Classification

Amyloidosis may be classified based on precursor of amyloidogenic protein into different subtypes, include:[4][5]

Type Amyloidogenic protein/ fibril Clinical syndrome
AL (primary amyloidosis) Light chains of immunoglobulines (most common type) Monoclonal gammopathy
AA (secondary amyloidosis) Serum amyloid A protein Chronic inflammatory diseases
AF Mutant transthyretin, A1-apolipoprotein, gelsolin, fibrinogen, etc. Familial polyneuropathy/cardiomyopathy/nephropathy
ATTRwt Wild-type transthyretin Senile restrictive cardiomyopathy _ Transthyretin-related amyloidosis wild-type
AH ß2-microglobulin Long-term hemodialysis

Amyloidosis also may classified by their extension of organ involvement as below:[6][7]

Classification subtypes Causes Important clinical findings
Systemic amyloidosis Primary amyloidosis (AL)
Secondary amyloidosis (AA)
Hereditary amyloidosis
Organ-specific amyloidosis Renal amyloidosis
Cardiac amyloidosis
Hepatic amyloidosis
Amyloid neuropathy
Gastrointestinal amyloidosis

Pathophysiology

  • Amyloid is an abnormal insoluble extracellular protein that deposits in the different tissues and causes organic dysfunction and a wide variety of clinical syndromes.[8][9]
  • These abnormal amyloids derived from misfolding and aggregation of normally soluble proteins.[10]
  • Amyloid deposition can disrupt tissue structure of involved organ and consequently leads to organ failure.[11]

Systemic Amyloidosis

Primary Amyloidosis (AL)

For more information about primary amyloidosis click here.

Secondary Amyloidosis (AA)

For more information about secondary amyloidosis click here.

Hereditary Amyloidosis

Organ-specific Amyloidosis

Microscopic Pathology

In microscopy pathology of amyloidosis, amyloid is detectable as:[16][13]

  • Typical green birefringence under polarized light after Congo red staining (appears in red under normal light)
  • Linear non-branching fibrils (indefinite length with an approximately same diameter)
  • Distinct X-ray diffraction pattern consistent with Pauling's model of a cross-beta fibril

Case Studies

Case #1

  1. 1.0 1.1 1.2 Kyle RA (June 2011). "Amyloidosis: a brief history". Amyloid. 18 Suppl 1: 6–7. doi:10.3109/13506129.2011.574354001. PMID 21838413.
  2. 2.0 2.1 Sipe JD, Cohen AS (June 2000). "Review: history of the amyloid fibril". J. Struct. Biol. 130 (2–3): 88–98. doi:10.1006/jsbi.2000.4221. PMID 10940217.
  3. Khan MF, Falk RH (November 2001). "Amyloidosis". Postgrad Med J. 77 (913): 686–93. PMC 1742163. PMID 11677276.
  4. Real de Asúa D, Costa R, Galván JM, Filigheddu MT, Trujillo D, Cadiñanos J (2014). "Systemic AA amyloidosis: epidemiology, diagnosis, and management". Clin Epidemiol. 6: 369–77. doi:10.2147/CLEP.S39981. PMC 4218891. PMID 25378951.
  5. Misumi Y, Ando Y (July 2014). "[Classification of amyloidosis]". Brain Nerve (in Japanese). 66 (7): 731–7. PMID 24998818.
  6. Bilginer Y, Akpolat T, Ozen S (August 2011). "Renal amyloidosis in children". Pediatr. Nephrol. 26 (8): 1215–27. doi:10.1007/s00467-011-1797-x. PMC 3119800. PMID 21360109.
  7. Khoor A, Colby TV (February 2017). "Amyloidosis of the Lung". Arch. Pathol. Lab. Med. 141 (2): 247–254. doi:10.5858/arpa.2016-0102-RA. PMID 28134587.
  8. Gillmore JD, Hawkins PN (October 2013). "Pathophysiology and treatment of systemic amyloidosis". Nat Rev Nephrol. 9 (10): 574–86. doi:10.1038/nrneph.2013.171. PMID 23979488.
  9. 9.0 9.1 Baker KR, Rice L (2012). "The amyloidoses: clinical features, diagnosis and treatment". Methodist Debakey Cardiovasc J. 8 (3): 3–7. PMC 3487569. PMID 23227278.
  10. 10.0 10.1 Pepys MB (2006). "Amyloidosis". Annu. Rev. Med. 57: 223–41. doi:10.1146/annurev.med.57.121304.131243. PMID 16409147.
  11. Jerzykowska S, Cymerys M, Gil LA, Balcerzak A, Pupek-Musialik D, Komarnicki MA (2014). "Primary systemic amyloidosis as a real diagnostic challenge - case study". Cent Eur J Immunol. 39 (1): 61–6. doi:10.5114/ceji.2014.42126. PMC 4439975. PMID 26155101.
  12. Desport E, Bridoux F, Sirac C, Delbes S, Bender S, Fernandez B, Quellard N, Lacombe C, Goujon JM, Lavergne D, Abraham J, Touchard G, Fermand JP, Jaccard A (August 2012). "Al amyloidosis". Orphanet J Rare Dis. 7: 54. doi:10.1186/1750-1172-7-54. PMC 3495844. PMID 22909024.
  13. 13.0 13.1 13.2 13.3 Khan MF, Falk RH (November 2001). "Amyloidosis". Postgrad Med J. 77 (913): 686–93. PMC 1742163. PMID 11677276.
  14. Desport E, Bridoux F, Sirac C, Delbes S, Bender S, Fernandez B, Quellard N, Lacombe C, Goujon JM, Lavergne D, Abraham J, Touchard G, Fermand JP, Jaccard A (August 2012). "Al amyloidosis". Orphanet J Rare Dis. 7: 54. doi:10.1186/1750-1172-7-54. PMC 3495844. PMID 22909024.
  15. Merlini G, Seldin DC, Gertz MA (May 2011). "Amyloidosis: pathogenesis and new therapeutic options". J. Clin. Oncol. 29 (14): 1924–33. doi:10.1200/JCO.2010.32.2271. PMC 3138545. PMID 21483018.
  16. 16.0 16.1 Röcken C, Shakespeare A (February 2002). "Pathology, diagnosis and pathogenesis of AA amyloidosis". Virchows Arch. 440 (2): 111–122. doi:10.1007/s00428-001-0582-9. PMID 11964039.
  17. Mahmood S, Palladini G, Sanchorawala V, Wechalekar A (February 2014). "Update on treatment of light chain amyloidosis". Haematologica. 99 (2): 209–21. doi:10.3324/haematol.2013.087619. PMC 3912950. PMID 24497558.
  18. Blancas-Mejía LM, Ramirez-Alvarado M (2013). "Systemic amyloidoses". Annu. Rev. Biochem. 82: 745–74. doi:10.1146/annurev-biochem-072611-130030. PMC 4044913. PMID 23451869.

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