Amyloidosis: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
Line 7: Line 7:
   
   
==Overview==
==Overview==
In 1639, Nicolaus Fontanus [[Autopsy|autopsied]] a young man who had [[ascites|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 microscope|electron microscopic]] examination. Amyloidosis may be classified based on [[precursor]] of amyloidogenic [[protein]] into different subtypes, include AL amyloidosis ([[Light chain|Light chains]] of [[Immunoglobulin|immunoglobulines]]), AA amyloidosis ([[Serum amyloid A|Serum amyloid A protein]]), AF amyloidosis (Mutant [[transthyretin]], [[Apolipoprotein A1|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 ([[AL amyloidosis|primary amyloidosis]], [[AA amyloidosis|secondary amyloidosis]], hereditary amyloidosis) and Organ-specific amyloidosis ([[cardiac amyloidosis]], [[Hepatic amyloidosis with intrahepatic cholestasis|hepatic amyloidosis]], [[renal amyloidosis]], etc.). [[Amyloid]] is an abnormal insoluble [[extracellular]] [[protein]] that deposits in the different tissues and causes organic dysfunction. These abnormal [[Amyloid|amyloids]] derived from misfolding and aggregation of normally soluble [[Protein|proteins]]. In systemic amyloidosis, [[amyloid]] gradually accumulate and [[amyloid]] deposition is widespread in the viscera, [[blood vessel]] walls, and in the different [[Connective tissue|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 [[Polarization|polarized]] light after [[Congo red]] staining, linear non-branching [[Fibril|fibrils]], distinct [[X-rays|X-ray]] diffraction pattern consistent with Pauling's model of a cross-beta fibril.
<br />


== Historical Perspective ==
== Historical Perspective ==
*In 1639, Nicolaus Fontanus [[Autopsy|autopsied]] a young man who had [[ascites|ascitis]], [[jaundice]], [[liver abscess]] and [[splenomegaly]] and his report has been the first description of amyloidosis.
*In 1639, Nicolaus Fontanus [[Autopsy|autopsied]] a young man who had [[ascites|ascitis]], [[jaundice]], [[liver abscess]] and [[splenomegaly]] and his report has been the first description of amyloidosis.
*In 1854, Rudolph Virchow introduced the term of [[amyloid]] as an macroscopic abnormality in some tissues.
*In 1854, Rudolph Virchow introduced the term of [[amyloid]] as an macroscopic abnormality in some tissues.
*In 1867, Weber reported the first case of amyloidosis associated with [[multiple myeloma]].<ref name="pmid218384133">{{cite journal |vauthors=Kyle RA |title=Amyloidosis: a brief history |journal=Amyloid |volume=18 Suppl 1 |issue= |pages=6–7 |date=June 2011 |pmid=21838413 |doi=10.3109/13506129.2011.574354001 |url=}}</ref>
*In 1867, Weber reported the first case of amyloidosis associated with [[multiple myeloma]].
*In 1922, Bennhold introduced [[Congo red|Congo red staining]] of [[amyloid]] that remains the [[Gold standard (test)|gold standard]] for [[diagnosis]].
*In 1922, Bennhold introduced [[Congo red|Congo red staining]] of [[amyloid]] that remains the [[Gold standard (test)|gold standard]] for [[diagnosis]].
*In 1959, Cohen and Calkins used ultra-thin sections of amyloidotic tissues and assessed by [[Electron microscope|electron microscopic]] examination, explained the presence of non-branching [[Fibril|fibrils]] with indeterminate length and variable width.<ref name="pmid10940217">{{cite journal |vauthors=Sipe JD, Cohen AS |title=Review: history of the amyloid fibril |journal=J. Struct. Biol. |volume=130 |issue=2-3 |pages=88–98 |date=June 2000 |pmid=10940217 |doi=10.1006/jsbi.2000.4221 |url=}}</ref><ref name="pmid218384133">{{cite journal |vauthors=Kyle RA |title=Amyloidosis: a brief history |journal=Amyloid |volume=18 Suppl 1 |issue= |pages=6–7 |date=June 2011 |pmid=21838413 |doi=10.3109/13506129.2011.574354001 |url=}}</ref>
*In 1959, Cohen and Calkins used ultra-thin sections of amyloidotic tissues and assessed by [[Electron microscope|electron microscopic]] examination, explained the presence of non-branching [[Fibril|fibrils]] with indeterminate length and variable width.<ref name="pmid218384133">{{cite journal |vauthors=Kyle RA |title=Amyloidosis: a brief history |journal=Amyloid |volume=18 Suppl 1 |issue= |pages=6–7 |date=June 2011 |pmid=21838413 |doi=10.3109/13506129.2011.574354001 |url=}}</ref>


== Classification ==
== PClassification ==


=== Amyloidosis may be classified based on [[precursor]] of amyloidogenic [[protein]] into different subtypes, include: ===
=== Amyloidosis may be classified based on [[precursor]] of amyloidogenic [[protein]] into different subtypes, include: ===
Line 113: Line 113:
|}
|}


== 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.
*
*These abnormal [[Amyloid|amyloids]] derived from misfolding and aggregation of normally soluble [[Protein|proteins]].
*[[Amyloid]] deposition can disrupt tissue structure of involved organ and consequently leads to organ failure.
===Systemic Amyloidosis===
*In systemic amyloidosis, [[amyloid]] gradually accumulate and [[amyloid]] deposition is widespread in the viscera, [[blood vessel]] walls, and in the different [[Connective tissue|connective tissues]].<ref name="pmid23227278">{{cite journal |vauthors=Baker KR, Rice L |title=The amyloidoses: clinical features, diagnosis and treatment |journal=Methodist Debakey Cardiovasc J |volume=8 |issue=3 |pages=3–7 |date=2012 |pmid=23227278 |pmc=3487569 |doi= |url=}}</ref><ref name="pmid16409147">{{cite journal |vauthors=Pepys MB |title=Amyloidosis |journal=Annu. Rev. Med. |volume=57 |issue= |pages=223–41 |date=2006 |pmid=16409147 |doi=10.1146/annurev.med.57.121304.131243 |url=}}</ref>
====Primary Amyloidosis (AL)====
*[[AL amyloidosis|Primary (AL) amyloidosis)]] is the most common type of amyloidosis. It results from aggregation and deposition of monoclonal [[Immunoglobulin|immunoglobulin (Ig)]] [[Light chain|light chains]] that usually produced by [[plasma cell]] clones.
*Change in the [[secondary structure]] or [[tertiary structure]] of a monoclonal [[light chain]] results in abnormal folding of the [[light chain]] that abnormally form [[amyloid]] [[Fibril|fibrils]].
*This type of amyloidosis most frequently involve the [[kidney]] (usually [[proteinuria]] with the [[nephrotic syndrome]]) and the [[heart]].
*In [[AL amyloidosis|primary (AL) amyloidosis]] survival rate depends on:
**Type of organ involvement ([[amyloid]] heart disease is the main prognostic factor)
**The severity of different organs involvement
**[[Hematology|Haematological]] response to treatment
*The median [[Survival analysis|survival]] of patients with [[AL amyloidosis]] is aproximately 3.8 years.
For more information about primary amyloidosis click [[AL amyloidosis|'''here''']].


====Secondary Amyloidosis (AA)====
*[[AA amyloidosis|Secondary amyloidosis]] is associated with chronic [[inflammation]] (such as [[tuberculosis]] or [[rheumatoid arthritis]]).<ref name="pmid116772762">{{cite journal |vauthors=Khan MF, Falk RH |title=Amyloidosis |journal=Postgrad Med J |volume=77 |issue=913 |pages=686–93 |date=November 2001 |pmid=11677276 |pmc=1742163 |doi= |url=}}</ref>
*[[AA amyloidosis|Secondary or reactive amyloidosis (AA)]] is approximately 45% of all systemic amyloidosis.
*[[Pathogenesis]] of [[AA amyloidosis|secondary amyloidosis]] is multifactorial that include:
**[[Primary structure]] of the [[precursor]] protein
**Acute phase response
**Nonfibril [[Protein|proteins]] ([[amyloid]] P component, [[Apolipoprotein E|apo E]], [[Glycosaminoglycan|GAGs]], [[Proteoglycan|proteoglycans]] and [[basement membrane]] [[Protein|proteins]])
**[[Receptor (biochemistry)|Receptors]]
**[[Lipid metabolism]]
**[[Protease|Proteases]]
For more information about secondary amyloidosis click '''[[AA amyloidosis|here]]'''.
====Hereditary Amyloidosis====
*Hereditary (or familial) amyloidosis are [[Autosome|autosomal]] [[Dominance relationship|dominant]] diseases that [[inherited]] variant [[Protein|proteins]] cause the production and deposition of [[amyloid]] fibrils.<ref name="pmid116772762">{{cite journal |vauthors=Khan MF, Falk RH |title=Amyloidosis |journal=Postgrad Med J |volume=77 |issue=913 |pages=686–93 |date=November 2001 |pmid=11677276 |pmc=1742163 |doi= |url=}}</ref>
*Hereditary amyloidosis are due to amyloidogenic [[Mutation|mutations]] and subsequently deposition of [[Amyloid|amyloids]], include:
**[[Transthyretin|Transthyretin (TTR)]] (most common [[inherited]] [[mutation]])
**[[Fibrinogen]]
**[[Apolipoprotein A1]]
**[[Apolipoprotein A2]]
**[[Lysozyme]]
**[[Gelsolin]] [[Gene|genes]]
===Organ-specific Amyloidosis===
*In this type of amyloidoses, [[amyloid]] deposition occurs only in the origin organ or tissue of [[precursor]] [[protein]].
*Some [[Neurodegenerative disease|neurodegenerative disorders]] such as [[Parkinson's disease]], [[Alzheimer's disease|Alzheimer]], and [[Huntington's disease]] may occur in localised amyloidosis.
*Localised amyloidoses can accure due to deposition of [[intracellular]] and/or [[extracellular]] [[amyloid]].
**[[Huntington's disease]]: [[intracellular]] [[protein]] deposition
**[[Parkinson's disease]]: [[intracellular]] [[protein]] deposition
**[[Alzheimer's disease]]: [[intracellular]] ([[Tau protein]] [[Fibril|fibrils]]) and [[extracellular]] ([[amyloid]] β fibrils) deposition
===Microscopic Pathology===
In microscopy pathology of amyloidosis, [[amyloid]] is detectable as:<ref name="pmid119640392">{{cite journal |vauthors=Röcken C, Shakespeare A |title=Pathology, diagnosis and pathogenesis of AA amyloidosis |journal=Virchows Arch. |volume=440 |issue=2 |pages=111–122 |date=February 2002 |pmid=11964039 |doi=10.1007/s00428-001-0582-9 |url=}}</ref><ref name="pmid116772762">{{cite journal |vauthors=Khan MF, Falk RH |title=Amyloidosis |journal=Postgrad Med J |volume=77 |issue=913 |pages=686–93 |date=November 2001 |pmid=11677276 |pmc=1742163 |doi= |url=}}</ref>
*Typical green [[birefringence]] under [[Polarization|polarized]] light after [[Congo red]] staining (appears in red under normal light)
*Linear non-branching [[Fibril|fibrils]] (indefinite length with an approximately same diameter)
*Distinct [[X-rays|X-ray]] diffraction pattern consistent with Pauling's model of a cross-beta fibril
*
*


==Epidemiology and Demographics==
== Natural History, Complications and Prognosis ==
===Incidence===
 
*The incidence of amyloidosis is approximately 1.2 per 100,000 individuals per year worldwide.<ref name="pmid1167727622">{{cite journal |vauthors=Khan MF, Falk RH |title=Amyloidosis |journal=Postgrad Med J |volume=77 |issue=913 |pages=686–93 |date=November 2001 |pmid=11677276 |pmc=1742163 |doi= |url=}}</ref>
 
===Prevalence===
 
*The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
*In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
*The prevalence of [disease/malignancy] is estimated to be [number] cases annually.
 
===Mortality rate===
 
*The mortality rate of systemic amyloidosis is approximately 100 per 100,000 deaths in developed countries.<ref name="pmid164091472">{{cite journal |vauthors=Pepys MB |title=Amyloidosis |journal=Annu. Rev. Med. |volume=57 |issue= |pages=223–41 |date=2006 |pmid=16409147 |doi=10.1146/annurev.med.57.121304.131243 |url=}}</ref>


=== Age===
*In amyloidosis, insoluble fibrils of amyloid are deposited in body organs, causing organ dysfunction and eventually death.<ref name="pmid232272782">{{cite journal |vauthors=Baker KR, Rice L |title=The amyloidoses: clinical features, diagnosis and treatment |journal=Methodist Debakey Cardiovasc J |volume=8 |issue=3 |pages=3–7 |date=2012 |pmid=23227278 |pmc=3487569 |doi= |url=}}</ref>
*In AL amyloidosis untreated individuals have the worst prognosis. In this group of patients median survival is one to two years.<ref name="pmid11677276">{{cite journal |vauthors=Khan MF, Falk RH |title=Amyloidosis |journal=Postgrad Med J |volume=77 |issue=913 |pages=686–93 |date=November 2001 |pmid=11677276 |pmc=1742163 |doi= |url=}}</ref>


*In amyloidosis, the mean age of presentation is 55-60 years.<ref name="pmid214940832">{{cite journal |vauthors=Shin YM |title=Hepatic amyloidosis |journal=Korean J Hepatol |volume=17 |issue=1 |pages=80–3 |date=March 2011 |pmid=21494083 |pmc=3304630 |doi=10.3350/kjhep.2011.17.1.80 |url=}}</ref>
In patients with amyloidosis the most frequent complications include:<ref name="pmid26155101">{{cite journal |vauthors=Jerzykowska S, Cymerys M, Gil LA, Balcerzak A, Pupek-Musialik D, Komarnicki MA |title=Primary systemic amyloidosis as a real diagnostic challenge - case study |journal=Cent Eur J Immunol |volume=39 |issue=1 |pages=61–6 |date=2014 |pmid=26155101 |pmc=4439975 |doi=10.5114/ceji.2014.42126 |url=}}</ref>


===Race===
*Heart failure
*Nephrotic syndrome
*Hepatomegaly
*Peripheral neuropathy


*Hereditary amyloidosis subtypes include a substitution of an amino acid that is detected in approximately 4% of the black population.<ref name="pmid116772763">{{cite journal |vauthors=Khan MF, Falk RH |title=Amyloidosis |journal=Postgrad Med J |volume=77 |issue=913 |pages=686–93 |date=November 2001 |pmid=11677276 |pmc=1742163 |doi= |url=}}</ref>
In primary (AL) amyloidosis survival rate depends on:<ref name="pmid22909024">{{cite journal |vauthors=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 |title=Al amyloidosis |journal=Orphanet J Rare Dis |volume=7 |issue= |pages=54 |date=August 2012 |pmid=22909024 |pmc=3495844 |doi=10.1186/1750-1172-7-54 |url=}}</ref>
*[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].


===Gender ===
*Type of organ involvement (amyloid heart disease is the main prognostic factor)
*The severity of different organs involvement
* Haematological response to treatment


*Men are more commonly affected by amyloidosis than women.<ref name="pmid21494083">{{cite journal |vauthors=Shin YM |title=Hepatic amyloidosis |journal=Korean J Hepatol |volume=17 |issue=1 |pages=80–3 |date=March 2011 |pmid=21494083 |pmc=3304630 |doi=10.3350/kjhep.2011.17.1.80 |url=}}</ref>
*The median survival of patients with AL amyloidosis is aproximately 3.8 years.<ref name="pmid21483018">{{cite journal |vauthors=Merlini G, Seldin DC, Gertz MA |title=Amyloidosis: pathogenesis and new therapeutic options |journal=J. Clin. Oncol. |volume=29 |issue=14 |pages=1924–33 |date=May 2011 |pmid=21483018 |pmc=3138545 |doi=10.1200/JCO.2010.32.2271 |url=}}</ref>
*In primary (AL) amyloidosis 27% of patients dying within 1 year from diagnosis.
* The major determinant of outcome in amyloidosis is the extent of cardiac involvement.
**Cardiac amyloidosis is the cause of death in 75% of the patients who died, including sudden death in 25%.


==Case Studies==
==Case Studies==

Revision as of 17:08, 24 October 2019

Amyloidosis Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

• Primary amyloidosis
• Secondary amyloidosis
• Familial amyloidosis
• Wild-type (senile) amyloidosis
• Cardiac amyloidosis
• Beta-2 microglobulin related amyloidosis
• Gelsolin related amyloidosis
• Lysozyme amyloid related amyloidosis
• Leucocyte cell-derived chemotaxin 2 related amyloidosis
• Fibrinogen A alpha-chain associated amyloidosis

Pathophysiology

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

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Amyloidosis On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Amyloidosis

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Amyloidosis

CDC on Amyloidosis

Amyloidosis in the news

Blogs on Amyloidosis

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for Amyloidosis

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


Historical Perspective

PClassification

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

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:

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

Natural History, Complications and Prognosis

  • In amyloidosis, insoluble fibrils of amyloid are deposited in body organs, causing organ dysfunction and eventually death.[2]
  • In AL amyloidosis untreated individuals have the worst prognosis. In this group of patients median survival is one to two years.[3]

In patients with amyloidosis the most frequent complications include:[4]

  • Heart failure
  • Nephrotic syndrome
  • Hepatomegaly
  • Peripheral neuropathy

In primary (AL) amyloidosis survival rate depends on:[5]

  • Type of organ involvement (amyloid heart disease is the main prognostic factor)
  • The severity of different organs involvement
  • Haematological response to treatment
  • The median survival of patients with AL amyloidosis is aproximately 3.8 years.[6]
  • In primary (AL) amyloidosis 27% of patients dying within 1 year from diagnosis.
  • The major determinant of outcome in amyloidosis is the extent of cardiac involvement.
    • Cardiac amyloidosis is the cause of death in 75% of the patients who died, including sudden death in 25%.

Case Studies

Case #1

  1. ↑ Kyle RA (June 2011). "Amyloidosis: a brief history". Amyloid. 18 Suppl 1: 6–7. doi:10.3109/13506129.2011.574354001. PMID 21838413.
  2. ↑ Baker KR, Rice L (2012). "The amyloidoses: clinical features, diagnosis and treatment". Methodist Debakey Cardiovasc J. 8 (3): 3–7. PMC 3487569. PMID 23227278.
  3. ↑ Khan MF, Falk RH (November 2001). "Amyloidosis". Postgrad Med J. 77 (913): 686–93. PMC 1742163. PMID 11677276.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
Retrieved from "https://www.wikidoc.org/index.php?title=Amyloidosis&oldid=1585588"