Amyloidosis overview: Difference between revisions
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{{Amyloidosis}} | {{Amyloidosis}} | ||
{{CMG}}; {{AE}} | {{CMG}}; {{AE}} | ||
== Overview == | == Overview == | ||
==Historical Perspective== | ==Historical Perspective== | ||
In 1639, Nicolaus Fontanus [[Autopsy|autopsied]] a young man who had [[ascites]], [[jaundice]], [[liver abscess]], and [[splenomegaly]] and his report has been the first description of amyloidosis. There is no significant data regarding the historical perspective of amyloidosis throughout the 18th century. Rudolph Virchow and Weber are the prominent figures with substantial work on amyloidosis during the 19th century. In 1922, Bennhold introduced [[Congo red|Congo Red staining]] of [[amyloid]] that remains the [[Gold standard (test)|gold standard]] for [[diagnosis]]. | |||
==Classification== | ==Classification== | ||
Amyloidosis may be classified on the basis of type of amyloidogenic protein and associated clinical syndromes into primary (AL) amyloidosis, secondary (AA) amyloidosis, familial (AF) amyloidosis, transthyretin (ATTRwt) amyloidosis and dialysis-associated (AH) amyloidosis. It can also be classified based on extent of [[organ system]] involvement | |||
==Pathophysiology== | ==Pathophysiology== | ||
[[Amyloid]] is | [[Amyloid]] is an abnormal insoluble [[extracellular]] [[protein]] that deposits in the different tissues and causes organic dysfunction and a wide variety of clinical syndromes. 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]]. [[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. [[AA amyloidosis|Secondary amyloidosis]] is associated with chronic [[inflammation]] (such as [[tuberculosis]] or [[rheumatoid arthritis]]). Hereditary (or familial) amyloidosis are [[Autosome|autosomal]] [[Dominance relationship|dominant]] diseases that [[inherited]] variant [[Protein|proteins]] cause the production and deposition of [[amyloid]] fibrils. Some [[Neurodegenerative disease|neurodegenerative disorders]]<nowiki/>such as [[Parkinson's disease]], [[Alzheimer's disease|Alzheimer]], and [[Huntington's disease]] may occur in localised amyloidosis. On microscopic pathology, typical green [[birefringence]] under [[Polarization|polarized]] light after [[Congo red]] staining (appears in red under normal light) | ||
==Causes== | ==Causes== | ||
Hereditary amyloidosis can be caused by [[genetic mutations]] in different genes. Causes of acquired amyloidosis can include [[tuberculosis]], [[Familial mediterranean fever|familial Mediterranean fever]], [[rheumatoid arthritis]], [[multiple myeloma]], [[ankylosing spondylitis]], and [[psoriatic arthritis]]. | |||
==Differentiating Amyloidosis from other Diseases== | ==Differentiating Amyloidosis from other Diseases== | ||
Amyloidosis needs to be differentiated from acute [[myocarditis]], [[bronchiectasis]], [[multiple myeloma]] and other systemic diseases . | Amyloidosis needs to be differentiated from acute [[myocarditis]], [[bronchiectasis]], [[multiple myeloma]] and other systemic diseases . | ||
== Epidemiology and Demographics == | |||
The [[incidence]] of amyloidosis is approximately 1.2 per 100,000 individuals per year worldwide. The [[prevalence]] of AL amyloidosis increased significantly between 2007 and 2015, from 1.6 per 100,000 in 2007 to 4.0 per 100,000 in 2015. The [[mortality rate]] of systemic amyloidosis is approximately 100 per 100,000 deaths in developed countries. In amyloidosis, the mean age of presentation is 55 - 60 years. Men are more commonly affected by amyloidosis than women. | |||
==Risk Factors== | ==Risk Factors== | ||
There are no established risk factors for amyloidosis. Some inflammatory conditions might increase the likelihood of [[amyloid]] deposition in the body. | |||
==Screening== | ==Screening== | ||
There is insufficient evidence to recommend routine [[Screening (medicine)|screening]] for amyloidosis. | |||
==Natural History, Complications and Prognosis== | ==Natural History, Complications and Prognosis== | ||
In amyloidosis, insoluble fibrils of [[amyloid]] are deposited in [[organs]], causing [[Multiple organ dysfunction syndrome|organ dysfunction]] and eventually death. [[Patient|Patients]] with amyloidosis may eventually suffer from [[heart failure]], [[nephrotic syndrome]], [[hepatomegaly]] and [[peripheral neuropathy]]. In primary amyloidosis, the [[survival rate]] depends upon the type of [[Organ (anatomy)|organ]] involvement and the [[hematological]] response to treatment. In AL amyloidosis, untreated individuals have the worst [[prognosis]]. In this group of patients, the [[median]] [[Survival rate|survival]] is one to two years. | |||
==Diagnosis== | ==Diagnosis== | ||
===Diagnostic | ===Diagnostic Study of Choice=== | ||
The diagnostic study of choice in amyloidosis is [[Tissue (biology)|tissue]] [[biopsy]] of the affected [[Organ (anatomy)|organ]]. [[Congo red|Congo Red staining]] will show apple green birefringence of the tissue sample under polarized light, and subtyping of [[Light chain|light chains]](for light chain amyloidosis) can be done via [[mass spectrometry]]. [[Bone marrow biopsy]] and organ-specific laboratory measurements are also important ancillary [[Test|tests]]. | |||
===History and Symptoms=== | ===History and Symptoms=== | ||
In amyloidosis, the range of [[symptoms]] depends on specific [[Tissue (biology)|tissues]] and [[organs]] involved. [[Symptoms]] can be quite diverse. | |||
===Physical Examination=== | ===Physical Examination=== | ||
Common findings in amyloidosis include [[petechiae]], [[ecchymosis]], [[parotid gland]] | Common findings in amyloidosis include [[petechiae]], [[ecchymosis]], [[parotid gland enlargement]], increased [[intraocular pressure]], [[enlarged tongue]], [[hepatomegaly]], [[carpal tunnel syndrome]], and [[Raynaud's phenomenon]]. | ||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
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===Electrocardiogram=== | ===Electrocardiogram=== | ||
[[Electrocardiogram]] is particularly useful for cardiac amyloidosis. Findings on [[electrocardiogram]] include low voltage [[QRS complexes]], left and right ventricular [[Hypertrophy (medical)|hypertrophy]], [[Left atrium|left atrial]] abnormalities, pathological [[Q wave|Q waves]], and [[Atrioventricular block|AV block]]. | |||
===Chest X-Ray=== | |||
[[Chest x-ray]] findings in a case of amyloidosis include a coin lesion. | |||
=== | === CT Scan === | ||
[[Computed tomography|CT scan]] can be done to assess for [[amyloid]] deposition in particular [[organs]]. It can also be done to rule out other causes of [[Organ failure|organ dysfunction]]. However, [[MRI]] is more sensitive than [[CT-scans|CT]] in the diagnosis of amyloidosis. | |||
===MRI=== | ===MRI=== | ||
[[MRI]] is commonly done to assess for [[amyloid]] deposition in particular organs. It can also be done to rule out other causes of organ dysfunction. A cardiac [[MRI]] is used when an [[echocardiogram]] fails to differentiate amyloidosis from [[hypertrophic cardiomyopathy]]. | |||
===Echocardiography=== | ===Echocardiography=== | ||
Echocardiography is | [[Echocardiography]] is critical in the [[diagnosis]] of cardiac amyloidosis. [[Echocardiogram]] should be done at [[diagnosis]] and routinely thereafter to monitor response to therapy. | ||
===Other Imaging Findings=== | ===Other Imaging Findings=== | ||
Tissue | Tissue [[doppler]] echocardiography and myocardial strain rate imaging has been shown to be very sensitive for the assessment of myocardial dysfunction in [[restrictive cardiomyopathy]]. The developmend of [[serum amyloid P component]] (SAP) scans has given physicians the ability to specifically locate [[amyloid]] deposits. | ||
===Other Diagnostic Studies=== | ===Other Diagnostic Studies=== | ||
A tissue [[biopsy]] or fat [[aspirate]] should be done to confirm the presence or type of [[amyloid]] protein which is involved in the [[pathogenesis]] of the disease. | |||
==Treatment== | ==Treatment== | ||
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===Medical Therapy=== | ===Medical Therapy=== | ||
There are few available treatments for primary amyloidosis. Since the disease is typically discovered at an advanced stage, the initial treatment is aimed at preventing further [[Organ (anatomy)|organ]] damage and correcting the effects of [[organ failure]]. The most commonly used regimen for AL amyloidosis is CyBorD, which consists of [[cyclophosphamide]], [[bortezomib]], and [[dexamethasone]]. | |||
===Surgery=== | ===Surgery=== | ||
[[Organ transplant|Organ-specific transplant]] may need to be done, depending on the organ involved. However, [[surgery]] is not commonly done in patients with amyloidosis, since it is usually a systemic disease that requires treatment of the underlying cause. | |||
==Prevention== | |||
=== Primary Prevention === | |||
There is no role for [[primary prevention]] in amyloidosis. | |||
===Prevention=== | === Secondary Prevention === | ||
There is no role for secondary prevention in amyloidosis. | |||
==References== | ==References== | ||
Latest revision as of 04:50, 21 November 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Historical Perspective
In 1639, Nicolaus Fontanus autopsied a young man who had ascites, jaundice, liver abscess, and splenomegaly and his report has been the first description of amyloidosis. There is no significant data regarding the historical perspective of amyloidosis throughout the 18th century. Rudolph Virchow and Weber are the prominent figures with substantial work on amyloidosis during the 19th century. In 1922, Bennhold introduced Congo Red staining of amyloid that remains the gold standard for diagnosis.
Classification
Amyloidosis may be classified on the basis of type of amyloidogenic protein and associated clinical syndromes into primary (AL) amyloidosis, secondary (AA) amyloidosis, familial (AF) amyloidosis, transthyretin (ATTRwt) amyloidosis and dialysis-associated (AH) amyloidosis. It can also be classified based on extent of organ system involvement
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. In systemic amyloidosis, amyloid gradually accumulate and amyloid deposition is widespread in the viscera, blood vessel walls, and in the different connective tissues. Primary (AL) amyloidosis) is the most common type of amyloidosis. It results from aggregation and deposition of monoclonal immunoglobulin (Ig) light chains that usually produced by plasma cell clones. Secondary amyloidosis is associated with chronic inflammation (such as tuberculosis or rheumatoid arthritis). Hereditary (or familial) amyloidosis are autosomal dominant diseases that inherited variant proteins cause the production and deposition of amyloid fibrils. Some neurodegenerative disorderssuch as Parkinson's disease, Alzheimer, and Huntington's disease may occur in localised amyloidosis. On microscopic pathology, typical green birefringence under polarized light after Congo red staining (appears in red under normal light)
Causes
Hereditary amyloidosis can be caused by genetic mutations in different genes. Causes of acquired amyloidosis can include tuberculosis, familial Mediterranean fever, rheumatoid arthritis, multiple myeloma, ankylosing spondylitis, and psoriatic arthritis.
Differentiating Amyloidosis from other Diseases
Amyloidosis needs to be differentiated from acute myocarditis, bronchiectasis, multiple myeloma and other systemic diseases .
Epidemiology and Demographics
The incidence of amyloidosis is approximately 1.2 per 100,000 individuals per year worldwide. The prevalence of AL amyloidosis increased significantly between 2007 and 2015, from 1.6 per 100,000 in 2007 to 4.0 per 100,000 in 2015. The mortality rate of systemic amyloidosis is approximately 100 per 100,000 deaths in developed countries. In amyloidosis, the mean age of presentation is 55 - 60 years. Men are more commonly affected by amyloidosis than women.
Risk Factors
There are no established risk factors for amyloidosis. Some inflammatory conditions might increase the likelihood of amyloid deposition in the body.
Screening
There is insufficient evidence to recommend routine screening for amyloidosis.
Natural History, Complications and Prognosis
In amyloidosis, insoluble fibrils of amyloid are deposited in organs, causing organ dysfunction and eventually death. Patients with amyloidosis may eventually suffer from heart failure, nephrotic syndrome, hepatomegaly and peripheral neuropathy. In primary amyloidosis, the survival rate depends upon the type of organ involvement and the hematological response to treatment. In AL amyloidosis, untreated individuals have the worst prognosis. In this group of patients, the median survival is one to two years.
Diagnosis
Diagnostic Study of Choice
The diagnostic study of choice in amyloidosis is tissue biopsy of the affected organ. Congo Red staining will show apple green birefringence of the tissue sample under polarized light, and subtyping of light chains(for light chain amyloidosis) can be done via mass spectrometry. Bone marrow biopsy and organ-specific laboratory measurements are also important ancillary tests.
History and Symptoms
In amyloidosis, the range of symptoms depends on specific tissues and organs involved. Symptoms can be quite diverse.
Physical Examination
Common findings in amyloidosis include petechiae, ecchymosis, parotid gland enlargement, increased intraocular pressure, enlarged tongue, hepatomegaly, carpal tunnel syndrome, and Raynaud's phenomenon.
Laboratory Findings
Laboratory findings in amyloidosis include elevated erythrocyte sedimentation rate, increased BUN level, serum creatinine, protein, casts, or fat bodies in urine. Serum troponin, B-type natriuretic peptide, and beta-2-microglobulin are prognostic markers for heart failure. Amyloid deposits can be identified histologically by Congo red staining and viewing under polarized light where amyloid deposits produce a distinctive 'apple green birefringence'. Alternatively, thioflavin T stain may be used. An abdominal fat pad aspiration, rectal mucosa biopsy, or bone marrow biopsy can help confirm the diagnosis. They reveal positive findings in 80% patients.
Electrocardiogram
Electrocardiogram is particularly useful for cardiac amyloidosis. Findings on electrocardiogram include low voltage QRS complexes, left and right ventricular hypertrophy, left atrial abnormalities, pathological Q waves, and AV block.
Chest X-Ray
Chest x-ray findings in a case of amyloidosis include a coin lesion.
CT Scan
CT scan can be done to assess for amyloid deposition in particular organs. It can also be done to rule out other causes of organ dysfunction. However, MRI is more sensitive than CT in the diagnosis of amyloidosis.
MRI
MRI is commonly done to assess for amyloid deposition in particular organs. It can also be done to rule out other causes of organ dysfunction. A cardiac MRI is used when an echocardiogram fails to differentiate amyloidosis from hypertrophic cardiomyopathy.
Echocardiography
Echocardiography is critical in the diagnosis of cardiac amyloidosis. Echocardiogram should be done at diagnosis and routinely thereafter to monitor response to therapy.
Other Imaging Findings
Tissue doppler echocardiography and myocardial strain rate imaging has been shown to be very sensitive for the assessment of myocardial dysfunction in restrictive cardiomyopathy. The developmend of serum amyloid P component (SAP) scans has given physicians the ability to specifically locate amyloid deposits.
Other Diagnostic Studies
A tissue biopsy or fat aspirate should be done to confirm the presence or type of amyloid protein which is involved in the pathogenesis of the disease.
Treatment
There is no treatment for primary amyloidosis. The initial target in the treatment of this disorder is to correct the organ failure, as the disease is discovered at an advanced stage.
Medical Therapy
There are few available treatments for primary amyloidosis. Since the disease is typically discovered at an advanced stage, the initial treatment is aimed at preventing further organ damage and correcting the effects of organ failure. The most commonly used regimen for AL amyloidosis is CyBorD, which consists of cyclophosphamide, bortezomib, and dexamethasone.
Surgery
Organ-specific transplant may need to be done, depending on the organ involved. However, surgery is not commonly done in patients with amyloidosis, since it is usually a systemic disease that requires treatment of the underlying cause.
Prevention
Primary Prevention
There is no role for primary prevention in amyloidosis.
Secondary Prevention
There is no role for secondary prevention in amyloidosis.