Amyloidosis
Last updated: May 9, 2022
Summary
Amyloidosis is a collective term for the extracellular deposition of abnormal proteins, either in a single organ (localized amyloidosis) or throughout the body (systemic amyloidosis). The different subtypes of amyloidosis are categorized according to the origin of the deposited proteins (e.g., AA, AL). These abnormal proteins are produced as a result of various diseases. The most common form of systemic amyloidosis in developed nations is light chain amyloidosis (AL deposition), which is caused by plasma cell dyscrasias such as multiple myeloma. The second most common systemic form – reactive amyloidosis (AA deposition) – is secondary to chronic inflammation and typically presents with nephrotic syndrome. Depending on which organs are affected, amyloidosis may also present with hepatomegaly, macroglossia, cardiac conduction abnormalities, and symptoms of restrictive cardiomyopathy. Abdominal fat or rectal mucosa biopsies are used to diagnose systemic amyloidosis. When stained with a Congo red dye, amyloid deposits exhibit an apple-green birefringence under polarized light. No definitive therapy for amyloidosis exists. Instead, the underlying disease should be treated. If amyloidosis progresses rapidly, melphalan and corticosteroids can be used to control the underlying disease.
Overview
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Definition: : Amyloidosis is the extracellular aggregation and subsequent deposition of different types of insoluble protein or protein fragments (amyloid) in various organs.
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Composition of amyloid
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Pathogenesis: accumulation of amyloid → cellular injury and apoptosis [1]
Types of amyloidosis
Systemic amyloidosis
Light-chain amyloidosis (AL-amyloidosis) [2]

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Etiology: secondary disease
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Chronic inflammatory conditions (e.g., IBD, rheumatoid arthritis, SLE, vasculitis, familial Mediterranean fever)
- Chronic infectious diseases (e.g., tuberculosis, bronchiectasis, leprosy, osteomyelitis)
- Certain tumors (e.g., renal cell carcinoma, lymphomas)
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Pathophysiology: chronic inflammatory process → ↑ production of acute phase reactant SAA (serum amyloid-associated protein) → deposition of AA (amyloid-associated) protein in various organs
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Clinical features
Amyloidosis should always be considered in patients with a long-standing inflammatory and/or infectious disease who present with kidney, liver, or GI involvement.
Overview [2][7][8]
Overview of localized amyloidosis
Overview |
Localized amyloidosis | Amyloid protein | Associated condition |
Senile cardiac amyloidosis |
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Normal (wild-type) transthyretin (ATTRwt) → deposition in cardiac ventricles → cardiac dysfunction (less drastic than in AL amyloidosis) [10]
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Isolated atrial amyloidosis |
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Cerebral amyloidosis |
- Aβ (cleaved from the APP)
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Endocrine amyloidosis |
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Hereditary amyloidosis
Overview |
Condition | Familial amyloid cardiomyopathy | Familial amyloid polyneuropathy (FAP) | Familial Mediterranean fever (FMF) |
Amyloid protein |
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Pattern of inheritance |
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Age of onset |
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Affected sites |
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- Peripheral and autonomic nerves
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Additional information |
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- Common in Portugal, Sweden, Japan, and among people of Irish descent
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- Common among individuals of Mediterranean descent (e.g., Sephardic Jews, Arabs, Turks)
- Two types of FMF
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Diagnostics
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Biopsy of tissue sample with Congo red stain: The type of tissue sample depends on the extent of disease and organ involvement. [14]
- Dysfunctional organ tissue (e.g., kidney, nerve) in case of single organ involvement
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Abdominal fat or rectal mucosa are preferred in case of systemic amyloidosis (i.e., multiple organs and/or tissues involved).
- Findings
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Tests to diagnose the underlying disease [15]


Treatment
References
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http://www.pathologyoutlines.com/topic/coagulationamyloidosis.html.
Updated: July 1, 2010.
Accessed: May 24, 2017.
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Zhou Y, Khalid S, Abbass A, Hughes L, Hazday M. A Heart too Stiff to Beat: A Case of Familial Transthyretin Amyloidosis Cardiomyopathy. Cureus. 2017
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Marin-Argany M, Lin Y, Misra P, et al. Cell Damage in Light Chain Amyloidosis: FIBRIL INTERNALIZATION, TOXICITY AND CELL-MEDIATED SEEDING.. J Biol Chem. 2016; 291
(38): p.19813-25.
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