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Amyloidosis

Last updated: May 24, 2021

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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.

Systemic amyloidosis

Light-chain amyloidosis (AL-amyloidosis) [2]

Reactive amyloidosis (AA-amyloidosis)

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 of systemic amyloidosis [2][7][8]

Systemic amyloidosis Light-chain amyloidosis (formerly called primary amyloidosis) Reactive amyloidosis (formerly called secondary amyloidosis) Hemodialysis-associated amyloidosis
Amyloid protein
Underlying cause
Age of onset
  • 64 years [9]
  • Any age
Affected organ
Additional information
  • Rapidly progressive clinical course
  • The progression of the disease can be slowed by controlling the underlying condition.
  • Almost all individuals on long-term hemodialysis will develop amyloidosis at some point.

Overview of localized amyloidosis

Localized amyloidosis Amyloid protein Associated condition
Senile cardiac amyloidosis
  • Normal (wild-type) transthyretin (ATTRwt) → deposition in cardiac ventricles → cardiac dysfunction (less drastic than in AL amyloidosis) [10]
  • Old age
Isolated atrial amyloidosis
  • Physiological in old age
Cerebral amyloidosis
  • APrP
Endocrine amyloidosis

Hereditary amyloidosis

Condition Familial amyloid cardiomyopathy Familial amyloid polyneuropathy (FAP) Familial Mediterranean fever (FMF)
Amyloid protein
Pattern of inheritance
Age of onset
  • > 20 years
  • < 20 years
Affected sites
  • Peripheral and autonomic nerves
Additional information
  • Common in Portugal, Sweden, Japan, and among people of Irish descent
  • Common among individuals of Mediterranean descent (e.g., Sephardic Jews, Arabs, Turks)
  • Two types of FMF

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  2. Slobodnick A, Shah B, Krasnokutsky S, Pillinger MH. Update on colchicine, 2017. Rheumatology (Oxford). 2017; 57 (suppl_1): p.i4-i11. doi: 10.1093/rheumatology/kex453 . | Open in Read by QxMD
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  14. Siddiqi OK, Ruberg FL. Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med. 2018; 28 (1): p.10-21. doi: 10.1016/j.tcm.2017.07.004 . | Open in Read by QxMD
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