• Clinical science

Amyloidosis

Abstract

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.

Pathophysiology

  • Definition: Amyloidosis refers to the extracellular deposition of different types of insoluble protein in various organs.
  • Composition of amyloid
    • Fibrillar component (90–95% of amyloid): β-sheet fibrils
    • Non-fibrillar component is usually the same in all types of amyloid and makes up 5–10% of amyloid

Types of amyloidosis

Systemic amyloidosis

Light-chain amyloidosis (AL-amyloidosis)

Reactive amyloidosis (AA-amyloidosis)

Amyloidosis should always be considered in a patient with a long-standing inflammatory and/or infectious disease who presents with kidney, liver, or GI involvement.

Overview of systemic amyloidosis

Type of systemic amyloidosis Amyloid protein Underlying cause Age of onset

Organs most commonly affected

Additional information
Light-chain amyloidosis
  • > 40 years
  • Most common form of amyloidosis in the western world
  • Rapidly progressive clinical course
Reactive amyloidosis
  • Serum amyloid-associated protein (SAA) AA amyloid protein
  • Any age
  • Most common form of amyloidosis in the developing world
  • The progression of the disease can be slowed by controlling the underlying condition.
Hemodialysis-associated amyloidosis
  • Joints and tendons
  • Almost all individual on long-term hemodialysis will develop amyloidosis at some point

Localized amyloidosis

Affected organ Amyloid protein Associated condition
Senile cardiac amyloidosis
  • Old age
Isolated atrial amyloidosis
  • Old age
Cerebral amyloidosis
  • APrP
Endocrine amyloidosis
  • Amyloid at insulin injection site (AIns)

Hereditary amyloidosis

Condition Amyloid protein Pattern of inheritance Age of onset Affected sites Additional information
Familial amyloid cardiomyopathy
  • > 20 years
  • Common in African Americans
Familial amyloid polyneuropathy (FAP)
  • Peripheral and autonomic nerves
  • Common in Portugal, Sweden, Japan, and among people of Irish descent
Familial Mediterranean fever (FMF)
  • AA aymloid protein
  • < 20 years
  • Common among individuals of Mediterranean descent (e.g., Sephardic Jews, Arabs, Turks)
  • Two types of FMF:
    • Type 1 FMF
    • Type 2 FMF

References:[1][2][3][4][5][6][7]

Diagnostics

References:[8][9]

Treatment

References:[6][10]

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last updated 09/05/2018
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