- 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.
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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)
- Most common form of amyloidosis in developed nations
- Etiology: associated with plasma cell dyscrasias (e.g., multiple myeloma, Waldenström macroglobulinemia)
- Pathophysiology: increased production of the light chains of immunoglobulins → deposition of AL (amyloid light chain) protein in various organs
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Clinical presentation: rapidly progressive clinical course
- Heart: restrictive cardiomyopathy, atrioventricular block
- Kidney: nephrotic syndrome, type II renal tubular acidosis, nephrogenic diabetes insipidus
- Tongue: macroglossia → obstructive sleep apnea
- Autonomic nervous system: autonomic neuropathy
- Gastrointestinal tract: malabsorption
- Bleeding disorders
Reactive amyloidosis (AA-amyloidosis)
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Etiology: secondary disease
- 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)
- Pathophysiology: chronic inflammatory process → increased 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
- Kidney: nephrotic syndrome, type II renal tubular acidosis, nephrogenic diabetes insipidus
- Adrenal glands: primary adrenal insufficiency
- Liver and spleen: hepatomegaly, splenomegaly
- Gastrointestinal tract: malabsorption
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 | |
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Light-chain amyloidosis |
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Reactive amyloidosis |
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Hemodialysis-associated amyloidosis |
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Localized amyloidosis
Affected organ | Amyloid protein | Associated condition | |
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Senile cardiac amyloidosis |
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Isolated atrial amyloidosis |
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Cerebral amyloidosis |
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Endocrine amyloidosis |
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Hereditary amyloidosis
Condition | Amyloid protein | Pattern of inheritance | Age of onset | Affected sites | Additional information |
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Familial amyloid cardiomyopathy |
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Familial amyloid polyneuropathy (FAP) |
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Familial Mediterranean fever (FMF) |
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References:[1][2][3][4][5][6][7]
Diagnostics
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Biopsy of abdominal fat or rectal mucosa with Congo red stain
- Pink to reddish appearance
- Apple-green birefringence under polarized light
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Tests to diagnose the underlying disease
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Light chain amyloidosis
- Serum electrophoresis: monoclonal gammopathy
- Urine test for Bence-Jones proteins (see multiple myeloma)
- Reactive amyloidosis: ESR, CRP, chest x-ray
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Light chain amyloidosis
References:[8][9]
Treatment
- No definitive therapy exists
- Adequate treatment of the underlying disease may stall disease progression.
- If amyloidosis progresses rapidly (e.g., light chain amyloidosis): corticosteroids, melphalan
References:[6][10]