Amyloidosis: Definition, Types, Diagnosis and Treatment

What is amyloidosis?

Amyloidosis is a condition associated with several disorders, where abnormal fibrillar proteins, known as amyloid, are deposited in extracellular tissue. This deposition can cause tissue damage and impair organ function as these proteins form rigid, mesh-like structures.

Unfortunately, humans lack the enzymes to break down these amyloid proteins, making them insoluble in water and alcohol. As a result, individuals with amyloidosis are more prone to complications from the condition.

Types of Amyloidosis

1. AL (Amyloid Light Chains)
   • Derived from immunoglobulin light chains produced by plasma cells.
   • Commonly associated with plasma cell disorders like multiple myeloma.
   • Found in primary (1ry) amyloidosis.
2. AA (Amyloid Associated)
   • Derived from serum amyloid A (SAA), an acute phase reactant.
   • Linked to chronic inflammatory conditions, such as rheumatoid arthritis.
   • Found in secondary (2ry) amyloidosis.
3. Aβ Amyloid
   • Derived from amyloid precursor protein (APP), a large transmembrane glycoprotein.
   • Deposited in cerebral vessels and is a hallmark of Alzheimer’s disease.
4. TTR (Transthyretin)
   • Transthyretin transports thyroxine and retinol.
   • Found in:
     • Senile systemic amyloidosis (affecting the heart in aged individuals).
     • Familial amyloid polyneuropathies (due to mutant TTR).
5. β2-Macroglobulin
   • A normal serum protein that isn’t effectively filtered through dialysis.
   • Levels increase with long-term dialysis, leading to amyloidosis.

Classification of Amyloidosis

• Localized Amyloidosis: Limited to a single organ.
  • Examples: Senile cardiac amyloidosis (TTR), Senile cerebral amyloidosis (Aβ), Endocrine amyloidosis (medullary thyroid carcinoma, type II diabetes).
• Systemic Amyloidosis: Involves multiple organ systems.
  • Primary Amyloidosis: Linked to plasma cell disorders (e.g., multiple myeloma).
  • Secondary Amyloidosis: Results from chronic conditions like tuberculosis (TB), bronchiectasis, and chronic osteomyelitis.
  • Hereditary Amyloidosis: Inherited forms, often involving TTR mutations.

Clinical Features

The presentation of amyloidosis depends on the magnitude of amyloid deposits and the affected organs. This can be discovered incidentally or present with serious clinical problems.

• Kidneys: Leads to nephrotic syndrome and potentially renal failure.
• Spleen: May cause “sago spleen” or “lardaceous spleen.”
• Liver: Causes moderate to marked hepatomegaly.
• Heart: Restrictive cardiomyopathy, heart failure, arrhythmias, or constrictive pericarditis.
• Gastrointestinal Tract: Can cause macroglossia, motility abnormalities, and malabsorption.

Diagnosis

Diagnosis is based on histopathological evaluation:

• Light Microscopy: Shows amorphous, eosinophilic, hyaline, extracellular substance using H&E stain.
• Congo Red Staining: Under polarized light, amyloid shows apple-green birefringence.

Treatment of Amyloidosis

• AA type: Can stabilize if the underlying chronic disease is controlled.
• AL type: May respond to treatments for multiple myeloma.
• Transplants: Stem cell transplants, liver, and renal transplants have shown varying results, though disease recurrence is possible.

Prognosis

Prognosis is depend on the type of the amyloidosis. If left untreated, the prognosis is poor, with a median survival of 1–2 years. The most common cause of death is myocardial amyloidosis, leading to cardiac failure or fatal arrhythmias.

Amyloidosis and Thyroid Neoplasms

• Medullary Cell Carcinoma is a thyroid neoplasm associated with amyloidosis.