Diffuse

Amyloidosis

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Amyloidosis

  • Epidemiology
  1. Overall Prevalence: <200,000 in U.S. affected
  • Pathophysiology
  1. Disturbed endogenous Protein Metabolism
    1. Primary
    2. Secondary to chronic tissue breakdown
  2. Organ dysfunction arises from extracellular amyloid deposition is soft tissue and organs
    1. Amyloid Proteins are beta-sheet, insoluble polymeric Protein fibrils
    2. More than 20 specific amyloidogenic Proteins, pathogenic in humans, have been identified
    3. Heterogeneous group of conditions with manifestations depending on the deposited Protein
  • Types
  1. Many classification systems have been used (e.g. systemic, hereditary, localized)
    1. Modern classification is specific to the chemical analysis of the deposited Protein
  2. Common Types
    1. Amyloidosis Immunoglobulin Light Chain Fragment (AL, immunocyte dyscrasia, primary Amyloidosis)
      1. Incidence: 1 per 100,000 (1000 to 3000 new cases/year in U.S.)
      2. Small plasma cell clones produce misfolded monoclonal light chain Immunoglobulin fragments that deposit in tissues
      3. May be associated with Multiple Myeloma and other plasma cell dyscrasias
      4. Broad Protein deposition in the heart, Kidneys, liver and Gastrointestinal Tract
      5. Also deposits in the Peripheral Nervous System and Autonomic Nervous System
    2. Amyloidosis A Protein (AA, reactive Amyloidosis, secondary Amyloidosis)
      1. Reactive Amyloidosis to chronic inflammatory disease (e.g. Rheumatoid Arthritis, chronic infections)
      2. Associated with serum amyloid A deposition in jidneys, Gastrointestinal Tract and heart
    3. Amyloid Transport Protein Transthyretin (ATTR, senile systemic Amyloidosis)
      1. Less common Amyloidosis type (represents 10-20% of cases at tertiary centers)
      2. Associated with Alzheimer Disease, Neuropathy as well as heart deposition
    4. Dialysis-Related Amyloidosis (beta2M type)
      1. Associated with high serum concentrations of Protein precursors (beta2M)
      2. Associated with amyloid deposition in osteoarticular tissue, Gastrointestinal Tract and circulatory system
  3. Hereditary Amyloidosis
    1. Familial Mediterranean Fever
      1. Associated with serum amyloid associated (SAA) precursor Protein, and the AA fibril Protein
    2. Familial Amyloidotic Neuropathy
      1. Associated with the transthyretin precursor Protein, and the ATTR fibril Protein
    3. Apolipoprotein 1 (AApoA1)
      1. Amyloid deposition in the heart, Kidneys, liver, Peripheral Nervous System and skin
    4. Mutant Fibrinogen A alpha (AFib)
      1. Amyloid deposition in Kidneys and liver
    5. Lysozyme (ALys)
      1. Amyloid deposition in Kidneys and liver
  4. Endocrine Amyloidosis
    1. Thyroid
      1. Associated with the Calcitonin precursor Protein, and the A Cal fibril Protein
      2. Associated with development of Medullary carcinoma
    2. Islets of Langerhans
      1. Associated with the islet amyloid precursor Protein, and the AIAPP fibril Protein
      2. Associated with Type 2 Diabetes Mellitus
  5. Other Localized Amyloidosis
    1. Finnish-type (AGel, Gelsolin)
      1. Amyloid deposition in the Cornea resulting in Corneal lattice dystrophy and Corneal Neuropathy
  • Symptoms
  1. Asthenia
  2. Weight loss
  3. Paresthesias
  4. Organ specific symptoms (depending on amyloid deposition sites)
  • Signs
  • Organ Specific
  1. Macroglossia
  2. Hypertension
  3. Lymphadenopathy
  4. Hepatomegaly
  5. Splenomegaly
  6. Purpura
  7. Nephrotic Syndrome
  8. Edema
  9. Joint Pain, Muscle pain
  10. Serous cavity fluid
  • Labs
  1. Tissue Biopsy under Congo red or thioflavine-T staining
    1. Exam of Gingiva, Rectum, involved tissues
    2. Apple-Green birefringence in polarized light
  2. Plasma cell clone analysis
    1. Serum and urine electrophoresis (SPEP and UPEP) with immnofixation and free light chains
      1. Serum Immunoglobulins altered
    2. Immunofluorescence in situ hybridization (FISH)
    3. Skeletal Survey
  3. Gene Sequencing
    1. Hereditary Amyloidosis
  • Resources
  1. Bustamante (2023) Amyloidosis, StatPearls, Treasure Island, FL, accessed 4/22/2023
    1. https://www.ncbi.nlm.nih.gov/books/NBK470285/
  • References
  1. Baloor and Nayak (2018) Exam Preparatory Manual for Undergraduate Medicine, Jaypee Brothers Medical Publication
  2. Baker (2012) Methodist Debakey Cardiovasc J +PMID: 23227278 [PubMed]