Amyloidosis

Amyloidosis (plural: amyloidoses)is a heterogeneous disease, or even considered a constellation of diseases, resulting in the deposition of relatively similar proteins. It has many causes and can affect essentially any organ system.

Epidemiology 

The disease may have a male predilection. It typically affects middle-aged individuals around 60 years ⁵.

Clinical presentation

In view of the vast variety of clinical forms of amyloidosis, the potential spectrum of symptoms and signs is extremely broad, and can present in almost any way.

Pathology

Amyloid comprises a group of proteins characterised by certain physical properties. There are at least 15 amyloid proteins, derived from diverse precursors. Some demonstrate the structural morphology of immunoglobulins (amyloid, i.e. amyloid light chain).

Subtypes

• primary amyloidosis: associated with monoclonal plasma cell dyscrasias
• secondary amyloidosis: usually occurs secondary to a tissue destructive and inflammatory process
  • tuberculosis
  • rheumatoid arthritis
  • multiple myeloma
  • Crohn disease
  • ankylosing spondylitis
  • Sjogren syndrome
  • dermatomyositis
• hereditary amyloidosis: can be seen with familial Mediterranean fever (FMF)
• senile amyloidosis
• localised amyloidosis: sometimes classified as a separate entity with the above four accounting for the systemic forms
• dialysis related-related amyloidosis ⁷:can occur with either haemodialysis or peritoneal dialysis

In certain scenarios, the amyloid proteins are produced and deposited locally, whereas in others, the protein is distributed systemically. 

Systemic amyloidosis

The majority occur in the systemic form:

• AL (amyloid light chain)
  • synthesised by plasma cells, and seen in conditions with monoclonal proliferation of these cells
• AA (amyloid associated)
  • derived from SAA (serum amyloid A) protein which is synthesised by the liver and forms part of the HDL3 lipoproteins
  • typically seen in chronic inflammatory disease or familial Mediterranean fever
• Aß₂M (amyloid ß₂-microglobulin)
  • derived from ß₂-microglobulin
  • seen in patients on haemodialysis or peritoneal dialysis
• ATTR (amyloid transthyretin)
  • seen in senile systemic amyloidosis / neuropathic/neuropathic cerebral angiopathy
  • is the most common form of familial amyloidosis ⁵

Localised amyloidosis

Accounts for ≈15% of amyloidosis:

• A₄ß₂ (beta-amyloid protein): seen in Alzheimer disease
• AANF (atrial natriuretic factor): isolated atrial amyloidosis
• AIAPP (islet amyloid peptide): deposited in the pancreas in patients with type II diabetes mellitus
• ACal: seen in medullary islet cell tumour

Organ-specific amyloidosis

Amyloid deposition can occur in essentially any part of the body, although some are more common and have specific imaging findings. These conditions are best discussed separately:

• breast amyloidosis
• cardiac amyloidosis
• cerebral amyloid deposition diseases
  • Alzheimer disease
  • cerebral amyloid angiopathy
  • cerebral amyloid angiopathy-related inflammation
  • cerebral amyloidoma
• gastrointestinal amyloidosis
• hepatic amyloidosis
• pulmonary amyloidosis
• renal amyloidosis
• skeletal amyloidosis
  • amyloid arthropathy
• splenic amyloidosis
• tracheobronchial amyloidosis
• urinary tract amyloidosis

Microscopic appearance

Amyloid is an insoluble extracellular proteinaceous substance composed of cross-ß-pleated sheets which display apple-green birefringence when viewed under polarised light after being treated with Congo red stain ¹.

Associations 

• multiple myeloma (with primary amyloidosis)