Background
- Amyloidoses are a group of acquired and hereditary disorders characterised by extracellular deposition of insoluble proteins, which can be localised or systemic
- Clinical presentation depends on the organs involved
Types
- Reactive (AA) amyloidosis
- Increased production of serum amyloid A as part of prolonged or recurrent acute inflammatory response
- e.g. Chronic infection (TB, bronchiectasis, chronic abscess, osteomyelitis); Chronic inflammatory disease (chronic untreated/poorly controlled rheumatoid arthritis; familial Mediterranean fever)
- Most patients present with non-selective proteinuria or nephrotic syndrome
- May also have hepatosplenomegaly
- On investigations there may be signs of hepatorenal problems e.g. raised urea and low serum albumin
- Increased production of serum amyloid A as part of prolonged or recurrent acute inflammatory response
- Light Chain amyloidosis (AL)
- Increased production of monoclonal light chains
- e.g. monoclonal gammopathies e.g. myeloma, benign gammopathies and plasmacytoma
- Presents with features of restrictive cardiomyopathy, peripheral neuropathy/autonomic neuropathy, carpal tunnel syndrome, proteinuria, spontaneous purpura, amyloid nodules and plaques
- Macroglossia occurs rarely but is pathognomonic
- Prognosis is often poor
- Increased production of monoclonal light chains
- Dialysis associated (Aβ2M) amyloidosis
- Accumulation of circulating β2 microglobulin due to failure of renal catabolism in renal failure
- associated with dialysis / renal failure
- often 5-10 years from start of dialysis
- associated with dialysis / renal failure
- Presents with carpal tunnel syndrome, chronic arthropathy and pathological fractures due to amyloid bone cysts formation
- Accumulation of circulating β2 microglobulin due to failure of renal catabolism in renal failure
- Senile systemic amyloidosis
- Normal deposition of transthyretin protein in tissues in older patients (>70)
- Normal process of aging
- Usually asymptomatic
- Normal deposition of transthyretin protein in tissues in older patients (>70)
- Hereditary systemic amyloidosis
- Multiple forms – many mutations of the transthyretin gene; often autosomal dominant
- Peripheral and autonomic neuropathy, cardiomyopathy (renal involvement is unusual- ~10%)
- Many asymptomatic
Presentation
- Amyloidosis should be considered in all cases of unexplained nephrotic syndrome, cardiomyopathy and peripheral neuropathy
Investigation/Diagnosis
- Biopsy confirms diagnosis (affected organ, rectum or subcutaneous fat)
- apple-green birefringent amyloid deposits (Congo red dye)
- Quantitative scintigraphy with radiolabelled SAP can estimate total body load
Management
- Largely supportive; prevent further deposition by treatment of any underlying cause, where possible
- Liver transplantation may be an option