Amyloidosis

Disorder characterised by extracellular deposits of misfolded proteins

Aetiology

• Over 30 identified causative protiens

• Inherited and acquired forms

Pathophysiology

• Deposition of extracellular amyloid (insoluble protein fibrils) in tissues or organs

• Occurs due to abnormal folding of proteins which then aggregate and become insoluble
• Breakdown of usual degradation pathways for abnormally folded proteins

Types of amyloidosis

• Production of abnormal immunglobulin light chains from plasma chains

• Light chains enter the bloodstream and cause amyloid deposits

• Commonly affects heart, bowel, skin, nerves, kidneys

• Age at diagnosis 55-60 years

• Associated with systemic inflammation

• Production of acute phase protein - serum amyloid A protein

• Develops in approx. 5% of patients with chronic inflammatory conditions or chronic infections
• RA, IBD, psoriasis
• TB, osteomyelitis, bronchectasis

• Commonly affects liver, spleen, kidneys, adrenals

• Dialysis (Aβ2M)

• Hereditary and old age (ATTR)

Clinical presentation

• Depends on organs or tissues involved

• Renal - nephrotic range proteinuria +/- impaired renal function

• Cardiac - cardiomyopathy

• Nerves - peripheral or autonomic neuropathy

• Hepatomegaly/splenomegaly, deranged LFTs

• GI - malabsorption

Renal investigations

• Urinalysis and uPCR

• Blood tests - renal function, markers of inflammation, protein electrophoresis, SFLC

• Renal biopsy - congo red staining givens green apple bifringence under polarised light
• Abdominal fat pad or rectal biopsy can be used if renal biopsy not possible/inconclusive

• SAP scan - shows extend of disease

Management

• No curative treatment - aim to reduce further deposition and preserve organ function

• AA - treat underlying condition

• AL - immunosuppression
• Steroids, chemotherapy, stem cell transplant

• Refer to National Amyloidosis Centre (UCL)