Definition
Amyloidosis is a group of disorders characterised by extracellular deposition of insoluble, misfolded protein in a β-pleated sheet configuration. Deposits accumulate in organs and progressively disrupt their function.
Main types
- AL (primary) amyloidosis — immunoglobulin light chains produced by a clonal plasma cell disorder (associated with myeloma)
- AA (secondary/reactive) amyloidosis — serum amyloid A, an acute-phase reactant, deposited in the setting of chronic inflammation (rheumatoid arthritis, inflammatory bowel disease, chronic infection, familial Mediterranean fever)
Clinical presentation
Amyloidosis is a great multisystem mimic:
- Renal: heavy proteinuria and nephrotic syndrome (kidneys often normal-sized or enlarged)
- Cardiac: restrictive cardiomyopathy, heart failure, low-voltage ECG, conduction disease (a leading cause of death in AL)
- Neurological: peripheral and autonomic neuropathy, carpal tunnel syndrome
- GI/hepatic: hepatomegaly, malabsorption
- AL-specific clues: macroglossia and periorbital purpura
Investigations
- Biopsy with Congo red stain → apple-green birefringence under polarised light (the diagnostic hallmark); rectal or abdominal fat-pad biopsy is often used
- Typing of the deposit (immunohistochemistry, mass spectrometry)
- Serum free light chains and immunofixation for AL; screen for myeloma
- SAP scintigraphy to assess distribution and monitor burden
- Echocardiography and cardiac biomarkers for cardiac involvement
Management
- AL: treat the plasma cell clone — chemotherapy regimens (e.g. bortezomib-based), sometimes autologous stem cell transplant
- AA: treat the underlying inflammatory disease to lower serum amyloid A
- Supportive management of organ failure (heart failure, nephrotic syndrome, dialysis)
MRCP-specific traps
- Nephrotic syndrome with normal-sized or large kidneys should prompt thoughts of amyloid (or diabetes/HIV), not the small kidneys of most CKD.
- Periorbital purpura and macroglossia point specifically to AL disease.
- In AA amyloid, controlling the inflammatory driver can halt or even regress deposition.
Summary
Amyloidosis is misfolded-protein deposition — AL (light chains, plasma cell disorder) or AA (serum amyloid A, chronic inflammation). It causes nephrotic syndrome, restrictive cardiomyopathy and neuropathy. Diagnose with Congo red (apple-green birefringence); treat the clone in AL and the inflammation in AA.
nephrologyhaematologymultisystemmrcp part 2