Amyloidosis

Expansion

Whatever the precursor protein, the deposit is the same: extracellular beta pleated sheet fibrils, resistant to degradation.

Types

• AL (primary) - immunoglobulin light chains, from a plasma cell dyscrasia or myeloma. The commonest in the UK
• AA (secondary) - serum amyloid A, an acute phase protein, from chronic inflammation: rheumatoid arthritis, inflammatory bowel disease, chronic infection, bronchiectasis, familial Mediterranean fever
• ATTR - transthyretin, either hereditary or wild type (senile), causing cardiac amyloid in the elderly
• Beta-2 microglobulin - long term dialysis, causing carpal tunnel syndrome
• Localised: cerebral (Alzheimer’s), medullary thyroid carcinoma (calcitonin), type 2 diabetes (islet amyloid)

Clinical features: nephrotic syndrome and renal failure, restrictive cardiomyopathy with heart failure and low voltage ECG despite thick walls on echo, hepatosplenomegaly, peripheral and autonomic neuropathy, macroglossia, and periorbital purpura after minor trauma, which is close to specific for AL.

Diagnosis: Congo red staining showing apple green birefringence under polarised light, on a biopsy of the affected organ, rectum, or abdominal fat pad. Then type it by immunohistochemistry or mass spectrometry, since treatment differs entirely.