A 57-year-old woman presents with nephrotic syndrome and renal dysfunction. Investigation reveals a serum free light chain excess and a modest bone marrow infiltration with malignant phenotype plasma cells. Imaging reveals her to have enlarged kidneys and a rectal biopsy reveals amyloid deposits stained with Congo red.
What further assessments and investigations are appropriate?
What is the optimal management of the woman's disease?
What is the role of stem cell transplantation in the management of amyloid?
Amyloidosis describes a group of conditions characterized by the deposition of extracellular protein molecules in an ordered structure to make linear fibrils 7.5–10 nm wide arranged in characteristic β-sheets. These β-sheets produce apple-green birefringence under polarized light when stained with Congo red. Amyloidosis was first reported in 1854 by Virchow and he coined the name due to the apparent affinity of the protein material for iodine.1 Originally, the amyloidoses were classified as either primary (occurring in those with no underlying pathology) or secondary (occurring in those with chronic inflammation or infection). However, with the discovery that several different proteins could cause amyloidosis, the revised categorization is based on the protein precursor, as illustrated in Table 37.1. AL amyloidosis is the commonest form, which is a protein conformation disorder associated with a clonal plasma cell dyscrasia.2 Multiple organ disease results from the deposition of monoclonal immunoglobulin light chain fragments in insoluble fibrils, which associate in vivo with the normal plasma protein serum amyloid P (SAP) component, and the accumulation of the fibrils progressively disrupts the normal tissue structure leading to organ dysfunction, e.g. of the kidneys, heart and liver. Deposition of the amyloid fibrils evokes little or no local reaction in the tissues.
Table 37.1Nomenclature and classification of amyloid and amyloidoses |Favorite Table|Download (.pdf) Table 37.1 Nomenclature and classification of amyloid and amyloidoses
|Amyloid type ||Protein precursor ||Protein type or variant ||Associated clinical syndromes |
|AL ||κ, λ ||Aκ, Aλ ||Primary amyloidosis, plasma cell myeloma, Waldenström’s macroglobulinaemia |
|AH ||IgG1 ||Aγ1 ||Heavy chain disease associated |
|AA ||ApoSAA ||AA ||Reactive/secondary amyloidosis |
| || || ||Familial Mediterranean fever |
|ATTR ||Transthyretin ||Met30 ||Hereditary amyloidosis: |
| || ||Met111 ||Familial amyloidotic polyneuropathies |
| || || ||Familial amyloidotic cardiomyopathy |
|AApoAI ||Apolipoprotein A-I ||Arg26 ||Familial amyloidotic polyneuropathy |
| || ||Arg60 ||Ostertag-type familial amyloidosis |
|Agel ||Gelsolin ||Asn187 ||Finnish-type familial amyloidosis |
|Aβ2-m ||β2-microglobulin || ||Dialysis associated |
|Aβ ||β-protein precursor A4 ||β A4 protein ||Alzheimer’s disease, Down’s syndrome |
| || ||Gln695 ||Hereditary cerebral haemorrhage with amyloid (Dutch) |
|Acys ||Cystatin-C ||Leu68 ||Hereditary cerebral haemorrhage with amyloid (Icelandic) |
|Ascr ||PrPc ||PrPc, PrPCJD ||Spongiform encephalopathies |
|Acal ||(Pro)calcitonin ||(Pro)calcitonin ||Medullary carcinoma of thyroid |
|AANF ||Atrial natriuretic factor ||Atrial natriuretic factor ||Isolated atrial amyloidosis |
|AIAPP ||Islet-associated peptide ||Islet-associated peptide ||Amyloid of the islets, diabetes mellitus type II |
|A Lys ||Lysozyme ||Thr56 ||Hereditary non-neuropathic systemic amyloidosis |
|A Fib ||Fibrinogen α chain ||Leu554 ||Hereditary ...|