Amyloidosis Diagnosis and Treatment

Introduction to Amyloidosis

The American College of Cardiology notes that the main types of amyloidosis are AL (light chain), ATTR (transthyretin), AA (reactive), isolated atrial, and dialysis-related amyloidosis, each requiring specific treatment approaches based on the underlying protein abnormality 1, 2, 3
The American College of Cardiology recommends considering amyloidosis in patients with multisystem disorders involving heart, kidney, liver, or nervous system, with a focus on accurate diagnosis and differentiation between types 1, 2, 3

AL amyloidosis is the most common type, affecting approximately 10 people per million/year, and is caused by increased production of light chain portions of antibodies by plasma cells in bone marrow 4, 5, 1, 6
The American College of Cardiology states that AL amyloidosis is often associated with multiple myeloma or Waldenström's macroglobulinemia, with cardiac involvement occurring in up to 50% of cases 1, 3
ATTR amyloidosis has two subtypes: hereditary and acquired (wild-type), with hereditary ATTR amyloidosis caused by mutation in TTR gene, resulting in abnormal "variant" TTR 1, 6
AA amyloidosis results from chronic inflammatory or infectious diseases, such as rheumatoid arthritis, Crohn's disease, or ulcerative colitis, and is caused by deposition of amyloid type A protein in organs 1, 6

The American College of Cardiology recommends high-dose melphalan followed by autologous stem cell transplantation (ASCT) as a treatment option for AL amyloidosis, with daratumumab-CyBorD as first-line therapy for transplant-eligible patients 7
For transplant-ineligible patients, daratumumab-CyBorD is the preferred first-line option, with alternative options including CyBorD (cyclophosphamide, bortezomib, dexamethasone) 7
The American College of Cardiology notes that medication considerations for AL amyloidosis include daratumumab, proteasome inhibitors, and immunomodulatory agents, with close monitoring for cardiac decompensation during therapy essential 7

Accurate diagnosis of amyloidosis requires serum free light chain assay (sFLC), serum immunofixation electrophoresis (SIFE), and urine immunofixation electrophoresis (UIFE) 7
Tissue biopsy with Congo Red staining showing characteristic apple-green birefringence under polarized light is also necessary, with typing of amyloid protein using mass spectrometry (gold standard), immunohistochemistry, or immunofluorescence 7

The American College of Cardiology states that cardiac involvement is the main driver of disease prognosis and mortality, with collaboration between hematologists, cardiologists, and nephrologists crucial 7
Differentiation between AL and ATTR amyloidosis is essential as management differs significantly, with patients with AL amyloidosis at higher risk for treatment-related toxicity than those with multiple myeloma 7
Close monitoring for cardiac decompensation during therapy is essential, with no absolute contraindications to plasma cell-directed therapies existing based solely on ejection fraction or cardiac status in AL cardiac amyloidosis 7