Macroglossia+Heart Failure Symptoms+Low Voltage on ECG…Could this be amyloid?

Ben Kitchens gave an excellent Resident Update Talk today on amyloidosis and its management. Check out the slides below and key points:

  • Extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins
  • Point mutations, deletions, and premature stop codons may result in structural changes predisposing to fibril formation
  • Dr. Rudolph Virchow in 1854 first adopted the term “amyloid” to refer to tissue deposits of material that stained in a similar manner to cellulose when exposed to iodine
  • There are several forms of amyloidosis including AL, AA, dialysis-related, heritable, organ-specific
  • AL amyloidosis is the most common in the U.S. and is caused by the deposition of monoclonal light chains, more often λ than κ
  • Hepatic amyloid involvement has been reported in up to 90 percent of patients with AL amyloid
  • Diagnosis requires characteristic findings on tissue biopsy and evidence that the amyloid deposits are composed of clonal light chains
  • An abdominal fat pad aspirate or bone marrow biopsy may be positive in up to 80% of patients. If negative but suspicion remains high, then more invasive biopsy of clinically relevant tissue is needed
  • Amyloid deposits consist of amorphous eosinophilic material that demonstrates apple-green birefringence when stained with Congo red and viewed under polarized light
  • After a diagnosis is established, a cardiac assessment is critical, including electrocardiography and transthoracic echocardiography, which may show interventricular septal hypertrophy, restrictive physiology, and occasional “sparkling” changes in the myocardium
  • Cardiac involvement is associated with poorer prognosis
  • Treatment consists of melphalan and dexamethasone chemotherapy to eradicate the clonal plasma cells responsible for producing the pathogenic light chain. Autologous hematopoietic stem cell transplantation should be considered in younger patients without significant comorbidities
  • Patients with poor performance status, major comorbidities, involvement of three or more organs, and advanced cardiac amyloidosis are not considered transplant candidates
  • Bortezomib and lenalidomide regimens have also been used, particularly for relapsed disease