Who is involved in the workup of a patient with suspected amyloidosis?

Multidisciplinary Team Approach to Amyloidosis Workup

Amyloidosis workup requires a coordinated multidisciplinary team led by specialists specific to the amyloid type and affected organs, with cardiologists and hematologists playing central roles, particularly for cardiac amyloidosis. 1

Core Multidisciplinary Team

The workup of suspected amyloidosis involves several specialists:

• Hematologists: Essential for all suspected cases, particularly AL amyloidosis

  • Evaluate monoclonal protein screens
  • Perform and interpret bone marrow biopsies
  • Guide plasma cell-directed therapy
  • Differentiate between AL amyloidosis, multiple myeloma, and MGUS 2

• Cardiologists: Critical when cardiac involvement is suspected

  • Interpret cardiac imaging
  • Manage cardiac manifestations
  • Collaborate with hematologists for cardiotoxicity monitoring during treatment
  • Assess candidacy for heart transplantation 2, 1

• Nephrologists: Involved when renal involvement is present

  • Manage nephrotic syndrome and chronic kidney disease
  • Interpret serum free light chain concentrations in kidney impairment
  • Determine need for kidney biopsy
  • Assess suitability for kidney transplantation 2

• Pathologists: Critical for diagnosis confirmation

  • Perform Congo red staining and interpretation
  • Conduct immunohistochemistry or immunogold immunoelectron microscopy
  • Coordinate mass spectrometry-based analysis for definitive typing 2

Expanded Team Based on Organ Involvement

Additional specialists may be involved depending on specific organ manifestations:

• Neurologists: For peripheral or autonomic neuropathy

• Gastroenterologists: For GI complications including:

  • Malabsorption
  • Small intestinal bacterial overgrowth
  • Severe nausea, vomiting, diarrhea, constipation
  • GI bleeding 2

• Geneticists: For hereditary forms of amyloidosis (especially ATTRv)

• Transplant specialists: For end-stage disease management requiring organ transplantation 1

Diagnostic Workflow

1. Initial Suspicion and Screening:

   • Monoclonal protein studies (serum free light chains, serum and urine immunofixation)
   • Cardiac biomarkers and imaging when cardiac involvement is suspected

2. Tissue Diagnosis:

   • Biopsy of affected organ or surrogate sites (abdominal fat pad, bone marrow)
   • Congo red staining to confirm amyloid deposits

3. Amyloid Typing:

   • Immunohistochemistry/immunofluorescence
   • Mass spectrometry (gold standard) for definitive typing
   • Genetic testing for hereditary forms 2, 1

Common Pitfalls in Amyloidosis Workup

• Delayed diagnosis: Due to nonspecific and vague symptoms, leading to poor outcomes 1
• Misdiagnosis: Particularly in elderly patients with ATTR due to coincidental MGUS 2, 1
• Incomplete typing: Relying solely on immunohistochemistry without mass spectrometry can lead to misclassification 3
• Inadequate coordination: Failure to involve all relevant specialists can result in suboptimal management 1

Referral to Specialized Centers

For complex cases, referral to specialized amyloidosis centers is recommended, particularly when:

• Diagnosis is uncertain
• Multiple organ involvement is present
• Advanced treatment options like stem cell transplantation are being considered
• Genetic forms are suspected
• Mass spectrometry-based typing is required 2, 1

The multidisciplinary approach ensures comprehensive evaluation, accurate diagnosis and typing, and appropriate treatment selection, which are essential for improving outcomes in this complex disease.