Localized vs Systemic Amyloidosis

Key Differences

Localized amyloidosis results from local synthesis of amyloid protein, whereas systemic amyloidosis involves widespread deposition of amyloid proteins produced at distant sites, often affecting multiple organs, including the heart, as noted by the American College of Cardiology 1, 2
Systemic amyloidosis typically affects multiple organs simultaneously, particularly the heart, causing heart failure, and the kidneys, causing renal failure, as reported by the American College of Cardiology 1, 2
The American College of Cardiology recommends distinguishing between localized and systemic amyloidosis, as systemic disease requires aggressive systemic therapy and has higher mortality 3

Localized amyloidosis affects a single organ or tissue, commonly occurring in the tracheobronchial tree, causing cough, hemoptysis, and wheezing, as described in Chest 4, 5
Systemic amyloidosis affects multiple organs, including the heart, causing heart failure, and the nervous system, causing neuropathy, as noted in Chest 4

Systemic amyloidosis has distinct types, including AL (light chain) amyloidosis, associated with plasma cell disorders, and ATTR (transthyretin) amyloidosis, either hereditary or wild-type, as reported by the American College of Cardiology 1, 2
The American College of Cardiology notes that AL amyloidosis is the most common type of systemic amyloidosis, associated with plasma cell disorders 3

Systemic amyloidosis diagnosis requires positive serum free light chain assay, serum and urine immunofixation, and evidence of multi-organ involvement, as recommended by the American College of Cardiology 3
Typing of amyloid protein using mass spectrometry, immunohistochemistry, or immunofluorescence is necessary for systemic amyloidosis diagnosis, as noted by the American College of Cardiology 3

Systemic amyloidosis requires systemic therapy targeting the underlying protein production, including chemotherapy, daratumumab, proteasome inhibitors, or stem cell transplantation for AL amyloidosis, as recommended by the American College of Cardiology 3
The American College of Cardiology notes that systemic amyloidosis has a poorer prognosis, particularly with cardiac involvement 3

Systemic amyloidosis commonly affects vital organs including heart, kidneys, liver, and nervous system simultaneously, according to the American College of Cardiology 6, 7
Even when amyloidosis appears confined to one organ, subclinical involvement of other organs may be present but not yet detectable 8
The American College of Cardiology recommends extensive workup to exclude systemic involvement, as initial presentation may mask more widespread disease 7, 9

All cases of suspected localized amyloidosis require serum and urine immunofixation to exclude systemic AL amyloidosis, as recommended by the American College of Cardiology 7, 9
Bone marrow biopsy and abdominal fat aspiration should be considered as screening tools for systemic involvement 7
Fine-needle aspiration of abdominal fat has varying sensitivity: 84% for AL cardiac amyloidosis, 45% for hereditary ATTR, and 15% for wild-type ATTR 9, 10

Systemic amyloidosis, particularly with cardiac involvement, has significantly worse outcomes, with median survival dropping from 13 months to just 4 months when heart failure symptoms develop in AL amyloidosis 6, 11
The number and type of organs involved significantly impact survival, with cardiac involvement being the most important prognostic factor regardless of other organ involvement 8
Age ≥65 years is associated with worse survival in amyloidosis, and cytogenetic abnormalities, particularly hyperdiploidy, are associated with poor prognosis in AL amyloidosis 8

Autologous stem cell transplantation remains the standard of care for eligible patients with systemic AL amyloidosis (approximately 20% of patients), according to the Blood Cancer Journal 8, 12
Collaboration between cardiologists and hematologists is essential in managing patients with suspected or established AL amyloidosis, as recommended by the American College of Cardiology 13
Monitoring for cardiotoxicity of AL amyloidosis therapies is crucial in treatment planning 13