Is localized amyloidosis a different disease process from systemic amyloidosis?

Localized Amyloidosis vs. Systemic Amyloidosis: Distinct Disease Processes

Yes, localized amyloidosis is a fundamentally different disease process from systemic amyloidosis, with distinct pathophysiology, clinical manifestations, and prognosis. 1

Key Differences Between Localized and Systemic Amyloidosis

Pathophysiology

• Localized amyloidosis results from local synthesis of amyloid protein at the site of deposition, rather than from circulating proteins produced elsewhere in the body 2
• Systemic amyloidosis involves widespread deposition of amyloid proteins produced at distant sites (often bone marrow) and transported through the bloodstream to multiple organs 1

Clinical Presentation

• Localized amyloidosis affects a single organ or tissue without evidence of systemic involvement, commonly occurring in:
  • Tracheobronchial tree (causing cough, hemoptysis, wheezing) 1
  • Urinary tract (21% of localized cases) 3
  • Larynx (14% of localized cases) 3
  • Skin, soft tissues, oropharynx, lung, bladder, colon, conjunctiva, and lymph nodes 2, 4
• Systemic amyloidosis typically affects multiple organs simultaneously, particularly:
  • Heart (causing heart failure) 1
  • Kidneys (causing renal failure) 1
  • Nervous system (causing neuropathy) 1

Protein Composition

• In localized AL amyloidosis, there is a more balanced distribution between kappa and lambda light chains, unlike systemic AL where lambda chains predominate 5
• Systemic amyloidosis has several distinct types:
  • AL (light chain) amyloidosis - most common type, associated with plasma cell disorders 6
  • ATTR (transthyretin) amyloidosis - either hereditary or wild-type 1
  • AA (reactive) amyloidosis - associated with chronic inflammatory conditions 1

Diagnostic Approach

• Localized amyloidosis diagnosis requires:
  • Congo red-positive biopsy of affected tissue showing characteristic apple-green birefringence 6, 3
  • Negative serum and urine immunofixation (to rule out systemic disease) 3
  • No evidence of clonal plasma cells in bone marrow 3
• Systemic amyloidosis diagnosis requires:
  • Positive serum free light chain assay, serum and urine immunofixation 6
  • Evidence of multi-organ involvement 6
  • Typing of amyloid protein using mass spectrometry, immunohistochemistry, or immunofluorescence 6

Treatment and Prognosis

• Localized amyloidosis:
  • Primarily treated with local excision of amyloid deposits (61% of cases) 3
  • Excellent prognosis with 10-year survival of 78%, comparable to general population 3
  • No progression to systemic disease observed in long-term follow-up (mean 7.6 years) 2
  • Local recurrence occurs in approximately 17% of cases 3
• Systemic amyloidosis:
  • Requires systemic therapy targeting the underlying protein production 6
  • For AL amyloidosis: chemotherapy, daratumumab, proteasome inhibitors, or stem cell transplantation 6
  • Poorer prognosis, particularly with cardiac involvement 6

Clinical Implications

• Distinguishing between localized and systemic amyloidosis is crucial as:
  • Localized disease requires only local treatment and has excellent prognosis 3, 7
  • Systemic disease requires aggressive systemic therapy and has higher mortality 6
• Initial laboratory evaluation for suspected localized amyloidosis can be limited to serum and urine immunofixation in most patients 3
• Patients with localized pulmonary amyloidosis have a 5-year overall survival of 90.6% 7

Theoretical Mechanisms

• Localized AL amyloidosis may represent a unique form of plasma cell neoplasm where the produced light chains are toxic to the plasma cells themselves, causing a form of "cellular suicide" that limits disease spread 5
• This self-limiting nature may explain why localized amyloidosis rarely progresses to systemic disease 2, 5