Amyloidosis

Epidemiology

  • 30% of patients with Amyloidosis have pulmonary symptoms

Etiology

  • Idiopatic Amyloidosis:
  • Multiple Myeloma (see [[Multiple Myeloma]])
  • Sjogren’s Syndrome (see [[Sjogrens Syndrome]])
  • Rheumatoid Arthritis (see Rheumatoid Arthritis]])

Physiology

  • Airway or parenchymal involvement by primary or secondary amyloidosis (with protein deposited in airway)
  • Ig light chains are the only type of proteins that deposit to any significant extent in the lungs
  • Systemic amyloidosis: Ig light chain deposition in lungs, heart, GI tract, skin, kidney, skeletal muscle
  • Localized pulmonary amyloidosis: formation of Ig light chains by local B-cells or plasma cells (supported by observed formation of amyloid from calcitonin in medullary thyroid ca mets to lung)
  • Upper Airway: amyloid infiltration of vocal cords or tongue

Pathology

  • Nodular pattern: see below
  • Diffuse alveolar septal pattern: amorphous material infiltrates the interstitium and walls of pulmonary arteries, arterioles, and veins (EM reveals dense deposits in alveolar capillary BM)
  • Congo Red stain under polarized light: reveals characteristic “apple green” birefringence
  • PAS: stains alpha glycoprotein of amyloid

Diagnosis

  • FOB: EBB of endobronchial disease with Congo red stain reveals green birefringence under polarized light
    • Endobronchial plaques (usually multiple) or endobronchial papillary lesion (usually single): areas may calcify and form tracehobroncho-pathia osteoplastica/ areas may bleed severly after EBB (laser prbably is preferred)
    • TBB: should be performed with caution in diffuse cases (due to risk of bleeding from infiltrated vessels and factor 10 binding by amyloid/ report of fatal air embolism)
  • FNA: used in some cases for diagnosis, but bleeding risk is higher
  • CXR/Chest CT Pattern
    • Nodular pattern (due to mucosal large airway involvement or parenchymal macronodules): 2-4 cm nodules (sometimes <15 cm) with no lobar predilection (occasionally peripheral/occasionally cavitate/ occasionally calcified)
    • Extremely rare etiology of solitary pulmonary nodule
    • Mediastinal lymphadenopathy: may be massive and calcified in some cases (mimicking Sarcoid, NHL)
    • Large airway mucosal involvement
      • Plaques: usually present with wheezing/ fair prognosis
      • Papillary lesion: usually asymptomatic/good prognosis
    • Diffuse pattern (due to alveolar septal and pulmonary vascular involvement): diffuse interstitial infiltrates
      • Kerley B lines: thickened inter-lobular septa (seen at periphery of lung) due to pulmonary lymphatic obstruction
      • HRCT: small areas of calcification seen
      • Pleural effusion may be seen (although rarely without other CXR findings or associated CHF)
  • SPEP: positive for monoclonal gammopathy (90% of cases)
  • Rectal Mucosal Bx (or Abdominal SQ Fat Bx): safe and sensitive for AL type amyloid

Clinical

Pulmonary Manifestations

  • Nodular CXR pattern: usually asymptomatic/ good prognosis
    • Typical pattern in: localized lower respiratory tract amyloid
    • Complications: airway obstruction/ hemoptysis/ pulmonary AV fistula within a nodule (one case report)
  • Diffuse CXR pattern: usually symptomatic (with restrictive PFT’s and hypoxemia)/ progressive with poor prognosis
    • Typical pattern in: Myeloma and Systemic Amyloidosis cases (this is an uncommon pattern in localized lower respiratory tract amyloid)
    • Complications: pulmonary HTN (due to vascular infiltration)/ spontaneous hemoptysis (due to medial dissection of medium-size PA)/ diaphragmatic weakness (due to infiltration)

Upper Airway Manifestations

  • Macroglossia (due to infiltration of tongue/ may cause OSA or obstruction)
    is seen in 22% of primary amyloidosis cases

    • Unlikely to produce significant UA obstruction

Cardiac Manifestations

  • xx

Other Manifestations

Treatment

  • Nodular Pulmonary Involvement
    • Surgical resection of lung nodules: usually not necessary
  • Diffuse Pulmonary Involvement: supportive therapy
    • Colchicine (as used in FMF) and DMSO have been proposed but not proven

References

  • Shah KB, Inoue Y, Mehra MR. Amyloidosis and the heart: a comprehensive review. Arch Intern Med 2006;166:1805-1813