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
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