Amyloidosis is a group of diseases caused by extracellular deposition of misfolded proteins (amyloid fibrils) in tissues, leading to organ dysfunction. The protein type determines the disease subtype and treatment.
Treat the underlying inflammatory disease. Control RA, Crohn, FMF (colchicine for FMF). Reducing SAA levels can halt progression and even allow regression of amyloid deposits.
| Drug | Type | Dose | Notes |
|---|---|---|---|
| Daratumumab (Darzalex) AL 1ST LINE | AL | 16 mg/kg IV weekly x 8, then q2 weeks, then monthly | Anti-CD38 monoclonal antibody. Combined with CyBorD. ANDROMEDA, NEJM 2021 |
| Bortezomib (Velcade) | AL | 1.3 mg/m2 SQ weekly (part of CyBorD) | Proteasome inhibitor. Targets plasma cells. Peripheral neuropathy is dose-limiting toxicity. |
| Cyclophosphamide | AL | 300 mg/m2 PO weekly (part of CyBorD) | Alkylating agent. Dose adjust for renal function. |
| Dexamethasone | AL | 20-40 mg PO weekly (part of CyBorD) | Steroid component. Monitor glucose, infections. |
| Tafamidis (Vyndamax) | ATTR | 80 mg PO daily | TTR stabilizer for ATTR cardiac amyloidosis. Reduced mortality and CV hospitalization. ATTR-ACT, NEJM 2018 |
| Midodrine | Supportive | 5-10 mg PO TID | For orthostatic hypotension from autonomic neuropathy. Hold if supine BP >180. |
Patient: 64M with progressive dyspnea, bilateral LE edema, and orthostatic hypotension. Echo: thick walls (IVS 16 mm), small LV cavity, diastolic dysfunction, EF 50%. ECG: low voltage + pseudo-infarct pattern. NT-proBNP 9200, troponin 0.18. Macroglossia on exam.
Key findings: Classic cardiac AL amyloidosis: thick walls + low voltage on ECG = pathognomonic discordance (hypertrophy causes high voltage, but amyloid infiltration causes low voltage). Macroglossia is virtually diagnostic for AL type.
Management:
Teaching point: The ECG-echo discordance (low voltage + thick walls) is the signature finding of cardiac amyloidosis. HCM and hypertensive heart disease cause thick walls WITH high voltage. If the walls are thick but voltage is low โ think amyloid.
Patient: 82M with HFpEF refractory to standard therapy. History of bilateral carpal tunnel surgery, lumbar spinal stenosis. Echo: concentric LVH (IVS 15 mm), grade III diastolic dysfunction. Technetium pyrophosphate scan: grade 3 uptake. SPEP/sFLC normal.
Key findings: Wild-type ATTR (ATTRwt), transthyretin amyloidosis from age-related misfolding. No plasma cell dyscrasia (SPEP/sFLC normal). Tc-PYP scan grade 2-3 = diagnostic for ATTR without biopsy (if SPEP/sFLC negative). Bilateral carpal tunnel + spinal stenosis are early manifestations.
Management:
Teaching point: ATTR is now recognized as a common cause of HFpEF in elderly men, prevalence may be 10-15% of HFpEF patients > 80. Bilateral carpal tunnel + HFpEF + thick walls should trigger Tc-PYP scan. Tafamidis is disease-modifying.
Patient: 58F with progressive LE edema, foamy urine. Albumin 1.8, 24h urine protein 8.2 g/day, Cr 1.6. sFLC: lambda 420 mg/L (elevated), ratio abnormal. Renal biopsy: Congo red positive in glomeruli and vessels.
Key findings: AL amyloidosis presenting as nephrotic syndrome (renal is the most common organ involved in AL). Lambda light chain predominance. Must assess cardiac involvement, asymptomatic cardiac amyloid can coexist.
Management:
Teaching point: In any patient with unexplained nephrotic syndrome + monoclonal protein, think AL amyloidosis. The combination of nephrotic-range proteinuria + abnormal sFLC ratio is the classic presentation. Always check cardiac biomarkers, occult cardiac involvement determines prognosis.
Mr. Franklin is a 62-year-old man presenting with 6 months of progressive dyspnea on exertion, lower extremity edema, and 15-lb weight loss. He also reports numbness/tingling in both feet and lightheadedness when standing. Exam: macroglossia, periorbital purpura, elevated JVP, bilateral pitting edema. Labs: troponin 0.15 (elevated), NT-proBNP 8,400 (markedly elevated), creatinine 1.8, albumin 2.1, 24h urine protein 5.2 g/day. ECG: low voltage + pseudo-infarct pattern. Echo: thick walls (IVS 16mm) + diastolic dysfunction + small LV cavity. Free kappa/lambda ratio markedly abnormal (lambda predominant). Fat pad biopsy: Congo red positive, apple-green birefringence under polarized light.