What are the diagnostic steps and treatment approaches for a patient presenting with suspected amyloidosis?

From the Guidelines

Diagnosing and treating amyloidosis requires a systematic approach beginning with clinical suspicion based on presenting symptoms, and the most recent evidence suggests that tissue biopsy remains the gold standard for diagnosis, with abdominal fat pad aspiration often used as a less invasive initial approach, followed by organ-specific biopsies if needed, as recommended by the 2023 ACC expert consensus decision pathway 1. The diagnostic process starts with non-invasive tests including:

• Serum and urine protein electrophoresis
• Free light chain assay
• Cardiac biomarkers (troponin, BNP) Tissue biopsy is crucial for diagnosis, with Congo red staining of tissue samples revealing characteristic apple-green birefringence under polarized light. Additional testing includes:
• Genetic analysis for hereditary forms
• Typing of the amyloid protein using mass spectrometry or immunohistochemistry, with mass spectrometry-based analysis (LC-MS/MS) being the gold standard for tissue diagnosis, as reported in the 2023 ACC expert consensus decision pathway 1. Treatment depends on the amyloid type and affected organs. For AL amyloidosis, chemotherapy regimens such as bortezomib (Velcade), cyclophosphamide, and dexamethasone (CyBorD) target the underlying plasma cell disorder, with autologous stem cell transplantation considered for eligible patients, as discussed in the comprehensive review of AL amyloidosis 1. ATTR amyloidosis may be treated with TTR stabilizers like tafamidis (20-80mg daily) or TTR silencers such as patisiran or inotersen. Supportive care is essential and includes:
• Diuretics for heart failure
• Pacemakers for conduction abnormalities
• Dialysis for renal failure Early diagnosis and treatment are crucial as they can significantly improve prognosis by preventing further amyloid deposition and organ damage, highlighting the importance of collaboration between hematologists and cardiologists in the management of patients with presumed or established AL amyloidosis, as emphasized in the 2023 ACC expert consensus decision pathway 1.

From the FDA Drug Label

VYNDAQEL and VYNDAMAX are indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.

The diagnostic steps and treatment approaches for a patient presenting with suspected amyloidosis are not directly addressed in the provided drug labels. Key points:

• The labels discuss the treatment of cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) with tafamidis.
• They do not provide information on diagnostic steps for amyloidosis.
• Treatment approaches mentioned are specific to ATTR-CM and involve the use of tafamidis to reduce cardiovascular mortality and cardiovascular-related hospitalization 2, 2, 2.

From the Research

Diagnostic Steps for Amyloidosis

• The diagnosis of amyloidosis often requires a biopsy of an involved organ or tissue to confirm the presence of amyloid fibrils 3.
• Cardiac transthyretin amyloidosis may be diagnosed without a biopsy if stringent criteria are met 3.
• Laser capture microdissection and tandem mass spectrometry (LCM-MS) can be used to identify the amyloidogenic protein and subtype the amyloidosis 3.
• Protein typing by mass spectrometry, optical and/or electronic immunomicroscopy, and measurement of serum free light chains are recommended for evaluating a monoclonal plasma cell proliferative disorder 4.
• Serum and urinary immunofixation are also recommended for evaluating a monoclonal plasma cell proliferative disorder 4.

Treatment Approaches for Amyloidosis

• The treatment of amyloidosis depends on the type and severity of the disease, as well as the organs involved 5.
• Light chain (AL) amyloidosis can be treated with reference to patterns applied in multiple myeloma 5.
• Three drugs (tafamidis, patisiran, and inotersen) are available to treat grade 1 or 2 polyneuropathy in ATTRv amyloidosis, and further agents are being tested in clinical trials 5.
• Tafamidis is expected to be approved soon for the treatment of cardiac ATTR amyloidosis 5.
• Early diagnosis and treatment are crucial to improve patient survival and quality of life 6.

Clinical Suspicion and Diagnosis

• High clinical suspicion is required to facilitate early diagnosis of amyloidosis 7.
• The signs and symptoms that should raise suspicion for the potential diagnosis of amyloidosis are usually nonspecific, and establishing the diagnosis can be difficult 6.
• A rapid, targeted diagnostic evaluation and subsequent initiation of treatment should be performed in a specialized center if clinical suspicion is high 5.
• All MGUS patients should be routinely screened for AL amyloidosis by a focused history and physical examination and routine assessment of urine albumin 6.