From the Guidelines
The most effective way to diagnose amyloidosis is through a combination of tissue biopsy with Congo red staining and mass spectrometry-based analysis, as recommended by the most recent and highest quality study 1. This approach involves taking a small sample of affected tissue and examining it under polarized light after staining to confirm the presence of amyloid deposits. When positive, the characteristic apple-green birefringence confirms the presence of amyloid deposits. The diagnostic workup should also include blood and urine tests to identify the specific type of amyloidosis, such as serum and urine protein electrophoresis, free light chain assay, and immunofixation to detect monoclonal proteins in AL amyloidosis. Additional testing may include cardiac biomarkers (troponin, BNP), echocardiography, and advanced imaging like cardiac MRI with gadolinium or nuclear scintigraphy with bone tracers, which can help assess organ involvement. Genetic testing is essential when hereditary amyloidosis is suspected, as recommended by 1 and 1. Some key points to consider in the diagnosis of amyloidosis include:
- Tissue biopsy with Congo red staining is the gold standard diagnostic approach
- Mass spectrometry-based analysis is necessary to determine the precursor protein
- Blood and urine tests are necessary to identify the specific type of amyloidosis
- Cardiac biomarkers and advanced imaging are necessary to assess organ involvement
- Genetic testing is essential when hereditary amyloidosis is suspected
- A comprehensive approach is necessary because amyloidosis can affect multiple organs and presents with varied symptoms, making early and accurate diagnosis crucial for appropriate treatment selection and improved outcomes, as noted in 1.
From the Research
Diagnosis of Amyloidosis
The diagnosis of amyloidosis can be challenging due to its clinical heterogeneity and the lack of a single diagnostic test. However, several approaches can be taken to confirm the diagnosis:
- Biopsy of an involved organ or tissue is often required to confirm the diagnosis of amyloidosis 2
- Cardiac transthyretin amyloidosis may be diagnosed without a biopsy if stringent criteria are met 2
- Laser capture microdissection and tandem mass spectrometry (LCM-MS) can be used to identify the amyloidogenic protein and subtype amyloidosis 2
- Technetium scintigraphy can aid in the noninvasive diagnosis of transthyretin (ATTR) amyloidosis 3
- A comprehensive multidisciplinary diagnostic algorithm can facilitate the early and efficient detection of amyloidosis 4
Clinical Suspicion and Investigation
Clinical suspicion is crucial for early diagnosis, and certain signs and symptoms should raise suspicion for amyloidosis:
- Nonspecific signs and symptoms, such as macroglossia and periorbital purpura, may indicate light chain (AL) amyloidosis 5
- Cardiac amyloidosis is a major determinant of survival, and early detection is essential 5
- Patients with monoclonal gammopathy of undetermined significance (MGUS) should be routinely screened for AL amyloidosis 5
- A focused history, physical examination, and routine assessment of urine albumin can help identify patients at risk of amyloidosis 5
Diagnostic Techniques and Limitations
Various diagnostic techniques have limitations, and a combination of approaches may be necessary:
- Immunohistochemistry and other antibody-based methods may not be reliable for amyloid subtyping 2
- LCM-MS is a more reliable method for identifying the amyloidogenic protein 2
- Technetium scintigraphy has improved the diagnosis of ATTR amyloidosis, but its availability and interpretation may vary 3
- A comprehensive diagnostic algorithm can help minimize uninformative investigations and reduce the time to diagnosis 4