TY - JOUR
T1 - How I Treat amyloidosis
T2 - The importance of accurate diagnosis and amyloid typing
AU - Leung, Nelson
AU - Nasr, Samih H.
AU - Sethi, Sanjeev
PY - 2012/10/18
Y1 - 2012/10/18
N2 - Amyloidosis is a rare group of diseases characterized by deposition of amyloid fibrils in soft tissues. More than 28 types of amyloid have been identified. They all share common ultrastructural and chemical characteristics. Treatments are available for many types but are type specific. Therefore, confirmation and typing of amyloid are essential before initiating treatment. Monoclonal protein studies should be performed on suspected cases, but the diagnosis requires a tissue biopsy. Congo red stain and electron microscopy are helpful to discriminate between amyloid and other pathologic fibrils. Once amyloid is confirmed, typing should be performed. Immunofluorescence and immunohistochemistry are frequently used and are helpful, but this approach has limitations, such as availability, specificity and sensitivity of commercial antibodies. Genetic mutational analysis is vital for ruling in and out hereditary amyloidoses but is unhelpful in nonmutated forms. The most advanced technique of amyloid typing is laser microdissection followed by mass spectrometry. Using proteomics, laser microdissection followed by mass spectrometry can directly identify proteins with or without mutations. Finally, imaging studies, such as cardiac MRI with gadolinium and 123I-labeled SAP scintigraphy not only assist in evaluation of patients with known amyloidosis but cardiac MRI has detected amyloid in patients previously unsuspected of the disease.
AB - Amyloidosis is a rare group of diseases characterized by deposition of amyloid fibrils in soft tissues. More than 28 types of amyloid have been identified. They all share common ultrastructural and chemical characteristics. Treatments are available for many types but are type specific. Therefore, confirmation and typing of amyloid are essential before initiating treatment. Monoclonal protein studies should be performed on suspected cases, but the diagnosis requires a tissue biopsy. Congo red stain and electron microscopy are helpful to discriminate between amyloid and other pathologic fibrils. Once amyloid is confirmed, typing should be performed. Immunofluorescence and immunohistochemistry are frequently used and are helpful, but this approach has limitations, such as availability, specificity and sensitivity of commercial antibodies. Genetic mutational analysis is vital for ruling in and out hereditary amyloidoses but is unhelpful in nonmutated forms. The most advanced technique of amyloid typing is laser microdissection followed by mass spectrometry. Using proteomics, laser microdissection followed by mass spectrometry can directly identify proteins with or without mutations. Finally, imaging studies, such as cardiac MRI with gadolinium and 123I-labeled SAP scintigraphy not only assist in evaluation of patients with known amyloidosis but cardiac MRI has detected amyloid in patients previously unsuspected of the disease.
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U2 - 10.1182/blood-2012-03-413682
DO - 10.1182/blood-2012-03-413682
M3 - Article
C2 - 22948045
AN - SCOPUS:84868157601
SN - 0006-4971
VL - 120
SP - 3206
EP - 3213
JO - Blood
JF - Blood
IS - 16
ER -