Amyloidosis is caused by the deposition of amyloid proteins in tissue and organs. It may have a primary cause, may be inherited, or may be secondary to other diseases.
Immunoglobulin light chain (AL) amyloidosis (also called primary systemic amyloidosis) is the most common type of amyloidosis.
Amyloidosis usually presents with unexplained weight loss, fatigue, and edema resistant to diuretic therapy.
Immunofixation of the serum and urine confirms the presence of monoclonal light chains in AL amyloidosis. Biopsy verification of amyloid deposits is essential. Accurate classification of amyloid deposit in tissues is necessary prior to initiating appropriate therapy.
Treatment includes appropriate management of resulting clinical syndromes, such as nephrotic syndrome, neuropathy, cardiomyopathy, and conduction disorders.
Treatment for AL amyloidosis is high-dose myeloablative chemotherapy with autologous stem cell transplantation (in selected patients) or systemic therapy, or both.
Amyloidosis is caused by the deposition of amyloid proteins in tissue and organs. Any histologic tissue specimen that binds Congo red and demonstrates green birefringence when viewed under polarized light is, by definition, an amyloid deposit.
Deposits of amyloid may be localized in tissue or part of a systemic process. Progressive deposition of amyloid is disruptive to tissue and organ function and manifests its clinical sequelae by the dysfunction of those organs in which it deposits.
History and exam
Key diagnostic factors
- jugular venous distention
- lower extremity edema
- periorbital purpura
- eyelid petechiae
Other diagnostic factors
- weight loss
- dyspnea on exertion
- peripheral neuropathy
- autonomic neuropathy
- nausea or vomiting
- abdominal cramps
- alternating bowel habit
- lightheaded/orthostatic hypotension
- submandibular salivary gland enlargement
- shoulder pad sign
- diffuse muscular weakness
- Carpal tunnel syndrome
- monoclonal gammopathy of undetermined significance (MGUS)
- inflammatory polyarthropathy
- chronic infections
- inflammatory bowel disease
- familial periodic fever syndromes
- Castleman disease
1st investigations to order
- serum immunofixation
- urine immunofixation
- immunoglobulin free light chain assay
- comprehensive metabolic profile
- 24-hour urine collection
Investigations to consider
- tissue biopsy
- mass spectrometry
- immuno-electron microscopy
- immuno-histochemical studies
- genetic testing
- serum troponin level
- N-terminal pro-B-type natriuretic peptide
- echocardiogram (with tissue Doppler and global longitudinal strain)
- cardiac MRI
- scintigraphy (bone)
immunoglobulin light chain (AL) amyloidosis
secondary (AA) amyloidosis (non-familial)
familial periodic fever syndromes
transthyretin (TTR) amyloidosis
relapsed or refractory AL amyloidosis
Morie A. Gertz, MD, MACP
Seidler Jr. Professor of Medicine
Consultant in Hematology
Chair Emeritus of the Department of Medicine
Mayo Distinguished Clinician
Mayo Clinic College of Medicine
MAG has received personal fees from Ionis/Akcea, Alnylam, Prothena, Janssen, Annexon, Appellis, Amgen, Medscape, Physicians Education Resource, and Research to Practice; and grants and personal fees from Spectrum. MAG has received personal fees from AbbVie and Celgene for a Data Safety Monitoring board, and personal fees from Sanofi for workforce training. MAG has received speaker fees from Teva, Johnson & Johnson, Medscape, and DAVA Oncology; and advisory board fees from Pharmacyclics and Procalara. MAG has participated in the development of educational materials for the i3Health Educational Program development. MAG has received royalties from Springer Publishing. MAG has received grant funding from the Amyloidosis Foundation, International Waldenstrom's Macroglobulinemia Foundation, and National Cancer Institute (SPORE MM SPORE 5P50 CA186781-04). MAG has stock options in Aurora Bio. MAG is an author of references cited in this topic.
Donna Reece, MD
Associate Professor of Medicine
Program for Multiple Myeloma and Related Diseases
Princess Margaret Hospital
DR has been reimbursed by Millennium Pharmaceuticals, Inc and Johnson & Johnson, the manufacturers of bortezomib, for attending several conferences, for speaking at educational meetings, and for consulting work. She has also been reimbursed by Celgene, the manufacturer of lenalidomide and thalidomide, for attending several symposia and serving as a speaker.
Jeffrey Zonder, MD
Assistant Professor of Medicine and Oncology
Division of Hematology/Oncology
Wayne State University School of Medicine
Barbara Ann Karmanos Cancer Institute
JZ declares that he has no competing interests.
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