Immunoglobulin light-chain (AL) amyloidosis should be considered in any patient presenting with nephrotic range proteinuria; infiltrative cardiomyopathy or heart failure with preserved ejection fraction; hepatomegaly without specific imaging findings; peripheral neuropathy, particularly if a monoclonal protein is present; and any patient with atypical myeloma, smoldering myeloma, or monoclonal gammopathy of undetermined significance (MGUS) that is unwell. When a patient is seen with a compatible syndrome, the patient should have immunofixation of serum, immunofixation of urine, and κ and λ immunoglobulin free light chains. If all of these tests are normal, it is less likely that the patient has immunoglobulin light-chain (AL) amyloidosis.
If any of the above tests are positive, further investigation for amyloidosis should be undertaken. The diagnostic test of choice is subcutaneous fat aspiration. The second would be a marrow biopsy. With those two tests, 83% of patients will have a positive result when the sample is stained with Congo red and viewed with green birefringence.
All patients with biopsy-proven amyloidosis should have the deposits analyzed by laser capture microdissection mass spectroscopy to definitively classify the exact protein subunit composing the amyloid. This technique does not distinguish between systemic and localized amyloidosis.
The prognosis in AL amyloidosis is determined by three tests: (1) the NT-proBNP, (2) serum troponin, and (3) the difference between the involved and uninvolved immunoglobulin free light chains. These three tests can be combined to stage the patient.
Treatment of AL amyloidosis is either traditional systemic chemotherapy or high-dose chemotherapy with stem cell transplantation. Fit patients would be expected to have low morbidity with this modality of treatment. The majority of patients, however, will not be candidates for transplantation and should be treated with traditional systemic chemotherapy; and the combination of cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is frequently used. Daratumumab is also efficacious in AL amyloidosis.
Acronyms and Abbreviations
ACE, angiotensin converting enzyme; AL, immunoglobulin light chain amyloidosis; A Lect 2, amyloid composed of leukocyte chemotactic factor 2; aPTT, activated partial thromboplastin time; ARB, angiotensin II receptor blocker; ARF, ADP-ribosylation factor; ATTRwt, wild type transthyretin amyloidosis; C-Pi B, Pittsburgh compound B; CRAB, Calcemia, renal insufficiency, anemia, or bone disease; CyBorD, cyclophosphamide, bortezomib, and dexamethasone; dFLC, difference between involved and uninvolved free light chains; eGFR, estimated glomerular filtration rate; HFpEF, heart failure with preserved ejection fraction; MGUS, monoclonal gammopathy of undetermined significance; MRI, magnetic resonance imaging; NT-ProBNP, N-terminal pro type B natriuretic peptide; PT, Prothrombin time, TTR, transthyretin.
Amyloidosis is a heterogeneous group of diseases characterized by tissue infiltration with misfolded protein. For more than 100 years, amyloid has been defined by its staining properties. Divry and Florkin first used Congo red to detect amyloid in the brain of patients with Alzheimer disease.1 Common to all forms of amyloidosis, the deposits bind Congo red dye and demonstrate green birefringence under polarized light.2 This remains the standard procedure required to confirm a diagnosis of amyloidosis. Amyloid deposits are always ...