AL amyloid

AL amyloidosis ('Light chain' amyloidosis) arises when a clonal population of plasma cells in the bone marrow produces excess immunoglobulin light chains that misfold into a beta-pleated sheet configuration, forming insoluble amyloid fibrils. These fibrils deposit extracellularly in various organs, causing progressive dysfunction. Unlike AA amyloidosis (associated with chronic inflammatory conditions, derived from serum amyloid A protein) or transthyretin (ATTR) amyloidosis, AL amyloidosis is directly linked to an underlying plasma cell dyscrasia, most commonly a small clone of monoclonal plasma cells, and about 10-15% of patients have overt multiple myeloma. Clinical manifestations are protean and depend on organ involvement: restrictive cardiomyopathy (thickened ventricular walls, diastolic dysfunction, arrhythmias, heart failure), nephrotic syndrome (from glomerular deposition, often with heavy proteinuria), hepatomegaly, peripheral/autonomic neuropathy, macroglossia (classic but less common finding), periorbital purpura ('raccoon eyes') after minor trauma, and carpal tunnel syndrome. Diagnosis requires tissue biopsy (abdominal fat pad, bone marrow, or affected organ) showing apple-green birefringence under polarized light after Congo red staining. Immunohistochemistry or mass spectrometry confirms the light chain subtype. Serum free light chain assay and serum/urine protein electrophoresis with immunofixation are used for screening monoclonal protein. Cardiac biomarkers (BNP, troponin) and echocardiography assess cardiac involvement, a major determinant of prognosis. Treatment targets the underlying plasma cell clone, using regimens similar to multiple myeloma (e.g., bortezomib-based combinations, sometimes with autologous stem cell transplant), aiming to reduce light chain production and halt further amyloid deposition. Prognosis is highly dependent on cardiac involvement, with untreated cardiac AL amyloidosis carrying a poor prognosis (median survival of months) if advanced.