Multisystem Light Chain Amyloidosis: Diagnostic and Therapeutic Challenges

Amyloid light (AL) chain amyloidosis is a rare, progressive multisystem disorder caused by the deposition of misfolded monoclonal light chains, which are produced by clonal plasma cells and commonly affect the kidneys and heart. The overall prognosis depends on the extent of organ involvement and timely diagnosis. A previously healthy 57-year-old man presented with a two-month history of progressive lower limb edema and exertional dyspnea. Initial investigations revealed elevated troponin, hypoalbuminemia, and nephrotic-range proteinuria. Coronary angiography was normal, but echocardiography showed restrictive cardiomyopathy. Renal biopsy after light and immunofluorescence microscopy was reported as membranous nephropathy. However, there was no response to proteinuria to sacubitril/valsartan, sodium-glucose co-transporter 2 (SGL2) inhibitor, and steroid therapy. The treatment was escalated with additional immunosuppressive treatments, including cyclosporine and rituximab. Subsequently, Congo red staining of the renal biopsy confirmed a diagnosis of amyloidosis. Further, a hematologic workup showed marked lambda (λ) light chain predominance with a suppressed kappa (κ)/λ ratio, and fluorescence in situ hybridization (FISH) analysis revealed a t (11;14) translocation, confirming AL amyloidosis. The patient was treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone (Dara-VCD), which was complicated by cytomegalovirus (CMV) gastritis. Despite receiving three cycles of therapy, the patient's condition deteriorated due to advanced cardiac failure, autonomic neuropathy, and a severe CMV infection. He ultimately succumbed to the illness 18 months after the initial presentation. This case highlights the diagnostic complexity of AL amyloidosis and the importance of early recognition. Clinicians should consider AL amyloidosis in patients with unexplained nephrotic syndrome and heart failure.