Diagnostic challenges in AL amyloidosis-associated neuropathy

Systemic light chain (AL) amyloidosis is a severe disorder caused by clonal plasma cell dyscrasia, leading to misfolded immunoglobulin light chains that deposit as amyloid fibrils and cause progressive organ dysfunction. Peripheral neuropathy, the most common neurological manifestation, occurs in up to one-third of patients. Early recognition is essential to initiate therapy directed at the underlying plasma cell clone, yet diagnosis is frequently delayed because of heterogeneous clinical presentations and the need for tissue confirmation. Delays are particularly common when neuropathy is the first symptom. A 79-year-old man with prior rectal cancer, hypertension, and hepatic steatosis presented with rapidly progressive, asymmetric distal weakness and sensory loss affecting all limbs. Electroneuromyography demonstrated severe length-dependent axonal sensorimotor polyneuropathy with prominent distal denervation. Serum studies revealed a weak IgM kappa monoclonal protein (1.5 g/L), and bone marrow aspiration showed a small kappa-restricted plasma cell clone. Fat pad and bone marrow biopsies were negative for amyloid. The working diagnosis was monoclonal gammopathy–associated neuropathy, and treatment with rituximab was initiated, but symptoms progressed and re-treatment remained ineffective. Sural nerve biopsy did not detect amyloid. Months later, the patient developed a rash; skin biopsy demonstrated light chain amyloid deposition, confirming AL amyloidosis. By then, his clinical status had declined to the point that chemotherapy was not feasible, and the patient passed away shortly thereafter. This case illustrates the diagnostic difficulty of AL amyloidosis when neuropathy is the initial manifestation. Fat pad, bone marrow, and nerve biopsies may remain negative even in advanced disease. When clinical suspicion persists, skin biopsy can establish the diagnosis, including when cutaneous signs appear late.