CONCLUSION

Peripheral neuropathy associated with AL amyloidosis presents with painful paresthesias, numbness and weakness affecting the lower more than upper limbs. Initially, small fiber sensory modalities may be more severely affected than large fiber modalities. The neuropathy shows relentless progression to become a generalized, debilitating sensorimotor neuropathy. Symptoms of autonomic dysfunction are present in two thirds of patients. Autonomic involvement should be confirmed by formal autonomic testing. Electrodiagnostic studies show a length-dependent axonal neuropathy or diffuse polyradiculoneuropathy. Carpal tunnel syndrome can be found in 25% of patients.⁴ In our case, the painful paresthesias, distal weakness, autonomic dysfunction, and weight loss prompted us to abandon the previous diagnosis of CIDP.

What evaluations are necessary to establish the diagnosis of AL amyloidosis? Immunofixation of the serum and of the urine detects a monoclonal protein in 90% of patients. There is a predominance of λ light chains. An immunoassay of serum FLCs gives abnormal results in 99% in combination with serum immunofixation. The absolute level of the abnormal FLC also has prognostic implications in patients undergoing stem cell transplantation.⁵ The diagnosis requires confirmation of positive amyloid staining on a tissue biopsy and supporting evidence that the amyloid is of the AL type. Congo red staining of a bone marrow biopsy specimen demonstrates amyloid deposits in half of the patients, whereas a subcutaneous fat aspirate is positive in 80%. If either one of these biopsy results are negative or equivocal, a sural nerve biopsy is helpful in patients with amyloid neuropathy. The amyloid deposits in the nerve can frequently be identified as AL type by immunohistochemical staining with specific κ and λ antisera. In situations of uncertain immunostaining, familial amyloid neuropathy must be excluded by DNA sequencing of the gene encoding transthyretin.⁶

The prognosis is determined by the presence of cardiac involvement and the number of affected organs. Patients with overt congestive heart failure have the worst outcome. Cardiac involvement is assessed by echocardiogram and serum cardiac biomarkers. Current therapies target the production of immunoglobulin light chains with the goal of preventing further fibril formation. The strategies continue to evolve but consist of either conventional chemotherapy or high-dose melphalan with peripheral blood stem cell transplantation (PBSCT).⁷ Owing to the high treatment-related mortality rate of about 15%, only a relatively small group of AL patients are suitable candidates for such therapy. Patients who undergo stem cell transplantation have an estimated 5-year survival rate of 60%.⁸ The response of the peripheral neuropathy to PBSCT has not been adequately studied. A randomized trial comparing high-dose melphalan followed by PBSCT with standard chemotherapy has raised questions about the efficacy of transplantation.⁹