Musculoskeletal Manifestations of Light Chain Amyloidosis: A Systematic Review

Diagnosing amyloid arthropathy remains challenging because its manifestations often mimic those of other inflammatory musculoskeletal diseases. This review aimed to describe the clinical, biological, and imaging characteristics of musculoskeletal involvement in light-chain (AL) Amyloidosis.

We conducted a review in accordance with the PRISMA guidelines. We searched SCOPUS and MEDLINE for case reports and series published between January 2000 and December 2023 that detailed musculoskeletal manifestations of AL amyloidosis. To minimize the risk of omitting relevant articles, we also manually searched the reference lists of the articles identified in the initial search. Reports describing isolated cardiac amyloidosis or patients under active chemotherapy were excluded.

We identified 140 patients, all of whom presented with musculoskeletal manifestations as the initial manifestation of systemic AL amyloidosis. The mean age was 62.6 ± 11.6 years. Musculoskeletal findings included joint involvement in 33.6% of cases, muscular symptoms in 10.7%, carpal tunnel syndrome in 30%, and bone lesions in 12.1%. Among patients with joint disease, 42 (30%) had a rheumatoid arthritis-like presentation, and five (3.6%) exhibited features resembling giant cell arteritis. Diagnosis was confirmed by positive immunostaining for lambda light chains in all cases. Multiple myeloma was identified in 37.5% of patients. Of the 46 patients with available treatment data and a median follow-up of 11.5 months (range: 6-23 months), 25 (17.8%) achieved hematologic remission after chemotherapy, whereas 21 (15%) died during follow- up.

Our review offers a more comprehensive picture of the diverse musculoskeletal manifestations of AL amyloidosis. It showed that amyloid arthropathy can mimic common rheumatologic disorders, especially rheumatoid arthritis. Publication bias was identified as the main study limitation.

Our findings suggest that the diagnosis of AL amyloidosis should be considered when joint involvement is associated with macroglossia, nephrotic syndrome, polyneuropathy, periorbital purpura, cutaneous lesions, or heart failure.