TITLE:
Light-Chain Amyloidosis: Orthopedic Manifestations and Clues to Early Diagnosis
AUTHORS:
Gustavo Alberto Gutiérrez-Barros, Gabriela María Morales-Donado, Miguel Elías de Jesús Babilonia-Morelo, Valeria Paola Durán-Martínez, Jaime José Oñate-López, Jaime José Barrios-Arrieta, María Camila Vásquez-Velasco, Luis Enrique Vélez-Cantor, Juan Camilo Lara-Gálvez
KEYWORDS:
Immunoglobulin Light-Chain Amyloidosis, Musculoskeletal Manifestations, Orthopedic Surgery, Carpal Tunnel Syndrome, Tissue Biopsy, Mass Spectrometry, Early Diagnosis
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.10,
October
26,
2026
ABSTRACT: Importance: Systemic immunoglobulin light-chain (AL) amyloidosis is a clonal disorder in which survival depends largely on organ involvement at diagnosis. Musculoskeletal manifestations may precede recognition of cardiac or renal disease, but their overlap with common orthopedic disorders complicate early identification. Objective: To synthesize evidence on the musculoskeletal manifestations of AL amyloidosis, their temporal relationship with systemic diagnosis, and the diagnostic utility of tissues obtained during orthopedic procedures. Evidence Review: PubMed/MEDLINE was systematically searched for publications from January 1, 2016, through August 27, 2026. A total of 350 records were retrieved, and 13 publications were included in the AL-specific synthesis: two primarily addressing orthopedic manifestations and eleven primarily addressing diagnosis. Reviews and cohorts involving multiple amyloid types were used as contextual evidence and were not counted among the included publications. Heterogeneity in populations, tissues, typing methods, and outcomes required narrative synthesis. Findings: Clinical suspicion increases when orthopedic manifestations are bilateral, recurrent, or multifocal or coexist with monoclonal gammopathy or organ involvement. Interpretation of the reported temporal associations is limited by patient selection and retrospective documentation. In the orthopedic cohorts used as contextual evidence, deposits were predominantly transthyretin-derived, and new diagnoses of systemic AL amyloidosis were uncommon. Congo red positivity demonstrates amyloid but does not identify its precursor; a concomitant monoclonal gammopathy does not establish the composition of the deposit. Evaluation should integrate serum and urine immunofixation, serum free light-chain measurement, and tissue typing. A negative peripheral biopsy does not exclude AL amyloidosis when clinical suspicion remains high. Conclusions and Relevance: Musculoskeletal manifestations may facilitate recognition of AL amyloidosis but lack sufficient specificity in isolation. Suggestive patterns may prompt targeted, multidisciplinary diagnostic evaluation. Available evidence does not demonstrate a clinical benefit from screening orthopedic tissues or support its universal application; prospective studies are needed to assess its effects on disease stage at diagnosis and clinical outcomes.