Musculoskeletal pathology as an early warning sign of systemic amyloidosis: a systematic review of amyloid deposition and orthopedic surgery

Abstract

Background Transthyretin and immunoglobulin light-chain amyloidoses cause amyloid deposition throughout various organ systems. Recent evidence suggests that soft tissue amyloid deposits may lead to orthopedic conditions before cardiac manifestations occur. Pharmacologic treatments reduce further amyloid deposits in these patients. Thus, early diagnosis improves long term survival. Questions/purposes The primary purpose of this systematic review was to characterize the association between amyloid deposition and musculoskeletal pathology in patients with common orthopedic conditions. A secondary purpose was to determine the relationship between amyloid positive biopsy in musculoskeletal tissue and the eventual diagnosis of systemic amyloidosis. Methods We performed a systematic review using PRISMA guidelines. Inclusion criteria were level I-IV evidence articles that analyzed light-chain or transthyretin amyloid deposits in common orthopedic surgeries. Study methodological quality, risk of bias, and recommendation strength were assessed using MINORS, ROBINS-I, and SORT. Results This systematic review included 24 studies for final analysis (3606 subjects). Amyloid deposition was reported in five musculoskeletal pathologies, including carpal tunnel syndrome (transverse carpal ligament and flexor tenosynovium), hip and knee osteoarthritis (synovium and articular cartilage), lumbar spinal stenosis (ligamentum flavum), and rotator cuff tears (tendon). A majority of studies reported a mean age greater than 70 for patients with TTR or AL positive amyloid. Conclusions This systematic review has shown the presence of amyloid deposition detected at the time of common orthopedic surgeries, especially in patients ≥70 years old. Subtyping of the amyloid has been shown to enable diagnosis of systemic light-chain or transthyretin amyloidosis prior to cardiac manifestations. Level of evidence Level IV.

Clinical relevance of amyloid in prostate samples: a report on 40 patients

“…As patients could potentially present with musculoskeletal conditions prior to systemic manifestations, orthopaedic surgeons may play a role in early diagnosis. 43 Hearing impairment was even more frequent than CTS in our patients (n = 22; 55% versus n = 17; 42.5%). ATTR-related hearing loss is already known, although there is little in the literature on the subject.…”

“…ATTR and AL are difficult diseases to diagnose due to non‐specific symptoms, overlapping diagnoses and under‐recognition by physicians. As patients could potentially present with musculoskeletal conditions prior to systemic manifestations, orthopaedic surgeons may play a role in early diagnosis 43 …”

Transthyretin Cardiac Amyloidosis: A Cardio-Orthopedic Disease

“…The presence of amyloidosis and its typing has also been systematically searched for in biopsies of common orthopedic surgeries regardless of the demonstration of systemic amyloidosis. Wininger et al in a large systematic review of amyloid deposition in patients undergoing lumbar spinal decompression found the presence of ATTR on 64/157 (41%) surgical specimens [ 35 ]. In two different studies, the thickness of the ligamentum flavum was found to be significantly greater in patients with LSS and ATTR positive biopsy than in those with negative biopsy.…”

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“…Later studies using NMR analysis further confirmed this hypothesis [ 6 ]. Due to the ubiquitous presence of proteins in the body’s cells, amyloidosis is clinically considered a systemic disease [ 7 ]. For example, amyloid accumulation plays a special role in the pathogenesis of Alzheimer disease (AD), Parkinson’s disease, or transthyretin amyloidosis [ 8 ].…”