Amyloid Arthropathy: A Review

Abstract

Amyloid arthropathy is a joint disease associated with systemic amyloidosis. Herein, we present a model case and review the clinicopathologic features and pathophysiology of this disorder. Amyloid arthropathy results from elevation of serum amyloidogenic proteins and their deposition as aggregates in synovial fluid and articular tissues. The most common proteins are beta-2-microglobulin in the context of long-term hemodialysis therapy and immunoglobulin light chains associated with plasma cell proliferations. We provide a comprehensive update on the pathogenesis, clinical manifestations, and pathologic features of amyloid arthropathy. We provide detailed insights on amyloid protein deposition and aggregation in joints and proper details for diagnosis.

Synoviale Veränderungen bei Erkrankungen des rheumatologischen Formenkreises und Differenzialdiagnosen

“…Heute ist es nicht nur erforderlich, diese Krankheitsbilder zu erkennen und eine Amyloidose zu diagnostizieren, sondern auch eine Subtypisierung vorzunehmen. Häufige Amyloidosen stellen dabei AL-Amyloidosen (Leichtkettenamyloidosen) bei Plasmozytomen und B‑Zell-Lymphomen, AA-Amyloidosen bei chronisch-entzündlichen Erkrankungen, Transthyretin-Amyloidose (ATTR) und dialyseassoziierte Amyloidosen dar, die jeweils ein unterschiedliches therapeutisches Vorgehen erfordern [ 1 , 2 ].…”

“…Abb 1. 8 a Übersicht eines HE-gefärbten histologischen Schnittpräparats mit mehreren epitheloidzelligen Granulomen.…”

Disease-relevant β2-microglobulin variants share a common amyloid fold

“…As a consequence, its concentration in serum increases up to ~60-fold, which results in the formation and deposition of amyloid fibrils of wt-β 2 m and its truncated variant β 2 m-ΔN6 (along with other truncated forms 27 ) in the joints. The resulting imbalance in osteoclast/osteoblast function caused by proteotoxicity associated with amyloid assembly, gives rise to a destructive joint arthropathy termed DRA 28,29 . By contrast with β 2 m-ΔN6 which forms amyloid fibrils rapidly at mildly acidic pH characteristic of arthritic joints (pH 6.2), wt-β 2 m does not readily aggregate into amyloid fibrils at this pH, unless co-solvents, cellular factors or other additives are included 30,31 .…”