Alnylam Pharmaceuticals, Cambridge, MA, US.
Baylor Scott & White Heart and Vascular Hospital, Dallas, TX, US.
BMC Musculoskelet Disord. 2023 Sep 22;24(1):751. doi: 10.1186/s12891-023-06853-5.
Hereditary and wild-type transthyretin-mediated (ATTRv and ATTRwt) amyloidoses result from the misfolding of transthyretin and aggregation of amyloid plaques in multiple organ systems. Diagnosis of ATTR amyloidosis is often delayed due to its heterogenous and non-specific presentation. This review investigates the association of musculoskeletal (MSK) manifestations with ATTR amyloidosis and the delay from the onset of these manifestations to the diagnosis of ATTR amyloidosis.
This systematic review utilized Medline and EMBASE databases. Search criteria were outlined using a pre-specified patient, intervention, comparator, outcome, time, study (PICOTS) criteria and included: amyloidosis, ATTR, and MSK manifestations. Publication quality was assessed utilizing Joanna Briggs Institute (JBI) critical appraisal checklists. The search initially identified 7,139 publications, 164 of which were included. PICOTS criteria led to the inclusion of epidemiology, clinical burden and practice, pathophysiology, and temporality of MSK manifestations associated with ATTR amyloidosis. 163 publications reported on ATTR amyloidosis and MSK manifestations, and 13 publications reported on the delay in ATTR amyloidosis diagnosis following the onset of MSK manifestations.
The MSK manifestation most frequently associated with ATTR amyloidosis was carpal tunnel syndrome (CTS); spinal stenosis (SS) and osteoarthritis (OA), among others, were also identified. The exact prevalence of different MSK manifestations in patients with ATTR amyloidosis remains unclear, as a broad range of prevalence estimates were reported. Moreover, the reported prevalence of MSK manifestations showed no clear trend or distinction in association between ATTRv and ATTRwt amyloidosis. MSK manifestations precede the diagnosis of ATTR amyloidosis by years, and there was substantial variation in the reported delay to ATTR amyloidosis diagnosis. Reports do suggest a longer diagnostic delay in patients with ATTRv amyloidosis, with 2 to 12 years delay in ATTRv versus 1.3 to 1.9 years delay in ATTRwt amyloidosis.
These findings suggest that orthopedic surgeons may play a role in the early diagnosis of and treatment referrals for ATTR amyloidosis. Detection of MSK manifestations may enable earlier diagnosis and administration of effective treatments before disease progression occurs.
遗传性和野生型转甲状腺素蛋白介导的（ATTRv 和 ATTRwt）淀粉样变是由于转甲状腺素蛋白错误折叠和在多个器官系统中聚集淀粉样斑块引起的。由于其异质性和非特异性表现，ATTR 淀粉样变的诊断常常被延误。本综述研究了肌肉骨骼（MSK）表现与 ATTR 淀粉样变的关系，以及这些表现出现到诊断为 ATTR 淀粉样变之间的时间延迟。
本系统综述使用了 Medline 和 EMBASE 数据库。使用预先指定的患者、干预、对照、结局、时间、研究（PICOTS）标准来制定搜索标准，并包括：淀粉样变性、ATTR 和 MSK 表现。使用 Joanna Briggs 研究所（JBI）的批判性评价清单评估发表质量。最初的搜索确定了 7139 篇文献，其中 164 篇被纳入。PICOTS 标准纳入了与 ATTR 淀粉样变相关的 MSK 表现的流行病学、临床负担和实践、病理生理学和时间性。163 篇文献报告了 ATTR 淀粉样变和 MSK 表现，13 篇文献报告了 MSK 表现出现后 ATTR 淀粉样变诊断的延迟。
与 ATTR 淀粉样变最常相关的 MSK 表现是腕管综合征（CTS）；也发现了脊椎狭窄症（SS）和骨关节炎（OA）等其他表现。在 ATTR 淀粉样变患者中，不同 MSK 表现的确切患病率尚不清楚，因为报告的患病率范围很广。此外，报告的 MSK 表现的患病率在 ATTRv 和 ATTRwt 淀粉样变之间没有明显的趋势或区别。MSK 表现先于 ATTR 淀粉样变的诊断数年出现，并且报告的 ATTR 淀粉样变诊断的延迟时间存在很大差异。报告表明，ATTRv 淀粉样变患者的诊断延迟时间更长，ATTRv 患者的延迟时间为 2 至 12 年，而 ATTRwt 淀粉样变患者的延迟时间为 1.3 至 1.9 年。
这些发现表明，矫形外科医生可能在 ATTR 淀粉样变的早期诊断和治疗转诊中发挥作用。检测 MSK 表现可能会在疾病进展发生之前更早地诊断和进行有效的治疗。
