Carpal Tunnel & Amyloidosis

Amyloidosis is a rare disease, a group of disorders characterized by the abnormal deposition of amyloid protein in various tissues and organs.

Amyloidosis can manifest with carpal tunnel syndrome (CTS) as an initial or presenting symptom (Sperry BW et al. J Amer Coll Cardiol. 2018;72:2040-2050). Amyloidosis is commonly diagnosed late when irreversible damage has been done to organs, of particular concern is cardiac involvement. ATTR amyloidosis, both hereditary (ATTRv) and wild-type (ATTRwt), is known to frequently manifest with bilateral carpal tunnel syndrome as an early symptom (Milandri et al. Eur J Heart Fail, 2020; 22:507-515). However, this association is often underrecognized, leading to delayed diagnosis and management.

Amyloidosis can present with a wide spectrum of clinical manifestations, ranging from asymptomatic to severe systemic involvement.

In the context of CTS, patients may present with typical symptoms such as hand numbness, tingling, and weakness, but with underlying amyloid deposition contributing to nerve compression. Hand surgeons need to be aware of the diverse clinical presentations of amyloidosis and consider this differential diagnosis in patients presenting with atypical or refractory CTS (Grogan M and Dispenzieri A. J Amer Coll Cardiol. 2022;80:978-981).

Exact prevalence rates vary, however, several studies have reported a significant association between bilateral carpal tunnel syndrome and ATTR amyloidosis, especially in older patients or those with a history of amyloidosis.

Published data has suggested that amyloidosis accounted for approximately 7% of all cases of carpal tunnel syndrome in patients undergoing carpal tunnel release surgery, and 15% of patients diagnosed with bilateral carpal tunnel syndrome were subsequently diagnosed with ATTR amyloidosis, highlighting the importance of considering amyloidosis in the differential diagnosis of bilateral carpal tunnel syndrome (Sood RF et al. J Bone Joint, Surg, Am. 2021;103:1284-1294; Grogan M and Dispenzieri A. J Amer Coll Cariol. 2022;80:978-981). Another prospective screening study of 98 patients undergoing bilateral carpal tunnel release (CTR) that included men aged ≥50 years and women ≥60 years, amyloid deposits were found in 10% (7 of 10 ATTR, including 2 with hereditary ATTR); of the 10 patients with amyloid of the tenosynovium tissue.¹

Diagnosing amyloidosis can be challenging due to its heterogeneous nature and overlap with other conditions. Furthermore, traditional diagnostic modalities such as electromyography (EMG) and nerve conduction studies (NCS) may demonstrate findings consistent with CTS without indicating the underlying cause of nerve compression.

By advancing diagnostic techniques such as biopsy, imaging studies (e.g., MRI, ultrasound), and serum and urine protein electrophoresis in the evaluation of suspected amyloidosis-associated CTS as part of standard practice when certain criteria are met.

Hand surgeons can be instrumental in the early recognition and management of CTS in patients with amyloidosis and can collaborate closely with other healthcare professionals to ensure comprehensive care and address systemic manifestations of the disease.