A systematic review exploring the link between chronic venous disease and neuropathy

Patients with chronic venous disease (CVD) often experience pain and heaviness; however, many report additional neuropathic symptoms, such as burning, tingling, and decreased sensations. Despite these occurrences, the nature and pathophysiology of neuropathy in patients with CVD are unclear. The objective of this systematic review was to estimate the prevalence and features of neuropathy in patients with CVD, identify methods for assessing neuropathy in this population, and explore potential pathophysiological mechanisms underlying its development.

This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with the protocol registered on International Prospective Register of Systematic Reviews (PROSPERO; CRD420251124308). The MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched from 1947 to August 2025. The eligibility criteria included studies examining patients with CVD who underwent objective neuropathy assessments. Studies involving patients with comorbidities predisposing them to peripheral neuropathy were excluded. Studies without objective neuropathy assessments were also excluded.

Of 2313 articles retrieved from the search, eight articles were included in this review. The majority of studies investigated sensory neuropathy. The most common objective neuropathy assessment methods were testing vibration detection thresholds, which was performed in five studies, and temperature discrimination, which was performed in four studies. Other assessment methods included the Neuropathy Disability Score, nerve conduction studies, monofilament testing, tendon reflex testing, and skin biopsies. Various nerve fibers responsible for different functions were affected, including A-alpha, A-beta, A-delta, and C-fibers. Furthermore, patients with more severe CVD (C5-C6) had significantly worse neuropathy.

The included studies reported neuropathy prevalence ranging from 33% to 100%; however, direct comparability was greatly limited by heterogeneous assessment methods and the lack of pooled confidence intervals. There was evidence of both sensory and motor neuropathy in patients with CVD. Potential pathophysiological mechanisms underlying neuropathy in patients with CVD include venous hypertension translating to increased endoneurial pressure and ischemia, venous microangiopathy, and axonal hypoxia. Sensory impairment due to nerve injury associated with CVD may increase the risk of skin trauma potentially leading to venous leg ulceration. This systematic review underscores the potential association between neuropathy and patients with CVD and suggest that neuropathy may be associated with more severe CVD.