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 CVD are unclear. The objective of this systematic review was to estimate the prevalence and the features of neuropathy found in patients with CVD, identify methods of assessing neuropathy in patients with CVD and explore potential pathophysiological mechanisms of neuropathy development in CVD.

This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with the protocol registered on PROSPERO (CRD420251124308). The MEDLINE, EMBASE and Cochrane CENTRAL databases were searched from 1947 to August 2025. The eligibility criteria included studies examining CVD patients with objective neuropathy assessments. Studies where patients had co-morbidities predisposing to peripheral neuropathy were excluded. Studies without objective neuropathy assessment were also excluded.

Of 2313 articles retrieved from the search, 8 articles were included in this review. The majority of studies investigated sensory neuropathy. The most common objective neuropathy assessment was testing vibration detection thresholds, which was performed in five of the studies, and temperature discrimination, performed in four studies. Other methods of assessment were the Neuropathy Disability Score, nerve conduction studies, monofilament tests, tendon reflex tests, and skin biopsies. Various nerve fibres responsible for different functions were found to be affected including A-alpha, A-beta, A-delta and C-fibres. Furthermore, patients with more severe CVD (C5-C6) had significantly worse neuropathy.

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