Diabetes is one of the fastest growing global health emergencies of the 21st century.1 In 2021, the International Diabetes Federation estimated that 537 million adults aged 20–79 years had diabetes worldwide (10.5 %). This is projected to increase to 643 million by 2030 (11.3 %) and 783 million by 2045 (12.5 %).1

Diabetic neuropathies are among the most prevalent chronic complications of diabetes, encompassing a heterogenous group of conditions caused by nerve damage with diverse clinical manifestations.2 The most common form, diabetic peripheral neuropathy (DPN), affects up to ~50 % of patients with diabetes.2, 3, 4 DPN may be associated with chronic neuropathic pain (painful DPN [pDPN]), a complex pain pathology estimated to affect >100 million people worldwide.5

pDPN is characterized by burning or stabbing pain alongside paresthesia (prickling/tingling), allodynia (pain sensitization to innocuous stimuli), hyperalgesia (heightened sensitivity to painful stimuli), sensory loss, and/or numbness.5,6 It is one of the most distressing complications of diabetes and can cause increased disability, sleep disturbances, impaired daily functioning and work productivity, reduced quality of life (QoL), psychosocial impairment, and emotional distress.2,5,7,8 In a European study of 576 patients with pDPN, 74 % reported impaired sleep, 54 % had negatively impacted daily activities, and 75 % had missed work in the past year due to their pain, with 15 % stopping work entirely.7

DPN typically follows a “stocking and glove” pattern of symptoms, starting in the toes and spreading proximally through the feet and legs.5,9,10 Once established in the lower limbs, further disease progression may affect the fingers and hands.9 In a study of 141 patients with type 2 diabetes, 77 (55 %) had DPN (n = 34 had lower-limb DPN only, n = 7 had upper-limb DPN only, and n = 36 had both lower- and upper-limb DPN).11 DPN of the feet is more prevalent and the complications and impact are generally well-recognized12; however, there remains a paucity of evidence for DPN of the hands. Nonetheless, the clinical importance of DPN of the hands should not be underestimated, as impaired manual dexterity and hand performance are associated with reduced QoL and loss of independence.11,13 A cross-sectional analysis of the UK BioBank (N = 148,828; n = 13,744 with chronic neuropathic pain) found that patients reported pain of the hands as one of the most bothersome pain locations, alongside feet and legs.14

Recommended treatments for pDPN include systemic oral treatments such as antiepileptics and antidepressants.15 The topical capsaicin 179 mg (8 % weight per weight) cutaneous patch (high-concentration capsaicin patch [HCCP]) is approved for treatment of pDPN in the EU, and in the US for pDPN of the feet.16,17 HCCP should be applied to intact, non-irritated, dry skin and remain in place for 30 min (EU and US label) for the feet and up to 60 min for other anatomical locations (EU label only).16,17 HCCP has also been recommended as first-line therapy for pDPN by the American Association of Clinical Endocrinology (AACE), American Academy of Neurology (AAN), and Deutsche Diabetes Gesellschaft (DDG) guidelines.18, 19, 20 The efficacy of HCCP has been demonstrated and its tolerability established in several randomized controlled trials (RCTs), including a double-blind, placebo-controlled trial evaluating a single HCCP (STEP)21 and an open-label RCT evaluating the efficacy of multiple HCCPs over 12 months (PACE).22,23

HCCP comprises a patented matrix technology that allows high concentrations of capsaicin to enter the epidermis and activate transient receptor potential vanilloid 1 (TRPV1) receptors on sensory nerve fibers.24 Exposure to high concentrations of capsaicin leads to reversible desensitization of these nerve fibers, which are involved in neuropathic pain, leading to subsequent pain relief.24 Interestingly, HCCP may also have disease-modifying effects, with the regeneration of TRPV1-expressing nerve fiber terminals and subsequent restoration of nerve function 1–3 months after a single treatment.25,26 However, as diabetes is a chronic condition that continually injures nerve fibers, repeated HCCP treatments are required. This is supported by a post-hoc analysis of the PACE clinical trial that demonstrated that continued HCCP treatment improved outcomes in patients with pDPN, allowing those not achieving sufficient pain relief from one HCCP treatment to respond to successive treatments.27

Although HCCP has been available for some time, data on the use and outcomes of HCCP in clinical practice in patients with pDPN affecting body locations other than the feet are relatively scarce. There also remains a need for further evidence on repeat treatments of HCCP in clinical practice for patients with pDPN. In particular, pDPN of the hands remains underrepresented in the literature, despite evidence of its clinical importance.11 Our research aims to highlight the burden of pDPN, including in less well-studied body locations, and to describe treatment patterns, outcomes, and tolerability associated with repeat treatments of HCCP in a large patient cohort. This manuscript reports real-world data for successive HCCP treatments on neuropathic pain, affective distress, QoL, impact on daily activities, and use of concomitant pain medication in patients with pDPN of the hands, feet, or legs.