Pharmacological management of pain in digital ulcers of systemic sclerosis: A PRISMA-driven systematic review

Digital ulcers represent a severe manifestation of digital vasculopathy in systemic sclerosis, occasionally with the contribution of microtrauma and calcinosis. These ulcers are often challenging to heal and extremely painful. Regarding analgesic approaches, there is a lack of consensus on best practices, leading to physician experience-guided approaches rather than standardized protocols. To assess the published evidence on the effectiveness of oral and topical analgesics and local anaesthetics for pain reduction in digital ulcer of systemic sclerosis, we conducted a PRISMA-driven systematic review. A search in PubMed and Cochrane databases was performed using the keyword search terms 'digital ulcers', 'finger ulcers', 'systemic sclerosis', 'scleroderma', 'pain management', 'analgesics', 'anaesthetics' and 'painkillers', with the Boolean terms 'AND' and 'OR'. Original studies and case reports were considered for inclusion. Results were screened by title, abstract and full-text. We identified a total of 26 results, of which 5 original papers were included: 2 prospective observational studies, 1 prospective case series, 1 retrospective case series and 1 case report. The evaluated pharmacological strategies were digital nerve block with lidocaine and mepivacaine (one study), oral extended-release oxycodone (two studies), local lidocaine (one study), local lidocaine and prilocaine, local morphine and sublingual morphine (one study). Overall, digital nerve block appeared to provide complete or near-complete pain relief. Oral and topical strategies resulted in reduced pain intensity, although levels remained in the mild-to-moderate range. Concerning adverse outcomes, all strategies were generally well tolerated, with only mild effects reported across studies. Despite limitations, the available evidence suggests that the evaluated analgesics and anaesthetics may provide pain relief for digital ulcer in patients with systemic sclerosis. Future larger-scale studies employing standardized protocols are necessary to further assess the efficacy, optimal dosing and long-term outcomes of these interventions.