Reduced perfusion in systemic sclerosis digital ulcers (both fingertip and extensor) can be increased by topical application of glyceryl trinitrate

• Published in: Microvascular research 2017-05, Vol.111, p.32-36
• Main Authors: Hughes, M., Moore, T., Manning, J., Wilkinson, J., Dinsdale, G., Roberts, C., Murray, A., Herrick, A.L.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Adult; Aged; Blood Flow Velocity; Cross-Over Studies; Digital ischaemia; Digital ulcers; Double-Blind Method; Female; Fingers - blood supply; Glyceryl trinitrate; Humans; Ischemia - diagnosis; Ischemia - drug therapy; Ischemia - physiopathology; Laser-Doppler Flowmetry; Male; Microcirculation - drug effects; Microvascular; Middle Aged; Nitroglycerin - administration & dosage; Perfusion Imaging - methods; Raynaud Disease - diagnosis; Raynaud Disease - drug therapy; Raynaud Disease - physiopathology; Recovery of Function; Regional Blood Flow; Scleroderma; Scleroderma, Systemic - diagnosis; Scleroderma, Systemic - drug therapy; Scleroderma, Systemic - physiopathology; Skin Ulcer - diagnosis; Skin Ulcer - drug therapy; Skin Ulcer - physiopathology; Systemic sclerosis; Time Factors; Treatment Outcome; Vasodilation - drug effects; Vasodilator Agents - administration & dosage
• ISSN: 0026-2862; 1095-9319
• DOI: 10.1016/j.mvr.2016.12.008

In patients with systemic sclerosis (SSc), fingertip digital ulcers (DUs) are believed to be ischaemic, and extensor surface DUs a result of mechanical factors/microtrauma. Our aim was to assess blood flow response to topical glyceryl trinitrate (GTN) compared to placebo in SSc DUs, looking for differences in pathophysiology between fingertip and extensor lesions. This was a double-blind, randomised, crossover, placebo-controlled study. Sixteen (6 fingertip, 10 extensor) DUs were each studied twice (one day apart): once with GTN and once with placebo ointment. Perfusion at the DU centre (‘DUCore’) and periphery (‘DUPeriphery’), as measured by laser Doppler imaging was performed before and immediately after ointment application, then every 10min, up to 90min post-application. We calculated the area under the response curve (AUC) and the ratio of peak perfusion to baseline, then compared these between GTN and placebo. Perfusion was lower in the DUCore compared to the DUPeriphery (ratio of 0.52). The microvessels of the DUCore were responsive to GTN, with an increase in perfusion, with a similar effect in both fingertip and extensor DUs. The AUC and peak/baseline perfusion difference in means (ratio, 95% confidence interval) between GTN and placebo at the DUCore were 1.2 (1.0–1.6) and 1.2 (1.0–1.5) respectively, and at the DUPeriphery were 1.1 (0.8–1.6) and 1.0 (0.9–1.2) respectively. DUs (both fingertip and extensor) were responsive to topical GTN, with an increase in perfusion to the ischaemic DU centre. If both fingertip and extensor DUs have a (potentially reversible) ischaemic aetiology, this has important treatment implications. •SSc fingertip DUs are believed to be ischaemic, whereas, extensor surface DUs are a result of mechanical factors/microtrauma.•DUs (both fingertip and extensor) were responsive to topical GTN, in particular the ischaemic centre.•If both fingertip and extensor DUs have a ischaemic aetiology, this has important treatment implications.