title: Reduced perfusion in systemic sclerosis digital ulcers (both fingertip and extensor) can be increased by topical application of glyceryl trinitrate.
abstract: 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.
authors.affiliation: Centre for Musculoskeletal Research, The University of Manchester, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. Electronic address: Michael.Hughes-6@postgrad.manchester.ac.uk.
authors.forename: M
authors.initials: M
authors.lastname: Hughes
authors.affiliation: Centre for Musculoskeletal Research, The University of Manchester, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; Department of Rheumatology, Salford Royal NHS Foundation Trust, Salford, United Kingdom.
authors.forename: T
authors.initials: T
authors.lastname: Moore
authors.affiliation: Department of Rheumatology, Salford Royal NHS Foundation Trust, Salford, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Manning
authors.affiliation: Research and Development, Salford Royal NHS Foundation Trust, Salford, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Wilkinson
authors.affiliation: Centre for Musculoskeletal Research, The University of Manchester, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: G
authors.initials: G
authors.lastname: Dinsdale
authors.affiliation: Centre for Biostatistics, Institute of Population Health, School of Medicine, The University of Manchester, Manchester, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Roberts
authors.affiliation: Centre for Musculoskeletal Research, The University of Manchester, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; Photon Science Institute, The University of Manchester, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Murray
authors.affiliation: Centre for Musculoskeletal Research, The University of Manchester, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, United Kingdom.
authors.forename: A L
authors.initials: AL
authors.lastname: Herrick
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005385:Fingers / Q000098:blood supply*; D006801:Humans; D007511:Ischemia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage*; D055420:Perfusion Imaging / Q000379:methods; D011928:Raynaud Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D020127:Recovery of Function; D012039:Regional Blood Flow; D012595:Scleroderma, Systemic / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012883:Skin Ulcer / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D014665:Vasodilator Agents; D005996:Nitroglycerin
keywords: Digital ischaemia; Digital ulcers; Glyceryl trinitrate; Microvascular; Scleroderma; Systemic sclerosis