The Challenge of Scleroderma Ulcers

Charles C Clements P Furst DE . Systemic sclerosis: Hypothesis-driven treatment strategies. Lancet 2006;367(9523):1683–91.

Pope JE Bellamy N . Sample size calculations in scleroderma: A rational approach to choosing outcome measurements in scleroderma trials. Clin Invest Med 1995;18:1–10.

Hachulla E Gressin V Guillevin L . Early detection of pulmonary arterial hypertension in systemic sclerosis: A French nationwide prospective multicenter study. Arthritis Rheum 2005;52:3792–800.

Tuffanelli DL Winkelmann RK . Systemic scleroderma, a clinical study of 727 cases. Arch Dermatol 1961;84:359–71.

Ferri C Valentini G Cozzi F . Systemic sclerosis: Demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine (Baltimore) 2002;81:139–53.

Alivernini S De Santis M Tolusso B . Skin ulcers in systemic sclerosis: Determinants of presence and predictive factors of healing. J Am Acad Dermatol 2009;60:426–35.

Ostojic P Damjanov N Pavlov-Dolijanovic S Radunovic G . Peripheral vasculopathy in patients with systemic sclerosis: Difference in limited and diffuse subset of disease. Clin Hemorheol Microcirc 2004;31:281–5.

Steen VD . Autoantibodies in systemic sclerosis. Semin Arthritis Rheum 2005;35:35–42.

Reveille JD Fischbach M McNearney T . Systemic sclerosis in 3 US ethnic groups: A comparison of clinical, sociodemographic, serologic, and immunogenetic determinants. Semin Arthritis Rheum 2001;30:332–46.

Nietert PJ Mitchell HC Bolster MB . Racial variation in clinical and immunological manifestations of systemic sclerosis. J Rheumatol 2006;33:263–8.

Sunderkotter C Herrgott I Bruckner C . Comparison of patients with and without digital ulcers in systemic sclerosis: Detection of possible risk factors. Br J Dermatol 2009;160:835–43.

Milburn PB Singer JZ Milburn MA . Treatment of scleroderma skin ulcers with a hydrocolloid membrane. J Am Acad Dermatol 1989;21(2 Pt 1):200–4.

Hachulla E Clerson P Launay D . Natural history of ischemic digital ulcers in systemic sclerosis: Single-center retrospective longitudinal study. J Rheumatol 2007;34:2423–30.

Gahhos F Ariyan S Frazier WH Cuono CB . Management of sclerodermal finger ulcers. J Hand Surg [Am] 1984;9:320–7.

Merkel PA Herlyn K Martin RW . Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenon. Arthritis Rheum 2002;46:2410–20.

Harrison BJ Silman AJ Hider SL Herrick AL . Cigarette smoking as a significant risk factor for digital vascular disease in patients with systemic sclerosis. Arthritis Rheum 2002;46:3312–6.

Markus YM Bell MJ Evans AW . Ischemic scleroderma wounds successfully treated with hyperbaric oxygen therapy. J Rheumatol 2006;33:1694–6.

Filho JP Sampaio-Barros PD Parente JB . Rhythmic external compression of the limbs: A method for healing cutaneous ulcers in systemic sclerosis. J Rheumatol 1998;25:1540–3.

Sparsa A Lesaux N Kessler E . Treatment of cutaneous calcinosis in CREST syndrome by extracorporeal shock wave lithotripsy. J Am Acad Dermatol 2005;53(5 Suppl 1):S263–5.

Chamberlain AJ Walker NP . Successful palliation and significant remission of cutaneous calcinosis in CREST syndrome with carbon dioxide laser. Dermatol Surg 2003;29:968–70.

Cukierman T Elinav E Korem M Chajek-Shaul T . Low dose warfarin treatment for calcinosis in patients with systemic sclerosis. Ann Rheum Dis 2004;63:1341–3.

Yoshida S Torikai K . The effects of warfarin on calcinosis in a patient with systemic sclerosis. J Rheumatol 1993;20:1233–5.

Robertson LP Marshall RW Hickling P . Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline. Ann Rheum Dis 2003;62:267–9.

van Ingen IL Jansen MM Barrera P . Topical opioids for painful ulcers in systemic sclerosis. Ann Rheum Dis 2008;67:427.

Colakoglu M Cobankara V Akpolat T . Effect of clonazepam on Raynaud's phenomenon and fingertip ulcers in scleroderma. Ann Pharmacother 2007;41:1544–7.

Butalia S Palda VA Sargeant RJ . Does this patient with diabetes have osteomyelitis of the lower extremity? JAMA 2008;299:806–13.

Block JA Sequeira W . Raynaud's phenomenon. Lancet 2001;357(9273):2042–8.

Rademaker M Cooke ED Almond NE . Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: A double blind randomised study. BMJ 1989;298:561–4.

Sarkozi J Bookman AA Mahon W . Nifedipine in the treatment of idiopathic Raynaud's syndrome. J Rheumatol 1986;13:331–6.

Weber A Bounameaux H . Effects of low-dose nifedipine on a cold provocation test in patients with Raynaud's disease. J Cardiovasc Pharmacol 1990;15:853–5.

Thompson AE Shea B Welch V . Calcium-channel blockers for Raynaud's phenomenon in systemic sclerosis. Arthritis Rheum 2001;44:1841–7.

Russell IJ Lessard JA . Prazosin treatment of Raynaud's phenomenon: A double blind single crossover study. J Rheumatol 1985;12:94–8.

Pope J Fenlon D Thompson A . Prazosin for Raynaud's phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev 2000;(2):CD000956.

Surwit RS Gilgor RS Allen LM Duvic M . A double-blind study of prazosin in the treatment of Raynaud's phenomenon in scleroderma. Arch Dermatol 1984;120:329–31.

Brotzu G Falchi S Mannu B . The importance of presynaptic beta receptors in Raynaud's disease. J Vasc Surg 1989;9:767–71.

Dziadzio M Denton CP Smith R . Losartan therapy for Raynaud's phenomenon and scleroderma: Clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial. Arthritis Rheum 1999;42:2646–55.

Coleiro B Marshall SE Denton CP . Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford) 2001;40:1038–43.

Rustin MH Almond NE Beacham JA . The effect of captopril on cutaneous blood flow in patients with primary Raynaud's phenomenon. Br J Dermatol 1987;117:751–8.

Franks AG Jr . Topical glyceryl trinitrate as adjunctive treatment in Raynaud's disease. Lancet 1982;1(8263):76–7.

Teh LS Manning J Moore T . Sustained-release transdermal glyceryl trinitrate patches as a treatment for primary and secondary Raynaud's phenomenon. Br J Rheumatol 1995;34:636–41.

Denton CP Fiorentino D Herrick A . A multi-center crossover study of MQX-503, a topical formulation of nitroglycerin, in patients with Raynaud's phenomenon. Presented at American College of Rheumatology; November 2007; Boston, MA.

Foresta C Ferlin A De Toni L . Circulating endothelial progenitor cells and endothelial function after chronic tadalafil treatment in subjects with erectile dysfunction. Int J Impot Res 2006;18:484–8.

Proietti M Aversa A Letizia C . Erectile dysfunction in systemic sclerosis: Effects of long-term inhibition of phosphodiesterase type-5 on erectile function and plasma endothelin-1 levels. J Rheumatol 2007;34:1712–7.

Fries R Shariat K von Wilmowsky H Bohm M . Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy. Circulation 2005;112:2980–5.

Colglazier CL Sutej PG O'Rourke KS . Severe refractory fingertip ulcerations in a patient with scleroderma: Successful treatment with sildenafil. J Rheumatol 2005;32:2440–2.

Gore J Silver R . Oral sildenafil for the treatment of Raynaud's phenomenon and digital ulcers secondary to systemic sclerosis. Ann Rheum Dis 2005;64:1387.

Zachariae H Halkier-Sorensen L Bjerring P Heickendorff L . Treatment of ischaemic digital ulcers and prevention of gangrene with intravenous iloprost in systemic sclerosis. Acta Derm Venereol 1996;76:236–8.

Wigley FM Wise RA Seibold JR . Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study. Ann Intern Med 1994;120:199–206.

Wigley FM Seibold JR Wise RA . Intravenous iloprost treatment of Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis. J Rheumatol 1992;19:1407–14.

Wigley FM Korn JH Csuka ME . Oral iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis: A multicenter, placebo-controlled, double-blind study. Arthritis Rheum 1998;41:670–7.

Badesch DB Tapson VF McGoon MD . Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med 2000;132:425–34.

Chung L Fiorentino D . A pilot trial of treprostinil for the treatment and prevention of digital ulcers in patients with systemic sclerosis. J Am Acad Dermatol 2006;54:880–2.

Channick RN Simonneau G Sitbon O . Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: A randomised placebo-controlled study. Lancet 2001;358(9288):1119–23.

Korn JH Mayes M Matucci Cerinic M . Digital ulcers in systemic sclerosis: Prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis Rheum 2004;50:3985–93.

Seibold JR . Bosentan prevents occurrence but does not speed healing of digital ulcers in patients with systemic sclerosis. Presented at American College of Rheumatology; October 2005, San Diego, CA.

Chamaillard M Heliot-Hosten I Constans J Taieb A . Bosentan as a rescue therapy in scleroderma refractory digital ulcers. Arch Dermatol 2007;143:125–6.

Ramos-Casals M Brito-Zeron P Nardi N . Successful treatment of severe Raynaud's phenomenon with bosentan in four patients with systemic sclerosis. Rheumatology (Oxford) 2004;43:1454–6.

Steed DL Attinger C Colaizzi T . Guidelines for the treatment of diabetic ulcers. Wound Repair Regen 2006;14:680–92.

LeGrand EK . Preclinical promise of becaplermin (rhPDGF-BB) in wound healing. Am J Surg 1998;176(2A Suppl):48S–54S.

Yoon J Giacopelli J Granoff D Kobayashi W . Treatment of scleroderma skin ulcers using becaplermin gel and hydrocolloid membrane. J Am Podiatr Med Assoc 2002;92:350–4.

Ferri C Giuggioli D Sebastiani M Colaci M . Treatment of severe scleroderma skin ulcers with recombinant human erythropoietin. Clin Exp Dermatol 2007;32:287–90.

Beckett VL Conn DL Fuster V . Trial of platelet-inhibiting drug in scleroderma. Double-blind study with dipyridamole and aspirin. Arthritis Rheum 1984;27:1137–43.

Chung L . Therapeutic options for digital ulcers in patients with systemic sclerosis. J Dtsch Dermatol Ges 2007;5:460–5.

Sambo P Amico D Giacomelli R . Intravenous N-acetylcysteine for treatment of Raynaud's phenomenon secondary to systemic sclerosis: A pilot study. J Rheumatol 2001;28:2257–62.

Murrell DF . A radical proposal for the pathogenesis of scleroderma. J Am Acad Dermatol 1993;28:78–85.

Murrell GA Francis MJ Bromley L . Modulation of fibroblast proliferation by oxygen free radicals. Biochem J 1990;265:659–65.

Ames PR Stephens JW Steuer A Gumpel JM . Prolonged healing of malleolar ulcers after fibrinolytic treatment in a woman with systemic sclerosis. Br J Rheumatol 1998;37:107–9.

Ciompi ML Bazzichi L Melchiorre D . A placebo-controlled study on urokinase therapy in systemic sclerosis. Biomed Pharmacother 1996;50:363–8.

Derk CT Jimenez SA . Statins and the vasculopathy of systemic sclerosis: Potential therapeutic agents? Autoimmun Rev 2006;5:25–32.

Sule SD Wigley FM . Treatment of scleroderma: An update. Expert Opin Investig Drugs 2003;12:471–82.

Clancy RM . Preventing and repairing vascular damage in scleroderma: Should we focus beyond vasodilatation to recruitment of endothelial precursor cells? Arthritis Rheum 2006;54:1730–2.

Kuwana M Kaburaki J Okazaki Y . Increase in circulating endothelial precursors by atorvastatin in patients with systemic sclerosis. Arthritis Rheum 2006;54:1946–51.

Abou-Raya A Abou-Raya S Helmii M . Statins as immunomodulators in systemic sclerosis. Ann N Y Acad Sci 2007;1110:670–80.

Abou-Raya A Abou-Raya S Helmii M . Statins: Potentially useful in therapy of systemic sclerosis-related Raynaud's phenomenon and digital ulcers. J Rheumatol 2008;35:1801–8.

Giuggioli D Sebastiani M Cazzato M . Autologous skin grafting in the treatment of severe scleroderma cutaneous ulcers: A case report. Rheumatology (Oxford) 2003;42:694–6.

Ichiki Y Kitajima Y . Successful treatment of scleroderma-related cutaneous ulcer with suction blister grafting. Rheumatol Int 2008;28:299–301.

Han KR Kim C Park EJ . Successful treatment of digital ulcers in a scleroderma patient with continuous bilateral thoracic sympathetic block. Pain Physician 2008;11:91–6.