Clinical Rheumatology

, Volume 28, Issue 7, pp 807–813 | Cite as

A score of risk factors associated with ischemic digital ulcers in patients affected by systemic sclerosis treated with iloprost

  • Paola CaramaschiEmail author
  • Nicola Martinelli
  • Alessandro Volpe
  • Sara Pieropan
  • Ilaria Tinazzi
  • Giuseppe Patuzzo
  • Helal Mahamid
  • Lisa Maria Bambara
  • Domenico Biasi
Original Article


A single series of patients affected by systemic sclerosis (SSc) and cyclically treated with iloprost was reviewed in order to evaluate the incidence of digital ulcers (DUs) and to compare the characteristics between the patients with and without this painful and disabling vascular complication. The record charts of 85 SSc patients were revised. Ischemic DUs and scleroderma contracture ulcers were separately considered. Twenty-nine subjects developed ischemic DUs during the course of the disease; whereas, scleroderma contracture ulcers occurred in six subjects. Ischemic DUs were associated with younger age at scleroderma onset, a longer disease duration, a longer time delay from scleroderma diagnosis to iloprost therapy, a bigger skin involvement, the presence of joint contractures, a videocapillaroscopic late pattern, a history of smoking, and of corticosteroids therapy. After the exclusion of four subjects with concomitant peripheral arterial disease, a forward-stepwise logistic regression analysis showed that only four variables, i.e., age at scleroderma onset, delay in beginning iloprost therapy, history of smoking, and presence of joint contractures remained significantly associated with ischemic DUs. In a score reflecting the sum of these four risk factors, the prevalence of ischemic DUs increased progressively from the lowest to the highest value of the score. The predictivity of this model was evaluated by the receiver-operating characteristics curve, with an estimated area under the curve of 0.836 with 95% confidence interval from 0.736 to 0.937. All the patients with scleroderma contracture ulcers were characterized by both diffuse pattern of disease and positivity for anti-Scl70 antibody. In this retrospective study, scleroderma patients with ischemic DUs are characterized by early disease onset, delay in beginning iloprost therapy, smoking habit, and presence of joint contraction. A score reflecting the sum of these factors may be useful to predict the risk of developing ischemic DUs.


Digital ulcers Iloprost Smoking Systemic sclerosis 





  1. 1.
    Marasini B, Cugno M, Bassani C, Stanzani M, Bottasso B, Agostoni A (1992) Tissue-type plasminogen activator and von Willebrand factor plasma levels as markers of endothelial involvement in patients with Raynaud’s phenomenon. Int J Microcirc Clin Exp 11:375–382PubMedGoogle Scholar
  2. 2.
    Ferri C, Valentini G, Cozzi F et al (2002) Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine (Baltimore) 81:139–153CrossRefGoogle Scholar
  3. 3.
    Mawdsley AH (2006) Patient perception of UK scleroderma services—results of an anonymous questionnaire. Rheumatology 45:1573PubMedCrossRefGoogle Scholar
  4. 4.
    Rodnan G, Myerowitz R, Justh G (1980) Morphologic changes in the digital arteries of patients with progressive systemic sclerosis (scleroderma) and Raynaud phenomenon. Medicine (Baltimore) 59:393–408Google Scholar
  5. 5.
    Denton C, Korn J (2003) Digital ulceration and critical digital ischemia in scleroderma. Scleroderma Care Res 1:12–16Google Scholar
  6. 6.
    Nihtyanova SI, Brough GM, Black CM, Denton CP (2008) Clinical burden of digital vasculopathy in limited and diffuse cutaneous systemic sclerosis. Ann Rheum Dis 67:120–123PubMedCrossRefGoogle Scholar
  7. 7.
    Walker UA, Tyndall A, Czirjak L et al (2007) Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group database. Ann Rheum Dis 66:754–763PubMedCrossRefGoogle Scholar
  8. 8.
    Herrick AL, Heaney M, Hollis S, Jayson MI (1994) Anticardiolipin, anticentromere and anti-Scl-70 antibodies in patients with systemic sclerosis and severe digital ischaemia. Ann Rheum Dis 53:540–542PubMedCrossRefGoogle Scholar
  9. 9.
    Wigley FM, Wise RA, Miller R, Needleman BW, Spence RJ (1992) Anticentromere antibody as a predictor of digital ischemic loss in patients with systemic sclerosis. Arthritis Rheum 35:688–693PubMedCrossRefGoogle Scholar
  10. 10.
    Ostojic P, Damjanov N, Pavlov-Dolijanovic S, Radunovic G (2004) Peripheral vasculopathy in patients with systemic sclerosis: difference in limited and diffuse subset of disease. Clin Hemorheol Microcirc 31:281–285PubMedGoogle Scholar
  11. 11.
    Chung L, Fiorentino D (2006) Digital ulcers in patients with systemic sclerosis. Autoimmun Rev 5:125–128PubMedCrossRefGoogle Scholar
  12. 12.
    Subcommittee for scleroderma criteria of the American Rheumatism Association diagnostic and therapeutic criteria committee (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23:581–590CrossRefGoogle Scholar
  13. 13.
    LeRoy EC, Black CM, Fleischmajer R et al (1988) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205PubMedGoogle Scholar
  14. 14.
    Akesson A, Fiori G, Krieg T, van den Hoogen FHJ, Seibold JR (2002) Assessment of skin, joint, tendon and muscle involvement. Clin Exp Rheumatol 21(Suppl 29):S5–8Google Scholar
  15. 15.
    Cutolo M, Sulli A, Pizzorni C, Accardo S (2000) Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J Rheumatol 27:155–160PubMedGoogle Scholar
  16. 16.
    Wigley FM, Wise A, Seibold J et al (1994) Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study. Ann Intern Med 120:199–206PubMedGoogle Scholar
  17. 17.
    Wigley FM, Seibold J, Wise A, McCloskey D, Dole WP (1992) Intravenous iloprost treatment of Raynaud’s phenomenon and ischemic ulcers secondary to systemic sclerosis. J Rheumatol 19:1407–1414PubMedGoogle Scholar
  18. 18.
    Torley HJ, Madhok R, Capell HA et al (1991) A double blind, randomised, multicentre comparison of two doses of intravenous iloprost in the treatment of Raynaud’s phenomenon secondary to connective tissue diseases. Ann Rheum Dis 50:800–804PubMedCrossRefGoogle Scholar
  19. 19.
    Pope J, Fenlon D, Thompson A et al (2000) Iloprost and cisaprost for Raynaud’s phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev 2:CD000953PubMedGoogle Scholar
  20. 20.
    Della Bella S, Molteni M, Mocellin C, Fumagalli S, Bonara P, Scorza R (2001) Novel mode of action of iloprost: in vitro down-regulation of endothelial cell adhesion molecules. Prostaglandins Other Lipid Mediat 65:73–83PubMedCrossRefGoogle Scholar
  21. 21.
    Filaci G, Cutolo M, Scudeletti M et al (1999) Cyclosporin A and iloprost treatment of systemic sclerosis: clinical results and interleukin-6 serum changes after 12 months of therapy. Rheumatology 38:992–996PubMedCrossRefGoogle Scholar
  22. 22.
    Della Bella S, Molteni M, Mascagni B, Zulian C, Compasso S, Scorza R (1997) Cytokine production in scleroderma patients: effects of therapy with either iloprost or nifedipine. Clin Exp Rheumatol 15:135–141PubMedGoogle Scholar
  23. 23.
    Stratton R, Shiwen X, Martini G et al (2001) Iloprost suppresses connective tissue growth factor production in fibroblasts and in the skin of scleroderma patients. J Clin Invest 108:241–250PubMedGoogle Scholar
  24. 24.
    Caramaschi P, Volpe A, Tinazzi I, Bambara LM, Carletto A, Biasi D (2006) Does cyclically iloprost infusion prevent severe isolated pulmonary hypertension in systemic sclerosis? Preliminary results. Rheumatol Int 27:203–205PubMedCrossRefGoogle Scholar
  25. 25.
    Korn JH, Mayes M, Matucci-Cerinic M et al (2004) Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis Rheum 50:3985–3893PubMedCrossRefGoogle Scholar
  26. 26.
    Harrison BJ, Silman AJ, Hider SL, Herrick AL (2002) Cigarette smoking as a significant risk factor for digital vascular disease in patients with systemic sclerosis. Arthritis Rheum 46:3312–3316PubMedCrossRefGoogle Scholar
  27. 27.
    Powell JT (1998) Vascular damage from smoking: disease mechanisms at the arterial wall. Vasc Med 3:21–28PubMedGoogle Scholar
  28. 28.
    Veale DJ, Collidge TA, Belch JJ (1995) Increased prevalence of symptomatic macrovascular disease in systemic sclerosis. Ann Rheum Dis 54:853–855PubMedCrossRefGoogle Scholar
  29. 29.
    Ho M, Veale D, Eastmond C, Nuki G, Belch J (2000) Macrovascular disease and systemic sclerosis. Ann Rheum Dis 59:39–43PubMedCrossRefGoogle Scholar
  30. 30.
    Simeon CP, Armadans L, Fonollosa V et al (2003) Mortality and prognostic factors in Spanish patients with systemic sclerosis. Rheumatology 42:71–75PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2009

Authors and Affiliations

  • Paola Caramaschi
    • 1
    Email author
  • Nicola Martinelli
    • 1
  • Alessandro Volpe
    • 1
  • Sara Pieropan
    • 1
  • Ilaria Tinazzi
    • 1
  • Giuseppe Patuzzo
    • 1
  • Helal Mahamid
    • 1
  • Lisa Maria Bambara
    • 1
  • Domenico Biasi
    • 1
  1. 1.Dipartimento di Medicina Clinica e SperimentaleUniversità di VeronaVeronaItaly

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