Management of Systemic Sclerosis-Related Skin Disease: A Review of Existing and Experimental Therapeutic Approaches

Rheumatic Disease Clinics of North America

Volumn 41, Issue 3, 2015, Pages 399-417

  Volkmann, Elizabeth R ^a   Furst, Daniel E ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Cyclophosphamide (CYC); Diffuse cutaneous systemic sclerosis (DcSSc); Digital ulcers (DU); Hematopoietic stem cell transplantation (HSCT); Limited cutaneous systemic sclerosis (LcSSc); Methotrexate (MTX); Modified Rodnan skin score (mRSS); Raynaud's phenomenon (RP)

Indexed keywords

ACETYLCYSTEINE; ALPHA INTERFERON; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BOSENTAN; CALCIUM CHANNEL BLOCKING AGENT; COLLAGEN; COLLAGEN TYPE 1; CYCLOPHOSPHAMIDE; ERGOT DERIVATIVE; FIBRONECTIN; HYPERIMMUNE CAPRINE SERUM; ILOPROST; IMATINIB; IMMUNOGLOBULIN; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 6; MATRIX PROTEIN; METHOTREXATE; MYCOPHENOLATE MOFETIL; NIFEDIPINE; PENICILLAMINE; PLACEBO; RECOMBINANT RELAXIN; RITUXIMAB; SILDENAFIL; TADALAFIL; TOCILIZUMAB; TRANSFORMING GROWTH FACTOR BETA ANTIBODY; TUMOR NECROSIS FACTOR INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION; DIFFERENTIAL DIAGNOSIS; DRUG FATALITY; EOSINOPHILIC FASCIITIS; HEMATURIA; HISTOPATHOLOGY; HISTORY; HUMAN; INFECTION; INFLAMMATORY DISEASE; INTERSTITIAL LUNG DISEASE; MORPHEA; MULTICENTER STUDY (TOPIC); NEOPLASM; NEPHROGENIC SYSTEMIC FIBROSIS; NEUTROPENIA; PHASE 3 CLINICAL TRIAL (TOPIC); PHYSICAL EXAMINATION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RAYNAUD PHENOMENON; REVIEW; RHEUMATOID ARTHRITIS; SCLERODERMA; SCLEROMYXEDEMA; SKIN BIOPSY; SKIN DISEASE; SYSTEMIC SCLEROSIS; TREATMENT FAILURE; ANIMAL; HEMATOPOIETIC STEM CELL TRANSPLANTATION; PATHOLOGY; RAYNAUD DISEASE; SCLERODERMA, SYSTEMIC;

ANIMALS; CYCLOPHOSPHAMIDE; DIAGNOSIS, DIFFERENTIAL; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; METHOTREXATE; RAYNAUD DISEASE; SCLERODERMA, SYSTEMIC; TREATMENT FAILURE;

EID: 84937966982     PISSN: 0889857X     EISSN: 15583163     Source Type: Journal    
DOI: 10.1016/j.rdc.2015.04.004     Document Type: Review

References (90)

1. LeRoy E.C., Black C., Fleischmajer R., et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988, 15:202-205.
2. van den Hoogen F., Khanna D., Fransen J., et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 2013, 65:2737-2747.
3. Clements P.J., Medsger T.A., Feghali C.A. Cutaneous involvement in systemic sclerosis. Systemic sclerosis 2004, 129-150. Lippincott Williams and Wilkins, New York. 2nd edition. P.J. Clements, D.E. Furst (Eds.).
4. Steen V.D., Ziegler G.L., Rodnan G.P., et al. Clinical and laboratory associations of anticentromere antibody in patients with progressive systemic sclerosis. Arthritis Rheum 1984, 27:125-131.
5. Medsgar T.A. Natural history of systemic sclerosis and the assessment of disease activity, severity, functional status, and psychologic well-being. Rheum Dis Clin North Am 2003, 29:255-273.
6. Reveille J.D., Fischbach M., McNearney T., et al. Systemic sclerosis in 3 US ethnic groups: a comparison of clinical, sociodemographic, serologic, and immunogenetic determinants. Semin Arthritis Rheum 2001, 30:332-346.
7. Herrick A.L., Oogarah P.K., Freemont A.J., et al. Vasculitis in patients with systemic sclerosis and severe digital ischaemia requiring amputation. Ann Rheum Dis 1994, 53:323-326.
8. Furst D.E., Clements P.J., Steen V.D., et al. The modified Rodnan skin score is an accurate reflection of skin biopsy thickness in systemic sclerosis. J Rheumatol 1998, 25:84-88.
9. Clements P.J., Lachenbruch P.A., Ng S.C., et al. Skin score. A semiquantitative measure of cutaneous involvement that improves prediction of prognosis in systemic sclerosis. Arthritis Rheum 1990, 33:1256-1263.
10. Khanna D., Furst D.E., Hays R.D., et al. Minimally important difference in diffuse systemic sclerosis: results from the D-penicillamine study. Ann Rheum Dis 2006, 65:1325-1329.
11. Bendeck S.E., Jacobe H.T. Ultrasound as an outcome measure to assess disease activity in disorders of skin thickening: an example of the use of radiologic technique to assess skin disease. Dermatol Ther 2007, 20:86-92.
12. Smith V., Riccieri V., Pizzorni C., et al. Nailfold capillaroscopy for prediction of novel future severe organ involvement in systemic sclerosis. J Rheumatol 2013, 40:2023-2028.
13. Torres J.E., Sanchez J.L. Histopathological differentiation between localized and systemic sclerosis. Am J Dermatopathol 1998, 20:242-245.
14. Prescott R.J., Freemont A.J., Jones C.J., et al. Sequential dermal microvascular and perivascular changes in the development of scleroderma. J Pathol 1992, 166:255-263.
15. Domsic R.T., Rodriguez-Reyna T., Lucas M., et al. Skin thickness progression rate: a predictor of mortality and early internal organ involvement in diffuse scleroderma. Ann Rheum Dis 2011, 70:104-109.
16. Steen V.D., Medsger T.A. Improvement in skin thickening in systemic sclerosis associated with improved survival. Arthritis Rheum 2001, 44:2828-2835.
17. Krieg T., Takehara K. Skin disease: a cardinal feature of systemic sclerosis. Rheumatology (Oxford) 2009, 48:14-18.
18. Bode B.Y., Yocum D.E., Gall E.P., et al. Methotrexate (MTX) in scleroderma: experience in ten patients. Arthritis Rheum 1990, 33(Suppl 9):S66.
19. van den Hoogen F.H., Boerbooms A.M., van de Putte L.B., et al. Low dose methotrexate treatment in systemic sclerosis. J Rheumatol 1991, 18:1763-1764.
20. Seibold J.R., McCloskey D.A., Furst D.E. Pilot trial of methotrexate (MTX) in treatment of early diffuse scleroderma. Arthritis Rheum 1994, 37(Suppl 16):R35.
21. van den Hoogen F.H., Boerbooms A.M., Swaak A.J., et al. Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial. Br J Rheumatol 1996, 35:364-372.
22. Pope J.E., Bellamy N., Seibold J.R., et al. A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma. Arthritis Rheum 2001, 44:1351-1358.
23. Johnson S.R., Feldman B.M., Pope J.E., et al. Shifting our thinking about uncommon disease trials: the case of methotrexate in scleroderma. J Rheumatol 2009, 36:323-329.
24. Kowal-Bielecka O., Landewé R., Avouac J., et al. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis 2009, 68:620-628.
25. Tashkin D.P., Elashoff R., Clements P.J., Scleroderma Lung Study Research Group, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006, 354:2655-2666.
26. Tashkin D.P., Elashoff R., Clements P.J., Scleroderma Lung Study Research Group, et al. Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. Am J Respir Crit Care Med 2007, 176:1026-1034.
27. Furst D.E., Tseng C.H., Clements P.J., et al. Adverse events during the Scleroderma Lung Study. Am J Med 2011, 124:459-467.
28. Naraghi K., van Laar J.M. Updated on stem cell transplantation for systemic sclerosis: recent trial results. Curr Rheumatol Rep 2013, 15:326.
29. Binks M., Passweg J.R., Furst D., et al. Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease. Ann Rheum Dis 2001, 60:577-584.
30. Farge D., Passweg J., van Laar J.M., EBMT/EULAR Registry, et al. Autologous stem cell transplantation in the treatment of systemic sclerosis. Ann Rheum Dis 2004, 63:974-981.
31. Nash R.A., McSweeney P.A., Nelson J.L., et al. Allogeneic marrow transplantation in patients with severe systemic sclerosis: resolution of dermal fibrosis. Arthritis Rheum 2006, 54:1982-1986.
32. Vonk M.C., Marjanovic Z., van den Hoogen F.H., et al. Long-term follow-up results after autologous haematopoietic stem cell transplantation for severe systemic sclerosis. Ann Rheum Dis 2008, 67:98-104.
33. van Laar J.M., Farge D., Sont J.K., et al. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA 2014, 311:2490-2498.
34. Furst D.E., Clements P.J., Harris R., et al. Measurement of clinical change in progressive systemic sclerosis: a 1 year double-blind placebo-controlled trial of N-acetylcysteine. Ann Rheum Dis 1979, 38:356-361.
35. Clements P.J., Furst D.E., Wong W.K., et al. High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: analysis of a two-year, double-blind, randomized, controlled clinical trial. Arthritis Rheum 1999, 42:1194-1203.
36. Denton C.P., Merkel P.A., Furst D.E., et al. Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multi-center, randomized, placebo-controlled phase I/II trial of CAT-192. Arthritis Rheum 2007, 56:323-333.
37. Khanna D., Clements P.J., Furst D.E., et al. Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2009, 60:1102-1111.
38. Black C.M., Silman A.J., Herrick A.I., et al. Interferon-alpha does not improve outcome at one year in patients with diffuse cutaneous scleroderma: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 1999, 42:299-305.
39. Pope J., McBain D., Petrlich L., et al. Imatinib in active diffuse cutaneous systemic sclerosis: Results of a six-month, randomized, double-blind, placebo-controlled, proof-of-concept pilot study at a single center. Arthritis Rheum 2011, 63:3547-3551.
40. Seibold J.R., Denton C.P., Furst D.E., et al. Randomized, prospective, placebo-controlled trial of bosentan in interstitial lung disease secondary to systemic sclerosis. Arthritis Rheum 2010, 62:2101-2108.
41. Denton C.P., Engelhart M., Tvede N., et al. An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis. Ann Rheum Dis 2009, 68:1433-1439.
42. Murdaca G., Spano F., Contatore M., et al. Potential use of TNF-α inhibitors in systemic sclerosis. Immunotherapy 2014, 6:283-289.
43. Postlethwaite A.E., Wong W.K., Clements P., et al. A multicenter, randomized, double-blind, placebo-controlled trial of oral type I collagen treatment in patients with diffuse cutaneous systemic sclerosis: I. Oral type I collagen does not improve skin in all patients, but may improve skin in late-phase disease. Arthritis Rheum 2008, 58:1810-1822.
44. Whitfield M.L., Finlay D.R., Murray J.I., et al. Systemic and cell type-specific gene expression patterns in scleroderma skin. Proc Natl Acad Sci U S A 2003, 100:12319-12324.
45. Hasegawa M., Hamaguchi Y., Yanaba K., et al. B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis. Am J Pathol 2006, 169:954-966.
46. Smith V., Van Praet J.T., Vandooren B., et al. Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann Rheum Dis 2010, 69:193-197.
47. Jordan S., Distler J.H., Maurer B., on behalf of the EUSTAR Rituximab Study Group, et al. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis 2014, 74:1188-1194.
48. Daoussis D., Liossis S.N., Athanassios C., et al. Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology (Oxford) 2010, 49:271-280.
49. Scala E., Pallotta S., Frezzolini A., et al. Cytokine and chemokine levels in systemic sclerosis: relationship with cutaneous and internal organ involvement. Clin Exp Immunol 2004, 138:540-546.
50. Khan K., Xu S., Nihtyanova S., et al. Clinical and pathological significance of interleukin 6 overexpression in systemic sclerosis. Ann Rheum Dis 2012, 71:1235-1242.
51. Elhai M., Meunier M., Matucci-Cerinic M., EUSTAR (EULAR Scleroderma Trials and Research group), et al. Outcomes of patients with systemic sclerosis-associated polyarthritis and myopathy treated with tocilizumab or abatacept: a EUSTAR observational study. Ann Rheum Dis 2013, 72:1217-1220.
52. Shima Y., Kuwahara Y., Murota H., et al. The skin of patients with systemic sclerosis softened during the treatment with anti-IL-6 receptor antibody tocilizumab. Rheumatology (Oxford) 2010, 49:2408-2412.
53. Khanna D, Denton CP, van Laar JM, et al. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis: Week 24 data from a Phase 2/3 Trial. Abstract presentation at the American College of Rheumatology Annual Meeting. Boston, November 15-18, 2014.
54. Levy Y., Amital H., Langevitz P., et al. Intravenous immunoglobulin modulates cutaneous involvement and reduces skin fibrosis in systemic sclerosis: an open-label study. Arthritis Rheum 2004, 50:1005-1007.
55. Amital H., Rewald E., Levy Y., et al. Fibrosis regression induced by intravenous gammaglobulin treatment. Ann Rheum Dis 2003, 62:175-177.
56. Omair M., Alahmadi A., Johnson S.R. Safety and effectiveness of mycophenolate in systemic sclerosis: a systemic review. Arthritis Rheum 2013, 65(Suppl 10):2599. [abstract].
57. Derk C.T., Grace E., Shenin M., et al. A prospective open-label study of mycophenolate mofetil for the treatment of diffuse systemic sclerosis. Rheumatology (Oxford) 2009, 48:1595-1599.
58. Medoza F.A., Nagle S.J., Lee J.B., et al. A prospective observational study of mycophenolate mofetil treatment in progressive diffuse cutaneous systemic sclerosis of recent onset. J Rheumatol 2012, 39:1241-1247.
59. Walker K.M., Pope J., Canadian Scleroderma Research Group (CSRG) Treatment of systemic sclerosis complications: what to use when first-line treatment fails-a consensus of systemic sclerosis experts. Semin Arthritis Rheum 2012, 42:42-55. participating members of the Scleroderma Clinical Trials Consortium (SCTC).
60. Quillinan N.P., McIntosh D., Vernes J., et al. Treatment of diffuse systemic sclerosis with hyperimmune caprine serum (AIMSPRO): a phase II double-blind placebo-controlled trial. Ann Rheum Dis 2014, 73:56-61.
61. Rademaker M., Cooke E.D., Almond N.E., et al. 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, 298:561-564.
62. Scorza R., Caronni M., Mascagni B., et al. Effects of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud's phenomenon. A randomized, controlled study. Clin Exp Rheumatol 2001, 19:503-508.
63. Wigley F.M., Korn J.H., Csuka M.E., et al. Oral iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis: a multicenter, placebo-controlled, double-blind study. Arthritis Rheum 1998, 41:670-677.
64. Shenoy P.D., Kumar S., Jha L.K., et al. Efficacy of tadalafil in secondary Raynaud's phenomenon resistant to vasodilator therapy: a double-blind randomized cross-over trial. Rheumatology (Oxford) 2010, 49:2420-2428.
65. Herrick A.L., van den Hoogen F., Gabrielli A., et al. Modified-release sildenafil reduces Raynaud's phenomenon attack frequency in limited cutaneous systemic sclerosis. Arthritis Rheum 2011, 63:775-782.
66. Caglayan E., Axmann S., Hellmich M., et al. Vardenafil for the treatment of Raynaud phenomenon: a randomized, double-blind, placebo-controlled crossover study. Arch Intern Med 2012, 172:1182-1184.
67. Chung L., Shapiro L., Fiorentino D., et al. MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud's phenomenon: a randomized, controlled trial. Arthritis Rheum 2009, 60:870-877.
68. Dziadzio M., Denton C.P., Smith R., et al. Losartan therapy for Raynaud's phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial. Arthritis Rheum 1999, 42:2646-2655.
69. Pope J., Fenlon D., Thompson A., et al. Prazosin for Raynaud's phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev 2000, (2). CD000956.
70. Coleiro B., Marshall S.E., Denton C.P., et al. Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford) 2001, 40:1038-1043.
71. Uppal L., Dhaliwal K., Butler P.E. A prospective study of the use of botulinum toxin injections in the treatment of Raynaud's syndrome associated with scleroderma. J Hand Surg Eur Vol 2014, 39:876-880.
72. Galluccio F., Matucci-Cerinic M. Two faces of the same coin: Raynaud's phenomenon and digital ulcers in systemic sclerosis. Autoimmun Rev 2011, 10:241-243.
73. Matucci-Cerinic M., Denton C.P., Furst D.E., et al. Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 2011, 70:32-38.
74. Wigley F.M., Seibold J.R., Wise R.A., et al. Intravenous iloprost treatment of Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis. J Rheumatol 1992, 19:1407-1414.
75. Seibold J.R., Wigley F.M., Schiopu E., et al. Digital ischemic ulcers in scleroderma treated with oral treprostinil diethanolamine: a randomized, double-blind, placebo-controlled, multicenter study. Arthritis Rheum 2011, 63(Suppl):S968. [abstract].
76. Markus Y.M., Bell M.J., Evans A.W. Ischemic scleroderma wounds successfully treated with hyperbaric oxygen therapy. J Rheumatol 2006, 33:1694-1696.
77. Fiori G., Galluccio F., Braschi F., et al. Vitamin E gel reduces time of healing of digital ulcers in systemic sclerosis. Clin Exp Rheumatol 2009, 27:51-54.
78. 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, 35:1801-1808.
79. Wasserman A., Brahn E. Systemic sclerosis: bilateral improvement of Raynaud's phenomenon with unilateral digital sympathectomy. Semin Arthritis Rheum 2010, 40:137-146.
80. Tomaino M.M., Goitz R.J., Medsger T.A. Surgery for ischemic pain and Raynaud's phenomenon in scleroderma: a description of treatment protocol and evaluation of results. Microsurgery 2001, 21:75-79.
81. Hazen P.G., Walker A.E., Carney J.F., et al. Cutaneous calcinosis of scleroderma. Successful treatment with intralesional adrenal steroids. Arch Dermatol 1982, 118:366-367.
82. Bottomley W.W., Goodfield M.J., Sheehan-Dare R.A. Digital calcification in systemic sclerosis: effective treatment with good tissue preservation using the carbon dioxide laser. Br J Dermatol 1996, 135:302-304.
83. Sultan-Bichat N., Menard J., Perceau G., et al. Treatment of calcinosis cutis by extracorporeal shock-wave lithotripsy. J Am Acad Dermatol 2012, 66:424-429.
84. Merlino G., Germano S., Carlucci S. Surgical management of digital calcinosis in CREST syndrome. Aesthetic Plast Surg 2013, 37:1214-1219.
85. Dinsdale G., Murray A., Moore T., et al. A comparison of intense pulsed light and laser treatment of telangiectases in patients with systemic sclerosis: a within-subject randomized trial. Rheumatology (Oxford) 2014, 53:1422-1430.
86. Daoussis D., Antonopoulos I., Liossis S.N., et al. Treatment of systemic sclerosis-associated calcinosis: a case report of rituximab-induced regression of CREST-related calcinosis and review of the literature. Semin Arthritis Rheum 2012, 41:822-829.
87. Cunningham B.B., Landells I.D., Langman C., et al. Topical calcipotriene for morphea/linear scleroderma. J Am Acad Dermatol 1998, 39:211-215.
88. Shima Y., Yamamoto Y., Ikeda T., et al. A patient with localized scleroderma successfully treated with etretinate. Case Rep Dermatol 2014, 6:200-206.
89. Palmieri G.M., Sebes J.I., Aelion J.A., et al. Treatment of calcinosis with diltiazem. Arthritis Rheum 1995, 38:1646-1654.
90. Vayssairat M., Hidouche D., Abdoucheli-Baudot N., et al. Clinical significance of subcutaneous calcinosis in patients with systemic sclerosis. Does diltiazem induce its regression?. Ann Rheum Dis 1998, 57:252-254.