Systemic Sclerosis Treatment & Management
- Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD more...
Different treatment regimens for systemic sclerosis exist. The therapeutic approach depends on the presentation of the disease and complexity of symptoms. In a recent review of the literature, calcium channel blockers, prostanoids, tadalafil, and bosentan received the strongest recommendations for their effectiveness for Raynaud phenomenon and digital ulcers.
In pruritus, the following agents are sometimes helpful:
Camphor and menthol
Psoralen UV-A (PUVA) treatment
In patients with calcinosis, surgery may be of some benefit, but healing time is often prolonged.
When Raynaud phenomenon is present, the most effective nonpharmacologic method of preventing Raynaud episodes is avoiding exposure to cold temperature and wearing layers of warm, loose-fitting clothing, including socks and gloves. Also, smoking cessation is advised. In the pharmacologic regimen, consider the use of agents such as calcium-channel blockers, vasodilating drugs, intravenous prostaglandins, prostacyclin analogs, or aspirin.
In patients with kidney involvement, ACE or angiotensin II inhibitor therapy is indicated.
In patients with GI tract involvement, proton pump inhibitors (eg, omeprazole) and H2 blockers can help to control reflux symptoms.
In patients with lung involvement, calcium-channel blockers (eg, nifedipine), prostaglandins (eg, prostacyclin), and cyclophosphamide have been used with variable success. When inflammatory myositis is present, the use of high doses of corticosteroids (eg, prednisolone with a starting dose of 1 mg/kg/d) is suggested.
Antifibrotic agents have been investigated, although results have varied and none is clearly shown to be of consistent benefit. These have included D-penicillamine, interferon alfa and interferon gamma, and immunomodulatory agents. Immunomodulatory agents have included the following:
Corticosteroids (in inflammatory myositis, pericarditis, refractory arthritis, or alveolitis)
Methotrexate (15 mg/wk) 
Mycophenolate mofetil may benefit patients with diffuse progressive cutaneous systemic sclerosis of recent onset, a small prospective study suggested 
Low-dose intravenous cyclophosphamide [43, 44]
Statins [45, 46]
Immunosuppressive drugs with autologous peripheral hematopoietic stem cell transplantation 
Because of their antifibrotic properties, the tyrosine kinase inhibitors imatinib mesylate and nintedanib may be potential therapies.[44, 45, 48, 49, 50]
The cutaneous telangiectasias can be treated. The number of pulsed dye laser treatments required to effectively clear systemic sclerosis/CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome telangiectasia was approximately 2-fold higher than with sporadic telangiectasias, a finding attributed to thickened collagen fibers and blood vessels. Pulsed dye laser (PDL) and intense pulsed light (IPL) may be used, both being effective, although the former produces a better cosmetic result but with more adverse effects than the latter.
The symptoms of systemic sclerosis are diverse; therefore, consider consultations with the following specialists, if applicable:
Neoplastic diseases may complicate the disease course. Examples include breast carcinoma; multiple myeloma; lymphoma; and cancer of the ovary, esophagus, colon, or rectum.
Female patients should be evaluated for breast cancer. Epidemiologic studies have suggested that patients with scleroderma have an increased risk of cancer. However, large-scale case-control studies are needed to substantiate a possible association between scleroderma—both cutaneous and systemic—and breast cancer.
Park JS, Park MC, Song JJ, Park YB, Lee SK, Lee SW. Application of the 2013 ACR/EULAR classification criteria for systemic sclerosis to patients with Raynaud's phenomenon. Arthritis Res Ther. 2015 Mar 22. 17(1):77. [Medline]. [Full Text].
Sakkas LI. New developments in the pathogenesis of systemic sclerosis. Autoimmunity. 2005 Mar. 38(2):113-6. [Medline].
Nguyen C, Berezne A, Baubet T, et al. Association of Gender with Clinical Expression, Quality of Life, Disability, and Depression and Anxiety in Patients with Systemic Sclerosis. PLoS One. 2011 Mar 9. 6(3):e17551. [Medline]. [Full Text].
Mathai SC, Hummers LK, Champion HC, et al. Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease. Arthritis Rheum. 2009 Feb. 60(2):569-77. [Medline].
Alba MA, Velasco C, Simeón CP, Fonollosa V, Trapiella L, Egurbide MV, et al. Early- versus Late-Onset Systemic Sclerosis: Differences in Clinical Presentation and Outcome in 1037 Patients. Medicine (Baltimore). 2014 Mar. 93(2):73-81. [Medline].
Hissaria P, Roberts-Thomson PJ, Lester S, Ahern MJ, Smith MD, Walker JG. Cigarette smoking in patients with systemic sclerosis - reduces overall survival. Arthritis Rheum. 2011 Mar 24. [Medline].
Jung S, Martin T, Schmittbuhl M, Huck O. The spectrum of orofacial manifestations in systemic sclerosis: a challenging management. Oral Dis. 2016 May 19. [Medline].
Mozzetta A, Antinone V, Alfani S, et al. Mental health in patients with systemic sclerosis: a controlled investigation. J Eur Acad Dermatol Venereol. 2008 Mar. 22(3):336-40. [Medline].
Kwakkenbos L, van Lankveld WG, Vonk MC, Becker ES, van den Hoogen FH, van den Ende CH. Disease-related and psychosocial factors associated with depressive symptoms in patients with systemic sclerosis, including fear of progression and appearance self-esteem. J Psychosom Res. 2012 Mar. 72(3):199-204. [Medline].
Hudson M, Steele R, Taillefer S, Baron M; Canadian Scleroderma Research. Quality of life in systemic sclerosis: Psychometric properties of the World Health Organization Disability Assessment Schedule II. Arthritis Rheum. 2008 Jan 31. 59(2):270-278. [Medline].
Ungprasert P, Srivali N, Kittanamongkolchai W. Systemic sclerosis and risk of venous thromboembolism: A systematic review and meta-analysis. Mod Rheumatol. 2015 Apr 7. 1-17. [Medline].
Malcarne VL, Hansdottir I, McKinney A. Medical signs and symptoms associated with disability, pain, and psychosocial adjustment in systemic sclerosis. J Rheumatol. 2007 Feb. 34(2):359-67. [Medline].
Jarzabek-Chorzelska M, Blaszczyk M, Jablonska S, Chorzelski T, Kumar V, Beutner EH. Scl 70 antibody--a specific marker of systemic sclerosis. Br J Dermatol. 1986 Oct. 115(4):393-401. [Medline].
Spencer-Green G, Alter D, Welch HG. Test performance in systemic sclerosis: anti-centromere and anti-Scl-70 antibodies. Am J Med. 1997 Sep. 103(3):242-8. [Medline].
Dogan S, Akdogan A, Atakan N. Nailfold capillaroscopy in systemic sclerosis: Is there any difference between videocapillaroscopy and dermatoscopy?. Skin Res Technol. 2013 Mar 25. [Medline].
Aozasa N, Asano Y, Ashida R, et al. Systemic sclerosis with an unusual rapid development of huge calcinosis (tumoral calcinosis). J Dermatol. 2011 Mar 2. [Medline].
Wielosz E, Borys O, Zychowska I, Majdan M. Gastrointestinal involvement in patients with systemic sclerosis. Pol Arch Med Wewn. 2010 Apr. 120(4):132-6. [Medline].
Schieir O, Thombs BD, Hudson M, Boivin JF, Steele R, Bernatsky S, et al. Prevalence, severity, and clinical correlates of pain in patients with systemic sclerosis. Arthritis Care Res (Hoboken). 2010 Mar. 62(3):409-17. [Medline].
Troldborg A, Nielsen BD, Kolstad HA, Olesen AB, Søndergaard KH. [Silica exposure and the risk of systemic sclerosis.]. Ugeskr Laeger. 2013 Feb 18. 175(8):501-503. [Medline].
Kawakami T, Tsutsumi Y, Soma Y. Limited cutaneous systemic sclerosis induced by paclitaxel in a patient with breast cancer. Arch Dermatol. 2009 Jan. 145(1):97-8. [Medline].
Itoh M, Yanaba K, Kobayashi T, Nakagawa H. Taxane-induced scleroderma. Br J Dermatol. 2007 Feb. 156(2):363-7. [Medline].
Chen JK, Chung L, Fiorentino DF. Characterization of patients with clinical overlap of morphea and systemic sclerosis: A case series. J Am Acad Dermatol. 2016 Jun. 74 (6):1272-4. [Medline].
Muangchan C, Harding S, Khimdas S, Bonner A, Baron M, Pope J. C - reactive protein (CRP) is associated with high disease activity in systemic sclerosis: results from the Canadian Scleroderma Research Group (CSRG). Arthritis Care Res (Hoboken). 2012 May 3. [Medline].
Waszczykowska E, Kukulski K, Sysa-Jedrzejowska A, Dziankowska-Bartkowiak B, Gierach D, Omulecki A. Evaluation of esophageal passage in selected connective tissue diseases. J Med. 1997. 28(3-4):163-74. [Medline].
Arif T, Masood Q, Singh J, Hassan I. Assessment of esophageal involvement in systemic sclerosis and morphea (localized scleroderma) by clinical, endoscopic, manometric and pH metric features: a prospective comparative hospital based study. BMC Gastroenterol. 2015 Feb 15. 15(1):24. [Medline]. [Full Text].
de Groote P, Gressin V, Hachulla E, et al. Evaluation of cardiac abnormalities by Doppler echocardiography in a large nationwide multicentric cohort of patients with systemic sclerosis. Ann Rheum Dis. 2008 Jan. 67(1):31-6. [Medline].
Foocharoen C, Pussadhamma B, Mahakkanukrauh A, Suwannaroj S, Nanagara R. Asymptomatic cardiac involvement in Thai systemic sclerosis: prevalence and clinical correlations with non-cardiac manifestations (preliminary report). Rheumatology (Oxford). 2015 Apr 10. [Medline].
Kepez A, Akdogan A, Sade LE, et al. Detection of Subclinical Cardiac Involvement in Systemic Sclerosis by Echocardiographic Strain Imaging. Echocardiography. 2008 Feb. 25(2):191-197. [Medline].
Waszczykowska A, Gos R, Waszczykowska E, Dziankowska-Bartkowiak B, Jurowski P. Assessment of skin microcirculation by laser Doppler flowmetry in systemic sclerosis patients. Postepy Dermatol Alergol. 2014 Feb. 31(1):6-11. [Medline]. [Full Text].
De Santis M, Bosello SL, Capoluongo E, Inzitari R, Peluso G, Lulli P, et al. A vascular endothelial growth factor deficiency characterises scleroderma lung disease. Ann Rheum Dis. 2012 Mar 27. [Medline].
Blaszczyk M, Jarzabek-Chorzelska M, Jablonska S, et al. Autoantibodies to nucleolar antigens in systemic scleroderma: clinical correlations. Br J Dermatol. 1990 Oct. 123(4):421-30. [Medline].
Bruns M, Herrmann K, Haustein UF. Immunologic parameters in systemic sclerosis. Int J Dermatol. 1994 Jan. 33(1):25-32. [Medline].
Van Praet JT, Smith V, Haspeslagh M, Degryse N, Elewaut D, De Keyser F. Histopathological cutaneous alterations in systemic sclerosis: a clinicopathological study. Arthritis Res Ther. 2011 Feb 28. 13(1):R35. [Medline].
Ohtsuka T. Relation between elevated high-sensitivity C-reactive protein and anti-mitochondria antibody in patients with systemic sclerosis. J Dermatol. 2008 Feb. 35(2):70-5. [Medline].
Van Praet JT, Van Steendam K, Smith V, et al. Specific anti-nuclear antibodies in systemic sclerosis patients with and without skin involvement: an extended methodological approach. Rheumatology (Oxford). 2011 Feb 17. [Medline].
García de la Peña Lefebvre P, Nishishinya MB, Pereda CA, Loza E, Sifuentes Giraldo WA, Román Ivorra JA, et al. Efficacy of Raynaud's phenomenon and digital ulcer pharmacological treatment in systemic sclerosis patients: a systematic literature review. Rheumatol Int. 2015 Apr 1. [Medline].
Wigley FM, Korn JH, Csuka ME, 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 Apr. 41(4):670-7. [Medline].
Krasagakis K, Dippel E, Ramaker J, Owsianowski M, Orfanos CE. Management of severe scleroderma with long-term extracorporeal photopheresis. Dermatology. 1998. 196(3):309-15. [Medline].
Seyger MM, van den Hoogen FH, van Vlijmen-Willems IM, van de Kerkhof PC, de Jong EM. Localized and systemic scleroderma show different histological responses to methotrexate therapy. J Pathol. 2001 Apr. 193(4):511-6. [Medline].
Mendoza FA, Nagle SJ, Lee JB, Jimenez SA. A Prospective Observational Study of Mycophenolate Mofetil Treatment in Progressive Diffuse Cutaneous Systemic Sclerosis of Recent Onset. J Rheumatol. 2012 Apr 1. [Medline].
Hider SL, Woodhead M, Taylor PM, Bruce IN. Lung fibrosis in systemic sclerosis treated with a combination of ciclosporin and azathioprine. Clin Exp Rheumatol. 2006 Mar-Apr. 24(2):215. [Medline].
Valentini G, Paone C, La Montagna G, et al. Low-dose intravenous cyclophosphamide in systemic sclerosis: an open prospective efficacy study in patients with early diffuse disease. Scand J Rheumatol. 2006 Jan-Feb. 35(1):35-8. [Medline].
Varai G, Earle L, Jimenez SA, Steiner RM, Varga J. A pilot study of intermittent intravenous cyclophosphamide for the treatment of systemic sclerosis associated lung disease. J Rheumatol. 1998 Jul. 25(7):1325-9. [Medline].
Furukawa S, Yasuda S, Amengual O, Horita T, Atsumi T, Koike T. Protective effect of pravastatin on vascular endothelium in patients with systemic sclerosis: a pilot study. Ann Rheum Dis. 2006 Aug. 65(8):1118-20. [Medline].
Blagojevic J, Matucci-Cerinic M. Are statins useful for treating vascular involvement in systemic sclerosis?. Nat Clin Pract Rheumatol. 2009 Feb. 5(2):70-1. [Medline].
Verrecchia F, Laboureau J, Verola O, et al. Skin involvement in scleroderma--where histological and clinical scores meet. Rheumatology (Oxford). 2007 May. 46(5):833-41. [Medline].
Huang J, Beyer C, Palumbo-Zerr K, Zhang Y, Ramming A, Distler A, et al. Nintedanib inhibits fibroblast activation and ameliorates fibrosis in preclinical models of systemic sclerosis. Ann Rheum Dis. 2015 Apr 9. [Medline].
Chung L, Fiorentino DF, Benbarak MJ, et al. Molecular framework for response to imatinib mesylate in systemic sclerosis. Arthritis Rheum. 2009 Jan 29. 60(2):584-591. [Medline].
Pannu J, Asano Y, Nakerakanti S, et al. Smad1 pathway is activated in systemic sclerosis fibroblasts and is targeted by imatinib mesylate. Arthritis Rheum. 2008 Aug. 58(8):2528-37. [Medline].
Halachmi S, Gabari O, Cohen S, Koren R, Amitai DB, Lapidoth M. Telangiectasis in CREST syndrome and systemic sclerosis: correlation of clinical and pathological features with response to pulsed dye laser treatment. Lasers Med Sci. 2013 Mar 14. [Medline].
Dinsdale G, Murray A, Moore T, Ferguson J, Wilkinson J, Richards H, 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 Mar 28. [Medline].
Scope A, Sadetzki S, Sidi Y, et al. Breast cancer and scleroderma. Skinmed. 2006 Jan-Feb. 5(1):18-24. [Medline].
Riera R, Andrade LE, Souza AW, Kayser C, Yanagita ET, Trevisani VF. Lidocaine for systemic sclerosis: a double-blind randomized clinical trial. Orphanet J Rare Dis. 2011 Feb 7. 6:5. [Medline]. [Full Text].