Disease Info

Disease: Systemic Sclerosis

Systemic Sclerosis (SSc)

Systemic sclerosis (SSc), or scleroderma, is a chronic connective tissue disease, characterized by tissue inflammation, fibrosis and vascular obliteration in the skin and internal organs, particularly lungs, heart, and digestive tract. There are two main subsets of SSc: diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc), but sometimes the skin involvement can be absent (“SSc sine scleroderma”).

The disease is mainly characterized by Raynaud’s phenomenon, that typically represents the first features of the disease. Raynaud’s phenomenon is a spasm of arteries which causes recurrent episodes of reduced blood flow particularly in the fingers, in the nose and the ears. These districts, if exposed to cold temperatures, may change colour, becoming white or red/blue.

The other signs that usually appear after months or years may include:
– Skin thickness (lcSSc: fingers, hands, feet, face; dcSSc: the whole body);
– Painful calcium deposits under the skin (calcinosis);
– Esophageal dysmotility (with gastroesophageal reflux and difficulties in swallowing) and malabsorbtion
– Difficulties in breathing due to pulmonary fibrosis and pulmonary arterial hypertension
– Modification of the heart rhythm due to cardiac involvement
– Digital ulcers that reduce the hand function and the quality of life

The cause of SSc is still unknown, but the disease probably originates from an autoimmune reaction which involves the microcirculation and leads to tissue inflammation, overproduction of collagen and eventually fibrosis. It is more common in women.

The diagnosis is based on typical clinical manifestations, on the detection of specific antibodies and on evidence of specific capillary alteration on capillaroscopy (observation of nailfold capillaries with a microscope). Specific exams such as computed tomography (CT), electrocardiogram, echo of the heart and kidney, esophageal and gastric fibroscopy may be used to investigate internal organ involvement.


List of useful references

New directions for patient-centred care in scleroderma: the Scleroderma Patient-centred Intervention Network (SPIN)
Thombs BD, Jewett LR, Assassi S, Baron M, Bartlett SJ, Maia AC, et al.
Clin Exp Rheumatol. 2012 Mar-Apr;30(2 Suppl 71):S23-9

Frequency and impact of symptoms experienced by patients with systemic sclerosis: results from a Canadian National Survey
Bassel M, Hudson M, Taillefer SS, Schieir O, Baron M, Thombs BD.
Rheumatology (Oxford). 2011 Apr;50(4):762-7.

Social/economic costs and health-related quality of life in patients with scleroderma in Europe
López-Bastida J, Linertová R, Oliva-Moreno J, Serrano-Aguilar P, Posada-de-la-Paz M, Kanavos P, et al.
Eur J Health Econ. 2016 Apr;17 Suppl 1:109-17

Patient participation in patient-reported outcome instrument development in systemic sclerosis
Pauling JD, Frech TM, Domsic RT, Hudson M.
Clin Exp Rheumatol. 2017 Sep-Oct;35 Suppl 106(4):184-192.

Patients’ Perspectives and Experiences Living with Systemic Sclerosis: A Systematic Review and Thematic Synthesis of Qualitative Studies
Nakayama A, Tunnicliffe DJ, Thakkar V, Singh-Grewal D, O’Neill S, Craig JC, et al.
J Rheumatol. 2016 Jul;43(7):1363-75.

Challenges and strategies for coping with scleroderma: implications for a scleroderma-specific self-management program
Milette K, Thombs BD, Maiorino K, Nielson WR, Körner A, Peláez S.
Disabil Rehabil. 2018 May 9:1-10.

Consensus best practice pathway of the UK Systemic Sclerosis Study group: management of cardiac disease in systemic sclerosis
Bissell LA, Anderson M, Burgess M, Chakravarty K, Coghlan G, Dumitru RB, et al.
Rheumatology (Oxford). 2017 Jun 1;56(6):912-921.

Cardiovascular magnetic resonance in rheumatology: Current status and recommendations for use
Mavrogeni SI, Kitas GD, Dimitroulas T, Sfikakis PP, Seo P, Gabriel S, et al.
Int J Cardiol. 2016 Aug 15;217:135-48.

Expert consensus for performing right heart catheterisation for suspected pulmonary arterial hypertension in systemic sclerosis: a Delphi consensus study with cluster analysis
Avouac J, Huscher D, Furst DE, Opitz CF, Distler O, Allanore Y, EPOSS group.
Ann Rheum Dis. 2014 Jan;73(1):191-7.

Consensus best practice pathway of the UK Scleroderma Study Group: digital vasculopathy in systemic sclerosis
Hughes M, Ong VH, Anderson ME, Hall F, Moinzadeh P, Griffiths B, et al.
Rheumatology (Oxford). 2015 Nov;54(11):2015-24.

Defining Skin Ulcers in Systemic Sclerosis: Systematic Literature Review and Proposed World Scleroderma Foundation (WSF) Definition
Suliman YA, Bruni C, Johnson SR, Praino E, Alemam M, Borazan N, et al.
J Scleroderma Relat Disord. 2017;2(2)115-120.

Digital ulcers in scleroderma: staging, characteristics and sub-setting through observation of 1614 digital lesions
Amanzi L, Braschi F, Fiori G, Galluccio F, Miniati I, Guiducci S, et al.
Rheumatology (Oxford). 2010 Jul;49(7):1374-82.

Points to consider for skin ulcers in systemic sclerosis
Galluccio F, Allanore Y, Czirjak L, Furst DE, Khanna D, Matucci-Cerinic M.
Rheumatology (Oxford). 2017 Sep 1;56(suppl_5):v67-v71.

Points to consider-Raynaud’s phenomenon in systemic sclerosis
Cutolo M, Smith V, Furst DE, Khanna D, Herrick AL.
Rheumatology (Oxford). 2017 Sep 1;56(suppl_5):v45-v48

Recommendations for the care of oral involvement in patients with systemic sclerosis
Alantar A, Cabane J, Hachulla E, Princ G, Ginisty D, Hassin M, et al.
Arthritis Care Res (Hoboken). 2011 Aug;63(8):1126-33.

Screening and therapy for malnutrition and related gastro-intestinal disorders in systemic sclerosis: recommendations of a North American expert panel
Baron M, Bernier P, Côté LF, Delegge MH, Falovitch G, Friedman G, et al.
Clin Exp Rheumatol. 2010 Mar-Apr;28(2 Suppl 58):S42-6.

Consensus best practice pathway of the UK scleroderma study group: gastrointestinal manifestations of systemic sclerosis
Hansi N, Thoua N, Carulli M, Chakravarty K, Lal S, Smyth A, et al.
Clin Exp Rheumatol. 2014 Nov-Dec;32(6 Suppl 86):S-214-21.

UK Scleroderma Study Group (UKSSG) guidelines on the diagnosis and management of scleroderma renal crisis
Lynch BM, Stern EP, Ong V, Harber M, Burns A, Denton CP.
Clin Exp Rheumatol. 2016 Sep-Oct;34 Suppl 100(5):106-109

Management of systemic sclerosis-associated interstitial lung disease
Roofeha D, Jaafara S, Vummidib D, and Khanna D
Curr Opin Rheumatol 2019, 31:241–249

The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements
Hoffmann-Vold A-M, Maher TM, Philpot EE, Ashrafzadeh A, Barake R, Barsotti S, et al.
Lancet Rheumatol 2020; 2: e71–83

European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes
Knobler R, Moinzadeh P, Hunzelmann N, Kreuter A, Cozzio A, Mouthon L, et al.
J Eur Acad Dermatol Venereol. 2017 Sep;31(9):1401-1424

Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group
Avouac J, Fransen J, Walker UA, Riccieri V, Smith V, Muller C, et al.
Ann Rheum Dis. 2011 Mar;70(3):476-81.

Scleroderma (systemic sclerosis): classification, subsets and pathogenesis
LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, et al.
J Rheumatol. 1988 Feb;15(2):202-5.

2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative
van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al.
Ann Rheum Dis. 2013 Nov;72(11):1747-55

Diagnostic criteria, severity classification and guidelines of systemic sclerosis
Asano Y, Jinnin M, Kawaguchi Y, Kuwana M, Goto D, Sato S, et al
J Dermatol. 2018 Apr 23.

Reporting items for capillaroscopy in clinical research on musculoskeletal diseases: a systematic review and international Delphi consensus
Ingegnoli F, Herrick AL, Schioppo T, Bartoli F, Ughi N, Pauling JD, et al.
Rheumatology 2020;0:1–9.

EUSTAR biobanking: recommendations for the collection, storage and distribution of biospecimens in scleroderma research
Beyer C, Distler JH, Allanore Y, Aringer M, Avouac J, Czirják L, et al.
Ann Rheum Dis. 2011 Jul;70(7):1178-82.

BSR and BHPR guideline for the treatment of systemic sclerosis
Denton CP, Hughes M, Gak N, Vila J, Buch MH, Chakravarty K, et al.
Rheumatology (Oxford). 2016 Oct;55(10):1906-10.

Update of EULAR recommendations for the treatment of systemic sclerosis
Kowal-Bielecka O, Fransen J, Avouac J, Becker M, Kulak A, Allanore Y, et al.
Ann Rheum Dis. 2017 Aug;76(8):1327-1339.

Is there a role for TNFa antagonists in the treatment of SSc? EUSTAR expert consensus development using the Delphi technique
Distler JH, Jordan S, Airo P, Alegre-Sancho JJ, Allanore Y, Balbir Gurman A, et al.
Clin Exp Rheumatol. 2011 Mar-Apr;29(2 Suppl 65):S40-5.

Recommendations for the management and treatment of systemic sclerosis
Sampaio-Barros PD, Zimmermann AF, Müller Cde S, Borges CT, Freire EA, Maretti GB, et al.
Rev Bras Reumatol. 2013 May-Jun;53(3):258-75.

Cardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party and collaborating partners
Farge D, Burt RK, Oliveira M-C, Mousseaux E, Rovira M, Marjanovic Z, et al.
Bone Marrow Transplant. 2017 Nov;52(11):1495-1503.

Guidelines of the Brazilian society of bone Marrow transplantation on hematopoietic stem cell transplantation as a treatment for the autoimmune diseases systemic sclerosis and multiple sclerosis
Rodrigues MC, Hamerschlak N, de Moraes DA, Simões BP, Rodrigues M, Ribeiro AA, et al.
Rev Bras Hematol Hemoter. 2013;35(2):134-43.

Consensus statement concerning cardiotoxicity occurring during haematopoietic stem cell transplantation in the treatment of autoimmune diseases, with special reference to systemic sclerosis and multiple sclerosis
Saccardi R, Tyndall A, Coghlan G, Denton C, Edan G, Emdin M, et al.
Bone Marrow Transplant. 2004 Nov;34(10):877-81.

Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma
Sullivan KM, Goldmuntz EA, Keyes-Elstein L, McSweeney PA, Pinckney A, Welch B, et al.
N Engl J Med. 2018 Jan 4;378(1):35-47.

Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis. A Randomized Clinical Trial
van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, et al.
JAMA. 2014 Jun 25;311(24):2490-8.

Twenty-two points to consider for clinical trials in systemic sclerosis, based on EULAR standards
Khanna D, Furst DE, Allanore Y, Bae S, Bodukam V, Clements PJ, et al.
Rheumatology (Oxford). 2015 Jan;54(1):144-51.

Systemic sclerosis-associated interstitial lung disease-proposed recommendations for future randomized clinical trials
Khanna D, Brown KK, Clements PJ, Elashoff R, Furst DE, Goldin J, et al.
Clin Exp Rheumatol. 2010 Mar-Apr;28(2 Suppl 58):S55-62.

Raynaud’s syndrome in children: systematic review and development of recommendations for assessment and monitoring
Pain CE, Constantin T, Toplak N, Moll M, Iking-Konert C, Piotto DP, et al.
Clin Exp Rheumatol. 2016 Sep-Oct;34 Suppl 100(5):200-206.

Systemic sclerosis and the COVID-19 pandemic: World Scleroderma Foundation preliminary advice for patient management
Matucci-Cerinic M, Bruni C, Allanore Y, Clementi M, Dagna L, Damjanov NS et al.
Ann Rheum Dis. 2020;79:724-726.
International Consensus Criteria for the Diagnosis of Raynaud’s Phenomenon
Maverakis E, Patel F, Kronenberg D, Chung L, Fiorentino D, Allanore Y, et al.
J Autoimmun. 2014 Feb-Mar; 0: 60-65.

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