The objective of this study is to investigate the impact of skin sclerosis burden on an internal organ involvement over a 1-year period, as measured by time-adjusted accrual-modified Rodnan skin score (TA-mRSS), and to evaluate association between TA-mRSS patterns and laboratory tests in patients with systemic sclerosis (SSc). This prospective study was conducted at Siriraj Hospital (Bangkok, Thailand) during the November 2013–November 2016. SSc patients by ACR/EULAR 2013 or ACR 1980 criteria were eligible. TA-mRSS was classified as low, intermediate, or high, and then compared between groups. Correlation between the arithmetic mean of laboratory tests and TA-mRSS was assessed by multiple linear regression analysis. A total of 118 patients, with 81.4% women, median (IQR) age 49.8 (43.8, 55.1) years, disease duration from onset of non-Raynaud symptoms to first visit of 3.3 (1, 6.8) years, 78% dcSSc, and 75.3% anti-Scl-70 positivity, were analyzed. TA-mRSS over 1 year ranged from 0 to 37.44. The high skin sclerosis burden group had a median TA-mRSS > 7.26 (> 67th percentile). Patients with high TA-mRSS were dcSSc, high initial and average mRSS, and had tendon friction rub, digital ischemic complications, usual interstitial pneumonia, diastolic dysfunction, gastrointestinal dysmotility, and low serum albumin. In multiple linear regression analysis, the arithmetic mean of hemoglobin (B = − 1.007, 95% CI − 1.779 to − 0.236), erythrocyte sedimentation rate (B = − 0.078, 95% CI − 0.126 to − 0.029), serum glutamic oxaloacetic transaminase (B = 0.073, 95% CI 0.026–0.12), creatine phosphokinase (B = 0.012, 95% CI 0.003–0.021), and albumin (B = − 4.117, 95% CI − 6.958 to − 1.276) were associated with TA-mRSS. This study found a higher cumulative course of mRSS over a 1-year period to be significantly associated with severe internal organ involvement.
Scleroderma Systemic Skin sclerosis Modified Rodnan skin score Severe organ involvement
This is a preview of subscription content, log in to check access.
The authors gratefully acknowledge the patients who participated in this study, Ms. Kemajira Karnketklang for assistance with statistical analysis, and Mr. Kevin P. Jones and Dr. Malik Ajaz for assistance with medical research manuscript editing.
Study conception: CM. Study design: TW and CM. Acquisition of data: TW and CM. Analysis and interpretation of data: TW and CM. Drafting of manuscript: TW and CM. Critical revision: TW and CM.
This study was an unfunded study.
Compliance with ethical standards
Conflict of interest
The authors hereby declare no personal or professional conflicts of interest regarding any aspect of this study.
Clements P, Lachenbruch P, Siebold J et al (1995) Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis. J Rheumatol 22:1281–1285PubMedGoogle Scholar
Steen VD, Medsger TA Jr (2000) Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum 43:2437–2444CrossRefGoogle Scholar
Clements PJ, Hurwitz EL, Wong WK, Seibold JR, Mayes M, White B et al (2000) Skin thickness score as a predictor and correlate of outcome in systemic sclerosis: high-dose versus low-dose penicillamine trial. Arthritis Rheum 43:2445–2454CrossRefGoogle Scholar
Wirz EG, Jaeger VK, Allanore Y, Riemekasten G, Hachulla E, Distler O et al (2016) Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis: a 10-year longitudinal study from the EUSTAR database. Ann Rheum Dis 75:1285–1292CrossRefGoogle Scholar
Avouac J, Walker UA, Hachulla E, Riemekasten G, Cuomo G, Carreira PE et al (2016) Joint and tendon involvement predict disease progression in systemic sclerosis: a EUSTAR prospective study. Ann Rheum Dis 75:103–109CrossRefGoogle Scholar
Maurer B, Graf N, Michel BA, Müller-Ladner U, Czirják L, Denton CP et al (2015) Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database. Ann Rheum Dis 74:1124–1131CrossRefGoogle Scholar
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
Van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A et al (2013) 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis 72:1747–1755CrossRefGoogle Scholar
LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr et al (1988) Scleroderma (systemic sclerosis): classification, subsets, and pathogenesis. J Rheumatol 15:202–205PubMedGoogle Scholar
Postlethwaite AE, Wong WK, Clements P, Chatterjee S, Fessler BJ, Kang AH et al (2008) 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 58:1810–1822CrossRefGoogle Scholar
Walker UA, Tyndall A, Czirják L, Denton C, Farge-Bancel D, Kowal-Bielecka O 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 66:754–763CrossRefGoogle Scholar
Simeón-Aznar CP, Fonollosa-Plá V, Tolosa-Vilella C, Espinosa-Garriga G, Ramos-Casals M, Campillo-Grau M et al (2012) Registry of the Spanish network for systemic sclerosis: clinical pattern according to cutaneous subsets and immunological status. Semin Arthritis Rheum 41:789–800CrossRefGoogle Scholar
Perera A, Fertig N, Lucas M, Rodriguez-Reyna TS, Hu P, Steen VD et al (2007) Clinical subsets, skin thickness progression rate, and serum antibody levels in systemic sclerosis patients with anti-topoisomerase I antibody. Arthritis Rheum 56:2740–2746CrossRefGoogle Scholar
Domsic RT, Rodriguez-Reyna T, Lucas M, Fertig N, Medsger TA Jr (2011) Skin thickness progression rate: a predictor of mortality and early internal organ involvement in diffuse scleroderma. Ann Rheum Dis 70:104–109CrossRefGoogle Scholar
Hasegawa M, Asano Y, Endo H, Fujimoto M, Goto D, Ihn H et al (2012) Investigation of prognostic factors for skin sclerosis and lung function in Japanese patients with early systemic sclerosis: a multicenter prospective observational study. Rheumatology (Oxford) 51:129–133CrossRefGoogle Scholar
Jung M, Bonner A, Hudson M, Baron M, Pope JE, Canadian Scleroderma Research Group (CSRG) (2014) Myopathy is a poor prognostic feature in systemic sclerosis: results from the Canadian Scleroderma Research Group (CSRG) cohort. Scand J Rheumatol 43:217–220CrossRefGoogle Scholar
Baron M, Hudson M, Steele R, Canadian Scleroderma Research Group (CSRG) (2010) Is serum albumin a marker of malnutrition in chronic disease? The scleroderma paradigm. J Am Coll Nutr 29:144–151CrossRefGoogle Scholar
Muangchant C, Pope JE (2013) The significance of interleukin-6 and C-reactive protein in systemic sclerosis: a systematic literature review. Clin Exp Rheumatol 31:122–134PubMedGoogle Scholar
Gasparyan AY, Ayvazyan L, Yessirkepov M, Kitas GD (2015) Colchicine as an anti-inflammatory and cardioprotective agent. Expert Opin Drug Metab Toxicol 11:1781–1794CrossRefGoogle Scholar
Alarcon-Segovia D, Ramos-Niembro F, Ibanez de Kasep G, Alcocer J, Tamayo RP (1979) Long-term evaluation of colchicine in the treatment of scleroderma. J Rheumatol 6:705–712PubMedGoogle Scholar
Shand L, Lunt M, Nihtyanova S, Hoseini M, Silman A, Black CM et al (2007) Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis: application of a latent linear trajectory model. Arthritis Rheum 56:2422–2431CrossRefGoogle Scholar
Hunzelmann N, Genth E, Krieg T, Lehmacher W, Melchers I, Meurer M et al (2008) The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement. Rheumatology 47:1185–1192CrossRefGoogle Scholar
Walker UA, Tyndall A, Czirják L, Denton CP, Farge-Bancel D, Kowal-Bielecka O et al (2009) Geographical variation of disease manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials and Research (EUSTAR) group database. Ann Rheum Dis 68:856–862CrossRefGoogle Scholar
Moinzadeh P, Aberer E, Ahmadi-Simab K, Blank N, Distler JH, Fierlbeck G (2015) Disease progression in systemic sclerosis-overlap syndrome is significantly different from limited and diffuse cutaneous systemic sclerosis. Ann Rheum Dis 74:730–737CrossRefGoogle Scholar
Foocharoen C, Netwijitpan S, Mahakkanukrauh A, Suwannaroj S, Nanagara R (2016) Clinical characteristics of scleroderma overlap syndromes: comparisons with pure scleroderma. Int J Rheum Dis 19:913–923CrossRefGoogle Scholar
Pakozdi A, Nihtyanova S, Moinzadeh P, Ong VH, Black CM, Denton CP (2011) Clinical and serological hallmarks of systemic sclerosis overlap syndromes. J Rheumatol 38:2406–2409CrossRefGoogle Scholar
Caramaschi P, Biasi D, Volpe A, Carletto A, Cecchetto M, Bambara LM (2007) Coexistence of systemic sclerosis with other autoimmune diseases. Rheumatol Int 27:407–410CrossRefGoogle Scholar