Abstract
Introduction/objectives
This study aims to evaluate the role of fat free mass index (FFMI) and phase angle (PhA) as markers to predict occurrence of new digital ulcers in systemic sclerosis (SSc) patients.
Methods
Body composition evaluation from bioelectrical impedance and clinical assessment were performed in SSc patients at enrollment and after 12 months follow-up.
Results
Seventy-nine SSc patients (67 female) with a mean age of 53 ± 13 years were enrolled. In SSc patients with a digital ulcers history, FFMI value is lower (p < 0.05) and phase angle (PhA) value is higher (p < 0.01) than SSc patients without a digital ulcers history. After 12 months of follow-up, 30 patients (38%) presented at least one new episode of digital ulcers. Patients with reduced FFMI had a relative risk of 6.7 for new digital ulcers (CI 2.1–21.8, p < 0.001). Patients with reduced PhA had a relative risk of 10.1 for new digital ulcers (CI 3.5–29.5, p < 0.0001). In multivariate analysis, FFMI and PhA were associated with major vascular complication (digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis). FFMI loss, assessed as delta between follow-up and baseline, is higher in SSc with short duration (≤ 3 years) than SSc patients with long duration [0.4 (0–0.50) vs − 0.10 (− 0.2–0)].
Conclusion
In SSc patients, reduction of the FFMI and PhA represents after 12 months a risk factor for development of new digital ulcers and major vascular complication.
Key Points • Fat free mass index represents a risk factor for development of digital ulcers • Phase angle represents a risk factor for development of digital ulcers • Body compositions in systemic sclerosis are a marker of activity disease |
Similar content being viewed by others
References
Campbell PM, LeRoy EC (1975) Pathogenesis of systemic sclerosis: a vascular hypothesis. Semin Arthritis Rheum 4:351–368
Denton CP, Khanna D (2017) Systemic sclerosis. Lancet 390:1685–1699
Marighela TF, Genaro Pde S, Pinheiro MM, Szejnfeld VL, Kayser C (2013) Risk factors for body composition abnormalities in systemic sclerosis. Clin Rheumatol 32:1037–1044
Siegert E, March C, Otten L, Makowka A, Preis E, Buttgereit F, Riemekasten G, Müller-Werdan U, Norman K (2018) Prevalence of sarcopenia in systemic sclerosis: assessing body composition and functional disability in patients with systemic sclerosis. Nutrition 55-56:51–55
Krause L, Becker MO, Brueckner CS, Bellinghausen CJ, Becker C, Schneider U, Haeupl T, Hanke K, Hensel-Wiegel K, Ebert H, Ziemer S, Ladner UM, Pirlich M, Burmester GR, Riemekasten G (2010) Nutritional status as marker for disease activity and severity predicting mortality in patients with systemic sclerosis. Ann Rheum Dis 69:1951–1957
Giuggioli D, Manfredi A, Lumetti F, Colaci M, Ferri C (2018) Scleroderma skin ulcers definition, classification and treatment strategies our experience and review of the literature. Autoimmun Rev 17:155–164
Caramaschi P, Martinelli N, Volpe A, Pieropan S, Tinazzi I, Patuzzo G, Mahamid H, Bambara LM, Biasi D (2009) A score of risk factors associated with ischemic digital ulcers in patients affected by systemic sclerosis treated with iloprost. Clin Rheumatol 28:807–813
Rosato E, Barbano B, Gigante A, Molinaro I, Quarta S, Pisarri S, Amoroso A, Cianci R, Salsano F (2014) Increased intrarenal arterial stiffness may predict the occurrence of new digital ulcers in systemic sclerosis. Arthritis Care Res (Hoboken) 66:1380–1385
van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE, Riemekasten G, Clements PJ, Denton CP, Distler O, Allanore Y, Furst DE, Gabrielli A, Mayes MD, van Laar JM, Seibold JR, Czirjak L, Steen VD, Inanc M, Kowal-Bielecka O, Müller-Ladner U, Valentini G, Veale DJ, Vonk MC, Walker UA, Chung L, Collier DH, Csuka ME, Fessler BJ, Guiducci S, Herrick A, Hsu VM, Jimenez S, Kahaleh B, Merkel PA, Sierakowski S, Silver RM, Simms RW, Varga J, Pope JE (2013) 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 65:2737–2747
LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, Rowell N, Wollheim F (1988) Scleroderma (systemic sclerosis): classification, subsets, and pathogenesis. J Rheumatol 15:202–205
Clements P, Lachenbruch P, Siebold J, White B, Weiner S, Martin R, Weinstein A, Weisman M, Mayes M, Collier D (1995) Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis. J Rheumatol 22:1281–1285
Medsger TA Jr, Silman AJ, Steen VD et al (1999) A disease severity scale for systemic sclerosis: development and testing. J Rheumatol 26:2159–2167
Valentini G, Iudici M, Walker UA, Jaeger VK, Baron M, Carreira P, Czirják L, Denton CP, Distler O, Hachulla E, Herrick AL, Kowal-Bielecka O, Pope J, Müller-Ladner U, Riemekasten G, Avouac J, Frerix M, Jordan S, Minier T, Siegert E, Ong VH, Vettori S, Allanore Y (2017) The European Scleroderma Trials and Research group (EUSTAR) task force for the development of revised activity criteria for systemic sclerosis: derivation and validation of a preliminarily revised EUSTAR activity index. Ann Rheum Dis 76:270–276
Amanzi L, Braschi F, Fiori G, Galluccio F, Miniati I, Guiducci S, Conforti ML, Kaloudi O, Nacci F, Sacu O, Candelieri A, Pignone A, Rasero L, Conforti D, Matucci-Cerinic M (2010) Digital ulcers in scleroderma: staging, characteristics and sub-setting through observation of 1614 digital lesions. Rheumatology (Oxford) 49:1374–1382
Cederholm T, Bosaeus I, Barazzoni R, Bauer J, van Gossum A, Klek S, Muscaritoli M, Nyulasi I, Ockenga J, Schneider SM, de van der Schueren MAE, Singer P (2015) Diagnostic criteria for malnutrition: an ESPEN consensus statement. Clin Nutr 34:335–340
Muscaritoli M, Anker SD, Argilés J, Aversa Z, Bauer JM, Biolo G, Boirie Y, Bosaeus I, Cederholm T, Costelli P, Fearon KC, Laviano A, Maggio M, Fanelli FR, Schneider SM, Schols A, Sieber CC (2010) Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics”. Clin Nutr 29:154–159
Caimmi C, Caramaschi P, Venturini A, Bertoldo E, Vantaggiato E, Viapiana O, Ferrari M, Lippi G, Frulloni L, Rossini M (2018) Malnutrition and sarcopenia in a large cohort of patients with systemic sclerosis. Clin Rheumatol 37:987–997
Spanjer MJ, Bultink IEM, de van der Schueren MAE, Voskuyl AE (2017) Prevalence of malnutrition and validation of bioelectrical impedance analysis for the assessment of body composition in patients with systemic sclerosis. Rheumatology (Oxford) 56:1008–1012
Matsubara Y, Matsumoto T, Aoyagi Y, Tanaka S, Okadome J, Morisaki K, Shirabe K, Maehara Y (2015) Sarcopenia is a prognostic factor for overall survival in patients with critical limb ischemia. J Vasc Surg 61:945–950
Brown JC, Harhay MO, Harhay MN (2016) Sarcopenia and mortality among a population-based sample of community-dwelling older adults. J Cachexia Sarcopenia Muscle 7:290–298
Cruz-Jentoft AJ, Sayer AA (2019) Sarcopenia. Lancet 393:2636–2646
Hughes M, Herrick AL (2017) Digital ulcers in systemic sclerosis. Rheumatology (Oxford) 56:14–25
Hendrickse P, Degens H (2019) The role of the microcirculation in muscle function and plasticity. J Muscle Res Cell Motil 40:127–140
Díaz BB, González DA, Gannar F, Pérez MCR, de León AC (2018) Myokines, physical activity, insulin resistance and autoimmune diseases. Immunol Lett 203:1–5
Gigante A, Margiotta D, Navarini L, Barbano B, Gasperini ML, D'Agostino C, Amoroso A, Afeltra A, Rosato E (2018) Serum level of endostatin and digital ulcers in systemic sclerosis patients. Int Wound J 15:424–428
Cheng Q, Hu J, Yang P, Cao X, Deng X, Yang Q, Liu Z, Yang S, Goswami R, Wang Y, Luo T, Liao K, Li Q (2017) Sarcopenia is independently associated with diabetic foot disease. Sci Rep 7:8372
Lieffers JR, Bathe OF, Fassbender K, Winget M, Baracos VE (2012) Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery. Br J Cancer 107:931–936
Viertel M, Bock C, Reich M, Löser S, Plauth M (2019) Performance of CT-based low skeletal muscle index, low mean muscle attenuation, and bioelectric impedance derived low phase angle in the detection of an increased risk of nutrition related mortality. Clin Nutr 38:2375–2380
Selberg O, Selberg D (2002) Norms and correlates of bioimpedance phase angle in healthy human subjects, hospitalized patients, and patients with liver cirrhosis. Eur J Appl Physiol 86:509–516
Maggiore Q, Nigrelli S, Ciccarelli C, Grimaldi C, Rossi GA, Michelassi C (1996) Nutritional and prognostic correlates of bioimpedance indexes in hemodialysis patients. Kidney Int 50:2103–2108
Faisy C, Rabbat A, Kouchakji B, Laaban JP (2000) Bioelectrical impedance analysis in estimating nutritional status and outcome of patients with chronic obstructive pulmonary disease and acute respiratory failure. Intensive Care Med 26:518–525
Tanaka S, Ando K, Kobayashi K et al (2019) Low bioelectrical impedance phase angle is a significant risk factor for frailty. Biomed Res Int:6283153
Gigante A, Gasperini ML, Iacolare A, Fegatelli DA, Villa A, Muscaritoli M, Rosato E (2020) Phase angle in systemic sclerosis: a marker for pulmonary function and disease severity. Clin Rheumatol 39:1699–1701. https://doi.org/10.1007/s10067-020-05034-2
Gigante A, Gasperini ML, Rosato E, Navarini L, Margiotta D, Afeltra A, Muscaritoli M (2020) Phase angle could be a marker of microvascular damage in systemic sclerosis. Nutrition 73:110730
Baron M, Hudson M, Steele R, Canadian Scleroderma Research Group (2009) Malnutrition is common in systemic sclerosis: results from the Canadian scleroderma research group database. J Rheumatol 36:2737–2743
Bauer J, Morley JE, Schols AMWJ, Ferrucci L, Cruz-Jentoft AJ, Dent E, Baracos VE, Crawford JA, Doehner W, Heymsfield SB, Jatoi A, Kalantar-Zadeh K, Lainscak M, Landi F, Laviano A, Mancuso M, Muscaritoli M, Prado CM, Strasser F, Haehling S, Coats AJS, Anker SD (2019) Sarcopenia: a time for action. An SCWD Position Paper J Cachexia Sarcopenia Muscle 10:956–996
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Disclosures
None.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Rosato, E., Gigante, A., Iacolare, A. et al. Reduction of fat free mass index and phase angle is a risk factor for development digital ulcers in systemic sclerosis patients. Clin Rheumatol 39, 3693–3700 (2020). https://doi.org/10.1007/s10067-020-05141-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-020-05141-0