Juvenile systemic scleroderma and ecology (literature review and author’s research)

V.Ya. Mikuksts, O.V. Syniachenko, O.Е. Chernyshova


The paper deals with a literature review and the results of author’s research of ecology role in juvenile systemic sclerosis (SSc). The development of SSc and the rate of its progression in children is closely linked to the adverse environmental factors, in particular, to the degree of contamination of inorganic and organic compounds — pollutants in the atmosphere (heavy metals, carbon monoxide, nitrates, quartz and other industrial products), which increase matrix metalloproteinase activity, induce synthesis of proinflammatory cytokines and autoantibodies, modify vascular endothelial function and production of chemoattractant proteins, collagens, fibronectin and connective tissue biopolymers, thereby enhancing the fibrosing processes. In the Eastern Ukraine the prevalence of juvenile SSc depends on carbon dioxide levels, 3,4-benzopyrene and phenol in the inspired air, and lead and lithium in drinking water, which primarily impacts lungs, heart and musculoskeletal system diseases.


systemic scleroderma; children; ecology; course; pathogenesis; review


Barnes J, Mayes MD. Epidemiology of systemic sclerosis: incidence, prevalence, survival, risk factors, malignancy, and environmental triggers. Curr Opin Rheumatol. 2012;24(2):165-70. doi: 10.1097/BOR.0b013e32834ff2e8.

Bello S, Rinaldi A, Trabucco S, Serafino L, Bonali C, Lapadula G. Erasmus syndrome in a marble worker. Reumatismo. 2015;67(3):116-22. doi: 10.4081/reumatismo.2015.826.

Boverhof DR, Krieger SM, Hotchkiss JA, Stebbins KE, Thomas J, Woolhiser MR. Assessment of the immunotoxic potential of trichloroethylene and perchloroethylene in rats following exposure. J Immunotoxicol. 2012;20(11):95-8. doi: 10.3109/1547691X.2012.735275.inhalation

Capusan I. Scleroderma or scleroedema? Comments on the case published in 1753 by Dr. Carlo Curzio of Naples. G Ital Dermatol Minerva Dermatol. 1971;46(1):40-47.

Cartin-Ceba R, Kashiouris M, Plataki M, Kor DJ, Gajic O, Casey ET. Risk factors for development of acute kidney injury in critically ill patients: a systematic review and meta-analysis of observational studies. Crit Care Res Pract. 2012;20(12):691013. doi: 10.1155/2012/691013.

Chaouch N, Mjid M, Zarrouk M, et al. Erasmus’ syndrome with pseudo-tumour masses. Rev Mal Respir. 2011;28(7):924-7. doi: 10.1016/j.rmr.2011.06.003.

Charni Chaabane S, Coomans de Brachène A, Essaghir A, et al. PDGF-D expression is down-regulated by TGFβ in fibroblasts. PLoS One. 2014;9(10):108656. doi: 10.1371/journal.pone.0108656.

Chifflot H, Fautrel B, Sordet C. Incidence and prevalence of systemic sclerosis: a systematic literature review. Semin Arthr Rheum. 2013;37(4):223-35.

Corsaro GB, Gabusi V, Pilisi A. Health risk assessment in the metal scrap recycle: the case of Brescia. G Ital Med Lav Ergon. 2012;34(3):259-66.

Dospinescu P, Jones GT, Basu N. Environmental risk factors in systemic sclerosis. Curr Opin Rheumatol. 2013;25(2):179-83. doi: 10.1097/BOR.0b013e32835cfc2d.

Elie MR, Clausen CA, Geiger CL. Reduction of benzo[a]pyrene with acid-activated magnesium metal in ethanol: a possible application for environmental remediation. J Hazard Mater. 2012;15(2):77-85. doi: 10.1016/j.jhazmat.2011.11.089.

Estevez-Carmona MM, Melendez-Camargo E, Ortiz-Butron R, Pineda-Reynoso M, Franco-Colin M, Cano-Europa E. Hypothyroidism maintained reactive oxygen species-steady state in the kidney of rats intoxicated with ethylene glycol: effect related to an increase in the glutathione that maintains the redox environment. Toxicol Ind Health. 2012;4(4):75-8. doi: 10.1177/0748233712442710.

Fabri M, Krieg T. Pathogenesis of systemic sclerosis. Hautarzt. 2007;58(10):838-43.

Ghahramani N. Silica nephropathy. Int J Occup Environ Med. 2010;1(3):108-15.

Giacomelli R, Liakouli V, Berardicurti O, et al. Interstitial lung disease in systemic sclerosis: current and future treatment. Rheumatol Int. 2017;6(1):142-8. doi: 10.1007/s00296-016-3636-7.

Kerley-Hamilton JS, Trask HW, Ridley CJ, et al. Inherent and benzo[a]pyrene-induced differential aryl hydrocarbon receptor signaling greatly affects life span, atherosclerosis, cardiac gene expression, and body and heart growth in mice. Toxicol Sci. 2012;126(2):391-404. doi: 10.1093/toxsci/kfs002.

Kerneis S, Boëlle PY, Grais RF, et al. Mortality trends in systemic sclerosis in France and USA, 1980-1998: an age-period-cohort analysis. Eur J Epidemiol. 2010;25(1):55-61. doi: 10.1007/s10654-009-9403-2.

Kim H, Kim NH, Kang HJ, et al. Successful long-term use of imatinib mesylate in pediatric patients with sclerodermatous chronic GVHD. Pediatr Transplant. 2012;16(8):910-2. doi: 10.1111/petr.12004.

Kuo CF, Grainge MJ, Valdes AM, et al. Familial risk of Sjögren’s sndrome and Co-aggregation of autoimmune diseases in affected families: a nationwide population study. Arthritis Rheumatol. 2015;67(7):1904-12. doi: 10.1002/art.39127.

Lafyatis R, York M. Innate immunity and inflammation in systemic sclerosis. Curr Opin Rheumatol. 2009;21(6):617-22. doi: 10.1097/BOR.0b013e32832fd69e.

Liu X, Mayes MD, Tan FK, et al. Correlation of interferon-inducible chemokine plasma levels with disease severity in systemic sclerosis. Arthritis Rheum. 2013;65(1):226-35. doi: 10.1002/art.37742.

Ludwicka-Bradley A, Bogatkevich G, Silver RM. Thrombin-mediated cellular events in pulmonary fibrosis associated with systemic sclerosis (scleroderma). Clin Exp Rheumatol. 2014;22(3):38-46.

Magnant J, Diot E. Systemic sclerosis: epidemiology and environmental factors. Presse Med. 2006;35(12):1894-901.

Makol A, Reilly MJ, Rosenman KD. Prevalence of connective tissue disease in silicosis (1985-2006) — a report from the state of Michigan surveillance system for silicosis. Am J Ind Med. 2011;54(4):255-62. doi: 10.1002/ajim.20917.

Marie I, Gehanno JF. Environmental risk factors of systemic sclerosis. Semin Immunopathol. 2015;37(5):463-73. doi: 10.1007/s00281-015-0507-3.

Mora GF. Systemic sclerosis: environmental factors. J Rheumatol. 2009;36(11):2383-96. doi: 10.3899/jrheum.090207.

Morry J, Ngamcherdtrakul W, Gu S, et al. Dermal delivery of HSP47 siRNA with NOX4-modulating mesoporous silica-based nanoparticles for treating fibrosis. Biomaterials. 2015;66(10):41-52. doi: 10.1016/j.biomaterials.2015.07.005.

Murdaca G, Contatore M, Gulli R, Mandich P, Puppo F. Genetic factors and systemic sclerosis. Autoimmun Rev. 2016;15(5):427-32. doi: 10.1016/j.autrev.2016.01.016.

Nikpour M, Stevens WM, Herrick AL, Proudman SM. Epidemiology of systemic sclerosis. Best Pract Res Clin Rheumatol. 2010;24(6):857-69. doi: 10.1016/j.berh.2010.10.007.

Nishijima C, Hayakawa I, Matsushita T. Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis. Clin Exp Immunol. 2014;138(2):357-63.

Phuong J, Kim S, Thomas R, Zhang L. Predicted toxicity of the biofuel candidate 2,5-dimethylfuran in environmental and biological systems. Environ Mol Mutagen. 2012;53(6):478-87. doi: 10.1002/em.21702.

Postlethhwaite AE, Shigemitsu H, Kanangat S. Cellular origins of fibroblasts: possible implications for organ fibrosis in systemic sclerosis. Curr Opin Rheumatol. 2014;16(6):733-8.

Rocha MC, Santos LM, Bagatin E, et al. Genetic polymorphisms and surface expression of CTLA-4 and PD-1 on T cells of silica-exposed workers. Int J Hyg Environ Health. 2012;215(6):562-9. doi: 10.1016/j.ijheh.2011.10.010.

Rubio-Rivas M, Moreno R, Corbella X. Occupational and environmental scleroderma. Systematic review and meta-analysis. Clin Rheumatol. 2017;14(1):223-9. doi: 10.1007/s10067-016-3533-1.

Vilela FA, Carneiro S, Ramos-e-Silva M. Treatment of morphea or localized scleroderma: review of the literature. J Drugs Dermatol. 2010;9(10):1213-9.

Volkmann ER, Tashkin DP, Roth MD, et al. Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease. Arthritis Res Ther. 2016;18(1):305-15. doi: 10.1186/s13075-016-1203-y.

Wang C, Li H, Yang R, et al. MicroRNA array analysis of microRNAs related to systemic scleroderma. Rheumatol Int. 2012;32(2):307-13. doi: 10.1007/s00296-010-1615-y.

Wei P, Yang Y, Guo X, et al. Identification of an association of TNFAIP3 polymorphisms with matrix metalloproteinase expression in fibroblasts in an integrative study of systemic sclerosis-associated genetic and environmental factors. Arthritis Rheumatol. 2016;68(3):749-60. doi: 10.1002/art.39476.

Wilson D, Zaqout M, Heo JH, Park EK, Oak CH, Ueno S. Nuclear factor-kappa B is not involved in titanium dioxide-induced inflammation. J UOEH. 2012;34(2):183-91.

Yang Y, Wei P, Guo X. Impact of age and autoantibody status on the gene expression of scleroderma fibroblasts in response to silica stimulation. Eur J Inflamm. 2013;11(3):631-9.

York MR. Novel insights on the role of the innate immune system in systemic sclerosis. Expert Rev Clin Immunol. 2011;7(4):481-9. doi: 10.1586/eci.11.40.

You L, Zhu X, Shrubsole MJ, et al. Renal function, bisphenol A, and alkylphenols: results from the National Health and Nutrition Examination Survey (NHANES 2003-2006). Environ Health Perspect. 2011;119(4):527-33. doi: 10.1289/ehp.1002572.

Zbinden G, Grimm L. Thrombogenic effects of xenobiotics. Arch Toxicol Suppl. 2005;8(1):131-41.

Zhang S, Zhang K, Jiang M, Zhao J. Hutchinson-Gilford progeria syndrome with scleroderma-like skin changes due to a homozygous missense LMNA mutation. J Eur Acad Dermatol Venereol. 2016;30(3):463-5. doi: 10.1111/jdv.12840.

Zulian F, Athreya BH, Laxer R, et al. Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study. Rheumatology. 2016;45(5):614-20.

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