Document Type : Case Report

Authors

1 Instituto de Estudos em Saúde Coletiva / Universidade Federal do Rio de Janeiro Hospital Universitário Clementino Fraga Filho / Universidade Federal do Rio de Janeiro

2 Faculty of Medicine, Rio de Janeiro Federal University, Rio de Janeiro, Brazil

3 Collective Health Studies Institute, Rio de Janeiro Health Institute, Rio de Janeiro, Brazil

10.22038/apjmt.2023.21877

Abstract

Introduction: Systemic Lupus Erythematosus (SLE) cases have been growing over the years, and the role of environmental agents are at the center of investigations. However, few studies have addressed the role of solvents. Therefore, we reported an SLE case in a patient with long-term low-level exposure to organic solvents in the workplace.
Case Report: A 58-year-old black female attended a teaching hospital evaluation due to oral ulcers, 14 kilos loss, and leukopenia. Her occupational history revealed a 24-year exposure to organic solvents with inadequate protection. After investigation, we made an SLE diagnosis related to solvents based on clinical presentation and laboratory tests (anemia, leukopenia, hypocomplementemia, positive antinuclear antibodies, and biomarkers of exposure). The patient’s treatment included corticosteroids, immunosuppressive, and antimalarial drugs. As a result, she gradually improved in clinical and laboratory conditions.
Discussion: We addressed the potential role of solvents in developing SLE in this case report regarding a patient chronically exposed to them. SLE is a multifactorial disease triggered in genetically-prone individuals by environmental exposure. Although few studies have addressed the relationship between solvents and SLE with mixed results, strong evidence links them with other autoimmune diseases. There is biological plausibility for solvents triggering SLE, as autoimmune diseases share clinical presentation, genetic factors, and physiopathologic mechanisms. 
Conclusion: Our case highlights the potential role of solvents in developing SLE. Although there are mixed results on this relationship, strong evidence associates them with other autoimmune diseases. Considering the wide use of solvents in many contexts and the similarity between autoimmune diseases, we recommend further investigations.

Keywords

  1. Aringer M. EULAR/ACR classification criteria for SLE. Semin Arthritis Rheum. 2019;49(3S):S14-S17.
  2. Barber MRW, Drenkard C, Falasinnu T, Hoi A, Mak A, Kow NY, et al. Global epidemiology of systemic lupus erythematosus. Nat Rev Rheumatol. 2021 Sep;17(9):515-532. doi: 10.1038/s41584-021-00668-1.
  3. Woo JMP, Parks CG, Jacobsen S, Costenbader KH, Bernatsky S. The role of environmental exposures and gene-environment interactions in the etiology of systemic lupus erythematous. J Intern Med. 2022 Jun;291(6):755-778. doi: 10.1111/joim.13448.
  4. Zucchi D, Elefante E, Schilirò D, Signorini V, Trentin F, Bortoluzzi A, Tani C. One year in review 2022: systemic lupus erythematosus. Clin Exp Rheumatol. 2022 Jan;40(1):4-14. doi: 10.55563/clinexprheumatol/nolysy.
  5. Leffers HCB, Lange T, Collins C, Ulff-Møller CJ, Jacobsen S. The study of interactions between genome and exposome in the development of systemic lupus erythematosus. Autoimmun Rev. 2019 Apr;18(4):382-392. doi: 10.1016/j.autrev.2018.11.005.
  6. Khan MF, Wang H. Environmental Exposures and Autoimmune Diseases: Contribution of Gut Microbiome. Front Immunol. 2020 Jan 10;10:3094. doi: 10.3389/fimmu.2019.03094.
  7. Kilburn KH, Warshaw RH. Prevalence of symptoms of systemic lupus erythematosus (SLE) and of fluorescent antinuclear antibodies associated with chronic exposure to trichloroethylene and other chemicals in well water. Environ Res. 1992 Feb;57(1):1-9. doi: 10.1016/s0013-9351(05)80014-3.
  8. Cooper GS, Wither J, Bernatsky S, Claudio JO, Clarke A, Rioux JD; CaNIOS GenES Investigators, Fortin PR. Occupational and environmental exposures and risk of systemic lupus erythematosus: silica, sunlight, solvents. Rheumatology (Oxford). 2010 Nov;49(11):2172-80. doi: 10.1093/rheumatology/keq214. 
  9. Gold LS, Ward MH, Dosemeci M, De Roos AJ. Systemic autoimmune disease mortality and occupational exposures. Arthritis Rheum. 2007;56(10):3189-3201. doi: 10.1002/art.22880.
  10. Gulati G, Brunner HI. Environmental triggers in systemic lupus erythematosus. Semin Arthritis Rheum. 2018 Apr;47(5):710-717. doi: 10.1016/j.semarthrit.2017.10.001.
  11. Schur PH, Hahn BH. Epidemiology and pathogenesis of systemic lupus erythematosus. Available at: https://www.uptodate.com/contents/epidemiology-and-pathogenesis-of-systemic-lupus-erythematosus?search=lupus%20environmental&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3. Accessed: 14 Sep 2022.
  12. Pollard KM, Christy JM, Cauvi DM, Kono DW. Environmental Xenobiotic Exposure and Autoimmunity. Curr Opin Toxicol. 2018;10:15-22. doi: 10.1016/j.cotox.2017.11.009. Epub 2017 Nov 21. 
  13. Parks CG, De Roos AJ. Pesticides, chemical and industrial exposures in relation to systemic lupus erythematosus. Lupus. 2014 May;23(6):527-36. doi: 10.1177/0961203313511680.
  14. Manno M, Viau C, Cocker J, Colosio C, Lowry L, Mutti A, et al. Biomonitoring for occupational health risk assessment (BOHRA). Toxicol Lett. 2010 Jan 15;192(1):3-16. doi: 10.1016/j.toxlet.2009.05.001.
  15. Vanderberg LN, Blumberg B. Alternative Approaches to Dose–Response Modeling of Toxicological Endpoints for Risk Assessment: Nonmonotonic Dose Responses for Endocrine Disruptors. In: McQueen CA editor. Comprehensive Toxicology. 3rd Amsterdam: Elsevier; 2018.p.39–58. doi:10.1016/b978-0-12-801238-3.64298-8. 
  16. Edwards CJ, Cooper C. Early environmental exposure and the development of lupus. Lupus. 2006;15(11):814-9. doi: 10.1177/0961203306069347.
  17. Parks CG, de Souza Espindola Santos A, Barbhaiya M, Costenbader KH. Understanding the role of environmental factors in the development of systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2017 Jun;31(3):306-320. doi: 10.1016/j.berh.2017.09.005.
  18. Li X, Sundquist J, Sundquist K, Zöller B. Occupational risk factors for systemic lupus erythematosus: a nationwide study based on hospitalizations in Sweden. J Rheumatol. 2012 Apr;39(4):743-51. doi: 10.3899/jrheum.110789.
  19. Khan MF, Kaphalia BS, Prabhakar BS, Kanz MF, Ansani GAS. Trichloroethylene-induced autoimmune response in female MRL+/+ mic. Toxicology and Applied Pharmacology. 1995 Sep; 134(1):155-160. https://doi.org/10.1006/taap.1995.1179.
  20. Cai P, König R, Boor PJ, Kondraganti S, Kaphalia BS, Khan MF, Ansari GA. Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice. Toxicol Appl Pharmacol. 2008 Apr 1;228(1):68-75. doi: 10.1016/j.taap.2007.11.031
  21. Keil DE, Peden-Adams MM, Wallace S, Ruiz P, Gilkeson GS. Assessment of trichloroethylene (TCE) exposure in murine strains genetically-prone and non-prone to develop autoimmune disease. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2009 Apr;44(5):443-53. doi: 10.1080/10934520902719738.
  22. Purdue M, Zhang L, Vermeulen R, Smith MT, Hu W, Rhee J,et al. Occupational trichloroethylene exposure and antinuclear antibodies: a cross-sectional study in China. Occup Environ Med. 2022 May 3:oemed-2022-108266. doi: 10.1136/oemed-2022-108266.
  23. Peden-Adams MM, Eudaly JG, Lee AM, Miller J, Keil DE, Gilkeson GS. Lifetime exposure to trichloroethylene (TCE) does not accelerate autoimmune disease in MRL +/+ mice. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2008 Oct;43(12):1. doi: 10.1080/10934520802232063.
  24. Barragán-Martínez C, Speck-Hernandez CA, Montoya-Ortiz G, Mantilla RD, Anaya JM, Rojas-Villarraga A. Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis. PloS One. 2012;7(12):e51506. doi: 10.1371/journal.pone.0051506.
  25. Parks CG, Meyer A, Beane Freeman LE, Hofmann JN, Sandler DP. Farming tasks and the development of rheumatoid arthritis in the agricultural health study. Occup Environ Med. 2019 Apr;76(4):243-249. doi: 10.1136/oemed-2018-105361.
  26. Barbhaiya M, Costenbader KH. Environmental exposures and the development of systemic lupus erythematosus. Curr Opin Rheumatol. 2016 Sep;28(5):497-505. doi: 10.1097/BOR.0000000000000318. 
  27. Cooper GS, Parks CG, Treadwell EL, St Clair EW, Gilkeson GS, Dooley MA. Occupational risk factors for the development of systemic lupus erythematosus. J Rheumatol. 2004 Oct.31:1928–1933.
  28. Finckh A, Cooper GS, Chibnik LB, Costenbader KH, Watts J, Pankey H, et al. Occupational silica and solvent exposures and risk of systemic lupus erythematosus in urban women. Arthritis Rheum. 2006 Nov.54:3648–3654. doi: 10.1002/art.22210.
  29. Hjuler Boudigaard S, Stokholm ZA, Vestergaard JM, Mohr MS, Søndergaard K, Torén K, et al. A follow-up study of occupational styrene exposure and risk of autoimmune rheumatic diseases. Occup Environ Med. 2020 Feb;77(2):64-69. doi: 10.1136/oemed-2019-106018. 
  30. Sahri M, Widajati N. Evaluation of Toluene Exposure in Workers at Industrial Area of Sidoarjo, Indonesia by Measurement of Urinary Hippuric Acid. Asia Pacific Journal of Medical Toxicology. 2013;2(4): 145-149. doi: 10.22038/apjmt.2013.2038.
  31. Lin YS, Kupper LL, Rappaport SM. Air samples versus biomarkers for epidemiology. Occup Environ Med. 2005 Nov;62(11):750-60. doi: 10.1136/oem.2004.013102. 
  32. Nsonwu-Anyanwu A, Nsonwu M, Bebia D, Fabian U, Offor S, Egete P, et al. Chronic Exposure to Toluene and Heavy Metals and Changes in Indices of Liver Function, Inflammation and Oxidative DNA Damage among Automobile Workers. Asia Pacific Journal of Medical Toxicology. 2021;10(2): 53-60. doi: 10.22038/apjmt.2021.18229.