Pathogenetic aspects of the development of psoriatic arthritis in people with generalized chronic periodontitis

The pathogenetic mechanisms of progression of chronic periodontitis and psoriatic arthritis have common components in immune and inflammatory responses.

The pathogenesis of chronic periodontitis involves interaction of microbial and immunological components. As a chronic immune-mediated inflammatory disease and a consequence of an infectious trigger that originally affects gingival soft tissue, periodontitis is typically characterized by periodontal destruction and damage to adjacent connective tissues. Neutrophils contribute to the development of periodontitis and participate in its progression by recruiting T helper 17 cells and stimulating synthesis of the receptor activator of the nuclear factor kappa-β ligand (RANKL), contributing to bone resorption.

Macrophages as producers of proinflammatory cytokines (interleukin (IL)-1β, IL-6, IL-22, IL-23, tumor necrosis factor (TNF)), free radicals, and matrix metalloproteinases contribute to the chronic course of the disease. Tissue destruction results in generation of reactive oxygen species by neutrophils, which, against the background of a decrease in the antioxidant potential, leads to development of oxidative stress. These processes together lead to tooth mobility, formation of periodontal pockets, and bone resorption.

The key factors in the formation of psoriatic arthritis against the background of periodontitis are overproduction of proinflammatory cytokines in target tissues (skin, joints, gingival microflora) and development of an excessive systemic immune response to the microbiota inhabiting the epithelial and periodontal tissues. A statistically confirmed correlation of the progression of periodontal destruction with the presence of psoriatic arthritis proves the significance of the effects of inflammation as a background for the progression of a comorbidity. Increased IL-17 synthesis plays a crucial role in the development of immune responses of pathological bone remodeling and bone resorption in periodontitis and psoriatic arthritis.

1. Tibúrcio-Machado C.S., Michelon C., Zanatta F.B., Gomes M.S., Marin J.A., Bier C.A. The global prevalence of apical periodontitis: a systematic review and meta-analysis. Int. Endod. J. 2021;54(5):712–735. DOI: 10.1111/iej.13467.

2. Jakovljevic A., Nikolic N., Jacimovic J., Pavlovic O., Miličić B., Beljić-Ivanović K.R. et al. Prevalence of Apical Periodontitis and Conventional Nonsurgical Root Canal Treatment in General Adult Population: An Updated Systematic Review and Meta-analysis of Cross-sectional Studies Published between 2012 and 2020. J. Endod. 2020;46(10):1371–1386. DOI: 10.1016/j.joen.2020.07.007.

3. Nijakowski K., Gruszczyński D., Surdacka A. Oral Health Status in Patients with Inflammatory Bowel Diseases: A Systematic Review. International Journal of Environmental Research and Public Health. 2021;18(21):11521. DOI: 10.3390/ijerph182111521.

4. González-Febles J., Sanz M. Periodontitis and rheumatoid arthritis: What have we learned about their connection and their treatment? Periodontology 2000. 2021;87(1):181–203. DOI: 10.1111/prd.12385.

5. Xiao F., Li C., Lin Y., Peng Z., Xu X., Wen Y. et al. Increased risk of periodontitis occurrence in patients with rheumatoid arthritis and its association with the levels of IL-1β and TNF-a in gingival crevicular fluid. Annals of Palliative Medicine. 2021;10(8):9078–9087. DOI: 10.21037/apm-21-1782.

6. Dannewitz B., Holtfreter B., Eickholz P. Periodontitis-therapy of a widespread disease. Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz. 2021;64(8):931–940. DOI: 10.1007/s00103-021-03373-2.

7. Блашкова С.Л., Мартьянова М.В. Роль средств гигиены в предупреждении кариеса и заболеваний пародонта у лиц молодого возраста. Российская стоматология. 2016;9(4):51–53. DOI: 10.17116/rosstomat20169451-53.

8. Сабирова А.И., Акрамов И.А., Рамазанова З.Д., Сергеева В.В., Ибишева Л.К. Современные аспекты эпидемиологических вопросов заболеваний тканей пародонта. The Scientific Heritage. 2021;73(2):31–38. DOI: 10.24412/92150365-2021-73-2-31-38.

9. Аванесов А.М., Кульченко А.А., Меладзе З.А., Арзуни В.А., Цветкова Е.П., Мариничева Е.Г. и др. Оценка состояния пародонта на фоне применения витамина Е в комплексе лечебных мероприятий при генерализованном пародонтите. Научное обозрение. Медицинские науки. 2014;1:23–24.

10. Barros F.C., Sampaio J.N., Figueredo C.M., Carneiro S., Fischer R.G. Higher prevalence of periodontitis and decayed, missing and filled teeth in patients with psoriasis. European Journal of Dentistry. 2020;14(3):366–370. DOI: 10.1055/S0040-1713465.

11. Madianos P.N., Bobetsis Y.A., Offenbacher S. Adverse pregnancy outcomes (APOs) and periodontal disease: pathogenic mechanisms. Journal of Clinical Periodontology. 2013;40(14):170–180. DOI: 10.1111/jcpe.12082.

12. Monson C.A., Silva V., Porfírio G., Riera R., Tweed J.A., Petri V., Atallah Á.N. Oral Health Issues in Psoriasis: An Overview of the Literature. International Journal of Clinical Dermatology & Research. 2016;4(4):94–98. DOI: 10.19070/2332-2977-1600025.

13. Monson C.A., Porfírio G.J., Riera R., Tweed J.A., Petri V., Nagi A. et al. Periodontal Aspects for Psoriasis: A Systematic Review. Journal of Clinical Research in Dermatology. 2016;3(1):1–8. DOI: 10.15226/2378-1726/3/4/00141.

14. Egeberg A., Mallbris L., Gislason G., Hansen P.R., Mrowietz U. Risk of periodontitis in patients with psoriasis and psoriatic arthritis. J. Eur. Acad. Dermatol. Venereol. 2017;31(2):288– 293. DOI: 10.1111/jdv.13814.

15. Ancuta C., Ancuta E., Chirieac R.M., Anton C.R., Surlari Z., Iordache C. TNF inhibitors and periodontal inflammation in psoriatic arthritis. Rev. Chim. 2017;68(8):1914–1918. DOI: 10.37358/RC.17.8.5790.

16. Esberg A., Johansson L., Johansson I., Dahlqvist S.R. Oral microbiota identifies patients in early onset rheumatoid arthritis. Microorganisms. 2021;9(8):1657. DOI: 10.3390/microorganisms9081657.

17. Lundmark A., Hu Y.O.O., Huss M., Johannsen G., Andersson A.F., Yucel-Lindberg T. Identification of salivary microbiota and its association with host inflammatory mediators in periodontitis. Front. Cell Infect. Microbiol. 2019;(9):216. DOI: 10.3389/fcimb.2019.00216.

18. Banjar W., Alshammari M.H. Genetic factors in pathogenesis of chronic periodontitis. Journal of Taibah University Medical Sciences. 2014;9(3):245–247. DOI: 10.1016/j.jtumed.2014.04.003.

19. Yousef A. AlJehani. Risk Factors of Periodontal Disease: Review of the Literature. International Journal of Dentistry. 2014;2014:182513. DOI: 10.1155/2014/182513.

20. Fadel H.T., Flytström I., Calander A., Bergbrant I.M., Heijl L., Birkhed D. Profiles of dental caries and periodontal disease in individuals with or without psoriasis. Journal of Periodontology. 2013;84(4):477–485. DOI: 10.1902/jop.2012.120119.

21. Noguchi S., Ukai T., Kuramoto A., Yoshinaga Y., Nakamura H., Takamori Y. et al. The histopathological comparison on the destruction of the periodontal tissue between normal junctional epithelium and long junctional epithelium. Journal of Periodontal Research. 2017;52(1):74–82. DOI: 10.1111/jre.12370.

22. Cavalla F., Osorio C., Paredes R., Valenzuela M.A., GarcíaSesnich J., Sorsa T. et al. Matrix metalloproteinases regulate extracellular levels of SDF-1/CXCL12, IL-6 and VEGF in hydrogen peroxide-stimulated human periodontal ligament fibroblasts. Cytokine. 2015;73(1):114–121. DOI: 10.1016/j.cyto.2015.02.001.

23. Han M.X., Ding C., Kyung H.M. Genetic polymorphisms in pattern recognition receptors and risk of periodontitis: Evidence based on 12,793 subjects. Human Immunology. 2015;76(7):496–504. DOI: 10.1016/j.humimm.2015.06.006.

24. Song B., Zhang Y., Chen L., Zhou T., Huang W., Zhou X. et al. The role of Toll-like receptors in periodontitis. Oral Diseases. 2017;23(2):168–180. DOI: 10.1111/odi.12468.

25. Hajishengallis G., Korostoff J.M. Revisiting the Page & Schroeder model: The good, the bad and the unknowns in the periodontal host response 40 years later. Periodontology 2000. 2017;75(1):116–151. DOI: 10.1111/prd.12181.

26. Cekici A., Kantarci A., Hasturk H., Van Dyke T.E. Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontology 2000. 2014;64(1):57–80. DOI: 10.1111/prd.12002.

27. Gupta M., Chaturvedi R., Jain A. Role of monocyte chemoattractant protein-1 (MCP-1) as an immune-diagnostic biomarker in the pathogenesis of chronic periodontal disease. Cytokine. 2013;61(3):892–897. DOI: 10.1016/j.cyto.2012.12.012.

28. Braga T.T., Agudelo J.S., Camara N.O. Macrophages during the fibrotic process: M2 as friend and foe. Front. Immunology. 2015;6:602. DOI: 10.3389/fimmu.2015.00602.

29. Huang N., Dong H., Luo Y., Shao B. Th17 Cells in Periodontitis and Its Regulation by A20. Front. Immunology. 2021;12:125–137. DOI: 10.3389/fimmu.2021.742925.

30. Kikuta J., Wada Y., Kowada T., Wang Z., Sun-Wada G.H., Nishiyama I. et al. Dynamic visualization of RANKL and Th17-mediated osteoclast function. The Journal of Clinical Investigation. 2013;123(2):866–873. DOI: 10.1172/JCI65054.

31. Belibasakis G.N., Bostanci N. The RANKL-OPG system in clinical periodontology. Journal of Clinical Periodontology. 2012;39(3):239–248. DOI: 10.1111/j.1600051X.2011.01810.x.

32. Almubarak A., Tanagala K.K.K., Papapanou P.N., Lalla E., Momen-Heravi F. Disruption of monocyte and macrophage homeostasis in periodontitis. Front. Immunol. 2020;11:330. DOI: 10.3389/fimmu.2020.00330.

33. Смирнова С.В., Смольникова М.В. Иммунопатогенез псориаза и псориатического артрита. Медицинская иммунология. 2014;16(2):127–138.

34. Fang C., Wu L., Zhao M.J., Deng T., Gu J.M., Guo X.P. et al. Periodontitis exacerbates benign prostatic hyperplasia through regulation of oxidative stress and inflammation. Oxid. Med. Cell Longev. 2021;2021:2094665. DOI: 10.1155/2021/2094665.

35. Коротаева T.В., Корсакова Ю.Л., Логинова Е.Ю., Губарь Е.Е., Чамурлиева М.Н. Псориатический артрит. Клинические рекомендации по диагностике и лечению. Современная ревматология. 2018;12(2):22–35. DOI: 10.14412/1996-7012-2018-2-22-35.

36. Mease P., Hall S., FitzGerald O., van der Heijde D., Merola J F., Avila-Zapata F. et al. Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N. Engl. J. Med. 2017;377(16):1537–1550. DOI: 10.1056/NEJMoa1615975.

37. FitzGerald O., Haroon M., Giles J T., Winchester R. Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype. Arthritis Research and Therapy. 2015;17(1):115. DOI: 10.1186/s13075-015-0640-3.

38. Kavanaugh A., Gladman D.D., Edwards C.J., Schett G., Guerette B., Delev N. et al. Long-term experience with apremilast in patients with psoriatic arthritis: 5-year results from a PALACE 1-3 pooled analysis. Arthritis Res. Ther. 2019;21(1):118. DOI: 10.1186/s13075-019-1901-3.

39. Coates L.C., Savage L.J., Chinoy H., Laws P.M., Lovell C.R., Korendowych E. et al. Assessment of two screening tools to identify psoriatic arthritis in patients with psoriasis. Journal of the European Academy of Dermatology and Venereology: JEADV. 2018;32(9):1530–1534. DOI: 10.1111/jdv.14971.

40. Emmungil H., İlgen U., Direskeneli R.H. Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects. Turk. J. Med. Sci. 2021;51(4):1601–1614. DOI: 10.3906/sag2011-235.

41. Chimenti M.S., Triggianese P., De Martino E., Conigliaro P., Fonti G.L., Sunzini F. et al. An update on pathogenesis of psoriatic arthritis and potential therapeutic targets. Expert Review of Clinical Immunology. 2019;15(8):823–836. DOI: 10.1080/1744666X.2019.1627876.

42. Tateiwa D., Yoshikawa H., Kaito T. Cartilage and Bone Destruction in Arthritis: Pathogenesis and Treatment Strategy: A Literature Review. Cells. 2019;8(8):818. DOI: 10.3390/cells8080818.

43. Eder L., Aydin S.Z. Imaging in psoriatic arthritis-insights about pathogenesis of the disease. Current Rheumatology Reports. 2018;20(12):77. DOI: 10.1007/s11926-018-0793-6.

44. Coras R., Kavanaugh A., Boyd T., Huynh Q., Pedersen B., Armando A.M. et al. Proand anti-inflammatory eicosanoids in psoriatic arthritis. Metabolomics: Ofcial Journal of the Metabolomic Society. 2019;15(4):65. DOI: 10.1007/s11306019-1527-0.

45. Adebajo A., Boehncke W.H., Gladman D.D., Mease P.J. Psoriatic arthritis and psoriasis: pathology and clinical aspects. Springer. 2016;45:52. DOI: 10.1007/978-3-319-19530-8.

46. Celis R., Cuervo A., Ramírez J., Cañete J.D. Psoriatic synovitis: singularity and potential clinical implications. Front. Medicine. 2019;6:14. DOI: 10.3389/fmed.2019.00014.

47. Paine A., Ritchlin C. Bone remodeling in psoriasis and psoriatic arthritis: an update. Current Opinion in Rheumatology. 2016;28(1):66–75. DOI: 10.1097/BOR.0000000000000232.

48. Bartosińska J., Michalak-Stoma A., Juszkiewicz-Borowiec M., Kowal M., Chodorowska G. The Assessment of selected bone and cartilage biomarkers in psoriatic patients from Poland. Mediators of InÀammation. 2015;2015:194535. DOI: 10.1155/2015/194535.

49. Mishra S., Johnson L., Agrawal S., Rajput S. Assessment of Periodontal status in Patients with Psoriatic Arthritis: A retrospective, case-control study. Journal of Clinical and Experimental Dentistry. 2021;13(8):776–783. DOI: 10.4317/jced.58125.

50. Wójcik P., Biernacki M., Wroński A., Łuczaj W., Waeg G., Žarković N. et al. Altered lipid metabolism in blood mononuclear cells of psoriatic patients indicates differential changes in psoriasis vulgaris and psoriatic arthritis. International Journal of Molecular Sciences. 2019;20(17):4249. DOI: 10.3390/ijms20174249.

51. Üstün K., Sezer U., Kısacık B., Şenyurt S.Z., Özdemir E.Ç., Kimyon G. et al. Periodontal disease in patients with psoriatic arthritis. InÀammation. 2013;36(3):665–669. DOI: 10.1007/s10753-012-9590-y.

52. Carvalho A.L., Hedrich C.M. The Molecular pathophysiology of psoriatic arthritis – the complex interplay between genetic predisposition, epigenetics factors, and the microbiome. Front. Molecular Biosciences. 2021;8:190–205. DOI: 10.3389/fmolb.2021.662047.

53. Захватов А.Н., Беляев А.Н., Tарасова T.В., Аванесов А.М., Захаркин И.А., Чекмаева А.А. Патогенетическая коррекция цитокинового дисбаланса при экспериментальном посттравматическом артрите. Ульяновский медико-биологический журнал. 2018;3:101–108. DOI: 10.23648/UMBJ.2018.31.17221.

54. Hawkes J.E., Chan T.C., Krueger J.G. Psoriasis pathogenesis and the development of novel targeted immune therapies. The Journal of Allergy and Clinical Immunology. 2017;140(3):645–653. DOI: 0.1016/j.jaci.2017.07.004.

55. Blauvelt A., Chiricozzi A. The Immunologic role of IL-17 in psoriasis and psoriatic arthritis pathogenesis. Clinical Reviews in Allergy & Immunology. 2018;55(3):379–390. DOI: 10.1007/s12016-018-8702-3.

56. Seeling M., Hillenhoff U., David J.P., Schett G., Tuckermann J., Lux A. et al. Inflammatory monocytes and Fcγ receptor IV on osteoclasts are critical for bone destruction during inflammatory arthritis in mice. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(26):10729– 10734. DOI: 10.1073/pnas.1301001110.