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Association of Time Under Immunosuppression and Different Med Oral Patol Oral Cir Bucal. 2018 May 1;23 (3):e326-34. Periodontal bacteria and immunosuppression Journal section: Medically compromised patients in Dentistry doi:10.4317/medoral.22238 Publication Types: Research http://dx.doi.org/doi:10.4317/medoral.22238 Association of time under immunosuppression and different immunosuppressive medication on periodontal parameters and selected bacteria of patients after solid organ transplantation Gerhard Schmalz 1, Lisa Berisha 1, Horst Wendorff 1, Florian Widmer 1, Anna Marcinkowski 1, Helmut Tes- chler 2, Urte Sommerwerck 2, Rainer Haak 1, Otto Kollmar 3, Dirk Ziebolz 1 1 Department of Cariology, Endodontology and Periodontology, University of Leipzig 2 Department of Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital Essen, University Duisburg- Essen, Germany 3 Department of General and Visceral Surgery, HELIOS Dr. Horst Schmidt-Kliniken, Wiesbaden, Germany Correspondence: Schmalz G, Berisha L, Wendorff H, Widmer F, Marcinkowski A, Tes- University Leipzig chler H, Sommerwerck U, Haak R, Kollmar O, Ziebolz D. Association of Dept. of Cariology time under immunosuppression and different immunosuppressive medi- Endodontology and Periodontology cation on periodontal parameters and selected bacteria of patients after Liebigstr. 12 solid organ transplantation. Med Oral Patol Oral Cir Bucal. 2018 May D 04103 Leipzig, Germany 1;23 (3):e326-34. [email protected] http://www.medicinaoral.com/medoralfree01/v23i3/medoralv23i3p326.pdf Article Number: 22238 http://www.medicinaoral.com/ © Medicina Oral S. L. C.I.F. B 96689336 - pISSN 1698-4447 - eISSN: 1698-6946 eMail: [email protected] Indexed in: Received: 18/10/2017 Science Citation Index Expanded Accepted: 23/12/2017 Journal Citation Reports Index Medicus, MEDLINE, PubMed Scopus, Embase and Emcare Indice Médico Español Abstract Background: Aim of this study was to investigate the association of the time under immunosuppression and dif- ferent immunosuppressive medication on periodontal parameters and selected periodontal pathogenic bacteria of immunosuppressed patients after solid organ transplantation (SOT). Material and Methods: 169 Patients after SOT (lung, liver or kidney) were included and divided into subgroups according their time under (0-1, 1-3, 3-6, 6-10 and >10 years) and form of immunosuppression (Tacrolimus, Cy- closporine, Mycophenolate, Glucocorticoids, Sirolimus and monotherapy vs. combination). Periodontal probing depth (PPD) and clinical attachment loss (CAL) were assessed. Periodontal disease severity was classified as healthy/mild, moderate or severe periodontitis. Subgingival biofilm samples were investigated for eleven selected potentially periodontal pathogenic bacteria using polymerasechainreaction. Results: The mean PPD and CAL as well as prevalence of Treponema denticola and Capnocytophaga species was shown to be different but heterogeneous depending on time under immunosuppression (p<0.05). Furthermore, only the medication with Cyclosporine was found to show worse periodontal condition compared to patients with- out Cyclosporine (p<0.05). Prevalence of Porphyromonas gingivalis, Tannerella forsythia and Fusobacterium nu- cleatum was reduced and prevalence of Parvimonas micra and Capnocytophaga species was increased in patients under immunosuppression with Glucocorticoids, Mycophenolate as well as combination therapy. Conclusions: Time under and form of immunosuppression might have an impact on the clinical periodontal and microbiological parameters of patients after SOT. Patients under Cyclosporine medication should receive in- creased attention. Differences in subgingival biofilm, but not in clinical parameters were found for Glucocorti- coids, Mycophenolate and combination therapy, making the clinical relevance of this finding unclear. Key words: Immunosuppression, organ transplantation, periodontitis, periodontal bacteria. e326 Med Oral Patol Oral Cir Bucal. 2018 May 1;23 (3):e326-34. Periodontal bacteria and immunosuppression Introduction periodontal disease parameters, but not with prevalence Periodontitis (P) is an inflammatory disease with a mul- of selected periodontal pathogenic bacteria. tifactorial character (1). Although P is primarily caused by an opportunistic infection with potentially periodon- Material and Methods tal pathogenic bacteria, host response, general diseases This clinical, observational cross-sectional study was (e.g. diabetes mellitus, rheumatoid arthritis, medica- reviewed and approved by the ethics committee of the tion) and environmental factors are involved in the ae- University Medical Center Göttingen, Germany (No. tiopathogenesis of periodontal inflammation (1). 43/9/07) and by the ethics committee of the University Considering the role of host response in this context, Hospital Essen (13-5689-BO). Research was conducted factors influencing the immune reaction of the host in full accordance with the World Medical Associa- might be of relevance. Therefore, an immunosuppres- tion’s Declaration of Helsinki. The patients were in- sive therapy could have an impact on periodontitis se- formed verbally, as well as in writing, about the study verity and progression via alterations in periodontal tis- and provided written informed consent to participate. sues, gingival overgrowth or ulceration and migration - Patients of junctional epithelium (2-5). For this study, a group consisting of patients after solid One special group receiving life-long immunosup- organ transplantation from previous studies (6-8,15), pressive therapy consists of patients after solid organ has been composed. For this, previously defined, spe- transplantation (SOT). Recent studies showed high cific in- and exclusion criteria were used to select fitting prevalence of periodontal diseases in this patient group patients for this study. Patients after liver and kidney (liver, lung, kidney), but did not investigate the immu- transplantation in the Department of General, Visceral nosuppression separately (6-8). Consequently, up until and Pediatric Surgery of the University Medical Center now the clinical influence on periodontal parameters Göttingen (recruited between February to July 2012), caused by immunosuppressive medication appears to be and patients after lung transplantation from the lung unclear. Especially the duration of immunosuppressive transplant unit of the Ruhrlandklinik, Essen, Germany therapy, but also the specific drug as monotherapy or (recruited between February and October 2014) were combination could be of relevance in this respect. investigated during their routine follow up visit. In development and progression of P, potentially peri- SOT (kidney, liver, lung), irrespective of time under im- odontal pathogenic bacteria play an important role. It munosuppression and regular subsequent appointment has been shown, that an ecological shift in the subgingi- in one of the two transplant centers was the inclusion val microbiota is a key component (9,10) Although their criterion for this study. The following exclusion criteria epidemiological relevance is discussed controversially, were formulated: age <18 years, presence of any addi- periodontal pathogenic bacteria as classified by Socran- tional infectious diseases, especially HIV, seizure and sky et al. 1998 (11) are an important element of cur- nervous disorder, as well as pregnancy. Furthermore, rent understanding of pathogenesis of P. The influence the inability to undergo complete oral investigation and of immunosuppression on periodontal bacteria is still toothlessness leaded to exclusion from the study. unclear. Few available data for immunosuppressed pa- - Recording of general medical conditions tients after organ transplantation showed microbiologi- Each patient was asked to complete a questionnaire to cal changes indeed (12-14). However, on the other hand record the general medical conditions. Thereby, immu- differences between immunosuppressed transplant re- nosuppressive and further medication, diabetes status, cipients and not immunosuppressed patients were not smoking habits (smoker = currently smoking, former found in recent investigations (6,15). Similarly to peri- smoker = currently non-smoking but smoked within the odontal condition, the influence of duration of immu- past 5 years and non-smoker = never smoking or non- nosuppressive therapy and the specific drug as mono- smoking for at least 5 years), causal underlying disease therapy or combination is unclear. for transplantation and time under immunosuppression Therefore, the aim of this multicenter observational were evaluated. Regarding time under immunosuppres- cross-sectional study was to investigate the association sion patients were divided into five groups (0-1 year, 1-3 of the duration of immunosuppression and different im- years, 3-6 years, 6-10 years and >10 years) for analy- munosuppressive medication with periodontal parame- sis. For the analysis of influence of different immuno- ters and selected periodontal pathogenic bacteria of im- suppressive medication, only the immunosuppressive munosuppressed patients after SOT. For this, patients drugs, which were taken by at least 15 patients, were after transplantation of three different organs (kidney, included for analysis. liver, and lung) from previous studies by this working - Periodontal examination group should be investigated as one large cohort (6- All of the patients were examined under standardized 8,15). It was hypothesized that the duration and form of conditions by
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