Is poor oral health a risk factor for idiopathic granulomatous mastitis?

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Semih SAĞLIK, Şilan Bilek Olgaç This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4007006/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Mar, 2024 Read the published version in Biomolecules and Biomedicine → Version 1 posted You are reading this latest preprint version Abstract OBJECTIVE: Idiopathic granulomatous mastitis is a rare inflammatory disease of the breast that clinically and radiologically can be confused with carcinoma. Although its etiology remains unclear, it is stated that it may be related to pregnancy, lactation, hormonal imbalance, autoimmunity, smoking, α1-antitrypsin deficiency and various microorganisms. This study aimed to evaluate the relationship between idiopathic granulomatous mastitis and oral health. PATIENTS AND METHODS: Our study included 42 female patients diagnosed with idiopathic granulomatous mastitis as a result of histopathological evaluations between September 2018 and October 2023. The reference group consisted of 47 female patients with clinically, radiologically and laboratory proven non-specific mastitis and 36 healthy female individuals. The oral health of all individuals included in the study was evaluated by an experienced dentist using "Decayed, Missing and Filled Teeth" (DMFT) and "Simplified Oral Hygiene Index" (OHI-S) index values. RESULTS: The ages of idiopathic granulomatous mastitis patients included in the study ranged between 29-51 years (mean age 34.88±4.87). The most common clinical findings were pain (n=38), palpable breast mass (n=32), erythema (n=22), induration (n=14) and dermal sinus (n=10). When OHI-S and DMFT index values of the individuals included in the study were compared, both OHI-S and DMFT index values of individuals diagnosed with idiopathic granulomatous mastitis were statistically significantly higher than those of the reference group (p<0.05). CONCLUSIONS Our findings suggest that poor oral health may be involved in the etiology of idiopathic granulomatous mastitis. Therefore, it may be useful to consider oral health in the etiology of IGM in future studies and to investigate oral microbiota in samples obtained from the target tissue. Idiopathic granulomatous mastitis Oral Health Dental health “Decayed Missing and Filled Teeth” (DMFT) “Simplified Oral Hygiene Index” (OHI-S) Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Idiopathic granulomatous mastitis (IGM) is a rare inflammatory disease of the breast which clinically and radiologically may be confused with carcinoma [1]. It was first described by Kessler and Wolloch in 1972 [2]. Clinically, it most commonly manifests with breast pain, skin erythema, palpable mass, nipple retraction, oedema, ulceration and fistula [3]. It frequently shows unilateral involvement and has a recurrence rate of 16-50%. Since it clinically and radiologically mimics malignant lesions, histopathological examination is necessary for differential diagnosis [4]. Although the etiology of IGM is still uncertain, it is stated that it may be related with pregnancy, lactation, hormonal imbalance, autoimmunity, smoking, α1-antitrypsin deficiency and various microorganisms [3,5]. The definitive diagnosis of IGM is possible by excluding histopathological features as well as secondary causes which lead to granulomatous inflammation such as sarcoidosis, granulomatous polyangiitis, tuberculosis and fungal infection [5]. On histopathological examination, the diagnosis is made with the detection of non-caseified multiple granulomas with inflammatory reaction disrupting the breast lobules [6]. Poor oral health is recognised as an important public health problem worldwide. Numerous epidemiological studies have shown that alterations in the oral microbiome not only affect the presence and severity of oral lesions but are also associated with various systemic diseases [7-16]. The oral microbiota (OMB) may cause systemic disease through various mechanisms. Among the most accepted ones are the spread of oral infection outside the oral cavity, inclusion of microbial toxins into the systemic circulation and systemic inflammation caused by immunological reactions against soluble pathogen antigens [17,18]. The aim of this study is to evaluate the relationship between idiopathic granulomatous mastitis and oral health. MATERIALS AND METHODS Our study included 42 female patients who were evaluated ultrasonographically (USG) between September 2018 and October 2023, and were diagnosed with IGM as a result of clinical, laboratory, radiological and histopathological evaluations, each of which had a USG-guided tru-cut breast biopsy. Hematoxylin+Eosin (H+E) staining for histopathological examination, Gram staining for the detection of microorganisms, Ziehl-Neelsen (ZN) staining for tuberculosis and Periodic acid-Schiff (PAS) staining for fungal infection were performed on all pathological preparations to exclude secondary granulomatous mastitis agents. In addition, serum ACE level and chest X-ray were analysed for sarcoidosis, C-ANCA PR-3 levels and spot urine protein/creatinine ratio by ELISA and immunofluorescence for granulomatous polyangiitis. Patients with a history of trauma or foreign body were not included in the study. Breast biopsy tissue samples of the patients showed chronic active inflammation as well as inflammatory cells including polymorphonuclear leukocytes, lymphocytes, plasma cells and granuloma structures consisting of epithelioid histiocytes and multinuclear giant cells. The reference group consisted of 47 female patients with clinically, radiologically and laboratory proven non-specific mastitis and 36 healthy female persons. Patients with systemic disease, periodontal treatment within the last six months, history or suspicion of known malignancy, diabetes mellitus, previous tuberculosis or contact history and recently vaccinated tetanus patients were excluded. Oral examinations were performed by an experienced dentist after informed consent was obtained from all individuals included in the study. In our study, "Decayed, Missing and Filled Teeth" (DMFT) and "Simplified Oral Hygiene Index" (OHI-S) indices were used to evaluate oral health. The DMFT index is calculated by considering the number of decayed, missing and filled teeth reflecting the prevalence of caries [19]. While calculating the DMFT index, the condition of all teeth was determined by clinical and radiographic evaluation. It was calculated by summing the number of untreated caries (Decayed-D), missing teeth (Missing-M) and filled teeth (Filled-F). If a tooth had both caries and filling, only one was scored. OHI-S index is an index system that reflects the oral hygiene status of the individual and consists of plaque and calculus components. In this index system, 3 regions including right-posterior region, left-posterior region and anterior region are evaluated in the lower and upper jaw [20]. In total, 12 separate measurements for both plaque and calculus were performed on 6 teeth. In our study, buccal surfaces of upper first molars, lingual surfaces of lower first molars, and labial surfaces of upper right and lower left incisors were evaluated. Plaque and calculus indices were calculated separately and the sum was obtained as oral hygiene index. Statistical Analysis SPSS 20.0 software (Statistical Package for the Social Sciences, Chicago, IL) is used for data analysis. Data related to qualitative variables are expressed as number (n) and percentage (%), and quantitative variables are expressed as mean (mean) ± and standard deviation (sd). In the evaluation of the study data, whether the continuous variables were normally distributed is analysed by Shapiro-Wilk test. Student-t test is used for pairwise independent group comparisons and one-way anaova for comparisons of more than two groups followed by TUKEY test for intergroup differences. Depending on the sample sizes, the Chi-square test or Fisher’s exact test were performed for categorical variables. The relationship between all quantities is analysed by Pearson correlation coefficient. The significance level for statistical results is accepted as p<0.05. RESULTS The ages of the IGM patients included in the study ranged between 29-51 years (mean age 34.88±4.87). The most common clinical findings were pain (n=38), palpable breast mass (n=32), erythema (n=22), induration (n=14) and dermal sinus (n=10) (Figure 1). While bilateral breast involvement was not observed in any patient, 25 patients had right breast involvement and 17 patients had left breast involvement. USG was performed in all patients and mammography was performed in two patients. All patients with IGM underwent USG-guided tru-cut biopsy for both diagnosis and malignancy exclusion and the diagnosis was confirmed histopathologically (Figure 2). Clinical and ultrasonographic findings of the patients are shown in table 1. The cases included in the study were categorised into three groups. Group 1 included healthy female subjects without any known systemic and breast disease, group 2 included female patients with clinical, radiological and laboratory diagnosis of non-specific mastitis and group 3 included female patients with histopathological diagnosis of IGM. The smoking history, menopausal status, lactation and hormonal contraceptive use history, pregnancy history, body mass index (BMI) values and external brushing habits of the individuals in all three groups are given in table 2. When the OHI-S and DMFT index values of the individuals in the groups were compared, both OHI-S and DMFT index values of the individuals diagnosed with IGM were statistically significantly higher than the individuals in group 1 and group 2 (p<0.05). No statistically significant difference was found between group 2 and group 3 in both OHI-S and DMFT index values (p=0.820, p=0.980, respectively) (Table 3 and Figure 3). DISCUSSION This study was conducted to investigate whether OHI-S and DMFT index values, which are oral health indicators, are associated with IGM. The main finding was that these indices were statistically significantly higher in patients with IGM compared with reference group individuals. Age, BMI, menopausal status, breastfeeding, pregnancy, oral contraceptives, smoking history and tooth brushing habits were not significantly different between the three groups. Although IGM is frequently observed in young middle ages (3rd and 4th decade), it has been reported in the literature that it may be observed in a wider age range (11-83 years) [3]. In our study, the mean age of our IGM cases was 34 years, which was consistent with the literature. Although IGM is usually seen in young women with a history of lactation, male cases have rarely been reported in the literature [21]. IGM may present clinically with different symptoms and clinical findings including painful or painless palpable mass, skin redness, tenderness, sinus formation, ulcer, nipple discharge and abscess [22,23]. The most common clinical finding is palpable painful mass [4,22]. In our study, the most common clinical finding in patients with IGM was palpable painful breast mass. Fever is generally not an expected symptom [24]. In our study, none of the patients diagnosed with IGM had fever septoma or finding. In IGM, unilateral breast involvement is usually observed with right breast predominance and rarely bilateral involvement is observed [1,4-6]. In our study, all IGM patients had unilateral involvement with right breast dominance. Various factors including autoimmunity, oral contraceptive use, infectious agents, hormonal imbalances, pregnancy, hyperprolactinaemia, alpha-1 antitrypsin deficiency have been accused in the aetiology of IGM, but none of these have been proven [1,3,5,22,23]. Since it usually affects women in the reproductive age group with a history of pregnancy and lactation, it has been thought that these factors may be the main underlying causes in the aetiology [5,25,26]. In lactation, it is thought that extravasation of secretion damages the epithelium and triggers granulomatous inflammatory response [27]. However, the presence of male patients in the literature as well as a wide age range (11-83 years) and patients without a history of lactation show that only lactation and pregnancy cannot be held responsible in the etiology [3,28,29]. On the other hand, the fact that 5 patients (11,9%) had no history of lactation and 1 patient (2,5%) was in the postmenopausal period in our study indicates the presence of other risk factors in the etiology. Another factor blamed in the etiology is the use of oral contraceptives (OCS), which is considered a potential risk factor because they increase breast secretion. Binesh et al. reported that the frequency of OCS use in IGM was 36% [30]. Aghajanzadeh et al. reported that OCS users were more prone to IGM infection [31]. However, Altintoprak et al. found that the relationship between IGM and OCS varied between 0-42% and therefore, there was no significant relationship between OCS and IGM (3). In our study, the presence of a history of oral contraceptive use in only 28,5% (12 patients) of our IGM patients reduces the role of this factor in the etiology. Smoking is one of the other factors accused in the etiology of the disease. Since the relationship between smoking and IGM varies between 0-77% in literature studies, it is not yet possible to mention that smoking is an etiological factor [32,33]. Asoglu et al. [32] reported that 77% of patients with IGM had a history of smoking, whereas Baslaim et al. [33] reported that none of the patients with IGM had a history of smoking. In addition, Prasad et al. [34] reported that only 2 patients (2,74%) had a history of smoking in a study conducted in 73 patients. In our study, only 5 patients (11,9%) had a history of smoking, which makes it difficult for smoking to be an etiological risk factor. Autoimmunity has been the most accepted theory in the etiology because of good response to steroid and immunosuppressive therapies in the treatment of IGM. In addition, immunohistochemical demonstration of T-lymphocyte predominance in biopsy specimens in literature studies supports this view [29,35,36]. It has been reported that autoimmune response to fat or protein-rich secretion extravasated from breast lobules may cause chronic inflammation [37]. Especially T cell-mediated inflammation has been held responsible for non-caseified granuloma formation [35]. However, an etiological cause that would trigger this mechanism has not been identified [38]. In the literature, the association of autoimmune diseases including erythema nodosum, rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE) and psoriasis with IGM has been mentioned, but this constitutes only a small portion of all cases [39-41]. In our study, one patient had psoriasis and two patients had rheumatoid arthritis, which constituted only 7,1% of all patients. Some microbiological agents have been accused in the etiology of IGM. Some bacterial species, especially Corynebacterium, Streptococci and Propionibacterium have been isolated histopathologically. The most frequently isolated species is Corynebacterium species [42-45]. In a study conducted by Taylor et al. [46] on 62 patients, Corynebacterium species were isolated in 55% of the cases and fever and fistula were observed more frequently in these cases. However, since Corynebacterium species are members of normal skin flora, it is not possible to distinguish whether these organisms cause infection or contamination [47]. However, it has been reported in the literature that no microbiological agent positivity was detected in molecular-based analyses performed on many flora bacteria and the most common infective agents and no growth was found in culture samples [3,48]. In addition, the role of bacteriological agents in the etiology of IGM is reduced because IGM patients do not benefit from antibiotic treatment and clinical improvement is not achieved. In our study, we did not detect any bacteriological agent in culture samples obtained from IGM cases. Since there is no typical imaging finding in the diagnosis of IGM, it is difficult to make a diagnosis with radiological methods [49]. USG is the first preferred imaging method because the patient population is young [50]. Hypoechoic, heterogeneous lesions with tubular configuration, hypoechoic mass with lobule contour, multiloculated abscess collections, fistulisation to the skin or axillary lymphadenopathy may be visualised on ultrasonography [29]. Doppler USG examination usually shows increased vascularity in the affected breast parenchyma [51]. Mammography is recommended to exclude microcalcifications in cases of suspected malignancy, but usually does not provide specific information. Microcalcifications are generally not an expected imaging finding in patients with IGM [50,52]. The most common imaging findings on USG examination in our patients included hypoechoic, heterogeneous, tubular lesions in 28,5% (12 patients), multiloculated abscess collections in 23,8% (10 patients), and a well-circumscribed hypoechoic mass lesion in 19% (8 patients). We also detected axillary lymphadenopathy in 14,2% (6 patients). Since diagnosis with imaging findings may lead to misdiagnosis and treatment, histopathological examination is essential for definitive diagnosis. Fine needle aspiration biopsy (FNAB) is a low-sensitivity method with a limited diagnostic role [53]. In the literature, studies have been conducted on patients who were misdiagnosed as carcinoma by FNAB and therefore were treated incorrectly [54-56]. Therefore, tru-cut biopsy or extensive breast tissue sampling is required for diagnosis [57]. In all of our IGM patients, the diagnosis was made by tru-cut biopsy and the patients were followed up and treated accordingly. The oral cavity provides an ideal environment for microorganisms due to temperature, humidity and nutrient abundance [58]. There is a dynamic interaction between these microorganisms and the organism and if this balance is disturbed for any reason, it may cause microbial imbalance called dysbiosis [59,60]. In case of dysbiosis, some microbial colonies become more widespread and may cause pathogenic effects on the organism [60]. It has been shown that dysbiotic change may cause local diseases such as dental caries and periodontal disease and may be involved in the etiology of a number of systemic diseases such as cardiovascular disease, pneumonia, malignancy, diabetes, obesity, autoimmune disease, cystic fibrosis, cerebral or hepatic abscesses [8-16]. Poor oral hygiene predisposes to the colonisation of pathogenic microorganisms in periodontal tissues. Since periodontal tissues are anatomically close to the blood circulation, endotoxins and/or cytokines released from these pathogenic microorganisms directly or indirectly pass into the systemic circulation, causing bacteraemia and inflammation in distant organs [17,61,62]. It has been found that systemic concentrations of some proinflammatory cytokines increase in case of periodontal inflammation and serum values of these biomarkers decrease significantly after treatment [61,63,64]. Therefore, poor oral health affects not only periodontal inflammatory processes but also systemic inflammatory status. Periodontal inflammation or chronic bacteraemia predisposes to the development of a systemic immune reaction. In recent studies, P. gingivalis and T. denticola have been found to trigger a systemic immune response [65,66]. Some periodontal pathogens have been shown to exacerbate various microvascular complications such as nephropathy, retinopathy and neuropathy in patients with diabetes and to increase cardiorenal mortality twofold [62,67]. Some periodontal pathogens, especially F. nucleatum , have been shown to cause adverse pregnancy outcomes such as low birth weight or stillbirth [68,69]. Cestari et al. [70] reported that periodontal inflammation predisposes to Alzheimer's disease and proinflammatory cytokines are increased in these patients. Zhang et al. [71] suggested that some periodontal pathogens initiate a systemic inflammatory response via haematogenous pathway in mouse models and may subsequently lead to systemic osteoporosis. Bernhard et al. [72] suggested that due to the detection of abundant periodontal pathogens in subgingival biofilm samples taken from breast cancer cases, the inflammation caused by these pathogens may indirectly contribute to breast cancer. Sfreddo et al. [73] reported that the risk of developing breast cancer in women diagnosed with periodontitis was two to three times higher than in healthy control group women. Silva et al. [12] suggested that a strain variant of S. constellatus in the periodontal pocket formed through genetic recombination may have the potential to form abscesses in the brain. Additionally, numerous studies have shown that periodontal inflammation plays an active role in triggering or exacerbating autoimmune diseases such as SLE, primary sclerosing cholangitis, RA, Sjögren's syndrome and autoimmune hepatitis [74-77]. To the best of our knowledge, this is the first study to examine the relationship between poor oral health and IGM. In this study, OHI-S index values indicating oral hygiene deficiency and DMFT index values indicating poor oral health were found to be higher in patients with histopathological diagnosis of IGM compared to patients without this diagnosis, which led us to associate IGM with poor oral health. CONCLUSION In conclusion, our findings suggest that poor oral health may be involved in the etiology of IGM. Therefore, it may be useful to consider oral health in the etiology of IGM in future studies and to investigate oral microbiota in samples taken from the target tissue. In addition, if our findings are confirmed in future studies with a larger number of patients, precautions and information about poor oral health may help to reduce the incidence of IGM. Declarations Conflict of Interest The authors declare that they have no conflicts of interest. Ethics Approval This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethics Committee Approval was obtained from the Siirt University Non-Invasive Ethics Committee ( Decision No: 86081). Informed Consent Written informed consent was obtained from the study participants. Funding The authors received no financial support for this study. Acknowledgments We would like to express our sincere gratitude to all parties who generously contributed to this study. Authors’ Contributions All authors equally contribute to the present manuscript preparation. Availability of data and materials The research data of this study can be requested from the corresponding author. 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Vacuum-assisted biopsy and steroid therapy for granulomatous lobular mastitis: report of three cases. Surg Today 2009; 39, 695-699. Bani‐Hani KE, Yaghan RJ, Matalka II, Shatnawi NJ. Idiopathic granulomatous mastitis: time to avoid unnecessary mastectomies. Breast J 2004; 10(4), 318-322. Lee JH, Oh KK, Kim EK, Kwack KS, Jung WH, Lee HK. Radiologic and clinical features of idiopathic granulomatous lobular mastitis mimicking advanced breast cancer. YMJ 2006; 47(1), 78-84. Pala EE, Ekmekci S, Kılıc M, Dursun A, Colakoglu G, Karaali C et al. Granulomatous mastitis: a clinical and diagnostic dilemma. Turkish Journal of Pathology, 2022; 38(1), 40. Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH et al. The human oral microbiome. J Bacteriol 2010; 192(19), 5002-5017. Goodacre R. Metabolomics of a superorganism. J Nutr 2007; 137(1), 259S-266S. Tamboli CP, Neut C, Desreumaux P, Colombel JF. Dysbiosis in inflammatory bowel disease, 2004; Gut 53(1), 1. Peng X, Cheng L, You Y, Tang C, Ren B, Li Y et al. Oral microbiota in human systematic diseases. Int J Oral Sci 2022; 14(1), 14. Issrani R, Reddy J, Dabah THEM, Prabhu N, Alruwaili MK, Munisekhar MS et al. Exploring the mechanisms and association between oral microflora and systemic diseases. Diagnostics 2022; 12(11), 2800. Torrungruang K, Katudat D, Mahanonda R, Sritara P, Udomsak A. Periodontitis is associated with elevated serum levels of cardiac biomarkers-Soluble ST2 and C-reactive protein. J Clin Periodontol 2019; 46, 809–818 Esparbès P, Legrand A, Bandiaky ON, Chéraud-Carpentier M, Martin H, Montassier E et al. Subgingival microbiota and cytokines profile changes in patients with periodontitis: A pilot study comparing healthy and diseased sites in the same oral cavities. Microorganisms 2021; 9(11), 2364. Chukkapalli SS, Rivera MF, Velsko IM, Lee JY, Chen H, Zheng D et al. Invasion of oral and aortic tissues by oral spirochete Treponema denticola in ApoE−/− mice causally links periodontal disease and atherosclerosis. Infection and immunity 2014; 82(5), 1959-1967. Velsko IM, Chukkapalli SS, Rivera MF, Lee JY, Chen H, Zheng D et al. Active invasion of oral and aortic tissues by Porphyromonas gingivalis in mice causally links periodontitis and atherosclerosis. PloS one 2014; 9(5), e97811. Bui FQ, Almeida-da-Silva CLC, Huynh B, Trinh A, Liu J, Woodward J et al. Association between periodontal pathogens and systemic disease. Biomedical journal, 2019; 42(1), 27-35. Han YW, Wang X. Mobile microbiome: oral bacteria in extra-oral infections and inflammation. J Dent Res 2013; 92(6), 485-491. Han YW. Fusobacterium nucleatum: a commensal-turned pathogen. Curr Opin Microbiol 2015; 23, 141-147. Cestari JA, Fabri GM, Kalil J, Nitrini R, Jacob-Filho W, de Siqueira JT et al. Oral infections and cytokine levels in patients with Alzheimer’s disease and mild cognitive impairment compared with controls. J. Alzheimers Dis 2016; 52, 1479–1485. Zhang ZY, Xie MR, Liu Y, Li YX, Wu K, Ding YM. Effect of periodontal pathogens on total bone volume fraction: A phenotypic study. Curr Med Sci 2020; 40, 753-760. Bernhard VR, Faveri M, Santos MS, Gomes MDCM, Batitucci RG, Tanaka CJ et al. Subgingival microbial profile of women with breast cancer: a cross-sectional study. Cancer Res 2019; 39, 1-7. Sfreddo CS, Maier J, De David SC, Susin C, Moreira CHC. Periodontitis and breast cancer: a case‐control study. Community Dent Oral Epidemiol 2017; 45(6), 545-551. Huang X, Huang X, Huang Y, Zheng J, Lu Y, Mai Z et al. The oral microbiome in autoimmune diseases: friend or foe?. J Transl Med 2023; 21(1), 1-24. Liu C, Chu D, Kalantar‐Zadeh K, George J, Young HA, Liu G. Cytokines: from clinical significance to quantification. Adv Sci 2021; 8(15), 2004433. Gao L, Cheng Z, Zhu F, Bi C, Shi Q, Chen X. The oral microbiome and its role in systemic autoimmune diseases: A systematic review of big data analysis. Front Big Data 2022; 5, 927520. Nikitakis NG, Papaioannou W, Sakkas LI, Kousvelari E. The autoimmunity–oral microbiome connection. Oral Dis 2017; 23(7), 828-839. Tables Tables 1 to 3 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.docx Table2.docx Table3.docx Cite Share Download PDF Status: Published Journal Publication published 14 Mar, 2024 Read the published version in Biomolecules and Biomedicine → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4007006","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":277835573,"identity":"0e26b5e5-d9d4-4faf-960c-8bc1c891d9f2","order_by":0,"name":"Semih SAĞLIK","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYDCCAwwMzEBKRoK9AUgZWBCvhUeC5wBIiwQpWiQSQFwitPDdPv50c8GfWh7Jmc+vbvhRIMHA396dgFeL5Lkcs9sz247zSEvnlN3sATpM4szZDXi1GJzhYbvN23CMR046J+0GD1CLgUQuIS3sz27z/AFqkTyTdvMPcVoYzG7zsNXwSEuwH7tNlC2SZ3jMbvO2HeCR7Mlhuy1jIMFD0C98EIfVyUkcP/7s5ps/NnL87b34tUDBYSDmMQCxeIhRDgJ1QMz+gFjVo2AUjIJRMMIAAPkFRy3YNvjuAAAAAElFTkSuQmCC","orcid":"","institution":"Siirt University","correspondingAuthor":true,"prefix":"","firstName":"Semih","middleName":"","lastName":"SAĞLIK","suffix":""},{"id":277835575,"identity":"02947d01-79c5-4424-a1db-41c284439d39","order_by":1,"name":"Şilan Bilek Olgaç","email":"","orcid":"","institution":"Siirt University","correspondingAuthor":false,"prefix":"","firstName":"Şilan","middleName":"Bilek","lastName":"Olgaç","suffix":""}],"badges":[],"createdAt":"2024-03-02 21:20:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4007006/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4007006/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.17305/bb.2024.10324","type":"published","date":"2024-03-14T18:04:21+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":52543186,"identity":"9661cdaf-c0f7-4dda-af88-b9f222406a6c","added_by":"auto","created_at":"2024-03-12 17:48:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":825358,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea-d:\u003c/strong\u003e A 34-year-old woman (a) with idiopathic granulomatous mastitis who presented with pain, swelling and erythema in the areolar region of the left breast. On USG examination, an irregular hypoechoic lesion (circle) in the breast tissue, an area of collection (star) consistent with a superficial abscess under the skin and a lymph node showing asymmetric cortical thickening (open arrow) in the axilla (b,c). USG-guided tru-cut biopsy of an irregular hypoechoic lesion (closed arrow) in the same patient (d).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4007006/v1/2c10b281f3a9b3af1eb74f77.png"},{"id":52543187,"identity":"a6b88eb8-9c35-49dc-923b-f0f913834456","added_by":"auto","created_at":"2024-03-12 17:48:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":683189,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea-d:\u003c/strong\u003e USG-guided tru-cut biopsy of lesions in the breast parenchyma from four different patients with idiopathic granulomatous mastitis.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4007006/v1/ed0badb3304347828fe0dd6f.png"},{"id":52543189,"identity":"03fdd649-b08e-4886-8cf9-7ffb523e81b1","added_by":"auto","created_at":"2024-03-12 17:48:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":127823,"visible":true,"origin":"","legend":"\u003cp\u003eBox plots A and B show the comparison of OHI-S and DMFT index values between groups. The horizontal lines inside each box represent the mean values and the lower and upper rows of each box represent the minimum and maximum values, respectively.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4007006/v1/575884b61549f8f4d49c4c8e.png"},{"id":52784175,"identity":"b67b60d8-bd35-4de6-a84b-33ca37d5c898","added_by":"auto","created_at":"2024-03-15 18:04:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1678128,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4007006/v1/91f45d4e-78fe-4b8d-ab22-7b73a904f2f2.pdf"},{"id":52543185,"identity":"078e4472-b6d6-42bf-9727-cc52f8ef2808","added_by":"auto","created_at":"2024-03-12 17:48:52","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":14402,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4007006/v1/e80db07aa5e7d7450035289a.docx"},{"id":52543470,"identity":"2ced88c3-16a8-4870-b0d4-d4b4e429f3b4","added_by":"auto","created_at":"2024-03-12 17:56:53","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":15292,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-4007006/v1/fdc6801594103bb2a155df83.docx"},{"id":52543191,"identity":"33d19ede-f93a-4b6c-9c1d-0f2aad2035bb","added_by":"auto","created_at":"2024-03-12 17:48:53","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":14926,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-4007006/v1/3aef234f2f00cba350a00b11.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Is poor oral health a risk factor for idiopathic granulomatous mastitis?","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eIdiopathic granulomatous mastitis (IGM) is a rare inflammatory disease of the breast which clinically and radiologically may be confused with carcinoma [1].\u0026nbsp;It was first described by Kessler and Wolloch in 1972 [2]. Clinically, it most commonly manifests with breast pain, skin erythema, palpable mass, nipple retraction, oedema, ulceration and fistula [3]. It frequently shows unilateral involvement and has a recurrence rate of 16-50%.\u0026nbsp;Since it clinically and radiologically mimics malignant lesions, histopathological examination is necessary for differential diagnosis [4].\u0026nbsp;Although the etiology of IGM is still uncertain, it is stated that it may be related with pregnancy, lactation, hormonal imbalance, autoimmunity, smoking, \u0026alpha;1-antitrypsin deficiency and various microorganisms [3,5].\u0026nbsp;The definitive diagnosis of IGM is possible by excluding histopathological features as well as secondary causes which lead to granulomatous inflammation such as sarcoidosis, granulomatous polyangiitis, tuberculosis and fungal infection\u0026nbsp;[5]. On histopathological examination, the diagnosis is made with the detection of non-caseified multiple granulomas with inflammatory reaction disrupting the breast lobules [6].\u003c/p\u003e\n\u003cp\u003ePoor oral health is recognised as an important public health problem worldwide. Numerous epidemiological studies have shown that alterations in the oral microbiome not only affect the presence and severity of oral lesions but are also associated with various systemic diseases [7-16]. The oral microbiota (OMB) may cause systemic disease through various mechanisms. Among the most accepted ones are the spread of oral infection outside the oral cavity, inclusion of microbial toxins into the systemic circulation and systemic inflammation caused by immunological reactions against soluble pathogen antigens [17,18].\u003c/p\u003e\n\u003cp\u003eThe aim of this study is to evaluate the relationship between idiopathic granulomatous mastitis and oral health.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS ","content":"\u003cp\u003eOur study included 42 female patients who were evaluated ultrasonographically (USG) between September 2018 and October 2023, and were diagnosed with IGM as a result of clinical, laboratory, radiological and histopathological evaluations, each of which had a USG-guided tru-cut breast biopsy. Hematoxylin+Eosin (H+E) staining for histopathological examination, Gram staining for the detection of microorganisms, Ziehl-Neelsen (ZN) staining for tuberculosis and Periodic acid-Schiff (PAS) staining for fungal infection were performed on all pathological preparations to exclude secondary granulomatous mastitis agents. In addition, serum ACE level and chest X-ray were analysed for sarcoidosis, C-ANCA PR-3 levels and spot urine protein/creatinine ratio by ELISA and immunofluorescence for granulomatous polyangiitis. Patients with a history of trauma or foreign body were not included in the study. Breast biopsy tissue samples of the patients showed chronic active inflammation as well as inflammatory cells including polymorphonuclear leukocytes, lymphocytes, plasma cells and granuloma structures consisting of epithelioid histiocytes and multinuclear giant cells. The reference group consisted of 47 female patients with clinically, radiologically and laboratory proven non-specific mastitis and 36 healthy female\u0026nbsp;persons. Patients with systemic disease, periodontal treatment within the last six months, history or suspicion of known malignancy, diabetes mellitus, previous tuberculosis or contact history and recently vaccinated tetanus patients were excluded.\u003c/p\u003e\n\u003cp\u003eOral examinations were performed by an experienced dentist after informed consent was obtained from all individuals included in the study. In our study, \u0026quot;Decayed, Missing and Filled Teeth\u0026quot; (DMFT) and \u0026quot;Simplified Oral Hygiene Index\u0026quot; (OHI-S) indices were used to evaluate oral health. The DMFT index is calculated by considering the number of decayed, missing and filled teeth reflecting the prevalence of caries [19]. While calculating the DMFT index, the condition of all teeth was determined by clinical and radiographic evaluation. It was calculated by summing the number of untreated caries (Decayed-D), missing teeth (Missing-M) and filled teeth (Filled-F). If a tooth had both caries and filling, only one was scored.\u003c/p\u003e\n\u003cp\u003eOHI-S index is an index system that reflects the oral hygiene status of the individual and consists of plaque and calculus components. In this index system, 3 regions including right-posterior region, left-posterior region and anterior region are evaluated in the lower and upper jaw [20]. In total, 12 separate measurements for both plaque and calculus were performed on 6 teeth. In our study, buccal surfaces of upper first molars, lingual surfaces of lower first molars, and labial surfaces of upper right and lower left incisors were evaluated. Plaque and calculus indices were calculated separately and the sum was obtained as oral hygiene index.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSPSS 20.0 software (Statistical Package for the Social Sciences, Chicago, IL) is used for data analysis. Data related to qualitative variables are expressed as number (n) and percentage (%), and quantitative variables are expressed as mean (mean) \u0026plusmn; and standard deviation (sd).\u003c/p\u003e\n\u003cp\u003eIn the evaluation of the study data, whether the continuous variables were normally distributed is analysed by Shapiro-Wilk test. \u0026nbsp;Student-t test is used for pairwise independent group comparisons and one-way anaova for comparisons of more than two groups followed by TUKEY test for intergroup differences. Depending on the sample sizes, the Chi-square test or Fisher\u0026rsquo;s exact test were performed for categorical variables. The relationship between all quantities is analysed by Pearson correlation coefficient. \u0026nbsp;The significance level for statistical results is accepted as p\u0026lt;0.05.\u0026nbsp;\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe ages of the IGM patients included in the study ranged between 29-51 years (mean age 34.88\u0026plusmn;4.87). The most common clinical findings were pain (n=38), palpable breast mass (n=32), erythema (n=22), induration (n=14) and dermal sinus (n=10) (Figure 1). While bilateral breast involvement was not observed in any patient, 25 patients had right breast involvement and 17 patients had left breast involvement. USG was performed in all patients and mammography was performed in two patients. All patients with IGM underwent USG-guided tru-cut biopsy for both diagnosis and malignancy exclusion and the diagnosis was confirmed histopathologically (Figure 2). Clinical and ultrasonographic findings of the patients are shown in table 1.\u003c/p\u003e\n\u003cp\u003eThe cases included in the study were categorised into three groups. Group 1 included healthy female subjects without any known systemic and breast disease, group 2 included female patients with clinical, radiological and laboratory diagnosis of non-specific mastitis and group 3 included female patients with histopathological diagnosis of IGM. The smoking history, menopausal status, lactation and hormonal contraceptive use history, pregnancy history, body mass index (BMI) values and external brushing habits of the individuals in all three groups are given in table 2.\u003c/p\u003e\n\u003cp\u003eWhen the OHI-S and DMFT index values of the individuals in the groups were compared, both OHI-S and DMFT index values of the individuals diagnosed with IGM were statistically significantly higher than the individuals in group 1 and group 2 (p\u0026lt;0.05). No statistically significant difference was found between group 2 and group 3 in both OHI-S and DMFT index values (p=0.820, p=0.980, respectively) (Table 3 and Figure 3).\u0026nbsp;\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study was conducted to investigate whether OHI-S and DMFT index values, which are oral health indicators, are associated with IGM. The main finding was that these indices were statistically significantly higher in patients with IGM compared with reference group individuals. \u0026nbsp;Age, BMI, menopausal status, breastfeeding, pregnancy, oral contraceptives, smoking history and tooth brushing habits were not significantly different between the three groups.\u003c/p\u003e\n\u003cp\u003eAlthough IGM is frequently observed in young middle ages (3rd and 4th decade), it has been reported in the literature that it may be observed in a wider age range (11-83 years) [3]. \u0026nbsp;In our study, the mean age of our IGM cases was 34 years, which was consistent with the literature. Although IGM is usually seen in young women with a history of lactation, male cases have rarely been reported in the literature [21].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIGM may present clinically with different symptoms and clinical findings including painful or painless palpable mass, skin redness, tenderness, sinus formation, ulcer, nipple discharge and abscess [22,23]. The most common clinical finding is palpable painful mass [4,22]. \u0026nbsp;In our study, the most common clinical finding in patients with IGM was palpable painful breast mass. Fever is generally not an expected symptom [24]. In our study, none of the patients diagnosed with IGM had fever septoma or finding. \u0026nbsp; In IGM, unilateral breast involvement is usually observed with right breast predominance and rarely bilateral involvement is observed [1,4-6]. \u0026nbsp;In our study, all IGM patients had unilateral involvement with right breast dominance.\u003c/p\u003e\n\u003cp\u003eVarious factors including autoimmunity, oral contraceptive use, infectious agents, hormonal imbalances, pregnancy, hyperprolactinaemia, alpha-1 antitrypsin deficiency have been accused in the aetiology of IGM, but none of these have been proven [1,3,5,22,23]. Since it usually affects women in the reproductive age group with a history of pregnancy and lactation, it has been thought that these factors may be the main underlying causes in the aetiology [5,25,26]. \u0026nbsp;In lactation, it is thought that extravasation of secretion damages the epithelium and triggers granulomatous inflammatory response [27]. \u0026nbsp;However, the presence of male patients in the literature as well as a wide age range (11-83 years) and patients without a history of lactation show that only lactation and pregnancy cannot be held responsible in the etiology [3,28,29]. On the other hand, the fact that 5 patients (11,9%) had no history of lactation and 1 patient (2,5%) was in the postmenopausal period in our study indicates the presence of other risk factors in the etiology.\u003c/p\u003e\n\u003cp\u003eAnother factor blamed in the etiology is the use of oral contraceptives (OCS), which is considered a potential risk factor because they increase breast secretion. Binesh et al. reported that the frequency of OCS use in IGM was 36% [30]. \u0026nbsp;Aghajanzadeh et al. reported that OCS users were more prone to IGM infection [31]. \u0026nbsp;However, Altintoprak et al. found that the relationship between IGM and OCS varied between 0-42% and therefore, there was no significant relationship between OCS and IGM (3). In our study, the presence of a history of oral contraceptive use in only 28,5% (12 patients) of our IGM patients reduces the role of this factor in the etiology.\u003c/p\u003e\n\u003cp\u003eSmoking is one of the other factors accused in the etiology of the disease. Since the relationship between smoking and IGM varies between 0-77% in literature studies, it is not yet possible to mention that smoking is an etiological factor [32,33]. \u0026nbsp;Asoglu et al. [32] reported that 77% of patients with IGM had a history of smoking, whereas Baslaim et al. [33] reported that none of the patients with IGM had a history of smoking. In addition, Prasad et al. [34] reported that only 2 patients (2,74%) had a history of smoking in a study conducted in 73 patients. In our study, only 5 patients (11,9%) had a history of smoking, which makes it difficult for smoking to be an etiological risk factor.\u003c/p\u003e\n\u003cp\u003eAutoimmunity has been the most accepted theory in the etiology because of good response to steroid and immunosuppressive therapies in the treatment of IGM. In addition, immunohistochemical demonstration of T-lymphocyte predominance in biopsy specimens in literature studies supports this view [29,35,36]. It has been reported that autoimmune response to fat or protein-rich secretion extravasated from breast lobules may cause chronic inflammation [37]. \u0026nbsp;Especially T cell-mediated inflammation has been held responsible for non-caseified granuloma formation [35]. \u0026nbsp; However, an etiological cause that would trigger this mechanism has not been identified [38]. \u0026nbsp;In the literature, the association of autoimmune diseases including erythema nodosum, rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE) and psoriasis with IGM has been mentioned, but this constitutes only a small portion of all cases [39-41]. In our study, one patient had psoriasis and two patients had rheumatoid arthritis, which constituted only 7,1% of all patients.\u003c/p\u003e\n\u003cp\u003eSome microbiological agents have been accused in the etiology of IGM. Some bacterial species, especially \u003cem\u003eCorynebacterium, Streptococci\u003c/em\u003e and \u003cem\u003ePropionibacterium\u003c/em\u003e have been isolated histopathologically. The most frequently isolated species is \u003cem\u003eCorynebacterium\u003c/em\u003e species [42-45]. In a study conducted by Taylor et al. [46] on 62 patients, \u003cem\u003eCorynebacterium\u003c/em\u003e species were isolated in 55% of the cases and fever and fistula were observed more frequently in these cases. However, since \u003cem\u003eCorynebacterium\u003c/em\u003e species are members of normal skin flora, it is not possible to distinguish whether these organisms cause infection or contamination [47]. \u0026nbsp;However, it has been reported in the literature that no microbiological agent positivity was detected in molecular-based analyses performed on many flora bacteria and the most common infective agents and no growth was found in culture samples [3,48]. \u0026nbsp;In addition, the role of bacteriological agents in the etiology of IGM is reduced because IGM patients do not benefit from antibiotic treatment and clinical improvement is not achieved. In our study, we did not detect any bacteriological agent in culture samples obtained from IGM cases.\u003c/p\u003e\n\u003cp\u003eSince there is no typical imaging finding in the diagnosis of IGM, it is difficult to make a diagnosis with radiological methods [49]. USG is the first preferred imaging method because the patient population is young [50]. \u0026nbsp;Hypoechoic, heterogeneous lesions with tubular configuration, hypoechoic mass with lobule contour, multiloculated abscess collections, fistulisation to the skin or axillary lymphadenopathy may be visualised on ultrasonography [29]. \u0026nbsp;Doppler USG examination usually shows increased vascularity in the affected breast parenchyma [51]. \u0026nbsp;Mammography is recommended to exclude microcalcifications in cases of suspected malignancy, but usually does not provide specific information. Microcalcifications are generally not an expected imaging finding in patients with IGM [50,52]. \u0026nbsp;The most common imaging findings on USG examination in our patients included hypoechoic, heterogeneous, tubular lesions in 28,5% (12 patients), multiloculated abscess collections in 23,8% (10 patients), and a well-circumscribed hypoechoic mass lesion in 19% (8 patients). We also detected axillary lymphadenopathy in 14,2% (6 patients).\u003c/p\u003e\n\u003cp\u003eSince diagnosis with imaging findings may lead to misdiagnosis and treatment, histopathological examination is essential for definitive diagnosis. Fine needle aspiration biopsy (FNAB) is a low-sensitivity method with a limited diagnostic role [53]. \u0026nbsp;In the literature, studies have been conducted on patients who were misdiagnosed as carcinoma by FNAB and therefore were treated incorrectly [54-56]. Therefore, tru-cut biopsy or extensive breast tissue sampling is required for diagnosis [57]. \u0026nbsp;In all of our IGM patients, the diagnosis was made by tru-cut biopsy and the patients were followed up and treated accordingly.\u003c/p\u003e\n\u003cp\u003eThe oral cavity provides an ideal environment for microorganisms due to temperature, humidity and nutrient abundance [58]. \u0026nbsp;There is a dynamic interaction between these microorganisms and the organism and if this balance is disturbed for any reason, it may cause microbial imbalance called dysbiosis [59,60]. In case of dysbiosis, some microbial colonies become more widespread and may cause pathogenic effects on the organism [60]. \u0026nbsp;It has been shown that dysbiotic change may cause local diseases such as dental caries and periodontal disease and may be involved in the etiology of a number of systemic diseases such as cardiovascular disease, pneumonia, malignancy, diabetes, obesity, autoimmune disease, cystic fibrosis, cerebral or hepatic abscesses [8-16].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePoor oral hygiene predisposes to the colonisation of pathogenic microorganisms in periodontal tissues. Since periodontal tissues are anatomically close to the blood circulation, endotoxins and/or cytokines released from these pathogenic microorganisms directly or indirectly pass into the systemic circulation, causing bacteraemia and inflammation in distant organs [17,61,62]. It has been found that systemic concentrations of some proinflammatory cytokines increase in case of periodontal inflammation and serum values of these biomarkers decrease significantly after treatment [61,63,64]. Therefore, poor oral health affects not only periodontal inflammatory processes but also systemic inflammatory status.\u003c/p\u003e\n\u003cp\u003ePeriodontal inflammation or chronic bacteraemia predisposes to the development of a systemic immune reaction. In recent studies, P. gingivalis and T. denticola have been found to trigger a systemic immune response [65,66]. Some periodontal pathogens have been shown to exacerbate various microvascular complications such as nephropathy, retinopathy and neuropathy in patients with diabetes and to increase cardiorenal mortality twofold [62,67]. Some periodontal pathogens, especially \u003cem\u003eF. nucleatum\u003c/em\u003e, have been shown to cause adverse pregnancy outcomes such as low birth weight or stillbirth [68,69]. Cestari et al. [70] reported that periodontal inflammation predisposes to Alzheimer\u0026apos;s disease and proinflammatory cytokines are increased in these patients. Zhang et al. [71] suggested that some periodontal pathogens initiate a systemic inflammatory response via haematogenous pathway in mouse models and may subsequently lead to systemic osteoporosis. Bernhard et al. [72] suggested that due to the detection of abundant periodontal pathogens in subgingival biofilm samples taken from breast cancer cases, the inflammation caused by these pathogens may indirectly contribute to breast cancer. Sfreddo et al. [73] \u0026nbsp;reported that the risk of developing breast cancer in women diagnosed with periodontitis was two to three times higher than in healthy control group women. Silva et al. [12] suggested that a strain variant of S. constellatus in the periodontal pocket formed through genetic recombination may have the potential to form abscesses in the brain. Additionally, numerous studies have shown that periodontal inflammation plays an active role in triggering or exacerbating autoimmune diseases such as SLE, primary sclerosing cholangitis, RA, Sj\u0026ouml;gren\u0026apos;s syndrome and autoimmune hepatitis [74-77].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo the best of our knowledge, this is the first study to examine the relationship between poor oral health and IGM. In this study, OHI-S index values indicating oral hygiene deficiency and DMFT index values indicating poor oral health were found to be higher in patients with histopathological diagnosis of IGM compared to patients without this diagnosis, which led us to associate IGM with poor oral health.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn conclusion, our findings suggest that poor oral health may be involved in the etiology of IGM. Therefore, it may be useful to consider oral health in the etiology of IGM in future studies and to investigate oral microbiota in samples taken from the target tissue. In addition, if our findings are confirmed in future studies with a larger number of patients, precautions and information about poor oral health may help to reduce the incidence of IGM.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles of the Declaration of Helsinki. Ethics Committee Approval was obtained from the Siirt University Non-Invasive Ethics Committee ( Decision No: 86081).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the study participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no financial support for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to express our sincere gratitude to all parties who generously contributed to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors equally contribute to the present manuscript preparation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research data of this study can be requested from the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eMartinez‐Ramos D, Simon‐Monterde L, Suelves‐Piqueres C, Queralt‐Martin R, Granel‐Villach L, Laguna‐Sastre JM et al. 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Oral Dis 2017; 23(7), 828-839.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Idiopathic granulomatous mastitis, Oral Health, Dental health, “Decayed, Missing and Filled Teeth” (DMFT) , “Simplified Oral Hygiene Index” (OHI-S)","lastPublishedDoi":"10.21203/rs.3.rs-4007006/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4007006/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eOBJECTIVE:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIdiopathic granulomatous mastitis is a rare inflammatory disease of the breast that clinically and radiologically can be confused with carcinoma. Although its etiology remains unclear, it is stated that it may be related to pregnancy, lactation, hormonal imbalance, autoimmunity, smoking, α1-antitrypsin deficiency and various microorganisms. This study aimed to evaluate the relationship between idiopathic granulomatous mastitis and oral health.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePATIENTS AND METHODS:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study included 42 female patients diagnosed with idiopathic granulomatous mastitis as a result of histopathological evaluations between September 2018 and October 2023. The reference group consisted of 47 female patients with clinically, radiologically and laboratory proven non-specific mastitis and 36 healthy female individuals. The oral health of all individuals included in the study was evaluated by an experienced dentist using \"Decayed, Missing and Filled Teeth\" (DMFT) and \"Simplified Oral Hygiene Index\" (OHI-S) index values.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRESULTS:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ages of idiopathic granulomatous mastitis patients included in the study ranged between 29-51 years (mean age 34.88±4.87). The most common clinical findings were pain (n=38), palpable breast mass (n=32), erythema (n=22), induration (n=14) and dermal sinus (n=10). When OHI-S and DMFT index values of the individuals included in the study were compared, both OHI-S and DMFT index values of individuals diagnosed with idiopathic granulomatous mastitis were statistically significantly higher than those of the reference group (p\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONCLUSIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur findings suggest that poor oral health may be involved in the etiology of idiopathic granulomatous mastitis. Therefore, it may be useful to consider oral health in the etiology of IGM in future studies and to investigate oral microbiota in samples obtained from the target tissue.\u003c/p\u003e","manuscriptTitle":"Is poor oral health a risk factor for idiopathic granulomatous mastitis?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-12 17:48:48","doi":"10.21203/rs.3.rs-4007006/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2e4cdc39-e80c-47cd-8787-ef6eb2ebf77b","owner":[],"postedDate":"March 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-03-15T18:04:21+00:00","versionOfRecord":{"articleIdentity":"rs-4007006","link":"https://doi.org/10.17305/bb.2024.10324","journal":{"identity":"biomolecules-and-biomedicine","isVorOnly":true,"title":"Biomolecules and Biomedicine"},"publishedOn":"2024-03-14 18:04:21","publishedOnDateReadable":"March 14th, 2024"},"versionCreatedAt":"2024-03-12 17:48:48","video":"","vorDoi":"10.17305/bb.2024.10324","vorDoiUrl":"https://doi.org/10.17305/bb.2024.10324","workflowStages":[]},"version":"v1","identity":"rs-4007006","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4007006","identity":"rs-4007006","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}