Oral GVHD Post-Cardiac Xenograft Valve Replacement: A Case Report

Oral GVHD Post-Cardiac Xenograft Valve Replacement: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Oral GVHD Post-Cardiac Xenograft Valve Replacement: A Case Report Sarah M. Nizar Feteih, Mohammed S. Shihata This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5191347/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Dec, 2024 Read the published version in Journal of Cardiothoracic Surgery → Version 1 posted 11 You are reading this latest preprint version Abstract Background: Graft versus host disease (GVHD) is an autoimmune disease that affects the oral cavity as well as other parts of the body. Oral GVHD occurs in 45%–83% of cases, and chronic GVHD observed in 30%–50% of cases usually manifests as an oral presentation. Case presentation: In this case report, a 13-year-old girl was referred to the periodontics clinic from the pediatric dentistry clinics for proper diagnosis and management of the oral presentations observed after receiving a prosthetic valve replacement 2 years post-surgery. In this study, the xenograft type used was mainly investigated, as similar soft tissue grafts are used in the oral cavity with no GVHD oral manifestations being observed. This brings about an interesting discussion of the use of xenografts in different areas of the human body, but with different presentations. Conclusions: Thus, future investigations on early diagnostic tools, including saliva or blood examinations, are needed to create preventive methods or lessen the extent of GVHD in patients. autoimmune disease graft versus host disease oral cavity tissue grafts xenografts Figures Figure 1 Background Graft versus host disease (GVHD) is an autoimmune disease that affects the oral cavity [ 1 ] as well as other body parts, such as the skin, gastrointestinal tract, and liver. Chronic graft versus host disease (cGVHD) or acute (aGVHD) occurs depending on whether the lesions occur after a given history of the patient, which could include undergoing allogeneic hematopoietic stem cell transplantation. The chronic form is observed in 30–50% of allogeneic hematopoietic stem cell transplantation cases, and typically have an oral presentation. Moreover, in 50–70% of cases, acute forms occur in allogeneic transplant patients [ 2 ]. Oral cGVHD occurs in 45–83% of cases [ 3 ]. In this form of the disease, the oral cavity is possibly the only affected area [ 5 ]. The increasing use of hematopoietic cells over bone marrow transplants, use of donors that are not fully human leukocyte antigen (HLA)-compatible[ 5 ] regardless of their blood ties to the recipient, and high number of transplants performed per year in all age groups, there is an increase in the number of elderly people suffering from GVHD [ 6 ]. According to a previous study [ 7 ], the updated list of risk factors for cGVHD includes HLA incompatibility, sex incompatibility (e.g., a male recipient and a female donor), absence of blood ties between the donor and recipient, older donors and recipients, mobilized peripheral blood transplantation, and childbirth in female donors [ 8 ]. Immunopathogenesis of the disease is not completely clear, although it is known that donor T cell reactivity against recipient cells is the main triggering factor of GVHD in the form of exacerbated inflammatory responses, direct or indirect [ 9 ]. There are general diagnostic criteria for the diagnose of cGVHD [ 10 ] considering the appearance of clinical lichenoid lesions, hyperkeratotic plaques, and limited oral apertures secondary to sclerosis. Distinctive clinical features of cGVHD entail xerostomia, appearance of mucoceles, mucosal atrophy, pseudomembranes, and ulcerations. However, such manifestations alone may not be enough for the diagnosis. Oral manifestations may also appear in the acute and chronic presentations of the disease such as mucositis, gingivitis, erythema, and pain [ 11 ]. This autoimmune reaction can be mild, moderate, or severe, depending on the organs involved, oral presentation, symptoms, and the patient’s ability to perform daily activities or limited to such in lifestyle. The establishment of specific biomarkers would facilitate early diagnostic measures for such patients [ 12 ]. Case presentation A 13-year-old girl was referred to the periodontics unit from the pediatric dentistry unit for proper diagnosis and treatment because of cGVHD oral presentations. The oral manifestations were noticed two years earlier, when she complained of halitosis; the lesions persisted. Her current medications are presented in Table 1; she has no known allergies. She was asymptomatic until the age of 8 years, and her medical history revealed the following: moderate-to-severe congenital mitral regurgitation (MR), moderate TR, and large LA. Her blood pressure during her initial visit was 112/73 mmHg. Her weight and height measurements are presented in Table 2. Her cardiac history started with a fluttering sensation of moderate intensity in the chest, and she constantly experienced shortness of breath. These symptoms were exacerbated by stress and relieved by rest. The course progressed as expected by the cardiology clinic at King Faisal Specialist Hospital and Research Center-Jeddah (KFSHRC-J), Saudi Arabia. Before that, the patient had undergone MR valve repair in 2020 at an outside hospital (KSA) followed by an assessment and diagnosis with atrial septal defect (ASD) and MR. This assessment revealed a murmur, for which the patient later underwent cardiac surgery for ASD closure, mitral valve (MV) replacement, and tricuspid valve (TV) repair (July 2021) at KFSHRC-J. Her cardiac surgical history included valvuloplasty, MV with cardiopulmonary bypass, ASD repair, secundum with cardiopulmonary bypass, with or without a patch. She visited our dental clinics in July 2021 for dental restorations and dental cleaning for her dental decay, exfoliating teeth and gingivitis, gingival recession, and calculus deposits. She was treated under conscious sedation for her proposed dental treatment under the care of pediatric dentistry for cardiac clearance before her second surgery. She periodically visited the cardiology unit and underwent several investigations, including radiography, EKG, and thyroid testing because she was underweight for her age. Her lab results revealed high TSH and FT4 levels, which were to be followed up in six months. In October 2023, the patient was referred to the periodontics unit for the diagnosis and management of such oral lesions. Upon oral examination (Figure 1), there were oral manifestations of GVHD-like lesions (reticular forms) all around the gingival and alveolar mucosa (attached photos; Feteih, 2023): (a), lower lip (labial) mucosa (b), cheek mucosa (c), tongue tip (d), and palatal marginal gingiva and (e) upper labial mucosa. Considering the patient’s history of cardiac surgery with soft tissues for valve replacement, along with the chronicity of stay and occurrence of oral lesions thereafter (2 years ago), GVHD as an oral manifestation was suspected. The child and her father denied involvement of any other body part in manifestation of symptoms. The patient underwent a thorough oral exam, and the photos and radiographs were taken with the patient’s consent. Upon cardiology consultation, her soft tissue valve replacement (xenograft: bovine origin, instead of mechanical valves) was discussed to prevent the lifelong use of anticoagulants (e.g., Coumadin), helping patients in that matter, along with the results obtained with soft tissue valve grafts, and discussions regarding whether such a thing has been encountered before. The cardiologist confirmed seeing another rare case which was much more severe and that this patient would be followed up regularly at the cardiology unit as the following was rendered in October 2023 (Tables 3 and 4). Chronic Problems Previously Documented Congenital MR Generalized gingival recessions, inflammation, and halitosis. Assessment Summary Moderate-to-severe MR, moderate TR, and large LA. S/P MV repair in Makkah a year earlier (2020). S/P MV replacement (Tissue Valve) and TV repair on July 12, 2021. Current Cardiac Complaints No current cardiac complaints and the patient is doing well. Echocardiography Bioprosthesis was observed in the mitral position with good opening and mobility, with a peak and mean PG of 12 mmHg and 7 mmHg, respectively. Trace MR MR. No TS. Mild+ TR with a PSPG of 16 mmHg No AS. No AI. No PS. Trace PI with an end-diastolic velocity of 149 cm/s Dilated LA. Moderately depressed LV systolic dysfunction with an EF of 50% by M‐mode and 51% by Simpson’s method. Mildly depressed RV function. No pericardial effusion. Otherwise, for oral lesions, oral local gels or mouthwashes containing corticosteroids would be permissible and would not affect her cardiac situation, and the soft tissue valve would remain in place, as the patient’s cardiac condition is stable. Moreover, from a cardiovascular perspective, the patient would be fit for dental procedures as long as SBE prophylaxis (2 gm of amoxicillin 1 h before the intervention) is practiced, and the patient would continue on the same medication for six months. Dental Treatment Plan The patient was referred for a dental cleaning, after an initial consultation with periodontics for the oral presentations referred for. Oral hygiene instructions (OHI) including (but not limited to) tongue scraping/cleaning were addressed along with periodic follow-ups with periodontics for monitoring oral such lesions along OHI reinforcement. Oral rinses or topical corticosteroid were prescribed accordingly for the manifestations after her cardio follow-up. The patient was periodically followed up for 8 months from the initial oral exam, and the manifestations expressed were stable. Discussion and Conclusions GVHD is known to occur in allograft transplants; however, in this case report the use of soft tissue valves as xenografts, which may induce expositions similar to allografts, lead to oral presentations, which are rare. A study reported “the importance of glutaraldehyde in decreasing the immune response” with the use of xenograft prosthetic valves (e.g., bovine, porcine) [ 13 ]. This would give rise to substantial discussions regarding the identification of biomarkers that would help in the early detection of cGVHD to help reduce its manifestations as much as possible in its earlier stages, as it triggers the immune system, and it is yet unclear how it exerts its effect within the human body, as complex and dynamic as it is. Despite the increased demand for the use of xenografts and allografts as graft materials in dentistry, and the use of bone or tissue grafts in a highly vascular region (oral cavity) are known to yield positive results and better soft tissue healing with some materials; nonetheless, GVHD is not usually observed with the use of such materials. Thus, such a report remains an interesting topic for further discussion, from an immunologic perspective along other specialties, to generate lab explorations for future prevention or decreasing its displays. Abbreviations ASD Atrial septal defect HSCT Hematopoietic stem cell transplantation MR Mitral regurgitation MV Mitral valve OHI Oral hygiene instructions TV Tricuspid valve Declarations There are no financial nor non-financial conflicts, including and not limited to, relationships such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; expert testimony or patent-licensing arrangements. Non-financial conflicts include personal or professional relationships, affiliations, academic competition, intellectual passion, knowledge or beliefs that might affect objectivity. Ethics approval and consent to participate This study was approved by the Human Subjects Ethics Board of King Faisal Specialist Hospital and Research Center - Jeddah (IRB approval no. 2023-CR-34) and was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2013. The patient’s guardian had a written informed consent obtained for the publication of these. Consent for publication All the needed documents have been granted the consent for publication. Availability of data and materials All data are available upon request. Competing interests The authors declare that they have no competing interests. Funding None. Equipment and Medications supplied by King Faisal Specialist Hospital and Research Centre, Jeddah. There are no known financial relationships between any author and commercial firm that may pose any conflict of interest. Authors’ contributions All authors have made substantial contributions to conception and design of the study. SMNF have been involved in data collection and data analysis. SMNF have been involved in data interpretation. SMNF have been involved in drafting the manuscript. SMNF, MSS have been involved in revising the manuscript critically and have given final approval of the version to be published. Acknowledgements Special thanks to Amany Al-Semiery for referring this patient case from her pediatric unit and to the entire Cardiac team for their support at KFSHRC,J. Authors’ information As supplemented from authors. Declaration of generative AI and AI-assisted technologies in the writing process During the preparation of this work the author(s) used [Enago] in order to [improve the quality of the written paper and proof read it to ensure it is devoid from plagiarism]. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication. References Treister NS, Cook EF Jr, Antin J, Lee SJ, Soiffer R, Woo SB. Clinical evaluation of oral chronic graft-versus-host disease. Biol Blood Marrow Transpl. 2008;14:110–5. Elad S, Zeevi I, Or R, Resnick IB, Dray L, Shapira MY. Validation of the National Institutes of Health (NIH) scale for oral chronic graft-versus-host disease (cGVHD). Biol Blood Marrow Transpl. 2010;16:62–9. Mays JW, Fassil H, Edwards DA, Pavletic SZ, Bassim CW. Oral chronic graft-versus-host disease: current pathogenesis, therapy, and research. Oral Dis. 2013;19:327–46. Treister NS, Cook EF Jr, Antin J, Lee SJ, Soiffer R, Woo SB. Clinical evaluation of oral chronic graft-versus-host disease. Biol Blood Marrow Transpl. 2008;14:110–5. Kuten-Shorrer M, Woo SB, Treister NS. Oral graft-versus-host disease. Dent Clin North Am. 2014;58:351–68. Linhares YP, Pavletic S, Gale RP, Chronic GVHD. Where are we? Where do we want to be? Will immunomodulatory drugs help? Bone Marrow Transpl. 2013;48:203–9. Margaix-Muñoz M, Bagán JV, Jiménez Y, Sarrión MG, Poveda-Roda R. Graft-versus-host disease affecting oral cavity. A review. J Clin Exp Dent. 2015;7:e138–45. Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009;373:1550–61. Meier JK, Wolff D, Pavletic S, Greinix H, Gosau M, Bertz H. Oral chronic graft-versus-host disease: report from the International Consensus Conference on clinical practice in cGVHD. Clin Oral Investig. 2011;15:127 – 39. Dignan FL, Amrolia P, Clark A, Cornish J, Jackson G, Mahendra P. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol. 2012;158:46–61. de la Rosa García E, Bologna Molina R, Vega González Tde J. Graft-versus-host disease, an eight-case report and literature review. Med Oral Patol Oral Cir Bucal. 2006;11:e486–92. Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transpl. 2015;21:389–401. Manji RA, Lee W, Cooper DKC. Xenograft bioprosthetic heart valves: past, present and future. Int J Surg. 2015;23:280–84. Tables Table 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table14.docx Cite Share Download PDF Status: Published Journal Publication published 26 Dec, 2024 Read the published version in Journal of Cardiothoracic Surgery → Version 1 posted Editorial decision: Revision requested 18 Nov, 2024 Reviews received at journal 29 Oct, 2024 Reviews received at journal 26 Oct, 2024 Reviewers agreed at journal 22 Oct, 2024 Reviews received at journal 19 Oct, 2024 Reviewers agreed at journal 18 Oct, 2024 Reviewers agreed at journal 16 Oct, 2024 Reviewers invited by journal 16 Oct, 2024 Editor assigned by journal 03 Oct, 2024 Submission checks completed at journal 03 Oct, 2024 First submitted to journal 02 Oct, 2024 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5191347","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":379665631,"identity":"50ac8ca4-2bc2-4e22-b5b4-610c09aa3547","order_by":0,"name":"Sarah M. 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Shihata","email":"","orcid":"","institution":"King Faisal Specialist Hospital and Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"S.","lastName":"Shihata","suffix":""}],"badges":[],"createdAt":"2024-10-02 07:38:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5191347/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5191347/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13019-024-03200-0","type":"published","date":"2024-12-26T15:57:44+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":71478020,"identity":"89c945df-e207-4e2d-ae5f-a1638a8c0f45","added_by":"auto","created_at":"2024-12-16 05:28:12","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":126295,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"FinalPhotosGraftvsHostDiseasejpeg.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5191347/v1/e80363868b3a8414a57d691b.jpg"},{"id":72641134,"identity":"c3e4d99e-c6aa-496d-a389-4012cb03e97a","added_by":"auto","created_at":"2024-12-30 16:11:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":448226,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5191347/v1/7fb01550-afad-4b58-b9e7-a46c1612b5e1.pdf"},{"id":71478019,"identity":"8d808982-0a5a-4ba5-9501-e6665fc45422","added_by":"auto","created_at":"2024-12-16 05:28:11","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":43895,"visible":true,"origin":"","legend":"","description":"","filename":"Table14.docx","url":"https://assets-eu.researchsquare.com/files/rs-5191347/v1/36fe681e10006bfb8cf694ea.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Oral GVHD Post-Cardiac Xenograft Valve Replacement: A Case Report","fulltext":[{"header":"Background","content":"\u003cp\u003eGraft versus host disease (GVHD) is an autoimmune disease that affects the oral cavity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] as well as other body parts, such as the skin, gastrointestinal tract, and liver. Chronic graft versus host disease (cGVHD) or acute (aGVHD) occurs depending on whether the lesions occur after a given history of the patient, which could include undergoing allogeneic hematopoietic stem cell transplantation. The chronic form is observed in 30\u0026ndash;50% of allogeneic hematopoietic stem cell transplantation cases, and typically have an oral presentation. Moreover, in 50\u0026ndash;70% of cases, acute forms occur in allogeneic transplant patients [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOral cGVHD occurs in 45\u0026ndash;83% of cases [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In this form of the disease, the oral cavity is possibly the only affected area [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe increasing use of hematopoietic cells over bone marrow transplants, use of donors that are not fully human leukocyte antigen (HLA)-compatible[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] regardless of their blood ties to the recipient, and high number of transplants performed per year in all age groups, there is an increase in the number of elderly people suffering from GVHD [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAccording to a previous study [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], the updated list of risk factors for cGVHD includes HLA incompatibility, sex incompatibility (e.g., a male recipient and a female donor), absence of blood ties between the donor and recipient, older donors and recipients, mobilized peripheral blood transplantation, and childbirth in female donors [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eImmunopathogenesis of the disease is not completely clear, although it is known that donor T cell reactivity against recipient cells is the main triggering factor of GVHD in the form of exacerbated inflammatory responses, direct or indirect [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere are general diagnostic criteria for the diagnose of cGVHD [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] considering the appearance of clinical lichenoid lesions, hyperkeratotic plaques, and limited oral apertures secondary to sclerosis. Distinctive clinical features of cGVHD entail xerostomia, appearance of mucoceles, mucosal atrophy, pseudomembranes, and ulcerations. However, such manifestations alone may not be enough for the diagnosis. Oral manifestations may also appear in the acute and chronic presentations of the disease such as mucositis, gingivitis, erythema, and pain [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis autoimmune reaction can be mild, moderate, or severe, depending on the organs involved, oral presentation, symptoms, and the patient\u0026rsquo;s ability to perform daily activities or limited to such in lifestyle. The establishment of specific biomarkers would facilitate early diagnostic measures for such patients [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 13-year-old girl was referred to the periodontics unit from the pediatric dentistry unit for proper diagnosis and treatment because of cGVHD oral presentations. The oral manifestations were noticed two years earlier, when she complained of halitosis; the lesions persisted.\u003c/p\u003e\n\u003cp\u003eHer current medications are presented in Table 1; she has no known allergies. She was asymptomatic until the age of 8 years, and her medical history revealed the following: moderate-to-severe congenital mitral regurgitation (MR), moderate TR, and large LA. Her blood pressure during her initial visit was 112/73 mmHg. Her weight and height measurements are presented in Table 2. Her cardiac history started with a fluttering sensation of moderate intensity in the chest, and she constantly experienced shortness of breath. These symptoms were exacerbated by stress and relieved by rest. The course progressed as expected by the cardiology clinic at King Faisal Specialist Hospital and Research Center-Jeddah (KFSHRC-J), Saudi Arabia. Before that, the patient had undergone MR valve repair in 2020 at an outside hospital (KSA) followed by an assessment and diagnosis with atrial septal defect (ASD) and MR. This assessment revealed a murmur, for which the patient later underwent cardiac surgery for ASD closure, mitral valve (MV) replacement, and tricuspid valve (TV) repair (July 2021) at KFSHRC-J.\u003c/p\u003e\n\u003cp\u003eHer cardiac surgical history included valvuloplasty, MV with cardiopulmonary bypass, ASD repair, secundum with cardiopulmonary bypass, with or without a patch. She visited our dental clinics in July 2021 for dental restorations and dental cleaning for her dental decay, exfoliating teeth and gingivitis, gingival recession, and calculus deposits. She was treated under conscious sedation for her proposed dental treatment under the care of pediatric dentistry for cardiac clearance before her second surgery. She periodically visited the cardiology unit and underwent several investigations, including radiography, EKG, and thyroid testing because she was underweight for her age. Her lab results revealed high TSH and FT4 levels, which were to be followed up in six months.\u003c/p\u003e\n\u003cp\u003eIn October 2023, the patient was referred to the periodontics unit for the diagnosis and management of such oral lesions. Upon oral examination (Figure 1), there were oral manifestations of GVHD-like lesions (reticular forms) all around the gingival and alveolar mucosa (attached photos; Feteih, 2023): (a), lower lip (labial) mucosa (b), cheek mucosa (c), tongue tip (d), and palatal marginal gingiva and (e) upper labial mucosa.\u003c/p\u003e\n\u003cp\u003eConsidering the patient\u0026rsquo;s history of cardiac surgery with soft tissues for valve replacement, along with the chronicity of stay and occurrence of oral lesions thereafter (2 years ago), GVHD as an oral manifestation was suspected. The child and her father denied involvement of any other body part in manifestation of symptoms.\u003c/p\u003e\n\u003cp\u003eThe patient underwent a thorough oral exam, and the photos and radiographs were taken with the patient\u0026rsquo;s consent.\u003c/p\u003e\n\u003cp\u003eUpon cardiology consultation, her soft tissue valve replacement (xenograft: bovine origin, instead of mechanical valves) was discussed to prevent the lifelong use of anticoagulants (e.g., Coumadin), helping patients in that matter, along with the results obtained with soft tissue valve grafts, and discussions regarding whether such a thing has been encountered before. The cardiologist confirmed seeing another rare case which was much more severe and that this patient would be followed up regularly at the cardiology unit as the following was rendered in October 2023 (Tables 3 and 4).\u003c/p\u003e\n\u003ch2\u003eChronic Problems Previously Documented\u003c/h2\u003e\n\u003cp\u003eCongenital MR\u003c/p\u003e\n\u003cp\u003eGeneralized gingival recessions, inflammation, and halitosis.\u003c/p\u003e\n\u003ch2\u003eAssessment Summary\u003c/h2\u003e\n\u003cp\u003eModerate-to-severe MR, moderate TR, and large LA.\u003c/p\u003e\n\u003cp\u003eS/P MV repair in Makkah a year earlier (2020).\u003c/p\u003e\n\u003cp\u003eS/P \u0026nbsp; \u0026nbsp; \u0026nbsp;MV \u0026nbsp; \u0026nbsp; replacement \u0026nbsp; \u0026nbsp; \u0026nbsp;(Tissue \u0026nbsp; \u0026nbsp; Valve) \u0026nbsp; \u0026nbsp; and \u0026nbsp; \u0026nbsp; \u0026nbsp;TV \u0026nbsp; \u0026nbsp; repair \u0026nbsp; \u0026nbsp; on \u0026nbsp;July 12, \u0026nbsp;2021.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCurrent Cardiac Complaints\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo current cardiac complaints and the patient is doing well.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEchocardiography\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBioprosthesis was observed in the mitral position with good opening and mobility, with a peak and mean PG of 12 mmHg and 7 mmHg, respectively. Trace MR\u003c/p\u003e\n\u003cp\u003eMR. No TS. Mild+ TR with a PSPG of 16 mmHg\u003c/p\u003e\n\u003cp\u003eNo AS. No AI. No PS. Trace PI with an end-diastolic velocity of 149 cm/s\u003c/p\u003e\n\u003cp\u003eDilated LA. Moderately depressed LV systolic dysfunction with an EF of 50% by M‐mode and 51% by Simpson\u0026rsquo;s method. Mildly depressed RV function. No pericardial effusion.\u003c/p\u003e\n\u003cp\u003eOtherwise, for oral lesions, oral local gels or mouthwashes containing corticosteroids would be permissible and would not affect her cardiac situation, and the soft tissue valve would remain in place, as the patient\u0026rsquo;s cardiac condition is stable. Moreover, from a cardiovascular perspective, the patient would be fit for dental procedures as long as SBE prophylaxis (2 gm of amoxicillin 1 h before the intervention) is practiced, and the patient would continue on the same medication for six months.\u003c/p\u003e\n\u003ch2\u003eDental Treatment Plan\u003c/h2\u003e\n\u003cp\u003eThe patient was referred for a dental cleaning, after an initial consultation with periodontics for the oral presentations referred for. Oral hygiene instructions (OHI) including (but not limited to) tongue scraping/cleaning were addressed along with periodic follow-ups with periodontics for monitoring oral such lesions along OHI reinforcement.\u003c/p\u003e\n\u003cp\u003eOral rinses or topical corticosteroid were prescribed accordingly for the manifestations after her cardio follow-up. The patient was periodically followed up for 8 months from the initial oral exam, and the manifestations expressed were stable.\u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eGVHD is known to occur in allograft transplants; however, in this case report the use of soft tissue valves as xenografts, which may induce expositions similar to allografts, lead to oral presentations, which are rare. A study reported \u0026ldquo;the importance of glutaraldehyde in decreasing the immune response\u0026rdquo; with the use of xenograft prosthetic valves (e.g., bovine, porcine) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This would give rise to substantial discussions regarding the identification of biomarkers that would help in the early detection of cGVHD to help reduce its manifestations as much as possible in its earlier stages, as it triggers the immune system, and it is yet unclear how it exerts its effect within the human body, as complex and dynamic as it is.\u003c/p\u003e \u003cp\u003eDespite the increased demand for the use of xenografts and allografts as graft materials in dentistry, and the use of bone or tissue grafts in a highly vascular region (oral cavity) are known to yield positive results and better soft tissue healing with some materials; nonetheless, GVHD is not usually observed with the use of such materials. Thus, such a report remains an interesting topic for further discussion, from an immunologic perspective along other specialties, to generate lab explorations for future prevention or decreasing its displays.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eASD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAtrial septal defect\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHSCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHematopoietic stem cell transplantation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMitral regurgitation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMitral valve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOHI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOral hygiene instructions\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTricuspid valve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eThere are no financial nor non-financial conflicts, including and not limited to, relationships such as honoraria; educational grants; participation in speakers\u0026rsquo; bureaus; membership, employment, consultancies, stock ownership, or other equity interest; expert testimony or patent-licensing arrangements. Non-financial conflicts include personal or professional relationships, affiliations, academic competition, intellectual passion, knowledge or beliefs that might affect objectivity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Human Subjects Ethics Board of King Faisal Specialist Hospital and Research Center - Jeddah (IRB approval no. 2023-CR-34) and was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2013.\u0026nbsp;The patient\u0026rsquo;s guardian had a written informed consent obtained for the publication of these.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the needed documents have been granted the consent for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data are available upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone. Equipment and Medications supplied by King Faisal Specialist Hospital and Research Centre, Jeddah. There are no known financial relationships between any author and commercial firm that may pose any conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have made substantial contributions to conception and design of the study. SMNF have been involved in data collection and data analysis. SMNF have been involved in data interpretation. SMNF have been involved in drafting the manuscript. SMNF, MSS have been involved in revising the manuscript critically and have given final approval of the version to be published.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSpecial thanks to Amany Al-Semiery for referring this patient case from her pediatric unit and to the entire Cardiac team for their support at KFSHRC,J.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs supplemented from authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of generative AI and AI-assisted technologies in the writing process\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the preparation of this work the author(s) used [Enago] in order to [improve the quality of the written paper and proof read it to ensure it is devoid from plagiarism]. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTreister NS, Cook EF Jr, Antin J, Lee SJ, Soiffer R, Woo SB. Clinical evaluation of oral chronic graft-versus-host disease. Biol Blood Marrow Transpl. 2008;14:110\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElad S, Zeevi I, Or R, Resnick IB, Dray L, Shapira MY. Validation of the National Institutes of Health (NIH) scale for oral chronic graft-versus-host disease (cGVHD). Biol Blood Marrow Transpl. 2010;16:62\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMays JW, Fassil H, Edwards DA, Pavletic SZ, Bassim CW. Oral chronic graft-versus-host disease: current pathogenesis, therapy, and research. Oral Dis. 2013;19:327\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTreister NS, Cook EF Jr, Antin J, Lee SJ, Soiffer R, Woo SB. Clinical evaluation of oral chronic graft-versus-host disease. Biol Blood Marrow Transpl. 2008;14:110\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuten-Shorrer M, Woo SB, Treister NS. Oral graft-versus-host disease. Dent Clin North Am. 2014;58:351\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLinhares YP, Pavletic S, Gale RP, Chronic GVHD. Where are we? Where do we want to be? Will immunomodulatory drugs help? Bone Marrow Transpl. 2013;48:203\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMargaix-Mu\u0026ntilde;oz M, Bag\u0026aacute;n JV, Jim\u0026eacute;nez Y, Sarri\u0026oacute;n MG, Poveda-Roda R. Graft-versus-host disease affecting oral cavity. A review. J Clin Exp Dent. 2015;7:e138\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009;373:1550\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeier JK, Wolff D, Pavletic S, Greinix H, Gosau M, Bertz H. Oral chronic graft-versus-host disease: report from the International Consensus Conference on clinical practice in cGVHD. Clin Oral Investig. 2011;15:127\u0026thinsp;\u0026ndash;\u0026thinsp;39.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDignan FL, Amrolia P, Clark A, Cornish J, Jackson G, Mahendra P. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol. 2012;158:46\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede la Rosa Garc\u0026iacute;a E, Bologna Molina R, Vega Gonz\u0026aacute;lez Tde J. Graft-versus-host disease, an eight-case report and literature review. Med Oral Patol Oral Cir Bucal. 2006;11:e486\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJagasia MH, Greinix HT, Arora M, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transpl. 2015;21:389\u0026ndash;401.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManji RA, Lee W, Cooper DKC. Xenograft bioprosthetic heart valves: past, present and future. Int J Surg. 2015;23:280\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 to 4 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":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"autoimmune disease, graft versus host disease, oral cavity, tissue grafts, xenografts","lastPublishedDoi":"10.21203/rs.3.rs-5191347/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5191347/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eGraft versus host disease (GVHD) is an autoimmune disease that affects the oral cavity as well as other parts of the body. Oral GVHD occurs in 45%–83% of cases, and chronic GVHD observed in 30%–50% of cases usually manifests as an oral presentation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e In this case report, a 13-year-old girl was referred to the periodontics clinic from the pediatric dentistry clinics for proper diagnosis and management of the oral presentations observed after receiving a prosthetic valve replacement 2 years post-surgery. In this study, the xenograft type used was mainly investigated, as similar soft tissue grafts are used in the oral cavity with no GVHD oral manifestations being observed. This brings about an interesting discussion of the use of xenografts in different areas of the human body, but with different presentations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Thus, future investigations on early diagnostic tools, including saliva or blood examinations, are needed to create preventive methods or lessen the extent of GVHD in patients.\u003c/p\u003e","manuscriptTitle":"Oral GVHD Post-Cardiac Xenograft Valve Replacement: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-16 05:28:07","doi":"10.21203/rs.3.rs-5191347/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-18T20:19:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-29T18:12:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-26T11:44:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"217307325015772390038285518351438615665","date":"2024-10-23T00:08:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-19T05:59:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"283243034197586011139154093238557609420","date":"2024-10-18T18:25:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"10692914915214362447651175302012036449","date":"2024-10-16T23:35:13+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-10-16T16:43:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-03T09:42:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-03T09:39:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cardiothoracic Surgery","date":"2024-10-02T07:34:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2789ef1e-299e-4d3c-9558-acd37e24a335","owner":[],"postedDate":"December 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-30T16:08:32+00:00","versionOfRecord":{"articleIdentity":"rs-5191347","link":"https://doi.org/10.1186/s13019-024-03200-0","journal":{"identity":"journal-of-cardiothoracic-surgery","isVorOnly":false,"title":"Journal of Cardiothoracic Surgery"},"publishedOn":"2024-12-26 15:57:44","publishedOnDateReadable":"December 26th, 2024"},"versionCreatedAt":"2024-12-16 05:28:07","video":"","vorDoi":"10.1186/s13019-024-03200-0","vorDoiUrl":"https://doi.org/10.1186/s13019-024-03200-0","workflowStages":[]},"version":"v1","identity":"rs-5191347","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5191347","identity":"rs-5191347","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}