Diagnosis, Treatment and Application in Dentistry Studies 2025 – II

DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II Editor Aylin ÇALIŞ Lyon 2025 DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II Editor Aylin ÇALIŞ Lyon 2025 Diagnosis, Treatment and Application in Dentistry Studies 2025 – II Editor • Assoc. Prof. Dr. Aylin ÇALIŞ • Orcid: 0000-0003-3206-9697 Cover Design • Motion Graphics Book Layout • Motion Graphics First Published • October 2025, Lyon e-ISBN: 978-2-38236-942-5 DOI: 10.5281/zenodo.17421982 copyright © 2025 by Livre de Lyon All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the Publisher. The author or authors of the relevant section are responsible for any copyright infringement that may occur due to the images and graphics used in the book. The editor or publisher does not assume responsibility in this regard. Publisher • Livre de Lyon Address • 37 rue marietton, 69009, Lyon France website • http://www.livredelyon.com e-mail • [email protected] i PREFACE The field of Oral and Maxillofacial Surgery represents a convergence of clinical precision, biological complexity, and technological innovation. This book unites a broad spectrum of topics ranging from the effects of microgravity on craniofacial health to non-carious cervical lesions, from bone graft biomaterials to jaw osteomyelitis, and from burning mouth syndrome to epidermolysis bullosa each exploring a unique interface between pathology, systemic physiology, and patient-centered care. Authored by experienced clinicians and academic researchers, the chapters reflect a multidisciplinary approach grounded in evidence-based practice. Collectively, they emphasize the importance of understanding pathophysiological mechanisms, selecting appropriate biomaterials, and integrating medical and psychological perspectives into comprehensive oral healthcare. The purpose of this volume is not only to compile current scientific knowledge but also to inspire inquiry and critical thinking among young scholars and practitioners. Dentistry today extends far beyond restorative procedures it encompasses prevention, molecular biology, regenerative medicine, and the continuous pursuit of improving patients’ quality of life. We extend our deepest gratitude to all contributors for their dedication and scholarly excellence. It is our hope that this book will serve as a lasting academic reference and a source of inspiration for future research in oral and maxillofacial science. ACKNOWLEDGEMENTS The completion of this book would not have been possible without the dedication, insight, and collaborative spirit of all the contributing authors. Each chapter represents not only scientific expertise but also a shared commitment to advancing oral and maxillofacial science through interdisciplinary research and clinical excellence. This book is dedicated to all professionals who pursue knowledge with curiosity, compassion, and scientific rigor in the service of oral and craniofacial health. Editor Aylin ÇALIŞ iii CONTENTS PREFACE i CHAPTER I. THE EFFECTS OF MICROGRAVITY ON ORAL AND CRANIOFACIAL HEALTH: A COMPREHENSIVE REVIEW 1   BaşakYAZKAN&AminSAEDRAHİM CHAPTER II. NON-CARIOUS CERVICAL LESIONS: ETIOLOGICAL AND CLINICAL PERSPECTIVES – LITERATURE REVIEW 15   DamlaYILMAZ&ZeynepDERELI CHAPTER III. BONE GRAFT MATERIALS AND TETRACALCIUM PHOSPHATE: CLASSIFICATION AND CHARACTERISTICS 31   DoğaçMevlütSALTAN CHAPTER IV. JAWBONE OSTEOMYELITIS IN ALL ASPECTSLİTERATURE REVIEW 39   EdaETİK&BaşakKESKİNYALÇIN CHAPTER V. BURNING MOUTH SYNDROME (BMS) in DENTISTRY 63   GayeKESER&FilizNAMDARPEKİNER CHAPTER VI. EPIDERMOLYSIS BULLOSA (EB) 79   SUAYYAĞMURÜNAL&GAYEKESER& FİLİZNAMDARPEKİNER 1 CHAPTER I THE EFFECTS OF MICROGRAVITY ON ORAL AND CRANIOFACIAL HEALTH: A COMPREHENSIVE REVIEW Başak YAZKAN1* & Amin SAEDRAHİM2 1(Associate Professor Dr.), Muğla Sıtkı Koçman University Faculty of Dentistry, Restorative Dentistry Department, Muğla, Turkey E-mail: [email protected] ORCID: 0000-0003-4827-0547 2(Bacholar Student), Aydın Adnan Menderes University Faculty of Dentistry, Aydın, Turkey E-mail: aminsdr[email protected] *Corresponding author: [email protected] Introduction Microgravity poses significant risks to oral and craniofacial health, yet systematic reviews of its multifactorial effects remain limited. This study comprehensively evaluates microgravity-induced alterations in bone remodeling, salivary dynamics, oral microbiome composition, periodontal integrity, and temporomandibular joint (TMJ) function. Synthesizing empirical evidence, we identify key challenges, including osteopenia of craniofacial bones, salivary hypofunction, pathogenic biofilm proliferation, and TMJ dysfunction exacerbated by masticatory muscle coordination loss. Cephalad fluid shifts under microgravity may further induce gingival edema, while prolonged missions accelerate alveolar bone resorption, increasing caries and periodontal disease risks. Proposed countermeasures include: (1) pre-flight interventions (dental screenings, prophylactic therapy); (2) in-flight strategies (vacuum-adapted toothbrushes, sugar-free gum for salivation, pH-stabilizing mouthwashes); and 8   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II coordination, and fluid redistribution, potentially increasing TMJ stress and dysfunction. These physiological adaptations pose unique challenges for astronauts, leading to discomfort, temporomandibular disorders (TMDs), and impaired oral function. 4.1.KeyContributingFactors Fluid Shifts & Pressure Changes: Microgravity-driven cephalad fluid shifts increase intracranial and intraoral pressure, causing engorgement of peri-TMJ soft tissues. This may result in joint stiffness, pain, and restricted mobility (6-9). Musculoskeletal Adaptations: Reduced gravitational loading accelerates bone mineral density (BMD) loss and muscle atrophy in the craniofacial region. Astronaut studies reveal significant BMD reductions in weight-bearing bones, potentially compromising TMJ structural integrity over time (3, 7). Mandibular bone loss is directly linked to malocclusion, altered occlusal forces, and heightened joint disorder risk (8, 11). Neuromuscular Dysregulation: Microgravity disrupts proprioception and neuromuscular coordination, impairing masticatory muscle function. Altered neural signaling may lead to jaw clenching, bruxism, and dysfunctional movements, exacerbating TMJ stress (4). Chronic effects include muscle fatigue, joint misalignment, and increased loading on articular discs and ligaments, predisposing astronauts to TMDs (5, 14). Psychological Stress: Spaceflight-induced psychological stress can trigger bruxism and parafunctional habits, further compounding TMJ strain (10). Dietary & Masticatory Changes: Processed, rehydrated space foods alter chewing mechanics, increasing TMJ workload. Reduced masticatory loading deprives the jawbone of osteogenic stimuli, accelerating bone resorption and chronic joint dysfunction (14, 15). Head-down bed rest (HDBR) studies—a microgravity analog—demonstrate THE EFFECTS OF MICROGRAVITY ON ORAL AND CRANIOFACIAL . . .   9 measurable declines in bite force and masticatory efficiency, underscoring the need for targeted countermeasures (1, 16). 5. Countermeasures and Management Strategies Pre-flightPreparations: -Comprehensive dental evaluations to identify pre-existing conditions. -Custom-fitted occlusal splints to distribute joint loading and prevent excessive stress during missions (7). In-flightInterventions: -Targeted resistance training for masticatory muscles to maintain strength. -Jaw mobility exercises to preserve coordination. -Neuromuscular stimulation techniques to counteract microgravityinduced atrophy (3, 12). -Dietary modifications incorporating foods requiring balanced masticatory forces to sustain normal TMJ function (5, 13). TechnologicalSolutions: -Advanced telemedicine systems for remote TMJ monitoring. -Intraoral imaging technologies enabling real-time assessment of joint mobility, occlusal relationships, and muscle activity patterns. -Specialized space-adapted oral appliances designed to provide joint stabilization, redistribute mechanical loads, and compensate for weightlessness effects (9, 11). ComprehensiveApproach: The multifactorial nature of microgravity’s impact on the TMJ— encompassing fluid shifts, muscle atrophy, neuromuscular alterations, and dietary challenges—demands an integrated management strategy. Current evidence underscores the need for: -Continued research into targeted interventions. -Technological development of space-optimized solutions. -Multidisciplinary collaboration to preserve TMJ integrity, prevent longterm complications, and ensure astronaut oral health during extended missions. 10   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II 6. Conclusion Microgravity critically impacts human oral health, particularly through: -Accelerated bone loss from reduced loading. -Salivary changes disrupting oral homeostasis. -Microbiome dysbiosis increasing infection risks. -Periodontal degradation due to immune and fluid shifts. -TMJ dysfunction from altered biomechanics. -While current strategies (targeted exercise, pharmacotherapy, and specialized oral care) offer partial protection, long-duration missions demand: -Advanced predictive models of microgravity effects. -Personalized countermeasures combining genomics and AI monitoring. -Space-optimized biomaterials for oral devices. Addressing these challenges is essential for maintaining astronaut health in extended space exploration. REFERENCES 1. Carnovali, M., Zava, S., Banfi, G., Rizzo, A. M., & Mariotti, M. (2024). Vibration rather than microgravity affects bone metabolism in adult zebrafish scale model. Cells, 13(6), 509. 2. Walle, M., Gabel, L., Whittier, D. E., Liphardt, A. 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The role of physiotherapy in the European Space Agency strategy for preparation and reconditioning of astronauts before and after long-duration space flight. Musculoskeletal Science and Practice, 27(S1), S15–S22. 13. Comfort, P., McMahon, J. J., Jones, P. A., Cuthbert, M., Kendall, K., Lake, J. P., & Haff, G. G. (2021). Effects of spaceflight on musculoskeletal health: A systematic review and meta-analysis, considerations for interplanetary travel. Sports Medicine (Auckland, N.Z.), 51(10), 2097–2114. 14. Moussa, M. S., Goldsmith, M., & Komarova, S. V. (2023). Craniofacial bones and teeth in spacefarers: Systematic review and meta-analysis. JDR Clinical and Translational Research, 8(2), 113–122. 12   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II 15. Bakr, M. M., Caswell, G. M., Hussein, H., Shamel, M., & Al-Ankily, M. M. (2024). Considerations for oral and dental tissues in holistic care during long-haul space flights. 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K., Khaled, B., Bradley, A., Graves, J. L., Jr, & Thomas, M. D. (2022). Adaptation to simulated microgravity in Streptococcus mutans. NPJ Microgravity, 8(1), 17. 27. International Journal of Dentistry (2021). Retracted: Evaluation by an aeronautic dentist on the adverse effects of a six-week period of microgravity on the oral cavity. International Journal of Dentistry, 2021, 9102451. 28. Morrison, M. D., Thissen, J. B., Karouia, F., Mehta, S., Urbaniak, C., Venkateswaran, K., Smith, D. J., & Jaing, C. (2021). Investigation of spaceflight- THE EFFECTS OF MICROGRAVITY ON ORAL AND CRANIOFACIAL . . .   13 induced changes to astronaut microbiomes. Frontiers in Microbiology, 12, Article 659179. 29. Subspecialty Group of Oncology, Society of Pediatrics, Chinese Medical Association, & Subspecialty Group of Hematology. (2020). Zhonghua er ke za zhi = Chinese Journal of Pediatrics, 58(10), 790–795. 30. Doshi, D. J., & Tamgadge, S. (2024). 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National Aeronautics and Space Administration. 35. Yuce, E., Koçer, G., & Çini, T. A. (2016). Current concepts of oral and maxillofacial rehabilitation and treatment in aviation. General Dentistry, 64(5), 44–48. 36. Sibonga, J. D., Evans, H. J., Sung, H. G., Spector, E. R., Lang, T. F., Oganov, V. S., Bakulin, A. V., Shackelford, L. C., & LeBlanc, A. D. (2007). Recovery of spaceflight-induced bone loss: Bone mineral density after longduration missions as fitted with an exponential function. Bone, 41(6), 973–978. 37. Lambrecht, G., Petersen, N., Weerts, G., Pruett, C., Evetts, S., Stokes, M., & Hides, J. (2017). The role of physiotherapy in the European Space Agency strategy for preparation and reconditioning of astronauts before and after longduration space flight. Musculoskeletal Science and Practice, 27(S1), S15–S22. 15 CHAPTER II NON-CARIOUS CERVICAL LESIONS: ETIOLOGICAL AND CLINICAL PERSPECTIVES – LITERATURE REVIEW Damla YILMAZ ¹ & Zeynep DERELI ² ¹ (Research Assistant) Necmettin Erbakan University Department of Restorative Dentistry E-mail: [email protected] ORCID ID: 0009-0008-2602-877X ² (Assistant Professor) Necmettin Erbakan University Department of Restorative Dentistry E-mail: zynpur[email protected] ORCID ID: 0000-0003-2317-9069 1. Introduction Tooth wear refers to the irreversible loss of dental hard tissues caused by destructive processes that are not related to dental caries. This process may occur as part of physiological aging or as a result of pathological conditions. When the loss of hard tissue appears at the cemento-enamel junction, it is described as a non-carious cervical lesion (NCCL) (1-3). Tooth wear in general is linked to physical or chemical factors that gradually damage the tooth surface (4). As people now keep their natural teeth for longer, and due to the influence of diet, oral hygiene habits, and parafunctional activities, tooth wear has become more frequent in older adults (5, 6). NCCLs represent a specific type of tooth wear characterized by the absence of microbial involvement (7). These lesions usually form near the cervical region, which is more prone to damage because of its thin enamel, irregular prism structure, concentration of non-axial occlusal forces, and higher acid sensitivity at the dentin–enamel junction (8, 9). 16   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II The etiology of NCCLs is multifactorial, involving abrasion, erosion, and tensile stress, often acting together (5, 10). In addition to these mechanical and chemical influences, recent studies have also examined the role of psychological factors such as stress and anxiety in the development of cervical lesions. 2. NonCarious Cervical Lesions 2.1.Atrittion Attrition describes the progressive loss of dental surfaces that occurs through direct contact between opposing teeth. It may occur as part of aging (physiological attrition) or in a more destructive way (pathological attrition). Habits such as clenching and grinding (bruxism), occlusal disharmony, and premature contacts are major contributors to pathological attrition (6, 11). At the early stage, attrition lesions often appear as small, smooth, and polished flat surfaces known as wear facets. Typically, a similar lesion is present on the opposing tooth, reflecting the direct contact mechanism. Pathological and physiological attrition are most commonly observed on the occlusal, incisal, and palatal surfaces of maxillary teeth, and on the labial surfaces of mandibular teeth (6, 13). Figure 1. Clinical presentation of attrition (38) In addition, attrition may interact with other wear mechanisms. For example, enamel particles generated during tooth contact can create additional abrasive effects. When food is involved during mastication, the combined process of attrition and abrasion is referred to as demastication (10). 2.2.Abrasion Dental abrasion is defined as the wear of hard tissues due to abnormal mechanical actions not related to tooth-to-tooth contact. The most common NON-CARIOUS CERVICAL LESIONS: ETIOLOGICAL AND CLINICAL . . .   17 cause is inappropriate toothbrushing, especially when done with too much force, horizontal scrubbing movements, or with hard-bristled toothbrushes and highly abrasive toothpastes (14). Studies show that abrasion is more common on canines and premolars, because these teeth often receive greater brushing pressure (11). Clinically, abrasion usually appears as wedge-shaped or rounded notches at the cervical areas of teeth. The surfaces of these lesions often look smooth and shiny because of continuous brushing or other mechanical wear. Apart from toothbrushing, other habits can also cause abrasion, such as using toothpicks, nail biting, chewing tobacco, or holding objects like pens and hairpins between the teeth (15). Figure 2. Clinical presentation of cervical abrasion (39) Abrasion rarely happens alone. It often works together with erosion and abfraction. For example, enamel softened by acid is more easily worn down by brushing, which speeds up the loss of tissue in the cervical region. This shows that abrasion should be considered as part of a wider process when studying non-carious cervical lesions (10). 2.3.Erosion Dental erosion is defined as the progressive loss of hard tooth structure through chemical dissolution by acids of non-bacterial origin. These acids may derive from extrinsic sources, such as citrus fruits, carbonated beverages, and sports drinks, or from intrinsic sources, including gastroesophageal reflux and eating disorders (19). Clinically, erosion is characterized by smooth, glazed, and rounded surfaces, often accompanied by increased translucency of enamel. The cervical 24   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II From a preventive perspective, clinical advice should focus on reducing the frequency of acidic intake, consuming acidic items with meals, avoiding prolonged contact with teeth, and applying neutralizing strategies such as rinsing with water or milk after consumption (25). Beverage pH Erosive Potential Cola ~2.5 High Carbonated fruit drinks ~2.9 Very high Tomato juice ~3.7 Moderate Orange juice ~3.8 Very high Sparkling/mineral water ~3.0 Very low Wine (white/red) 3.0–3.5 High Sports drinks 2.9–3.2 High Tea (unsweetened) 4.9–5.5 Very low Milk 6.6–6.9 Non-erosive Table 4. pH of Common Beverages and Their Erosive Potential 7. Oral Hygiene Habits and Non-Carious Cervical Lesions Oral hygiene practices, particularly toothbrushing behavior, have a significant influence on the development of non-carious cervical lesions (NCCLs). Excessive force during toothbrushing may traumatize the periodontium and contribute to gingival recession. When combined with the abrasive effect of dentifrices, this excessive pressure can lead to cervical abrasion (16). Clinical studies indicate that right-handed individuals more frequently develop abrasion lesions on the left side, while left-handed individuals exhibit more lesions on the right. Furthermore, abrasion is often detected in the half of the dental arch that is brushed first, which is attributed to the tendency to apply greater pressure at the beginning of the brushing routine (17,18). The type of toothbrush also plays a role in cervical wear. Mediumor hard-bristled toothbrushes produce more surface loss compared to soft-bristled brushes, increasing the risk of abrasion when used improperly (16). The abrasivity, pH, and amount of toothpaste are additional variables associated with NCCLs. Toothpastes with abrasive particles or low pH values enhance the risk of cervical wear, especially under conditions of strong brushing pressure. NON-CARIOUS CERVICAL LESIONS: ETIOLOGICAL AND CLINICAL . . .   25 Incorrect techniques such as horizontal scrubbing have been consistently linked to higher prevalence of cervical abrasion (18). 8. Management and Treatment of Non-Carious Cervical Lesions The treatment of non-carious cervical lesions (NCCLs) requires a multifactorial approach, since no single etiological factor is responsible for lesion formation. Management strategies can be divided into preventive measures, symptom management, and restorative or surgical treatment when necessary. 8.1.PreventiveMeasures Patient education is fundamental. Brushing modifications—including the use of soft-bristled brushes, gentle circular techniques instead of horizontal scrubbing, and less abrasive toothpastes—reduce mechanical wear (14, 15). Dietary counseling focuses on limiting acidic food and drink intake, avoiding prolonged sipping, and neutralizing acids by rinsing with water or milk after exposure (10). In patients with occlusal overload or parafunctional habits, correction of premature contacts and the use of occlusal splints are recommended (7). Addressing psychosocial contributors such as bruxism associated with stress and anxiety may also reduce progression (21). 8.2.SymptomManagement Dentin hypersensitivity is a frequent complaint in NCCLs. First-line options include desensitizing toothpastes containing potassium nitrate, stannous fluoride, or strontium salts (15). In-office interventions such as fluoride varnishes, resin sealants, and oxalate applications may provide additional benefit (14). For recession-associated hypersensitivity, periodontal coverage procedures can be considered (39). 8.3.RestorativeTreatment Restorations are indicated when lesions are deep, progressive, symptomatic, or compromise esthetics. Resin composites are widely used because of their esthetics and adhesion to dentin, but their longevity depends on proper adhesive protocols (22). Glass ionomer cements (GICs) are advantageous in high caries-risk patients due to fluoride release and chemical bonding to dentin, although they show lower wear resistance (10). 26   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II Resin-modified glass ionomer cements (RMGICs) combine fluoride release with improved mechanical properties, making them suitable for cervical restorations (22). In extensive lesions, laminate veneers or crowns may be required for structural and esthetic rehabilitation (42). 8.4.CombinedandMultidisciplinaryApproaches Because NCCLs often result from the interaction of abrasion, erosion, and abfraction, treatment frequently requires a combined approach. For example, restorative therapy can be paired with periodontal root coverage surgery in gingival recession cases (39). Occlusal adjustments, night guards, and psychological support for stress-related bruxism further enhance long-term success (21). 9. Conclusion Non-carious cervical lesions (NCCLs) represent a multifactorial condition involving the interplay of mechanical, chemical, biological, and behavioral factors. Attrition, abrasion, erosion, and abfraction contribute individually and synergistically to cervical tissue loss, while biological determinants such as tooth morphology and saliva further modulate susceptibility. Oral hygiene practices, dietary habits, and psychological influences, including stress and anxiety, act as significant behavioral cofactors that can accelerate lesion development. Accurate diagnosis of NCCLs requires careful assessment of their etiology, clinical features, and associated risk factors. Preventive strategies, including modification of oral hygiene techniques, dietary counseling, and occlusal management, are essential to reduce progression. Symptom control, particularly for dentin hypersensitivity, and restorative interventions using composite resins or glass ionomer cements are indicated in advanced cases. In addition, multidisciplinary collaboration—including periodontal, restorative, and psychological management—enhances longterm outcomes. Ultimately, a comprehensive and individualized approach that addresses both etiological and behavioral factors is crucial for the successful management of NCCLs and for improving patient function, comfort, and quality of life. NON-CARIOUS CERVICAL LESIONS: ETIOLOGICAL AND CLINICAL . . .   27 REFERENCES 1. Kitchin PC. The prevalence of tooth root exposure, and the relation of the extent of such exposure to the degree of abrasion in different age classes. J Dent Res. 1941;20:565-581. 2. Lussi A, Schaffner M, Hotz P, et al. Dental erosion in a population of Swiss adults. Community Dent Oral Epidemiol. 1991;19:286-290. 3. Hattab FN, Yassin OM. 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J Oral Rehabil. 2004;31(2):117-123. doi:10.1046/j.0305-182X.2003.01223.x 9. Kolak V, Pesic D, Melih I, et al. Epidemiological investigation of non-carious cervical lesions and possible etiological factors. J Clin Exp Dent. 2018;10(7):e648-e656. doi:10.4317/jced.54860 10. Grippo JO, Simring M, Coleman TA. Abfraction, abrasion, biocorrosion, and the enigma of noncarious cervical lesions: a 20-year perspective. J Esthet Restor Dent. 2012;24(1):10-23. doi:10.1111/j.1708-8240.2011.00487.x 11. Litonjua LA, Andreana S, Bush PJ, Cohen RE. Tooth wear: attrition, erosion, and abrasion. Quintessence Int. 2003;34(6):435-446. 12. Wood I, Jawad Z, Paisley C, Brunton P. Non-carious cervical tooth surface loss: a literature review. J Dent. 2008;36:759-766. 13. d’Incau E, Couture C, Maureille B. Human tooth wear in the past and the present: tribological mechanisms, scoring systems, dental and skeletal compensations. Arch Oral Biol. 2012;57(3):214-229. 14. Addy M, Hunter ML. Can tooth brushing damage your health? Effects on oral and dental tissues. Int Dent J. 2003;53 Suppl 3:177-186. 28   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II 15. Bartlett DW, Shah P. A critical review of non-carious cervical (wear) lesions and the role of abfraction, erosion, and abrasion. J Dent Res. 2006;85(4):306-312. 16. Brandini DA, De Sousa ALB, Trevisan CL, et al. Noncarious cervical lesions and their association with toothbrushing practices: in vivo evaluation. Oper Dent. 2011;36:581-589. 17. Osborne-Smith KL, Burke FJT, Wilson NHF. The aetiology of the noncarious cervical lesion. Int Dent J. 1999;49:139-143. 18. Lussi A, Jaeggi T. Erosion—diagnosis and risk factors. Clin Oral Investig. 2008;12 Suppl 1:S5-S13. 19. Zero DT, Lussi A. Erosion—chemical and biological factors of importance to the dental practitioner. Int Dent J. 2005;55 Suppl 1:285-290. 20. Nascimento GG, Leite FRM, Correa MB, Horta BL, Peres MA, Demarco FF. Occlusal problems, mental health issues and non-carious cervical lesions. Clin Oral Investig. 2021;25(11):6517-6524. 21. Peumans M, Kanumilli P, De Munck J, Van Landuyt K, Lambrechts P, Van Meerbeek B. Clinical effectiveness of contemporary adhesives: a systematic review of current clinical trials. Dent Mater. 2005;21(9):864-881. 22. Zero DT. Etiology of dental erosion—extrinsic factors. Eur J Oral Sci. 1996;104(2):162-177. 23. Jaeggi T, Lussi A. Prevalence, incidence and distribution of erosion. Monogr Oral Sci. 2006;20:44-65. 24. Jarvinen VK, Rytömaa II, Heinonen OP. Risk factors in dental erosion. J Dent Res. 1991;70(6):942-947. 25. Linkosalo E, Markkanen H. Dental erosion in relation to lactovegetarian diet. Scand J Dent Res. 1985;93(5):436-441. 26. Gedalia I, Brayer L, Kaufman E, et al. Tooth enamel softening with a cola-type drink and rehardening with milk or saliva. J Oral Rehabil. 1991;18(6):501-506. 27. Meurman JH, Ten Cate JM. Pathogenesis and modifying factors of dental erosion. Eur J Oral Sci. 1996;104(2):199-206. 28. Hugoson A, Bergendal T, Ekfeldt A, Helkimo M. Occurrence and severity of dental erosion in Swedish men and women. Community Dent Oral Epidemiol. 1988;16(5):333-336. 29. Souza PG, Machado AC, Pereira AG, Teixeira RR, Espíndola FS, Soares PV. The dentin chemical degradation and saliva roles on noncarious cervical lesions – literature review. Rev Odonto Ciênc. 2017;32(4):199-203. doi:10.15448/1980-6523.2017.4.28634 NON-CARIOUS CERVICAL LESIONS: ETIOLOGICAL AND CLINICAL . . .   29 30. Buzalaf MA, Hannas AR, Kato MT. Saliva and dental erosion. J Appl Oral Sci. 2012;20(5):493-502. 31. Young WG, Khan F. Sites of dental erosion are saliva-dependent. J Oral Rehabil. 2002;29(1):35-43. 32. Grippo JO. Abfractions: a new classification of hard tissue lesions of teeth. J Esthet Dent. 1991;3(1):14-19. doi:10.1111/j.1708-8240.1991.tb00799.x 33. Veeraboina N, Doshi D, Kulkarni S, et al. Association of state and trait anxiety with oral health status among adult dental patients. Acta Biomed. 2020;91(3):e2020070. doi:10.23750/abm.v91i3.8986 34. Peruzzo DC, Benatti BB, Ambrosano GM, et al. A systematic review of stress and psychological factors as possible risk factors for periodontal disease. J Periodontol. 2007;78:1491-1504. 35. Kesim SI, Unalan D, Esen C, Ozturk A. The relationship between periodontal disease severity and state-trait anxiety levels. J Pak Med Assoc. 2012;62(12):1304-1308. 36. Solis AC, Lotufo RF, Pannuti CM, et al. Association of periodontal disease to anxiety and depression symptoms, and psychosocial stress factors. J Clin Periodontol. 2004;31:633-638. 37. Oral Health Group. An overview on dental wear [Internet]. Toronto: Oral Health Group; 2018 [cited 2025 Sep 8]. Available from: https://www. oralhealthgroup.com/features/an-overview-on-dental-wear/ 38. Pini-Prato G, Franceschi D, Cairo F, Nieri M, Rotundo R. Classification of dental surface defects in areas of gingival recession. J Periodontol. 2010;81(6):885-890. 39. Indiadens. What is tooth enamel erosion? Symptoms, causes, and treatment [Internet]. New Delhi: Indiadens; 2022 Aug 9 [cited 2025 Sep 8]. Available from: https://www.indiadens.com/what-is-tooth-enamel-erosionsymptoms-causes-and-treatment/ 40. Clark GT. Dental erosion from abrasion & abfraction [Internet]. Orofacial Pain and Oral Medicine. 2019 Aug 8 [cited 2025 Sep 8]. Available from: https://ostrowonline.usc.edu/dental-erosion-from-abrasion-abfraction/ 41. Heintze SD, Forjanic M, Rousson V. Clinical effectiveness of direct anterior restorations – a meta-analysis. Dent Mater. 2006;22(4):345-352. 31 CHAPTER III BONE GRAFT MATERIALS AND TETRACALCIUM PHOSPHATE: CLASSIFICATION AND CHARACTERISTICS Doğaç Mevlüt SALTAN1 1DDS, Institude of Graduate Studies in Health Sciences, Istanbul University Faculty of Dentistry, Department of Oral Implantology, İstanbul, Türkiye E-mail: [email protected] ORCID: 0009-0000-3497-109X 1. Introduction The selection of an appropriate graft material is essential for successful bone regeneration. Autografts, while considered the gold standard due to their osteogenic and osteoconductive properties, are limited by availability and associated morbidity. Consequently, alternative grafts, including allografts, xenografts, and alloplasts, are frequently used. These materials, such as calcium phosphates and bioactive glasses, offer varying degrees of biocompatibility, resorption rates, and biological activity. Understanding the properties and clinical implications of each graft type is vital for optimizing treatment outcomes in bone repair. 2. Definition and Types of Bone Grafts In the field of oral and maxillofacial surgery in dentistry, various materials are utilized to repair or replace bone defects. The selection of material is influenced by factors such as tissue vitality, defect size, shape, and volume. While small bone defects may heal spontaneously, larger defects, losses, or pathological fractures necessitate surgical intervention and the use of bone substitutes. (1) Autologous bone, harvested from the patient’s own body, is regarded as the gold standard for bone grafting; however, it is associated with certain disadvantages, including 32   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II uncertain prognosis, the need for additional surgery at the donor site, and limited availability. For mediumand small-sized defects, alternative options include allografts (harvested from human donors), xenografts (harvested from animals), and synthetic materials with osteoconductive properties. (2) 2.1AutogenousBoneGraft Autografts are considered the gold standard materials for bone grafting in both medical and dental fields, as they possess many of the essential qualities deemed optimal for a bone graft. They are reported to be biocompatible, nontoxic, osteogenic (bone-forming), osteoinductive (bone formation-promoting), and osteoconductive (supporting bone growth). Particularly in critical-size defects (>5 mm), they serve as a fundamental base for rapid and effective bone regeneration. In the center of such large defects, vascularization is typically reduced. When compared to other graft materials, autogenous bone grafts are classified as the fastest to vascularize and the most osteogenic. (3) However, this procedure has several disadvantages. Surgical intervention at the bone harvesting site, uncertain prognosis, and the risk of infection are complications that may arise during the process. Additionally, the quantity and quality of the donor bone may be insufficient due to age-related issues or underlying metabolic conditions, such as osteoporosis and diabetes, which may compromise the patient’s overall health. (3,4) 2.2Allografts Allografts are derived from demineralized, freeze-dried bone. Although they are obtained from the same species, they are often harvested from cadavers. These graft materials may exhibit osteoinductive and osteoconductive properties. Alloplasts, such as hydroxyapatite and tricalcium phosphate, can either be synthetic or naturally occurring, varying in size, and possess only osteoconductive properties. The use of grafts depends on the size and location of the bone defect. (5) Small defects with four intact walls can be repaired with either alloplasts or a combination of allografts and alloplasts, whereas the loss of three or more bone walls may require the addition of autologous bone along with the graft. The larger the defect, the greater the need for autologous bone. (5) 2.2.1TypesofAllografts: Fresh or Fresh-Frozen Bone Allografts: These are frozen at -80°C to prevent enzymatic degradation of the bone, without undergoing additional BONE GRAFT MATERIALS AND TETRACALCIUM PHOSPHATE . . .   33 irradiation, lyophilization, or demineralization processes. They are acellular and exhibit the highest osteoinductive and osteoconductive properties due to the presence of BMPs. However, due to the risk of disease transmission and the potential for an increased immune response, the use of these grafts has been largely discontinued. (5,6) Dry and Frozen Bone Allografts: These allografts are dried and frozen without demineralization, which helps to reduce antigenicity. They possess only osteoconductive potential. (5) Demineralized Dry and Frozen Bone Allografts: This type of allograft undergoes drying and freezing processes, with the inorganic component of the bone being removed, leaving only the organic portion containing BMPs. These materials exhibit both osteoconductive and osteoinductive properties. (6) The use of allografts for bone repair generally requires sterilization, which often leads to the inactivation of proteins naturally present in healthy bone. The extracellular matrix of bone tissue contains bone growth factors, proteins, and other biologically active substances necessary for osteoinduction and successful bone healing. Desired factors and proteins are removed from the mineralized tissue using demineralizing agents such as hydrochloric acid. (7) The advantages of allografts include their availability in sufficient quantity, size, and shape, their ability to provide predictable results, and the elimination of the need for an additional donor site surgery. On the other hand, the potential for disease transmission from donor to recipient, although extremely low, necessitates additional testing for HIV, Hepatitis B, Hepatitis C, and Treponema serological markers. Disadvantages of this grafting category include immune response and lower recanalization compared to autologous grafts. (8) 2.3Xenografts Xenografts are graft materials derived from different species. In dentistry, the xenograft materials typically used are bovine-derived, and during their preparation, the bone proteins from the cattle are removed, leaving only the inorganic component. (9) Recent studies have demonstrated that xenografts derived from equine bone have shown success when used in implant surgeries. The key difference between these xenografts and those derived from bovine bone lies in the method of preparation, where equine bone is treated with digestive enzymes to remove proteins without being exposed to high temperatures. (10) Among the disadvantages of xenografts are the differences in bone characteristics compared to human bones, the potential for processing procedures 40   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II the bone, teeth, and surrounding anatomical structures. Identifying the causative pathogens, administering targeted antibiotic therapy, and performing timely surgical debridement are crucial steps in controlling the infection. Continuous monitoring and follow-up are also necessary to prevent recurrence and ensure long-term treatment success. 2. Definition Osteomyelitis is a progressive disease that arises from damage to bone tissue through infectious and inflammatory processes caused by microorganisms. The disease may affect only a portion of the bone, but it can also extend to the medullary canal, cortex, periosteum, and surrounding soft tissues (1). Osteomyelitis is primarily characterized by localized bone destruction due to infectious agents, followed by necrotic processes and new bone formation, representing an inflammatory process of bone and bone marrow (2,3). Although it is a rare condition, some studies report the annual incidence of osteomyelitis as ranging from 2 to 30 cases per 100,000 individuals. In an analysis encompassing 251 osteomyelitis cases, a higher incidence was observed in men, with a reported male-to-female ratio of 2:1 (4). In adults, osteomyelitis is frequently associated with diabetes (5), intravenous (IV) drug use, or open fractures, with the highest incidence observed in individuals over 50 years of age. Osteomyelitis affecting the oral and maxillofacial region, particularly following odontogenic infections or traumatic surgical interventions, represents a significant source of morbidity. Its management typically requires prolonged treatment, considerable resources, and a multidisciplinary approach. Osteomyelitis not only poses a clinical challenge at the individual level but also constitutes a significant public health concern due to its economic burden on healthcare systems. Additionally, the emergence of antibiotic resistance and the potential for recurrence further complicate effective disease management. 3. History The earliest records of osteomyelitis date back to 2500 BCE in Hindu inscriptions. Hippocrates, around 400 CE, described trauma-associated bone infections and the spontaneous discharge of sequestra (bone necrosis). In the 17th century, Howship and Havers provided detailed descriptions of bone anatomy, and Pervical Pott described sequestrum removal (sequestrectomy). In 1830, Brodie published nine cases of chronic bone abscesses, and in 1834, Nelaton JAWBONE OSTEOMYELITIS IN ALL ASPECTSLİTERATURE REVIEW   41 was the first to use the term “osteomyelitis” in scientific literature. Osteomyelitis in the jaws has affected humanity throughout history. A notable example is a 1.6-million-year-old Hominid (Homo erectus) fossil, estimated to belong to a 12-year-old individual, which exhibits odontogenic osteomyelitis around the first molar, likely contributing to early death. From past to present, both the number and clinical presentation of maxillofacial osteomyelitis cases have changed significantly. Historically, it was considered highly contagious, often required multiple complex surgical interventions, could lead to facial deformities, and resulted in loss of affected bone and teeth. However, since the second half of the 20th century, there has been a dramatic decrease in osteomyelitis cases involving the jaw and skeletal bones, largely due to the inclusion of antibiotics as a therapeutic agent in treatment. Features distinguishing osteomyelitis in the maxillofacial region from other forms include the involvement of different pathogen groups, the presence of teeth, varying vascular density, and mandibular mobility. Consequently, it may differ from other osteomyelitis forms while also exhibiting various subtypes of jaw osteomyelitis according to different classification systems. 4. Etiology Various local and systemic factors contribute to the development of osteomyelitis. Local factors include dental caries, trauma, chronically infected teeth, infections spreading from adjacent anatomical structures, progressive chronic periodontal disease, neoplasms (6), and prior exposure to radiotherapy. The presence of these underlying conditions weakens host defenses and increases susceptibility to infection. Systemic factors facilitating the development of osteomyelitis in the jaw include diabetes mellitus, malnutrition, cancer, autoimmune disorders, corticosteroid and other immunosuppressive therapies, leukemia, anemia, alcohol and tobacco use, history of prior surgical procedures, herpes simplex, herpes zoster, cytomegalovirus infections, and agranulocytosis (7). 5. Etiological Factors in Osteomyelitis The etiology and progression of osteomyelitis are determined by the multifactorial interaction of host-related systemic factors, microbial characteristics, iatrogenic influences, and applied treatment modalities. Systemic conditions that compromise host immunity—such as diabetes 42   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II mellitus, malignancies, HIV infection, chronic kidney disease, malnutrition, immunosuppressive therapy, and prior radiotherapy—increase susceptibility to infection (7). Behavioral factors, notably smoking, further exacerbate this predisposition. Microbial factors influencing disease severity and treatment outcomes include pathogen virulence, biofilm formation capacity, and antimicrobial resistance patterns. In addition, ecological dynamics within the normal flora—modulated by environmental conditions such as pH, temperature, oxygen tension, and nutrient availability—can trigger the transition from commensalism to pathogenicity (8). Clinically, successful infection control depends on meticulous surgical technique, appropriate implant selection, and comprehensive debridement. Considering the complexity of these interacting factors, individualized and comprehensive diagnostic and therapeutic strategies that account for both patient-specific and pathogen-specific variables are essential. 6. Pathogenesis of Osteomyelitis Microscopic examination of acute osteomyelitis foci reveals acute suppurative inflammation resulting from bacterial or other microbial invasion (9). Various inflammatory mediators and leukocytes induce tissue necrosis, leading to the destruction of bone trabeculae and the bone matrix. During the inflammatory process, vascular structures undergo progressive obliteration, resulting in reduced local perfusion. This ischemia plays a critical role in the pathogenesis of bone necrosis. Abnormal bone growth around the joint in response to infection, referred to as the osteophytic layer, is described as a “box for dead bone.” Channels within this layer facilitate pus drainage and are known as “cloacae” (10). Initially, the necrotic bone (sequestrum) maintains contact with healthy bone; over time, granulation tissue formation separates the necrotic bone from viable bone, promoting sequestration and facilitating removal of devitalized structures. This separation is an important indicator of progression from acute to chronic osteomyelitis. The sequestrum surface is rough and porous, containing pus, and its bone cells are non-viable, lacking osteoclastic or osteoblastic activity. Proteolytic enzymes dissolve the organic components of the sequestrum. Necrotic bone may persist within the inflammatory site or be eliminated by the body (11). Following spontaneous or surgical removal of the sequestrum, new bone regeneration commences. In chronic osteomyelitis, new bone formation occurs around necrotic bone, accompanied by mononuclear cell infiltration (lymphocytes, histiocytes, plasma cells). New bone formation JAWBONE OSTEOMYELITIS IN ALL ASPECTSLİTERATURE REVIEW   43 surrounding necrotic tissue under the endosteum and periosteum is termed the involucrum. A detailed understanding of osteomyelitis pathophysiology enables the development of more effective treatment strategies, facilitating elimination of primary causative factors and control of secondary contributors to prevent disease progression. 7. Classification of Osteomyelitis Osteomyelitis exhibits diverse characteristics, and considering patient population variability along with multiple criteria is crucial for determining the optimal treatment approach. Management largely depends on whether the disease is clinically categorized as “acute” or “chronic.” For long bones, the first widely accepted staging system was developed by Waldvogel and Medoff, based on infection pathophysiology, duration, and route of spread (12). This classification addresses osteomyelitis through hematogenous spread. A more comprehensive system was proposed by Cierny et al. (13) and Mader and Calhoun (14), which considers both the anatomical location of infection and the patient’s physiological status. The four main components of the CiernyMader classification are patient condition, functional loss due to disease, site of involvement, and degree of bone necrosis. This system defines 12 clinical stages for adult osteomyelitis. Debridement techniques, dead space management, and antibiotic therapy are planned according to these stages. 7.1ClassificationBasedonLocalization Osteomyelitis can be classified according to the anatomical site of involvement. Intramedullary osteomyelitis is confined to the endosteal focus, and since the infection is limited to the medullary cavity, bone grafting is generally not required. Subperiosteal osteomyelitis develops from periapical or periodontal foci, leading to pus accumulation beneath the periosteum. This process causes pressure-induced ischemia, resulting in chronic abscess formation and localized cortical bone infection. Periosteal osteomyelitis is restricted to the bone surface. Treatment involves debridement of the infected area until healthy, well-vascularized tissue exhibiting the Paprika sign is reached (15). 7.2ClassificationBasedonDuration A new classification system proposed by the Department of CranioMaxillofacial Surgery at the University of Zurich divides osteomyelitis into three 44   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II forms based on clinical presentation, disease course, and radiographic findings: acute, secondary chronic, and primary chronic osteomyelitis. According to Mercuri and Marx (16), acute osteomyelitis is typically characterized by the appearance of clinical symptoms within the first month after the initial infection, distinguishing it from subacute or chronic forms. If pathological persistence extends beyond this period, the condition is classified as chronic osteomyelitis. Acute osteomyelitis usually presents as a sudden-onset, rapidly progressing infection, often associated with trauma or hematogenous spread. Chronic osteomyelitis is further subdivided into primary chronic osteomyelitis (PCO) and secondary chronic osteomyelitis (SCO). 7.2.1AcuteOsteomyelitis Acute osteomyelitis presents suddenly and is characterized by clinical features such as swelling, edema, trismus (restricted mandibular movement), impaired jaw function, fatigue, high fever, paresthesia or anesthesia of the lower lip (Vincent’s sign), regional lymphadenopathy, increased tooth mobility, malocclusion, and halitosis (7). Radiographic findings typically become apparent approximately 10 days after onset (17). Decreased bone density, destruction, necrosis, and radiolucent areas are observed. Trabecular degeneration occurs, and bone contours appear indistinct. Root resorption may be evident, and the loss of trabecular bone can obscure dental follicles. 7.2.2ChronicOsteomyelitis Following suppuration in the acute or subacute phase, the disease may progress to a chronic stage, reflected in both clinical course and presentation (Figure 1A). In the chronic phase, pain and swelling are generally milder than during the acute phase. The severe, sharp pain characteristic of acute osteomyelitis is replaced by a persistent, dull discomfort. Localized edema and painful swelling due to acute abscess formation diminish, and firmer tenderness resulting from periosteal reactions is observed. Halitosis, common in acute abscesses, is less frequently reported in chronic osteomyelitis. Tooth mobility and displacement may occur in the affected region, resulting from increased intraosseous pressure or as a consequence or triggering factor of osteomyelitis, potentially leading to malocclusion. Chronic osteomyelitis is further classified based on the presence of suppuration into chronic suppurative osteomyelitis and chronic non-suppurative (sclerosing) osteomyelitis (3,18,19). Acute osteomyelitis and the subsequent secondary chronic osteomyelitis are JAWBONE OSTEOMYELITIS IN ALL ASPECTSLİTERATURE REVIEW   45 generally characterized by marked suppuration, sequestration, abscess, or fistula formation. (Figure 1) Figure 1: Clinical and surgical appearance of chronic osteomyelitis in the mandibular region: (A) Exposed necrotic bone visible through the oral mucosa, (B) necrotic bone observed in the surgical field following incision and flap elevation, (C) According to Hudson, Topazian, and Bernier et al. (3,18,19), chronic osteomyelitis may present clinically in five distinct forms. 7.2.2.1ChronicDiffuseSclerosingOsteomyelitis(CDSO) Chronic diffuse sclerosing osteomyelitis (CDSO) is thought to arise from a proliferative response of host bone to infectious stimuli. However, it is also considered a variant of non-infectious chronic osteomyelitis, characterized by recurrent pain and swelling in the cheek region (20). No specific age range has been established for this condition. Diagnosis of CDSO is supported by clinical, radiological, and histopathological findings. Due to its unclear etiology, treatment approaches vary. Some researchers regard CDSO as a localized variant of SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis), which also includes Sternocostoclavicular Hyperostosis (SCCH) and Chronic 46   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II Recurrent Multifocal Osteomyelitis (CRMO). Alternatively, CDSO may result from tendoperiostitis secondary to excessive masticatory muscle activity (21). Treatment options range from physical therapy to surgical intervention, with successful outcomes reported when muscle relaxants are combined with physiotherapy. 7.2.2.2ChronicFocalSclerosingOsteomyelitis(CondensingOsteitis) Chronic focal sclerosing osteomyelitis is a periapical lesion resulting from reactive bone formation triggered by persistent dental pulp inflammation. It typically arises in the mandibular molar region due to low-grade pulpal infection secondary to deep caries. Both infectious agents and vascular structures play key roles in this osteomyelitis form. In some cases, osteoblast-mediated bone formation becomes pronounced in response to chronic infection. Newly formed bone generally exhibits cortical characteristics, while marrow spaces are reduced, leading to loss of trabecular bone. Regions where marrow spaces are preserved show significant inflammatory activity and cellular infiltration. In cases involving large bone segments, impaired circulation may reduce the effectiveness of antibiotic therapy. The chronic nature of the disease is partly associated with thrombotic events in the inferior alveolar artery and vein (22). 7.2.2.3 Chronic Non-Suppurative Sclerosing Osteomyelitis (Garre Osteomyelitis) Garre osteomyelitis is characterized by localized periosteal thickening due to mild chronic irritation or low-grade infection, typically caused by lowvirulence, likely anaerobic microorganisms. It predominantly affects children and young adults. The main symptom is mild but persistent pain, often accompanied by swelling and tenderness. Radiographically, bone expansion and sclerosis are observed. The mandible is most frequently affected, with lesions usually unifocal and unilateral. Clinical presentation may be asymptomatic or involve mild-to-moderate pain, trismus, low-grade fever, and fatigue. Subperiosteal bone deposits can cause firm swelling and facial asymmetry. Although often associated with carious teeth, it may also occur in individuals with healthy teeth and no evident infectious factors. Radiographically, the “onion-skin” appearance, characterized by radiopaque layers parallel to the cortical bone surface, is typical (23). Removal of the causative factor and antibiotic therapy usually lead to resolution, with bone remodeling restoring normal architecture. Surgical remodeling may be required in cases with significant bone proliferation JAWBONE OSTEOMYELITIS IN ALL ASPECTSLİTERATURE REVIEW   47 7.2.2.4SAPHOSyndrome SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) is considered in some studies as part of CDSO and in others as a distinct disease entity. It is a chronic autoimmune condition involving the joints, bones, and skin, more common in women and typically affecting individuals under 30 years of age. SAPHO-related osteomyelitis presents with pain and swelling but without suppuration. Symptoms have sudden onset, persist long-term, and alternate between exacerbation and remission. In some cases, the entire mandible may be affected. Panoramic radiographs show decreased bone volume, while CT imaging demonstrates sclerosis of cancellous bone and periosteal reactions. Cortical bone may exhibit radiopaque areas, and periosteal bone deposits are present. Bone expansion may also occur. 7.2.2.5ChronicRecurrentMultifocalOsteomyelitis(CRMO) Chronic recurrent multifocal osteomyelitis (CRMO) is an autoimmune disorder characterized by bone pain, fever, flares, and remission periods. It is frequently associated with other autoimmune diseases and is considered an idiopathic, autoinflammatory condition of unknown etiology. Some studies link CRMO to SAPHO syndrome, though CRMO primarily affects younger individuals, distinguishing it from SAPHO. Recently, adult cases have also been reported, indicating that it is not limited to children and adolescents (24). Clinically, CRMO presents with slowly developing localized bone pain, tenderness, and swelling, with symmetric and multifocal involvement. Symptom duration may range from a few days to several years, and its insidious onset often obscures the precise onset time of the disease. 7.2.3OsteomyelitisDuetoSpecificInfections 7.2.3.1ActinomycoticOsteomyelitis Actinomycotic osteomyelitis is caused by Gram-positive anaerobic bacteria, primarily Actinomyces israelii and Actinomyces viscosus, with A. israelii being the most common. These infections typically involve soft tissues and rarely spread to bone following tooth extraction or surgical procedures. Radiographic evaluation assesses the extent of inflammation, while culture tests identify the causative organism. Treatment involves surgical drainage combined with a 3–4 month course of penicillin-based antibiotics (25). 48   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II 7.2.3.2TuberculousOsteomyelitis Tuberculous osteomyelitis is caused by Mycobacterium tuberculosis and typically spreads hematogenously from the lungs or via contamination of extraction sites by infected saliva. Treatment consists of an 18–20 month regimen of isoniazid (INH), streptomycin, and para-aminosalicylic acid (PAS) (26). 7.2.3.3SyphiliticOsteomyelitis Syphilitic osteomyelitis, now rare, may occur in the neonatal period or as part of tertiary syphilis. Congenital syphilis due to Treponema pallidum often results in symmetric skeletal lesions, particularly affecting the epiphyses of long tubular bones such as the humerus and radius. Clinical features include delayed healing after dental extractions, jaw fractures, and pyogenic osteomyelitis. Treatment involves penicillin-based antibiotics for both osteomyelitis and syphilis (27). 7.2.3.4Coccidioidomycosis Coccidioides immitis primarily affects the pulmonary pleura and spreads hematogenously in approximately 1% of cases. Facial bone osteomyelitis may involve the maxilla, frontal, parietal bones, or mandible, and is associated with granulomatous inflammation and subcutaneous abscesses. Diagnosis is based on complement fixation tests, histopathological biopsy with fungal staining, microbial culture, and coccidioidin skin testing. Treatment includes intravenous amphotericin B, surgical debridement, and adjuvant therapy using leukocyte extracts from individuals with positive coccidioidin skin tests (28). 7.2.3.5HerpesZosterOsteomyelitis Varicella-Zoster virus infection can lead to painful vesicular eruptions along nerve branches. In some cases, involvement of the inferior alveolar nerve may cause thrombosis and subsequent osteonecrosis (29). This is more commonly observed in elderly patients or those undergoing chemotherapy or radiotherapy. 7.2.4OsteomyelitisCausedbyChemicalAgents Chemical agents such as arsenic, mercury, and phosphorus may induce necrosis in dental procedures. Arsenic, historically used for pulp devitalization, can cause gingival necrosis if it leaks from cavities or spreads from the tooth JAWBONE OSTEOMYELITIS IN ALL ASPECTSLİTERATURE REVIEW   49 apex to surrounding tissues (30). Treatment involves removal of arsenic followed by irrigation with warm oxygenated water or bicarbonate solution. Mercury, found in some dental materials, can lead to necrotizing stomatitis, osteonecrosis, tooth mobility, and systemic symptoms such as anemia, fatigue, and shock. Management includes chelation therapy and supportive care for affected organs. Phosphorus exposure, typically in industrial settings, initially causes gingivitis and gum ulcers, eventually impairing bone vascularization, leading to bone destruction and tooth mobility. 7.3ClassificationBasedonDevelopmentMechanism Osteomyelitis can develop via exogenous or hematogenous routes. In exogenous osteomyelitis, infections originating from soft tissues or joints can rapidly spread to adjacent bone (31). This type of osteomyelitis frequently occurs in conditions associated with vascular insufficiency, such as diabetes and peripheral vascular disease, where reduced perfusion diminishes immune response. Another route for exogenous osteomyelitis is inoculation, in which pathogens or microorganisms enter the body through external sources, including open fractures, metallic implants or prostheses, human or animal bites, and penetrating injuries. Open fractures and surgical contamination are among the most common causes. Exogenous osteomyelitis is typically polymicrobial, with Staphylococcus aureus being the most frequently isolated organism, followed by S. epidermidis, S. pyogenes, Enterococcus species, gram-negative bacilli, and anaerobes. Hematogenous osteomyelitis occurs when microorganisms are transported via the bloodstream to establish an infection focus within the bone. The infection may originate from a primary site elsewhere in the body or result from bacteremia after dental procedures, such as tooth brushing. Microorganisms colonize bone tissue, leading to infection. Brodie abscess, a localized form of osteomyelitis more common in young adults, typically affects the long bones of the lower extremities before epiphyseal closure (32). In adults, the metaphysealepiphyseal region is most frequently involved. Clinically, it presents with mild pain and localized tenderness. S. aureus is isolated in approximately 67% of cultures in cases involving low-virulence pathogens. Recurrence occurs in 15.6% of cases, necessitating additional interventions (33). Radiographically, the abscess may mimic a tumor; thus, biopsy is often required for definitive diagnosis. Treatment generally consists of 48 hours of intravenous (IV) antibiotics followed by six weeks of oral antibiotics. Local antibiotic therapy may also be used as an adjunct or alternative. 56   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II observation of perfusion in the healthy bone after necrotic tissue excision, (E) platelet-rich fibrin (PRF) preparation obtained from the patient, (F) application of PRF onto the bone surface, (G) coverage of the area with a resorbable membrane, and (H) closure of the surgical site with primary sutures. Despite these advances, the establishment of standardized treatment protocols and validation through large-scale clinical studies remain essential. 12. Conclusion Effective management of jaw osteomyelitis requires early diagnosis and a multidisciplinary treatment strategy. Integration of advanced imaging techniques, pathogen-targeted antimicrobial therapy, and timely surgical intervention significantly improves clinical outcomes. Interdisciplinary teams comprising oral and maxillofacial surgeons, infectious disease specialists, radiologists, and clinical microbiologists play a critical role in accurately identifying the underlying etiology, developing individualized treatment protocols, and minimizing the risk of complications. Long-term clinical follow-up is particularly crucial in cases involving extensive bone destruction or reconstructive procedures, both for monitoring bone regeneration and preventing recurrence. Such a collaborative, evidence-based approach not only enhances therapeutic efficacy but also contributes substantially to functional rehabilitation and overall patient quality of life. 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The use of leucocyte and platelet-rich fibrin in socket management and ridge preservation: a split-mouth, JAWBONE OSTEOMYELITIS IN ALL ASPECTSLİTERATURE REVIEW   61 randomized, controlled clinical trial. J Clin Periodontol. 2016;43(11):990-999. doi:10.1111/jcpe.12612 55) Miron RJ, Zhang Y. Autologous liquid platelet rich fibrin: a novel drug delivery system. Acta Biomater. 2018;75:35-51. doi:10.1016/j. actbio.2018.05.021 63 CHAPTER V BURNING MOUTH SYNDROME (BMS) IN DENTISTRY Gaye KESER1 & Filiz NAMDAR PEKİNER2 1(Assoc. Prof.) Marmara University, Faculty of Dentistry, Department of Dentomaxillofacial Radiology, Istanbul/Turkey E-mail:[email protected] ORCID: 0000-0001-7564-4757 2(Prof.) Marmara University, Faculty of Dentistry, Department of Dentomaxillofacial Radiology, Istanbul/Turkey E-mail: [email protected] ORCID: 0000-0001-7426-5587 1. Introduction Burning Mouth Syndrome (BMS) is defined as a chronic intraoral burning or dysesthetic sensation of the oral mucosa, recurring daily for at least 2 hours per day over more than 3 months, without any identifiable clinical lesions or laboratory abnormalities to account for the symptoms . (1-10) In other words, BMS is an idiopathic orofacial pain condition characterized by a persistent burning pain in a clinically normal mouth (often described as a scalding, tingling, or numb sensation) that cannot be attributed to any local or systemic cause). (2,3,5) This condition has been known by various terms historically including glossodynia, stomatodynia, oral dysesthesia, burning tongue, and stomatopyrosis all referring to the same clinical phenomenon of burning pain in the oral tissues. (3,4) In 2004 the International Headache Society first classified BMS as “an intraoral burning sensation for which no medical or dental cause can be found,” emphasizing that by definition, BMS is a diagnosis of exclusion after ruling out identifiable causes. (7) Recent international pain classification 64   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II systems (ICOP 2020) have formalized similar criteria, underscoring the chronic daily nature of the pain and the lack of objective findings. (8) (Table 1) Table 1. Some definitions and diagnostic criteria of Burning Mouth Syndrome (BMS) (5). Organization Definition IASP (2016) “A chronic intraoral burning sensation that has no identifiable cause either local or systemic disease.” IHS (2018) “An intraoral burning or dysesthesia sensation, recurring daily for more than 2 h per day over more than 3 months, without clinically evident causative lesions.” WHO (2018) “A chronic orofacial pain with an intraoral burning or dysaesthetic sensation that recurs for more than 2 h per day on 50% of the days over more than 3 months, without evident causative lesions on clinical investigation and examination.” IASP. Burning Mouth Syndrome. 2016. International Headache Society. 13.11 Burning Mouth Syndrome (BMS), ICHD-3 the International Classification of Headache Disorders 3rd edition World Health Organization. Burning Mouth Syndrome.2018. Because of the complex symptomatology and lack of clinical signs, BMS can be challenging to recognize. It is crucial for dental practitioners to understand that BMS is essentially a neuropathic pain syndrome of the oral cavity, one that may involve both peripheral nerve dysfunction and central neural mechanisms in the absence of detectable lesions. (11,12) The condition can significantly impact quality of life despite the normal clinical appearance, making empathetic acknowledgement of the patient’s pain an important aspect of management. In summary, BMS is an idiopathic chronic burning pain in the mouth with normal clinical exam and no identifiable cause, requiring a diagnosis of exclusion and a multidisciplinary management approach. (4,5,7) 2. Epidemiology 2.1.Prevalence Published epidemiologic studies of BMS report highly variable prevalence rates, owing to differences in study populations and diagnostic criteria. (9,12) BURNING MOUTH SYNDROME (BMS) IN DENTISTRY   65 Overall, BMS is considered an uncommon condition in the general population, but not rare in certain subgroups. Population-based research suggests a prevalence in the general adult population on the order of around 1–3%. For example, a recent systematic review and meta-analysis estimated the pooled global prevalence of BMS at 1.73% (approximately 1 in 58 people) in the general population. (13) Among patients seen in dental or oral medicine clinics (i.e. those actively seeking care for oral symptoms), the prevalence is higher, roughly 5–8% in various studies (10,14) reflecting that many BMS sufferers are symptomatic enough to seek professional help. Older literature showed a very wide range of prevalence values (from under 0.1% up to 15–40% in select groups) (15), but these extremes often included patients with any oral burning symptom or very specific subpopulations. When strict diagnostic criteria are applied, the true prevalence of BMS is at the lower end of that range. For instance, a rigorous population-based study in Olmsted County, Minnesota (USA) found a point prevalence of only 0.11% (about 1 in 1000) for clinically confirmed BMS. Notably, that study diagnosed only 149 cases of BMS in a population of ~140,000, highlighting that strict case definitions yield lower prevalence figures. (16) 2.2.GenderandAgeDistribution BMS exhibits a striking gender bias, predominantly affecting women. Female-to-male ratio estimates vary from about 3:1 up to 7:1, with most reports around 3–5 women for every man with BMS. (4,17) The disparity is especially pronounced in the peri-menopausal and post-menopausal age groups. Up to 90% of BMS patients are women in the 50–70 year age range, coinciding with hormonal changes of menopause. (18) The typical age of onset is in the 5th to 7th decades of life and studies report mean ages around 55–65 years. (19,20) BMS is uncommon in patients under 30; it virtually never occurs in children or young adults. A large Taiwanese nationwide study similarly found the prevalence of diagnosed BMS increased steadily with each older age bracket, individuals aged 60–69 had about double the risk, and those >70 about 2.6-fold risk, compared to those in their 40s. (21) Advancing age is thus a major risk factor. The female predominance has been hypothesized to relate to post-menopausal hormonal changes and other gender-specific factors. (1) Notably, even among men who develop BMS, the mean age is in later adulthood, and often similar psychosocial or medical backgrounds may be present. 72   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II characteristic pattern and excluding other potential diagnoses. It is imperative when evaluating BMS-like symptoms to consider and rule out other causes of oral burning or pain. A thorough history and examination, along with targeted lab tests, will usually differentiate the above conditions from BMS. For example, one clue: if visible redness is present on an area that burns, it’s likely not BMS but rather a secondary cause like atrophic candidiasis or contact reaction. BMS’s hallmark is pain without clinical signs. (4,5,12,32,37) In summary, the clinical features of BMS center on a chronic bilateral oral burning pain, often accompanied by taste changes and dry mouth sensation, in the context of a normal oral examination. The pain follows certain patterns (continuous vs. increasing through day) and is uniquely relieved by certain stimuli (eating) and unaffected by others (sleep). Dentists and dental students should familiarize themselves with these features to recognize BMS. It is equally important to remember what should not be seen in BMS – any positive clinical finding should redirect the diagnosis to something other than BMS. Educating the patient that the absence of visible signs does not mean their pain isn’t “real” is also a key part of managing this challenging syndrome, as many patients are frustrated that “everything looks normal” despite their suffering. 5. Diagnostic Criteria and Procedures BMS is primarily a diagnosis of exclusion, since no single laboratory or imaging test confirms the status. (4,5,8,12) Diagnosis relies on careful clinical history, thorough oral and cranial nerve examination, and targeted investigations to rule out local, systemic, or neurological causes. Scala’s criteria remain widely accepted, requiring daily bilateral burning for at least 4–6 months, normal mucosa, and absence of identifiable causes. (4) The International Classification of Headache Disorders (ICHD-3) and the International Classification of Orofacial Pain (ICOP) provide similar criteria, emphasizing intraoral burning >2 hours/day over >3 months with no clinical or laboratory abnormalities. (6,7) Supportive findings include xerostomia, dysgeusia, and psychological comorbidities. (4,5,8,9,12) The diagnostic work-up involves a detailed history of onset, pattern, and triggers of pain, along with psychosocial assessment for stress, anxiety, or depression. Clinical examination must exclude oral lesions such as BURNING MOUTH SYNDROME (BMS) IN DENTISTRY   73 candidiasis, lichen planus, or denture-related trauma, while systemic evaluations should rule out deficiencies (iron, vitamins B1, B2, B6, B12, folate, zinc), diabetes, thyroid disease, and autoimmune conditions such as Sjögren’s. (14,37) Laboratory tests (CBC, ferritin, vitamin assays, glucose, thyroid function, autoimmune markers) and adjunctive tools like salivary flow measurements or Candida cultures are recommended where indicated. (38-40) Despite standardized criteria, BMS diagnosis is often delayed, as patients typically undergo multiple consultations and empiric treatments without clear explanation. Clinicians must carefully distinguish BMS from secondary cases where a systemic or local cause is identified and treated. (8,9,12,14) Specialized procedures such as quantitative sensory testing, blink reflex studies, or lidocaine block tests highlight altered peripheral and central pain processing, though these remain research tools rather than routine clinical diagnostics. (37-39) Studies by Pekiner et al. underline the importance of comprehensive screening, demonstrating differences in salivary trace elements and cytokines in BMS patients, along with associated anxiety and depression profiles. (1-3,34) Ultimately, diagnosis requires clinician–patient communication to validate the condition as a genuine neuropathic pain syndrome and to prepare for multimodal management. 6. Treatment and Management Strategies Management of BMS can be challenging due to its multifactorial nature and the absence of a singular definitive cause. An individualized, multi-modal approach is often necessary, addressing any identifiable contributing factors and employing therapies aimed at neuropathic pain relief and symptom management for BMS. The overarching goals are to reduce the oral burning sensation, improve any associated symptoms (dry mouth, taste disturbances), and improve the patient’s overall comfort and quality of life. A combination of pharmacologic treatments, non-pharmacologic therapies, and supportive measures is typically used. (12,14,35) It is important for both clinician and patient to understand that no single universally effective “cure” exists for BMS some trial and error is commonly required to find the most effective regimen, and often partial relief rather than total elimination of pain is achieved at least initially. (37,38) Nonetheless, many patients can attain significant improvement with proper management. 74   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II 6.1.Non-PharmacologicandAdjunctiveTherapies Patient education and reassurance is perhaps the most important supportive measure is to explain that the pain is real but benign, and that management aims for control rather than cure. This reassurance alone can significantly reduce patient distress. (5,34,38,40) Psychological interventions address the significant psychosocial overlay of BMS. Cognitive Behavioral Therapy (CBT) has demonstrated efficacy in reducing pain perception and improving coping. (37) Correcting parafunctional habits through habit-reversal techniques or splints may contribute to symptom reduction. (34) 6.2.SystemicPharmacologicTherapies Systemic pharmacotherapy is often required in BMS, though responses are variable Oral clonazepam or diazepam may help but are limited by risks of sedation and dependence; hence the topical route is favored. (5,14,34,36) Tricyclic antidepressants (e.g., amitriptyline), SSRIs (e.g., paroxetine, sertraline), and SNRIs (e.g., duloxetine) are widely used in neuropathic pain syndromes and may provide both analgesic and anxiolytic benefits. (37) However, side effects such as xerostomia limit their tolerability. Gabapentin and pregabalin are used off-label with some success in neuropathic pain, including BMS. Their combination with alpha-lipoic acid has been studied with positive results in subsets of patients. (37,40) Limited evidence exists for tramadol or other anticonvulsants; carbamazepine is generally ineffective, as BMS does not behave like trigeminal neuralgia. (34,36) The prognosis of BMS is variable. Classic natural history studies describe a “rule of thirds”: approximately one-third of patients remit spontaneously, onethird partially improve, and one-third remain symptomatic long-term. However, contemporary multimodal care likely shifts more patients into the improvement category. Importantly, BMS does not progress to structural disease; its burden lies primarily in reduced quality of life. (34,36,40) The management of Burning Mouth Syndrome requires an individualized, patient-centered strategy. While many patients achieve partial relief rather than complete remission, with persistence and a multi-pronged regimen tailored to individual needs, meaningful improvement in symptoms and quality of life is attainable. Current evidence underscores that BMS is a heterogeneous, neuropathic pain disorder with complex biopsychosocial dimensions. Ongoing research into neuroinflammatory pathways, pain modulation mechanisms, and BURNING MOUTH SYNDROME (BMS) IN DENTISTRY   75 precision-guided therapy holds promise for more effective management in the future. 7. Conclusion BMS is a multifactorial, predominantly neuropathic pain disorder of the oral cavity that presents with a characteristic clinical phenotype—chronic daily burning in a clinically normal mouth, often accompanied by dysgeusia and subjective xerostomia. For dentists and dental students, the essential takeaways are threefold: first, BMS remains a diagnosis of exclusion, requiring meticulous history, comprehensive intraoral and systemic evaluation, and targeted investigations to rule out secondary causes; second, its pathophysiology is heterogeneous, spanning peripheral small-fiber neuropathy, altered gustatory– trigeminal interactions, central dopaminergic and pain-modulatory dysfunction, and modulatory influences of hormonal and psychological factors; and third, management is individualized and multimodal, combining correction of reversible contributors (when present) with evidence-informed topical and systemic therapies, adjunctive non-pharmacologic strategies, and sustained patient education. While a universal cure is lacking, most patients achieve meaningful symptomatic improvement through tailored combinations administered within a supportive, empathic therapeutic alliance. 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Asian J Oral Maxillofac Surg. 2011;23(4):161-6. 79 CHAPTER VI EPIDERMOLYSIS BULLOSA (EB) SUAY YAĞMUR ÜNAL1 & GAYE KESER2 & FİLİZ NAMDAR PEKİNER3 1(Asst. Prof.) Nişantaşı University, Faculty of Dentistry, Department of Dentomaxillofacial Radiology, Istanbul/Turkey E-mail: [email protected] ORCID: 0000-0002-8559-7461 2(Assoc. Prof.) Marmara University, Faculty of Dentistry, Department of Dentomaxillofacial Radiology, Istanbul/Turkey E-mail: [email protected] ORCID: 0000-0001-7564-4757 3(Prof.) Marmara University, Faculty of Dentistry, Department of Dentomaxillofacial Radiology, Istanbul/Turkey E-mail: [email protected] ORCID: 0000-0001-7426-5587 1. Introduction Epidermolysis bullosa (EB) is a group of rare inherited disorders marked by extreme fragility of the skin and mucous membranes, leading to blistering after minimal trauma. Most cases present at birth or in early infancy, although milder forms may be diagnosed later. The incidence is estimated at 20 per million live births, with a prevalence of about 11 per million (1). The unifying feature of EB is structural weakness at the dermal–epidermal junction. Depending on the gene defect, tissue separation occurs at different levels: intraepidermal in EB simplex (keratin mutations), within the lamina lucida in junctional EB (laminin-332 or collagen XVII defects), beneath the 80   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II basement membrane in dystrophic EB (collagen VII deficiency), or at multiple levels in Kindler syndrome (kindlin-1 mutations) (2). Clinically, EB ranges from localized, mild blistering to severe, multisystem disease. Shared features include recurrent blisters, chronic wounds, pain, and infection risk. Severe forms may cause deformities from scarring (such as pseudosyndactyly and contractures) and predispose to aggressive squamous cell carcinoma. Extracutaneous manifestations include oral and esophageal fragility, ocular involvement, genitourinary strictures, enamel defects, and growth impairment from malnutrition. Given this heterogeneity, precise classification and diagnosis are essential for management (3) (Figure 1). EPIDERMOLYSIS BULLOSA (EB)   81 Figure 1. Summary of the clinical, genetic, and pathophysiological features of major epidermolysis bullosa subtypes. 88   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II (“mitten” hands and feet), joint contractures, microstomia, and ankyloglossia. Esophageal strictures cause dysphagia and malnutrition, often requiring gastrostomy feeding. Nutrient deficiencies and chronic inflammation contribute to anemia and growth retardation. Other features include ocular erosions with potential scarring, chronic granulation tissue, and recurrent infections. By adolescence or early adulthood, over 90% of patients develop aggressive cutaneous squamous cell carcinomas in chronic wounds, which are the leading cause of death. Despite severe physical disability, cognitive development remains normal (8,26) (Figure 2). Figure 2. Clinical presentation of recessive dystrophic epidermolysis bullosa in a 3-year-old female patient. The upper panel shows widespread facial involvement with hemorrhagic bullae, erosions, crusted lesions, and postinflammatory changes. The lower panel demonstrates hand involvement with erosions, hemorrhagic and crusted bullae, scarring, and early pseudosyndactyly. Hands are covered with protective non-adherent dressings to minimize trauma and secondary infection. Intermediate RDEB manifests with generalized blistering but less mutilation. Scarring and contractures occur, but hand function may be EPIDERMOLYSIS BULLOSA (EB)   89 preserved longer, and mucosal involvement is variable. Patients often survive into adulthood, with a lower—though still elevated—risk of squamous cell carcinoma compared to the severe subtype (28). Dominant DEB (DDEB): DDEB is generally milder, with blistering localized to trauma-prone areas such as hands, feet, knees, and elbows. Lesions heal with small atrophic scars, and nail dystrophy—thickened, absent, or malformed nails—is a common feature. Some patients present only with nail involvement or limited scarring, and symptoms often improve after puberty. Mucosal disease is rare, and the risk of squamous cell carcinoma is minimal, close to baseline population levels. Life expectancy is normal, though disease severity can vary within families due to differences in expression of mutant collagen VII (24). 4.3.Diagnosis DEB is suspected in patients with scarring blistering and confirmed by demonstrating defects in type VII collagen. On skin biopsy, immunofluorescence mapping shows absent or markedly reduced collagen VII at the dermal– epidermal junction in severe RDEB, with altered or reduced staining in milder forms. Cleavage occurs below the lamina densa, so markers such as laminin or collagen IV localize to the blister roof, leaving the dermis unstained. Electron microscopy may reveal few or absent anchoring fibrils in the papillary dermis, a hallmark of collagen VII deficiency (2,8). Genetic testing of COL7A1 is now the gold standard, identifying pathogenic variants and determining inheritance. A single heterozygous mutation supports DDEB, whereas biallelic mutations confirm RDEB. Mutation type also predicts severity, with truncating variants usually linked to severe disease. Molecular diagnosis further enables prenatal testing and is critical for eligibility in emerging geneand cell-based therapies (10). Clinical diagnosis alone can be misleading: mild DEB may resemble EBS, while generalized blistering in infants could reflect any EB subtype. The presence of scarring strongly favors DEB, while enamel hypoplasia suggests JEB. Laboratory evaluation should also screen for complications, including anemia, nutritional deficiencies, and squamous cell carcinoma risk. Chronic ulcers or proliferative lesions require biopsy to exclude malignancy (27). 90   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II 4.4.Management Severe recessive DEB requires comprehensive multidisciplinary care, while dominant DEB management is generally less intensive. The goals are to prevent trauma, optimize wound healing, preserve function, and monitor for complications. Skin and wound care: Protective bandaging and padding reduce friction and new blistering. Blisters should be drained and covered with non-adherent dressings. Chronic wounds often need antimicrobial dressings (e.g., silverbased). Granulation tissue can be treated with topical steroids or silver nitrate. Any suspicious chronic ulcer must be biopsied to exclude squamous cell carcinoma (SCC); dermatologic surveillance is essential, at least annually from adolescence (13). Hand and foot care: Pseudosyndactyly in RDEB may be surgically released to restore function, though recurrence is common. Postoperative splinting and physiotherapy help maintain mobility. Daily stretching exercises and orthotic support delay contractures. In DDEB, interventions are usually limited to nail care and protection from trauma (26). Mucosal and gastrointestinal management: Esophageal dilations relieve strictures, while gastrostomy tubes often provide nutritional support in children with severe dysphagia. A high-calorie, high-protein diet with micronutrient supplementation (iron, zinc, calcium, vitamin D) is recommended. Constipation from reduced mobility, scarring, or opioid use requires regular bowel regimens. Dental care is vital, though complicated by microstomia and scarring (24). Pain and itch control: Pain management combines systemic opioids, adjuncts for neuropathic pain (e.g., gabapentin), and topical analgesics. Sedation may be needed for extensive dressing changes. Itch is treated with antihistamines or gabapentin, while psychological support and coping strategies improve longterm quality of life (9,16). Preventive monitoring: Regular labs track anemia and nutritional deficiencies. Cardiac evaluation and bone density scans are recommended, given risks of cardiomyopathy and osteoporosis. Endocrine support may be needed for delayed puberty. SCC screening is critical, with frequent dermatology follow-up in high-risk patients (6). Emerging therapies: Several novel treatments are under evaluation. Topical gene therapy with beremagene geperpavec (B-VEC), approved in 2023, enables local collagen VII production and accelerates wound healing. Oleogel-S10 (birch bark extract) promotes re-epithelialization. Systemic options under study include EPIDERMOLYSIS BULLOSA (EB)   91 losartan for fibrosis, bisphosphonates for osteoporosis, and recombinant collagen VII infusions. High-risk approaches such as bone marrow transplantation and mesenchymal stem cell infusions are experimental. Autologous gene-corrected skin grafts show promising early results (15). Genetic counseling: In DDEB, each child of an affected parent has a 50% risk; in RDEB, carrier parents confer a 25% risk to each child. Prenatal testing can be offered in severe families (10). 5. Kindler Syndrome 5.1.PathophysiologyandGenetics Kindler syndrome (KS), sometimes classified as a subtype of EB, is a rare genodermatosis that differs from the classic EB types in that blister formation can occur at multiple levels of the skin. It is caused by mutations in the FERMT1 gene (also called KIND1), which encodes the protein kindlin-1. Kindlin-1 is involved in integrin signaling and in anchoring the actin cytoskeleton to the extracellular matrix in basal keratinocytes. It plays a role in maintaining the adhesion of the epidermis, though its function is not limited to a single basement membrane zone layer. Kindler syndrome is inherited in an autosomal recessive manner: biallelic loss-of-function mutations in FERMT1 result in absence or dysfunction of kindlin-1. As a consequence, basal keratinocytes have impaired attachment and signaling, leading to skin fragility. A hallmark of KS is that blistering occurs at variable levels – sometimes intraepidermal and sometimes at the dermal-epidermal junction – which reflects the complex role of kindlin-1 in the adhesion structures. In early life, cleavage is often intraepidermal (resembling EB simplex), whereas later, chronic damage leads to more junctional/dermal separation and scarring (resembling features of dystrophic EB). Kindlin-1 is also expressed in other tissues (e.g. colon, gingiva); its deficiency explains some of the non-cutaneous manifestations of Kindler syndrome (29,30). 5.2.ClinicalFeatures Kindler syndrome (KS) presents with trauma-induced blistering from birth, followed by progressive skin changes. Infants typically develop acral blisters on the hands and feet after minor trauma, resembling other EB subtypes. A distinguishing feature is photosensitivity in early childhood, with exaggerated erythema and blistering on sun-exposed sites. Over time, patients develop poikiloderma—mottled hypoand hyperpigmentation, telangiectasia, 92   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II and epidermal atrophy—which begins on sun-exposed areas and later becomes generalized. By adolescence, the skin appears thin, wrinkled, and atrophic, while blistering tends to diminish (31) (Figure 3). Figure 3. Clinical features of recessive dystrophic epidermolysis bullosa in an adult patient. The upper panel shows ocular involvement with chronic conjunctival inflammation, ectropion, and scarring of the eyelids. The middle panel demonstrates hand deformities with contractures, scarring, and nail dystrophy. The lower panel reveals perioral involvement with angular cheilitis and enamel defects consistent with longstanding disease. Other hallmarks include palmoplantar hyperkeratosis, mild pseudosyndactyly, and occasional flexion contractures, though less severe than in EPIDERMOLYSIS BULLOSA (EB)   93 dystrophic EB. Nail dystrophy may occur, but hair is usually unaffected. Mucosal fragility is prominent, with chronic gingivitis and aggressive periodontitis leading to early tooth loss. Additional complications include esophageal and urethral strictures, phimosis in males, and ocular changes such as ectropion. Patients often develop striae and atrophic scars even from minor trauma (32). Photosensitivity often lessens in adulthood, but poikiloderma and atrophy persist. KS carries an increased risk of squamous cell carcinoma, particularly of the lips and oral mucosa, with cutaneous SCC also reported. Severe longterm morbidity arises from mucosal cancers and strictures. The clinical picture is distinct: early acral blistering with photosensitivity evolves into widespread atrophy and pigmentary change, setting KS apart from other EB subtypes (33). 5.3.Diagnosis Kindler syndrome should be suspected in children with congenital acral blistering combined with photosensitivity and early-onset poikiloderma. Because these features overlap with other disorders—such as dystrophic EB, poikiloderma congenita, or xeroderma pigmentosum—genetic testing provides definitive diagnosis. Sequencing of FERMT1 typically reveals biallelic pathogenic variants (2). If genetic testing is unavailable, skin biopsy with immunofluorescence may show variable cleavage planes, though standard panels do not routinely assess kindlin-1. In specialized laboratories, absent kindlin-1 expression can be demonstrated immunohistochemically. Electron microscopy may reveal basement membrane duplication and variable levels of separation, findings more subtle than in other EB subtypes. Clinically, early and diffuse poikiloderma (usually evident by age 5–10) strongly supports KS, as poikiloderma is otherwise rare or late in EB (34). Severe periodontal disease is another diagnostic clue, with gingival fragility and early tooth loss disproportionate to other EB types. Because KS is rare, patients are often initially misdiagnosed as atypical EB or as having separate blistering and photosensitivity disorders (35). Once confirmed, monitoring should include regular dental care and oral cancer screening due to the high risk of mucosal squamous cell carcinoma. Endoscopic evaluation is indicated if symptoms suggest strictures of the esophagus, urethra, or colon. Genetic counseling is essential, as KS is autosomal recessive, often associated with parental consanguinity or geographic founder mutations. Prenatal testing can be offered to at-risk families (36). 94   DIAGNOSIS, TREATMENT AND APPLICATION IN DENTISTRY STUDIES 2025 - II 5.4.Management There is no curative therapy for Kindler syndrome; treatment focuses on minimizing trauma, protecting against UV damage, and addressing mucocutaneous complications. Sun protection: Rigorous photoprotection is essential in childhood. Patients should avoid direct sun exposure, use broad-spectrum sunscreens (SPF 50+ with UVA coverage), and wear protective clothing, hats, and sunglasses. Although photosensitivity often decreases in adulthood, lifelong UV protection helps reduce cumulative skin damage and cancer risk (37). Blister and wound care: Blisters should be drained and covered with non-adherent dressings. Acral areas remain prone to trauma, so protective padding may be useful. Chronic erosions should be managed with moist wound-healing techniques. Signs of infection require prompt topical or systemic antibiotics (38). Skin hydration and keratoderma: Regular emollients reduce dryness and itching, while keratolytic creams (urea, lactic acid) and careful paring can manage palmoplantar hyperkeratosis. Cushioned insoles and protective gloves help reduce pressure-related injury (39). Oral and dental care: Aggressive dental management is critical due to severe periodontitis. Frequent dental cleanings, antiseptic rinses, and softbristle brushing are recommended. Topical corticosteroids may relieve gingival inflammation. Despite interventions, many patients lose teeth early; dentures or implants may be considered, though fragility of mucosa complicates implant use. Microstomia can be addressed with stretching exercises or devices (40). Monitoring strictures: Esophageal, urethral, and anal strictures should be suspected in patients with dysphagia, urinary difficulties, or painful defecation. Endoscopic dilation, urethroplasty, or surgical interventions may be required. Gastrostomy tubes may provide supplemental nutrition if swallowing becomes difficult (41). Cancer surveillance: KS carries increased risk of mucosal squamous cell carcinoma, particularly affecting the lips and oral cavity. Regular dental exams and patient education for early recognition of suspicious lesions are essential. Skin cancers may also arise in areas of chronic poikiloderma. Early biopsy and excision, sometimes with Mohs surgery, improve outcomes. Radiation therapy is used cautiously due to skin sensitivity (35). Supportive care and counseling: Psychosocial support, connection with EB patient groups, and genetic counseling are integral to care. As KS is autosomal EPIDERMOLYSIS BULLOSA (EB)   95 recessive, siblings have a 25% recurrence risk, and prenatal testing can be offered to affected families (42). Although no disease-specific therapies exist, ongoing research into integrin signaling and keratinocyte biology may eventually yield targeted interventions. With careful multidisciplinary care, many patients achieve reasonable quality of life into adulthood, despite significant chronic morbidity. 6. Conclusion Epidermolysis bullosa represents a heterogeneous group of inherited disorders unified by fragility of the skin and mucous membranes. Despite major differences in genetic basis and clinical severity, all subtypes share the challenge of recurrent blistering, chronic wounds, and systemic complications that profoundly affect patients and their families. Advances in molecular diagnostics have improved classification and facilitated genetic counseling, while multidisciplinary supportive care remains the cornerstone of management. In recent years, progress in gene therapy, protein replacement, and regenerative medicine has provided hope for disease-modifying treatments. Although curative options are not yet widely available, ongoing research has already led to promising clinical trials. Continued collaboration between clinicians, researchers, and patient organizations is essential to translate these advances into accessible therapies and to improve quality of life and long-term outcomes for individuals living with EB. References 1. Fine, J. D., Johnson, L. B., Weiner, M., et al. (2016). Epidemiology of inherited epidermolysis bullosa based on incidence and prevalence estimates from the National EB Registry. JAMA Dermatology, 152(11), 1231–1238. https://doi.org/10.1001/jamadermatol.2016.2473 2. Has, C., Castiglia, D., del Rio, M., et al. 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