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Pulp Obliteration in a Patient with Sclerodermatous Chronic Graft-versus-Host Disease
Case Report/Clinical Technique
Pulp Obliteration in a Patient with Sclerodermatous Chronic Graft-versus-Host Disease Camilla Borges Ferreira Gomes, DMD, MSc,*† Nathaniel Simon Treister, DMD, DMSc,†‡ Brian Miller, DMD,§ Philippe Armand, MD, PhD,‡ and Bernard Friedland, BChD, MSc, JDk Abstract Dental pulp calcification is a common finding associated with localized dental trauma, genetic disorders, and systemic inflammatory diseases. Chronic graft-versus-host disease (cGVHD) is a frequent complication after allogeneic hematopoietic cell transplantation (allo-HCT) characterized by immune-mediated injury to the skin, mouth, eyes, liver, and other tissues, resulting in significant disability and reduced quality of life. We report a patient with sclerodermatous cGVHD who presented with general pulp calcification in all teeth 5 years after allo-HCT. A review of full mouth dental radiographs obtained just before allo-HCT revealed normal-appearing pulp chambers. Based on prior reports of generalized pulp calcification associated with progressive systemic sclerosis, we hypothesized that the etiology was likely related to the presence of cGVHD with associated vascular and fibrotic tissue changes within the pulp vasculature. Clinicians should consider cGVHD in the differential diagnosis of generalized pulp calcification. (J Endod 2016;-:1–3)
Key Words Allogeneic hematopoietic cell transplantation, dental pulp obliteration, oral chronic graft-versus-host disease, pulp calcification
D
ental pulp calcification is characterized by the deposition of diffuse hard tissue in the coronal pulp and occasionally extending to the root canal space, leading radiographically to a decrease in the size or complete obliteration of the pulp chamber (1–4). Many etiologic factors have been associated with pulp calcification of individual teeth including trauma, orthodontic treatment, caries, and periodontal disease (1). Generalized pulp calcifications have been reported in patients with genetic disorders (eg, dentin dysplasia and dentinogenesis imperfecta), syndromes (eg, Van der Woude and Marfan syndromes) (4, 5), chronic inflammatory diseases (eg, cardiovascular disease and progressive systemic sclerosis [PSS]) (2, 6), and advanced age (1). Although the exact mechanism of pulp calcification is still unknown, damage to the neurovascular supply to the pulp has been related to this occurrence (7). Chronic graft-versus-host disease (cGVHD) is an immunologically mediated condition that frequently develops after allogeneic hematopoietic cell transplantation (alloHCT) and is associated with significant functional impairment, disability, and decreased quality of life (8–10). The oral cavity and skin are the 2 most frequently affected organs. Oral mucosal involvement often presents with lichenoid inflammation and ulcers resulting in oral pain and sensitivity with eating and drinking (11). cGVHD may also involve fascial tissue with obliteration of the vasculature and excessive collagen deposition, leading to limited mobility and activity, dyspnea, and chronic ulcers (12–14). This sclerodermatous complication appears in 10%–15% of patients with cGVHD; it is characterized by clinical manifestations similar to PSS, including plaques of dermal sclerosis and joint contractures (12, 15). We report a case of a patient with extensive sclerodermatous cGVHD who presented with generalized pulp chamber obliteration 5 years after allo-HCT.
Case Report From the *Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, S~ao Paulo, Brazil; † Division of Oral Medicine and Dentistry, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts; ‡Department of Medical Oncology/Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts; §Miller Lung Dental Group, South Attleboro, Massachusetts; and kDepartment of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts. Address requests for reprints to Dr Camilla Borges Ferreira Gomes, Department of Oral Diagnosis, School of Dentistry, State University of Campinas, Av Limeira 901, CEP 13414018, Piracicaba, SP, Brazil. E-mail address: camillabfgomes@ hotmail.com 0099-2399/$ - see front matter Copyright ª 2016 American Association of Endodontists. http://dx.doi.org/10.1016/j.joen.2016.01.009
JOE — Volume -, Number -, - 2016
A 43-year-old man with advanced chronic lymphocytic leukemia underwent routine dental clinical and radiographic evaluation before undergoing allo-HSCT. The dental radiographs were within normal limits and without evidence of caries (Fig. 1). He received a reduced intensity conditioning peripheral blood stem cell graft from his matched sister; conditioning consisted of low-dose busulfan and fludarabine and GVHD prophylaxis of tacrolimus and methotrexate. By day 180, cGVHD was noted to have affected the skin, mouth, and liver, and therapy was initiated with prednisone. Oral cavity involvement was characterized by typical lichenoid inflammation with white reticular changes, erythema, and ulcerations, which were managed effectively with ancillary dexamethasone solution rinses (0.5 mg/mL) and localized applications of clobetasol propionate gel 0.05%. Cutaneous cGVHD was characterized by an erythematous rash on the hands with hyper- and hypopigmentation over the waistline, bilateral axillae, and neck. The skin was treated with tacrolimus 0.1% ointment and clobetasol propionate 0.05% cream. Subsequently, he developed sclerotic changes and mobility impairment. He received additional treatment including rituximab and mycophenolate mofetil. He also developed bronchiolitis obliterans syndrome and was started on fluticasone, montelukast, and azithromycin. With treatment, his cGVHD, including the sclerodermatous and pulmonary components, stabilized. Five years after allo-HCT, the patient underwent a routine dental examination including a new full mouth series of intraoral radiographs. He was asymptomatic, and upon clinical examination, there were no signs of oral cGVHD, caries, or other
Pulp Obliteration and cGVHD
1
Case Report/Clinical Technique
Figure 1. Full mouth series of intraoral radiographs obtained as part of the dental screening evaluation before allo-HCT, showing normal-appearing teeth and bone with well-defined pulp spaces.
lesions. A radiographic evaluation showed widespread obliterated pulp chambers and root canals of the entire dentition (Fig. 2). Pulp testing with ethyl chloride–soaked cotton and direct application to the buccal/facial surfaces revealed a minimal response without lingering with teeth #18, 19, 21, 24, 25, 29, 30, and 31; all other teeth were nonresponsive. Potential causes, including trauma, dentin dysplasia, dentinogenesis imperfecta, and other syndromes, were ruled out by history and a clinical examination. Given the documented normal radiographic appearance of the teeth before alloHCT, the history of extensive sclerodermatous cGVHD, and the onset and generalized pattern of the pulpal obliteration, a diagnosis was made of sclerosis of the pulp chambers related to sclerodermatous cGVHD. Thus, because the teeth were all asymptomatic and without evidence of necrosis, no specific treatment was recommended.
Discussion Generalized pulp calcification has been associated with a number of systemic conditions such as cardiovascular disease and PSS (1, 2, 6). Although it might be related to vascular abnormalities involving the microvasculature of the pulp chamber and reactive dentin synthesis, the pathophysiologic mechanism is not well understood (2). When individual teeth are affected, it may be a response to long-standing local irritation (eg, dental trauma or caries) that initiates an inflammatory process within the pulp tissue, with subsequent vascular changes and calcifications produced by pulpal responses (1, 3). However, when the findings are generalized, there are typically no significantly associated localized factors present (16). PPS is an autoimmune disorder associated with vascular abnormalities characterized by excessive production and deposition of collagen within the skin and internal organs (17). A related sclerotic phenotype results as a consequence of intense and continuous inflammation and vascular changes, causing an autoimmunity foreign body reaction, fibroblastic activation, and collagen deposition, which can subsequently undergo calcification (17–19).
Figure 2. Full mouth series obtained 5 years after allo-HCT showing complete calcification and opacification of the dental pulp of all teeth.
2
Gomes et al.
Sclerodermalike manifestations, characterized by patchy areas of sclerotic plaques and thickened reticular dermis often resulting in join contracture, are 1 of the possible manifestations of cGVHD (12, 20). Although the pathogenesis of sclerodermatous cGVHD is unclear, the similarities in the sclerotic clinical presentation of the skin and subcutaneous tissues suggest that it might be related to PSS. Spontaneous resolution of these sclerodermatous lesions may occur; other patients respond to immunosuppressive treatment or extracorporeal photopheresis, whereas some patients have a relentlessly progressive and sometimes fatal course (15, 18). Oral sclerodermalike lesions, which are characterized by limitation of mouth opening, limited tongue mobility, and dysphagia, are rarely observed in cGVHD patients (11, 21–23). Oral radiographic features correlated to PSS are widening of the periodontal ligament space and varying degrees of bone resorption in the mandible. Pulp calcification leading to obliteration of the root canal may be an associated manifestation of this condition (6, 23). This is the first report of a patient with extensive sclerodermatous cGVHD who developed generalized dental pulp obliteration. Given the similarities clinically and histopathologically between PSS and sclerodermatous cGVHD, we hypothesized that the finding of pulp and canal obliteration in this patient is likely related to chronic inflammation affecting the vasculature of the dental pulp, resulting in specific vascular changes, which produced a collagen-fibrotic material and calcification of the pulp chamber. Although electric pulp testing also was not performed, we would not have expected there to be a response given the extent of pulp obliteration, and, regardless, given that the patient was asymptomatic, the approach to management would not have been affected even with a positive finding. Clinicians should be aware that teeth undergoing pulp calcification are asymptomatic, and endodontic therapy is not recommended in the absence of symptoms, radiographic signs of caries, or periapical disease (3, 6, 12). In conclusion, we report a case of generalized pulp calcification in a patient with extensive long-standing sclerodermatous cGVHD after allo-HCT. Although this finding had no impact on the health and function of the patient’s dentition, it illustrates the potentially protean clinical manifestations of cGVHD and the wide range of tissues that can be affected. Clinicians and endodontists in particular should be aware of this possible finding.
Acknowledgments The authors deny any conflicts of interest related to this study.
References 1. Goga R, Chandler NP, Oginni AO. Pulp stones: a review. Int Endod J 2008;41: 457–68. 2. Nayak M, Kumar J, Prasad LK. A radiographic correlation between systemic disorders and pulp stones. Indian J Dent Res 2010;21:369–73. 3. McCabe PS, Dummer PM. Pulp canal obliteration: an endodontic diagnosis and treatment challenge. Int Endod J 2012;45:177–97. 4. Kantaputra PN, Sumitsawan Y, Schutte BC, Tochareontanaphol C. Van der Woude syndrome with sensorineural hearing loss, large craniofacial sinuses, dental pulp stones, and minor limb anomalies: report of a four-generation Thai family. Am J Med Genet 2002;108:275–80. 5. Bauss O, Neter D, Rahman A. Prevalence of pulp calcifications in patients with Marfan syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106: e56–61. 6. Jung S, Minoux M, Maniere MC, et al. Previously undescribed pulpal and periodontal ligament calcifications in systemic sclerosis: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:e47–51. 7. Robertson A. A retrospective evaluation of patients with uncomplicated crown fractures and luxation injuries. Endod Dent Traumatol 1998;14:245–56. 8. Perez-Simon JA, Sanchez-Abarca I, Diez-Campelo M, et al. Chronic graft-versus-host disease: Pathogenesis and clinical management. Drugs 2006;66:1041–57.
JOE — Volume -, Number -, - 2016
Case Report/Clinical Technique 9. Treister NS, Cook EF Jr, Antin J, et al. Clinical evaluation of oral chronic graft-versushost disease. Biol Blood Marrow Transplant 2008;14:110–5. 10. DePalo J, Chai X, Lee SJ, et al. Assessing the relationship between oral chronic graftversus-host disease and global measures of quality of life. Oral Oncol 2015;51: 944–9. 11. Schubert MM, Correa ME. Oral graft-versus-host disease. Dent Clin North Am 2008; 52:79–109. viii-ix. 12. Skert C, Patriarca F, Sperotto A, et al. Sclerodermatous chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: incidence, predictors and outcome. Haematologica 2006;91:258–61. 13. Fleming JN, Schwartz SM. The pathology of scleroderma vascular disease. Rheum Dis Clin North Am 2008;34:41–55. vi. 14. White JM, Creamer D, du Vivier AW, et al. Sclerodermatous graft-versus-host disease: clinical spectrum and therapeutic challenges. Br J Dermatol 2007;156: 1032–8. 15. Pines M, Snyder D, Yarkoni S, Nagler A. Halofuginone to treat fibrosis in chronic graft-versus-host disease and scleroderma. Biol Blood Marrow Transplant 2003; 9:417–25.
JOE — Volume -, Number -, - 2016
16. Sener S, Cobankara FK, Akgunlu F. Calcifications of the pulp chamber: prevalence and implicated factors. Clin Oral Investig 2009;13:209–15. 17. Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med 2009;360: 1989–2003. 18. Boin F, Hummers LK. Scleroderma-like fibrosing disorders. Rheum Dis Clin North Am 2008;34:199–220. ix. 19. Inamoto Y, Storer BE, Petersdorf EW, et al. Incidence, risk factors, and outcomes of sclerosis in patients with chronic graft-versus-host disease. Blood 2013;121: 5098–103. 20. Ratanatharathorn V, Ayash L, Lazarus HM, et al. Chronic graft-versus-host disease: clinical manifestation and therapy. Bone Marrow Transplant 2001;28:121–9. 21. Kuten-Shorrer M, Woo SB, Treister NS. Oral graft-versus-host disease. Dent Clin North Am 2014;58:351–68. 22. Mays JW, Fassil H, Edwards DA, et al. Oral chronic graft-versus-host disease: current pathogenesis, therapy, and research. Oral Dis 2013;19:327–46. 23. Anbiaee N, Tafakhori Z. Early diagnosis of progressive systemic sclerosis (scleroderma) from a panoramic view: report of three cases. Dentomaxillofac Radiol 2011;40:457–62.
Pulp Obliteration and cGVHD
3
Pulp Obliteration in a Patient with Sclerodermatous Chronic Graft-versus-Host Disease Camilla Borges Ferreira Gomes, DMD, MSc,*† Nathaniel Simon Treister, DMD, DMSc,†‡ Brian Miller, DMD,§ Philippe Armand, MD, PhD,‡ and Bernard Friedland, BChD, MSc, JDk Abstract Dental pulp calcification is a common finding associated with localized dental trauma, genetic disorders, and systemic inflammatory diseases. Chronic graft-versus-host disease (cGVHD) is a frequent complication after allogeneic hematopoietic cell transplantation (allo-HCT) characterized by immune-mediated injury to the skin, mouth, eyes, liver, and other tissues, resulting in significant disability and reduced quality of life. We report a patient with sclerodermatous cGVHD who presented with general pulp calcification in all teeth 5 years after allo-HCT. A review of full mouth dental radiographs obtained just before allo-HCT revealed normal-appearing pulp chambers. Based on prior reports of generalized pulp calcification associated with progressive systemic sclerosis, we hypothesized that the etiology was likely related to the presence of cGVHD with associated vascular and fibrotic tissue changes within the pulp vasculature. Clinicians should consider cGVHD in the differential diagnosis of generalized pulp calcification. (J Endod 2016;-:1–3)
Key Words Allogeneic hematopoietic cell transplantation, dental pulp obliteration, oral chronic graft-versus-host disease, pulp calcification
D
ental pulp calcification is characterized by the deposition of diffuse hard tissue in the coronal pulp and occasionally extending to the root canal space, leading radiographically to a decrease in the size or complete obliteration of the pulp chamber (1–4). Many etiologic factors have been associated with pulp calcification of individual teeth including trauma, orthodontic treatment, caries, and periodontal disease (1). Generalized pulp calcifications have been reported in patients with genetic disorders (eg, dentin dysplasia and dentinogenesis imperfecta), syndromes (eg, Van der Woude and Marfan syndromes) (4, 5), chronic inflammatory diseases (eg, cardiovascular disease and progressive systemic sclerosis [PSS]) (2, 6), and advanced age (1). Although the exact mechanism of pulp calcification is still unknown, damage to the neurovascular supply to the pulp has been related to this occurrence (7). Chronic graft-versus-host disease (cGVHD) is an immunologically mediated condition that frequently develops after allogeneic hematopoietic cell transplantation (alloHCT) and is associated with significant functional impairment, disability, and decreased quality of life (8–10). The oral cavity and skin are the 2 most frequently affected organs. Oral mucosal involvement often presents with lichenoid inflammation and ulcers resulting in oral pain and sensitivity with eating and drinking (11). cGVHD may also involve fascial tissue with obliteration of the vasculature and excessive collagen deposition, leading to limited mobility and activity, dyspnea, and chronic ulcers (12–14). This sclerodermatous complication appears in 10%–15% of patients with cGVHD; it is characterized by clinical manifestations similar to PSS, including plaques of dermal sclerosis and joint contractures (12, 15). We report a case of a patient with extensive sclerodermatous cGVHD who presented with generalized pulp chamber obliteration 5 years after allo-HCT.
Case Report From the *Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, S~ao Paulo, Brazil; † Division of Oral Medicine and Dentistry, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts; ‡Department of Medical Oncology/Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts; §Miller Lung Dental Group, South Attleboro, Massachusetts; and kDepartment of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts. Address requests for reprints to Dr Camilla Borges Ferreira Gomes, Department of Oral Diagnosis, School of Dentistry, State University of Campinas, Av Limeira 901, CEP 13414018, Piracicaba, SP, Brazil. E-mail address: camillabfgomes@ hotmail.com 0099-2399/$ - see front matter Copyright ª 2016 American Association of Endodontists. http://dx.doi.org/10.1016/j.joen.2016.01.009
JOE — Volume -, Number -, - 2016
A 43-year-old man with advanced chronic lymphocytic leukemia underwent routine dental clinical and radiographic evaluation before undergoing allo-HSCT. The dental radiographs were within normal limits and without evidence of caries (Fig. 1). He received a reduced intensity conditioning peripheral blood stem cell graft from his matched sister; conditioning consisted of low-dose busulfan and fludarabine and GVHD prophylaxis of tacrolimus and methotrexate. By day 180, cGVHD was noted to have affected the skin, mouth, and liver, and therapy was initiated with prednisone. Oral cavity involvement was characterized by typical lichenoid inflammation with white reticular changes, erythema, and ulcerations, which were managed effectively with ancillary dexamethasone solution rinses (0.5 mg/mL) and localized applications of clobetasol propionate gel 0.05%. Cutaneous cGVHD was characterized by an erythematous rash on the hands with hyper- and hypopigmentation over the waistline, bilateral axillae, and neck. The skin was treated with tacrolimus 0.1% ointment and clobetasol propionate 0.05% cream. Subsequently, he developed sclerotic changes and mobility impairment. He received additional treatment including rituximab and mycophenolate mofetil. He also developed bronchiolitis obliterans syndrome and was started on fluticasone, montelukast, and azithromycin. With treatment, his cGVHD, including the sclerodermatous and pulmonary components, stabilized. Five years after allo-HCT, the patient underwent a routine dental examination including a new full mouth series of intraoral radiographs. He was asymptomatic, and upon clinical examination, there were no signs of oral cGVHD, caries, or other
Pulp Obliteration and cGVHD
1
Case Report/Clinical Technique
Figure 1. Full mouth series of intraoral radiographs obtained as part of the dental screening evaluation before allo-HCT, showing normal-appearing teeth and bone with well-defined pulp spaces.
lesions. A radiographic evaluation showed widespread obliterated pulp chambers and root canals of the entire dentition (Fig. 2). Pulp testing with ethyl chloride–soaked cotton and direct application to the buccal/facial surfaces revealed a minimal response without lingering with teeth #18, 19, 21, 24, 25, 29, 30, and 31; all other teeth were nonresponsive. Potential causes, including trauma, dentin dysplasia, dentinogenesis imperfecta, and other syndromes, were ruled out by history and a clinical examination. Given the documented normal radiographic appearance of the teeth before alloHCT, the history of extensive sclerodermatous cGVHD, and the onset and generalized pattern of the pulpal obliteration, a diagnosis was made of sclerosis of the pulp chambers related to sclerodermatous cGVHD. Thus, because the teeth were all asymptomatic and without evidence of necrosis, no specific treatment was recommended.
Discussion Generalized pulp calcification has been associated with a number of systemic conditions such as cardiovascular disease and PSS (1, 2, 6). Although it might be related to vascular abnormalities involving the microvasculature of the pulp chamber and reactive dentin synthesis, the pathophysiologic mechanism is not well understood (2). When individual teeth are affected, it may be a response to long-standing local irritation (eg, dental trauma or caries) that initiates an inflammatory process within the pulp tissue, with subsequent vascular changes and calcifications produced by pulpal responses (1, 3). However, when the findings are generalized, there are typically no significantly associated localized factors present (16). PPS is an autoimmune disorder associated with vascular abnormalities characterized by excessive production and deposition of collagen within the skin and internal organs (17). A related sclerotic phenotype results as a consequence of intense and continuous inflammation and vascular changes, causing an autoimmunity foreign body reaction, fibroblastic activation, and collagen deposition, which can subsequently undergo calcification (17–19).
Figure 2. Full mouth series obtained 5 years after allo-HCT showing complete calcification and opacification of the dental pulp of all teeth.
2
Gomes et al.
Sclerodermalike manifestations, characterized by patchy areas of sclerotic plaques and thickened reticular dermis often resulting in join contracture, are 1 of the possible manifestations of cGVHD (12, 20). Although the pathogenesis of sclerodermatous cGVHD is unclear, the similarities in the sclerotic clinical presentation of the skin and subcutaneous tissues suggest that it might be related to PSS. Spontaneous resolution of these sclerodermatous lesions may occur; other patients respond to immunosuppressive treatment or extracorporeal photopheresis, whereas some patients have a relentlessly progressive and sometimes fatal course (15, 18). Oral sclerodermalike lesions, which are characterized by limitation of mouth opening, limited tongue mobility, and dysphagia, are rarely observed in cGVHD patients (11, 21–23). Oral radiographic features correlated to PSS are widening of the periodontal ligament space and varying degrees of bone resorption in the mandible. Pulp calcification leading to obliteration of the root canal may be an associated manifestation of this condition (6, 23). This is the first report of a patient with extensive sclerodermatous cGVHD who developed generalized dental pulp obliteration. Given the similarities clinically and histopathologically between PSS and sclerodermatous cGVHD, we hypothesized that the finding of pulp and canal obliteration in this patient is likely related to chronic inflammation affecting the vasculature of the dental pulp, resulting in specific vascular changes, which produced a collagen-fibrotic material and calcification of the pulp chamber. Although electric pulp testing also was not performed, we would not have expected there to be a response given the extent of pulp obliteration, and, regardless, given that the patient was asymptomatic, the approach to management would not have been affected even with a positive finding. Clinicians should be aware that teeth undergoing pulp calcification are asymptomatic, and endodontic therapy is not recommended in the absence of symptoms, radiographic signs of caries, or periapical disease (3, 6, 12). In conclusion, we report a case of generalized pulp calcification in a patient with extensive long-standing sclerodermatous cGVHD after allo-HCT. Although this finding had no impact on the health and function of the patient’s dentition, it illustrates the potentially protean clinical manifestations of cGVHD and the wide range of tissues that can be affected. Clinicians and endodontists in particular should be aware of this possible finding.
Acknowledgments The authors deny any conflicts of interest related to this study.
References 1. Goga R, Chandler NP, Oginni AO. Pulp stones: a review. Int Endod J 2008;41: 457–68. 2. Nayak M, Kumar J, Prasad LK. A radiographic correlation between systemic disorders and pulp stones. Indian J Dent Res 2010;21:369–73. 3. McCabe PS, Dummer PM. Pulp canal obliteration: an endodontic diagnosis and treatment challenge. Int Endod J 2012;45:177–97. 4. Kantaputra PN, Sumitsawan Y, Schutte BC, Tochareontanaphol C. Van der Woude syndrome with sensorineural hearing loss, large craniofacial sinuses, dental pulp stones, and minor limb anomalies: report of a four-generation Thai family. Am J Med Genet 2002;108:275–80. 5. Bauss O, Neter D, Rahman A. Prevalence of pulp calcifications in patients with Marfan syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106: e56–61. 6. Jung S, Minoux M, Maniere MC, et al. Previously undescribed pulpal and periodontal ligament calcifications in systemic sclerosis: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:e47–51. 7. Robertson A. A retrospective evaluation of patients with uncomplicated crown fractures and luxation injuries. Endod Dent Traumatol 1998;14:245–56. 8. Perez-Simon JA, Sanchez-Abarca I, Diez-Campelo M, et al. Chronic graft-versus-host disease: Pathogenesis and clinical management. Drugs 2006;66:1041–57.
JOE — Volume -, Number -, - 2016
Case Report/Clinical Technique 9. Treister NS, Cook EF Jr, Antin J, et al. Clinical evaluation of oral chronic graft-versushost disease. Biol Blood Marrow Transplant 2008;14:110–5. 10. DePalo J, Chai X, Lee SJ, et al. Assessing the relationship between oral chronic graftversus-host disease and global measures of quality of life. Oral Oncol 2015;51: 944–9. 11. Schubert MM, Correa ME. Oral graft-versus-host disease. Dent Clin North Am 2008; 52:79–109. viii-ix. 12. Skert C, Patriarca F, Sperotto A, et al. Sclerodermatous chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: incidence, predictors and outcome. Haematologica 2006;91:258–61. 13. Fleming JN, Schwartz SM. The pathology of scleroderma vascular disease. Rheum Dis Clin North Am 2008;34:41–55. vi. 14. White JM, Creamer D, du Vivier AW, et al. Sclerodermatous graft-versus-host disease: clinical spectrum and therapeutic challenges. Br J Dermatol 2007;156: 1032–8. 15. Pines M, Snyder D, Yarkoni S, Nagler A. Halofuginone to treat fibrosis in chronic graft-versus-host disease and scleroderma. Biol Blood Marrow Transplant 2003; 9:417–25.
JOE — Volume -, Number -, - 2016
16. Sener S, Cobankara FK, Akgunlu F. Calcifications of the pulp chamber: prevalence and implicated factors. Clin Oral Investig 2009;13:209–15. 17. Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med 2009;360: 1989–2003. 18. Boin F, Hummers LK. Scleroderma-like fibrosing disorders. Rheum Dis Clin North Am 2008;34:199–220. ix. 19. Inamoto Y, Storer BE, Petersdorf EW, et al. Incidence, risk factors, and outcomes of sclerosis in patients with chronic graft-versus-host disease. Blood 2013;121: 5098–103. 20. Ratanatharathorn V, Ayash L, Lazarus HM, et al. Chronic graft-versus-host disease: clinical manifestation and therapy. Bone Marrow Transplant 2001;28:121–9. 21. Kuten-Shorrer M, Woo SB, Treister NS. Oral graft-versus-host disease. Dent Clin North Am 2014;58:351–68. 22. Mays JW, Fassil H, Edwards DA, et al. Oral chronic graft-versus-host disease: current pathogenesis, therapy, and research. Oral Dis 2013;19:327–46. 23. Anbiaee N, Tafakhori Z. Early diagnosis of progressive systemic sclerosis (scleroderma) from a panoramic view: report of three cases. Dentomaxillofac Radiol 2011;40:457–62.
Pulp Obliteration and cGVHD
3