ORIGINAL CONTRIBUTIONS
Restoring lost gingival pigmentation in the esthetic zone A case report Thomas Spinell, DMD, MS; Dennis Tarnow, DDS
O
ral pigmentation is most intense in the keratinized mucosa around the incisors, and depth of pigmentation positively correlates with age.1 Various methods have been described to reduce gingival pigmentation for esthetic purposes, but only a few case reports are available on how to regain gingival pigmentation.2-5 Despite complete removal of pigmented gingiva, repigmentation may occur in the long term by melanocytes derived from the surrounding soft tissue.6 However, in cases in which pigmentation is lost, regaining pigmentation cannot be guaranteed. The time frame is unknown; hypothetically, it could even depend on the etiology of the loss of pigmentation. There are 4 pigments involved in pigmentation: carotenoids (yellow), oxygenated hemoglobin in the capillaries (red), reduced hemoglobin in the venules (blue), and melanin (brown). Melanin is the main determinant.7 The physiological oral pigmentation is found on the entire oral mucosa but varies. It is genetically determined and ranges from the darkest brown to the lightest pinkish-white. An increased intensity in pigmentation derives from an enhanced melanocytic activity rather than an increased number of melanocytes. Various pathologic alterations, systemic diseases, endocrine disorders, or systemic medications may lead to changes in oral pigmentation.1,8-12 Melanocytes are a derivative of the neural crest and lie in the stratum basale of the epithelium.13 As the
ABSTRACT Background and Overview. There is insufficient literature on the lack of oral pigmentation in the esthetic zone. The aim of this case report was to illustrate the potential impact of loss of gingival pigmentation in the esthetic zone, describe its surgical treatment, and discuss the limited literature on this topic. Case Description. An African American woman with high smile line had localized loss of gingival melanin pigmentation as a complication after implant failure and attempted guided bone regeneration in site 8. A highly pigmented free gingival graft was collected from the facialattached gingiva of the maxillary posterior teeth and placed onto the previously de-epithelialized recipient bed in the maxillary front. Some pigmentation of the graft was preserved and was visible a few weeks after surgery; some pigmentation recovered over time. At 6 months after surgery, the patient was satisfied with the esthetics. Complete recovery of pigmentation took 12 months, at which time the patient was ready to proceed with the final prosthetic work. Conclusions and Practical Implications. Gingival pigmentation can be restored using a free gingival graft from a highly pigmented area. When surgical procedures are performed in such cases, loss of gingival pigmentation should be part of the informed consent. However, further research, including histology, is needed. Key Words. Gingiva; pigmentation; esthetics; high smile line; melanocytes; free gingival graft. JADA 2015:146(6):402-405 http://dx.doi.org/10.1016/j.adaj.2014.12.021
Dr. Spinell is a postdoctoral periodontal graduate, Division of Periodontics, Section of Oral and Diagnostic Sciences, Columbia University College of Dental Medicine, and a postdoctoral research fellow, Department of Operative Dentistry and Periodontology, Ludwig-Maximilians-University, Goethe Strasse 70, D-80336 Munich, Germany. Address correspondence to Dr. Spinell at Columbia University College of Dental Medicine, 630 W. 168th St., PH-7 E 110, New York, NY 10032, e-mail [email protected]. Dr. Tarnow is a clinical professor, Division of Periodontics, Section of Oral and Diagnostic Sciences, Columbia University College of Dental Medicine, New York, NY. Copyright ª 2015 American Dental Association. All rights reserved.
402 JADA 146(6) http://jada.ada.org
June 2015
ORIGINAL CONTRIBUTIONS
only melanin-producing human cell, they are mostly responsible for the protection of DNA in the skin from ultraviolet radiation.14 The function of melanin in the oral epithelium is not well understood. The melanin in the keratinoFigure 1. Localized loss of gingival pigmentation in a patient with high smile line (A), with fixed cytes, not in the melanocytes, temporary prostheses in numbers 7 to 9 (B). determines skin color.7 Through the process of melanogenesis, melanin is packed into melanosomes. These are transpigmented tissue; or transplanting pigmented gingiva ported through dendrites and get then transferred to from the posterior teeth to the front.21,22 keratinocytes.15,16 Several experiments have shown that The patient opted to go with one of the surgical sothe physiology of the pigmentation depends on the lutions. Using a pedicle would have maintained the blood melanocytes and its melanocytic activity and even more supply to the tissue, but the donor area would have been on the keratinocytes and on interacting Langerhans healing by secondary intention, risking an additional cells.17 Furthermore, the melanin distribution in the persisting pink hue in the esthetic zone. perinuclear area within keratinocytes depends on race The free gingival graft was chosen from an area and may have an impact on skin color.18 outside of the esthetic zone. Initially, the recipient bed Keratinocytes have been shown to induce melanocytic was de-epithelialized, and the donor tissue was collected cell mitosis especially through the mitogen basic fibrofrom the maxillary right posterior facial attached gingiva blast growth factor.17,19 Because of these interactions of a using a template (Figures 2A and 2B). The graft was then melanocyte with its surrounding epidermal keratinocytes sutured in place with 6-0 Vicryl sutures, and pressure through growth factors and the expression of cell surface was applied to the graft to facilitate plasmatic circulation molecules, a melanocyte and its interacting keratinocytes (Figure 2C). The donor site healed by secondary intenhave been defined as the epidermal melanin unit tion without any further intervention. Follow-up pictures system.20 are shown for 1 and 6 weeks and for 6, 12, and 20 months In this case report and review of the literature, we after surgery (Figures 3A-D and 4). The final bridge, seek to contribute to the understanding of the processes shown in Figure 4B, was placed at 15 months after surinvolved in the treatment of lost gingival pigmentation. gery. Over the follow-up period, the recipient site gradually gained pigmentation. The patient noticed a CASE REPORT significant improvement at 8 weeks after surgery and was A 35-year-old healthy African American woman with satisfied at 6 months after surgery. Comparison between generalized gingival melanosis visited the periodontal the baseline and 20 months’ postoperative time points clinic at Columbia University College of Dental Medicine illustrates the gain in pigmentation and maturation in with symptoms of light pink gingival lesions in the the long term (Figure 4). papilla area facially between the central and lateral right DISCUSSION upper incisors (Figure 1). Two years earlier, the patient had had an implant placed at site number 8, which then This successful gain in pigmentation is in line with the had to be removed at second-stage surgery because of a observations reported by Marcuschamer and colleagues5 and Fowler and colleagues,4 who found an entire band of lack of osseointegration. Consequently, a guided bone repigmented gingiva after 4 and 6 months, respectively, regeneration procedure was attempted by the surgeon; however, the tissue sloughed during the healing process, and complete pigmentation restored at 12 months. which occurred by secondary intention, leaving the pa- Fowler and colleagues4 performed a frenectomy in the tient with a light pink patch in the papilla area between maxillary front and placed a free gingival graft into the denuded recipient bed. Marcuschamer and colleagues5 upper right central and lateral incisor. The patient felt self-conscious when smiling and therefore requested that published a case report about the use of a free gingival her esthetic appearance be corrected. At that point, the graft to gain gingival pigmentation in the esthetic zone. decision had already been made by the patient and her After guided bone regeneration with flap advancement and coronal positioning of the mucogingival junction, prosthodontist to place a tooth-supported bridge from the pink mucosal tissue apical to the mucogingival numbers 7 to 9, avoiding a further guided bone regenjunction had become visible. eration procedure and implant placement. On the basis of these case reports, one could thus The proposed treatment options included staining the gingival tissue, as practiced by certain African and Asian conclude that the placement of a free gingival graft is a valuable option to regain pigmentation. ethnic groups; performing a pedicle flap from adjacent
JADA 146(6) http://jada.ada.org
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ORIGINAL CONTRIBUTIONS
Figure 2. Collecting graft from maxillary posterior attached gingiva using a template (A, B) and placement in the deepithelialized recipient bed (C).
graft color. A pedicle graft maintaining the blood supply to the pigmented tissue may be a more promising treatment option. However, availability in the adjacent surgical area may be limited. For the treatment of skin leukoderma, several methods have been described showing promising results of up to 90% to 100% success in regard to color matching, irrespective of the surgical method, comparing ultrathin epidermal sheets, autologous cultured melanocytes, or basal cell layer suspension.24,25 A combination of techniques may be considered. Falabella and colFigure 3. Follow-up images showing epithelial sloughing at 1 week (A) and visible pigmentation in grafted site at 6 weeks (B), 6 months (C), and 12 months (D). leagues26 obtained 100% success in 7 out of 8 patients and 80% success in 1 patient with additional minigrafting after epidermal blister grafting or grafting of cultured cells. To enhance or fasten repigmentation, radiotherapy or certain proteins affecting the melanin formation may be useful.27 Proteins modulating the Figure 4. Before surgery (A) and 20 months after surgery (B) with final prosthesis in place. pathway of tyrosinase expression and/or activity have been identiNevertheless, several details need to be elucidated fied in skin treatment and may be applied in the treatfurther. Graft thickness, which affects the healing proment of oral pigmentation.28 Another possibility to enhance the outcome is the cess, and graft size may play a role in successful recovery.23 The larger the graft, the longer it may take to implantation of cultured melanocytes alone or in comachieve the target color in the center of the graft because bination with keratinocytes.25 Böttcher-Haberzeth and colleagues29 showed the tissue-engineering possibilities the cells derive from the surrounding tissue if no melanocytes are successfully transplanted. Hence, the graft of adding melanocytes in vitro to dermal–epidermal fullcollecting and handling in particular may be critical in thickness skin analogs in rat models. Bioengineered skin substitutes show promising properties; however, terms of cell survival and maintenance of the original
404 JADA 146(6) http://jada.ada.org
June 2015
ORIGINAL CONTRIBUTIONS
in regard to color, measured as the melanin and hemoglobin indexes, the split thickness graft resulted in the most authentic, natural skin–like result in white patients. Interestingly, the melanin index was highest in the bioengineered Hyalomatrix skin graft group.30 CONCLUSIONS
To date, repigmentation of the attached gingiva has been shown to work successfully in a few cases using a free gingival graft. Nevertheless, more research is necessary to reveal the underlying mechanism and molecular details of the gingival pigmentation repair process. Clinicians performing procedures in the esthetic zone of a patient with gingival pigmentation have to be aware of the possibility of loss of pigmentation, must ensure that patients provide appropriate informed consent, and should understand the surgical technique and healing time when restoring pigmentation defects. n Disclosure. Drs. Spinell and Tarnow did not report any disclosures. The authors greatly appreciate the support of Dr. Jacqulin Glick of the Division of Periodontics and the prosthetic work of Dr. Yelena Shapiro of the Department of Prosthodontics, Columbia University College of Dental Medicine, New York, NY. 1. Lenane P, Powell FC. Oral pigmentation. J Eur Acad Dermatol Venereol. 2000;14(6):448-465. 2. Kathariya R, Pradeep AR. Split mouth de-epithelization techniques for gingival depigmentation: a case series and review of literature. J Indian Soc Periodontol. 2011;15(2):161-168. 3. Hirschfeld I, Hirschfeld L. Oral pigmentation and a method of removing it. Oral Surg Oral Med Oral Pathol. 1951;4(8):1012-1016. 4. Fowler EB, Breault LG, Galvin BG. Enhancing physiologic pigmentation utilizing a free gingival graft. Pract Periodontics Aesthet Dent. 2000; 12(2):193-196. 5. Marcuschamer E, Tsukiyama T, Moroi H, Hawley CE, Griffin TJ. Restoration of gingival and esthetic deformities following flap advancement: the physiologically pigmented gingival graft—a case report. Int J Periodontics Restorative Dent. 2013;33(5):591-597. 6. Perlmutter S, Tal H. Repigmentation of the gingiva following surgical injury. J Periodontol. 1986;57(1):48-50. 7. Jimbow K, Quevedo WC Jr, Fitzpatrick TB, Szabo G. Some aspects of melanin biology: 1950-1975. J Invest Dermatol. 1976;67(1):72-89. 8. Kawasaki G, Yoshitomi I, Yanamoto S, Yamada S, Mizuno A, Umeda M. Pigmentation of the oral mucosa by PCB poisoning in Yusho patients. Arch Oral Biol. 2013;58(9):1260-1264. 9. Beehner ME, Houston GD, Young JD. Oral pigmentation secondary to minocycline therapy. J Oral Maxillofac Surg. 1986;44(7):582-584.
10. Lamey PJ, Carmichael F, Scully C. Oral pigmentation, Addison’s disease and the results of screening for adrenocortical insufficiency. Br Dent J. 1985;158(8):297-298. 11. Ippen H. Clinical aspects of pigmentation disorders due to oral contraceptives [in German]. Arch Dermatol Forsch. 1972;244:500-503. 12. Hall PF. The influence of hormones on melanogenesis. Australas J Dermatol. 1969;10(3):125-139. 13. Rawles ME. Origin of pigment cells from the neural crest in the mouse embryo. Physiol Zool. 1947;20(3):248-266. 14. Yamaguchi Y, Takahashi K, Zmudzka BZ, et al. Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis. FASEB J. 2006;20(9):1486-1488. 15. Ando H, Niki Y, Ito M, et al. Melanosomes are transferred from melanocytes to keratinocytes through the processes of packaging, release, uptake, and dispersion. J Invest Dermatol. 2012;132(4):1222-1229. 16. Schroeder HE. Melanin containing organelles in cells of the human gingiva. J Periodontal Res. 1969;4(1):1-18. 17. Prunieras M. Interactions between keratinocytes and dendritic cells. J Invest Dermatol. 1969;52(1):1-17. 18. Thong HY, Jee SH, Sun CC, Boissy RE. The patterns of melanosome distribution in keratinocytes of human skin as one determining factor of skin colour. Br J Dermatol. 2003;149(3):498-505. 19. Scott GA, Haake AR. Keratinocytes regulate melanocyte number in human fetal and neonatal skin equivalents. J Invest Dermatol. 1991;97(5): 776-781. 20. Fitzpatrick TB, Breathnach AS. The epidermal melanin unit system [in German]. Dermatol Wochenschr. 1963;147:481-489. 21. Rawal SY, Burrell R, Hamidi CS, Kalmar JR, Tatakis DN. Diffuse pigmentation of maxillary attached gingiva: four cases of the cultural practice of gingival tattoo. J Periodontol. 2007;78(1):170-176. 22. Telang GH, Ditre CM. Blue gingiva, an unusual oral pigmentation resulting from gingival tattoo. J Am Acad Dermatol. 1994;30(1):125-126. 23. Mormann W, Schaer F, Firestone AR. The relationship between success of free gingival grafts and transplant thickness. Revascularization and shrinkage—a one year clinical study. J Periodontol. 1981;52(2):74-80. 24. Olsson MJ, Juhlin L. Long-term follow-up of leucoderma patients treated with transplants of autologous cultured melanocytes, ultrathin epidermal sheets and basal cell layer suspension. Br J Dermatol. 2002;147(5):893-904. 25. Njoo MD, Westerhof W, Bos JD, Bossuyt PM. A systematic review of autologous transplantation methods in vitiligo. Arch Dermatol. 1998; 134(12):1543-1549. 26. Falabella R, Barona M, Escobar C, Borrero I, Arrunategui A. Surgical combination therapy for vitiligo and piebaldism. Dermatol Surg. 1995; 21(10):852-857. 27. Suga Y, Butt KI, Takimoto R, Fujioka N, Yamada H, Ogawa H. Successful treatment of vitiligo with PUVA-pigmented autologous epidermal grafting. Int J Dermatol. 1996;35(7):518-522. 28. Bae-Harboe YS, Park HY. Tyrosinase: a central regulatory protein for cutaneous pigmentation. J Invest Dermatol. 2012;132(12):2678-2680. 29. Böttcher-Haberzeth S, Klar AS, Biedermann T, et al. “Trooping the color”: restoring the original donor skin color by addition of melanocytes to bioengineered skin analogs. Pediatr Surg Int. 2013;29(3):239-247. 30. Nicoletti G, Brenta F, Bleve M, et al. Long-term in vivo assessment of bioengineered skin substitutes: a clinical study [published online ahead of print June 24, 2014]. J Tissue Eng Regen Med, http://dx.doi.org/10.1002/term.1939.
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Restoring lost gingival pigmentation in the esthetic zone A case report Thomas Spinell, DMD, MS; Dennis Tarnow, DDS
O
ral pigmentation is most intense in the keratinized mucosa around the incisors, and depth of pigmentation positively correlates with age.1 Various methods have been described to reduce gingival pigmentation for esthetic purposes, but only a few case reports are available on how to regain gingival pigmentation.2-5 Despite complete removal of pigmented gingiva, repigmentation may occur in the long term by melanocytes derived from the surrounding soft tissue.6 However, in cases in which pigmentation is lost, regaining pigmentation cannot be guaranteed. The time frame is unknown; hypothetically, it could even depend on the etiology of the loss of pigmentation. There are 4 pigments involved in pigmentation: carotenoids (yellow), oxygenated hemoglobin in the capillaries (red), reduced hemoglobin in the venules (blue), and melanin (brown). Melanin is the main determinant.7 The physiological oral pigmentation is found on the entire oral mucosa but varies. It is genetically determined and ranges from the darkest brown to the lightest pinkish-white. An increased intensity in pigmentation derives from an enhanced melanocytic activity rather than an increased number of melanocytes. Various pathologic alterations, systemic diseases, endocrine disorders, or systemic medications may lead to changes in oral pigmentation.1,8-12 Melanocytes are a derivative of the neural crest and lie in the stratum basale of the epithelium.13 As the
ABSTRACT Background and Overview. There is insufficient literature on the lack of oral pigmentation in the esthetic zone. The aim of this case report was to illustrate the potential impact of loss of gingival pigmentation in the esthetic zone, describe its surgical treatment, and discuss the limited literature on this topic. Case Description. An African American woman with high smile line had localized loss of gingival melanin pigmentation as a complication after implant failure and attempted guided bone regeneration in site 8. A highly pigmented free gingival graft was collected from the facialattached gingiva of the maxillary posterior teeth and placed onto the previously de-epithelialized recipient bed in the maxillary front. Some pigmentation of the graft was preserved and was visible a few weeks after surgery; some pigmentation recovered over time. At 6 months after surgery, the patient was satisfied with the esthetics. Complete recovery of pigmentation took 12 months, at which time the patient was ready to proceed with the final prosthetic work. Conclusions and Practical Implications. Gingival pigmentation can be restored using a free gingival graft from a highly pigmented area. When surgical procedures are performed in such cases, loss of gingival pigmentation should be part of the informed consent. However, further research, including histology, is needed. Key Words. Gingiva; pigmentation; esthetics; high smile line; melanocytes; free gingival graft. JADA 2015:146(6):402-405 http://dx.doi.org/10.1016/j.adaj.2014.12.021
Dr. Spinell is a postdoctoral periodontal graduate, Division of Periodontics, Section of Oral and Diagnostic Sciences, Columbia University College of Dental Medicine, and a postdoctoral research fellow, Department of Operative Dentistry and Periodontology, Ludwig-Maximilians-University, Goethe Strasse 70, D-80336 Munich, Germany. Address correspondence to Dr. Spinell at Columbia University College of Dental Medicine, 630 W. 168th St., PH-7 E 110, New York, NY 10032, e-mail [email protected]. Dr. Tarnow is a clinical professor, Division of Periodontics, Section of Oral and Diagnostic Sciences, Columbia University College of Dental Medicine, New York, NY. Copyright ª 2015 American Dental Association. All rights reserved.
402 JADA 146(6) http://jada.ada.org
June 2015
ORIGINAL CONTRIBUTIONS
only melanin-producing human cell, they are mostly responsible for the protection of DNA in the skin from ultraviolet radiation.14 The function of melanin in the oral epithelium is not well understood. The melanin in the keratinoFigure 1. Localized loss of gingival pigmentation in a patient with high smile line (A), with fixed cytes, not in the melanocytes, temporary prostheses in numbers 7 to 9 (B). determines skin color.7 Through the process of melanogenesis, melanin is packed into melanosomes. These are transpigmented tissue; or transplanting pigmented gingiva ported through dendrites and get then transferred to from the posterior teeth to the front.21,22 keratinocytes.15,16 Several experiments have shown that The patient opted to go with one of the surgical sothe physiology of the pigmentation depends on the lutions. Using a pedicle would have maintained the blood melanocytes and its melanocytic activity and even more supply to the tissue, but the donor area would have been on the keratinocytes and on interacting Langerhans healing by secondary intention, risking an additional cells.17 Furthermore, the melanin distribution in the persisting pink hue in the esthetic zone. perinuclear area within keratinocytes depends on race The free gingival graft was chosen from an area and may have an impact on skin color.18 outside of the esthetic zone. Initially, the recipient bed Keratinocytes have been shown to induce melanocytic was de-epithelialized, and the donor tissue was collected cell mitosis especially through the mitogen basic fibrofrom the maxillary right posterior facial attached gingiva blast growth factor.17,19 Because of these interactions of a using a template (Figures 2A and 2B). The graft was then melanocyte with its surrounding epidermal keratinocytes sutured in place with 6-0 Vicryl sutures, and pressure through growth factors and the expression of cell surface was applied to the graft to facilitate plasmatic circulation molecules, a melanocyte and its interacting keratinocytes (Figure 2C). The donor site healed by secondary intenhave been defined as the epidermal melanin unit tion without any further intervention. Follow-up pictures system.20 are shown for 1 and 6 weeks and for 6, 12, and 20 months In this case report and review of the literature, we after surgery (Figures 3A-D and 4). The final bridge, seek to contribute to the understanding of the processes shown in Figure 4B, was placed at 15 months after surinvolved in the treatment of lost gingival pigmentation. gery. Over the follow-up period, the recipient site gradually gained pigmentation. The patient noticed a CASE REPORT significant improvement at 8 weeks after surgery and was A 35-year-old healthy African American woman with satisfied at 6 months after surgery. Comparison between generalized gingival melanosis visited the periodontal the baseline and 20 months’ postoperative time points clinic at Columbia University College of Dental Medicine illustrates the gain in pigmentation and maturation in with symptoms of light pink gingival lesions in the the long term (Figure 4). papilla area facially between the central and lateral right DISCUSSION upper incisors (Figure 1). Two years earlier, the patient had had an implant placed at site number 8, which then This successful gain in pigmentation is in line with the had to be removed at second-stage surgery because of a observations reported by Marcuschamer and colleagues5 and Fowler and colleagues,4 who found an entire band of lack of osseointegration. Consequently, a guided bone repigmented gingiva after 4 and 6 months, respectively, regeneration procedure was attempted by the surgeon; however, the tissue sloughed during the healing process, and complete pigmentation restored at 12 months. which occurred by secondary intention, leaving the pa- Fowler and colleagues4 performed a frenectomy in the tient with a light pink patch in the papilla area between maxillary front and placed a free gingival graft into the denuded recipient bed. Marcuschamer and colleagues5 upper right central and lateral incisor. The patient felt self-conscious when smiling and therefore requested that published a case report about the use of a free gingival her esthetic appearance be corrected. At that point, the graft to gain gingival pigmentation in the esthetic zone. decision had already been made by the patient and her After guided bone regeneration with flap advancement and coronal positioning of the mucogingival junction, prosthodontist to place a tooth-supported bridge from the pink mucosal tissue apical to the mucogingival numbers 7 to 9, avoiding a further guided bone regenjunction had become visible. eration procedure and implant placement. On the basis of these case reports, one could thus The proposed treatment options included staining the gingival tissue, as practiced by certain African and Asian conclude that the placement of a free gingival graft is a valuable option to regain pigmentation. ethnic groups; performing a pedicle flap from adjacent
JADA 146(6) http://jada.ada.org
June 2015 403
ORIGINAL CONTRIBUTIONS
Figure 2. Collecting graft from maxillary posterior attached gingiva using a template (A, B) and placement in the deepithelialized recipient bed (C).
graft color. A pedicle graft maintaining the blood supply to the pigmented tissue may be a more promising treatment option. However, availability in the adjacent surgical area may be limited. For the treatment of skin leukoderma, several methods have been described showing promising results of up to 90% to 100% success in regard to color matching, irrespective of the surgical method, comparing ultrathin epidermal sheets, autologous cultured melanocytes, or basal cell layer suspension.24,25 A combination of techniques may be considered. Falabella and colFigure 3. Follow-up images showing epithelial sloughing at 1 week (A) and visible pigmentation in grafted site at 6 weeks (B), 6 months (C), and 12 months (D). leagues26 obtained 100% success in 7 out of 8 patients and 80% success in 1 patient with additional minigrafting after epidermal blister grafting or grafting of cultured cells. To enhance or fasten repigmentation, radiotherapy or certain proteins affecting the melanin formation may be useful.27 Proteins modulating the Figure 4. Before surgery (A) and 20 months after surgery (B) with final prosthesis in place. pathway of tyrosinase expression and/or activity have been identiNevertheless, several details need to be elucidated fied in skin treatment and may be applied in the treatfurther. Graft thickness, which affects the healing proment of oral pigmentation.28 Another possibility to enhance the outcome is the cess, and graft size may play a role in successful recovery.23 The larger the graft, the longer it may take to implantation of cultured melanocytes alone or in comachieve the target color in the center of the graft because bination with keratinocytes.25 Böttcher-Haberzeth and colleagues29 showed the tissue-engineering possibilities the cells derive from the surrounding tissue if no melanocytes are successfully transplanted. Hence, the graft of adding melanocytes in vitro to dermal–epidermal fullcollecting and handling in particular may be critical in thickness skin analogs in rat models. Bioengineered skin substitutes show promising properties; however, terms of cell survival and maintenance of the original
404 JADA 146(6) http://jada.ada.org
June 2015
ORIGINAL CONTRIBUTIONS
in regard to color, measured as the melanin and hemoglobin indexes, the split thickness graft resulted in the most authentic, natural skin–like result in white patients. Interestingly, the melanin index was highest in the bioengineered Hyalomatrix skin graft group.30 CONCLUSIONS
To date, repigmentation of the attached gingiva has been shown to work successfully in a few cases using a free gingival graft. Nevertheless, more research is necessary to reveal the underlying mechanism and molecular details of the gingival pigmentation repair process. Clinicians performing procedures in the esthetic zone of a patient with gingival pigmentation have to be aware of the possibility of loss of pigmentation, must ensure that patients provide appropriate informed consent, and should understand the surgical technique and healing time when restoring pigmentation defects. n Disclosure. Drs. Spinell and Tarnow did not report any disclosures. The authors greatly appreciate the support of Dr. Jacqulin Glick of the Division of Periodontics and the prosthetic work of Dr. Yelena Shapiro of the Department of Prosthodontics, Columbia University College of Dental Medicine, New York, NY. 1. Lenane P, Powell FC. Oral pigmentation. J Eur Acad Dermatol Venereol. 2000;14(6):448-465. 2. Kathariya R, Pradeep AR. Split mouth de-epithelization techniques for gingival depigmentation: a case series and review of literature. J Indian Soc Periodontol. 2011;15(2):161-168. 3. Hirschfeld I, Hirschfeld L. Oral pigmentation and a method of removing it. Oral Surg Oral Med Oral Pathol. 1951;4(8):1012-1016. 4. Fowler EB, Breault LG, Galvin BG. Enhancing physiologic pigmentation utilizing a free gingival graft. Pract Periodontics Aesthet Dent. 2000; 12(2):193-196. 5. Marcuschamer E, Tsukiyama T, Moroi H, Hawley CE, Griffin TJ. Restoration of gingival and esthetic deformities following flap advancement: the physiologically pigmented gingival graft—a case report. Int J Periodontics Restorative Dent. 2013;33(5):591-597. 6. Perlmutter S, Tal H. Repigmentation of the gingiva following surgical injury. J Periodontol. 1986;57(1):48-50. 7. Jimbow K, Quevedo WC Jr, Fitzpatrick TB, Szabo G. Some aspects of melanin biology: 1950-1975. J Invest Dermatol. 1976;67(1):72-89. 8. Kawasaki G, Yoshitomi I, Yanamoto S, Yamada S, Mizuno A, Umeda M. Pigmentation of the oral mucosa by PCB poisoning in Yusho patients. Arch Oral Biol. 2013;58(9):1260-1264. 9. Beehner ME, Houston GD, Young JD. Oral pigmentation secondary to minocycline therapy. J Oral Maxillofac Surg. 1986;44(7):582-584.
10. Lamey PJ, Carmichael F, Scully C. Oral pigmentation, Addison’s disease and the results of screening for adrenocortical insufficiency. Br Dent J. 1985;158(8):297-298. 11. Ippen H. Clinical aspects of pigmentation disorders due to oral contraceptives [in German]. Arch Dermatol Forsch. 1972;244:500-503. 12. Hall PF. The influence of hormones on melanogenesis. Australas J Dermatol. 1969;10(3):125-139. 13. Rawles ME. Origin of pigment cells from the neural crest in the mouse embryo. Physiol Zool. 1947;20(3):248-266. 14. Yamaguchi Y, Takahashi K, Zmudzka BZ, et al. Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis. FASEB J. 2006;20(9):1486-1488. 15. Ando H, Niki Y, Ito M, et al. Melanosomes are transferred from melanocytes to keratinocytes through the processes of packaging, release, uptake, and dispersion. J Invest Dermatol. 2012;132(4):1222-1229. 16. Schroeder HE. Melanin containing organelles in cells of the human gingiva. J Periodontal Res. 1969;4(1):1-18. 17. Prunieras M. Interactions between keratinocytes and dendritic cells. J Invest Dermatol. 1969;52(1):1-17. 18. Thong HY, Jee SH, Sun CC, Boissy RE. The patterns of melanosome distribution in keratinocytes of human skin as one determining factor of skin colour. Br J Dermatol. 2003;149(3):498-505. 19. Scott GA, Haake AR. Keratinocytes regulate melanocyte number in human fetal and neonatal skin equivalents. J Invest Dermatol. 1991;97(5): 776-781. 20. Fitzpatrick TB, Breathnach AS. The epidermal melanin unit system [in German]. Dermatol Wochenschr. 1963;147:481-489. 21. Rawal SY, Burrell R, Hamidi CS, Kalmar JR, Tatakis DN. Diffuse pigmentation of maxillary attached gingiva: four cases of the cultural practice of gingival tattoo. J Periodontol. 2007;78(1):170-176. 22. Telang GH, Ditre CM. Blue gingiva, an unusual oral pigmentation resulting from gingival tattoo. J Am Acad Dermatol. 1994;30(1):125-126. 23. Mormann W, Schaer F, Firestone AR. The relationship between success of free gingival grafts and transplant thickness. Revascularization and shrinkage—a one year clinical study. J Periodontol. 1981;52(2):74-80. 24. Olsson MJ, Juhlin L. Long-term follow-up of leucoderma patients treated with transplants of autologous cultured melanocytes, ultrathin epidermal sheets and basal cell layer suspension. Br J Dermatol. 2002;147(5):893-904. 25. Njoo MD, Westerhof W, Bos JD, Bossuyt PM. A systematic review of autologous transplantation methods in vitiligo. Arch Dermatol. 1998; 134(12):1543-1549. 26. Falabella R, Barona M, Escobar C, Borrero I, Arrunategui A. Surgical combination therapy for vitiligo and piebaldism. Dermatol Surg. 1995; 21(10):852-857. 27. Suga Y, Butt KI, Takimoto R, Fujioka N, Yamada H, Ogawa H. Successful treatment of vitiligo with PUVA-pigmented autologous epidermal grafting. Int J Dermatol. 1996;35(7):518-522. 28. Bae-Harboe YS, Park HY. Tyrosinase: a central regulatory protein for cutaneous pigmentation. J Invest Dermatol. 2012;132(12):2678-2680. 29. Böttcher-Haberzeth S, Klar AS, Biedermann T, et al. “Trooping the color”: restoring the original donor skin color by addition of melanocytes to bioengineered skin analogs. Pediatr Surg Int. 2013;29(3):239-247. 30. Nicoletti G, Brenta F, Bleve M, et al. Long-term in vivo assessment of bioengineered skin substitutes: a clinical study [published online ahead of print June 24, 2014]. J Tissue Eng Regen Med, http://dx.doi.org/10.1002/term.1939.
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