Abstract
Objective
Vitamin C/Ascorbic acid inhibits tyrosinase enzyme causing melanin biosynthesis suppression. This study aimed to compare the efficacy of intra-mucosal injection (mesotherapy) with topical gel as non-surgical methods for managing gingival hyperpigmentation.
Materials and methods
Twenty healthy non-smokers with mild to severe hyperpigmented gingiva were randomly assigned for Mesotherapy (G1); intra-mucosal injection of ascorbic acid (1/week/3 weeks); or Gel (G2), topical ascorbic acid gel (1/day/3 months). Pigmentation index (DOPI), patient satisfaction, as well as histological analysis for Fontana-Masson-stained specimens were performed at baseline and after 6 months. Comparison between groups and changes by time were analyzed using Mann-Whitney and Friedman’s tests, respectively.
Results
The median DOPI significantly decreased after 1 month in G1 (P value < 0.001, r = 0.9) compared with non-significant change in G2. No pain experienced during or after treatment in both groups. G1 patients showed significantly higher satisfaction with treatment than G2. Mean area fraction of melanin forming cells was significantly reduced in both groups after 6 months, but the effect size was higher in G1 (r = 0.886) than in G2 (r = 0.797).
Conclusions
Vitamin C mesotherapy showed better and early effect than topical gel, and both techniques were not painful and esthetically satisfying in managing gingival hyperpigmentation.
Clinical relevance
Gingival melanin pigmentation causes esthetic concerns for significant number of patients. Investigating non-surgical depigmentation techniques to decrease postoperative complications and patient discomfort, pain and long healing period associated with surgical methods would be clinically significant.
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Data availability
Data available on request from the authors.
Change history
02 August 2021
A Correction to this paper has been published: https://doi.org/10.1007/s00784-021-04110-4
References
Pavlic V, Brkic Z, Marin S, Cicmil S, Gojkov-Vukelic M, Aoki A (2018) Gingival melanin depigmentation by Er:YAG laser: A literature review. J. Cosmet. Laser Ther. 20:85–90. https://doi.org/10.1080/14764172.2017.1376092
Feller L, Masilana A, Khammissa RAG, Altini M, Jadwat Y, Lemmer J (2014) Melanin: The biophysiology of oral melanocytes and physiological oral pigmentation. Head Face Med 10:1–7. https://doi.org/10.1186/1746-160X-10-8
Caton GJ, Armitage G, Berglundh T et al (2018) A new classification scheme for periodontal and peri-implant diseases and conditions – Introduction and key changes from the 1999 classification. J Clin Periodontol 45:S1–S8. https://doi.org/10.1111/jcpe.12935
Sommer L (2011) Generation of melanocytes from neural crest cells. Pigment Cell Melanoma Res 24:411–421. https://doi.org/10.1111/j.1755-148X.2011.00834.x
Cichorek M, Wachulska M, Stasiewicz A, Tymińska A (2013) Skin melanocytes: Biology and development. Postepy Dermatol Alergol. 30:30–41. https://doi.org/10.5114/pdia.2013.33376
Sreeja C, Ramakrishnan K, Vijayalakshmi D, Devi M, Aesha I, Vijayabanu B (2015) Oral pigmentation: A review. J Pharm Bioallied Sci 7:S403–S408. https://doi.org/10.4103/0975-7406.163471
Holmstrup P, Plemons J, Meyle J (2018) Non–plaque-induced gingival diseases. J Clin Periodontol 45:S28–S43. https://doi.org/10.1111/jcpe.12938
Lin YH, Tu YK, Lu CT, Chung WC, Huang CF, Huang MS, Lu HK (2014) Systematic review of treatment modalities for gingival depigmentation: A random-effects poisson regression analysis. J Esthet Restor Dent 26:162–178. https://doi.org/10.1111/jerd.12087
Luk AK, Kong H (2016) Non-ablative melanin depigmentation of gingiva. 24–27 https://blog.dentsplysirona.com/en/non-ablative-melanin-depigmentation-of-gingiva/
Chatterjee A, Singh N, Malhotra P, Ajmera N (2012) Gingival Pigmentation and Its Treatment modalities. J Dent Sci Oral Rehabil 8:11–14 https://pubmed.ncbi.nlm.nih.gov/23420974/
Venkata P, Rao N, Penmetsa GS (2015) Gingival depigmentation by cryosurgery and laser application - a comparative clinical study. Br J Med Med Res 5:1403–1412. https://doi.org/10.9734/BJMMR/2015/12870
Karydis A, Bland P, Shiloah J (2012) Management of oral melanin pigmentation. J Tenn Dent Assoc 92:10–17 https://pubmed.ncbi.nlm.nih.gov/23420974/
Malhotra S (2014) Gingival esthetics by depigmentation. JpmcpCom 79–84. http://www.jpmcp.com/pdffo rnet/79-84.pdf
Dadlani H, Bhardwaj A, Grover H, Yadav A, Lal S (2014) Evaluation of patient response and recurrence of pigmentation following gingival depigmentation using laser and scalpel technique: A clinical study. J Indian Soc Periodontol 18:586–592. https://doi.org/10.4103/0972-124X.142450
Kaur H, Jain S, Sharma R (2010) Duration of reappearance of gingival melanin pigmentation after surgical removal - A clinical study. J Indian Soc Periodontol 14:101–105. https://doi.org/10.4103/0972-124X.70828
Suragimath G, Lohana MH, Varma S (2016) A split mouth randomized clinical comparative study to evaluate the efficacy of gingival. Laser Appl Med Sci Res Cent 7:227–232. https://doi.org/10.15171/jlms.2016.40
Sharma T, Agrawal C, Shah M (2020) An Overview on Gingival Depigmentation Procedures : Case Series and Follow up. Acta Scientific Dental Sciences 4:29–32. https://doi.org/10.31080/ASDS.2020.04.0856
Alasmari DS (2018) An insight into gingival depigmentation techniques: The pros and cons. Int J Health Sci (Qassim). 12:84–89 https://pubmed.ncbi.nlm.nih.gov/30202412/
Patil KP, Joshi V, Waghmode V, Kanakdande V (2015) Gingival depigmentation: A split mouth comparative study between scalpel and cryosurgery. Contemp Clin Dent 6:S97–S101. https://doi.org/10.4103/0976-237X.152964
Gustafson CB, Yang C, Dickson KM, Shao H, Van Booven D, Harbour JW, Liu ZJ, Wang G (2015) Epigenetic reprogramming of melanoma cells by vitamin C treatment. Clin Epigenetics 7:1–11. https://doi.org/10.1186/s13148-015-0087-z
Yussif NM, Koranyb NS, Abbassc MM (2017) Evidence of the Effect of Intraepidermic Vitamin C Injection on Melanocytes and Keratinocytes in Gingival Tissues: In Vivo Study. Dentistry. 7:417. https://doi.org/10.4172/2161-1122.1000417
Iraji F, Nasimi M, Asilian A, Faghihi G, Mozafarpoor S, Hafezi H (2019) Efficacy of mesotherapy with tranexamic acid and ascorbic acid with and without glutathione in treatment of melasma: A split face comparative trial. J Cosmet Dermatol 18:1416–1421. https://doi.org/10.1111/jocd.12874
Sanadi RM, Deshmukh RS (2020) The effect of Vitamin C on melanin pigmentation - A systematic review. J Oral Maxillofac Pathol 24:374–382. https://doi.org/10.4103/jomfp.JOMFP_207_20
Shimada Y, Tai H, Tanaka A, Ikezawa-Suzuki I, Takagi K, Yoshida Y, Yoshie H (2009) Effects of Ascorbic Acid on Gingival Melanin Pigmentation In Vitro and In Vivo. J Periodontol 80:317–323. https://doi.org/10.1902/jop.2009.080409
Sheel V, Purwar P, Dixit J, Rai P (2015) Ancillary role of vitamin C in pink aesthetics. BMJ Case Rep 2015:bcr2014208559. https://doi.org/10.1136/bcr-2014-208559
McCarthy FM, Malamed SF (1979) Physical evaluation system to determine medical risk and indicated dental therapy modifications. J Am Dent Assoc 99:181–184. https://doi.org/10.14219/jada.archive.1979.0271
Yussif NM, Abdel Rahman AR, ElBarbary A (2019) Minimally invasive non-surgical locally injected vitamin C versus the conventional surgical depigmentation in treatment of gingival hyperpigmentation of the anterior esthetic zone: A prospective comparative study. Clin Nutr Exp 24:54–65. https://doi.org/10.1016/j.yclnex.2018.12.003
Dummett CO, Gupta OP (1964) Estimating the epidimiology of oral pigmentation. J Natl Med Assoc 56:419–420 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2610754/
Melzack R (1975) The McGill Pain Questionnaire: Major properties and scoring methods. Pain 1:277–299. https://doi.org/10.1016/0304-3959(75)90044-5
Miot HA, Brianezi G, Tamega A d A, Miot LDB (2012) Techniques of digital image analysis for histological quantification of melanin. An Bras Dermatol 87:608–611. https://doi.org/10.1590/S0365-05962012000400014
Telang P (2013) Vitamin C in dermatology. Indian Dermatol Online J 4:143–146. https://doi.org/10.4103/2229-5178.110593
Yussif NM, Zayed SO, Hasan A, Sadek S (2016) Evaluation of injectable Vitamin C as a depigmenting agent in physiologic gingival melanin hyperpigmentation: A clinical trial. Rep Opin 8. https://doi.org/10.7537/marsroj08061607
Choi HI, Park JI, Kim HJ, Kim DW, Kim SS (2009) A novel L-ascorbic acid and peptide conjugate with increased stability and collagen biosynthesis. BMB Rep 42:743–746. https://doi.org/10.5483/BMBRep.2009.42.11.743
Kimura S, Hirai A, Shimizu H (1981) Epidermal vacuolation: An artifact due to injection of local anesthetics. Arch Dermatol Res 270:413–419. https://doi.org/10.1007/BF00403785
Lee ES, Kim JH, Im S, Lee KB, Sohn S, Kang WH (2001) Application of computerized image analysis in pigmentary skin diseases. Int J Dermatol 40:45–49. https://doi.org/10.1046/j.1365-4362.2001.00084.x
Acknowledgement
The authors want to acknowledge resources and staff in Oral Pathology Laboratory, in Faculty of Dentistry, Ain Shams University, Cairo, Egypt.
Part of this work was presented during 2nd International conference of Faculty of Dentistry ASU (20-22 October- 2016) under the title “Gingival depigmentation should we modulate or irradicate melanocytes”
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Conceptualization: [Mohamed El-Mofty]; Methodology: [Ola Ezzatt]; Formal analysis and investigation: [Sarah Elkot], [Dalia Yossri], [Amira Ghoneim]; Writing - original draft preparation: [Ola Ezzatt], [Sarah Elkot]; Writing - review and editing: [Mohamed El-Mofty], Supervision: [Mohamed El-Mofty].
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All procedures performed in this study involving human participants were in accordance with the ethical standards of the research ethical committee in faculty of dentistry Ain Shams University and was approved under the number (FDASU-REC D041602) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The trial was registered at https://clinicaltrials.gov/ under the number (NCT03252418).
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The authors declare that they have no conflict of interest and do not have any financial interest in the companies whose materials are included in this article.
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All needed information about the study were given to the patients and informed consent term was obtained from every individual participant included in the study.
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The original version of this article was revised: The authors made the description more clinically applicable and refined the description to eliminate any conflict to the practitioners during practicing the technique. The information in reference 32 was also modified to coincide with the reference citation.
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El-Mofty, M., Elkot, S., Ghoneim, A. et al. Vitamin C mesotherapy versus topical application for gingival hyperpigmentation: a clinical and histopathological study. Clin Oral Invest 25, 6881–6889 (2021). https://doi.org/10.1007/s00784-021-03978-6
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DOI: https://doi.org/10.1007/s00784-021-03978-6