A comparative study of the effectiveness and safety of injectable combination therapy of keloid and hypertrophic scars with 5-fluorouracil and betamethasone
Evgeniya V. Ikonnikova , Larisa S. Kruglova , Nataliya E. Manturova , Marina A. Petrii
Russian Journal of Skin and Venereal Diseases ›› 2020, Vol. 23 ›› Issue (6) : 432 -442.
A comparative study of the effectiveness and safety of injectable combination therapy of keloid and hypertrophic scars with 5-fluorouracil and betamethasone
therapy for their reliable removal. Standard methods of treatment often give unpredictable results, are accompanied by various complications, and require the use of expensive equipment.
AIM: To investigate the efficacy and safety of intralesional injection of a combination of 5-fluorouracil (5-FU) and betamethasone for the treatment of keloids and hypertrophic scars.
MATERIALS AND METHODS: The study involved 26 patients who were divided into two equal groups. Patients in group A received intralesional injections of betamethasone, and those in group B received 5-FU and betamethasone. Three injections were performed with an interval of 3 weeks. The scars were assessed at the beginning of the treatment, on the 3rd and 6th week during the treatment, and 4 and 16 weeks after the end of the treatment. The dynamics of scar condition was evaluated by the average decrease in the scar height and density, changes in subjective sensations, and the presence or absence of complications.
RESULTS: At 4 weeks after the end of the therapy, the total effectiveness of reducing the initial scar height was significantly higher in group B (10 patients; 76.9%) than in group A (6; 46.1%). In the comparison of long-term results at 16 weeks after treatment, 92.3% of the patients from group B and 53.8% of the patients from group A showed cessation of scar growth, flattening and softening, diminished itching and pain, smoothing of the scar contour, and a decrease in the color of the border between the scar and surrounding tissues.
CONCLUSIONS: The combination of betamethasone with 5-FU is safer and more effective than monotherapy with betamethasone or 5-FU in the treatment of keloid and hypertrophic scars, with a faster and more pronounced decrease in the height and density of the scar, erythema, and subjective sensations. This mode of therapy is characterized by a low relapse rate with prolonged follow-up. The article is of interest to practicing cosmetologists, dermatologists, and plastic surgeons.
hypertrophic scars / keloid scars / 5-fluorouracil / betamethasone
| [1] |
Grishenkova LN, Gorbachev FA, Anishchenko SL, Kuzmichev VA, Savrasova NA, Merkulova EP. Fractures of the bones of the middle zone of the face: forensic medical examination. Minsk: Higher School; 2015. (in Russian) |
| [2] |
Гришенкова Л.Н., Горбачев Ф.А., Анищенко С.Л., Кузьмичев В.А., Саврасова Н.А., Меркулова Е.П. Переломы костей средней зоны лица: судебно-медицинская экспертиза: учебное пособие. Минск: Вышэйшая школа; 2015. |
| [3] |
Bayat A, McGrouther DA, Ferguson MW. Skin scarring. Br Med J. 2003;326(7380):88-92. doi: 10.1136/bmj.326.7380.88 |
| [4] |
Bayat A., McGrouther D.A., Ferguson M.W. Skin scarring. BMJ. 2003;326(7380):88-92. doi: 10.1136/bmj.326.7380.88. |
| [5] |
Stenko AG, Talibova AM, Kruglova LS, Korchazhkina NB. The use of a conjugate of hyaluronidase for the prevention and treatment of cicatricial deformations. Kremlin Medicine Journal. Russian Journal. 2018;(1):114-9. (in Russian) |
| [6] |
Стенько А.Г., Талыбова А.М., Круглова Л.С., Корчажкина Н.Б. Применение конъюгированной гиалуронидазы для профилактики и лечения рубцовых деформаций // Кремлевская медицина. Клинический вестник. 2018;(1):114-9. |
| [7] |
Berman B, Maderal A, Raphael B. Keloids and hypertrophic scars: pathophysiology, classification, and treatment. Dermatol Surg. 2017;1:3-18. doi: 10.1097/DSS.0000000000000819 |
| [8] |
Berman B., Maderal A., Raphael B. Keloids and hypertrophic scars: pathophysiology, classification, and treatment. Dermatol Surg. 2017;1:3-18. doi: 10.1097/DSS.0000000000000819 |
| [9] |
Maksimova NV, Lyundup AV, Lubimov RO, Melnichenko GA, Nikolenko VN. Pathophysiological aspects of wound healing in health and in diabetic foot. Annals of the Russian Academy of Medical Sciences. 2014;(11-12):110-7. (in Russian) |
| [10] |
Максимова Н.В., Люндуп А., Любимов Р.О., Мельниченко Г.А., Николенко В.Н. Патофизиологические аспекты заживления ран в норме и при синдроме диабетической стопы // Вестник Российской академии медицинских наук. 2014;(11-12):110-7. |
| [11] |
Zhidkova YuYu, Penevskaya NA, Stepanova EF. Prerequisites for improving the pharmacoprophylaxis of hypertrophic and keloid scars. Scientific Statements of the Belgorod State University. Series: Medicine. Pharmacy. 2012:1-12. (in Russian) |
| [12] |
Жидкова Ю.Ю., Пеньевская Н.А., Степанова Э.Ф. Предпосылки к совершенствованию фармакопрофилактики гипертрофических и келоидных рубцов // Научные ведомости Белгородского государственного университета. Серия: Медицина. Фармация. 2012:1-12. |
| [13] |
Schastlivtsev IV, Lobastov KV, Tsaplin SN, Mkrtychev DS. Modern view of the hemostasis system: cell theory. Medical Advice. Russian Journal. 2019;(16):72-7. doi: 10.21518/2079-701X-2019-16-72-77. (in Russian) |
| [14] |
Счастливцев И.В., Лобастов К.В., Цаплин С.Н., Мкртычев Д.С. Современный взгляд на систему гемостаза: клеточная теория // Медицинский совет. 2019;(16):72-7. doi: 10.21518/2079-701X-2019-16-72-77 |
| [15] |
Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17(1-2):113-25. doi: 10.2119/molmed.2009.00153 |
| [16] |
Gauglitz G.G., Korting H.C., Pavicic T., Ruzicka T., Jeschke M.G. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17(1-2):113-25. doi: 10.2119/molmed.2009.00153 |
| [17] |
Lee HJ, Jang YJ. Recent understandings of biology, prophylaxis and treatment strategies for hypertrophic scars and keloids. Int J Mol Sci. 2018;19(3):711. doi: 10.3390/ijms19030711 |
| [18] |
Lee H.J., Jang Y.J. Recent understandings of biology, prophylaxis and treatment strategies for hypertrophic scars and keloids. Int J Mol Sci. 2018;19(3):711. doi: 10.3390/ijms19030711 |
| [19] |
Kruglova LS, Techieva SG, Stenko AG, Shmatova AA. Modern view of innovative methods of treatment of pathological cicatricial deformities. Clinical Dermatology and Venereology. Russian Journal. 2014;(5):105-17. (in Russian) |
| [20] |
Круглова Л.С., Течиева С.Г., Стенько А.Г., Шматова А.А. Современный взгляд на инновационные методы терапии патологических рубцовых деформации? // Клиническая дерматология и венерология. 2014;5:105-117. |
| [21] |
Ozerskaya OS. Skin scars. Experimental and Clinical Dermatocosmetology. Russian Journal. 2004;(4):50-8. (in Russian) |
| [22] |
Озерская О.С. Рубцы кожи // Экспериментальная и клиническая дерматокосметология. 2004;(4):50-8. |
| [23] |
Podlyashuk EL, Head VP. Bucky therapy in dermatocosmetology. Radiology and Practice. Russian Journal. 2009;(4):26-30. (in Russian) |
| [24] |
Подлящук Е.Л., Голова В.П. Букки-терапия в дерматокосметологии // Радиология и практика. 2009;(4):26-30. |
| [25] |
Kurganskaya IG. Complex correction of pathological skin scars. Dis. St.Petersburg; 2011. (in Russian) |
| [26] |
Курганская И.Г. Комплексная коррекция патологических рубцов кожи: Автореф. дис. … канд. мед. наук. СПб.; 2011. |
| [27] |
Stepankina ES, Barmin EV, Stepankin SN, Trofimov EI. Causes and pathogenesis of the formation of pathological skin scars (literature review). Herald of Restorative Medicine. Russian Journal. 2017;(1):103-10. (in Russian) |
| [28] |
Степанкина Е.С., Бармин Е.В., Степанкин С.Н., Трофимов Е.И. Причины и патогенез формирования патологических рубцов кожи (обзор литературы) // Вестник восстановительной медицины. 2017;(1):103-10. |
| [29] |
Bock O, Schmid-Ott G, Malewski P, Mrowietz U. Quality of life of patients with keloid and hypertrophic scarring. Arch Dermatol. 2006;297(10):433-8. doi: 10.1007/s00403-006-0651-7. |
| [30] |
Bock O., Schmid-Ott G., Malewski P., Mrowietz U. Quality of life of patients with keloid and hypertrophic scarring. Arch Dermatol. 2006;297(10):433-8. doi: 10.1007/s00403-006-0651-7 |
| [31] |
Stenko AG, Shchukina ЕV, Shmatova AA, Shuginina OI, Zhukova OV, Techieva SG. Conservative treatment of patients with cicatricial changes in the skin by electrode pharmacophoresis. Russian Journal of Skin and Venereal Diseases. 2014;17(1):58-61. (in Russian) |
| [32] |
Стенько А.Г., Щукина Е.В., Шматова А.А., Шугинина О.И., Жукова О.В., Течиева С.Г. Консервативное лечение пациентов с рубцовыми изменениями кожи методом электродного фармафореза // России?скии? журнал кожных и венерических болезнеи?. 2014;(1):58-61. |
| [33] |
Ogawa R. Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis. Int J Mol Sci. 2017;18(3):606. doi: 10.3390/ijms18030606 |
| [34] |
Klyuchareva SV, Nechaeva OS, Kurgan IG. Pathological scars in the practice of a dermatocosmetologist: new possibilities of therapy with Egallohit (Galaderm). Bulletin of Aesthetic Medicine. Russian Journal. 2009;(2):41-9. (in Russian) |
| [35] |
Ключарева С.В., Нечаева О.С., Курганская И.Г. Патологические рубцы в практике дерматокосметолога: новые возможности терапии препаратом «Эгаллохит» («Галадерм») // Вестник эстетическои? медицины. 2009;(2):41-9. |
| [36] |
Kozlov VA, Mushkovskaya SS, Konovalskaya SB. Keloid scars. Difficulties in diagnosis and treatment. Clinical Dentistry. Russian Journal. 2015;(1):28-30. (in Russian) |
| [37] |
Козлов В.А., Мушковская С.С., Коновальская С.Б. Келоидные рубцы. Трудности диагностики и лечения // Клиническая стоматология. 2015;(1):28-30. |
| [38] |
Guller AE, Shekhter AB. Clinical type and histological structure of cutaneous scars as predictive factors of therapeutic outcome. Annals of Plastic, Reconstructive and Aesthetic Surgery. Russian Journal. 2007;(4):19-31. (in Russian) |
| [39] |
Гуллер А.Е., Шехтер А.Б. Клинический тип и гистологическая структура кожных рубцов как прогностические факторы исхода лечения // Анналы пластической, реконструктивной и эстетической хирургии. 2007;(4):19-31. |
| [40] |
Atiyeh BS, Costagliola M, Hayek SN. Keloid or hypertrophic scar: the controversy: review of the literature. Ann Plastic Surg. 2005;54(6):676-80. |
| [41] |
Atiyeh B.S., Costagliola M., Hayek S.N. Keloid or hypertrophic scar: the controversy: review of the literature. Ann Plastic Surg. 2005;54(6):676-80. |
| [42] |
Ozerskaya OS. Skin scars and their dermatocosmetological correction. St.Petersburg: Art of Russia; 2007:57-74. (in Russian) |
| [43] |
Озерская О.С. Рубцы кожы и их дерматокосметологическая коррекция. СПб.: Искусство России; 2007:57-74. |
| [44] |
Baitinger VF, Paityan KG. Morphologic and functional characteristics of pathological skin scars: state of the art. Issues of Reconstructive and Plastic Surgery. Russian Journal. 2013;(1):28-34. (in Russian) |
| [45] |
Байтингер В.Ф., Пайтян К.Г. Морфофункциональные особенности патологических кожных рубцов: состояние вопроса // Вопросы реконструктивной и пластической хирургии. 2013;(1):28-34. |
| [46] |
Del Toro D, Dedhia R, Tollefson TT. Advances in scar management: prevention and management of hypertrophic scars and keloids. Curr Opin Otolaryngol Head Neck Surg. 2016;24(4):322-9. doi: 10.1097/MOO.0000000000000268 |
| [47] |
Del Toro D., Dedhia R., Tollefson T.T. Advances in scar management: prevention and management of hypertrophic scars and keloids. Curr Opin Otolaryngol Head Neck Surg. 2016;24(4):322-9. doi: 10.1097/MOO.0000000000000268 |
| [48] |
Zabnenkova OV. Clinical experience in the correction of hypertrophic, keloid and atrophic scars. Doctor. Russian Journal. 2007;(2):32-4. (in Russian) |
| [49] |
Забненкова О.В. Клинический опыт коррекции гипертрофических, келоидных и атрофических рубцов // Врач. 2007;(2):32-4. |
| [50] |
Felipe BR, Cleyton DS, Jayme AFJ. Update on hypertrophic scar treatment. Clinics. 2014;69(8):565-73. doi: 10.6061/clinics/2014(08)11. |
| [51] |
Felipe B.R., Cleyton D.S., Jayme A.F.J. Update on hypertrophic scar treatment. Clinics. 2014;69(8):565-73. doi: 10.6061/clinics/2014(08)11 |
| [52] |
Rakhmatulina MR, Karamova AE, Saitburkhanov RR. Federal clinical guidelines for the management of patients with keloid and hypertrophic scars. Moscow: Russian Society of Dermatovenereologists and Cosmetologists; 2015. (in Russian) |
| [53] |
Рахматулина М.Р., Карамова А.Э., Сайтбурханов Р.Р. Федеральные клинические рекомендации по ведению больных c келоидными и гипертрофическими рубцами. М.: Российское общество дерматовенерологов и косметологов; 2015. |
| [54] |
Arndt KA, ed. Correction of scars. Transl. from Engl. Moscow: Practical Medicine (Red Elsevier); 2009. (in Russian) |
| [55] |
Арндт К.А., ред. Коррекция рубцов. Пер. с англ. М.: Практическая Медицина (Рид Элсивер); 2009. |
| [56] |
Alster TS, Nanni CA. Pulsed dye laser treatment of hypertrophic burn scars. Plast. Reconstr. Surg. 1998;102(6):2190-5. |
| [57] |
Alster T.S., Nanni C.A. Pulsed dye laser treatment of hypertrophic burn scars. Plast. Reconstr. Surg. 1998;102(6):2190-5. |
| [58] |
Tanzi EL, Alster TS. Laser treatment of scars. Skin Ther Lett. 2004;9(1):4-7. |
| [59] |
Tanzi E.L., Alster T.S. Laser treatment of scars. Skin Ther Lett. 2004;9(1):4-7. |
| [60] |
Har-Shai Y, Amar M, Sabo E. Intralesional cryotherapy for enhancing the involution of hypertrophic scars and keloids. Plast Reconstr Surg. 2003;111(6):1841-52. |
| [61] |
Har-Shai Y., Amar M., Sabo E. Intralesional cryotherapy for enhancing the involution of hypertrophic scars and keloids. Plast Reconstr Surg. 2003;111(6):1841-52. |
| [62] |
Karpova TN, Ponomarenko GN, Samtsov AV. Electroand ultraphonophoresis collagenase for correction of dermal scars. Bulleten of the Russian Military Medical Academy. 2009;(1):89-94. (in Russian) |
| [63] |
Карпова Т.Н., Пономаренко Г.Н., Самцов А.В. Электрои ультрафонофорез коллагеназы в коррекции рубцов кожи // Вестник Росcийской Военно-медицинской академии. 2009;(1):89-94. |
| [64] |
Gold MH, McGuire M, Mustoe TA, Pusic A, Sachdev M, Waibel J, Murcia C; International Advisory Panel on Scar Management. Updated international clinical recommendations on scar management: part 2 – algorithms for scar prevention and treatment. Dermatol Surg. 2014;40(8):825-31. doi: 10.1111/dsu.0000000000000050 |
| [65] |
Gold M.H., McGuire M., Mustoe T.A., Pusic A., Sachdev M., Waibel J., Murcia C.; International Advisory Panel on Scar Management. Updated international clinical recommendations on scar management: part 2 – algorithms for scar prevention and treatment. Dermatol Surg. 2014;40(8):825-31. doi: 10.1111/dsu.0000000000000050 |
| [66] |
Vertieva EYu, Olisova OYu, Kochergin NG, Pinson IYa. Review of pathogenetic mechanisms and methods of scar correction. Russian Journal of Skin and Venereal Diseases. 2015;18(1):51-7. (in Russian) |
| [67] |
Вертиева Е.Ю., Олисова О.Ю., Кочергин Н.Г., Пинсон И.Я., Обзор патогенетических механизмов и методов коррекции рубцов // Российский журнал кожных и венерических болезней. 2015;18(1):51-7. |
| [68] |
Sun P, Lu X, Zhang H, Hu Z. The efficacy of drug injection in the treatment of pathological scar: A network meta-analysis. Aesthetic Plast Surg. 2019. doi: 10.1007/s00266-019-01570-8. |
| [69] |
Sun P., Lu X., Zhang H., Hu Z. The efficacy of drug injection in the treatment of pathological scar: A network meta-analysis. Aesthetic Plast Surg. 2019. doi: 10.1007/s00266-019-01570-8 |
| [70] |
Xu SJ, Teng JY, Xie J, Shen MQ, Chen DM. Comparison of the mechanisms of intralesional steroid, interferon or verapamil injection in the treatment of proliferative scars. Zhonghua Zheng Xing Wai Ke Za Zhi. 2009;25(1):37-40. |
| [71] |
Xu S.J., Teng J.Y., Xie J., Shen M.Q., Chen D.M. Comparison of the mechanisms of intralesional steroid, interferon or verapamil injection in the treatment of proliferative scars. Zhonghua Zheng Xing Wai Ke Za Zhi. 2009;25(1):37-40. |
| [72] |
Voronkov AV, Stepanova EF, Zhidkova YuYu, Gamzeleva OYu. Modern approaches to pharmacological correction of pathological scars. Basic Research. Russian Journal. 2014;3(2):301-8. (in Russian) |
| [73] |
Воронков А.В., Степанова Э.Ф., Жидкова Ю.Ю., Гамзелева О.Ю. Современные подходы фармакологической коррекции патологических рубцов // Фундаментальные исследования. 2014;3(2):301-8. |
| [74] |
Berman B, Maderal A, Raphael B. Keloids and hypertrophic scars: pathophysiology, classification, and treatment. Dermatol Surg. 2017;43(Suppl 1):S3-18. doi: 10.1097/DSS.0000000000000819 |
| [75] |
Berman B., Maderal A., Raphael B. Keloids and hypertrophic scars: pathophysiology, classification, and treatment. Dermatol Surg. 2017;43(Suppl 1):S3-18. doi: 10.1097/DSS.0000000000000819 |
| [76] |
Robles DT, Moore E, Draznin M, Berg D. Keloids: pathophysiology and management. Dermatol Online J. 2007;13(3):9. |
| [77] |
Robles D.T., Moore E., Draznin M., Berg D. Keloids: pathophysiology and management. Dermatol Online J. 2007;13(3):9. |
| [78] |
Nanda S, Reddy BS. Intralesional 5-fluorouracil as a treatment modality of keloids. Dermatol Surg. 2004;30(1):54-7. |
| [79] |
Nanda S., Reddy B.S. Intralesional 5-fluorouracil as a treatment modality of keloids. Dermatol Surg. 2004;30(1):54-7. |
| [80] |
Liu W, Wu X, Gao Z, Song N. Remodelling of keloid tissue into normal-looking skin. J Plast Reconstr Aesthet Surg. 2008;61(12):1553-4. |
| [81] |
Liu W., Wu X., Gao Z., Song N. Remodelling of keloid tissue into normal-looking skin. J Plast Reconstr Aesthet Surg. 2008;61(12):1553-4. |
| [82] |
Blumenkranz M, Hernandez E, Ophir A, Norton EW. 5-fluorouracil: new applications in complicated retinal detachment for an established antimetabolite. Ophthalmology. 1984;91(2):122-30. |
| [83] |
Blumenkranz M., Hernandez E., Ophir A., Norton E.W. 5-fluorouracil: new applications in complicated retinal detachment for an established antimetabolite. Ophthalmology. 1984;91(2):122-30. |
| [84] |
Fitzpatrick RE. Treatment of inflamed hypertrophic scars using intralesional 5-FU. Dermatol Surg. 1999;25(3):224-32. |
| [85] |
Fitzpatrick R.E. Treatment of inflamed hypertrophic scars using intralesional 5-FU. Dermatol Surg. 1999;25(3):224-32. |
| [86] |
Shah VV, Aldahan AS, Mlacker S, Alsaidan M, Samarkandy S, Nouri K. 5-Fluorouracil in the treatment of keloids and hypertrophic scars: a comprehensive review of the literature. Dermatol Ther. (Heidelb) 2016;6(2):169-83. doi: 10.1007/s13555-016-0118-5 |
| [87] |
Shah V.V., Aldahan A.S., Mlacker S., Alsaidan M., Samarkandy S., Nouri K. 5-Fluorouracil in the treatment of keloids and hypertrophic scars: a comprehensive review of the literature. Dermatol Ther. (Heidelb) 2016;6(2):169-83. doi: 10.1007/s13555-016-0118-5. |
Eco-Vector
/
| 〈 |
|
〉 |