|
瘢痕疙瘩的临床研究现状
|
Abstract:
瘢痕疙瘩是一种特殊的病理性瘢痕,在临床上极难治愈,具有治疗抵抗和治疗后高复发的特征。目前关于其发病机制临床上主要集中在两个学说,“炎症学说”和“肿瘤学说”。瘢痕疙瘩的发病特点和诊疗手段是整形外科的热点话题,这种特点表现在人种、性别、年龄、遗传、部位、诱因等特异性。关于其治疗方案也是多种多样,各有其优缺点。本文主要对目前瘢痕疙瘩的发病机制、发病特点以及治疗方式的研究进展进行综述。
Keloid is a special pathological scar, which is very difficult to cure clinically. It has the characteristics of treatment resistance and high recurrence after treatment. At present, its pathogenesis is mainly focused on two theories, “inflammation theory” and “tumor theory”. The pathogenesis and diagnosis and treatment of keloid is a hot topic in plastic surgery. This characteristic is manifested in the specificity of race, gender, age, heredity, location, inducement and so on. There are also various treatment schemes, each with its advantages and disadvantages. This paper mainly reviews the research progress of the pathogenesis, characteristics and treatment of keloid.
[1] | Rodrigues, M., Kosaric, N., Bonham, C.A., et al. (2019) Wound Healing: A Cellular Perspective. Physiological Reviews, 99, 665-706. https://doi.org/10.1152/physrev.00067.2017 |
[2] | Shaker, S.A., Ayuob, N.N. and Hajrah, N.H. (2011) Cell Talk: A Phenomenon Observed in the Keloid Scar by Immunohistochemical Study. Applied Immunohistochemistry & Molecular Morphology, 19, 153-159.
https://doi.org/10.1097/PAI.0b013e3181efa2ef |
[3] | Gauglitz, G.G., Korting, H.C., Pavicic, T., et al. (2011) Hypertrophic Scarring and Keloids: Pathomechanisms and Current and Emerging Treatment Strategies. Molecular Medicine, 17, 113-125.
https://doi.org/10.2119/molmed.2009.00153 |
[4] | Zhang, M., Xu, Y., Liu, Y., et al. (2016) Chemokine-Like Factor 1 (CKLF-1) Is Overexpressed in Keloid Patients: A Potential Indicating Factor for Keloid-Predisposed Individuals. Med-icine (Baltimore), 95, e3082.
https://doi.org/10.1097/MD.0000000000003082 |
[5] | Abdou, A.G., Maraee, A.H. and Saif, H.F. (2014) Immunohistochemical Evaluation of COX-1 and COX-2 Expression in Keloid and Hypertrophic Scar. The American Journal of Dermatopathology, 36, 311-317.
https://doi.org/10.1097/DAD.0b013e3182a27b83 |
[6] | Tanaka, R., Umeyama, Y., Hagiwara, H., et al. (2019) Keloid Patients Have Higher Peripheral Blood Endothelial Progenitor Cell Counts and CD34(+) Cells with Normal Vasculogenic and Angiogenic Function That Overexpress Vascular Endothelial Growth Factor and Interleukin-8. International Journal of Dermatology, 58, 1398-1405.
https://doi.org/10.1111/ijd.14575 |
[7] | Messadi, D.V., Doung, H.S., Zhang, Q., et al. (2004) Activation of NFkap-paB Signal Pathways in Keloid Fibroblasts. Archives of Dermatological Research, 296, 125-133. https://doi.org/10.1007/s00403-004-0487-y |
[8] | Makino, S., Mitsutake, N., Nakashima, M., et al. (2008) DHMEQ, a Novel NF-kappaB Inhibitor, Suppresses Growth and Type I Collagen Accumulation in Keloid Fibroblasts. Journal of Dermatological Science, 51, 171-180.
https://doi.org/10.1016/j.jdermsci.2008.03.003 |
[9] | Fujita, M., Yamamoto, Y., Jiang, J.J., et al. (2019) NEDD4 Is Involved in Inflammation Development during Keloid Formation. Journal of Investigative Dermatology, 139, 333-341. https://doi.org/10.1016/j.jid.2018.07.044 |
[10] | Lim, C.P., Phan, T.T., Lim, I.J., et al. (2006) Stat3 Contributes to Keloid Pathogenesis via Promoting Collagen Production, Cell Proliferation and Migration. Oncogene, 25, 5416-5425. https://doi.org/10.1038/sj.onc.1209531 |
[11] | Haisa, M., Okochi, H. and Grotendorst, G.R. (1994) Elevated Levels of PDGF Alpha Receptors in Keloid Fibroblasts Contribute to an Enhanced Response to PDGF. Journal of Investigative Dermatology, 103, 560-563.
https://doi.org/10.1111/1523-1747.ep12396856 |
[12] | Younai, S., Nichter, L.S., Wellisz, T., et al. (1994) Modula-tion of Collagen Synthesis by Transforming Growth Factor- Beta in Keloid and Hypertrophic Scar Fibroblasts. Annals of Plastic Surgery, 33, 148-151.
https://doi.org/10.1097/00000637-199408000-00005 |
[13] | Ohtsuru, A., Yoshimoto, H., Ishihara, H., et al. (2000) Insulin-Like Growth Factor-I (IGF-I)/IGF-I Receptor Axis and Increased Invasion Activity of Fibroblasts in Keloid. Endocrine Journal, 47, S41-S44.
https://doi.org/10.1507/endocrj.47.SupplMarch_S41 |
[14] | De Felice, B., Wilson, R.R., Nacca, M., et al. (2004) Molecular Characterization and Expression of p63 Isoforms in Human Keloids. Molecular Genetics and Genomics, 272, 28-34. https://doi.org/10.1007/s00438-004-1034-4 |
[15] | Satish, L., Lyons-Weiler, J., Hebda, P.A., et al. (2006) Gene Expression Patterns in Isolated Keloid Fibroblasts. Wound Repair and Regeneration, 14, 463-470. https://doi.org/10.1111/j.1743-6109.2006.00135.x |
[16] | Seifert, O., Bayat, A., Geffers, R., et al. (2008) Identifica-tion of Unique Gene Expression Patterns within Different Lesional Sites of Keloids. Wound Repair and Regeneration, 16, 254-265.
https://doi.org/10.1111/j.1524-475X.2007.00343.x |
[17] | Yoo, M.G. and Kim, I.H. (2014) Keloids and Hyper-trophic Scars: Characteristic Vascular Structures Visualized by Using Dermoscopy. Annals of Dermatology, 26, 603-609. https://doi.org/10.5021/ad.2014.26.5.603 |
[18] | Jumper, N., Paus, R. and Bayat, A. (2015) Functional Histopathol-ogy of Keloid Disease. Histology and Histopathology, 30, 1033-1057. |
[19] | Hahn, J.M., Glaser, K., McFarland, K.L., et al. (2013) Keloid-Derived Keratinocytes Exhibit an Abnormal Gene Expression Profile Consistent with a Distinct Causal Role in Keloid Pathology. Wound Repair and Regeneration, 21, 530-544. https://doi.org/10.1111/wrr.12060 |
[20] | Ma, X., Chen, J., Xu, B., et al. (2015) Keloid-Derived Keratinocytes Ac-quire a Fibroblast-Like Appearance and an Enhanced Invasive Capacity in a Hypoxic Microenvironment in Vitro. Inter-national Journal of Molecular Medicine, 35, 1246-1256. https://doi.org/10.3892/ijmm.2015.2135 |
[21] | Ichioka, S. ando, T., Shibata, M., et al. (2008) Oxygen Consumption of Keloids and Hypertrophic Scars. Annals of Plastic Surgery, 60, 194-197. https://doi.org/10.1097/SAP.0b013e318053ec1d |
[22] | Kemble, J.V. and Brown, R.F. (1976) Enzyme Activity in Human Scars, Hypertrophic Scars and Keloids. British Journal of Dermatology, 94, 301-305. https://doi.org/10.1111/j.1365-2133.1976.tb04387.x |
[23] | Ueda, K., Furuya, E., Yasuda, Y., et al. (1999) Keloids Have Continuous High Metabolic Activity. Plastic and Reconstructive Surgery, 104, 694-698. https://doi.org/10.1097/00006534-199909010-00012 |
[24] | Juckett, G. and Hartman-Adams, H. (2009) Management of Keloids and Hypertrophic Scars. American Family Physician, 80, 253-260. |
[25] | Mari, W., Alsabri, S.G., Tabal, N., et al. (2015) Novel Insights on Understanding of Keloid Scar: Article Review. Journal of the American College of Clinical Wound Specialists, 7, 1-7. https://doi.org/10.1016/j.jccw.2016.10.001 |
[26] | Poetschke, J. and Gauglitz, G.G. (2016) Current Options for the Treatment of Pathological Scarring. Journal of the American College of Clinical Wound Special-ists, 14, 467-477. https://doi.org/10.1111/ddg.13027 |
[27] | Arno, A.I., Gauglitz, G.G., Barret, J.P., et al. (2014) Up-to-Date Approach to Manage Keloids and Hypertrophic Scars: A Useful Guide. Burns, 40, 1255-1266. https://doi.org/10.1016/j.burns.2014.02.011 |
[28] | LeFlore, I.C. (1980) Misconceptions Regarding Elective Plastic Surgery in the Black Patient. Journal of the National Medical Association, 72, 947-948. |
[29] | Bloom, D. (1956) Heredity of Keloids; Review of the Literature and Report of a Family with Multiple Keloids in Five Generations. New York State Journal of Medicine, 56, 511-519. |
[30] | Young, W.G., Worsham, M.J., Joseph, C.L., et al. (2014) Incidence of Keloid and Risk Factors Following Head and Neck Surgery. JAMA Facial Plastic Surgery, 16, 379-380. https://doi.org/10.1001/jamafacial.2014.113 |
[31] | Glass, D.A. 2nd (2017) Current Understanding of the Genetic Causes of Keloid Formation.Journal of Investigative Dermatology Symposium Proceedings, 18, S50-S53. https://doi.org/10.1016/j.jisp.2016.10.024 |
[32] | Burd, A. (2006) Keloid Epidemiology: Population Based Studies Needed. Journal of Plastic, Reconstructive & Aesthetic Surgery, 59, 105. https://doi.org/10.1016/j.bjps.2005.07.012 |
[33] | Ly, N. and McCaig, L.F. (2002) National Hospital Ambulatory Medical Care Survey: 2000 Outpatient Department Summary. Advance Data, No. 327, 1-27. |
[34] | Huang, C. and Ogawa, R. (2013) Pharmacological Treatment for Keloids. Expert Opinion on Pharmacotherapy, 14, 2087-2100. https://doi.org/10.1517/14656566.2013.826651 |
[35] | Monstrey, S., Middelkoop, E., Vranckx, J.J., et al. (2014) Updated Scar Management PRACTICAL Guidelines: Non-Invasive And Invasive Measures. Journal of Plastic, Recon-structive & Aesthetic Surgery, 67, 1017-1025.
https://doi.org/10.1016/j.bjps.2014.04.011 |
[36] | Lu, W.S., Zheng, X.D., Yao, X.H., et al. (2015) Clinical and Epi-demiological Analysis of Keloids in Chinese Patients. Archives of Dermatological Research, 307, 109-114. https://doi.org/10.1007/s00403-014-1507-1 |
[37] | Shih, B., Garside, E., McGrouther, D.A., et al. (2010) Molecular Dissection of Abnormal Wound Healing Processes Resulting in Keloid Disease. Wound Repair and Regeneration, 18, 139-153.
https://doi.org/10.1111/j.1524-475X.2009.00553.x |
[38] | Al-Attar, A., Mess, S., Thomassen, J.M., et al. (2006) Keloid Pathogenesis and Treatment. Plastic and Reconstructive Surgery, 117, 286-300. https://doi.org/10.1097/01.prs.0000195073.73580.46 |
[39] | Ogawa, R., Okai, K., Tokumura, F., et al. (2012) The Relationship between Skin Stretching/Contraction and Pathologic Scarring: The Important Role of Mechanical Forces in Keloid Generation. Wound Repair and Regeneration, 20, 149-157. https://doi.org/10.1111/j.1524-475X.2012.00766.x |
[40] | Butzelaar, L., Niessen, F.B., Talhout, W., et al. (2017) Different Properties of Skin of Different Body Sites: The Root of Keloid Formation? Wound Repair and Regeneration, 25, 758-766. https://doi.org/10.1111/wrr.12574 |
[41] | Gold, M.H., Berman, B., Clementoni, M.T., et al. (2014) Up-dated International Clinical Recommendations on Scar Management: Part 1—Evaluating the Evidence. Dermatologic Surgery, 40, 817-824. |
[42] | Robles, D.T. and Berg, D. (2007) Abnormal Wound Healing: Keloids. Clinics in Dermatol-ogy, 25, 26-32.
https://doi.org/10.1016/j.clindermatol.2006.09.009 |
[43] | Bran, G.M., Goessler, U.R., Hormann, K., et al. (2009) Keloids: Current Concepts of Pathogenesis (Review). International Journal of Molecular Medicine, 24, 283-293. https://doi.org/10.3892/ijmm_00000231 |
[44] | Goldenberg, G. and Luber, A.J. (2013) Use of Intralesional Cryosur-gery as an Innovative Therapy for Keloid Scars and a Review of Current Treatments. The Journal of Clinical and Aes-thetic Dermatology, 6, 23-26. |
[45] | Huang, C. and Ogawa, R. (2013) Roles of Lipid Metabolism in Keloid Development. Lipids in Health and Disease, 12, 60. https://doi.org/10.1186/1476-511X-12-60 |
[46] | Macintyre, L. and Baird, M. (2006) Pressure Garments for Use in the Treatment of Hypertrophic Scars—A Review of the Problems Associated with Their Use. Burns, 32, 10-15. https://doi.org/10.1016/j.burns.2004.06.018 |
[47] | Ripper, S., Renneberg, B., Land-mann, C., et al. (2009) Adherence to Pressure Garment Therapy in Adult Burn Patients. Burns, 35, 657-664. https://doi.org/10.1016/j.burns.2009.01.011 |
[48] | Mustoe, T.A. (2008) Evolution of Silicone Therapy and Mecha-nism of Action in Scar Management. Aesthetic Plastic Surgery, 32, 82-92. https://doi.org/10.1007/s00266-007-9030-9 |
[49] | Mustoe, T.A., Cooter, R.D., Gold, M.H., et al. (2002) Interna-tional Clinical Recommendations on Scar Management. Plastic and Reconstructive Surgery, 110, 560-571. https://doi.org/10.1097/00006534-200208000-00031 |
[50] | Butler, P.D., Longaker, M.T. and Yang, G.P. (2008) Current Progress in Keloid Research and Treatment. Journal of the American College of Surgeons, 206, 731-741. https://doi.org/10.1016/j.jamcollsurg.2007.12.001 |
[51] | de Oliveira, G.V., Nunes, T.A., Magna, L.A., et al. (2001) Silicone versus Nonsilicone Gel Dressings: A Controlled Trial. Dermatologic Surgery, 27, 721-726. https://doi.org/10.1097/00042728-200108000-00005 |
[52] | Saulis, A.S., Mogford, J.H. and Mustoe, T.A. (2002) Effect of Mederma on Hypertrophic Scarring in the Rabbit Ear Model. Plastic and Reconstructive Surgery, 110, 177-183. https://doi.org/10.1097/00006534-200207000-00029 |
[53] | Wong, T.W., Chiu, H.C. and Chang, C.H., et al. (1996) Silicone Cream Occlusive Dressing—A Novel Noninvasive Regimen in the Treatment of Keloid. Dermatology, 192, 329-333. https://doi.org/10.1159/000246405 |
[54] | Kikuchi, K., Kadono, T. and Takehara, K. (1995) Effects of Var-ious Growth Factors and Histamine on Cultured Keloid Fibroblasts. Dermatology, 190, 4-8. https://doi.org/10.1159/000246625 |
[55] | Kupietzky, A. and Levi-Schaffer, F. (1996) The Role of Mast Cell-Derived Histamine in the Closure of an in Vitro Wound. Inflammation Research, 45, 176-180. https://doi.org/10.1007/BF02285158 |
[56] | Gold, M.H., McGuire, M., Mustoe, T.A., et al. (2014) Updated Interna-tional Clinical Recommendations on Scar Management: Part 2—Algorithms for Scar Prevention and Treatment. Derma-tologic Surgery, 40, 825-831. |
[57] | Berman, B., Maderal, A. and Raphael, B. (2017) Keloids and Hypertrophic Scars: Pathophysiology, Classification, and Treatment. Dermatologic Surgery, 43, S3-S18. https://doi.org/10.1097/DSS.0000000000000819 |
[58] | Wolfram, D., Tzankov, A., Pülzl, P., et al. (2009) Hyper-trophic Scars and Keloids—A Review of Their Pathophysiology, Risk Factors, and Therapeutic Management. Dermato-logic Surgery, 35, 171-181.
https://doi.org/10.1111/j.1524-4725.2008.34406.x |
[59] | Atiyeh, B.S. (2007) Nonsurgical Management of hyper-trophic scars: Evidence-Based Therapies, Standard Practices, and Emerging Methods. Aesthetic Plastic Surgery, 31, 468-492. https://doi.org/10.1007/s00266-006-0253-y |
[60] | Robles, D.T., Moore, E., Draznin, M., et al. (2007) Ke-loids: Pathophysiology and Management. Dermatology Online Journal, 13, 9. https://doi.org/10.5070/D32M43548R |
[61] | Sadeghinia, A. and Sadeghinia, S. (2012) Comparison of the Efficacy of Intralesional Triamcinolone Acetonide and 5-Fluorouracil Tattooing for the Treatment of Keloids. Dermatologic Sur-gery, 38, 104-109.
https://doi.org/10.1111/j.1524-4725.2011.02137.x |
[62] | Khan, M.A., Bashir, M.M. and Khan, F.A. (2014) Intrale-sional Triamcinolone Alone and in Combination with 5-Fluorouracil for the Treatment of Keloid and Hypertrophic Scars. Journal of Pakistan Medical Association, 64, 1003-1007. |
[63] | Gupta, S. and Kalra, A. (2002) Efficacy and Safety of In-tralesional 5-Fluorouracil in the Treatment of Keloids. Dermatology, 204, 130-132. https://doi.org/10.1159/000051830 |
[64] | 赵敬军. 5-氟尿嘧啶在增生性瘢痕和瘢痕疙瘩治疗中的应用研究Meta分析[C]//2016中国中西医结合学会医学美容学术年会暨第二届泛亚国际医学美容大会论文集. 北京: 北京万方数据股份有限公司, 2016: 84-85. |
[65] | 刘欣健, 崔正军, 张树堂, 等. 曲安奈德联合5-氟尿嘧啶与单独曲安奈德治疗瘢痕疙瘩效果的荟萃分析[J]. 中华烧伤杂志, 2020, 36(12): 1191-1198. |
[66] | Jones, C.D., Guiot, L., Samy, M., et al. (2015) The Use of Chemotherapeutics for the Treatment of Keloid Scars. Dermatology Reports, 7, 5880. https://doi.org/10.4081/dr.2015.5880 |
[67] | Trisliana, P.A., Lazzeri, D., Su, W., et al. (2014) Recent Developments in the Use of Intralesional Injections Keloid Treatment. Archives of Plastic Surgery, 41, 620-629. https://doi.org/10.5999/aps.2014.41.6.620 |
[68] | Saray, Y. and Güle?, A.T. (2005) Treatment of Keloids and Hyper-trophic Scars with Dermojet Injections of Bleomycin: A Preliminary Study. International Journal of Dermatology, 44, 777-784.
https://doi.org/10.1111/j.1365-4632.2005.02633.x |
[69] | Ogawa, R., Akaishi, S., Huang, C., et al. (2011) Clinical Applications of Basic Research That Shows Reducing Skin Tension Could Prevent and Treat Abnormal Scarring: The Importance of Fascial/Subcutaneous Tensile Reduction Sutures and Flap Surgery for Keloid and Hypertrophic Scar Re-construction. Journal of Nippon Medical School, 78, 68-76.
https://doi.org/10.1272/jnms.78.68 |
[70] | Mourad, B., Elfar, N. and Elsheikh, S. (2016) Spray versus Intralesional Cryotherapy for Keloids. Journal of Dermatological Treatment, 27, 264-269. https://doi.org/10.3109/09546634.2015.1088129 |
[71] | Hochman, B., Isoldi, F.C., Furtado, F., et al. (2015) New Approach to the Understanding of Keloid: Psychoneuroimmune-Endocrine Aspects. Clinical, Cosmetic and Investiga-tional Dermatology, 8, 67-73.
https://doi.org/10.2147/CCID.S49195 |
[72] | Shen, J., Lian, X., Sun, Y., et al. (2015) Hypofractionated Elec-tron-Beam Radiation Therapy for Keloids: Retrospective Study of 568 Cases with 834 Lesions. Journal of Radiation Re-search, 56, 811-817.
https://doi.org/10.1093/jrr/rrv031 |
[73] | Wilson, A.M. (2013) Eradication of Keloids: Surgical Excision Followed by a Single Injection of Intralesional 5-Fluorouracil and Botulinum Toxin. The Canadian Journal of Plastic Surgery, 21, 87-91.
https://doi.org/10.1177/229255031302100208 |
[74] | Xiao, Z., Zhang, F. and Cui, Z. (2009) Treatment of Hyper-trophic Scars with Intralesional Botulinum Toxin Type A Injections: A Preliminary Report. Aesthetic Plastic Surgery, 33, 409-412. https://doi.org/10.1007/s00266-009-9334-z |
[75] | Gauglitz, G.G., Bureik, D., Dombrowski, Y., et al. (2012) Botulinum Toxin A for the Treatment of Keloids. Skin Pharmacology and Physiology, 25, 313-318. https://doi.org/10.1159/000342125 |
[76] | Huang, C., Liu, L., You, Z., et al. (2019) Managing Keloid Scars: From Radiation Therapy to Actual and Potential Drug Deliveries. International Wound Journal, 16, 852-859. https://doi.org/10.1111/iwj.13104 |
[77] | Shin, J.Y., Yun, S.K., Roh, S.G., et al. (2017) Efficacy of 2 Representative Topical Agents to Prevent Keloid Recurrence after Surgical Excision. Journal of Oral and Maxillofacial Surgery, 75, 401.e1-401.e6.
https://doi.org/10.1016/j.joms.2016.10.009 |
[78] | Viera, M.H., Caperton, C.V. and Berman, B. (2011) Advances in the Treatment of Keloids. Journal of Drugs in Dermatology, 10, 468-480. |
[79] | Berman, B., Harrison-Balestra, C., Perez, O.A., et al. (2009) Treatment of Keloid Scars Post-Shave Excision with Imiquimod 5% Cream: A Prospective, Double-Blind, Placebo-Controlled Pilot Study. Journal of Drugs in Dermatology, 8, 455-458. |
[80] | Kim, S.W. (2021) Management of Keloid Scars: Noninvasive and Invasive Treatments. Archives of Plastic Surgery, 48, 149-157. https://doi.org/10.5999/aps.2020.01914 |