台灣皮膚科醫學會青春痘治療共識研討會 青春痘光電雷射治療 王修含醫師 台大醫學士台大電機學院生醫電子碩士台大工學院機械工程學士 王修含皮膚科診所院長台大皮膚部兼任主治醫師 1 1
Anatomic pathology normal sebaceous follicle comedo inflammatory acne lesion + rupture of follicular wall + secondary inflammation Lancet. 2012;379(9813):361-72. 2 2
http://www.indianwomenshealth.com/acne-121.aspx Journal of Dermatological Treatment. 2008; 19: 199 209 3 3
Acne pathogenesis through innate immune activation Am J Clin Dermatol. 2014 Dec;15(6):479-88. 4
Hyperkeratinization Am J Clin Dermatol. 2014 Dec;15(6):479-88. 5
Optical and electrical based therapies 4. 3. 1. 2. 6 6
選擇性光熱分解 (Selective Photothermolysis) Pulsed dye laser (PDL): Vbeam II, 595nm 418nm 542nm 577nm 7 7
Optical and electrical based therapies for acne UV light Visible light blue red Intense pulsed light LED Radiofrequency Lasers KTP laser 532 nm Infrared lasers: 1064, 1320, 1450, 1540 nm etc Pulsed dye laser 585~595 nm DermatolTher. 2005 May-Jun;18(3):253-66. Indian J Dermatol Venereol Leprol. 2013 May-Jun;79(3):300-9. J CosmetLaser Ther. 2014 Dec 23:1-7. 8 8
Treatment targets 1. Bacteria: Propionebacterium acnes 2. Sebaceous glands Rationale Photochemical therapy Photothermal therapy Dermatol Ther. 2005;18(3):253-66. 9 9
Modalities Lasers Surg Med. 2005 Dec;37(5):333-42. 10 10
Target chromophores J Cosmet Laser Ther. 2014 Dec 23:1-7. 11
1. Killing Bacteria (P. acnes) 痤瘡桿菌代謝過程中, 會產生內生性紫質 (porphyrins), 某些可見光可活化這些物質, 產生單態氧 (singlet oxygen) 等自由基, 破壞細胞壁的脂質而消滅細菌 Typical porphyrin absorption spectrum Lasers Surg Med. 2005 Dec;37(5):333-42. Soret band ~400nm Q bands: 450~700 nm Met Based Drugs. 2008;2008:276109. Curr Med Chem. 2013;20(4):562-8. 12 12
Porphyrinsof P. acnes Protoporphyrin IX (PP9) Auto-fluorescent P. acnes under Wood s lamp the terminal product of metabolic reactions Environmental factors Anaerobic conditions: protoporphyrin IX (PP9) semianaerobicconditions: uroporphyrin III (UP3) & coproporphyrin III (CP3) formed from the corresponding porphyrinogens, which are earlier steps in the reaction pathway leading to protoporphyrinix. Curr Med Chem. 2013;20(4):562-8. 13
Porphyrinbiosynthesis pathways in humans and P. acnes Curr Med Chem. 2013;20(4):562-8. 14
Modalities Visible lights Typical porphyrin absorption spectrum Intense pulsed light (IPL) Lasers Met Based Drugs. 2008;2008:276109. Photodynamic therapy (PDL) 15 15
Protoporphyrin IX (PpIX, PP9) absorption curve 第九型前吡喀紫質之吸收曲線 λ= 415 504 576 538 630 nm Dermatol Ther. 2005;18(3):253-66. Lasers Surg Med. 2005 Dec;37(5):333-42. 16 16
Photodynamic therapy (PDT) Topical 5-aminolevulinic acid (ALA) λ=415 504 576 538 630 nm 上皮細胞會將 ALA 轉化為 PP9, 累積在上皮與毛囊皮脂腺 ALA 可促進痤瘡桿菌合成內生性紫質 SE: 疼痛 泛紅 水腫 結痂 皮膚片狀剝落 治療初期惡化 Dermatol Ther. 2005 May-Jun;18(3):253-66. 17 17
Studies on PDL for acne vulgaris Indian J Dermatol Venereol Leprol. 2013;79(3):300-9. 18 18
Visible light 王修含醫師攝 藍光波長 ( 例如 420-470 nm) 具有較佳的抑菌效果 藍光在皮膚的穿透深度僅約 200 μm 可結合效能較差, 但穿透較深的紅光波長 (600-1000 nm) 紅光可限制巨噬細胞釋放細胞激素 (cytokine), 具抗發炎能力, 有研究者認為藍光也有抗發炎的效果 如果只以紅光治療, 青春痘病灶數目與皮脂腺分泌量都有降低的現象 結合紅藍光的治療, 抑制發炎的效果優於單獨使用外用藥過氧化苯 (benzoyl peroxide) 或僅照射藍光 Expert Opin Pharmacother. 2011;12(4):493-501. 19 19
Red light: Anti-inflammatory property Red light deeper penetration up to the sebaceous glands anti-inflammatory properties by influencing cytokine release from macrophages Indian J Dermatol Venereol Leprol. 2013;79(3):300-9. Lasers Surg Med. 1989;9(5):497-505. Laser Ther. 2011;20(3):205-15. 20 20
KTP laser: 532 nm KTP 綠光雷射 (potassium titanyl phosphate laser) 538 nm 21 21
Dye laser: 585-595 nm Pulsed dye laser (PDL): Vbeam II, 595nm ( 脈衝式染料雷射 ) 418nm 542nm 576 nm Absorption (Log scale) 577nm 700-1000nm Chromophores: melanin, oxyhemoglobin, water http://www.infodepilacion-en.com/depilacion_04.html 22 22
Alexandrite laser: 755 nm 630 nm Wavelength 755nm Porphyrin absorption? minimal Photothermal effect 23 23
2. Destruction of sebaceous glands 破壞皮脂腺 Blausen gallery 2014 Lasers Surg Med. 2005 Dec;37(5):333-42. 24 24
Modalities Lasers Intense pulsed light Radiofrequency α dispersion: ~khz, ionic diffusion at cell membrane β dispersion: ~MHz, polarization of cell membrane γ dispersion: ~GHz, polarization of water Phys Med Biol. 1996 Nov;41(11):2231-49. 25 25
Laser-Tissue interaction 1. Photochemical interaction Diode lasers biostimulation, photodynamic therapy 2. Thermal interaction Most Dermatologic lasers 3. Photoablation Excimer lasers: ArF, KrF,XeCl, XeF refractive corneal surgery 4. Plasma-induced ablation Nd:YLF, Nd:YAG, Ti: sapphire ophthalmic & cares surgery 5. Photodisruption Nd:YLF, Nd:YAG, Ti: sapphire ophthalmic surgery, lithotripsy Niemz MH, Laser-Tissue Interactions: Fundamentals and Applications, Springer Berlin Heidelberg, New York, 3rd enlarged ed. (2003). 26 26
Tissue Thermal Reaction Temperature Tissue thermal reaction 37 C Normal body temperature 45 C Hyperthermia 50 C 1.Decreased enzyme activity 2.Cellular immobility 60 C 1. Denaturation of protein & collagen 2. Tissue coagulation/ cell necrosis 80 C Increased membrane permeability 100 C 1. Vaporization of water 2. Thermal decomposition/ ablation > 100 C Carbonization > 300 C Melting Niemz MH, Laser-Tissue Interactions: Fundamentals and Applications, Springer Berlin Heidelberg, New York, 3rd enlarged ed. (2003). 27 27
Target chromophores J Cosmet Laser Ther. 2014 Dec 23:1-7. 28
Water : absorption coefficient 200 cm -1 29 29
Water absorption by wavelength Absorption (Log scale) cm -1 200 cm -1 1927 nm (Tm fiber laser) = 100 1440 nm (Diode laser) = 20 30 30
Diode laser: 1450nm ( 台灣廠商俗稱 油切雷射 ) Before After Lasers Surg Med. 2005 Dec;37(5):333-42. 31 31
Nd:YAG laser (1064nm) 製圖 : 王修含醫師 http://www.dmt-hk.com/wpcontent/uploads/2013/07/picture1.png 32
A special multi-functional laser for acne treatment: Pulsed Dye Laser 33
Dye laser: 585-595 nm Pulsed dye laser (PDL): Vbeam II, 595nm ( 脈衝式染料雷射 ) 418nm 542nm 577nm Absorption (Log scale) 700-1000nm Chromophores: melanin, oxyhemoglobin, water http://www.infodepilacion-en.com/depilacion_04.html 34 34
Vascular destruction PDL Abnormal vasculature Oxyhemoglobin (RBC) irradiated Heat production, conducted to endothelium Coagulation & necrosis of vessels Destruction of vessels Resolution of lesions 35 35
IPL vs. PDL vs. LED Both PDL and IPL were found to treat acne effectively PDL showed a more sustained effect. Effect for acne treatment PDL >IPL >LED J Eur Acad Dermatol Venereol. 2010;24(7):773-80. J Cosmet Laser Ther. 2014 Dec 23:1-7. 36 36
PDL: Roles of TGF-β PDL: upregulationof TGF-β (Transforming growth factor beta, TGF-beta) resolution of inflammatory acne lesions. Inhibit CD4+ T-lymphocyte-mediated inflammation induce keratinocyte(kc) growth arrest interfere with comedone formation DAXX Pathway a potent stimulus for neocollagenesis SMAD Pathway Br J Dermatol. 2006;155(4):748-55. J Eur Acad Dermatol Venereol. 2010;24(7):773-80. J Cosmet Laser Ther. 2014 Dec 23:1-7. 37 37
Hyperkeratinization Am J Clin Dermatol. 2014 Dec;15(6):479-88. 38
2015/3/3 Evaluation of parameters Diameter of vessles Pulse duration? 圖片 王修含醫師提供 Thermal relaxation time of vessels? diameter of 10-100 µm: 1-10 ms port-wine stain vessel (0.1-mm) : 10 ms leg vein (1-mm ): 1 s 王修含 醫師/ Shiou-Han Wang, MD 圖片 王修含醫師提供 39 39
Summary of Pulsed dye laser: 585-595 nm Activation of prophyrins/protoporphyrin killing bacteria Photothermal effect suppresion of sebaceous glands TGF-β anti-inflammatory effect KC growth arrest anti-comedone formation neocollagenesis 40 40
臨床實例討論 41 41
Limitations Side effects Pain Erythema Burn Recurrence Temporary & incomplete Follow-up treatments Combination with topical & oral treatment 42 42
Review: Targets of treatment Lasers Surg Med. 2005 Dec;37(5):333-42. 43 43
Mechanisms Conclusion Killing bacteria Suppression of sebaceous glands Anti-inflammation Anti-comedoneformation Combined therapy Combination of multiple lasers Combination of traditional medical treatment 44 44
謝謝指教! 45 45
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台灣皮膚科醫學會青春痘治療共識研討會 青春痘雷射光電治療 王修含醫師 台大醫學士台大電機學院生醫電子碩士台大工學院機械工程學士 王修含皮膚科診所院長台大皮膚部兼任主治醫師
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