sequentially through a bipolar electrode tip with epidermal cooling. Three treatments were given at 3-week intervals to 20 patients with mild to moderate rhytids and skin laxity. Optical and RF fluences ranged from 30 to 40J/cm 2 and from 50 to 85J/cm 3 , respec- tively.The prospective study showed a mean clinical improvement of superficial rhytids at 6 months of 1.63/4. For skin laxity of the jowl and cheek, improve- ment scores reached 2.00/4 at 6 months. Patient assessments were similar. Side-effects were mild. In a combined study 62 of ELOS with both IPL and a diode laser (Fig. 6.8), overall effectiveness scores in multiple measures of photodamage was approximately 26%. NONABLATIVE TECHNOLOGIES FOR SKIN TIGHTENING From the evidence that collateral heating of the dermis while targeting vascular and pigmented lesions created new collagen and decreased wrinkles sprang the idea of bulk dermal heating. Bulk dermal heating requires rela- tively deep energy deposition over a period of seconds as opposed to microseconds, with cooling to protect the epidermis.The intent of tissue tightening is to actu- ally lift or firm tissue in a three-dimensional manner. This is not the same as stimulating collagen to fill in superficial scars or wrinkles, but a deeper shift in tissue volumes, leading to a remodeling of the entire soft tissue envelope, a completely new aesthetic capability. Collagen fibers consist of protein chains held in a triple helix.When collagen is heated, non-colavent bonds linking the protein strands together are rup- tured, producing an amorphous arrangement of ran- domly coiled chains. 63 As the chains rearrange, fibers of the denatured collagen become shorter and thicker. Heat-induced contraction of collagen and long-term fibroblastic stimulation are is the basis for the treat- ment of skin laxity. 64 For exposures lasting several seconds, the denaturation temperature of collagen has been estimated at 65°C. 65,66 In practice,however, collagen denaturation has a complex dependence on temperature described by the Arrhenius reaction-rate equation.This relationship may not hold for very short time exposures to heat, because the kinetics of collagen denaturation are not known. 66 There are two technologies supported by peer- reviewed literature at present for evaluation: RF and broadband infrared (IR) light. Radiofrequency-based tissue tightening RF energy interacts with tissue to generate a current of ions that, when passed through tissues, encounters resistance.This resistance, or impedance, generates 62 Clinical procedures in laser skin rejuvenation Fig.6.9 Partially denatured collagen after Thermage treatment as 160 microns by electron microscopy. (Reproduced courtesy of Dr.Brian Zelickson and Thermage Corp.) 06 Carniol-8028.qxd 8/23/2007 3:32 PM Page 62 Nonablative technology for treatment of aging skin 63 Table 6.5 Studies of the use of radiofrequency (RF) for skin tightening Ref No. of Fluence Areas Adverse Follow-up patients (J/cm 2 ) treated Efficacy effects (months) 73 40 — Face, 70% of patients Moderate pain 1, 2, 3 anterior noticed significant during treatment; neck improvement in 3/40 patients skin laxity and experienced texture at 3 months superficial blistering 74 15 52 (only Face 14/15 patients responded; Minimal 6–14 for 2 nasolabial folds: 50% of discomfort patients patients had at least 50% during treatment treated with improvement; cheek contour: in all patients; 1cm 2 tip) 60% had 50% improvement; superficial mandibular line: 27% had at burn (1 patient) least 50% improvement; marionette lines: 65% had at least 50% improvement. 69 86 58–140 Periorbital Fitzpatrick wrinkle scores Minimal erythema, 6 wrinkles, improved by 1 point or edema, 2nd-degree brow more in 83.2% of patients; burn; small residual position) 50% of patients satisfied scar at 6 months in to very satisfied; 61.5% of 3 patients eyebrows lifted by 0.5mm 70 16 — Cheeks, jaw 5 of 15 patients contacted Mild, transient 6 line, upper neck were satisfied with results erythema and edema 78 17 125–144 Brow, jowls, Gradual tightening Mild, temporary 4 nasolabial folds, erythema puppet lines 75 50 97–144 Mild to Significant improvement Mild and temporary 6 (cheeks) moderate in most patients; patient edema, erythema, 74–110 skin laxity satisfaction was similar rare dysesthesia (neck) in neck to observed clinical and cheek improvement 68 24 — Upper third Objective data showed Pain during 4–14 weeks of face; brow non-uniform (asymmetric) treatment; elevation; improvement; patient redness forehead, satisfaction low; 72.7% temporal said they would not have regions the procedure again; results not predictable 57 7 73.5 Face; laxity, About 16% median None 2–6 wrinkles, pores, improvement in wrinkles pigmentation, and skin laxity; about 16% texture improvement in texture, pores, and pigmentation; patients satisfied; improvement maintained 2–6 months 06 Carniol-8028.qxd 8/23/2007 3:32 PM Page 63 heat in proportion to the amount of impedance. Tissues with high impedance will be heated more than tissues of low impedance. 67 Traditional RF devices used in skin surgery deliver therapeutic energy through the tip of an electrode in contact with skin. The concentrated thermal energy produces heat at the surface of the skin, which injures both the dermis and epidermis. 68 To reduce heat-induced epidermal injury while heating the der- mis, developed the ThermaCool, a device that delivers RF energy to the skin via a thin capacitive coupling membrane that distributes RF energy over the tissue volume beneath the membrane’s surface (rather than concentrating the RF energy at the skin surface) while cooling the epidermis by cryogen spray. 69,70 Although the deep dermal layer can theoretically reach tempera- tures exceeding 65°C, permitting the heat-sensitive collagen bonds to go beyond their 60° denaturation threshold, the temperature of the epidermis is main- tained between 35°C and 45°C. 68 A study of the histo- logical and ultrastructural effects of RF energy suggested that collagen fibrils contract immediately after treatment and that production of new collagen is induced by tissue contraction and heat-mediated wounding (Fig. 6.9). 71 The first clinical study of the ThermaCool assessed skin contraction, gross pathology, and histological changes for a range of RF doses. 70,72 Iyer et al 73 reported that 70% of patients noticed skin laxity improvement 3 months after a single RF treatment and that improvement increased with additional treat- ments. A subsequent report described a prototype device designed to produce heat in the dermal layer of tissue while protecting the epidermis by cryogen spray 64 Clinical procedures in laser skin rejuvenation Fig.6.10 Before (a) and 8 months after (b) tissue tightening treatments:one radiofrequency treatment on the left side of the face and two broadband infrared light device treatments on the right.Note the decreased depth of the nasolabial folds and marionette lines,the firming of the skin over the mid cheek and the restoration of the shape of the face toward an oval,instead of a rectangle.(Photographs courtesy of Amy Forman Taub MD.) a b 06 Carniol-8028.qxd 8/23/2007 3:32 PM Page 64 cooling. 74 Of the 15 patients,14 responded to a single treatment without wounding or scarring. Pain was used to indicate the tolerability of treatment. Patients resumed normal activities immediately after treat- ment. Other RF studies that followed are summarized in Table 6.5. In each study, patients had a single treat- ment, local anesthesia was used during treatment, and results were evaluated by comparing pre- and post- treatment photographs. Improvements with a single treatment were gradual and subtle and lasted for sev- eral months. Higher fluences were required with thick skin. 69 When low fluences were used, improvements were less pronounced. 70,75 Initially, it was believed that the highest fluences would yield the best results. However, this was accom- panied by significant patient discomfort and a rela- tively high rate of significant side-effects, 76 such as scars and changes in skin surface textures (e.g., inden- tation or waffling). A different model based on a lower-fluence, multiple-pass protocol was shown via ultrastructural analysis of collagen fibril architecture to provide much more collagen deposition deeper in the dermis than the high-fluence protocol. 77 This is believed to yield more consistent results, higher patient tolerability, and fewer complications. Recent advances include specialized tips for more superficial areas (eyelids) and body areas (arms and abdomen). Infrared light-based tissue tightening A broadband infrared light tightening device has recently been developed as an alternative technology for tissue tightening (Titan, Cutera, Brisbane, CA). This generates energy of up to 50J/cm 2 energy at 1100–1800nm wavelengths, with pre- and postcool- ing being built into the multisecond pulse.The long wavelengths of near- and mid-IR radiation offer three major advantages over shorter wavelengths: (1) deeper penetration into the dermal layer (2) less absorption by melanin, and (3) reduced risk in dark-skinned patients. 56 This device targets the dermis at a depth of 1–2mm, which is more superficial than the RF device. The author has found this to be an advantage for thin- ner skin, whereas the RF technology may be better for thicker skin with more subcutaneous tissue attached – but these observations are anecdotal. However, in many skin types, the results may be similar (Fig. 6.10). Studies of the use of infrared light in tissue tightening are summarized in Table 6.6. THE FUTURE AND CONCLUSIONS A major advantage of nonablative techniques is that treatment requires little or no downtime for patients. The importance of this feature is evident from the Nonablative technology for treatment of aging skin 65 Table 6.6 Studies of the use of broadband infrared (IR) light for skin tightening Device No. of (No. of Fluence Local Treatment Adverse Follow-up Ref patients treatments) (J/cm 2 ) anesthesia target Efficacy effects (months) 79 25 1100– 20–40 For first 5 Forehead; Immediate Small Up to 12 1800nm patients lower improvement in 22 burns (1–3) face and patients, persisted neck for follow-up period; all patients satisfied 80 42 1100– 30–38 Sometimes Face, Improvement Transient 4 1800nm neck, moderate or minor (2) abdomen higher in 52.4% swelling of patients and erythema, rare blister 06 Carniol-8028.qxd 8/23/2007 3:32 PM Page 65 growth and proliferation of nonablative devices since they were introduced in the late 1990s. Disadvantages are that efficacy is modest and multiple treatments are required to achieve results. Future efforts will be focused on increasing efficacy and reducing the num- ber of treatments, making treatment more affordable for more patients. REFERENCES 1. Fitzpatrick R, Rostan E, Marchell N. Collagen tightening induced by carbon dioxide laser versus erbium:YAG laser. Lasers Surg Med 2000;27:395–403. 2. Nelson J, Majaron B, Kelly K. What is nonablative photorejuvenation of human skin? Semin Cutan Med Surg 2002;21:238–50. 3. Grema H, Greve B, Raulin C. Facial rhytids – subsurfac- ing or resurfacing? A review, Lasers Surg Med 2003;32: 405–12. 4. Herne K, Zachary C. New facial rejuvenation techniques. Semin Cutan Med Surg 2000;19:221–31. 5. Ross E, Sajben F, Hsia J,et al. Nonablative skin remodel- ing: selective dermal heating with a mid-infrared laser and contact cooling combination. Lasers Surg Med 2000; 26:186–95. 6. Kelly K, Nelson J, Lask G, Geronemus R, Bernstein L. Cryogen spray cooling in combination with nonablative laser treatment of facial rhytids.Arch Dermatol 1999; 135:691–4. 7. Goldberg D. Full-face nonablative dermal remodeling with a 1320nm Nd:YAG laser. Dermatol Surg 2000; 26:915–18. 8. Goldberg D. New collagen formation after dermal remodeling with an intense pulsed light source. J Cutan Laser Ther 2000;2:59–61. 9. Trelles M, Allones I, Luna R. Facial rejuvenation with a nonablative 1320nm Nd:YAG laser: a preliminary clinical and histologic evaluation. Dermatol Surg 2001; 27:111–16. 10. Fournier N, Dahan S, Barneon G, et al. Nonablative remodeling: a 14-month clinical ultrasound imaging and profilometric evaluation of a 1540 nm Er:Glass laser. Dermatol Surg 2002;28:926–31. 11. Bitter P. Noninvasive rejuvenation of photodamaged skin using serial, full-face intense pulsed light treatments. Dermatol Surg 2000;26:835–42. 12. Weiss R, McDaniel D, Geronemus R,Weiss M. Clinical trial of a novel non-thermal LED array for reversal of photoaging: clinical, histologic, and surface profilometric results. Lasers Surg Med 2005;36:85–91. 13. Zelickson B, Kilmer SL, Bernstein E, et al. Pulsed dye laser therapy for sun damaged skin. Lasers Surg Med 1999;25:229–36. 14. Rostan E, Bowes L, Iyer S, Fitzpatrick R.A double-blind, side-by-side comparison study of low fluence long pulse dye laser to coolant treatment for wrinkling of the cheeks. J Cosmet Laser Ther 2001;3:129–36. 15. Lee M. Combination 532-nm and 1064-nm lasers for noninvasive skin rejuvenation and toning. Arch Dermatol 2003;139:1265–76 [Erratum: 2004;140:625]. 16. Menaker G,Wrone D,Williams R, Moy R.Treatment of facial rhytids with a nonablative laser: a clinical and histo- logic study. Dermatol Surg 1999;25:440–4. 17. Goldberg D. Non-ablative subsurface remodeling: clinical and histologic evaluation of a 1320-nm Nd:YAG laser. J Cutan Laser Ther 1999;1:153–7. 18. Sadick N,Alexiades-Armenakis M, Bitter P Jr, Hruza G, Mulholland R. Enhanced full-face skin rejuvenation using synchronous intense pulsed optical and conducted bipolar radiofrequency energy (ELOS): introducing selective radiophotothermolysis. J Drugs Dermatol 2005; 4:181–6. 19. Goldberg D, Amin S. Russell B,et al. Combined 633-nm and 830-nm LED treatment of photoaging skin. J Drugs Dermatol 2006;5:748–53. 20. Manstein D, Herron G, Sink R,Tanner H, Anderson R. Fractional photothermolysis: a new concept for cuta- neous remodeling using microscopic patterns of thermal injury. Lasers Surg Med 2004;34:426–38. 21. Weiss R,Weiss M, Beasley K, Munavalli G. Our approach to non-ablative treatment of photoaging. Lasers Surg Med 2005;37:2–8. 22. Geronemus R. Fractional photothermolysis: current and future applications. Lasers Surg Med 2006;38:169–76. 23. Kauvar A, Rosen N, Khrom T. A newly modified 595-nm pulsed dye laser with compression handpiece for the treatment of photodamaged skin. Lasers Surg Med 2006;38:808–13. 24. Bjerring P, Clement M, Heickendorff L, Egevist H, Kiernan M. Selective non-ablative wrinkle reduction by laser. J Cutan Laser Ther 2000;2:9–15. 25. Tanghetti E, Sherr E, Alvarado S. Multipass treatment of photodamage using the pulse dye laser. Dermatol Surg 2003;29:686–90. 26. Hsu T, Zelickson B, Dover J, et al. Multicenter study of the safety and efficacy of a 585 nm pulsed-dye laser for the nonablative treatment of facial rhytids. Dermatol Surg 2005;31:1–9. 27. Goldberg D, Cutler K. Nonablative treatment of rhytids with intense pulsed light. Lasers Surg Med 2000;26: 196–200. 28. Negishi K, Tezuka Y, Kushikata N, Wakamatsu S. Photorejuvenation for Asian skin by intense pulsed light. Dermatol Surg 2001;27:627–631; discussion 632. 66 Clinical procedures in laser skin rejuvenation 06 Carniol-8028.qxd 8/23/2007 3:32 PM Page 66 29. Huang Y, Liao Y, Lee S, Hong H. Intense pulsed light for the treatment of facial freckles in Asian skin. Dermatol Surg 2002;28:1007–12. 30. Goldberg D, Samady J. Intense pulsed light and Nd:YAG laser non-ablative treatment of facial rhytids. Lasers Surg Med 2001;28:141–4. 31. Sadick N,Weiss R, Kilmer S, Bitter P. Photorejuvenation with intense pulsed light: results of a multi-center study. J Drugs Dermatol 2004;3:41–9. 32. Brazil J, Owens P. Long-term clinical results of IPL photorejuvenation. J Cosmet Laser Ther 2003;5:168–74. 33. Kligman D, Zhen Y. Intense pulsed light treatment of photoaged facial skin. Dermatol Surg 2004;30:1085–90. 34. Carniol P, Farley S, Friedman A. Long-pulse 532-nm diode laser for nonablative facial skin rejuvenation. Arch Facial Plast Surg 2003;5:511–13. 35. Tan M, Dover J,Hsu T,Arndt K, Steward B. Clinical eval- uation of enhanced nonablative skin rejuvenation using a combination of a 532 and a 1,064nm laser. Lasers Surg Med 2004;34:439–45. 36. Butler E, McClellan S, Ross E. Split treatment of photo- damaged skin with KTP 532nm laser with 10mm hand- piece versus IPL: a cheek-to-cheek comparison. Lasers Surg Med 2006;38:124–8. 37. McDaniel D,Weiss R, Geronemus R, Ginn L, Newman J. Light-tissue interactions I: Photothermolysis vs photomodu- lation laboratory findings. Lasers Surg Med 2002;14:25. 38. Weiss R,Weiss M, Geronemus R, McDaniel D. A novel non-thermal non-ablative full panel LED photomodula- tion device for reversal of photoaging: digital microscopic and clinical results in various skin types. J Drugs Dermatol 2004;3:605–10. 39. Russell B, Kellet N, Reilly L. Study to determine the effi- cacy of combination LED light therapy (633nm and 830nm) in facial skin rejuvenation. J Cosmet Laser Ther 2005;7:196–200. 40. Nestor M, Gold M, Kauvar A, et al.The use of photody- namic therapy in dermatology: results of a consensus conference. J Drugs Dermatol 2006;5:140–154. 41. Ruiz-Rodriguez R, Sanz-Sanchez T, Cordoba S. Photo- dynamic rejuvenation, Dermatol Surg 2002;28:742–4. 42. Touma D,Yaar M,Whitehead S, Konnikov N, Gilchrest BA.A trial of short incubation, broad-area photodynamic therapy for facial actinic keratoses and diffuse photodam- age.Arch Dermatol 2004;140:33–40. 43. Lowe N, Lowe P.A pilot study to determine the efficacy of ALA–PDT photorejuvenation for the treatment of facial ageing. J Cosmet Laser Ther 2005;7:159–62. 44. Hall J, Keller P, Keller G. Dose response of combination photorejuvenation using intense pulsed light-activated photodynamic therapy and radiofrequency energy. Arch Facial Plast Surg 2004;6:374–8. 45. Bhatia A, Dover J, et al.Adjunctive use of topical amino- levulinic acid with intense pulsed light in the treatment of photoaging. Paper presented at: Controversies and Conversations in Cutaneous Laser Surgery, Mt Tremblant, Canada,August 2004. 46. Gold M, Bradshaw V, Boring M, Bridges T, Biron J. Split- face comparison of photodynamic therapy with 5- aminolevulinic acid and intense pulsed light versus intense pulsed light alone for photodamage. Dermatol Surg 2006;32:795–801. 47. Dover J, Bhatia A, Stewart B, Arndt K.Topical 5-aminole- vulinic acid combined with intense pulsed light in the treat- ment of photoaging.Arch Dermatol 2005;141:1247–52. 48. Gold M. Intense pulsed light therapy for photorejuvena- tion enhanced with 20% aminolevulinic acid photody- namic therapy. J Lasers Med Surg 2003; 15(Suppl):47. 49. Goldman M, Atkin D, Kincad S. PDT/ALA in the treat- ment of actinic damage: real world experience. J Lasers Med Surg 2002;14(Suppl):24. 50. Avram D, Goldman M, Effectiveness and safety of ALA– IPL in treating actinic keratoses and photodamage. J Drugs Dermatol 2004;3(1 Suppl):S36-S39. 51. Alster T,Tanzi E,Welsh E. Photorejuvenation of facial skin with topical 20% 5-aminolevulinic acid and intense pulsed light treatment: a split-face comparison study. J Drugs Dermatol 2005;4:35–8. 52. Lupton JR,Williams CN,Alster TS.Nonablative laser skin resurfacing using a 1540nm erbium glass laser: a clinical and histologic analysis. Dermatol Surg 2002;28:833–5. 53. Fournier N, Mordon S. Nonablative remodeling with a 1,540nm erbium:glass laser. Dermatol Surg 2005;31: 1227–35. 54. Lee M. Combination visible and infrared lasers for skin rejuvenation. Semin Cutan Med Surg 2002;21:288–300. 55. Tanzi E, Williams C, Alster T. Treatment of facial rhytids with a nonablative 1,450-nm diode laser: a con- trolled clinical and histologic study. Dermatol Surg 2003;29:124–8. 56. Dayan SH,Vartanian AJ, Menaker G, Mobley SR, Dayan AN. Nonablative laser resurfacing using the long-pulse (1064-nm) Nd:YAG laser.Arch Facial Plast Surg 2003; 5:310–15. 57. Taylor M, Prokopenko I. Split-face comparison of radiofrequency versus long-pulse Nd-YAG treatment of facial laxity. J Cosmet Laser Ther 2006;8:17–22. 58. Dang YY, Ren QS, Liu HX, Ma JB, Zhang JS. Comparison of histologic, biochemical, and mechanical properties of murine skin treated with the 1064-nm and 1320-nm Nd:YAG lasers. Exp Dermatol 2005;14:876–82. 59. Dang Y, Ren Q, Hoecker S, et al. Biophysical, histological and biochemical changes after non-ablative treatments with the 595 and 1320nm lasers: a comparative study. Nonablative technology for treatment of aging skin 67 06 Carniol-8028.qxd 8/23/2007 3:32 PM Page 67 Photodermatol Photoimmunol Photomed 2005;21: 204–9. 60. Orringer JS, Voorhees JJ, Hamilton T, et al. Dermal matrix remodeling after nonablative laser therapy. J Am Acad Dermatol 2005;53:775–82. 61. Doshi S,Alster T. 1,450 nm long-pulsed diode laser for nonablative skin rejuvenation. Dermatol Surg 2005;31: 1223–6. 62. Alexiades-Armenakas M. Rhytides, laxity, and photoag- ing treated with a combination of radiofrequency, diode laser, and pulsed light and assessed with a comprehensive grading scale. J Drugs Dermatol 2006; 5:731–8. 63. Lennox MA. Febrile convulsions in childhood; a clinical and electroencephalographic study. Am J Dis Child 1949;78:868–82. 64. Ruiz-Esparza J. Near painless, nonablative, immediate skin contraction induced by low-fluence irradiation with new infrared device: a report of 25 patients. Dermatol Surg 2006;32:601–10. 65. Koch D. Histological changes and wound healing response following noncontact holmium:YAG laser thermal keratoplasty.Trans Am Ophthalmol Soc 1996; 94:745–802. 66. Ross E, McKinlay J,Anderson R.Why does carbon diox- ide resurfacing work? A review. Arch Dermatol 1999; 135:444–54. 67. Taub A. Harnessing radiofrequency energy. Skin Aging 2003;11:52–8. 68. Bassichis BA, Dayan S,Thomas JR. Use of a nonablative radiofrequency device to rejuvenate the upper one-third of the face. Otolaryngol Head Neck Surg 2004;130:397–406. 69. Fitzpatrick R, Geronemus R, Goldberg D, et al.Multicenter study of noninvasive radiofrequency for periorbital tissue tightening. Lasers Surg Med 2003;33:232–42. 70. Hsu T, Kaminer M.The use of nonablative radiofrequency technology to tighten the lower face and neck. Semin Cutan Med Surg 2003;22:115–23. 71. Zelickson B, Kist D, Bernstein E, et al. Histological and ultrastructural evaluation of the effects of a radiofre- quency-based nonablative dermal remodeling device: a pilot study.Arch Dermatol 2004;140:204–9. 72. Kilmer S.A new, nonablative radiofrequency device: pre- liminary results. In: Controversies and Conversations in Cutaneous Laser Surgery. Chicago: American Medical Association Press, 2002:95–100. 73. Iyer S, Suthamjariya K, Fitzpatrick R. Using a radiofre- quency energy device to treat the lower face: a treatment paradigm for a nonsurgical facelift. Cosmet Dermatol 2003;16:37–40. 74. Ruiz-Esparza J, Gomez J.The medical face lift: a noninva- sive, nonsurgical approach to tissue tightening in facial skin using nonablative radiofrequency. Dermatol Surg 2003;29:325–32. 75. Alster T,Tanzi E. Improvement of neck and cheek laxity with a nonablative radiofrequency device: a lifting experi- ence. Dermatol Surg 2004;30:503–7. 76. Narins RS,Tope WD, Pope K, Ross E. Overtreatment effects associated with a radiofrequency tissue-tightening device: rare, preventable,and correctable with subcision and autolo- gous fat transfer. Dermatol Surg 2006;32:115–24. 77. Kist D, Burns AJ, Sanner R, Counters J, Zelickson B. Ultrastructural evaluation of multiple pass low energy versus single pass high energy radio-frequency treatment. Lasers Surg Med 2006;38:150–4. 78. Narins D, Narins R. Non-surgical radiofrequency facelift. J Drugs Dermatol 2003;2:495–500. 79. Ruiz-Esparza J. Near painless, nonablative, immediate skin contraction induced by low-fluence irradiation with new infrared device: a report of 25 patients. Dermatol Surg 2006;32:601–10. 80. Taub A,Battle E Jr, Nikolaidis G. Multicenter clinical per- spectives on a broadband infrared light device for skin tightening, J Drugs Dermatol 2006;5:771–8. 68 Clinical procedures in laser skin rejuvenation 06 Carniol-8028.qxd 8/23/2007 3:32 PM Page 68 INTRODUCTION Acne vulgaris is an exceedingly common multifactorial disease of the pilosebaceous unit, believed to affect approximately 40 million adolescents and 25 million adults in the USA alone. 1 It is thought to be physiologic in adolescence due to its affect on nearly 85% of young people between the ages of 12 and 24 years. 2 However, 12% of adult women and 3% of adult men will have clinical acne until the age of 44. 3 Many authors have described that, in addition to long-term scarring, which can be disfiguring, patients with acne often carry signif- icant psychosocial morbidity, including anxiety, sleep disturbances, clinical depression, and suicide. 4–8 In many cases, acne can be successfully treated using conventional topical or oral medications such as antibacterials, antimicrobials, and retinoids. However, this approach often has drawbacks involving side-effect profiles, length of treatment, and patient compli- ance. 9–13 With oral retinoids, practitioners are faced with federally mandated paperwork that takes not only time, but also several patient visits in order to deliver treatment. 14,15 For the subset of patients who have failed these treatment modalities, laser and light-based systems have emerged as standalone and adjunct therapies. These devices work by targeting the components of the pilosebaceous unit that lead to acne lesions, namely either the resident bacterium Propionibacterium acnes, inflammation, or the pilosebaceous unit itself. THE BUILDING BLOCKS OF ACNE VULGARIS In order to select the appropriate device for treating acne, it is essential to understand the pathogenesis of the acne lesion itself (Fig. 7.1). Acne vulgaris can be broken down into lesion types based on pathogenesis and severity: comedones, inflamed papules, nodules, and cysts. The majority of data involving laser and light-based therapies are based on the treatment of the non-cystic form of acne vulgaris. Simply put, acne has four main pathophysiological features: hyperkeratinization, sebum production, bacterial proliferation, and inflammation.The early comedone is produced when there is abnormal pro- liferation and differentiation of keratinocytes in the infundibulum, forming a keratinous plug.This leads to impaction and distention of the lower infundibu- lum, creating a bottleneck affect.As the shed keratino- cytes form concretions, the sebum in the follicle thus becomes entrapped.This stage represents the nonin- flammatory closed comedone. As accumulation increases, so too does the force inside the follicle itself, eventually leading to rupture of the comedo wall, with extrusion of the immunogenic contents and subsequent inflammation. Depending on the nature of the inflammatory response, pustules, nod- ules, and cysts can form. One factor in the pathogenesis of acne vulgaris is the role of the resident P.acnes found deep within the seba- ceous follicle. 16–18 P.acnes is a slow-growing, gram-posi- tive anaerobic bacillus. It contributes to the milieu of acne production in the lipid-rich hair follicle by pro- ducing proinflammatory cytokines (e.g., interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α)), as well as many lipases, neuraminidases, phosphatases, and proteases.True colonization with P. acnes occurs 1–3 years prior to sexual maturity, when numbers can reach approximately 10 6 /cm 2 , predominantly on the face and upper thorax. 19 Although some suggest that the absolute number of P. acnes does not correlate with clinical severity, 16 it is common belief that the 7. Lasers, light, and acne Kavita Mariwalla and Thomas E Rohrer 07 Carniol-8028.qxd 8/23/2007 10:28 AM Page 69 70 Clinical procedures in laser skin rejuvenation Sebum Resident P. acnes Hair shaft Pore Sebaceous lobule The pilosebaceous unit Hair shaft Pore Retained keratin and lamellar concretions Inflammation Sebaceous lobule regression P. acnes proliferation Inflammatory papule/pustule Fig.7.1 The pathogenesis of acne.Lasers & light based devices target either the pilosebaceous unit,to decrease sebum production or improve sebum flow out of the gland,or the resident Propionibacterium acnes to combat acne vulgaris.Comedones result from hyperkeravatosis at the level of the infundibulum along with increased sebum secretion.As the accumulated keratin and sebum form a plug,inflammation and proliferation of P.acnes produces the clinically inflammatory acne papule. 07 Carniol-8028.qxd 8/23/2007 10:28 AM Page 70 proinflammatory mediators released by these bacteria are at least partially responsible for the clinical acne lesion. In practice, acne is predominantly found on the face and to a lesser degree on the back, chest, and shoul- ders.The majority of studies using laser and light-based systems target acne on the face, although we present data from a limited number of studies performed else- where on the body. CLINICAL EXPERIENCE AND CONSIDERATIONS Patient screening As new laser- and light-based systems emerge for the treatment of acne vulgaris, the selection of patients and the type of device to use for each one can seem daunting. In our clinical practice, we use a series of simple guidelines before initiating laser or light-based therapies. 1. Is the patient a topical or oral medication failure? 2. Has the patient tried isotretinoin or are there circumstances that make isotretinoin a less-than- ideal medication for the patient? 3. Is the patient’s acne mainly comedonal or are there inflammatory acne papules as well? To what extent is the patient’s acne nodulocystic? 4. Does the patient have acne and acne scarring? It is important to keep in mind that most laser systems will work to some extent.Topical and oral medications should be optimized and are generally continued during the initial phase of treatment with any of the devices. Occasionally, laser and light-based treatments may be used as first-line therapy, with or without topical and oral medications, in patients presenting with both active acne and acne scars who also want treatment of their scars. The patient encounter In the initial evaluation of the patient, it is important to set realistic expectations. Although many patients see dramatic improvement with laser and light-based therapy, some see little to no improvement. Compared with conventional therapy, laser and light devices require no daily routine, are not altered by antibiotic resistance, have few systemic side-effects, and are easy to administer, and some (infrared and radiofrequency devices) offer significant textural improvement of acne scars. On the other hand, these modalities are much more expensive, involve some degree of patient dis- comfort during treatment, have post-treatment recov- ery/downtime due to erythema, and require multiple trips to the dermatologist’s office.As with any laser procedure, patients’ skin phototype and underlying psychosocial disturbances should be considered. Choosing the appropriate laser In most practices, the choice of device depends on what is available to the practitioner.When multiple devices are available, it is crucial to keep in mind the area of involvement and the presence of scarring. For example, in large areas such as the chest and back, treatment with infrared lasers with a 4–6mm spot size is generally too time-consuming and painful for the patient. Instead, for wide treatment areas, light-based therapy with or without δ-aminolevulinic acid can be used. In cases of significant acne scarring, infrared lasers are often used, since these devices are also fre- quently employed to improve the texture of the skin, including scars.The ultimate decision, however, is up to the individual practitioner and the patient, and should be evaluated in terms of what the treatment is targeting: the sebaceous gland or P.acnes itself. TARGETING P.ACNES P. acnes produces and accumulates endogenous por- phyrins, namely protoporphyrin, uroporphyrin, and coproporphyrin III, 20,21 as part of its normal metabolic and reproductive processes.These porphyrins absorb light energy in the near-ultraviolet (UV) and blue regions of the spectrum, and can be visualized by Wood’s lamp (365nm) examination, under which they fluoresce coral red. 22 Porphyrins have two main absorption peaks, the Soret band (400–420nm) and the Q-bands (500–700 nm), which make them susceptible to excitation by lasers and Lasers,light,and acne 71 07 Carniol-8028.qxd 8/23/2007 10:28 AM Page 71 [...]... in human skin and thus penetrates poorly Red light, while less effective in photoactivating porphyrins,35 has increased depth of penetration into the epidermis to reach the porphyrins in the sebaceous follicles Red light can also potentially induce anti-inflammatory effects by stimulating cytokine release from macrophages.36 07 Carniol-8028.qxd 74 8/23/2007 10:28 AM Page 74 Clinical procedures in laser. .. improvement to near 50% reduction 07 Carniol-8028.qxd 78 8/23/2007 10:28 AM Page 78 Clinical procedures in laser skin rejuvenation Glycine + Succinyl CoA → ALA → Prophobilinogen → Hydoxymethylbilane → Uroporphyrinogen III → (Uroporphyrinogen) III → Protoporphyrinogen III → Protoporphyrin IX → Heme ↑ Ferrochelatase Fig 7.6 Devices using topical application of δ-aminolevulinic acid (ALA) are effective because... Paithankar et al68 demonstrated that the 145 0 nm diode laser with cryogen spray cooling 07 Carniol-8028.qxd 82 8/23/2007 10:28 AM Page 82 Clinical procedures in laser skin rejuvenation (Smoothbeam, Candela Corp., Wayland, MA) could induce thermal injury confined to the dermis histologically after irradiation of ex vivo human skin Using rabbit ear skin as an in vivo model, treatment with the Smoothbeam produced... later, following four treatments with a 595 nm pulsed-dye laser and a 145 0 nm infrared laser (Smoothbeam Laser, Candela Corp.,Wayland MA) medications during four treatments spaced 4 6 weeks apart (12– 14 J/cm2) They noted a mean 54. 6% improvement in lesions counts which persisted for the 6-month follow-up period of the study The 595 nm PDL has been used in combination with the 145 0 nm diode laser in a study... an average pain rating of 5.6 on a scale of 1 (minimum) to 10 (maximum) with the high-energy single pass and 1.3 with the lower-energy double pass The 145 0 nm laser in combination with other therapies Using the 145 0 nm laser as an adjunct in patients who were on oral and/or topical acne treatments, Friedman et al 74 observed an 83% decrease in inflammatory facial acne lesion counts following three treatments... improvement in papulopustular lesions in skin phototypes III and IV with four biweekly treatments (F-36 W/Blue V, Waldmann, Villingen-Schwenningen, Germany) and worsening of nodulocystic acne in 20% of patients (n =28) Using a different blue light source (Blu-U, DUSA Pharmaceuticals, Inc., Wilmington, MA), Gold et al 34 found an average 36% reduction in inflammatory acne lesion counts after 4 weeks of... SmoothBeam 145 0 nm laser (Candela Corp, MA; 13.5– 14 J/cm2, 6 mm spot size, and dynamic cooling spray at 30 40 ms) Photographs of the patients at baseline and at 3, 6, and 12 weeks post treatment were evaluated by an independent observer, who counted the total number of acne lesions Wang et al77 found no statistically 07 Carniol-8028.qxd 84 8/23/2007 10:28 AM Page 84 Clinical procedures in laser skin rejuvenation. .. laser The 532 nm (green) potassium titanyl phosphate (KTP) laser has as its target chromophores oxyhemoglobin and melanin.As such, it is typically used to treat telangiectasia and superficial pigmented lesions However, since this laser has a greater optical penetration depth into skin than blue light, it has the innate 07 Carniol-8028.qxd 76 8/23/2007 10:28 AM Page 76 Clinical procedures in laser skin. .. 35-dynamic cooling spray 35 ms, 6 mm spot size, and no overlapping whole-face treatment) every 4 6 weeks.They noted that initially there was an average 74. 8% reduction in total acne lesion counts (maximum 88.5%, minimum 49 .4% ), which showed only a slight deterioration to 71.8% at 18 months (maximum 88.5%, minimum 47 .9%) A pilot study demonstrated the safety of the 145 0 nm laser in the treatment of inflammatory... small (n = 2 for each) Nonetheless, the PDT laser combination was well tolerated, with minimal erythema lasting 1–2 days without evidence of crusting, blistering, or dyspigmentation This pilot study demonstrated that PDL 07 Carniol-8028.qxd 80 8/23/2007 10:28 AM Page 80 Clinical procedures in laser skin rejuvenation Dynamic cooling device spray Stratum corneum Laser pulse Epidermis Dermis Hair Sebaceous . remained clear at 8-month follow-up. A subsequent study by the same group 57 78 Clinical procedures in laser skin rejuvenation Fig.7.6 Devices using topical application of δ -aminolevulinic. through the skin s own healing process. However, the treated regions remained lesion- free for extended periods of time, leading Lloyd and 80 Clinical procedures in laser skin rejuvenation Laser pulse Thermal. 1,064nm laser. Lasers Surg Med 20 04; 34: 439 45 . 36. Butler E, McClellan S, Ross E. Split treatment of photo- damaged skin with KTP 532nm laser with 10mm hand- piece versus IPL: a cheek-to-cheek