Permanent Hair Removal by Normal-Mode Ruby Laser

OBSERVATION Permanent Hair Removal by Normal-Mode Ruby Laser

Christine C. Dierickx, MD; Melanie C. Grossman, MD; William A. Farinelli; R. Rox Anderson, MD

Objective: To assess the permanence of hair removal after laser exposure, 4 participants still had obvious, sig- by normal-mode ruby laser treatment. nificant hair loss at all laser-treated sites compared with the unexposed shaved and wax-epilated control sites. In Methods: Hair removal was measured for 2 years after all 4 participants, there was no significant change in hair a single treatment with normal-mode ruby laser pulses counts 6 months, 1 year, and 2 years after laser expo- (694 nm, 270 microseconds, 6-mm beam diameter). sure. Laser-induced alopecia correlated histologically with miniaturized, velluslike hair follicles. No scarring and no Observations: Six test areas on the thighs or backs of permanent pigmentary changes were observed. 13 volunteers were exposed to normal-mode ruby laser pulses at fluences of 30 to 60 J/cm2 delivered to both Conclusions: Permanent, nonscarring alopecia can be shaved and wax-epilated skin. In addition, there was a induced by a single treatment with high-fluence ruby la- shaved and wax-epilated control site. Terminal hairs were ser pulses. Miniaturization of the terminal hair follicles manually counted before and after laser exposure. Tran- seems to account for this response. sient alopecia occurred in all 13 participants after laser exposure, consistent with induction of telogen. Two years Arch Dermatol. 1998;134:837-842

NWANTED HAIR is a ma- hair growth delay consistent with induc- jor cosmetic and surgi- tion of telogen. Ruby lasers have been com- cal problem. Many tem- mercialized for hair removal, but the ques- porary hair removal tion remains whether permanent hair loss methods exist, includ- can be induced by selective photother- ing shaving, wax epilation, and use of molysis. Four study participants6 had clini- U 1,2 chemical depilatories. Electrolysis is a cally obvious hair loss at the final fol- well-established method for permanent de- low-up visit 6 months after exposure, each struction of terminal hair follicles. How- of these with less than 50% regrowth of ever, the method is tedious, and efficacy terminal hairs. We decided to follow up has been reported to range from 15% to the participants of this first study at 1 and 50% permanent hair loss.3 Scarring can oc- 2 years after laser exposure to evaluate the cur after electrolysis, especially if inex- permanence of hair removal. pertly performed.4 RESULTS For editorial comment see page 867 HAIR LOSS Results at 6 months’ follow-up have been Damage to hair follicles based on the published previously6 but did not ad- 5 theory of selective photothermolysis has dress the question of permanent hair been reported recently.6 Thirteen volun- From the Wellman Laboratories loss. Of the 13 participants, 7 were fol- teers with brown or black hair were ex- lowed up for 2 years after laser exposure. of Photomedicine, Harvard posed to normal-mode ruby laser pulses Medical School, Boston, Mass (694 nm, 270 microseconds, 6-mm beam (Drs Dierickx and Anderson 2 and Mr Farinelli), and the diameter) at fluences of 30 to 60 J/cm delivered to both shaved and wax-epilated This article is also available on our Laser and Skin Surgery Center Web site: www.ama-assn.org/derm. of New York City, New York, skin sites on the thighs or back. In all 13 NY (Dr Grossman). participants, laser exposures produced a

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 PARTICIPANTS AND METHODS DATA ANALYSIS Hair loss was defined as the percentage of terminal hairs Thirteen adult volunteers (12 men and 1 woman) con- absent after treatment compared with the number before sented to participate, as previously described.6 All had treatment. For each site, at each follow-up visit, hair loss fair skin (Fitzpatrick type I, II, or III) and brown or was calculated. Results for each experimental condition black hair. Test sites were chosen on the back or poste- were pooled for all participants. The mean ± SD for each rior aspect of the thighs based on uniformity and density condition was calculated. A paired t test was used to of terminal hairs. Eight 3 ϫ 2-cm areas were mapped and determine significant differences (PϽ.05) between post- photographed. Baseline hair counts were obtained from treatment and pretreatment hair counts for each experi- each site by manually counting and marking terminal mental condition at the 6-, 12-, and 24-month observa- hairs. Before laser exposure, half of the test sites were tion times. shaved and half were epilated with cold wax (My-Epil, Laboratoire Suzy, Montreuil, France). Sites were irradi- LASER AND DELIVERY APPARATUS ated with a normal-mode ruby laser, described below, at fluences of 0 (unexposed control), 30, 40, and 60 J/cm2. A normal-mode, flashlamp-pumped, 694-nm ruby laser Laser pulses were given in a contiguous, nominally with a 270-microsecond pulse duration and a 6-mm spot- nonoverlapping pattern that covered the entire test site. size was used (model 936R4H-2, Lasermetrics, Winter Clinical evaluation, terminal hair counts, and pho- Park, Fla). The beam was steered via an articulated arm tographs were obtained 1, 3, 6, 12, and 24 months after into an actively cooled “hand piece” designed to maxi- laser exposure. One participant who had obvious alope- mize delivery of light into the reticular dermis while mini- cia in all laser exposure sites at all of these follow-up vis- mizing epidermal injury. A planoconvex sapphire lens its consented to biopsy examination. Three-millimeter (approximately 20-mm focal length) was used to provide punch biopsy samples were obtained before treatment a convergent beam at the skin surface and to increase and at 1 year after laser exposure from a site with alope- beam coupling into the skin compared with air as an cia treated at 60 J/cm2 after shaving. Tissue specimens external medium. The sapphire lens was cooled to 4°C to were processed for light microscopy of horizontal sec- provide heat conduction from the epidermis before, dur- tions with a technique using trisection or quadrisection ing, and after each laser pulse. The convex surface of the that maintains all sections in the same anatomic orienta- cold sapphire lens was pressed firmly against the skin tion (deep to superficial) on the microscope slides.7 All before delivery of each laser pulse. Delivered pulse energy specimens were stained with hematoxylin-eosin for light into air was measured with a laser energy meter (model microscopy. 351, Scientech, Boulder, Colo).

At 1 year and 2 years after laser treatment, 4 of these 7 in the shaved sites for all fluences compared with the participants still had obvious hair loss confined to laser- untreated control site. treated sites and 3 had complete or nearly complete hair regrowth. In all 7 participants, there was no significant HISTOLOGICAL FINDINGS change in terminal hair counts 6 months, 1 year, and 2 years after laser exposure. Terminal and velluslike (miniaturized) hairs were iden- Figure 1, left, illustrates hair loss on a partici- tified on the transverse sections and counted by estab- pant’s back 1 year after laser exposure. The hair loss is lished criteria.8-10 Terminal-velluslike hair ratios were fluence dependent, with the greatest loss at the highest calculated from the follicular counts, and fibrous tracts fluence (60 J/cm2). Figure 1, right, illustrates the same were recorded as absent or present. Results are shown sites 2 years after treatment. The same amount of hair in the Table. The total number of hairs was identical in loss is still present. Figure 2, top and bottom, show the control and laser-treated sites. However, in the the same site on an upper thigh treated with 60 J/cm2 laser-treated sites, there was a reduction in large termi- at 3 months and 2 years, respectively. No substantial nal hairs with a reciprocal increase in small velluslike change in the clinical appearance of the alopecia is hairs. The average hair shaft diameter measured from seen. Neither pigment changes nor scarring was seen the histological sections also decreased after laser treat- in any participant at the 12- and 24-month follow-up ment (Figure 4). There were no signs of fibrous tracts, visits. and normal-appearing sebaceous glands were still pre- Hair loss at 6, 12, and 24 months after a single sent around the miniaturized hair follicles. laser exposure in the 4 participants showing permanent hair loss are plotted vs fluence in Figure 3. Sites COMMENT treated with 60 J/cm2 (highest fluence) after shaving had the greatest hair loss, 64.3% ± 1.1%. Statistically The results of this study show that permanent loss of significant hair loss was seen at 6 months for all flu- terminal (coarse) hair can result from a single treat- ences at both shaved and epilated sites compared with ment with high-fluence, normal-mode ruby laser the unexposed shaved and epilated control sites. At 1 pulses. The lack of change in any participant’s termi- year and 2 years, there was significantly less hair only nal hair counts beyond 6 months after laser exposure

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 Figure 1. Left, Test sites on the back 1 year after ruby laser treatment. Site 1 was treated with 30 J/cm2, site 2 was treated with 40 J/cm2, and site 3 was treated with 60 J/cm2. Site 4 was left untreated and served as a control. A fluence-dependent regrowth is apparent. Right, Two years after a single laser treatment, the same degree of hair loss is still present.

suggests that 6 months’ follow-up may be sufficient to not to hair loss after Q-switched ruby laser pulses.13 assess final outcome after treatment for hair removal. Consistent with this behavior, permanent hair loss has The mechanisms by which high-fluence, normal- not been reported in humans after Q-switched laser mode ruby laser pulses induce selective damage to treatment despite a decade of widely using Q-switched hair follicles6 are based on the principles of selective ruby and Nd:YAG lasers for tattoo removal. The ther- photothermolysis.5 At 694 nm, light penetrates well mal relaxation time of whole hair follicles is between 1 into and through the dermis, and follicular melanin is and 100 milliseconds, depending on size. Thermal by far the dominant chromophore in the dermis.11 relaxation of human terminal hair follicles has never Laser pulse width also seems to play an important been measured but is estimated to be about 10 to 50 role, as suggested by the thermal transfer theory.5 milliseconds.6,14,15 Thermal conduction during the laser pulse heats a The 0.27-millisecond ruby laser pulses used in this region around each microscopic site of optical energy study were clearly long enough to cause thermal coagu- absorption. The spatial scale of thermal confinement lation and vaporization injury of hair follicles,6 leading and resulting thermal or thermomechanical damage to a growth delay6 in all participants and permanent is therefore strongly related to laser pulse width. hair loss in some. However, in theory, the longer-pulse Q-switched (nanosecond domain) laser pulses effec- (3-millisecond) ruby laser now commercially available tively damage individual pigmented cells within hair for hair removal may be more ideal for several reasons. follicles by confinement of heat at the spatial level of First, it is still unknown which “targets” in hair follicles melanosomes,12 leading in animals to leukotrichia but are responsible for permanent hair loss. A somewhat

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40 % Hair Loss 30

0 60-S 40-S 30-S Con-S 60-E 40-E 30-E Con-E Fluence, J/cm2 Figure 3. Hair loss in the 4 participants with clinical alopecia 6 months, 1 year, and 2 years after laser exposure for each fluence (60, 40, and 30 J/cm 2) in shaved (S) and epilated (E) sites compared with unexposed control (Con-S and Con-E) sites.

Histological Findings*

Before Laser 1 y After Treatment Laser Exposure Terminal hairs, No. 3 1 Velluslike hairs, No. 1 3 Total hairs, No. 4 4 Terminal-velluslike ratio 3:1 1:3 Figure 2. Hair loss in a test site on the thigh treated with 60 J/cm2 3 months Average (mean±SD) hair 68.7 ± 44.2 22.5 ± 12.2 (top) and 2 years (bottom) after treatment. Alopecia is still present at 2 years. shaft diameter, µm Fibrous tracts Absent Absent

*Hair counts were done on transverse sections at ϫ4 magnification. longer pulse width should allow more thermal conduction and damage to nonpigmented regions of the hair follicle but retain confinement on the spatial scale of the the follicle that control formation of the bulb with each follicle itself. Second, the efficiency of extracting heat anagen cycle. from the epidermis during each laser pulse into cold The histological picture of miniaturized follicles sapphire in contact with the skin surface should be after ruby laser pulses corresponds with the histological improved with the longer laser pulse. picture of androgenetic alopecia.8,9,17 Male baldness is The biologic mechanisms by which ruby laser characterized by a proportional reduction in size of the pulses cause permanent loss of terminal hair remain papilla and the matrix.16 Therefore, the terminal fol- unknown. However, this study strongly suggests that licles are gradually transformed to velluslike follicles. miniaturization of coarse terminal hair follicles to vel- “Loss” of hair in androgenetic alopecia only relates to luslike hair follicles is involved, producing nonscarring the loss of terminal hairs and is similar to “loss” of hair alopecia. Only 1 participant with laser-induced alopecia after ruby laser treatment. The follicles are not actually was examined histologically 1 year after laser exposure, lost but produce hairs that are shorter, finer, and less and more should be studied as the number of people pigmented. These miniaturized follicles still have arrec- with laser-induced alopecia grows. In this participant, tor pili muscles.8 Pluripotent stem cells of the bulge—a however, there was an absence of fibrosis or any rem- region of follicular epithelium near the insertion of the nant of laser-damaged hair follicles, a decrease in termi- arrector pili muscles—regenerate epidermis during wound nal hair follicles, and a reciprocal increase in miniature healing.18,19 To the extent that ruby laser–induced alo- hair follicles. These histological findings are also consis- pecia is like male pattern alopecia, wound healing should tent with clinical observations. A miniaturized terminal not be largely affected after laser hair removal. hair or secondary vellus hair is arbitrarily defined as We hypothesize and suggest that the 2 distinct having a cross-sectional hair shaft diameter of less than responses—growth delay and permanent hair loss— 30 mm.9 Because the size of a hair depends on the size are caused by induction of telogen and miniaturization of the papilla and the hair bulb,16 ruby laser pulses seem of terminal hair follicles, respectively. Numerous to miniaturize the papilla and the bulb either by direct observations are explained by this hypothesis. In all 13 photothermal injury or by injury to other structures of participants, whether they had measurable permanent

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 of terminal hairs after a given treatment that is stable for a period longer than the complete growth cycle of hair follicles at the given body site. Telogen may last for 3 to 7 months on the thighs and chest,21,22 after which the follicle will recycle into anagen, which also lasts 3 to 7 months on the body. Our observation period of 24 months after a single laser treatment therefore spans 2 to 4 complete growth cycles, depending on the length of the telogen phase. The data show gradual reappearance of terminal hair up to 6 months after laser exposure, which is consistent with recovery of terminal hair follicles within 1 growth cycle. Thereaf- ter, the data show no significant difference in hair counts 6 months, 1 year, and 2 years later, which is consistent with no further recovery of terminal hair follicles. This strongly suggests that whatever terminal hair follicles were inactivated at 6 months were also missing for at least 2 years, although we did not map and track individual hair follicles in this study. For studies of laser or other treatments intended to induce hair loss, we suggest that measurements be carried out until a steady state is achieved, which in this study seems to be between 6 months and 1 year. A distinction also needs to be made between permanent and complete hair loss. Complete hair loss refers to a lack of regrowing hairs (ie, a significant reduction in the number of regrowing hairs to zero). Complete hair loss may be either temporary or permanent. Ruby laser treatment usually produces complete hair loss for 1 to 3 months, followed by partial permanent hair loss. Finally, it is likely, but as yet unproven, that the Figure 4. Routine hematoxylin-eosin–stained section (magnification ϫ40) of sensitivity of human hair follicles to laser pulses varies untreated (top) and normal-mode ruby laser–treated (bottom) areas. with the hair growth cycle. In this study of responses Miniaturized follicles were present after laser treatment; the mean (± SD) diameter of the hair shafts diminished from 68.7 ± 44.2 to 22.5 ± 12.2 µm. after a single treatment, the hairs “resistant” to permanent inactivation by laser treatment may have been mainly in the telogen stage at the time of exposure. On hair loss or not, there was a growth delay consistent in the thighs, up to 72% of the hairs are in telogen.21 Selec- length with telogen. Presence of the hair shaft during tive photothermolysis requires absorption of light, and laser exposure was not essential to induce growth the bulb of a telogen hair is unpigmented because of delay, which occurred at all fluences in both shaved cessation of melanogenesis during catagen.23 On the and epilated sites in all participants.6 Presumably, other hand, as anagen progresses, the bulb and papillae there is enough ample melanin present because epila- descend deeply into the dermis and beyond such that tion typically breaks the hair shaft above, in the upper late anagen hairs may also be relatively resistant to laser third of, or at the midlevel of the bulb.20 In contrast, pulse injury. By this reasoning, follicles should be most permanent hair loss after a single laser exposure was easily inactivated by laser pulses during early anagen. If significant only in sites that were shaved (hair shaft so, the reliable induction of telogen with a single laser present) rather than wax epilated and was fluence treatment, as we suggest, has profound clinical implica- dependent. Both responses are clinically significant tions. As the “surviving” terminal follicles transition and may be separately desirable to different patients. into anagen, after growth delay, a second treatment may Growth delay that provides a few months of hairless be more effective than the first. On the contrary, a sec- skin is far more reliable and requires lower fluences ond treatment given too early or too late may have little than permanent hair loss. Permanent hair loss occurred effect. We are presently investigating these interesting in this study in only 4 of the 13 participants after a questions. single treatment. Knowledge of the hair cycle and particularly of Accepted for publication December 8, 1997. the length of telogen is essential for interpretation of This study was supported by funds from the Wellman the results of this study. At present, no consensus Laboratory of Photomedicine, Harvard Medical School, exists on a definition for treatment-induced “perma- Boston, Mass. nent” hair loss despite frequent use of the term to Presented in part at the 1997 American Society for La- describe the effects of electrolysis. We suggest, and ser Medicine and Surgery, Phoenix, Ariz, April 4, 1997. hereby use, the following specific definition: “perma- We thank Thomas Flotte, MD, for his assistance with nent” hair loss is a significant reduction in the number the histology slides.

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 Reprints: R. Rox Anderson, MD, Wellman Laborato- 11. Anderson RR, Parrish JA. The optics of human skin. J Invest Dermatol. 1981; ries of Photomedicine, Bartlett Extension 6, 50 Blossom St, 77:13-19. 12. Polla L, Margolis RJ, Dover JS, et al. Melanosomes are a primary target of Q- Boston, MA 02114. switched ruby laser irradiation in guinea pig skin. J Invest Dermatol. 1987;89: 281-286. REFERENCES 13. Dover JS, Margolis RJ, Polla LL, et al. Pigmented guinea pig skin irradiated with Q-switched ruby laser pulses: morphologic and histologic findings. Arch Der- matol. 1989;125:43-49. 1. Kvedar JC, Gibson M, Krusinski PA. Hirsutism: evaluation and treatment. JAm 14. Van Gemert MJC, Welch AJ. Time constants in thermal laser medicine. Lasers Acad Dermatol. 1985;12:215-225. Surg Med. 1989;9:405-421. 2. Richards RN, Marguerite U, Meharg G. Temporary hair removal in patients with 15. Anderson RR. Laser-tissue interactions. In: Goldman MP, Fitzpatrick RE, eds. hirsutism: a clinical study. Cutis. 1990;45:199-202. Cutaneous Laser Surgery: The Art and Science of Selective Photothermolysis. 3. Wagner RF. Physical methods for the management of hirsutism. Cutis. 1990; St Louis, Mo: Mosby–Year Book Inc; 1994:1-18. 45:19-26. 16. Van Scott EJ, Ekel TM. Geometric relationships between the matrix of the hair 4. Kligman AM, Peters L. Histologic changes of human hair follicles after electroly- bulb and its dermal papilla in normal and alopecic scalp. J Invest Dermatol. 1958; sis: a comparison of 2 methods. Cutis. 1984;34:169-176. 31:281-287. 5. Anderson RR, Parrish JA. Selective photothermolysis: precise microsurgery by 17. Abell E. Pathology of male pattern alopecia. Arch Dermatol. 1984;120:1607- selective absorption of pulsed radiation. Science. 1983;220:524-527. 1608. 6. Grossman MC, Dierickx C, Farinelli W, Flotte T, Anderson RR. Damage to hair 18. Sun T, Cotsarelis G, Lavker RM. Hair follicular stem cells: the bulge-activation follicles by normal-mode ruby laser pulses. J Am Acad Dermatol. 1996;35:889- hypothesis. J Invest Dermatol. 1991;96(suppl 5):77S-78S. 894. 19. Lavker RM, Miller S, Wilson C, et al. Hair follicle stem cells: their location, role in 7. Frishberg DP, Sperling LC, Guthrie VM. Transverse scalp sections: a proposed hair cycle, and involvement in skin tumor formation. J Invest Dermatol. 1993; method for laboratory processing. J Am Acad Dermatol. 1996;35:220-222. 101(suppl 1):16S-26S. 8. Whiting DA. Diagnostic and predictive value of horizontal sections of scalp bi- 20. Bassukas ID, Hornstein OP. Effects of plucking on the anatomy of the anagen opsy specimens in male pattern androgenetic alopecia. J Am Acad Dermatol. 1993; hair bulb: a light microscopic study. Arch Dermatol Res. 1989;281:188-192. 28:755-763. 21. Seago SV, Ebling FJB. The hair cycle on the human thigh and upper arm. Br J 9. Headington JE. Transverse microscopic anatomy of the human scalp. Arch Der- Dermatol. 1985;113:9-16. matol. 1984;120:449-456. 22. Saitoh M, Uzuka M, Sakamoto M. Human hair cycle. J Invest Dermatol. 1970; 10. Whiting DA. The value of horizontal sections of scalp biopsies. J Cutan Aging 54:65-81. Cosmet Dermatol. 1990;1:165-173. 23. Kligman AM. The human hair cycle. J Invest Dermatol. 1959;33:307-316.

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