Induction of De Novo Hair Regeneration in Scars After Fractionated Carbon Dioxide Laser Therapy in Three Patients THOMAS M. BEACHKOFSKY, MD, J. SCOTT HENNING, DO,y
AND
CHAD M. HIVNOR, MDy
The authors have indicated no significant interest with commercial supporters.
F
or many years, the human hair follicle was thought to form only during primary development and to be unable to be regenerated if destroyed or lost.1 Although its complex development has been intensely studied, the morphologic stages and numerous biochemical cascades characteristic of human hair follicle growth and development are poorly understood. Consequently, it is a source of intense research.2 More than 50 years ago, Kligman and Strauss1 described the regeneration of vellus hair follicles and sebaceous glands on the face after dermabrasion. Gillman and Penn3 showed similar findings during healing of incised wounds. Although the validity of these findings has been questioned,4 numerous researchers have shown post-traumatic de novo hair follicle regeneration in many nonhuman mammalian species, including mice,5 rats,6 rabbits,7 and guinea pigs,8 although there continues to be a paucity of human studies, and published case reports are rare and offer incomplete detail.5,6,9,10 Here we present original case reports of three patients with scarring of distinct etiologies. All experienced new hair growth within fractionated carbon dioxide (CO2) laser treatment areas. We believe these incidental findings may represent de novo hair
follicle regeneration inside the borders of post-traumatic hypertrophic scarring or grafting.
Methods Three patients aged 15 to 25 sought evaluation and treatment in the dermatology clinic at Wilford Hall Medical Center for cosmesis, contracture, or pruritus consequent to hypertrophic scarring caused by toxic epidermal necrolysis and traumatic burns. All received fractionated CO2 laser treatments at various settings: 0.1 mm spot size, 20 to 40 mJ, 5% to 15% density.
Report of a Case Series Case 1: A 15-year-old Hispanic girl presented for evaluation and treatment of scars covering 90% of her body surface area 5 years after an episode of toxic epidermal necrolysis. Test spots of erbiumdoped yttrium aluminum garnet (YAG) and CO2, 1,550-nm fractionated laser therapy were delivered. Because of notable improvement of the CO2 laser test spots, this treatment was extended to her entire body. After one treatment with the fractionated CO2 laser, she noted improvement of her ability to sweat.11 Three to 4 months after treatment, she had terminal hair growth, which was particularly within the scarring on her lower extremity. She previously
U.S. Air Force, Kunsan Air Base, Republic of Korea; yDepartment of Dermatology, Wilford Hall Medical Center,
Lackland Air Force Base, Texas & 2011 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg 2011;37:1365–1368 DOI: 10.1111/j.1524-4725.2011.01934.x 1365
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Figure 1. Terminal hair growth on the thigh of patient number 1 after one treatment with a fractionated carbon dioxide laser.
Figure 2. Terminal hair growth on the thigh of patient number 1 after one treatment with a fractionated carbon dioxide laser.
had no hair growth within the scarring (Figures 1 and 2).
areas of STSG, after burn injuries sustained from an explosive device in Afghanistan. His primary complaints were pruritus and contractures. Test spots treated with pulse dye laser (PDL) alone were compared with test spots treated with a combination of PDL and fractionated CO2 laser therapy. The pruritus improved in both sites, but the site treated with PDL alone resulted in recurrent pruritus at 6 months, whereas the combination treatment had resolution of pruritus as well as hair regeneration at 3 months that persisted at 1-year follow-up (Figures 5 and 6).
Case 2: A 21-year-old man presented for evaluation and treatment of burn scars obtained after faling into a fire 19 years before. He had undergone femoral split-thickness skin grafts (STSGs) and harvested lower abdominal full-thickness skin grafts (FTSGs). He received two treatments of fractionated CO2 laser therapy delivered 2 months apart. After fractionated CO2 laser therapy to the FTSG site, he had terminal hair growth in the treated area (Figures 3 and 4).
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Case 3: A 25-year-old man presented with hypertrophic scars of the anterior upper legs, including
All three patients described developed hair growth, and one developed the ability to sweat after
Figure 3. Terminal hair growth in the area of a full-thickness skin graft on the wrist of patient number 2 after two treatments with a fractionated carbon dioxide laser.
Figure 4. Terminal hair growth in the area of a full-thickness skin graft on the palm of patient number 2 after two treatments with a fractionated carbon dioxide laser.
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TABLE 1. Summary of Carbon Dioxide Laser Treatment in Three Cases of Traumatic Scarring
Case
Grafting
Time to improvement (months)
1
None
3–4
2
STSG/FTSG (hair growth in FTSG) Harvest site for STSG with significant hypertrophic scarring
3–4
3 Figure 5. Terminal hair growth on the anterior thigh of patient number 3 treated with a combination of pulse dye laser and fractionated carbon dioxide laser therapy.
treatment with fractionated CO2 laser therapy. In one patient, we also found that the combination of PDL and fractionated CO2 laser therapy demonstrated better management than with PDL alone. These results are summarized in Table 1.
Comments We present three unique cases with incidental findings of hair regrowth or regeneration after fractionated CO2 laser therapy. Each patient presented with what was thought to be permanent hair loss due to follicular damage resulting from distinct injuries, yet each patient demonstrated new-onset hair growth after fractionated CO2 laser therapy. Moreover, since this article was submitted, we have continued to
5–6
Symptoms improved Increased sweat NA
Decreased pruritus
STSG, split-thickness skin graft; FTSG, full-thickness skin graft.
witness post-treatment terminal hair regrowth in patients believed to have hair follicle loss. Recently, Ito et al.12 introduced the idea that nonhair follicle stem cells in the epidermis could acquire competence to form hair follicles in response to wounding. They also showed that this process could be modified through manipulation of the Wnt signaling pathway. It is possible that a similar mechanism occurred in the patients we treated. It may also be that fractionated CO2 laser therapy leads to Wnt activation and thus de novo hair synthesis. These and other questions merit future research. We believe the findings demonstrated in these cases illustrate de novo human hair synthesis. As such, they represent a novel finding that challenges current dogma. Future research is warranted to build on these findings and address questions generated by the observations presented here.
References Figure 6. Terminal hair growth on the anterior thigh of patient number 3 treated with a combination of pulse dye laser and fractionated carbon dioxide laser therapy.
1. Kligman AM, Strauss JS. The formation of vellus hair follicles from human adult epidermis. J Invest Dermatol 1956;27:19–23. 2. Schmidt-Ullrich R, Paus R. Molecular principles of hair follicle induction and morphogenesis. Bioessays 2005;27:247–61.
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3. Gillman T, Penn J. Studies on the repair of cutaneous wounds. I. Healing of incised wounds, with reference to epidermal reactions to sutures, and the pathogenesis of carcinoma in scars. Med Proc (Johannesburg) 1956;2:121. 4. Straile WE. Dermal-epidermal interaction in sensory hair follicles. In: Montagna W, Dobson RL, editors. Advances in biology of skin, Vol 9. New York: Pergamon Press, Inc.; 1967. p. 317–91. 5. Lacassagne A, Latarjet R. Action of methylcholanthrene on certain scars of the skin in mice. Cancer Res 1946;6:183–8.
9. Muller SA. Hair neogenesis. J Invest Dermatol 1971;56:1–9. 10. Sun ZY, Diao JS, Guo SZ, Yin GQ. A very rare complication: new hair growth around healing wounds. J Int Med Res 2009;37:583–6. 11. Neiner J, Hivnor CM. Buried Alive: functional eccrine coils buried under scar tissue. Arch Dermatol 2010, in press. 12. Ito M, Yang Z, Andl T, et al. Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 2007;447:316–20.
6. Mikhail GR. Hair neogenesis in rat skin. Arch Dermatol 1963;88:713–28. 7. Billingham RE, Russell PS. Incomplete wound contracture and the phenomenon of hair neogenesis in rabbits’ skin. Nature 1956;177:791–2. 8. Silberberg M, Silberberg R. Hair growth in the skin of guinea pigs painted with 20-methylcholanthrene. Arch Pathol (Chic) 1947;44:297–306.
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Address correspondence and reprint requests to: Chad M. Hivnor, MD, Wilford Hall Medical Center, 59 MDW/ SG05D/Dermatology, 2200 Bergquist Drive Ste 1, Lackland Air Force Base, TX 78236-9908, or e-mail:
[email protected]