Rapid Recurrence of Keloid after Pulse Dye Laser Treatment PO-YU SHIH, MD, HUA-HSIN CHEN, MD, CHIEN-HSUN CHEN MD,y HONG-SHANG HONG, MD PHD,y AND CHIH-HSUN YANG, MDy The authors have indicated no significant interest with commercial supporters. K eloids and hypertrophic scarring are frequently encountered in the clinical setting and can be quite difficult to treat. Keloids, in particular, are prone to overgrowth, and as disease activity can remain active for or be reactivated after years of dormancy, great deformity can arise. Differing hypotheses regarding the formation of keloids have led to a myriad of treatments as the pathogenesis behind keloidal growth has not yet been fully elucidated. Pulse dye laser (PDL) has been suggested as an effective therapeutic modality for hypertrophic scars and keloids. We report a case of rapid recurrence of keloid within 1 week of PDL treatment for telangiectasia. suggested for treatment of residual erythema and telangiectasia. One course of PDL (Candela ScleroPLUS, Candela Corp., Wayland, MA) was used the week after the last IL steroid injection at 585-nm wavelength delivering a fluence of 8.0 J/cm2 with pulse duration of 1,500 ms and 5-mm spot size with concomitant cryogenic cooling (30/20 ms; Figure 1). At postoperative follow-up 1 week later, the previously flattened keloid had enlarged substantially, with accompanying erythema, pruritus, and pain (Figure 2). On review, the patient reported no new medication, topical agent, or lifestyle changes within that week. Subsequently, IL steroid injections were given biweekly for over 4 months with modest Case Report A 21-year-old healthy woman with Fitzpatrick Skin Phototype IV presented for treatment of large keloids over the V-region of her chest. Her medical history was unremarkable except for facial acne vulgaris treated with a short course of oral doxycycline and topical agents including adapalene. Her keloids were treated with intralesional (IL) injections of triamcinolone acetonide (diluted to 20 mg/mL weekly for six visits, 10 mg/mL biweekly for eight visits, 5 mg/mL biweekly for five visits, and 5 mg/mL monthly for five visits). The protrusion of the keloids gradually decreased, and marked improvement of pruritus was noted. Although the size of the keloid had also stabilized, she was still very dissatisfied with the resulting telangiectasia and redness. PDL was Figure 1. Baseline photograph of flattened keloid after repeated IL corticosteroid injections, just before PDL therapy for telangiectasia. Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taiwan; yChang Gung University College of Medicine, Linkou, Taiwan & 2008 by the American Society for Dermatologic Surgery, Inc. Published by Blackwell Publishing ISSN: 1076-0512 Dermatol Surg 2008;34:1124–1127 DOI: 10.1111/j.1524-4725.2008.34225.x 1124 SHIH ET AL Figure 2. Appearance at follow-up 1 week later. Substantial enlargement of the keloid combined with increased erythema, pruritus, and pain were noted. response in terms of keloidal size and pruritus. However, as more corticosteroids were used, local telangiectasia, erythema, and atrophy became much more prominent and thereby even less satisfactory for the patient. Discussion Keloids are frequently encountered in the clinical setting and can be quite difficult to treat. Differing hypotheses regarding the formation of keloids have led to a myriad of treatments as the pathogenesis behind keloidal growth has not yet been fully elucidated. The complex interplay of growth factors, cytokines, extracellular matrix components, and collagen equilibrium is still the subject of intensive research. Of note, transforming growth factor-b (TGF-b), especially isotypes 1 and 2, has been shown to be expressed in greater levels in keloidal fibroblasts compared with those derived from normal skin and may be major contributing factors to the process of proliferative scars.1–4 TGF-b1, in particular, has been shown to play a role in regulation of collagen and matrix metalloproteinase (MMP) production in cultured keloidal fibroblasts. Increased production of MMPs, in turn, had a role in the high migratory activity of cultured keloid fibroblasts.5 In recent years, the 585-nm PDL alone or in combination with other therapies such as topical 5-fluorouracil and IL steroids has become a popular technique in keloid treatment.6–9 The effect of PDL has been thought to be mediated by selective damage of the microvasculature causing decreased cellular function, laser-induced heating of collagen fiber disulfide bonds or collagenolysis after cytokine stimulation.7,10 The end result is a decrease in vessel size with significantly finer and loosely interwoven collagen parallel to the epidermis.11 However, PDL has also been effective in treatment of facial wrinkles12 and for photorejuvenation,13 the basis of which was believed to be due to dermal thermal injury resulting in collagen denaturation, fibroblast stimulation, and subsequent neocollagen formation.14 In particular, in vitro studies of keloidal fibroblasts irradiated with low-fluence PDL (3 J/cm2) have shown increase of TGF-b1 levels, as has upregulation of other factors leading to increased collagen synthesis. This effect was not seen at a slightly higher fluence.15 Another study using high-fluence PDL (10–1814 J/cm2, average 14 J/cm2) showed suppression of TGF-b1 expression.16 Whether there is a dose-related effect with regard to TGF-b1 expression requires further exploration. While numerous studies have shown the effectiveness of PDL in treatment of vascular lesions, keloidal and hypertrophic scars, and photorejuvenation and wrinkle improvement, the adverse effects associated to PDL alone have been rare. Of note, one review of adverse effects in 500 patients treated with the PDL found only atrophic scarring (0.8%), hyperpigmentation (1%), hypopigmentation (2.6%), and dermatitis (2%) but no hypertrophic scarring was noted.17 Subsequently, however, limited cases with delayedonset hypertrophic scarring have been reported18,19 as have mild scarring and texture changes at higher fluences (12 J/cm2).20 More common side effects associated with higher fluences were primarily purpura and pigmentary changes.21 With these in mind, selection of appropriate laser parameters was challenging for this patient. As her primary complaint was that of residual telangiectasia, parameters for 34:8:AUGUST 2008 1125 RAPID RECURRENCE OF KELOID treatment of facial telangiectasia were used as preliminary guidelines. However, this selection would entail a therapy with moderate-high fluence of 9.0 J/cm2 (range 8.5–10.0 J/cm2),22 energy levels even higher than which she was given. Another consideration would be the treatment site; a reduction of at least 10% to 20% in fluence for areas prone to scarring such as the anterior chest or neck or areas where tissue is delicate such as the periorbital regions has been advised.23 Thus given the location of her telangiectasia (the chest), the nature of the lesion (new-onset telangiectasia after treatment of keloid with IL corticosteroids), and her Fitzpatrick phototype (Type IV), a lower fluence (8.0 J/cm2) was used. Nevertheless, rapid recurrence of keloid was still noted within 1 week’s time. It is possible that this scarring phenomenon and other side effects of PDL may be more pronounced in darker-skinned individuals since more melanin is present in the skin. As more energy is absorbed by the melanin and surrounding soft tissue causing tissue injury, lesser fluence would be transduced and available for absorption by hemosiderin, the target chromophore in keloidal blood vessels, thus decreasing overall treatment efficacy. Skin redness has been shown to have a similar effect as pigmentation.21 Several cases of hypertrophic scarring in laser use, including PDL, in conjunction with isotretinoin use have been reported.24 These have led to the clinical avoidance of laser treatment in patients under isotretinoin therapy. Although our patient had previously used a retinoid derivative, adapalene, the topical agent had been discontinued many months previously and had only been used over the face. Moreover, there have been no reports of adapalenerelated keloid development. Thus, it is unlikely to have been significant in this keloidal recurrence. Therefore, while it remains statistically uncommon for keloid formation or recurrence to develop after PDL therapy, clinicians should be aware that lasers with photorejuvenative effects, such as PDL, may be responsible for activation of keloid development. 1126 D E R M AT O L O G I C S U R G E RY References 1. Burd A, Huang L. Hypertrophic response and keloid diathesis: two very different forms of scar. Plast Reconstr Surg 2005;116:150e–7e. 2. Smith P, Mosiello G, Deluca L, et al. TGF-beta2 activates proliferative scar fibroblasts. J Surg Res 1999;82:319–23. 3. Mukhopadhyay A, Tan EK, Khoo YT, et al. Conditioned medium from keloid keratinocyte/keloid fibroblast coculture induces contraction of fibroblast-populated collagen lattices. Br J Dermatol 2005;152:639–45. 4. Polo M, Smith PD, Kim YJ, et al. Effect of TGF-beta2 on proliferative scar fibroblast cell kinetics. Ann Plast Surg 1999;43:185–90. 5. Fujiwara M, Muragaki Y, Ooshima A. 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Treatment response of keloidal and hypertrophic sternotomy scars. Arch Dermatol 2002;138: 1149–55. 12. Bjerring P, Egevist H, Clement M, et al. Selective non-ablative wrinkle reduction by laser. J Cutan Laser Ther 2000;2:9–15. 13. Michel JL. ED2000s: 585 nm collagen remodeling pulsed dye laser. J Cosmet Laser Ther 2003;5:201–3. 14. Kelly KM, Majaron B, Nelson S. Nonablative laser and light rejuvenation. Arch Facial Plast Surg 2001;3:230–5. 15. Yu HY, Chen DF, Wang Q, et al. Effects of lower fluence pulsed dye laser irradiation on production of collagen and the mRNA expression of collagen relative gene in cultured fibroblasts in vitro. Chin Med J 2006;119:1543–7. 16. Kuo YR, Wu WS, Jeng SF, et al. Suppressed TGF-b1 expression is correlated with up-regulation of matrix metalloproteinase-13 in keloid regression after flashlamp pulsed-dye laser treatment. Lasers Surg Med 2005;36:38–42. 17. Levine VJ, Geronemus RG. 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Treatment of facial telangiectasia with variable-pulse high fluence pulsed-dye laser: comparison of efficacy with fluences immediately above and below the purpura threshold. Dermatol Surg 2003;29:681–5. 23. Rothfleisch JE, Kosann MK, Levine VJ, et al. Laser treatment of congenital and acquired vascular lesions. Dermatol Clin 2002;1:1–18. 24. Bernestein LJ, Geronemus RG. Keloid formation with the 585-nm pulsed dye laser during isotretinoin treatment. Arch Dermatol 1997;133:111–2. Address correspondence and reprint requests to: Hua-Hsin Chen, MD, Department of Dermatology, Division of Dermatologic Surgery, Chang Gung Memorial Hospital, 199 Tun-Hwa North Road, Taipei 105, Taiwan, or e-mail: [email protected] 34:8:AUGUST 2008 1127