Adverse effects associated with the 577- and 585-nanometer pulsed dye laser in the treatment of cutaneous vascular lesions: A study of 500 patients

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1 THERAPY Adverse effects associated with the 577- and 585-nanometer pulsed dye laser in the treatment of cutaneous vascular lesions: A study of 500 patients Vi&i J. Levine, MD, and Roy G. Geronemus, MD New York, New York Background: The flashlamp-pumped pulsed dye laser has been used in the treatment of cutaneous vascular disorders since Although this laser is now widely used for the treatment of port-wine stains, telangiectases, and hemangiomas, the incidence of adverse reactions has not been clearly defined in a large series of patients. Objective: We assessed the incidence of adverse effects associated with the use of the pulsed dye laser in the treatment of vascular lesions. Methods: We studied 500 patients undergoing pulsed dye laser treatments for port-wine stains, telangiectases, and hemangiomas. All patients were examined during the course of their treatment to assess the incidence of adverse effects associated with the use of the pulsed dye laser. Results: There were no cases of hypertrophic scarring. The incidence of atrophic scarring was less than 0.1%. A spongiotic dermatitis was seen in 11 of 297 patients (0.04%) after multiple treatments of port-wine stains. Hyperpigmentation was seen in five of 500 patients (I%), whereas transient hypopigmentation was seen in 13 (2.6%). Conclusion: These findings demonstrate that the flashlamp-pumped pulsed dye laser is safe for the treatment of port-wine stains, telangiectases, and hemangiomas in children and adults. (J AM ACAD DERMATOL 1995;32:613-7.) The development of the flashlamp-pumped pulsed dye laser marked the beginning of a new era in the treatment of cutaneous vascular lesions. Before its development continuous-wave lasers (argon, continuous-wave dye, carbon dioxide) were the mainstay of therapy for port-wine stains and other vascular malformations. Although these lasers were successful in the treatment of many vascular lesions, textural and pigmentary changes were commonly seen and limited their applicability., 2 Three important factors determine how cutaneous blood vessels are altered by lasers: pulse duratioq3 spot size,4 and wavelength.5 The inappropriate combination of these could be responsible for many of the adverse effects. In the early 1980s the flashlamp-pumped pulsed dye laser (577 nm) was the first to incorporate these three factors into its design, Presented at the annual meeting of the American Society for Dermatologic Surgery, Charleston, SK., March 27, Reprint requests: Roy G. Geronemus, MD, Laser and Skin Surgery Center of New York, 3 17 E. 34th St., Suite 11 North, New York, NY by the American Academy of Dermatology, Inc /95 $ /l/61534 to damage cutaneous blood vessels selectively.6 The wavelength of 577 nm matches one of the absorption bands of oxyhemoglobin, the main chromophore in blood vessels. The wavelength was later changed to 585 nm to increase the depth of injury from 0.5 to 1.2 mm without sacrificing selectivity.5 Although the two other absorption peaks of oxyhemoglobin are stronger (418 and 542 nm), competition is greater for absorption of these wavelengths by melanin in the epidermis overlying the dermal blood vessels.7 Its pulse duration is 300 to 500 microseconds, which is shorter than the thermal relaxation time of cutaneous blood vessels.3 This restricts thermal damage to the cutaneous blood vessels and spares the surrounding dermal collagen.8 The pulsed dye laser was initially used to treat port-wine stains in both children and adults, with only the rare occurrence of scarring.9-12 The pulsed dye laser has also been used to treat \linear spider and matted telangiectases, superficial venous lakes, angiomas, and pyogenic granulomas. 13, l4 Poikiloderma of Civatte and rosacea respond favorably to pulsed dye laser treatment.15> l6 Experimentally, the pulsed dye laser improves the 613

2 614 Levine and Geronemus Journal of the American Academy of Dermatology April 1995 Fig. 1. Atrophic scarring on forehead of infant with port-wine stain (arrow). efficacy of sclerotherapy in the treatment of leg telangiectases. l7 Most recently the pulsed dye laser has been used in the treatment of capillary and cavernous hemangiomas. In the management of childhood hemangiomas, intervention with the pulsed dye laser may prevent further growth and promote involution of superficial and capillary hemangiomas In both children and adults the side effects associated with this laser have been minimal. In the series of Tan et a1.9 in 5.7% of children with port-wine stains treated with the pulsed dye laser small depressed scars developed in areas traumatized after treatment. Transient hyperpigmentation lasting 3 to 4 months occurred in 57% of the children. A retrospective study of 73 patients with port-wine stain (age range, 3 months to 14 years) treated with the pulsed dye laser demonstrated transient atrophic scarring with complete resolution (5.7%) and hypopigmentation (l%). In the series of Garden et al. O of 52 patients with port-wine stains (age range, 14 to 61 years), hypopigmentation, epidermal changes, and/or isolated 3 mm circular areas of cutaneous depression developed in four patients. Transient hypopigmentation or hyperpigmentation developed in less than 10% of patients. Only one patient had persistent hyperpigmentation at 18 months. One pyogenic granuloma developed in the lasertreated area. In a series of 25 capillary and cavernous hemangiomas treated with the pulsed dye laser, atrophy developed in four. l8 Transient hyperpigmentation and hypopigmentation occurred in 21% and lo%, respectively. No fibrosis or hypertrophic scarring was seen. The only report of hypertrophic scarring was on the chest of a white patient with a port-wine stain who received a test treatment with the pulsed dye laser (fluence, 6.5 J/cm2).17 This study examined the side effects of the pulsed dye laser in the treatment of various vascular lesions in infants, children, and adults on the basis of direct observation of 500 patients. MATERIAL Patients AND METHODS A total of 500 patients were examined from September 1992 through July These patients had been undergoing pulsed dye laser treatments from 1986 to 1993 for the treatment of port-wine stain, hemangioma, poikiloderma of Civatte, telangiectasia, spider angioma, cherry angioma, or erythematous scars. The age of the patients at the start of treatment ranged from 3 days to 70 years. Informed consent was obtained before the procedure, and the risks and benefits were explained. Laser A flashlamp-pumped pulse dye laser (Candela SPTL- 1 or SPTL-lA, Candela Corp., Wayland, Mass.) was used for all treatments. The laser was tuned to 577 nm before October After that, the wavelength was adjusted to 585 nm to increase the depth of vascular injury. The pulsed duration was 450 microseconds, and the laser beam was transmitted down a 1 mm fiber by a planoconvex lens and focused as a 3 or 5 mm spot beam. An energy meter (Ophir, Jerusalem, Israel) calibrated to f 10% accuracy was used to measure energy densities. Procedure A small test site was exposed to 5.75 to 9.0 J/cm2 depending on the type of vascular lesion, age of the patient, location of the lesion, and the spot size used. Higher-energy fluences were generally used in the treatment of hemangiomas, hypertrophic port-wine stains, and venous lesions. Lower fluences were used in children and smalldiameter-vessel telangiectases. Subsequent treatment doses were adjusted on the basis of patient response. Multiple nonoverlapping pulses were delivered to the affected site. Patients were re-treated (at no sooner than 2- to 8-weekintervals) until optimal lightening, as judged by physician and patient, was achieved. Treatment was performed with no anesthesia, local anesthesia, or general anesthesia depending on the size of the lesion and the

3 Journal of the American Academy of Dermatology Volume 32, Number 4 Levine and Geronemus 615 Fig. 2. A, Port-wine stain of neck in man before treatment. B, Same patient after multiple treatments with flashlamp-pumped pulsed dye laser. Moderate degree of depigmentation developed within treated area. ability of the patient to cooperate. Local anesthesia consisted of (1) a eutectic mixture of 2.5% lidocaine and 2.5% prilocaine cream (EMLA cream, Astra Pharmaceuticals, Westboro, Mass.) under occlusion for 30 to 60 minutes before treatment, or (2) 2% lidocaine without epinephrine locally or regionally. In children general anesthesia was performed with halothane in combination with nitrous oxide and oxygen and in adults with propofol alone or in combination with midazolam, fentanyl, enflurane, nitrous oxide, and oxygen. Immediately after treatment the skin was covered with a hydrogel formulation of water and polyethylene (Vigilon, C. R. Bard, Nutley, N.J.). Patients were instructed to apply a topical antibiotic ointment if crusts developed at the site. Strict sun avoidance was recommended. During a follow-up visit each patient was examined by the physician-investigators for any adverse effects including atrophic scarring, hypertrophic scarring, hyperpigmentation of at least 6 months duration, hypopigmentation of at least 6 months duration, and dermatitis within the treatment site. RESULTS Of the 500 patients, 72 were younger than 1 year of age and 109 were between 1 and 13 years old. The remaining 3 19 patients were older than 13 years of age. The vascular lesions treated were port-wine stain (297 patients), hemangioma (43) telangiectasia of face (96) spider angiomas (22), cherry angiomas (two), erythematous scar ( 13), telangiectasia of lower extremities (four); poikiloderma of Civatte (seven), and miscellaneous lesions (16). During the treatment period 128 of 297 patients (43%) with a port-wine stain received one to five treatments. The number of treatments ranged from 11 to 20 in 56 of 297 patients (19%). Atrophic scars Atrophic scarring occurred in four patients (0.8%). The scarring was limited to a small area of the face in patients with port-wine stains (Fig. 1). The age range was 8 to 12 years. The number of treatments ranged from 8 to 16. The fluence used was 6 to 7.5 J/cm.2 All patients with atrophic scarring were treated during the early stages of the pulsed dye laser s development, when problems with the dosage meter were common. Hyperpigmentation The incidence of hyperpigmentation of at least 6 months duration was 1% (five patients) in the following locations: legs (two patients), forehead (one patient), back (one patient), and cheeks (one patient). Most of these patients (y1= 4) had undergone one to five treatments. Hyperpigmentation devel-

4 616 Levine and Geronemus Journal of the American Academy of Dermatology April 1995 Fig. 3. Erythematous scaly patch that developed within port-wine stain on chest during course of treatment with flashlamp-pumped pulsed dye laser. oped in two patients with facial telangiectasia and in one patient with lower limb telangiectasia. The skin types of these patients were II (n = 3), III (n = 1); and IV (n = 1). The fluences ranged from 7.25 to 7.50 J/cm.2 Hypopigmentation The incidence of hypopigmentation of at least 6 months duration was 2.6%. Hypopigmentation occurred on the cheeks (five patients), neck (five), chest (one), and thighs (two). Eleven patients had a port-wine stain, and two had telangiectasia. The majority (six patients) had undergone 10 treatments. The fluences ranged from 6 to 7.50 J/cm2 (Fig. 2). Dermatitis While 11 patients with port-wine stains underwent treatment, a pruritic scaly patch developed within the lesion (Fig. 3). These patients had no history of a dermatitis. Sixty-four percent of patients in whom a dermatitis developed were 13 years of age or younger. All had a personal or family history of atopy. In 82% of patients the dermatitis developed after at least five treatments. Histopathologic examination revealed a spongiotic dermatitis. In all patients the dermatitis resolved or improved with topical corticosteroid therapy. DISCUSSION To date, this is the largest study to assess the safety of the pulsed dye laser in the treatment of vascular lesions. It corroborates the results of previous studies; that is, the pulsed dye laser is safe in the treatment of a variety of vascular lesions in all anatomic locations in infants, children, and adults. It is a low-risk procedure even in patients with portwine stains who have had multiple treatments. Atrophic scarring was observed exclusively in children with a port-wine stain. All had treatment in the early developmental stage of the pulsed dye laser when the operation of the dosage meter was not consistent. It is probable that these patients inadvertently received a higher fluence. Hypertrophic scarring has been reported only once after pulsed dye laser treatment and was not seen in this study.20 Spongiotic dermatitis was seen only in patients with a port-wine stain who had undergone multiple treatments. All had a personal or family history of atopy. Also of interest is the absence of pyogenic granulomas as a consequence of pulsed dye laser therapy. This has been noted elsewhere and in the authors practice, but not in this study of 500 patients. r The pulsed dye laser solves many of the problems associated with the use of continuous wave lasers. The incidence of argon laser-induced hypertrophic scarring has been reported to be as high as 40% in children. > 2 The absence of hypertrophic scarring in children after pulsed dye laser treatment makes it safe for this group. 21s 22 Although permanent pigmentary alteration is common after irradiation with the argon laser, it is rarely persistent after pulsed dye laser treatment. Atrophic scarring, another sequela of the argon laser, infrequently occurs after pulsed dye laser treatment. The benefit/risk ratio of the pulsed dye laser is high because it adheres to the principles necessary for selective photothermolysis. Because this is not the case with the continuous-wave lasers, nonspecific thermal damage to dermal appendagesurrounding blood vessels is inevitable, resulting in hypertrophic scarring, atrophic scarring, and pigmentary alteration. REFERENCES 1. Dixon JA, Huether S, Rotering R. Hypertrophic scarring in argon laser treatment of port-wine stains. Plast Reconstr Surg 1984;73: Noe JM, Barsky SH, Geer DE, et al. Port wine stains and

5 Journal of the American Academy of Dermatology Volume 32. Number 4 Levine and Geronemus 617 the response to argon laser therapy: successful treatment and predictive role of color, age, and biopsy. Plast Reconstr Surg 1980;65: Garden JM, Tan OT, Kerschmann R, et al. Effect of dye laser pulse duration on selective cutaneous vascular injury radiation. J Invest Dermatol 1986;87: Tan OT, Motemed M, Welch AJ, et al. Spot-size effects in guinea pig caused by pulsed irradiation. J Invest Dermatol 1988;90: Tan OT, Murray S, Kurban AK. Action spectrum of vascular specific injury using pulsed irradiation. J Invest Dermatol 1989;92: Anderson RR, Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulse radiation. Science 1983;2200: Anderson RR, Parrish JA. Microvasculature can be selectively damaged using dye lasers: a basic theory and experimental evidence in human skin. Lasers Surg Med 1981; 1: Tan OT, Carney JM, Margolis R, et al. Histologic responses of port-wine stains treated by argon, carbon dioxide and tunable dye lasers: a preliminary report. Arch Dermatol 1986;122: Tan OT, Sherwood K, Gilchrest BA. Treatment of children with port-wine stains using the flashlamp-pumped pulsed tunable dye laser. N Engl J Med 1989;320: Garden JM, Polla LL, Tan OT. Pulsed dye laser therapy of port-wine stains: pulse duration effects and long-term re sponses. Arch Dermatol 1988;124: Reyes B, Geronemus R. Treatment of port-wine stains during childhood with the flashlamp-pumped pulsed dye laser. J AM ACAD DERMATOL 1990;23: Ashinoff R, Geronemus RG, Flashlamp-pumped pulsed dye laser for port-wine stains in infancy: early versus later treatment. J AM ACAD DERMATOL 1990;24: Gonzalez E, Gange RW, Momtaz KT. Treatment of telangiectases and other benign vascular lesions with the 577 nm pulsed dye laser. J AM ACAD DERMATOL 1992; 27: Geronemus RG. Treatment of spider telangiectases in children using the flashlamppumped pulsed dye laser. Pediatr Dermatol 1991;8: Geronemus RG. Poikiloderma of Civatte. Arch Dermatol 1990;126: Lowe NJ, Behr KL, Fitzpatrick R, et al. Flashlamppumped pulsed dye laser for rosacea-associated telangiectasia and erythema. J Dermatol Surg On& 1991;17: Goldman MD, Martin DE, Fitzpatrick RE, et al. Pulse dye laser treatment of telangiectasia with and without subtherapeutic sclerotherapy. J AM ACAD DERMATOL 1990;23: Garden JM, Bakus AD, Paller AS. Treatment of cutaneous hemangiomas by the flashlamp-pumped pulsed dye laser: prospective analysis. J Pediatr 1992,120: Ashinoff R, Geronemus RG. Capillary hemangiomas and treatment with the flashlamp-pumped dye laser. Arch Dermatol 1991;127: Swinehart JM. Hypertrophic scarring resulting from flashlamp-pumped pulsed dye laser surgery. J AM ACAD DER- MATOL 1991;25: Geronemus RG. Pulsed dye laser treatment of vascular lesions in children. J Dermatol Surg Oncol 1993;19: Tan OT, Morrison P, Kurban A. 585 nm for the treatment of port-wine stains. Plast Reconstr Surg 1990;86: