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1 Treatment of Angiokeratoma of Fordyce with Long-Pulse Neodymium-Doped Yttrium Aluminium Garnet Laser MUSTAFA ÖZDEMIR, MD, IBRAHIM BAYSAL, MD, BURHAN ENGIN, MD, AND SUNA ÖZDEMIR, MD y BACKGROUND Angiokeratomas are typically asymptomatic, blue-to-red papules with a scaly surface located on the scrotum, shaft of penis, labia majora, inner thigh, or lower abdomen. The treatment of angiokeratomas may be necessary if they bleed and lead to patient anxiety. OBJECTIVE To determine the safety and effectiveness of long-pulse 1,064 neodymium-doped yttrium aluminium garnet (Nd:YAG) laser for the treatment of angiokeratomas of Fordyce. MATERIALS AND METHODS Ten consecutive patients with angiokeratoma of Fordyce were treated with long-pulse Nd:YAG laser in two to six sessions. The three authors independently assessed improvement of the lesion based on digital photographs taken before the treatment and 2 months after the end of the treatment. RESULTS Significant (475%, o100%) and moderate (450%, o75%) improvement was seen in six and two patients, respectively. Complete improvement was achieved in one patient. Transient swelling, purpura, bleeding, and some pain in the treated area were noted in all patients as short-term side effects. There were no permanent side effects. CONCLUSION The long-pulse Nd:YAG laser is a highly effective and safe treatment for angiokeratoma of Fordyce. The authors have indicated no significant interest with commercial supporters. Angiokeratomas are typically asymptomatic, 2- to 5-mm, dark red to-black papules with a scaly surface located on the tongue, scrotum, shaft of penis, labia majora, inner thigh, lower limbs, or abdomen. The precise incidence of angiokeratomas of Fordyce is unknown, but they are considered more common in men than in women of all ages. The pathophysiology of angiokeratomas remains unknown, although it has been proposed that an increase in venous pressure may contribute to their formation. Angiokeratomas are characterized by ecstatic capillaries and acanthotic and hyperkeratotic epidermis. Many therapeutic methods, including laser, electrocoagulation, excision, and cryotherapy, may be used in the treatment of angiokeratomas. 1 3 Various laser systems have been used for the treatment of angiokeratomas, 4 6 but some of them have side effects, including scarring, and are not in popular use. The aim of the present study was to assess the efficacy and complication of long-pulse neodymium-doped yttrium aluminium garnet (Nd:YAG) laser in the treatment of angiokeratomas of Fordyce. Materials and Methods Ten patients with angiokeratomas of Fordyce were recruited for the study between October 2005 and April The diagnosis was based on clinical findings. In one woman, the diagnosis was confirmed by histologic examination. Exclusion criteria were history of bleeding disorders or coagulopathy. In addition, patients with hypertrophic scar formation due to any traumatic process were not included in the study. The institutional ethics committee approved the treatment process. All patients were given a detailed description of the Department of Dermatology, Meram Medical Faculty, Selçuk University, Konya, Turkey; y Department of Gynecology and Obstetrics, Meram Medical Faculty, Selçuk University, Konya, Turkey & 2008 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: Dermatol Surg 2009;35:92 97 DOI: /j x 92

Ö ZDEMIR ET AL purpose and possible outcomes of treatment. Informed consent was obtained to participate in the study and to allow clinical photographs before and after the treatment.

2 Ö ZDEMIR ET AL purpose and possible outcomes of treatment. Informed consent was obtained to participate in the study and to allow clinical photographs before and after the treatment. There were eight male and two female patients, mean age 7 SD was (range 24 61). The lesions were located on the scrotum in five patients, glans penis in one, labia majora in two, penile shaft in one, and scrotum and penile shaft in one. Duration of the disease was years (range 1 33 years). Lesions ranged from 1 to 8 mm in diameter and varied in color from dark reddish purple to blue and in number from a few to several dozen (Figures 1A, 2A). The lesions had grown in size and number with time in all patients. Seven patients had been previously treated with cryotherapy, electrocauterization, or both. One patient (Patient 1) had previously been treated with pulsed dye laser for three sessions 3 years before, and there was moderate effect. Because of a social problem, he did not continue this laser treatment. One patient had Fitzpatrick skin type II, eight had type III, and one had type IV. The patients were treated with a long-pulse Nd:YAG laser (Lynton Lasers Ltd., Cheshire, United Kingdom). Because the diameter of the angiokeratoma papules are generally 2 to 5 mm, a 5 mm spot size was used. The laser spacer detected end point reactions such as transient grayness or blanching of the angiokeratoma papules or an audible popping sound before the study in the first patient with numerous lesions. Low-level (63 J/cm 2 ) energy fluence was used at the beginning. If the end point reactions were not observed, the fluence was increased 10 J/cm 2 on a neighboring area. In addition, the number of pulses and the delay (ms) between pulses were prepared in order to provide the end point reaction. This reaction was seen at a fluence of 92, pulse sequencing of 3, and a delay time of 15 ms in this patient. Finally, the whole lesion of the patient was treated at this fluence, pulse sequencing, and delay time. This setting was used in all sessions with all patients. A colorless gel approximately 1 to 2 mm thick was applied to the treatment area before each shot to protect the epidermis from thermal injury and to aid in delivering the light uniformly to the treated area. Figure 1. (A) Multiple large lesions of angiokeratomas of Fordyce situated in a diffuse pattern on the scrotum before treatment. (B) Significant separation in a diffuse pattern of the lesions after two sessions. (C) Significant improvement after four sessions. 35:1:JANUARY

Nd:YAG IN ANGIOKERATOMA OF FORDYCE Figure 2. (A) Penile angiokeratomas of Fordyce before the treatment. (B) Significant improvement after one session. (C) Significant improvement after one session.

3 Nd:YAG IN ANGIOKERATOMA OF FORDYCE Figure 2. (A) Penile angiokeratomas of Fordyce before the treatment. (B) Significant improvement after one session. (C) Significant improvement after one session. The laser spacer (5 mm) was placed in contact and kept parallel to the skin. The treated areas were cooled using ice packs before and after the treatment. Because the laser treatment was generally well tolerated, topical anesthetics were not used during the laser application in all patients. After the treatment, topical dexpanthenol combined with chlorhexidin (Bepanthene Plus Cream, Roche, Istanbul, Turkey) was applied to the treated areas to help protect the skin after sessions and to prevent microbial contamination. The treatment interval was 8 weeks. The treatments were continued until acceptable improvement was achieved. Patients were warned to avoid scratching or picking scabs or blisters after the treatment. To evaluate treatment outcome, photographs were taken using a digital camera (Sony Sybershot Digital still camera DSC P71, 3.2-megapixel resolution, Tokyo, Japan) before treatment and at the 2-month follow-up visit. The three authors (MÖ, BE, IB) independently evaluated the photographs using a grade system in which treatment response was categorized into six grades: Grade 1, no change after laser treatment; Grade 2, mild improvement (1 25% clearing); Grade 3, some improvement (26 50% clearing); Grade 4, moderate improvement (51 75% clearing); Grade 5, significant improvement (76 99% clearing); and Grade 6, complete improvement (100% clearing). Short- and long-term side effects and complications of the treatment were noted. The same clinician (MÖ) applied the laser to the lesion. Numerical parameters were expressed as means 7 standard deviations. Results Patient demographic data are shown in Table 1. The number of Nd:YAG treatment sessions was (range 2 6). Results of the treatment are shown in Table 2. Nine patients completed the study. One patient left the study after three sessions because of social problems. Three sessions were performed on this patient and moderate improvement was achieved. At the overall clinical assessment 2 months after the last treatment, significant and moderate 94 DERMATOLOGIC SURGERY

4 Ö ZDEMIR ET AL TABLE 1. Demographic Data Patient Number Age Sex Fitzpatrick Skin Type Duration of Disease, Years Location of Angiokeratomas 1 53 M III 33 Scrotum 2 44 F III 10 Labia majora 3 61 M III 21 Glans penis 4 35 M III 10 Scrotum 5 24 M II 3 Scrotum 6 37 M III 1 Scrotum 7 42 M IV 7 Scrotum 8 51 F III 15 Labia majora 9 43 M III 13 Scrotum and penile shaft M III 27 Penile shaft improvement were seen in six and two patients, respectively. One patient achieved complete improvement. There was no worsening of lesions in any patients (Figures 1B, C, 2B, C). In the first session, transient swelling, purpura, bleeding, and mild pain on the treated area were noted in all patients as short-term side effects (lasting 7 10 days without any permanent changes). After the following sessions, similar short-term side effects were noted, although a small atrophic scar (2 mm) developed on a treated papule located on the penile shaft of one patient, which was considered to be caused by insufficient or unsuitable wound care by the patient after the laser application. These small atrophic scars did not lead to any problems with penile erection or sexual dysfunction. The follow-up period was months (range months). Two patients who had scrotal angiokeratomas reported a few new lesions at the end of this period. Discussion Our results show the efficacy of the long-pulse 1,064 Nd:YAG laser for the treatment of angiokeratoma of Fordyce. Further developments of long-pulse Nd:YAG systems has allowed the delivery of a macropulse consisting of a series of synchronized minipulses, the macropulse being varied depending on the size and depth of vascular structures. The laser emits a wavelength of 1,064 nm, which penetrates into large vascular structures and causes minimal damage to the surrounding skin. Long-pulse TABLE 2. Results of Treatment Patient Number Number of Treatments Improvement, % Clinician (MO ) Reviewer 1 (BE) Reviewer 2 (IB) Overall Improvement, % Long-term Side Effects None None None None None None None None Atrophic scar (all reviewers) None 35:1:JANUARY

5 Nd:YAG IN ANGIOKERATOMA OF FORDYCE Nd:YAG laser has offered better results in leg veins up to 4 mm in diameter. In addition, it has been used for hair removal and the treatment of various vascular abnormalities, including reticular leg veins, port-wine stain, and venous lakes. 7,8 The papules of angiokeratoma of Fordyce are benign and asymptomatic, although they may bleed if traumatized, during intercourse, or from scratching. They do not usually require treatment, but if treatment is needed, locally destructive methods, including laser, electrocoagulation, excision, and cryotherapy, may be used, 1,9 but these treatment modalities have various degrees of side effects. Electrocoagulation and cryotherapy may not be suitable for diffuse patterns. Excision is not practical if more than a few lesions exist. Application of liquid nitrogen may lead to residual hypopigmentation and scarring. In addition, topical anesthetics are generally applied before these treatments. In the treatment of angiokeratomas, various laser systems have been reported to be of benefit in a number of clinical trials. Although the efficacy and safety of these systems have been shown, some of them are not popular and are not used today. 1 6 Successful improvement has been reported with several vascular lasers. In some studies, the hyperkeratotic epidermis was removed using ablative lasers such as carbon dioxide and erbiumdoped yttrium aluminium garnet lasers, whereas residual lesions were coagulated using the potassium-titanyl-phosphate (KTP) laser. 10,11 Successful resolution of angiokeratoma papules has been reported with single treatments using the 578-nm copper laser, 578-nm argon laser, 532-nm KTP laser, and frequency-doubled Nd:YAG laser, resulting in minimal scarring. 5,10,12 The pulsed-dye lasers have been used widely in the treatment of vascular abnormalities, 13 although they have limited depth of penetration and do not usually completely remove the lesion. In a recent study, the pulsed-dye laser has been described as a nonablative and successful approach to the treatment of angiokeratoma, with minimum side effects. 14 However, partial response has been achieved in some patients with this laser because multiple large lesions of angiokeratomas situated in a diffuse pattern on the scrotum have not been treated completely. To the best our knowledge, the use of the long-pulse Nd:YAG laser has not been reported in the treatment of angiokeratoma of Fordyce. We achieved significant improvement in this patient population with this laser. Complete improvement or a decrease in the lesion diameter was achieved in solitary lesions of angiokeratomas after one session. The residual small lesions were improved after an additional session in some patients. Significant separation in a diffuse pattern of the lesions was achieved after two to three sessions. The separated residual lesions of angiokeratomas were improved after one or two sessions, as in solitary lesions. Moderate improvement was observed in two patients who had angiokeratoma located in a diffuse pattern on the scrotum; the major complaint was bleeding, and some treatment modalities, including electrocoagulation, cryotherapy, and pulsed-dye laser were used 1 to 6 years ago. Significant separation and cessation of bleeding were achieved in these diffuse lesions after three sessions. The two patients accepted this as a good result, and they did not want to continue the treatment. Because skin penetration depths of long-pulse Nd:YAG laser are high, it may improve the vascular malformation of angiokeratomas accompanied by hyperkeratosis and multiple large lesions of angiokeratomas situated in a diffuse pattern. In treatment of these lesions, the Nd:YAG laser may provide an advantage over the pulsed-dye laser. In the literature, only one case of acral variant of angiokeratoma of Mibelli treated with long-pulse Nd:YAG laser treatment has been reported. 15 Functional and cosmetic improvement was achieved in this patient, but because the patient s treatment has not been completed, whole treatment outcomes have not been reported. In summary, our results indicate that the long-pulse Nd:YAG laser is a highly effective treatment modality for angiokeratoma of 96 DERMATOLOGIC SURGERY

6 Ö ZDEMIR ET AL Fordyce. In general, a single session is enough for complete improvement in solitary lesions. Acceptable improvement may be achieved after two to six sessions depending on the dissemination of the lesions. It would be better to extend the follow-up period after the completion of treatment to determine whether the post-laser treatment outcomes are long lasting. We propose that long-pulse Nd:YAG laser is an effective and safe therapeutic option in the treatment of angiokeratoma of Fordyce. References 1. Schiller P, Itin P. Angiokeratomas: an update. Dermatology 1996;193: Carrasco L, Izquierdo MJ, Farina MC, et al. Strawberry glans penis: a rare manifestation of angiokeratomas involving the glans penis. Br J Dermatol 2000;142: Gioglio L, Porta C, Moroni M, et al. Scrotal angiokeratoma (Fordyce): histopathological and ultrastructural findings. Histol Histopathol 1992;7: Bechara FG, Jansen T, Wilmert M, et al. Angiokeratoma Fordyce of the glans penis: combined treatment with erbium: YAG and 532 nm KTP (frequency doubled neodymium: YAG) laser. J Dermatol 2004;31: Lapins J, Emtestam L, Marcusson JA. Angiokeratomas in Fabry s disease and Fordyce s disease: successful treatment with copper vapour laser. Acta Dermatol Venereol 1993;73: Occella C, Bleidl D, Rampini P, et al. Argon laser treatment of cutaneous multiple angiokeratomas. Dermatol Surg 1995;21: Sadick NS. Long-term results with a multiple synchronized-pulse 1,064 nm Nd:YAG laser for the treatment of leg venulectasias and reticular veins. Dermatol Surg 2001;27: Landthaler M, Hohenleutner U. Laser therapy of vascular lesions. Photodermatol Photoimmunol Photomed 2006;22: Agger P, Osmundsen PE. Angiokeratoma of the scrotum (Fordyce). A case report on response to surgical treatment of varicocele. Acta Dermatol Venereol 1970;50: Bechara FG, Jansen T, Wilmert M, et al. Angiokeratoma Fordyce of the glans penis: combined treatment with erbium: YAG and 532 nm KTP (frequency doubled neodymium: YAG) laser. J Dermatol 2004;31: Yang CH, Ohara K. successful surgical treatment of verrucous hemangioma: a combined approach. Dermatol Surg 2002;28: Hobbs ER, Ratz JL. Argon laser treatment of angiokeratomas. J Dermatol Surg Oncol 1987;13: Garden JM, Bakus AD. Clinical efficacy of pulsed dye laser in the treatment of vascular lesions. J Dermatol Surg Oncol 1993;19: Lapidoth M, Ad-El D, David M, Azaria R. Treatment of angiokeratoma of Fordyce with pulsed dye laser. Dermatol Surg 2006;32: Sommer S, Merchant WJ, Sheehan-Dare R. Severe predominantly acral variant of angiokeratoma of Mibelli: response to long-pulse Nd:YAG (1064 nm) laser treatment. J Am Acad Dermatol 2001;45: Address correspondence and reprint requests to: Mustafa Özdemir, MD, Selçuk Üniversitesi, Meram Tp Fakültesi, Dermatoloji Anabilim Dal, Meram, Konya, Turkey, or mustafaozdemir@yahoo.com 35:1:JANUARY

Treatment of Leg Telangiectasia (Spider Veins) with Magma Long Pulse ND - Laser 1064 nm Case Study

Clinical Study Treatment of Leg Telangiectasia (Spider Veins) with Magma Long Pulse ND - Laser 1064 nm Case Study Sharona Levi-Friedman CRA, E. Krieger MD, Formatk Systems Ltd. Tirat- Carmel, Israel. 1.