Bleomycin Tattooing as a Promising Therapeutic Modality in Large Keloids and Hypertrophic Scars

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1 Bleomycin Tattooing as a Promising Therapeutic Modality in Large Keloids and Hypertrophic Scars FARAHNAZ FATEMI NAEINI, MD, JAMSHID NAJAFIAN, MD, AND KOOROSH AHMADPOUR, MD BACKGROUND Cryotherapy combined with intralesional triamcinolon injection is the most common traditional therapy for hypertrophic scars and keloids. The literature contains few articles on the use of bleomycin tattoo for treatment of these conditions. OBJECTIVE This study compares the efficacy of bleomycin tattoo with that of cryotherapy combined with intralesional triamcinolon injection for the treatment of keloids and hypertrophic scars. MATERIALS AND METHODS Forty-five patients with hypertrophic scars or keloids were randomly divided into two groups. Group A was treated with bleomycin tattoo, and group B, with cryotherapy combined with intralesional triamcinolon injection. There were four therapeutic sessions at 1-month intervals. All patients were followed for 3 months after the end of treatment. RESULTS Therapeutic response in lesions less than 100 mm 2 was higher than 88% in both groups, but in larger lesions, the therapeutic response to bleomycin was significantly better than cryotherapy combined with intralesional triamcinolon injection (p=.03). In group A, no relationship was observed between therapeutic response and lesion size (p=.58); however, in group B smaller lesions (o100 mm 2 ) displayed better therapeutic response (p=.007). CONCLUSIONS Bleomycin tattoo may be more effective than cryotherapy combined with intralesional triamcinolon injection in treatment of larger keloids and hypertrophic scars (size4100 mm 2 ). Farahnaz Fatemi Naeini, MD, Jamshid Najafian, MD, and Koorosh Ahmadpour, MD, have indicated no significant interest with commercial supporters. Keloids and hypertrophic scars develop as a result of dermal tissue proliferation after skin injury. Previous reviews have suggested that making a clinical distinction between hypertrophic and keloidal scars may be difficult, because features of both may be present in the same lesion. Hence, some researchers have suggested that the two be considered together, owing to their remarkable similarity. 1 These proliferative scars are characterized by increased collagen and glycosaminoglycan content, as well as increased collagen turnover. 2 Hypertrophic scars are distributed in all races but keloids are more common in races with pigmented skin. 3 The mechanism underlying such lesions has yet to be fully understood; nonetheless, it is thought to involve local histologic factors in connection with a hereditary component in most cases. The common cause of these lesions is burning, surgery, and vaccination. These lesions are more prevalent between the ages of 10 and 30 years. 4 In pregnancy and adulthood, the keloid may All authors are affiliated with the Department of Dermatology, Isfahan University of Medical Sciences, Isfahan, Iran & 2006 by the American Society for Dermatologic Surgery, Inc. Published by Blackwell Publishing ISSN: Dermatol Surg 2006;32: DOI: /j x 1023

2 BLEOMYCIN TATTOOING THERAPY FOR KELOIDS AND HYPERTROPHIC SCARS grow to a larger size. These lesions contain neuropeptide and nerve endings; therefore, they may cause symptoms like pain and itching. 5 Early reports on keloids date back to 1700 B.C. A well-established treatment for the lesion, however, is nonexistent. The therapeutic management of hypertrophic scars and keloids includes occlusive dressings, 6 compression therapy, 7 intralesional corticosteroid injections, 6 cryotherapy, 6 intralesional 5-fluorouracil, 8,9 excision, 10 radiation therapy, 10 laser therapy, 11,12 interferon therapy, 13 and other promising, lesser known therapies directed at collagen synthesis. 14,15 Bleomycin tattooing has been used in only a few studies for the treatment of hypertrophic scars and keloids. 16,17 In this study, the therapeutic efficacy of bleomycin tattoo was compared with that of cryotherapy combined with triamcinolon injection, as judged by changes in lesions size. Materials and Methods This prospective clinical trial included 45 patients diagnosed with hypertrophic scars or keloids. All patients gave their verbal consent before the start of treatment. The study protocol conformed to the guidelines of the 1975 Declaration of Helsinki and was approved by our institutional review board. To avoid possible drug complications, pregnant women and children aged less than 15 years were excluded from the study. Patients were divided in to two groups. Group A (17 female and 6 male patients) was treated with bleomycin tattoo and group B (14 female and 8 male patients) was treated with cryotherapy combined with intralesional triamcinolon injection. In group A, the lesions were first anesthetized with 2% intralesional lidocaine. The bleomycin was dripped onto the lesion. Multiple punctures were then made on the lesions by means of a syringe and a 25-gauge needle (40 punctures/ 5mm 2 ), similar to the procedure used by Espana and colleagues, 17 to ensure that only a very small quantity of bleomycin penetrated the lesion. In each case, the maximum applied dose was 2 ml/cm 2 of skin, at a concentration of 1.5 IU/mL, and a maximum of 10 IU of bleomycin was given per session. In group B, the authors used one freezing cycle lasting 30 seconds (liquid nitrogen applied by cotton wool swabs) and injected triamcinolone acetonide (40 mg/ml) into the lesion (usually ml but no more than 80 mg in one session). In the beginning of study, each patient was assessed with regard to four clinical aspects: lesion size (mm 2 ), symptoms (including pain and/or tenderness and/or pruritus), and color and thickness of lesion (maximum thickness of the lesions in millimeters, measured by the same researcher on each visit). In the following visits, the patients were assessed for flattening of the lesion, symptoms (i.e., presence or absence of symptoms; only patients with no symptoms at all were regarded as symptom-free), and color changes. At the end of the study, therapeutic response was defined as reduction in lesion thickness relative to its initial thickness. The following scale was used: complete flattening = 100%; highly significant flattening = 80%; significant flattening = 60% to 80%; and favorable flattening = 50%. Recurrence was defined as increasing in thickness and/or recurrence of any symptoms. After data collection, statistical analysis was performed using descriptive statistics, the t test, the Spearman correlation test, and the chi-square test. Results This study included 45 patients, 66% of whom were aged between 15 and 30 years, and 34% were aged more than 30 years. In group A, 22 patients (95.6%) had skin type III and 1 patient (4.4%) had skin type IV. Group B comprised 18 patients (82%) with skin type III and 4 patients (18%) with skin type II or IV. In group A, 17 patients (73.9%) had keloids and 6 patients (26.1%) had hypertrophic scars. In group B, 15 patients (68.2%) had keloids and 7 patients (31.8%) had hypertrophic scars. The mean age of patients was 28 years in group A and DERMATOLOGIC SURGERY

3 NAEINI ET AL years in group B. Thirty patients had only one lesion and 15 had multiple lesions. In group A, lesions were seen on the shoulder and back in 8 patients, in the presternal region in 5 patients, at the site of cesarean section in 3 patients, and at various sites in 7 patients. In group B, lesions were seen in the presternal region in 6 patients, on the back in 6 patients, at the site of cesarean section in 2 patients, and at various other sites in 8 patients. In group A, the lesions had existed for 6 months to 8 years; were secondary to surgery (5 patients), acne (5 patients), burns (3 patients), and vaccination (2 patients); and were spontaneous (2 patients) or due to other causes (6 patients). In group B, lesions had existed for 6 months to 6 years; were secondary to surgery (8 patients), acne (4 patients), accidental cuts (2 patients), and burns (2 patients); and were spontaneous (2 patients) or due to other causes (4 patients). Tables 1 and 2 summarize the demographic and clinical information pertaining to patients/lesions in both groups. Table 3 shows lesion sizes. Symptoms, including pruritus, pain, and/or tenderness, were seen in 91% of the patients in group A and 77% of those in group B. Table 4 shows therapeutic responses, complications, and disappearance of symptoms in both groups. The relative mean resolution scores in groups A and B were and %, respectively. A t test showed a better therapeutic response in the group treated with bleomycin than in the other group (p=.001). This difference in therapeutic response was significant for patients aged less than 30 years TABLE 1. Patient Characteristics in Group A Patient Number Sex Age (years) Skin Type Localization Time of Course Type of Scar Trigger Factor Lesion Size (mm 2 ) 1 Male 15 III Presternal 6 months Keloid Acne Female 17 III Ear lobe 1 year Keloid Ear piercing Female 20 III Forearm 3 years Keloid Cut Female 15 III Back 1 year Hypertrophic scar Acne Female 19 III C-section area 1 year Keloid Surgery Female 21 III Arm 1 year Hypertrophic scar Vaccination Female 36 III Presternal 8 years Keloid Spontaneous Male 24 III Presternal 3 years Keloid Acne Male 26 III Back 1 year Hypertrophic scar Cut Female 16 III Back 5 years Keloid Burn Female 46 III Presternal 2 years Hypertrophic scar Surgery Female 21 III Back 8 months Keloid Acne Female 20 III Abdomen 6 years Keloid Burn Male 21 III Neck 7 years Hypertrophic scar Burn Male 22 III Shoulder 9 months Keloid Accident Female 25 III Shoulder 2 years Keloid Acne Female 70 III Leg 2 years Keloid Surgery Female 27 III C-section area 6 years Keloid Surgery Female 31 III Presternal 11 months Hypertrophic scar Spontaneous Female 29 IV Shoulder 3 years Keloid Vaccination Female 31 III C-section area 5 years Keloid Surgery Female 55 III Shoulder 1 year Keloid Accident Male 22 III Leg 1 year Keloid Accident 30 C-section, cesarean section. 32:8:AUGUST

4 BLEOMYCIN TATTOOING THERAPY FOR KELOIDS AND HYPERTROPHIC SCARS TABLE 2. Patient Characteristics in Group B Patient Number Sex Age (years) Skin Type Localization Time of Course Time of Scar Trigger Factor Lesion Size (mm 2 ) 1 Male 13 III Forearm 1 year Keloid Cut Male 19 III Presternal 6 months Hypertrophic scar Surgery Female 21 III C-section area 2 years Hypertrophic scar Surgery Female 17 III Back 1 year Hypertrophic scar Acne Male 17 III Back 2 years Keloid Acne 72 6 Male 24 III Thigh 1 year Keloid Surgery Female 18 II Ear lobe 1 year Hypertrophic scar Ear piercing 25 8 Female 36 III Presternal 2 years Keloid Surgery 80 9 Female 32 III Presternal 1 year Hypertrophic scar Spontaneous Female 15 IV Abdomen 4 years Keloid Burn Female 31 III Back 2 years Keloid Acne Female 20 II Abdomen 3 years Hypertrophic scar Surgery Male 24 III Back 5 years Keloid Burn Female 34 III Shoulder 6 months Hypertrophic scar Cut Male 22 III Presternal 1 year Keloid Acne Female 55 III Back 1 year Keloid Accident Female 33 III C-section area 4 years Keloid Surgery Female 35 II Arm 6 years Keloid Vaccination Female 33 III Presternal 2 years Keloid Surgery Female 35 III Thigh 3 years Keloid Surgery Male 25 III Presternal 1 year Keloid Spontaneous Male 20 III Back 1 year Keloid Accident 300 C-section, cesarean section. TABLE 3. Frequency of Lesion Sizes in Both Groups Lesion Size (mm2) Group o100 7 (30.4) 6 (27) (43.6) 13 (59) (26) 3 (14) Data are reported as number (%). TABLE 4. Therapeutic Responses, Complications, and Disappearance of Symptoms in Both Groups (%) Measure A Group Therapeutic response Hyperpigmentation 75 0 Hypopigmentation 0 18 Telangiectasia 0 20 Disappearance of symptoms A B B (p o.001), but not significant for patients more than 30 years (p=.16). In both groups, the therapeutic response was not dependent on duration of disease, location, or number of lesions. In the bleomycin group, the size of lesion did not affect the rate of resolution (p=.58). In the other group, however, lesions less than 100 mm 2 showed a significantly better response than larger lesions (p=.007). Therapeutic response in lesions less than 100 mm 2 exceeded 88% in both groups, but in larger lesions, the therapeutic response to 1026 DERMATOLOGIC SURGERY

5 NAEINI ET AL bleomycin was significantly better than cryotherapy combined with triamcinolon injection (p=.03). The common complication of bleomycin tattoo was hyperpigmentation, which was observed in 75% of patients. This complication was not observed in group B. The most common complications in group B were telangiectasia (20%) and hypopigmentation (18%), which were not seen in group A. After treatment, symptoms had disappeared in 69% of patients in group A and 49% of those in group B. All patients were followed for 3 months, with no recurrence in either group. Discussion Espana and colleagues 17 reported 53.8% complete response and 38.4% excellent response (more than 90% resolution) after one to five sessions of treatment of keloids and hypertrophic scars with bleomycin tattoo. Sample size in the study by Espana and colleagues was smaller than in our study. Bodokh and Brun 16 treated 31 keloids and 5 hypertrophic scars with three to five intralesional infiltrations of bleomycin. They obtained a total regression of 84%. In the current study, relative mean resolution score in the bleomycin group was % (complete response in 47% of patients, therapeutic response higher than 80% in 30%, and 60% 80% in 18% of the patients). The difference between the results obtained in these studies may be accounted for by the difference of methods, sample sizes, and lesion types. In the study by Bodokh and Brun, bleomycin was used intralesionally, so the amount of drug penetrating the lesion was probably greater than in our method. The difference in results may also be partly due to inaccuracy of clinical differentiation between keloids and hypertrophic scars (hypertrophic scars are obviously more responsive to different treatment modalities). The relative mean resolution score in group B (treated with cryotherapy combined with triamcinolon injection) was , correlating well with the results of other studies. 6 Thus far, this study is the only attempt at comparing the therapeutic efficacy of cryotherapy combined with triamcinolon injection with bleomycin tattooing based on the size of lesions. In this study, the response of small lesions to both treatment regimens was favorable. Therapeutic response to cryotherapy and intralesional steroid injections, however, decreased with increase in lesion size, whereas response to bleomycintattooremainedunchanged. This finding confirms the recommendation by some authors to use intralesional steroid injection only for minor, small-sized keloids. Twenty-two percent of our patients remained symptomatic after four sessions of treatment with bleomycin. This is in contrast with the study by Espana and coworkers, reporting that all of the patients became symptom-free after treatment. The most common complication in the bleomycin group was hyperpigmentation (observed in 75% of patients), which was higher than in other reports. This may be due to our patients skin type (in the Middle East, skin types III IV are more prevalent). Unlike complications such as telangiectasia and atrophy in group B, which may be permanent, however, hyperpigmentation is temporary. Bleomycin is a polypeptide antibiotic with antitumor, antibacterial, and antiviral activity. It has no immunosuppressive action, and its toxicity is confined to the skin and the lungs 18 It is effective against squamous cell carcinoma and induces remission in mycosis fungoid and other lymphomas. It has been used intralesionally for treatment of intractable warts. Small volumes of drug used to this end do not cause systemic toxicity. 19 Implantation of bleomycin from a surface application using a bifurcated needle or a sterile lancet may be better tolerated. 20 According to results of this study and those of the study by Espana and colleagues, bleomycin tattooing is safe, and only a very small quantity of bleomycin penetrates the lesions. Recent studies have shown that intralesional bleomycin 32:8:AUGUST

6 BLEOMYCIN TATTOOING THERAPY FOR KELOIDS AND HYPERTROPHIC SCARS injections bring about significant improvement in keloids and hypertrophic scars. 16,17 Many studies have examined the pathophysiology of keloidal scars from the cellular level, but the exact underlying mechanisms are yet to be fully understood. Researches have shown that hypertrophic scar fibroblasts have a moderate increase in their basal level of collagen production, but they still respond normally to growth factors. 21 In contrast, fibroblasts from keloidal scars produce high levels of collagen, 22 elastin, 23 fibronectin, 24,25 and proteoglycan 26 and show abnormal responses to stimulation. 27 Collagen type I is predominantly produced by keloidal fibroblasts, 28 and these cells have been shown to have a greater capacity to proliferate. 29 Transforming growth factor b (TGF-b) types 1 and 2, which stimulates fibroblasts to proliferate and synthesize procollagen RNA, is increased in keloidal scars. 30,31 It has been shown that in wounds, formation of scar tissue increases the lysyl-oxidase derived from the amino acid lysine, thus fomenting the maturation of collagen. The concentration of lysyl-oxidase may be normal or raised in keloids and hypertrophic scars and increased in some conditions involving heightened collagen synthesis. 17 Recent studies have pointed to a highly significant reduction in lysyl-oxidase in cultures of human dermal fibroblasts as a result of the action of bleomycin. 17 If TGFb is added to the culture, bleomycin also inhibits the collagen synthesis resulting from this growth factor. 17 Hence, the effect of bleomycin in keloids and hypertrophic scars may be due to a reduction of collagen synthesis and/or increased destruction due to inhibition of lysyl-oxidase or TGFb-1, as suggested by Espana and colleagues. 17 In contrast, lower rates of apoptosis have been observed in keloidal fibroblasts, 32 and it has been suggested that keloidal fibroblasts resist physiologic cell death, continuing to proliferate and produce collagen. 33 Until now, no study has been performed to determine the effect of bleomycin on the rate of fibroblast apoptosis and physiologic cell death. Whereas intralesional bleomycin in the treatment of warts induces keratinocyte apoptosis, 34 the authors presume one of the mechanisms for the therapeutic effect of bleomycin in keloids and hypertrophic scars to be the effect of this drug on fibroblast apoptosis; this hypothesis has yet to be borne out by further in vitro and in vivo studies. Conclusion Given the findings of this study and a few others on the efficacy of bleomycin in treating keloids and hypertrophic scars, owing to the favorable therapeutic results obtained especially in larger lesions (even larger than 100 mm 2 ), and also in view of the negligible absorption of this drug into the circulation, the authors recommend bleomycin tattooing as an appropriate mode of treatment for larger lesions in covered areas. References 1. Sherris DA, Larabee WF, Murakami CS. Management of contractures, hypertrophic scars and keloidal scars. Otolaryngol Clin North Am 1995;28: Brissett AE, Sherris DA. Scar contractures, hypertrophic scars, and keloids. Facial Plast Surg 2001;17: Shaffer JJ, Tayler SC, Cook BF. Keloid scars: a review with a critical look at therapeutic options. J Am Acad Dermatol 2002;46: Berman B, Beieley H. Keloids. J Am Acad Dermatol 1995;33: Burton JL, Lovel CR. Disorders of connective tissue. In: Champion RH, Burton JL, Burns DA, Breathnach SM, editors. Rooks textbook of dermatology, 6th ed. Boston: Blackwell Science, 1998:p Lahiri A, Tsiliboti D, Gaze NR. Experience with difficult keloids. Br J Plast Surg 2001;54: Gailloud-Matthieu MC, Raffoul W, Egloff DV. Hypertrophic scars and keloids: which therapeutic options today. Rev Med Suisse Romande 1999;119: Gupta S, Kalra A. Efficacy and safety of intralesional 5-fluorouracil in the treatment of keloids. Dermatology 2002;204: Nanda S, Reddy BS. Intralesional 5-fluorouracil as a treatment modality of keloids. Dermatol Surg 2004;30:54 6; discussion Ragoowansi R, Cornes PG, Moss AL, Glees JP. Treatment of keloids by surgical excision and immediate postoperative single-fraction radiotherapy. Plast Reconstr Surg 2003;111: Connell PG, Harland CC. Treatment of keloid scars with pulsed dye laser and 1028 DERMATOLOGIC SURGERY

7 NAEINI ET AL intralesional steroid. J Cutan Laser Ther 2000;2: Kumar K, Kapoor BS, Rai P, Shukla HS. In-situ irradiation of keloid scars with Nd: YAG laser. J Wound Care 2000;9: Berman B, Flores F. Recurrence rates of excised keloids treated with postoperative triamcinolone acetonide injections or interferon alfa-2b injections. J Am Acad Dermatol 1997;37:(5 Pt 1): Copcu E, Sivrioglu N, Oztan Y. Combination of surgery and intralesional verapamil injection in the treatment of the keloid. J Burn Care Rehabil 2004;25: Alster TS, Tanzi EL. Hypertrophic scars and keloids: etiology and management. Am J Clin Dermatol 2003;4: Bodokh Y, Brun P. Treatment of keloid with intralesional bleomycin [in French]. Ann Dermatol Venereol 1996;123: Espana A, Solano T, Quintanilla E. Bleomycin in the treatment of keloids and hypertrophic scars by multiple needle punctures. Dermatol Surg 2001;27: Breathnach SM, Griffiths GE, Chalmers RJ, et al. Systemic therapy. In: Burns T, Breathnach S, Cox N, Griffiths C,, editors. Rooks textbook of dermatology, 7th ed. Boston: Blackwell Science, 2004:p Berth-Jones J. Topical therapy. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rooks textbook of dermatology, 7th ed. Boston: Blackwell Science, 2004:p Sterling JC. Virus infection. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rooks textbook of dermatology, 7th ed. Boston: Blackwell Science, 2004:p Younai S, Nichter LS, Wellisz T, et al. Modulation of collagen synthesis by transforming growth factor beta in keloid and hypertrophic scar fibroblasts. Ann Plast Surg 1994;33: Abergel RP, Pizzurro D, Meeker CA, et al. Biochemical composition of the connective tissue in keloids and analysis of collagen metabolism in keloid fibroblast cultures. J Invest Dermatol 1985;84: Russell SR, Trupin JS, Kennedy RZ, et al. Glucocorticoid regulation of elastin synthesis in human fibroblasts: down regulation in fibroblasts from normal dermis but not from keloids. J Invest Dermatol 1995;105: Babu M, Diegelmann R, Oliver N. Fibronectin is overproduced by keloid fibroblasts during abnormal wound healing. Mol Cell Biol 1989;9: Kischer CW, Hendrix MJ. Fibronectin (FN) in hypertrophic scars and keloids. Cell Tissue Res 1983;231: McCoy BJ, Cohen IK. Effects of various sera on growth kinetics and collagen synthesis by keloid and normal dermal fibroblasts. Plast Reconstr Surg 1981;67: Bettinger DA, Yager DR, Diegelmann RF, Cohen IK. The effect of TGF-beta on keloid fibroblast proliferation and collagen synthesis. Plast Reconstr Surg 1996;98: Uitto J, Perejda AJ, Abergel RP, et al. Altered steady state ratio of type I/III procollagen mrnas correlates with selectively increased type I procollagen biosynthesis in cultured keloid fibroblasts. Proc Natl Acad Sci USA 1985;82: Calderon M, Lawrence WT, Banes AJ. Increased proliferation of keloid fibroblasts in vitro. J Surg Res 1996;61: Smith PD, Siegler K, Wanf X, Robson MC. Transforming growth factor beta 2 increased DNA synthesis and collagen production in keloid fibroblasts. Surg Forum 1998;49: Smith P, Mosiello G, Deluca L, et al. TGF-beta2 activates proliferative scar fibroblasts. J Surg Res 1999;82: Ladin DA, Hou Z, Patel D, et al. p53 and apoptosis alterations in keloids and keloid fibroblasts. Wound Repair Regen 1998;6: Sayah DN, Soo C, Shaw WW, et al. Downregulation of apoptosis-related genes in keloid tissues. J Surg Res 1999;87: Breathnach SM. Drug reactions. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rooks text book of dermatology, 7th ed.. Boston: Blackwell Science, 2004:p Address correspondence and reprint requests to: F. Fatemi, MD, Mailbox 905, Alzahra Hospital, Isfahan, Iran, or fatemi_farahnaz@ yahoo.com. COMMENTARY In spite of the large number of treatment options available for keloids, none is satisfactory due to either the side effects or the recurrence rate associated with these. Hence, the search for the perfect treatment for this cosmeticaly and at times functionally disabling disease continues. Bleomycin, with its limited and temporary side effects, could prove to be a valuable addition in the armamentarium of drugs that we have for this condition. Especially the tatoo technique ensures minimal systemic absorption and, hence, very few side effects and uniform delivery of the drug to the lesion. The commonest encountered problem with intradermal injection is pain, which usually subsides within 48 hours in most of the cases. The other 32:8:AUGUST

8 BLEOMYCIN TATTOOING THERAPY FOR KELOIDS AND HYPERTROPHIC SCARS problem, which is more so encountered in pigmented skin, is hyperpigmentation. I personally disagree with the authors that the duration of keloid does not affect the results. Definitely keloids of recent origin are more responsive to all forms of therapy. I believe that the treatment of keloids needs to be individualized, and a combination is needed in most cases. Judicious use of cryotherapy, intralesional steroids, fluorouracil, and bleomycin, in combination or rotation, can cure almost all lesions. This study gains importance in light of the fact that they have compared a well-established technique, that is, intralesional steroids and cryotherapy with bleomycin tatoo, which has the potential to become a very popular treatment choice for this condition in the future. SONI NANDA, MD New Delhi, India 1030 DERMATOLOGIC SURGERY

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