LASER TREATMENT OF IN DARK SKIN AND

Ph.D. dissertation

Department of Dermatology and Allergology Albert Szent-Györgyi Medical Center University of Szeged

2011

Szeged, Hungary

LASER TREATMENT OF SCARS IN DARK SKIN AND WARTS

Ph.D. dissertation

Ashraf Mohamed Abdel Magid Badawi M.B.B.Ch, M.Sc. (Dermatology and Andrology) Lecturer of Dermatology

Supervisor: Lajos Kemény M.D., Ph.D., D.Sc.

Department of Dermatology and Allergology Albert Szent-Györgyi Medical Center University of Szeged

2011

Szeged, Hungary

Table of Contents Page LIST OF PUBLICATIONS 3 List of articles related to the subject of the dissertation 3 List of articles indirectly related to the subject of the dissertation 3 1. LIST OF ABBREVIATIONS 4 2. INTRODUCTION 5 2.1. Background 5 2.1.1. Laser treatment of scars 5 2.1.2. Laser treatment of warts 6 2.2. Aims 8 3. PATIENTS AND METHODS 9 3.1. Treatments of scars 9 3.1.1. Scars treatment in dark skin 9 3.1.2. Post scars treatment 12 3.2. Treatment of warts 14 3.2.1. Treatments of genital warts 14 3.2.2. Treatments of plane warts 15 4. RESULTS 16 4.1. Treatments of scars 16 4.1.1. Treatment of scars in dark skin types 16 4.1.2. Treatment of chickenpox scars 21 4.2. Treatments of warts 24 4.2.1. Treatments of genital warts 24 4.2.2. Treatments of plane warts 27 5. DISCUSSION 29 5.1. Laser treatment of scars 29 5.2. Laser treatment of warts 31 6. SUMMARY AND NEW FINDINGS 36 7. ACKNOWLEDGEMENTS 38 8. REFERENCES 39

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LIST OF PUBLICATIONS

Publications related to the subject of the dissertation 1. Badawi A, Tome MA, MD, Ayse N Turley AN, Kemeny L: Successful treatment of post chickenpox scars with microdermabrasion and sub-millisecond Nd:YAG (1064 nm) laser. Cosmetic Dermatology 2. Badawi A, Tome MA, Atteya A, Sami N, Morsy IA: Retrospective analysis of non- ablative treatment in dark skin types using the sub-millisecond Nd:YAG 1,064nm laser. Lasers Surg Med. 2011;43:130-6. IF: 2,605 3. Badawi A, Shokeir HA, Salem AM, Soliman M, Fawzy S, Samy N, Salah M: Treatment of genital warts in males by pulsed dye laser. J Cosmet Laser Ther. 2006;8:92-5. 4. Samy N, Salah M, Soliman M, Badawi A: Plane warts can be managed successfully using long pulsed Nd-YAG laser. Kosmetische Medizin 2008;1:14-8.

Publications indirectly related to the subject of the dissertation

1. Badawi A, Soliman M, Sobhi R, Fawzy S, Shokeir H, Salem AM: Microdermabrasion in Cosmetic Dermatology: A Clinical Study. Cosmetic Dermatology. 2006;19:191-6. 2. Sami NA, Attia AT, Badawi A: Phototherapy in the treatment of vulgaris. J Drugs Dermatol. 2008;7:627-32. 3. Salem AM, Shokeir H, Badawi A, ElMorsy I: Effective Reduction of Fine and Coarse Hair in Patients with Skin Types III-V by Long-Pulsed Alexandrite Laser at 5- & 20- Millisecond Pulse Durations. Cosmetic Dermatology Vol. 2003;16:39-42.

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1. LIST OF ABBREVIATIONS

CO2: Carbon dioxide Er:YAG: Erbium:yttrium-aluminum-garnet Er:YSGG: Erbium:yttrium-scandium-galium-garnet PIH: Post inflammatory Hyperpigmentation Nd:YAG: Neodymium:yttrium-aluminum-garnet Hz: Hertz PDL: Pulsed Dye Laser MDA: Microdermabrasion STDs: Sexually transmitted diseases Msec: Millisecond n: Number of cases µs: Micro second J/cm2: Joul per centimeter square mm: Millimiter SPF: Sun Protective Factor

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2. INTRODUCTION

2.1. BACKGROUND

2.1.1. Laser treatment of scars

The use of lasers to treat atrophic scarring conditions in darker skin types presents a significant challenge to laser practitioners.

Treatment options are limited due to increased risks of pigmentary complications including hypo- and hyper-pigmentation. This is especially true when attempting to treat large areas with atrophic scarring.

Post chickenpox scars are usually more common in adults and its treatment represents a major challenge for cosmetic dermatologists.

Current methods of treating scarring include traditional fully ablative erbium and carbon dioxide (CO2) treatments as well as non-ablative and ablative fractional resurfacing with CO2, erbium:yttrium-aluminum-garnet (Er:YAG), and erbium:yttrium-scandium-galium-garnet

(Er:YSGG) lasers [1-8]. These options can be challenging for skin type IV patients and not feasible for patients with skin types V and VI without significant pre- and post-treatment skin conditioning and a hyper-pigmentation risk. With traditional fully ablative CO2 resurfacing, studies showed hyper-pigmentation rates of 20% to 30% in Fitzpatrick skin type III and nearly 100% in skin type IV if treatment is performed without pre-treatment prophylaxis [9-

11]. Further, 19% of traditional resurfacing patients experience some form of hypo- pigmentation. A recent study on the treatment of acne scarring with fractionated Er:YAG laser reported a Post inflammatory Hyperpigmentation (PIH) incidence of 50% in 15 subjects with skin types IV-VI [12].

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When the 1064 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser with the option of sub-millisecond pulse width is used with 300-500 micro second pulse durations, a 5 mm spot size and repetition rates of 5-10 Hz, it offers the ability to focus heat in the papillary and upper reticular dermis. The sub-millisecond 1064 nm Nd:YAG laser has been proven to stimulate new collagen synthesis [13]. It is therefore feasible that deliberate sub-millisecond

1064 nm Nd:YAG laser treatments could result in substantial reduction in scarring by stimulating collagen formation resulting in smoothing of the skin. [14-19]

2.1.2. Laser treatment of warts

Warts are benign epithelial neoplasm of the skin and mucosa resulting from human infection. They are a common dermatologic complaint, with an estimated incidence of

10% in children and young adults.

Verruca plana (flat warts) are less exophytic than common warts, frequently presenting as several or dozen of subtle papules 2-6 mm in diameter elevated above the surface less than a millimetre or so. These can be quite subtle, and may be missed by a casual observer.

Pigmentary disturbances may be the most disturbing part of the flat infection to the patient. These are frequently a problem on the face and the glabrous skin of non- immunocompromised individuals. At present, therapies aim to remove the rather than specifically target human papillomavirus infection [14-19].

The four morphologic types of genital warts are condylomata acuminata, which have a cauliflowerlike appearance; papular warts, which are fleshcolored, dome-shaped papules, usually 1–4 mm in diameter; keratotic warts, which have a thick, crust-like layer and may

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resemble common skin warts or seborrheic ; and flat-topped papules, which appear macular to slightly raised.

In general, condylomata are most frequently detected on moist, partially keratinized epithelium, papular and keratotic warts on fully keratinized epithelium, and flat papular warts on either partially or fully keratinized epithelium [20-22].

Treatment of warts can be difficult, with most approaches relying on physical destruction of infected keratinocytes.

Common therapeutic approaches include liquid nitrogen, , topically applied acids, electro surgery, application, bleomycin injection.

Genital wart therapies are classified as patient-applied or provider-administered.

Patient-applied treatments include podofilox solution and gel, and cream [23,24].

To self-treat, patients must be able to identify and reach the warts and to follow the treatment application instructions. The provider-administered treatments include topical treatments

(cryotherapy, podophyllin resin, trichloroacetic acid, bichloroacetic acid, and external application and intraurethral instillation of bacillus Calmette–Guerin); excisional treatments

(curettage, electrosurgery, scissors excision, , and laser therapy); or injectable treatments ( or 5-/epinephrine gel implant) [25–33].

Many types of lasers have been used for the management of warts. Carbon dioxyde laser vaporization for infected tissue was used [29].

Tuncel et al. [33] used the pulsed dye laser (PDL) for treatment of perianal warts in children.

They found the pulsed dye laser to be effective and less traumatic compared with other treatment options.

To date, there have been no trial evaluating the efficacy of long pulsed Nd-YAG laser in the treatment of common warts.

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2.2. Aims

The primary objective of our retrospective study was to determine the safety and efficacy of

the unique pulse modality of submillisecond to reduce the signs of atrophic scarring, texture

and PIH secondary to the acne condition in darker skin types. The secondary objective is to

assess the incidence of PIH resulting from the laser treatments.

As the post chickenpox scars are representing a clinical and therapeutic challange specially in

dark skin so we also wanted to evaluate the safety and efficacy of using Microdermabrasion

(MDA) and the sub-millisecond 1064 nm Nd:YAG laser in facial chickenpox scarring cases

in adult men with skin type IV and V.

Our further aim was to determine the safety and efficacy of the flashlamp pumped pulsed dye

laser for the treatment of uncomplicated genital warts in adult males and the safety and

efficacy of Nd:YAG laser in treatment of plane warts.

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3. PATIENTS AND METHODS

3.1. Treatments of scars 3.1.1. Scar treatment in dark skin

STUDY DESIGN AND METHODS:

This is a retrospective study evaluating the safety and efficacy of a sub-millisecond 1064 nm

Nd:YAG laser. Treatments were conducted at the National Institute of Laser Enhanced

Sciences, Dermatology Unit, at Cairo University, Egypt and at Saheroun Hospital, Khartoum,

Sudan on 22 patients with Fitzpatrick skin types III (n = 2), IV (n = 4), V (n = 14), VI (n = 2) who had atrophic scarring such as acne scarring. All patients who were treated over a six month period between February and July of 2008 were included in the study.

Treatments were performed using 300-500 µs pulse duration, 14-16 J/cm2 and 5-7 Hz repetition rate. The hand piece was held 1-2 cm off the surface of the skin (about the width of an index finger) during delivery. Treatments were performed without topical anesthesia. No prophylactic therapy was used before or after treatment to control PIH resulting from laser treatments. On average, each patient received 6 treatments (minimum 5, maximum 7). The average interval between treatments was 24.5 days with a range from 18.7 to 33.0 days.

Follow-up photographs were taken, on average, 9 months (range of 3 to 10 months) after the final treatment. Patient ages ranged from 18-47 years with a mean of 28.6 years. The average number of pulses per procedure was 11,700 pulses ranging from 8,000 to 13,900 pulses. The patient to patient variation in the number of pulses was associated with the size of the surface area treated, not with the treatment indication. Treatment parameters used on each patient are listed in Table 1.

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Table 1. Treatment Parameters and Follow-up Times # of Pulses # of Days Follow-up Post per # of Between Final Treatment Patient Age Treatment Treatments Treatments (months) 1 25 10,000 6 20.2 9 2 22 11,500 5 21 3 3 36 12,400 7 22.5 9 4 26 11,800 7 31 9 5 29 13,400 7 23 8 6 42 10,000 5 24.2 9 7 24 10,400 7 23.2 8 8 27 12,000 7 26.8 9 9 22 13,700 6 18.7 10 10 29 11,800 6 22 10 11 23 12,000 6 23.1 9 12 40 10,200 5 29 10 13 28 15,000 6 22.6 9 14 18 12,500 6 20.6 9 15 21 12,000 6 22.2 10 16 25 13,800 7 27.3 9 17 30 13,900 5 21.7 9 18 26 8,600 6 28.6 9 19 31 9,700 5 21 10 20 27 12,400 5 26.7 10 21 32 12,300 6 30.7 9 22 47 8,000 6 33 9 AVERAGE 28.64 11,700 6 24.5 9

To optimize laser results, the skin was treated with microdermabrasion (MDA) throughout the sub-millisecond 1064 nm Nd:YAG laser treatment series. Ten sessions of MDA were administered with an interval of 7 to 10 days between each session. A minimum of 3 days was allowed between MDA and laser treatments.

Following the MDA treatment, the whole face was treated with the sub-millisecond 1064 nm

Nd:YAG laser. No additional passes were applied on the areas of atrophic scarring. The hand piece was held 1-2 cm off the face with continuous motion to build heat and erythema in the treatment area prior to moving to an adjacent part of the face. The surface area for each

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treatment region was approximately 5 cm x 5 cm. The total and average number of pulses per treatment, and the total number of treatments per patient are also shown in Table 1.

Three independent physician reviewers (two dermatologists and one plastic surgeon) were asked to identify the before and after treatment photos which were presented to the physicians for assessment in random order. After selecting the before and after image, reviewers were asked to rank the degree of improvement in scarring, texture and PIH using a four-point scale

(0 = < 25%, 1 = 25-50%, 2 = 51-75%, 3 = 76-100%). Any indication which did not apply to a patient was marked as N/A. The median improvement score was calculated based on scores from all three reviewers. When the before photo was incorrectly selected as the after photo (1 case only), the negative value of the improvement score was used in calculating the median score taking into account the magnitude of deterioration as assessed by the reviewer. This was done instead of excluding this case to avoid any bias in the data analysis.

Patients were evaluated for erythema, edema, purpura, blistering, crusting, hypo- and hyper- pigmentation, and scarring. Patients were also asked if they observed any adverse reaction of the above or any other skin reaction they consider adverse between visits.

Statistical Analysis

Statistical analysis was performed using Minitab statistical package, version 15.1.20.0

(Minitab Inc., State College, Pennsylvania). For statistical testing, two-sided one-sample

Wilcoxon signed rank test was used, and P values less than .05 were considered statistically significant. Additionally, the medians and spread of the data were displayed in box plot graph.

Kappa agreement analysis [34,35] was performed to measure the inter-reviewer reliability of before and after photos assessments and the kappa coefficient was reported.

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3.1.2. Post chickenpox scars treatment

Regarding the Post-chickenpox scar group, Fifteen male patients aged 35 to 48 years (mean,

42 years) with Fitzpatrick skin type IV and V presented with a history of chickenpox infection

3 months earlier which left numerous scars over the face and forehead (Figure 9 1a, 1c, and

2a). All patients reported the occurrence of skin lesions few days after the onset of the fever.

This was followed by scab formation over the skin lesions which started to fall off within 10 days of the onset of their appearance which resulted in scars. Gentian violet lotion or topical antibiotic ointment was applied topically over the skin lesions and antibiotic was administered orally for 1 week. No other intervention had been administered before the patients presented to us. Exclusion criteria included any prior trial for treatment of the scars, any concomitant systemic disease, and any active .

Patients were referred to our clinic seeking treatment for their facial scars. Treatments were performed without topical anesthesia. No prophylactic therapy was used before or after treatment to control postinflammatory hyperpigmentation (PIH) resulting from laser treatments.

The treatment regimen was started with MDA utilizing aluminum oxide crystals, followed by the session with the sub-millisecond 1064-nm Nd:YAG laser. The MDA sessions were repeated every 7 days for 8 sessions and the laser session was repeated every 3-4 weeks for 5-6 sessions. A minimum of 3 days was allowed between MDA and laser treatments.

Treatment was performed without topical anesthesia and no prophylactic therapy was administered before or after treatment to control post inflammatory hyperpigmentation (PIH) resulting from laser treatments. Treatment was performed over 6 months.

The following parameters used during laser treatments: 5-mm spot size, 14 J/cm2, and 0.4- millisecond pulse width with a repetition rate of 5 Hz. The face was divided into squares of 5 x 5 cm and laser pulses were delivered with a continuous motion. The hand piece was moved

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to the adjacent treatment area when erythema developed. Erythema was seen after an average of 500 pulses per treatment square. The laser treatment was conducted with no pre- or post- cooling of the skin while defocusing the hand piece 1 to 2 cm above the skin using multiple passes of the treatment area.

The patients were followed up for a period ranging between 3 and 12 months after the last laser session. There was no downtime or any incidence of adverse effects such as pigmentary changes or scab formation after the procedure. The post treatment erythema persisted for 20 to 30 minutes immediately after each laser session and completely faded away afterwards. The patients were asked to utilize sun block with at least SPF 30 in between the sessions.

A questionnaire was administered to all participants 4 weeks after the last laser session regarding changes in scarring and skin texture as well as PIH. These 3 parameters were graded on a 4-point scale (2=marked improvement; 1=mild improvement; 0=no change; -

1=worsening). The same questionnaire also was administered to the treating physicians to grade changes observed in each participant.

Photographs were taken before treatment and 3 months (or more) after the last laser session. Blinded assessments were performed by 3 independent physicians using before and after photographs (unlabeled) that were not arranged in chronologic order. Reviewers were asked to identify the before and after photographs and evaluate the degree of improvement or worsening observed in scarring, skin texture, and PIH using a 4-point scale (2=marked improvement; 1=mild improvement; 0=no change; -1=worsening). No statistical analysis was performed.

Adverse effects were evaluated immediately after each laser treatment and 2 and 4 weeks after each laser session.

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3.2. Treatment of warts 3.2.1. Treatments of genital warts

General examination for the whole body, including the , was done for signs of sexually transmitted diseases (STDs) (for example, vesicles, ulcers, warts, mucous patches, lymph node enlargement).

Local genital examination was done while the patients were completely uncovered from the umbilicus down to the knee. The skin of the lower abdomen, penis, , perineum, perianal area, upper thighs, and the urethral meatus were inspected under good illumination for the presence of warts and other STDs. In all settings, patients with genital warts were examined and treated for other STDs. Whenever possible, their wives or current sexual partners were also offered examinations and treatments for macroscopically visible warts and other STDs. Examination of the anogenital warts was done and the following data were recorded: site, number, type, area, presence of complications such as ulcerations or bleeding. The wart area was estimated as follows: the two largest perpendicular diameters were measured, and the wart area was defined as the product of the two measurements.

Finally, a total of 174 adult males with 550 uncomplicated anogenital warts and with no history of topical or systemic therapy for warts during the last 2 months were included and treated by pulsed dye laser. A pulsed dye laser (585 nm, 450 s pulse duration; Cynosure,

USA) was used with the following parameters: spot size 5–7 mm according to the size of the lesions, and fluence 9–10 J/cm2.

Overlapping pulses were done, up to three to four pulses, until the appearance of grayish discoloration of the lesions which was an end point for lesion coagulation.

Treatments were repeated every 2 weeks with a maximum of three sessions. Topical antibiotic ointments were prescribed between the sessions to be used for a period of 7–10 days following every session. The number of warts, and the area of warts at presentation and at the

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end of treatment was recorded. Any adverse reactions were also recorded. Patients were followed-up for at least 4 months after the warts had cleared.

3.2.2. Treatments of plane warts

Fifty patients with a total of 326 verrucae were enrolled in the study over 8 months period.

They were 23 males and 27 females, with a mean age of 26.5 (12-41) years old. All patients were complaining of flat warts mainly on the forehead, cheeks, chin, neck, arms and the dorsum of the hands. Inclusion criteria included no treatment of lesions within the past month, and no history of constitutional or iatrogenic immunosuppression. All patients gave informed consent.

The study was completed by 42 patients, which completion defined as clearance of all visible warts or a maximum of 3 treatment sessions on the same lesion.

Treatment sessions consisted of treatment with the long pulsed Nd-YAG laser (1064 nm,

Coolglide, Cutera, RIT 220 Excl.) with 20-30 msec pulse duration and fluence between 95–

110 J/cm2, with 5,7 mm spot size according to the size of the lesion, applying double or triple overlapping pulses. Our endpoint was light greyish discoloration of the lesion.

Following treatment, there was slight peri-lesional erythema. Very minimal heat sensation or sometimes slight burning pain was experienced especially in children. Topical anaesthetic cream of 5 % lidocaine and 3.5 % prilocaine was used only in cases of children or with patients of low pain threshold. Treatment sessions were carried every 2 weeks with a maximum of 3 sessions on the same lesion. All patients and health care providers wore protective eyewear and micropore laser masks. A smoke evacuator was used as a precaution against potential aerosolised viral particles. Photographs were obtained at the initial visit and at 3 months follow up after the last treatment session.

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4. RESULTS 4.1. Treatments of scars 4.1.1. Treatment of scars in dark skin types

Blinded Photo Assessments

Two reviewers correctly identified all photos (22/22). The third reviewer incorrectly labeled one pair of before and after images and was not able to identify another pair of photos due to insufficient image quality (20/22). The reviewers were highly consistent (inter-reviewer reliability, kappa of 0.88) in identification of before and after photos (kappa coefficient: poor

< 0.20, fair 0.21-0.40, moderate 0.41-0.60, good 0.61-0.80, and very good 0.81-1.00).

Of the sixty-six possible image reviews for each category (22 images each reviewed by 3 physicians), one was determined by one reviewer as insufficient quality to grade before and after. Additionally, 4 images were excluded from scarring analysis, 4 were excluded from texture analysis and 5 were excluded from pigment analysis. Images were excluded due to insufficient focus, color balance and or lighting.

The results of the blinded photo assessments indicated clinically and statistically median improvement of 2 in scarring, 2.3 in texture and 2 in PIH (P < 0.001). Figure 1 displays the median improvement scores and the variability of data for all three conditions (scale of 0-3).

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Improvement in Scarring, Texture and Post Inflamatory Hyper-pigmentation (PIH)

3.0

2.5 ) 3 - 0 (

e 2.0 r o c S

t 1.5 n e m e

v 1.0 o r p m I 0.5

0.0

Scarring Texture PIH

Figure 1. Median improvement of 2 in scarring, 2.3 in texture and 2 in pigment based on blinded photo assessments by three reviewers. The box illustrates the 25th percentile to the

75th percentile with a line placed at the median (50% percentile). The bottom and top ends of whiskers show the minimum and maximum respectively.

Figures 2 to 8 display photos from seven different patients with follow-up times. Subject characteristics and treatment parameters used on a particular patient can be found in Table 1.

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Figure 2. Nd-YAG laser treatment of scars. 1a: Patient 1 baseline, 1b: patient 1 9-months post final treatment (6 sessions).

Figure 3. Nd-YAG laser treatment of scars. 3a: Patient 3 baseline, 3b: patient 3 9-months post final treatment (7 sessions).

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Figure 4. Nd-YAG laser treatment of scars. 4a: Patient 4 baseline, 4b: patient 4 9-months post final treatment (7 sessions).

Figure 5. Nd-YAG laser treatment of scars. 13a: Patient 13 baseline, 13b: patient 13 9- months post final treatment (6 sessions).

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Figure 6. Nd-YAG laser treatment of scars. 14a: Patient 14 baseline, 14b: patient 14 9- months post final treatment (6 sessions).

Figure 7. Nd-YAG laser treatment of scars. 15a: Patient 15 baseline, 15b: patient 15 10- months post final treatment (6 sessions).

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Figure 8. Nd-YAG laser treatment of scars. 20a: Patient 20 baseline, 20b: patient 20 10- months post final treatment (5 sessions).

Figures 2 to 8. Patients’ photos (1, 3, 4, 13, 14, 15, 20) at baseline and at follow-up visit after final treatment.

Transient mild edema and erythema were observed in all patients and resolved within 2 hours after treatment.

No transient or permanent complications such as blistering, crusting, purpura, scarring, transient or permanent hyper- or hypo-pigmentation were noted.

There was no single patient who reported any adverse effects during or after the treatment sessions till the end of the follow up period in this study.

4.1.2. Treatment of chickenpox scars All 15 participants were included in the analysis. The mean length of follow-up after the final laser session was 9.1 months. Questionnaire results demonstrated marked improvement in scarring, skin texture, and PIH as observed by participant and physician evaluation (Figures 9

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and 10). Results of the participant assessment revealed mean scores in scarring, skin texture, and PIH of 1.8, 1.9, and 1.8, respectively. Physician evaluation of improvement revealed mean scores of 1.9, 1.9, and 1.8, respectively (2=marked improvement; 1=mild improvement). Participant and physician evaluation did not reveal scores of no change or worsening for the 3 parameters.

For the blinded photographic assessments, all 3 reviewers correctly identified the chronology of 13 participant photographs (13/15). Of the 90 possible photograph reviews for each category (15 before and 15 after photographs reviewed by 3 physicians), 2 were determined by 1 reviewer as insufficient quality to judge before and after photographs. Additionally, 4 photographs were excluded from skin texture analysis and 5 were excluded from PIH analysis. Photographs were excluded due to insufficient focus, color balance, or lighting. The results of the blinded photographic assessments indicated clinically significant improvements in scarring, skin texture, and PIH, with mean scores (based on all 3 reviewers) of 1.9, 1.8, and

1.8, respectively (2=marked improvement; 1=mild improvement). None of the reviewers scored these parameters as no change or worsening.

Transient mild edema and erythema were observed in all participants and resolved within a maximum of 2 hours after treatment. No transient or permanent complications such as blistering, crusting, purpura, scarring, or transient or permanent hyperpigmentation or hypopigmentation were noted at 2 or 4 weeks. None of the participants reported any adverse effects during or after the treatment sessions through the end of the follow-up period.

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1(a): Baseline 1(b): 10 months post-final treatment (5 sessions)

1(c): Baseline 1(d): 10 months post-final treatment (5 sessions)

1(e): Baseline 1(f): 10 months post-final treatment (5 sessions)

Figure 9. Case 1 at baseline (1a, 1c, 1e) and after 8 sessions of Microdermabrasion and 5 sessions of laser treatment (1b, 1d, 1f)

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2(a): Baseline 2(b): 3 months post-final treatment (5 sessions)

2(c): Baseline 2(d): 3 months post-final treatment (5 sessions) (Close-up)

Figure 10. Case 2 at baseline (2a, 2c) and after 8 sessions of microdermabrasion and 5 sessions of laser treatment (2b, 2e)

4.2. Treatments of warts 4.2.1. Treatments of genital warts

The mean age of patients included was 31.33 + 4.7 years (range from 22 to 49). The mean duration of lesions was 4.29 + 3.15 months (range from 1 to 48).

The number of warts ranged from one to 14 per patient (average 3.82 + 4.33). Warts were frequently present with more than one lesion on one anatomical site. Warts were also present more frequently on different genital sites (104 patients, 59.78%) and on one genital site in 70

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patients (40.22%). Among those latter patients, lesions were present on the penis in 39

(22.41%), on the scrotum in 11 (6.32%), on the urethral meatus in four (2.29%), and on the

Peri-anal area in 16 (9.2%). The mean area of lesions was 26.9 mm2 and the area varied from

6 mm2 to 64 mm2. With regard to the morphological type of warts detected, it was predominantly condylomatous in 129 patients, papular in 31, keratotic in nine, and flat-topped papules in five patients.

Complete clearance of 528 anogenital warts (96%) treated by pulsed dye laser occurred after one to three sessions. A few small warts of short duration occurring on one anatomical site cleared significantly after fewer sessions and resulted in earlier clearance. Patients with fewer than three and with an area less than 20 mm2 cleared most frequently after one session. Other factors such as a patient’s age and the morphological type did not affect the treatment results.

Overlapping pulses (three to four) revealed better clearance of warts than single and even double pulsing. Side effects were infrequent and transient, mostly in the form of mild pain at treatment and transient hypopigmentation after treatment. Patients were followed-up for at least 4 months (up to 9 months in some cases).

Complete resolution and healing of skin without scaring or texture changes were found in the majority of cases (Figure 11 and 12).

Lesion recurrence rate was 5%. Recurrence was defined as a new wart at the same site detected within the 4-month follow-up period after clearance of lesions.

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Figure 11. Penile condylomata acuminate: before treatment

Figure 12. After treatment (three sessions).

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4.2.2. Treatments of plane warts

Of the 50 patients initially enrolled, 42 patients with a total of 256 warts completed the study.

The 8 patients who withdrew, were for reasons unrelated to treatment. In the evaluation of treatment response, complete response was defined as complete absence of clinically apparent warts without any textural changes such as fibrosis or scar formation. Partial response was defined as greater than 50% reduction in wart size or number.

Complete response was observed in 35 patients (83.3 %) (Figure 13-15), while partial response was observed in 7 patients (16.7 %). No case showed no response to the lesion treatment. The mean number of treatments to achieve complete response was 2.00, while the mean number of treatments to achieve partial response was 2.65. Postoperative complications such as transient post inflammatory hypopigmentation was observed only in 4 cases and only

1 case experienced transient post inflammatory hyperpigmentation and was given hydroquinone 4% cream. The recurrence of warts during follow up period was reported only in 2 cases. As regards patient satisfaction, ninety two percent of all patients even those who experienced partial response were satisfied with the treatment they were given.

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A Before treatment B Immediately after treatment C After 2 laser treatments Patient 1

A Before treatment B Immediately after treatment C After 2 laser treatments Patient 2

A Before treatment B Immediately after treatment C After 2 laser treatments Patient 3

Figure 13. Nd:YAG laser treatments of plane warts; A) Before treatment, B) Immediately after Nd:YAG laser treatment showing mild erythema and edema and C) After 2 laser treatments with complete clearance of the lesion without any textural changes or scaring.

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5. DISCUSSION

5.1. Laser treatment of scars

Retrospective photographic analysis of 22 cases of scars in our study and 15 cases of post chickenpox scars indeed shows that sub-millisecond 1064 nm Nd:YAG laser may be a viable treatment modality capable of generating improvement in texture, scarring and PIH secondary to the acne condition in darker skin types. Blinded photo assessments by three independent physicians indicated that six treatments performed, on average, 24.5 days apart resulted in clinically and statistically significant improvement in atrophic scarring, texture and PIH in patients with skin types III-VI. High consistency between reviewers was observed in identifying before and after photos.

It is noteworthy to state that The non-invasive treatments with the sub-millisecond 1064 nm

Nd:YAG laser: (1) Improved the existing PIH from acne scarring; (2) Did not induce additional PIH; (3) Did not require pre- or post-treatment agents to control PIH in dark skin patients; (4) Did not require anesthetic.

The percentage of subjects with skin types IV and V included in studies for the treatment of atrophic scarring are very limited compared to lighter skin types due to pigmentation concerns

[1-3]. Even with the use of hydroquinone pre- and post-treatment, a recently published prospective study of 15 subjects with skin types IV-VI and acne scarring using Er:YAG laser showed a 50% rate of the PIH [12]. In the same study, the pain levels were reported to increase as the skin type went from IV to VI and as the number of passes went from 1 to 8.

One challenge faced in this retrospective study was not all patient photos had sufficient image quality. As a result, a couple of photos were excluded from the data analysis. The second challenge was the data only captured an overall percentage improvement without assessments

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of severity and types of scars at baseline and follow-up. This was due to the lack of high resolution standardized photos. In future studies, high resolution photos of scarring (using macro lens settings without flash [7] or a three-dimensional optical profiling system) should be used for objective assessment of scar severity and type [6, 8]. Lastly, it would be beneficial to collect data on patient satisfaction in addition to physician assessments.

The theory behind combining MDA treatments with laser treatments was to reduce the thickness of the stratum corneum thereby allowing greater light penetration to the papillary dermis. Thus, MDA treatments performed before the laser treatments were mild in intensity to prevent discomfort or complications from deep dermal abrasions [36]. The conservative

MDA settings used in this study were not considered effective to treat acne scarring and PIH and were unlikely to have had an effect on the observed improvement 37-39]. Nonetheless, randomized split face studies would be required to definitely determine whether MDA is necessary or has an additional benefit when used in combination with laser treatments.

In previous studies, the sub-millisecond 1064 nm Nd:YAG laser therapy has been shown to stimulate collagen [13] and to improve scar severity [40]. However, no assessment has been performed on secondary improvement to texture and pigment. We hypothesize that the sub- millisecond Nd:YAG laser works through two parallel actions to safely stimulate collagen and improve discoloration. The first mechanism involves discrete cellular damage caused by direct absorption in hemoglobin, melanin and water during each pulse and bulk heating from cumulative pulsing in a region. As a result, damage created through direct absorption and through sustained time at elevated temperature initiates a healing response, prompting collagen stimulation [41,42].

Nd:YAG is absorbed by melanin and hemoglobin and is subsequently used for vascular and hair reduction treatments. Pulse durations in these treatments are in the 10-100ms range,

30

roughly 30-300 times longer than the pulse durations used in this study. The short pulse durations used in sub-millisecond treatment does not change the characteristics of chromophore absorption. At these short pulse durations, the laser energy is heating fine structures during each pulse, thus more selectively targeting the microvasculature in the papillary dermis and melanocytes within the epidermis without actually damaging the epidermis or larger vessels in the dermis.

The second mechanism of action occurs through bulk heating. The laser uses a 5 mm spot pulsing at 5-10 Hz to deliver large amounts of energy in relatively short bursts to a finite area of tissue. Heat conducts to surrounding tissue over time to create bulk heating in each treatment. The degree of bulk heating is a function of total energy delivered per unit area per unit time. The goal during treatment is to deliver energy to an area of tissue faster than the body can extract the heat. For this reason, skin cooling is not desired during treatment. This bulk heating occurs gradually and non-selectively through heat conduction, so no structures are specifically targeted. This allows for safe treatment, even on type VI skin.

5.2. Laser treatment of warts

Management of genital warts presents a problem of increasing magnitude to genitourinary medicine and Dermatology specialists.

Choice of treatment is guided by patient preference, with consideration given to the patient’s age and ability to comply with moderately complicated directions, to the location and number of warts, and to the clinician’s training. Many conventional lines of therapy are used, the aim of which is to destroy the infected tissue; however, none are consistently effective, making genital warts a therapeutic challenge.

Laser therapy had been used for the treatment of genital warts since the 1970s [43].

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CO2, argon, Nd:YAG and Er:YAG lasers have been used, especially for refractory genital warts, giant condyloma acuminatum or Buschke–Lowenstein tumor, with variable degrees of safety and efficacy [44–48].

The pulsed dye laser was used initially for selective photothermolysis of vascular lesions, whereby the wavelength is selectively absorbed by the oxyhemoglobin, leading to destruction of the vascular component of the tissue. It was also used in the management of other non- vascular lesions, depending on the photothermal effect of laser on the cutaneous tissue + its selective photothermolysis effect. The pulsed dye laser was used for the management of simple and recalcitrant verrucae vulgaris on different sites of the body using fluencies ranging from 6 to 9 J/cm2 [49]. Other studies reported higher fluencies of 9.4 J/cm2 giving variable clearance rates [50].

Tuncel et al. [33] used the pulsed dye laser for the management of perianal warts in children with a fluence of 7.5 J/cm2. In our study, we used higher fluencies of 9–10 J/cm2, which ensured greater destruction of the vascular component of the lesions.

The overlapping pulses increased the photothermal effect of the laser radiation leading to coagulation of the lesions and immediate graying of the warty tissue. The technique was done as an outpatient procedure and did not require any infiltration anesthesia as in electrocautery or surgery, which is another advantage of the pulsed dye laser in the treatment of genital warts. It is safe in comparison to the toxicity of , which are continuously investigated in an attempt to increase efficacy and decrease toxicity [23]. In the light of results from our study, in which there was a significant number of patients presenting with multiple and/or large size 5 lesions, complete resolution and healing of skin without scaring or texture changes were found in the majority of cases. This is in contrast with what is usually found with other traditional treatments such as electrocautery, surgical excision, cryotherapy or CO2 laser.

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Lesion clearance rate in our study was 96%, which is superior to that achieved by the more widely used treatment modalities (32–88%) [24,51]. Better results (smaller number of sessions and earlier clearance) were observed with lesions of short duration and in cases with a small number of warts occurring on one anatomical site. On the other hand, failure of treatment that occurred only in 4% of cases was observed in highly recalcitrant lesions with a large number of warts, which might be attributed to increased fibrosis and hyperkeratosis due to previous attempts of treatment. Lesion recurrence rate (5%) was also less than reported with other treatment modalities (8–22%) [25]. Post-treatment recurrence rates are not well defined in most studies because in most cases either too few subjects have been studied or follow-up protocols had not been standardized [51].

Common warts are hyperkeratotic papulonodules most often seen on the hand, arms and legs, but can seen anywhere on the glabrous skin. Common verrucae represent the most frequent clinical lesions produced by human papillomavirus [52]. Verruca plana (flat warts) are less exophytic than common warts, frequently presenting as several or dozen of subtle papules 2–6 mm in diameter elevated above the surface less than a millimetre or so. These can be quite subtle, and may be missed by a casual observer. Pigmentary disturbances may be the most disturbing part of the infection to the patient. These lesions are frequently a problem on the face and the glabrous skin of non-immunocompromised individuals. At present, therapies aim to remove the lesion rather than specifically target human papillomavirus infection. Many different types of therapy have been used in treatment of verrucae.

Commonly used methods of physical destruction include: electrodessication, cryosurgery and laser therapy. Chemical destruction is induced with salicylic acid, cantharidin, among others.

Chemotherapeutic agents include podophillin resin and 5-fluorouracil. More recently immunomodulators such as interferon, systemic retinoids have been used [53–55].

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Many types of lasers have been used for the management of warts. Carbon dioxyde laser vaporization for infected tissue was used [56]. Results were not superior than the ordinary electrocautery which remove blindly the infected tissue as well and may sometimes lead to textural changes. Several investigators have demonstrated the efficacy of 585 nm pulsed dye laser in treating warts [57–62]. The mechanism of action may be a result of intense heating of dermal vessels with collateral damage of virally infected keratinocytes. This theory is based on the presence of dilated and congested vessels at the base of most of verrucae [63] and the mechanism of selective photothermolysis [64] that result in targeting of haemoglobin by pulsed dye laser. To our knowledge, one report used KTP laser at 532 nm wavelength for treatment of recalcitrant pigmented warts, through selective photothermolysis and propagation of photoacoustic waves [65].

Nd-YAG laser hyperthermia proved to be effective in treatment of resistant warts with significant clearance of the lesions and absence of viral particles [66], but it cannot be performed on very sensitive areas for example lesions on the face, neck or cheeks. Patients will not tolerate the procedure since it is done without anaesthesia and needs laser exposure time of 1-2 min in comparison to the pulsed lasers with micro and milliseconds pulse durations. Thus laser hyperthermia is not practical for large number of lesions.

The Nd-YAG laser is one of the most versatile and interesting lasers in dermatological laser medicine. Almost no other laser has such a wide spectrum of applications. Depending on wavelength (1064 nm) and mode (continuous, Q-switched, long pulsed), it is applied on benign pigmented, vascular lesions and permanent hair reduction [67, 68], due to the fact that

1064nm is absorbed by all the skin chromophores.

Reports using long pulsed Nd-YAG laser as an effective line of treatment for vascular lesions such as telengietasia and venous lakes [69], encouraged us to use this laser system for thermal

34

destruction of resistant flat warts. With its deeper penetration and lower absorption coefficient for melanin, there is less concern for collateral epidermal damage [70].

Unlike ablative treatment modalities, with long pulsed Nd-YAG laser therapy, no wound was created, especially if the lesions were on exposed parts of the body mostly head and neck as in our study, thus avoiding prolonged post operative pain, crusting, scarring or downtime.

Applying the pulsed mode of laser system, made the technique tolerable by the patients, most of whom returned to work or normal activities immediately postoperatively. There was no need for local infiltration anaesthesia (only topical anaesthetic cream was used for selected cases) was another advantage. The limited number of sessions up to three sessions in our protocol was to be comparable to other treatment modalities such as topical retinoids, chemical cautery also for the cost benefit wise. Most of the patients who experienced partial response was due to their large number of warty lesions, most of the lesions were not de novo, they were being treated before and lasted for more than six months. The risk of high incidence of post inflammatory hyperpigmentation is minimized by preferentially sparing epidermal pigment. The procedure proved to be acceptable and effective by the patients. Our results are comparable to pulsed dye laser treatment modalities which was another positive point, with an advantage over the pulsed dye laser of having no post laser purpura and no consumables such as dye kit.

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6. SUMMARY AND NEW FINDINGS

Preliminary data collected in our retrospective study suggest that sub-millisecond 1064 nm

Nd:YAG laser treatments are safe and effective for treating atrophic scarring in patients with darker skin types, delivering clinically and statistically significant results with reduced risk of pigment complications. This offers a new standard of care or first treatment option for patients with a high risk of pigmentary complications. Prospective studies with the sub- millisecond Nd:YAG laser alone are required to further assess treatment outcomes considering the effect of number treatments as well as to determine targeted treatment parameters for improved effects on scars of various severity and type. Further, randomized split face studies are needed to show the treatment effect and the incidence of PIH compared to non-treated and treated controls with alternative treatments.

A further study was conducted to evaluate the safety and efficacy of the combination of the

MDA and the sub-millisecond 1064-nm Nd:YAG laser in treatment of the post chickenpox scars in dark skin patients and the result of our study poved our treatment protocol to be safe and effective treatment modality for the postchickenpox scarring and induced hyperpigmentation in all skin types.

In our study of genital warts in males, the pulsed dye laser has been found to be a safe, effective, and satisfactory treatment for genital warts. It is capable of selectively destroying warts without damaging the surrounding skin.

Regarding the plane warts, we concluded that Long Pulsed Nd-YAG laser can be added to the long list of traditional treatment of plane warts as an effective, safe and well tolerated method with minimal complications. We recommend the following inclusion criteria for long pulsed

Nd-YAG laser treatment of plane warts: limited numbers of warty lesions, especially on very sensitive areas, lasted for less than six months with no previous attempt of treatment. In

36

Patients with previous criteria, long pulsed Nd-YAG laser would be significantly more costly effective than other treatment modalities.

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7. ACKNOWLEDGEMENTS

I believe finishing this work, is the best opportunity to express my deepest gratitude and appreciation to Professor Lajos Kemény, Professor of Dermatology, and Head of the

Department of Dermatology and Allergology, Albert Szent-Györgyi Clinical Center

University of Szeged for his continuous teaching, encouragement, and constructive criticism.

Profesor Kemény’s role in my clinical and academic progress is unforgettable. Many thanks for his advice and generous supervision during this work.

I also would like to express my heartfelt thanks and sincere gratitude to Prof. Dr. Hisham

Shokeir, Professor of Dermatology, and Dean of the National Institute of Laser Enhanced

Sciences, Cairo University for whom I’m greatly indebted for his valuable guidance, creative ideas during the studies we conducted along my clinical career. As a matter of fact, without the efforts of Prof. Shokeir, this work would have never been complete.

Today, I can not forget to thank all my colleagues in the Dermatology unit, National Institute of Laser Enhanced Sciences, Cairo University, especially Prof. Dr. Mona Soliman, Dr. Manal

Salah, Dr. Nevine Samy, Dr Abeer Atteya, and Dr. Mohamed Tome, Al Rebat University,

Khartoum, Sudan, from whom I have learned alot in the field of Laser applications in

Dermatology.

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Appendix

45

Study

Successful Treatment of Chickenpox Scars With Microdermabrasion and a Nonablative, Submillisecond, 1064-nm Nd:YAG Laser

Ashraf Badawi, MD; Mohamed A. Tome, MD; Ayse Turley, DDS, MPH; Lajos Kemeny, MD, PhD, DSc

The use of lasers in patients with darker skin types presents a remarkable challenge to laser practitio- ners, especiallyCOS when treating large areas of atrophicDERM scarring following chickenpox infection. Treatment options often are limited because of an increased risk for pigmentary complications, including hypopig- mentation and hyperpigmentation. This retrospective study evaluated the efficacy of a nonablative, sub- millisecond, 1064-nm Nd:YAG laser used in combination with microdermabrasion (MDA) therapy over 6 months to treat facial chickenpox scarring in 15 males with Fitzpatrick skin type IV or V. Participants wereDo treated at a fluence of 14Not to 16 J/cm2 and a pulse duration Copy of 0.4 milliseconds with a repetition rate of 5 Hz. Five to 6 laser treatments were performed on each participant every 3 to 4 weeks and 8 MDA treatments were performed 7 to 10 days apart. The mean follow-up time was 9.1 months after the final treatment session (range, 3–12 months). Both the participants and the treating physicians were asked to complete a questionnaire regarding changes in scarring and skin texture as well as postinflamma- tory hyperpigmentation (PIH) using a 4-point scale (25marked improvement; 15mild improvement; 05no change; 215worsening). Blinded assessments were performed by 3 independent physicians using before and after photographs (unlabeled) that were not arranged in chronologic order. Reviewers were instructed to identify the before and after photographs and evaluate the degree of improvement

Drs. Badawi and Kemeny are from the Department of Dermatology and Allergology, Albert Szent-Györgyi Medical Center, University of Szeged, Hungary. Dr. Badawi also is from the Dermatology Unit, National Institute of Laser Enhanced Sciences, Cairo University, Egypt. Dr. Tome is from the Department of Dermatology, Faculty of Medicine, Al Ribat University, Khartoum, Sudan. Dr. Turley is from Cutera, Inc, San Francisco, California. Dr. Badawi is a consultant for Amico Group, distributor for Cynosure, Inc, and Sciton, Inc, in the Middle East. Drs. Tome and Kemeny report no conflicts of interest in relation to this article. Dr. Turley is an employee of Cutera, Inc. Correspondence: Ashraf Badawi, MD, 8 Abu Al Maali St Agouza, Apartment 14, Giza, Cairo, Egypt ([email protected]). www.cosderm.com VOL. 24 NO. 8 • AUGUST 2011 • Cosmetic Dermatology® 389 Treatment of Chickenpox Scars

or worsening in scarring, skin texture, and PIH secondary to chickenpox infection. Clinically significant improvements in scarring, skin texture, and PIH were evaluated. Ultimately, data collected in this study suggest that a nonablative, submillisecond, 1064-nm Nd:YAG laser used in combination with MDA therapy is an effective treatment method for atrophic chickenpox scarring in patients with darker skin types, delivering clinically significant results with reduced risks for pigmentary complications and patient discomfort. Cosmet Dermatol. 2011;24:389-394.

hickenpox, also known as varicella, is a microdermabrasion (MDA) therapy over 6 months highly contagious disease caused by the to treat facial chickenpox scarring in 15 males with varicella-zoster virus. The disease rapidly Fitzpatrick skin type IV or V. spreads through direct contact with secre- tions from chickenpox vesicles as well METHODS Cas through the air when an infected person coughs or Study Population sneezes. Varicella remains contagious until all pustules Patients presented to our clinic seeking treatment of facial crust over, and it is possible for a person who has never chickenpox scars. The study included 15 males aged had chickenpox or been immunized against it to become 35 to 48 years (mean, 42 years) with Fitzpatrick skin infected simply by being in the same room as someone type IV or V who reported a history of chickenpox infec- with the disease.1 tion 3 months prior that resulted in numerous atrophic Symptoms typically appear 10 to 21 days following ini- scars on the face and forehead. All participants reported tial exposure to the varicella-zoster virus and tend to be the occurrence of skin lesions within 3 to 7 days of worse in adultsCOS compared to children.2 Early symptoms DERM onset of fever, followed by scab formation that resulted of chickenpox may include body aches, fever, fatigue, in scarring within 10 days of initial appearance. Gentian and irritability. A characteristic papular rash of up to violet lotion or topical antibiotic ointment was applied to 500 itchy blisters eventually appears over the entire body, the lesions and antibiotics were orally administered for usually lasting 5 to 7 days and healing as scabs. The rash 1 week. Participants received no other treatment prior also can spread to the mouth or other internal parts of to inclusion in the study. Exclusion criteria included any the body.2 Patients who previously received the varicella prior trial for treatment of the scars, any concomitant sys- vaccineDo may sometimes develop symptomsNot on exposure, temic diseaseCopy or , and any active skin infection. but the presentation usually is mild, with a rash of only 50 or fewer red papules that rarely become vesicles.3,4 Treatment Regimen Although chickenpox usually is self-limited, it can cause Treatment began with MDA therapy utilizing aluminum more serious complications in immunocompromised oxide crystals, followed by nonablative, submillisecond, patients (eg, young children; older adults; patients with 1064-nm Nd:YAG laser therapy. Microdermabrasion treat- AIDS, lupus, or leukemia) such as secondary skin infec- ments were repeated every 7 to 10 days for 8 sessions and tions, pneumonia, and encephalitis.2 Secondary bacterial laser treatments were repeated every 3 to 4 weeks for 5 to infection of skin lesions manifesting as impetigo, cel- 6 sessions. Microdermabrasion and laser treatments were lulitis, or erysipelas is the most common complication performed a minimum of 3 days apart. Treatment was per- in healthy children, with staphylococci and streptococci formed without topical anesthesia and no prophylactic ther- being the most commonly implicated bacterial patho- apy was administered before or after treatment to control gens. Bacterial superinfection often is a predisposition for postinflammatory hyperpigmentation (PIH) resulting from chickenpox scarring.5-9 laser treatments. Treatment was performed over 6 months. Chickenpox scars usually are more common in adults The parameters for all laser treatments included a and scar treatment often represents a major challenge for 5-mm spot size, fluences of 14 to 16 J/cm2, and a pulse cosmetic dermatologists, especially when dealing with duration of 0.4 milliseconds with a repetition rate of 5 Hz. patients with darker skin types because of the higher Treatment sites were divided into smaller areas measur- risk for pigmentary complications. This retrospective ing 535 cm. Laser pulses were delivered in a continu- study evaluated the efficacy of a nonablative, submillisec- ous motion while defocusing the handpiece 1 to 2 cm ond, 1064-nm Nd:YAG laser used in combination with above the skin using multiple passes of the treatment area.

390 Cosmetic Dermatology® • AUGUST 2011 • VOL. 24 NO. 8 www.cosderm.com Treatment of Chickenpox Scars

Participant Demographicsa

Participant Fitzpatrick No. of MDA No. of Laser Follow-up No. Age, y Skin Type Sessions Sessions Period, mo

1 45 V 8 5 10

2 43 IV 8 5 3

3 37 V 8 6 9

4 47 IV 8 6 8

5 36 V 8 6 12

6 42 V 8 6 10

7 41 IV 8 6 9

8 48 IV 8 6 9 9 COS35 IV DERM8 6 10 10 44 V 8 6 12

11 46 V 8 6 6 12Do39 NotV 8 Copy5 8 13 40 V 8 5 9

14 44 IV 8 6 10

15 43 IV 8 6 12

Abbreviation: MDA, microdermabrasion. aThe mean age was 42 years; mean number of MDA sessions was 8; mean number of laser sessions was 5.7; and mean follow-up period was 9.1 months.

The handpiece was moved to an adjacent treatment area sunscreen with a sun protection factor of at least 30 in when erythema developed in the targeted area, typically between sessions. after an average of 500 pulses per treatment square. Each session was conducted without cooling the skin before or Evaluations after laser treatment. A questionnaire was administered to all participants Participants were followed for 3 to 12 months after 4 weeks after the last laser session regarding changes the final laser session. There was no downtime after the in scarring and skin texture as well as PIH. These procedure. Participants also were instructed to utilize 3 parameters were graded on a 4-point scale (25marked www.cosderm.com VOL. 24 NO. 8 • AUGUST 2011 • Cosmetic Dermatology® 391 Treatment of Chickenpox Scars improvement; 15mild improvement; 05no change; Adverse effects were evaluated immediately after 215worsening). The same questionnaire also was each laser treatment and 2 and 4 weeks after each administered to the treating physicians to grade changes laser session. observed in each participant. Photographs were taken before treatment and 3 months RESULTS (or more) after the last laser session. Blinded assessments All 15 participants were included in the analysis (Table). were performed by 3 independent physicians using before The mean length of follow-up after the final laser session and after photographs (unlabeled) that were not arranged was 9.1 months. Questionnaire results demonstrated in chronologic order. Reviewers were asked to identify marked improvement in scarring, skin texture, and PIH the before and after photographs and evaluate the degree as observed by participant and physician evaluation of improvement or worsening observed in scarring, (Figures 1 and 2). Results of the participant assessment skin texture, and PIH using a 4-point scale (25marked revealed mean scores in scarring, skin texture, and PIH improvement; 15mild improvement; 05no change; of 1.8, 1.9, and 1.8, respectively. Physician evaluation 215worsening). No statistical analysis was performed. of improvement revealed mean scores of 1.9, 1.9, and

COS DERMA B Do Not Copy

C D

Figure 1. Participant with chickenpox scarring at baseline (A and C) and following 5 sessions of laser treatments and 8 sessions of microderm- abrasion (B and D).

392 Cosmetic Dermatology® • AUGUST 2011 • VOL. 24 NO. 8 www.cosderm.com Treatment of Chickenpox Scars

A B

Figure 2. Participant with chickenpox scarring at baseline (A) and following 5 sessions of laser treatments and 8 sessions of microdermabra- sion (B). COS DERM

1.8, respectively (25marked improvement; 15mild after treatment. No transient or permanent complications improvement).Do Participant and physicianNot evaluation did such as Copy blistering, crusting, purpura, scarring, or tran- not reveal scores of no change or worsening for the sient or permanent hyperpigmentation or hypopigmenta- 3 parameters. tion were noted at 2 or 4 weeks. None of the participants For the blinded photographic assessments, all 3 review- reported any adverse effects during or after the treatment ers correctly identified the chronology of 13 participant sessions through the end of the follow-up period. photographs (13/15). Of the 90 possible photograph reviews for each category (15 before and 15 after pho- COMMENT tographs reviewed by 3 physicians), 2 were determined The use of lasers to treat atrophic scarring in darker skin by 1 reviewer as insufficient quality to judge before and types presents a remarkable challenge to laser practi- after photographs. Additionally, 4 photographs were tioners. Current treatment modalities, including deep excluded from skin texture analysis and 5 were excluded dermal peels, ablative and nonablative fractional laser from PIH analysis. Photographs were excluded due to resurfacing, and surgical techniques, are not widely insufficient focus, color balance, and/or lighting. The available to patients with Fitzpatrick skin types IV to VI results of the blinded photographic assessments indicated because of increased risks for pigmentary complications. clinically significant improvements in scarring, skin tex- These complications are particularly likely when treating ture, and PIH, with mean scores (based on all 3 reviewers) large areas of facial scarring, including scars following of 1.9, 1.8, and 1.8, respectively (25marked improve- chickenpox infection. ment; 15mild improvement). None of the reviewers The procedure evaluated in this study combined MDA scored these parameters as no change or worsening. and laser therapy to optimize results of atrophic scar Transient mild edema and erythema were observed in treatment in darker skin types. Microdermabrasion was all participants and resolved within a maximum of 2 hours included to improve the structure of the epidermis by www.cosderm.com VOL. 24 NO. 8 • AUGUST 2011 • Cosmetic Dermatology® 393 Treatment of Chickenpox Scars decreasing the population of keratinocytes and stimulat- 2. Vinzio S, Lioure B, Goichot B. Varicella in immunocompromised ing the proliferation of the living cell layer, microcircula- patients. Lancet. 2006;368:2208. 10-12 3. Chartrand SA. Varicella . Pediatr Clin North Am. tion, and lymphatic drainage. The laser treatments 2000;47:373-394. were intended to induce sustained volumetric heating by 4. American Academy of Pediatrics Committee on Infectious increasing the temperature of the dermis to approximately Diseases. Prevention of varicella: recommendations for use of vari- 40°C and maintaining it for a minimum of 2 minutes. The cella in children, including a recommendation for a rou- goal of the sustained volumetric heating of the dermis tine 2-dose varicella immunization schedule. Pediatrics. 2007;120: 221-231. was to initiate a mild inflammatory reaction leading to the 5. Aebi C, Ahmed A, Ramilo O. Bacterial complications of primary deposition of fibroblasts followed by the synthesis of new varicella in children. Clin Infect Dis. 1996;23:698-705. collagen in the treated area.13-15 6. Higuchi S, Toichi E, Kore-eda S, et al. An adult case of Fournier’s Ultimately, data collected in this study suggest that gangrene preceded by varicella. Acta Dermatol Kyoto Engl Ed. a nonablative, submillisecond, 1064-nm Nd:YAG laser 1997;92:375-380. 7. Advisory Committee on Immunization Practices. Recommended used in combination with MDA is an effective treatment adult immunization schedule: United States, 2009. Ann Intern Med. method for atrophic chickenpox scarring in patients with 2009;150:40-44. darker skin types, delivering clinically significant results 8. Choo PW, Donahue JG, Manson JE, et al. The epidemiol- with reduced risks for pigmentary complications and ogy of varicella and its complications. J Infect Dis. 1995;172: 706-712. patient discomfort. 9. Papadopoulos AJ, Schwartz RA, Janniger CK. Chickenpox. Cutis. It is noteworthy that existing PIH improved in all partici- 2000;65:355-358. pants following the procedure; it also is clinically signifi- 10. Karimipour DJ, Karimipour G, Orringer JS. Microdermabra- cant that the laser treatment did not induce additional PIH sion: an evidence-based review. Plast Reconstr Surg. 2010;125: or require anesthetics or additional treatment agents before 372-377. 11. Tsai RY, Wang CN, Chan HL. Aluminum oxide crystal microderm- and after therapy sessions to control PIH. The treatment abrasion: a new technique for treating facial scarring. Dermatol modality evaluated in this study may offer a new standard Surg. 1995;21:539-542. of care and first-line treatment option for patients with atro- 12. Shim EK, Barnette D, Hughes K, et al. Microdermabrasion: phic scarring and a high risk for pigmentary complications. a clinical and histopathologic study. Dermatol Surg. 2001;27: COS DERM524-530. 13. Schmults CD, Phelps R, Goldberg DJ. Nonablative facial remodel- CONCLUSION ing: erythema reduction and histologic evidence of new collagen The combination of MDA therapy and nonablative, sub- formation using a 300-microsecond 1064-nm Nd:YAG laser. Arch millisecond, 1064-nm Nd:YAG laser treatment is an effec- Dermatol. 2004;140:1373-1376. tive treatment modality for chickenpox scarring and PIH 14. Lipper G, Perez M. Nonablative acne scar reduction after a series of treatments with a short-pulsed 1,064-nm neodymium:YAG laser. in darker skin types. Dermatol Surg. 2006;32:998-1006. Do Not15. TrellesCopy MA, Alvarez X, Martín-Vázquez MJ, et al. Assessment of the REFERENCES efficacy of nonablative long-pulsed 1064-nm Nd:YAG laser treat- 1. Schwartz RA, Jordan MC, Rubenstein DJ. Bullous chickenpox. J Am ment of wrinkles compared at 2, 4, and 6 months. Facial Plast Surg. Acad Dermatol. 1983;9:209-212. 2005;21:145-153. n

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394 Cosmetic Dermatology® • AUGUST 2011 • VOL. 24 NO. 8 www.cosderm.com Lasers in Surgery and Medicine 43:130–136 (2011)

Retrospective Analysis of Non-Ablative Scar Treatment in Dark Skin Types Using the Sub-Millisecond Nd:YAG 1,064 nm Laser

1,2 3 2 2 Ashraf Badawi, MD, Mohamed A. Tome, MD, Abeer Atteya, MD PhD, Nevine Sami, MD PhD, and 4 Iman A.L. Morsy, MD 1Department of Dermatology and Allergology, Albert Szent-Gyorgyi Medical Center, University of Szeged, Hungary 2Dermatology Unit, National Institute of Laser Enhanced Sciences, Cairo University, Egypt 3Department of Dermatology, Faculty of Medicine, Al Rebat University, Khartoum, Sudan 4Department of Dermatology, Faculty of Medicine, Alexandria University, Egypt

Background: The use of lasers to treat atrophic scarring Conclusions: Preliminary data collected in this retrospec- conditions in darker skin types presents a significant chal- tive study suggest that sub-millisecond 1,064 nm Nd:YAG lenge to laser practitioners. Current treatment modalities, laser treatment is a safe and effective treatment for atrophic including deep dermal peels; ablative; non-ablative; and scarring in patients with darker skin types, delivering fractional laser resurfacing and surgical techniques, are clinically and statistically significant results with reduced limited in skin types IV through VI due to increased risks risk of pigment complications and patient discomfort. of hyper- and hypo-pigmentation. This is especially true Lasers Surg. Med. 43:130–136, 2011. when attempting to treat large areas of acne scarring. ß 2011 Wiley-Liss, Inc. This study investigates the treatment of atrophic scarring with a non-ablative sub-millisecond-pulsed 1,064 nm Key words: non-ablative; Nd:YAG; darker skin types; Nd:YAG laser in darker skin types. atrophic scar; post-inflammatory hyper-pigmentation Objective: To evaluate the safety and efficacy of a sub- (PIH); laser millisecond 1,064 nm Nd:YAG laser for the treatment of BACKGROUND atrophic scarring in Fitzpatrick skin types III–VI through retrospective photographic analysis. Darker skin presents a significant challenge to laser prac- Methods: A retrospective analysis was conducted of all titioners. Treatment options are limited due to increased patients (n ¼ 22) who received sub-millisecond Nd:YAG risks of pigmentary complications including hypo- and laser treatments for atrophic scarring over a 6-month hyper-pigmentation. This is especially true when attempt- period. Patients had Fitzpatrick skin types III–VI and were ing to treat large areas with atrophic scarring. treated for the indication of atrophic scarring using the Current methods of treating scarring include traditional 2 fluence of 14–16 J/cm , pulse duration of 300–500 micro- fully ablative erbium and carbon dioxide (CO2) treatments seconds and repetition rate of 5–7 Hz. An average of six as well as non-ablative and ablative fractional resurfacing treatments was performed on each patient approximately with CO2, erbium:yttrium-aluminum-garnet (Er:YAG), 3 weeks apart and the mean follow-up time after the final and erbium:yttrium-scandium-galium-garnet (Er:YSGG) treatment was 9 months (range of 3–10 months). Blinded lasers [1–8]. These options can be challenging for skin type photographic assessments were performed by three inde- IVpatientsandnotfeasibleforpatientswithskintypesV–VI pendent physicians using photos unlabeled for before and without significant pre- and post-treatment skin condition- after and arranged in non-chronological order. Reviewers ing and a hyper-pigmentation risk. With traditional fully were asked to determine before and after photos and the ablative CO2 resurfacing, studies showed hyper-pigmenta- degree of improvement in scarring, textural change, and tion rates of 20–30% in Fitzpatrick skin type III and post-inflammatory hyper-pigmentation (PIH) secondary to nearly 100% in skin type IV if treatment is performed the acne or scarring condition. Degree of improvement was graded using a four-point scale: 0 ¼ <25%, 1 ¼ 25–50%, 2 ¼ 51–75%, 3 ¼ 76–100%. Ashraf Badawi received no funding or financial support for this work and has no commercial association or financial Results: Based on blinded photo assessments by three relationship with any other institution. independent reviewers, clinically and statistically signifi- *Corresponding to: Dr. Ashraf Badawi, MD, Department of cant median improvement of 2 in scarring, 2.3 in texture, Dermatology and Allergology, Albert Szent-Gyorgyi Medical Center, University of Szeged, Hungary. and 2 in pigment were observed (one-sample Wilcoxon E-mail: [email protected] signed rank test, P < 0.001). Reviewers were highly con- Accepted 24 November 2010 Published online 15 February 2011 in Wiley Online Library sistent (inter-reviewer reliability) in identification of before (wileyonlinelibrary.com). and after photos (kappa of 0.88). DOI 10.1002/lsm.21031

ß 2011 Wiley-Liss, Inc. SUBMILLISECOND ND:YAG LASER IN SCAR TREATMENT 131 without pre-treatment prophylaxis [9–11]. Further, 19% of Laser Enhanced Sciences, Dermatology Unit, at Cairo traditional resurfacing patients experience some form of University, Egypt and at Saheroun Hospital, Khartoum, hypo-pigmentation. A recent study on the treatment of Sudan on 22 patients with Fitzpatrick skin types III acne scarring with fractionated Erbium-doped YAG (n ¼ 2), IV (n ¼ 4), V (n ¼ 14), VI (n ¼ 2) who had atrophic laser reported a post-inflammatory hyper-pigmentation scarring such as acne scarring. All patients who were (PIH) incidence of 50% in 15 subjects with skin types treated over a 6-month period between February and July IV–VI [12]. of 2008 were included in the study. When the 1,064 nm neodymium-doped yttrium Treatmentswereperformedusing300–500 microseconds aluminum garnet (Nd:YAG) laser with the option of sub- pulseduration,14–16 J/cm2 and5–7 Hzrepetitionrate.The millisecond pulse width is used with 300–500 microsecond hand piece was held 1–2 cm off the surface of the skin (about pulse durations, a 5 mm spot size and repetition rates of 5– the width of an index finger) during delivery. Treatments 10 Hz, it offers the ability to focus heat in the papillary and were performed withouttopicalanesthesia.Noprophylactic upper reticular dermis. The sub-millisecond 1,064 nm therapy was used before or after treatment to control PIH Nd:YAG laser has been proven to stimulate new collagen resulting from laser treatments. On average, each patient synthesis [13]. It is therefore feasible that deliberate sub- received six treatments (minimum 5, maximum 7). The millisecond1,064 nmNd:YAGlasertreatmentscouldresult average interval between treatments was 24.5 days with in substantial reduction in scarring by stimulating collagen a range from 18.7 to 33.0 days. Follow-up photographs were formation resulting in smoothing of the skin. taken,onaverage,9months(rangeof3–10months)afterthe finaltreatment.Patientagesrangedfrom18to47yearswith OBJECTIVES a mean of 28.6 years. The average number of pulses per The primary objective of this retrospective study is to procedure was 11,700 pulses ranging from 8,000 to 13,900 determine the safety and efficacy of this unique pulse pulses. The patient-to-patient variation in the number of modality to reduce the signs of atrophic scarring, texture, pulses was associated with the size of the surface area and PIH secondary to the acne condition in darker skin treated, not with the treatment indication. Treatment types. The secondary objective is to assess the incidence of parameters used on each patient are listed in Table 1. PIH resulting from the laser treatments. To optimize laser results, the skin was treated with micro- dermabrasion (MDA) throughout the sub-millisecond STUDY DESIGN AND METHODS 1,064 nm Nd:YAG laser treatment series. Ten sessions of This is a retrospective study evaluating the safety and MDA were administered with an interval of 7–10 days efficacy of a sub-millisecond 1,064 nm Nd:YAG laser. between each session. A minimum of 3 days was allowed Treatments were conducted at the National Institute of between MDA and laser treatments.

TABLE 1. Treatment Parameters and Follow-Up Times

No. of pulses No. of No. of days Follow-up post-final Patient Age per treatment treatments between treatments treatment (months) 1 25 10,000 6 20.2 9 2 22 11,500 5 21 3 3 36 12,400 7 22.5 9 4 26 11,800 7 31 9 5 29 13,400 7 23 8 6 42 10,000 5 24.2 9 7 24 10,400 7 23.2 8 8 27 12,000 7 26.8 9 9 22 13,700 6 18.7 10 10 29 11,800 6 22 10 11 23 12,000 6 23.1 9 12 40 10,200 5 29 10 13 28 15,000 6 22.6 9 14 18 12,500 6 20.6 9 15 21 12,000 6 22.2 10 16 25 13,800 7 27.3 9 17 30 13,900 5 21.7 9 18 26 8,600 6 28.6 9 19 31 9,700 5 21 10 20 27 12,400 5 26.7 10 21 32 12,300 6 30.7 9 22 47 8,000 6 33 9 Average 28.64 11,700 6 24.5 9 132 BADAWI ET AL.

Following the MDA treatment, the whole face was treated and five were excluded from pigment analysis. Images were with the sub-millisecond 1,064 nm Nd:YAG laser. No excluded due to insufficient focus, color balance, and/or additional passes were applied on the areas of atrophic lighting. scarring. The hand piece was held 1–2 cm off the face with The results of the blinded photo assessments indicated continuous motion to build heat and erythema in the treat- clinically and statistically median improvement of 2 in ment areaprior tomovingtoanadjacentpart oftheface.The scarring, 2.3 in texture, and 2 in PIH (P < 0.001). surface area for each treatment region was approximately Figure 1 displays the median improvement scores and the 5cm 5 cm square. The total and average number of variability of data for all three conditions (scale of 0–3). pulses per treatment, and the total number of treatments Figure 2 displays photos from seven different patients per patient are also shown in Table 1. with follow-up times. Subject characteristics and treatment Three independent physician reviewers (two dermatolo- parameters used on a particular patient can be found in gists and one plastic surgeon) were asked to identify the Table 1. before and after treatment photos which were presented to Transient mild edema and erythema were observed in all the physicians for assessment in random order. After select- patients and resolved within 2 hours after treatment. ing the before and after image, reviewers were asked to rank No transient or permanent complications such as blister- the degree of improvement in scarring, texture, and PIH ing, crusting, purpura, scarring, transient or permanent using a four-point scale (0 ¼ <25%, 1 ¼ 25–50%, 2 ¼ 51– hyper- or hypo-pigmentation were noted. 75%, 3 ¼ 76–100%). Any indication which did not apply to a There was no single patient who reported any adverse patient was marked as N/A. The median improvement score effects during or after the treatment sessions till the end of was calculated based on scores from all three reviewers. the follow-up period in this study. When the before photo was incorrectly selected as the after photo (onecaseonly), the negativevalue of theimprovement score was used in calculating the median score taking into DISCUSSION account the magnitude of deterioration as assessed by the Retrospective photographic analysis of 22 cases in this reviewer. This was done instead of excluding this case to study indeed shows that sub-millisecond 1,064 nm Nd:YAG avoid any bias in the data analysis. laser may be a viable treatment modality capable of gener- Patients were evaluated for erythema, edema, purpura, ating improvement in texture, scarring, and PIH secondary blistering, crusting, hypo- and hyper-pigmentation, and to the acne condition in darker skin types. Blinded photo scarring. Patients were also asked if they observed any assessments by three independent physicians indicated adverse reaction of the above or any other skin reaction they that six treatments performed, on average, 24.5 days apart consider adverse between visits. resulted in clinically and statistically significant improve- ment in atrophic scarring, texture, and PIH in patients with Statistical Analysis skin types III–VI. High consistency between reviewers was Statistical analysis was performed usingMinitab statisti- observed in identifying before and after photos. cal package, version 15.1.20.0 (Minitab, Inc., State College, It is noteworthy to state that (1) the non-invasive treat- PA). For statistical testing, two-sided one-sample Wilcoxon ments with the sub-millisecond 1,064 nm Nd:YAG laser signed rank test was used, and P values <0.05 were con- improved the existing PIH from acne scarring; (2) did not sidered statistically significant. Additionally, the medians induce additional PIH; (3) did not require pre- and post- and spread of the data were displayed in box plot graph. treatment agents to control PIH in dark skin patients; Kappa agreement analysis [14,15] was performed to (4) did not require anesthetic. measure the inter-reviewer reliability of before and after The percentage of subjects with skin types IV and V photos assessments and the kappa coefficient was reported. included in studies for the treatment of atrophic scarring are very limited compared to lighter skin types due to pig- RESULTS mentation concerns [1–3]. Even with the use of hydro- quinone pre- and post-treatment, a recently published Blinded Photo Assessments prospective study of 15 subjects with skin types IV–VI Two reviewers correctly identified all photos (22/22). The and acne scarring using Erbium-doped YAG laser showed thirdreviewerincorrectlylabeledonepairofbeforeandafter a 50% rate of the PIH [12]. In the same study, the pain levels images and was not able to identify another pair of photos were reported to increase as the skin type went from IV to VI duetoinsufficientimagequality(20/22).Thereviewerswere and as the number of passes went from 1 to 8. highly consistent (inter-reviewer reliability, kappa of 0.88) One challenge faced in this retrospective study was not all inidentificationofbeforeandafterphotos(kappacoefficient: patient photos had sufficient image quality. As a result, a poor <0.20, fair 0.21–0.40, moderate 0.41–0.60, good 0.61– couple of photos were excluded from the data analysis. 0.80, and very good 0.81–1.00). The second challenge was the data only captured an overall Of the 66 possible image reviews for each category (22 percentage improvement without assessments of severity images each reviewed by three physicians), one was deter- and types of scars at baseline and follow-up. This was due to mined by one reviewer as insufficient quality to grade before the lack of high-resolution standardized photos. In future and after. Additionally, four images were excluded from studies,high-resolutionphotosofscarring(usingmacrolens scarring analysis, four were excluded from texture analysis, settings without flash [7] or a three-dimensional optical SUBMILLISECOND ND:YAG LASER IN SCAR TREATMENT 133

Fig. 1. Median improvement of 2 in scarring, 2.3 in texture, and 2 in pigment based on blinded photo assessments by three reviewers. The box illustrates the 25th percentile to the 75th percentile with a line placed at the median (50% percentile). The bottom and top ends of whiskers show the minimum and maximum, respectively. profiling system) should be used for objective assessment of Nd:YAG is absorbed by melanin and hemoglobin and is scar severity and type [6,8]. Lastly, it would be beneficial to subsequently used for vascular and hair reduction treat- collect data on patient satisfaction in addition to physician ments. Pulse durations in these treatments are in the 10– assessments. 100 milliseconds range, roughly 30–300 times longer than The theory behind combining MDA treatments with laser the pulse durations used in this study. The short pulse treatments was to reduce the thickness of the stratum cor- durations used in sub-millisecond treatment does not neum thereby allowing greater light penetration to the pap- change the characteristics of chromophore absorption. At illary dermis. Thus, MDA treatments performed before the these short pulse durations, the laser energy is heating fine laser treatments were mild in intensity to prevent discom- structures during each pulse, thus more selectively target- fort or complications from deep dermal abrasions [16]. The ing the microvasculature in the papillary dermis and mel- conservative MDA settings used in this study were not anocytes within the epidermis without actually damaging considered effective to treat acne scarring and PIH and were the epidermis or larger vessels in the dermis. unlikely to have had an effect on the observed improvement The second mechanism of action occurs through bulk [17–19]. Nonetheless, randomized split face studies would heating. The laser uses a 5 mm spot pulsing at 5–10 Hz to be required to definitely determine whether MDA is necess- deliverlargeamountsofenergyinrelativelyshortburststoa ary or has an additional benefit when used in combination finite area of tissue. Heat conducts to surrounding tissue with laser treatments. over time to create bulk heating in each treatment. The In previous studies, the sub-millisecond 1,064 nm degree of bulk heating is a function of total energy delivered Nd:YAG laser therapy has been shown to stimulate collagen per unit area per unit time. The goal during treatment is to [13] and to improve scar severity [20]. However, no assess- deliver energy to an area of tissue faster than the body can ment has been performed on secondary improvement to extract the heat. For this reason, skin cooling is not desired texture and pigment. We hypothesize that the sub-milli- during treatment. This bulk heating occurs gradually and second Nd:YAG laser works through two parallel actions non-selectively through heat conduction, so no structures to safely stimulate collagen and improve discoloration. The are specifically targeted. This allows for safe treatment, firstmechanisminvolvesdiscretecellulardamagecausedby even on type VI skin. direct absorption in hemoglobin, melanin, and water during each pulse and bulk heating from cumulative pulsing in a region. As a result, damage created through direct absorp- CONCLUSIONS tion and through sustained time at elevated temperature Preliminary data collected in this retrospective study initiates a healing response, prompting collagen stimu- suggest that sub-millisecond 1,064 nm Nd:YAG laser treat- lation [21,22]. ments are safe and effective for treating atrophic scarring in Fig. 2. Patient photos (1, 3, 4, 13, 14, 15, 20) at baseline and at follow-up visit after final treatment. Patient 1: (a) Baseline, (b) 9 months post-final treatment (six sessions). Patient 3: (a) Baseline, (b) 9 months post-final treatment (seven sessions). Patient 4: (a) Baseline, (b) 9 months post-final treatment (seven sessions). Patient 13: (a) Baseline, (b) 9 months post-final treatment (six sessions). Patient 14: (a) Baseline, (b) 9 months post-final treatment (six sessions). Patient 15: (a) Baseline, (b) 10 months post-final treatment (six sessions) Patient 20: (a) Baseline, (b) 10 months post-final treatment (five sessions). SUBMILLISECOND ND:YAG LASER IN SCAR TREATMENT 135

Fig. 2. (Continued )

patients with darker skin types, delivering clinically and 6. ChapasAM,BrightmanL,SukalS,HaleE,DanielD,Bernstein LJ, Geronemus RG. Successful treatment of acneiform scar- statistically significant results with reduced risk of pigment ringwithCO2 ablativefractionalresurfacing.LasersSurgMed complications. This offers a new standard of care or first 2008;40(6): 381–386. treatment option for patients with a high risk of pigmentary 7. Deng H, Yuan D, Yan C, Lin X, Ding X. A 2940 nm fractional complications. Prospective studies with the sub-millisecond photothermolysis laser in the treatment of acne scarring: A pilot study in China. J Drugs Dermatol 2009;8(11): 978–980. Nd:YAGlaseralonearerequiredtofurtherassesstreatment 8. Walgrave SE, Ortiz AE, MacFalls HT, Elkeeb L, Truitt AK, outcomes considering the effect of number treatments as Tournas JA, Zelickson BD, Zachary CB. Evaluation of a novel well as to determine targeted treatment parameters for fractional resurfacing device for treatment of acne scarring. Lasers Surg Med 2009;41(2): 122–127. improved effects on scars of various severity and type. 9. Dover J, Arndt K, Geronemus RG, Alora MB. Laser resurfac- Further, randomized split face studies are needed to show ing. In: Dover Jeffrey S., Arndt Kenneth A. editors. Illustrated the treatment effect and the incidence of PIH compared cutaneous & aesthetic laser surgery. Stanford: Appleton & Lange 2000: 81–112. to non-treated and treated controls with alternative 10. Goldman MP, Weiss RA. Laser resurfacing with the treatments. UPCO2þEr:YAG lasers. In: Goldman Mitchel P., Weiss Robert editors. Advanced techniques in dermatologic surgery. ACKNOWLEDGMENTS New York: Taylor & Francis 2006: 219–239. 11. Fitzpatrick RE. Skin resurfacing with carbon dioxide and The authors would like acknowledge the cooperation erbium lasers. 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ORIGINAL ARTICLE

Treatment of genital warts in males by pulsed dye laser

ASHRAF BADAWI1,2, HISHAM A. SHOKEIR1, AHMED M. SALEM3, MONA SOLIMAN1, SAHAR FAWZY4, NEVINE SAMY1 & MANAL SALAH1

1National Institute of Laser Enhanced Sciences (NILES), University of Cairo, El-Giza, Egypt, 2Szeged University, Hungary, 3Department of Andrology and Sexually Transmitted Diseases, Cairo University Hospital, Cairo, Egypt, and 4Department of Dermatology and Venereology, Azhar University, Cairo, Egypt

Abstract Objective: To determine the safety and efficacy of the flashlamp-pumped pulsed dye laser for the treatment of uncomplicated genital warts in adult males. Methods: This was a prospective observational study set in the outpatient clinics of the Department of Andrology and Sexually Transmitted Diseases, National Institute of Laser Enhanced Sciences, the Dermatology Clinic, Cairo University, and the Department of Dermatology and Venereology, Suez Canal University. A total of 174 adult male patients with 550 uncomplicated anogenital warts were included. Selective photothermolysis and photocoagulation of the lesions with the flashlamp-pumped pulsed dye laser was carried out. A pulsed dye laser (wavelength 585 nm, 450 s pulse duration; Cynosure, USA) was used with the following settings: spot size 5–7 mm; fluence 9–10 J/cm2. Results: Complete resolution of treated warts was achieved in 96% of lesions. Side effects were limited, transient and infrequent. Lesion recurrence rate was 5%. Conclusion: The pulsed dye laser has been found to be safe, effective and satisfactory for the treatment of anogenital warts in males. It could be used to selectively destroy warts without damaging the surrounding skin.

Key words: Genital warts, pulsed dye laser

Introduction that are visible with colposcopic magnification of A written description of condylomatous warts of the epithelium that has been treated with a mild acetic genital tract and anus dates as far back as the first acid (vinegar) solution, or as SILs that are diagnosed century AD (1,2). Within the first decade of the last microscopically on the basis of characteristic century, the viral etiology of genital warts was cytologic and histologic features (7). demonstrated (3). At least 35 of over 100 different A number of years after initial infection, some human papillomavirus (HPV) types primarily infect individuals with HPV are at risk of developing genital epithelium (4,5). Although most external (8). Individuals presenting genital warts are positive for HPV 6 or 11 DNA, and with genital warts rarely report symptoms other than most invasive squamous cell cancers of the genital the appearance of new bumps or growths on their tract and anus are positive for HPV 16, 18, 31, 33, genitalia. Occasionally, patients will report itching, or 45 DNA, squamous intraepithelial lesions (SILs) burning, pain, or bleeding. Some, perhaps most, of the cervix, vagina, , penis and anus are individuals with genital warts never become aware of associated with many different HPV types (6). their presence (9). Genital HPV infections are transmitted primarily In males, most genital warts occur on the penis, through sexual contact, with an average incubation scrotum, urethral meatus and perianal area (10). period of 2 months. The majority of newly acquired Because genital warts frequently occur with more genital HPV infections appear to be subclinical and than one lesion on the genital site and with lesions asymptomatic. Clinically visible manifestations of on different genital sites, it is important to examine HPV include warts that may be condylomatous, the entire genitalia. Use of (3–5%) papular, flat, or keratotic in appearance. Subclinical solution to detect ‘subclinical’ HPV infections of infections may appear as flat ‘aceto-white’ lesions the external genitalia is not recommended because

Correspondence: Ashraf Badawi, National Institute of Laser Enhanced Sciences (NILES) and Szeged University, Hungary. E-mail: [email protected]

(Received 2 December 2005; accepted 22 March 2006) ISSN 1476-4172 print/ISSN 1476-4180 online # 2006 Taylor & Francis DOI: 10.1080/14764170600617490 Treatment of genital warts by PDL 93 the predictive value and therapeutic benefit of this General examination for the whole body, includ- procedure has not been established (11). ing the oral mucosa, was done for signs of sexually The four morphologic types of genital warts are transmitted diseases (STDs) (for example, vesicles, condylomata acuminata, which have a cauliflower- ulcers, warts, mucous patches, lymph node like appearance; papular warts, which are flesh- enlargement). colored, dome-shaped papules, usually 1–4 mm Local genital examination was done while the in diameter; keratotic warts, which have a thick, patients were completely uncovered from the umbi- crust-like layer and may resemble common skin licus down to the knee. The skin of the lower warts or ; and flat-topped abdomen, penis, scrotum, perineum, perianal area, papules, which appear macular to slightly raised. upper thighs, and the urethral meatus were In general, condylomata are most frequently inspected under good illumination for the presence detected on moist, partially keratinized epithelium, of warts and other STDs. In all settings, patients papular and keratotic warts on fully keratinized with genital warts were examined and treated for epithelium, and flat papular warts on either partially other STDs. Whenever possible, their wives or or fully keratinized epithelium (10,12,13). Genital current sexual partners were also offered examina- wart therapies are classified as patient-applied or tions and treatments for macroscopically visible provider-administered. warts and other STDs. Examination of the anogen- Patient-applied treatments include podofilox ital warts was done and the following data were solution and gel, and imiquimod cream (14,15). recorded: site, number, type, area, presence of To self-treat, patients must be able to identify and complications such as ulcerations or bleeding. The reach the warts and to follow the treatment applica- wart area was estimated as follows: the two largest tion instructions. The provider-administered treat- perpendicular diameters were measured, and the ments include topical treatments (cryotherapy, wart area was defined as the product of the two podophyllin resin, trichloroacetic acid, bichloroace- measurements. tic acid, and external application and intraurethral Finally, a total of 174 adult males with 550 instillation of bacillus Calmette–Guerin); excisional uncomplicated anogenital warts and with no history of topical or systemic therapy for warts during the treatments (curettage, electrosurgery, scissors exci- last 2 months were included and treated by pulsed sion, or laser vaporization); or injectable treatments dye laser. A pulsed dye laser (585 nm, 450 s pulse (interferon or 5-fluorouracil/epinephrine gel implant) duration; Cynosure, USA) was used with the (15–24). following parameters: spot size 5–7 mm according Tuncel et al. (24) used the pulsed dye laser for to the size of the lesions, and fluence 9–10 J/cm2. treatment of perianal warts in children. They found Overlapping pulses were done, up to three to four the pulsed dye laser to be effective and less traumatic pulses, until the appearance of grayish discoloration compared with other treatment options. To the best of the lesions which was an end point for lesion of our knowledge, there are no previous studies coagulation. evaluating the role of the pulsed dye laser in the Treatments were repeated every 2 weeks with a treatment of genital warts in adult males. maximum of three sessions. Topical antibiotic Based on these data, the aim of this study was to ointments were prescribed between the sessions to determine the safety and efficacy of the flashlamp- be used for a period of 7–10 days following every pumped pulsed dye laser for the treatment of session. The number of warts, and the area of warts uncomplicated genital warts in adult males. at presentation and at the end of treatment was recorded. Any adverse reactions were also recorded. Patients were followed-up for at least 4 months after Patients and methods the warts had cleared. The present study was carried out on adult males with anogenital warts. They were recruited from patients attending the outpatient clinics of Results the Department of Andrology and Sexually The mean age of patients included was 31.33¡4.7 Transmitted Diseases, National Institute of Laser years (range from 22 to 49). The mean duration of Enhanced Sciences, the Dermatology Clinic, Cairo lesions was 4.29¡3.15 months (range from 1 to 48). University, and the Department of Dermatology and The number of warts ranged from one to 14 per Venereology, Azhar University. History taking was patient (average 3.82¡4.33). Warts were frequently done with special emphasis on age, marital status present with more than one lesion on one anatomical and extramarital relations, including homosexual site. Warts were also present more frequently on practice, duration and course of lesions, associated different genital sites (104 patients, 59.78%) and on urethral discharge, genital ulceration, skin rash, one genital site in 70 patients (40.22%). Among previous treatments, and any similar condition in those latter patients, lesions were present on the the patient’s wife or sexual partner(s). penis in 39 (22.41%), on the scrotum in 11 (6.32%), 94 A. Badawi et al. on the urethral meatus in four (2.29%), and on the majority of cases (Figure 1). Lesion recurrence rate perianal area in 16 (9.2%). The mean area of lesions was 5%. Recurrence was defined as a new wart at the was 26.9 mm2 and the area varied from 6 mm2 to 64 same site detected within the 4-month follow-up mm2. With regard to the morphological type of warts period after clearance of lesions. detected, it was predominantly condylomatous in 129 patients, papular in 31, keratotic in nine, and Discussion flat-topped papules in five patients. Complete clearance of 528 anogenital warts Management of genital warts presents a problem of (96%) treated by pulsed dye laser occurred after increasing magnitude to genitourinary medicine. one to three sessions. A few small warts of short Choice of treatment is guided by patient preference, duration occurring on one anatomical site cleared with consideration given to the patient’s age and significantly after fewer sessions and resulted in ability to comply with moderately complicated earlier clearance. Patients with fewer than three and directions, to the location and number of warts, 2 with an area less than 20 mm cleared most and to the clinician’s training. Many conventional frequently after one session. Other factors such as lines of therapy are used, the aim of which is to a patient’s age and the morphological type did not destroy the infected tissue; however, none are affect the treatment results. Overlapping pulses consistently effective, making genital warts a ther- (three to four) revealed better clearance of warts apeutic challenge. Laser therapy had been used for than single and even double pulsing. Side effects the treatment of genital warts since the 1970s (25). were infrequent and transient, mostly in the form of CO2, argon, Nd:YAG and Er:YAG lasers have been mild pain at treatment and transient hypopigmenta- used, especially for refractory genital warts, giant tion after treatment. Patients were followed-up for at condyloma acuminatum or Buschke–Lowenstein least 4 months (up to 9 months in some cases). tumor, with variable degrees of safety and efficacy Complete resolution and healing of skin without (26–30). scaring or texture changes were found in the The pulsed dye laser was used initially for selective photothermolysis of vascular lesions, whereby the wavelength is selectively absorbed by the oxyhemo- globin, leading to destruction of the vascular component of the tissue. It was also used in the management of other non-vascular lesions, depend- ing on the photothermal effect of laser on the cutaneous tissue¡its selective photothermolysis effect. The pulsed dye laser was used for the management of simple and recalcitrant verrucae vulgaris on different sites of the body using fluencies ranging from 6 to 9 J/cm2 (31). Other studies reported higher fluencies of 9.4 J/cm2 giving variable clearance rates (32). Tuncel et al. (24) used the pulsed dye laser for the management of perianal warts in children with a fluence of 7.5 J/cm2. In our study, we used higher fluencies of 9–10 J/cm2, which ensured greater destruction of the vascular component of the lesions. The overlapping pulses increased the photothermal effect of the laser radiation leading to coagulation of the lesions and immediate graying of the warty tissue. The technique was done as an outpatient procedure and did not require any infiltration anesthesia as in electrocautery or surgery, which is another advantage of the pulsed dye laser in the treatment of genital warts. It is safe in comparison to the toxicity of podophyllotoxins, which are continu- ously investigated in an attempt to increase efficacy and decrease toxicity (18). In the light of results from our study, in which there was a significant number of patients presenting with multiple and/or large size 5 lesions, complete resolution and healing Figure 1. A penile condylomata acuminate: (A) before treatment; of skin without scaring or texture changes were (B) after treatment (three sessions). found in the majority of cases. This is in contrast Treatment of genital warts by PDL 95 with what is usually found with other traditional 13. Meisels A, Fotin R. Condylomatous lesions of the cervix and treatments such as electrocautery, surgical excision, vagina. I. Cytologic patterns. Acta Cytol. 1976;20:505. cryotherapy or CO laser. 14. Kinghorn GR, McMillan A, Mulcahy F, Drake S, Lacey C, 2 Bingham JS. An open, comparative, study of the efficacy of Lesion clearance rate in our study was 96%, which 0.5% 6 podophyllotoxin lotion and 25% podophyllotoxin is superior to that achieved by the more widely used solution in the treatment of condylomata acuminate in males treatment modalities (32–88%) (11,15). Better and females. Int J STD AIDS. 1993;4:194. results (smaller number of sessions and earlier 15. Beutner KR, Ferenczy A. Therapeutic approaches to genital clearance) were observed with lesions of short warts. Am J Med. 1997;102:28. duration and in cases with a small number of warts 16. Von Krogh G. Management of anogenital warts (condylo- mata acuminata). Eur J Dermatol. 2001;11:598. occurring on one anatomical site. On the other hand, 17. Beutner KR, Tyring SK, Trofatter KF Jr, Douglas JM Jr, failure of treatment that occurred only in 4% of cases Spruance S, Owens LL, et al. Imiquimod, a patient- was observed in highly recalcitrant lesions with a applied immunoresponse modifier for treatment of external large number of warts, which might be attributed to genital warts. Antimicrob Agents Chemother. 1998;42: increased fibrosis and hyperkeratosis due to previous 789–94. 18. Bohle A, Doehn C, Kausch I, Jocham D. Treatment of attempts of treatment. Lesion recurrence rate (5%) recurrent penile condylomata acuminata with external appli- was also less than reported with other treatment cation and intraurethral instillation of bacillus Calmette- modalities (8–22%) (16). Post-treatment recurrence Guerin. J Urol. 1998;160:394. rates are not well defined in most studies because in 19. Metawea BA, Elnashar AM, Ismail IK, Kasem W. most cases either too few subjects have been studied Application of viable bacillus Calmette-Guerin topically as a or follow-up protocols had not been standardized primary treatment in condylomata acuminata. MSc Thesis. Cairo: Cairo University Press; 2002. (11). 20. Gay C, Terzibachian JJ, Gabelle C, Reviron S, Ramanah R, In conclusion, the pulsed dye laser has been found Mougin C. Carbon dioxide laser vaporization of genital to be a safe, effective, and satisfactory treatment for condyloma in pregnancy. Gynecol Obstet Fertil. 2003; genital warts. 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Bacteriol Rev. 1967;31:110. 1999;25:377. ÜBERSICHTEN REVIEWS

Flache Warzen können erfolgreich mit einem langgepulsten Nd-YAG Laser behandelt werden Plane warts can be managed success- fully using long pulsed Nd-YAG laser

Nevien Samy1, Manal Salah2, Mona Soliman3,Ashraf Badawi4

Schlüsselwörter Key Words Nd-YAG laser, flache Warzen Nd-YAG laser, plane warts

Zusammenfassung Summary Hintergrund: Die am häufigsten vorkommenden Warzen sind flache Background: Most common warts are flat warts. To date, no treatment Warzen. Bis heute gibt es keine Behandlungsmethode die 100prozentig method has been totally safe and effective in clearing warts. Traditional sicher und effektive ist in der Entfernung von Warzen. Herkömmliche treatment modalities have focused on the destruction of infected tissue Behandlungsmethoden fokussieren auf die Zerstörung infizierten through a variety of techniques. Objective: Evaluation of long pulsed Nd- Gewebes mittels vielfältiger Techniken. Ziel: Evaluierung des YAG laser for the treatment of plane warts. Selecting the most effective langgepulsten Nd-YAG Lasers in der Behandlung flacher Warzen. laser parameters for destruction without any side effects. Selektion der wirksamsten Laserparameter für die Destruktion, ohne Patients and Methods: Forty-two patients were enrolled in the study. Nebenwirkungen. Patients complained from recalcitrant plane warts on the forehead, Patienten und Methodik: 42 Patienten nahmen an der Studie teil. Die cheeks, chin, neck, arms and dorsum of the hands. Treat-ment was Patienten klagten über persistierende Warzen auf Stirn, Wangen, Kinn, carried using long pulsed Nd-YAG laser (1064 nm) apply-ing double or Hals, Armen und Handrücken. Zur Behandlung wurde ein langgepulster triple overlapping pulses. Our end point was light greyish discoloration Nd-YAG Laser (1064 nm) eingesetzt und doppelt oder dreifach of the lesion. überlappende Impulse angewandt. Unser Endpunkt war die leicht Results: Thirty-five cases experienced complete clearance of their warty gräuliche Verfärbung der Läsion. Ergebnisse: Bei 35 Patienten wurde lesions without any complications, while partial response was observed ohne Komplikationen eine vollständige Remission der Warzen erreicht, in 7 patients. Four cases complained about post inflammatory während bei 7 Patienten nur eine Teilremission erreicht wurde. 4 hypopigmentation which lasted for eight weeks with spontaneous Patienten klagten über postinflammatorische Hypopigmentation, die aber resolution. One case experienced post inflammatory hyperpigmentation. nach 8 Wochen spontan verschwand. Bei einem Patienten kam es zu Two cases had recurrence of their lesions after three months. All the postinflamma-torischer Hyperpigmentation. Nur in zwei Fällen kam es zu cases were followed up for at least six months after the last treatment rezidiven innerhalb von drei Monaten. Alle Fälle wurden mindestens session. sechs Monate nach der letzten Behandlung nachuntersucht. Fazit: Der Conclusion: Long pulsed Nd-YAG laser can be used for treatment of langgepulste Nd-YAG Laser kann effektiv und sicher, ohne plane warts as an effective, safe method with minimal complica-tions. Komplikationen, in der Behandlung flacher Warzen eingesetzt werden.

Introduction Nd-YAG laser in the treatment of common warts. Our goal was to deter- mine response rates in such a fashion. Warts are benign epithelial neoplasm of the skin and mucosa result-ing from human papilloma virus infection. They are a common der-matologic Material and Methods complaint, with an estimated incidence of 10% in children and young adults. Treatment of warts can be difficult, with most approaches relying Fifty patients with a total of 326 verrucae were enrolled in the study over 8 on physical destruction of infected keratinocytes. Common therapeutic months period. They were 23 males and 27 females, with a mean age of approaches include liquid nitrogen, cryother-apy, topically applied acids, 26.5 (12-41) years old. All patients were complaining of flat warts mainly electro surgery, cantharidin application, bleomycin injection [1-6]. There on the forehead, cheeks, chin, neck, arms and the dorsum of the hands. have been several retrospective reviews of the use of pulsed dye laser, Inclusion criteria included no treatment of lesions within the past month, CO2 laser, KTP laser and Er-YAG laser therapy for warts. Initial reports and no history of constitutional or iatrogenic immunosuppression. All appeared promising with significant clearance rates [7-11]. However, more patients gave informed consent. The study was completed by 42 patients, recent studies have suggested that success may be more modest [10-12]. which completion defined as clearance of all visible warts or a maximum To date, there have been no trial evaluating the efficacy of long pulsed of 3 treatment ses-sions on the same lesion.

1 Lecturer of Dermatology, Dermatology Unit, NILES, Cairo University, Cairo, Egypt. 2 Assistant Professor of Dermatology, Dermatology Unit, NILES, Cairo University, Cairo, Egypt. 3 Professor f Dermatology, Dermatology Unit, NILES, Cairo University, Cairo, Egypt. 4 Lecturer of Dermatology, Dermatology Unit, NILES, Cairo University, Cairo, Egypt, Visiting Lecturer, Szeged University, Hungary.

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Treatment sessions consisted of treatment with the long pulsed Nd-YAG Many types of lasers have been used for the management of warts. laser (1064 nm, Coolglide, Cutera, RIT 220 Excl.) with 20-30 msec. pulse Carbon dioxyde laser vaporization for infected tissue was used [17]. duration and fluence between 95-110 J/cm2, with 5,7 mm spot size Results were not superior than the ordinary electrocautery which remove according to the size of the lesion, applying double or triple overlapping blindly the infected tissue as well and may sometimes lead to textural pulses. Our endpoint was light greyish discoloration of the lesion. changes. Several investigators have demonstrated the efficacy of 585 nm pulsed dye laser in treating warts [7-12]. The mechanism of action may be Following treatment, there was slight perilesional erythema. Very minimal a result of intense heating of dermal vessels with collateral damage of heat sensation or sometimes slight burning pain was experienced virally infected keratinocytes. This theory is based on the presence of especially in children. Topical anaesthetic cream of 5% lido-caine and dilated and congested vessels at the base of most of verrucae [18] and 3.5% prilocaine was used only in cases of children or with patients of low the mechanism of selective photother-molysis [19] that result in targeting pain threshold. Treatment sessions were carried every 2 weeks with a of haemoglobin by pulsed dye laser. To our knowledge, one report used maximum of 3 sessions on the same lesion. All patients and health care KTP laser at 532 nm wave-length for treatment of recalcitrant pigmented providers wore protective eyewear and micropore laser masks. A smoke warts, through selec-tive photothermolysis and propagation of evacuator was used as a precaution against potential aerosolised viral photoacoustic waves [20]. particles. Photographs were obtained at the initial visit and at 3 months follow up after the last treatment session. Nd-YAG laser hyperthermia proved to be effective in treatment of resistant warts with significant clearance of the lesions and absence of viral Results particles [21], but it cannot be performed on very sensitive areas for example lesions on the face, neck or cheeks. Patients will not tolerate the Of the 50 patients initially enrolled, 42 patients with a total of 256 warts procedure since it is done without anaesthesia and needs laser exposure completed the study. The 8 patients who withdrew, were for reasons time of 1-2 min in comparison to the pulsed lasers with micro and unrelated to treatment. In the evaluation of treatment response, complete milliseconds pulse durations. Thus laser hyper-thermia is not practical for response was defined as complete absence of clinically apparent warts large number of lesions. without any textural changes such as fibro-sis or scar formation. Partial response was defined as greater than 50 % reduction in wart size or The Nd-YAG laser is one of the most versatile and interesting lasers in number. dermatological laser medicine. Almost no other laser has such a wide spectrum of applications. Depending on wavelength (1064 nm) and mode Complete response was observed in 35 patients (83.3%) Fig. 1-3, while (continuous, Q-switched, long pulsed), it is applied on benign pigmented, partial response was observed in 7 patients (16.7%). No case showed no vascular lesions and permanent hair reduction [22, 23], due to the fact response to the lesion treatment. The mean number of treatments to that 1064nm is absorbed by all the skin chro-mophores. Reports using achieve complete response was 2.00, while the mean number of long pulsed Nd-YAG laser as an effective line of treatment for vascular treatments to achieve partial response was 2.65. Postoperative lesions such as telengietasia and venous lakes [24], encouraged us to use complications such as transient post inflammatory hypopig-mentation was this laser system for thermal destruction of resistant flat warts. With its observed only in 4 cases and only 1 case experienced transient post deeper penetration and lower absorption coefficient for melanin, there is inflammatory hyperpigmentation and was given hydroquinone 4% cream. less concern for col-lateral epidermal damage [25]. The recurrence of warts during follow up period was reported only in 2 cases. As regards patient satisfaction, ninety two percent of all patients Unlike ablative treatment modalities, with long pulsed Nd-YAG laser even those who experienced partial response were satisfied with the therapy, no wound was created, especially if the lesions were on exposed treatment they were given. parts of the body mostly head and neck as in our study, thus avoiding prolonged post operative pain, scarring or downtime. Applying the pulsed Discussion mode of laser system, made the technique toler-able by the patients, most of whom returned to work or normal activ-ities immediately Common warts are hyperkeratotic papulonodules most often seen on the postoperatively. There was no need for local infiltration anaesthesia (only hand, arms and legs, but can seen anywhere on the glabrous skin. topical anaesthetic cream was used for selected cases) was another Common verrucae represent the most frequent clinical lesions produced advantage. by human papillomavirus [13]. Verruca plana (flat warts) are less exophytic than common warts, frequently presenting as sev-eral or dozen The limited number of sessions up to three sessions in our protocol was to of subtle papules 2-6 mm in diameter elevated above the surface less be comparable to other treatment modalities such as topical retinoids, than a millimetre or so. These can be quite subtle, and may be missed by chemical cautery also for the cost benefit wise. Most of the patients who a casual observer. Pigmentary disturbances may be the most disturbing experienced partial response was due to their large number of warty part of the flat wart infection to the patient. These lesions are frequently a lesions, most of the lesions were not de novo, they were being treated problem on the face and the glabrous skin of non-immunocompromised before and lasted for more than six months. The risk of high incidence of individuals. At present, therapies aim to remove the lesion rather than post inflammatory hyperpigmentation is minimized by preferentially specifically target human papillomavirus infection. Many different types of sparing epidermal pigment. The proce-dure proved to be acceptable and therapy have been used in treatment of verrucae. Commonly used effective by the patients. Our methods of physical destruction include: electrodessication, cryosurgery and laser therapy. Chemical destruction is induced with salicylic acid, cantharidin, among others. Chemotherapeutic agents include podophillin resin and 5-fluorouracil. More recently immunomodulators such as interferon, systemic retinoids have been used [14-16].

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A Before treatment B Immediately after treatment C After 2 laser treatments

Figure 1

A Before treatment B Immediately after treatment C After 2 laser treatments Figure 2

A Before treatment B Immediately after treatment C After 2 laser treatments

Figure 3

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ÜBERSICHTEN REVIEWS References results are comparable to pulsed dye laser treatment 1 Cobb MW (1990) Human papillomavirus infection. J Am Acad Dermatol 22: modalities which was another positive point, with an 547-66. 2 Bunney MH, Nolan MW, Williams DA (1976) An assessment of methods advantage over the pulsed dye laser of having no post of treating viral warts by comparative treatment trials based on a standard laser purpura and no consumables such as dye kit. design. Br J Dermatol 94: 667-79. 3 Gibbs RC, Scheiner AM (1978) Long-term follow-up evaluation of Conclusion and Recommendations patients with electrosurgically treated warts. Cutis 21: 383-4. Long Pulsed Nd-YAG laser can be added to the long 4 Shumer SM, O Keefe EJ (1983) Bleomycin in the treatment of recalcitrant trant warts. 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Patients with previous criteria, long pulsed Nd-YAG 9 Vargas H, Hove CR, Dupree ML, William EF (2002) The treatment of facial verrucae with pulsed dye laser. Laryngoscope 9: 1573-6. laser would be significantly more costly effective than 10 Kopera D (2003) Verrucae vulgares: flashlamp-pumped pulsed dye laser other treat-ment modalities. treatment in 134 patients. Int J Dermatol 11: 905-8. 11 Wu C, Langan S, Kilmurray M, Lawlor D, Watson R (2003) Efficacy of pulsed dye laser for viral warts- an internal audit. Ir Med J 3: 80,82-3. Address of Correspondence: 12 Komericki P, Akkilic M, Kopera D (2006) Pulsed dye laser treatment of Dr. Ashraf Badawi Dermatology genital warts. Lasers Surg Med 38: 273-6. Unit 13 Kilkenny M, Marks R (1996) The descriptive epidemiology of warts in the community. Australas J Dermatol 2: 80-86. 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März 2008, Friedrich-Schiller- 19 Anderson RR, Parrish JA (1983) Selective photothermolysis: precise Universität, Jena Veranstalter: microsurgery by selective absorption of pulsed radiation. Science 220: 524- Arbeitsgemeinschaft Dermatologische Histologie 7. 20 Li Y, Yang K (2001) Treatment of recalcitrant-pigmented flat warts using (ADH) der DDG frequency doubled Q-switched Nd-YAG laser. Lasers Surg Med 29: 244-7. Ansprechpartner: 21 Alxander P, Talal A, Wolfgang B, Ulrich H, Michael L (1994) Nd-YAG laser Mandy Wagner, Conventus GmbH hyperthermia in the treatment of recalcitrant verrucae vulgares (Regensburgs technique). Acta Tel. 03641 3533222, [email protected] Derm Venerol 74: 212-214. 22 Groot D, Rao J, Johnston P, Nakatsui T (2003) Algorithm for using a long Frühjahrstagung der Sächsischen Dermatologischen pulsed Nd-YAG laser in the treatment of deep cutaneous vascular lesions. Dermatol Surg 29: 35-42. Gesellschaft e.V. in Zusammenarbeit mit dem 23 Dierickx C (2002) Hair removal by lasers and intense pulsed Berufsverband der niedergelassenen Dermatologen e.V. light sources. Dermatologic clinics 20: 135-146. 24 Bekhor PS (2006) Long pulsed Nd-YAG laser treatment of venous lakes: report of series of 34 cases. Dermatol Surg 32: 151-4. 15. März 2008, Universitätsklinikum Leipzig AöR, OKL 25 Divya R, Eric C, Nathan S, Uebelhoer D, Thomas E (2006) Laser (Hörsaal) Veranstalter: treatment of vascular lesions. Clinics in Dermatology 24: 8-15. Klinik für Dermatologie, Venerologie und Allergologie Ansprechpartner: Jan C. Simon in Leipzig Prof. Dr. OÄ Dr. Regina Treudler Tel. 0341 9718690, Fax 0341 9718609 [email protected]

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