Effective keloid management using a combinatorial continuous‐wave and repeat fractionated ablative CO2 laser regimen

Keloids are benign proliferative scars that form as a result of dysregulated growth and collagen deposition in response to cutaneous injury. Laser therapies have emerged as promising options for the treatment of keloids, with performance varying by laser type and lesion characteristics.


| INTRODUC TI ON
Keloids are benign proliferative scars that form as a result of dysregulated growth and collagen deposition in response to cutaneous injury.Histopathologically, they extend beyond the confines of the original wound margins and feature large, disorganized and densely packed collagen fibers alongside dilated blood vessels and α-smooth muscle actin-expressing fibroblasts. 1 Minor keloids are focally raised and itchy scars that extend over normal tissue, develop within 1 year of injury and do not regress on their own.Major keloids are larger and more raised (>0.5 mm), can continue to spread with time, are often resistant to therapy and more prone to recur. 2 Treatment algorithms are largely dictated by lesion size, tension and severity, patient skin and healing profiles, central complaints and treatment history. 3First-line therapies generally include conservative measures, such as intralesional corticosteroid injections, topical chemotherapeutics and immune-response modifiers and/or silicone gel or sheeting.Refractory keloids are managed more aggressively with cytotoxic agents and later with surgical, radiation or laser therapy.Surgical procedures are employed to radically resect the lesion or to reduce infected mass, yet can leave a scar longer than the length of the original keloid.Radiation therapy has been proven particularly effective in reducing keloid-associated inflammation, pain and itch, alongside gradual improvements in scar color and thickness. 4Yet, it involves exposure to high doses of radiation and is therefore generally reserved for nonresectable or large keloids, and for those refractory to nonsurgical alternatives.Cryotherapy is limited to small-sized keloids, is associated with prolonged healing times and can result in permanent pigmentation, skin atrophy, and severe pain. 5,6Laser therapies have emerged as promising keloid management options, with performance varying by laser types and lesion characteristics. 7,8A systematic review of the outcomes of laser therapy in patients with excessive scarring found CO 2 and Er:YAG 2940 nm lasers most effective in improving lesion height, pliability, and erythema. 9mmon adverse effects include hyper/hypopigmentation and blistering.Despite the broad range of treatment options, recurrence rates are high, reaching 50%-100%, 2,10 37% 11 and 24% 12 following surgical resection, radiotherapy and cryotherapy, respectively.For this reason, it has become common practice to concomitantly or sequentially apply multiple modalities, with specific paradigms tailored to patient and lesion profiles. 13Such combinatorial approaches act have additive effects by tackling several core determinants of scar composition and persistence.On a similar token, combinations of laser types or emission patterns with distinct modes of action are expected to yield more favorable outcomes by enabling the stepwise management through which the first modality facilitates penetration and effectiveness of the adjunct methods. 14For instance, a long-pulse laser is expected to impart a knife-like, acute and diffuse thermal effect within the thick, high-tension areas of the keloid, while a fractionated, short-pulsed laser is expected to modulate fibroblast activities and collagen fiber morphology, promoting gradual skin rejuvenation and resurfacing.The current work retrospectively assessed the 6 month outcomes of combined single-session continuous wave and repeat fractionated CO 2 laser treatment of keloids in 22 adult patients.

| PATIENTS AND ME THODS
This retrospective analysis reviewed charts of patients with keloid scars managed with combination laser therapy between November Adult patients over the age of 18 years, with Fitzpatrick skin type II-V, presenting with a keloid scar on the face or any other part of the body, and without any active skin infections, were eligible to undergo treatment.Patients who had undergone any form of keloid treatment in the preceding 4 weeks or laser or isotretinoin therapy in the preceding 6 months, or with a history of adverse reactions to previous laser therapy, were not eligible to participate in the study.
Similarly, pregnancy and smoking were contraindicated.Before treatment, the target area was cleaned with a standard commercial make-up remover and then with an antiseptic solution.Scars were initially treated with a CO 2 laser Platform (Alma Laser Ltd., Caesarea, Israel), a highly flexible system for char-free tissue ablation, excision, incision, and coagulation of soft tissue control via pulse duration and mode of energy delivery.First, a single session in continuous wave mode (Hylight Hybrid applicator, 5 W, 100 ms) was used to reduce the initial height and thickness of the lesion, followed 5 weeks later by a 5-session pixelated protocol (Pixel 7x7 Hybrid applicator, 80 mJ/ pixel, 130 ms pulse duration) delivered at 4-week intervals to promote tissue repair.Patients were instructed to rinse the area several times a day and to refer to the clinic in case of infection.Scar characteristics were assessed before treatment and 6 months after the last treatment session.

| Assessments
Baseline and after photographs of all laser-treated regions were obtained under identical lighting, patient position, camera settings, and image processing conditions.Treatment efficacy was assessed using the Patient and Observer Scar Assessment Scale (POSAS), which integrates lesion vascularity, pigmentation, thickness, relief, pliability, and surface area scores, together with patient ratings of scar pain, itching, color, stiffness, irregularity, and change.In each 10-point subscale, "1" indicates "normal" and "10"indicates "worst possible".
Total scores in the observer portion range between 6 and 60, with lower scores indicating better appearance.In the patient portion, which contains two additional subscales, total scores range between 8 and 80. Scars were also assessed using the Vancouver Scar Scale, which grades pigmentation (0-2), vascularity (0-3), and height and thickness (0-3).Patient satisfaction was scored using the standard 10-point Numeric Rating Scale, with "0" representing "very much unsatisfied" and "10" representing "very much satisfied".The same scale was used to rate pain sensation, with "0" representing "no pain at all" and "10" representing "worst possible pain."Descriptive statistics were summarized, with continuous variables presented as mean, median, minimum, maximum and percentage and categorical variables presented as count and percentage.

| RE SULTS
Twenty-two consecutive patient files were included in this analysis.
Seventeen patients were female and mean age was 24.3 ± 9.3 years.
Skin types were type IV (72.7%) and type V (27.3%).Overall, 23 keloids were treated, 13 (56.5%) of which were on the ear lobe and 4 (17.4%) were on the arm or hand.Other locations included the cheek, pubis, throat, buttocks, philtrum, and arm pit, occurring in one patient each.The size of the keloids ranged from 5 to 10 cm and the time since the injury ranged from 3 months to 35 years.
Overall Vancouver scores improved from 5.6 ± 2. Patients were highly satisfied with treatment outcomes (9.9 ± 0.4) and all said they were likely to recommend the treatment to others.

| DISCUSS ION
The presented analysis demonstrated that the combined application of fully and pixelated ablative lasers is a safe and effective tool for the management of keloids in a wide range of body regions.The sequential treatment regimen led to more than 50% reductions in key keloid characteristics, including color, thickness, and irregularity.
Patients reported on marked reductions in scar-associated pain and itchiness, and were overall highly satisfied with the aesthetic results.
Adverse events were minimal and tolerable and were self-resolving.
Scarring affects approximately 100 million people in the developed world each year, with deep skin injuries occasionally leading to more severe scarring. 15The global market for the treatment of hypertrophic and keloid scars is expected to reach $15.7 billion by 2030.However, current treatments are lacking. 16In a costeffectiveness analysis of fractional versus non-fractional CO 2 laser for the treatment of acne scars, the non-fractional ablative CO 2 laser, which had the same price and warranty as the fractional version, was found to require fewer treatment sessions to achieve satisfactory results but was associated with more adverse effects and is not commonly used for cosmetic purposes.The review F I G U R E 1 Physician and patient ratings of key keloid features 6 months after multi-mode ablative CO 2 laser treatment.Keloids were treated with a single continuous wave CO 2 laser session (Hylight Hybrid applicator, 5 W, 100 ms), and 5 weeks later, with a 5-series pixelated CO 2 laser regimen (Pixel 7x7 Hybrid applicator, 80 mJ/pixel, 130 ms), delivered on a monthly basis.(A) Physician and (B) patient ratings of key keloid features as measured using the 10-point Patient and Observer Scar Assessment Scale (POSAS) in which "1" indicates "normal" and "10" indicates "worst possible", or the Vancouver Scar Scale, which grades pigmentation (0-2), vascularity (0-3), and height and thickness (0-3).
concludes that fractional CO 2 laser therapy is a safe and effective procedure for acne scars. 17e CO 2 laser used in this study is a highly flexible system for tissue ablation, excision, incision, and coagulation of soft tissue, allowing complete control of treatment parameters, including the level and depth of ablation and thermal effect via pulse duration and energy delivery mode.The laser was used in two delivery modes.
First, the non-fractionated continuous wave mode induced uniform thermal ablation of the treated tissue patch. 18This regimen was specifically designed to impart a knife-edge effect that reduces the initial height and thickness of the lesion.[21] Fully ablative laser resurfacing (e.g., CO 2 , Er:YAG) is a wellestablished skin rejuvenation technology that has been the gold standard for years.The procedure has a serious side effect profile that includes scarring, discoloration, acne aggravation, and skin infection.Fractional ablative devices maintain the resurfacing power of fully ablative lasers with less downtime and are considered significantly safer. 22Several other works have demonstrated the clinically measurable effects of fractional CO 2 on scar appearance, thickness, pliability, as well as on symptomatic relief. 9,21riations in the tensile forces in different skin regions have been suggested to contribute to keloid composition and response to treatment, [23][24][25][26] with chest and trunk lesions showing significantly higher recurrence rates compared to keloids at other locations. 11e majority of keloids treated in this patient cohort were on the earlobe, a site particularly amenable to treatments due to the low wound tension and minimal mechanical forces.Further studies will be needed to determine the generalizability of the treatment parameters implemented in this work, particularly in high-tension anatomical locations.This analysis included patients who were all treated by the same surgeon and with the same regimen, which minimized the number of confounding factors in the study.Selection bias was avoided by including patients consecutively treated in the clinic with the presented protocol within the 1.5-year study period.
The weaknesses of this study included its retrospective design, as well as the relatively short follow-up period.While distinct cosmetic improvements were documented, the durability of response remains to be determined.Currently, a minimum follow-up of 15 months is recommended, with many works advocating a 3-year follow-up to allow for early detection of recurrences. 24,27In case of recurrence, many aspects of the treatment protocol, For example, dosing, duration, intersession intervals, can be calibrated to improve outcomes.In particular, shortening of the 5-week interval implemented between the two modes of treatment may ensure more durable responses, as has been shown in patients treated with radiotherapy following surgical keloid excision. 27,28After establishment of the feasibility of keloid management with the combined continuous wave and pixelated ablative laser regimen, additional studies can be designed to monitor larger patient cohorts for longer follow-up periods.Due to lack of a control group, it was not possible to assess the contribution of the combined protocol to immediate and long-term outcomes.Further F I G U R E 2 Keloid response to multi-mode ablative CO 2 laser treatment.Keloids were treated with a single continuous wave CO 2 laser session (Hylight Hybrid applicator, 5 W, 100 ms), and 5 weeks later, with a 5-series pixelated CO 2 laser regimen (Pixel 7x7 Hybrid applicator, 80 mJ/pixel, 130 ms), delivered on a monthly basis.(A) Male, skin type V patient with a 1 cm earlobe keloid and (B) female, skin type IV patient with 2 cm earlobe keloid before and after the full treatment regimen.
| 11 HAUCUJA controlled studies with longer follow-up periods will be necessary to fully assess these points.0][31] Genetic predisposition and systemic morbidities, such as hypertension 32 and immunological disorders, 33 have been reported to aggravate keloids.Similarly, naïve and immature keloids have been demonstrated to be more amenable to a wide range of treatment options as compared to those which have previously failed treatment. 34

| CON CLUS ION
This study demonstrated the efficacy and safety of keloid management using a combination of two ablative laser delivery modes all with a single laser platform.The treatment regimen promoted lesion flattening, followed by long-term stimulation of reparative processes to restore the normal balance between collagen synthesis and breakdown.The clinical and aesthetic improvements in a variety of treated regions were mirrored by high patient satisfaction.
Comparative prospective studies will be necessary to determine durability of response, to individualize laser parameters to scar and patient characteristics and to assess combination of the regimen with additional treatment modalities.

ACK N OWLED G M ENTS
The author would like to acknowledge the editorial assistance of Dr. Yehudit Posen.

FU N D I N G I N FO R M ATI O N
This research received no external funding.

CO N FLI C T O F I NTER E S T S TATEM ENT
The authors report there are no competing interests to declare.

DATA AVA I L A B I L I T Y S TAT E M E N T
All data is contained within the article only.No supplementary material exists.

E TH I C S S TATEM ENT
Ethical approval was obtained from the ethics committee at Metropolitan Autonomous University Xochimilco Unit, Mexico City.

I N FO R M ED CO N S ENT
This is a retrospective collection of anonymized data from previously recorded routine assessments and does not present risk of exposure of personal data of patients.Waiving informed consent will not adversely affect the rights and welfare of the subjects.Consequently, informed consent is not required, in agreement with the Mexican low.

R E FE R E N C E S
2021 and May 2022.The data collection was approved by the Ethics Committee of the Metropolitan Autonomous University, approval Number: UAM-AA-2021-01.All patients provided their consent before undergoing treatment.
2 before treatment to 1.7 ± 2.1 at the 6-month follow-up assessment.In parallel, mean patient-rated scar-associated pain and itch improved from 4.0 ± 3.1 and 4.4 ± 2.5 to 2.2 ± 1.6 and 2.1 ± 1.5 by the end of the follow-up period (Figure 1B).At the same time, they reported on improvements in keloid color (2.5 points), rigidity (3.2 points), and thickness (3.2 points).Patient-rated overall keloid scores improved from 37 ± 17.6 at baseline to 16.1 ± 8.5 within 6 months of the final treatment session.Patients found the laser treatments to be fairly tolerable, with pain scored 2.5 ± 1.3 and lasting an average of 17.5 ± 18.2 min (range: 10-60 min).All participants experienced erythema and swelling following each treatment, which resolved within 2-3 days, with no intervention.With the exception of one patient treated in an area of repeated ear piercing, no scar growth was observed during the 6 month study period.