Combination of fractional CO₂ laser with laser-assisted drug delivery in the treatment of hypertrophic and atrophic scars

INTRODUCTION

The formation of scars is nature’s tell-tale sign of injury. It reflects the body’s abnormal response to the wound-healing process. Scars can be a source of distress, and patients often suffer from low self-esteem. Scars are classified into hypertrophic and atrophic types. Atrophic scars are associated with loss of collagen compared to hypertrophic scars, which are associated with excess collagen deposition and decreased collagenase activity.¹ Scar formation is influenced by genetic factors and the capacity of an individual to respond to inciting stimulus.²

Hypertrophic and keloid scars are more common in darker-skinned individuals and occur mainly on the trunk. Various management options available for prophylaxis of hypertrophic scars are pressure therapies, silicone gel sheeting, and flavonoids (quercetin and kaempferol). The current treatment strategies include intralesional steroids, cryotherapy, surgical manipulation, radiotherapy, and laser therapy. Emerging therapies include interferon-α2b injections, 5 fluorouracil, bleomycin, etc.³

Atrophic scars occur as a result of loss of dermal and epidermal tissue. They usually occur due to inflammatory conditions such as acne, after trauma, burns, connective tissue disorders like discoid lupus erythematosus, inherited conditions like Ehlers-Danlos syndrome, and primary anetoderma. Treatment modalities for atrophic scars include lasers- ablative and non-ablative, dermabrasion, autologous fat transfer, chemical peels, injectables, subcision, etc.

Various drugs used along with ablative lasers in dermatology are corticosteroids,⁴ lidocaine,⁵ vitamin C,⁶ tranexamic acid,⁷ 5 fluorouracil,⁸ methotrexate,⁹ imiquimod,¹⁰ tretinoin,¹¹ antifungals,¹² minoxidil,¹³ growth factors, botulinum toxin, etc.¹⁴

MATERIAL AND METHODS

It was a hospital-based prospective study carried out over 2 years. All consecutive patients aged 6 years and older, having either atrophic or hypertrophic scars attending the outpatient department of a tertiary care hospital who gave informed consent after they were explained the whole treatment protocol were included in the study.

The patients were included irrespective of the duration and size of the scar. A total of 97 patients participated in the study. Sixty-four patients with hypertrophic scars, 31 with atrophic scars, and 2 with both atrophic and hypertrophic scars resulting from burns, infection, surgery, and traumatic injuries were included. Pregnant and lactating females, patients with active infection at the site of treatment, patients having a past or present history of photosensitivity, patients on isotretinoin or having a history of intake of isotretinoin in the past 6 months, and history of other concomitant skin disease or connective disorder were excluded from the study.

After applying topical anesthetic cream (7% lidocaine and 7% tetracaine), treatment was carried out. Treatment was carried out with a fractional CO₂ laser (Cis F1, Sellas Premium CO₂ Laser, input 600 VA, manufactured by Dinona Inc. Iksan Branch, South Korea) with an F100 handpiece. A pulse width of 0.04 ms was used, and the pulse repetition rate was 10 Hz. The density pulse position amplitude (PPA) taken was 64–81. Treatment was carried out in stamping mode. Fluence used was from 30 to 50 mJ/cm². The patients were given a single pass without overlapping the spot. Laser treatment was followed by immediate post-operative topical application of triamcinolone acetonide suspension at 10 mg/mL concentration for hypertrophic scars and topical vitamin C serum for atrophic scars. After the treatment, patients were prescribed sunblock and emollients and instructed to avoid sun exposure and use cosmetics immediately post-procedure.

A total of 3–6 treatment sessions were performed. Photographs were taken at every session before delivering the laser. A final assessment was performed at the last follow-up visit. Patients were evaluated based on photographs and Manchester scar scale. Adverse effects, if any, were also monitored at each follow-up visit. All the findings were noted in a predesigned proforma, and the results were framed.

RESULTS

Sixty-four patients having hypertrophic scars and 31 patients with atrophic scars received treatment. Two patients having both atrophic and hypertrophic scars were also included. The study consisted of 35 (36.08%) males and 62 (63.91%) females. The mean age of the study group was 25.8 + 7.2 years, ranging from 6 to 40 years. The mean duration of scars was 3.83 years. The skin type of the majority of patients was type III (63 patients), followed by type II in 27 patients and type IV in 7 patients [Tables 1-3].

A total of 20 patients completed six treatment sessions, 26 received five sessions, and the remaining 37 and 14 patients received 4 and 3 treatment sessions, respectively. The duration, site, type, and etiology of scars are given in Table 3. The modified Manchester score was calculated at the end of the treatment in all the patients as shown in [Tables 4 and 5]. We observed maximum improvement in scar distortion and texture in both atrophic and hypertrophic post-laser-assisted drug delivery (LADD) [Figures 1-5]. The average overall improvement was 1.43 ± 0.21 in atrophic scars and 1.58 ± 0.48 in hypertrophic scars.

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Figure 1:

Patient with post-burn hypertrophic scar (a) before treatment, (b) showing significant improvement after 3 sessions and (c) 6 sessions.

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Figure 2:

Post acne scarring (a and b) pre-treatment, (c and d) showing significant improvement after 5 sessions.

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Figure 3:

Hypertrophic scarring (a) pre-treatment, (b) immediately after procedure, (c) after 3 sessions showing significant flattening of scar with only pigment remaining.

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Figure 4:

Post-surgical scar (a) before treatment, (b) after 3 sessions.

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Figure 5:

Post-traumatic scar (a) before treatment, (b) immediately after treatment, (c) after one session, (d) after 2 sessions.

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We divided the side effects after treatment into immediate and delayed categories [Table 6]. A transient erythema was seen in almost all the patients immediately after treatment.

DISCUSSION

Scar treatment is a complex process and needs a combination of various methods. The effect of scars is not only just physical but also impacts the person’s social and emotional health. There are various techniques which have been used to assist the delivery of drugs across the stratum corneum to reach the desired level into deeper skin tissues. Some of the modes used include dermabrasion, microneedling, radiofrequency, iontophoresis, curettage, and lasers. LADD is an emerging technology for targeted delivery of specific molecules into the skin. It bypasses the stratum corneum and enables the diffusion of drugs to desired targets. When hydrophilic vehicles are used, ablative and Q-switched lasers are preferred, and non-ablative and IPL are preferred for lipophilic vehicles.¹⁵

Pulsed dye laser helps treat erythema and pruritus associated with scars, while fractional CO₂ laser helps debulk and resurface scars.¹⁶

The CO₂ laser was one of the earliest laser systems used in dermatology. It is not pigment-selective and targets both pigmented and non-pigmented skin lesions. It emits a wavelength of 10,600 nm, and this laser’s chromophores are intracellular and extracellular water. The CO₂ laser is a tissue-selective process as only the target tissue is ablated, and surrounding normal tissue is minimally involved.¹⁷

Fractional lasers also act through transepidermal delivery of the drugs, referred to as “laser-assisted drug delivery.”¹⁸ LADD was used for the first time in 1987.¹⁹ It has been used in dermatological disorders such as burn scars, skin malignancies, and inflammatory disorders such as lichen planus and alopecia areata.^4,20 In addition to collagen remodeling and stimulating collagen production in the dermis, fractional lasers lead to the development of microthermal ablative zones (MTZ), which form channels enabling uniform and controlled delivery of the drugs. The skin surrounding MTZs remains unaffected, thus leading to rapid re-epithelization and reduced downtime.

LADD finds its use in a wide range of dermatological conditions. It has been used to treat scars, actinic keratosis, Bowen’s disease, basal cell carcinoma, vitiligo, melasma, alopecia, and amyloidosis. Application of drug after laser leads to increase absorption of the topical products as fractional lasers produce microscopic ablated channels in the epidermis.²¹

LADD using a fractional CO₂ laser is a good treatment option for hypertrophic and atrophic scars. It works by stimulating production and remodeling of collagen fibers in the dermis. In addition to the resurfacing ability of the fractional laser itself, it disrupts the skin’s barrier function, thus allowing non-lipid soluble substances to cross the barrier. The pliability of scar tissue is increased, adhesions are broken down, and the drug can enter the dense fibrotic tissue of the scars with the assistance of a laser. It also helps in uniform delivery of the drug throughout the lesion.

Intralesional triamcinolone acetonide is the first-line treatment for hypertrophic scars. Side effects such as fat atrophy, persistent erythema, and telangiectasias are comparatively less when using triamcinolone acetonide with LADD. The pain associated with intralesional injections is also not associated with laser-associated drug delivery. Further, in treating scars involving large areas, laser-assisted delivery prevents the side effects of steroids by increasing the bioavailability and decreasing the drug dose.

We found an excellent response to LADD in both atrophic and hypertrophic scars. A statistically significant improvement was seen in all the parameters; however, scar texture and distortion showed maximum improvement. Earlier studies also found maximum improvement in texture and distortion of scars [Figures 1-5].²²

The side effects after LADD reported in the literature, like foreign body reactions after the use of vitamin C and increased bacterial infections after laser application, were not reported in our study.^23,24

Cavalle et al. assessed the drug delivery of betamethasone in keloids after the application of a 2940 nm Erbium YAG laser. Seventy keloids were treated, and the median improvement noticed was 50%.²⁵

Waibel et al. treated 15 patients with hypertrophic scars with five sessions of ablative CO₂ laser at an interval of 2–3 months between the sessions. They used triamcinolone acetonide 10– 20 mg/mL immediately after the laser. Patients were followed after 6 months, and improvement in parameters-scars, atrophy, dyschromia, and contour was 2.73. The parameter texture showed the best results, and dyschromia showed the lowest improvement.¹⁸

This study shows that LADD is a safe and effective treatment option for cutaneous scars.

CONCLUSION

Thus, LADD improves the efficacy of the drug by increasing the absorption and adding the synergistic effect of the laser. Furthermore, the procedure is less painful with a lesser number of side effects. The number of visits to the hospital decreases as the improvement is observed early with LADD.