Carboxytherapy versus its Combination with Fractional CO2 Laser for the Treatment of Striae Distensae: An Objective, Right-to-left, Comparative Study

J Clin Aesthet Dermatol. 2024;17(10):E69–E75.

by Moetaz El-Domyati, MD; Wael Hosam El-Din, MD; Walid Medhat, MD; Yasmin Khaled, MSc; and Michel R. Ibrahim, MD

All authors are affiliated with the Department of Dermatology, STDs and Andrology, Faculty of Medicine at Minia University in Al-Minya, Egypt. 

FUNDING: No funding was provided for this article.

DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article.

ABSTRACT: Background. Striae distensae (SD) is a common cutaneous disorder which appears as linear lesions seen mainly in women. Since previously described in 1889, SD has presented a significant challenge regarding its evaluation and treatment. Carboxytherapy was recently reported as an effective treatment for SD.

Objectives. We sought to objectively compare the clinical effectiveness of carbon dioxide therapy (CDT) as monotherapy versus a combination of CDT and fractional CO₂ laser in the treatment of SD.

Methods. This randomized prospective study included twenty cases with bilateral and symmetrical SD. Each patient was treated with CDT only on the right (Rt) side of the body, while the left (Lt) side received a combination of CDT and fractional C0₂ laser.

Results. Clinical evaluation revealed a clearly significant clinical improvement in SD lesions after both techniques regarding length, width, texture, and pigment changes. Although the Lt side showed slightly better improvement, however no statistically significant difference could be observed between both sides. In the meantime, the objective improvement observed by the 3D camera and histometric analysis correlated with the clinical improvement. Special stains showed collagen deposition which became more compact, dense and better organized, accompanied by evident increase in elastic fibers in a normal linear microfibrillar pattern after treatment on both sides.

Conclusion. CDT demonstrated efficacy and safety as a minimally invasive modality for management of SD, as it induces collagen remodeling and better organization of elastic fibers with minimal side effects and downtime.

Keywords: Striae distensae, stretch marks, carbon dioxide therapy, carboxytherapy, fractional CO2 laser, collagen, elastic fibers

Introduction

Striae distensae (SD), also known as stretch marks, is a common dermatologic disorder which appears as linear lesions seen in individuals of all ages mainly in females.¹ SD are usually associated with several physiologic conditions such as puberty, pregnancy, weight gain or loss, obesity, and in association with Cushing’s disease, as well as topical and systemic steroids.^2,3 Striae gravidarum refers to SD occurring with pregnancy, usually after the 24th week.^4,5 Lesions usually involve the abdomen, breasts, thighs, and buttocks in females, whereas in males, SD may be present on the shoulders, thighs, and lower back. SD affect nearly 90 percent of pregnant women, 70 percent of adolescent females, and 40 percent of adolescent males.^6,7.

Early lesions of SD may be itchy and usually appear pink to red; consequently, the term striae rubra (SR). Lesions may slowly lighten and become white and atrophic, which are subsequently described as striae alba (SA). While SD may gradually fade, it is typically considered to be permanent.⁸ 

The pathogenesis of SD is not fully understood. However, current accepted hypothesis suggests that fibrillin and elastin are altered or damaged by stretching forces. Genetic factors and hormonal changes accompanying puberty or pregnancy are also thought to play a role.^9,10 

Histologically SD, especially SA, resembles scars that display attenuated flat epidermis with loss of rete ridges (RR), fraying and splitting with horizontal orientation of collagen bundles, dilation of blood vessels, as well as aggregation and disintegration of elastic fibers.^11,12

Although SD is not a life-threatening condition, it may create an outstanding psychological load for patients. Since previously described in 1889, SD has presented a significant challenge regarding its evaluation and treatment.^6,13 A consistently effective treatment has yet to be determined. Several treatment methods have been applied with variable degrees of success such as topical retinoids, chemical peels, microdermabrasion, microneedling, intense pulsed light, lasers (pulsed dye, resurfacing, excimer), radiofrequency, and ultrasound. A significant need remains for an effective and safe treatment modality for SD.^14–19

Previously published articles demonstrated that fractional CO₂ laser was effective in treatment of SD lesions.^{1,4, 20–23} Meanwhile, recently carboxytherapy (ie, carbon dioxide therapy [CDT]) was presented as a promising modality for management of SD as it is an effective, easy, safe, simple, and inexpensive means to induce collagen and better reorganization of elastic fibers. It showed significant improvement in treatment of SD, with minimal downtime.²⁴

This study was conducted to objectively evaluate and clinically and histologically compare the effectiveness of CDT as monotherapy versus a combination of fractional CO₂ laser and CDT in the treatment of SD. 

Methods

This randomized right (Rt) to left (Lt) prospective study included twenty patients with bilateral and symmetrical SD on different parts of the body, either SA (n=12) or SR (n=8). All participants were female. The patient’s age ranged from 17 to 36 years old with Fitzpatrick Skin Types III to IV. They were collected from the outpatient Dermatology Clinic of Minia University Hospital. 

Informed consents were signed by all patients. All participants underwent clinical assessment, pre- and post-treatment photography and skin biopsies. The Ethical Committee and the Committee for Postgraduate Studies and Research of Faculty of Medicine, Minia University approved this study.

A full clinical evaluation was performed. Patients with some cutaneous disorders such as active skin infections, recurrent herpes activation, connective tissue disorders, or with history of keloid as well as bleeding disorders were excluded from the study. Patients receiving blood thinning medication, systemic retinoids, or who received any previous treatment for SD, such as microneedling, laser or light therapy, within a year of study initiation were also excluded. Pregnant or lactating participants, patients using carbonic anhydrase inhibitors or with systemic illness such as severe anemia, diabetes, respiratory, cardiac, or liver disorder were also excluded from our study. 

In each patient, a pair of SD lesions with similar shape and size and nearly symmetrical site, were selected. Each patient was treated as follows: 

The right side: Carboxytherapy only was used (8 sessions, one session every 2 weeks). 

The left side: Combined carboxytherapy and fractional CO₂ laser treatment was used (6 CDT sessions and 2 fractional CO₂ laser sessions; one after the 2nd and the other after the 4th CDT session, one session every two weeks).

Device and treatment protocol. Carboxytherapy. Skin sterilization using povidone iodine followed by 70% ethyl alcohol was done; then intradermal infusion of CO₂ was performed by carboxy-gun, connected to CO₂ cylinder (Concerto Carboxy and Meso-gun, 602-0845, Lyion Cosmo Trade, France) as previously described by El-Domyati et al.²⁴

The use of carboxy-gun allowed for sterile delivery of medical CO₂ gas. The gas was injected directly into the SD at an angle of 15°, while the bevel border was up. Infusion of CO₂ resulted in bulging which could be seen and felt; this indicates the injection of the whole area. Erythema together with tissue distension was used as a clinical endpoint of CO₂ injection. The carboxy-gun parameters were adjusted according to device manufacturing as follows: needle gauge 32, 3mm depth and 15cc of CO₂ that might be increased up to 45cc in large areas of SD. Then, the injected area was gently massaged. Before starting infusion, cases were notified about the resulting emphysema; which will disappear in five minutes. Skin stabilizer of carboxy-gun allowed controlling the depth of infusion, and care was taken with every needle’s movement to keep the skin stretched and the maneuver is consistent. In cases with several closely related SD lesions, infusion was performed to the whole area (not to each individual lesion). We noticed that 15cc of CO₂ gas can spread intradermally and diffuse to cover an area of about 2 to 3cm in diameter. The least distance between the injection sites was about 4cm, which allowed the injected CO₂ to cover the affected area entirely.

Fractional CO₂ laser. The fractional CO₂ (surgical CO₂ laser system, Dream pulse CO₂ laser, DS-40UB- Multixel Scanner type, manufactured by Daeshin Enterprise CO., LTD, Korea) laser session used was 40 mJ energy, pulse width 4 ms, and scanning area 10×10mm. The treatment was performed applying the hand piece to the skin and moving it across the lesions with individual pulses applied one next to the other.¹⁴ Participants were informed to clean the site of laser therapy with sterile normal saline solution, use mupirocin and zinc oxide ointment and use sterile petroleum jelly gauze after resurfacing procedure.

Assessment of therapeutic response. Clinical evaluation. The clinical changes and improvement in SD regarding width, length, number, texture, color mismatch and skin atrophy were assessed by the patients, two physicians and two independent observers, before and after four months of starting treatment. This assessment was based on the following scale: no improvement=0%, mild=1–25%, moderate=26–50%, good=51–75% and very good=76–100% improvement.

3D skin analysis. Skin topography was evaluated in treated sites in vivo using Antera 3D camera (skin imaging device) before treatment (baseline) and four months after the start of treatment (post treatment) as previously described by El-Domyati et al.²⁴

Histological evaluation and histometry.Using local anesthesia (lidocaine 2.5%), skin biopsies had been taken from SD lesions using 5mm punch before treatment (baseline) and four months after the start of treatment (post treatment). Specimens were stained with hematoxylin and eosin (H&E), orcein (elastic fibers) and Masson trichrome (collagen fibers) stains. All histological evaluations and measurements were performed using light microscope (Accu-Scope #3025 Five Headed (A 3025-5)-OLYMPUS), with a built-in camera (Olympus, digital camera E-330 SLR, Japan).

Histometric analysis using a computer-based software (analySIS® Five by Olympus Soft Imaging Solutions GmbH, Johann-Krane-Weg 39, D-48149 Münster, Germany) was done on H&E stained sections. Epidermal thickness was estimated as the mean length between the uppermost epidermis, excluding the horny layer, and the dermoepidermal junction. Five measurements at least were performed for every section.

Statistical analysis. For statistical analysis of the data, the Software Package for Statistical Science (SPSS) for Windows (Version 16; Chicago, Illinois) was used. Mean ± standard deviation (SD) was calculated for quantitative data, whereas number and percent were expressed for qualitative data. Statistical analysis was done using dependent (paired) t test. Correlations between clinical results and the improvement detected by 3D camera were studied using Pearson’s test to calculate the correlation coefficient (r value) and its significance. Significance was shown in terms of P-value, which was significant when it was ≤0.05 and highly significant when ≤0.001.

Results

Clinical evaluation. The present study demonstrates a significant clinical improvement in SD lesions after both techniques (either CDT alone or combined CDT with fractional CO₂ laser) regarding length & width, texture, and pigment changes (RT side: P=0.03, 0.01, 0.04 while Lt side: P=0.02, 0.001, 0.04 respectively). Although the Lt side which received combined treatment showed slightly better improvement, no statistically significant difference could be observed between both sides (P=0.6, 0.7, 0.8 respectively) (Table 1, Figure 1). SR showed better response than the more mature SA. No adverse effects or complications could be noticed except for erythema and bulging of the injected site after CDT which resolved completely within one hour.

Antera 3D Camera Skin Analysis proved improvement in skin indentation index (large, medium and small) and skin texture (large, medium and small) after four months of treatment for SD (P<0.05) (Table 2, Figure 2). Most parameters showed better improvement on the Lt. side (combined) of skin exhibiting SD, but those differences were statistically insignificant (P>0.05). A significant positive correlation (P<0.05) was observed between the percent of clinical and 3D analysis improvement in textural changes on both sides.

Histological evaluation and histometric analysis. Before treatment, thin and flattened epidermis with attenuated RR could be noticed in most skin biopsies. Interestingly in response to treatment, there was overall morphological and architectural improvement of the epidermis with development of RR (marked undulations of the dermoepidermal junction) (Fig. 3-A). 

Histometric analysis revealed a highly significant increase in the mean thickness of the epidermis from 44.8±6.9μm before treatment to 66.5±10.9μm after 4 months of treatment (P< 0.0001**) on Rt. side (CDT) and from 45.1±7.7μm to 68±11.8μm (P< 0.0001**) on the Lt. side (combined). Although there was highly significant improvement on both sides, no statistically significant difference could be observed between the 2 sides by comparing both treatment modalities (P = 0.47) (Fig. 3-A).

Before treatment, disorganization of collagen bundles (Masson Trichrome stain) with marked decrease in dermal elastic fibers (Orcien stain), which appeared fragmented, thick, and curled were observed. However, dermal changes in the form of collagen deposition which became more compact, dense, and better organized, accompanied by marked increase in elastic fibers in a normal linear microfibrillar pattern could be observed after treatment (Fig. 3-B&C).

Discussion

Striae distensae is a relatively common complaint in cosmetic dermatology. Clinically, SD are linear or fusiform lesions that vary in length and width depending on the anatomical area and condition in which they develop. However, there are only few conclusive studies regarding effective treatments for SD.^25,26

One of the various methods for management of SD, fractional photothermolysis is a novel modality.^20,23,27,28 In 2006, FDA approved fractional resurfacing laser for management of acne scars. This technique ablates a fraction of the skin leaving areas of normal skin to repopulate the ablated areas. Once the injury has been done, the skin starts a very ordered and rapid sequence of repair, resulting in the rapid clinical effects.¹⁵ Many reports have showed the efficacy of fractional laser in management of different types of scars.^27,29 Considering the similar histological characteristics in SA and scars and successful treatment of scars with fractional laser, recently clinicians have shown special interest towards using fractional laser for treating SD, especially SA.^27,29

CDT refers to injection of CO₂ subcutaneously or transcutaneously for therapeutic purposes.^30,31 Typically, the body deals with CDT as O2 deficiency and subsequently, goes to correct the O2/ CO₂ levels imbalance by enhancing the blood supply and producing many growth factors, such as the vascular endothelial growth factor, to start neogenesis of capillaries. Therefore, skin elasticity is improved through the release of growth factors and their angiogenic effect, turnover of collagen, and the eradication of adiposities. These changes enhance skin regeneration and improvement of SD lesions.^4,31,32

Recently, CDT has been applied progressively in aesthetic practice for treatment of localized fat deposition, cellulite, alopecia, dark peri-ocular circles, and most recently for abdominal fat reduction^33,34 and face rejuvenation.³⁵ Because CDT may lead to surprising, impressive improvement, even after just one session, in many patients with photoaging, scars, SD, or cellulite. So, it was assumed that several other factors might play a crucial role in inducing such improvement. These factors include; mechanical lessening by CO₂ flow, mechanical tension on the cells (particularly in rejuvenation) and pressure (especially in treatment of localized fat deposits) which result from relatively strong gas flow during CO₂ injection,³¹, as well as the effect of temporary acidosis.^4,31,36,37

In the current study, we evaluated and compared the efficacy of CDT versus combined CDT and fractional CO₂ laser in the management of SD of various causes in 20 female patients. The Rt sides of our cases were treated with CDT as monotherapy while the Lt side received a combined treatment to evaluate if fractional CO₂ laser will add to the effect of CDT.

The present study demonstrates a clearly significant clinical improvement in SD lesions after both techniques (either CDT alone or combined CDT with CO₂ fractional laser) regarding length, width, texture, and pigment changes. Although the Lt side which received combined treatment showed slightly better improvement, no statistically significant difference could be observed between both sides. A very good clinical improvement in SR was observed, while good and moderate clinical improvement could be noticed in the more mature SA.

Maia-Figueiró et al³⁸ concluded that infusion of CO₂ intradermally induces local increase of blood flow with a consequent increase in tissue oxygenation, and it also stimulates fibroblasts and the synthesis of elastin and collagen with subsequent skin retraction resulting in skin rejuvenation and sagging reduction. In addition, Pinheiro et al³⁹ observed remodeling of collagen fibers after CDT. 

In the present study Antera 3D camera objective analysis confirmed improvement of both skin indentations and skin texture in SD lesions, on both sides especially on the left side (combined). The use of Antera 3D permitted us to precisely analyze indentations, texture, scars, skin color, redness, and pigmentation in an objective coherent manner. Benefits of this camera are eventual 3D view, that analyze the skin texture (roughness) as well as indentations (indentation index), spot-on automatic matching, compare “before and after” images, create a report, also it can save a data archive of your images.

Histologically, both techniques showed a highly significant increase in epidermal thickness on both sides. There was no statistically significant difference in the mean increase of the epidermal thickness between the two sides. Simultaneously, dermal changes in the form of collagen deposition which became more compact, dense, and better organized; associated with evident increase in elastic fibers in a normal linear microfibrillar pattern could be observed on both sides. 

The present study showed a noticeable increase in collagen remodeling after 4 months of treatment with CDT. This agrees with previous reports that documented remodeling of collagen as well as elastic fibers after CDT.^{30, 38,39}

Meanwhile, after four months of combined treatment on the Lt. side, there was a highly significant increase in epidermal thickness with increase in the amount of collagen and elastic fibers. This agrees with previous studies that reported an overall increase in epidermal thickness and amount of collagen and elastic fibers in all SD patients treated only with fractional CO₂ laser.^18,23 

By comparing the two treatment modalities, we observed slightly more improvement on the Lt side receiving combined treatment in all the study parameters although this improvement was not statistically significant. All previously mentioned results confirm that CDT alone is a good modality in management of SD and that fractional CO₂ laser do not significantly add to its effect, despite higher financial expenses.

In conclusion, CDT alone proved to be a new effective and safe minimally invasive modality for management of SD, as it induces collagen remodeling and better organization of elastic fibers with minimal side effects and downtime. Combination of fractional CO₂ with CDT (combined treatment) did not add much in cases of SD.

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