A retrospective comparative cohort study of ultra-pulse CO₂ lattice laser and glucocorticoids in the treatment of vulvar epithelial nonneoplastic lesions

Introduction

Non-neoplastic lesions of vulvar epithelium are a cluster of long-term disorders with degenerative and pigmented alterations of the female vulvar skin and mucous membranes (1). The pathological alterations often observed in non-neoplastic lesions of the vulvar epithelium lichen simplex chronicus (LSC) and lichen sclerosus. The prevalence of the disease is 1.38%, with a high incidence in perimenopausal women (2).

Many methods are currently being applied to treat the disease, such as drugs, freezing, smooth muscle electrical stimulation, and other treatment strategies. The choice of therapy therefore requires a scientific approach and a comparison of efficacy in order to provide an evidentiary basis for clinical decision-making.

In recent years, Li et al. have found that CO₂ lattice laser can remarkably improve regional cutaneous microcirculation due to the micropore thermal effect (1,2). Moreover, a few cases of nonneoplastic lesions of the vulvar epithelium treated with the CO₂ lattice laser have been reported.

Vulvar lichen sclerosis (VLS) is a rare chronic inflammatory non-neoplastic skin lesion of the female vulva. The main clinical manifestations are vulvar itching and burning pain. Abnormal anatomical structure and abnormal shape can lead to dysuria, painful inter-course, and unsatisfactory sex life, which will affect the life of couples and cause great troubles to women’s physiology and psychology. At present, VLS is an incurable disease. The main purpose of treatment is to control the subjective and objective symptoms of patients. The main treatment method is local application of glucocorticoids. After 3–4 months of continuous local treatment of glucocorticoids, more than 50% of the patients’ clinical symptoms disappear and lesions such as hyperkeratosis, bleeding and chafing are significantly improved. It should be emphasized that as the frequency of dosing decreases and patients experience recurrence of symptoms or signs, the frequency of dosing needs to be readjusted and increased, and therefore patient compliance with dosing decreases. A series of adverse reactions, such as skin atrophy, pigmentation, telangiectasia, and secondary infection. In recent years, fractional CO₂ laser has been gradually accepted by patients due to its almost non-invasive therapeutic advantages, but its specific therapeutic effect and adverse reactions are still unclear. Some clinical data are urgently needed to confirm its efficacy and adverse reactions, so as to provide patients with better treatment recommendations.

We compared local glucocorticoid and CO₂ partial laser therapy to study the difference of curative effect of different pathological types of non-tumor vulvar epithelial lesions and provide scientific basis for the treatment of these diseases. We present the following article in accordance with the TREND reporting checklist (available at https://atm.amegroups.com/article/view/10.21037/atm-23-677/rc).

Methods

Patients

From November 2016 to July 2018, 178 cases of vulvar LSC or lichen sclerosus were confirmed with vulvar biopsy at our institute. The exclusion criteria were the following: (I) those who were pregnant or had recently expressed the desire to have children; (II) those with light allergies; (III) those with critical underlying general medical problems; (IV) and those participants with mental or spiritual disorders that prevented them from completing follow-up visits. Finally, 160 patients were enrolled in this trial. This study is a double-blind trial. After matching according to age, pathological subtype, and severity of the disease, the patients were divided into two groups: a group treated with topical hormone and a group treated with CO₂ lattice laser therapies. There were 80 cases in each group, including 40 with LSC and 40 with lichen sclerosus. The baseline data are shown in Table 1. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Ethics Board of West China Second Hospital (No. 20180063) and informed consent was taken from all the patients.

Therapeutics

Ultrapulse CO₂ lattice laser

With the CO₂ laser multifunctional platform (Femilift, Alma Lasers), each person received a course of 3 sessions at 4-week intervals. This therapy last 1 week.

Progesterone/betamethasone cream therapy

Patients applied 1 gram of progesterone cream and betamethasone cream to the affected area in the morning and evening, respectively, once a day for 3 months and were instructed to keep the vulva clean and dry.

Clinical follow-up and efficacy evaluation indicators

The patients were followed up on the first, third, and sixth months after treatment. The efficacy was evaluated with the Patient Global Impression of Change (PGI-C) subjective symptom improvement scale (3) and clinical efficacy evaluation scale (4). The formula was applied to calculate the curative effect index: [Cure (n) + Effective (n)]/Total (n) × 100% (5).

Statistical methods

SAS 9.3 software (SAS Institute) was used to conduct the statistical analysis. The comparison of the data of normal distribution uses t test or analysis of variance, and the data that does not conform to the normal distribution is described as the median. The case number, constituent ratios, and the disordered classified data were calculated. χ² test was used to compare the classified counting data. Double-tailed test is used. P<0.05 indicated a statistically significant difference.

Results

Clinical baseline data

There were 80 patients in each group: 40 patients with chronic LSC and 40 patients with lichen sclerosus. The specific data are displayed in Table 1.

Comparison of curative effects

PGI-C scale

The results of the subjective improvement of the two groups (CO₂ lattice laser group and glucocorticoid group) at 1, 3, and 6 months after treatment clearly indicated that the laser treatment was superior to the glucocorticoid treatment (P<0.05). At 1 month after therapy, the subjective improvement rate was the highest with 82.5% in the laser group (66/80) and 65% in the glucocorticoid group (52/80). However, this disease is prone to recurrence. As a result, the number of people with subjective significant improvement over 2 courses of treatment gradually decreased as the time after treatment increased. The numbers of obviously improved participants at 1-, 3- and 6-month treatment were 66, 62, and 50, respectively in the laser cohort, and 52, 49, and 40 in the glucocorticoid cohort. The percentage at 6-month therapy dropped to 50%, which confirmed that the treatment was effective for a long time. The specific data are displayed in Table 2.

Clinical efficacy score

The two types of treatment methods (CO₂ lattice laser and glucocorticoids) at 1, 3, and 6 months were evaluated with curative effect index, which suggested obvious differences in the treatment effects between the treatment types (P<0.05, Table 3). The overall efficacy of treatment received in the laser treatment group was greater. In the glucocorticoid group, the efficacy rate decreased gradually after 1, 3, and 6 months of treatment, with 72.5%, 57.50%, and 52.50% respectively. In contrast, the total efficacy rate of the laser treatment group remained stable at 87.5% after 3 and 6 months of treatment (Figures 1,2). The specific data are displayed in Table 4.

Figure 1 A 35-year-old female with lichen simplex chronicus before and 3 months after CO2 lattice laser (A) and 3 months after treatment (B). The vulvar color turned red, and the itching score reduced from 8 to 3. Symptoms of self-conscious itching were considerably improved.

Figure 2 A 29-year-old female with lichen sclerosus, before treatment (A) and 3 months after treatment with CO₂ lattice laser (B). The local whitening changed to a healthy color, and the itching score reduced from 5 to 1 with obvious improvements.

Therapeutic effects of the different pathological subtypes

PGI-C score

After 1 month of treatment, the PGI-C showed an improvement rate of 80% (32 of 40) for LSC, which was higher than that for lichen sclerosus (50%). A marked difference in subjective improvement was found between the two pathological subtypes at the 3-month (P=0.006) and 6-month (P=0.024) treatments for laser therapy. The subjective improvement of the LSC group was better than that of lichen sclerosus group. In the glucocorticoid cohort, considerable discrepancies in subjective improvement were found between LSC and lichen sclerosus 1 month after initial treatment (P=0.008). The subjective improvement in the LSC was greater than that in Lichen sclerosus at 3 and 6 months. The specific data are displayed in Table 5.

Comparison of clinical efficacy of the different pathological subtypes

In the glucocorticoid group, the clinical effects of different pathological subtypes were obviously different. The effectiveness of therapy for LSC was better than that for lichen sclerosus At 6-month treatment, the effective rate of LSC was similar to that of lichen sclerosus. The 3- and 6-month clinical efficacy following therapy showed that there were statistical differences between the pathological types, with the efficacy for LSC being greater than that for lichen sclerosus (3 months: 95% vs. 75%; 6 months: 95% vs. 70%). The specific data are displayed in Table 6.

Discussion

In this study, we compared the efficacy of CO₂ lattice laser and glucocorticoids in the treatment of vulvar epithelial nonneoplastic lesions. The results of PGI-C score are consistent with those of Kraus et al. as well as Leis et al. who reported on 4 cases of vulvar LSC treated with CO₂ lattice laser (6,7). Another comparative study of vulvar epithelial nonneoplastic lesions treated with dot-matrix CO₂ laser was performed. The findings revealed a remarkable improvement in the itching of the vulva and pain during intercourse without adverse effects (8,9). This may be related to the thermal response of the laser inducing tissue edema and the release of HSP70 and transforming growth factor beta (TGF) (10), which in turn improves skin circulation and nutrition in the localized nonneoplastic lesions of the vulvar epithelium and repairs damaged tissue from local scratching (1). In our study, the efficacy of CO₂ lattice laser and glucocorticoids was more than 50% at 1, 3, and 6 months of treatment. This finding is similar to that of Mautz et al. (11), who reported that patients with vulvar LSC treated with CO₂ laser had a normal regenerating epithelium of the vulvar tissue and prolonged duration of symptoms (2–3 years).

The main manifestations of vulvar epithelial nonneoplastic lesions are vulvar pruritus or/and pain, vulvar skin roughness, hypopigmentation, skin chap, atrophy, adhesion, and even carcinogenesis, which can seriously affect the quality of life (12-15). Recently, patients with this disease appear to be increasingly younger, with the youngest patient in our hospital being 7 years old. However, the pathogenesis of the disease is currently not clear and thus has been continuously examined in clinical practice. However, there is a lack of an optimal therapeutic approach, which is a challenge for both medical professionals and patients.

In the present study, two different therapeutics were compared in the treatment of two disease subtypes. The subjective improvement in the laser-treated group was higher, and the proportion of significant improvement in patients’ symptoms was the highest. CO₂ has been discovered effectively to block hyperkeratosis in clinic (16). The blood supply can be improved and nutrition of the skin can be increased in the local nonneoplastic lesions of vulvar epithelium (17,18). Local scratching-damaged tissue can be repaired to maintain the integrity and elasticity of vulvar skin (19). In our study, we found that both treatments were clinically more effective for both types of lesions; the overall efficacy at 1, 3, and 6 months after treatment was above 50%, with the laser treatment group experiencing the most pronounced effect. This result is consistent with that of Mautz et al. (11), who reported that twenty-three adult women received CO₂ laser treatment, which significantly improved the scores of all scales from baseline to T4 questionnaire. CO₂ laser has been proven to be effective for VLS symptoms and can be regarded as a substitute for corticosteroids during maintenance treatment (20).

In the comparisons of both subjective improvement and clinical efficacy, the response of LSC to laser therapy was more favorable (21-23). Borghi et al. found that patients with lichen sclerosus were often associated with other autoimmune disorders (24). He et al. tested 8 kinds of autoantibodies in 142 patients with lichen sclerosus and found that 48% of the patients were positive for autoantibodies (25). Krapf et al. recorded the clinical manifestations and long-term follow-up of 40 cases with Vulvar lichen Sclerosus (26), their results also showed that the HLADQB10201 allele was present in 80% of patients and 41.8% of controls (RR: 3.71; P≤0.0042). Altogether, various pathological types show different therapeutic responses, and the reasons for this need to be further investigated. The mechanism of combined treatment of the two may be: the thermal, photochemical, and pressure effects of hormone combined with CO₂ can stimulate the healing of newly formed squamous epithelial wounds by resecting local vulvar lesions. Combined treatment of the two can enhance the expression of VEGF in tissues in a short period of time, effectively improve the microvascular status of local vulvar lesions, promote tissue angiogenesis and repair of damaged tissues, and increase the number of microvessels in the dermis, Thereby improving the state of local ischemia and hypoxia, and promoting the rehabilitation of diseased skin; At the same time, combined treatment of both can reverse the disorder of cell cycle in vulvar lesions, thereby improving the condition of vulvar lesions.

This study had a few limitations that should be noted. First, the sample size of this study was small; however, it could meet the requirement of statistical efficiency. In the follow-up study, we will expand the sample size for further exploration. Second, the follow-up period was only 6 months, and a longer follow-up is needed to continue to obtain more clinical data. Finally, there are few methods to evaluate the efficacy and a lack of standardized treatment guidelines. Therefore, there is a need to develop an expert consensus or clinical guidelines in the future in order to provide more authoritative indicators for clinical evaluation.

Conclusions

In this study, the clinical efficacy and subjective improvement provided by 2 therapeutics for vulvar epithelial nonneoplastic lesions were compared. It was found that the 2 therapeutics for vulvar epithelial nonneoplastic lesions could achieve better subjective improvement in the early stage after treatment. However, ultra-pulse CO₂ lattice laser could achieve higher subjective improvement and continue to obtain better therapeutic effect, suggesting that the CO₂ lattice laser is a better choice for the treatment of this disease. Different pathological types responded differently to the treatments. For both subjective improvement or the clinical effect, the response to CO₂ for LSC laser was better than that for lichen sclerosus. Our findings suggest the need to change the treatment strategy to favor laser treatment for better results when drugs are not effective in order to improve the quality of life of patients.

Acknowledgments

Funding: This study was supported by the National Key Research and Development Program of China (No. 2021YFC2009100), Research Projects of Sichuan Science and Technology Department (No. 2023YFQ0070), and Key Research Projects of Sichuan Science and Technology Department (No. 2023YFG0128).

Footnote

Reporting Checklist: The authors have completed the TREND reporting checklist. Available at https://atm.amegroups.com/article/view/10.21037/atm-23-677/rc

Data Sharing Statement: Available at https://atm.amegroups.com/article/view/10.21037/atm-23-677/dss

Peer Review File: Available at https://atm.amegroups.com/article/view/10.21037/atm-23-677/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-23-677/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Ethics Board of West China Second Hospital (No. 20180063) and informed consent was taken from all the patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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