
==== Front
Skin Res Technol
Skin Res Technol
10.1111/(ISSN)1600-0846
SRT
Skin Research and Technology
0909-752X
1600-0846
John Wiley and Sons Inc. Hoboken

10.1111/srt.70065
SRT70065
Original Article
Original Article
A Preliminary Study Using High‐Frequency Ultrasound to Evaluate Vulvar Skin With Lichenoid Vulvar Dermatoses
Ma Jingyi https://orcid.org/0009-0009-4227-3115
1 2
Song Yan 1 2
Xv Jun 3
Shen Kaikai 2
Wu Ming 2
Chen Jiyun 2
Zhao Xinyu 1 2
Zhu Haohui 1 2 zhh761126@163.com

Zhang Xijun https://orcid.org/0000-0002-7273-4711
1 2 sophia3936@163.com

1 Zhengzhou University People's Hospital Zhengzhou China
2 Department of Ultrasound Henan Provincial People's Hospital Zhengzhou China
3 Department of Obstetrics and Gynecology Henan Provincial People's Hospital Zhengzhou China
* Correspondence: Xijun Zhang (sophia3936@163.com) | Haohui Zhu (zhh761126@163.com)

19 9 2024
9 2024
30 9 10.1111/srt.v30.9 e7006530 8 2024
02 8 2024
04 9 2024
© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.
https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

ABSTRACT

Background

Lichenoid vulvar dermatoses (LVD) are inflammatory diseases primarily affecting the vulva and anus. This study aims to evaluate the skin changes in patients with LVD using high‐frequency ultrasound.

Methods

Forty‐five patients with LVD, who attended Henan Provincial People's Hospital from November 2021 to March 2024, were selected. According to the pathological conclusions, patients were divided into two groups: the vulvar lichen sclerosus (VLS) group (n = 24) and the vulvar lichen simplex chronicus (VLSC) group (n = 21). Thirty age‐ and BMI‐matched healthy women were selected as the control group. We assessed the epidermal thickness, subepidermal low echogenic band (SLEB) thickness, dermal thickness, and vascular index (VI) among the three groups. Receiver operating characteristic curve (ROC) analysis was performed to determine the diagnostic efficacy of these ultrasound parameters for LVD. Binary logistic regression was used to investigate risk factors influencing LVD pathology in VLS patients.

Results

Epidermal thickness, SLEB thickness, dermal thickness, and VI were increased in the VLS and VLSC groups compared to the control group (p < 0.05). There were no statistically significant differences in ultrasound parameters between the VLS and VLSC groups (p > 0.05). The ROC curves showed that the area under the curve (AUC) value for the dermis (AUC = 0.882) was the largest for VLS, and VI (AUC = 0.917), it was the largest for VLSC. Binary logistic regression indicated that having an allergic disease was a risk factor for VLS between VLS and VLSC groups (OR = 6.797, p = 0.028).

Conclusion

High‐frequency ultrasound can detect thickening of the skin and increasing VI in patients with LVD, which can be helpful in the evaluation and management of LVD.

high‐frequency ultrasound
lichenoid vulvar dermatoses
skin
superb microvascular imaging
Natural Science Foundation of Henan Province 10.13039/501100006407 222300420356 Henan Provincial Science and Technology Research Project 10.13039/501100017700 222102310053 Natural Science Foundation of China 10.13039/501100001809 82171963 82371980 source-schema-version-number2.0
cover-dateSeptember 2024
details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.4.8 mode:remove_FC converted:20.09.2024
Jingyi Ma and Yan Song contributed equally to this article.

Funding: This work was supported by the Natural Science Foundation of Henan Province (222300420356), Henan Provincial Science and Technology Research Project (222102310053), and Natural Science Foundation of China (82171963, 82371980)
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pmc1 Introduction

Lichenoid vulvar dermatoses (LVD) are inflammatory diseases primarily affecting the vulva and anus. LVD includes vulvar lichen sclerosus (VLS), vulvar lichen planus (VLP), and vulvar lichen simplex chronicus (VLSC) [1]. Among these, VLS and VLSC are the most common forms of vulvar inflammatory dermatoses.

VLS is a prevalent inflammatory condition that predominantly affects adolescent and postmenopausal women. Patients with VLS experience severe itching and may suffer from varying degrees of sexual dysfunction, leading to significant financial and psychological burdens [2]. Women with VLSC typically complain of persistent itching that is alleviated by rubbing or scratching. If left untreated for prolonged periods, LVD can result in scarring and increase the risk of vulvar intraepithelial neoplasia and squamous cell carcinoma [3]. Therefore, early detection, diagnosis, and treatment of LVD are crucial.

Currently, the diagnosis of VLSC or VLS primarily relies on pathologic biopsy and clinical expertise. However, due to its invasive nature, pathology biopsies cannot be performed frequently. High‐frequency ultrasound, particularly with recent advancements, allows for visualization and measurement of the epidermis, dermis, and subcutaneous tissue [4]. It has become increasingly valuable in the monitoring of inflammatory dermatoses due to its noninvasive nature and feasibility in assessing skin lesions [5, 6]. Superb microvascular imaging (SMI)is an innovation in microvascular imaging that utilizes adaptive algorithms to filter clutter and motion artifacts, thereby enhancing the visualization of low‐velocity microvessels. SMI is superior to conventional flow imaging in detecting small vessels and microvasculature with high sensitivity [7]. This noninvasive and reproducible method enables quantitative and accurate evaluation of microvascular status. We aim to identify ultrasound features specific to LVD.

This study aims to quantitatively analyze skin and microvascular changes in LVD using high‐frequency ultrasound and superb microvascular imaging technology. The objective is to provide a more objective, non‐invasive, and convenient method for clinical diagnosis of LVD.

2 Materials and Methods

2.1 Ethical Considerations

The study protocol was approved by the ethics committee of Henan Provincial People's Hospital and informed consent was obtained from the patients.

2.2 Patients

This prospective study was conducted in the Department of Ultrasound, Henan Provincial People's Hospital from November 2021 to March 2024, and included 45 female participants. Based on the pathological conclusions, the patients were divided into two groups: the VLS group (n = 24) and the VLSC group (n = 21). Additionally, 30 age‐ and BMI‐matched healthy female volunteers were recruited during the same period to serve as a control group.

Inclusion criteria were as follows: (1) females of age 18–70 years, (2) confirmed diagnosis of VLS or VLSC based on pathological examination, (3) no history of receiving physicotherapeutics or glucocorticoids in the last 3 months, (4) voluntary participation in the ultrasonic examination.

Exclusion criteria were as follows: (1) the presence of other diseases affecting the vulvar regions, (2) coexisting skin conditions such as psoriasis, (3) pregnancy or lactation, and (4) absence of pathology results.

2.3 Ultrasonic Examination and Parameters

The Canon Aplio i900 color Doppler ultrasound (Canon Medical Systems Corporation, Japan) equipped with a PLI‐2004 BX (probe frequency 8–24 MHz) line array probe was used for image acquisition in this study. The SKIN condition was employed to optimize imaging depth and focus on the near field. The imaging parameters of SMI mode were consistent throughout the experiment and color gain (CG) was fixed at 38 dB.

Patients were positioned supine with legs apart to fully expose the perineal area. The examination focused on the most pruritic area within the perineal region. A disposable film was used to cover the probe, and a couplant was applied between the film and the perineal skin. Couplant was generously applied externally to ensure optimal contact, and the probe was placed vertically on the perineal region. Images were captured and stored once stabilized and clear (Figure 1A–F).

FIGURE 1 (A) Gray‐scale ultrasound images of the control group, (B) VI measurement image of microvascular blood flow for the control group, (C) Gray‐scale ultrasound images of the VLS group, (D) VI measurement image of microvascular blood flow for the VLS group, (E) Gray‐scale ultrasound images of the VLSC group, and (F) VI measurement image of microvascular blood flow for the VLSC group.

Epidermal thickness, subepidermal low echogenic band (SLEB) thickness, and dermal thickness of each patient were measured using ImageJ 2.0 software (National Institutes of Health, USA). Blood vessels within the dermis were observed in SMI mode, and the image showing the richest and largest blood flow signal was selected. A region of interest (ROI) was defined to obtain vascular index (VI) parameter measurements.

Each ultrasound parameter was measured three times, and the results were averaged for analysis.

2.4 Statistics Analysis

Statistical analyses were conducted using SPSS version 27.0 software (IBM, Armonk, NY).

Normally distributed continuous data were presented as the mean ± standard deviation. For homogeneous variances among the three groups, comparisons were performed using one‐way ANOVA, with pairwise comparisons conducted using the LSD‐t test. In the case of heterogeneous variance, comparisons among the three groups were conducted using the Welch method, and pairwise comparisons were made using Tamhane's T2 test.

Non‐normally distributed continuous data were presented as median (interquartile range). The comparison among the three groups was conducted using the Kruskal–Wallis H‐test, and further pairwise comparisons were using the Bonferroni correction method.

Categorical variables were presented as frequencies and percentages, and group comparisons were made using the χ 2‐test.

The diagnostic efficacy of each ultrasound parameter in patients with lichenoid lesions was analyzed by receiver operating characteristic curve (ROC curve).

Factors that showed significant differences between the VLS and VLSC groups were included in the Binary logistic regression to identify risk factors associated with VLS.

Intraclass correlation coefficients (ICC) were calculated to detect inter‐ and intra‐observer repeatability.

Statistically significant was set at a two‐sided p‐value < 0.05.

3 Results

3.1 Comparison of General Information Among the Three Groups

Table 1 presents the general information of all patients who participated in the study. In both the VLS group and the VLSC group, all 45 patients reported varying degrees of itching, with some experiencing symptoms for decades. There was no statistically significant difference in age among the three groups (p > 0.05). The median disease duration in the VLS group was 28.50 (59.00) months, while the median disease duration in the VLSC group was 13.00 (21.00) months, and the difference was statistically significant (p < 0.05).

TABLE 1 Clinical parameters.

Groups	n	Age (years)	Disease duration (months)	With/without a history of allergic diseases (n)	
VLS group	24	42.04 ± 13.12	28.50 (59.00) *	10/14 *	
VLSC group	21	35.14 ± 7.97	13.00 (21.00)	2/19	
Control group	30	36.80 ± 12.76	/	/	
F/Z/x2		2.310	−2.529	4.388	
p‐value		0.110	0.011	0.036	
* p < 0.05 vs. VLSC Group.

John Wiley & Sons, Ltd.

3.2 Comparison of Ultrasound Parameters Among the Three Groups

Table 2 summarizes the ultrasound parameters for the three groups. Epidermal thickness, SLEB thickness, dermal thickness, and vascular index (VI) were all significantly increased in both the VLS and VLSC groups compared to the control group (p < 0.05). There was no statistically significant difference in ultrasound parameters between the VLS and VLSC groups (p > 0.05) (Figure 2A–D).

TABLE 2 Ultrasound parameters.

Groups	Epidermal thickness (mm)	SLEB thickness (mm)	Dermal thickness (mm)	VI	
VLS group (n = 24)	0.23 ± 0.06 *	0.16 ± 0.11 *	1.34 ± 0.37 *	2.7 (6.65) *	
VLSC group (n = 21)	0.23 ± 0.07 *	0.18 ± 0.11 *	1.27 ± 0.37 *	3.0 (5.4) *	
Control group (n = 30)	0.19 ± 0.04	0.00 (0.01)	0.88 ± 0.19	0.28 (0.30)	
F/H	7.159	33.846	20.684	33.236	
p‐value	0.002	<0.001	<0.001	<0.001	
* p < 0.05 vs. control group.

John Wiley & Sons, Ltd.

FIGURE 2 The bar chart showed differential changes of epidermis (A), SLEB (B), dermis (C), and VI (D), among the three groups. *p < 0.05 vs. control group, **p < 0.01 vs. control group, and ***p < 0.001 vs. control group.

3.3 Diagnostic Performance of Ultrasound Parameters

Table 3 summarizes the diagnostic performance of all ultrasound parameters for the VLS and VLSC groups.

TABLE 3 The diagnostic performance of all ultrasound parameters.

Groups	Ultrasound parameters	AUC	p‐value	95% Confidence interval	Sensitivity	Specificity	
VLS group	Epidermis	0.736	0.003	0.594–0.878	0.625	0.833	
VLS group	SLEB	0.876	0.000	0.777–0.975	0.833	0.833	
VLS group	Dermis	0.882	0.000	0.796–0.968	0.750	0.833	
VLS group	VI	0.874	0.000	0.770–0.977	0.667	1.000	
VLSC group	Epidermis	0.696	0.018	0.549–0.843	0.667	0.833	
VLSC group	SLEB	0.899	0.000	0.806–0.992	0.905	0.767	
VLSC group	Dermis	0.837	0.000	0.721–0.952	0.714	0.867	
VLSC group	VI	0.917	0.000	0.822–1.000	0.905	0.625	
John Wiley & Sons, Ltd.

3.3.1 Diagnostic Performance of Ultrasound Parameters for the VLS Group

ROC curves (Figure 3A) evaluated the diagnostic efficacy of all ultrasound parameters for VLS. Epidermis, SLEB, dermis, and VI showed good diagnostic performance, with the dermis having the largest AUC value, with the greatest Youden index at a cutoff value of 1.07, a sensitivity of 0.75, and a specificity of 0.833.

FIGURE 3 This ROC curve (A) is for the VLS group and this ROC curve (B) is for the VLSC group.

3.3.2 Diagnostic Performance of Ultrasound Parameters for the VLSC Group

ROC curves (Figure 3B) were used to analyze the diagnostic efficacy of all ultrasound parameters for VLSC. Epidermis, SLEB, dermis, and VI demonstrated good diagnostic value, with VI having the largest AUC value, with the greatest Youden index at a cutoff value of 0.625, a sensitivity of 0.905, and a specificity of 0.900.

3.4 Binary Logistic Regression

Variables with statistically significant differences between the VLS and VLSC group (disease duration and history of allergic diseases) were included in binary logistic regression, and the results indicated that a history of allergic disease was an independent risk factor for VLS (OR = 6.797, p = 0.028) (Table 4).

TABLE 4 Binary logistic regression analysis.

Characteristic	B	SE coeff.	Wald	p‐value	OR	95% CI	
Disease duration ≥22 months	0.998	0.661	2.279	0.131	2.714	0.742–9.923	
With a history of allergic diseases	1.916	0.870	4.848	0.028	6.797	1.234–37.425	
Abbreviations: B, regression coefficients; CI, confidence interval; OR, odds ratio; SE coeff., standard error of coefficient.

John Wiley & Sons, Ltd.

3.5 Repeatability Test

Ten patients were randomly selected for repeatability testing. Both the same observer and another observer measured the parameters of these 10 patients 1 week apart. Results in Table 5 showed good consistency (ICC > 0.75, p < 0.001), indicating excellent intra‐ and inter‐observer reliability.

TABLE 5 Repeatability test.

	Intra‐observer reliability	Inter‐observer reliability	
	ICC	95% CI	ICC	95% CI	
Epidermis	0.979	0.922–0.995	0.957	0.841–0.989	
SLEB	0.982	0.930–0.996	0.964	0.871–0.991	
Dermis	0.986	0.949–0.997	0.953	0.831–0.988	
John Wiley & Sons, Ltd.

4 Discussion

VLS is characterized by chronic inflammation with white patches on the vulvar skin [8]. VLSC presents as thick‐scaly plaques due to persistent itching–scratching [9]. In recent years, LVD has gained attention, driven by concerns over the invasive nature and high cost of pathology biopsies, which some patients may refuse. Ultrasound offers a non‐invasive and convenient alternative for diagnosing LVD, making it particularly valuable in clinical practice.

Our study found increased epidermal thickness in both VLS and VLSC groups compared to controls. Yu Fu et al. [10] measured pathologic pictures of VLS and found no change in full epidermal thickness in VLS compared to the control. In terms of pathology, VLS is epidermal thinning [11]. Possible reasons include variability in the presentation of VLS lesions and the impact of chronic itching, which can lead to epidermal thickening [12]. Additionally, differences in hair presence in the vulvar area may influence measurements. Our study did not require hair removal potentially affecting epithelial thickness measurements [13]. For VLSC, in terms of histopathology, the lesions were characterized by epidermal thickening, hyperkeratosis, spongiosis, and acanthosis [14, 15]. Our findings were consistent with the histopathology.

In both the VLS and VLSC lesions, the presence of SLEB was observed with high‐frequency ultrasound, which is consistent with previous studies [16, 17]. This band's thickness correlates with factors like age and inflammatory cell infiltration, relevant to both conditions [16]. Both VLS and VLSC have different degrees of inflammatory infiltrate, and even some VLS have dermal collagenization [8, 15]. The thickness of the SLEB was related to age explaining the fact that in our study the thickness of the SLEB in the control group was not zero. There was no statistical difference in age between the three groups, and we still attributed the difference in SLEB thickness between the three groups to disease.

Increased dermal thickness observed in VLS and VLSC aligns with previous findings, reflecting histological features such as dermal edema and inflammatory cell infiltration [11, 18]. Histologic features of VLS include dermal edema, inflammatory cell infiltration, and collagen homogenization [12, 19]. VLSC also contains inflammatory cell infiltration but no dermal collagen homogenization [9]. These pathologic features are reflected on ultrasound as increased dermal thickness. Ultrasound's inability to distinguish specific pathologic feature and only dermal thickening is observed.

VI, reflecting the ratio of vascular area to the entire region of interest [20], was increased in both the VLS and VLSC groups, consistent with dermoscopic findings of irregular linear vessels [21]. Previous studies using different imaging techniques also support these findings [22, 23], attributing increased VI to inflammatory processes affecting blood vessel integrity. VLS and VLSC have different degrees of inflammatory infiltrate. In the early stages of the disease, inflammatory cells cause blood vessels to distort. As the disease progresses, collagen and fibrosis diminish the visibility of blood vessels [20, 24]. Therefore, the VI in the VLSC group was increased than the VI in the VLS, but there was no statistical difference between the two groups. In brief, VI was increased in both the VLS and VLSC groups compared to the control group.

ROC analysis demonstrated good diagnostic performance for epidermal thickness, SLEB, dermal thickness, and VI in diagnosing LVD. These parameters provide valuable insights into disease severity and progression, supporting ultrasound's role in evaluating LVD.

Our study identified a history of allergic disease as an independent risk factor for VLS, aligning with observations of autoimmune associations in VLS [25, 26]. This underscores the autoimmune nature of VLS, supported by serum antibody studies [27]. We hypothesize that VLS may be an autoimmune phenomenon [28].

5 Limitations

Several limitations merit consideration. This study was single‐center with a small sample size, necessitating larger studies for broader validation. The use of a disposable film during ultrasound to protect sensitive vulvar areas might have affected epidermal thickness measurements. Additionally, the exclusion of vulvar lichen planus patients and the lack of posttreatment evaluations are limitations that should be addressed in future research.

6 Conclusions

Epidermal thickness, SLEB thickness, dermal thickness, and VI were increased in LVD patients compared to the control group. High‐frequency ultrasound quantitatively assesses skin changes in VLS and VLSC lesions, offering a valuable non‐invasive diagnostic tool for LVD. Future research should address current study limitations to enhance ultrasound's utility in inflammatory dermatoses.

Ethics Statement

This study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital. All patients in this study provided informed written consent.

Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgments

This work was supported by the Natural Science Foundation of Henan Province (222300420356), Henan Provincial Science and Technology Research Project (222102310053), and the Natural Science Foundation of China (82171963, 82371980).

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.
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