Retrospective analysis of the clinical characteristics and patient‐reported outcomes in vulval lichen planus: Results from a single‐center study

Vulval lichen planus (VLP) is a rare, but often chronic, inflammatory disease whose symptoms include genital pain, discomfort, and dyspareunia. The clinical manifestations include erythema, erosions, and scarring. The aim of this study was to longitudinally investigate patient‐reported outcomes and clinical findings in patients with VLP. Patients (>18 years) with histologically confirmed VLP were included in the retrospective analysis. Patient demographics, clinical features, symptomatology, quality of life, management, clinical outcomes, and comorbidities associated with VLP were analyzed. Twenty‐four patients were identified with a mean (standard deviation [SD]) follow‐up time of 19.3 (13.8) months. Classical VLP with glazed erythema was found in seven (29.2%) patients, erosive VLP was present in 15 (62.5%) patients, and hypertrophic VLP in two (8.3%). Seven patients had additional cutaneous involvement, while six patients had both vulval and oral mucosal involvement. The labia minora was the most frequently affected anatomical site (83.3%), followed by the clitoris (58.3%). Scarring lesions were found in 62.5% (n = 15) of patients. All study participants received treatment with potent and/or superpotent topical corticosteroids but 50% required systemic therapy (acitretin, corticosteroids, or hydroxychloroquine). Five (20.8%) patients underwent surgery due to adhesions and scarring resulting from VLP. One patient was diagnosed with a vulval squamous cell carcinoma during long‐term follow‐up. The mean (SD) Dermatology Life Quality Index score was 8.4 (5.5) at presentation and 8.9 (6.8) at the end of follow‐up. In conclusion, VLP was associated with moderate quality of life impairments which persisted despite treatment, suggesting that current treatments for VLP are inadequate.

(>18 years) with histologically confirmed VLP were included in the retrospective analysis. Patient demographics, clinical features, symptomatology, quality of life, management, clinical outcomes, and comorbidities associated with VLP were analyzed. Twenty-four patients were identified with a mean (standard deviation [SD]) follow-up time of 19.3 (13.8) months. Classical VLP with glazed erythema was found in seven (29.2%) patients, erosive VLP was present in 15 (62.5%) patients, and hypertrophic VLP in two (8.3%). Seven patients had additional cutaneous involvement, while six patients had both vulval and oral mucosal involvement. The labia minora was the most frequently affected anatomical site (83.3%), followed by the clitoris (58.3%). Scarring lesions were found in 62.5% (n = 15) of patients. All study participants received treatment with potent and/or superpotent topical corticosteroids but 50% required systemic therapy (acitretin, corticosteroids, or hydroxychloroquine). Five (20.8%) patients underwent surgery due to adhesions and scarring resulting from VLP. One patient was diagnosed with a vulval squamous cell carcinoma during long-term follow-up. The mean (SD) Dermatology Life Quality Index score was 8.4 (5.5) at presentation and 8.9 (6.8) at the end of follow-up. In conclusion, VLP was associated with moderate quality of life impairments which persisted despite treatment, suggesting that current treatments for VLP are inadequate.

K E Y W O R D S
clinical characteristics, patient-reported outcomes, quality of life, treatment, vulval lichen planus

| INTRODUC TI ON
Vulval lichen planus (VLP) is a rare disease with a broad spectrum of clinical presentation, ranging from diffuse erythema to severe erosions or hyperkeratotic plaques, and may be accompanied by scarring and loss of the normal vulval architecture. [1][2][3] The incidence of VLP is unknown, 4 but is estimated at 1/4000 women. The disease may be restricted to the vulva or also affect the vagina, oral mucosa, and/or the skin. Vulvovaginal-gingival syndrome is a severe variant of VLP in which erosions develop on the vulval, vaginal, and gingival mucosal surfaces. 5 A biopsy should be considered to confirm that diagnosis 3 and exclude other dermatoses including mucous membrane pemphigoid (MMP), bullous pemphigoid (BP), pemphigus vulgaris (PV), and lichen sclerosus. MMP, BP, and PV are autoimmune blistering diseases. MMP is clinically characterized by erosions and erythema, whereas the clinical hallmarks of BP are blisters and/or eczema or an urticarial rash on the trunk, but may be accompanied by blisters or erosions in the mouth or vulva. PV manifests clinically with erosions in the oral cavity and/or on the trunk, and may also affect the vulva. Vulval lichen sclerosus (VLS) typically shows porcelain-white papules and plaques, and may often be associated with erosions, fissures, introital narrowing, and scarring. VLP and VLS are both immunologically-mediated diseases of the genitalia, sharing overlaying clinical features, and biopsies of VLP/VLS may be difficult to distinguish. 6 Cases of an overlap of VLP and VLS have been described, leading to the discussion of whether VLP and VLS are a continuum, rather than independent entities. 7,8 Patients with VLP should undergo gynecological assessment to exclude vaginal involvement. The major aims of treatment are symptomatic relief and the prevention and/or limitation of scarring. 9 Whilst the application of potent/superpotent topical steroids remains the mainstay of treatment, 9 topical calcineurin inhibitors can be considered. 10 Systemic treatments, including corticosteroids, retinoids, hydroxychloroquine, and methotrexate, are usually used for treatmentresistant and erosive variants of VLP. 9,11 Regular follow-up is recommended to monitor disease activity and to allow early detection of malignant transformation. 9 To date, longitudinal data on patient-reported outcomes, such as the quality of life as well as treatment outcomes and clinical manifestations, remain scant. 12,13 Thus, the aim of this retrospective single-center cohort study was to longitudinally characterize the quality of life, clinical presentation, and treatment outcomes in patients with VLP.

| Study population and definition of eligible cases
The retrospective cohort study encompassed biopsy-proven VLP between January 2017 and December 2020 managed in the dermatological referral outpatient clinic of University of Lübeck, Germany. The patients were diagnosed with VLP according to consensus clinicopathological diagnostic criteria: glazed erythema, erosions, hyperkeratotic borders/plaques, Wickham striae in surrounding skin, vaginal inflammation, pain/burning sensation, and typical histological features (band-like lymphohistiocytic infiltrate along the dermoepidermal junction, basal layer degeneration). 3 The study was approved by the institutional ethical committee (21-008) and performed in accordance with the Declaration of Helsinki.

| Definition of covariates
The medical records of patients were systematically reviewed and the following variables were retrieved: clinical features; Dermatology Life Quality Index (DLQI) 14 scores at the onset of the disease and the last recorded follow-up; and treatment modalities as well as comorbidities. The electronic case records were screened for the presence of the following signs and/or symptoms at initial presentation based on the clinical diagnostic criteria of VLP: glazed erythema, erosions, hyperkeratotic borders/plaques, and pain/burning sensation. 3,15 The printed DLQI questionnaire was handed out to the patients at baseline and at the regular follow-up visits at the outpatient department.

| Demographic and clinical features
The present study included 24 female patients with VLP ( Table 1).
The mean (SD) and median (range) age of study participants was

| Symptomatology and quality of life
Ten (41.7%) patients reported a prominent burning sensation at their initial presentation. The mean (SD) DLQI score was 8.4 (5.5) at initial presentation and 8.9 (6.8) at the end of follow-up. The DLQI did not show any significant improvement despite treatment (p = 0.342).

| DISCUSS ION
Our study demonstrated that VLP was associated with moderate impairments in quality of life, which largely persisted despite treatment. In addition, 41.7% of patients reported painful burning sensations as a presenting symptom. These data underscore the negative impact of VLP on quality of life. The rate of vulval scarring reached 62.5%, in line with literature reporting scarring rates of up to 95%. 17 In this cohort, one patient with erosive VLP developed a HPV-independent vulval SCC. Of note, a recent study showed no association of lichen planus with HPV-independent vulval SCC. 18 However, longstanding erosive lesions on mucosal sites, especially in patients who carry sexually acquired and oncogenic HPV, are at higher risk of malignant transformation. 19 Long-term follow-up is mandatory for patients with VLP to monitor disease activity and to exclude an SCC at an early timepoint. 9 Warning flags are chronic erosive lesions, ulcers with thickened edges, or enlarging nodules.
The pathomechanism driving the association of VLP with SCC is yet to be established. However, we might assume that chronic and  Limitations of the current study include the relatively small number of patients identified and its retrospective nature. It is also worth noting that due to the lack a control group, the relative risk of VIN was compared to that in the general population, thus may have resulted in some degree of selection bias, given that the patients were attending a tertiary referral center.
In conclusion, the current retrospective cohort study revealed that in more than half of patients with VLP present with concomitant oral lesions, the labia minora is the most frequently involved anatomical structure, and the glazed erythema is the most frequent manifestation.
Half of the study participants were managed by systemic drugs and 20% underwent surgical intervention. Patients with VLP experience a moderate impairment in quality of life which does not considerably improve under treatment. The current study increases the awareness of the chronic course of VLP and its enormous impact on quality of life. Our findings suggest that the current treatment is insufficient to minimize the disease's burden. Further research is required to estimate the utility of different therapeutic modalities utilized to manage this disease.

ACK N OWLED G M ENTS
Open Access funding enabled and organized by Projekt DEAL.

CO N FLI C T O F I NTE R E S T
None declared.