Perineural Inflammation as a Novel Feature in Lichen Sclerosus: A Case Series of Histologic and Clinical Features.

ABSTRACT: Lichen sclerosus (LS) is a frequently encountered inflammatory skin disorder characterized by whitened, atrophic patches that can cause pain and pruritus. The underlying cause of this condition remains unknown. Primarily affecting the genital area, this condition carries an increased risk of developing cutaneous cancers and frequently co-occurs with autoimmune disorders. Our retrospective study aimed to explore histologic features of LS, with a particular focus on a newly established finding and its potential implications. We examined 53 histologic cases of LS collected over 2 years. Experienced pathologists evaluated and reached a consensus on the assignment of histologic features. Patient charts were manually reviewed to gather relevant demographic and clinical data. Statistical analysis was performed using IBM SPSS Statistics (2021). Of the 53 total patients identified as meeting criteria for inclusion in this study, only 8 (15%) were male. Eight cases (15%) demonstrated perineural inflammatory infiltrate. Notably, half of all samples from male patients exhibited perineural inflammatory infiltrate. A statistically significant increase ( P < 0.01) in the presence of dermal plasma cells was identified in cases with perineural inflammation versus cases without this feature. The findings of our study highlight the recurrent nature of perineural inflammation in LS, providing valuable insights into this condition. Furthermore, we observed a notable correlation between perineural inflammation, male patients, and the presence of dermal plasma cells. These discoveries contribute to a better understanding of the underlying mechanisms of LS and suggest avenues for future research into the condition.

Photodynamic therapy for male genital lichen sclerosus with urethral stricture-Case report.

Male genital lichen sclerosus (MGLSc) typically impacts the external genitalia, resulting in balanitis, erectile pain, urination symptoms, and/or urinary retention. Urethral stricture develops in up to 20 % of these patients, which is usually found in the distal part of the urethra but can, in severe instances, impact the entire urethra and cause structural changes. Patients with skin lesions limited to the foreskin and partially extending to the glans can typically be cured by circumcision, but the recurrence rate of stricture is high when the glans or urethra is extensively involved. In the following case report, we describe a 45-year-old man with a history of MGLSc for 3 years and urethral stricture for 2 years, and these conditions remained untreated after circumcision. We emphasize that treatment with 5-aminolevulinic acid-induced photodynamic therapy (ALA-PDT) may further improve outcomes in such severe cases.

[Genital lichen sclerosus and lichen planus]. / Genitaler Lichen sclerosus und Lichen planus.

Lichen sclerosus (LS) and lichen planus (LP) are chronic inflammatory dermatoses of unknown aetiology. They pose the most important differential diagnoses of inflammatory dermatoses in the genital area. There is often a delay in diagnosing LS and LP and subsequently treatment is initiated late in the course of the disease, which will lead to scarring and a decreased quality of life. There is an increased risk of the development of malignancies in the genital area in both diseases; however, early and continuous treatment with potent topical steroids will decrease this risk.

Affirming Long-Term Outcomes After Contemporary Urethroplasty: The Adverse Impact of Increasing Stricture Length, Lichen Sclerosus, Radiation, and Infectious Strictures.

PURPOSE: There is a paucity of reported long-term outcomes after contemporary urethroplasty. Our objective is to determine the long-term success of modern urethroplasty and identify factors associated with stricture recurrence in this context. MATERIALS AND METHODS: Patients undergoing urethroplasty from July 2003 to May 2013 with at least 100 months of follow-up were identified. Long-term outcomes including stricture recurrence and patient satisfaction were evaluated by review of regional/provincial electronic records and telephone interview. Urethroplasty failure was defined as a recurrent stricture (<16F) confirmed on cystoscopy. Cox regression was used to evaluate variables associated with long-term stricture recurrence. RESULTS: A total of 733 patients were identified with ≥ 100 months follow-up. Median patient age was 45 years, stricture length was 4.7 cm, and 85.8% failed prior endoscopic treatment. At a median follow-up of 12.3 years, 89 recurrences were observed. Cumulative incidence of stricture recurrence was 6%, 10%, and 12% after 1, 5, and 10 years, respectively. From a patient-reported perspective, 89% of patients reported being satisfied with the outcome of surgery. On multivariable analyses, increasing stricture length (HR 1.1, 95% CI 1.05-1.15; P < .001) and stricture etiology (P < .001), in particular lichen sclerosus (HR 4.46, 95% CI 2.25-9.53), radiation (HR 4.25, 95% CI 1.65-10.9), and infectious strictures (HR 5.27, 95% CI 2.03-13.7), were independently associated with stricture recurrence. CONCLUSIONS: This study affirms the widely held belief that modern urethroplasty provides high long-term patency and patient-reported satisfaction. Patients with longer strictures as well as those with lichen sclerosus, radiation, and infectious etiologies have a higher hazard of stricture recurrence in the long term.

Comorbidities in Male Patients With Lichen Sclerosus: A Case-Control Study.

OBJECTIVE: Lichen sclerosus (LS) is a chronic inflammatory skin disease. In male patients, it usually involves the glans penis and foreskin and can cause phimosis or meatal stenosis. The aim of this cross-sectional case-control study was to identify clinically important comorbidities in male patients with LS. MATERIALS AND METHODS: By searching Turku University Hospital electronic health records, the authors identified 630 male patients diagnosed with LS between 2004 and 2020. To investigate possible comorbidities, the authors compared this patient group to a 10-fold larger control group. RESULTS: The incidence of LS increased during the study period, from 5 to 27.5 per 100,000 men. Patients were most often diagnosed at 21 to 25 years of age. Patients with LS exhibited markedly increased risks of penile carcinoma (odds ratio [OR], 81.0; 95% CI = 10.82-3516.7; p < .001) and carcinoma in situ of the penis (OR = 60.5; 95% CI = 7.32-2738.9; p < .001). Patients also more commonly exhibited lichen planus (OR = 16.8; 95% CI = 8.97-32.39; p < .001), psoriasis (OR = 3.3; 95% CI = 1.80-5.70; p = .004), angina pectoris (OR = 1.8; 95% CI = 1.10-2.81; p = .013), obesity (OR = 2.6; 95% CI = 1.72-3.77; p < .001), type 2 diabetes (OR = 2.3; 95% CI = 1.74-3.09; p < .001), and hypertension (OR = 1.9; 95% CI = 1.53-2.37; p < .001). The most commonly performed urological procedures were operation for phimosis, uroflowmetry, and ultrasound measurement of residual urine. CONCLUSIONS: Genital malignancies, other dermatological conditions, and diseases related to metabolic syndrome should be considered when treating patients with LS.

Comorbidity in patients with Lichen sclerosus: a retrospective cohort study.

Lichen sclerosus (LS) is a chronic lymphocyte mediated inflammatory mucocutaneous disease of unknown aetiology with a predilection for the anogenital region, and affecting both sexes. The disease is characterized by pain, intolerable itching and scarring. In late stages of LS, disfiguring scarring can drastically alter the structural anatomical architecture of the genitals. The association between genital LS and different malignant tumours is a concern that needs to be further investigated. An association between LS and several autoimmune diseases has been confirmed in recent studies. All registered citizens of Region Jönköping, Sweden were included in the present study. Patients diagnosed with LS (n = 5680) between 2001 and 2021 were identified using ICD-10 code L90.0 and selected as cases. All other individuals (n = 362 568) served as controls. Odds ratios (ORs) for the selected comorbidity were calculated and adjusted for age and sex. The cumulative incidence of LS for the entire population over a 20-year period was 1.54% (15.4 per 1000 people). The cumulative incidences over a 20-year period for females and males were 2.13% and 0.97%, respectively. This study confirmed the association between LS and vulvar cancer (OR = 17.4; 95% CI 12.1-25.3), penis cancer (OR = 9.1; 95% CI 4.3-18.9), prostate cancer (OR = 2.0; 95% CI 1.6-2.4) and breast cancer (OR = 1.6; 95% CI 1.4-1.8). LS was also associated with Crohn´s disease (OR = 2.0; 95% CI 1.6-2.6) and diabetes mellitus type 1 (OR = 1.9; 95% CI 1.6-2.1). The present study revealed novel important data regarding the association of LS with cancer and autoimmune diseases, emphasising the importance of sufficient treatment and follow-up of patients with LS. However, future studies are needed to confirm these results and the potential role of LS in the development of cancer.

Long-term consequences of juvenile vulvar lichen sclerosus: A cohort study of adults with a histologically confirmed diagnosis in childhood or adolescence.

INTRODUCTION: Vulvar lichen sclerosus (VLS) occurs in at least one in 900 girls. There is limited knowledge as to what extent the disease persists in adulthood and what the repercussions in adulthood may be. The aim of this study is to evaluate the long-term consequences of VLS diagnosed in childhood or adolescence. MATERIAL AND METHODS: The population of females histologically diagnosed with VLS in childhood or adolescence in the Netherlands between 1991 and 2015 was identified through the national pathology database. Histological specimens were retrieved and re-evaluated. Potential participants for whom the diagnosis was reconfirmed and who are now adults, were then traced and surveyed. Descriptive statistics were calculated and compared with the literature. Main outcome measures are the demographics of the cohort, their scores on standardized quality of life (QoL) and sexuality questionnaires and answers to additional questions regarding patients' experience with the disease. The questionnaires used were the Dermatology Life Quality Index (DLQI), the Skindex-29, the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R). Secondary outcome measures include obstetric history and histological features found in the original tissue specimens. RESULTS: A total of 81 women participated, median age 29.0 years, median follow-up from childhood diagnosis 19.5 years. Both QoL and sexuality were somewhat affected in 51.9% of cases. Less than half (45%) reported having regular check-ups. Forty-five (56%) reported symptoms within the past year; of those with symptoms, 14 (31%) were not under surveillance. Cesarean section rate (14.5%) was comparable to the general population, and there were more high-grade obstetric anal sphincter injuries with vaginal deliveries than expected. Sixteen respondents (20%) were not aware of the childhood diagnosis prior to this study. CONCLUSIONS: Symptoms due to VLS are reported by most adults diagnosed as juveniles. QoL and sexuality are affected and correlate to recent symptoms. VLS as a juvenile does not preclude a vaginal delivery. Women diagnosed with VLS in childhood or adolescence are often lost to follow-up.

Urinary microbiome differences between lichen sclerosus induced and non-lichen sclerosus induced urethral stricture disease.

OBJECTIVE: To describe differences in the urinary microbiome of patients with pathologically confirmed lichen sclerosus (LS) urethral stricture disease (USD) vs non-lichen sclerosus (non-LS) USD pre- and post-operatively. METHODS: Patients were pre-operatively identified and prospectively followed, all underwent surgical repair and had tissue samples obtained to make a pathological diagnosis of LS. Pre- and post-operative urine samples were collected. Bacterial genomic DNA was extracted. Alpha and beta diversity measurements were calculated and compared. A zero-inflated negative binomial model was utilized to compare taxa abundances between disease status and surgery status. RESULTS: Urine samples were obtained from both cohorts, 69 samples in total: 36 samples were obtained pre-operatively and 33 samples were obtained post-operatively. Ten patients provided both a pre-operative and post-operative urine sample. Twenty-six patients had pathological evidence of LS and 33 patients did not. There was a statistically significant difference in alpha diversity between the pre-operative urine samples of patients with non-LS USD and LS USD, (p = 0.01). There was no significant difference in alpha diversity within post-operative urine samples between patients with non-LS USD and LS USD, (p = 0.1). A significant difference was observed in Weighed UniFrac distances with respect to disease and operative status, (p = 0.001 and 0.002). CONCLUSIONS: LS USD have significant alterations in diversity and differential abundance of urine microbiota compared to non-LS USD controls. These findings could be used to guide further investigations into the role of the urinary microbiome in LS USD pathogenesis, severity of presentation, and stricture recurrence.

Genital and extragenital oncological risk in women with vulvar lichen sclerosus: A multi-center Italian study.

Vulvar lichen sclerosus is a chronic inflammatory disease involving vulvar skin. The risk of developing invasive vulvar cancer for women with LS is reported in the literature, but the risk of extra-vulvar tumors has been under-investigated. This multicentric study aims to estimate the risk of developing cancers in a cohort of women with a diagnosis of vulvar lichen sclerosus. METHODS: A cohort of women diagnosed with and treated for vulvar lichen sclerosus in three Italian gynecological and dermatological clinics (Turin, Florence, and Ferrara) was retrospectively reviewed. Patient data were linked to cancer registries of the respective regions. The risk of subsequent cancer was estimated by dividing the number of observed and expected cases by the standardized incidence ratio. RESULTS: Among 3414 women with a diagnosis of vulvar lichen sclerosus corresponding to 38,210 person-years of follow-up (mean 11.2 years) we identified 229 cancers (excluding skin cancers and tumors present at the time of diagnosis). We found an increased risk of vulvar cancer (standardized incidence ratio = 17.4; 95 % CL 13.4-22.7), vaginal cancer (standardized incidence ratio = 2.7; 95 % CL 0.32-9.771), and oropharyngeal cancer (standardized incidence ratio = 2.5; 95 % CL 1.1-5.0), and a reduced risk of other gynecological tumors (cervical, endometrial, ovarian) and breast cancer. CONCLUSIONS: Patients with vulvar lichen sclerosus should undergo annual gynecological check-up with careful evaluation of the vulva and vagina. The increased risk of oropharyngeal cancer also suggests the need to investigate oropharyngeal cavity symptoms and lesions in patients with vulvar lichen sclerosus.

A comparative study of two single-stage oral mucosal substitution urethroplasty (Kulkarni and Asopa) in the surgical treatments of lichen sclerosus urethral strictures.

Long-segment lichen sclerosus (LS) urethral stricture is a challenge for urologists. Limited data are available for surgeons to make a surgical decision between Kulkarni and Asopa urethroplasty. In this retrospective study, we investigated the outcomes of these two procedures in patients with LS urethral stricture. Between January 2015 and December 2020, 77 patients with LS urethral stricture underwent Kulkarni and Asopa procedures for urethroplasty in the Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China). Of the 77 patients, 42 (54.5%) underwent the Asopa procedure and 35 (45.5%) underwent the Kulkarni procedure. The overall complication rate was 34.2% in the Kulkarni group and 19.0% in the Asopa group, and no difference was observed ( P = 0.105). Among the complications, no statistical difference was observed in the incidence of urethral stricture recurrence ( P = 0.724) or glans dehiscence ( P = 0.246) except for postoperative meatus stenosis ( P = 0.020). However, the recurrence-free survival rate between the two procedures was significantly different ( P = 0.016). Cox survival analysis showed that antiplatelet/anticoagulant therapy use ( P = 0.020), diabetes ( P = 0.003), current/former smoking ( P = 0.019), coronary heart disease ( P < 0.001), and stricture length ( P = 0.028) may lead to a higher hazard ratio of complications. Even so, these two techniques can still provide acceptable results with their own advantages in the surgical treatment of LS urethral strictures. The surgical alternative should be considered comprehensively according to the patient characteristics and surgeon preferences. Moreover, our results showed that antiplatelet/anticoagulant therapy use, diabetes, coronary heart disease, current/former smoking, and stricture length may be contributing factors of complications. Therefore, patients with LS are advised to undergo early interventions for better therapeutic effects.

Female genital lichen sclerosus is connected with a higher depression rate, decreased sexual quality of life and diminished work productivity.

Female genital lichen sclerosus is an underdiagnosed, distressing, chronic dermatosis affecting the well-being of women. The aim of this retrospective case-control study was to assess whether the disease is connected with work productivity and activity impairment, depression and decreased sexual quality of life. Fifty-one female patients with genital lichen sclerosus and forty-five healthy women were enrolled to the study and filled out an online survey including: Work Productivity and Activity Impairment: General Health (WPAI:GH), Patient Health Questionnaire-9 (PHQ-9) and The Sexual Quality of Life-Female (SQOL-F) questionnaires. The results showed that women with genital lichen sclerosus are at risk of having a diminished work productivity, are more often screened for depression and have a decreased sexual quality of life. The study highlights the importance of a multidisciplinary approach to treating female genital lichen sclerosus.

Alpha, Beta, and Gamma Human Papillomaviruses in Genital Lichen Sclerosus: A Retrospective Cross-Sectional Study.

BACKGROUND: Lichen sclerosus (LS) is an inflammatory disease mostly arising at the genital level. It is unclear whether human papillomaviruses (HPVs) have an etiological significance in LS, and data on their prevalence in patients with LS are controversial. OBJECTIVES: The authors assessed alpha, beta, and gamma HPV prevalence in patients with genital LS. The association of HPV positivity with demographic and clinical factors was also investigated. METHODS: One hundred thirty-two formalin-fixed, paraffin-embedded LS samples (2016-2020) were retrieved from the archives of a pathology department. Alpha HPVs were genotyped with the INNO-LiPA HPV Genotyping Extra II kit. Beta and gamma HPVs were searched by multiplex Polymerase Chain Reaction. Immunostaining for p16 INK4a was performed on high-risk HPV-positive samples. RESULTS: Patients had a median age of 61 years, were mostly women ( n = 73, 55.3%), and with an early disease stage ( n = 79, 59.8%). Alpha HPVs were detected in 12/132 cases (9.1%). Among the 5 high-risk HPV-positive cases, only 2 displayed a strong and diffuse p16 INK4a staining. Beta genus was the most prevalent (35/132, 26.5%) and HPV5 was the most frequent beta genotype (25/132, 18.9%). There were 3 gamma HPV-positive cases among those with a valid result (3/131, 2.3%). Multiple infections with genotypes belonging to different genera were infrequent (3/131, 2.3%). No significant differences in the prevalence of the individual genera were observed according to sex and disease stage. CONCLUSIONS: Of the 3 HPV genera, beta genus showed the highest prevalence. Further research is needed to clarify whether the presence of beta HPVs in genital LS has a clinical significance.

A prospective pilot study to assess for histologic changes on vulvar biopsies in postmenopausal women with lichen sclerosus treated with fractionated CO2 laser therapy.

OBJECTIVES: To investigate the histologic characteristics of vulvar tissues before and after completion of fractionated carbon dioxide (CO2 ) laser therapy (FxCO2) for vulvar lichen sclerosus (LS). The secondary objective was to assess subjective improvement in symptoms via the Skindex-16 questionnaire. METHODS: This prospective single-arm study was conducted from April 2021 to August 2022 at one academic medical center. Ten postmenopausal women with biopsy-proven LS planning FxCO2 laser treatment were enrolled. Exclusion criteria included prior transvaginal mesh for prolapse, topical corticosteroid use within 8 weeks, prior pelvic radiation, malignancy, active genital infection, or pregnancy. The vulvovaginal SmartXide2-V2-LR laser system fractionated CO2 laser (DEKA) was utilized to treat visually affected areas of vulvar and perianal LS with a single pass. Subjects underwent three treatments 4-6 weeks apart. Subjects completed the Skindex-16 questionnaire and had vulvar biopsy at baseline and at 4 weeks after completion of fractionated CO2 laser therapy. Blinded histologic slides were scored by one dermatopathologist (Michael A. Cardis) rating from 1 to 5 the degree of dermal sclerosis, inflammation, and epidermal atrophy. Change scores were calculated as the difference between pre- and post-treatment scores for each subject. RESULTS: The 10 subjects enrolled had a mean age of 61 and most were white, privately insured, and had a college/graduate-level education. Post-fractionated CO2 laser treatment vulvar biopsies showed significant improvement in sclerosis and epidermal atrophy compared with pretreatment baseline biopsy specimens (p < 0.05) with no statistically significant change found in inflammation score. Skindex-16 and FSFI scores showed a trend towards improvement (p > 0.05 for both). A statistically significant correlation was found between change in sclerosis and Skindex-16 symptoms scores with an average change of 21.4 units in Skindex-16 symptoms score for every one-point change in histologic sclerosis score (p = 0.03). CONCLUSIONS: In postmenopausal women with vulvar LS undergoing fractionated CO2 laser, symptomatic improvements correlated with histologic change in degree of sclerosis on vulvar biopsy. These results demonstrate FxCO2 laser therapy as a promising option for the treatment of LS and suggest that further studies should assess degree of sclerosis on histopathology.

The influence of lichen sclerosus on women's sexual health from a biopsychosocial perspective: a mixed methods study.

BACKGROUND: Women with lichen sclerosus (LS) may suffer sexually because of dyspareunia, fissures, and introital narrowing. However, the literature remains limited on the biopsychosocial aspects of LS and its impact on sexual health. AIM: To examine the biopsychosocial aspects and impact of LS on the sexual health of Danish women with vulvar LS. METHODS: The study was conducted with a mixed methods approach, including women with LS from a Danish patient association. The quantitative sample consisted of 172 women who completed a cross-sectional online survey that included 2 validated questionnaires: the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS). The qualitative sample consisted of 5 women with LS who volunteered for audiotaped, individual, semistructured interviews. OUTCOMES: This mixed methods study combined data from 2 quantitative questionnaires (FSFI and FSDS) with qualitative interviews to achieve a comprehensive insight into the biopsychosocial aspects of sexual health in women living with LS. RESULTS: The sexual function of women with LS was considerably affected, with FSFI scores below the cutoff value of 26.55, indicating a risk of sexual dysfunction. On average, 75% of the women were sexually distressed, with a total FSDS score of 25.47. Furthermore, 68% of the sexually active women were considerably affected in terms of sexual function and sexual distress, thus meeting international criteria for sexual dysfunction. However, a negative impact on sexual function was not always related to sexual distress and vice versa. The qualitative analysis identified 4 overarching themes: (1) decrease in or loss of sexual activity, (2) interference with relationship dynamics, (3) importance of sex and intimacy - loss and restoration, and (4) worries about sexual insufficiency. CLINICAL IMPLICATIONS: Insight into the influence of LS on sexual health is important for health care professionals, including doctors, nurses, sex therapists, and physiotherapists, to provide the best guidance, support, and management for women with LS. STRENGTHS AND LIMITATIONS: The strengths of the study are its use of a mixed methods design and the inclusion of sexual function and sexual distress. A limitation is related to the properties of the FSFI regarding women with no sexual activity. CONCLUSIONS: LS has a considerable influence on women's sexual health in terms of sexual function and sexual distress, as supported by quantitative and qualitative measures. Our understanding of the complex interactions among sexual activity, intimate relations, and causes of psychological distress has been enriched.