Is Lichen Sclerosus Still an Enigma in 2023?

🔍 Key Finding Lichen sclerosus (LS) is a common, underdiagnosed, inflammatory mucocutaneous condition predominantly affecting the anogenital areas of postmenopausal women, with a complex pathogenesis involving genetic predisposition, immune dysregulation, and oxidative stress, and for which long-term topical corticosteroids remain the first-line treatment. While surgical intervention may be necessary for anatomical complications or failed topical treatment, LS carries a risk of malignant transformation, necessitating lifelong monitoring.

🔬 Methodology Overview

• Design: Narrative review.
• Data Sources: Published literature.
• Selection Criteria: Papers relevant to lichen sclerosus, encompassing pathogenesis, clinical features, diagnosis, and treatment.
• Analysis Approach: Qualitative synthesis of current knowledge and research findings.
• Scope: To provide an updated overview of lichen sclerosus for clinicians and researchers, fostering translational research.

📊 Results

• LS affects women more commonly than men, with a female-to-male ratio between 3:1 and 10:1.
• Bimodal presentation of vulvar LS, with peaks in prepubertal girls (average age 7.6 years) and peri/postmenopausal women (average age 52.6 years).
• In men, onset is relatively stable, with peaks in the third decade and after 60 years of age.
• Estimated incidence of LS in both sexes is 0.1% to 0.3%. Prevalence in general gynecology practice for VLS is 1.7%.
• Extragenital LS (eLS) comprises 15-20% of LS cases, often occurring with genital LS, but can be isolated (6% of eLS cases).
• VLS progresses to vulvar squamous cell carcinoma (SCC) in 3.5% to 7% of women, while 65% of vulvar carcinomas arise in the context of pre-existing VLS.
• Penile SCC occurs in 4% to 13.4% of male genital LS (MGLS) cases, with 12% of penile SCC entirely attributable to MGLS and 29.4% arising in combination with HPV.

💡 Clinical Impact Lichen sclerosus (LS) is a chronic, underdiagnosed inflammatory mucocutaneous condition predominantly affecting anogenital areas in postmenopausal women, and to a lesser extent, men, prepubertal children, and adolescents, causing significant quality of life impairment due to chronic whitish atrophic patches, itching, soreness, and potential progression to squamous cell carcinoma. Early diagnosis and long-term treatment with ultrapotent or potent topical corticosteroids, along with regular follow-up and patient education, are crucial for symptom management, prevention of complications like scarring and sexual/urinary dysfunction, and early detection of malignancy.

🤔 Limitations

• Underestimated prevalence and incidence: The true prevalence and incidence of LS are likely underestimated due to asymptomatic cases and frequent misdiagnosis or lack of recognition.
• Limited understanding of pathogenesis: While the paper presents various factors involved in LS pathogenesis (genetic predisposition, immune dysregulation, oxidative stress, etc.), the exact sequence of events and their interactions are incompletely understood.
• Limited treatment options: Current treatment options for LS are limited, with topical corticosteroids being the first-line therapy despite potential side effects and the need for long-term application. Alternative treatments like calcineurin inhibitors are considered off-label and may not be as effective.
• Lack of high-quality studies for some treatments: Some treatments, such as laser therapy and regenerative therapies, have poor levels of evidence and lack long-term data to support their widespread use. Studies on photodynamic therapy have shown conflicting results.
• Limited data on long-term safety of some treatments: While long-term use of topical corticosteroids appears safe, the long-term safety of other treatments, such as JAK inhibitors, is not well-established.
• Limited focus on patient-reported outcomes: While the paper mentions the importance of assessing quality of life, it doesn’t delve deeply into the impact of LS and its treatment on patients’ psychological well-being and sexual health, which are significant concerns.
• Variability in PRP preparation and application: The paper notes that studies on platelet-rich plasma (PRP) have a low level of evidence due to a lack of standardization in its preparation and application, making it difficult to draw firm conclusions about its efficacy.

✨ What It Means For You Doctors should be aware of the increased risk of metabolic syndrome and cardiovascular comorbidities in female LS patients, prompting consideration for screening and management of these conditions. Additionally, the review highlights the importance of long-term follow-up for LS patients due to the risk of recurrence and malignant transformation, even after years of remission. Finally, clinicians should consider the significant impact of LS on psychosexual health and quality of life in both men and women, emphasizing the need for a holistic approach to patient care.

Reference De Luca DA, Papara C, Vorobyev A, Staiger H, Bieber K, Thaçi D, Ludwig RJ. Lichen sclerosus: The 2023 update. Frontiers in Medicine. 2023;10:1106318. https://doi.org/10.3389/fmed.2023.1106318