Lichen Sclerosus et Atrophicus

BackgroundHuman papillomaviruses (HPVs) are sexually transmitted human carcinogens that may play a role in the oncogenesis of penile cancer.ObjectivesTo investigate the role of HPV infection and expression of the tumour suppressor protein p16INK4A in the pathogenesis of penile cancer.MethodsBy means of polymerase chain reaction amplification and reverse hybridization line probe assay to detect HPV infection, and immunohistochemical staining for p16INK4A and Ki67, we analysed 26 penile squamous cell carcinomas (SCCs) and 20 independent penile lichen sclerosus (LS) lesions from 46 patients.ResultsHPV DNA was found in 54% of penile SCCs and 33% of penile LS cases in single and multiple infections. High-risk HPV 16 was the predominant HPV type detected. No relationship between Ki67 expression and HPV infection was observed. Strong immunostaining for p16INK4A correlated with HPV 16/18 infection in both penile LS and penile SCC. In our penile SCC series the cancer margins were also associated with penile LS in 13 of 26 lesions, and HPV was detected in seven of the 13 SCC cases associated with LS and in six of the 11 SCC lesions not involving LS.ConclusionsOur study shows a high prevalence of HPV 16 and p16INK4A expression in penile lesions, consistent with an active role for HPV in interfering with the retinoblastoma pathway. High-risk HPV infection could be involved in the tumorigenic process in 50% of penile cancers, and the use of prophylactic HPV vaccines has the potential to prevent these cancers.

BackgroundLichen sclerosus is a chronic inflammatory disease with a predilection of the anogenital region. Because of the potential side effects of repeated local application of potent glucocorticosteroids, equally-effective, safer therapeutic options are required, especially in the treatment of children.Case presentationsWe report on the efficacy of twice-daily application of pimecrolimus 1% cream in four prepubertal girls (range of age: 4 to 9 years) who suffered from anogenital lichen sclerosus. After three to four-month treatment, all patients had almost complete clinical remission including relief from itch, pain and inflammation. Only minor improvement was observed for the white sclerotic lesions. No significant side effects have been observed.ConclusionsTopical pimecrolimus appears to be an effective and safe treatment for children with anogenital lichen sclerosus. The clinical benefits observed in the four patient presented particularly include relief of pruritus, pain and inflammation. Vehicle-controlled studies on a larger number of patients are now warranted to substantiate our promising findings, and to investigate long-term efficacy and safety of topical pimecrolimus in anogenital lichen sclerosus.

The etiology of vulvar lichen sclerosus (LS) remains unclear; however, alterations in cutaneous and gut microbiota may be contributing to the pathogenesis of this inflammatory condition. To explore this hypothesis, we conducted a pilot case-control study, obtaining dermal swab and stool samples from prepubertal girls with vulvar LS (n = 5), girls with nonspecific vulvovaginitis (n = 5), and healthy controls (n = 3). Samples (n = 56) were subjected to total DNA extractions. Resulting DNA was purified, subjected to PCR (targeting the V3V4 region of the 16S rRNA gene), sequenced, and analyzed using QIIME, MetagenomeSeq, and DESeq2 software packages. Our findings showed that there were significant differences in the cutaneous and gut microbiotas of girls with LS compared to controls. On the skin, girls with LS had a statistically significantly higher relative abundance of Porphyromonas spp., Parvimonas spp., Peptoniphilus spp., Prevotella spp., Dialister spp., and Peptostreptococcus spp., but a lower relative abundance of Cornyebacterium compared to the control group. In the gut samples, girls with LS had a significantly higher relative abundance of Dialister spp., Clostridiales spp., Paraprevotella spp., Escherichia coli, Bifidobacterium adolescentis, and Akkermansia muciniphila, and a lower relative abundance of Roseburia faecis and Ruminococcus bromii compared to controls. These results suggest a potential association between cutaneous and gut dysbiosis and pediatric vulvar LS. Future studies involving larger samples sizes are warranted to further evaluate this association.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis that primarily affects the genital mucosa in both sexes. Although most prevalent in women and characterized by distinct age peaks, its clinical presentation, marked by ivory-white atrophic patches and plaques, often overlaps with other conditions. Delayed diagnosis, frequently due to asymptomatic progression, poses a significant risk of malignant transformation. The etiology of LS is multifactorial, involving a complex interplay of genetic, epigenetic, environmental, and autoimmune factors. Pathogenetically, the disease is characterized by several co-occurring features, including an immune imbalance with elevated pro-inflammatory cytokines, impaired T-regulatory (Treg) cell activity, a persistent local inflammatory state, and dysregulated collagen metabolism with associated fibrosis and scarring. Furthermore, the production of autoantibodies against extracellular matrix protein 1 (ECM1) disrupts skin integrity, while the generation of reactive oxygen species (ROS) further exacerbates tissue damage, autoimmunity, and tumorigenesis. Despite its severe impact on patient quality of life, current diagnostic and therapeutic strategies remain limited. While potent topical corticosteroids represent the gold standard first-line treatment-with topical calcineurin inhibitors serving as a second-line alternative-the lack of a fully elucidated etiopathogenesis continues to restrict curative options. However, recent translational research is paving the way for innovative regenerative therapies. This review provides an updated comprehensive overview of the latest advancements in LS pathogenesis and explores emerging therapeutic landscapes.