Significant Correlation Between Cutaneous Abundance of Streptococcus and Psoriasis Severity in Patients with FBXL19 Gene Variants.

Psoriasis results from both genetic predisposition and environmental triggers, such as Streptococcal infections. This study aimed to explore the correlation between the abundance of the Streptococcus genus on the skin and psoriasis severity in individuals carrying specific psoriasis-associated genetic variants. Studying 39 chronic plaque psoriasis patients, the elbow skin microbiome and 49 psoriasis-related single nucleotide polymorphisms (SNPs) were analysed using a MiSeq instrument for 16S rDNA sequencing, and CLC Genomic Workbench for processing and analysis. Through multivariate linear regression analysis, a positive correlation was found between Streptococcus genus abundance and psoriasis severity in patients with certain FBXL19 gene-related heterozygous SNPs (rs12924903, rs10782001, rs12445568). Conversely, a negative association was observed in patients with homozygous genotypes. Moreover, we identified an association between Streptococcus abundance and psoriasis severity in patients with genetic variants related to IL-22, ERAP1, NOS2, and ILF3. This is the first study highlighting a positive association between Streptococcus skin colonization and psoriasis severity in patients with heterozygous genotypes within the FBXL19 gene region. FXBL19 targets the IL-33/IL1RL1 axis, crucial in infectious diseases and innate immunity promotion. These novel results suggests an intricate interaction among host genetics, Streptococcus skin colonization, and psoriasis inflammation, offering potential avenues for novel treatment approaches.

Incidence of Dermatitis Herpetiformis in Sweden 2005 to 2018: A Nationwide Retrospective Cohort Study.

Dermatitis herpetiformis has been investigated in the past; however, only a limited number of studies have reported its incidence based on validated nationwide population-based registries. To address this gap, the aims of this study are to estimate the incidence of dermatitis herpetiformis in Sweden and to validate the National Patient Register (NPR) for diagnosis of dermatitis herpetiformis. A population-based open cohort study was conducted, including all patients diagnosed with dermatitis herpetiformis (International Classification of Diseases 10th revision; ICD-10 code L13.0) in Sweden from 2005 to 2018 (n = 1,724), identified from the NPR. The diagnosis of dermatitis herpetiformis in the NPR was validated using medical records, histopathological and immunopathological data, yielding a positive predictive value (PPV) of 62.5%. The mean annual incidence of dermatitis herpetiformis was 0.93/100,000 (95% confidence interval 0.79-1.08), female to male ratio 1:1, and mean age at diagnosis 60.9 years. In conclusion, this large nationwide cohort study showed a low validity for diagnosis of dermatitis herpetiformis in the NPR, and the adjusted incidence rate of dermatitis herpetiformis in Sweden was estimated to be 0.93/100,000, which is lower than that in previous Swedish studies.

GlycoTAIL and FlexiTAIL as Half-Life Extension Modules for Recombinant Antibody Fragments.

Many therapeutic proteins are small in size and are rapidly cleared from circulation. Consequently, half-life extension strategies have emerged to improve pharmacokinetic properties, including fusion or binding to long-lasting serum proteins, chemical modifications with hydrophilic polymers such as PEGylation, or, more recently, fusion to PEG mimetic polypeptides. In the present study, two different PEG mimetic approaches, the GlycoTAIL and the FlexiTAIL, were applied to increase the hydrodynamic radius of antibody fragments of different sizes and valencies, including scFv, diabody, and scFv-EHD2 fusion proteins. The GlycoTAIL and FlexiTAIL sequences of varying lengths are composed of aliphatic and hydrophilic residues, with the GlycoTAIL furthermore comprising N-glycosylation sites. All modified proteins could be produced in a mammalian expression system without reducing stability and antigen binding, and all modified proteins exhibited a prolonged half-life and increased drug disposition in mice. The strongest effects were observed for proteins comprising a FlexiTAIL of 248 residues. Thus, the GlycoTAIL and FlexiTAIL sequences represent a flexible and modular system to improve the pharmacokinetic properties of proteins.

Sex and Age Influence the Associated Risk of Depression in Patients with Psoriasis: A Retrospective Population Study Based on Diagnosis and Drug-Use.

BACKGROUND: The reported prevalence of depression among individuals with psoriasis varies substantially, and the effect of gender on depression distribution has revealed conflicting results. In addition, using medication to identify cases is uncommon. OBJECTIVE: To study the prevalence of pharmacologically treated depression among individuals with and without psoriasis in a Swedish population using ICD-10 codes and data from the Swedish Prescribed Drug Register. METHODS: A retrospective case-control population-based study was performed including all living individuals (age ≥18 years) in Region Jönköping, southern Sweden (n = 273,536). ICD-10 codes for the diagnosis of psoriasis (L40.*) and depression (F32.* and F33.*), and data on pharmacological treatment from the Swedish Prescribed Drug Register, were extracted from electronic medical records between April 9, 2008 and January 1, 2016. The extraction date was January 1, 2016. RESULTS: The risk of pharmacologically treated depression was increased in individuals with psoriasis (age- and sex-adjusted OR 1.55; CI 1.43-1.68); 21.1% of women with psoriasis received pharmacological treatment for depression during the study period compared to 14.2% in the control population. Prevalence figures for depression were significantly higher in women with psoriasis compared to men. The risk of suffering from depression was highest among male and female patients with psoriasis under the age of 31 years. CONCLUSIONS: Depression is common among patients with psoriasis. The results of the current study underline the need for dermatologists to adopt a holistic approach, looking beyond the skin, when handling patients with psoriasis in every-day clinical practice.

Low-Level Endothelial TRAIL-Receptor Expression Obstructs the CNS-Delivery of Angiopep-2 Functionalised TRAIL-Receptor Agonists for the Treatment of Glioblastoma.

Glioblastoma (GBM) is the most malignant and aggressive form of glioma and is associated with a poor survival rate. Latest generation Tumour Necrosis Factor Related Apoptosis-Inducing Ligand (TRAIL)-based therapeutics potently induce apoptosis in cancer cells, including GBM cells, by binding to death receptors. However, the blood-brain barrier (BBB) is a major obstacle for these biologics to enter the central nervous system (CNS). We therefore investigated if antibody-based fusion proteins that combine hexavalent TRAIL and angiopep-2 (ANG2) moieties can be developed, with ANG2 promoting receptor-mediated transcytosis (RMT) across the BBB. We demonstrate that these fusion proteins retain the potent apoptosis induction of hexavalent TRAIL-receptor agonists. Importantly, blood-brain barrier cells instead remained highly resistant to this fusion protein. Binding studies indicated that ANG2 is active in these constructs but that TRAIL-ANG2 fusion proteins bind preferentially to BBB endothelial cells via the TRAIL moiety. Consequently, transport studies indicated that TRAIL-ANG2 fusion proteins can, in principle, be shuttled across BBB endothelial cells, but that low TRAIL receptor expression on BBB endothelial cells interferes with efficient transport. Our work therefore demonstrates that TRAIL-ANG2 fusion proteins remain highly potent in inducing apoptosis, but that therapeutic avenues will require combinatorial strategies, such as TRAIL-R masking, to achieve effective CNS transport.

Increased Risk of Squamous Cell Carcinoma of the Skin and Lymphoma Among 5,739 Patients with Bullous Pemphigoid: A Swedish Nationwide Cohort Study.

Evidence about the association of bullous pemphigoid and the risk of cancer is conflicting. Patients diagnosed with bullous pemphigoid (n = 5,739) between 2005 and 2016 were matched with a control cohort from the general population (n = 17,168) to estimate their overall and specific risk of cancer. The risk of squamous cell cancer of the skin (cSCC) was increased in patients with bullous pemphigoid (hazard ratio (HR) 1.3; 95% confidence interval (CI) 1.1-1.6). The risk of lymphoma within one year after bullous pemphigoid diagnosis was also increased (HR 3.1; 95% CI 1.3-7.6). While overall cancer risk prior to diagnosis of bullous pemphigoid was similar in cases and controls (prevalence odds ratio (POR) 1.0; 95% CI 0.9-1.0), the risk of male genital cancer within one year prior to diagnosis of bullous pemphigoid was lower in cases (POR 0.4; 95% CI 0.2-0.8). Clinicians must be aware of the increased risk of cSCC and lym-phoma in patients with bullous pemphigoid.

Significant Differences in the Bacterial Microbiome of the Pharynx and Skin in Patients with Psoriasis Compared with Healthy Controls.

Studies have shown differences in the skin and gut bacterial microbiomes in patients with psoriasis, but the pharyngeal microbiome has not been studied previously. The aim of this study was to investigate differences in the bacterial microbiome of the pharynx and skin of patients with psoriasis compared with healthy controls. Swabs were taken from the pharynx and elbow skin of 39 patients with psoriasis and 70 controls. Microbiomes were characterized by sequencing 16S rRNA genes on the Illumina MiSeq platform. Significant differences were found in alpha and beta diversity in the skin, but not in the pharynx. Significant differences were also found between several phyla and genera in both skin and pharynx. The severity of psoriasis did not correlate with any genera in the pharynx, but with Capnocytophaga, Leptotrichia, Abiotrophia and Tannerella in the skin. The composition of the pharyn-geal and skin microbiome may be of importance in the patho-genesis of psoriasis.

Prevalence of Psoriasis and Psoriatic Arthritis and Patient Perceptions of Severity in Sweden, Norway and Denmark: Results from the Nordic Patient Survey of Psoriasis and Psoriatic Arthritis.

Optimal clinical management of psoriasis and psoriatic arthritis (PsA) Optimal clinical management of psoriasis and psoriatic arthritis (PsA) requires understanding of the impact on patients. The NORdic PAtient survey of Psoriasis and PsA (NORPAPP) aimed to obtain current data on disease prevalence and patient perceptions in Sweden, Denmark and Norway. Among 22,050 individuals questioned, the reported prevalence of psoriasis and/or PsA was 9.7% (5.7% physician-diagnosed plus 4.0% self-diagnosed only); prevalence was similar in Sweden (9.4%) and Denmark (9.2%) but significantly higher in Norway (11.9%). Of those reporting a physician's diagnosis, 74.6% reported psoriasis alone, 10.3% PsA alone and 15.1% both. Patients with PsA perceived their disease to be more severe than those with psoriasis; patients with PsA and psoriasis reported greater disease severity than those with each condition alone. Patient's perceptions of psoriasis severity correlated weakly (Spearman's rho 0.42) with clinical severity; both patient perceptions and clinical measures are important in the assessment and management of psoriasis.

Significant Changes in the Skin Microbiome in Patients with Chronic Plaque Psoriasis after Treatment with Narrowband Ultraviolet B.

Changes in the skin microbiome have been shown to promote cutaneous inflammation. The skin microbiome of patients with chronic plaque type psoriasis was analysed before and after treatment with narrowband ultraviolet B (UVB). Swab samples of the microbiome were taken from lesional and non-lesional skin of 26 patients. Microbiotas were characterized by sequencing 16S rRNA bacterial genes on the Illumina MiSeq platform. Lesional skin microbiome diversity correlated with psoriasis severity (measured with the Psoriasis Area and Severity Index; PASI). There was a significantly lower abundance of the phylum Firmicutes and the genus Staphylococcus in lesional skin compared with non-lesional skin before UVB treatment. Responders (> 75% target Psoriasis Severity Index (PSI) improvement) had significantly lower abundance of the phyla Firmicutes in lesional and non-lesional skin and lower abundance of the genera Staphylococcus, Finegoldia, Anaerococcus, Peptoniphilus, Gardnerella, Prevotella and Clostridium in lesional skin after UVB treatment. Pseudomonas significantly decreased in lesional and non-lesional skin of treatment responders. These results suggest that skin microbiome alterations after UVB treatment could be related to treatment and treatment response.

UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins-TGF-ß1-FAP-α.

BACKGROUND: Ultraviolet radiation (UVR) is the major risk factor for development of malignant melanoma. Fibroblast activation protein (FAP)-α is a serine protease expressed on the surface of activated fibroblasts, promoting tumour invasion through extracellular matrix (ECM) degradation. The signalling mechanism behind the upregulation of FAP-α is not yet completely revealed. METHODS: Expression of FAP-α was analysed after UVR exposure in in vitro co-culture systems, gene expression arrays and artificial skin constructs. Cell migration and invasion was studied in relation to cathepsin activity and secretion of transforming growth factor (TGF)-ß1. RESULTS: Fibroblast activation protein-α expression was induced by UVR in melanocytes of human skin. The FAP-α expression was regulated by UVR-induced release of TGF-ß1 and cathepsin inhibitors prevented such secretion. In melanoma cell culture models and in a xenograft tumour model of zebrafish embryos, FAP-α mediated ECM degradation and facilitated tumour cell dissemination. CONCLUSIONS: Our results provide evidence for a sequential reaction axis from UVR via cathepsins, TGF-ß1 and FAP-α expression, promoting cancer cell dissemination and melanoma metastatic spread.

Expression of low-density lipoprotein-related receptors 5 and 6 (LRP5/6) in psoriasis skin.

Low-density lipoprotein-related receptors 5 and 6 (LRP5/6) are transmembrane receptors with key functions in canonical Wnt signalling. Wnt ligands are thought to play an important role in innate immunity and psoriasis, and recent studies assigned LRP5/6 anti-inflammatory properties. The objective of this study was to investigate the expression of LRP5 and LRP6 in lesional and non-lesional skin in peripheral blood and in mononuclear cells of patients with chronic plaque type psoriasis compared with control individuals. To investigate the effect of UV-B radiation, LRP5/6 skin gene expression was analysed before and after narrowband UV-B treatment. Our results showed significantly decreased gene expression of LRP5 and LRP6 in lesional skin and in peripheral blood from patients with psoriasis compared with non-lesional skin and healthy control skin. Immunohistochemistry did not reveal differences in protein expression of LRP5/6. Narrowband UV-B treatment induced a significant increase in LRP5 and LRP6 gene expression in lesional skin. Decreased gene expression of LRP5/6 in lesional skin and upregulation after nb UV-B treatment suggest a possible role for LRP5/6 in psoriasis.

Psoriasis and Pro-angiogenetic Factor CD93: Gene Expression and Association with Gene Polymorphism Suggests a Role in Disease Pathogenesis.

CD93 is involved in angiogenesis and inflammation, both of which are key processes in the pathogenesis of psoriasis. CD93 was studied in serum, peripheral blood mononuclear cells and skin of patients with psoriasis and controls. Furthermore, allele frequencies for CD93 single-nucleotide polymorphisms rs2749812 and rs2749817 were assessed in patients with psoriasis compared with controls and the effect of narrowband ultraviolet B (NB-UVB) treatment on CD93 gene expression was evaluated in the skin of patients with psoriasis. CD93 gene expression was significantly increased in lesional and non-lesional skin from patients with psoriasis compared with controls. Immunohistochemistry revealed CD93 staining in dermal endothelial cells in lesional skin, and psoriasis was significantly associated with rs2749817 CD93 gene polymorphism. NB-UVB treatment of patients with psoriasis did not alter skin CD93 gene expression. Increased protein expression of CD93 psoriatic skin and association with the rs2749817 polymorphism suggests that CD93 plays a role in psoriasis disease pathogenesis.

Bullous Pemphigoid: Validation of the National Patient Register in Two Counties in Sweden, 2001 to 2012.

Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Since 2001, data from all specialized outpatient and inpatient care institutions in Sweden, have been registered with the National Patient Register (NPR), based on a unique personal identification number. Previous validations of the register have shown high accuracy for various non-dermatological autoimmune diseases. In order to validate the diagnosis of BP, all residents aged < 20 years in 2 counties in Sweden (539,000 inhabitants) diagnosed with bullous pemphigoid (ICD-10; L12.0, L12.8, L12.9) in the period 2001 to 2012 were identified in the NPR. Medical records, as well as immuno- and histopathological data, were reviewed for this study. A total of 323 patients with BP were identified in the NPR. Of these, 178 patients had a directly confirmed diagnosis of BP from immuno- and histopathological data, reviewed by a dermatopathologist. For the remaining 145 patients medical records were retrieved and further reviewed by 2 dermatologists. Of these, 105 patients had a confirmed diagnosis of BP. The medical records of 16 patients were missing, and 24 patients were not classified as having BP. Overall, a positive predictive value of 92% (283/307) was found for BP in the NPR. In conclusion, the present validation of medical records and immuno- and histopathological data showed high validity for the diagnosis of BP in the Swedish NPR.

Transforming Growth Factor Beta Gene Signatures are Spatially Enriched in Keloid Tissue Biopsies and Ex vivo-Cultured Keloid Fibroblasts.

The keloid lesion is recognised as a spatially heterogeneous mass both in cellular and acellular composition and biological activity. Here, we have utilised a bioinformatic approach to determine whether this spatial heterogeneity is also evident at the molecular level and to identify key upstream regulators of signalling pathways enriched in the lesion in a spatially-restricted manner. Differentially expressed genes (20% change, p < 0.05) obtained from microarray datasets derived from whole keloid biopsies and ex vivo-cultured keloid fibroblasts, both from distinct regions of the keloid lesion (leading edge, centre, and top) have been analysed to show that the TGFß family plays a significant but spatially dependent role in regulation of keloid gene expression. Furthermore, we have identified additional upstream signalling molecules involved in driving keloid biology and provide information on therapeutic targets whose modulation might be expected to lead to significant therapeutic efficacy.

Identification and characterization of RNA guanine-quadruplex binding proteins.

Guanine quadruplex (G-quadruplex) motifs in the 5' untranslated region (5'-UTR) of mRNAs were recently shown to influence the efficiency of translation. In the present study, we investigate the interaction between cellular proteins and the G-quadruplexes located in two mRNAs (MMP16 and ARPC2). Formation of the G-quadruplexes was confirmed by biophysical characterization and the inhibitory activity on translation was shown by luciferase reporter assays. In experiments with whole cell extracts from different eukaryotic cell lines, G-quadruplex-binding proteins were isolated by pull-down assays and subsequently identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The binding partners of the RNA G-quadruplexes we discovered included several heterogeneous nuclear ribonucleoproteins, ribosomal proteins, and splicing factors, as well as other proteins that have previously not been described to interact with nucleic acids. While most of the proteins were specific for either of the investigated G-quadruplexes, some of them bound to both motifs. Selected candidate proteins were subsequently produced by recombinant expression and dissociation constants for the interaction between the proteins and RNA G-quadruplexes in the low nanomolar range were determined by surface plasmon resonance spectroscopy. The present study may thus help to increase our understanding of the mechanisms by which G-quadruplexes regulate translation.

Immunoliposomes for Targeted Delivery of an Antifibrotic Drug.

Excessive extracellular matrix formation in organs and tissues arises from an imbalance between the synthesis and degradation of matrix proteins, especially collagen. This condition interferes with proper wound healing and regeneration, and to date, no specific treatment is available. In the present study, we propose a targeted drug delivery system consisting of cell-specific immunoliposomes (ILs) loaded with deferoxamine (DFO) as an antifibrotic drug. ILs were functionalized with polyethylene glycol (PEG) to improve the steric stability and prolong their half-life. In addition, a single-chain Fv (scFv) antibody fragment that specifically targets fibroblast activation protein (FAP) was incorporated. An in vitro fibrosis model was employed to test this construct. This model consisted of highly activated pro-fibrotic fibroblasts with 2- to 6-fold induction of selected fibrosis markers: cell/matrix deposited collagen I, total soluble collagen, and α smooth muscle actin. The activation was accompanied by a significant and cell-specific elevation of FAP expression and activity, thereby confirming that FAP is an adequate target for antifibrotic drug delivery. Purified anti-FAP scFv was shown to bind specifically to these cells without influencing the FAP enzymatic activity. DFO was demonstrated to have a dose-dependent antifibrotic activity as quantified by collagen deposition. Specific binding and intracellular uptake of DiI-labeled ILs into the activated fibroblasts were shown by flow cytometry and microscopy. Finally, DFO-loaded ILs targeted to FAP caused a significant reduction in the collagen deposition, whereas no effect was observed using liposomes that lacked the targeting antibody fragment. These results suggest that the FAP-specific scFv-conjugated liposomes have considerable potential for cell-specific targeting applicable as a therapy for excessive collagen deposition during fibrosis. In general, through liposome encapsulation, bioactive molecules, such as DFO, that have broad effects and poor cell penetration can be converted into cell-specific composites for targeted drug delivery.

Increased expression of the Wnt signalling inhibitor Dkk-1 in non-lesional skin and peripheral blood mononuclear cells of patients with plaque psoriasis.

Psoriasis is a common inflammatory skin disease characterised by abnormal keratinocyte proliferation, increased dermal angiogenesis and systemic inflammation. The cell signalling cascades provoked by Wnt proteins and their inhibitors, such as Dickkopf-1, play crucial roles to maintain homeostasis of a variety of tissues, including skin, and are also involved in angiogenesis and innate immunity. This study was designed to investigate the distribution of Dickkopf-1, in lesional and non-lesional skin, in serum and in peripheral blood mononuclear cell (PBMCs) of patients with psoriasis compared with healthy controls. Our results showed significantly increased mRNA and protein expression of Dickkopf-1 in non-lesional compared with lesional skin and healthy control skin. No significant differences of Dickkopf-1 serum levels were observed, but Dickkopf-1 protein expression was significantly increased in patients' PBMC. Increased levels of Dickkopf-1 in PBMC, suggest a possible role of Dickkopf-1 in the chronic systemic inflammation of psoriasis. Increased levels of Dickkopf-1 in non-lesional psoriasis skin offers new insights in the local inflammatory processes in psoriasis skin since Wnt signalling regulates angiogenesis. In conclusion, Dickkopf-1 may be a possible target for future treatment options.

Immuno-LipoTRAIL: Targeted delivery of TRAIL-functionalized liposomal nanoparticles.

The TNF-related apoptosis-inducing ligand (TRAIL) is a powerful inducer of apoptosis in tumor cells; however, clinical studies with recombinant soluble TRAIL were rather disappointing. Here, we developed TRAIL-functionalized liposomes (LipoTRAIL, LT) to mimic membrane-displayed TRAIL for efficient activation of death receptors DR4 and DR5 and enhanced induction of apoptosis, which were combined with an anti-EGFR single-chain Fv fragment (scFv) for targeted delivery to EGFR-positive tumor cells. These immuno-LipoTRAILs (ILTs) bound specifically to EGFR-expressing cells (Colo205) and exhibited increased cytotoxicity compared with that of nontargeted LTs. Compared to that of the soluble TRAIL, the plasma half-life of the functionalized liposomes was strongly extended, and increased antitumor activity of LT and ILT was demonstrated in a xenograft tumor model. Thus, we established a multifunctional liposomal TRAIL formulation (ILT) with improved pharmacokinetic and pharmacodynamic behavior, characterized by targeted delivery and increased induction of apoptosis due to multivalent TRAIL presentation.

Lichen Sclerosus-Incidence and Comorbidity: A Nationwide Swedish Register Study.

Background: Data on the incidence and comorbidity of Lichen sclerosus (LS), based on validated nationwide population-based registries, remains scarce. Objective: To explore the incidence and association of comorbidities with LS in Sweden, emphasizing its potential links to malignancies and autoimmune disorders. Methods: A population-based retrospective open cohort study was conducted using the National Patient Register to identify all individuals diagnosed with LS (ICD-10 code L90.0) from 1 January 2001 to 1 January 2021. The study included 154,424 LS patients and a sex and age matched control group of 463,273 individuals to assess the incidence and odds ratios for various cancers and premalignant conditions. Results: The incidence of LS in Sweden was 80.9 per 100,000 person per year, with higher incidence in females (114.4) than in males (47.2). LS patients showed an increased odds ratio for vulvar cancer (OR = 8.3; 95% CI = 7.5-9.0), penile cancer (OR = 8.9; 95% CI = 7.3-11.0), prostate cancer (OR = 1.2; 95% CI = 1.1-1.2), testicular cancer (OR = 1.4; 95% CI = 1.1-1.7), bladder cancer (OR = 1.1; 95% CI = 1.1-1.2), breast cancer (OR = 1.4; 95% CI = 1.3-1.4), leukoplakia of the vulva (OR = 253.5; 95% CI = 221.9-289.6), and leukoplakia of the penis (OR = 5.1; 95% CI = 4.9-5.4). Conclusions: This study underscores the significantly increased association of various cancers and premalignant conditions in LS patients, highlighting the critical need for efficacious treatment and diligent follow-up. The association between LS and autoimmune diseases further necessitates comprehensive investigation to understand the underlying mechanisms and clinical management implications. Future research is essential to confirm these findings and elucidate the role of LS in cancer development.

The impact of genital lichen sclerosus in men and women on quality of life: a prospective cohort study.

Background: Genital lichen sclerosus (LS) is a chronic inflammatory skin disorder that affects both sexes of all ages. The clinical characteristics include erosions, redness, and white plaques with atrophic skin, with symptoms such as pruritus, pain, dysuria, and dyspareunia. Objective: This prospective cohort study aimed to assess quality of life (QoL) in men and women with genital LS, both before and after treatment, using the Dermatology Quality of Life Index (DLQI) questionnaire. Methods: Patients diagnosed with genital LS were enrolled continuously in the study and were asked to complete the DLQI questionnaire before treatment and again after individualized treatment 12 weeks apart. Results: This study included 136 patients (48 females and 88 males) diagnosed with genital LS, with a median age of 62 years (range 18-86). The results showed a statistically significant decrease (P < .001) in DLQI score before treatment (median 6.0 [interquartile range (IQR), 1.0-11.0]) compared to after treatment (median 2.0 [IQR, 0.0-4.0)]. In males and females, the median DLQI scores before treatment were 3.0 (IQR, 0.0-10.0) and 8.0 (IQR, 4.5-11.5), respectively, and after treatment were 1.0 (IQR, 0.0-3.0) and 4.0 (IQR, 0.0-9.0), respectively. Females scored significantly higher (P < .001) than males. Limitations: The study's limited generalizability stems from a small sample size of 136 patients, potentially restricting the application of findings to a broader population with genital lichen sclerosus. Additionally, the 12-week follow-up period may not adequately capture the long-term effects of interventions on quality of life. Reliance on self-reported data through the DLQI questionnaire introduces the possibility of bias, as participants may not accurately represent their symptoms and quality of life. The absence of a control group hinders the ability to attribute observed changes solely to the treatment, and the lack of detail on specific interventions makes it challenging to assess the effectiveness of individualized treatment approaches. The wide age range among participants (18-86 years) introduces potential confounding variables, as different age groups may respond differently to treatment. Conclusion: The study findings confirmed that individuals with genital LS experience a small decline in QoL, as observed in both males and females. This study also highlights that effective management of genital LS can significantly improve QoL in both sexes.