Genetic analyses unravel the causal association of cytokine levels on lichen simplex chronicus risk: insights from a mendelian randomization study.

Lichen simplex chronicus (LSC) presents a challenge in dermatology due to its elusive pathogenic mechanisms. While associations between circulating inflammatory cytokines and LSC were observed, the definitive causal dynamics remain to be elucidated. Our study used a two-sample Mendelian randomization (MR) approach to investigate causal relationships. We applied a suite of MR methodologies, including IVW, Weighted Median, MR-Egger, Weighted Mode, Simple Mode, MR-PRESSO, and the Steiger test, to ensure robust causal inference. Our analysis confirmed the causal impact of genetically determined cytokine levels on LSC risk, particularly MMP-10 (OR = 0.493, P = 0.004) and DNER (OR = 0.651, P = 0.043) in risk attenuation. We also found a positive causal correlation between GDNF levels (OR = 1.871, P = 0.007) and LSC prevalence. Notably, bidirectional causality was observed between DNER and LSC. Consistency across various MR analyses and sensitivity analyses confirmed the absence of horizontal pleiotropy, validating the causal estimates. This pioneering MR investigation unveils a novel genetically anchored causal relationship between the circulating levels of MMP-10, DNER, and GDNF and LSC risk. Although further validation is requisite, our findings augment the understanding of cytokine mediation in LSC and underscore prospective avenues for research.

A large sample-based case-control study of related risk factors of two types of lichenoid vulvar disease (LVD).

PURPOSE: The purpose of this study is to identify the associated factors of two types of lichenoid vulvar disease (LVD) and to compare the differences in related factors between the different pathological types of lichenoid vulvar disease (LVD). METHODS: The study conducted at the West China second Hospital of Sichuan University included a total of 1770 patients with biopsy-confirmed vulvar lichen simplex chronicus (VLSC)and vulvar lichen sclerosus(VLS), along with 1209 patients with normal vulvovagina as control. Further pathological subtype analysis was carried out on 163 cases of vulvar lichen simplex chronicus and 51 cases of vulvar lichen sclerosus. In addition, Univariate chi-square test and multivariate logistic regression were used to analyze the lichenoid vulvar disease group and vulvovaginal normal control group. RESULTS: Univariate analysis revealed that there were statistically significant differences (P < 0.05) in factors between the LVD group and the control group, except for living type, sleep habit, history of drinking, and allergic diseases. There was no significant difference in late sleep, spicy diet, and coffee intake in the factors of life and eating habits and the concomitant disease factors. Furthermore, univariate analysis showed that except for eating seafood, humid living environment, residence, caffeinated drinks, hypertension, and vaginitis, there were statistical differences in the related factors of LVSC. CONCLUSION: The incidence about lichenoid vulvar disease is influenced by various factors such as dietary habits, living environment, mental stress, concomitant diseases, hormone levels and so on, and there were no significant differences in these factors between VLS and VLSC except for income, work stress, systemic immune diseases, and menopause.

Dupilumab for the Treatment of Prurigo Nodularis.

Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by the presence of pruritic nodules. Dupilumab was approved by the US Food and Drug Administration in September 2022 and Health Canada in July 2023 for the treatment of PN. Dupilumab is a human monoclonal immunoglobulin G4 antibody that binds the interleukin (IL)-4 receptor alpha subunit, blocking intercellular signalling of IL-4 and IL-13. Inhibition of these cytokines downregulates the inflammatory response and improves disease severity and pruritus. Two randomized controlled trials have shown dupilumab to be effective in reducing pruritus and lesion count in patients with PN. The approval of dupilumab for PN represents the first approved therapy for PN and may indicate a paradigm shift in the way this condition is treated.

Psychopathology Associated with Chronic Pruritus: A Systematic Review.

There are no previous studies of the psychopathology associated with different aetiologies of chronic pruritus. A systematic review was performed of cohort and case-control studies comparing healthy controls with patients with chronic pruritus related to primary dermatoses, systemic diseases, psychogenic pruritus, idiopathic pruritus, prurigo nodularis and/or lichen simplex chronicus. The review was registered in PROSPERO and performed according to the PRISMA statement, which allowed the inclusion of 26 studies. The quality of eligible studies was assessed using the modified Newcastle-Ottawa Scale. Most of the studies concern primary dermatoses and systemic diseases. Sleep disorders are a common comorbidity interrelated with pruritus, anxiety and depressive symptoms, in primary dermatoses. Sleep disorders are linked with pruritus and depressive symptoms in end-stage renal disease and hepatobiliary disease. Depressive and anxiety symptoms are associated with psychogenic pruritus. Psychogenic pruritus, lichen simplex chronicus and some primary dermatoses are linked with personality characteristics. Further studies are required to explore in depth the psychopathology linked with psychogenic pruritus and prurigo nodularis, as well as psychopathology linked with other primary dermatoses and systemic disorders associated with chronic pruritus, and to better differentiate psychogenic pruritus from psychopathological characteristics linked with other aetiologies of chronic pruritus, in order to improve the management of patients with chronic pruritus.

Annular Lichenoid Dermatitis of Youth: Its Pathogenesis, Diagnosis, and Management.

Annular lichenoid dermatitis of youth (ALDY) is a newly described controversial benign lichenoid inflammatory cutaneous disorder often characterized by annular patches with hypopigmented center and surrounding erythematous border. Primarily, it affects the trunk and groin of young patients. Since its first description in 2003, additional patients have been reported, leading to better characterization of the entity; nevertheless, the pathogenesis is still unclear, and several hypotheses have been provided about possible triggering or causative factors. It tends to follow a chronic course, with some lesions spontaneously remitting, while others may be persistent or recur post-treatment. No standard validated treatment has been indicated so far for this disorder. Commonly prescribed topical treatment includes corticosteroids and calcineurin inhibitors with variable response.

A real-world observational study of dupilumab treatment in adult patients with prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a chronic inflammatory skin condition that has a significant unmet needs for effective treatment options. OBJECTIVE: To assess the efficacy and safety of dupilumab in adult patients with PN refractory to traditional therapies. METHODS: This ongoing, real-life study examined dupilumab treatment in 8 adult patients diagnosed with PN for at least 6 months. The included patients were prescribed 300 mg dupilumab biweekly for at least 16 weeks. Efficacy was the primary outcome by means of multiple standardized scale measurements while safety was also reported. RESULTS: PN patients treated with dupilumab showed notable clinical improvement. After 16 weeks of dupilumab treatment, the mean Investigator Global Assessment (IGA) score reduced from 3.75 to 1.50. Patients mean Numerical Rating Scale Itch Intensity (NRSI), Dermatology Life Quality Index (DLQI), and Hospital Anxiety and Depression Scale (HADS) ratings reduced from 8.625, 15.13, and 14.50 to 1.563, 4.625, and 1.000 respectively. The majority of the patients (87.5%) reported dupilumab as effective while no adverse events have been reported. STUDY LIMITATIONS: This study was limited to a small cohort of adult PN patients and a short-time observation period. CONCLUSIONS: Dupilumab is effective and tolerable in adult PN patients with significant improvement in skin lesions, itching, and quality of life.

The blood proteomic signature of prurigo nodularis reveals distinct inflammatory and neuropathic endotypes: A cluster analysis.

BACKGROUND: Prurigo nodularis (PN) is an extremely pruritic, chronic inflammatory skin disease. Little is known about systemic inflammation in PN. OBJECTIVE: To characterize plasma inflammatory biomarkers in patients with PN and investigate the presence of disease endotypes. METHODS: In this cross-sectional study, Olink proteomic analysis was performed on plasma samples from patients with PN (n = 29) and healthy controls (n = 18). RESULTS: Patients with PN had increased levels of 8 circulating biomarkers compared to controls, including tumor necrosis factor, C-X-C Motif Chemokine Ligand 9, interleukin-12B, and tumor necrosis factor receptor superfamily member 9 (P < .05). Two PN clusters were identified in cluster 1 (n = 13) and cluster 2 (n = 16). Cluster 2 had higher levels of 25 inflammatory markers than cluster 1. Cluster 1 had a greater percentage of patients with a history of myelopathy and spinal disc disease compared with cluster 2 (69% vs 25%, P = .03). Patients in cluster 2 were more likely to have a history of atopy (38% in cluster 2 vs 8% in cluster 1, P = .09). LIMITATIONS: Small sample size precludes robust subgroup analyses. CONCLUSION: This study provides evidence of neuroimmune-biased endotypes in PN and can aid clinicians in managing patients with PN that are nonresponsive to traditional therapies.

Occult squamous cell carcinoma within lichenoid dermatitis: three examples of cryptic cancer detection.

Lichenoid dermatitis can be a perplexing entity encompassing an array of cutaneous disorders. Two hundred forty-three (243) cases of otherwise unclassifiable lichenoid dermatitis were examined histologically employing a special cytokeratin stain. Occult squamous cell carcinoma was detected in three of the 243 cases, uncovered by special immunohistochemistry staining within histologic specimens of lichenoid dermatitis. We recommend staining for cutaneous cancer becoming a routine practice in evaluating cutaneous lichenoid dermatitis.