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Expert Review of Clinical Immunology Jul 2024Vitiligo is a chronic, autoimmune condition characterized by skin depigmentation caused by inflammatory-mediated melanocyte degradation. Treatment of vitiligo is... (Review)
Review
INTRODUCTION
Vitiligo is a chronic, autoimmune condition characterized by skin depigmentation caused by inflammatory-mediated melanocyte degradation. Treatment of vitiligo is challenging due to the chronic nature of the condition. Ruxolitinib cream 1.5% was recently approved by the Food and Drug Administration (FDA) as a Janus kinase 1 and 2 inhibitor for use in nonsegmental vitiligo for those 12 years and older.
AREAS COVERED
The purpose of this review is to describe the role of ruxolitinib in treating nonsegmental vitiligo.We searched PubMed using search terms nonsegmental vitiligo, jak inhibitor, and ruxolitinib. Clinicaltrials.gov was used to identify clinical trial data including efficacy, pharmacodynamics, pharmacokinetics, safety, and tolerability.
EXPERT OPINION
In both phase II and phase III (TRuE-V1 and TRuE-V2) trials, ruxolitinib cream 1.5% improved repigmentation with minimal adverse effects. Topical ruxolitinib is a much needed new vitiligo treatment option. Real life efficacy may not match that seen in clinical trials if the hurdle of poor adherence to topical treatment is not surmounted.
Topics: Nitriles; Humans; Vitiligo; Pyrimidines; Pyrazoles; Skin Pigmentation; Janus Kinase 1; Skin Cream; Janus Kinase 2; Janus Kinase Inhibitors
PubMed: 38879876
DOI: 10.1080/1744666X.2024.2326858 -
Archives of Dermatological Research Jun 2024Vitiligo is considered an autoimmune disease, and its treatment is challenging. We assessed and compared the effect of fractional erbium:yttrium-aluminum-garnet (Er:YAG)... (Randomized Controlled Trial)
Randomized Controlled Trial
Vitiligo is considered an autoimmune disease, and its treatment is challenging. We assessed and compared the effect of fractional erbium:yttrium-aluminum-garnet (Er:YAG) laser-assisted delivery of platelet-rich plasma versus microneedling (Mn) with platelet-rich plasma (PRP) in enhancing skin repigmentation in localized stable vitiligo patients. In total, 40 patients with localized stable vitiligo were selected in a random manner into two similar groups (20 each). Group (A) was subjected to fractional Er:YAG laser combined with platelet-rich plasma and Group (B) was subjected to microneedling combined with platelet-rich plasma. The procedure was repeated every 2 weeks for up to 6 months. Each individual was assessed clinically utilizing Vitiligo Area Scoring Index (VASI). Fractional Er:YAG + PRP group achieved better pigmentation100% (excellent 30%, very good 15%, good 30% and satisfactory 25%) which is comparable to Mn + PRP where 80% of cases demonstrate repigmentation (20% very good, 10% good and 50% mild). When comparing the VASI scores for both groups after therapy to the baseline VASI, there was a statistically significant decrease [p = 0.001 for group(A) and 0.003 for group(B)]. Regarding the treatment side effects, there was significantly (p = 0.048) side effects among cases treated with microneedling group(B) (25%) than those fractional Er:Yag laser therapy group(A) (5%). Both forms of therapy demonstrated induction of repigmentation of vitiligo, but fractional Er:YAG laser efficacy is greater when combined with platelet-rich plasma.Clinical trials.gov identifier: NCT05511493.
Topics: Humans; Vitiligo; Platelet-Rich Plasma; Lasers, Solid-State; Female; Male; Adult; Treatment Outcome; Skin Pigmentation; Needles; Young Adult; Middle Aged; Adolescent; Dry Needling; Combined Modality Therapy; Percutaneous Collagen Induction
PubMed: 38878236
DOI: 10.1007/s00403-024-03035-8 -
Archives of Dermatological Research Jun 2024
Topics: Humans; Vitiligo; Metabolic Syndrome; Female; Male; Middle Aged; Adult; Aged; Risk Factors
PubMed: 38878093
DOI: 10.1007/s00403-024-03117-7 -
Archives of Dermatological Research Jun 2024The adhesive properties of vitiligo melanocytes have decreased under oxidative stress., cytoskeleton proteins can control cell adhesion. Paeoniflorin (PF) was proved to...
BACKGROUND
The adhesive properties of vitiligo melanocytes have decreased under oxidative stress., cytoskeleton proteins can control cell adhesion. Paeoniflorin (PF) was proved to resist hydrogen peroxide (HO)-induced oxidative stress in melanocytes via nuclear factorE2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.
OBJECTIVES
This study was to investigate whether PF exerts anti-oxidative effect through influencing cytoskeleton markers or potential signaling pathway.
METHODS
Human Oxidative Stress Plus array was used to identify the differentially expressed genes between HO + PF group and HO only group, in PIG1 and PIG3V melanocyte cell lines respectively. Western blotting was used to verify the PCR array results and to test the protein expression levels of cytoskeleton markers including Ras homolog family member A (RhoA), Rho-associated kinase 1 (ROCK1) and antioxidative marker Nrf2. Small interfering RNA was used to knock down PDZ and LIM domain 1 (PDLIM1).
RESULTS
PF increased the expressions of PDLIM1, RhoA and ROCK1 in HO-induced PIG1, in contrast, decreased the expressions of PDLIM1 and ROCK1 in HO-induced PIG3V. Knockdown of PDLIM1 increased the expressions of RhoA and Nrf2 in PF-pretreated HO-induced PIG1, and ROCK1 and Nrf2 in PF-pretreated HO-induced PIG3V.
CONCLUSIONS
PF regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in HO-induced melanocytes. In PIG1, PF promotes PDLIM1 to inhibit RhoA/ROCK1 pathway or activates Nrf2/HO-1 pathway, separately. In PIG3V, PF directly downregulates ROCK1 in PDLIM1-independent manner or upregulates Nrf2 dependent of PDLIM1.
Topics: NF-E2-Related Factor 2; rho-Associated Kinases; Melanocytes; Humans; Glucosides; Oxidative Stress; rhoA GTP-Binding Protein; Hydrogen Peroxide; Signal Transduction; LIM Domain Proteins; Monoterpenes; Cell Line
PubMed: 38878083
DOI: 10.1007/s00403-024-03154-2 -
Journal of Cosmetic and Laser Therapy :... Jun 2024Laser hair removal is a commonly used method in dermatology which is based on selective thermolysis and utilizes the appropriate wavelength, pulse width, and energy...
Laser hair removal is a commonly used method in dermatology which is based on selective thermolysis and utilizes the appropriate wavelength, pulse width, and energy density to damage hair follicles. Given the prevalence of skin diseases such as psoriasis, dermatitis, and vitiligo, and the increasing popularity of laser hair removal, the aim of this study was to investigate the safety of laser hair removal in individuals with skin diseases. This retrospective study was conducted at the laser department of Razi Hospital on 99 patients who underwent laser hair removal. The exacerbation of disease after laser therapy was significantly associated with active skin disease ( = .021) and laser treatment at the site of the disease ( < .001). The incidence of Koebner phenomenon was significantly associated with age ( = .017) and the number of sessions with the ND-YAG device ( = .034). It is crucial to exercise caution when performing laser treatment on individuals with active skin disease and to avoid treating the affected area were possible. If necessary, it is recommended to delay laser treatment until the disease is under control for patients with active skin disease or those who wish to receive laser treatment at the site of the disease.
PubMed: 38874021
DOI: 10.1080/14764172.2024.2367448 -
EClinicalMedicine Jul 2024Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor,...
Once-daily upadacitinib versus placebo in adults with extensive non-segmental vitiligo: a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study.
BACKGROUND
Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental vitiligo.
METHODS
This was a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study completed at 33 clinical centres in the United States, Canada, France, and Japan. Eligible patients were aged 18-65 years with non-segmental vitiligo and had a Facial Vitiligo Area Scoring Index (F-VASI) ≥0.5 and a Total Vitiligo Area Scoring Index (T-VASI) ≥5. Patients were randomly assigned (2:2:2:1:1) using an interactive response technology to receive upadacitinib 6 mg (UPA6), upadacitinib 11 mg (UPA11), upadacitinib 22 mg (UPA22), or placebo (PBO; preassigned to switch to either UPA11 or UPA22 in period 2) once daily for 24 weeks (period 1). For weeks 24-52 (period 2), patients randomly assigned to upadacitinib continued their treatment, and patients receiving PBO switched to their preassigned upadacitinib dose in a blinded fashion. The primary endpoint was the percent change from baseline in F-VASI at week 24. Efficacy was analysed in the intention-to-treat population, and safety was examined in all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT04927975.
FINDINGS
Between June 16, 2021, and June 27, 2022, 185 patients (including 115 [62%] who were female and 70 [38%] who were male) were randomly assigned to UPA6 (n = 49), UPA11 (n = 47), UPA22 (n = 43), or PBO (n = 46). At week 24, the LS mean difference versus PBO in the percent change from baseline in F-VASI was -7.60 (95% CI -22.18 to 6.97; p = 0.3037) for UPA6, -21.27 (95% CI -36.02 to -6.52; p = 0.0051) for UPA11, and -19.60 (95% CI -35.04 to -4.16; p = 0.0132) for UPA22. The LS mean difference versus PBO in the percent change from baseline in T-VASI was -7.45 (95% CI -16.86 to 1.96; p = 0.1198) for UPA6, -10.84 (95% CI -20.37 to -1.32; p = 0.0259) for UPA11 and -14.27 (95% CI -24.24 to -4.30; p = 0.0053) for UPA22. Ongoing treatment with upadacitinib induced continuous skin repigmentation over time without reaching a plateau through week 52. The rates for study drug discontinuation and serious treatment-emergent adverse events (TEAEs) were higher in the UPA22 group than in the UPA11 and UPA6 groups. Eight serious TEAEs, including one death of unknown cause and one case of infiltrating lobular breast carcinoma, were reported through 52 weeks; only two serious TEAEs (coronary artery arteriosclerosis [UPA6 (n = 1)] and non-fatal ischemic stroke [UPA11 (n = 1)]) were deemed by the investigator to have a reasonable possibility of being related to study drug. The one case of breast cancer in the UPA11 group was deemed unrelated to study drug, and the one death of unknown cause in the UPA22 group was reviewed and adjudicated and was deemed to be unrelated to study drug. The most common TEAEs were COVID-19, headache, acne, and fatigue. No new safety signals were observed.
INTERPRETATION
Upadacitinib monotherapy led to substantial repigmentation of both facial and total body vitiligo lesions and may offer an effective treatment option for adults with extensive non-segmental vitiligo. Based on these findings, upadacitinib 15 mg is being investigated in adults and adolescents with non-segmental vitiligo in an ongoing phase 3 randomised controlled trial.
FUNDING
AbbVie Inc.
PubMed: 38873632
DOI: 10.1016/j.eclinm.2024.102655 -
International Journal of Women's... Jun 2024
PubMed: 38873620
DOI: 10.1097/JW9.0000000000000157 -
Frontiers in Psychology 2024According to many studies, vitiligo has a negative psychological influence on the patient's life. Multiple factors contribute to the severity of the vitiligo disease...
According to many studies, vitiligo has a negative psychological influence on the patient's life. Multiple factors contribute to the severity of the vitiligo disease burden, among which the most important are self-esteem, stress, and stigma. We aimed to measure the importance of health-related life quality in assessing disease burden in patients with vitiligo. We formulated an HA, which is the principal hypothesis, claiming a single fundamental factor that characterizes the life quality of patients with vitiligo. We also formulated 10 important research questions related to the quality of life that can be generally formulated for patients with dermatological illnesses but particularly suited for vitiligo patients. These research questions capture fundamental aspects of the health-related quality of life of vitiligo patients influenced by symptoms and feelings, daily activities, leisure, job and education, personal relationships, and treatment. These also cover specific aspects related to the quality of life, such as skin-caused sexual difficulties, difficulties in social relationships, and difficulties in performing sports, among others. The Dermatology Life Quality Index (DLQI) questionnaire measures the health-related quality of life of persons suffering from skin diseases. We applied this generic questionnaire to patients with vitiligo. Following a set of inclusion and exclusion criteria, we obtained 114 carefully selected patients who responded to all the questions. This study also validated the DLQI questionnaire on persons who suffer from vitiligo. We investigated whether DLQI has acceptable internal consistency by applying Cronbach's alpha internal consistency indicator (Cα). The obtained Cα = 0.914 indicates excellent internal consistency. We also examined whether all the questions in the questionnaire were mathematically consistent, which we finally proved. It was not necessary to remove any of the questionnaire questions. To prove our HA, a Principal Axis Factoring (PAF) was applied, verifying the assumptions regarding the Average Variance Extracted (AVE) and Convergent Validity (CV). HA proved that applying PAF on DLQI resulted in extracting a single general vitiligo latent factor of life quality, with an initial eigenvalue = 5.671, SS loadings = 5.2, and 52 % of the total cumulative variance explained. Diverse statistical analyses were applied to analyze the 10 formulated research questions. The results of the analysis of the research questions are presented and discussed in the manuscript. One of the conclusions related to the analysis of a research question was that sex had the lowest correlation with the latent life quality factor identified for vitiligo patients.
PubMed: 38873521
DOI: 10.3389/fpsyg.2024.1333723 -
Frontiers in Medicine 2024The coronavirus disease 2019 (COVID-19) pandemic subverted people's lives and potentially affected the management and prognosis of pre-existing dermatoses. The study...
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic subverted people's lives and potentially affected the management and prognosis of pre-existing dermatoses. The study aims to identify factors influencing the outcomes of dermatoses during a rapid and widespread Omicron outbreak in China following the adjustment of the COVID-19 policy.
MATERIALS AND METHODS
This retrospective observational study involved outpatients visiting the dermatology department at a tertiary referral hospital in Beijing, China between December 2022 and February 2023. Demographics, COVID-19 characteristics, treatment modalities, and dermatosis outcomes were subjected to statistical analysis.
RESULTS
The odds ratio (OR) for vitiligo aggravation during COVID-19 was 0.497 [95% confidence interval (CI): 0.254-0.973, = 0.038] compared to total patients with various dermatoses. Psoriasis patients with a maximum body temperature (T) over 38.6°C during COVID-19 were 2.833 times more likely to experience dermatosis aggravation (OR: 2.833 [1.029-7.803], = 0.041). Moreover, autoimmune bullous disease (AIBD) patients receiving biologics treatment exhibited a reduced likelihood of aggravation during the COVID-19 outbreak (OR: 0 [0-0.531], = 0.011).
CONCLUSION
Vitiligo exhibits lower aggravation rates during COVID-19 than other dermatoses. A higher body temperature during COVID-19 infection can increase the risk of psoriasis aggravation. Biologics treatment reduces the risk of AIBD aggravation during the COVID-19 outbreak.
PubMed: 38873214
DOI: 10.3389/fmed.2024.1417358 -
Frontiers in Immunology 2024Chronic inflammatory skin diseases are multifactorial diseases that combine genetic predisposition, environmental triggers, and metabolic disturbances associated with... (Review)
Review
Chronic inflammatory skin diseases are multifactorial diseases that combine genetic predisposition, environmental triggers, and metabolic disturbances associated with abnormal immune responses. From an immunological perspective, the better understanding of their physiopathology has demonstrated a large complex network of immune cell subsets and related cytokines that interact with both epidermal and dermal cells. For example, in type-1-associated diseases such as alopecia areata, vitiligo, and localized scleroderma, recent evidence suggests the presence of a type-2 inflammation that is well known in atopic dermatitis. Whether this type-2 immune response has a protective or detrimental impact on the development and chronicity of these diseases remains to be fully elucidated, highlighting the need to better understand its involvement for the management of patients. This mini-review explores recent insights regarding the potential role of type-2-related immunity in alopecia areata, vitiligo, and localized scleroderma.
Topics: Humans; Vitiligo; Animals; Alopecia Areata; Th2 Cells; Cytokines; Dermatitis, Atopic; Scleroderma, Localized; Inflammation; Skin
PubMed: 38868763
DOI: 10.3389/fimmu.2024.1405215