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John E. Harris, MD, PhD
Mehdi Rashighi, MD
Dori Goldberg, MD
Bassel Mahmoud, MD, PhD, FAAD
Subin Jacob-George, PA-C
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Total:
displaying 10 out of
100
results
Safety and efficacy of ruxolitinib cream for the treatment of vitiligo: A randomised controlled trial secondary analysis at 3 years
Tuesday, December 03, 2024
Source:
Skin health and disease
No abstract
Single-Cell RNA Sequencing Reveals Molecular Signatures that Distinguish Allergic from Irritant Contact Dermatitis
Saturday, September 28, 2024
Source:
The Journal of investigative dermatology
Allergic contact dermatitis (ACD) is a pruritic skin disease caused by environmental chemicals that induce cell-mediated skin inflammation within susceptible individuals. Irritant contact dermatitis (ICD) is caused by direct damage to the skin barrier by environmental insults. Diagnosis can be challenging because both types of contact dermatitis can appear similar by visual examination, and histopathological analysis does not reliably distinguish ACD from ICD. To discover specific biomarkers of...
Repigmentation by body region in patients with vitiligo treated with ruxolitinib cream over 52 weeks
Tuesday, July 16, 2024
Source:
Journal of the European Academy of Dermatology and Venereology : JEADV
No abstract
Performing Suction Blister Skin Biopsies
Wednesday, June 26, 2024
Source:
Current protocols
Traditional skin sampling methods include punch or shave biopsies to produce a solid tissue sample for analysis. These biopsy procedures are painful, require anesthesia, and leave permanent scars. This unit describes a suction blister skin biopsy method that can be used in place of traditional biopsy methodologies as a minimally invasive, non-scarring skin sampling technique. The induction of suction blisters uses an instrument with a chamber that applies negative pressure and gentle heat to the...
Improvement in light tolerance with oral Polypodium leucotomos extract in a patient with nonsegmental vitiligo treated with narrow-band UV-B phototherapy
Monday, June 17, 2024
Source:
JAAD case reports
No abstract
Once-daily upadacitinib versus placebo in adults with extensive non-segmental vitiligo: a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study
Friday, June 14, 2024
Source:
EClinicalMedicine
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.
Advancements in Targeted Therapies for Vitiligo: Prioritizing Equity in Drug Development
Friday, May 31, 2024
Source:
Cutis
No abstract
IL-12/IL-23-Independent Function of BATF3-Dependent Dendritic Cells Is Required for Initiation of Disease in a Mouse Model of Vitiligo
Saturday, April 20, 2024
Source:
The Journal of investigative dermatology
No abstract
Multispecies-targeting siRNAs for the modulation of JAK1 in the skin
Friday, February 02, 2024
Source:
Molecular therapy. Nucleic acids
Identifying therapeutic oligonucleotides that are cross-reactive to experimental animal species can dramatically accelerate the process of preclinical development and clinical translation. Here, we identify fully chemically-modified small interfering RNAs (siRNAs) that are cross-reactive to Janus kinase 1 (JAK1) in humans and a large variety of other species. We validated the identified siRNAs in silencing JAK1 in cell lines and skin tissues of multiple species. JAK1 is one of the four members...
Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine ligand-receptor pairs that drive disease
Tuesday, January 23, 2024
Source:
bioRxiv : the preprint server for biology
Chemokines play critical roles in the recruitment and activation of immune cells in both homeostatic and pathologic conditions. Here, we examined chemokine ligand-receptor pairs to better understand the immunopathogenesis of cutaneous lupus erythematosus (CLE), a complex autoimmune connective tissue disorder. We used suction blister biopsies to measure cellular infiltrates with spectral flow cytometry in the interface dermatitis reaction, as well as 184 protein analytes in interstitial skin...
Vitiligo progression in a patient undergoing romosozumab treatment for osteoporosis
Wednesday, November 15, 2023
Source:
JAAD case reports
No abstract
Rational design of a JAK1-selective siRNA inhibitor for the modulation of autoimmunity in the skin
Sunday, November 05, 2023
Source:
Nature communications
Inhibition of Janus kinase (JAK) family enzymes is a popular strategy for treating inflammatory and autoimmune skin diseases. In the clinic, small molecule JAK inhibitors show distinct efficacy and safety profiles, likely reflecting variable selectivity for JAK subtypes. Absolute JAK subtype selectivity has not yet been achieved. Here, we rationally design small interfering RNAs (siRNAs) that offer sequence-specific gene silencing of JAK1, narrowing the spectrum of action on JAK-dependent...
Baseline Levels of Circulating Inflammatory Biomarkers Stratify Patients with Vitiligo Who Significantly Repigment after Treatment with Ruxolitinib Cream
Monday, October 16, 2023
Source:
JID innovations : skin science from molecules to population health
CONCLUSION: This analysis identified potential differences between patients who achieved ≥50% improvement in facial Vitiligo Area Scoring Index at 24 weeks and those who did not that require deeper scientific interrogation and may be important in stratifying therapeutic benefit for patients with vitiligo.
Expanding the White Armor of Vitiligo
Friday, October 13, 2023
Source:
The Journal of investigative dermatology
No abstract
Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the International Vitiligo Task Force Part 1: towards a new management algorithm
Monday, September 25, 2023
Source:
Journal of the European Academy of Dermatology and Venereology : JEADV
CONCLUSIONS: These new treatment algorithms are intended to guide clinical decision-making in clinical practice. Promising novel therapies for vitiligo are on the horizon, further highlighting the need for reliable outcome measurement instruments and greater emphasis on shared decision-making.
Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations
Saturday, September 16, 2023
Source:
Journal of the European Academy of Dermatology and Venereology : JEADV
CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.
Mental Health and Psychosocial Quality-of-Life Burden Among Patients With Vitiligo: Findings From the Global VALIANT Study
Wednesday, August 30, 2023
Source:
JAMA dermatology
CONCLUSIONS AND RELEVANCE: This qualitative study found that, globally, patients with vitiligo reported being substantially affected in their emotional well-being, daily lives, and psychosocial health; the burden was typically greatest among patients with more than 5% affected BSA, darker skin types, and lesions on the face or hands. Survey findings suggest that patients reported having altered their behavior, expressed clear discontent, and have symptoms consistent with depression, which may be...
Exploring the natural and treatment history of vitiligo: perceptions of patients and healthcare professionals from the global VALIANT study
Wednesday, July 26, 2023
Source:
The British journal of dermatology
CONCLUSIONS: Patients with vitiligo and HCPs reported similar treatment goals and expressed frustration with the lack of effective therapies. Patients reported high rates of initial misdiagnosis; many ceased seeking healthcare because they perceived that vitiligo could not be treated. The findings highlight the need for earlier diagnosis and improved disease management for vitiligo.
Lesional CD8+ T-Cell Number Predicts Surgical Outcomes of Melanocyte-Keratinocyte Transplantation Surgery for Vitiligo
Friday, July 21, 2023
Source:
The Journal of investigative dermatology
The melanocyte-keratinocyte transplantation procedure (MKTP) treats stable and recalcitrant vitiligo. Despite careful selection of candidates based on clinical stability, the success of the procedure is unpredictable. The aim of our study was to define the immunological profile of stable vitiligo lesions undergoing MKTP and correlate them with clinical outcomes. We included 20 MKTP candidates with vitiligo and a patient with piebaldism as a control. Prior to MKTP, T-cell subsets and chemokines...
Assessing risk amid uncertainty inside and outside the dermatology clinic
Sunday, July 02, 2023
Source:
Journal of the American Academy of Dermatology
No abstract
Vitiligo induced by dupilumab treatment: A case series
Friday, April 28, 2023
Source:
Journal of the European Academy of Dermatology and Venereology : JEADV
No abstract
Narrowband ultraviolet B phototherapy in pediatric vitiligo: A retrospective study
Thursday, February 16, 2023
Source:
Journal of the American Academy of Dermatology
No abstract
Adolescent extra-truncal progressive macular hypomelanosis
Monday, February 06, 2023
Source:
Pediatric dermatology
Two adolescent females presented to outpatient clinic with isolated, non-scaly, asymptomatic hypopigmented macules and patches on the arm(s). Both cases had Wood's lamp exams notable for extralesional punctiform coral-red perifollicular fluorescence on the back and faint intralesional enhancement. In one case, biopsy was performed and deemed consistent with progressive macular hypomelanosis. The patient had complete response to antimicrobial therapy and sun exposure.
CXCL9 Links Skin Inflammation and Fibrosis through CXCR3-Dependent Upregulation of Col1a1 in Fibroblasts
Saturday, January 28, 2023
Source:
The Journal of investigative dermatology
Morphea is characterized by initial inflammation followed by fibrosis of the skin and soft tissue. Despite its substantial morbidity, the pathogenesis of morphea is poorly studied. Previous work showed that CXCR3 ligands CXCL9 and CXCL10 are highly upregulated in the sera and lesional skin of patients with morphea. We found that an early inflammatory subcutaneous bleomycin mouse model of dermal fibrosis mirrors the clinical, histological, and immune dysregulation observed in human morphea. We...
Activation of the NLRP1 inflammasome in human keratinocytes by the dsDNA mimetic poly(dA:dT)
Tuesday, January 24, 2023
Source:
Proceedings of the National Academy of Sciences of the United States of America
The accrual of cytosolic DNA leads to transcription of type I IFNs, proteolytic maturation of the IL-1 family of cytokines, and pyroptotic cell death. Caspase-1 cleaves pro-IL1β to generate mature bioactive cytokine and gasdermin D which facilitates IL-1 release and pyroptotic cell death. Absent in melanoma-2 (AIM2) is a sensor of dsDNA leading to caspase-1 activation, although in human monocytes, cGAS-STING acting upstream of NLRP3 mediates the dsDNA-activated inflammasome response. In healthy...
Real-world evidence on atopic dermatitis: Baseline characteristics and predictors of treatment choice in the TARGET cohort
Thursday, December 15, 2022
Source:
Journal of the American Academy of Dermatology
No abstract
Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: A randomized phase 2b clinical trial
Saturday, November 12, 2022
Source:
Journal of the American Academy of Dermatology
CONCLUSIONS: Oral ritlecitinib was effective and well tolerated over 48 weeks in patients with active nonsegmental vitiligo.
Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo
Wednesday, October 19, 2022
Source:
The New England journal of medicine
CONCLUSIONS: In two phase 3 trials, application of ruxolitinib cream resulted in greater repigmentation of vitiligo lesions than vehicle control through 52 weeks, but it was associated with acne and pruritus at the application site. Larger and longer trials are required to determine the effect and safety of ruxolitinib cream in patients with vitiligo. (Funded by Incyte; TRuE-V1 and TRuE-V2 ClinicalTrials.gov numbers, NCT04052425 and NCT04057573.).
Addition of Narrow-Band UVB Phototherapy to Ruxolitinib Cream in Patients With Vitiligo
Tuesday, July 05, 2022
Source:
The Journal of investigative dermatology
No abstract
A Keratinocyte-Tethered Biologic Enables Location-Precise Treatment in Mouse Vitiligo
Tuesday, July 05, 2022
Source:
The Journal of investigative dermatology
Despite the central role of IFN-γ in vitiligo pathogenesis, systemic IFN-γ neutralization is an impractical treatment option owing to strong immunosuppression. However, most patients with vitiligo present with
Regulatory T Cells Require CCR6 for Skin Migration and Local Suppression of Vitiligo
Friday, July 01, 2022
Source:
The Journal of investigative dermatology
Vitiligo is an autoimmune skin disease caused by melanocyte-targeting autoreactive CD8+ T cells. Regulatory T cells (Tregs) have been implicated in restraining vitiligo severity in both mouse models and human patients; however, whether they must be present in the skin for their suppressive function is still unclear. We observed uneven distribution of Tregs within different anatomical locations of mouse skin, which correlated with reduced depigmentation after vitiligo induction. We specifically...
Vitiligo of the arm after COVID-19 vaccination
Monday, June 27, 2022
Source:
JAAD case reports
No abstract
RNAi-based modulation of IFN-γ signaling in skin
Thursday, April 28, 2022
Source:
Molecular therapy : the journal of the American Society of Gene Therapy
Aberrant activation of interferon (IFN)-γ signaling plays a key role in several autoimmune skin diseases, including lupus erythematosus, alopecia areata, vitiligo, and lichen planus. Here, we identify fully chemically modified small interfering RNAs (siRNAs) that silence the ligand binding chain of the IFN-γ receptor (IFNGR1), for the modulation of IFN-γ signaling. Conjugating these siRNAs to docosanoic acid (DCA) enables productive delivery to all major skin cell types local to the injection...
Systemic therapies in vitiligo: a review
Tuesday, February 08, 2022
Source:
International journal of dermatology
Vitiligo is characterized by the development of depigmented macules and patches. Autoimmunity has been established as a factor in disease pathogenesis, leading to utilization of immunosuppressive agents. Topical immunosuppressants are commonly used; however, this treatment modality is often cumbersome and inefficient, as many patients have active disease with extensive body surface area involvement. Prompt and aggressive treatment of vitiligo is important, as this may prevent progression and...
scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in Treg function
Monday, September 13, 2021
Source:
Science translational medicine
Vitiligo is an autoimmune skin disease characterized by the targeted destruction of melanocytes by T cells. Cytokine signaling between keratinocytes and T cells results in CD8^(+) T cell infiltration of vitiligo lesions, but the full scope of signals required to coordinate autoimmune responses is not completely understood. We performed single-cell RNA sequencing on affected and unaffected skin from patients with vitiligo, as well as healthy controls, to define the role of each cell type in...
AIM2 regulates anti-tumor immunity and is a viable therapeutic target for melanoma
Thursday, July 29, 2021
Source:
The Journal of experimental medicine
The STING and absent in melanoma 2 (AIM2) pathways are activated by the presence of cytosolic DNA, and STING agonists enhance immunotherapeutic responses. Here, we show that dendritic cell (DC) expression of AIM2 within human melanoma correlates with poor prognosis and, in contrast to STING, AIM2 exerts an immunosuppressive effect within the melanoma microenvironment. Vaccination with AIM2-deficient DCs improves the efficacy of both adoptive T cell therapy and anti-PD-1 immunotherapy for "cold...
Editorial: Immunology of Vitiligo
Monday, July 12, 2021
Source:
Frontiers in immunology
No abstract
Gene Expression Profiling in the Skin Reveals Strong Similarities between Subacute and Chronic Cutaneous Lupus that Are Distinct from Lupus Nephritis
Monday, June 21, 2021
Source:
The Journal of investigative dermatology
Subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus are represented in the majority of cutaneous lupus subtypes, each of which has variable implications for systemic manifestations such as lupus nephritis. On dermatologic examination, subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus are distinct. However, it is often difficult to diagnose the subtype from histology alone. Our study utilized whole-genome microarray expression analysis...
Efficacy of ruxolitinib cream in vitiligo by patient characteristics and affected body areas: Descriptive subgroup analyses from a phase 2, randomized, double-blind trial
Saturday, June 05, 2021
Source:
Journal of the American Academy of Dermatology
No abstract
Treatment recommendations for patients with vitiligo during COVID-19
Monday, May 24, 2021
Source:
The Australasian journal of dermatology
No abstract
Resident Memory T Cells in Autoimmune Skin Diseases
Thursday, May 20, 2021
Source:
Frontiers in immunology
Tissue resident memory T cells (TRM) are a critical component of the immune system, providing the body with an immediate and highly specific response against pathogens re-infecting peripheral tissues. More recently, however, it has been demonstrated that TRM cells also form during autoimmunity. TRM mediated autoimmune diseases are particularly destructive, because unlike foreign antigens, the self-antigens are never cleared, continuously activating self-reactive TRM T cells. In this article, we...
Gaining Insight into Vitiligo Genetics through the Lens of a Large Epidemiologic Study
Tuesday, March 23, 2021
Source:
The Journal of investigative dermatology
Several epidemiologic studies and GWASs have implicated genetic factors in the pathogenesis of vitiligo. The report by Kim et al. (2020) describes a prospective cohort study from Korea that has the greatest statistical power to date in addressing the epidemiology of vitiligo inheritance. The authors reported the incidence risk ratios in individuals whose first-degree relatives or spouses are affected, providing clear evidence that both genetic and nongenetic factors influence the pathogenesis of...
Translational Research in Vitiligo
Friday, March 19, 2021
Source:
Frontiers in immunology
Vitiligo is a disease of the skin characterized by the appearance of white spots. Significant progress has been made in understanding vitiligo pathogenesis over the past 30 years, but only through perseverance, collaboration, and open-minded discussion. Early hypotheses considered roles for innervation, microvascular anomalies, oxidative stress, defects in melanocyte adhesion, autoimmunity, somatic mosaicism, and genetics. Because theories about pathogenesis drive experimental design, focus, and...
Ruxolitinib cream for the treatment of vitiligo - Authors' reply
Sunday, November 29, 2020
Source:
Lancet (London, England)
No abstract
International observational atopic dermatitis cohort to follow natural history and treatment course: TARGET-DERM AD study design and rationale
Saturday, November 28, 2020
Source:
BMJ open
INTRODUCTION: As new topical and systemic treatments become available for atopic dermatitis (AD), there is a need to understand how treatments are being used in routine clinical practice, their comparative effectiveness and their long-term safety in diverse clinical settings.
Type I interferon signaling limits viral vector priming of CD8+ T cells during initiation of vitiligo and melanoma immunotherapy
Sunday, October 11, 2020
Source:
Pigment cell & melanoma research
Vitiligo is an autoimmune skin disease in which epidermal melanocytes are targeted for destruction by CD8^(+) T cells specific for melanocyte/melanoma-shared antigens. IFNγ is the central cytokine driving disease, but the role of type I IFN in vitiligo remains unclear. We investigated the functional role of type I IFN during vitiligo progression using two different mouse models: one induced with a vaccinia virus (VV) vaccine and one induced with dendritic cells to prime autoimmune T cells....
Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial
Monday, July 13, 2020
Source:
Lancet (London, England)
BACKGROUND: Vitiligo is a chronic autoimmune disease resulting in skin depigmentation and reduced quality of life. There is no approved treatment for vitiligo repigmentation and current off-label therapies have limited efficacy, emphasising the need for improved treatment options. We investigated the therapeutic potential of ruxolitinib cream in patients with vitiligo and report the efficacy and safety results up to 52 weeks of double-blind treatment.
Jak Inhibitors Reverse Vitiligo in Mice but Do Not Deplete Skin Resident Memory T Cells
Friday, May 29, 2020
Source:
The Journal of investigative dermatology
No abstract
Vitiligo: Mechanisms of Pathogenesis and Treatment
Wednesday, February 05, 2020
Source:
Annual review of immunology
Vitiligo is an autoimmune disease of the skin that targets pigment-producing melanocytes and results in patches of depigmentation that are visible as white spots. Recent research studies have yielded a strong mechanistic understanding of this disease. Autoreactive cytotoxic CD8^(+) T cells engage melanocytes and promote disease progression through the local production of IFN-γ, and IFN-γ-induced chemokines are then secreted from surrounding keratinocytes to further recruit T cells to the skin...
Proceeding Report of the Second Vitiligo International Symposium-November 9-10, 2018, Detroit, Michigan, USA
Tuesday, January 28, 2020
Source:
Pigment cell & melanoma research
No abstract
Jak Inhibition Prevents Bleomycin-Induced Fibrosis in Mice and Is Effective in Patients with Morphea
Monday, January 20, 2020
Source:
The Journal of investigative dermatology
No abstract
Standardizing serial photography for assessing and monitoring vitiligo: A core set of international recommendations for essential clinical and technical specifications
Monday, November 04, 2019
Source:
Journal of the American Academy of Dermatology
CONCLUSIONS: This consensus-based protocol for vitiligo photography will harmonize imaging for both clinical practice, translational research, and clinical trials. It can improve outcome assessment, foster multicenter collaboration, and promote better communication with patients regarding outcomes of treatment.
The Role of Memory CD8+ T Cells in Vitiligo
Wednesday, June 19, 2019
Source:
Journal of immunology (Baltimore, Md. : 1950)
Vitiligo is an autoimmune skin disease mediated by autoreactive CD8^(+) T cells that destroy the pigment-producing cells of the epidermis, melanocytes, leading to areas of depigmentation. Patients with vitiligo require lifelong treatment to regain and maintain their pigment. Clinical observations uncovered the importance of autoimmune memory in vitiligo because cessation of treatment frequently led to relapse of disease at the site of previous lesions. A subset of memory T cells known as CD8^(+)...
T-cell positioning by chemokines in autoimmune skin diseases
Saturday, April 13, 2019
Source:
Immunological reviews
Autoimmune skin diseases are complex processes in which autoreactive cells must navigate through the skin tissue to find their targets. Regulatory T cells in the skin help to mitigate autoimmune inflammation and may in fact be responsible for the patchy nature of these conditions. In this review, we will discuss chemokines that are important for global recruitment of T cell populations to the skin during disease, as well as signals that fine-tune their localization and function. We will describe...
Validation of a physician global assessment tool for vitiligo extent: Results of an international vitiligo expert meeting
Friday, April 05, 2019
Source:
Pigment cell & melanoma research
Currently, vitiligo lacks a validated Physician Global Assessment (PGA) for disease extent. This PGA can be used to stratify and interpret the numeric scores obtained by the Vitiligo Extent Score (VES). We investigated the interrater reliability of a 5-point PGA scale during an international vitiligo workshop. Vitiligo experts from five different continents rated photographs of non-segmental vitiligo patients with varying degrees of extent with the PGA score. Good interrater agreements...
Patient satisfaction and physician productivity in shared medical appointments for vitiligo
Wednesday, March 27, 2019
Source:
Journal of the American Academy of Dermatology
CONCLUSION: SMAs were successful in a vitiligo clinic for both patient and provider. The SMA is a solution to improve access to dermatologists without compromising patient benefit, experience, or satisfaction.
Treatment with Modified Heat Shock Protein Repigments Vitiligo Lesions in Sinclair Swine
Saturday, November 24, 2018
Source:
The Journal of investigative dermatology
HSP70i is secreted by stressed melanocytes, is associated with human vitiligo lesions, and functionally contributes to a mouse model of vitiligo. Henning et al. report that treatment with a modified version of the protein reversed depigmentation in Sinclair swine, a useful animal model of vitiligo. These studies provide the rationale for testing in human studies.
Resident Memory and Recirculating Memory T Cells Cooperate to Maintain Disease in a Mouse Model of Vitiligo
Wednesday, November 14, 2018
Source:
The Journal of investigative dermatology
Tissue resident memory T cells (Trm) form in the skin in vitiligo and persist to maintain disease, as white spots often recur rapidly after discontinuing therapy. We and others have recently described melanocyte-specific autoreactive Trm in vitiligo lesions. Here, we characterize the functional relationship between Trm and recirculating memory T cells (Tcm) in our vitiligo mouse model. We found that both Trm and Tcm sensed autoantigen in the skin long after stabilization of disease, producing...
Mouse Model for Human Vitiligo
Wednesday, September 26, 2018
Source:
Current protocols in immunology
Vitiligo is an autoimmune skin disease in which the pigment-producing melanocytes are destroyed by autoreactive CD8^(+) T cells. As a result, patients develop disfiguring white spots on the skin. This article discusses the first mouse model of vitiligo that develops epidermal depigmentation, similar to disease in human patients. To achieve epidermal depigmentation, mice are genetically engineered to retain melanocytes in the skin epidermis. Induction of disease occurs by adoptive transfer of...
Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo
Friday, July 20, 2018
Source:
Science translational medicine
Vitiligo is an autoimmune disease of the skin mediated by CD8^(+) T cells that kill melanocytes and create white spots. Skin lesions in vitiligo frequently return after discontinuing conventional treatments, supporting the hypothesis that autoimmune memory is formed at these locations. We found that lesional T cells in mice and humans with vitiligo display a resident memory (T(RM)) phenotype, similar to those that provide rapid, localized protection against reinfection from skin and...
Fas ligand promotes an inducible TLR-dependent model of cutaneous lupus-like inflammation
Tuesday, June 12, 2018
Source:
The Journal of clinical investigation
Toll-like receptors TLR7 and TLR9 are both implicated in the activation of autoreactive B cells and other cell types associated with systemic lupus erythematosus (SLE) pathogenesis. However, Tlr9-/- autoimmune-prone strains paradoxically develop more severe disease. We have now leveraged the negative regulatory role of TLR9 to develop an inducible rapid-onset murine model of systemic autoimmunity that depends on T cell detection of a membrane-bound OVA fusion protein expressed by MHC class II+...
Alopecia areata is a medical disease
Sunday, March 18, 2018
Source:
Journal of the American Academy of Dermatology
No abstract
Building and Crossing the Translational Bridge: 2016 Alopecia Areata Research Summit Highlights
Sunday, December 24, 2017
Source:
The journal of investigative dermatology. Symposium proceedings
Alopecia areata (AA) is a common autoimmune skin disease that results in the loss of hair on the scalp and elsewhere on the body and affects over 146 million people worldwide at some point in their lives. Founded in 1981, the National Alopecia Areata Foundation is a nonprofit organization that supports research to find a cure or acceptable treatment for AA, supports those with the disease, and educates the public about AA. The National Alopecia Areata Foundation conducts research summits every 2...
Vitiligo-like depigmentation in patients receiving programmed cell death-1 inhibitor reflects active vitiligo
Saturday, December 16, 2017
Source:
Journal of the American Academy of Dermatology
No abstract
Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure
Tuesday, August 22, 2017
Source:
Journal of the American Academy of Dermatology
CONCLUSION: Treatment of vitiligo with JAK inhibitors appears to require light exposure. In contrast to treatment with phototherapy alone, repigmentation during treatment with JAK inhibitors may require only low-level light. Maintenance of repigmentation may be achieved with JAK inhibitor monotherapy. These results support a model wherein JAK inhibitors suppress T cell mediators of vitiligo and light exposure is necessary for stimulation of melanocyte regeneration.
Vitiligo: Mechanistic insights lead to novel treatments
Sunday, August 06, 2017
Source:
The Journal of allergy and clinical immunology
Vitiligo is an autoimmune disease of the skin characterized by patchy depigmentation. Current treatments are moderately effective at reversing disease by suppressing autoimmune inflammation in the skin and promoting melanocyte regeneration. Recent basic and translational research studies have significantly improved our understanding of disease pathogenesis, which is now leading to emerging treatment strategies based on targeted therapy. Here we discuss important clinical characteristics of...
Current and emerging treatments for vitiligo
Saturday, June 17, 2017
Source:
Journal of the American Academy of Dermatology
Clinicians should be aware that vitiligo is not merely a cosmetic disease and that there are safe and effective treatments available for vitiligo. It is important to recognize common and uncommon presentations and those with active disease, as well as their implications for clinical management; these were discussed in the first article in this continuing medical education series. Existing treatments include topical and systemic immunosuppressants, phototherapy, and surgical techniques, which...
New discoveries in the pathogenesis and classification of vitiligo
Saturday, June 17, 2017
Source:
Journal of the American Academy of Dermatology
Vitiligo is a common autoimmune disease that progressively destroys melanocytes in the skin, resulting in the appearance of patchy depigmentation. This disfiguring condition frequently affects the face and other visible areas of the body, which can be psychologically devastating. The onset of vitiligo often occurs in younger individuals and progresses for life, resulting in a heavy burden of disease and decreased quality of life. Presentation patterns of vitiligo vary, and recognition of these...
Optimizing Vitiligo Management: Past, Present, and Future
Tuesday, March 21, 2017
Source:
Dermatologic clinics
No abstract
Vitiligo Pathogenesis and Emerging Treatments
Tuesday, March 21, 2017
Source:
Dermatologic clinics
The pathogenesis of vitiligo involves interplay between intrinsic and extrinsic melanocyte defects, innate immune inflammation, and T-cell-mediated melanocyte destruction. The goal of treatment is to not only halt disease progression but also promote repigmentation through melanocyte regeneration, proliferation, and migration. Treatment strategies that address all aspects of disease pathogenesis and repigmentation are likely to have greatest efficacy, a strategy that may require combination...
Chemical-Induced Vitiligo
Tuesday, March 21, 2017
Source:
Dermatologic clinics
Chemical-induced depigmentation of the skin has been recognized for more than 75 years, first as an occupational hazard but then extending to those using household commercial products as common as hair dyes. Since their discovery, these chemicals have been used therapeutically in patients with severe vitiligo to depigment their remaining skin and improve their appearance. Because chemical-induced depigmentation is clinically and histologically indistinguishable from nonchemically induced...
Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity
Monday, March 06, 2017
Source:
Journal of the American Academy of Dermatology
CONCLUSION: Measuring CXCL9 directly in the skin might be effective in clinical trials as an early marker of treatment response. Additionally, use of the modified suction-blister technique supports investigation of inflammatory skin diseases using powerful tools like flow cytometry and protein quantification.
The Vitiligo Working Group recommendations for narrowband ultraviolet B light phototherapy treatment of vitiligo
Tuesday, February 21, 2017
Source:
Journal of the American Academy of Dermatology
CONCLUSION: This set of expert recommendations by the VWG is based on the prescribing practices of phototherapy experts from around the world to create a unified, broadly applicable set of recommendations on the use of NBUVB in vitiligo.
CXCR3 Depleting Antibodies Prevent and Reverse Vitiligo in Mice
Saturday, January 28, 2017
Source:
The Journal of investigative dermatology
No abstract
A double-blind, placebo-controlled, phase-II clinical trial to evaluate oral simvastatin as a treatment for vitiligo
Sunday, December 18, 2016
Source:
Journal of the American Academy of Dermatology
No abstract
CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses
Saturday, November 05, 2016
Source:
The Journal of experimental medicine
It is well established that Ly6C^(hi) monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found that BM Ly6C^(hi) monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6C^(hi) monocytes consist of two distinct subpopulations (CXCR4^(hi) and CXCR4^(lo) subpopulations)...
Understanding mechanisms of autoimmunity through translational research in vitiligo
Friday, October 21, 2016
Source:
Current opinion in immunology
Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular...
Keratinocyte-Derived Chemokines Orchestrate T-Cell Positioning in the Epidermis during Vitiligo and May Serve as Biomarkers of Disease
Saturday, October 01, 2016
Source:
The Journal of investigative dermatology
Vitiligo is an autoimmune disease of the skin that results in the destruction of melanocytes and the clinical appearance of white spots. Disease pathogenesis depends on IFN-γ and IFN-γ-induced chemokines to promote T-cell recruitment to the epidermis where melanocytes reside. The skin is a complex organ, with a variety of resident cell types. We sought to better define the microenvironment and distinct cellular contributions during autoimmunity in vitiligo, and we found that the epidermis is a...
Sampling Serum in Patients With Vitiligo to Measure Disease Activity in the Skin
Thursday, August 25, 2016
Source:
JAMA dermatology
No abstract
Understanding autoimmunity of vitiligo and alopecia areata
Thursday, May 19, 2016
Source:
Current opinion in pediatrics
PURPOSE OF REVIEW: Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include nontargeted approaches, such as corticosteroids, topical calcineurin inhibitors, narrow band ultraviolet B phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments.
Vitiligo
Thursday, May 19, 2016
Source:
Nature reviews. Disease primers
Vitiligo is an acquired depigmenting disorder that affects 0.5% to 2% of the world population. Three different forms are classified according to the distribution of lesions; namely non-segmental, segmental and mixed vitiligo. Vitiligo is associated with polymorphisms in genes involved in the immune response and in melanogenesis. However, environmental factors are required for the development of manifest disease. In general, the diagnosis is clinical and no laboratory tests or biopsies are...
Melanocytes in psoriasis: convicted culprit or bullied bystander?
Wednesday, March 02, 2016
Source:
Pigment cell & melanoma research
No abstract
Neutrophils Self-Regulate Immune Complex-Mediated Cutaneous Inflammation through CXCL2
Sunday, January 24, 2016
Source:
The Journal of investigative dermatology
Deposition of immune complexes (ICs) in tissues triggers acute inflammatory pathology characterized by massive neutrophil influx leading to edema and hemorrhage, and is especially associated with vasculitis of the skin, but the mechanisms that regulate this type III hypersensitivity process remain poorly understood. Here, using a combination of multiphoton intravital microscopy and genomic approaches, we re-examined the cutaneous reverse passive Arthus reaction and observed that IC-activated...
Interfering with the IFN-γ/CXCL10 pathway to develop new targeted treatments for vitiligo
Thursday, January 07, 2016
Source:
Annals of translational medicine
No abstract
Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA)
Tuesday, December 22, 2015
Source:
Journal of the American Academy of Dermatology
No abstract
Cellular stress and innate inflammation in organ-specific autoimmunity: lessons learned from vitiligo
Sunday, December 20, 2015
Source:
Immunological reviews
For decades, research in autoimmunity has focused primarily on immune contributions to disease. Yet recent studies report elevated levels of reactive oxygen species and abnormal activation of the unfolded protein response in cells targeted by autoimmunity, implicating cellular stress originating from the target tissue as a contributing factor. A better understanding of this contribution may help to answer important lingering questions in organ-specific autoimmunity, as to what factors initiate...
Melanocyte Regeneration in Vitiligo Requires WNT beneath their Wings
Tuesday, November 17, 2015
Source:
The Journal of investigative dermatology
Melanocytes in patients with vitiligo possess intrinsic abnormalities that contribute to its pathogenesis. Regazzetti et al. report that CXCL10 expression reflects subtle inflammation in normal-appearing skin but not in stable depigmented lesions, supporting the hypothesis that melanocytes themselves initiate autoimmune inflammation prior to clinically evident disease. In addition, they find that oxidative stress in melanocytes impairs WNT signaling and that targeting this pathway induces...
Vitiligo is not a cosmetic disease
Sunday, October 18, 2015
Source:
Journal of the American Academy of Dermatology
No abstract
Requirement for CD28 in Effector Regulatory T Cell Differentiation, CCR6 Induction, and Skin Homing
Sunday, September 27, 2015
Source:
Journal of immunology (Baltimore, Md. : 1950)
The skin, similar to most nonlymphoid tissues, contains substantial numbers of T cells. Among these, memory T cells serve a sentinel role to protect against pathogens, and regulatory T cells (Tregs) terminate immune responses as a check against unrestrained inflammation. Previously, we created conditional knockout mice with Treg-specific deletion of CD28. Although these mice have normal numbers of Tregs, these cells have lower levels of CTLA-4, PD-1, and CCR6, and the animals develop systemic...
Use of permanent hair dyes and risk of vitiligo in women
Tuesday, July 28, 2015
Source:
Pigment cell & melanoma research
No abstract
IFN-γ in Vitiligo, Is It the Fuel or the Fire?
Thursday, June 11, 2015
Source:
Acta dermato-venereologica
No abstract
Simvastatin prevents and reverses depigmentation in a mouse model of vitiligo
Friday, December 19, 2014
Source:
The Journal of investigative dermatology
Vitiligo is a common autoimmune disease of the skin that results in disfiguring white spots. There are no Food and Drug Administration (FDA)-approved treatments, and current treatments are time-consuming, expensive, and of low efficacy. We sought to identify new treatments for vitiligo, and first considered repurposed medications because of the availability of safety data and expedited regulatory approval. We previously reported that the IFN-γ-induced chemokine CXCL10 is expressed in lesional...
Immunology and skin in health and disease
Wednesday, December 03, 2014
Source:
Cold Spring Harbor perspectives in medicine
The skin is a complex organ that, in addition to providing a strong barrier against external insults, serves as an arena for a wide variety of inflammatory processes, including immunity against infections, tumor immunity, autoimmunity, and allergy. A variety of cells collaborate to mount functional immune responses, which are initiated by resident populations and evolve through the recruitment of additional cell populations to the skin. Inflammatory responses are quite diverse, resulting in a...
CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo
Friday, February 14, 2014
Source:
Science translational medicine
Vitiligo is an autoimmune disease of the skin that results in disfiguring white spots. There are no U.S. Food and Drug Administration-approved treatments for vitiligo, and most off-label treatments yield unsatisfactory results. Vitiligo patients have increased numbers of autoreactive, melanocyte-specific CD8(+) T cells in the skin and blood, which are directly responsible for melanocyte destruction. We report that gene expression in lesional skin from vitiligo patients revealed an interferon-γ...
Innate immune mechanisms in vitiligo: danger from within
Tuesday, November 19, 2013
Source:
Current opinion in immunology
Vitiligo is an autoimmune disease of the skin in which melanocytes are destroyed by antigen-specific T cells, resulting in patchy depigmentation. Although adaptive immunity plays a clear role in disease progression, initiating factors are largely unknown. Many studies report that cellular stress pathways are dysregulated in melanocytes from vitiligo patients, suggesting that melanocyte-intrinsic defects participate in disease pathogenesis. Recent studies reveal that melanocyte stress generates...
Vitiligo and alopecia areata: apples and oranges?
Friday, October 18, 2013
Source:
Experimental dermatology
Vitiligo and alopecia areata are common autoimmune diseases of the skin. Vitiligo is caused by the destruction of melanocytes and results in the appearance of white patches on any part of the body, while alopecia areata is characterized by patchy hair loss primarily on the scalp, but may also involve other areas as well. At first glance, the two diseases appear to be quite different, targeting different cell types and managed using different treatment approaches. However, the immune cell...
A network of high-mobility group box transcription factors programs innate interleukin-17 production
Tuesday, April 09, 2013
Source:
Immunity
How innate lymphoid cells (ILCs) in the thymus and gut become specialized effectors is unclear. The prototypic innate-like γδ T cells (Tγδ17) are a major source of interleukin-17 (IL-17). We demonstrate that Tγδ17 cells are programmed by a gene regulatory network consisting of a quartet of high-mobility group (HMG) box transcription factors, SOX4, SOX13, TCF1, and LEF1, and not by conventional TCR signaling. SOX4 and SOX13 directly regulated the two requisite Tγδ17 cell-specific genes, Rorc and...
Cavitation rheology as a potential method for in vivo assessment of skin biomechanics
Wednesday, January 30, 2013
Source:
Plastic and reconstructive surgery
No abstract
A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8⁺ T-cell accumulation in the skin
Friday, February 03, 2012
Source:
The Journal of investigative dermatology
Vitiligo is an autoimmune disease of the skin causing disfiguring patchy depigmentation of the epidermis and, less commonly, hair. Therapeutic options for vitiligo are limited, reflecting in part limited knowledge of disease pathogenesis. Existing mouse models of vitiligo consist of hair depigmentation but lack prominent epidermal involvement, which is the hallmark of human disease. They are thus unable to provide a platform to fully investigate disease mechanisms and treatment. CD8(+) T cells...
EGR-2 is not required for in vivo CD4 T cell mediated immune responses
Saturday, October 02, 2010
Source:
PloS one
CONCLUSIONS: Our results indicate that EGR-2 is not required to mount normal acute in vivo immune responses against foreign antigens, and suggest instead that it may serve to regulate the response to chronic antigenic exposure, such as that which occurs to autoantigens.
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John E. Harris, MD, PhD
Mehdi Rashighi, MD
Dori Goldberg, MD
Bassel Mahmoud, MD, PhD, FAAD
Subin Jacob-George, PA-C
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