Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo.

Background: Vitiligo is a chronic autoimmune disease that causes skin depigmentation. A cream formulation of ruxolitinib (an inhibitor of Janus kinase 1 and 2) resulted in repigmentation in a phase 2 trial involving adults with vitiligo.

Methods: We conducted two phase 3, double-blind, vehicle-controlled trials (Topical Ruxolitinib Evaluation in Vitiligo Study 1 [TRuE-V1] and 2 [TRuE-V2]) in North America and Europe that involved patients 12 years of age or older who had nonsegmental vitiligo with depigmentation covering 10% or less of total body-surface area.

Alopecia areata: Recent advances and emerging therapies.

Alopecia areata is an acquired, chronic, non-scarring hair disorder of the skin affecting 0.5-2% of the general population worldwide. Multiple mechanisms are involved in the disease, namely genetic predisposition, environmental triggers, impaired hair growth, and altered inflammatory and immune responses.

An integrated analysis of herpes virus infections from eight randomized clinical studies of baricitinib in adults with moderate-to-severe atopic dermatitis.

Background: Atopic dermatitis (AD) is associated with an increased risk for viral infections including those caused by herpes simplex virus and varicella zoster virus.

Objectives: This study examined treatment-emergent (TE) herpes simplex infection including eczema herpeticum (EH), and herpes zoster (HZ), in adult patients with AD receiving ≥1 dose of baricitinib (BARI), an oral selective inhibitor of Janus kinase 1/2.

Methods: We evaluated data from six double-blinded, randomized, placebo-controlled (PC) trials and two long-term extension studies, within three analysis sets: PC, 2-4-mg BARI extended and All-BARI-AD.

The humanistic burden of vitiligo: a systematic literature review of quality-of-life outcomes.

Despite historical mischaracterization as a cosmetic condition, patients with the autoimmune disorder vitiligo experience substantial quality-of-life (QoL) burden. This systematic literature review of peer-reviewed observational and interventional studies describes comprehensive evidence for humanistic burden in patients with vitiligo. PubMed, EMBASE, Scopus and the Cochrane databases were searched through February 10, 2021, to qualitatively assess QoL in vitiligo.

Vitiligo Skin T Cells Are Prone to Produce Type 1 and Type 2 Cytokines to Induce Melanocyte Dysfunction and Epidermal Inflammatory Response Through Jak Signaling.

Vitiligo is a T cell-mediated inflammatory skin disorder characterized by the loss of epidermal melanocytes. However, the contribution of melanocytes to the physiopathology of the disease in response to the T-cell microenvironment remains unclear. Here, using NanoString technology and multiplex ELISA, we show that active vitiligo perilesional skin is characterized by prominent type 1 and 2 associated immune responses.

Targeting Innate Immunity to Combat Cutaneous Stress: The Vitiligo Perspective.

Multiple factors are involved in the process leading to melanocyte loss in vitiligo including environmental triggers, genetic polymorphisms, metabolic alterations, and autoimmunity. This review aims to highlight current knowledge on how danger signals released by stressed epidermal cells in a predisposed patient can trigger the innate immune system and initiate a cascade of events leading to an autoreactive immune response, ultimately contributing to melanocyte disappearance in vitiligo. We will explore the genetic data available, the specific role of damage-associated-molecular patterns, and pattern-recognition receptors, as well as the cellular players involved in the innate immune response.

Efficacy and Safety of Tacrolimus 0.1% for the Treatment of Facial Vitiligo: A Multicenter Randomized, Double-Blinded, Vehicle-Controlled Study.

Background: Topical calcineurin inhibitors are used off label in the treatment of vitiligo, and there is a lack of placebo-controlled, blinded studies to support their use.

Objective: This study aimed to compare the efficacy of tacrolimus 0.1% ointment with that of the vehicle for repigmentation in adult patients with facial vitiligo.

An update on Vitiligo pathogenesis.

Vitiligo, the most common depigmenting disorder of the skin, is undergoing a period of intense advances in both disease understanding and therapeutic possibilities leading the way to the beginning of a new era for the disorder. Its pathophysiology has gathered the attention of researchers for years, and many advances have been made in the clarification of the interaction between different factors that result in depigmented macule formation. The complex interplay between non-immunological and immunological factors in vitiligo is key for the development of the disease, and the participation of cells other than melanocytes, such as keratinocytes, fibroblasts, natural killer cells, and innate lymphoid cells, has been shown.

Vitiligo, From Physiopathology to Emerging Treatments: A Review.

Vitiligo is a chronic inflammatory skin disease leading to the loss of epidermal melanocytes. To date, treatment options for vitiligo patients are limited, lack sustained efficacy, and are mainly based on off-label use of immunosuppressive agents, such as systemic or topical steroids or topical calcineurin inhibitors, in association with the use of ultraviolet light. However, recent insights into the understanding of the immune pathogenesis of the disease have led to the identification of several therapeutic targets and the development of targeted therapies that are now being tested in clinical trials.

Novel variants in the BLOC1S3 gene in patients presenting a mild form of Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) associates oculocutaneous albinism and systemic affections including platelet dense granules anomalies leading to bleeding diathesis and, depending on the form, pulmonary fibrosis, immunodeficiency, and/or granulomatous colitis. So far, 11 forms of autosomal recessive HPS caused by pathogenic variants in 11 different genes have been reported. We describe three HPS-8 consanguineous families with different homozygous pathogenic variants in BLOC1S3 (NM_212550.

Type-1 cytokines regulate MMP-9 production and E-cadherin disruption to promote melanocyte loss in vitiligo.

Loss of melanocytes is the pathological hallmark of vitiligo, a chronic inflammatory skin depigmenting disorder induced by exaggerated immune response, including autoreactive CD8 T cells producing high levels of type 1 cytokines. However, the interplay between this inflammatory response and melanocyte disappearance remains to be fully characterized. Here, we demonstrate that vitiligo skin contains a significant proportion of suprabasal melanocytes, associated with disruption of E-cadherin expression, a major protein involved in melanocyte adhesion.

Phenotype and function of circulating memory T cells in human vitiligo.

Background: Vitiligo is a chronic inflammatory skin disorder characterized by the loss of melanocytes. While a T helper cell (Th)1/cytotoxic T cell (Tc)1-skewed immune response is now well demonstrated in vitiligo, recent data suggest that the T-cell component could be more complex, involving different combinatorial T-cell subsets.

Objectives: To analyse the phenotype and function of circulating CD4 and CD8 memory T-cell subsets in patients with stable and active vitiligo, in comparison with patients with psoriasis and healthy controls.

PADDAS syndrome associated with hair dysplasia caused by a de novo missense variant of PUM1.

PUM1 has been very recently reported as responsible for a new form of developmental disorder named PADDAS syndrome. We describe here an additional patient with early onset developmental delay, epilepsy, microcephaly, and hair dysplasia, with a de novo heterozygous missense variant of PUM1: c.3439C > T, p.

Imbalance of peripheral follicular helper T lymphocyte subsets in active vitiligo.

Vitiligo is an autoimmune disease characterized by the presence of several autoantibodies, some of which are directed against melanocyte components and have been shown to be associated with the progression of the disease. However, the mechanism involved in the production of autoantibodies remains unclear. Follicular helper CD4 T cells (TFH) are specialized in B-cell activation and antibody production, especially the TFH cell subsets type 2 and type 17.

Association of skin hyperpigmentation disorders with digital ulcers in systemic sclerosis: Analysis of a cohort of 239 patients.

Background: Skin pigmentation disorders in systemic sclerosis (SSc) have been sparsely described in the literature. Nevertheless, they could be a diagnostic and/or severity marker.

Objectives: To assess the association between pigmentation disorders and systemic involvement in patients with SSc.