Publications by authors named "Alain Taïeb"

220 Publications

European Task Force on Atopic Dermatitis (ETFAD): position on vaccination of adult patients with atopic dermatitis against COVID-19 (SARS-CoV-2) being treated with systemic medication and biologics.

J Eur Acad Dermatol Venereol 2021 Feb 15. Epub 2021 Feb 15.

Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.

The coronavirus disease 2019 (COVID-19) pandemic is caused by rapid spread of different strains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severity of infection ranges from mild, or even asymptomatic, to very severe. Signs and symptoms include fatigue, fever, exanthemas, upper respiratory illness, loss of smell and taste, pneumonia, severe acute respiratory syndrome, and multi-organ failure. Risk factors for a severe or lethal course include age, male gender, obesity, diabetes, cardiovascular disease, and immune suppression .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jdv.17167DOI Listing
February 2021

Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta blockade.

Proc Natl Acad Sci U S A 2021 Feb;118(7)

Inserm, Biothérapie des Maladies Génétiques Inflammatoires et Cancers (BMGIC), UMR 1035, University of Bordeaux, F-33076 Bordeaux, France.

Propranolol, a nonselective β-adrenergic receptor (ADRB) antagonist, is the first-line therapy for severe infantile hemangiomas (IH). Since the incidental discovery of propranolol efficacy in IH, preclinical and clinical investigations have shown evidence of adjuvant propranolol response in some malignant tumors. However, the mechanism for propranolol antitumor effect is still largely unknown, owing to the absence of a tumor model responsive to propranolol at nontoxic concentrations. Immunodeficient mice engrafted with different human tumor cell lines were treated with anti-VEGF bevacizumab to create a model sensitive to propranolol. Proteomics analysis was used to reveal propranolol-mediated protein alteration correlating with tumor growth inhibition, and Aquaporin-1 (AQP1), a water channel modulated in tumor cell migration and invasion, was identified. IH tissues and cells were then functionally investigated. Our functional protein association networks analysis and knockdown of ADRB2 and AQP1 indicated that propranolol treatment and AQP1 down-regulation trigger the same pathway, suggesting that AQP1 is a major driver of beta-blocker antitumor response. Examining AQP1 in human hemangioma samples, we found it exclusively in a perivascular layer, so far unrecognized in IH, made of telocytes (TCs). Functional in vitro studies showed that AQP1-positive TCs play a critical role in IH response to propranolol and that modulation of AQP1 in IH-TC by propranolol or shAQP1 decreases capillary-like tube formation in a Matrigel-based angiogenesis assay. We conclude that IH sensitivity to propranolol may rely, at least in part, on a cross talk between lesional vascular cells and stromal TCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2018690118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896303PMC
February 2021

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

J Invest Dermatol 2021 Feb 4. Epub 2021 Feb 4.

Department of Dermatology, Henri Mondor University Hospital, Créteil, France; Epidemiology in Dermatology and Evaluation of Therapeutics (EpidermE), Université Paris-Est Créteil Val de Marne (UPEC), Créteil, France. Electronic address:

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.

Design: This study was a 24-week multicenter randomized parallel double-blind study with a 24-week post-treatment follow-up extension.

Population: Participants included were adult patients with recent facial vitiligo target lesions (<2 years) without changes in pigmentation or size over the previous 3 months.

Intervention: Patients received either tacrolimus 0.1% ointment or vehicle twice daily.

Main Outcomes And Measures: The primary outcome was a therapeutic success, defined as a change ≥75% in the repigmentation of the target lesion between baseline and week 24, measured by ImageJ software. Secondary outcome measures were a variation of the physicians' global assessment scores and patients' satisfaction scores, safety data, and the rate of relapse at week 48.

Results: A total of 42 patients were included. Therapeutic success was achieved in 65% of tacrolimus-treated patients versus 0% of vehicle-treated patients at week 24 (P < 0.0001). Only 40% of relapse was observed at 48 weeks.

Conclusions And Relevance: Twice-daily tacrolimus 0.1% ointment showed superior efficacy to that of the vehicle through the 24 weeks of intervention and 24 weeks of follow-up in adult patients with facial vitiligo.

Trial Registration: This study was registered at ClinicalTrials.gov (identifier: NCT02466997).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2020.12.028DOI Listing
February 2021

Congenital haemangiomas: a single-centre retrospective review.

BMJ Paediatr Open 2020 7;4(1):e000816. Epub 2020 Dec 7.

Dermatology, CHU de Bordeaux, Bordeaux, France.

Objective: Congenital haemangiomas (CHs) are rare, benign vascular tumours that are fully developed at birth. Three subtypes of CHs have been described based on clinical behaviour: rapidly involuting CHs (RICHs), non-involuting CHs (NICHs) and partially involuting CHs (PICHs). We explore in our study clinical, evolutionary and paraclinical characteristics of the three CH subtypes.

Design: Children with CH attending our department of paediatric dermatology at Bordeaux University Hospital over a 13-year period were retrospectively included. Epidemiological, clinical and evolutionary data, photographs and imaging results were reviewed. All available tissue samples were histologically examined.

Results: We included 57 patients: 22 with RICH, 22 with NICH and 13 with PICH. Males predominated (ratio 1.7); the most common CH location was on the limbs. RICH, NICH and PICH exhibited overlapping characteristics; all were single telangiectatic lesions with pale peripheral halos. At birth, NICHs were flat but RICHs and PICHs bulky. The median age at complete RICH involution was 12 months. One-third of CHs that appeared RICH-like at birth underwent incomplete involution to become PICHs. Heart failure and thrombocytopenia were rare complications. PICHs were frequently ulcerated. Pain was common for NICH and PICH. The imaging and histological data of the three CH subtypes were rather similar.

Conclusions: We describe the characteristics and evolution of the three CH subtypes using a case series. Certain overlapping features were apparent, reinforcing the hypothesis that RICH, NICH and PICH lie on the same pathological spectrum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjpo-2020-000816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722829PMC
December 2020

Hydrolyzed Rice Protein-Based Formulas, a Vegetal Alternative in Cow's Milk Allergy.

Nutrients 2020 Aug 31;12(9). Epub 2020 Aug 31.

Department of Paediatrics, Saint Antoine Paediatric Hospital, Saint Vincent de Paul Hospital, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Catholic University of Lille, 59000 Lille, France.

Formulas adapted to infant feeding, although most of the time made from cow's milk proteins, can be made from hydrolyzed rice protein but they must be classified as "formulas for specific medical needs", according to European regulations. The nutritional quality of rice proteins is thus suitable to be used in infant formulas giving that it is supplemented by certain amino acids which can be lacking. Besides, hydrolysis is required to facilitate their water solubility and digestibility. Owing to a low allergenicity of rice and to the absence of the cross-allergy between milk proteins and rice proteins, these formulas are adapted to the diet of children with cow's milk protein allergy (CMPA), which explains their growing use in some countries. However, CMPA, an expanding disorder, has consequences for growth, bone mineralization, and often has an association with allergy to other foods, including cow's milk extensive hydrolysate, so that a surveillance of the adaption of hydrolyzed rice protein formulas (HRPF) to CMPA, the absence of unexpected side effects, and the appropriate response to its various health hazards seems mandatory. This paper analyses the health problem deriving from CMPA, the industrial development of hydrolyzed rice protein formulas, and the limited number of clinical studies, which confirms, at the moment, a good allergic tolerance and safety. The goal is to better advise heath care professionals on their use of HRPFs during CMPA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12092654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551844PMC
August 2020

Effectiveness and safety of secukinumab in patients with moderate-severe psoriasis: A multicenter real-life study.

Dermatol Ther 2020 11 18;33(6):e14044. Epub 2020 Aug 18.

Department of Biomedical Sciences and Human Oncology, Section of Dermatology, University of Bari, Bari, Italy.

This study assessed the effectiveness and safety of secukinumab in patients with moderate-severe psoriasis vulgaris in a real-world setting. A total of 120 patients (35.8% women; mean age 49.8 years) were enrolled. Mean PASI significantly decreased from 12.0 ± 6.6 at baseline to 4.7 ± 3.2 and 2.3 ± 4.0 at 3 and 12 months, respectively (P < .001). Patients with two or more lines of prior biological therapies had poorer persistence to therapy at 12 months (71%) vs those who were bio-naïve (93%) or patients with only one prior failure with a biological agent (88%) (log-rank = 9.33; P = .009). Multivariate regression analysis showed that patients beyond the second line of treatment had an increased risk of discontinuing secukinumab (HR: 3.6; 95% CI 1.3-10.2), while those without comorbidities had a lower risk (HR: 0.31; 95% CI 0.1-0.8). Our study confirms the effectiveness and safety of secukinumab in a real-life setting for psoriatic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dth.14044DOI Listing
November 2020

Dysregulation of CCN3 (NOV) expression in the epidermis of systemic sclerosis patients with pigmentary changes.

Pigment Cell Melanoma Res 2020 11 20;33(6):895-898. Epub 2020 Jul 20.

Inserm, BMGIC, UMR1035, University of Bordeaux, Bordeaux, France.

Systemic sclerosis (SSc) is a severe disease whose pathophysiology remains partly unknown, combining autoimmune, vascular, and fibrotic features. Recently, we evidenced a link between vasculopathy and pigmentary changes in SSc. CCN3 (NOV) is a matricellular protein implicated in both angiogenesis and pigmentation regulation, in particular melanocyte adhesion to the basal layer. We decided to study CCN3 expression in SSc epidermis. We show that in SSc patients with pigmentary changes compared to patients with normal pigmentation, CCN3 is specifically downregulated in situ in melanocytes and upregulated in keratinocytes. Moreover, the number of melanocytes is significantly decreased in SSc patients with a disease duration of more than 5 years compared to the other patients. Altogether, our findings could provide new insights on the mechanisms of pigmentary changes in SSc patients, as well as treatment adaptation in a personalized manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pcmr.12912DOI Listing
November 2020

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

JCI Insight 2020 06 4;5(11). Epub 2020 Jun 4.

INSERM U1035, Biotherapy of genetic diseases, inflammatory disorders and cancers (BMGIC), Immunodermatology ATIP-AVENIR, University of Bordeaux, FHU ACRONIM, Bordeaux, France.

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. This phenomenon is also observed in lesional psoriatic skin. Importantly, apoptotic melanocytes were mainly observed once cells were detached from the basal layer of the epidermis, suggesting that additional mechanism(s) could be involved in melanocyte loss. The type 1 cytokines IFN-γ and TNF-α induce melanocyte detachment through E-cadherin disruption and the release of its soluble form, partly due to MMP-9. The levels of MMP-9 are increased in the skin and sera of patients with vitiligo, and MMP-9 is produced by keratinocytes in response to IFN-γ and TNF-α. Inhibition of MMP-9 or the JAK/STAT signaling pathway prevents melanocyte detachment in vitro and in vivo. Therefore, stabilization of melanocytes in the basal layer of the epidermis by preventing E-cadherin disruption appears promising for the prevention of depigmentation occurring in vitiligo and during chronic skin inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.133772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308056PMC
June 2020

Is Hyperpigmentation in Systemic Sclerosis a Perivascular Dermal Tattoo?

J Invest Dermatol 2020 Nov 29;140(11):2308-2312.e2. Epub 2020 Mar 29.

Department of Rheumatology, National Reference Center for Systemic Autoimmune Rare Diseases, Hopital Pellegrin, Bordeaux, France; University of Bordeaux, CNRS, Immunoconcept, UMR 5164, Bordeaux, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2020.03.937DOI Listing
November 2020

Response to low-dose intravenous immunoglobulin in a case of recalcitrant Darier disease.

JAAD Case Rep 2020 Mar 19;6(3):189-191. Epub 2020 Feb 19.

Department of Dermatology, National Reference Center for Rare Skin Diseases, Bordeaux University Hospitals, Bordeaux, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jdcr.2020.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033304PMC
March 2020

Decreased CCN3 in Systemic Sclerosis Endothelial Cells Contributes to Impaired Angiogenesis.

J Invest Dermatol 2020 07 16;140(7):1427-1434.e5. Epub 2020 Jan 16.

University of Bordeaux, Inserm, BMGIC, UMR1035, Bordeaux, France; Department of Dermatology and Pediatric Dermatology, National Center for Rare Skin Disorders, Hôpital Saint André, Bordeaux, France.

Systemic sclerosis (SSc) is a rare and severe connective tissue disease combining autoimmune and vasculopathy features, ultimately leading to organ fibrosis. Impaired angiogenesis is an often silent and life-threatening complication of the disease. We hypothesize that CCN3, a member of the CCN family of extracellular matrix proteins, which is an antagonist of the profibrotic protein CCN2 as well as a proangiogenic factor, is implicated in SSc pathophysiology. We performed skin biopsies on 26 patients with SSc, both in fibrotic and nonfibrotic areas for 17 patients, and collected 18 healthy control skin specimens for immunohistochemistry and cell culture. Histological analysis of nonfibrotic and fibrotic SSc skin shows a systemic decrease of papillary dermis surface as well as disappearance of capillaries. CCN3 expression is systematically decreased in the dermis of patients with SSc compared with healthy controls, particularly in dermal blood vessels. Moreover, CCN3 is decreased in vitro in endothelial cells from patients with SSc. We show that CCN3 is essential for endothelial cell migration and angiogenesis in vitro. In conclusion, CCN3 may represent a promising therapeutic target for patients with SSc presenting with vascular involvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2019.11.026DOI Listing
July 2020

NKG2D Defines a Subset of Skin Effector Memory CD8 T Cells with Proinflammatory Functions in Vitiligo.

J Invest Dermatol 2020 06 24;140(6):1143-1153.e5. Epub 2019 Dec 24.

INSERM U1035, BMGIC, Immuno-dermatology, University of Bordeaux, Bordeaux, France; FHU ACRONIM, University of Bordeaux, Bordeaux, France. Electronic address:

Vitiligo is an autoimmune disease that results from the loss of melanocytes, associated with skin infiltration of CD8 effector memory T cells with a Tc1 skewed immune response. NKG2D is an activating receptor found on immune cells, in particular natural killer and activated CD8 T cells, that are able to produce a high amount of IFN-γ. Here we found that NKG2D expression was increased in vitiligo skin CD8 effector memory T cells and was promoted by IL-15. Phenotypic and functional analyses showed that NKG2D CD8 skin effector memory T cells displayed an activated phenotype and produced elevated levels of both IFN-γ and tumor necrosis factor-α. Additional experiments revealed that vitiligo skin dendritic cells expressed the NKG2D ligands MICA-MICB, and in vitro experiments showed that these ligands could be induced on dendritic cells by IFN-α. Cultures of IFN-α-stimulated dendritic cells with skin NKG2D CD8 T cells potentiated the production of type 1 cytokines, which was next inhibited by blocking the NKG2D/MICA-MICB interaction. These data show that NKG2D is a potential marker of pathogenic skin CD8 effector memory T cells during vitiligo. Therefore, targeting NKG2D could be an attractive strategy in vitiligo, a disease for which there is a strong need of innovative treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2019.11.013DOI Listing
June 2020

Diaper dermatitis prevalence and severity: Global perspective on the impact of caregiver behavior.

Pediatr Dermatol 2020 Jan 2;37(1):130-136. Epub 2019 Dec 2.

Procter & Gamble, Cincinnati, OH, USA.

Objectives: To compare prevalence and severity of diaper dermatitis (DD) in infants and toddlers (babies) across three countries (China, USA, and Germany), including diapered skin measures and caregiver practices.

Methods: A cross-sectional study of 1791 babies (~600 from each country) was recruited at each clinical site. Based on regional toilet-training habits, exclusively diaper-wearing infants were recruited between ages 2-8 months in China and 2-18 months in the USA and Germany. DD was measured, as well as skin pH, transepidermal water loss (TEWL), and relative humidity (RH) in the diapered region. Caregiver habits were collected via a questionnaire and included information on hygienic practices.

Results: Diaper dermatitis was highest in the perianal area, followed by the intertriginous, genital, and buttock regions. In general, DD was significantly lower in babies in China, highest in Germany, and intermediate in the USA. This rank ordering of DD by geography was also observed in baby age 2-8 months. The lower DD observed in China was associated with lower skin pH and TEWL on diapered skin and decreased RH in the diaper. Chinese caregivers had the highest rate of prophylactic topical product usage, the most robust cleaning of the diapered area, lack of cleansing after urine-only diaper changes, and Chinese infants spent the least time in an overnight diaper.

Conclusions: These data suggest caregiver behaviors including prophylactic use of topical products, thorough cleaning after stooling and reduced time in an overnight diaper are associated with less DD, lower superficial skin pH, and enhanced skin barrier.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pde.14047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027557PMC
January 2020

Hereditary Mucoepithelial Dysplasia Results from Heterozygous Variants at p.Arg557 Mutational Hotspot in SREBF1, Encoding a Transcription Factor Involved in Cholesterol Homeostasis.

J Invest Dermatol 2020 06 29;140(6):1289-1292.e2. Epub 2019 Nov 29.

Paediatric Dermatology Department, Bordeaux University Hospital, Bordeaux, France; University of Bordeaux, INSERM, U1211, Bordeaux, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2019.10.014DOI Listing
June 2020

TNFα inhibitor-induced urticaria: a class effect.

Eur J Dermatol 2019 Oct;29(5):543-544

Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disease, Hôpital Saint André, University Hospital of Bordeaux, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/ejd.2019.3625DOI Listing
October 2019

Epidermal keratin 5 expression and distribution is under dermal influence.

Pigment Cell Melanoma Res 2020 05 26;33(3):435-445. Epub 2019 Nov 26.

INSERM U1035, Bordeaux, France.

Human skin melanin pigmentation is regulated by systemic and local factors. According to the type of melanin produced by melanocytes, the transfer and degradation of melanosomes differ, thus accounting for most variations between ethnicities. We made the surprising observation that in a drastically changed environment, white and black phenotypes are reversible since Caucasian skin grafted onto nude mice can become black with all black phenotypic characteristics. Black xenografts differed essentially from other grafts by the levels of epidermal FGF-2 and keratin 5. In vitro analysis confirmed that FGF-2 directly regulates keratin 5. Interestingly, this phenomenon may be involved in human pathology. Keratin 5 mutations in Dowling-Degos Disease (DDD) have already been associated with the pheomelanosome-eumelanosome transition. In a DDD patient, keratin 5 was expressed in the basal and spinous layers, as observed in black xenografts. Furthermore, in a common age-related hyperpigmentation disorder like senile lentigo (SL), keratin 5 distribution is also altered. In conclusion, modulation of keratin 5 expression and distribution either due to mutations or factors may account for the development of pigmentary disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pcmr.12844DOI Listing
May 2020

Standardizing serial photography for assessing and monitoring vitiligo: A core set of international recommendations for essential clinical and technical specifications.

J Am Acad Dermatol 2020 Dec 31;83(6):1639-1646. Epub 2019 Oct 31.

INSERM U 1035, University of Bordeaux; Department of Dermatology, Bordeaux University Hospitals, Bordeaux, France.

Background: Clinical photography is an important component of the initial assessment and follow-up of patients with vitiligo in clinical practice and research settings. Standardization of this photographic process is essential to achieve useful, high-quality, and comparable photographs over time.

Objective: The aim is to develop an international consensus for a core set of recommendations for standardized vitiligo clinical photography.

Methods: Based an international meeting of vitiligo experts, a standard operating procedure was developed for vitiligo photography in daily practice and research settings. This protocol was subsequently reviewed by 20 vitiligo experts until agreement was reached.

Results: The resulting protocol includes a set of 10 and 15 photographs for clinical practice and research purposes, respectively. The photographic series are based on anatomic units included in the Vitiligo Extent Score. Furthermore, graphic representations of standardized positioning and suggestions for guidelines to standardize the process (background color, lighting, position marking, scales, materials, instruments) for both color and ultraviolet photographs are described.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2019.10.055DOI Listing
December 2020

UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis.

Oncogenesis 2019 Sep 24;8(10):52. Epub 2019 Sep 24.

Univ. Bordeaux, INSERM, BMGIC, UMR 1035, F-33076, Bordeaux, France.

The leading cause of cutaneous squamous cell carcinomas (cSCCs) is exposure to ultraviolet radiation (UV). Unlike most other cancers, the incidence rates of cSCCs are still on the rise and the treatment options currently available are limited. We have recently found that dihydroorotate dehydrogenase (DHODH), which is the rate-limiting enzyme in the de novo pyrimidine synthesis pathway, plays a critical role in UVB-induced energy metabolism reprogramming. Using a multistage model of UVB radiation-induced skin cancer, we show that UVB-induced DHODH upregulation is mainly regulated transcriptionally by STAT3. Our results indicate that chronic inhibition of DHODH by leflunomide (LFN) blocks UVB-induced tumor initiation. Human tumor xenograft studies showed that LFN treatment reduces growth of established tumors when used in combination with a genotoxic agent, 5-fluorouracil (5-FU). Our data suggest that DHODH is a promising target for chemoprevention and combination therapy of UVB-induced cSCCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41389-019-0161-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760220PMC
September 2019

Focus Theme Issue: "Vitiligo and other pigmentary disorders".

Exp Dermatol 2019 06;28(6):639-641

INSERM U 1035, University of Bordeaux, Bordeaux, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/exd.13974DOI Listing
June 2019

Isolation and Culture of Epidermal Melanocytes.

Methods Mol Biol 2019 ;1993:33-46

Department of Dermatology and Pediatric Dermatology, Bordeaux University Hospitals, INSERM U 1035, University of Bordeaux, Bordeaux, France.

Melanocytes which represent around 5% of epidermal cells are located in the basal layer. To culture melanocytes we used trypsin digestion instead of dispase to obtain a cell suspension containing only basal keratinocytes and melanocytes. Melanocytes are cells which need a great attention. Indeed they dedifferentiate easily in culture as soon as they are in pure culture. Factors secreted by contaminating keratinocytes allow melanocytes to stay dendritic but by regulating their number avoid their growth. In order to age, phototype and other individual dependent factors regulate the behavior of melanocytes in vitro. Thus, microscopic examination of melanocytes has to be performed each day to adapt conditions of culture to each primary cell culture. This is the secret to have a nice melanocyte culture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-4939-9473-1_3DOI Listing
February 2020

Intravenous immunoglobulins for delayed wound healing associated with toxic epidermal necrolysis.

Eur J Dermatol 2019 Apr;29(2):229-231

Department of Adult and Pediatric Dermatology.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/ejd.2019.3518DOI Listing
April 2019

Validation of a physician global assessment tool for vitiligo extent: Results of an international vitiligo expert meeting.

Pigment Cell Melanoma Res 2019 09 9;32(5):728-733. Epub 2019 May 9.

Department of Dermatology, Ghent University Hospital, Ghent, Belgium.

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 (intraclass correlation coefficient >0.6) were observed between the raters overall and within each continent. All hypotheses to evaluate construct validity were confirmed. Median VES values per category were for limited 1.10 [IQR: 0.21-1.67], moderate 3.17 [IQR: 1.75-6.21], extensive 9.58 [IQR: 6.21-13.03] and very extensive 42.67 [IQR: 21.20-42.67]. Defined categories for vitiligo extent can be valuable for inclusion criteria and may impact future reimbursement criteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pcmr.12784DOI Listing
September 2019

A new phototherapy regimen during winter as an add-on therapy, coupled with oral vitamin D supplementation, for the long-term control of atopic dermatitis: study protocol for a multicentre, randomized, crossover, pragmatic trial - the PRADA trial.

Trials 2019 Mar 25;20(1):184. Epub 2019 Mar 25.

Univ Rennes, Rennes, France.

Background: Atopic dermatitis is a highly prevalent, chronic, relapsing disease in both adults and children. On the severity spectrum, lower-end patients benefit from small amounts of topical anti-inflammatory treatments (TAT), whereas higher-end patients need systemic immunosuppressants; in-between patients are treated with TAT and phototherapy. The major therapeutic challenge in this population is the long-term control of disease activity, and the current TAT-based pro-active strategy does not meet all their needs. Immunosuppressants are used as long-term control add-on treatments, but they are restricted to the most severely affected patients because of safety concerns. In addition, neither immunosuppressants nor other strategies have been properly evaluated in the long term despite long-term control having been acknowledged as one of the most important core outcome domains to be targeted in atopic dermatitis trials. Safe add-on therapies, rigorously evaluated for long-term control of the disease, are therefore needed. Phototherapy and vitamin D supplementation are both good candidates.

Methods: This is a multicenter, national, randomized, superiority, crossover trial testing add-on phototherapy (one winter under spaced sessions of phototherapy and one winter under observation) among subjects receiving standard care (i.e., TAT). On the same population, we will test the long-term control provided by oral supplementation of vitamin D versus placebo in a randomized, superiority, double-blind, parallel-group trial. The primary outcomes are (1) repeat measures of the PO-SCORAD severity score over 1 year and (2) cumulate consumption of TAT (number of tubes) during the winter. They will be tested following a hierarchical testing procedure. The secondary outcomes will be measures repeated over 2 years of investigator-based severity scores, patient-reported severity and quality of life scores, serum vitamin D levels, weeks during which the disease is well-controlled, inter-visit cumulate consumption of TAT, and synthetic patient-reported satisfaction at the end of each winter.

Discussion: This study includes two separate 2-year pragmatic trials designed to evaluate the efficacy of vitamin D supplementation and pro-active phototherapy for primary care atopic dermatitis patients receiving TAT on long-term control of disease activity. The experimental design enables the study of both interventions and exploration of the interaction between vitamin D and phototherapy. A pragmatic trial is particularly suited to the assessment of long-term control. This study explores the possibility of new and safe therapeutic strategies for the control of long-term atopic dermatitis, and is an example of efficacy research that is unlikely to be sponsored by industrialists. A potentially effective low-cost therapeutic strategy for long-term control is essential for patients and public health.

Trial Registration: ClinicalTrials.gov Identifier: NCT02537509 , first received: 1 September 2015.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-019-3276-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434814PMC
March 2019

Loss of Epidermal HIF-1α Blocks UVB-Induced Tumorigenesis by Affecting DNA Repair Capacity and Oxidative Stress.

J Invest Dermatol 2019 09 13;139(9):2016-2028.e7. Epub 2019 Mar 13.

University of Bordeaux, Institut National de la Santé et de la Recherche Médicale, Biothérapie des Maladies Génétiques Inflammatoires et Cancers, U1035, F-33000 Bordeaux, France; Centre de Référence pour les Maladies Rares de la Peau, Centre Hospitalier Universitaire de Bordeaux, France. Electronic address:

HIF-1α is constitutively expressed in mouse and human epidermis. It plays a crucial role in skin physiology, including the response of keratinocytes to UVR. However, little information is available about its role in photocarcinogenesis. Using a multistage model of UVB radiation-induced skin cancer, we show that the knockout of Hif-1α in the epidermis prevents tumorigenesis but at the same time triggers the formation of hyperkeratotic plaques. Our results indicate that the absence of oncogenic transformation in Hif-1α-ablated mice is related to increased DNA repair in keratinocytes, whereas the formation of hyperkeratotic plaques is caused by an increase in the levels of reactive oxygen species. Indeed, impairing the DNA repair machinery by ablating xeroderma pigmentosum C restored the UVB-induced neoplastic transformation of Hif-1α-ablated keratinocytes, whereas the development of hyperkeratotic plaques was blocked by chronic antioxidant treatment. We conclude that HIF-1α plays a procarcinogenic role in UVB-induced tumorigenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2019.01.035DOI Listing
September 2019

Isolated straight hair nevus in a White child.

Pediatr Dermatol 2019 Mar 21;36(2):260-261. Epub 2019 Feb 21.

Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Diseases, INSERM U 1035, University of Bordeaux, Bordeaux, France.

We report a 6-month-old girl born with a fronto-parietal patch of hair straighter than the remainder of the scalp hairs. We took a biopsy to rule out a congenital melanocytic nevus. We concluded after additional scanning electron microscopy study of the hair shafts that the lesion corresponds to a possible local mosaicism causing an isolated straight hair nevus phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pde.13740DOI Listing
March 2019

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

Pigment Cell Melanoma Res 2019 07 15;32(4):588-592. Epub 2019 Feb 15.

INSERM U1035, BMGIC, Immuno-dermatology ATIP-AVENIR, University of Bordeaux, Bordeaux, France.

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. To date, TFH cell subsets have not been studied in human vitiligo. This study in 44 vitiligo patients and 19 healthy controls showed an increase in circulating TFH cells associated with disease clinical progression. A more precise analysis of TFH cell phenotype demonstrated that vitiligo is characterized by populations of peripheral TFH cells responsible for helping B-cell function, such as TFH type 2 and type 17 which produce Th2- and TH17-related cytokines, respectively. These findings suggest a new mechanism involving TFH cell subsets in the pathogenesis of human vitiligo and leading to the production of autoantibodies and disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pcmr.12763DOI Listing
July 2019

CCN proteins as potential actionable targets in scleroderma.

Exp Dermatol 2019 01 11;28(1):11-18. Epub 2018 Dec 11.

University of Bordeaux, Inserm, BMGIC, UMR1035, Bordeaux, France.

Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease combining inflammatory, vasculopathic and fibrotic manifestations. Skin features, which give their name to the disease and are considered as diagnostic as well as prognostic markers, have not been thoroughly investigated in terms of therapeutic targets. CCN proteins (CYR61/CCN1, CTGF/CCN2, NOV/CCN3 and WISP1-2-3 as CCN4-5-6) are a family of secreted matricellular proteins implicated in major cellular processes such as cell growth, migration, differentiation. They have already been implicated in key pathophysiological processes of SSc, namely fibrosis, vasculopathy and inflammation. In this review, we discuss the possible implication of CCN proteins in SSc pathogenesis, with a special focus on skin features, and identify the potential actionable CCN targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/exd.13806DOI Listing
January 2019

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

J Am Acad Dermatol 2019 Feb 7;80(2):478-484. Epub 2018 Aug 7.

Department of Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, CHU de Bordeaux, Bordeaux, France; Inserm U1035, Biothérapie des Maladies Génétiques et Cancers, University of Bordeaux, Bordeaux, France. Electronic address:

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.

Methods: A total of 5 patterns of skin pigmentation disorders were defined: diffuse hyperpigmentation; hyperpigmentation of sun-exposed areas; hypopigmentation of the head, neck, and/or upper part of the chest; acral hypopigmentation; and diffuse hypopigmentation.

Results: A total of 239 patients were included; 88 patients (36.8%) had skin pigmentation disorders as follows: diffuse hyperpigmentation and hyperpigmentation of sun-exposed areas in 38.6% (n = 34) and 27.3% (n = 24) of patients, respectively; hypopigmentation of the face, neck, and/or chest in 10.2% of patients (n = 9); diffuse hypopigmentation in 12.5% (n = 11); and acral hypopigmentation in 17% (n = 15). Diffuse hyperpigmentation was associated with diffuse SSc (P = .001), increased modified Rodnan skin score (P = .001), and shorter duration of Raynaud phenomenon (P = .002) in univariate analysis but not in multivariate analysis. Moreover, diffuse hyperpigmentation was associated with digital ulcers (P = .005), as confirmed by multivariate analysis (odds ratio, 2.96; 95% confidence interval, 1.28-6.89).

Limitations: This was a single-center retrospective study of a cohort of patients with SSc.

Conclusion: Screening for skin pigmentation disorders could be useful in the management of patients with SSc to identify those with a high risk of development of digital ulcers, which is a symptom of vascular involvement in SSc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2018.07.033DOI Listing
February 2019