Publications by authors named "Khaled Ezzedine"

181 Publications

Surgical Interventions for Patients With Vitiligo: A Systematic Review and Meta-analysis.

JAMA Dermatol 2021 Feb 17. Epub 2021 Feb 17.

Epidemiology in Dermatology and Evaluation of Therapeutics, Département Infectieux/Immuno/Vaccin, Paris-Est University, Paris Est Créteil University, Créteil, France.

Importance: Surgical interventions are a key part of the therapeutic arsenal, especially in refractory and stable vitiligo. Comparison of treatment outcomes between the different surgical procedures and their respective adverse effects has not been adequately studied.

Objective: To investigate the reported treatment response following different surgical modalities in patients with vitiligo.

Data Sources: A comprehensive search of the MEDLINE, Embase, Web of Science, and Cochrane Library databases from the date of database inception to April 18, 2020, was conducted. The key search terms used were vitiligo, surgery, autologous, transplantation, punch, suction blister, and graft.

Study Selection: Of 1365 studies initially identified, the full texts of 358 articles were assessed for eligibility. A total of 117 studies were identified in which punch grafting (n = 19), thin skin grafting (n = 10), suction blister grafting (n = 29), noncultured epidermal cell suspension (n = 45), follicular cell suspension (n = 9), and cultured epidermal cell suspension (n = 17) were used.

Data Extraction And Synthesis: Three reviewers independently extracted data on study design, patients, intervention characteristics, and outcomes. Random effects meta-analyses using generic inverse-variance weighting were performed.

Main Outcomes And Measures: The primary outcomes were the rates of greater than 90%, 75%, and 50% repigmentation response. These rates were calculated by dividing the number of participants in an individual study who showed the corresponding repigmentation by the total number of participants who completed the study. The secondary outcomes were the factors associated with treatment response to the surgical intervention.

Results: Among the 117 unique studies and 8776 unique patients included in the analysis, rate of repigmentation of greater than 90% for surgical interventions was 52.69% (95% CI, 46.87%-58.50%) and 45.76% (95% CI, 30.67%-60.85%) for punch grafting, 72.08% (95% CI, 54.26%-89.89%) for thin skin grafting, 61.68% (95% CI, 47.44%-75.92%) for suction blister grafting, 47.51% (95% CI, 37.00%-58.03%) for noncultured epidermal cell suspension, 36.24% (95% CI, 18.92%-53.57%) for noncultured follicular cell suspension, and 56.82% (95% CI, 48.93%-64.71%) for cultured epidermal cell suspension. The rate of repigmentation of greater than 50% after any surgical intervention was 81.01% (95% CI, 78.18%-83.84%). In meta-regression analyses, the treatment response was associated with patient age (estimated slope, -1.1418), subtype of vitiligo (estimated slope, 0.3047), and anatomical sites (estimated slope, -0.4050).

Conclusions And Relevance: The findings of this systematic review and meta-analysis suggest that surgical intervention can be an effective option for refractory stable vitiligo. An appropriate procedure should be recommended based on patient age, site and size of the lesion, and costs.
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http://dx.doi.org/10.1001/jamadermatol.2020.5756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890456PMC
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).
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http://dx.doi.org/10.1016/j.jid.2020.12.028DOI Listing
February 2021

The Influence of Media Coverage and Governmental Policies on Google Queries Related to COVID-19 Cutaneous Symptoms: Infodemiology Study.

JMIR Public Health Surveill 2021 02 25;7(2):e25651. Epub 2021 Feb 25.

Assistance Publique des Hôpitaux de Paris (AP-HP), Département de dermatologie, Hôpital Henri Mondor, Créteil, France.

Background: During COVID-19, studies have reported the appearance of internet searches for disease symptoms before their validation by the World Health Organization. This suggested that monitoring of these searches with tools including Google Trends may help monitor the pandemic itself. In Europe and North America, dermatologists reported an unexpected outbreak of cutaneous acral lesions (eg, chilblain-like lesions) in April 2020. However, external factors such as public communications may also hinder the use of Google Trends as an infodemiology tool.

Objective: The study aimed to assess the impact of media announcements and lockdown enforcement on internet searches related to cutaneous acral lesions during the COVID-19 outbreak in 2020.

Methods: Two searches on Google Trends, including daily relative search volumes for (1) "toe" or "chilblains" and (2) "coronavirus," were performed from January 1 to May 16, 2020, with the United States, the United Kingdom, France, Italy, Spain, and Germany as the countries of choice. The ratio of interest over time in "chilblains" and "coronavirus" was plotted. To assess the impact of lockdown enforcement and media coverage on these internet searches, we performed an interrupted time-series analysis for each country.

Results: The ratio of interest over time in "chilblains" to "coronavirus" showed a constant upward trend. In France, Italy, and the United Kingdom, lockdown enforcement was associated with a significant slope change for "chilblain" searches with a variation coefficient of 1.06 (SE 0.42) (P=0.01), 1.04 (SE 0.28) (P<.01), and 1.21 (SE 0.44) (P=0.01), respectively. After media announcements, these ratios significantly increased in France, Spain, Italy, and the United States with variation coefficients of 18.95 (SE 5.77) (P=.001), 31.31 (SE 6.31) (P<.001), 14.57 (SE 6.33) (P=.02), and 11.24 (SE 4.93) (P=.02), respectively, followed by a significant downward trend in France (-1.82 [SE 0.45]), Spain (-1.10 [SE 0.38]), and Italy (-0.93 [SE 0.33]) (P<.001, P=0.004, and P<.001, respectively). The adjusted R values were 0.311, 0.351, 0.325, and 0.305 for France, Spain, Italy, and the United States, respectively, suggesting an average correlation between time and the search volume; however, this correlation was weak for Germany and the United Kingdom.

Conclusions: To date, the association between chilblain-like lesions and COVID-19 remains controversial; however, our results indicate that Google queries of "chilblain" were highly influenced by media coverage and government policies, indicating that caution should be exercised when using Google Trends as a monitoring tool for emerging diseases.
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http://dx.doi.org/10.2196/25651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909455PMC
February 2021

Vitiligo: A focus on pathogenesis and its therapeutic implications.

J Dermatol 2021 Mar 6;48(3):252-270. Epub 2021 Jan 6.

Department of Dermatology, AP-HP, Henri Mondor University Hospital, UPEC, Créteil, France.

Vitiligo is the most common depigmenting disorder affecting 0.1%-2% of the population worldwide. The characteristic white patches result from the selective loss of melanocytes. Sustained recent efforts have resulted in a detailed understanding of the genetic architecture of vitiligo. About 80% of vitiligo risk is attributable to genetic factors; and the rest (20%) is attributable to the environment. Over the past decade, substantial progress has been made in our understanding of the pathogenesis of vitiligo which is now clearly classified as an autoimmune disease. Melanocytes from patients with vitiligo are more susceptible to oxidative stress which begets the release of exosomes and inflammatory cytokines that will lead to activation of the innate immune response and subsequently to adaptive immune response through activation of autoreactive cytotoxic CD8+ T cells. These produce interferon-γ (IFN-γ) which promotes disease progression through IFN-γ-induced chemokine secretion from surrounding keratinocytes to further recruit T cells to the skin through a positive feedback loop. CD8 tissue-resident memory T cells are in turn responsible for long-term maintenance and potential relapse of vitiligo in human patients through cytokine-mediated recruitment of T cells from the circulation. This review summarizes the current knowledge on vitiligo and attempt to give an overview of the future in vitiligo treatment.
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http://dx.doi.org/10.1111/1346-8138.15743DOI Listing
March 2021

Systematic Literature Review and Network Meta-analysis of the Efficacy and Acceptability of Interventions in Actinic Keratoses.

Acta Derm Venereol 2021 Jan 4;101(1):adv00358. Epub 2021 Jan 4.

Department of Dermatology, Hôpital Henri Mondor, FR-94000 Creteil, France.

A systematic literature review was conducted to identify and qualitatively assess randomized controlled trials in immunocompetent patients ≥ 18 years with head- region lesions of actinic keratoses who were treated with field-directed, lesion-directed and other therapies. Network meta-analysis was used to quantitatively evaluate field-directed therapies (5-fluorouracil formulations, diclofenac sodium, imiquimod, ingenol mebutate, 5-aminolevulinic acid or methyl aminolevulinate plus photodynamic therapy) using complete clearance or partial clearance of actinic keratoses lesions, and adverse event-related withdrawals as a proxy of acceptability. Of 2,863 references identified, 75 trials reported in 151 publications were included. In summary, comparative network meta-analysis evaluation showed that 5-fluorouracil formulations were the most efficacious interventions examined. 5-fluorouracil 4%, which was recently approved, showed a comparable efficacy profile to 5-fluorouracil 5%, and had satisfactory acceptability outcomes.
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http://dx.doi.org/10.2340/00015555-3690DOI Listing
January 2021

Use of complete clearance for assessing treatment efficacy for 5-fluorouracil interventions in actinic keratoses: how baseline lesion count can impact this outcome.

J Mark Access Health Policy 2020 Oct 9;8(1):1829884. Epub 2020 Oct 9.

Market access and HEOR department, Pierre Fabre, Boulogne-Billancourt, France.

: Many trials in actinic keratoses (AK) use complete clearance rate (100% reduction in number of lesions) as the primary endpoint. We explore limitations (predominantly baseline factors) associated with this outcome. : This analysis assessed the effect of baseline lesion count on complete clearance rate using randomized controlled trials (RCTs) that evaluated 5-fluorouracil (5-FU) formulations, alone or with 10% salicylic acid solution, in patients with AK. : Correlation between baseline lesion count and complete clearance rate at week 8 was assessed using Pearson's coefficient. : Five RCTs assessing 5-FU (4%, 5%, or 0.5% in 10% salicylic acid solution) in 1,080 patients with AK were included. Mean lesion count at baseline ranged from 8.1 to 21.2 lesions per patient. Complete clearance rate was negatively associated with number of lesions at baseline. Correlation between mean number of lesions at baseline and complete clearance rate was strong (r = 0.94) and statistically significant (p < 0.001). : This analysis showed that, in a homogenous set of trials, complete clearance rates achieved with 5-FU interventions are inversely related to number of lesions at baseline. These findings highlight the limits of restricting treatment evaluation to complete clearance rate and the relevance of alternative measures.
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http://dx.doi.org/10.1080/20016689.2020.1829884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580760PMC
October 2020

Beyond the quality of life: A call for patients' own willingness to pay in chronic skin disease to assess psychosocial burden: A multi-center, cross-sectional prospective survey.

J Am Acad Dermatol 2020 Oct 3. Epub 2020 Oct 3.

Department of Dermatology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.09.088DOI Listing
October 2020

Impact of Atopic Dermatitis in Adolescents and their Parents: A French Study.

Acta Derm Venereol 2020 Oct 20;100(17):adv00294. Epub 2020 Oct 20.

Department of Dermatology, Hôpital Henri Mondor, FR-94000 Creteil, France.

Atopic dermatitis has a negative impact on quality of life in patients and their families. However, there have been very few studies of the impact of atopic dermatitis on adolescents and their relatives. The objective of this study was to evaluate the impact of atopic dermatitis in the daily lives of adolescents between 12 and 17 years of age in the French population and to assess the burden of the disease on their families. Quality of life was measured in 399 parents of adolescents with atopic dermatitis and in the adolescents themselves. Impairment of quality of life in the adolescents was associated with disease severity. Moreover, in children aged 12-14 years, quality of life was worse with increasing age, with decreasing disease duration, and when parents had atopic dermatitis. In children aged 15-17 years quality of life was worse when the parent who answered the questionnaire was male and when the parent was < 45 years old. The burden of atopic dermatitis was higher in parents of older children, in parents with children with higher disease severity, with shorter disease duration, in male parents, and in parents aged <45 years. The burden of atopic dermatitis in adolescents and their parents is considerable and should be taken into account in the management of atopic dermatitis.
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http://dx.doi.org/10.2340/00015555-3653DOI Listing
October 2020

A Method for Designing a Patient Burden Questionnaire in Dermatology.

Clin Cosmet Investig Dermatol 2020 6;13:521-528. Epub 2020 Aug 6.

Necker Enfants Malades Hospital, Paris, France.

Introduction: In recent years, the concept of "disease burden" has been given a central role in evaluating patient care, particularly in skin diseases. Measuring patient-reported outcomes (PRO) such as symptoms and disease burden may be useful.

Aim: To present a methodology that facilitates the development and validation of burden questionnaires for patients suffering from skin diseases.

Methodology: Based on past published burden questionnaires, a methodology for designing skin disease burden questionnaires was to be developed.

Results: Based on 16 burden questionnaires developed and published over the last 10 years, the authors propose a standardized methodology for the easy design and validation of disease burden questionnaires for patients with chronic skin diseases. The authors provide detailed guidance for the conception, development and validation of the questionnaires, including reliability, internal consistency, external validity, cognitive debriefing, testing-retesting, translation and cross-cultural adaptation, as well as for statistical analysis.

Conclusion: The proposed methodology enhances the design and validation of disease burden questionnaires in dermatology. Burden questionnaires may be used in clinical research as well as in daily clinical practice.
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http://dx.doi.org/10.2147/CCID.S260323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417926PMC
August 2020

Vitiligo: Targeted Therapies Add Color to Disease Pathophysiology.

J Invest Dermatol 2020 08;140(8):1498-1500

Department of Dermatology, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA.

There is excitement in the air for patients with vitiligo. For the first time in decades, we have early case studies showing that targeted therapies can repigment vitiliginous skin, and well-powered clinical trials are underway. However, at the time of this writing, there is no Food and Drug Administration-approved drug for vitiligo. In a randomized clinical trial by Khemis et al. report negative results on a randomized clinical trial testing the combination of apremilast, a phosphodiesterase 4 inhibitor, and narrowband-ultraviolet B versus placebo and narrowband-ultraviolet B in patients with nonsegmental vitiligo. The results of this trial are a reminder that clinical management of vitiligo is challenging at best, even when combining anti-inflammatory and/or immunomodulating agents with repigmenting agents. However, these negative trials are critical in improving our understanding of this complex and disfiguring disease.
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http://dx.doi.org/10.1016/j.jid.2020.01.033DOI Listing
August 2020

The Arabic Urticaria Activity Score and Chronic Urticaria Quality of Life Questionnaire: validation and correlations.

Int J Dermatol 2020 Aug 8;59(8):893-901. Epub 2020 Jul 8.

Department of Dermatology, Henri-Mondor University Hospital, Creteil, France.

Background: The international guideline for urticaria recommends the use of the Urticaria Activity Score 7 (UAS7) and the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) to assess patients with chronic spontaneous urticaria (CSU) for their disease activity and impact on quality of life, respectively. Over the last decade, both tools have been validated in many different languages but not in Arabic.

Objective: To validate the Arabic UAS7 and CU-Q2oL in patients with CSU in Lebanon.

Methods: After a structured translation process of both instruments into Arabic, their construct and known-groups validity as well as internal consistency reliability were tested in a longitudinal prospective study using a cluster sample of 152 Lebanese CSU patients. The study also included a repetitive administration of both instruments in 2-week intervals in 44 patients in order to assess their test-retest reliability.

Results: Both the Arabic UAS7 and CU-Q2oL demonstrated high internal consistency (Cronbach alpha of 0.95 and 0.82, respectively) and moderate-to-high test-retest reliability (intraclass coefficient of 0.61 and 0.91, respectively). Exploratory factor analysis of the Arabic CU-Q2oL revealed five components that explained 81.8% of the total variance. Significant correlations were found between the Arabic CU-Q2oL and the Dermatology Life Quality Index (DLQI) (r = 0.86) and mild-to-moderate correlations between the Arabic UAS7 and CU-Q2oL (r = 0.52) as well as the DLQI (r = 0.51).

Conclusions: Our findings demonstrate that the Arabic versions of the UAS7 and the CU-Q2oL are valid and reliable patient-reported outcome measures in patients with CSU in Lebanon.
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http://dx.doi.org/10.1111/ijd.15006DOI Listing
August 2020

Association Between Adult Acne and Dietary Behaviors: Findings From the NutriNet-Santé Prospective Cohort Study.

JAMA Dermatol 2020 08;156(8):854-862

Epidemiology in Dermatology and Evaluation of Therapeutics, EA7379, Paris-Est University, Paris Est Créteil University, Département Infectieux/Immuno/Vaccin, F-94000 Créteil, France.

Importance: Acne is a chronic, multifactorial inflammatory disease. The association between consumption of dairy products and fatty and sugary foods and occurrence and progression of acne remains unclear.

Objective: To assess the association between dietary behavior and current acne in adults.

Design, Setting, And Participants: A cross-sectional study was performed as part of the NutriNet-Santé study, which is an ongoing observational, web-based cohort study that was launched in France in May 2009. The present study was conducted from November 14, 2018, to July 8, 2019. A total of 24 452 participants completed an online self-questionnaire to categorize their acne status: never acne, past acne, or current acne. Associations between dietary behavior (food intake, nutrient intake, and the dietary pattern derived from a principal component analysis) and current or past acne were studied in multinomial logistic regression models adjusted for potential confounding variables (age, sex, physical activity, smoking status, educational level, daily energy intake, number of dietary records completed, and depressive symptoms).

Results: The 24 452 participants (mean [SD] age, 57 [14] years; 18 327 women [75%]) completed at least 3 dietary records. Of these, 11 324 individuals (46%) reported past or current acne. After adjustment, there was a significant association between current acne and the consumption of fatty and sugary products (adjusted odds ratio [aOR], 1.54; 95% CI, 1.09-2.16), sugary beverages (aOR, 1.18; 95% CI, 1.01-1.38), and milk (aOR, 1.12; 95% CI, 1.00-1.25). An energy-dense dietary pattern (high consumption of fatty and sugary products) was associated with current acne (aOR, 1.13; 95% CI, 1.05-1.18).

Conclusions And Relevance: In this study, consumption of milk, sugary beverages, and fatty and sugary products appeared to be associated with current acne in adults. Further large-scale studies are warranted to investigate more closely the associations between diet and adult acne.
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http://dx.doi.org/10.1001/jamadermatol.2020.1602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287950PMC
August 2020

Psychological Consequences of the Most Common Dermatoses: Data from the Objectifs Peau Study.

Acta Derm Venereol 2020 Jun 11;100(13):adv00175. Epub 2020 Jun 11.

Department of Dermatology and Venereology, University Hospital of Brest, FR-29200 Brest, France. E-mail:

The prevalence of psychological disorders in patients with common skin diseases was assessed in a large representative sample of the French adult population. General health, as measured by the EQ5D score, was significantly lower if patients reported having rosacea, atopic dermatitis, urticaria, fungal infections, psoriasis or acne. The proportions of participants reporting being extremely anxious or depressed were higher in those who reported having rosacea, atopic dermatitis or contact dermatitis. Difficulties in sexual and conjugal life were frequently reported by people with psoriasis, atopic dermatitis, contact dermatitis, urticaria and, in particular, acne. Sleep disorders were present in 30-50% of those who reported having acne, rosacea, eczema, psoriasis or urticaria. Sleep disorders may be related not only to pruritus, but also to disfiguring skin diseases. Anxiety and depression complications were mainly reported by those with disfiguring diseases. Sexual and conjugal dysfunctions were associated with all dermatoses (with the exception of warts).
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http://dx.doi.org/10.2340/00015555-3531DOI Listing
June 2020

Individual Burden of Psoriasis (I-BOP): Building and Validation of a New Scoring Tool for Patients with Psoriasis.

Clin Cosmet Investig Dermatol 2020 4;13:325-332. Epub 2020 May 4.

Resopso, Paris, France.

Background: Psoriasis impacts independently of its severity on patients' lifestyle and quality of life (QoL).

Aim: To build a tool for assessing the patient-reported psoriasis burden.

Methods: An expert group created a questionnaire using a standardized methodology building questionnaires assessing quality of life issues. The questionnaire was translated from French into a cultural and linguistically validated US English version.

Results: A conceptual questionnaire of 54 questions was created. The confirmatory analyses resulted in a 10-feature questionnaire divided into 4 internally consistent domains with a Cronbach's alpha coefficient of 0.9. It was reproducible and highly reliable. It correlated well with the Dermatology Life Quality Index (DLQI), Perceived Stress Scale (PSS), and SF-12 mental and SF12 physical scores.

Conclusion: This tool allows for the first time to assess the burden of psoriasis patients. Its use may allow improving medical and nonmedical patient care, thus improving their daily life.
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http://dx.doi.org/10.2147/CCID.S249776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213973PMC
May 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.
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http://dx.doi.org/10.1172/jci.insight.133772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308056PMC
June 2020

Perceived clinical severity of atopic dermatitis in adolescents: Comparison between patients' and parents' evaluation.

J Am Acad Dermatol 2021 Jan 15;84(1):164-165. Epub 2020 Apr 15.

Public Health, Hôpital Necker Enfants Malades, Paris, France; European Market Maintenance Assessment, Vincennes, France; Maison de la Dermatologie, Société Française des Sciences Humaines sur la Peau (SFSHP), Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.04.037DOI Listing
January 2021

Vitiligo: A Review.

Dermatology 2020 10;236(6):571-592. Epub 2020 Mar 10.

Department of Dermatology, AP-HP, Henri Mondor University Hospital, UPEC, Créteil, France,

Vitiligo, a common depigmenting skin disorder, has an estimated prevalence of 0.5-2% of the population worldwide. The disease is characterized by the selective loss of melanocytes which results in typical nonscaly, chalky-white macules. In recent years, considerable progress has been made in our understanding of the pathogenesis of vitiligo which is now clearly classified as an autoimmune disease. Vitiligo is often dismissed as a cosmetic problem, although its effects can be psychologically devastating, often with a considerable burden on daily life. In 2011, an international consensus classified segmental vitiligo separately from all other forms of vitiligo, and the term vitiligo was defined to designate all forms of nonsegmental vitiligo. This review summarizes the current knowledge on vitiligo and attempts to give an overview of the future in vitiligo treatment.
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http://dx.doi.org/10.1159/000506103DOI Listing
March 2020

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

Authors' reply to Del Giudice: the global prevalence and correlates of skin bleaching.

Int J Dermatol 2019 10 28;58(10):e185. Epub 2019 Jul 28.

Departments of Dermatology and Histopathology, Hillingdon Hospitals NHS Foundation Trust, Uxbridge, UK.

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http://dx.doi.org/10.1111/ijd.14583DOI Listing
October 2019

Vitamin D and the skin: what should a dermatologist know?

G Ital Dermatol Venereol 2019 Dec 12;154(6):669-680. Epub 2019 Jul 12.

Department of Dermatology, AP-HP, Henri Mondor University Hospital, Université Paris-Est Créteil, Créteil, France -

Although first discovered in 1931, vitamin D has seen an increased interest in the scientific community over the past decades, including the dermatology field. Vitamin D promotes calcium and phosphorus absorption; however, the actions of vitamin D are not confined to bone. Indeed, there is now overwhelming and compelling scientific data that vitamin D plays a crucial role in a plethora of cellular function and in extra-skeletal health. Except for fatty fish livers, very few foods naturally contain vitamin D; and the major source of vitamin D comes from skin exposure to sunlight via ultraviolet B. Keratinocytes are unique in the body as not only do they provide the primary source of vitamin D for the body, but they also possess both the enzymatic machinery to metabolize the vitamin D produced to active metabolites. This has been referred to as the photoendocrine vitamin D system. Vitamin D regulates keratinocytes proliferation and differentiation; and plays a role in the defense against opportunistic infections. Multiple factors are linked to vitamin D status; and a growing number of dermatologic diseases has been linked to vitamin D status such as atopic dermatitis, psoriasis, vitiligo, and cutaneous cancers. In this article, we reviewed the potential determinants of vitamin D status, as its implications in dermatologic diseases.
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http://dx.doi.org/10.23736/S0392-0488.19.06433-2DOI Listing
December 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.
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http://dx.doi.org/10.1111/pcmr.12784DOI Listing
September 2019

Navigating the landscape of core outcome set development in dermatology.

J Am Acad Dermatol 2019 Jul 13;81(1):297-305. Epub 2019 Mar 13.

Center for Evidence-Based Healthcare, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

The development of core outcome sets (COSs; ie, a minimum set of core outcomes that should be measured and reported in all trials or in clinical practice for a specific condition) in dermatology is increasing in pace. A total of 44 dermatology-related COS projects have been registered in the online Core Outcome Measures in Effectiveness Trials database (http://www.comet-initiative.org/studies/search) and include studies on 26 different skin diseases. With the increasing number of COSs in dermatology, care is needed to ensure the delivery of high-quality COSs that meet quality standards when using state-of-the-art methods. In 2015, the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) was established. CS-COUSIN is an international, multidisciplinary working group aiming to improve the development and implementation of COSs in dermatology. CS-COUSIN has developed guidance on how to develop high-quality COSs for skin diseases and supports dermatology-specific COS initiatives. Currently, 17 COS development groups are affiliated with CS-COUSIN and following standardized COS development processes. To ensure successful uptake of COSs in dermatology, researchers, clinicians, systematic reviewers, guideline developers, and other stakeholders should use existing COSs in their work.
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http://dx.doi.org/10.1016/j.jaad.2019.03.009DOI Listing
July 2019

Ustekinumab for skin reactions associated with anti-tumor necrosis factor-α agents in patients with inflammatory bowel diseases: A single-center retrospective study.

J Dermatol 2019 Apr 28;46(4):322-327. Epub 2019 Feb 28.

Department of Dermatology, Courlancy Clinic, Rheims, France.

Anti-tumor necrosis factor (TNF)-α agents may induce skin reactions, in particular in patients with inflammatory bowel diseases (IBD). The objective of this study was to determine the efficacy of ustekinumab in these patients. IBD patients facing therapeutic issues because of cutaneous reactions or tolerance issues, consequently treated with ustekinumab in our department, were included. Retrospective review of case records and clinical photographs was carried out. Twenty-six patients were included. Twenty-three patients were treated for Crohn's disease and three for ulcerative colitis. Fourteen patients presented psoriasiform lesions, nine eczematiform lesions, four anaphylactoid reactions, two alopecia areata-like lesions, one injection-site reaction, one cutaneous polyarteritis nodosa and five other skin reactions. Most of them resolved under ustekinumab. In detail, eczematiform lesions completely resolved in all cases, psoriasiform lesions completely resolved in 12 cases (85.7%) and had partial response in two cases (14.3%). Two cases of alopecia areata showed complete response (complete hair regrowth). Fourteen patients showed complete digestive response, 10 patients partial digestive response (seven of which needed IBD treatment optimization) and only two failure. In conclusion, ustekinumab is a drug of choice in patients with IBD who cannot tolerate TNF blockers.
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http://dx.doi.org/10.1111/1346-8138.14816DOI Listing
April 2019

Cross-cultural validation of a short-form of the Vitiligo Impact Patient scale (VIPs).

J Am Acad Dermatol 2019 Nov 11;81(5):1107-1114. Epub 2019 Feb 11.

FIMARAD, Hôpital Necker-Enfants Malades, Paris, France.

Background: There is a lack of short-form questionnaires evaluating the burden of vitiligo according to skin phototype.

Objective: To develop and validate a 12-item short-form of the Vitiligo Impact Patient scale (VIPs) that takes into account skin phototype.

Methods: Multicenter, prospective, cross-sectional study conducted in France (Créteil and Bordeaux) and the US (Worcester, Massachusetts, and Dallas, Texas).

Results: In total, 891 patients completed the questionnaire. Of these, 509 patients belonged to the French Development sample-313 with dark skin (DS) (phototypes IV to VI) and 196 with fair skin (FS) (phototypes I to III). The US validation sample comprised 382 patients-113 DS and 269 FS. There was a very high correlation between VIPs-FS and its 12-item short-form, VIPs-12-FS, in both the development and validation samples (respectively, rho = 0.96, P < .0001 and rho = 0.98, P < .0001). Similarly, the correlations between VIPs-DS and its short-form, VIPs-12-DS, in both the development and validation samples were very high (respectively, rho = 0.95, P < .0001 and rho = 0.96, P < .0001).

Limitations: Responsiveness of the 12-item short-forms should be confirmed.

Conclusions: These data enabled the development and validation of 12-item short-forms of the VIPs questionnaires for fair (VIPs-12-FS) and dark (VIPs-12-DS) skin.
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http://dx.doi.org/10.1016/j.jaad.2019.02.008DOI Listing
November 2019

Agreement Between Self-reported and Dermatologists' Diagnosis for Alopecia Areata and Atopic Dermatitis: A Bi-centric Prospective Study.

Acta Derm Venereol 2019 May;99(6):618-619

Department of Dermatology, University Hospital, FR-25000 Besançon, France.

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http://dx.doi.org/10.2340/00015555-3135DOI Listing
May 2019

Early-onset autoimmune vitiligo associated with an enhancer variant haplotype that upregulates class II HLA expression.

Nat Commun 2019 01 23;10(1):391. Epub 2019 Jan 23.

Human Medical Genetics and Genomics Program, University of Colorado School of Medicine, Aurora, 80045, CO, USA.

Vitiligo is an autoimmune disease in which melanocyte destruction causes skin depigmentation, with 49 loci known from previous GWAS. Aiming to define vitiligo subtypes, we discovered that age-of-onset is bimodal; one-third of cases have early onset (mean 10.3 years) and two-thirds later onset (mean 34.0 years). In the early-onset subgroup we found novel association with MHC class II region indel rs145954018, and independent association with the principal MHC class II locus from previous GWAS, represented by rs9271597; greatest association was with rs145954018del-rs9271597A haplotype (P = 2.40 × 10, OR = 8.10). Both rs145954018 and rs9271597 are located within lymphoid-specific enhancers, and the rs145954018del-rs9271597A haplotype is specifically associated with increased expression of HLA-DQB1 mRNA and HLA-DQ protein by monocytes and dendritic cells. Thus, for vitiligo, MHC regulatory variation confers extreme risk, more important than HLA coding variation. MHC regulatory variation may represent a significant component of genetic risk for other autoimmune diseases.
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http://dx.doi.org/10.1038/s41467-019-08337-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344500PMC
January 2019

Building a scale for measuring burden of hand eczema: BoHEM.

J Am Acad Dermatol 2019 06 23;80(6):1784-1785. Epub 2018 Dec 23.

FIMARAD (Filière de santé Maladies rares: maladies rares en dermatologie), Paris, France; European Market Maintenance Assessment, Fontenay sous-Bois, France. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2018.12.036DOI Listing
June 2019

Association of Frequency of Organic Food Consumption With Cancer Risk: Findings From the NutriNet-Santé Prospective Cohort Study.

JAMA Intern Med 2018 12;178(12):1597-1606

Centre de Recherche Epidémiologie et Statistique Sorbonne Paris Cité, Institut National de la Santé et de la Recherche Médicale (INSERM) U1153, Institut National de la Recherche Agronomique (INRA) U1125, Conservatoire National des Arts et Métiers, Université Paris 13, Equipe de Recherche en Epidémiologie Nutritionnelle, Bobigny, France.

Importance: Although organic foods are less likely to contain pesticide residues than conventional foods, few studies have examined the association of organic food consumption with cancer risk.

Objective: To prospectively investigate the association between organic food consumption and the risk of cancer in a large cohort of French adults.

Design, Setting, And Participants: In this population-based prospective cohort study among French adult volunteers, data were included from participants with available information on organic food consumption frequency and dietary intake. For 16 products, participants reported their consumption frequency of labeled organic foods (never, occasionally, or most of the time). An organic food score was then computed (range, 0-32 points). The follow-up dates were May 10, 2009, to November 30, 2016.

Main Outcomes And Measures: This study estimated the risk of cancer in association with the organic food score (modeled as quartiles) using Cox proportional hazards regression models adjusted for potential cancer risk factors.

Results: Among 68 946 participants (78.0% female; mean [SD] age at baseline, 44.2 [14.5] years), 1340 first incident cancer cases were identified during follow-up, with the most prevalent being 459 breast cancers, 180 prostate cancers, 135 skin cancers, 99 colorectal cancers, 47 non-Hodgkin lymphomas, and 15 other lymphomas. High organic food scores were inversely associated with the overall risk of cancer (hazard ratio for quartile 4 vs quartile 1, 0.75; 95% CI, 0.63-0.88; P for trend = .001; absolute risk reduction, 0.6%; hazard ratio for a 5-point increase, 0.92; 95% CI, 0.88-0.96).

Conclusions And Relevance: A higher frequency of organic food consumption was associated with a reduced risk of cancer. If these findings are confirmed, further research is necessary to determine the underlying factors involved in this association.
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http://dx.doi.org/10.1001/jamainternmed.2018.4357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583612PMC
December 2018