Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.

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. Recent progress in the understanding of immune pathophysiological mechanisms has opened interesting perspectives for innovative treatment strategies. Several strategies have been tested, with debated results. However, proof of concept in humans of targeting of the Interferon (IFN)γ/Th1 pathway and of the Janus Kinase (JAK) signaling pathway has led to the development of several topical and oral JAK inhibitors in this disease with high unmet needs. Our review covers novel immune mechanisms of the disease and promising therapeutic approaches already tested in clinical trials and/or under development.

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. Frequency, incidence rate (IR)/100 person-years (PYs) and clinical characteristics of TE-herpes simplex, EH and HZ were reported. RESULTS: In the All-BARI-AD dataset (n = 2531; 2247 PYs), herpes simplex was reported in 8.9% of patients (n = 224; IR = 10.3). Most herpes simplex events were rated as mild or moderate (93.3%), rarely led to permanent discontinuation (2.2%) and presented mostly as oral/perioral herpes simplex (51.3%). TE-EH occurred at a low frequency (All-BARI-AD 1.7% n = 43; IR = 2.0) and were reported in 0.5%, 0.2% and 1.4% of patients receiving placebo, 2-mg or 4-mg BARI respectively. In the All-BARI-AD dataset, most events were investigator-rated as mild/moderate (79.1%), affected ≤2% of the body surface area (74.2%) and occurred as single events (88.4%). Serious TE-EH (n = 11) occurred exclusively in patients with poor disease control (vIGA-AD™ score ≥3) at infection onset. TE-HZ was reported in 2.1% of BARI patients (n = 53; IR = 2.3), without a dose relationship during the PC period (IR = 2.7 and IR = 0.0) or the extended dataset (IR = 3.7 and IR = 1.7) for 2- or 4-mg BARI respectively. CONCLUSIONS: TE-herpes simplex was common, while occurrence of EH was uncommon. Most events of EH were localized with involvement of a small BSA and were linked to poor disease control. Events of HZ were rare in the PC dataset and without a dose dependent increase in frequency.

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. Two independent reviewers assessed articles for inclusion and extracted data for qualitative synthesis. A total of 130 included studies were published between 1996 and 2021. Geographical regions with the most studies were Europe (32.3%) and the Middle East (26.9%). Dermatology-specific instruments, including the Dermatology Life Quality Index (DLQI; 80 studies) and its variants for children (CDLQI; 10 studies) and families (FDLQI; 4 studies), as well as Skindex instruments (Skindex-29, 15 studies; Skindex-16, 4 studies), were most commonly used to measure humanistic burden. Vitiligo-specific instruments, including the Vitiligo-specific QoL (VitiQoL; 11 studies) instrument and 22-item Vitiligo Impact Scale (VIS-22; 4 studies), were administered in fewer studies. Among studies that reported total scores for the overall population, a majority revealed moderate or worse effects of vitiligo on patient QoL (DLQI, 35/54 studies; Skindex, 8/8 studies; VitiQoL, 6/6 studies; VIS-22, 3/3 studies). Vitiligo also had a significant impact on the QoL of families and caregivers; 4/4 studies reporting FDLQI scores indicated moderate or worse effects on QoL. In general, treatment significantly (P < 0.05) improved QoL, but there were no trends for types or duration of treatment. Among studies that reported factors significantly (P ≤ 0.05) associated with reduced QoL, female sex and visible lesions and/or lesions in sensitive areas were most common. In summary, vitiligo has clinically meaningful effects on the QoL of patients, highlighting that greater attention should be dedicated to QoL decrement awareness and improvement in patients with vitiligo.

Palmoplantar pustulosis and acrodermatitis continua of Hallopeau: demographic and clinical comparative study in a large multicentre cohort.

BACKGROUND: Acral pustular disease within the pustular psoriasis/psoriasis-like spectrum mainly includes palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH). Scarce data argue for a distinction between these two entities, but no study has compared the clinical and epidemiologic characteristics of ACH and PPP. OBJECTIVES: We aimed to perform a comparative description of the epidemiological and clinical characteristics of PPP and ACH in a multicentre retrospective cohort. METHODS: In this multicentre national retrospective cohort study, we compared the epidemiological characteristics, comorbidities and psoriasis characteristics of patients with PPP and ACH. RESULTS: A total of 234 patients were included: 203 (87%) with PPP, 18 (8%) with ACH and 13 (6%) with both, according to 2017 ERASPEN criteria. As compared with ACH, PPP was associated with female sex, smoking activity and higher median BMI (P = 0.01, P = 0.02 and P = 0.05 respectively). A family background of psoriasis was more frequent in PPP than ACH. Age of onset of palmoplantar disease was similar between PPP and ACH patients, median age 44 and 48 years respectively. Peripheral joint inflammatory involvement was the only rheumatic disease associated with ACH. The association with another psoriasis type was similar in PPP and ACH (57.6% and 61.1% respectively). CONCLUSION: Our study confirms in a large PPP cohort the predominance of females and a high prevalence of smoking and elevated body mass index but also shows an association of these features in PPP as compared with ACH. In addition, it highlights peripheral arthritis as the only arthritis endotype associated with ACH. Increased knowledge of the immunogenetic backgrounds underlying these two entities is warranted to better stratify pustular psoriasis or psoriasis-like entities for precision medicine.

CITY-PSO: Prescribing behaviour of French private-practice dermatologists in psoriasis management: An observational, multicentre, cross-sectional study.

BACKGROUND: Information regarding the prescribing behaviour of French private-practice dermatologists (PPDs) is scarce. OBJECTIVES: First, to describe the population of PPDs involved in psoriasis management. Second, to describe the population of adult patients treated for psoriasis and their management. METHODS: We published a call for participation targeting PPDs; we first asked respondents to complete a form regarding their prescribing behaviour, and then to include consecutive patients consulting for psoriasis during a one-month study period and to collect patient data. RESULTS: The 94 participating PPDs included 1022 patients of mean age 52.9±17.9 years. The average body mass index was 28, and 25% had vascular comorbidities. Two thirds of patients had chronic psoriasis, for which 45% had consulted at least 5 times. Psoriasis was mostly with plaques (70.8%) and 11.4% of patients had psoriatic arthritis. The average body surface area (BSA) affected was 10.1%. Among the 679 patients without initial systemic treatment, 159 were started on systemic treatment. The main agents initiated were phototherapy (n=63), methotrexate (n=40), acitretin (n=30) and apremilast (n=20). In multivariate analysis, a higher BSA [Odds Ratio (OR) 1.10, 95% Confidence Interval (CI): 1.07-1.13; P<10-4] and Dermatology Life Quality Index (DLQI) [OR 1.09, 95% CI: 1.03-1.15; P=0.04] were associated with prescription of systemic therapy at the end of the consultation. CONCLUSION: The main limitation of our study was that participating PPDs were strongly involved in psoriasis management, which accounts for the high proportion of moderate-to-severe psoriasis and prescription of systemic treatments. Such committed PPDs and the development of psoriasis networks are key factors for improving the quality of care provided to psoriasis patients.

[Dupilumab-related blepharoconjunctivitis: Recommendations of the CEDRE group. Atopic dermatitis, conjunctivitis and dupilumab: Which management approach?] / Blépharo-conjonctivites sous dupilumab : recommandations du groupe CEDRE. Dermatite atopique, conjonctivites et dupilumab : quelle prise en charge ?

Dupilumab is a recombinant monoclonal IgG4 type antibody which inhibits IL4 and IL13 signaling. It is indicated in moderate to severe atopic dermatitis (AD) in adults and adolescents over 12 years of age. Its side effects include conjunctivitis and blepharoconjunctivitis, affecting between 4.7% and 28% of patients depending on the study. The incidence of conjunctivitis in patients treated with dupilumab for AD appears to be higher than placebo in clinical studies. This increase was not observed in patients treated with dupilumab for asthma or sinonasal polyposis. The risk factors for conjunctivitis in patients with AD are disease severity, pre-existence of conjunctivitis and low concentrations of dupilumab, but the pathophysiology of this disease is poorly understood. A literature search carried out in April and May 2020 showed an increase in the number of publications on the subject, but there are currently no official joint dermatologist-ophthalmologist recommendations for prevention and management. The objective of this article is to provide an overview of the status of this subject, to address the main questions raised by this type of conjunctivitis and to suggest a course of action for starting and continuing treatment with dupilumab in patients with AD, according to the recommendations of the French Ophthalmologist/Dermatologist group CEDRE.

Vitiligo Treatment Impact score (VITs): development and validation of a vitiligo burden of treatment questionnaire using the ComPaRe Vitiligo e-cohort.

BACKGROUND: Vitiligo management is challenging and requires long-term adherence of patients who often complain of the burden associated with treatment. OBJECTIVE: To develop and validate a patient reported measurement of the burden of treatment in vitiligo. METHODS: The study was nested within the ComPaRe Vitiligo e-cohort, an online e-cohort of vitiligo patients in France. Items were derived from a literature review and from the qualitative analysis of a survey using open-ended questions of 204 patients with Vitiligo. Construct validity of the resulting instrument was assessed by comparing the instrument's score to the Dermatology Life Quality Index (DLQI), Vitiligo Impact Patient score (VIPs) and Treatment Burden Questionnaire (TBQ) scores. Reliability was assessed by test-retest with 15 ± 10 days of interval between both assessments. RESULTS: In total, 343 adult participants participated in the validation of the Vitiligo Treatment Impact score (VITs). The VITs is a 19-item questionnaire assessing the burden of treatment in patients with vitiligo with results suggesting four domains ('Finding a doctor', 'Phototherapy', 'Topical treatment' and 'Impact on outdoor activities and photoprotection'). The VITs total score was well correlated with the DLQI, VIP and TBQ scores. Agreement between test and retest was good (ICC 0.705, 95% CI 0.491-0.818). CONCLUSIONS: We developed a patient reported measurement of the burden of treatment in vitiligo with good psychometric properties.

Development of a shared decision-making tool in vitiligo: an international study.

BACKGROUND: Shared decision-making tools (SDMt) are visual tools developed to promote joint medical decisions between physicians and patients. There is a paucity of such tools in dermatology. OBJECTIVES: To develop and validate a SDMt for use in specialized consultation for vitiligo. METHODS: A prospective cross-sectional study was carried out from March 2019 to March 2020. We first conducted a qualitative study of topics discussed by patients and clinicians during therapeutic decision-making in the setting of a specialized consultation for vitiligo using an anchored-theory method, which allowed conceptualization of the SDMt. The usefulness of the SDMt was evaluated by a working group of multidisciplinary health workers and patients with vitiligo. Consensus on the final tool was obtained through an e-Delphi method. RESULTS: We recruited 30 patients with vitiligo for the qualitative study, which identified 91 topics related to therapeutic decision-making. Hierarchical clustering analysis confirmed the distribution of these topics in two subgroups (general treatment goals and priorities, and topics specific to each treatment). The consensus of a multidisciplinary group was used to develop the SDMt. The tool was comprised of eight A5 cards, which addressed face repigmentation; body repigmentation (limited area); body repigmentation (extended area); partial or complete depigmentation; coping with the disease; stabilization of disease; maintaining repigmentation; and disease information. Cognitive interviews confirmed the satisfaction, readability and usefulness of the SDMt. The SDMt was then translated and culturally validated in English. CONCLUSIONS: We developed a tool for shared decision-making in nonsegmental vitiligo, which we translated and cross-culturally validated in a US patient population with vitiligo to ensure its generalizability.

Out-of-pocket expenditures in France to manage psoriasis in adult patients: results from an observational, cross-sectional, non-comparative, multicentre study.

BACKGROUND: In 2018 in France, overall mean health-related out-of-pocket (OOP) expenditures were 214.00€/year/patient. AIM: To evaluate OOP expenditures for psoriasis patients in France. METHODOLOGY: Observational, cross-sectional, non-comparative, multicentre study in 3000 patients with clinically confirmed psoriasis who responded to a specific digital questionnaire collecting demographic and socio-economic characteristics, assessing the 3 domains (severity, psychosocial impact and past history and interventions) of the patient's Simplified Psoriasis Index (sa-SPI) and expenditures to manage psoriasis, including OOP. Multivariate linear regression was conducted to search for factors associated with higher OOP. RESULTS: In total, 2681 patients completed the questionnaire and, of those, 2562 provided clinically validated data. Overall, 60% were women; the mean age was 49.4 ± 14.8 years. 30% of the patients declared that they suffered from psoriatic arthritis. The final mean sa-SPI core was 10.86 ± 9.70. Of these 2562 patients, 243 (9.5%) had severe, 442 (17.3%) moderate and 1877 (73.3%) mild psoriasis. In addition, 932 (36.4%) patients reported facial involvement, 724 (28.25%) genital impairment and 1124 (43.8%) lesions on the limbs. Mean OOP expenditures to manage psoriasis per patient were 531.00€, 439.74€ ± 939.85€ for patients with mild, 791.06€ ± 1367.67€ with moderate and 1077.64€ ± 1680.14€ for patients with severe psoriasis. For patients with psoriasis in the genital area, the median amount of expenditures (251.17€; CI95% [138.35;363.99]) was significantly higher than that for the face (183.85€; CI95% [78.76;288.94]) or limbs (199.96€; CI95% [93.77;306.15); (P < 0.001). More than 90% of the patients had OOP expenditures for over-the-counter products (97.5%) and alternative care (92.0%), especially for emollients and/or hydrating products. CONCLUSION: In France, in 2019, OOP expenditures to manage psoriasis were on average more than twice as high as the overall mean health-related OOP expenditures estimated by the French Health Agency in 2018. These results should lead health authorities to review certain standards of healthcare reimbursement.