Protocol of a scoping review of outcome domains in dermatology.

INTRODUCTION: Core outcome sets (COSs) are agreed outcomes (domains (subdomains) and instruments) that should be measured as a minimum in clinical trials or practice in certain diseases or clinical fields. Worldwide, the number of COSs is increasing and there might be conceptual overlaps of domains (subdomains) and instruments within disciplines. The aim of this scoping review is to map and to classify all outcomes identified with COS projects relating to skin diseases. METHODS AND ANALYSIS: We will conduct a scoping review of outcomes of skin disease-related COS initiatives to identify all concepts and their definitions. We will search PubMed, Embase and Cochrane library. The search dates will be 1 January 2010 (the point at which Core Outcome Measures in Effectiveness Trials (COMET) was established) to 1 January 2024. We will also review the COMET database and C3 website to identify parts of COSs (domains and/or instruments) that are being developed and published. This review will be supplemented by querying relevant stakeholders from COS organisations, dermatology organisations and patient organisations for additional COSs that were developed. The resulting long lists of outcomes will then be mapped into conceptually similar concepts. ETHICS AND DISSEMINATION: This study was supported by departmental research funds from the Department of Dermatology at Northwestern University. An ethics committee review was waived since this protocol was done by staff researchers with no involvement of patient care. Conflicts of interests, if any, will be addressed by replacing participants with relevant conflicts or reassigning them. The results will be disseminated through publication in peer-reviewed journals, social media posts and promotion by COS organisations.

Association between acetaminophen use and vitiligo in US women and men.

BACKGROUND/OBJECTIVES: Exposure to chemical phenols, which can act as tyrosine analogues and result in anti-melanocyte autoimmunity, has been associated with vitiligo. Acetaminophen (N-acetyl-p-aminophenol) is an over-the-counter analgesic of phenolic origin. The risk of vitiligo with systemic exposure to acetaminophen has not yet been evaluated. METHODS: We examined the risk of vitiligo with regular use acetaminophen in women, the Nurses' Health Study (NHS) and in men, the Health Professionals Follow-up Study (HPFS). Regular acetaminophen use was asked biennially from 1990 in NHS and from 1986 in HPFS, and the year of clinician-diagnosed vitiligo was asked retrospectively in 2012 in the cohorts. RESULTS: In NHS, a total of 161 vitiligo cases were identified during a follow-up of 571,724 person-years; in HPFS, a total of 183 vitiligo cases were identified during a follow-up of 680,313 person-years. Regular use of acetaminophen was associated with an increased vitiligo risk in NHS but not HPFS. The multivariable relative risk (RR) was 1.52 (95% confidence interval [CI] 1.03-2.25) in NHS and 1.09 (95% CI 0.76-1.55) in HPFS. The higher risk of vitiligo was similar by duration of acetaminophen use in women; the multivariable RRs were 1.47 (95% CI 0.98-2.21) for acetaminophen use under 5 years, and 1.78 (95% CI 1.11-2.84) for acetaminophen use over 5 years. CONCLUSIONS: Acetaminophen may be associated with a higher risk of vitiligo in women.

Vitiligo prevalence and quality of life among adults in Europe, Japan and the USA.

BACKGROUND: Vitiligo, an autoimmune disorder characterised by skin depigmentation, is associated with reduced quality of life (QoL). Vitiligo may be under-reported, in part because of misconceptions that it is a cosmetic disease. OBJECTIVES: This survey sought to characterise vitiligo prevalence and explore the relationship between sociodemographic and clinical characteristics with QoL in a population-based, multinational study. METHODS: Participants aged ≥18 years were recruited via an online panel in Europe, Japan and the USA to answer questions regarding skin disorders they may have experienced. Those reporting vitiligo (diagnosed or undiagnosed) or vitiligo signs (experiencing loss of skin colour but unaware of vitiligo and not diagnosed) were included in the analyses of vitiligo prevalence. Participants who self-reported physician-diagnosed vitiligo were given a broader survey to characterise disease progression, management and QoL (as measured with the Vitiligo-specific QoL [VitiQoL] instrument). RESULTS: The total estimated vitiligo prevalence among 35 694 survey participants (Europe, n = 18 785; USA, n = 8517; Japan, n = 8392) was 1.3% (diagnosed, 0.6%; undiagnosed, 0.4%; vitiligo signs, 0.3%). Among 219 patients formally diagnosed with vitiligo (Europe, n = 150; USA, n = 48; Japan, n = 21), total VitiQoL scores were associated with age (P = 0.00017), disease extent (P < 0.0001), disease progression (P < 0.0001), disease management (P < 0.0001) and time since diagnosis (P = 0.0015). Behaviour scores varied based on skin phototype (P = 0.024) and ethnicity (P = 0.048). Higher total VitiQoL scores were reported in patients with head lesions (P = 0.027) and those with head and hand and/or wrist lesions (P = 0.018). Substantial high concern (rated 8-10 on an 11-point Likert scale) for lesions was found across all body areas and varied with geographical region. CONCLUSIONS: The vitiligo prevalence rate may be higher than previously reported, with a substantial proportion attributed to people who have not received a formal diagnosis. Among formally diagnosed patients with vitiligo, QoL was most severely impacted by more progressive and higher extent of disease.

Quality of life in neurofibromatosis 1: development and validation of a tool dedicated to cutaneous neurofibromas in adults.

BACKGROUND: Cutaneous neurofibromas (cNF), present in 95% of individuals with neurofibromatosis 1 (NF1), are considered as one of the greatest medical burden because of physical disfigurement. No specific score evaluates their impact on quality of life (QoL). OBJECTIVE: To develop a specific score assessing cNF-related QoL. METHODS: Through a multidisciplinary workshop including 10 patients, 3 expert-in-NF1 physicians, 3 health care workers (nurses and psychologist) and 1 methodologist, the French version of the Skindex-16 was modified by adding 3 items. The new cNF-Skindex was validated among patients with NF1 recruited in the ComPaRe online cohort, in France (N = 284). Construct validity was assessed by comparing it with the EQ-5D-5L, its visual analogue scale and the MYMOP2 and by assessing its association with patients' characteristics. Reliability was assessed by a test-retest. An English version of the tool was developed using a back-forward translation. RESULTS: A total of 228 individuals with NF1, with cNF answered the 19-item questionnaire. These items fitted into 3 domains: emotions, symptoms, functioning. One was dropped during analysis because >90% responders were not concerned. The cNF-Skindex significantly correlated with the EQ-5D-5L (N = 193) and MYMOP2 (N = 210) indicating good external validity: rs 0.38 (P < 0.001), and 0.58 (P < 0.001), respectively. Having >50 cNF was the only independent variable associated with the total score cNF-Skindex (ß = 15.88, 95%CI 6.96-24.81, P = 0.001), and with the 3 sub-scores: 'functioning' (ß = 2.65, 95%CI 0.71-4.59, P = 0.008), 'emotions' (ß = 17.03, 95%CI 4.11-29.96, P = 0.010) and 'symptoms' (ß = 3.90, 95%CI 1.95-5.85, P < 0.001). Test-retest reliability (N = 133) found an ICC at 0.96 demonstrating good reproducibility. CONCLUSION: The cNF-Skindex demonstrated excellent psychometric properties. The global and sub-scores were increased with higher number of cNF arguing for its use in further trials aiming to reduce their number or prevent their development. Cross-cultural validation and evaluation of its responsiveness are the next steps.

Identification of three clinical neurofibromatosis 1 subtypes: Latent class analysis of a series of 1351 patients.

BACKGROUND: Neurofibromatosis 1 (NF1) is one of the most common inherited disorders characterized by mutations in the tumour suppressor gene NF1. Its clinical manifestations are highly variable and unpredictable. A specific NF1 mutation does not predict the severity or complications of the disease. OBJECTIVE: The objective of this study was to build an empirical classification scheme without any a priori hypotheses to identify the underlying NF1 subtypes that best explain the observed heterogeneity. METHODS: We performed latent class analysis (LCA) of 1351 consecutive NF1 patients aged >17 years seen between 2002 and 2014. Data and phenotypic features were collected prospectively on a standardized form. RESULTS: The median age was 36.8 (17-81) years. A three-class model showed the best fit: 706 (52%) belonged to the LC1 'Cutaneous neurofibromas' class having preferentially cutaneous neurofibromas (99%), plexiform neurofibromas (63%) and blue-red macules (29%); 593 (44%) belonged to the LC2 'Subcutaneous neurofibromas' class characterized by the presence of at least 10 subcutaneous neurofibromas (21%) and a familial form (77%) and 52 (4%) belonged to the LC3 'Dysmorphic phenotype' class characterized by dysmorphic features (78%) and learning difficulties (87%). Patients in LC1 had a higher likelihood of developing scoliosis (RR = 1.7, 95% confidence interval (CI) [1.2-2.4]). Patients in LC2 were more likely to be men (RR = 1.4, 95% CI [1.1-1.7]). Patients in LC3 were at higher risk of having an optic pathway glioma (RR = 4.8, 95% CI [1.9-11.8]) and epilepsy (RR = 4.5, 95% CI [1.8-11.6]). CONCLUSION: Our findings invite the performance of a larger cohort study to test whether the various latent classes reflect different underlying genetic modifiers of these phenotypic traits.

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.

Characteristics of children and adolescents with atopic dermatitis who attended therapeutic patient education.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease. Therapeutic patient education (TPE) has been demonstrated to be effective in AD in reducing disease severity and improving coping and quality of life. OBJECTIVES: To describe the sociodemographic and clinical characteristics of children and adolescents with AD who had attended TPE sessions, as well as the characteristics of their parents, and compare them with those who did not attend TPE. METHODS: Parents of children with AD aged 6-17 years old were recruited from a representative sample of the French population contacted by e-mail. Sociodemographic data and clinical information were collected in patients and parents. Clinical severity was assessed by parents using a proxy version of the Patient-Oriented Eczema Measure (POEM). Attendance to TPE sessions was assessed by the following question 'did your child or one or both parents attended TPE for AD?'. Also, the number of sessions was recorded. Determinants of TPE attendance were evaluated by univariable and multivariable analyses. RESULTS: Data were collected on 1063 parents and children with AD. A total of 131 (12.3%) children and/or parents attended TPE sessions. Most of them attended 2-5 TPE sessions. In that group, there were 85 boys (64.9%), and severity evaluated by POEM was mild in 29.8%, moderate in 52.7% and severe in 17.6% of patients. In the multivariable model, attending TPE sessions was significantly associated with sex of the child (boy vs. girl), consultation with a dermatologist or a paediatrician, high clinical severity and presence of AD in parents. CONCLUSIONS: Despite recommendations, the use of TPE in children with AD is still low in France. There is a need for implementing such programmes in the management of the disease, in particular when the disease is severe.

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.

Prevalence of comorbidities in atopic dermatitis and psoriasis in the French population.

BACKGROUND: Atopic dermatitis (AD) and psoriasis (Pso) are highly prevalent chronic inflammatory skin diseases. They share similarities regarding severity and impact on quality of life but display differences regarding risk factors, comorbidities, and pathogenesis. OBJECTIVE: This study sought to assess the prevalence of AD and Pso among the French population, along with associated comorbidities, and to compare these data with those of the age- and gender-adjusted French population with neither AD nor Pso. METHODS: The survey was conducted by a polling institute between September 1 and November 30, 2016, with proportional quota sampling being applied to render the study population representative of the French population. In all, 20 012 individuals were selected from among 900,000 internet users aged≥15years. RESULTS: Overall, 20,012 adults (48.8% men; 51.2% women) completed a digital questionnaire. The prevalence of AD was 4.65% [95% confidence interval (CI) 4.36%-4.94%] and that of Pso was 4.42% [95% CI: 4.14%-4.71%]. More AD patients presented≥1 comorbidity compared to subjects without AD (57.04% vs. 49.2%, P<0.0001) and more Pso patients presented≥1 comorbidity compared to subjects without Pso (60.68% vs. 49.05%, P<0.0001). After adjustment for gender and age, hypertension and dyslipidemia, a greater prevalence of osteoarticular, respiratory and psychiatric diseases was noted in both AD and Pso patients, whereas increased prevalence of obesity was seen only in Pso patients. The prevalence of components of metabolic syndrome was higher among Pso than AD patients. CONCLUSION: Further studies are required to consolidate these findings, to better characterize the entire spectrum of AD and Pso comorbidities, and to better identify determinants and risk factors, along with targeted therapies.