Outcome Measures in Adult Vulvar Lichen Sclerosus: A Systematic Review.

OBJECTIVES: Core outcome domains (CODs) for treatment of adult vulvar lichen sclerosus (VLS) have recently been established through a Delphi study. A number of measuring tools are available for evaluating VLS. The aim of this study is to identify available standardized measurement tools for the major CODs for VLS that have recently been defined, namely, physical findings and quality of life (QoL) specific to VLS. MATERIALS AND METHODS: A systematic search through September 8, 2023, for measuring tools applicable to VLS regarding physical findings and QoL including sexual function or sexual well-being and self-image was performed. RESULTS: Thirty-five studies were included in the systematic review describing 26 tools covering the following 6 outcome domains: QoL-general health, QoL-lichen sclerosus specific, symptoms, clinical signs, emotional impact, and sexual functioning. CONCLUSIONS: In current research, there is no uniformity in use of measurement tools for evaluating VLS. The established CODs to evaluate treatment of VLS are applicable for evaluating disease course as well. A comprehensive study to reach consensus regarding measurement of physical findings, QoL-lichen sclerosus specific, sexuality, and self-image taking the predetermined CODs and other factors such as age into account is needed.

Outcome Measures in Adult Vulvar Lichen Sclerosus: A Case Series of Women Diagnosed as Juveniles.

OBJECTIVES: Studies on the consequences of juvenile vulvar lichen sclerosus (JVLS) in adulthood are limited. A number of measuring tools are available for analyzing adult vulvar lichen sclerosus (VLS), but these have not been applied in studies on JVLS. The aim is to study physical findings, quality of life, sexual well-being, and self-image in adult women with a history of juvenile VLS. MATERIALS AND METHODS: Adult women with a biopsy proven history of JVLS were recruited to be examined and surveyed using available standardized measurement tools. This took place in an outpatient setting by physicians who were not involved in the treatment of participants. RESULTS: Twenty-seven women (median age 29 years) with a history of JVLS and median time since biopsy of 19.5 years were recruited. Of these women, 59% currently had symptoms, 63% had signs of active disease, and 85% had moderate to severe architectural changes. Despite these residual signs, vulvar specific-quality of life and vulvar self-image scored favorably while generic health-related quality of life was somewhat effected. CONCLUSIONS: JVLS has consequences in adulthood involving physical findings and vulvar quality of life. The use of standardized outcome measures for clinical practice and research purposes facilitates a better understanding of the sequelae to JVLS.

Mental Health of School-Aged Children Treated with Propranolol or Atenolol for Infantile Hemangioma and Their Parents.

BACKGROUND: Infants with infantile hemangioma (IH) have been effectively treated with propranolol or atenolol. Concerns were raised about the mental health of these children at school age, due to central nervous system effects of propranolol and visible nature of IH. OBJECTIVE: This study aimed to compare the mental health at school age of children treated with propranolol to children treated with atenolol for IHs and their parents. METHODS: This two-centered cross-sectional study included children aged ≥6 years and treated with either propranolol or atenolol for IH during infancy. Children's outcomes were performance-based affect recognition (Dutch version of the Developmental Neuropsychological Assessment-II [NEPSY-II-NL]), parent-reported emotional and behavioral functioning (Child Behavioral Checklist [CBCL]), and health-related quality of life (KIDSCREEN-27). Parents' outcome was parenting stress (Parenting Stress Questionnaire [OBVL]). RESULTS: Data of 105 children (36 propranolol, 69 atenolol; 6.0-11.8 years) were analyzed. Mental health outcomes did not differ between both ß-blocker groups. Although overall functioning was in line with norms, children presented specific problems concerning affect recognition, parent-reported attention, and social quality of life. Parents showed increased physical symptoms, depressive symptoms, and parent-child relationship problems. CONCLUSION: No difference in mental health at school age was found between children treated with propranolol or atenolol for IH. Although few overall mental health problems were found, specific problems require follow-up. Follow-up of children should be directed toward affect recognition, attention, and social functioning in daily life. Problems reported by parents could be ameliorated by mental health support during and after their infant's ß-blocker treatment.

The construct validity, responsiveness, reliability and interpretability of the Recap of atopic eczema questionnaire (RECAP) in children.

BACKGROUND: The Recap of atopic eczema questionnaire (RECAP) was developed to measure eczema control in patients with atopic dermatitis (AD). Measurement properties of RECAP have not yet been validated in caregivers of children with AD. OBJECTIVES: To assess the construct validity, responsiveness, reliability and interpretability of the Dutch proxy version of RECAP. METHODS: A prospective validation study was conducted among children (<12 years) with AD and their caregivers (in a Dutch tertiary hospital). At three time points (T0, Baseline; T1, after 1-7 days; T2, after 4-8 weeks) RECAP and multiple reference instruments were completed by caregivers of children patients. Construct validity: Single and change-score validity (responsiveness) were tested with a priori hypotheses on correlations with reference instruments. Reliability: intraclass correlation coefficients (ICCagreement) and standard error of agreement (SEMagreement) were reported. Interpretability of single scores: Bands for perceived eczema control were proposed. Interpretability of change score: The smallest detectable change (SDC) and minimally important change (MIC) were determined. Two anchor-based methods based on receiver operating characteristic curve (ROC) and predictive modelling were used to determine the MIC. RESULTS: A total of 231 children with AD and their caregivers participated in the study. Of our a prior hypotheses for single-score and change-score validity, 77% and 80% were confirmed, respectively. Stronger correlation than hypothesized was found for all rejected hypotheses.Excellent reliability was found (ICCagreement: 0.94; 95% confidence interval (CI): 0.90-0.96). The SEMagreement was 1.9 points. The final banding was: 0-1 (completely controlled), 2-7 (mostly controlled), 8-12 (moderately controlled), 13-18 (a little controlled), 19-28 (not at all controlled). A cut-off point of ≥8 was selected to identify children whose AD is not under control. The SDC was 5.3 and the MIC value 1.5 and 3.6 for the ROC and predictive modelling approach respectively. No floor or ceiling effects were observed. CONCLUSIONS: The proxy version of RECAP is a valid, reliable and responsive measurement instrument for measuring eczema control in children with AD. An improvement of ≥6 points can be regarded as real and important change in children with AD.

Atopic Dermatitis in Children in the General Population: Baseline Characteristics, Medication Use, and Severity Measures in the Rotterdam Eczema Study.

Background: Real-life data on severity and treatments in children with atopic dermatitis (AD) are needed to evaluate self-management. Objectives: To determine severity and use of topical treatments in children with AD in the general population. Furthermore, we aim to determine agreement and correlation between objective and subjective AD severity measures. Methods: Data were used from the Rotterdam Eczema Study, an observational prospective cohort study with an embedded pragmatic open-label randomized controlled trial. Descriptive statistics were used for baseline characteristics, medication use, and severity. Strength of agreement and correlation were determined using kappa analysis and Pearson correlation. Results: In total, 367 children (mean age 5.7 years) were recruited. The mean eczema area and severity index (EASI) score was 2.1 (±3.2) and mean patient-oriented eczema measure (POEM) score was 10.3 (±6.1). The majority applied emollients on a daily basis (54.9%) and had not used topical corticosteroids (TCSs) over the past week (51%). Based on severity banding of POEM and EASI, 49.9% and 24.9% of the children were undertreated, respectively. No evidence was found for an agreement between EASI and POEM (kappa 0.028, n = 178, P = 0.451). A moderate correlation between POEM, EASI, infants' dermatitis quality of life index, and children's dermatology life quality index was found. POEM showed higher correlation with quality of life (QoL) than EASI. Conclusion: Emollients were used sufficiently in the study population. Based on signs or symptoms, 24.9% and 49.9% of children are undertreated, respectively. POEM scores correlated better with QoL than with EASI scores. We argue that EASI underestimates severity of AD, and treatment based on EASI scores may lead to undertreatment of AD. Treating physicians should be aware of suboptimal use of TCSs.

Effectiveness of antibacterial therapeutic clothing vs. nonantibacterial therapeutic clothing in patients with moderate-to-severe atopic dermatitis: a randomized controlled observer-blind pragmatic trial (ABC trial).

BACKGROUND: Increased Staphylococcus aureus (SA) colonization is considered an important factor in the pathogenesis of atopic dermatitis (AD). Antibacterial therapeutic clothing aims to reduce SA colonization and AD inflammation; however, its role in the management of AD remains poorly understood. OBJECTIVES: To investigate the effectiveness of antibacterial therapeutic clothing + standard topical treatment in patients with moderate-to-severe AD vs. standard therapeutic clothing + standard topical treatment; and, if effectiveness was demonstrated, to demonstrate its cost-effectiveness. METHODS: A pragmatic double-blinded multicentre randomized controlled trial (NCT04297215) was conducted in patients of all ages with moderate-to-severe AD. Patients were centrally randomized 1 : 1 : 1 to receive standard therapeutic clothing or antibacterial clothing based on chitosan or silver. The primary outcome was the between-group difference in Eczema Area and Severity Index (EASI) measured over 52 weeks. Secondary outcomes included patient-reported outcomes (PROs), topical corticosteroid (TCS) use, SA colonization, safety and cost-effectiveness. Outcomes were assessed by means of (generalized) linear mixed-model analyses. RESULTS: Between 16 March 2020 and 20 December 2021, 171 patients were enrolled. In total, 159 patients were included (54 in the standard therapeutic clothing group, 50 in the chitosan group and 55 in the silver group). Adherence was high [median 7 nights a week wear (interquartile range 3-7)]. Median EASI scores at baseline and at 4, 12, 26 and 52 weeks were 11.8, 4.3, 4.6, 4.2 and 3.6, respectively, in the standard therapeutic clothing group vs. 11.3, 5.0, 3.0, 3.0 and 4.4, respectively, in the chitosan group, and 11.6, 5.0, 5.4, 4.6 and 5.8, respectively, in the silver group. No differences in EASI over 52 weeks between the standard therapeutic clothing group, the chitosan group [-0.1, 95% confidence interval (CI) -0.3 to 0.2; P = 0.53] or the silver group (-0.1, 95% CI -0.3 to 0.2; P = 0.58) were found. However, a small significant group × time interaction effect between the standard and silver groups was found (P = 0.03), in which the silver group performed worse after 26 weeks. No differences between groups were found in PROs, TCS use, SA skin colonization and healthcare utilization. No severe adverse events or silver absorption were observed. CONCLUSIONS: The results of this study suggest no additional benefits of antibacterial agents in therapeutic clothing in patients with moderate-to-severe AD.

Therapeutic clothing use in atopic dermatitis in the Netherlands: A population based cohort study.

National prescription data for therapeutic clothing in atopic dermatitis was analysed to investigate the role of therapeutic clothing in atopic dermatitis. Therapeutic clothing is most frequently prescribed by dermatologists in a hospital setting. Most patients only receive one prescription of therapeutic clothing, suggesting a limited role for therapeutic clothing in the long-term management of atopic dermatitis.

Remote severity assessment in atopic dermatitis: Validity and reliability of the remote Eczema Area and Severity Index and Self-Administered Eczema Area and Severity Index.

Background: Reliable assessment of atopic dermatitis (AD) severity is necessary for clinical practice and research. Valid and reliable remote assessment is essential to facilitate remote care and research. Objectives: Assess the validity and reliability of the Eczema Area and Severity Index (EASI) based on images and patient-assessed severity based on the Self-Administered EASI (SA-EASI). Methods: Whole-body clinical images were taken during consultation from children with AD. After consultations, caregivers completed the SA-EASI and provided images from home. Four raters assessed all images twice using EASI. Results: A total of 1534 clinical images and 425 patient-provided images were collected from 87 and 32 children. Excellent (0.90) validity, good inter (0.77) and intrarater reliability (0.91), and standard error of measurement (4.31) was found for the EASI based on clinical images. Feasibility of patient-provided images showed limitations with missing images (43.8%) and quality issues (23.1%). However, good validity (0.86), inter (0.74) and intrarater reliability (0.94) were found when assessment was possible. Moderate correlation (0.60) between SA-EASI and EASI was found. Limitations: Low portion patient-provided images. Conclusion: AD severity assessment based on images strongly correlates with in-person AD assessment. Good measurement properties confirm the potential of remote assessment. Moderate correlation between SA-EASI and in-person EASI suggest limited value of self-assessment.

Biologicals for pediatric patients with atopic dermatitis: practical challenges and knowledge gaps.

Biologicals are becoming increasingly important in the therapeutic landscape of pediatric patients with moderate-to-severe atopic dermatitis (AD). Currently, dupilumab and tralokinumab are registered for the treatment of moderate-to-severe AD, and novel biologicals are expected to follow. Dupilumab was the first biological registered for AD in pediatric patients and was recently approved for patients aged six months to five years. Current and emerging biologicals may address the unmet need for effective and safe treatment options for pediatric AD patients, however, little is known about the practical implementation of biologicals in infants and preschoolers (aged <6 years), including the timing of treatment initiation, discontinuation, and long-term administration of the subcutaneous injections. Currently, only a small number of biologicals are approved for the treatment of infants and preschoolers for other inflammatory diseases. Consequently, data on the practical implementation of biological treatment remain scarce. In addition, long-term effects, impact on co-morbidities, and impact on live-accentuated vaccination are still unknown. With the introduction of biologicals for AD from the age of six months, potential challenges within the implementation of biologicals may arise. Therefore, we aim to discuss current practical challenges and knowledge gaps of the treatment with biologicals in infants and preschoolers with AD.

Perceived adherence and associated barriers to the national atopic dermatitis guideline: A survey among general practitioners.

BACKGROUND: General practitioners (GPs) have an important role in managing patients with atopic dermatitis (AD). Although pivotal, adherence to dermatological guidelines in general practice has not been assessed. OBJECTIVES: To assess GPs' perceived adherence and barriers to the Dutch AD guideline. METHODS: A survey was conducted among 391 GPs in the Netherlands between December 2021 and May 2022. GPs rated their perceived adherence and perceived barriers concerning five key recommendations of the AD guideline, following an existing framework. The correlation between perceived adherence and barriers was investigated using Spearman's rank correlation. RESULTS: A total of 213 GPs (54%) participated. Perceived adherence rates varied across recommendations (43.7% to 98.1%). Lowest adherence was reported for recommendations concerning topical corticosteroids (TCS). Across all recommendations, patient factors (65.6%; SD 11.6) and lack of applicability to specific patient groups (29.5%; SD 10.5) were reported most frequently as barriers. The overall correlation between adherence and barriers was strongest for knowledge (ρ .55; SD .10) and attitude-related factors (range: ρ .40--.62). CONCLUSION: GPs' perceived adherence and barriers vary substantially across recommendations of the AD guideline. In particular, GPs reported lower adherence to recommendations concerning TCS. Next to patient-related factors, strong correlations between adherence perceived by GPs and knowledge and attitude-related barriers suggest the importance of addressing these factors as well to improve adherence.

Long-term consequences of juvenile vulvar lichen sclerosus: A cohort study of adults with a histologically confirmed diagnosis in childhood or adolescence.

INTRODUCTION: Vulvar lichen sclerosus (VLS) occurs in at least one in 900 girls. There is limited knowledge as to what extent the disease persists in adulthood and what the repercussions in adulthood may be. The aim of this study is to evaluate the long-term consequences of VLS diagnosed in childhood or adolescence. MATERIAL AND METHODS: The population of females histologically diagnosed with VLS in childhood or adolescence in the Netherlands between 1991 and 2015 was identified through the national pathology database. Histological specimens were retrieved and re-evaluated. Potential participants for whom the diagnosis was reconfirmed and who are now adults, were then traced and surveyed. Descriptive statistics were calculated and compared with the literature. Main outcome measures are the demographics of the cohort, their scores on standardized quality of life (QoL) and sexuality questionnaires and answers to additional questions regarding patients' experience with the disease. The questionnaires used were the Dermatology Life Quality Index (DLQI), the Skindex-29, the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R). Secondary outcome measures include obstetric history and histological features found in the original tissue specimens. RESULTS: A total of 81 women participated, median age 29.0 years, median follow-up from childhood diagnosis 19.5 years. Both QoL and sexuality were somewhat affected in 51.9% of cases. Less than half (45%) reported having regular check-ups. Forty-five (56%) reported symptoms within the past year; of those with symptoms, 14 (31%) were not under surveillance. Cesarean section rate (14.5%) was comparable to the general population, and there were more high-grade obstetric anal sphincter injuries with vaginal deliveries than expected. Sixteen respondents (20%) were not aware of the childhood diagnosis prior to this study. CONCLUSIONS: Symptoms due to VLS are reported by most adults diagnosed as juveniles. QoL and sexuality are affected and correlate to recent symptoms. VLS as a juvenile does not preclude a vaginal delivery. Women diagnosed with VLS in childhood or adolescence are often lost to follow-up.

Prognostic Factors for Long-term Aesthetic Outcome of Infantile Haemangioma Treated with Beta-blockers.

Parents of infants treated with beta-blockers for infantile haemangioma are often concerned about the long-term aesthetic outcome. This cross-sectional study assessed the influence on the long-term aesthetic outcome of characteristics of the infantile haemangioma, the beta-blocker treatment, and the infant. The study included 103 children aged 6-12 years, treated with beta-blockers (propranolol or atenolol) for infantile haemangioma during infancy (age at treatment initiation ≤1 year) for ≥6 months. Dermatologists and parents scored the Patient Observer Scar Assessment Scale, and the child scored a visual analogue scale. Dermatologists identified whether telangiectasia, fibrofatty tissue, and atrophic scar tissue were present. The long-term aesthetic outcome of infantile haemangioma was judged more negatively by dermatologists and parents in case of a superficial component, ulceration, older age at treatment initiation, higher cumulative dose, and/or shorter follow-up time. According to children, infantile haemangioma located on the head had better aesthetic outcome than infantile haemangioma located elsewhere. Close monitoring, particularly of infantile haemangioma with a superficial component, is essential for early initiation of treatment, and to prevent or treat ulceration. These outcome data can support parental counselling and guide treatment strategy.

Safety and effectiveness of surgical excision of medium, large, and giant congenital melanocytic nevi: A systematic review and meta-analysis.

BACKGROUND: Treatment indications of congenital melanocytic naevi (CMN) have shifted from the prevention of malignant transformation more towards the improvement of appearance and psychosocial health. Surgical excision is often preferred, but its safety and effectiveness remain unclear. OBJECTIVE: To assess the outcomes of surgical excision of medium-to-giant CMN. PRIMARY OUTCOME: safety (complications). SECONDARY OUTCOME: effectiveness (satisfaction and CMN core outcomes). METHODS: PubMed, EMBASE, and CENTRAL were searched for studies on the excision of medium-to-giant CMN and/or CMN requiring reconstruction or serial excision. Meta-analyses of safety per patient were conducted, and pooled outcomes of safety and effectiveness were presented in summary-of-findings tables. RESULTS: A total of 1444 studies were found, of which 22 were included, evaluating 643 eligible patients. Study quality varied, and reporting of baseline characteristics and outcomes was heterogeneous. Pooled proportions were overall 9.8% for major wound-related complications, 1.2% for minor wound-related complications, 1.2% for scar-related complications, and 4.3% for anatomical deformities. For large/giant CMN, complication rates were, respectively, 23.1%, 2.9%, 12.9%, and 2.4%; and for CMN with eyelid involvement, 0.5%, 3.3%, 0.4%, and 54.2%. Patients rated their satisfaction with the cosmetic outcome as 24.4% excellent, 71.0% good, and 4.6% poor/moderate. Physicians rated this as 18.3% excellent, 70.1% good, and 11.7% poor/moderate. Thirty-five other outcomes of effectiveness were summarized. However, many were rarely reported. CONCLUSIONS: Surgical excision of CMN appears to be safe and effective in many cases, depending on CMN size and location. Major wound-related complications and scar-related complications occurred more frequently with large/giant CMN, whereas anatomical deformities occurred with the majority of CMN with eyelid involvement.

Long-term neurocognitive functioning of children treated with propranolol or atenolol for infantile hemangioma.

The purpose of this study was to compare long-term neurocognitive functioning (working memory, processing speed, and attention) between children who had been treated with either propranolol or atenolol for infantile hemangioma during infancy. All eligible children (n = 158) aged 6 years or older and treated with propranolol or atenolol as infants were invited to participate in this two-center cross-sectional study. The primary outcome was the Wechsler Intelligence Scale for Children-V Cognitive Proficiency Index (CPI), a measure of working memory, processing speed, and attention. Secondary outcomes were general intelligence, auditory, visuospatial, and narrative memory, as well as executive functioning and sleep. A total of 105 children, of whom 36 had been treated with propranolol (age 6.0-11.8 years, follow-up time 1.6-9.7 years, 19% male) and 69 had been treated with atenolol (age 6.9-9.7 years, follow-up time 4.5-8.4 years, 19% male), were analyzed. The CPI and other neurocognitive outcomes did not differ between the propranolol and atenolol groups and were in line with general population test norms. Post hoc analyses revealed lower CPI scores for males, both compared to participating females (10.3 IQ points, medium effect size) and compared to matched test norms (12.4 IQ points, medium effect size). CONCLUSIONS:  Long-term neurocognitive functioning did not differ between children treated with propranolol and those treated with atenolol for IH. Overall, propranolol and atenolol appear to be safe treatments for IH regarding long-term neurocognitive functioning. The substantially lower CPI scores in males warrant further investigation. TRIAL REGISTRATION:  Netherlands Trial Register, NL7703 https://www.trialregister.nl/trial/7703 What is Known: • Infants with infantile hemangioma are effectively treated with propranolol or atenolol. • Parents and professionals are concerned about long-term neurocognitive effects. WHAT IS NEW: • No long-term (≥ 6 years) differences in neurocognitive functioning were found between children treated with propranolol or atenolol. • Males treated with beta-blockers had substantially lower IQ scores than treated females and males from the general population, which is a matter of concern and should be considered when evaluating the risk/benefit ratio in less severe forms of infantile hemangioma.

Treatment Experiences with Intravenous Immunoglobulins, Ixekizumab, Dupilumab, and Anakinra in Netherton Syndrome: A Case Series.

BACKGROUND: Netherton syndrome (NS) is a rare potential life-threatening disorder that causes severe defects to the skin barrier. No effective treatment options are available for patients with NS and current therapy is mostly supportive. The effects of intravenous immunoglobulins (IVIGs), ixekizumab, and dupilumab have scarcely been reported. Additionally, the role of anakinra in patients with NS has never been investigated. OBJECTIVES: The objective was to report our experiences of treatment with IVIG, ixekizumab, dupi-lumab, and anakinra in patients with NS. METHODS: A retrospective case series, including 5 patients with NS, was performed in a tertiary referral hospital between 2016 and 2021. Patients were treated with IVIG, ixekizumab, dupilumab, and/or anakinra. Long-term experiences with treatment regimens and adverse events requiring medical attention were reported. RESULTS: IVIG, ixekizumab, dupilumab, and anakinra were well tolerated with no severe adverse events. The 2 patients that received IVIG showed clinical response for 6 months and 2.5 years. Ixekizumab was effective in 1 of our patients for 3.5 years, while in another patient ixekizumab lost its effect after 1.5 years. Dupilumab treatment did not result in persistent improvement of NS-related skin symptoms in 1 patient. Anakinra showed physician-assessed clinical response during the first months of treatment in 4 patients with NS. During anakinra treatment, no changes in blood levels of IL-1ß, IL-6, and TNF-α levels were measured at routine blood examinations. CONCLUSIONS: This case series suggests that the use of IVIG, ixekizumab, dupilumab, and anakinra in NS is safe and moderately effective on the short term. On the long term, a decline in effect was observed. Our experiences may help clinicians and researchers to provide adequate care and develop treatment for these severely affected patients. More international research, especially on the long term, is needed to determine if and which patients benefit most from the emerging therapies for NS.