Descriptive Study of the Clinical and Molecular Features of Epidermolysis Bullosa Patients in a Romanian European Reference Network-Skin Affiliated Reference Center.

BACKGROUND: During the last 10 years, in Romania, progress has been made for the welfare of patients suffering from epidermolysis bullosa (EB). In five university hospitals, affiliated with the National Program for the Treatment of Rare Diseases, highly trained specialists diagnose and treat patients with this rare condition. Regarding diagnosis, limitations still exist as immunofluorescence mapping and molecular genetic analysis are not accessible, and generally not reimbursed. Our objective is to present the experience in diagnosing EB patients at Colentina Clinical Hospital, highlighting genotype-phenotype correlations observed in our cohort of patients. METHODS: The records of the patients enrolled between 2012 and 2024 were analyzed considering clinical aspects, and, when available, immunofluorescence mapping, transmission electron microscopy, and genetic molecular analysis. RESULTS: Fifty-six patients were identified, of whom 31 cases were of dystrophic EB, three were of junctional EB, and 11 were of simplex EB. For 11 cases, the EB type could not be determined. Regarding EB simplex, two patients with KRT5 mutations and three patients with KRT14 mutations with various clinical expressions, from mild phenotype to severe forms, were identified. Three severe junctional EB patients were registered in our database and for one of the patients, two previously unreported mutations in the LAMA3 gene were identified. Regarding dystrophic EB, 31 cases were identified, of which 25 were recessive dystrophic cases and six were dominant dystrophic cases. Molecular genetic testing was performed for 15 patients, and the most common variant was c.425A>G, identified in six cases. DISCUSSIONS: Two previously unreported mutations were identified, namely, COL7A1 c.5416G>C, a heterozygous missense variant in a patient with a mild phenotype, mainly with nail involvement, and COL7A1 c.5960del, a variant that generates a frameshift in exon 72 resulting in a premature stop codon; this variant was identified in two siblings with a severe recessive dystrophic. CONCLUSION: Important steps have been made in identifying the correct and complete diagnosis, as well as the characterization of EB patients addressing our reference center. The findings underscore the pivotal role of molecular genetic testing in confirming diagnoses and elucidating inheritance patterns, especially in cases with atypical presentations or de novo mutations.

Responsiveness and Minimal Clinically Important Difference of the Infants and Toddlers Dermatology Quality of Life Questionnaire.

BACKGROUND: The Infants and Toddlers Dermatology Quality of Life (InToDermQoL) is the dermatology-specific proxy health-related quality of life (HRQoL) instrument for children from birth to 4 years. The aim of the present study was to confirm the responsiveness and establish minimal clinically important difference (MCID) for the InToDermQoL. METHODS: Parents of children with skin diseases were asked to fill in the InToDermQoL at the initial visit (T1) and subsequent consultation (T2). We hypothesized that correlations between change scores of the InToDermQoL and change scores of global assessment of clinical severity by dermatologists and by patients' parents should be above 0.3. The receiver operating characteristic (ROC) curves method was also used for confirmation of responsiveness and determination of MCIDs of the InToDermQoL. The area under the ROC curve (AUC) was used as an indicator of responsiveness. RESULTS: Results of 442 patients were included. Correlations between change scores of age-specific versions of the InToDermQoL and change scores of global assessment of clinical severity by dermatologists and by patients' parents were above 0.3 (0.46-0.74). AUCs for age-specific versions of the InToDermQoL were acceptable (above 0.7) or excellent (above 0.8). Estimated MCIDs for the InToDermQoL were as follows: 3 points of total score change for 0-11 months, 5 for 1-2 years and 3 or 4 for 3-4 years version. Estimated MCIDs for the InToDermQoL version for 1-2-year-old children was higher than MCIDs for the 3-4-year-old version despite the higher number of items in the latter. Therefore a MCID of 5 was recommended for both these versions. CONCLUSIONS: Responsiveness for all age-specific versions of the InToDermQoL questionnaire was confirmed. MCIDs for the InToDermQoL are proposed as follows: 3-point change of the total score for age version 0-11 months and 5-point for the age versions 1-2 years and 3-4 years.

Mild-to-moderate severity of psoriasis may be assessed remotely based on photographs and self-reported extent of skin involvement.

Background: Remote monitoring was used to assess and manage skin diseases. Objective: To investigate to what extent smartphone photographs along with a self-reported body region (BR) score can be used to evaluate psoriasis severity. Methods: Psoriasis severity was assessed in the clinic using the psoriasis area and severity index and the physician's global assessment. On the same day, the patients took a photograph of a representative lesion from 4 BR (head/neck, upper limbs, trunk, and lower limbs) and completed a questionnaire about BR score. The photographs were rated by 5 dermatologists. Intraclass correlation coefficients with 95% CIs were calculated. Results: Overall, 32 were included, of which 6% had almost clear, 69% had mild, and 25% had moderate psoriasis. Perfect agreement between the self-reported and the doctors' BR score was observed for 59%, and near-perfect agreement (deviation of maximum 1 score) was 92%. The intraclass correlation coefficient between clinical and photographic psoriasis area and severity index was 0.78 (95% CI, 0.55-0.90), and for physician's global assessment, perfect agreement was 53%. Conclusions: The agreement between psoriasis severity assessed clinically and by photographs was good in a study setting. This gives the opportunity to remotely assess psoriasis severity by combining photographs with self-reported BR scores.

Quality of life measurement in vitiligo. Position statement of the European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes with external experts.

Members of the European Academy of Dermatology and Venereology (EADV) Task Force on Quality of Life (QoL) and Patient Oriented Outcomes reviewed the instruments available for health-related (HR) QoL assessment in vitiligo and together with external vitiligo experts (including representatives of the EADV Vitiligo Task Force) have made practical recommendations concerning the assessment of QoL in vitiligo patients. The Dermatology Life Quality Index (DLQI) was the most frequently used HRQoL instrument, making comparison of results between different countries possible. Several vitiligo-specific instruments were identified. The vitiligo Impact Scale (VIS) is an extensively validated vitiligo-specific HRQoL instrument with proposed minimal important change and clinical interpretation for VIS-22 scores. VIS-22 was developed for use in India, where there are some specific cultural beliefs concerning vitiligo. The EADV Task Force on QoL and Patient Oriented Outcomes recommends use of the DLQI and the Children's Dermatology Life Quality Index (CDLQI) as dermatology-specific instruments in vitiligo. There is a strong need for a valid (including cross-cultural validation) vitiligo-specific instrument that can be either a new instrument or the improvement of existing instruments. This validation must include the proof of responsiveness.

Mild to moderate atopic dermatitis severity can be reliably assessed using smartphone-photographs taken by the patient at home: A validation study.

BACKGROUND: The use of photographs to diagnose and monitor skin diseases is gaining ground. OBJECTIVES: To investigate the validity and reliability of photographic assessments of atopic dermatitis (AD) severity. METHODS: AD severity was evaluated in the clinic by two assessors using the Eczema Area and Severity Index (EASI), SCOring Atopic Dermatitis (SCORAD), and Investigator's Global Assessment (IGA). Participants photographed the lesions with their own smartphone and completed a questionnaire about the extent of eczema the same day from home. The photographs were assessed twice with an 8 weeks interval by five dermatologists experienced in photographic evaluations. Intraclass correlation coefficients (ICC) with 95% confidence interval (CI) were applied. RESULTS: Seventy-nine participants were enrolled. The ICC between clinical EASI and photographic EASI was 0.88 (95% CI 0.81-0.93), and 0.86 (0.70-0.93) between clinical SCORAD and photographic SCORAD. Perfect agreement between clinical IGA and photograph IGA was observed for 62%, with the difference between the two never deviating with more than 1 score. The inter-rater ICC for photographic EASI and photographic SCORAD, respectively, was 0.90 (0.85-0.94), and 0.96 (0.91-0.98). The intra-rater agreements between the first and second assessments varied from 0.95 to 0.98 for photographic EASI, and from 0.86 to 0.94 for photographic SCORAD. CONCLUSION: There was high agreement between mild to moderate AD severity assessed clinically and based on smartphone photographs. Further, the photographic assessments can be reproduced with high reliability.

Remote Rating of Atopic Dermatitis Severity Using Photo-Based Assessments: Proof-of-Concept and Reliability Evaluation.

BACKGROUND: Digital imaging of dermatological patients is a novel approach to remote assessment and has recently become more relevant since telehealth and remote decentralized clinical trials are gaining ground. OBJECTIVE: We aimed to investigate whether photographs taken by a smartphone are of adequate quality to allow severity assessments to be made and to explore the usefulness of an established atopic dermatitis severity assessment instrument on photograph evaluation. METHODS: During scheduled visits in a previously published study, the investigating doctor evaluated the severity of atopic dermatitis using the Scoring AD (SCORAD) index and took photographs of the most representative lesions (target lesions) with both a smartphone and a digital single-lens reflex camera (DSLR). The photographs were then assessed by 5 dermatologists using the intensity items of the SCORAD (iSCORAD), which consists of erythema, oedema/papulation, excoriations, lichenification, oozing/crusts, and dryness (scale 0-3, maximum score 18). The mean iSCORAD of the photographs was calculated and compared with in-person assessments using Pearson correlation and Bland-Altman plots. Intraclass correlation coefficients were used for interrater reliability. RESULTS: A total of 942 photographs from 95 patients were assessed. The iSCORAD based on smartphone photographs correlated strongly with the evaluations performed in person (iSCORAD: r=0.78, P<.001; objective SCORAD: r=0.81, P<.001; and total SCORAD: r=0.78, P<.001). For iSCORAD specifically, a Bland-Altman plot showed a difference in mean score of 1.31 for in-person and remote iSCORAD. In addition, the interrater agreement between the 5 rating dermatologists was 0.93 (95% CI 0.911-0.939). A total of 170 lesions were photographed, and the difference in mean scores was 1.32, 1.13, and 1.43 between in-person and remote evaluations based on photographs taken by a DSLR camera, a smartphone without flash, and a smartphone with flash, respectively. CONCLUSIONS: In terms of quality, remote atopic dermatitis severity assessments based on photographs are comparable to in-person assessments, and smartphone photos can be used to assess atopic dermatitis severity to a similar degree as photographs from a DSLR camera. Further, the variation in how the dermatologists in this study rated the iSCORAD based on the photographs was very low.

Prevention of Hand Eczema among Nurse Apprentice (PREVEDERM): An Interventional Study.

BACKGROUND: Workers in the healthcare sector are at high risk of developing occupational hand eczema mainly due to frequent exposure to irritants and/or allergens. Amongst workers in healthcare, nurses are at higher risk of developing hand dermatitis. OBJECTIVES: To evaluate the effectiveness of a short educational intervention program in preventing occupational hand eczema in nurse apprentices, using two objective tools, namely TEWL and EH, and the HECSI score. METHODS: Data regarding professions, wet work exposure, activities performed during working hours, self-reported eczema were collected from 230 nurse students, divided in two study groups: the intervention and the control group (CG). The intervention group (IG) was given education about risks and proper skin care and was provided with cosmeceuticals to be used for skin care during hospital activity. The evaluation of skin properties was performed using questionnaires, HECSI score, measurement of transepidermal water loss (TEWL) and epidermal hydration (EH). RESULTS: A number of 139 apprentice nurses completed the study. Of those participants who completed the study, 19.1% from CG and 19.6% from IG reported, at T1, hand eczema in the last 3 months, while at T2 (3 months later), 59.52 % of the CG and only 11.34 % from the IG stated having eczema in the last 3 months. In the IG, results showed an improvement of CM with 17% and of TEWL with 16%, with only a 0.5% improvement of CM in CG and a marked impairment of TEWL by 33%. CONCLUSION: Hand eczema is a common occupational dermatosis affecting the medical staff, even during apprenticeship. Early preventive training programs are effective in reducing the burden of occupational contact dermatitis.

Initial validation of the epidermolysis bullosa-specific module of the Infants and Toddlers Dermatology Quality of Life questionnaire.

Children with epidermolysis bullosa (EB) experienced the highest quality of life impact among several skin conditions and have problems which had not been reported by parents of children with other skin diseases. The EB-specific module of the Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire was recently developed to measure the impact of disease-specific aspects in children from birth to the age of 4 years. The aim of this study was initial validation of the InToDermQoL-EB questionnaire. Parents of 44 children with EB from seven countries completed the InToDermQoL-EB questionnaire. Cronbach's alpha was .86, .89 and .91 for three age-specific versions. Differences between severity levels were all significant except for that between moderate and severe level in the version for 3- to 4-year-old children. All items of the three versions of the InToDermQoL-EB showed very high levels of relevance except "problems with defecation" in children younger than 1 year and "rejection by other children" in 3- to 4-year-old children. The three versions of the InToDermQoL-EB instrument showed good internal consistency and discriminated well between different severity levels. All InToDermQoL-EB items were confirmed as being of high relevance and the questionnaire may be used in practice and clinical trials.