"Quality of Life in Epidermolysis Bullosa" and "Epidermolysis Bullosa Burden of Disease": Italian translation, cultural adaptation, and pilot testing of two disease-specific questionnaires.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a clinically and genetically heterogeneous group of skin fragility disorders characterized by blister formation following minor trauma. Four major types are distinguished based on the level of cleavage within the skin. Most EB forms present severely disabling cutaneous and systemic signs and symptoms. Management relies on daily time-consuming and distressing topical medications, and symptomatic treatment of systemic findings. Disease manifestations, symptoms, and daily care strongly affect patient and caregiver quality of life (QoL). To date, there are two validated EB-specific questionnaires, the "Quality of Life in Epidermolysis Bullosa" (QOLEB) and the "Epidermolysis Bullosa Burden of Disease" (EB-BoD) for the evaluation of patient and family disease burden, respectively. The aim of our study was to develop an Italian translation of the two questionnaires and to pilot-test them. METHODS: The guidelines for translation and cross-cultural adaptation of health-related QoL measures were followed. Initially, two separate translations were generated for each questionnaire, and subsequently reconciled by an expert committee. This was followed by a back-translation process. The original texts and all translations underwent revision by the expert committee, resulting in definitive versions. The final versions were then tested in a pilot study involving cognitive debriefing in a group of 17 families, representative of all EB major types. RESULTS: The translation and reconciliation process led to minor changes to obtain semantic/idiomatic/cultural equivalence of the Italian versions with the original ones and to reconcile the questions with the answer options. The cognitive debriefing process showed a good understanding and did not require text modifications. CONCLUSIONS: The Italian versions of the QOLEB and EB-BoD provide valuable tools in everyday clinical practice of reference centers, and they allow the participation in multicenter international real-life observational studies as well as in controlled clinical trials. They enable the identification of disease-specific psychological and socioeconomic challenges for EB patients and their families, guiding targeted interventions to ensure appropriate and timely care.

Health-related quality of life and clinical severity in people with epidermolysis bullosa - A proposal for assessing nutritional compromise by body mass index (Birmingham Epidermolysis Bullosa Severity Score).

Introduction: Introduction and objectives: epidermolysis bullosa (EB) is a rare genetic disease characterised by skin fragility with blisters and erosions on the skin and/or mucous membranes. People with EB often experience several extracutaneous manifestations, including clinical and health-related quality of life (HRQoL) complications. Herein, we evaluate their HRQoL and clinical severity and propose an objective criterion for estimating nutritional compromise using the Birmingham Epidermolysis Bullosa Severity Score (BEBS) tool. Methods: this series of cases included people with EB, monitored by a multi-professional team. Clinical severity was assessed with the BEBS, using body mass index ranges by age, as an objective proposal, to estimate the degree of nutritional compromise. To assess HRQoL, the Children's Dermatology Life Quality Index (individuals aged 4-16 years) and the Quality of Life Evaluation in Epidermolysis Bullosa - Brazilian Portuguese (individuals 17 years and over) were used. Results: of the nine individuals with recessive dystrophic EB (88.9 % female and 12.91 (SD = 11.71) years), the mean total BEBS score was 24.47 (SD = 12.80) points on a scale of 0 to 100 points. Six participants had significant nutritional compromise according to the proposed criteria. Five of the six participants evaluated for HRQoL reported experiencing some impact, with individuals aged 17 and over being more affected and with greater clinical severity. Conclusions: individuals with greater clinical severity of EB experience a more significant impact on their HRQoL. The proposed quantitative criteria for assessing nutritional compromise may help standardise assessments by professionals monitoring the nutritional status of individuals with EB. Keywords: Quality of life. Epidermolysis bullosa. Body mass index.

Introducción: Introducción y objetivos: la epidermólisis bullosa (EB) es una rara enfermedad genética caracterizada por fragilidad de la piel con ampollas y erosiones. Las personas con EB experimentan manifestaciones extracutáneas y complicaciones clínicas y de calidad de vida relacionada con la salud (CVRS). Evaluamos la CVRS y la gravedad clínica y proponemos un criterio objetivo para estimar el deterioro nutricional con la herramienta Birmingham Epidermolysis Bullosa Severity Score (BEBS). Métodos: esta serie de casos incluyó pacientes con EB monitoreadas por un equipo multiprofesional. Se evaluó la gravedad clínica con el BEBS utilizando rangos de índice de masa corporal por edad. Para evaluar la CVRS se utilizaron el Children's Dermatology Life Quality Index (individuos de 4 a 16 años) y el Quality of Life Evaluation in Epidermolysis Bullosa ­ Brazilian Portuguese (individuos de 17 años y más). Resultados: de los nueve individuos con EB distrófica recesiva (88,9 % mujeres y 12,91 (DE = 11,71) años), la puntuación total media del BEBS fue de 24,47 (DE = 12,80) puntos en una escala de 0 a 100 puntos. Seis participantes tenían un deterioro nutricional significativo según los criterios propuestos. Cinco de los seis participantes evaluados en la CVRS informaron experimentar algún impacto, siendo los individuos de 17 años y más los más afectados y con mayor gravedad clínica. Conclusiones: los pacientes con mayor gravedad clínica experimentan un impacto más significativo en su CVRS. Los criterios cuantitativos propuestos para evaluar el deterioro nutricional pueden ayudar a estandarizar las evaluaciones de los profesionales que monitorean el estado nutricional de las personas con EB.

Patients' and parents' experiences during wound care of epidermolysis bullosa from a dyadic perspective: a survey study.

BACKGROUND: Epidermolysis bullosa is a rare, often severe, genetic disorder characterized by fragility of the skin and mucous membranes. Despite the important role of parents during wound care, an essential factor in adapting to this disease, studies focusing on the parent-child relationship during wound care are scarce. The current study is aimed at addressing this gap. METHODS: A quantitative study among 31 children (n = 21 ≤ 17 years; n = 10 17-25 years) and 34 parents (including 27 parent-child dyads) was conducted to examine the relationship between pain, itch, anxiety, positive and negative feelings, and coping strategies assessed with the newly developed Epidermolysis Bullosa Wound Care List. The majority of the analyses were descriptive and the results were interpreted qualitatively because of the small sample size. RESULTS: Children and parents both showed significantly more positive (i.e. 'protected', 'proud', 'calm', 'connected to each other' and 'courageous') than negative feelings (i.e. 'helpless', 'angry', 'insecure', 'guilty', 'gloomy' and 'sad') during wound care, with parents reporting both feelings more than children. The more children experienced pain, the more they were anxious, had negative feelings, were inclined to use distraction, to postpone wound care and to cry. The more parents experienced feelings (either positive or negative), the more likely they sought distraction. With regard to child-parent dyads the results showed that the more children expressed anxiety, the more parents experienced negative feelings. Furthermore, those who reported more negative feelings were more likely to hide their feelings, while those who reported more positive feelings were more inclined to show their feelings. Pain, itch and anxiety in the child were associated with more distraction or postponement of wound care by the parent. CONCLUSION: This study underlines the importance of paying attention to the relationship between feelings and coping strategies in child-parent dyads in the management of pain and anxiety during wound care. Further research could provide more insight how these feelings and coping strategies are related to the psychological well-being of both the child and the parent in the short term as well as in the long term.

Transcultural Validation of a Spanish Version of the Quality of Life in Epidermolysis Bullosa Questionnaire.

INTRODUCTION: Epidermolysis bullosa (EB) is a relatively infrequent genodermatosis for which there is still no cure, and which impacts the quality of life of those that are affected by it. The Quality of Life evaluation in Epidermolysis Bullosa (QoLEB) questionnaire was specifically developed for English-speaking persons with EB. OBJECTIVES: To undertake the transcultural adaptation and analysis of the psychometric properties of a Spanish version of the QoLEB questionnaire. METHOD: We designed an observational study to implement the process of translation and validation of the scale in accordance with World Health Organisation guidelines. We assessed the content validity of the Spanish version with the participation of 33 adult patients who presented with four principal subtypes of EB. The subjects were examined and evaluated using the QoLEB and Short Form-36 (SF-36) questionnaires. RESULTS: The Spanish version of the QoLEB displayed excellent internal consistency and content validity, α = 0.91. Test-retest reliability was likewise excellent (ps = 0.93), as was the reliability among subtypes (range ps = 0.82-0.93). The functional part of the QoLEB correlated well with the SF-36 physical component summary (ps = 0.70). The emotional QoLEB was moderately correlated with the SF-36 mental component summary (ps = 0.49). Significant discriminant validity existed between the global score of the questionnaire (p = 0.033) and the functional scale (p = 0.003). CONCLUSIONS: The Spanish version of the QoLEB questionnaire can be recommended for use in any subsequent studies seeking to assess the efficacy of possible treatments and care programmes in this group.

Epidermolysis Bullosa: A case study in Cyprus and the nursing care plan.

PURPOSE: To present a case study with Epidermolysis bullosa (EB) in Cyprus and to determine the nursing care plan, explaining the nursing interventions and showing the importance of nursing care of patients with EB. METHODS: Literature review on EB and semi-structured interviews commenced through a direct discussion with open-ended questions to the research subject as well as to a close relative describing his feelings, experiences, and concerns about the disease. FINDINGS: Thematic analysis approach was used to identify and analyze patterns in the data. Then, data were synthesized using the standardized nursing terminology of NANDA-I and the Nursing Interventions Classification. The accuracy of the diagnoses and the appropriateness of the nursing interventions were supported by the positive health outcomes of the patient. CONCLUSIONS: Nurses should apply evidence-based practice interventions for EB wound care, pain management, nutrition, psychological and social support to these patients. IMPLICATIONS FOR NURSING PRACTICE: Although EB is classified in the category of rare diseases, the presentation of a case study in Cyprus and the nursing care plan contribute further bibliographically to the holistic and at the same time individualized nursing practice.

Investigational Treatments for Epidermolysis Bullosa.

Epidermolysis bullosa (EB) is a heterogeneous group of rare inherited blistering skin disorders characterized by skin fragility following minor trauma, usually present since birth. EB can be categorized into four classical subtypes, EB simplex, junctional EB, dystrophic EB and Kindler EB, distinguished on clinical features, plane of blister formation in the skin, and molecular pathology. Treatment for EB is mostly supportive, focusing on wound care and patient symptoms such as itch or pain. However, therapeutic advances have also been made in targeting the primary genetic abnormalities as well as the secondary inflammatory footprint of EB. Pre-clinical or clinical testing of gene therapies (gene replacement, gene editing, RNA-based therapy, natural gene therapy), cell-based therapies (fibroblasts, bone marrow transplantation, mesenchymal stromal cells, induced pluripotential stem cells), recombinant protein therapies, and small molecule and drug repurposing approaches, have generated new hope for better patient care. In this article, we review advances in translational research that are impacting on the quality of life for people living with different forms of EB and which offer hope for improved clinical management.

Quality of life in people with epidermolysis bullosa: a systematic review.

PURPOSE: Individuals with epidermolysis bullosa (EB) present with various clinical manifestations of different severities that affect quality of life (QoL). This systematic review synthesizes the current evidence about the QoL of individuals with EB. METHODS: We included observational studies with people of all age groups, both sexes, and any EB type. Studies with qualitative methodology, chapters of books, meeting proceedings, and abstracts were excluded. RESULTS: In this study, 12 articles comprising 745 individuals were included. More than half of the articles observed lower QoL in individuals with recessive dystrophic EB (RDEB) or junctional EB (JEB). Three articles indicated that EB affected QoL more in women than in men, and one article identified that children with EB suffered more than adults with the disease. Pain was frequently reported. Seven articles identified difficulty in sports, two identified a need for bathing assistance, and three identified eating difficulties. Additionally, participants reported that family relationships and friendships were affected, and they experienced feelings of anxiety and depression. Some of the instruments used evaluated QoL in general dermatologic conditions, and one was specific to EB. CONCLUSION: QoL is more affected in people who have RDEB and JEB. Regarding sex and age, women and children need special care in their monitoring. It is necessary that guidelines on pain management be more disseminated and put into practice. Future studies should use standardized specific instruments to assess the QoL in EB individuals, while considering the particularities of the different age groups.

Oleogel-S10 Phase 3 study "EASE" for epidermolysis bullosa: study design and rationale.

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare, genetic diseases that affect the integrity of epithelial tissues, most notably the skin. Patients experience recurrent skin wounding, with severity depending on type, sub-type, and mutation. Oleogel-S10, a formulation of birch bark extract, has demonstrated efficacy in a Phase 2 trial assessing re-epithelialization of wounds in EB. EASE (NCT03068780, EudraCT 2016-002066-32) is a randomized, Phase 3, placebo-controlled study designed to determine the efficacy of Oleogel-S10 versus placebo in patients with EB. METHODS: EASE is a Phase 3, two-phase study comprising a 90-day, double-blind, randomized, placebo-controlled phase, followed by 24 months of open-label, single-arm follow-up. Patients with junctional EB, dystrophic EB, or Kindler syndrome and target wounds (10 - 50cm2) present for > 21 days and < 9 months, are randomized in a 1:1 ratio to receive wound dressings according to local standard of care with or without Oleogel-S10. Placebo is based on the Oleogel-S10 vehicle, which is sunflower oil formulated to have a consistency indistinguishable from that of the active product. The primary endpoint of the trial, directed by the US health authority according to the required study endpoints for chronic cutaneous ulcer and burn wounds, is to compare the efficacy of Oleogel-S10 versus placebo according to the proportion of patients with complete closure of the target wound within 45 ± 7 days of treatment. Additional EB-focused endpoints include wound burden, patient-reported outcomes, and safety. RESULTS: Results of the primary endpoint are anticipated to be available by H2 2019. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03068780 . EudraCT, 2016-002066-32. Registered on 3 March 2017.

Psychosocial recommendations for the care of children and adults with epidermolysis bullosa and their family: evidence based guidelines.

Epidermolysis Bullosa (EB) is a group of rare genetic disorders resulting in skin fragility and other symptoms. Commissioned by DEBRA International and funded by DEBRA Norway, this evidence-bases guideline provides recommendations to optimise psychosocial wellbeing in EB.An international multidisciplinary panel of social and health care professionals (HCP) and people living with EB was formed. A systematic international literature review was conducted by the panel following the Scottish Intercollegiate Guidelines Network (SIGN) methodology. The resulting papers underwent systematic selection and critique processes. Included papers were allocated to 6 different outcome groups to allow data synthesis and exploration: quality of life, coping, family, wellbeing, access to HCP and pain. Based on the evidence in those papers, recommendations were made for individuals living with EB, family and caregivers and HCP working in the field.Few studies have investigated interventions and which factors lead to better outcomes, but general recommendations can be made. EB is a complex disease impacting enormously on every aspect of psychosocial life. People and families living with EB need access to multidisciplinary support, including psychological guidance, in order to improve quality of life and psychosocial wellbeing. Interventions should stimulate social participation to prevent isolation. People with EB and their families should be able to access a supportive network. HCP should be well supported and educated about the complexity of EB. They should work collaboratively with those around the individual with EB (e.g. schools, employers etc.) to provide psychosocial opportunity and care.Attention should be paid to the psychosocial impact of EB as well as physical needs. Directions for research are indicated.

Impact of Painful Wound Care in Epidermolysis Bullosa During Childhood: An Interview Study with Adult Patients and Parents.

Epidermolysis bullosa (EB) is a group of rare inherited bullous skin disorders that differ in nature and severity. Currently, there is no cure for the disease. One of the complex problems of EB is the repetitive and painful care of skin wounds. The purpose of this study was to explore how adult patients and parents experienced the impact of wound care during childhood and which coping strategies they considered as helping. A qualitative study was performed, comprising semi-structured in-depth interviews with 7 adult patients and 6 parents. The impact, physically, psychologically and on daily life, was apparent for patients and parents. Helpful coping strategies were transferring care, regulating emotions, and dyadic strategies, such as supporting each other by distraction, encouragement, using rituals and collaboration. The most important finding of this study is the need for a more thorough investigation into the effectiveness of dyadic coping strategies.

Pain Quality Assessment Scale for Epidermolysis Bullosa.

Pain is one of the most debilitating symptoms in epidermolysis bullosa (EB) leading to reduced quality of life. Pain in EB comprises both neuropathic and non-neuropathic qualities. An assessment of pain qualities has not formerly been completed in EB. The Pain Quality Assessment Scale (PQAS) is an adjusted version of the validated Neuropathic Pain Scale and includes 20 pain qualities and descriptors. Patients with EB (n = 43) rated the pain qualities in the PQAS on 20 numerical scales and 1 multiple choice question. Pain was experienced by 39 patients (91%). In general, patients with EB experience intense and unpleasant pain on the surface of the skin; the hands and feet are most commonly affected. The subtypes, recessive dystrophic EB and junctional EB reported pain qualities pathognomonic of neuropathic pain. The PQAS adds value to the current practice of global pain intensity scoring in EB.

[Epidermolysis bullosa: oral manifestations and their treatments]. / Az epidermolysis bullosa szájüregi tünetei és annak ellátása.

The aim of this comprehensive article is to provide guidelines for the daily treatment of patients with epidermolysis bullosa, thus contributing to the attainment of their higher quality of life through the improvement of their oral health. Moreover, it is our intention to facilitate the cooperation among Hungarian general practitioners, dermatologists and dentists. Relying on recent research findings of the international literature, we intend to help general practitioners or dermatologists treating epidermolysis bullosa patients on a daily basis by identifying symptoms that require consulting an oral professional on the one hand, and to present the most important prevention strategies and further treatments advised for dentists on the other. Focusing on various aspects of dental treatment, we specify how a dentist can treat the patient without causing additional wounds or pain, and what kinds of therapy are justified by this approach. Orv Hetil. 2017; 158(40): 1577-1583.

Advancement in management of epidermolysis bullosa.

PURPOSE OF REVIEW: Epidermolysis bullosa is a hereditary skin disorder characterized by skin fragility. However, the disease can manifest in many different organ systems, therefore children born with epidermolysis bullosa may have life long, complex medical needs. In this review, we will use a system-based approach to highlight important aspects of disease management and recent advancements in each of the areas. In addition, we will overview some of the cutting edge therapeutic developments in epidermolysis bullosa. RECENT FINDINGS: Recent advancements in supportive care of epidermolysis bullosa with focus on wound, pain, pruritus and nutrition status were discussed. Clinical surveillance and complication prevention are critical to improve clinical outcomes. Generalized epidermolysis bullosa is a systemic disease with increased morbidity and mortality; therefore, complex care using a multidisciplinary approach will provide the greatest benefits for patients. Current targeted treatments for epidermolysis bullosa aim at restoring the skin integrity using protein, cell, and gene therapies. SUMMARY: Improvement in care of epidermolysis bullosa in recent years results from keen clinical observation, novel molecular targeting, and the embracement of translational research.

Social/economic costs and health-related quality of life in patients with epidermolysis bullosa in Europe.

BACKGROUND: The aim of this study was to determine the social/economic costs and health-related quality of life (HRQOL) of patients with epidermolysis bullosa (EB) in eight EU member states. METHODS: We conducted a cross-sectional study of patients with EB from Bulgaria, France, Germany, Hungary, Italy, Spain, Sweden and the United Kingdom. Data on demographic characteristics, health resource utilisation, informal care, labour productivity losses, and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. RESULTS: A total of 204 patients completed the questionnaire. Average annual costs varied from country to country, and ranged from €9509 to €49,233 (reference year 2012). Estimated direct healthcare costs ranged from €419 to €10,688; direct non-healthcare costs ranged from €7449 to €37,451 and labour productivity losses ranged from €0 to €7259. The average annual cost per patient across all countries was estimated at €31,390, out of which €5646 accounted for direct health costs (18.0 %), €23,483 accounted for direct non-healthcare costs (74.8 %), and €2261 accounted for indirect costs (7.2 %). Costs were shown to vary across patients with different disability but also between children and adults. The mean EQ-5D score for adult EB patients was estimated at between 0.49 and 0.71 and the mean EQ-5D visual analogue scale score was estimated at between 62 and 77. CONCLUSION: In addition to its negative impact on patient HRQOL, our study indicates the substantial social/economic burden of EB in Europe, attributable mostly to high direct non-healthcare costs.

[Hereditary epidermolysis bullosa in school children and adolescents. Clinical picture and interdisciplinary management]. / Epidermolysis bullosa hereditaria bei Schulkindern und Adoleszenten. Klinik und interdisziplinäres Management.

Hereditary epidermolysis bullosa (EB) represents a clinically heterogeneous group of congenital blistering disorders requiring multiprofessional care. EB is associated with a broad spectrum of potentially severe complications often reaching their full extent during school age and adolescence. This review aims at summarizing cutaneous manifestations of EB as well as extracutaneous complications of this complex disease and their interdisciplinary management.

Translation, cross-cultural adaptation and validation of the Quality of Life Evaluation in Epidermolysis Bullosa instrument in Brazilian Portuguese.

BACKGROUND: The Quality of Life Evaluation in Epidermolysis Bullosa (QoLEB) questionnaire was developed for use in English-speaking individuals. OBJECTIVES: The aims of this study were to translate the QoLEB into Brazilian Portuguese, to culturally adapt it, and to verify its reliability and validity. METHODS: The study followed the steps proposed by the World Health Organization, which include: translation; evaluation by a panel of experts and patients; back translation; and linguistic and cultural adaptation. All subjects were examined and assessed using the QoLEB and the Dermatology Life Quality Index (DLQI) or the Children's Dermatology Life Quality Index (CDLQI). Translation and cultural and linguistic adaptation were conducted by 10 patients, three translators, and the bilingual authors. RESULTS: The population was composed of 40 children (mean age: 8,15 years) and 17 adults (mean age: 33 years). Among the children, eight had epidermolysis bullosa (EB) simplex (EBS), one had junctional EB (JEB), and 31 had dystrophic EB (DEB). In the adult group, four of the subjects had EBS, one had JEB, and 12 had DEB. Mean ± standard deviation (SD) scores on the QoLEB in children were 10.60 ± 7.13 in EBS subjects, 9.71 ± 7.87 in children with dominant DEB (DDEB), and 14.25 ± 9.67 in children with recessive DEB (RDEB). Mean ± SD scores in adults were 12.50 ± 9.95 in EBS subjects, 12.00 ± 5.83 in DDEB subjects, and 20.20 ± 9.21 in RDEB subjects. The QoLEB-BP (Brazilian Portuguese) showed high internal consistency (Cronbach's α = 0.88) and high test-retest reliability (intraclass correlation coefficient: 0.70), confirming the internal consistency and reproducibility of this Portuguese version. There were significant correlations between QoLEB scores and both CDLQI (Pearson's r = 0.688, P < 0.002) and DLQI (Pearson's r = 0.807, P < 0.001) scores. CONCLUSIONS: Epidermolysis bullosa has marked impacts on the lives of EB patients and their families, which are strongly correlated with disease severity. The Brazilian Portuguese version of the QoLEB is validated and can be recommended for use in subsequent studies.

Development and validation of an epidermolysis bullosa family/parental burden score.

BACKGROUND: The notion of the individual burden associated with a disease has been introduced to determine 'disability' in the broadest sense: psychological, social, economic and physical. Subtypes of epidermolysis bullosa (EB) are rare, life-threatening, untreatable chronic genodermatoses. OBJECTIVES: To develop and validate a specific questionnaire assessing the burden on families of children with EB: Epidermolysis Bullosa Burden of Disease (EB-BoD). METHODS: Items were generated by a verbatim report from parents of children with EB. Subsequently, a study was implemented for psychometric analysis. An epidermolysis bullosa burden-of-disease questionnaire was refined via item reduction according to inter-question correlations, consensus among experts and exploratory factor analysis. Internal consistency was determined by calculating Cronbach's α. Concurrent validity was determined by calculating the correlation between EB-BoD and the Short-Form 12 items (SF-12) questionnaire. RESULTS: From a primary list of 30 items, EB-BoD was reduced to a 20-item questionnaire, covering four disease aspects based on the exploratory factor analysis. Construct validity was demonstrated and the EB-BoD questionnaire showed good internal consistency (Cronbach's α = 0·9). The resulting EB-BoD score was significantly correlated to the mental dimension of SF-12 (r = -0·61), but it was not correlated to it's physical dimension (r = 0·04). EB-BoD scores were significantly discriminating between EB subtypes. CONCLUSIONS: The EB-BoD questionnaire appears to be a useful assessment tool regarding medical and socioeconomic issues in patients with EB and their families. EB-BoD scores correlate well with the family/parental burden experienced by the families of patients with EB.