RESUMO
The hallmark of epidermolysis bullosa (EB) is fragile attachment of epithelia due to genetic variants in cell adhesion genes. We describe 16 EB patients treated in the ear, nose, and throat department of a tertiary pediatric hospital linked to the United Kingdom's national EB unit between 1992 and 2023. Patients suffered a high degree of morbidity and mortality from laryngotracheal stenosis. Variants in laminin subunit alpha-3 (LAMA3) were found in 10/15 patients where genotype was available. LAMA3 encodes a subunit of the laminin-332 heterotrimeric extracellular matrix protein complex and is expressed by airway epithelial basal stem cells. We investigated the benefit of restoring wild-type LAMA3 expression in primary EB patient-derived basal cell cultures. EB basal cells demonstrated weak adhesion to cell culture substrates, but could otherwise be expanded similarly to non-EB basal cells. In vitro lentiviral overexpression of LAMA3A in EB basal cells enabled them to differentiate in air-liquid interface cultures, producing cilia with normal ciliary beat frequency. Moreover, transduction restored cell adhesion to levels comparable to a non-EB donor culture. These data provide proof of concept for a combined cell and gene therapy approach to treat airway disease in LAMA3-affected EB.
Assuntos
Adesão Celular , Epidermólise Bolhosa , Laminina , Lentivirus , Humanos , Laminina/metabolismo , Laminina/genética , Epidermólise Bolhosa/genética , Epidermólise Bolhosa/metabolismo , Epidermólise Bolhosa/terapia , Epidermólise Bolhosa/patologia , Criança , Lentivirus/genética , Masculino , Feminino , Pré-Escolar , Terapia Genética/métodos , Vetores Genéticos/genética , Células Epiteliais/metabolismo , Células Cultivadas , Expressão Gênica , Adolescente , LactenteRESUMO
In the context of rare genetic diseases caused by nonsense mutations, the concept of induced stop codon readthrough (SCR) represents an attractive avenue in the ongoing search for improved treatment options. Epidermolysis bullosa (EB)-exemplary for this group of diseases-describes a diverse group of rare, blistering genodermatoses. Characterized by extreme skin fragility upon minor mechanical trauma, the most severe forms often result from nonsense mutations that lead to premature translation termination and loss of function of essential proteins at the dermo-epidermal junction. Since no curative interventions are currently available, medical care is mainly limited to alleviating symptoms and preventing complications. Complementary to attempts of gene, cell and protein therapy in EB, SCR represents a promising medical alternative. While gentamicin has already been examined in several clinical trials involving EB, other potent SCR inducers, such as ataluren, may also show promise in treating the hitherto non-curative disease. In addition to the extensively studied aminoglycosides and their derivatives, several other substance classes-non-aminoglycoside antibiotics and non-aminoglycoside compounds-are currently under investigation. The extensive data gathered in numerous in vitro experiments and the perspectives they reveal in the clinical setting will be discussed in this review.
Assuntos
Códon sem Sentido , Epidermólise Bolhosa , Humanos , Códon de Terminação , Gentamicinas/farmacologia , Gentamicinas/uso terapêutico , Aminoglicosídeos/farmacologia , Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Epidermólise Bolhosa/genética , Epidermólise Bolhosa/terapiaRESUMO
DEBRA International is undertaking a long-term initiative to develop clinical practice guidelines (CPGs) for epidermolysis bullosa (EB), to -improve the clinical care of people living with EB. Current neonatal care is based on evidence, clinical expertise and trial and error, with collaboration between the EB specialist team, parent or carer and patient, and is dependent on the neonate's individual presentation and type of EB. Early intervention based on research and clinical practice is needed to establish a foundation of knowledge to guide international practitioners to create and improve standards of care and to be able to work effectively with those newly diagnosed with EB. This CPG was created by an international panel with expertise working with persons with EB. The CPG focuses on neonatal care using a systematic review methodology covering four key areas: (i) diagnosis and parental psychosocial support; (ii) hospital management: medical monitoring, wound care and pain; (iii) feeding and nutrition; and (iv) discharge planning and EB education. These four areas highlight the importance of a multidisciplinary team approach, to provide a patient-specific holistic care model that incorporates the needs and wishes of the parents and carers. The Hospital Implementation Tool included promotes transfer of theory to clinical practice.
Assuntos
Epidermólise Bolhosa , Humanos , Recém-Nascido , Epidermólise Bolhosa/terapia , Epidermólise Bolhosa/diagnóstico , Pais , Alta do Paciente/normas , Equipe de Assistência ao Paciente/organização & administraçãoRESUMO
BACKGROUND: In contrast to clinical diagnosis via external examination, patient-related outcome measures (PROMs) allow access to patients' internal perceptions. In the case of epidermolysis bullosa (EB) - a rare disease characterized by a wide variety of symptoms and individual disease courses - it is important to integrate the patient's perspective into diagnostic processes. The Instrument for Scoring Clinical Outcomes of Research for EB (iscorEB) is an EB-specific measurement tool, combining a clinician score (iscorEB-c) and a patient questionnaire (iscorEB-p). OBJECTIVES: The aim of this study is to establish the iscorEB-p as an independent PROM tool by exploring its psychometric properties. METHODS: Sample-based psychometric testing and evaluation were performed on data collected via a multinational online cross-sectional study. RESULTS: Data analysis was performed with n = 95 participants across all EB types. The reliability and internal consistency of the iscorEB-p was excellent (α = 0.90). Principal component analysis with a varimax rotation resulted in a two-factor solution, explaining 55.6% of the total variance, with the distinct factors 'everyday life functioning' and 'specific EB symptoms'. Convergent validity was shown by high correlations to the Satisfaction With Life Scale (r = -0.52, P < 0.001), the Quality of Life in Epidermolysis Bullosa questionnaire (r = 0.72, P < 0.001) and the Epidermolysis Bullosa Family Burden of Disease questionnaire (r = -0.73, P < 0.001). CONCLUSIONS: The iscorEB-p is a reliable and valid instrument to assess patient-reported health status of people with EB.
Epidermolysis bullosa (EB) is a rare chronic condition characterized by fragility of the skin. Even minimal friction leads to the formation of blisters and wounds. People with EB are often called 'butterfly children' because their skin is as fragile as a butterfly's wings. EB affects about 500,000 people worldwide and there is currently no cure. As EB is a chronic disease, it is associated with constantly changing periods of better and worse health. To monitor the impact of EB on patients, it is important to record a range of relevant possible symptoms using a valid questionnaire. The Instrument for Scoring Clinical Outcomes of Research for EB (iscorEB) is such a measurement tool, combining a clinician score (iscorEB-c) and a patient questionnaire (iscorEB-p). However, until now, the patient questionnaire could only be used in addition to the clinician score. In this study, we aimed to emphasize patients' perspectives and strengthen the patient questionnaire so that it can be used independently. The questionnaire can support patients to assess even minimal changes over a period of the last 4 weeks. We collected data from 95 patients with EB from all over the world. Through statistical analysis, we found that the questionnaire is a useful new standalone instrument to obtain a patient-based view of their health status. Overall, our study findings suggest that the iscorEB-p is a reliable and valid tool and could be usefully applied in clinical practice, as an addition to quality-of-service monitoring and in future research studies.
Assuntos
Epidermólise Bolhosa , Medidas de Resultados Relatados pelo Paciente , Psicometria , Qualidade de Vida , Humanos , Epidermólise Bolhosa/diagnóstico , Epidermólise Bolhosa/psicologia , Epidermólise Bolhosa/terapia , Psicometria/normas , Masculino , Feminino , Adulto , Estudos Transversais , Reprodutibilidade dos Testes , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Criança , Inquéritos e Questionários/normas , Idoso , Índice de Gravidade de Doença , Pré-EscolarRESUMO
BACKGROUND: Epidermolysis bullosa (EB), characterized by skin fragility and blistering, often requires hospitalization. Training for inpatient management of EB is limited, with no unified recommendations available in North America. OBJECTIVE: To develop consensus-derived best practices for hands-on inpatient management of EB in both the neonatal and postneonatal period. METHODS: A modified Delphi method (expert-based input via 2 surveys and a final review) was implemented. Available guidelines from EB Clinical Research Consortium centers were analyzed to determine areas of focus and formulate statements to be voted on by EB Clinical Research Consortium members, experienced EB nurses, and select family members. Study participants evaluated statements using a Likert scale: statements with at least 70% agreement were accepted; statements with 30% or more disagreement were rejected. RESULTS: Ten areas of focus were identified. Delphi participants included 15 dermatologists, 8 nurses, and 6 nonhealth care caregivers. Consensus was established on 103/119 neonatal statements and 105/122 postneonatal statements; no statements were rejected. Most recommendations applied to both age groups. LIMITATIONS: Recommendations may require adjustment based on individual patient's clinical context. CONCLUSION: Using the Delphi method, a consensus-derived resource for hospital-based health care professionals who manage patients with EB has been developed to improve the quality of inpatient care.
Assuntos
Consenso , Técnica Delphi , Epidermólise Bolhosa , Humanos , Recém-Nascido , Epidermólise Bolhosa/terapia , Hospitalização , Guias de Prática Clínica como Assunto , Lactente , Feminino , Dermatologia/métodos , Dermatologia/normas , MasculinoRESUMO
BACKGROUND: Epidermolysis bullosa (EB) comprises a group of rare types of genodermatoses characterized by extreme mucocutaneous fragility, leading to blistering and/or erosions, even with minimal trauma. Continuous care through wound management is an integral part of daily life for the families and individuals affected. The aim of this study was to assess the social reality and impacts on families of having minor members diagnosed with EB in Spain. METHODS: A qualitative methodology was employed, utilizing four focus groups entailing participation by 24 parents (19 mothers and five fathers) of minors diagnosed with EB in Spain. RESULTS: Negative impacts on the family nucleus were evident in four priority areas of analysis: sociorelational, economic-labour, physical and psychoemotional, with significant differences observed based on the severity of the symptoms. CONCLUSION: Impacts on the family nucleus are noticeable from birth, influencing all other daily life routines and complicating family planning and organization. There is an imperative need to enhance the availability of sociohealth resources and to adopt an interdisciplinary approach to address their biopsychosocial needs. PATIENT OR PUBLIC CONTRIBUTION: The active participation of relatives of minors diagnosed with Epidermolysis Bullosa (EB) is invaluable to sociohealth professionals, legislators and researchers. A team member conducts their professional activities at DEBRA España (national patient association dedicated to enhancing the quality of life for individuals with EB and their families), actively engaging in all study phases.
Assuntos
Epidermólise Bolhosa , Grupos Focais , Pesquisa Qualitativa , Humanos , Espanha , Epidermólise Bolhosa/psicologia , Epidermólise Bolhosa/terapia , Feminino , Masculino , Criança , Adolescente , Adulto , Menores de Idade/psicologia , Qualidade de Vida , Pré-Escolar , Família/psicologia , Fatores SocioeconômicosRESUMO
Epidermolysis bullosa (EB) is a genodermatosis that lacks effective treatments and requires supportive care for its severe, life-threatening manifestations. Bone marrow transplantation (BMT) and its derived cells have been suggested to improve clinical symptoms and quality of life. A comprehensive search was conducted for publications evaluating BMT and bone marrow-derived mesenchymal stem cell (BM-MSC) therapy for EB in PubMed/MEDLINE, Google Scholar, and Cochrane databases from inception until June 2023. A total of 55 participants with severe forms of EB had BMT and/or BM-MSCs, with recessive dystrophic EB as the most common EB type; 53 (96.4%) patients had better wound healing, and 3 (5.5%) patients died of sepsis. The most common adverse events reported were graft failure, sepsis, graft-versus-host disease, and renal insufficiency. Allogeneic BMT is a high-risk procedure with possible benefits and adverse events. BM-MSCs revealed favorable outcomes to improve the safety of EB cell-based therapy by minimizing the risk of serious adverse events, reducing blisters, and accelerating wound healing. Further studies are needed to assess the treatment's long-term effects and clarify the risk/benefit ratio of procedure versus conventional therapy.
Assuntos
Transplante de Medula Óssea , Epidermólise Bolhosa , Transplante de Células-Tronco Mesenquimais , Humanos , Transplante de Medula Óssea/métodos , Epidermólise Bolhosa/terapia , Transplante de Células-Tronco Mesenquimais/métodos , CicatrizaçãoRESUMO
The monogenetic disease epidermolysis bullosa (EB) is characterised by the formation of extended blisters and lesions on the patient's skin upon minimal mechanical stress. Causal for this severe condition are genetic mutations in genes, leading to the functional impairment, reduction, or absence of the encoded protein within the skin's basement membrane zone connecting the epidermis to the underlying dermis. The major burden of affected families justifies the development of long-lasting and curative therapies operating at the genomic level. The landscape of causal therapies for EB is steadily expanding due to recent breakthroughs in the gene therapy field, providing promising outcomes for patients suffering from this severe disease. Currently, two gene therapeutic approaches show promise for EB. The clinically more advanced gene replacement strategy was successfully applied in severe EB forms, leading to a ground-breaking in vivo gene therapy product named beremagene geperpavec (B-VEC) recently approved from the US Food and Drug Administration (FDA). In addition, the continuous innovations in both designer nucleases and gene editing technologies enable the efficient and potentially safe repair of mutations in EB in a potentially permanent manner, inspiring researchers in the field to define and reach new milestones in the therapy of EB.
Assuntos
Epidermólise Bolhosa , Humanos , Epidermólise Bolhosa/genética , Epidermólise Bolhosa/terapia , Epidermólise Bolhosa/patologia , Pele/metabolismo , Epiderme/metabolismo , Vesícula , MutaçãoRESUMO
BACKGROUND: Epidermolysis bullosa (EB) is a rare, genetically and clinically heterogeneous group of skin fragility disorders. No cure is currently available, but many novel and repurposed treatments are upcoming. For adequate evaluation and comparison of clinical studies in EB, well-defined and consistent consensus-endorsed outcomes and outcome measurement instruments are necessary. OBJECTIVES: To identify previously reported outcomes in EB clinical research, group these outcomes by outcome domains and areas and summarize respective outcome measurement instruments. METHODS: A systematic literature search was performed in the databases MEDLINE, Embase, Scopus, Cochrane CENTRAL, CINAHL, PsycINFO and trial registries covering the period between January 1991 and September 2021. Studies were included if they evaluated a treatment in a minimum of three patients with EB. Two reviewers independently performed the study selection and data extraction. All identified outcomes and their respective instruments were mapped onto overarching outcome domains. The outcome domains were stratified according to subgroups of EB type, age group, intervention, decade and phase of clinical trial. RESULTS: The included studies (n = 207) covered a range of study designs and geographical settings. A total of 1280 outcomes were extracted verbatim and inductively mapped onto 80 outcome domains and 14 outcome areas. We found a steady increase in the number of published clinical trials and outcomes reported over the past 30â years. The included studies mainly focused on recessive dystrophic EB (43%). Wound healing was reported most frequently across all studies and referred to as a primary outcome in 31% of trials. Great heterogeneity of reported outcomes was observed within all stratified subgroups. Moreover, a diverse range of outcome measurement instruments (n = 200) was identified. CONCLUSIONS: We show substantial heterogeneity in reported outcomes and outcome measurement instruments in EB clinical research over the past 30â years. This review is the first step towards harmonization of outcomes in EB, which is necessary to expedite the clinical translation of novel treatments for patients with EB.
Assuntos
Epidermólise Bolhosa Distrófica , Epidermólise Bolhosa , Humanos , Epidermólise Bolhosa/terapia , Cicatrização , Sistema de Registros , Medidas de Resultados Relatados pelo PacienteRESUMO
Epidermolysis bullosa (EB) is a devastating genetic condition caused by mutations in genes that give rise to aberrant proteins. There are 16 different such proteins implicated in EB that are important in maintaining the integrity of the dermoepidermal junction. It is classified into four major subtypes: (i) EB simplex; (ii) junctional EB (JEB); (iii) dystrophic EB (DEB); and (iv) Kindler EB. Renal disease is a recognized complication of EB and the aetiology is complex. We describe our experience of managing five patients with EB and IgA nephropathy. We recommend that patients with recessive DEB and JEB routinely have the following monitored: renal function, urinary albumin/creatinine ratio, urine analysis, serum albumin levels and immunoglobulins; specifically serum IgA. Management of IgA nephropathy in the context of EB should be tailored to the individual and be carried out within a specialist multidisciplinary team. Our case series provides important insights into the treatment of IgA nephropathy in patients with EB and will help inform treatment in this rare genetic disease. Case series and reports like ours are key in gaining real-life data to quantify the actual risk of morbidity and mortality from each of the treatment modalities discussed.
Assuntos
Epidermólise Bolhosa , Glomerulonefrite por IGA , Adulto , Humanos , Epidermólise Bolhosa/sangue , Epidermólise Bolhosa/complicações , Epidermólise Bolhosa/genética , Epidermólise Bolhosa/terapia , Epidermólise Bolhosa Distrófica , Epidermólise Bolhosa Simples , Epidermólise Bolhosa Juncional , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/etiologia , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/terapiaRESUMO
There are little published data on the transition of care in EB. We conducted a survey study recruiting EB patients from the Dystrophic EB Research Association (debra) website and centers caring for high numbers of EB patients in the United States and internationally from Sept 17, 2019 to Nov 3, 2021. The majority of participants had not discussed the transition of care with their healthcare providers, nor the healthcare needs to be required as an adult. Ongoing pediatric subspecialty care was reported by 12% of adults, most commonly in pediatric dermatology. Identified barriers to transition included the perceived lack of adult providers' knowledge about EB patient healthcare needs. The results suggest the need for transition guidelines, early discussions with families about transition, and practical information for the adult providers accepting care.
Assuntos
Epidermólise Bolhosa Distrófica , Epidermólise Bolhosa , Criança , Adulto , Humanos , Transferência de Pacientes , Epidermólise Bolhosa/terapia , Inquéritos e Questionários , Pessoal de SaúdeRESUMO
BACKGROUND/OBJECTIVES: Gastrostomy tubes (G-tubes) are a feasible intervention for nutritional support in patients with epidermolysis bullosa (EB) who suffer from gastrointestinal involvement. However, some parents may be apprehensive about this surgical intervention. The purpose of this study is to assess caregiver satisfaction and experiences after G-tube insertion in children with EB. METHODS: Nine institutions sent an anonymous 89-item online questionnaire to caregivers of patients with EB and active G-tubes during an 8-week study period. The questionnaire consisted of eight sections and was formatted with multiple choice, Likert scales, dichotomous scales (yes/no), and free text. RESULTS: Twenty caregiver surveys were completed. All caregivers were parents (100%). The average age of G-tube placement was 2.7 years (SD: 2.1, range 0-8) and duration of the G-tube utilization was an average of 12.0 years (SD: 7.8, range 1-25). EB subtypes were dystrophic (n = 15/20, 75%), junctional (n = 3/20, 15%), and simplex (n = 2/10, 10%). Almost all caregivers (n = 18/20, 90%) reported high levels of satisfaction with G-tube management (scores > 20 on the modified SAGA-8 scale). More than half of caregivers (n = 12/20, 60%) reported that, retrospectively, they would have desired earlier adoption of the G-tube. Caregivers rated mealtimes as more enjoyable and easier both for themselves and the individual with EB post-G-tube placement. CONCLUSION: The survey demonstrates a high rate of satisfaction for G-tube use among caregivers of patients with EB across varying ages and household settings. The free-text responses provide unique insight into caregiver's individual experiences regarding G-tubes to be considered for future studies.
Assuntos
Epidermólise Bolhosa Distrófica , Epidermólise Bolhosa , Criança , Humanos , Recém-Nascido , Lactente , Pré-Escolar , Cuidadores , Gastrostomia/efeitos adversos , Nutrição Enteral , Estudos Retrospectivos , Epidermólise Bolhosa/terapiaRESUMO
Nonsense mutations trigger premature translation termination and often give rise to prevalent and rare genetic diseases. Consequently, the pharmacological suppression of an unscheduled stop codon represents an attractive treatment option and is of high clinical relevance. At the molecular level, the ability of the ribosome to continue translation past a stop codon is designated stop codon readthrough (SCR). SCR of disease-causing premature termination codons (PTCs) is minimal but small molecule interventions, such as treatment with aminoglycoside antibiotics, can enhance its frequency. In this review, we summarize the current understanding of translation termination (both at PTCs and at cognate stop codons) and highlight recently discovered pathways that influence its fidelity. We describe the mechanisms involved in the recognition and readthrough of PTCs and report on SCR-inducing compounds currently explored in preclinical research and clinical trials. We conclude by reviewing the ongoing attempts of personalized nonsense suppression therapy in different disease contexts, including the genetic skin condition epidermolysis bullosa.
Assuntos
Códon sem Sentido , Doenças Genéticas Inatas , Elongação Traducional da Cadeia Peptídica , Medicina de Precisão , Doenças Raras , Supressão Genética , Animais , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Códon sem Sentido/genética , Fibrose Cística/genética , Fibrose Cística/terapia , Epidermólise Bolhosa/genética , Epidermólise Bolhosa/terapia , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/terapia , Nefrite Hereditária/genética , Nefrite Hereditária/terapia , Degradação do RNAm Mediada por Códon sem Sentido , Elongação Traducional da Cadeia Peptídica/efeitos dos fármacos , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Doenças Raras/genética , Doenças Raras/terapia , Retinose Pigmentar/genética , Retinose Pigmentar/terapia , Síndrome de Shwachman-Diamond/genética , Síndrome de Shwachman-Diamond/terapia , Supressão Genética/efeitos dos fármacos , Supressão Genética/genética , Terminação Traducional da Cadeia Peptídica/efeitos dos fármacos , Aminoglicosídeos/farmacologiaRESUMO
OBJECTIVE: To identify cases and summarize outcomes of cutaneous malignancies in patients with epidermolysis bullosa (EB). DATA SOURCES: MEDLINE and EMBASE databases were searched on February 8, 2022. STUDY SELECTION: Original observational or experimental studies with cases of cutaneous malignancy in patients with inherited EB were included. DATA EXTRACTION: Data were extracted by two reviewers in duplicate. DATA SYNTHESIS: A total of 87 articles with 367 patients were included in this systematic review. Squamous cell carcinomas were the most common malignancy (94.3%) with a median survival of 60 months. The presence of metastasis was investigated at diagnosis in 77 patients; 18.8% of patients had detectable metastasis. Patients with squamous cell carcinoma with metastasis at diagnosis had significantly shorter median survival (16.8 months) than those without (72 months; P = .027). The remission rate was 47.6%. At the end of follow-up, 15.1% were alive with disease, and 41.6% were deceased. Other malignancies included malignant melanoma and basal cell carcinoma. The most common initial modes of management were excisions (71.9%) and amputations (17.6%). Other modes included chemotherapy (4.6%), radiation (3.9%), and no treatment (2.6%). The overall rate of recurrence or new lesions was 38.8%, with a median time of 16 months to recurrence or new lesions. Immediate recurrence was lowest following amputation (4.3%). There were no statistically significant differences in median survival among initial excision, amputation, and all other modes combined ( P = .30). CONCLUSIONS: Squamous cell carcinomas in patients with EB have a high likelihood of metastasis and mortality. Surgical excision is the most common intervention. There are no significant differences in survival among different initial management options. There is a need for research that documents and monitors outcomes of the treatment options.
Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Epidermólise Bolhosa , Melanoma , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Epidermólise Bolhosa/complicações , Epidermólise Bolhosa/terapia , Epidermólise Bolhosa/patologiaAssuntos
Epidermólise Bolhosa , Assistência ao Paciente , Relações Médico-Paciente , Humanos , Epidermólise Bolhosa/complicações , Epidermólise Bolhosa/mortalidade , Epidermólise Bolhosa/psicologia , Epidermólise Bolhosa/terapia , Atitude do Pessoal de Saúde , Atitude Frente a Morte , Criança , Adulto , Assistência ao Paciente/psicologiaRESUMO
Epidermolysis bullosa (EB) encompasses a heterogeneous group of inherited skin fragility disorders, with mutations in genes encoding the basement membrane zone (BMZ) proteins that normally ensure dermal-epidermal integrity. Of the four main EB types, recessive dystrophic EB (RDEB), especially the severe variant, represents one of the most debilitating clinical entities, with recurrent mucocutaneous blistering and ulceration leading to chronic wounds, infections, inflammation, scarring and ultimately cutaneous squamous cell carcinoma, which leads to premature death. Improved understanding of the molecular genetics of EB over the past three decades and advances in biotechnology have led to rapid progress in developing gene and cell-based regenerative therapies for EB. In particular, RDEB is at the vanguard of advances in human clinical trials of advanced therapeutics. Furthermore, the past decade has witnessed the emergence of a real collective, global effort involving academia and industry, supported by international EB patient organizations such as the Dystrophic Epidermolysis Bullosa Research Association (DEBRA), among others, to develop clinically relevant and marketable targeted therapeutics for EB. Thus, there is an increasing need for the practising dermatologist to become familiar with the concept of gene therapy, fundamental differences between various approaches, and their human applications. This review explains the principles of different approaches of gene therapy, summarizes its journey, and discusses its current and future impact in RDEB.
Assuntos
Carcinoma de Células Escamosas , Epidermólise Bolhosa Distrófica , Epidermólise Bolhosa , Neoplasias Cutâneas , Carcinoma de Células Escamosas/terapia , Epidermólise Bolhosa/genética , Epidermólise Bolhosa/patologia , Epidermólise Bolhosa/terapia , Epidermólise Bolhosa Distrófica/genética , Epidermólise Bolhosa Distrófica/patologia , Epidermólise Bolhosa Distrófica/terapia , Terapia Genética , Humanos , Neoplasias Cutâneas/terapiaRESUMO
BACKGROUND: Transition from pediatric to adult care is a critical component of health care for children with long-term needs. The characteristics of epidermolysis bullosa (EB) demand higher than average levels of provider support. There is consensus among health care professionals regarding the importance of transition; however, there is a scarcity of practical information regarding models for patients with EB. OBJECTIVE: To review transition of care programs in varying specialties. Highlight practical considerations to facilitate the development of programs for patients with EB and other complex dermatologic conditions. METHODS: Articles were identified via MEDLINE and EMBASE health literature databases and screened for relevance to transition of care. RESULTS: Various models for transition exist. A well-executed formal transition program, early introduction, interdisciplinary collaboration, and psychosocial support were themes associated with successful outcomes. LIMITATIONS: Transition of care programs that have not been described in the literature are not reflected in this review. CONCLUSIONS: Patients with EB have unique needs that affect transition and span expertise across traditional boundaries, such as dependency on others for daily skin care, failure to thrive, and risk of squamous cell carcinoma. Given the rarity of the disease, patients with EB will benefit from collaborative efforts to develop programs to optimize successful transition.
Assuntos
Epidermólise Bolhosa , Transição para Assistência do Adulto , Adulto , Criança , Consenso , Bases de Dados Factuais , Epidermólise Bolhosa/complicações , Epidermólise Bolhosa/terapia , Humanos , Transferência de PacientesRESUMO
BACKGROUND: Epidermolysis bullosa (EB) is a group of rare epithelial disorders caused by abnormal or absent structural proteins at the epidermal-dermal junction. As a result, patients experience blisters and wounds from mild shearing forces. Some forms of EB are complicated by resultant scarring and contractures. The perioperative anesthetic management of patients with EB is complex and requires a systems-based approach to limit harm. We reviewed our experience with providing general anesthesia to patients at our tertiary EB referral center, including adverse events related to anesthetic care, outcomes in the immediate perioperative period, and details of anesthetic management. METHODS: We retrospectively reviewed the charts of all patients with EB anesthetized at the Children's Hospital Colorado between January 2011 and December 2016. A subset of pediatric anesthesiologists cared for all patients using a standardized clinical care pathway. Patient demographics, detailed anesthetic methods, immediate perioperative outcomes, and adverse events were characterized. RESULTS: Over a 6-year period, 37 patients underwent 202 general anesthetics. Most patients (75.7%) had dystrophic EB (DEB). Female patients comprised 48.6%. The majority (56.7%) traveled >50 miles to receive care, and many (35.1%) traveled >150 miles for their care. Common adaptations to care included avoidance of electrocardiogram leads (88.6%) and temperature probes (91.6%). Nasal fiberoptic intubation (n = 160) was performed, or natural airway/mask (n = 27) was maintained for most patients. Supraglottic devices were not used for airway management during any of the anesthetics. Anesthesia preparation time was longer (average 25.8 minutes [standard deviation {SD} = 12.7]) than our average institutional time (14 minutes). Succinylcholine was never used, and nondepolarizing muscle relaxants were used in only 1.5% of patient encounters. Blood was transfused in 16.3% of cases and iron infused in 24.8%. Average length of stay in the postanesthesia care unit was comparable to our institutional average (average 40.1 [SD = 28.6] vs 39 minutes). New skin or mucosal injury occurred in 8 encounters (4%), and desaturation occurred in 43 cases (21.3%). There were no major adverse events. CONCLUSIONS: By using a specialized team and a standardized clinical care pathway, our institution was able to minimize adverse events caused by the anesthetic and surgical care of patients with EB. We recommend natural airway or nasal fiberoptic airway management, meticulous avoidance of shear stress on the skin, and a multidisciplinary approach to care. Supportive therapy such as perioperative blood transfusions and iron infusions are feasible for the treatment of chronic anemia in this population.
Assuntos
Anestésicos , Epidermólise Bolhosa , Anestésicos/uso terapêutico , Criança , Epidermólise Bolhosa/complicações , Epidermólise Bolhosa/diagnóstico , Epidermólise Bolhosa/terapia , Feminino , Humanos , Ferro , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
"How to" skin care manuals assist health care professionals caring for hospitalized patients with epidermolysis bullosa and other disorders. Manuals created by Epidermolysis Bullosa Clinical Research Consortium sites were collected and analyzed. Analysis of manuals revealed variable content. Creating a unified, optimized "how" to manual would benefit providers and patients.
Assuntos
Epidermólise Bolhosa Distrófica , Epidermólise Bolhosa , Epidermólise Bolhosa/terapia , Humanos , Pacientes InternadosRESUMO
Although dermatologists are well-trained in the medical management of complex skin disease, psychosocial care often exceeds a dermatologist's skillset. We aim to elucidate major factors to consider in the comprehensive management of pediatric epidermolysis bullosa (EB) and provide care recommendations. There are many types of trauma a child with EB may experience, from social to psychological to medical. We include information on trauma-informed care and advice for the dermatologist and multidisciplinary team regarding patient-centered and family-centered approaches to recognizing and reducing anxiety and trauma in EB patients.