Hereditary epidermolysis bullosa: clinical-epidemiological profile of 278 patients at a tertiary hospital in São Paulo, Brazil

Abstract Background Epidermolysis bullosa (EB) is a group of rare hereditary diseases, characterized by fragility of the skin and mucous membranes. Epidemiological data on EB in Brazil are scarce. Objectives To describe epidemiological aspects of patients with EB diagnosed in the Dermatology Department of a tertiary hospital, from 2000 to 2022. Methods An observational and retrospective study was conducted through the analysis of medical records. The evaluated data included clinical form, sex, family history, consanguinity, age at diagnosis, current age, time of follow-up, comorbidities, histopathology and immunomapping, presence of EB nevi and squamous cell carcinomas (SCC), cause of and age at death. Results Of 309 patients with hereditary EB, 278 were included. The most common type was dystrophic EB (DEB), with 73% (28.4% dominant DEB, 31.7% recessive DEB and 12.9% pruriginous DEB). Other types were junctional EB with 9.4%, EB simplex with 16.5% and Kindler EB with 1.1%. Women accounted for 53% and men for 47% of cases. Family history was found in 35% and consanguinity in 11%. The mean age at diagnosis was 10.8 years and the current age was 26 years. The mean time of follow-up was nine years. Esophageal stenosis affected 14%, dental alterations affected 36%, malnutrition 13% and anemia 29%. During diagnostic investigation, 72.6% underwent histopathological examination and 92% underwent immunomapping. EB nevi were identified in 17%. Nine patients had SCC. Eleven patients died. Study limitations Insufficient data included to medical records, loss to follow-up, and unavailability of genetic testing. Conclusions In this study, dystrophic EB predominated and the need for multidisciplinary care for comorbidities and complications was highlighted.

Advantages of whole-exome sequencing over immunomapping in 67 Brazilian patients with epidermolysis bullosa

Abstract Background Epidermolysis bullosa (EB) is characterized by skin fragility and blistering. In Brazil, the diagnosis is usually obtained through immunomapping, which involves a skin biopsy. Most recently, whole exome sequencing (WES) has become an important tool for the diagnosis of the subtypes of EB, providing information on prognosis as well as allowing appropriate genetic counseling for the families. Objective To compare the results of immunomapping and molecular analysis and to describe the characteristics of a Brazilian cohort of patients with EB. Methods Patients were submitted to clinical evaluation and WES using peripheral blood samples. WES results were compared to those obtained from immunomapping testing from skin biopsies. Results 67 patients from 60 families were classified: 47 patients with recessive dystrophic EB (DEB), 4 with dominant DEB, 15 with EB simplex (EBS), and 1 with junctional EB (JEB). Novel causative variants were: 10/60 (16%) in COL7A1 associated with recessive DEB and 3 other variants in dominant DEB; one homozygous variant in KRT5 and another homozygous variant in PLEC, both associated with EBS. Immunomapping was available for 59 of the 67 patients and the results were concordant with exome results in 37 (62%), discordant in 13 (22%), and inconclusive in 9 patients (15%). Study limitations Even though EB is a rare disease, for statistical purposes, the number of patients evaluated by this cohort can still be considered limited; other than that, there was a significant difference between the proportion of types of EB (only one case with JEB, against more than 50 with DEB), which unfortunately represents a selection bias. Also, for a small subset of families, segregation (usually through Sanger sequencing) was not an option, usually due to deceased or unknown parent status (mostly the father). Conclusion Although immunomapping has been useful in services where molecular studies are not available, this invasive method may provide a misdiagnosis or an inconclusive result in about 1/3 of the patients. This study shows that WES is an effective method for the diagnosis and genetic counseling of EB patients.

Cuidados de enfermagem para paciente pediátrico com dermatite atópica e epidermólise bolhosa: revisão integrativa / Nursing care for pediatric patients with atopic dermatitis and epidermolysis bullosa: integrative review / Atención de enfermería a pacientes pediátricos con dermatitis atópica y epidermólisis ampollosa: revisión integrativa

A Dermatite Atópica e a Epidermólise Bolhosa são doenças crônicas que afetam a estrutura morfológica e bioquímica da pele, provocando lesões e alterações sistêmicas nos indivíduos afetados, podendo ocasionar infecções generalizadas. Este estudo teve como objetivo avaliar e sintetizar as contribuições das pesquisas produzidas sobre os cuidados de enfermagem para crianças com dermatite atópica ou epidermólise bolhosa. Trata-se de uma revisão integrativa, cuja pergunta norteadora foi: "Quais são os cuidados de enfermagem para o paciente pediátrico com dermatite atópica ou epidermólise bolhosa?". Sua busca aconteceu nas bases de dados: Medline; CINAHL; LILACS e CUIDEN. Não houve restrição quanto ao ano de publicação e foram analisados estudos publicados nos idiomas inglês, português e espanhol. Como resultados foram incluídos 23 estudos, dois quais duas categorias foram elencadas: Assistência de Enfermagem às Crianças Portadoras de Dermatite Atópica e a Epidermólise Bolhosa e, Educação em Saúde. Evidenciou-se a necessidade de investimento em pesquisas bem delineadas sobre o tema, pois a raridade da condição, a escassez de referencial e a dificuldade em encontrar pacientes aptos para intervenções são fatores que contribuem neste cenário científico.

The Atopic Dermatitis and Epidermolysis Bullosa are chronic diseases that affect the morphological and biochemical structure of the skin, causing lesions and systemic changes in affected individuals, which can lead to generalized infections. This study aimed to evaluate and synthesize the contributions of research produced on nursing care for children with atopic dermatitis or epidermolysis bullosa. This is an integrative review, whose guiding question was: "What is the nursing care for pediatric patients with atopic dermatitis or epidermolysis bullosa?". Your search took place in the following databases: Medline; CINAHL; LILACS and CUIDEN. There was no restriction on the year of publication and studies published in English, Portuguese and Spanish were analyzed. As results, 23 studies were included, two of which two categories were listed: Nursing Care for Children with Atopic Dermatitis and Epidermolysis Bullosa and Health Education. The need for investment in well-designed research on the topic was highlighted, as the The rarity of the condition, the scarcity of references and the difficulty in finding patients suitable for interventions are factors that contribute to this scientific scenario.

La Dermatitis Atópica y la Epidermólisis Bullosa son enfermedades crónicas que afectan la estructura morfológica y bioquímica de la piel, provocando lesiones y cambios sistémicos en los individuos afectados, que pueden derivar en infecciones generalizadas. Este estudio tuvo como objetivo evaluar y sintetizar las contribuciones de las investigaciones producidas sobre los cuidados de enfermería al niño con dermatitis atópica o epidermólisis ampollosa. Se trata de una revisión integradora, cuya pregunta orientadora fue: "¿Cuál es el cuidado de enfermería al paciente pediátrico con dermatitis atópica o epidermólisis ampollosa?". Su búsqueda se realizó en las siguientes bases de datos: Medline; CINAHL; LILAS y CUIDEN. No hubo restricción en el año de publicación y se analizaron los estudios publicados en inglés, portugués y español. Como resultados se incluyeron 23 estudios, dos de los cuales se enumeraron dos categorías: Atención de Enfermería al Niño con Dermatitis Atópica y Epidermólisis Bullosa y Educación para la Salud.Se destacó la necesidad de invertir en investigaciones bien diseñadas sobre el tema, ya que la rareza de la condición, la escasez de referencias y la dificultad para encontrar pacientes aptos para las intervenciones son factores que contribuyen a este escenario científico.

Inherited epidermolysis bullosa dystrophica and squamous cell carcinoma- A case report

Epidermolysis bullosa dystrophica (EBD) is an inherited disease of the structural proteins in the upper dermis, characterized by blister formation at the site of trauma followed by scarring. Skin fragility and blistering are the hallmarks of this disease. Cutaneous squamous cell carcinoma (cSCC) is a dreadful complication in the epidermolysis bullosa (EB) patients and common cause of death. The recent advances in distinct tumor microenvironment explain the aggressive nature of SCC in recessive Recessive Dystrophic Epidermolysis Bullosa (RDEB) patients and the use of collagen VII re-expression as a possible therapeutic measure. Regular follow-up is a must in preventing complications.

Terminologia especializada de enfermagem para o cuidado com crianças e adolescentes com epidermólise bolhosa / Specialized nursing terminology for the care of children and adolescents with epidermolysis bullosa / Terminología especializada de enfermería para el cuidado de niños y adolescentes con epidermólisis ampollosa

RESUMO Objetivo: construir uma terminologia especializada de enfermagem para o cuidado com crianças e adolescentes com epidermólise bolhosa. Método: estudo metodológico, documental, construído entre os meses de janeiro a dezembro de 2021, em parceria com o Centro CIPE®, em João Pessoa - Brasil. Os dados foram analisados com utilização da ferramenta PorOnto e dos seguintes referenciais teóricos metodológicos: a Classificação Internacional para Prática de Enfermagem 2019/2020; e o mapeamento humano seguindo a ISO/TR 12300:2016 e o método de validação dos termos. Resultados: o processo de validação com juízes resultou em 480 termos para criança e adolescente com epidermólise bolhosa, os quais foram submetidos ao mapeamento, resultando em 207 constantes na CIPE® e 273 não constantes na CIPE®. Conclusão: evidencia-se um quantitativo maior de termos não constantes, isto pode ser justificado pela peculiaridade da doença e cuidados específicos com a criança e adolescentes. A construção da terminologia fortalece a elaboração de diagnósticos, resultados e intervenção de enfermagem.

ABSTRACT Objective: To build a specialized nursing terminology for the care of children and adolescents with epidermolysis bullosa. Method: Methodological, documentary study, built between the months of January to December 2021, in partnership with the ICNP® Center, in João Pessoa - Brazil. Data were analyzed using the PorOnto tool and the following theoretical methodological references: the International Classification for Nursing Practice 2019/2020, and human mapping following ISO/TR 12300:2016 and the term validation method. Results: The validation process with judges resulted in 480 terms for children and adolescents with epidermolysis bullosa, which were submitted to mapping, resulting in 207 constant ICNP® terms and 273 non-constant ICNP® terms. Conclusion: a higher number of non-constant terms is evidenced, which can be justified by the peculiarity of the disease and specific care with children and adolescents. The construction of terminology strengthens the development of diagnoses, outcomes, and nursing intervention.

RESUMEN Objetivo: construir una terminología especializada de enfermería para el cuidado de niños y adolescentes con epidermólisis ampollosa. Método: Estudio metodológico, documental, construido entre los meses de enero y diciembre de 2021, en colaboración con el Centro CIPE®, en João Pessoa - Brasil. Los datos fueron analizados utilizando la herramienta PorOnto y las siguientes referencias teóricas metodológicas: la Clasificación Internacional para la Práctica de Enfermería 2019/2020; y el mapeo humano siguiendo la norma ISO/TR 12300:2016 y el método de validación de términos. Resultados: El proceso de validación con jueces dio como resultado 480 términos para niños y adolescentes con epidermólisis ampollosa, que se sometieron a mapeo, dando como resultado 207 términos incluidos en la CIPE® y 273 términos no incluidos en la CIPE®. Conclusión: se evidencia una mayor cantidad de términos no constantes, lo que puede justificarse por la peculiaridad de la enfermedad y los cuidados específicos de niños y adolescentes. La construcción de la terminología refuerza la elaboración de diagnósticos, resultados e intervenciones médicas.

Síndrome de Bart: aplasia cutis congénita y epidermólisis bullosa / Bart's syndrome: aplasia cutis congenita and epidermolysis bullosa

La aplasia cutis congénita, también conocida como síndrome de Bart, ha sido asociada con todos los subtipos principales de epidermólisis bullosa. Esta enfermedad afecta a 1 por cada 10 000 recién nacidos vivos; solo se han descrito 500 casos en la literatura médica. Se caracteriza por afectar un miembro inferior con patrón en forma de S y presentar lesiones de epidermólisis bullosa en cualquier otra parte del cuerpo. Se presenta el caso de una neonata con las características clínicas mencionadas, hospitalizada en el Servicio de Neonatología del Hospital Pediátrico Universitario «José Luis Miranda». Este diagnóstico es principalmente clínico y se basa en la evidencia de áreas de pérdida cutánea con predominio en miembros inferiores, lesiones ampollares en piel y mucosas, y deformidades ungueales. Su pronóstico puede ser fatal. Este caso reviste gran interés por su baja incidencia; su diagnóstico precoz contribuyó a evitar complicaciones.

Aplasia cutis congenita, also known as Bart's syndrome, has been associated with all the major epidermolysis bullosa subtypes. This disease affects 1 in 10, 000 live births; only 500 cases have been described in medical literature. It is characterized by affecting a lower limb with an S-shaped pattern and presenting epidermolysis bullosa lesions in any other part of the body. We present a female neonate with the aforementioned clinical features, who was hospitalized in the Neonatology service at "José Luis Miranda" Pediatric University Hospital. This diagnosis is mainly clinical and is based on evidence of areas of skin loss predominantly on the lower limbs, bullous lesions on the skin and mucous membranes and nail deformities. Its prognosis can be fatal. This case is of great interest due to its low incidence; its early diagnosis helped to avoid complications.

Genetic diagnosis in two families with dystrophic epidermolysis bullosa / 中华皮肤科杂志

Objective:To analyze clinical characteristics of and causative genes in two families with dystrophic epidermolysis bullosa, and to reveal the pathogenesis of the disease and mechanisms underlying phenotypic differences between patients.Methods:DNA was extracted from peripheral blood samples of members from two families with dystrophic epidermolysis bullosa, and subjected to high-throughput sequencing and Sanger sequencing.Results:The clinical manifestations of the 2 probands in the 2 families were consistent with the diagnosis of dystrophic epidermolysis bullosa, and the symptoms of the proband in family 1 were more serious than those of other patients in the family. Genetic testing showed that all patients in family 1 carried a mutation c.6082G>C (p.G2028R) in the COL7A1 gene, and the proband and her phenotypically normal mother and uncle also carried a splice-site mutation c.7068+2 (IVS91) T>G in the COL7A1 gene, both of which were first reported. The proband in family 2 carried the mutations c.6081_6082 ins C (p.G2028Rfs*71) and c.1892G>A (p.W631X, first reported) in the COL7A1 gene, which were inherited from her father and mother, respectively.Conclusion:The two pathogenic mutations may be the molecular mechanism underlying the severe clinical phenotype in the proband in family 1; the first reported mutations enriched the mutation spectrum of the COL7A1 gene.

Cell therapy for hereditary epidermolysis bullosa / 中华皮肤科杂志

Hereditary epidermolysis bullosa (EB) is a rare mutilating and lethal single-gene genodermatosis, and places a heavy burden on society and families. Cell therapy has become a very promising method for the treatment of EB due to its excellent and stable clinical efficacy. This review summarizes progress in laboratory research and clinical application of stem cell- and somatic cell-based therapies in EB in recent years.

Epidermólisis bulosa distrófica recesiva en mujer embarazada. Reporte de caso / Recessive dystrophic epidermolysis bullosa in pregnant women. Case report

Resumen INTRODUCCIÓN: La epidermólisis bulosa engloba a un grupo de enfermedades caracterizadas por una fragilidad extrema de la piel y membranas mucosas, consecuencia de la formación de ampollas posterior a un traumatismo mínimo. Hay tres tipos principales de epidermólisis. Se comunica el caso para hacer notar las implicaciones del cuidado al momento del nacimiento, y las consideraciones anestésicas. CASO CLÍNICO: Paciente de 25 años en su segundo embarazo con epidermólisis bulosa distrófica recesiva. El nacimiento fue electivo mediante cesárea, con anestesia regional. CONCLUSIONES: Debe tenerse especial cuidado durante las intervenciones terapéuticas a fin de evitar la formación de bulas o exacerbar las existentes. Las fuerzas de fricción son más dañinas que las de compresión. La planeación multidisciplinaria es necesaria para un desenlace sin complicaciones.

Abstract BACKGROUND: Epidermolysis bullosa encompasses a group of diseases characterized by extreme fragility of the skin and mucous membranes, resulting in the formation of blisters after minimal trauma; There are three main types of epidermolysis. The case is presented to highlight the implications of care both at the time of birth, as well as anesthetic considerations. CLINICAL CASE: A 25-year-old patient in her second pregnancy with recessive dystrophic epidermolysis bullosa. The birth was elective by caesarean section under regional anesthesia. CONCLUSIONS: Special care must be taken during therapeutic interventions to avoid the formation of bullae or exacerbate those already present. Friction forces are more damaging than compression forces. Multidisciplinary planning is necessary for a smooth outcome.

Vivências de mães no cuidado a crianças e adolescentes com Epidermólise Bolhosa / Experiencias de madres en el cuidado de niños y adolescentes con Epidermólisis Ampollosa / Experiences of mothers in the care of children and adolescents with epidermolysis bullosa

Resumo Objetivo conhecer e analisar as vivências de mães no cuidado a crianças e adolescentes com Epidermólise Bolhosa. Método estudo descritivo de abordagem qualitativa desenvolvido junto a dez mães de crianças e adolescentes com Epidermólise Bolhosa de diferentes regiões do Brasil, a partir de entrevistas semiestruturadas, áudio e vídeo gravadas, por via remota, utilizando-se a plataforma Google Meet®, entre setembro e novembro de 2021. A técnica da análise temática direcionou a apreciação do material empírico. Resultados participaram do estudo mães com idade entre 23 e 53 anos. Duas categorias traduzem a vivência materna: i) O "baque" do diagnóstico e os desafios iniciais e ii) "Deixar de viver para viver para ele": as mudanças no cotidiano das famílias. Considerações finais e implicações para a prática as mães vivenciaram sentimentos de medo e insegurança diante do diagnóstico do filho e a rotina de cuidados, em especial, as trocas diárias de curativos, acarretaram sobrecarga física e emocional. Esses resultados podem subsidiar o acompanhamento dessas famílias de modo a instrumentalizá-las para o cuidado e apoiá-las emocionalmente.

Resumen Objetivo conocer y analizar la vida de las madres en el cuidado de niños y adolescentes con Epidermólisis Bullosa. Método estudio descriptivo de abordaje cualitativo desarrollado junto a diez madres de niños y adolescentes con Epidermólisis Bullosa de diferentes regiones de Brasil, a partir de entrevistas semiestructuradas con grabación de audio y video, por vía remota, utilizando la plataforma Google Meet®, entre septiembre y noviembre de 2021. La técnica de análisis temático dirigió la apreciación del material empírico. Resultados participaron en el estudio mujeres de entre 23 y 53 años. Dos categorías traducen la experiencia materna: i) El "shock" del diagnóstico y los retos iniciales; y ii) "Dejar de vivir para vivir por él": los cambios en la vida cotidiana de las familias. Consideraciones finales e implicaciones para la práctica las madres experimentaron sentimientos de miedo e inseguridad ante el diagnóstico de su hijo y la rutina de cuidados, especialmente los cambios de apósito diarios provocaron una sobrecarga física y emocional. Estos resultados pueden servir de apoyo para el seguimiento de estas familias, con el fin de poder cuidarlas y apoyarlas emocionalmente.

Abstract Objective to know and analyze mothers' experiences in caring for children and adolescents with Epidermolysis Bullosa. Method a descriptive qualitative study was developed with ten mothers of children and adolescents with epidermolysis bullosa from different regions of Brazil using semi-structured interviews recorded remotely using Google Meet® between September and November 2021. The thematic analysis technique guided the appreciation of the empirical material. Results mothers aged between 23 and 53 years participated in the study. Two categories translate the maternal experience: i) the "shock" of the diagnosis and the initial challenges and ii) "Stop living to live for them": the changes in the families' daily life. Final considerations and implications for practice mothers experienced fear and insecurity when their child was diagnosed, and the care routine, especially the daily dressing changes, caused a physical and emotional burden. These results can support the follow-up of these families to provide them with care tools and emotional support.

Cuidados de enfermagem com crianças e adolescentes com epidermólise bolhosa: revisão sistemática / Cuidados de enfermería a niños y adolescente con epidermólisis ampollosa: revisión sistemática / Nursing care for children and adolescents with epidermolysis bullosa: a systematic review

Resumo Objetivo Analisar a produção científica referente às ações/Intervenções de Enfermagem no ambiente hospitalar relacionadas ao cuidado com crianças e adolescentes com epidermólise bolhosa. Métodos Revisão sistemática, cuja busca se deu nas bases Cinahl, MEDLINE®/PubMed®, SCOPUS, LILACS e SciELO, realizada no período de setembro de 2020 a janeiro de 2021. Para a busca, foram utilizados os descritores "epidermólise bolhosa" AND "criança" AND "adolescente" AND "enfermagem", nas bases Lilacs e SciELO, e "epidermolysis bullosa" AND "children" AND "adolescent" AND, "nursing" nas demais bases em inglês. Resultados Houve maior registro de artigos publicados com base na pergunta norteadora tendo como país de origem os Estados Unidos (22%). A maioria da classificação era no nível VI (44%) da evidência científica. Ainda, 86% dos estudos envolveram pesquisas para o plano de cuidados. As evidências encontradas decorreram de opiniões de especialistas, estudos de casos e consenso. Os fatores de cuidados mais citados foram planos de cuidados voltados à pele; troca de fraldas; cuidados com as roupas e uso de coberturas antiaderentes. Conclusão As pesquisas reportaram dificuldades quanto à disponibilidade de materiais, tratamento e profissionais especializados, além das limitações dos conhecimentos na prática clínica voltada às características da epidermólise bolhosa. Dentre os cuidados, houve destaque para informação sobre a complexidade e as características da ferida como forma de antecipar as estratégias de cuidado.

Resumen Objetivo Analizar la producción científica referente a las acciones/intervenciones de enfermería en el ambiente hospitalario relacionadas con el cuidado a niños y adolescentes con epidermólisis ampollosa. Métodos Revisión sistemática, cuya búsqueda se realizó en las bases Cinahl, MEDLINE®/PubMed®, SCOPUS, LILACS y SciELO, realizada en el período de septiembre de 2020 a enero de 2021. Para la búsqueda se utilizaron los descriptores "epidermólisis ampollosa" AND "niño" AND "adolescente" AND "enfermería", en las bases Lilacs y SciELO, y "epidermolysis bullosa" AND "children" AND "adolescent" AND, "nursing" en las demás bases en inglés. Resultados Con base en la pregunta orientadora, hubo un mayor registro de artículos publicados que tenían como país de origen Estados Unidos (22 %). La mayoría de la clasificación era de nivel VI (44 %) de la evidencia científica. Además, el 86 % de los estudios incluyeron investigaciones en el plano de los cuidados. Las evidencias encontradas derivaban de opiniones de especialistas, estudios de casos y consenso. Los factores de cuidados más citados fueron planos de cuidados orientados a la piel, cambio de pañales, cuidados con la ropa y uso de coberturas antiadherentes. Conclusión Las investigaciones indicaron dificultades en cuanto a la disponibilidad de material, tratamiento y profesionales especializados, además de las limitaciones de conocimientos en la práctica clínica orientada hacia las características de la epidermólisis ampollosa. Entre los cuidados, se destacó la información sobre la complejidad y las características de la herida como forma de anticipar las estrategias de cuidado.

Abstract Objective To analyze the scientific production regarding actions/Nursing Interventions in hospital environments related to the care of children and adolescents with epidermolysis bullosa. Methods This is a systematic review, which was searched in the CINAHL, MEDLINE®/PubMed®, Scopus, LILACS and SciELO databases, carried out from September 2020 to January 2021. For the search, the descriptors "epidermólise bolhosa" AND "criança" AND "adolescente" AND "enfermagem" were used, in Portuguese, in the LILACS and SciELO databases, and "epidermolysis bullosa" AND "children" AND "adolescent" AND "nursing" in the other databases. Results There was a greater number of articles published based on the guiding question having the United States as the country of origin (22%). Most of the classification was at level VI (44%) of scientific evidence. Still, 86% of studies involved research for the care plan. The evidence found resulted from expert opinions, case studies and consensus. The most cited care factors were skin care plans, diaper changing, clothing care and non-stick coating use. Conclusion The surveys reported difficulties regarding the availability of materials, treatment and specialized professionals, in addition to limitations of knowledge in clinical practice focused on the characteristics of epidermolysis bullosa. Among the care, there was emphasis on information about the wound complexity and characteristics as a way of anticipating care strategies.

Maintenance of chronicity signatures in fibroblasts isolated from recessive dystrophic epidermolysis bullosa chronic wound dressings under culture conditions

BACKGROUND: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the COL7A1 gene, coding for type VII collagen (C7), an important component of anchoring fibrils in the basement membrane of the epidermis. RDEB patients suffer from skin fragility starting with blister formation and evolving into chronic wounds, inflammation and skin fibrosis, with a high risk of developing aggressive skin carcinomas. Restricted therapeutic options are limited by the lack of in vitro models of defective wound healing in RDEB patients. RESULTS: In order to explore a more efficient, non-invasive in vitro model for RDEB studies, we obtained patient fibroblasts derived from discarded dressings) and examined their phenotypic features compared with fibroblasts derived from non-injured skin of RDEB and healthy-donor skin biopsies. Our results demonstrate that fibroblasts derived from RDEB chronic wounds (RDEB-CW) displayed characteristics of senescent cells, increased myofibroblast differentiation, and augmented levels of TGF-ß1 signaling components compared to fibroblasts derived from RDEB acute wounds and unaffected RDEB skin as well as skin from healthy-donors. Furthermore, RDEB-CW fibroblasts exhibited an increased pattern of inflammatory cytokine secretion (IL-1ß and IL-6) when compared with RDEB and control fibroblasts. Interestingly, these aberrant patterns were found specifically in RDEB-CW fibroblasts independent of the culturing method, since fibroblasts obtained from dressing of acute wounds displayed a phenotype more similar to fibroblasts obtained from RDEB normal skin biopsies. CONCLUSIONS: Our results show that in vitro cultured RDEB-CW fibroblasts maintain distinctive cellular and molecular characteristics resembling the inflammatory and fibrotic microenvironment observed in RDEB patients' chronic wounds. This work describes a novel, non-invasive and painless strategy to obtain human fibroblasts chronically subjected to an inflammatory and fibrotic environment, supporting their use as an accessible model for in vitro studies of RDEB wound healing pathogenesis. As such, this approach is well suited to testing new therapeutic strategies under controlled laboratory conditions.

Atresia pilórica / Pyloric Atresia

Introducción: La atresia pilórica es una afección rara, que en el 40-50 por ciento de los casos se asocia a otras anomalías, frecuentemente con la epidermolisis bullosa, asociación conocida como síndrome de Carmi. Objetivo: Informar sobre la evolución de una paciente tratada por atresia pilórica que tenía además una epidermolisis bullosa. Presentación del caso: Recién nacida con antecedentes prenatales de polihidramnios, parto eutócico a las 30,4 semanas, sepsis ovular materna, peso al nacer 1430 gramos; múltiples lesiones en piel, ampollosas y aplasia cutis en pierna izquierda. Se ventiló desde sala de partos, La paciente no toleró la alimentación enteral mínima. Se realizó estudio radiográfico y no se visualizó paso de contraste al píloro. Se diagnosticó una atresia pilórica y se operó al cuarto día de nacida. La paciente tenía una atresia pilórica tipo 2: sustitución del tejido pilórico por tejido fibroso. Se hizo una gastroduodenostomía. En su evolución se incrementaron por día las lesiones en piel, y tuvo reapertura del ductus arterioso, trastornos hidroelectrolíticos, y hemidinámicos que provocaron el fallecimiento a los 14 días de nacida. Conclusiones: La atresia pilórica es una afección muy rara, que debe tenerse en cuenta en recién nacidos con epidermolisis bullosa por la frecuente asociación entre estas dos afecciones; además, cuando existen antecedentes de polihidramnios y no tolerancia a la alimentación enteral. Los pacientes con la asociación atresia pilórica y epidermolisis bullosa generalmente presentan una evolución desfavorable (AU)

Introduction: Pyloric atresia is a rare condition, which in 40-50 percent of cases is associated with other anomalies, often with epidermolysis bullosa, an association known as Carmi syndrome. Objective: To report on the evolution of a patient treated due to pyloric atresia who also had epidermolysis bullosa. Case presentation: Female newborn with prenatal history of polyhydramnios, eutocic delivery at 30.4 weeks, maternal ovular sepsis, birth weight 1430 grams, with multiple skin lesions, blisters and aplasia cutis in the left leg. She was ventilated from the delivery room. The patient did not tolerate minimal enteral feeding. A radiographic study was performed and no contrast passage to the pylorus was visualized. Pyloric atresia was diagnosed and operated on the fourth day of birth. The patient had pyloric atresia type 2: replacement of pyloric tissue by fibrous tissue. A gastroduodenostomy was done. In its evolution, skin lesions increased per day and reopening of the ductus arteriosus was performed, she had hydroelectrolyte disorders, and hemidynamic disorders that caused death at 14 days of birth. Conclusions: Pyloric atresia is a very rare condition, which should be taken into account in newborns with epidermolysis bullosa due to the frequent association between these two conditions, also when there is a history of polyhydramnios and no tolerance to enteral feeding. Patients with pyloric atresia and epidermolysis bullosa usually have an unfavorable outcome(AU)

Atresia pilórica / Pyloric Atresia

Introducción: La atresia pilórica es una afección rara, que en el 40-50 por ciento de los casos se asocia a otras anomalías, frecuentemente con la epidermolisis bullosa, asociación conocida como síndrome de Carmi. Objetivo: Informar sobre la evolución de una paciente tratada por atresia pilórica que tenía además una epidermolisis bullosa. Presentación del caso: Recién nacida con antecedentes prenatales de polihidramnios, parto eutócico a las 30,4 semanas, sepsis ovular materna, peso al nacer 1430 gramos; múltiples lesiones en piel, ampollosas y aplasia cutis en pierna izquierda. Se ventiló desde sala de partos, La paciente no toleró la alimentación enteral mínima. Se realizó estudio radiográfico y no se visualizó paso de contraste al píloro. Se diagnosticó una atresia pilórica y se operó al cuarto día de nacida. La paciente tenía una atresia pilórica tipo 2: sustitución del tejido pilórico por tejido fibroso. Se hizo una gastroduodenostomía. En su evolución se incrementaron por día las lesiones en piel, y tuvo reapertura del ductus arterioso, trastornos hidroelectrolíticos, y hemidinámicos que provocaron el fallecimiento a los 14 días de nacida. Conclusiones: La atresia pilórica es una afección muy rara, que debe tenerse en cuenta en recién nacidos con epidermolisis bullosa por la frecuente asociación entre estas dos afecciones; además, cuando existen antecedentes de polihidramnios y no tolerancia a la alimentación enteral. Los pacientes con la asociación atresia pilórica y epidermolisis bullosa generalmente presentan una evolución desfavorable(AU)

Introduction: Pyloric atresia is a rare condition, which in 40-50 percent of cases is associated with other anomalies, often with epidermolysis bullosa, an association known as Carmi syndrome. Objective: To report on the evolution of a patient treated due to pyloric atresia who also had epidermolysis bullosa. Case presentation: Female newborn with prenatal history of polyhydramnios, eutocic delivery at 30.4 weeks, maternal ovular sepsis, birth weight 1430 grams, with multiple skin lesions, blisters and aplasia cutis in the left leg. She was ventilated from the delivery room. The patient did not tolerate minimal enteral feeding. A radiographic study was performed and no contrast passage to the pylorus was visualized. Pyloric atresia was diagnosed and operated on the fourth day of birth. The patient had pyloric atresia type 2: replacement of pyloric tissue by fibrous tissue. A gastroduodenostomy was done. In its evolution, skin lesions increased per day and reopening of the ductus arteriosus was performed, she had hydroelectrolyte disorders, and hemidynamic disorders that caused death at 14 days of birth. Conclusions: Pyloric atresia is a very rare condition, which should be taken into account in newborns with epidermolysis bullosa due to the frequent association between these two conditions, also when there is a history of polyhydramnios and no tolerance to enteral feeding. Patients with pyloric atresia and epidermolysis bullosa usually have an unfavorable outcome(AU)

Epidermólisis bullosa adquirida en un paciente pediátrico / Acquired epidermolysis bullosa in a pediatric patient

Resumen Introducción: La epidermólisis bullosa adquirida es una enfermedad ampollar subepidérmica autoinmune, rara y crónica caracterizada por la formación de autoanticuerpos contra colágeno tipo VII. La presentación en la infancia es poco frecuente y con manifestaciones variables. Caso clínico: Se describe el caso de una paciente de sexo femenino de 12 años de edad que presentó lesiones ampollares y polimórficas en tórax y extremidades de varios meses de evolución. Por las características de las lesiones cutáneas, se realizó un estudio histopatológico y de inmunofluorescencia directa que confirmó el diagnóstico de epidermólisis bullosa adquirida, por lo que se administró tratamiento con corticoide y dapsona, con una respuesta clínica favorable durante el seguimiento. Conclusiones: La epidermólisis bullosa adquirida es inusual en la edad pediátrica. Por tanto, debe considerarse en el diagnóstico diferencial de otras enfermedades ampollares congénitas y adquiridas de la infancia. El diagnóstico definitivo se realiza a través del estudio de inmunofluorescencia, lo que permite instaurar rápidamente un tratamiento rápido y eficaz para controlar la enfermedad y evitar secuelas permanentes.

Abstract Background: Acquired epidermolysis bullosa is a rare and chronic autoimmune subepidermal bullous disease characterized by the formation of autoantibodies against type VII collagen. Presentation in childhood is rare and with several manifestations. Case report: We report the case of a 12-year-old female patient who presented bullous and polymorphic lesions on the chest and extremities of several months of evolution. Due to the characteristics of the skin lesions, a histopathological and direct immunofluorescence study was conducted, confirming the diagnosis of acquired epidermolysis bullosa. Subsequently, corticosteroid and dapsone treatment was administered, with favorable clinical response during follow-up. Conclusions: Acquired epidermolysis bullosa is unusual in pediatric age, so it should be considered in the differential diagnosis of other congenital and acquired bullous diseases of childhood. The definitive diagnosis is performed through an immunofluorescence, study, which allows for rapid and effective treatment to control the disease and avoid permanent sequelae.

Estratégias de enfrentamento na vivência da maternidade frente à epidermólise bolhosa / Estrategias de enfrentamiento en la vivencia de la maternidad frente a la epidermólisis bullosa / Coping strategies in the experience of motherhood against epidermolysis bullosa

Objetivos: conhecer as estratégias de enfrentamento utilizadas pela mãe de uma lactente com Epidermólise Bolhosa. Método: estudo de caso único com abordagem qualitativa realizado com a mãe de uma criança com seis meses de idade e diagnóstico clínico de Epidermólise Bolhosa. A coleta de dados ocorreu entre fevereiro e março de 2020 no domicílio da participante, por meio de entrevista em profundidade e observação. As narrativas foram submetidas à análise de conteúdo do tipo temática. Resultados: emergiram categorias temáticas, sendo elas "O (res) significar da maternidade após o diagnóstico de Epidermólise Bolhosa", que aborda os momentos de descoberta da doença rara, bem como a utilização da internet como recurso para o enfrentamento, que apresenta o movimento para aquisição de conhecimentos teóricos para possibilitar o cuidado materno realizados à criança. Conclusão: o estudo permitiu apreender as estratégias de enfrentamento utilizadas na vivência da maternidade diante do nascimento da criança com diagnóstico de Epidermólise Bolhosa.

Objetivo: conocer las estrategias de afrontamiento utilizadas por la madre de una lactante con Epidermólisis Bullosa. Método: estudio de caso único con enfoque cualitativo realizado con la madre de una niña de seis meses de edad y diagnóstico clínico de Epidermólisis Bullosa. La recogida de datos tuvo lugar entre febrero y marzo de 2020 en el domicilio de la participante, a través de una entrevista en profundidad y observación. Las narrativas fueron sometidas al análisis de contenido del tipo temático. Resultados: surgieron categorías temáticas, siendo ellas "O (res)significar de la maternidad después del diagnóstico de Epidermólisis Ampollar", que aborda los momentos de descubrimiento de la enfermedad rara, así como la utilización de internet como recurso para el enfrentamiento, que presenta el movimiento para adquirir conocimientos teóricos para posibilitar el cuidado materno realizado a la niña. Conclusión: el estudio permitió aprehender las estrategias de enfrentamiento utilizadas en la vivencia de la maternidad ante el nacimiento del niño con diagnóstico de Epidermólisis Ampollar.

Objective: to know the coping strategies used by the mother of an infant with Epidermolysis Bullosa. Method: a single case study with a qualitative approach conducted with the mother of a six-month-old child with clinical diagnosis of Epidermolysis Bullosa. Data collection occurred between February and March 2020 at the participant's home, through in-depth interviews and observation. The narratives were submitted to thematic content analysis. Results: thematic categories emerged, being "(Re)meaning motherhood after the diagnosis of Epidermolysis Bullosa", which addresses the moments of discovery of the rare disease, as well as the use of the internet as a resource for coping, that presents the movement to acquire theoretical knowledge to enable maternal care performed to the child. Conclusion: the study allowed the understanding of the coping strategies used in the experience of motherhood before the birth of the child diagnosed with Epidermolysis Bullosa.

Epidermolysis bullosa acquisita

Abstract Epidermolysis bullosa acquisita is a rare autoimmune disease, characterized by the synthesis of anti-collagen VII autoantibodies, the main component of hemidesmosome anchoring fibrils. The antigen-antibody binding elicits a complex inflammatory response, which culminates in the loss of dermo-epidermal adhesion of the skin and/or mucous membranes. Skin fragility with bullae, erosions, and milia in areas of trauma characterizes the mechanobullous form of the disease. In the inflammatory form of epidermolysis bullosa acquisita, urticarial inflammatory plaques with tense bullae, similar to bullous pemphigoid, or mucosal lesions can determine permanent scars and loss of functionality in the ocular, oral, esophageal, and urogenital regions. Due to the similarity of the clinical findings of epidermolysis bullosa acquisita with other diseases of the pemphigoid group and with porphyria cutanea tarda, the diagnosis is currently confirmed mainly based on the clinical correlation with histopathological findings (pauci-inflammatory subepidermal cleavage or with a neutrophilic infiltrate) and the demonstration of the presence of anti-collagen VII IgG in situ by direct immunofluorescence, or circulating anti-collagen VII IgG through indirect immunofluorescence and/or ELISA. There is no specific therapy for epidermolysis bullosa acquisita and the response to treatment is variable, usually with complete remission in children and a worse prognosis in adults with mucosal involvement. Systemic corticosteroids and immunomodulators (colchicine and dapsone) are alternatives for the treatment of mild forms of the disease, while severe forms require the use of corticosteroid therapy associated with immunosuppressants, intravenous immunoglobulin, and rituximab.

Hindi translation and validation of quality of life score in Indian patients with epidermolysis bullosa; and its correlation with the clinical severity assessment scores: A cross-sectional study

Background: Quality of life (QoL) has not been evaluated in Indian patients having epidermolysis bullosa (EB). Aims: The aims of the study were to measure health-related QoL in Indian patients having EB using the quality of life in epidermolysis bullosa (QoLEB) questionnaire, and to find its correlation with clinically measured disease severity. Methods: In this observational cross-sectional study, the QoLEB questionnaire was translated from English to Hindi (QoLEB-Hin) and culturally adapted without a change in concept following standard guidelines. QoLEB-Hin and three clinical scores that have been independently validated in EB, that is, Birmingham Epidermolysis Bullosa severity score (BEBs), Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB) and Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI), were administered to EB patients/their parents in the presence of an expert. This was followed by validity and correlation studies. Results: Fifty-four patients were recruited (19-females, 35-males; median age 5 years, range 0.025–36 years and 12 patients with an age >13 years). The parents answered the questions for 42 patients (age <13 years). Dystrophic epidermolysis bullosa was diagnosed in 32 (59.2%) patients (dominant dystrophic epidermolysis bullosa [DDEB]-19 [35.2%] and recessive dystrophic epidermolysis bullosa [RDEB]-13 [24.1%]). Junctional epidermolysis bullosa (JEB) and epidermolysis bullosa simplex (EBS) were each diagnosed in 11 (20.4%) patients. The mean ± standard deviation (SD) of QoLEB-Hin score of all epidermolysis bullosa patients was 11.3 ± 7.6 (range 0–28; median and interquartile range [IQR], 10, 10) and reflected an overall moderate degree of affliction on QoL of patients. Mean ± SD of QoLEB-Hin scores for EBS, JEB, DDEB and RDEB were 5.4 ± 3.7 (range, 1–13; median and IQR, 6, 6), 11 ± 6.2 (range, 1–22; median and IQR, 10, 6), 9 ± 5.7 (range, 0–19; median and IQR, 10, 10) and 20.1 ± 6.4 (range, 12–28; median and IQR, 19, 12.5), respectively (P < 0.001, Kruskal–Wallis analysis of variance). Cronbach’s alpha coefficient of 0.946 was obtained for all items indicating excellent internal consistency and reliability. Mean sample adequacy was 0.91; absolute fit based off diagonal values was 0.99; indices root mean square error of approximation and root mean square residual were 0.04 and 0.05, respectively, and Tucker Lewis index was >1 indicating overfit. The mean time taken to complete the questionnaire was 6.1 min (range, 6–8 min). QoLEB-Hin correlated significantly (P < 0.001) with BEBs (ρ = 0.79), iscorEB (ρ = 0.63) and EBDASI (ρ = 0.77). Three multiple linear regression models were used to ascertain the strength of relationship between QoL-Hin, and BEBs, iSCOREB and EBDASI, respectively, after adjusting for age, gender and disease subtype. The EBDASI clinical score accounted for approximately 74% (R2 = 0.736, P < 0.001) of the variability in QOL-Hin, as compared to 73% and 55% by BEBs (R2 = 0.731, P < 0.001) and iscorEB (R2 = 0.545, P < 0.001), respectively.Limitations: Parents filled out the questionnaires for many patients and probably led to an overall moderate degree of affliction of QoL. Comparison with Dermatology Life Quality Index and other QoL scores were not done in this study. Furthermore, the scoring was done at one point in time, and test-retest measurements could not be performed. Conclusion: This study validated QoLEB-Hin in an Indian population finding an overall moderate reduction in QoL due to EB. Maximally affected QoL was seen in patients with RDEB. Furthermore, QoLEB-Hin had a variable positive correlation and association with all clinical severity assessment scores

Manifestações bucais em portadores de epidermólise bolhosa residentes em um município baiano / Oral manifestations of epidermolysis bullosa in a municipality of the state of Bahia

Introdução: a Epidermólise Bolhosa hereditária (EB) é uma doença rara, caracterizada por formações de bolhas na pele e nas mucosas que sofrem mínimos traumas ou aparecem espontaneamente. As principais divisões de EB são Epidermólise Bolhosa Simples, Epidermólise Bolhosa Juncional, Epidermólise Bolhosa Distrófica e a Síndrome de Kindler. As manifestações bucais geralmente encontradas nos pacientes com EB são as bolhas no epitélio oral, microstomia, anquiloglossia, doença periondontal, hipoplasia do esmalte, cárie dentária, atrofia da maxila e prognatismo mandibular, variando para cada tipo da doença. Objetivo: relatar as manifestações bucais dos portadores de Epidermólise Bolhosa residentes no município de Barra da Estiva. Metodologia: trata-se de um estudo transversal, quantitativo e descritivo que foi desenvolvido no município de Barra da Estiva ­ BA com a população de portadores de Epidermólise Bolhosa, através da realização de anamnese e exame clínico. Estatística descritiva foi utilizada para tabular os dados coletados. Resultados: foram analisados 5 portadores de Epidermólise Bolhosa, a maioria do sexo masculino (60%), com média de idade de 5,6 anos. As manifestações bucais encontradas foram bolhas orais (100%), anquiloglossia (100%), língua despapilada (100%), hipoplasia de esmalte (80%), cárie (40%) e abertura de boca limitada em média de 28,6 mm. Conclusão: os portadores de Epidermólise Bolhosa apresentaram manifestações orais características da doença, tendo como consequências maiores dificuldades para realizar higienização bucal e tratamento odontológico, sendo necessário conhecimento prévio dos cirurgiões-dentistas para o atendimento desses pacientes.

Introduction: inherited Epidermolysis Bullosa (EB) is a rare disease, characterized by blistering of the skin and mucous membranes that suffer minimal trauma or appear spontaneously. The main divisions of EB are Simple Epidermolysis Bullosa, Junctional Epidermolysis Bullosa, Dystrophic Epidermolysis Bullosa and Kindler Syndrome. The oral manifestations usually found in patients with EB are blisters in the oral epithelium, microstomy, ankyloglossia, periodontal disease, enamel hypoplasia, dental caries, atrophy of the jaw and mandibular prognathism, varying for each type of disease. Objective: to report the oral manifestations of Epidermolysis Bullosa patients living in the municipality of Barra da Estiva. Methods: cross-sectional study, quantitative and descriptive that was developed in the municipality of Barra da Estiva-BA with the population of people with Epidermolysis Bullosa, through anamnesis and clinical examination. Descriptive statistics was used to tabulate the data collected. Results: 5 children with Epidermolysis Bullosa were analyzed, most male (60%), with an average age of 5,6 years. Oral manifestations found were oral blisters (100%), anquiloglossia (100%), loss of papillae of the tongue (100%), enamel hypoplasia (80%), tooth decay (40%) and mouth opening limited to the average of 28.6 mm. Conclusion: epidermolysis Bullosa children presented oral manifestations common to the disease, leading to difficulties in performing oral hygiene and dental treatment, requiring prior knowledge of dental surgeons for the care of these patients.

Epidermolysis bullosa dystrophica with renal failure

Inherited epidermolysis bullosa (EB) is a family of diseases with blistering of skin and mucous membrane even with mild trauma. It has different subtypes based on the affected protein. Epidermolysis bullosa dystrophica (EBD) is associated with mutations in the COL7A1 gene encoding type VII collagen leading to the fragility of skin and mucosal membranes. EBD may be dominant or recessive. They should be distinguished because increased prevalence of SCC is associated with the recessive form. Here we are reporting a case at our hospital presented with various clinical features, history, clinical spectrum, renal biopsy and gene analysis giving appropriate diagnosis for the disorder. Treatment remains challenge. A multidisciplinary approach is needed for the effective management of EBD.