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

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.

Multidisciplinary care for patients with epidermolysis bullosa from birth to adolescence: experience of one Italian reference center.

BACKGROUND: Epidermolysis bullosa (EB) is a disabling and chronic genodermatosis characterized by mucocutaneous fragility with blister formation after minimal trauma. Severity ranges between very mild forms to extremely severe or lethal subtypes. Depending on disease subtypes, blisters may be localized also in larynx, bladder, esophagus, and most frequent disease complications are malnutrition, chronic anemia, osteoporosis, limb contracture and early development of squamous cell carcinomas. EB is classified into four major groups: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler EB (KEB). No specific treatment is available; however, a multidisciplinary management is mandatory in order to treat the lesions, to prevent complication, and to give a psychological support to the patient and family members. OBJECTIVE: To report the experience on a therapeutic education plan of an Italian reference center for epidermolysis bullosa in the last 30 years. METHODS: In our study we included all patients with EB from 1990 to the present, dividing them into three age groups (< 5 years, > 5-12 years and > 12-18 years). The therapeutic plan involved all multidisciplinary team members, since born until adolescence. The multidisciplinary team has been progressively established; the dermatologists act as patient case manager, in collaboration with the pediatrician, endocrinologist, dietician, dentist, plastic surgeon, digestive surgeon, geneticist, psychologist and a dedicated nurse. Other dedicated specialists are involved upon patient needs. RESULTS: Two hundred fifteen patients have been recruited and followed in our hospital since 1990. One hundred forty patients (65%) are on follow-up, 27 patients (13%) died and only 11 (5%) were lost to follow-up. Our patients manifested the specific complications related to their EB subtype in keeping with the data reported in the literature. Eighteen (8%) patients affected with JEB severe died within the first year of life, 9 patients (5%) died for squamous cell carcinoma in adulthood and were affected with recessive DEB; only 1 patient died for squamous cell carcinoma at the age of 16. CONCLUSIONS: An adequate management of EB patients require a multidisciplinary approach with an educational plan to guarantee an appropriate treatment and to support and accompany patients and their families since birth along life. The dynamic educational plan adopted in our hospital showed good clinical and psychological outcome in our population, allowing adherence to treatment, reducing the frequency of complications and improving life expectancy and quality of life.

Epidemiological, clinical, pathological and genetic characteristics of epidermolysis bullosa in New Zealand.

OBJECTIVE: To establish the epidemiological, clinical, pathological and genetic characteristics of epidermolysis bullosa (EB) in New Zealand (NZ). METHODS: Participants were recruited through the Dystrophic Epidermolysis Bullosa Research Association of New Zealand (DEBRA NZ). Dedicated EB nurse medical records, Genetic Health Service NZ (GHSNZ) records and, where available, public hospital records were manually reviewed for relevant clinical data. RESULTS: Ninety-two participants took part in the study (56% participation rate). Forty-nine (53%) participants had EB simplex (EBS), 40 (43%) had dystrophic EB (DEB), and 3 (3%) had junctional EB (JEB). Point prevalence for EB of all types was 19.5 per million, and 10.4, 8.6 and 0.9 per million for EBS, DEB and JEB, respectively. Thirty-four participants had intermediate or severe EB. There were 29 paediatric cases and almost even numbers of males and females. Compared to NZ European and Maori, prevalence rates were lower for Pacific and Asian people and higher in the Middle Eastern/Latin American/African population. Eight out of 14 skin biopsy results were informative, and 14 of 15 genetic test results were informative. CONCLUSION: New Zealand has similar prevalence rates of EB compared with other national cohorts. This is likely to be an underestimate due to methodological limitations. Recent advancements in genomic testing have resulted in an improved diagnostic rate in our population. Further research into ethnic differences in prevalence, and exploring the characteristics of lethal forms of EB, is warranted. A dynamic registry may be helpful for the EB community in NZ.

Overview of complications associated with epidermolysis bullosa: A multicenter retrospective clinical analysis of 152 cases.

BACKGROUND/PURPOSE: Epidermolysis bullosa (EB) is a rare disease of skin and mucosa which may causes surgical complications. We review these in a large patient cohort from Saudi Arabia. METHODS: A retrospective study was conducted at 21 centers between 2003 and 2020. Demographic data and information on EB type [Simplex (EBA), Dystrophic (DEB) and Junctional (JEB)]. The dataset included clinical features, operations, surgical complications, and treatment. RESULTS: There were 152 (63 male) children with EB [EBS n = 93 (61.2%); DEB n = 30 (19.7%); JEB n = 25 (16.4%), and Kindler syndrome n = 4, (2.6%)]. Children with JEB and DEB tended to have a higher frequency of skin and musculoskeletal system complications (skin cancer, pseudosyndactyly and recurrent skin infection). Esophageal strictures were mostly seen in DEB (n = 19, 63%) and to a lesser extent in EBS (n = 20, 21%) and JEB (n = 4, 16%). Pyloric atresia was uncommon (n = 4) and limited to those with JEB. Percutaneous gastrostomy for feeding support was used in all types. Ankyloglossia was common but often recurred (76%) after division. Circumcision was usually safe and complication-free in male children except in those with severe JEB. Phimosis was reported in 10% of uncircumcised patients. CONCLUSIONS: Our series showed that surgeons play a key role in the management of some complications associated with EB. It is also important to be aware of the particular sub-type as this can predict the natural history and likely response to treatment. LEVEL OF EVIDENCE: 2.

Patient-reported outcomes and quality of life in recessive dystrophic epidermolysis bullosa: A global cross-sectional survey.

BACKGROUND: A spectrum of skin disease severity exists in patients with recessive dystrophic epidermolysis bullosa (RDEB). OBJECTIVE: To characterize the patient-reported outcomes and quality of life (QOL) in patients with RDEB. METHODS: A cross-sectional study of patients with RDEB surveyed through the global EBCare Registry. Patient-reported outcomes included skin disease severity, wound characteristics, pain, itch, extracutaneous symptoms, and medications. QOL was measured by using the validated Quality of Life in Epidermolysis Bullosa instrument. RESULTS: A total of 85 patients with RDEB reported 1226 wounds (937 recurrent wounds and 289 chronic open wounds). Overall skin disease severity was self-reported as mild (26%; 22/83), moderate (48%; 40/83), or severe (25%; 21/83). Worsening skin disease severity was significantly associated with larger wounds, increased opiate use, anemia, gastrostomy tube use, infections, osteoporosis, and squamous cell carcinoma. Larger wound size was associated with worse quality of life scores. LIMITATIONS: All data were self-reported from an online epidermolysis bullosa patient registry. CONCLUSIONS: This study shows a significant correlation between larger wound size with worsening skin disease severity and quality of life in participants with RDEB. Worsening skin disease severity significantly correlated with key clinical manifestations. These results show that patients with RDEB are able to self-report their skin disease severity and wounds.

Assessment of the Timing of Milestone Clinical Events in Patients With Epidermolysis Bullosa From North America.

Importance: Children with epidermolysis bullosa (EB) comprise a rare population with high morbidity and mortality. An improved understanding of the clinical trajectory of patients with EB, including age at time of clinical diagnosis and major clinical events, is needed to refine best practices and improve quality of life and clinical outcomes for patients with EB. Objectives: To describe demographics, clinical characteristics, milestone diagnostic and clinical events (such as initial esophageal dilation), and outcomes in patients with EB using the Epidermolysis Bullosa Clinical Characterization and Outcomes Database and to determine what characteristics may be associated with overall EB severity and/or disease progression. Design, Setting, and Participants: This cohort study included data on patients with EB who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2011, to June 30, 2017; 17 participating EB centers in the United States and Canada contributed data to this study. Exposures: Type of EB, including recessive dystrophic epidermolysis bullosa (RDEB), junctional epidermolysis bullosa (JEB), dominant dystrophic epidermolysis bullosa (DDEB), and epidermolysis bullosa simplex (EBS). Main Outcomes and Measures: Demographic information, clinical characteristics (including age at onset of signs of EB and subsequent clinical diagnosis), types of diagnostic testing performed, and milestone clinical events for patients with RDEB. Results: Of 644 enrolled patients from 17 sites included in this study, 323 were male (50.2%), with a mean (SD) age of 14.4 (11.7) years; 283 (43.9%) had RDEB, 194 (30.1%) had EBS, 104 (16.2%) had DDEB, and 63 (9.8%) had JEB. Signs of disease were present at birth in 202 patients with RDEB (71.4%), 39 with JEB (61.9%), 60 with DDEB (57.7%), and 74 with EBS (38.1%). For those with signs of disease at birth, a clinical diagnosis was made at the time of birth in 135 patients with RDEB (67.0%), 31 with DDEB (52.6%), 35 with EBS, (47.3%) and 18 with JEB (46.2%). Patients with JEB had the highest rate of any confirmatory testing (51 of 63 [81.0%]), followed by RDEB (218 of 283 [77.0%]), DDEB (71 of 104 [68.3%]), and EBS (100 of 194 [51.5%]). For all types of EB, both electron microscopy and immunofluorescence microscopy were performed at younger ages than genetic analysis. Among 283 patients with RDEB, 157 (55.5%) had esophageal dilation, 104 (36.7%) had gastrostomy tube placement, 62 (21.9%) had hand surgery, 18 (6.4%) developed squamous cell carcinoma, and 19 (6.7%) died. Conclusions and Relevance: The findings suggest that diagnostic testing for EB is more common for patients with severe phenotypes. Earlier diagnostic testing may enable improved characterizations of patients so that appropriate counseling and clinical care may be offered, especially pertaining to milestone events for those with RDEB.

Epidermólisis bullosa en el perú: estudio clínico y epidemiológico de pacientes atendidos en un hospital pediátrico de referencia nacional, 1993-2015 / Epidermolysis bullosa in peru: clinical and epidemiological study of patients treated in a national reference pediatric hospital, 1993-2015

RESUMEN Objetivos Describir las características clínicas y epidemiológicas de los pacientes diagnosticados con epidermólisis bullosa (EB), en el Instituto Nacional de Salud del Niño (INSN) en Lima, Perú; centro de referencia nacional para esta enfermedad. Material y métodos Estudio observacional, descriptivo y transversal. Se revisaron las historias clínicas y exámenes de laboratorio de los pacientes diagnosticados de EB atendidos en el INSN desde 1993 al 2015. Resultados Fueron registrados 93 pacientes. La edad promedio fue de 7,9 ± 5,6 años; el 53,8% (n=50) fueron hombres. Las formas clínicas correspondieron a EB distrófica con 41 (44,1%) casos, EB simple con 39 (41,9%) casos, EB de la unión con 8 (8,6%) y al síndrome de Kindler con 4 (4,3%) casos. No se pudo identificar la forma clínica en un caso. Procedían de Lima y Callao 48 casos (51,6%) y 45 casos (48,4%) de otras provincias del país. Entre las manifestaciones extracutáneas se registraron compromiso gastrointestinal (44,1%), ocular (37,6%), odontogénico (87,1%), nutricional (79,6%), además de pseudosindactilia (16,1%). Se halló desnutrición crónica (71,6%), desnutrición aguda (17,6%) y anemia en (62,4%). La mortalidad correspondió a 6 casos (6,5%). Conclusiones Se reportan 93 casos de EB en el INSN, la presentación clínica predominante fue la forma distrófica.

ABSTRACT Objectives To describe the clinical and epidemiological characteristics of patients diagnosed with epidermolysis bullosa (EB) at the Instituto Nacional de Salud (INSN) in Lima, Peru; a National Reference Center for this disease. Materials and methods Observational, descriptive and transversal study. We reviewed the clinical histories and laboratory tests of patients diagnosed with EB treated in INSN from 1993 to 2015. Results 93 patients were registered. The average age was 7.9 ± 5.6 years; 53.8% (n = 50) were boys. Clinical forms corresponded to dystrophic EB with 41 (44.1%) cases, simple EB with 39 (41.9%), union EB cases with 8 (8.6%) and Kindler syndrome with 4 (4.3%) cases. The clinical form could not be identified in a case. A total of 48 cases (51.6%) came from Lima and Callao, and 45 cases (48.4%) from other provinces of the country. Extracutaneous manifestations involved gastrointestinal (44.1%), ocular (37.6%), odontogenic (87.1%), and nutritional (79.6%) involvement, as well as pseudosindactilia (16.1%). Chronic malnutrition (71.6%), acute malnutrition (17.6%) and anemia (62.4%) were found. Mortality corresponded to 6 cases (6.5%). Conclusions 93 cases of EB were reported in INSN, the predominant clinical presentation was the dystrophic form.

Epidermólisis bullosa: piel de mariposa. A propósito de un caso / Epidermolysis bullosa: butterfly skin. Apropos of a case

La epidermólisis bullosa comprende un grupo heterogéneo de enfermedades ampollosas de la piel y las mucosas, son de origen congénito y hereditario. Hacer el diagnóstico no es difícil si se tiene experiencia dermatológica, pero su clasificación es compleja y para ello se necesita considerar la clínica, la genética, la microscopia y la evaluación de laboratorio. El tratamiento de esta enfermedad es también dificultoso y son necesarias ciertas medidas, para proteger al paciente, evitar la aparición de lesiones y las complicaciones derivadas de ellas. Se describe el tratamiento de estas lesiones en un recién nacido, al que se administraron antibióticos profilácticos y se colocaron vendajes en las lesiones. Se describieron todos los cuidados y recomendaciones para evitar, especialmente los roces y las presiones en estas lesiones, así como las temperaturas altas. Para la confección del presente trabajo se consultaron 18 materiales entre revistas y libros de Pediatría. El caso reportado fue un recién nacido con epidermólisis bullosa atendido en el Hospital Universitario "Dr. Mario Muñoz Monroy" de Colón, Matanzas. Se demostró lo poco frecuente y raro de esta patología para los especialistas del tema (AU).

The epidermolysis bullosa includes a heterogeneous group of bullous skin and mucous diseases of congenital and hereditary origin. Diagnosing them is not difficult if the specialist has dermatologic experience, but their classification is complex and it is necessary to take into account the clinical, genetic and microscopic factors, and the laboratory assessment. The treatment of this disease is also difficult and it is necessary to take certain measures to protect the patient, avoid the onset of lesions and the complications derived from them. The treatment of these lesions in a newborn is described. Prophylactic antibiotics were administered and bandages were put on the lesions. All the cares and recommendations to avoid rubbings and pressures on these lesions, and also the high temperatures, are described. To develop the current term, 18 materials (journals and pediatric books) were consulted. The reported case was the case of a newborn with epidermolysis bullosa attended in the University Hospital "Dr. Mario Muñoz Monroy" of Colon, Matanzas. It was demonstrated the low frequency and rarity of this pathology for the specialists of the theme (AU).

[Birth marks and neonatal skin disorders. From angel kiss to epidermolysis bullosa]. / Születési jegyek, újszülöttkori borelváltozások. Az angyalcsóktól az epidermolysis bullosáig.

INTRODUCTION: At present there are no exact epidemiologic data on the prevalence of neonatal skin disorders and birth marks in Hungary. AIM: The aim of the authors was to investigate the prevalence of skin disorders in mature healthy neonates after birth. METHOD: The survey was carried out in the Neonatal Care Unit at the Department of Obstetrics and Gynaecology at the University of Szeged between April, 2012 and May, 2013. RESULTS: A total of 2289 newborn infants underwent whole-body screening skin examinations. At least one skin manifestation was found in 63% of the neonates. The major groups of skin disorders were transient benign cutaneous lesions, vascular lesions, pigmented lesions, traumatic, iatrogenic, congenital or acquired disorders with skin injuries, developmental abnormalities and benign skin tumours. The most frequent transient cutaneous lesions were erythema toxicum neonatorum, sebaceous hyperplasia and desquamation. The most common vascular lesions were naevus simplex, haemangioma and haemangioma precursor lesion, while the most frequently observed pigmented lesions were congenital melanocytic naevi and Mongolian spot. CONCLUSIONS: In the vast majority of cases, special treatment was not necessary, but 5.27% of the neonates required local dermatologic therapy, and in 9.2% of neonates follow up was recommended.

Manifestações clínicas da epidermólise bolhosa: revisão de literatura / Clinical manifestations of epidermolysis bullosa: a literature review

Introdução: A epidermólise bolhosa é uma dermatose hereditária rara, caracterizada pelo desenvolvimento de bolhas na região cutâneo-mucosa de todo o corpo, em resposta ao trauma mínimo, ao calor ou a nenhuma causa aparente, podendo manifestar-se ao nascimento ou durante os primeiros anos de vida. Sua classificação é determinada pela modalidade de herança genética, distribuição anatômica das lesões e morbidez associada à doença, distinguindo-se em três grupos principais: epidermólise bolhosa simples, juncional e distrófica, que englobam mais de 30 entidades distintas. O desenvolvimento de bolhas em pele e mucosas e as deformidades decorrentes de tais lesões interferem sobremaneira na atenção à saúde bucal, assim, é importante que o cirurgião dentista conheça a epidermólise bolhosa e esteja preparado para assistir o paciente portador dela. Objetivo: Foi realizada ampla revisão da literatura acerca da epidermólise bolhosa, enfatizando suas manifestações clínicas e os principais aspectos que interferem com a saúde bucal dos pacientes acometidos por essa condição e com sua assistência odontológica. O objetivo foi subsidiar o profissional de saúde, possibilitando que o mesmo preste a adequada assistência ao paciente, contribuindo para a melhora de sua saúde bucal e consequentemente de sua qualidade de vida. Conclusão: As alterações primárias e secundárias da epidermólise bolhosa tornam um verdadeiro desafio para o cirurgião-dentista à condução do tratamento odontológico para o paciente com esta rara dermatose. Antes de iniciar o tratamento, é fundamental entrar em contato com a equipe de saúde responsável pelo acompanhamento clínico do paciente. Apesar de o tratamento odontológico reabilitador ser possível, sua condução é bastante desgastante, envolvendo riscos para o paciente. Assim, a promoção da saúde e a prevenção das doenças bucais devem ser enfatizadas e iniciadas o mais precocemente possível.

Introduction: Epidermolysis bullosa is a rare inherited skin condition characterized by the development of blisters on mucocutaneous regions of the body in response to minor traumas, heat or no apparent cause. It may manifest at birth or during the first years of life. Its classification is determined by genetics, anatomical distribution of the lesions and associated morbidity. It is divided into three main groups: epidermolysis bullosa simplex, junctional and dystrophic, covering over 30 different entities. The development of blisters in the skin and mucous membranes, and the deformities resulting from such lesions interfere excessively in the oral health, thus it is important for the dentist to know epidermolysis bullosa and to be prepared to assist patients with this condition. Objective: A comprehensive review of the literature on epidermolysis bullosa was conducted, emphasizing its clinical manifestations and the key issues that interfere with the oral health of patients suffering from the condition and with their dental care. The aim was to aid the health professionals, enabling them to provide adequate patient care, contributing to the improvement of their oral health and consequently their quality of life. Conclusion: The primary and secondary damages of epidermolysis bullosa become a real challenge for the dentist to conduct dental treatment for patients with this rare dermatosis. Before starting the treatment, it is essential to contact the health care team responsible for monitoring the patient's condition. A rehabilitating dental treatment is possible, but its conduction is very stressful, involving risks to the patient. Thus, health promotion and prevention of oral diseases should be emphasized and initiated as early as possible.

[Anaesthesia for children with epidermolysis bullosa]. / Epidermolysis bullosa - Anästhesieführung bei Kindern.

Epidermolysis bullosa (EB) is a heterogeneous group of inherited rare diseases, which are characterized by trauma-induced blister formation of the skin and mucosa. The underlying cause is a functional deficiency of structural proteins of the epidermis or the dermis. Depending on the level of the blister formation, EB is divided into EB simplex (intra-epidermal), junctional EB (within the lamina lucida), dystrophic EB (below the lamina lucida) and Kindler syndrome (variable level of split formation). Besides different distinct blister formation and pain symptoms secondary problems like anaemia, oesophageal stenosis, cardiomyopathy or squamous cell carcinoma may occur. Since causal therapies are not available strict prevention of friction and trauma is essential to avoid blister formation. Anaesthesia challenges exist in the field of bedding procedures, care of the skin, monitoring, airway management und analgesia. This article gives a review over the EB and highlights in detail the corresponding anaesthesia characteristics.

Epidermolysis bullosa care in Hungary.

Hereditary EB is a rare skin disease that occurs worldwide and in all racial groups. There are currently 60 families affected and about 150 patients with EB under care in Hungary. The care of patients with EB in Hungary is discussed.

Epidermolysis bullosa. Part 1: causes, presentation and complications.

This article is the first in a series of three focusing on the causes, clinical presentation, complications and care of adult patients affected by epidermolysis bullosa (EB), a group of rare genetic skin fragility disorders. Although the condition is rare, in some cases it presents extreme challenges both to those affected and those involved in the care of the EB patient; therefore, these articles may have relevance for other long-term disorders. While there is a wealth of information regarding the 'science' of EB there is dearth of information regarding the care of the adult EB patient, and this series of articles will endeavour to fill that gap. This article focuses mainly on those patients affected with the most severe form of EB found in the adult group, recessive dystrophic epidermolysis bullosa; with the part two looking at the care of the adult with EB from the nursing perspective, including wound management, and the experiences of a specialist EB psychotherapist being presented in the final article of the series. Readers will thus have an opportunity to gain an overall view of this difficult condition.

Artificial skin as a valuable adjunct to surgical treatment of a large squamous cell carcinoma in a patient with epidermolysis bullosa.

BACKGROUND: Among tissue-engineered skins, two bilayered cellular constructs and one cryopreserved dermal substitute have been approved for the treatment of epidermolysis bullosa. Nevertheless, the application of artificial skin technology to surgical treatment of squamous cell carcinomas in a patient with epidermolysis bullosa has never been reported. OBJECTIVE: To reconstruct the large defect remaining after squamous cell carcinoma excision in a patient with dominantly inherited dystrophic epidermolysis bullosa. METHODS: To apply a 10 x 15 cm Integra sheet (Integral Life-sciences Corporation, Plainsboro, NJ, USA) (an acellular collagen matrix coated with a thin polysiloxane elastomer) to the excised area and 3 weeks later to cover the Integra sheet with an ultrathin meshed skin graft. RESULTS: The graft take was complete, and the donor site totally regenerated, except for three small bullae at 7 weeks postoperatively. CONCLUSION: Integra offers the advantage of filling huge defects with its dermal layer of collagen fibers and provides an optimal graft bed. This first step makes it possible to use very thin grafts 3 weeks later.

[Hereditary epidermolysis bullosa in Tunisia: an epidemio-clinical and ultrastructural study]. / Les epidermolyses bulleuses héréditaires en Tunisie: etude epidémio-clinique et ultra-structurale.

Hereditary epidermolysis bullosa (EB) are a group of genodermatoses whose common primary feature is formation of blisters following minor trauma. The aim of the present study was to assess epidemiological, clinical, genetical and histological particularities of patients with hereditary epidermolysis bullosa.

Epidermolysis bullosa: scientific advances and therapeutic challenges.

Epidermolvsis bullosa (EB) is a heterogeneous group of inherited skin fragility and blistering disorders. Over the last 25 years research in EB has progressed from descriptive morphological studies through quantitative ultrastructural and biochemical analysis to molecular genetic approaches, including linkage analysis, gene cloning and sequencing, and mutation screening. Currently, 10 distinct causative genes are known to underlie different forms of EB, and this knowledge has been translated to improving the clinical management of patients with these disorders. For example, first trimester DNA-based prenatal diagnosis is now available in a number of centres in different countries, including Japan, the USA and the UK, and preimplantation genetic diagnosis is also possible. The development of novel forms of treatment for enhancing wound healing and reducing blistering are the subject of an international research effort. Programmes aimed at developing gene therapy for the major forms of EB have already reached the preclinical testing stages. Despite these impressive scientific advances, EB continues to be a devastating disease, in which the high incidence of aggressive squamous cell carcinoma has a major influence on both morbidity and life expectancy, especially in patients with the severe mutilating form of dystrophic EB.

Pyloric atresia: five new cases, a new association, and a review of the literature with guidelines.

BACKGROUND/PURPOSE: Pyloric atresia is an uncommon condition occurring in 1 of 100,000 live births. When occurring in isolation, the clinical course usually is uncomplicated after surgical treatment. However, it may occur in association with other congenital abnormalities. The authors present 5 new cases, 3 of associated abnormalities including 1 of esophageal atresia and 2 of agenesis of the gall bladder and malrotation. Agenesis of the gall bladder has not been described previously in combination with pyloric atresia. The literature has been reviewed and guidelines are suggested for the management. METHODS: The case records of 4 neonates who presented to the author's institution between January 1998 and June 1999 and 1 who presented at another center in 1991 were reviewed. A Medline literature search was performed, and guidelines were developed for the management of this condition based on our cases and the literature review. RESULTS: Patients 1 and 5 had no associated anomalies. Patient 2 had associated esophageal atresia, tracheoesophageal fistula, atrial septal defect, crossed renal ectopia, malrotation, and absent gall bladder. Patient 3 had a rectovestibular fistula, vaginal atresia, atrial septal defect, malrotation absent gallbladder, and absent extrahepatic portal vein. Patient 4 had epidermolysis bullosa. Patients 2 and 5 had unremarkable recoveries, patients 2 and 3 had markedly delayed gastric emptying that responded to cisapride. Patient 3 has portal hypertension and remains under close follow-up. Patient 4 died at 22 days of age of pseudomonas sepsis. CONCLUSIONS: Based on our cases and literature review, we have adopted the following guidelines: (1) All children with pyloric atresia should be screened for multiple anomalies. (2) Delayed gastric emptying should be considered early and may respond to prokinetic agents. (3) Association with Epidermolysis bullosa should not preclude surgical treatment. (4) A skin biopsy specimen should be taken at the time of surgery for electron microscopy if there is a family history of epidermolysis bullosa.

Mutations in keratin K9 in kindreds with epidermolytic palmoplantar keratoderma and epidemiology in Northern Ireland.

Epidermolytic palmoplantar keratoderma (EPPK, MIM #144200) is an autosomal dominant disorder in which hyperkeratosis confined to the palms and soles is characterized histologically by cytolysis of suprabasal keratinocytes. Mutations in the keratin 9 gene (KRT9), a type 1 keratin expressed exclusively in the suprabasal keratinocytes of palmoplantar epidermis, have previously been demonstrated in this disorder. Here, we have studied four Northern Irish kindreds presenting with EPPK. By direct sequencing of polymerase chain reaction products, heterozygous missense mutations in exon 1 of KRT9 were detected in all the families. These included a novel mutation M156T; as well as M156V in two kindreds; and R162Q in the remaining family. All mutations were confirmed by reverse strand sequencing and restriction enzyme analysis. The point prevalence of EPPK in Northern Ireland was found to be 4.4 per 100,000. To date, all reported EPPK mutations occur in the helix initiation motif at the start of the central coiled-coil rod domain of K9.

The generalized atrophic benign form of junctional epidermolysis bullosa. Experience with four patients in the United States.

We encountered four patients in the United States with the generalized atrophic benign form of junctional epidermolysis bullosa (epidermolysis bullosa atrophicans generalisata mitis, nonlethal junctional epidermolysis bullosa). Prior to the performance of definitive diagnostic studies, each patient had been thought for at least a decade to have either a dystrophic or simplex form of epidermolysis bullosa. Each patient had generalized blisters since birth that healed with atrophy and mild scarring but without milia or contractures. Two of the four patients had experienced laryngeal involvement during childhood. In each patient, correct diagnosis was finally established by either electron microscopic examination or immunofluorescence mapping of skin sections from induced blisters.