Congenital pyloric atresia associated with epidermolysis bullosa junctionalis: a novel lethal variant.

A term male baby was born vaginally to a primi mother. An antenatal ultrasound revealed polyhydramnios and a distended stomach in the baby. At birth, the baby had well-defined areas of peeling skin on the face and blisters on the forearm region. The abdominal X-ray revealed a single gastric bubble, which is consistent with pyloric atresia and needs surgery. Pyloroplasty was initially performed, but it was unsuccessful. Therefore, a feeding jejunostomy and gastrostomy were performed. However, the baby developed sepsis and septic shock and died at about 2 months of age. Skin biopsy revealed cleavage above the lamina densa, and genetic analysis indicated heterozygosity in ITGB4 exons 10 and 16, which are associated with epidermolysis bullosa junctionalis and pyloric atresia.

Totally endoscopic concomitant aortic and mitral valve surgery in junctional epidermolysis bullosa: a case report.

BACKGROUND: Junctional epidermolysis bullosa is a rare skin and mucosal disorder characterized by blister formation in response to minor trauma and extracutaneous manifestations. There have been no reports of cardiac surgery and prognostication in patients with epidermolysis bullosa due to skin and mucosal fragility. CASE PRESENTATION: A 55-year-old man presented with congenital junctional epidermolysis bullosa, hypertension, and vasospastic angina. He complained of dyspnea on exertion, and transthoracic echocardiography revealed severe aortic valve regurgitation, moderate aortic valve stenosis (tricuspid valve), and severe mitral valve regurgitation. Considering that the skin condition in the right chest wall was relatively healthy, the right thoracotomy approach was preferred and totally endoscopic concomitant mitral valve repair and aortic valve replacement were performed using a sutureless bioprosthetic valve (Perceval™ (Corcym, Group, Milan, Italy)). Polyurethane and silicon dressing foams were used to protect the skin at the site of contact with the bag valve mask, arterial pressure catheter, intravenous catheter, and the tracheal intubation tube. Vertical mattress sutures were used for the skin sutures. The postoperative course was uneventful, and the patient was discharged nine days after the operation. There was no indication for reoperation until three years follow-up period. CONCLUSIONS: The totally endoscopic concomitant aortic and mitral valve surgery using Perceval™ prosthesis can be performed safely in patients with junctional epidermolysis bullosa by adequate protection of the skin and mucosa.

Gross motor development in children with epidermolysis bullosa.

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare, congenital skin disorders, characterized by skin fragility and formation of blisters. The gross motor outcomes of children with EB are not known. OBJECTIVES: The primary objective of the study was to measure the proportion of gross motor delay in children with EB. The secondary objectives were to measure the difference in gross motor outcomes between EB sub-types and change in gross motor outcomes over time. METHODS: Children with EB, aged between one month and five and a half years of age, attending the Sydney Children's Hospital, Epidermolysis Bullosa Clinic, were eligible. Carers completed Ages and Stages Questionnaires, Third Edition, on behalf of their children. Questionnaires were scored, and outcomes were compared to age-expected norms. RESULTS: There were 24 participants to complete a questionnaire. Eleven participants completed additional questionnaires over the 24 month study duration. The proportion of children with EB with gross motor delay was greater than age-expected norms (29.17% vs. 2.5%). The delay occurred in children with recessive dystrophic (80%) and epidermolysis bullosa simplex (33.33%) sub-types, but not dominant dystrophic (0%). No children with Junctional EB or Kindler EB joined this study. CONCLUSIONS: This study demonstrates a difference in gross motor outcomes in children with EB. Children with recessive dystrophic and epidermolysis bullosa simplex should be prioritized for monitoring of, and intervention for, gross motor outcomes through multidisciplinary care. Further research investigating long-term outcomes for children with EB and the effectiveness of interventions would be beneficial.

[Cutaneous squamous cell carcinomas in EBDR: how can they be detected?] / Carcinomes épidermoïdes cutanés au cours de l'EBDR : comment les dépister ?

The occurrence of cutaneous squamous cell carcinoma is a frequent and potentially serious complication in people with recessive dystrophic epidermolysis bullosa and junctional epidermolysis bullosa with chronic leg sores. Early diagnosis of early-stage carcinomas enables limited surgical excision and rapid healing without sequelae. Screening during skin care of patients at risk is therefore of major interest, and any atypical lesion should be shown to a doctor specializing in the disease and biopsied at the slightest doubt, preferably in an expert center for the disease.

Clinical and molecular features in a cohort of Middle Eastern patients with epidermolysis bullosa.

BACKGROUND: Epidermolysis bullosa (EB) features skin and mucosal fragility due to pathogenic variants in genes encoding components of the cutaneous basement membrane. Based on the level of separation within the dermal-epidermal junction, EB is sub-classified into four major types including EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler EB (KEB) with 16 EB-associated genes reported to date. METHODS: We ascertained a cohort of 151 EB patients of various Middle Eastern ethnic backgrounds. RESULTS: The cohort was comprised of EBS (64%, 97/151), DEB (21%, 31/151), JEB (12%, 18/151), and KEB (3%, 5/151). KRT14 and KRT5 variants were most common among EBS patients with 43% (42/97) and 46% (45/97) of EBS patients carrying mutations in either of these two genes, respectively. Truncal involvement was more common in KRT14-associated EBS as compared to EBS due to KRT5 mutations (p < .05). Mutations in COL17A1 and laminin 332-encoding genes were identified in 55% (10/18) and 45% (8/18) of JEB patients. Scarring alopecia, caries, and EB nevi were most common among JEB patients carrying COL17A1 mutations as compared to laminin 332-associated JEB (p < .05). Abnormal nails were evident in most DEB and JEB patients while poikiloderma was exclusively observed in KEB (p < .001). CONCLUSIONS: EB patients of Middle Eastern origin were found to feature specific phenotype-genotype correlations of relevance to the diagnosis and genetic counseling of patients in this region.

Treatment With Ataluren for Wound Healing and Health Complications in a Patient With Junctional Epidermolysis Bullosa.

This case report describes an 11-year-old boy with widespread chronic wounds, frequent corneal erosions, dental caries, a tracheostomy, and failure to thrive.

Eye Involvement and Management in Inherited Epidermolysis Bullosa.

Inherited epidermolysis bullosa (EB) is a group of genetic rare diseases associated with skin fragility, which leads to the formation of blisters, erosions, and scars on the skin and mucous membranes. Epidermolysis bullosa includes four main types and some several clinical subtypes including EB simplex, junctional EB, dystrophic EB, and Kindler's EB. Ocular involvement ranged from 51 to 68% in EB and can cause irreversible damages if not properly managed. Corneal erosions are the most common finding among series, including our cohort. We review here clinical and pathological features of ocular involvement in EB and the main keys for management, with a focus on recent innovative therapies.

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.

Whole exome sequencing in a sample of Peruvian patients diagnosed with epidermolysis bullosa.

BACKGROUND: Epidermolysis bullosa (EB) is a complex and heterogeneous dermatological disease. Four main types of EB have been described, each of them with distinct characteristics: EB simplex (EBS), dystrophic EB (DEB), junctional EB (JEB) and Kindler EB (KEB). Each main type varies in its manifestations, severity, and genetic abnormality. METHODS: We sought mutations in 19 genes known to cause EB and 10 genes associated with other dermatologic diseases in 35 Peruvian pediatric patients of a rich Amerindian genetic background. Whole exome sequencing and bioinformatics analysis was performed. RESULTS: Thirty-four of 35 families revealed an EB mutation. Dystrophic EB was the most frequently diagnosed type, with 19 (56%) patients, followed by EBS (35%), JEB (6%), and KEB (3%). We found 37 mutations in seven genes; 27 (73%) were missense mutations; 22 (59%) were novel mutations. Five cases changed their initial diagnosis of EBS. Four were reclassified as DEB and one as JEB. Inspection into other non-EB genes revealed a variant, c.7130C>A, in the gene FLGR2, which was present in 31 of the 34 patients (91%). CONCLUSION: We were able to confirm and identify pathological mutations in 34 of 35 patients.

A Nonlethal Case of Junctional Epidermolysis Bullosa and Congenital Pyloric Atresia: Compound Heterozygosity in a Patient with a Novel Integrin Beta 4 Gene Mutation.

We report a case of nonfatal junctional epidermolysis bullosa and pyloric atresia in a newborn. We identified a substitution (c.914C>T) for the integrin ß4 gene that has been associated with favorable outcome. A novel mutation (c.2011T>G) of unknown significance was also found in this patient who is now thriving.

Newborn with severe epidermolysis bullosa: to treat or not to treat?

Epidermolysis bullosa (EB) is an inherited skin disease with four main subtypes that cannot be distinguished clinically at birth. All subtypes may present with widespread life-threatening blisters and fragile skin, making treatment and handling of the newborn with EB challenging. The prognosis of EB depends on the subtype, and therefore maximum treatment is necessary until the final diagnosis is known. In this case, it took 2 weeks before a final diagnosis was reached. In the meantime, we had several ethical discussions on the treatment level. The most important issues were management of pain and nutrition. For immediate pain relief, intranasal fentanyl worked best and gabapentin was successfully used for chronic pain. The feeding difficulties were handled first by a nasogastric feeding tube. Later a normal feeding bottle proved to be adequate.

Alternative Use of an Oral Endotracheal Tube Fastener in a Patient with Junctional Epidermolysis Bullosa.

This case report describes the alternative use of an oral endotracheal tube fastener in a pediatric patient with junctional epidermolysis bullosa. The patient underwent dental treatment in the operating room under general anesthesia and had a medical history of junctional epidermolysis bullosa, prior secondary anemia, clubbed feet, and past methicillin-resistant Staphylococcus aureus infection secondary to blistering. The oral endotracheal tube fastener was used in a nontraditional manner to avoid contact of the oral tube and tape with the epidermis and thus prevent blistering. Lubricated gauze was applied to the patient's eyes for protection, and lubricant was applied to the lips and perioral skin before intubation and during dental treatment. Postoperatively the patient exhibited minimal blistering secondary to intubation and dental treatment.