Search

We report the case of a 69-year-old male patient, observed for vesiculobullous lesions involving the oral mucosa ([figure 1][1]), trunk and extremities. There were also more evolved lesions with crusted surface and erythematous cicatricial plaques covered by milia cysts. ![Figure 1][2]

Background Nutritional management of children with epidermolysis bullosa (EB) presents multiple challenges including reduced oral intake compounded by mucosal fragility. Gastrostomy tube feeding is effective in improving nutritional status however there is limited data on the safety and tolerance of this technique in EB children. We aim to review the effectiveness and morbidity of our minimally invasive two-port laparoscopic-assisted gastrostomy (LAG) approach using Seldinger techniques with serial dilatations in children with EB. Methods A retrospective, observational cohort study was conducted on all consecutive EB patients who underwent LAG tube insertion between 2009-2019. Patient demographics, admission details and 12-month clinical outcomes were reported. Results 32 EB patients underwent LAG placement. Median age at insertion was 7.3 (IQR ± 6.3) years, with 8 (25.0%) and 3 (9.4%) of patients also undergoing oesophageal dilatation and fundoplication, respectively. Minor complications arose in 58.1% of patients including: peri-stomal overgranulation (25.8%), gastrostomy infection (22.6%), pain (22.6%), mild gastrostomy leakage (16.1%), blockage (9.7%) and device failure (3.2%). 2 patients (6.5%) developed major complications with extensive gastrostomy site leakage. Improvements in growth were reflected in mean height Z-scores (-1.99 to -1.71). Mean weight Z-scores improved in patients aged 0-10 years (-2.30 to -1.61) and mean BMI Z-scores increased in patients over 10 years (-2.71 to -1.46). No cases of gastrostomy-related mortality were reported. Conclusion LAG is well-tolerated in EB patients with improvements in growth and minimal morbidity 12-months post-gastrostomy insertion. An extended follow-up period is required to ascertain the long-term implications of gastrostomy feeding.

Background Transition from pediatric to adult care is a critical component of health care for children with long-term needs. The characteristics of epidermolysis bullosa (EB) demand higher than average levels of provider support. There is consensus among health care professionals regarding the importance of transition; however, there is a scarcity of practical information regarding models for patients with EB. Objective To review transition of care programs in varying specialties. Highlight practical considerations to facilitate the development of programs for patients with EB and other complex dermatologic conditions. Methods Articles were identified via MEDLINE and EMBASE health literature databases and screened for relevance to transition of care. Results Various models for transition exist. A well-executed formal transition program, early introduction, interdisciplinary collaboration, and psychosocial support were themes associated with successful outcomes. Limitations Transition of care programs that have not been described in the literature are not reflected in this review. Conclusions Patients with EB have unique needs that affect transition and span expertise across traditional boundaries, such as dependency on others for daily skin care, failure to thrive, and risk of squamous cell carcinoma. Given the rarity of the disease, patients with EB will benefit from collaborative efforts to develop programs to optimize successful transition.

Epidermolysis bullosa (EB) is a group of rare congenital genetic conditions that result in painful blistering of the skin and mucous membranes, which occur with minor trauma or friction. There are many types and subtypes of EB that need to be distinguished, as the management and prognosis of each can vary significantly. We aim to perform an up-to-date literature review on congenital EB for healthcare providers in pediatrics. We performed a review of existing literature in the English language on EB via PubMed Clinical Queries, using key words such as “epidermolysis bullosa”, “congenital” and “children”. We reviewed EB based on the following subheadings: epidemiology, diagnosis, therapy, prognosis, and clinical prediction guidelines. EB is due to mutation in a number of genes, some types are autosomal dominant while others are autosomal recessive. The underlying mechanism is a defect in attachment between or within the epidermis and dermis of the skin. There are four main types: epidermolysis bullosa simplex, dystrophic epidermolysis bullosa, junctional epidermolysis bullosa, and Kindler syndrome. The diagnosis is suspected based on symptoms and confirmed by skin biopsy and definitive genetic testing. The severity of EB can range from mild to fatal. Severe complications may arise in some EB types and subtypes within the eye, ear, nose, upper airway, gastrointestinal and genitourinary tracts. There is no cure for the condition to date. Optimal management must be multidisciplinary, and involves wound care, pain control, controlling infections, nutritional support, and prevention and treatment of complications. EB presents in different forms. Treatment is supportive. The prognosis of milder forms is good. Children severely affected with EB and their families live a misery life with impaired quality of life. Health care workers must be aware of the suffering in these families and proactively support them.

BACKGROUND Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling. OBJECTIVE To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB. METHODS A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal. RESULTS A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P

Epidermolysis bullosa (EB) encompasses a heterogeneous group of inherited skin fragility disorders, with mutations in genes encoding the basement membrane zone (BMZ) proteins that normally ensure dermal-epidermal integrity. Of the four main EB types, recessive dystrophic EB (RDEB), especially the severe variant, represents one of the most debilitating clinical entities, with recurrent mucocutaneous blistering and ulceration leading to chronic wounds, infections, inflammation, scarring and ultimately cutaneous squamous cell carcinoma, which leads to premature death. Improved understanding of the molecular genetics of EB over the past three decades and advances in biotechnology have led to rapid progress in developing gene and cell-based regenerative therapies for EB. In particular, RDEB is at the vanguard of advances in human clinical trials of advanced therapeutics. Furthermore, the past decade has witnessed the emergence of a real collective, global effort involving academia and industry, supported by international EB patient organizations such as the Dystrophic Epidermolysis Bullosa Research Association (DEBRA), among others, to develop clinically relevant and marketable targeted therapeutics for EB. Thus, there is an increasing need for the practising dermatologist to become familiar with the concept of gene therapy, fundamental differences between various approaches, and their human applications. This review explains the principles of different approaches of gene therapy, summarizes its journey, and discusses its current and future impact in RDEB.

Summary Background The rare inversa subtype of recessive dystrophic epidermolysis bullosa (RDEB-I) is characterized by predominant intertriginous skin blistering and marked mucosal involvement. Specific recessive missense mutations in the collagen VII triple helix are implicated in the disease. To date, otological complications have been reported infrequently in this patient group. Methods We conducted an observational, retrospective, double institution case record review of patients with RDEB-I who presented with otological complications between January 2000 and June 2020. Diagnosis was established on the basis of clinical features, family history and mutation analysis of the COL7A1 gene. Results In total, 11 (44%) of 25 patients with RDEB-I in our database (2 paediatric, 9 adult; mean age 40.9 years, range 8–72 years) experienced otological complications. Of these 11 patients, 10 (90.9%) had recurrent otitis externa, 7 (63.6%) had meatal stenosis and 7 (63.6%) had recurrent blistering of the external auditory canals. All 11 patients reported hearing difficulties, with conductive hearing loss confirmed by audiology testing in 6 (54.5%) of these. Of the 11 patients, 3 (27.3%) went on to have implantable hearing aids [2 bone-anchored hearing aids (BAHA) and 1 middle ear implant (MEI)] fitted with favourable outcome, while a fourth paediatric patient presented with a cholesteatoma that was surgically managed. Discussion We observed a higher prevalence of otological morbidity in RDEB-I than previously reported, and present the first case of cholesteatoma in epidermolysis bullosa (EB). Our data indicate that BAHA and MEI are safe and effective treatment options for hearing loss in EB. Clinicians should be vigilant in screening for ear symptoms in RDEB-I and consider early referral to an Ear, Nose and Throat specialist.

Background: Epidermolysis bullosa (EB) is an uncommon group of inherited disorders characterized by skin blistering after friction or mechanical trauma. EB affects patients and their families physically, socially, and emotionally. Objective: This study aimed to assess the family quality of life of these patients using the Family Dermatology Life Quality Index (FDLQI) questionnaire. Methods: In this cross-sectional study, we enrolled caregivers of patients with EB registered at the Molecular Dermatology Research Center, affiliated with Shiraz University of Medical Sciences, up to 2020. Participants filled out a demographic data collection form and the FDLQI questionnaire. The data were analyzed using SPSS software, version 22. Results: Overall, 80 participants, consisting of 65 mothers (81.2%) and 15 fathers (18.7%) as primary caregivers, were enrolled in this study. The average FDLQI score was 19.88 ± 4.71. The FDLQI scores of caregivers of patients with EB simplex was significantly lower than scores observed in those with other types of EB (p < .001). There was a significant positive association between the number of patients with EB in the family and FDLQI score (p = .049). FDLQI scores were lower in caregiving mothers who had a higher education (p < .001) and those who were employed (p < .001). Conclusion: Family quality of life is affected in patients with EB. Families with lower socioeconomic status and unemployed caregivers require special attention. More studies are needed to determine the parameters involved in the quality of life of patients with EB and their families.

Children born with the epidermolysis bullosa (so-called “butterfly children”) can eat only liquid or soft food due to the blisters on their mouth, tongue and esophagus. Due to their inactivity and permanent wounds, their fingers are curved and grown with a fist. Their eyes, anus and genitals are not spared either. The digestion is usually poor, so they often suffer from the constipation, and sometimes the intestine discharge can be performed only surgically. Due to frequent and numerous wounds, infections may develop, which can lead to sepsis. Wounds are caused by any kind of the pressure and re-bandaging of wounds is the most painful. These children can later be susceptible to other diseases, especially the skin cancer. More than 80% of children diagnosed with this disease become disabled in the first years of their lives, and some of them pass away immediately after birth. The average lifespan of the diseased is about 28 years. Here we have presented a rare case of a newborn male infant with a dystrophic epidermolysis bullousa, a congenital skin aplasia on the right leg and a nail dystrophy. Based on a typical clinical presentation, we think that it is Bart’s syndrome.

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

Background The clinical use of gentamicin always lies in its antimicrobial activity in the past as an aminoglycoside antibiotic. However, in the past decade, there were considerable interests in therapeutic approaches in treating hereditary diseases. Some of the genodermatosis is caused by nonsense mutations that create premature termination codons and lead to the production of truncated or non-functional proteins. Gentamicin could induce readthrough of nonsense mutations and enable the synthesis of full-length proteins. We focus on previous publications on topical application of gentamicin and review its utility in genetic skin diseases. Data sources We search the MEDLINE through PubMed, EMBASE databases, and the Clinical Trials Registry Platform from January 1960 to July 2020 using the key search terms "gentamicin, topical gentamicin, genodermatosis, genetic skin diseases". Results The application of gentamicin in genodermatosis yielded promising results, both in vivo and in vitro, including Nagashima-type palmoplantar keratosis, epidermolysis bullosa, Hailey-Hailey disease, hereditary hypotrichosis simplex of the scalp, etc. CONCLUSIONS: Topical gentamicin is a potential treatment option for genodermatosis caused by nonsense mutation.

Background. Patients with epidermolysis bullosa (EB) have higher risk of developing infectious diseases. Its prevention requires timely vaccination. For now, there are no studies showing vaccination coverage for this category of children. Objective. Our aim was to study vaccination coverage of children with EB according to national preventive vaccination programmes. Methods. This retrospective cross-sectional study examined medical records of patients with EB from Russian Federation and neighbouring countries. Vaccination coverage (completeness and timeliness) and age of immunization initiation were analyzed. Moreover, we have studied the spectrum of early post-vaccine reactions and the course of the post-vaccine period in children with EB vaccinated for the first time. Results. The study included medical records of 134 patients with EB aged from 8 months to 17 years 8 months. Vaccination was performed according to national immunization programs in 37 (28%) children, only 21 cases were carried out in a timely manner. Medical exemptions were the major reason for the refusal of vaccination in most cases (82%). 48 patients with EB were vaccinated against 12 vaccine preventable diseases in the hospital. The post-vaccine period was asymptomatic in 36 (76%) patients, 10 (20%) patients had tenderness and hyperemia at the injection site, 2 (4%) patients had subfebrile fever. Conclusion. Most children with EB are still unvaccinated or vaccinated untimely. Immunization of such children against vaccine preventable disease according to the individual plan can be pretty useful.

Three-dimensional (3D) bioprinting is a rapidly developing technology that has the potential to initiate a paradigm shift in the treatment of skin wounds arising from burns, ulcers and genodermatoses. Recessive dystrophic epidermolysis bullosa (RDEB), a severe form of epidermolysis bullosa, is a rare genodermatosis that results in mechanically induced blistering of epithelial tissues that leads to chronic wounds. Currently, there is no cure for RDEB, and effective treatment is limited to protection from trauma and extensive bandaging. The care of chronic wounds and burns significantly burdens the healthcare system, further illustrating the dire need for more beneficial wound care. However, in its infancy, 3D bioprinting offers therapeutic potential for wound healing and could be a breakthrough technology for the treatment of rare, incurable genodermatoses like RDEB. This viewpoint essay outlines the promise of 3D bioprinting applications for treating RDEB, including skin regeneration, a delivery system for gene-edited cells and small molecules, and disease modelling. Although the future of 3D bioprinting is encouraging, there are many technical challenges to overcome-including optimizing bioink and cell source-before this approach can be widely implemented in clinical practice.

EBS is a rare genodermatosis usually inherited in an autosomal dominant fashion, although rare autosomal recessive cases have been reported. In severe generalised EBS, infants exhibit severe symptoms at the onset which tend to improve with time. We report an adolescent with severe generalised epidermolysis bullosa simplex (EBS), the most severe form of EBS, with severe iron deficiency anaemia

Chronic wounds present a major disease burden in people with recessive dystrophic epidermolysis bullosa (RDEB), an inherited blistering skin disorder caused by mutations in COL7A1 encoding type VII collagen, the major component of anchoring fibrils at the dermal-epidermal junction. Treatment of RDEB wounds is mostly symptomatic, and there is considerable unmet need in trying to improve and accelerate wound healing. In this study, we defined transcriptomic profiles and gene pathways in RDEB wounds and compared these to intact skin in RDEB and healthy control subjects. We then used a reverse transcriptomics approach to discover drugs or compounds, which might restore RDEB wound profiles towards intact skin. Differential expression analysis identified >2000 differences between RDEB wounds and intact skin, with RDEB wounds displaying aberrant cytokine-cytokine interactions, Toll-like receptor signalling, and JAK-STAT signalling pathways. In-silico prediction for compounds that reverse gene expression signatures highlighted methotrexate as a leading candidate. Overall, this study provides insight into the molecular profiles of RDEB wounds and underscores the possible clinical value of reverse transcriptomics data analysis in RDEB, and the potential of this approach in discovering or repurposing drugs for other diseases.

Background. Children with congenital epidermolysis bullosa (CEB) can have vitamin D deficiency due to its malabsorption in intestine and reduced synthesis in skin as these patients have restrictions on staying in the sun. However, the prevalence of vitamin D insufficiency/deficiency among patients with CEB remains not fully studied due to the small samples' sizes in previously studies.Objective. Our aim was to study vitamin D provision in children with CEB.Methods. The study included children aged from 3 to 18 years old with simplex and dystrophic types of CEB hospitalized in our department. The serum level of 25(OH)D was determined via chemiluminescence immunoassay. Vitamin D deficiency was established at 25(OH)D concentration of 20-30 ng/ml, deficiency — < 10-20 ng/ml, deep deficiency — < 10 ng/ml.Results. The study included 129 children with CEB (62 (48%) males, median age 6 (3; 10) years). 101 patients had dystrophic type of disease, 28 — simplex. The median 25(OH)D serum concentration in children with CEB was 21.7 (13.0; 36.6) ng/ml. Vitamin D insufficiency was revealed in 36 (28%) patients, deficiency — in 38 (29%), deep deficiency — in 16 (12%). Independent predictors of 25(OH)D concentration were the type of CEB (concentration was higher in children with simplex type) and age (negative association), but not the patients' gender and the examination season, according to multivariate regression analysis.Conclusion. The study has shown low level of vitamin D provision in children with CEB, whilst 25(OH)D concentration depended on the type of disease and the age of patients.

We report on an adult Turkish patient with mild myopathy with a fiber-type disproportion and mitochondrial disorganization caused by genetic variants in the plectin gene (PLEC). Molecular genetic panel testing revealed two homozygous variants in PLEC (NM_000445.4): c.8306C>G (p.Pro2769Arg) and c.7506 + 5C>G (p. ?) that were classified as variants of unknown significance (class 3) following ACMG guidelines for variant classification in genetic diagnostics. A thorough reassessment of the patient revealed mild skin blistering (epidermolysis bullosa simplex, EBS). This illustrates the importance of deep phenotyping of neuromuscular patients.

Mesenchymal stromal cells (MSCs) are multi-potent stromal-derived cells capable of self-renewal that possess several advantageous properties for wound healing, making them of interest to the field of dermatology. Research has focused on characterizing the unique properties of MSCs, which broadly revolve around their regenerative and more recently discovered immunomodulatory capacities. Because of ease of harvesting and expansion, differentiation potential and low immunogenicity, MSCs have been leading candidates for tissue engineering and regenerative medicine applications for wound healing, yet results from clinical studies have been variable, and promising pre-clinical work has been difficult to reproduce. Therefore, the specific mechanisms of how MSCs influence the local microenvironment in distinct wound etiologies warrant further research. Of specific interest in MSC-mediated healing is harnessing the secretome, which is composed of components known to positively influence wound healing. Molecules released by the MSC secretome can promote re-epithelialization and angiogenesis while inhibiting fibrosis and microbial invasion. This review focuses on the therapeutic interest in MSCs with regard to wound healing applications, including burns and diabetic ulcers, with specific attention to the genetic skin disease recessive dystrophic epidermolysis bullosa. This review also compares various delivery methods to support skin regeneration in the hopes of combating the poor engraftment of MSCs after delivery, which is one of the major pitfalls in clinical studies utilizing MSCs.

Background Wound management is a critical factor when treating patients with the inherited skin fragility disease dystrophic epidermolysis bullosa (DEB). Due to genetic defects in structural proteins, skin and mucous epithelia are prone to blistering and chronic wounding upon minor trauma. Furthermore, these wounds are commonly associated with excessive pruritus and predispose to the development of life-threatening squamous cell carcinomas, underscoring the unmet need for new therapeutic options to improve wound healing in this patient cohort. Vitamin D3 is acknowledged to play an important role in wound healing by modulating different cellular processes that impact epidermal homeostasis and immune responses. In this study, we evaluate the safety and efficacy of low-dose calcipotriol, a vitamin D3 analogue, in promoting wound healing and reducing itch and pain in patients with DEB. Methods Eligible DEB patients, aged ≥ 6 years and with a known mutation in the COL7A1 gene, were recruited to a placebo-controlled, randomized, double blind, cross-over phase II monocentric clinical trial. Patients were required to have at least two wounds with a minimum size of 6 cm2 per wound. The primary objective was to evaluate efficacy of daily topical application of a 0.05 µg/g calcipotriol ointment in reducing wound size within a 4-week treatment regimen. Secondary objectives were to assess safety, as well as the impact of treatment on pruritus, pain, and bacterial wound colonization in these patients. Results Six patients completed the clinical trial and were included into the final analysis. Topical low-dose calcipotriol treatment led to a significant reduction in wound area at day 14 compared to placebo (88.4% vs. 65.5%, P P 0.05) and 1.83 vs 5.52 (P 0.0001) at days 14 and 28, respectively. Treatment with low-dose calcipotriol did not affect serum calcium levels and improved the species richness of the wound microbiome, albeit with no statistical significance. Conclusions Our results show that topical treatment with low-dose calcipotriol can accelerate wound closure and significantly reduces itch, and can be considered a safe and readily-available option to improve local wound care in DEB patients. TrialRegistration EudraCT: 2016–001,967-35. Registered 28 June 2016, https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001967-35/AT

Introduction: Pyloric atresia is a rare cause of congenital gastric outlet obstruction. It is often associated with epidermolysis bullosa (EB). Rarity and experience with 11 cases are the reason for this publication. Aims and Objectives: The aim and objective of this study is to present our experience of 11 cases of congenital pyloric atresia and correlate with available literature. Materials and Methods: This was retrospective cohort of 11 cases correlative comparative study. Data of all the 11 cases from 1982 to 2019 were collected, reviewed, and analyzed. The parameters studied included age, gender, antenatal diagnosis, postnatal diagnosis, preoperative management, intraoperative findings, postoperative course outcome, associated anomalies, and any genetic studies if done. All these parameters were compared with published data. Results: There were 11 cases in the present series with six boys and five girls. Most of them presented at varying periods from birth to day 1 of life. Eight cases of type 1 pyloric atresia, two cases of type 2 pyloric atresia, and one case of type 3 pyloric atresia constituted the cohort. Five out of 11 cases were associated with EB. Two out of six cases with isolated pyloric atresia and four out of five cases with EB died. Discussion: Congenital pyloric atresia may be isolated or associated with EB. Three varieties of pyloric atresia were described. Association with EB increases the mortality. Conclusions: Review and analysis of 11 cases of pyloric atresia compared with published literature is being reported.

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.

ispartof: J Am Acad Dermatol vol:87 issue:4 pages:872-874 ispartof: location:United States status: published

The public and health care providers are increasingly curious about the potential medical benefits of Cannabis. In vitro and in vivo studies of Cannabis have suggested it has favorable effects on regulating pain, pruritus, and inflammation, making it a potentially attractive therapeutic agent for many dermatologic conditions. The body of literature reporting on the role of cannabinoids in dermatology is in its infancy but growing. We review the current research, possible cutaneous adverse effects, and future directions for cannabinoids and their use in skin cancer, acne, psoriasis, pruritus, dermatitis, scleroderma, dermatomyositis, cutaneous lupus erythematous, epidermolysis bullosa, pain, and wound healing.

Background Epidermolysis bullosa (EB) patient anecdotes and case reports indicate that cannabinoid-based medicines (CBMs) may alleviate pain and pruritus and improve wound healing. CBM use has not been characterized in the EB patient population. Objectives To evaluate CBM use among EB patients, including CBM types, effects on symptoms (e.g., pain and pruritus), disease process (e.g., blistering, wounds, and inflammation), well-being (e.g., sleep, appetite) and concomitant medications. Methods English-speaking EB patients or caregivers completed an online international, anonymous, cross-sectional survey regarding CBM use. Respondents reported the types of CBMs, subsequent effects including perceived EB symptom alteration, changes in medication use, and side effects. Results Seventy-one EB patients from five continents reported using or having used CBMs to treat their EB. Missing question responses ranged between 0 (0%) and 33 (46%). Most used more than one CBM preparation (mean: 2.4 ± 1.5) and route of administration (mean: 2.1 ± 1.1). Topical and ingested were the most common routes. Pain and pruritus were reported retrospectively to decrease by 3 points (scale: 0–10; p overall EB symptoms (95%), pain (94%), pruritus (91%) and wound healing (81%). Most participants (79%) reported decreased use of pain medications. The most common side-effect was dry mouth (44%). Conclusions CBMs improve the perception of pain, pruritus, wound healing, and well-being in EB patients and reduced concomitant medication use. Nevertheless, a direct relation between the use of CBMs and reduction of the above-mentioned symptoms cannot be proven by these data. Therefore, future controlled studies using pharmaceutically standardised CBM preparations in EB are warranted to delineate the risks and benefits of CBMs.

Gene editing via homology-directed repair (HDR) currently comprises the best strategy to obtain perfect corrections for pathogenic mutations of monogenic diseases, such as the severe recessive dystrophic form of the blistering skin disease epidermolysis bullosa (RDEB). Limitations of this strategy, in particular low efficiencies and off-target effects, hinder progress toward clinical applications. However, the severity of RDEB necessitates the development of efficient and safe gene-editing therapies based on perfect repair. To this end, we sought to assess the corrective efficiencies following optimal Cas9 nuclease and nickase-based COL7A1-targeting strategies in combination with single- or double-stranded donor templates for HDR at the COL7A1 mutation site. We achieved HDR-mediated correction efficiencies of up to 21% and 10% in primary RDEB keratinocytes and fibroblasts, respectively, as analyzed by next-generation sequencing, leading to full-length type VII collagen restoration and accurate deposition within engineered three-dimensional (3D) skin equivalents (SEs). Extensive on- and off-target analyses confirmed that the combined treatment of paired nicking and single-stranded oligonucleotides constituted a highly efficient COL7A1-editing strategy, associated with a significantly improved safety profile. Our findings, therefore, represent a further advancement in the field of traceless genome editing for genodermatoses.

Background Epidermolysis bullosa (EB) is a rare disease characterized by blistering and erosion of the skin and mucus membranes in response to minor external forces. Research focusing on daily skin care in EB patients is sparse. Two international clinical practice guidelines (CPGs) have been published in English, but they have not yet been translated into other languages such as Japanese. Therefore, their recommendations have not been adapted to multiple geographic regions in the world. This multiple case series describes our approach to the skin care of 3 Japanese patients with EB. Results All 3 patients were diagnosed with genetic EB. A 13-year-old male patient had dominant dystrophic EB and suffered skin breakdown covering nearly 1% to 6% of his total body surface area (TBSA) during a 21-week data collection period. A 3-year-old male patient had EB simplex; he suffered skin breakdown covering 2% to 40% of his TBSA during a 36-week data collection period. The third case was a 5-year-old male patient with recessive dystrophic EB who experienced skin breakdown covering 2% to 40% of his TBSA during a 35-week data collection period. Blisters were punctured daily and treated with a soft silicone dressing. Daily application of moisturizers was undertaken to prevent the skin from drying out and itching. Conclusion Our experience suggests that application of published CPGs promoted wound healing. Nevertheless, given the nature of the disease, a complete resolution to an individual's vulnerability to skin lesions even with relatively minor trauma remains elusive. Additional research is needed to explore interventions for skin and ulcer care, along with symptom management, including pain and pruritus.

Congenital epidermolysis bullosa is known to be on the list of rare diseases for which there is no specific treatment. Determining thecontent and means of the rehabilitation program for patients with epidermolysis bullosa is not an easy task and involves a carefulselection of methods for each patient. Aim. The article analyzes the results of the use of non-drug methods in the complex rehabilitation of 90 children (from 6,5 to 18 years)with congenital epidermolysis bullosa. Material and methods. To assess the effectiveness of rehabilitation in the study before and after treatment we used methods ofclinical examination with skin state evaluation and standard psychological and pedagogical examination to determine the degree ofsocial adaptation of patients (analysis of medical and psychological and pedagogical documentation, structured conversation aboutsocial conditions of the child’s life, “Color diagnostic test of nervous and mental states and relations” (V.I. Timofeev and Y.I. Filimonenko),the method “Drawing of an unknown animal” (M.Z. Dukarevich, adaptation by A.L. Venger), “The T.V. Dembo-S.Y. Rubinstein Self-AssessmentResearch Method, the Self-Concept Scale” (E. Pierce, L. Harris, adapted by A. M. Prikhozhan), questionnaire “Assessment ofparental compliance” (D.E. Morisky, L.V. Green), questionnaire “Feeling, activity, mood” (V.A. Doskin, N.A. Lavrentieva, V.B. Sharay andM.P. Miroshnikov). The way in which diagnostics was organized varied taking into account the individual psychophysical capabilitiesof the child. Results. The effectiveness evaluation of the complex rehabilitation of children with epidermolysis bullosa showed an improvementin the clinical condition of the children (significant reduction/elimination of dryness and itching of the skin) and the indicators of wellbeing(mean value: before 30 points after 45, p ≤0.05), activity (mean value: before 25 after 34, p ≤0.05), mood (mean value: before 44,after 51, p ≤0.05) of patients (WAM questionnaire), an increase in the degree of parental commitment to treating children (Moriski-Green questionnaire) from medium to medium and high values. Conclusion. The inclusion of physical therapy and psychological and pedagogical methods of assistance in the process of rehabilitationtreatment increases its effectiveness, activates the compensatory potential of the child’s body, promotes harmonization of intrafamilyrelationships, and thus improves the quality of life of the child and his or her relatives.

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 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.

Staphylococcal scalded skin syndrome (SSSS) describes a spectrum of superficial blistering skin disorders caused by the exfoliative toxins of Staphylococcus aureus that originates from a focus of infection that may be a purulent conjunctivitis, otitis media, or occult nasopharyngeal infection. It usually begins with fever, irritability, and a generalized, paint, orange-red, macular erythema with cutaneous tenderness, and the rash progress from scarlatiniform to a blistering eruption in 24 to 48 hours. A diagnosis must distinguish SSSS from other skin diseases, such as toxic epidermal necrolysis, epidermolysis bullosa, bullous erythema multiforme, Streptococcal impetigo or listeriosis and thermal or chemical burns, all of which can manifest with similar symptoms. The prognosis of SSSS in children who are appropriately treated is good, with a mortality of less than 5%. A case was a three moths old boy hospitalized in Pediatric ward M. Djamil hospital with chief complain redness and peeling of the skin since 2 days before hospitalized. Culture of the skin, eyes and nose was Staphylococcus aureus, and patients was given ampicillin and gentamycin for seven days.

Epidermolysis bullosa (EB) is a group of rare, inherited diseases characterized by skin fragility and multiorgan system involvement that presents many anesthetic challenges. Although the literature regarding anesthetic management focuses primarily on the pediatric population, as life expectancy improves, adult patients with EB are more frequently undergoing anesthesia in nonpediatric hospital settings. Safe anesthetic management of adult patients with EB requires familiarity with the complex and heterogeneous nature of this disease, especially with regard to complications that may worsen during adulthood. General, neuraxial, and regional anesthetics have all been used safely in patients with EB. A thorough preoperative evaluation is essential. Preoperative testing should be guided by EB subtype, clinical manifestations, and extracutaneous complications. Advanced planning and multidisciplinary coordination are necessary with regard to timing and operative plan. Meticulous preparation of the operating room and education of all perioperative staff members is critical. Intraoperatively, utmost care must be taken to avoid all adhesives, shear forces, and friction to the skin and mucosa. Special precautions must be taken with patient positioning, and standard anesthesia monitors must be modified. Airway management is often difficult, and progressive airway deterioration can occur in adults with EB over time. A smooth induction, emergence, and postoperative course are necessary to minimize blister formation from excess patient movement. With careful planning, preparation, and precautions, adult patients with EB can safely undergo anesthesia.

Epidermolysis bullosa (EB) encompasses a phenotypically and genetically heterogeneous group of inherited skin disorders characterized by blistering and erosions of the skin with minimal trauma. Dystrophic EB (DEB), both dominant and recessive, can be associated with several extracutaneous manifestations, including musculoskeletal deformities. Congenital deformities of the feet have rarely been reported in the literature. We describe an infant with dominant DEB and congenital absence of the skin who presented with congenital brachydactyly of the bilateral great toes.

WHO defines malnutrition as severe if the z-scores are less than − 3 Standard deviation (SD), moderate if between − 2 and − 3 SD and mild if between − 2 SD to – 1 SD. This study was aimed to assess nutritional aspects of Indian children suffering from EB and to evaluate the effect of severity of EB on the severity of malnutrition. In this study, pediatric EB patients were evaluated prospectively for baseline nutritional status using anthropometric parameters and WHO growth charts, and its correlation with disease severity using instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa-iscorEB. In second phase, an individualized diet chart was given to meet the energy, protein and micronutrients needs and its effects were observed after 6 months. The median age of participants was 3 years (IQR-9). Of 57 patients, malnutrition was seen in 40.35% patients (22.81%-moderate and 17.54%-severe), and significantly correlated with iscorEB (r = 0.45, p

With recent advances in genetic engineering technology, gene therapy is now being considered as a treatment not only for congenital diseases but also acquired diseases, such as cancer. Gene therapeutic agents for hereditary immune disorders, haemophilia, retinal diseases, neurodegenerative diseases, and lymphoma have been approved in the United States and Europe. In the field of dermatology, clinical trials of gene therapy have been conducted, because the skin is an easily accessible organ that represents an attractive tissue for gene therapy. In recent years, gene therapy has been attempted for a variety of skin diseases, such as genodermatoses (including epidermolysis bullosa and Netherton syndrome), cutaneous lymphoma, and malignant melanoma. As a result, it is difficult to grasp the current status of gene therapy in dermatology. This review focuses on each of the gene-transfer techniques currently in use and describes the current status of gene therapy for skin diseases using each technology.

Pyloric atresia is a rare digestive malformation. It represents about 1% of intestinal atresias and is associated with some other genetic or anatomical alteration in 55% of the cases. In 20% of them, it is associated with epidermolysis bullosa, which is described as an established syndrome with a bad prognosis. We present two cases of consecutive siblings with this condition and fatal outcomes in both of them. We made a review of the literature and discussed the main topics.La atresia pilórica es una malformación digestiva poco frecuente y representa alrededor del 1 % de las atresias intestinales. En el 55 % de los casos, se asocia con alguna otra alteración genética o anatómica, especialmente la epidermólisis ampollosa, que se presenta en el 20 % de ellos, en una asociación que se describe como un síndrome de mal pronóstico. Se presentan dos casos de hermanos consecutivos con esta condición, ambos con un desenlace fatal. Se hizo, además, una revisión de la literatura y se expusieron los puntos más importantes.

Stem cells are precursor cells present in many tissues with ability to differentiate into various types of cells. This interesting property of plasticity can have therapeutic implications and there has been substantial research in this field in last few decades. As a result, stem cell therapy is now used as a therapeutic modality in many conditions, and has made its way in dermatology too. Stem cells can be classified on the basis of their source and differentiating capacity. In skin, they are present in the inter-follicular epidermis, hair follicle, dermis and adipose tissue, which help in maintaining normal skin homeostasis and repair and regeneration during injury. In view of their unique properties, they have been employed in treatment of several dermatoses including systemic sclerosis, systemic lupus erythematosus, scleromyxedema, alopecia, Merkel cell carcinoma, pemphigus vulgaris, psoriasis, wound healing, epidermolysis bullosa and even aesthetic medicine, with variable success. The advent of stem cell therapy has undoubtedly brought us closer to curative treatment of disorders previously considered untreatable. Nevertheless, there are multiple lacunae which need to be addressed including ideal patient selection, timing of intervention, appropriate conditioning regimens, post-intervention care and cost effectiveness. Further research in these aspects would help optimize the results of stem cell therapy.

We report a case of junctional epidermolysis bullosa with pyloric atresia (JEB-PA) with minimal skin involvement but severe protein-losing enteropathy and airway involvement. Genetic analysis revealed heterozygous mutations in the ITGB4 gene encoding integrin β4 protein. Parental testing confirmed inheritance of frameshift variant (c.794dupC) as maternal and splice site variant (c.1608C>T/p.Cys536Cys) as paternal. Immunofluorescence mapping of her skin revealed a subepidermal blister with decreased and frayed integrin β4 at both the floor and the roof of the blister, while the intestinal mucosa showed complete absence of integrin β4. We review the literature and discuss the differential expression of integrins in the skin and gastrointestinal tract, as well as the role of chronic inflammation in the pathogenesis of EB.

Epidermolysis bullosa (EB) refers to a group of genetic diseases characterized by blistering in response to minor trauma. It is divided into 3 major categories based on the depth of skin blistering, as follows: 1) EB simplex (EBS), 2) junctional EB, and 3) dystrophic EB. A fourth major type was recently proposed and encompasses Kindler syndrome, since this genodermatosis shares with the other 3 major EB types the presence of mechanically fragile skin and blisters, yet, in contrast to all other EB types, typically have cleavage planes within multiple levels of the basement membrane zone.1,2 The most recently updated classification of EB was published by Mellerio et al.3 EBS is most often caused by mutations within the genes encoding for keratin 5 and keratin 14, with the vast majority being autosomal dominantly transmitted.2 There are currently no approved therapies for any form of inherited EB. Treatments have focused on symptom relief, and the increasing understanding of the pathogenesis of EB is facilitating the development of novel evidence-based therapy approaches. Recent knowledge on disease-secondary mechanisms has led to the development and clinical testing of urgently needed symptom-relief therapies using small molecules and biologicals. For now, day-to-day management of EB focuses on the prevention of mechanical trauma, wound care, avoidance of infection, padding over bony prominences, protective bandaging, and loose-fitting clothes1 Herein, we present the case of a 49-year-old woman with known EBS-mottled pigmentation since birth who cleared after treatment of nasopharyngeal carcinoma.

Background Epidermolysis bullosa simplex (EBS) is the most common type of EB, a group of rare genodermatoses. Affected individuals suffer from skin blistering and report a high disease burden. In some EBS subtypes, plantar keratoderma (PK) has been described. Objectives This study investigated the presence and correlation of PK with body mass index, pain and mobility in EBS. Methods Individuals (n = 157) with genetically characterized EBS were included in this retrospective cohort study, and clinical data were collected over 16 years (referral patients to the largest German EB centre). Descriptive statistics and mixed linear models were used to assess correlations. Results PK was found in 75.8% of patients beginning at a mean age of 4.3 years. Both focal and diffuse PK were observed, and 60% of adults with localized and severe EBS were preobese or obese, with ˜30% of patients reporting severely reduced mobility. The presence of PK, especially diffuse PK, correlated significantly with local infections, obesity, pain and requirement of a wheelchair. Conclusion Along with treating skin fragility and blistering, PK should be considered a potential marker of increased morbidity and may represent a target of EBS therapy development.

BACKGROUND Infection is an important complication of epidermolysis bullosa (EB), and Staphylococcus aureus has been pointed out as the most common pathogen among this population. The objective of this study was to investigate the prevalence and antimicrobial resistance profile of S. aureus colonizing EB patients in Brazil. METHODS This cross-sectional multicenter study was conducted between December 2015 and December 2017. We included a total of 89 individuals with EB from medical centers across Brazil. Data were obtained through clinical and bacteriological investigation. S. aureus were identified by biochemical tests. The nuc and mecA genes were confirmed by PCR assay. Antimicrobial susceptibility was investigated by disk diffusion method. RESULTS The overall prevalence of S. aureus was 51.7% (46/89). Methicillin-resistant S. aureus (MRSA) was detected in 24.7% (19/77) of all S. aureus isolates, colonizing 15.7% (14/89) of all patients. Community-associated (CA)-MRSA strains were resistant against sulfamethoxazole/trimethoprim and levofloxacin (P

Epidermolysis bullosa (EB) is a rare inherited skin disorder characterised by skin fragility and blistering. In consideration of the daily wound caring issues of patients with EB, the aim of this s...

Introduction: Self-treatment with Lamotrigine rarely ends with toxicity, regardless of the suicidal intentions of the patient. The authors hereby present an illustrative case of the patient who has been treated with epilepsy therapy with Dandy-Walker syndrome and congenital epidermolysis bullosa (potentially skin-unwanted). Lamotrigine is a phenyltriazine-class, broad-spectrum antiepileptic and therapy of bipolar depression. Dandy-Walker syndrome is a pathological entity and represents the set of developmental, cerebral, but also other abnormalities of the organism. Epidermolysis bullosa is a hereditary, non-inflammatory skin disease with a mucous membrane of characteristic "bubbles". Case report: Our patient, a 37-year-old male was first admitted to the hospital department of Urgent Medicine of Clinical Center Kragujevac because he consumed two boxes of Lamotrigine tablets. In the receiving clinic, the patient showed respiratory failure and was urgently intubated. From medical documentation and hetero-anamnesis (obtained by his father), the authors found out that he was treated for epilepsy, Dandy-Walker syndrome, and congenital epidermolysis bullosa, which deteriorated with the use of Lamotrigine through potentially undesirable skin effects. During clinical observation, a lavage of gastric contents was conducted. The medical coal was used via nasogastric intubation as a detoxification method because of the patient's comatose state. Causative metabolic pathway of lamotrigine, the hemodialysis was performed. Conclusion: The case report of our patient points to the necessity of a multidisciplinary approach of the expert team, consisting of the clinical pharmacologist and toxicologist, neurologist, dermatologist, nephrologists, and other specialists, if necessary. Patients with Dandy-Walker syndrome require adequate socio-medical care.

The 2019 novel coronavirus pandemic has tremendously affected health-seeking behaviors. Fear of contracting the disease has been a major factor keeping patients from presenting to hospitals, even when urgent or emergent medical attention is needed. Hospitals limiting staff exposure and capacity to accommodate patients also limits opportunities to seek care. Although physical distancing is encouraged to curb infections, this call needs to be tempered with public health education for what constitutes emergencies and urgent medical conditions needing face-to-face attention. Measures to assuage fears among patients and their caregivers to ensure their safety in the hospital or health care setting need to be communicated and executed effectively. Epidermolysis bullosa is an inherited mechanobullous disorder that is usually stable, but in some patients with underlying comorbidities, close monitoring or face-to-face management is required . We present our experience and provide recommendations pertinent to epidermolysis bullosa patients of all subtypes during the coronavirus crisis.

Epidermolysis bullosa is a severe hereditary disease caused by mutations in genes encoding cutaneous basement membrane proteins. These mutations lead to dermal-epidermal junction failure and, as a result, to disturbances in the morphological integrity of the skin. Clinically, it manifests in the formation of blisters on the skin or mucosa that in some cases can turn into non-healing chronic wounds, which not only impairs patient’s quality of life, but also is a live-threatening condition. Now, the main approaches in the treatment of epidermolysis bullosa are symptomatic therapy and palliative care, though they are little effective and are aimed at reducing the pain, but not to complete recovery. In light of this, the development of new treatment approaches aimed at correction of genetic defects is in progress. Various methods based on genetic engineering technologies, transplantation of autologous skin cells, progenitor skin cells, as well as hematopoietic and mesenchymal stem cells are studied. This review analyzes the pathogenetic methods developed for epidermolysis bullosa treatment based on the latest achievements of molecular genetics and cellular technologies, and discusses the prospects for the use of these technologies for the therapy of epidermolysis bullosa.

Skin abnormalities are often indicative of cardiovascular diseases. Such a disease entity is called cardiocutaneous syndrome; however, the details regarding the involvement of bulla and nails remain largely unclear. A 49-year-old man with systemic bulla was admitted for heart failure. His bulla had previously been diagnosed as epidermolysis bullosa, but no known gene mutations for it had been identified. He had a triad of palmoplantar keratosis, curly and fine hair, and cardiomyopathy, which are characteristic of NAXOS-Carvajal syndrome. This case highlights the fact that bulla and brittle nails can accompany NAXOS-Carvajal syndrome, showing that these extra-cardiac findings can help identify otherwise overlooked serious cardiac conditions.