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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.

Introduction: Epidermolysis bullosa (EB) is a genetically inherited disease characterized by recurrent bullae and erosions on the skin with numerous signs of dental caries and poor oral hygiene. The aim of this study was to investigate the general clinical and oral findings of patients with EB. Materials and Methods: In this prospective study, the clinical and oral findings and family history of 26 cases with EB were evaluated. The type of EB, gender, age, parental consanguinity, dental caries, oral findings, distribution of lesions and presence of associated anomalies, clinical and oral findings correlated with gender were recorded. Results: All 26 patients with EB had a history of consanguinity and siblings with EB to varying degrees. In our study, malnutrition, anemia and growth retardation, gastrointestinal system complications, hair thinning, hand and nail deformity, ocular problems and renal disease (in one case) were observed with variable frequencies. When the intraoral findings of the patients were investigated, extensive dental caries in all EB types, enamel hypoplasia in junctional EB (JEB) and the presence of tooth-root to be extracted in dystrophic EB (DEB), intraoral bullae and lesions, ankyloglossia, vestibular sulcus insufficiency, microstomia and maxillary atrophy were observed. Three cases had restorative treatment and one case had prosthetic rehabilitation. Conclusions: Oral involvement can be seen with varying frequencies depending on the type of EB and the severity of the disease. It may result from delayed oral and dental rehabilitation due to physical disabilities, limitations and more pressing medical problems. Microstomy, pain from mucosal lesions, and restricted access to the mouth can be caused by poor oral hygiene. Oral complications and caloric needs of individuals with EB should be determined, and individual prophylaxis should be applied to prevent caries formation and protect teeth.

Today, more than 300 million people worldwide suffer from one or more rare diseases. Epidermolysis bullosa (EB) is a heterogeneous group of hereditary diseases characterized by a genetic predisposition to a hypersensitive body reaction to minor skin damage, characterized by the formation of blisters and erosions on the skin and mucous membranes, followed by scarring. It is one of the most severe hereditary dermatoses. In EB, pathological conditions also occur in the oral cavity. Thus, patients with EB require a special “atraumatic” approach to medical procedures, hygienic care, professional oral hygiene, etc. Purpose - to systematize clinical recommendations for oral care for patients with BE on the basis of a clinical case. Clinical case. We present a clinical case of a patient with a dystrophic EB and a diagnosis of acute chronic granulating periodontitis. Examination of the oral cavity revealed microstomia, multiple caries, erosions and ulcers on the oral mucosa, signs of chronic catarrhal gingivitis, as well as dentoalveolar anomalies. After achieving a satisfactory degree of mouth opening using a set of exercises for the maxillofacial muscles, treatment of the acute chronic granulating periodontitis of the tooth 23 was performed. As a result of the clinical observation and analysis of the literature, we systematized practical recommendations aimed at facilitating the treatment of oral diseases in patients with EB. Conclusions. Treatment of oral diseases in patients with EB is primarily aimed at preventing pain and preventing secondary infection of affected areas. Treatment of dental caries contributes to the correct position of the tongue, improved swallowing and phonetics, as well as to improvement in nutritional status and aesthetic appearance. Oral hygiene reduces the risk of injury to the oral and pharyngeal mucosa. In the treatment of patients with EB, it is important to use a multidisciplinary approach with the involvement of specialists of different specialties. Implementation of simple but effective recommendations made by pediatric dentists will increase the effectiveness of prevention of oral diseases in these children. The study was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent of parents and child was obtained for the study. No conflict of interests was declared by the authors., На сегодня более 300 млн человек в мире страдают одним или несколькими редкими (орфанными) заболеваниями. Буллезный эпидермолиз (БЭ) - гетерогенная группа наследственных заболеваний, характеризующаяся генетической предрасположенностью к сверхчувствительной реакции организма на незначительное повреждение кожи образованием волдырей и эрозий на кожных и слизистых покровах с последующим образованием рубцов. Является одним из самых тяжелых наследственных дерматозов. При БЭ патологические состояния возникают и в ротовой полости. Следовательно, пациенты с БЭ требуют особого «атравматического» подхода к выполнению медицинских манипуляций, проведения гигиенического ухода, санации полости рта и т.д. Цель - на примере клинического случая систематизировать клинические рекомендации по уходу за полостью рта у пациентов с БЭ. Клинический случай. Представлен клинический случай пациента с дистрофической формой БЭ и диагнозом «Обострение хронического гранулирующего периодонтита». При осмотре полости рта выявлена микростомия, множественный кариес, эрозии и язвы на слизистой оболочке полости рта, признаки хронического катарального гингивита, а также зубочелюстные аномалии. После достижения удовлетворительной степени открывания рта путем миогимнастики проведено лечение обострения хронического гранулирующего периодонтита зуба 23. В результате клинического наблюдения и анализа литературных источников систематизированы практические рекомендации, целью которых является облегчение лечения заболеваний полости рта у пациентов с БЭ. Выводы. Лечение заболеваний полости рта у пациентов с БЭ заключается прежде всего в предупреждении боли и предотвращении вторичного инфицирования элементов поражения. Лечение кариеса зубов способствует правильному положению языка, усовершенствованному глотанию и фонетике. Улучшается пищевой статус, а также эстетический вид. Санированная ротовая полость уменьшает риск травмирования слизистой оболочки полости рта и глотки. В лечении больных с БЭ важное значение имеет мультидисциплинарный подход с привлечением специалистов разных специальностей. Выполнение простых, но действенных рекомендаций детских стоматологов позволяет повысить эффективность профилактики заболеваний полости рта у этих детей. Исследование выполнено в соответствии с принципами Хельсинкской декларации. На проведение исследований получено информированное согласие родителей и ребенка. Авторы заявляют об отсутствии конфликта интересов., На сьогодні понад 300 млн осіб у світі страждають на одне або кілька рідкісних (орфанних) захворювань. Бульозний епідермоліз (БЕ) - гетерогенна група спадкових захворювань, що характеризується генетичною схильністю до надчутливої реакції організму на незначне пошкодження шкіри утворенням пухирів і ерозій на шкірних і слизових покривах із наступним утворенням рубців. Є одним із найтяжчих спадкових дерматозів. При БЕ патологічні стани виникають і в ротовій порожнині. Отже, пацієнти з БЕ потребують особливого «атравматичного» підходу до виконання медичних маніпуляцій, а також проведення гігієнічного догляду, санації порожнини рота тощо. Мета - на прикладі клінічного випадку систематизувати клінічні рекомендації з догляду за порожниною рота в пацієнтів із БЕ. Клінічний випадок. Наведено клінічний випадок пацієнта з дистрофічною формою БЕ та діагнозом «Загострення хронічного гранулюючого періодонтиту». Під час огляду порожнини рота виявлено мікростомію, множинний карієс, ерозії та виразки на слизовій оболонці порожнини рота, ознаки хронічного катарального гінгівіту, а також зубощелепні аномалії. Після досягнення задовільного ступеня відкривання рота шляхом міогімнастики проведено лікування загострення хронічного гранулюючого періодонтиту зуба 23. У результаті клінічного спостереження та аналізу літературних джерел систематизовано практичні рекомендації, метою яких є полегшення лікування захворювань порожнини рота в пацієнтів із БЕ. Висновки. Лікування захворювань порожнини рота в пацієнтів із БЕ полягає насамперед у попередженні болю та запобіганні вторинного інфікування елементів ураження. Лікування карієсу зубів сприяє правильному положенню язика, удосконаленому ковтанню та фонетиці. Поліпшується харчовий статус, а також естетичний вигляд. Санована ротова порожнина зменшує ризик травмування слизової оболонки порожнини рота та глотки. У лікуванні хворих із БЕ важливе значення має мультидисциплінарний підхід із залученням фахівців різних спеціальностей. Виконання простих, але дієвих рекомендацій дитячих стоматологів дає змогу підвищити ефективність профілактики захворювань порожнини рота в цих дітей. Дослідження виконано відповідно до принципів Гельсінської декларації. На проведення досліджень отримано інформовану згоду батьків та дитини. Автори заявляють про відсутність конфлікту інтересів.

Uvod: Bulozna epidermoliza je poimenovanje skupine dednih bolezni, za katero sta značilna krhkost kože in sluznic ter nastajanje mehurjev po površini telesa. Samostojnost pacientov je odvisna od izraženosti simptomov, predvsem ran, bolečine in sočasnih bolezni. Vloga zdravstvenega osebja pri osebah z bulozno epidermolizo je predvsem spodbujanje samooskrbe pacientov. Namen: Namen diplomskega dela je raziskati dejavnike, ki pozitivno vplivajo na samooskrbo pacientov z bulozno epidermolizo v domačem okolju in intervencije medicinskih sester pri ljudeh z bulozno epidermolizo. Metode dela: Uporabili smo deskriptivno metodo dela. Narejen je bil pregled strokovne in znanstvene literature, ki smo jo iskali v bibliografskih bazah CINAHL, MEDLINE in iskalniku ScienceDirect. Uporabljene besede v iskalnem nizu: epidermolysis bullosa, EB, self care, self efficiency, self management, self-sufficiency, self support, home, home enviroment, nurse, nurses, nursing, wound, wounds, skin, epidermis. V pregled smo vključili članke, objavljene v angleškem jeziku v obdobju od leta 2010 do leta 2022, ki so bili dostopni v celotnem obsegu besedila za člane knjižnice Univerze v Ljubljani. V analizo smo vključili 23 člankov. Rezultati: Domače okolje za paciente predstavlja glavno strukturo stabilnosti, varnosti in zavetja. Raziskave kažejo, kako pomembni sta spodbuda in podpora medicinskih sester pacientom. Paciente motiviramo k doseganju njihovih ciljev in povečanju samostojnosti. Izobraževanja medicinskih sester so izrednega pomena saj pripomorejo k prenosu znanja o oskrbi kože in ran na paciente. Njihovo znanje o bolezni prispeva k izboljšanju zdravstvene pismenosti pacientov in učinkovito izvajanje negovalnih intervencij. Medicinske sestre s poučevanjem pacientov glede samooskrbe ustvarjajo dober odnos z njimi. Razprava in zaključek: Glede na redkost bolezni sta šibka zdravstvena pismenost in samooskrba pacientov glavna dejavnika, ki vodita do počasnejšega celjenja ran, socialne izolacije in anksioznih motenj. Pri organiziranju zdravstvene oskrbe na domu so potrebni načrt zdravstvene nege in vnaprej določene intervencije, ki se bodo izvajale v domačem okolju. Izobraževalni programi za medicinske sestre, ki dajejo natančne informacije o zdravstvenih intervencijah, ki so usmerjene v obvladovanje bolezni in povečanje samostojnosti pacientov z bulozno epidermolizo, lahko izboljšajo prognozo bolezni in kakovost življenja. Introduction: Epidermolysis bullosa is a group of hereditary diseases characterized by a mechanical fragility of the skin and mucous membranes and blister formation all over the body. As regards wounds, pain, and comorbidities, patients' independence depends on how they express their symptoms. Healthcare personnel have a major role in supporting self-care and independence of patients with epidermolysis bullosa. Purpose: The purpose of this study is to identify the positive factors influencing better self-care and nurse interventions for people with epidermolysis bullosa living at home. Methods: We used a descriptive work method to perform a review of and scientific literature by searching the bibliographic data bases of CINAHL, MEDLINE and ScienceDirect. The literature search was conducted by using the keywords: epidermolysis bullosa, EB, self care, self efficiency, self management, self-sufficiency,r self support, home, home enviroment, nurse, nurses, nursing, wound wounds, skin, epidermis.In the review, we included articles published in the English language, published between 2010 and 2022, as well as those available in full text for members of the library of the University of Ljubljana. We included 23 articles in the analysis. Results: The home environment represents the main structure of stability, safety and shelter for patients with epidermolysis bullosa. Research shows the importance of nurses encouraging and supporting their patients, so they can find motivation to achieve their goals and increase their independence. Nurse education programmes are important to ensure the transfer of knowledge to patients and the delivery of skin and wound care. Their knowledge of the disease contributes to improving health literacy of patients, as well as to effective delivery of nursing interventions. By teaching patients about self-care, nurses create a good relationship with them. Discussion and conclusion: Given the rarity of the disease, poor health literacy and self-care are major factors leading to slower wound healing, social isolation and anxiety disorders. When organising health care at home, a nursing care plan, and predefined interventions to be carried out in the home environment are necessary. Nurse educational programmes which provide detailed information on health interventions aimed at managing the disease and increasing the independence of patients with epidermolysis bullosa can improve disease prognosis and the quality of life.

This work reports 30 cases of folliculitis decalvans (FD) in patients with dystrophic epidermolysis bullosa (DEB) among a cohort of 125 DEB patients seen between 2010 and 2021 in 2 French expert centers for the management of inherited epidermolysis bullosa. Such an association between two rare diseases cannot be fortuitous and implies a physiopathological link that we discuss in this paper. This association is a new significant fact to add to the reflexion on FD causes, suggesting that skin abnormality of DEB could act as a factor of a specific skin barrier alteration which could favor FD. Scarring alopecia with tufted folliculitis and pustules on inflamed skin at the vertex of a woman with dominant dystrophic epidermolysis bullosa.

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.

Paediatric patients with recessive dystrophic epidermolysis bullosa (RDEB) are at risk of vitamin D deficiency, owing to lack of sunlight from reduced mobility and having large areas of skin being covered with dressings, and to impaired nutritional intake and status.To establish an appropriate level of vitamin D supplementation in paediatric patients with RDEB.Patients with RDEB attending the EB tertiary multidisciplinary team clinic were enrolled. Serum levels of total 25(OH)D were retrospectively recorded for the study period 2012-2018. Data from clinical records on supplements, bone mineral density (BMD) Z scores, compliance, and use of enteral feeds and/or formula were also recorded.In total, 24 patients met the inclusion criteria: 20 with severe RDEB, 3 with RDEB inversa and 1 with intermediate RDEB. Of the 24 patients, 21 (88%) were advised to take a vitamin D3 supplement in line with Department of Health Guidelines (UK), with the remaining 3 patients receiving sufficient intake from formula or enteral feeds. Thirteen of the 24 (54%) had vitamin D deficiency or insufficiency despite advice to supplement; 9 of these 13 (69%) subsequently started or increased the dosage of vitamin D supplements and levels became sufficient (50 nmol/L), while the remaining 4 patients (31%) continued to have persistent insufficient levels due to noncompliance with supplements. Reasons for noncompliance were palatability, cost and forgetting to take the tablets. The dose required to maintain sufficient serum levels increased with age, up to 300% of the reference nutrient intake (RNI).All patients with RDEB require a supplement or a formula or enteral/sip feed containing vitamin D to maintain sufficient serum vitamin D. The dose required increases with age and can be up to three times higher than the RNI for the normal population. Compliance may improve using a once-weekly loading dose of vitamin D3. Vitamin D deficiency was not solely causative of a low BMD Z score.

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.

Revertant mosaicism (RM) is a phenomenon in which inherited mutations are spontaneously corrected in somatic cells. RM occurs in some congenital skin diseases, but genetic validation of RM in clinically revertant skin has been challenging, especially when homologous recombination (HR) is responsible for RM. Here, we introduce nanopore Cas9-targeted sequencing (nCATS) for identifying HR in clinically revertant skin. We took advantage of compound heterozygous COL7A1 mutations in a patient with recessive dystrophic epidermolysis bullosa who showed revertant skin spots. Cas9-mediated enrichment of genomic DNA (gDNA) covering the two mutation sites (>8 kb) in COL7A1 and subsequent MinION sequencing successfully detected intragenic crossover in the epidermis of the clinically revertant skin. This method enables the discernment of haplotypes of up to a few tens of kilobases of gDNA. Moreover, it is devoid of polymerase chain reaction amplification, which can technically induce recombination. We, therefore, propose that nCATS is a powerful tool for understanding complicated gene modifications, including RM.

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.

Patients with epidermolysis bullosa (EB) are susceptible to development of squamous cell carcinomas (SCC) at sites of chronic inflammation and fibrosis. While triterpenoids such as RTA 408 (Omaveloxolone) have been shown to reduce inflammation and inhibit tumour growth in various cancer models, the utility of this class of drugs in the treatment of SCC has not been investigated. Given the dual anti-inflammatory and anti-neoplastic properties of triterpenoids, we hypothesized RTA 408 would be an effective treatment for SCCs that arise in the chronic inflammatory setting in EB. We tested the effects of topical RTA 408 on a mouse model of non-Herlitz, junctional EB. RTA 408 significantly reduced phenotypic severity in the affected ears of Lamc2jeb mice. In cultures, RTA 408 reduced cell viability in EB-associated SCC cell lines and normal human epidermal keratinocytes. When administered in vivo, RTA 408 inhibited SCC tumour growth in mice without cutaneous or systemic toxicity. These results suggest that RTA 408 can be a promising new therapy to reduce inflammation and inhibit SCC growth in patients with EB.

Hereditary epidermolysis bullosa (EB) is a rare genodermatosis characterized by skin fragility and blistering of the skin and mucous membranes in reaction to minimal traumas. The development of cutaneous squamous cell carcinomas (cSCCs) is one of the most common medical complications in junctional and dystrophic forms of the disease. Complete surgical excision of cutaneous tumors represents the gold standard of treatment. However, not only recognition of cSCCs can be challenging in the affected skin but also wound closure after surgical excision poses a great therapeutic challenge in EB patients. The aim of our study was to analyze the postoperative outcomes of such patients in order to have a better knowledge of the main critical issues in their surgical management and oncological follow-up.We retrospectively identified a cohort of five EB patients treated at Modena University Hospital. Collected data included patient age and sex, date of cSCC diagnosis, relapses/recurrences, site of the neoplasm, number of surgical interventions, use of dermal substitutes, and postoperative infections.A total of 26 cSCCs were detected in our cohort. Forty-one surgical interventions were necessary to achieve excision of cSCCs with clear margins, varying from 1 to 4 surgical sessions per cSCC. Dermal substitutes were used in most cases but carried a higher infectious risk.EB patients tend to develop numerous cSCCs that often relapse even after complete excision with clear margins. These results stress the importance of early cSCC diagnosis and strict postsurgical follow-up.

Epidermolysis bullosa (EB) is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation. Here, we investigated five Chinese families with EB, and eight variants including a novel nonsense variant (c.47GA, p.W16*) in LAMA3, a known recurrent variant (c.74CT, p.P25L) in KRT5, 2 novel (c.2531TA, p.V844E; c.6811_6814del, p.R2271fs) and 4 known (c.6187CT, p.R2063W; c.7097GA, p.G2366D; c.8569GT, p.E2857*; c.3625_3635del, p.S1209fs) variants in COL7A1 were detected. Notably, this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay. Our study expands the mutation spectra of Chinese patients with EB.

The genodermatosis epidermolysis bullosa (EB) is a monogenetic disease, characterized by severe blister formation on the skin and mucous membranes upon minimal mechanical trauma. Causes for the disease are mutations in genes encoding proteins that are essential for skin integrity. In EB, one of these proteins is either functionally impaired or completely absent. Therefore, the development and improvement of DNA and RNA-based therapeutic approaches for this severe blistering skin disease is mandatory to achieve a treatment option for the patients.Currently, there are several forms of DNA/RNA therapies potentially feasible for EB. Whereas some of them are still at the preclinical stage, others are clinically advanced and have already been applied to patients. In particular, this is the case for a cDNA replacement approach successfully applied for a small number of patients with junctional EB.The heterogeneity of EB justifies the development of therapeutic options with distinct modes of action at a DNA or RNA level. In addition, splicing-modulating therapies, based on RNA

Although dermatologists are well-trained in the medical management of complex skin disease, psychosocial care often exceeds a dermatologist's skillset. We aim to elucidate major factors to consider in the comprehensive management of pediatric epidermolysis bullosa (EB) and provide care recommendations. There are many types of trauma a child with EB may experience, from social to psychological to medical. We include information on trauma-informed care and advice for the dermatologist and multidisciplinary team regarding patient-centered and family-centered approaches to recognizing and reducing anxiety and trauma in EB patients.

Mutational analysis and immunofluorescence antigen mapping (IFM) are recommended as the laboratory tools of choice for diagnosing EB. In the past, transmission electron microscopy (TEM) was considered the gold standard, and more recently, clinical diagnostic matrix (CDM) has shown good concordance with next-generation sequencing (NGS).In this prospective diagnostic study, a skin biopsy was taken for TEM and IFM in consecutive patients with EB (aged6 months) diagnosed clinically with CDM. Wherever possible, mutational analysis was done using targeted NGS.Of the 80 patients diagnosed with CDM, skin biopsy specimens of 42 patients were assessed using TEM, and of 59 patients using IFM. NGS was done in 39 patients. Taking NGS as the gold standard for diagnosing EB (n = 39 patients), the concordance with CDM, TEM, and IFM were estimated at 84.6% (33/39), 78.5% (11/14), and 76% (19/25) respectively. CDM showed a substantial agreement with NGS (k = 0.69, p 0.001).In comparison to NGS, the highest concordance was seen with CDM followed by TEM and IFM in diagnosing major subtypes of EB.

Nada Al-Yousuf,1,2 Hasan Alsetri,3 Eman Farid,4,5 Sara M George4 1Department of Ophthalmology, King Abdullah Medical City, Manama, Kingdom of Bahrain; 2Department of Surgery, College of Medicine, Manama, Kingdom of Bahrain; 3Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA; 4Department of Pathology, Salmaniya Medical Complex, Manama, Kingdom of Bahrain; 5Department of Microbiology, Immunology & Infectious diseases, College of medicine, Arabian Gulf University, Manama, Kingdom of BahrainCorrespondence: Nada Al-YousufDepartment of Ophthalmology, King Abdullah Medical City, 61, King Abdulaziz Avenue, Manama, Kingdom of Bahrain, Tel +973 77310071, Fax +973 77310001, Email nyousuf10@gmail.comPurpose: To describe the method used locally in amniotic membrane preparation and preservation for ocular surface reconstruction. To report the indications, surgical techniques, outcome and complications of amniotic membrane transplant using the locally prepared tissue. To examine the safety and efficacy of this less commonly studied method in amniotic membrane banking technique.Patients and Methods: Dimethylsulphoxide (DMSO) was used for the preparation and preservation of the amniotic membrane. A retrospective study was done from 2005 to 2017 to examine the indications of amniotic membrane transplant. The surgical techniques used for different indications are described. Surgical outcome and complications are reported.Results: The prepared tissue was used for the surgical management of a variety of disorders related to the ocular surface. Over the 12 years period from 2005 to 2017, a total of 135 cases were done. The most common indications for amniotic membrane transplant were pterygium surgery (41%), non-healing corneal ulcer (24%), others (13%), corneal perforation (10%), chemical burn (7%), bullous keratopathy (3%) and conjunctival-corneal scarring (2%). The most common surgical procedures used were inlay, overlay and combination (sandwich) techniques. Success rates for this ocular structure restoration procedure were the highest when treating corneal ulcers (81%), followed by pseudophakic bullous keratopathy (75%), then corneal perforations (70%). The recurrence rate for pterygium with amniotic membrane transplant was 14%. The most common complication was repeat amniotic membrane transplant. There were no complications related to the banking technique.Conclusion: This method of preparation and preservation of amniotic membranes is safe and effective for ocular surface disorders. Amniotic membrane transplants have high success rates when treating, corneal ulcers, corneal perforations, pseudophakic bullous keratopathy and epidermolysis bullosa.Keywords: pterygium, bullous keratopathy, corneal perforation, corneal ulcer, descemetocele, epidermolysis bullosa, ocular surface

Drug repurposing has the potential to discover new treatments for diseases with high unmet medical needs. Lee et al. (2021) combined transcriptomics and computational analysis of drug-target databases to identify novel therapies for epidermolysis bullosa simplex. Differential gene expression analysis of blister epidermis identified the phosphoinositide 3-kinase/protein kinase B/mTOR signaling pathway as central. A pilot study using a topical mTOR inhibitor showed marked improvement.

Jessica J Padniewski,1 Rob L Shaver,2 Brittney Schultz,2,3 David R Pearson2,3 1Department of Internal Medicine, Hennepin Healthcare, Minneapolis, MN, USA; 2University of Minnesota Medical School, Minneapolis, MN, USA; 3Department of Dermatology, University of Minnesota, Minneapolis, MN, USACorrespondence: David R PearsonUniversity of Minnesota Medical School, 516 Delaware St SE MMC 98, Minneapolis, MN, 55455, USAEmail pearsond@umn.eduAbstract: Autoimmune and inherited bullous disorders are rare skin diseases that may have a profound negative impact on quality of life (QOL). Common symptoms include pain, pruritus, and scarring, and complications may result in the loss of the ability to perform daily tasks. Diagnosis may have a negative psychological impact, and ongoing management may require a significant allocation of time and resources by both patients and providers. To provide patient-centered care, consideration of these factors is of utmost importance for the dermatologist treating patients with bullous disorders. Herein, we present a review of the primary literature evaluating QOL in autoimmune and inherited bullous disorders, including pemphigus, pemphigoid, epidermolysis bullosa, and Hailey-Hailey disease.Keywords: bullous disease, autoimmune blistering disease, pemphigus, pemphigoid, epidermolysis bullosa, Hailey-Hailey, quality of life, ABQOL, TABQOL, DLQI

Rezessive dystrophe Epidermolysis bullosa (RDEB) ist eine seltene genetische Hauterkrankung, die durch Mutationen im Gen COL7A1 verursacht wird. Neben großflächiger Blasenbildung der Haut mit Beteiligung der Schleimhäute haben die Patienten ein hohes Risiko, aggressive, stark metastasierende Plattenepithelkarzinome (SCC) zu entwickeln, die die häufigste Todesursache bei RDEB-Patienten sind. Aktuelle Studien haben ergeben, dass eine krebsspezifische Variante von SLCO1B3 (Ct-SLCO1B3) einen potenziellen Biomarker für RDEB-SCC darstellt. Ct-SLCO1B3 kodiert für ein verkürztes transporterähnliches Protein (ORF-C) und ein vermeintliches 43-aa-Peptid (ORF-D). In dieser Arbeit wurde die potenzielle Rolle von Ct-SLCO1B3 in der Tumorpathobiologie untersucht, indem drei RDEB-SCC-Zelllinien mit verminderter Ct-SLCO1B3-Expression mit Hilfe von CRISPR/Cas9-Technologie erzeugt wurden und so die Auswirkungen des reduzierten Tumormarkers auf das Verhalten der Zellen bestimmt wurde. Die Untersuchung der Morphologie, der Proliferation und der Fähigkeit der Zellen, Kolonieeinheiten zu bilden, zeigte im Allgemeinen keine signifikanten Unterschiede zwischen den RDEB-SCC-Elternzelllinien und ihren KO-Pendants. Darüber hinaus wurde die Auswirkung des Knock-outs auf das Überleben der Zellen untersucht, indem die Empfindlichkeit der Zellen gegenüber einer medikamentösen Behandlung bestimmt wurde. Es wurden mehrere Medikamente getestet, wobei keine signifikanten Unterschiede zwischen den elterlichen RDEB-SCC-Zelllinien und den Knock-out-Zelllinien beobachtet wurden. Während die Daten darauf hindeuten, dass Ct-SLCO1B3 nur eine minimale Rolle im Verhalten der Tumorzellen spielt und darüber hinaus keine aktive Transportfunktion hat, ist erwähnenswert, dass eine der untersuchten Zelllinien bei allen Medikamentenbehandlungen ein abweichendes Verhalten zeigte. Darüber hinaus schien diese Zelllinie stärker von dem Knock-out betroffen zu sein. Dieses zelllinienspezifische Verhalten unterstreicht die Notwendigkeit von patientenspezifischen Behandlungsstrategien. High-Content-Assays wie der in dieser Arbeit eingeführte "Cell-Painting"-Assay könnten die Untersuchung von patientenspezifischen Tumorverhaltens erleichtern. Weitere Forschungsarbeiten müssen jedoch durchgeführt werden, um die Rolle von Ct-SLCO1B3 in der Pathobiologie zu verstehen. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin disorder, which is caused by mutations in the gene COL7A1. Besides extensive blistering of the skin, with involvement of the mucous membranes, patients have a high risk of developing aggressive, highly metastatic squamous cell carcinomas (SCC), which is the number one cause of death in RDEB patients. Recent studies have found that a cancer-specific variant of SLCO1B3 (Ct-SLCO1B3) represents a potential biomarker for RDEB-SCC. Ct-SLCO1B3 encodes a truncated transporter-like protein (ORF-C), and a putative, 43-aa peptide (ORF-D). In this thesis, the potential role of Ct-SLCO1B3 in tumor pathobiology was investigated by generating three RDEB-SCC cell lines with decreased Ct-SLCO1B3 expression using CRISPR/Cas9 technology and thereby, determining the impact of the reduced tumor marker on the behaviour of the cells. In general, the investigation of the morphology, proliferation, and the cells’ ability to form colony units showed no significant dissimilarities between RDEB-SCC parental cell lines and their KO counterparts. Moreover, the impact of the knockout on cell survival was further investigated by determining the cell’s sensitivity to drug treatment. Several drugs were tested, with no significant differences between RDEB-SCC parental and knockout cell lines observed. While the data are highly suggestive that Ct-SLCO1B3 plays a minimal role in tumor cell behaviour and additionally has no active transport function, it is worth noting that one of the investigated cell lines showed different behaviour across all drug treatments. Furthermore, this particular cell line appeared to be more affected by the knockout. This cell line-specific behaviour underscores the need for patient-specific treatment strategies. High-content assays like the “Cell painting” assay established in this thesis, could facilitate investigation of patient-specific tumor behaviour. However, more research needs to be done to understand the role of Ct-SLCO1B3 in pathobiology.

The aim of the study was to gain insight into some domains of the quality of life of children with epidermolysis bullosa and their parents from perspectives of mothers. Semi-structured interview was used as method for data collection with six mothers of children with epidermolysis bullosa. Thematic analysis was a method of analysing data. The results show that the quality of life of parents of children with epidermolysis bullosa is determined by parents´ good health, job satisfaction and received support from different sources, as well as the family’s financial well-being and their limited possibilities of participating in leisure activities. The quality of life of children with epidermolysis bullosa is determined by the children’s affiliation to the community, poorer health condition of children, children’s abilities to perform certain everyday activities, as well as appropriate support from the formal support system. It is clear that this rare disease affects the quality of life of all family members. Families of children with epidermolysis bullosa need informational, practical, emotional, and financial support from informal and formal support system, especially from highly specialized and well networked professionals.

Objective: This scoping review aims to comprehend the nature and the extent of the available evidence regarding methods to assess patients with epidermolysis bullosa (EB). Introduction: Inherited EB is a rare genodermatosis characterized by extreme fragility of the skin and mucous membranes, which gives rise to the formation of blisters and ulcers following minor trauma. Due to its heterogeneous presentation, EB is significantly misdiagnosed, requiring a broader assessment to ensure an early clinical suspicion and better quality of care for the disease-related morbidities. Inclusion criteria: We will include human-based research articles based on qualitative or quantitative methods published in peer-reviewed journals that describe methods to assess EB patients, particularly those related to diagnosis, screening, classification, stratification, and follow-up. Only articles with full text available, published between 2018 and 2023, and written in English and Spanish will be included. Methods: The search strategy will be developed by a librarian and conducted on six databases. Selection of studies will be independently conducted by calibrated reviewers through the title, abstract, and full-text screening, followed by data charting. Quantitative (e.g., frequencies and percentages) and qualitative (e.g., classification of assessment methods) synthesis will be conducted.

Resumo Objetivo Analisar a produção científica referente às ações/Intervenções de Enfermagem no ambiente hospitalar relacionadas ao cuidado com crianças e adolescentes com epidermólise bolhosa. Métodos Revisão sistemática, cuja busca se deu nas bases Cinahl, MEDLINE®/PubMed®, SCOPUS, LILACS e SciELO, realizada no período de setembro de 2020 a janeiro de 2021. Para a busca, foram utilizados os descritores “epidermólise bolhosa” AND “criança” AND “adolescente” AND “enfermagem”, nas bases Lilacs e SciELO, e “epidermolysis bullosa” AND “children” AND “adolescent” AND, “nursing” nas demais bases em inglês. Resultados Houve maior registro de artigos publicados com base na pergunta norteadora tendo como país de origem os Estados Unidos (22%). A maioria da classificação era no nível VI (44%) da evidência científica. Ainda, 86% dos estudos envolveram pesquisas para o plano de cuidados. As evidências encontradas decorreram de opiniões de especialistas, estudos de casos e consenso. Os fatores de cuidados mais citados foram planos de cuidados voltados à pele; troca de fraldas; cuidados com as roupas e uso de coberturas antiaderentes. Conclusão As pesquisas reportaram dificuldades quanto à disponibilidade de materiais, tratamento e profissionais especializados, além das limitações dos conhecimentos na prática clínica voltada às características da epidermólise bolhosa. Dentre os cuidados, houve destaque para informação sobre a complexidade e as características da ferida como forma de antecipar as estratégias de cuidado. Resumen Objetivo Analizar la producción científica referente a las acciones/intervenciones de enfermería en el ambiente hospitalario relacionadas con el cuidado a niños y adolescentes con epidermólisis ampollosa. Métodos Revisión sistemática, cuya búsqueda se realizó en las bases Cinahl, MEDLINE®/PubMed®, SCOPUS, LILACS y SciELO, realizada en el período de septiembre de 2020 a enero de 2021. Para la búsqueda se utilizaron los descriptores “epidermólisis ampollosa” AND “niño” AND “adolescente” AND “enfermería”, en las bases Lilacs y SciELO, y “epidermolysis bullosa” AND “children” AND “adolescent” AND, “nursing” en las demás bases en inglés. Resultados Con base en la pregunta orientadora, hubo un mayor registro de artículos publicados que tenían como país de origen Estados Unidos (22 %). La mayoría de la clasificación era de nivel VI (44 %) de la evidencia científica. Además, el 86 % de los estudios incluyeron investigaciones en el plano de los cuidados. Las evidencias encontradas derivaban de opiniones de especialistas, estudios de casos y consenso. Los factores de cuidados más citados fueron planos de cuidados orientados a la piel, cambio de pañales, cuidados con la ropa y uso de coberturas antiadherentes. Conclusión Las investigaciones indicaron dificultades en cuanto a la disponibilidad de material, tratamiento y profesionales especializados, además de las limitaciones de conocimientos en la práctica clínica orientada hacia las características de la epidermólisis ampollosa. Entre los cuidados, se destacó la información sobre la complejidad y las características de la herida como forma de anticipar las estrategias de cuidado. Abstract Objective To analyze the scientific production regarding actions/Nursing Interventions in hospital environments related to the care of children and adolescents with epidermolysis bullosa. Methods This is a systematic review, which was searched in the CINAHL, MEDLINE®/PubMed®, Scopus, LILACS and SciELO databases, carried out from September 2020 to January 2021. For the search, the descriptors “epidermólise bolhosa” AND “criança” AND “adolescente” AND “enfermagem” were used, in Portuguese, in the LILACS and SciELO databases, and “epidermolysis bullosa” AND “children” AND “adolescent” AND “nursing” in the other databases. Results There was a greater number of articles published based on the guiding question having the United States as the country of origin (22%). Most of the classification was at level VI (44%) of scientific evidence. Still, 86% of studies involved research for the care plan. The evidence found resulted from expert opinions, case studies and consensus. The most cited care factors were skin care plans, diaper changing, clothing care and non-stick coating use. Conclusion The surveys reported difficulties regarding the availability of materials, treatment and specialized professionals, in addition to limitations of knowledge in clinical practice focused on the characteristics of epidermolysis bullosa. Among the care, there was emphasis on information about the wound complexity and characteristics as a way of anticipating care strategies.

To establish the epidemiological, clinical, pathological and genetic characteristics of epidermolysis bullosa (EB) in New Zealand (NZ).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.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 Māori, 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.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.

Epidermolysis bullosa (EB) is a group of inherited skin and mucosal fragility disorders resulting from mutations in genes encoding basement membrane zone (BMZ) components or proteins that maintain the integrity of BMZ and adjacent keratinocytes. More than 30 years have passed since the first causative gene for EB was identified, and over 40 genes are now known to be responsible for the protean collection of mechanobullous diseases included under the umbrella term of EB. Through the elucidation of disease mechanisms using human skin samples, animal models, and cultured cells, we have now reached the stage of developing more effective therapeutics for EB. This review will initially focus on what is known about blister wound healing in EB, since recent and emerging basic science data are very relevant to clinical translation and therapeutic strategies for patients. We then place these studies in the context of the latest information on gene therapy, read-through therapy, and cell therapy that provide optimism for improved clinical management of people living with EB.

Sang Trieutien,1,* Tam Vu Van,2,3,* My Tran Ngoc Thao,4 Son Trinh The,5 Khoa Tran Van,1 Tung Nguyen Thanh,5 Tuan Tran Van,5 Hanh Nguyen Thi6 1Department of Biology and Genetics, Vietnam Military Medical University, Hanoi, 12108, Vietnam; 2Director Office, Hai Phong Hospital of Obstetrics and Gynecology, Haiphong, 40000, Vietnam; 3Obstetrics and Gynecology Department, Haiphong University of Medicine and Pharmacy, Haiphong, 40000, Vietnam; 4Département de formation Biologie moléculaire et cellulaire, Sorbonne University, Paris, 75006, France; 5Military Institute of Clinical Embryology and Histology, Vietnam Military Medical University, Hanoi, 12108, Vietnam; 6Faculty of Biology, VNU University of Science, Vietnam National University, Hanoi, 12108, Vietnam*These authors contributed equally to this workCorrespondence: Son Trinh TheMilitary Institute of Clinical Embryology and Histology, Vietnam Military Medical University, Hanoi, 12108, VietnamEmail trinhthesonart@gmail.comBackground: Epidermolysis bullosa (EB) is a disorder characterized by the appearance of blisters, erosions and wounds in response to minimal trauma. The disease manifests with noticeable symptoms ranging from mild to severe, classified into four major types: epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB), dystrophic epidermolysis bullosa (DEB) and Kindler syndrome. Preimplantation genetic diagnosis for the disease remains the only available option for families at risk for the recurrence of the disorder without having to terminate an ongoing pregnancy.Materials and Methods: A novel COL7A1 mutation was used to design primers for the polymerase chain reaction (PCR) to amplify the segment spanning the mutation in the family and their in-vitro fertilization (IVF) embryos. Then, the PCR products were sequenced with Sanger sequencing to detect the alteration in the allele, and some embryos would go through NGS-based preimplantation screening for chromosomal abnormalities.Results: The established protocol for EB detected mutant allele in 6/9 embryos (66.6%), while the remaining 3 embryos (33.4%) appeared to not carry any mutation. Only one among 3 embryos was recommended to be transferred into the mother’s uterus.Conclusion: The established preimplantation genetic diagnosis procedure is helpful to families affected by epidermolysis bullosa caused by COL7A1 mutations but wish to have healthy children.Keywords: epidermolysis bullosa, rare dystrophic epidermolysis bullosa, EB, RDEB, skin disorder, COL7A1 gene mutation, preimplantation genetic diagnosis, PGD

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.

Recessive dystrophic epidermolysis bullosa, a devastating skin fragility disease characterized by recurrent skin blistering, scarring, and a high risk of developing squamous cell carcinoma is caused by mutations in COL7A1, the gene encoding type VII collagen, which is the major component of the anchoring fibrils that bind the dermis and epidermis. Ex vivo correction of COL7A1 by gene editing in patients' cells has been achieved before. However, in vivo editing approaches are necessary to address the direct treatment of the blistering lesions characteristic of this disease. We have now generated adenoviral vectors for CRISPR-Cas9 delivery to remove exon 80 of COL7A1, which contains a highly prevalent frameshift mutation in Spanish patients. For in vivo testing, a humanized skin mouse model was used. Efficient viral transduction of skin was observed after excisional wounds generated with a surgical punch on regenerated patient skin grafts were filled with the adenoviral vectors embedded in a fibrin gel. Type VII collagen deposition in the basement membrane zone of the wounded areas treated with the vectors correlated with restoration of dermal-epidermal adhesion, demonstrating that recessive dystrophic epidermolysis bullosa (RDEB) patient skin lesions can be directly treated by CRISPR-Cas9 delivery in vivo. This study was supported by grant ER18TRL714 from CIBERER and grants PI20/00615, PI21/00171 and RICORS/TERAV (RD21/0017/0027) from ISCIII, co-funded by the European Regional Development Fund and European Union – NextGenerationEU). G.T., A.J.T., and S.S. were supported by the Wellcome Trust (217112/Z/19/Z) and the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. G.T. was also supported by the University College London Therapeutic Acceleration Support fund. Authors are indebted to Esteban Chacón-Solano for help with protein analysis, Mirentxu Santos for design of animal experiments, Blanca Duarte, Nuria Illera, Eva Muñoz, and Almudena Holguín for grafting experiments, and to Edilia De Almeida for animal maintenance and care.

Uvod: Bulozna epidermoliza (lat. epidermolysis bullosa, EB) je dedna skupina genetskih bolezni, povezanih s krhkostjo kože. Ob minimalnih mehanskih poškodbah ali pa spontano zaradi krhkosti kože nastanejo na mestu poškodbe mehurji, erozije in brazgotine. Bolezen je posledica mutacij različnih genov z zapisom za različne beljakovine, ki povezujejo plasti kožnih celic. Bolezen je klasificirana v štiri osnovne tipe: EB simpleks, junkcijska EB, distrofična EB in Kindlerjev sindrom. Namen: Namen diplomskega dela je predstaviti zdravstveno obravnavo in nego novorojenčka z EB, zato smo diplomsko nalogo poglobili v to področje, saj to pomembno vpliva na kakovost življenja kasneje v otroštvu in odrasli dobi. Pomembno je, da so starši otrok z EB in zdravstveni delavci seznanjeni s primernimi in dostopnimi informacijami. Prav tako je delo namenjeno širši skupnosti ljudi. Metode dela: V diplomski nalogi smo uporabili deskriptivno metodo s sistematičnem pregledom literature. Pri iskanju smo uporabili časovni okvir in sicer od leta 2010 do 2021. Zbiranje podatkov je potekalo s pregledom in kritičnim izborom strokovne in znanstvene literature v slovenskem in angleškem jeziku. Rezultati: Zdravljenje ran pri novorojenčkih je drugačno kot pri otrocih ali odraslih in zahteva posebno nego. Koža je fiziološko in razvojno drugačna, zato mora biti načrt oskrbe individualen glede na starost, znake bolezni, zaplete in glede na bolnikove prioritete. Navadno rane bolnika očistimo in oskrbimo enkrat na dan oziroma po potrebi. Nego izvajamo na mehki podlagi in porabimo tehniko obračanja in dviga (angl. roll and lift). Vsak pritisk na kožo, na primer drgnjenje z brisačo ali plenico, lahko izzove nastanek novega mehurja. Še posebej občutljive so roke, komolec, zapestje, noge in kolena. Mehurje dosledno prediramo, saj se drugače razširijo. Pomembne so prehranske potrebe novorojenčkov z EB, ki so večje kot potrebe zdravih otrok, zaradi hitrega obnavljanja kože in hkrati potrebe po povečanem vnosu kalorij. Razprava in zaključek: Osnovni načeli oskrbe vseh bolnikov z EB sta preprečevanje nastanka mehurjev in preprečevanje sekundarnih okužb. Zaradi redkosti bolezni se večina družin novorojenčkov znajde v situaciji z malo ali nič izkušnjami kadar se sooča z EB bolezen. Ne glede na podtip je vsem bolnikom z EB skupno to, da na koži nastajajo mehurji in so zato na njej stalno prisotne rane. Pri bolnikih s to izčrpavajočo boleznijo je treba upoštevati posebne vidike gostitelja, procesa celjenja in rane, da bi proces celjenja olajšali. Introduction: Epidermolysis bullosa (lat. epidermolysis bullosa, EB) is a group of inherited genetic disorders associated with skin fragility. Minimal mechanical trauma or spontaneous skin fragility can lead to blistering, erosions and scarring. The disease is caused by mutations in different genes that code for different proteins that connect the layers of skin cells. The disease is classified into four basic types: EB simplex, junctional EB, dystrophic EB and Kindler syndrome. Purpose: The aim of this thesis is to present the medical management and care of the newborn with EB, and we have therefore delved into this area, as it has a significant impact on the quality of life later in childhood and adulthood. It is important that parents of children with disabilities and health professionals provided with appropriate and accessible information. The thesis will also be aimed for a wider community of people. Methods: In this thesis we used a descriptive method with a systematic literature review. The timeframe used for the search was 2010 to 2021. The data collection was carried out by reviewing and critically selecting the professional and scientific literature in Slovenian and English. Results: Wound healing in newborns is different that in children or adults so that is why it requires special care. Skin is physiologically and developmentally different, so the care plan needs to be individualised according to the age, signs of disease, complications and the patient's priorities. Patient wounds are usually cleaned and treated once a day or as needed. The treatment is carried out on a soft surface using a rolling and lifting technique. Any pressure on the skin, for example rubbing with a towel or nappy can provoke the formation of a new blister. Particularly sensitive are hands, elbows, wrists, feet and knees. We are consistently over-penetrating blisters, because otherwise they spread. The nutritional needs of newborns with EB are higher than those of healthy children, due to rapid skin repair and the need for increased calorie intake. Discussion and conclusion: The basic principles of care for all EB patients are to prevent blistering and to prevent secondary infections. Due to the rarity of the disease, most families of newborns find themselves with little or zero experience when faced with EB disease. Regardless of the subtype, all EB patients have in common blistering of the skin, which result in persistent wounds. Specific aspects of the host, the healing process and the wound need to be taken into account in patients with this debilitating disease to facilitate the healing process.