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CR McDonald, K Plevey, G Petrof, AE Martinez Paediatric Dermatology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UKCorrespondence: AE MartinezPaediatric Dermatology, Great Ormond Street Hospital for Children NHS Foundation Trust London, WC1N 3JH, UKTel +207 829 780Email Anna.martinez@gosh.nhs.ukAbstract: Epidermolysis bullosa (EB) is a group of rare genetic mucocutaneous fragility disorders. Patients with EB can experience blister formation following minor skin trauma, which can progress to chronic wounds. These wounds can be painful and difficult to manage. There are four major types of EB which are defined by the defective protein and the layer within the skin this protein is located. Junctional epidermolysis bullosa (JEB) is caused by mutations within the lamina lucida proteins which are located at the dermoepidermal junction. The prognosis of JEB varies considerably between the different subtypes of JEB, with JEB generalised severe being the most severe, with high mortality within the first 2 years of life. On the opposite end, patients with JEB localised would be expected to have normal life expectancy. In this review, we discuss the management of chronic wounds in paediatric patients with JEB, including suitable wound cleansing, recommended dressings and topical preparations for chronic wound treatments. We include chronic wounds over specific anatomical sites which are frequent in patients with JEB and their recommended management. Important differences between the subtypes of JEB, and specifics on dressings suitable in the neonatal and infancy period are highlighted. Symptom care of wounds in these children, such as pain, infection, pruritus and overgranulation are also addressed. Finally, we highlight the changes to practice which have occurred in recent years and novel treatments which have been trialled and can be considered.Keywords: junctional epidermolysis bullosa, paediatric JEB, wound management

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of delusional infestation (DI) in adults. B R18 (GPP) b Offer treatment for at least 1 year after symptoms have resolved to adults with DI and restart treatment if symptoms recur following cessation of treatment. Management B R9 (GPP) b Allow at least a 45-minute appointment for new patients and 30 minutes for subsequent follow-up appointments for adults with DI. B R10 ( b ^^ B ) b Offer* early referral to a specialist psychodermatology clinic, where available, to adults with DI. B R11 ( b ^^ B ) b Offer* psychiatric and psychological support in addition to dermatological treatment to adults with DI if acceptable to the patient. The guideline is presented as a detailed review with highlighted recommendations for practical use in dermatology clinics (see Summary of recommendations), in addition to a patient information leaflet (available on the BAD website: https://www.skinhealthinfo.org.uk/a-z-conditions-treatments) and a PowerPoint presentation on 'Communication skills when seeing a patient with delusional infestation' (File S1; see Supporting information). [Extracted from the article]

Summary: Background: The British Association of Dermatologists (BAD) develops and produces patient information leaflets (PILs) for British clinicians and the general public, and its website provides access to all the PILs. Health literacy across the UK remains variable. Readability instruments assess the comprehensibility of text, predominately using a composite of sentence length and/or word‐syllable number. Instruments usually report text readability categorized by United States (US) grades; ideally, health literature should be rated at US grade ≤ 6 (UK Year 7; age 11–12 years). Methods: In collaboration with the BAD, PILs on the BAD website (n = 203) were downloaded for readability assessment. PILs were processed prior to analysis using Readability Studio software (Oleander Software, Vandalia, OH, USA). Established readability metrics were used: Flesch–Kincaid (FK), Simple Measure of Gobbledygook (SMOG), Gunning fog index (GFI), Fry, FORCAST and Flesch Reading Ease (FRE). Results: The mean (95% CI) US grade levels for all BAD PILs were: 9.8 (9.7–10.0) for FK, 12.1 (12.0–12.3) for SMOG, 11.8 (11.6–11.9) for GFI, 11.5 (11.1–11.8) for Fry and 10.7 (10.6–10.8) for FORCAST. For FRE, the level is reported from a normal spectrum of 0–100, and was found to be 52.2 (95% CI 34.0–78.0) in this study. In the UK context, the mean readability levels of the BAD PILs were rated as Year 10 (age 14–15 years) for FK and Year 13 (aged 17–18 years) for SMOG. For FK, outputs, only 1.0% of PILs (2 of 203) were the recommended US grade ≤ 6 according to FK, and for SMOG rating, none was rated at this level. Discussion: The majority of BAD PILs have been written at a level that will be challenging for some patients to read. Reducing sentence length and aiming for shorter words will improve accessibility. [ABSTRACT FROM AUTHOR]

Click https://wileyhealthlearning.com/#/online-courses/a54fac75-89f4-4bf5-80a4-19e31765a7a4 for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: Background: Hidradenitis suppurativa (HS) can have significant psychological consequences and affect quality of life (QoL). This has been associated with disease severity. However, it has not been established whether these effects are more strongly related to the severity of the disease, as rated by the clinician, or to the patient's perception of their condition. Objectives: To examine the relationships between disease severity and illness perceptions, and depression, anxiety and QoL in HS. Methods: This study was cross‐sectional in design. In total, 211 patients with HS completed the Brief Illness Perception Questionnaire (BIPQ), the Patient's Health Questionnaire‐2 (PHQ‐2), the Generalized Anxiety Disorder‐2 (GAD‐2) and the Dermatology Life Quality Index (DLQI). HS severity was assessed by the clinician, using the Hurley staging system. Results: Patients with HS perceived their condition as chronic – having many symptoms, severe consequences and a negative emotional influence – and felt low personal control over their illness. Self‐reports showed significant levels of depression, anxiety and impaired QoL, which were strongly associated with illness perceptions. Hierarchical regression analyses revealed that illness perceptions explained a much greater proportion of variance in depression, anxiety and QoL than the traditional explanatory variable, disease severity. Conclusions: HS can severely impair psychological well‐being and QoL, which are more strongly associated with the person's beliefs about their illness than clinicians' severity assessments. Therefore, illness perceptions may be useful in the routine assessment of patients with HS and may provide a strong basis for interventions aimed at improving their psychological well‐being and QoL. What's already known about this topic? Hidradenitis suppurativa (HS) is known to be a highly distressing and debilitating skin condition that has a profound effect on quality of life (QoL), mood and anxiety.It has been assumed that these effects are directly related to disease severity.No previous studies have investigated patients' perceptions of their HS, and whether these are related to disease severity and/or their QoL and mood. What does this study add? This study examines the illness perceptions of patients with HS, and the extent to which these are related to clinician‐rated disease severity, mood and QoL. What are the clinical implications of this work? The results suggest that illness perceptions are a stronger indicator of which patients with HS are most likely to be depressed, anxious or impaired in their QoL, relative to this skin disease's clinical measurement.There is certainly scope for more routine assessment of patients' perceptions and for the development of interventions aimed at targeting negative illness beliefs with the aim of improving outcomes. Plain language summary available online [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is the most common inflammatory skin condition and affects people of all ages. New therapies, including the monoclonal antibody therapy dupilumab, offer excellent efficacy. However, in clinical trials, and emphasized in real-world observations, an unexpected increased frequency of ocular adverse effects has become apparent. The effectiveness of dupilumab and the unpredictability of ocular adverse effects mean that clinicians need guidance on counselling patients prior to treatment and on managing them if adverse effects arise. The British Association of Dermatologists (BAD) and Royal College of Ophthalmologists collaborated on this consensus guidance on managing dupilumab-related ocular surface disorders (DROSD). A multidisciplinary group was formed of adult and paediatric dermatologists and ophthalmologists with expertise in DROSD, patient representatives and the BAD Clinical Standards Unit. A literature search was conducted and the results reviewed. All recommendations were reviewed, discussed and voted on. The recommendations pertain to dermatology and ophthalmology management, and apply to people of all ages, unless otherwise stated. Importantly, initiation of dupilumab for AD should not be delayed for most eye disorders except acute new problems (e.g. infections) or potentially severe conditions (e.g. a history of corneal transplant; ophthalmology advice should be sought first). There is insufficient evidence to recommend lubricant drops prophylactically. Dermatologists should assess eye complaints to diagnose DROSD; a severity grading system is provided. DROSD management differs slightly in those aged < 7 years, as ocular complications may affect neuro-ocular development. Therefore, irrespectively of DROSD severity, this population should be referred for ophthalmology advice. In those aged ≥ 7 years, dermatologists should feel confident to trial treatment and reserve ophthalmology advice for severe or nonresponding cases. Discussion about dupilumab withdrawal should be prompted by a significant impact on quality of life, threat to sight, or other complications. Although dupilumab is a highly effective agent for treating AD, the risk of ocular adverse effects should not inhibit clinicians or patients from using it, but clinicians should be aware of them. If a patient develops DROSD, there are clear pathways to assess severity and offer initial management. Where this is ineffective, dermatologists should assess the urgency and seek advice from or initiate referral to ophthalmology. While the evidence reviewed for these guidelines reflects the extensive literature on dupilumab, we believe our advice has relevance for ocular surface disorders in patients with AD treated with tralokinumab and lebrikizumab., Competing Interests: Conflicts of interest MRA-J: speaker, adviser, honoraria, travel/research/departmental grants, from the Biotechnology and Biological Sciences Research Council, British Skin Foundation, UK-Irish Atopic eczema Systemic Therapy Register (A-STAR; ISRCTN11210918), AbbVie, Almirall, Amgen, Ducentis, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, UCB and Unilever. SJB: speaker honoraria (British Society for Paediatric Dermatology), research grants (Wellcome Trust, British Skin Foundation, European Lead Factory, BIOMAP Consortium, Pfizer Sosei Heptares). CF: chief investigator for the UK National Institute for Health Research-funded TREAT (ISRCTN15837754) and SOFTER (NCT03270566) trials, UK-Irish Atopic eczema Systemic Therapy Register (A-STAR), principal investigator BIOMAP Consortium, lead EU Trans-Foods consortium, departmental funding (Sanofi Genzyme, Pfizer), compensation from the British Journal of Dermatology and EuroGuiDerm (guidelines lead), speaker fees (Almirall, Bioderma, Sanofi). PH: speaker fees (Santen, Thea Pharmaceuticals), clinical trials principal investigator (Sifi Pharmaceuticals, Syneos Pharma, Novartis), research grants (Royal College of Surgeons, Edinburgh). ADI: consultancy honoraria (AbbVie, Arena Pharmaceuticals, Aslan, BenevolentAI, Chugai, Connect Biopharma, Dermavant, Genentech, LEO Pharma, Lilly, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB). GAJ: honorarium (Sanofi). SML: coinvestigator BIOMAP Consortium, research grants from Wellcome Trust. PL: honoraria and/or grants (AbbVie, Janssen, LEO Pharma, Eli Lilly, Sanofi, Novartis). DO’D: speaker honoraria (AbbVie, Pfizer). DO’K: speaker and adviser honoraria (Sanofi, AbbVie, Novartis, Janssen). GP: honoraria and/or grants (Sanofi, Amryt, Krystal Biotech, Incyte). AEP: investigator, speaker, adviser or research/educational support (AbbVie, Pfizer, Eli Lilly, LEO Pharma, Galderma, Almirall, Boehringer Ingelheim, UCB, Bristol Myers Squibb, Amgen, Novartis, Janssen). S Rauz: research grants from the Medical Research Council (MRC), National Institute for Health and Care Research (NIHR), Sight Research UK, and Fight for Sight. S Robbie: honorarium (LEO Pharma), adviser (Sanofi). SKG: grant (Sanofi). MS: travel grants or conference fees (LEO Pharma, UCB). RTW: investigator, speaker, adviser or educational support (AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, LEO Pharma, Janssen, Novartis, Pfizer, Sanofi, UCB), honoraria and consultancy (National Institute for Health and Care Excellence, clinical expert). The remaining authors declare no conflicts of interest., (© British Association of Dermatologists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

The hallmark of epidermolysis bullosa (EB) is fragile attachment of epithelia due to genetic variants in cell adhesion genes. We describe 16 EB patients treated in the ear, nose, and throat department of a tertiary pediatric hospital linked to the United Kingdom's national EB unit between 1992 and 2023. Patients suffered a high degree of morbidity and mortality from laryngotracheal stenosis. Variants in laminin subunit alpha-3 (LAMA3) were found in 10/15 patients where genotype was available. LAMA3 encodes a subunit of the laminin-332 heterotrimeric extracellular matrix protein complex and is expressed by airway epithelial basal stem cells. We investigated the benefit of restoring wild-type LAMA3 expression in primary EB patient-derived basal cell cultures. EB basal cells demonstrated weak adhesion to cell culture substrates, but could otherwise be expanded similarly to non-EB basal cells. In vitro lentiviral overexpression of LAMA3A in EB basal cells enabled them to differentiate in air-liquid interface cultures, producing cilia with normal ciliary beat frequency. Moreover, transduction restored cell adhesion to levels comparable to a non-EB donor culture. These data provide proof of concept for a combined cell and gene therapy approach to treat airway disease in LAMA3-affected EB., Competing Interests: Declaration of interests The authors declare no competing interests. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. For the purpose of open access, the corresponding author has applied a CC BY public copyright license to any author accepted manuscript version arising from this submission., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Dystrophic epidermolysis bullosa (DEB) is a subtype of an inherited skin disorder characterized by skin and mucosal fragility due to collagen VII (COL7A1) gene mutations. Esophageal strictures leading to chronic dysphagia and acute episodes are well recognized complications within this subtype. Sloughing of esophageal mucosa and the treatment of this emergency have heretofore received limited attention in the EB literature., Methods: We retrospectively reviewed the electronic medical records of the patients who had an acute episode of sloughing of the esophageal lining between 2008 and 2021 and extracted the information regarding their clinical presentation and management., Results: Six patients out of 210 with recessive DEB severe (RDEB-S) (n = 4), RDEB intermediate (RDEB-I) (n = 1) and dominant DEB (DDEB) (n = 1) were identified. The mean age at the time of the episode was 2.7 years. All patients had early-onset severe gastroesophageal reflux. Clinically, they presented with a coughing episode (n = 6), hematemesis (n = 6), vomiting (n = 6), and choking (n = 3), followed by coughing up a string like tissue of variable length, part of the esophageal mucosal lining. Four patients recovered with medical management only, two patients required gastrostomy insertions for feeding due to severe persistent dysphagia and one also required a Nissen's fundoplication to manage severe reflux. One patient had aspiration pneumonia., Conclusions: Sloughing of varying lengths of segments of the esophagus is an emergency. The lining coughed up needs to be cut at the mouth not pulled and the emergency services called immediately for urgent assessment and management. Expert multidisciplinary care is needed to manage this rare but serious condition., (© 2023 Wiley Periodicals LLC.)

Background: Desmosomes are complex cell junction structures that connect intermediate filaments providing strong cell-to-cell adhesion in tissues exposed to mechanical stress., Objectives: To identify causal variants in individuals with woolly hair and skin fragility of unknown genetic cause., Methods: This research was conducted using whole-genome sequencing, whole-exome sequencing, clinical phenotyping, haplotype analysis, single-cell RNA sequencing data analysis, immunofluorescence microscopy and transmission electron microscopy., Results: We identified homozygous predicted loss-of-function tuftelin-1 (TUFT1) variants in nine individuals, from three families, with woolly hair and skin fragility. One donor splice-site variant, c.60+1G>A, was present in two families, while a frameshift variant, p.Gln189Asnfs*49, was found in the third family. Haplotype analysis showed the c.60+1G>A substitution to be a founder variant in the Irish population that likely arose approximately 20 generations ago. Human and mouse single-cell RNA sequencing data showed TUFT1 expression to be enriched in the hair dermal sheath and keratinocytes. TUFT1 expression was highly correlated with genes encoding desmosomal components implicated in diseases with phenotypes that overlap with the cohort presented here. Immunofluorescence showed tuftelin-1 to be mainly localized to the peripheral cell membranes of keratinocytes in normal skin. Skin samples from individuals with TUFT1 variants showed markedly reduced immunoreactivity for tuftelin-1, with a loss of the keratinocyte cell membrane labelling. Light microscopy revealed keratinocyte adhesion, mild hyperkeratosis and areas of superficial peeling. Transmission electron microscopy showed panepidermal acantholysis with widening of intercellular spaces throughout the epidermis and desmosomal detachment through the inner plaques., Conclusions: Biallelic loss-of-function TUFT1 variants cause a new autosomal recessive skin/hair disorder characterized by woolly hair texture and early-onset skin fragility. Tuftelin-1 has a role in desmosomal integrity and function., Competing Interests: Conflicts of interest: The authors declare they have no conflicts of interest., (© The Author 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Netherton syndrome (NS; OMIM: 256500) is a rare autosomal recessively inherited disease due to SPINK5 mutations. Hair and inflammatory skin involvement are variable along with allergies. Morbidity and mortality are high, particularly in infancy. A detailed clinical analysis of a NS patient cohort should broaden the understanding of nutritional challenges and allergic comorbidities., Methods: In this retrospective monocentric cohort study, medical and dietetic records of pediatric NS patients, presenting between 1999 and 2018, were reviewed. The severity of skin involvement was assessed according to the extent of the body surface area (BSA) affected by erythema., Results: We identified 21 patients with NS (median age 11.6 years). Within the first 6 months of life, requirements for fluid and kcals/protein were high for all patients (average 228 ml/kg/day) and infants had an average of 1.9 feed changes (range 0-4) due to food intolerance. Clinical evidence for IgE-mediated food allergy was present in 84.2% (16/19 children, 2 no data) with a range of 1-12 food allergies per patient. In 75%, more than one food had to be avoided. Specific IgE levels were falsely positive in 38.3% and 8/18 patients (44.4%). One-third (5/15; 6 no data) of patients, all with severe disease, had anaphylactic reactions following ingestion of fish (n = 2), sesame (n = 1), cow's milk (n = 1), and both peanut and egg (n = 1)., Conclusions: Our data emphasize feeding difficulties in children with NS and reveal an unexpectedly higher prevalence of food allergies that gives evidence to the importance of early coordinated multidisciplinary care for overcoming these challenges in NS., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Children and adolescents with severe recessive dystrophic epidermolysis bullosa (RDEB-S) often have severe constipation in addition to gastrointestinal dysbiosis, due to frequent antibiotic use and reduced oral diet. Constipation is treated with long-term use of high daily doses of macrogol gel (Movicol Paediatric PlainTM or LaxidoTM). Constipation is refractory to increases in fibre and fluids, and impacts severely on quality of life., Aim: To study the initial impact and efficacy of using a multistrain probiotic supplement daily for 12 weeks in patients with RDEB-S. The authors sought to determine the impact of such a supplement on  gastrointestinal symptoms, stool consistency and the use of macrogol gel to treat constipation, as well as understanding patient reaction, palability and ease of use., Methods: Patients were identified through the epidermolysis bullosa tertiary multidisciplinary team clinic in July 2021. Patients were included if they had a diagnosis of RDEB-S, prescribed at least one sachet of macrogol gel and provided written consent to take part. Patients were provided, proprietary liquid multistrain probiotic supplement (Symprove™) with a high bacterial count, at a dose of 1 mL kg-1 once a day. Each patient completed an anonymous, nine-question, electronic survey to document symptoms and report overall findings at the start and end of a 12-week trial period., Results: Four patients with RDEB-S (two boys and two girls; age range 7-14 years) who met the inclusion criteria were approached to take part. All patients had chronic constipation requiring daily macrogol gel use (range 2-5 sachets per day). Three out of four (75%) completed the 12-week course. At baseline (before supplementation commenced), all three (100%) patients reported poor oral appetite, constipation, flatulence, abdominal bloating and pain, and frequent skin infections requiring oral antibiotics, with two of the three (66%) patients also having nausea. After 12 weeks of supplementation, all three patients (100%) reported a significant improvement in abdominal pain and bloating, nausea, stool consistency, stool frequency, flatulence and increased appetite. Two of the three patients (66%) were able to reduce their macrogol gel usage and the third patient (33%) was able to stop macrogol gel usage altogether during the study period. All three patients said they would choose to continue using the supplement if it was available., Conclusion: We have shown in this case series that giving a multistrain probiotic supplement in patients with RDEB-S has the potential to improve stool consistency and reduce or prevent the need for chronic macrogol gel use. Future larger-scale, placebo-controlled trials are needed to confirm these results., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: 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., Aim: To establish an appropriate level of vitamin D supplementation in paediatric patients with RDEB., Methods: 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., Results: 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)., Conclusion: 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., (© 2022 British Association of Dermatologists.)

Epidermolysis bullosa acquisita is a highly uncommon condition in the paediatric population. This article describes three children with this disease, different clinical presentation and management. It also reviews the most relevant articles on this topic., (© 2022 British Association of Dermatologists.)

Background: The National Health Service (NHS) epidermolysis bullosa (EB) service, established in 2002, offers comprehensive, free care to all patients in England and Wales., Objectives: To quantify prevalence, incidence and mortality of EB in England and Wales., Methods: Demographic data for patients in England and Wales were collected on a secure electronic database, prospectively from January 2002 to April 2021 and retrospectively for cases prior to 2002. Vital status was verified using central NHS data., Results: By March 2021, 2594 individuals were registered, of whom 2361 were living, which yielded a prevalence of 34·8 per million of the population for all EB types [EB simplex (EBS) 17 per million, dystrophic EB (DEB) 10·7 per million, junctional EB (JEB) 1 per million and Kindler EB 0·3 per million]. We recorded 1200 babies with EB born since 2002. The average incidence per million live births for EBS, DEB, JEB and Kindler EB was 32·5, 26·1, 8·9 and 0·9, respectively (total incidence for all types of EB was 67·8 per million). Birth rates fell progressively over the 19-year period for JEB-severe (JEB-S) (r = -0·56) and recessive DEB-severe (r = -0·44) and also for milder types of EB. We observed longer survival in JEB-S over the 19-year period (r 2  = 0·18) with a median survival of 12·7 months over the past 5 years., Conclusions: In this study, we provide the first accurate epidemiological data for EB in England and Wales. We believe the observed reduction in birth incidence of severe types of EB reflects an uptake of genetic counselling advice, whereas the reduction in milder types may be due to delayed presentation. A potential small trend towards longer survival of babies with JEB-S may reflect improved multidisciplinary care., (© 2022 British Association of Dermatologists.)

BACKGROUNDRecessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating, and life-threatening inherited skin fragility disorder that comes about due to a lack of functional type VII collagen, for which no effective therapy exists. ABCB5+ dermal mesenchymal stem cells (ABCB5+ MSCs) possess immunomodulatory, inflammation-dampening, and tissue-healing capacities. In a Col7a1-/- mouse model of RDEB, treatment with ABCB5+ MSCs markedly extended the animals' lifespans.METHODSIn this international, multicentric, single-arm, phase I/IIa clinical trial, 16 patients (aged 4-36 years) enrolled into 4 age cohorts received 3 i.v. infusions of 2 × 106 ABCB5+ MSCs/kg on days 0, 17, and 35. Patients were followed up for 12 weeks regarding efficacy and 12 months regarding safety.RESULTSAt 12 weeks, statistically significant median (IQR) reductions in the Epidermolysis Bullosa Disease Activity and Scarring Index activity (EBDASI activity) score of 13.0% (2.9%-30%; P = 0.049) and the Instrument for Scoring Clinical Outcome of Research for Epidermolysis Bullosa clinician (iscorEB‑c) score of 18.2% (1.9%-39.8%; P = 0.037) were observed. Reductions in itch and pain numerical rating scale scores were greatest on day 35, amounting to 37.5% (0.0%-42.9%; P = 0.033) and 25.0% (-8.4% to 46.4%; P = 0.168), respectively. Three adverse events were considered related to the cell product: 1 mild lymphadenopathy and 2 hypersensitivity reactions. The latter 2 were serious but resolved without sequelae shortly after withdrawal of treatment.CONCLUSIONThis trial demonstrates good tolerability, manageable safety, and potential efficacy of i.v. ABCB5+ MSCs as a readily available disease-modifying therapy for RDEB and provides a rationale for further clinical evaluation.TRIAL REGISTRATIONClinicaltrials.gov NCT03529877; EudraCT 2018-001009-98.FUNDINGThe trial was sponsored by RHEACELL GmbH & Co. KG. Contributions by NYF and MHF to this work were supported by the NIH/National Eye Institute (NEI) grants RO1EY025794 and R24EY028767.

Background/objectives: Laryngo-onycho-cutaneous syndrome (LOC) is a rare subtype of junctional epidermolysis bullosa (JEB), featuring aberrant granulation tissue formation in the skin, larynx, and eyes. So far, three mutations including the specific (founder) mutation in exon 39 of LAMA3 (c.151dup) have been identified, but sparse data exists regarding the natural history, the genotype-phenotype correlation, and its differentiation from other JEB types., Methods: We reviewed our pediatric EB database to identify English children with clinical and genetically diagnosed LOC within the last 15 years. Their demographic, clinical, and laboratory data were examined. We searched three databases for case reports of LOC between January 1986 and November 2020 and extracted clinical and molecular details., Results: We identified 6 LOC patients, all female (mean age 5.4 years). Periungual hypergranulation and skin fragility were the earliest presenting signs (0-3 months), followed by laryngeal stenosis, symblepharon (mean onset 10.7 and 11.8 months, respectively), and dental abnormalities. Five children developed anemia at an average of 19.2 months. We identified 22 published studies in English with 31 cases., Conclusions: This study delineates the disease course of LOC and highlights the overlap with some forms of JEB. Classical signs/symptoms including anemia appear early in life. Genetic analysis revealed three new LOC-associated variants and underscores the finding that interpretation of skin immunolabeling and molecular diagnostics can be challenging. We provide recommendations on management of this complex syndrome., (© 2021 Wiley Periodicals LLC.)