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Objectives: The 90-day double-blind phase (DBP) of the Phase 3 EASE study demonstrated accelerated wound healing for Oleogel-S10 (birch triterpenes) versus control gel in epidermolysis bullosa (EB). Here, we report safety and total wound burden results from the 24-month open-label phase (OLP) in which all patients received treatment with Oleogel-S10. Method(s): Total wound burden was assessed using EB Disease Activity and Scarring Index (EBDASI) and Body Surface Area Percentage (BSAP). Data are reported without visit windows to reflect a realworld situation more accurately, particularly considering the COVID- 19 pandemic. Result(s): The patient population was made up of dystrophic EB (n = 178, 86.8%) and junctional EB (n = 25, 12.2%);71.7% (n = 147) of patients were aged <18 years. 141 patients (68.8%) completed the OLP. The mean (SD) treatment duration for all patients was 584.7 (246.1) days. Adverse events were reported in 77.1% of all patients in the OLP versus 81.7% of those receiving Oleogel-S10 in the DBP. Mean BSAP for patients treated with Oleogel-S10 in the DBP reduced from 12.1% at study entry to 6.1% with 27 months of treatment. Similarly, the mean EBDASI skin activity score in the Oleogel-S10 group improved from 19.6 to 15.1 after 27 months. In addition, reductions in both BSAP and EBDASI from OLP baseline were observed in patients who transitioned from control gel to Oleogel-S10 in the OLP. Discussion(s): These data support a reassuring long-term safety profile of Oleogel-S10. Furthermore, the reduction in wound burden previously reported with 15 months of Oleogel-S10 treatment is maintained to the end of OLP. This is encouraging given the nature of this chronic genetic disorder in which there is regular cycling of patients' fragile wounds.
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Graft-versus-host disease (GvHD) is common after haematopoietic cell transplantation (HCT). Mucocutaneous manifestations are variable and may simulate autoimmune bullous dermatoses. However, the association of GvHD with autoimmune disorders, including bullous dermatoses, is also well recognized. We describe a patient with GvHD in whom severe and relapsing epidermolysis bullosa acquisita (EBA) was diagnosed 3 years after transplant and propose a causal association with GvHD. A 66-year-old woman developed GvHD following allogeneic HCT for acute myeloid leukaemia in 2016. This affected her gastrointestinal tract and skin but improved with oral corticosteroids and ciclosporin. In 2019 she presented with a widespread rash consisting of large, tense, haemorrhagic blisters. Histological features were in keeping with EBA. Direct immunofluorescence was also consistent with EBA, demonstrating linear positivity for IgG and C3 confined to the blister base, as was detection of collagen VII antibodies on indirect immunofluorescence. She was admitted and treated with high-dose oral steroids, ciclosporin and intravenous immunoglobulin (IVIg) with eventual resolution of blistering. Although further IVIg administration was planned as an outpatient, this coincided with the start of the COVID-19 pandemic and she elected not to attend and also stopped all medication. Despite this, her EBA remained quiescent until September 2021 when she was readmitted with a severe deterioration in blistering and significant dysphagia due to an oesophageal stricture, with a weight of 31.7 kg. Once again, she responded rapidly to oral prednisolone and IVIg. Dapsone was considered but precluded by G6PD deficiency and there were clinical and adherence concerns about using mycophenolate mofetil. Upon discharge she was again nonadherent to medication and failed to attend for planned IVIg. She flared and was admitted for a third time in December 2021, requiring gastrostomy for nutritional support;her weight at this time was 26.4 kg. Her EBA is currently well controlled on prednisolone and IVIg. EBA is a rare, acquired blistering disorder secondary to autoantibodies targeting type VII collagen. Previous studies have found circulating basement membrane zone (BMZ) antibodies in 24% of chronic GvHD patients, possibly generated in response to chronic BMZ damage (Hofmann SC, Kopp G, Gall C et al. Basement membrane antibodies in sera of haematopoietic cell recipients are associated with graft-versushost disease. J Eur Acad Dermatol Venereol 2010;24: 587-94). Corresponding clinical manifestations are rare, with bullous pemphigoid the most frequently reported. EBA is much less common with four previously reported cases [Brassat S, Fleury J, Camus M, et al. (Epidermolysa bullosa acquisita and graftversus- host disease). Ann Dermatol Venereol 2014;141: 369-73 (in French)]. As a fifth case of EBA, our patient provides further evidence of a likely pathophysiological relationship between GvHD and autoimmune subepidermal bullous dermatoses, and highlights the significant challenges of managing these vulnerable patient groups during the COVID-19 pandemic.
ABSTRACT
The blistering disease Epidermolysis bullosa acquisita is a genetic/autoimmune disorder deriving from alterations of the human protein Collagen alpha-1(VII) chain (CO7A1). Exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes a wide variety of autoimmune diseases and might be a risk factor for Epidermolysis bullosa acquisita;in order to further our understanding of the link between this blistering disease and SARS-CoV-2, this study analyzes the peptide-sharing between CO7A1 and SARS-CoV-2 proteome. Results indicate a high level of molecular mimicry between CO7A1 and SARS-CoV-2 and hCoV-229E, and hCoV-NL63, thus suggesting a potential role of COVID-19 as a risk factor for Epidermolysis bullosa acquisita. Copyright © by BIOLIFE, s.a.s. This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder.
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Introduction: Esophageal strictures in children are in most cases associated with a benign etiology. There are multiple conditions that are associated with esophageal strictures including congenital stenosis, secondary to surgical repair of esophageal atresia, caustic burns following ingestion of acids or alcalis, radiation therapy and secondary to some pathologies as gastroesophageal reflux disease, eosinophilic esophagitis, scleroderma, epidermolysis bulllosa and idiopathic. Esophageal dilation can be performed with different techniques that include endoscope dilators, dilations performed over the wire and using the endoscope itself. Some cases require other adjunctive techniques that improve the results after failed progressive dilation. This therapies includes medical treatment and surgical derivations, with some cases known as recalcitrant. Also, esophageal strictures and its management could produce motility disorders. There is no consensus in the literature regarding the management process, especially in frequency of interventions, use of adjunctive therapies and alternatives for conservative management. This problem is more evident in developing countries. Objective(s): The objective of this study was to describe the cases of esophageal strictures and its management in children between 2016 and 2022 in the Instituto Nacional de Pediatria in Mexico City. Method(s): This was a six year retrospective study involving pediatric patients with esophageal stricture. We retrospectively reviewed the medical records of 23 pediatric patients who underwent endoscopic treatments for esophageal strictures, between January 2016 and May 2022 in the Comprehensive Pediatric Gastroenterology Diagnostic Unit in the Instituto Nacional de Pediatria in Mexico City. Result(s): The mean age at diagnosis was 24 months (Q1 15, Q3 35), 12 patients were male (52%) and 11 patients were female (48%). The most prevalent etiology was caustic strictures in 10 patients (43%). Six patients (26%) had esophageal atresia (4 type III, 1 type I and 1 type V), all whose received surgical management in the first days of life. All required repeated pneumatic dilation (between 1 and 11) for the management of postsurgical stenosis. Other etiologies that were found include Schatzki Ring, congenital stenosis, esophageal fibrosis associated with congenital dyskeratosis, epidermolysis bullosa, graft-versus-host disease and gastroesophageal reflux disease (one patient for each cause). In one patient the etiology remains unknown. Seventeen patients had one stricture, 5 patients had two strictures and 1 had 3 strictures. Ten patients had esophageal pseudodiverticula and two had mucosal fold. Six patients underwent dilation with Savary-Guilliard dilators combined with pneumatic balloon dilation. Four patients received mitomycin- C as an adjuvant therapy during dilations. The average diameter of stenosis was increased from 7 mm (range 4-15 mm) to 13,5 mm (range 8-18mm). Two patients had severe complications, one had a esophageal perforation associated with dilation. The other one had a pneumothorax related with anesthetic management. In the outcome 6 patients are asymptomatic, 1 patient persist with dysphagia after completed treatment, 9 patients are under treatment, 1 patient died secondary to its underlying disease and 6 patients lost follow up. Conclusion(s): Post-corrosive esophagitis and post-esophageal atresia anastomotic strictures were the most frequent types of cicatricial esophageal strictures. The conservative treatment was the first management strategy in the majority of patients, being the endoscopic balloon dilation the first choice. The SARS-COV-2 sanitary emergency limited the progressive intervention rate and appropriate clinical follow up of patients, reason why there is an important loss of follow up in the described group. A number of patients are currently on management, reason why their outcomes will be assessed in the future.
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Background & Aim: Multilineage-differentiating stress enduring (Muse) cells, collectable as pluripotent surface marker SSEA-3-positive, are naturally existing non-tumorigenic pluripotent stem cells that distribute in the bone marrow, peripheral blood, connective tissue of every organ, and exhibit triploblastic differentiation and self-renewability at a single cell level. They are also contained in cultured MSCs and fibroblasts as several percent, and are expandable to a clinical scale. Circulating Muse cells, both endogenous and intravenously injected exogenous cells, selectively home to damaged tissue by sensing sphingosine-1-phosphate (S1P), one of the general alert signals produced by the damaged tissue, and then spontaneously differentiate into multiple tissue-constituent cells to replace damaged/ apoptotic cells. In this manner, they repair tissues. In addition, they have a specific immunomodulatory system, represented by HLA-G expression, allowing allogenic-Muse cells to directly administrate to patients without HLA-matching or long-term immunosuppressant (Figure Presented) treatment, and to remain in the host tissue as differentiated functional cells for more than half a year, as shown by animal models. Methods, Results & Conclusion: For these characteristics, intravenous drip is the main route of treatment and do not require surgery for their administration, nor do they require gene introduction or cytokine treatment to be rendered pluripotency and/or differentiation. Currently, clinical trials using intravenously administered donor- Muse cells have been conducted for myocardial infarction, stroke, epidermolysis bullosa, spinal cord injury, perinatal hypoxic ischemic encephalopathy, amyotrophic lateral sclerosis and COVID19-ARDS, all by intravenous drip of donor-derived Muse cell formula, CL2020, without HLA-matching or immunosuppressant treatment. The result of randomized, double-blind, placebo-controlled clinical trial in stroke patients confirmed safety and efficacy of Muse cell-based product for up to 52 weeks (1 year). Muse cells may safely provide beneficial effects compatible with the ‘body’s natural repair systems’ by a simple cost- effective strategy;collection, expansion and intravenous drip.
ABSTRACT
Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating, genetic, blistering condition caused by the absence of type VII collagen (C7) resulting in wounding. One major barrier to clinical trial development is the lack of understanding of the natural history of RDEB wounds, as the measurement of wound change has not been studied prospectively or validated. We conducted a longitudinal observational study of 13 participants with RDEB, that were not currently participating in interventional clinical trials. They used a mobile phone photography application with built-in machine learning to outline and track RDEB wounds autonomously. Participants used this mobile application to capture weekly photographs of chronic or recurrent wounds for up to six months and reported associated pain and itch. In total, 773 photos were collected from 72 wounds, of which 39 were chronic wounds (54.2%). The median time for wound closure (≥90% decrease in size from the first photo) was 249 days for chronic open wounds and 68 days for recurrent wounds. A chronic open wound was defined as a wound that has not healed for more than 12 weeks and a recurrent wound heals in less than 12 weeks, but re-opens. For chronic open wounds, wound size was positively correlated with pain and itch using spearman correlation coefficients (0.76, p<0.001 and 0.74, p<0.001, respectively). Wound size for recurrent wounds were also positively associated with pain and itch (0.37, p<0.001;0.32, p<0.005). The COVID-19 travel restrictions have shown the value of remote wound monitoring to assess the natural history of RDEB wounds. Challenges included patient difficulties in navigating the mobile application, uploading regularly, and limited participation due to enrollment in other clinical trials. The next step of this work is to compare our findings of the closure time for chronic versus recurrent wounds against published wound size data of 60 participants from a recent clinical trial, which will enable our group to test definitions of chronic and recurrent wound duration.
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The proceedings contain 42 papers. The topics discussed include: a pediatric case series of COVID-19-associated chilblain-like acral lesions;genital dermatology: a window to the gut. Three cases of genital cutaneous Crohn disease;Influence of biologics on COVID-19-positive patients: a case series;cutaneous thrombosis associated with skin necrosis following Oxford/AstraZeneca COVID-19 vaccination: a case report;reactive infectious mucocutaneous eruption (RIME) secondary to COVID-19 infection;adverse events following immunization (AEFI) with COVID-19 vaccines: case series and literature review;challenges in the management of toxic epidermal necrolysis and COVID-19: a case report;and a rare case of epidermolysis bullosa acquisita in one of identical twins.
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Jaimie Oldham, Sasha Dhoat, Catherine Harwood and Rebeca Goiriz I Department of Dermatology, Barts Health NHS Trust, London, UK i Graft-versus-host disease (GvHD) is common after haematopoietic cell transplantation (HCT). As a fifth case of EBA, our patient provides further evidence of a likely pathophysiological relationship between GvHD and autoimmune subepidermal bullous dermatoses, and highlights the significant challenges of managing these vulnerable patient groups during the COVID-19 pandemic. Previous studies have found circulating basement membrane zone (BMZ) antibodies in 24% of chronic GvHD patients, possibly generated in response to chronic BMZ damage (Hofmann SC, Kopp G, Gall C I et al i . [Extracted from the article] Copyright of British Journal of Dermatology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
ABSTRACT
Lymphangiomas (LG) are uncommon, rare congenital anomalies or acquired lymphatic dilations of a benign flow that can involve the skin [1, 2]. There are main groups of lymphangiomas: 1) a superficial variant, characterized by grouped vesicles (circumscriptum lymphangioma), 2) a deeper variant in the form of a cavernous lymphangioma. The prevalence of LG may be focal or diffuse. Secondary acquired LG with a rarer frequency are known [3, 4]. LG can be one of the manifestations of a symptom complex, for example, Gorham-Stout syndrome, which is characterized by progressive osteolysis [5]. The rare occurrence of LG, clinical diversity, undulating course of congenital forms, the possibility of an acquired nature of the disease causes a high risk of diagnostic errors in establishing the final diagnosis. At the Department of Dermatovenereology, Cosmetology and Additional Professional Education of Smolensk State Medical University for the period from 2018 to 2021, 5 patients (age from 5 to 17 years) with LG were observed. Of these: in four children, the disease existed from birth, in one girl it had an acquired character and developed after covid infection [4]. Gender characteristics: 4 girls (5, 6, 12 and 17 years old) and 1 boy (9 years old). All patients are urban residents. The time to establish the final diagnosis from the moment of seeking medical help ranged from 15 months to 12 (!) years, the average value being 6.5 years. The range of diagnoses of LG 'masks': herpetic infection, molluscum contagiosum, atopic dermatitis, contact dermatitis, epidermolysis bullosa. A frequent change in diagnoses was established in the same patient. Clinical case 1. The boy is 12 years old. The debut of skin lesions from birth and progression to 3 years of age, then spontaneous regression within 4 years (without signs of dermatosis). From 7 years to the present, there has been an increase in the number of rashes. Localization: the skin of the lateral surface of the trunk. Features of the rash: flesh-colored and/or reddish- purple bubbles. A pathognomonic symptom of 'frog calves' is found. The frequent autodestructive effect on the rash provokes its subsequent progression. Family history: his father is a liquidator of the atomic catastrophe in Chernobyl. Previous diagnoses: molluscum contagiosum, herpes zoster. Clinical case 2. The girl is 17 years old. The debut of the disease from birth. Lack of progression up to 5 years of age (up to 5 years of age did not apply to dermatologists). At the age of 5, she began to engage in rhythmic gymnastics (she continues to practice professionally at the present time) and noted an active increase in the number and size of the elements of the rash. She repeatedly consulted dermatologists: diagnoses of molluscum contagiosum (laser removal), herpetic infection (courses of antiherpetic therapy without effect) were assumed. The diagnosis was established 12 years after the moment of seeking medical help. Unilateral location of the rash along the inner surface of the right upper limb with transition to the axillary region;on the right lateral surface of the body, the right inguinal-femoral fold and the inner surface of the right thigh. Focuses of a rash in the form of different sizes of vesicular elements with a tendency to lymphorrhea and oozing, areas of maceration around. Single elements with a hemorrhagic component. The patient notes an increase in the inflammatory response and vesicle lymphorrhea after each workout. Dermatoscopy: yellow-pink lacunae alternating with single dark red lacunae. Histological examination: multiple dilated lymphatic vessels in the papillary and reticular dermis. Clinical case 3. Girl 6 years old. Sick from birth. The diagnosis of LG of the genitals was established at the age of 1, 5 years. Due to the localization of the rash in the external genital area, the girl's parents (at the age of 1 month) consulted an obstetrician-gynecologist, who suggested a hemangioma and referred to a dermatologist. The disease is of a family nature her grandmother (on the maternal side) and her lder brother have similar rashes on the skin of the trunk and in the mouth. The diagnosis was verified by histological examination. The pathological process is localized in the area of the labia majora and labia minora: multiple vesicular rashes with translucent contents, easily traumatized and accompanied by itching, were found. Conclusions: LG is a multidisciplinary problem, which is caused by mimicry of manifestations, varied localization and prevalence of the rash. To verify the diagnosis, the following algorithm should be followed: 1) the debut more often at birth or in the first months of life (with the exception of acquired forms of LG);2) the nature of evolution: a stable state or slow progression in the absence of traumatic factors;3) clinical features: the formation of grouped deep vesicles that resemble 'frog eggs'. The color of the bubbles is transparent or red-purple due to the hemorrhagic component. LG lesions may have hemangioma components. It should be remembered about the frequent localization of LG on the mucous membrane of the cheeks, tongue and floor of the oral cavity, which can manifest itself as bleeding from the elements of the rash when chewing or when providing dental care;4) biopsy reveals dilated lymphatic vessels in the upper layers of the dermis.
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The proceedings contain 17 papers. The topics discussed include: a helix-swapped C3d dimer mediated by immune evasion protein Sbi hints at a novel s. aureus complement modulation strategy;the role of factor H in macrophages;an antibody targeting complement factor H causes anti-tumor immunity through B-cell activation;C5aR2 deficiency ameliorates inflammation in antibody transfer experimental epidermolysis Bullosa Acquisita and suggests regulating action on the decisive C5a receptor 1;clinical and biomarker characteristics of patients with C3G enrolled in two phase 2 studies investigating the factor D inhibitor Danicopan;perceiver-based machine learning diagnosis of TMA in renal biopsies;and recurrence of atypical hemolytic uremic syndrome After COVID-19 vaccination.
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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.