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Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a skin fragility disorder characterised by life-long mechanically induced skin blistering, fibrosis-driven pseudosyndactyly, and multi-organ involvement. Preclinical studies have suggested mitigated progression by angiotensin II type I receptor blockade through losartan. We aimed to determine the safety and tolerability of systemic losartan treatment among children with RDEB, and to obtain initial data on its clinical benefit., Methods: We conducted an open-label, single-arm, phase 1/2 trial at the Medical Center-University of Freiburg, Germany. Children with molecularly-confirmed RDEB, aged 2-16 years (starting from the 25th month of life) were eligible. Key exclusion criteria comprised anaemia with haemoglobin <8 g/dl; hypotension (defined as age-related systolic blood pressure under the 5th percentile); cardiologic contraindications, requirement for any medications that are likely to cause interactions with losartan; renal artery stenosis or renal insufficiency with creatinine clearance <30 ml/min; severe liver failure; severe, untreated electrolyte disturbances; history of cancer or chronic viral infections; hypersensitivity to losartan or any of the excipients and known or persistent abuse of medication, drugs, or alcohol. Treatment duration with losartan comprised 10 months, encompassing 16 weeks up-dosing of losartan, 24 weeks full dose losartan (final target dose of 1.4 mg/kg), and 4 weeks losartan tapering, followed by 12 weeks follow-up without losartan. The primary endpoint was occurrence of a serious safety concern, defined as one of the following side effects of losartan: clinically relevant severe hypotension, immediate hypersensitivity reactions to the drug or clinical relevant severe hypo- and hyperkalaemia. EB-specific scores (the EBDASI activity and damage score, Birmingham Epidermolysis Bullosa Severity Score (BEBS)) and other clinical outcome parameters were evaluated at five clinical visits as secondary outcomes: pain (Wong-Baker FACES Scale for pain), quality of life (Quality Of Life in EB [QOLEB] questionnaire and Children's Dermatology Life Quality Index [CDLQI]), itch (Itch Assessment Scale for the Paediatric Burn Patients), dysphagia (Mayo Dysphagia Questionnaire-day 30 [MDQ-30]), pseudosyndactyly progression (our own morphometric scoring instrument), and hand function (Score of Colville and Terrill). All analyses (safety and efficacy) were performed in the safety population, defined as participants who received at least one dose of trial medication with losartan. This trial is registered with EudraCT, 2015-003670-32., Findings: Between Jul 28, 2017, and Feb 12, 2021, 29 children were enrolled. Of those 27 received the full treatment. Losartan was well tolerated, no treatment-related severe complications leading to a serious safety concern occurred. The patients revealed improvement in the RDEB clinical scores, namely a mean reduction at week 40 of -7.36 points (95%-CI: -16.13 to 1.41) in the EBDASI activity score and -10.50 points (95%-CI: -20.81 to -0.19) in the EBDASI damage score, while the Children's Dermatology Life Quality Index rose by 2.64 points (95%-CI: -4.55 to -0.90). Similar to the EBDASI score, the BEBS showed a mean reduction of -3 points, 95%-CI: -0.21 to -5,79, P = 0.036). In the Wong-Baker FACES Scale for Pain an improvement of at least one level was identified for 9 of 28 patients between baseline and at month 9 (95%-CI: 15.9%-52.4%; P = 0.57). Regarding the Quality of Life in EB Score, five of 28 patients showed an improvement in the total scale of at least one level at month 9 (95%-CI: 6.1%-36.9%; P = 0.71). With the Itch assessment scale for the paediatric burn patients an improvement of at least one level could be observed in 12 of 28 patients (95%-CI: 24.5%-62.8%; P = 0.24). The MDQ-30 showed no relevant difference at 9 months after treatment start, as compared to baseline. We observed improvement of finger span with our own morphometric scoring instrument of pseudosyndactyly progression, revealing an increase of the maximal distance between thumb and index finger at month 9 by 6.92 mm, 95%-CI [3.48, 10.37] P = 0.0009. With the Hand function assessment score of Colville and Terrill, an improvement of at least one level was documented for 3 of 28 patients, i.e., 10.7% (95%-CI: 2.3%-28.2%; P = 0.63)., Interpretation: Our results suggest that losartan was well tolerated by children with RDEB, and provide preliminary evidence that it may reduce disease burden. Further research with larger sample sizes and longer durations is needed to establish the treatment's long-term efficacy and safety., Funding: Debra International, the Department of Dermatology, Medical Center-University of Freiburg (Berta-Ottenstein Advanced Clinician Scientist Program of the Medical Faculty), and the German Research Foundation., Competing Interests: DK, TZ and LBT are founders of Crowd Pharma Losartan GmbH & Co. KG, a company established in 2021 to pursue development of losartan for epidermolysis bullosa. AN has received payments for invited talks by Amryt Pharma. AN, BS, DK and LBT have filed a patent for the use of losartan for the treatment of fibrotic diseases, in particular epidermolysis bullosa (EP 4 081 300 B1). All other authors declare no competing interests., (© 2024 The Author(s).)

Esophageal lichen planus is an underrecognized manifestation of lichen planus. It is typically diagnosed based on characteristic endoscopic findings, such as hyperkeratosis, trachealization, denudation and/or stenosis, along with the presence of a lichenoid infiltrate in histopathological examination. In cases where no other manifestation of lichen planus are found and direct immunofluorescence for fibrinogen along the basement membrane is negative, the term "lichenoid esophagitis" should be preferred. This distinction is critical, as it prompts a thorough evaluation for underlying diseases, including autoimmune conditions and viral infections. We report a case of a 69-year-old male with stenosing esophagitis resembling esophageal lichen planus on endoscopic evaluation. The condition was refractory to multiple dilation procedures and high-dose proton pump inhibitor therapy. Histopathological analysis revealed a dense lymphocytic infiltrate extending into the epithelial layer, while direct immunofluorescence microscopy for fibrinogen was negative. There were no other signs of lichen planus on the skin or mucous membranes. The patient's medical history included recurrent transient ischemic attack (non-cardiac), penile cancer and recurrent mucosal candidiasis. Laboratory findings revealed Epstein-Barr virus viremia and IgG hypergammaglobulinemia, raising suspicion of immunodeficiency. Further testing confirmed an active HIV infection, classified as category C3, and antiretroviral therapy was initiated. Following the initiation of antiretroviral therapy, the patient experienced rapid clinical and histopathological improvement of the lichenoid esophageal inflammation, although the esophageal stenosis persisted. Subsequent follow-up endoscopies confirmed resolution of the inflammatory component, underscoring the positive impact of addressing the underlying HIV infection on the esophagus. This case report highlights the importance of recognizing lichenoid esophagitis as a potential diagnosis in cases of unexplained chronic esophagitis, especially when standard treatments are ineffective. The presence of lichenoid inflammation without other manifestations of lichen planus should trigger an investigation into underlying conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Marschner, Schmitt-Graeff, Kreisel, Decker and Schauer.)

As of now, there exists no established therapy for ELP. Retinoids, which are standard in treating cutaneous LP, do not exhibit positive effects in ELP. While topical glucocorticosteroids often yield favorable responses in esophageal inflammation, some cases prove recalcitrant or refractory. In such instances, various immunosuppressive therapies have been attempted with variable success.This report details a severe case of ELP that showed resistance to prednisolone, acitretin, alitretinoin, adalimumab, tacrolimus, hydroxychloroquine plus mycophenolate mofetil, and cyclophosphamide. The initiation of the JAK inhibitor tofacitinib induced an impressive clinical, endoscopic, and histological remission. This positive response to a JAK inhibitor is discussed in the context of our evolving understanding of the immune-mediated pathogenesis of this disease., Competing Interests: FS was funded by the Berta-Ottenstein-Programme for Advanced Clinician Scientists, Faculty of Medicine, University of Freiburg. The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long-term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as a fast-acting adjuvant treatment option., Objectives: To assess the clinical efficacy of IA in addition to best medical treatment (BMT)., Methods: We conducted a multicentre (26 centres from Germany and Austria) randomized controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 female patients and 38 male patients, aged 42-72 years) comparing BMT (prednisolone 1.0 mg kg-1 per day plus azathioprine or mycophenolate) with adjuvant IA (BMT + IA). Central 1 : 1 randomization was done at the coordinating centre for clinical trials (KKS Marburg). The primary endpoint was analysed using Kaplan-Meier and Cox regression methods., Results: The study was ended prematurely owing to safety concerns after random allocation of 72 patients to BMT + IA (n = 34) or BMT (n = 38). The primary endpoint, time to complete remission on therapy, was not significantly different for the two groups [hazard ratio (HR) 1.35, 95% confidence interval (CI) 0.68-2.69; P = 0.39]. The cumulative dose of prednisolone was significantly lower in the BMT + IA group compared with BMT alone (difference -1214, 95% CI -2225 to -70; P = 0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group (HR 1.87, P = 0.17 in patients with baseline Pemphigus Disease Area Index ≥ 15). While more adverse events were observed in patients in the BMT group (29 vs. 25), severe adverse events were more frequent in patients in the BMT + IA group (17 events in 10 patients vs. 11 events in 8 patients)., Conclusions: In this study, adjuvant IA did not demonstrate a shorter time to clinical remission, but a corticosteroid-sparing effect was observed. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits., Competing Interests: Conflicts of interest N.v.B. has a joint project and a patent pending with Euroimmun and received honoraria from Fresenius Medical Care. E.S. has a scientific cooperation arrangement with Fresenius Medical Care and received honoraria from this company. M.H. and R.E. have received honoraria from Fresenius Medical Care., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

We describe a case of endocarditis caused by Streptobacillus moniliformis bacteria, a known cause of rat-bite fever, in a 32-year-old woman with pet rats in Germany. The patient had a strong serologic response, with high IgM and IgG titers. Serologic analysis is a promising tool to identify S. moniliformis bacterial infection.

Background: The occurrence of herpes zoster is rising globally. Future trends will be influenced by changes in population demographics and the growing number of patients at risk. Overall this poses a challenge for healthcare systems., Methods: In our interdisciplinary, single-centre retrospective analysis, we aimed to assess the burden of the disease within the Department of Dermatology and the Eye Centre from the Medical Centre, University of Freiburg from 2009-2022. We obtained data from 3034 cases coded using the ICD-10 B02.x. Patients were characterised by sex, age, year of treatment, and type of treatment (inpatient vs. outpatient)., Results: Overall we observed a 200% increase in the number of herpes zoster patients over the 13-year period. Upon closer analysis, this was mainly due to a rise in inpatient treatment for herpes zoster ophthalmicus., Conclusions: If the incidence of herpes zoster ophthalmicus continues to increase at the current rate the number of hospitalisations of zoster ophthalmicus would double by 2040, assuming guideline-appropriate treatment. Overall, the results show a growing need for inpatient ophthalmological care., (© 2023. The Author(s).)