Characterisation of IL‐1 family members in Sweet syndrome highlights the overexpression of IL‐1β and IL‐1R3 as possible therapeutic targets

Sweet syndrome (SS) as a prototypic neutrophilic dermatosis (NDs) shares certain clinical and histologic features with monogenic auto-inflammatory disorders in which interleukin (IL)-1 cytokine family members play an important role. This has led to the proposal that NDs are polygenic auto-inflammatory diseases and has fuelled research to further understand the role of IL-1 family members in the pathogenesis of NDs. The aim of this study was to characterise the expression of the IL-1 family members IL-1β, IL-36γ, IL-33 and IL-1R3 (IL-1RaP) in SS. The expression profile of IL-1β, IL-33, IL-36γ and their common co-receptor IL-1R3 was analysed by immunohistochemistry, in situ hybridisation and double immunofluorescence (IF) in healthy control skin (HC) and lesional skin samples of SS. Marked overexpression of IL-1β in the dermis of SS (p < 0.001), and a non-significant increase in dermal (p = 0.087) and epidermal (p = 0.345) IL-36γ expression compared to HC was observed. Significantly increased IL-1R3 expression within the dermal infiltrate of SS skin samples (p = 0.02) was also observed, whereas no difference in IL-33 expression was found between SS and HC (p = 0.7139). In situ hybridisation revealed a good correlation between gene expression levels and the above protein expression levels. Double IF identifies neutrophils and macrophages as the predominant sources of IL-1β. This study shows that IL-1β produced by macrophages and neutrophils and IL-1R3 are significantly overexpressed in SS, thereby indicating a potential pathogenic role for this cytokine and receptor in SS

Immune checkpoint inhibitor‐induced epidermal necrolysis: A narrative review evaluating demographics, clinical features, and culprit medications

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but can cause immune-related adverse events (irAEs). Severe cutaneous irAEs, including epidermal necrolysis, are rare but potentially life-threatening. There is limited understanding of the clinical features and management of ICI-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), so we aimed to analyze 95 cases of ICI-induced SJS/TEN (35 cases of SJS, 26 cases of TEN, two cases of SJS/TEN overlap, and 32 cases of unspecified) to increase knowledge of this condition among oncologists and dermatologists. We conducted a comprehensive search of PubMed for all relevant case reports published until the end of December 2022, and collected data on patient demographics, cancer type, ICI regimen, time to onset of SJS/TEN, clinical presentation, management strategies, and outcomes. PD-1 inhibitors were the most common ICIs associated with SJS/TEN (58.9%), followed by the combination of PD-1 and CTLA-4 inhibitors (11.6%), and PD-L1 inhibitors (6.3%). Lung cancer and melanoma were the most frequent malignancies treated (35.8% and 25.4%, respectively). SJS/TEN occurred most frequently within the first 4 weeks (51.7%), and corticosteroid monotherapy was the most commonly chosen systemic treatment (56.4%). The overall mortality rate of ICI-induced SJS/TEN was 30.8%. Our findings highlight the frequency and severity of ICI-induced SJS/TEN and the urgent need for predictive molecular biomarkers aimed at preventive measures and early intervention

Alitretinoin in the treatment of cutaneous T-cell lymphoma

Introduction In this survey, we analyzed data from patients suffering from the most common cutaneous T-cell lymphomas (CTCLs) subtypes mycosis fungoides (MF) and Sezary syndrome (SS), treated with the retinoid alitretinoin during a 7-year period at our outpatient department between 2015 and 2020. Materials and Methods We analyzed patient medical records including TNMB stage, side effects under therapy with alitretinoin, time to next treatment (TTNT), and previous photo documentation. Results A total of 35 patients with MF (n = 28) and SS (n = 7) were included in the study, of whom 69% were male and 31% were female. The mean age of onset was 56 +/- 15 years in MF and 65.4 +/- 10.8 years in SS with 51.4% having early stage (IA-IIA) and 48.6% having advanced stage (IIB-IVA) CTCL. Of these patients 37.2% responded to alitretinoin, 28.6% had a stable course, and 34.3% experienced progression. Alitretinoin was administered as a monotherapy (25.7%) or combined with five concomitant therapies (74.2%), most frequently with ECP (31.4%) and PUVA (11.4%). 63% did not report any side effects, most often hypertriglyceridemia (20%) was described. Conclusion Considering that nearly two thirds of the CTCL patients treated with alitretinoin showed a response or stable disease, together with a low number of side effects and low cost compared to bexarotene, alitretinoin may be a potential alternative in the treatment of less advanced CTCLs. This survey represents the largest number of recorded therapies with the retinoid alitretinoin in CTCLs in a European patient collective

3D printing and silicone models of primary skin lesions for dermatological education as remote learning tool

Background and objectives: The corona pandemic affects many aspects of life – with challenges in medical treatment undoubtedly of paramount importance. However, continuing medical education needs to be consistently provided. During a semester with lockdown-phases and limited student-to-patient-contact availability, we supplied silicone models of primary skin lesions to every student and asked them to evaluate this teaching tool. Methods: In two anonymous online surveys, we asked students enrolled in dermatology (n = 222) at the Medical Facility of the Ludwig Maximilian University of Munich in the winter semester 2020/2021 – subsequent to online teaching – about their understanding and self-assessment of primary skin lesions before and after receiving silicone models for practice. The models were produced by layering different types of silicone into negative 3D printed molds made from polylactide to attain different degrees of hardness and colors. Results: Data from 211 (95.0 %) and 213 (95.9 %) of the 222 students were analyzed before and after receiving the silicone models, respectively. In all questions the students stated a highly significant improvement in their skills (P < 0.001). The majority of students evaluated the silicone models positively and reported a better understanding and learning of primary skin lesions. Conclusions: This study demonstrates the benefit of haptic experience in dermatology teaching not only in the time of COVID-19, but also thereafter

Impact of allergic reactions and urticaria on mental health and quality of life

Background: Allergic diseases represent a major global health issue with more than one-third of the global population affected by at least one allergic condition. Allergic conditions can not only cause life-threatening anaphylactic reactions but also impact daily life with a significant influence on mental health and the quality of life (QoL). Objectives: This study aims to evaluate the health-related QoL and depression severity among patients presenting in a tertiary care allergy center. Methods: A cross-sectional study was conducted among 596 patients presenting with allergic symptoms or previously diagnosed allergies between October 2018 and April 2019. Patients were screened for depression and the QoL impairment by using three validated scales: the Beck Depression Inventory (BDI), the Dermatologic Life Quality Index (DLQI), and the three-level version of the EuroQol 5-Dimensional (EQ-5D-3L) scale. Results: One-third (34.8%) of the study population was male and two-thirds (65.2%) were female. About 73.7% (n = 427/579) of the patients suffered from at least one previously diagnosed allergic disease, most frequently to pollen (37.0%, n = 214/579) and food (27.3%, n = 158/579), and 20.0 % (n = 116/579) suffered from urticaria. About 19.3% of the total population suffered from depression. Urticaria, as well as insect venom, food/food additives, and drug allergies significantly affected the QoL and depression severity (p < 0.001), reflected by higher DLQI and BDI scores, and lower scores in the EQ5D-3L index. Conclusion: Our results provide evidence for a possible correlation of allergies (e.g. against insect venom, food/food additives, and drugs) and/or urticaria with a reduced QoL and a higher depression rate. Patients particularly indicated restrictions for the dimensions, pain/discomfort as well as anxiety/depression. It might be beneficial to implement a standardized questionnaire as a regular screening method for evaluating the mental health status of patients with allergies and/or urticaria. (C) 2022 Codon Publications. Published by Codon Publications

First ex vivo cultivation of human Demodex mites and evaluation of different drugs on mite proliferation

Background Demodex spp. mites are the most complex resident of the human skin microbiome. Although they are considered commensals, they can be pathophysiologically relevant in inflammatory skin diseases like rosacea. Until now, there is no culture system available for these mites except for using live vertebrate hosts. Objectives Our aim was to establish an ex vivo culture of human Demodex mites and to characterize the sebogenesis-dependent mite density. Methods Demodex mites were cultivated in pilosebaceous units of human skin explants, called human organotypic skin explant culture (hOSEC). Furthermore, different sebogenesis-modifying additives were evaluated. Mites and mite survival were evaluated using light and fluorescence microscopy. Results After 90 days of incubation, living Demodex mites - including eggs, larvae and nymphs - were detected in the dissected skin samples. Incubation for 30 days with anabolic steroids (testosterone and trenbolone) as well as retinol and retinoic acid (isotretinoin) yielded a reduced mite density. Conclusions With this technique, mites can be cultivated ex vivo for the first time, thereby establishing new ways to investigate Demodex spp. The sebostatic effect of isotretinoin might explain the mechanism of action in the off-label treatment of rosacea. We anticipate our findings to be the basis of an accelerated research on our most complex commensal, its life, biology and physiology