Zusammenfassung Hintergrund und Zielsetzung Während Brentuximab vedotin (BV) oder Strahlentherapie (RTx) gängige Behandlungsoptionen für CD30‐positive kutane T‐Zell‐Lymphome (CTCL) sind, wurde über die Wirksamkeit und Verträglichkeit ihrer gleichzeitigen oder aufeinanderfolgenden Anwendung nur selten berichtet. In dieser retrospektiven Analyse haben wir daher die Kombination von BV und RTx bei CD30‐positiven CTCL‐Patienten untersucht. Patienten und Methodik Wir schlossen 14 CD30‐positive CTCL‐Patienten aus sechs deutschen Tumorzentren ein, die mit BV behandelt wurden; eine RTx wurde innerhalb eines Zeitraums von 3 Monaten vor und bis zu 3 Monaten nach der BV‐Behandlung durchgeführt. Die RTx wurde hauptsächlich als niedrig dosiertes Schema angewendet. Ergebnisse Unerwünschte Ereignisse jeden Schweregrades traten bei 71% der Patienten auf, darunter häufige Nebenwirkungen wie periphere Neuropathie, Neutropenie und Radiodermatitis. Dreizehn Patienten erreichten eine vollständige oder partielle Remission als bestes Gesamtansprechen, jedoch zeigten 50% aller Patienten ein Fortschreiten der Erkrankung. Bei einer medianen Nachbeobachtungszeit von 14,4 Monaten betrug das mediane progressionsfreie Überleben 12,0 Monate, mit einer 1‐Jahres‐Rate von 34,0%. Schlussfolgerungen Die simultane oder sequenzielle Therapie mit BV und RTx war machbar und wurde gut vertragen. Künftige randomisierte Untersuchungen sind erforderlich, um die Vorteile dieses kombinierten Behandlungskonzeptes sowie die angemessene Dosierung von BV und RTx prospektiv zu ermitteln.

RAS/RAF/MEK/ERK1/2 mitogen-activated protein kinase (MAPK) pathway-based treatments, typically combination therapies with inhibitors for oncogenic BRAF V600 (BRAFi) and MEK1/2 (MEKi), are important treatment alternatives to immunotherapy in advanced BRAF-mutated melanoma. However, their benefit is limited by frequent therapy resistance, i.e. persistence and progression/metastasis of tumor cells under sustained treatment. Furthermore, approximately 50% of the patients, including the NRAS-mutated subset, lack targetable BRAF oncogenes and profit poorly from MEKi. Recent preclinical studies suggest co-inhibition of the MEK5/ERK5 MAPK pathway, which in different MAPK-activated tumors is compensatorily activated by MEKi, as promising strategy to overcome therapy resistance and trigger apoptosis and/or sustained cell cycle arrest. In NRAS-mutant melanoma, compensatory ERK5 activation is accompanied by the induction of the Krüppel-like factors KLF2 and KLF4 but their role in MEKi resistance remains unclear. Using RNA interference and CRISPR/Cas9, we examined their contribution to MEKi resistance through RNA sequencing and functional assays. Surprisingly, KLF2 and KLF4 were dispensable for the proliferative and anti-apoptotic effects of compensatory ERK5 activation in MEKi-exposed melanoma. Instead, we identified AXL, a key receptor tyrosine kinase associated with metastasis and phenotypic switching, as critical ERK5/KLF4 target induced during MEKi resistance. Genetic loss of KLF4 or AXL depletion reduced melanoma cell migration and invasion, suggesting a key role of KLF4 in the regulation of invasiveness. Our study describes a novel ERK5/KLF4/AXL signaling axis that drives MEKi resistance and metastatic potential in NRAS-mutant melanoma and highlights this axis as a potential target to improve MAPK-directed and potentially immune therapies.

Psoriasis is a chronic inflammatory disease often accompanied by musculoskeletal symptoms and psoriatic arthritis (PsA). Early identification of PsA remains challenging, underscoring the need for interdisciplinary care between dermatology and rheumatology. To evaluate the diagnostic and therapeutic impact of an interdisciplinary dermatology-rheumatology board (IDRB) for patients with psoriasis, we initiated a non-randomized, prospective bicentric study. A total of 182 patients with psoriasis were enrolled at baseline (V0), of whom 111 completed the 12-month follow-up (V2). Forty-seven (25.8

Background:Lupus erythematosus (LE) is a chronic autoimmune disease that significantly impacts patients' quality of life. Photosensitivity is a key impairment that severely limits the quality of life, especially in cutaneous lupus erythematosus (CLE), where exposure to sunlight can lead to rashes, exacerbations, and pain. In systemic lupus erythematosus (SLE), other manifestations such as joint pain, fatigue, and organ damage may contribute to decreased physical function and emotional distress. Mobile health apps (MHA) offer potential support for comprehensive disease management for the symptoms mentioned above. However, there is a lack of systematic analysis of available lupus management apps. Objective:This study aims to systematically identify publicly available German or English MHA for lupus management as well as to assess their quality by surveying both patients and physicians. Methods:A systematic search and assessment of German or English mobile apps for patients with lupus, available in the Google Play Store and Apple App Store, was conducted independently by two reviewers. The two apps that met all relevant criteria were then reviewed independently by seven physicians using the German Mobile Application Rating Scale (MARS) and the System Usability Scale (SUS). Subsequently, they were reviewed by five patients (three with SLE and two with CLE), using the user version of MARS (uMARS) and SUS. Additionally, the Affinity for Technology Interaction (ATI) scale was collected from both patients and physicians to evaluate the technical affinity in both groups. Results:In total, 29 apps were available on the Apple Store and 26 on the Google Store, with 18 apps being present and downloadable on both platforms. Of the 18 apps, 16 were excluded because they did not meet the inclusion and exclusion criteria. Only two apps, Lupus Log and Lupus Minder met all the required criteria and were included in the study. The mean MARS scores varied from 2.61/5 to 4.17/5 and mean SUS from 17.5/100 to 100/100 between physicians. The app with the highest mean overall MARS score was Lupus Log, which was rated with 3.91/5 on average by the physicians. Patients evaluated the app with a comparably mean uMARS score (3.95/5). Technical affinity, objectified by ATI, was higher in patients than physicians (3.9 vs 3.68). Conclusions:Systematic identification and evaluation showed high-quality apps for patient-centered lupus MHA as indicated by MARS and uMARS scores greater than 3 for both Lupus Log and Lupus Minder.

DNA methylation provides a stable record of cellular identity, capturing epigenetic programs that distinguish specialized cell states despite a shared genome. Because malignant transformation and tumour progression are accompanied by extensive epigenetic remodeling, we hypothesized that the methylome of melanocytic lesions contains biologically and clinically relevant information for both diagnosis and disease progression. In a cohort of 1,001 tissue samples prospectively collected across eight German university hospitals profiled using Illumina Infinium MethylationEPIC arrays, we compared machine-learning models based on selected Cytosine phosphate Guanine (CpG) methylation sites with models incorporating biology-guided features, including epigenetic age acceleration, cell type composition and copy-number variation burden. In an external test set, the best diagnostic classifier was CpG-based and distinguished melanocytic nevi, noninvasive melanoma and invasive melanoma with a macro-averaged area under the receiver operating characteristic curve of 0.919 (95

Purpose:Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with significant unmet therapeutic needs. However, information on patient preferences for HS therapies is hitherto scarce. Our aim was to investigate the impact of treatment experience on patient preferences for pharmacological and surgical treatment of HS using conjoint analysis. Patients and Methods:Discrete choice experiments were applied for the attributes treatment modality (tablets, subcutaneous injections, surgery with secondary intention healing or primary closure), probability of sustained therapeutic success, probability of mild or severe adverse events, and duration of treatment or wound healing. These attributes were subsequently correlated with treatment experience. Results:Overall, 216 patients with HS considered therapeutic success as most important (Relative Importance Score (RIS):36.2), followed by the treatment modality (RIS:24.0). Patients experienced with biologics favoured subcutaneous injections most (PWU:18.1 vs. -0.5, p=0.020), whereas biologic-naïve patients preferred tablets. Patients who had undergone surgery with secondary intention healing valued this approach (PWU:4.1 vs. -24.8, p=0.004) and therapeutic success (RIS:37.5 vs. 31.6, p=0.017) higher and the duration of wound healing lower (RIS:18.9 vs. 23.3, p=0.037) than others. Conclusion:Individual preferences were depending significantly on treatment experience. Incorporation of this aspect could help to improve personalized care of patients with HS.

Background : Digital health monitoring delivered via smartphone applications and ecological momentary assessment (EMA) can capture high-frequency symptom trajectories in chronic inflammatory skin diseases, but real-world engagement and retention vary substantially across studies and can complicate inference. We pooled five prospective clinical trials to harmonize clinic visits, patient-reported outcomes (PROs), and smartphone app–derived EMA logs and to quantify engagement, retention, and clinical anchoring of EMA signals. Methods : We harmonized five prospective dermatology studies (psoriasis and chronic hand/foot eczema spanning from 2018 to 2025, including two randomized controlled trials and three non-randomized studies, conducted at University Hospital Würzburg and University Medical Center Mannheim, into a relational dataset with patient-, visit-, and EMA-level tables. All participants were provided access to the smartphone monitoring app; actual use was voluntary and quantified from timestamped logs. In the app-assigned cohort, baseline characteristics were summarized overall and by engagement group (no use vs any use). Early engagement was quantified as active days in the first 28 days after first activity and retention as time from first to last observed activity, summarized with Kaplan–Meier curves. EMA pruritus and pain trajectories were summarized weekly over 26 weeks and anchored to clinic symptom assessments at baseline and 6 months. Associations between early engagement and 6-month improvement were evaluated using adjusted models. Results : The harmonized baseline clinical dataset included 550 app-assigned participants (95.6% psoriasis). Baseline disease burden was moderate (median Dermatology Life Quality Index (DLQI) 6 [IQR (Interquartile range) 2–14]; median pruritus 2 [1–5]; median pain 1 [0–3]). Baseline characteristics were broadly comparable between engagement groups (no use n=211 vs any use n=339) with similar baseline PROs and symptoms. Engagement in the first 28 days was low and right-skewed (median 2 active days [1–4]), and retention showed early drop-off with heterogeneous retention across trials (retained 68.4% at day 28; 29.8% at day 182). Weekly EMA trajectories aligned with clinic anchors and separated by clinical response strata (ΔDLQI quintiles). Higher early engagement showed a graded association with greater adjusted 6-month improvement, with wider uncertainty at very high engagement. Conclusions: In a multi-trial pooled dermatology cohort, EMA symptom tracking was feasible and clinically interpretable when anchored to visit-based assessments, while engagement and retention varied substantially across studies. Harmonized, reproducible data structures integrating clinic-based assessments, PROs, and EMA logs can support effective trialing of digital interventions and enable robust quantification of engagement heterogeneity and between-visit symptom trajectories.

Perioperative immune-checkpoint inhibition (ICI) using pembrolizumab (3 doses of pembrolizumab 200 mg every 3 weeks before surgery and 15 doses afterwards) in advanced resectable melanoma has shown substantial pathological response rates and improved event-free survival (EFS) compared to postoperative (adjuvant) ICI. Real-world evidence on efficacy and safety of perioperative ICI in melanoma remains limited. In this retrospective single-centre study, 20 patients with resectable stage IIIB–IV melanoma were treated with perioperative pembrolizumab. Radiological and pathological responses, early survival outcomes and treatment-related adverse events were analysed at a median follow-up of 13.9 months. Eighteen patients (18/20) underwent surgery. A pathological complete response was observed in 44% (8/18), while 56% (10/18) showed a pathological non-response. No patient (0/18) had a pathological partial response. One-year EFS was 66.5% (95% confidence interval (CI) 47.3–93.3), 1-year relapse-free survival 77.6% (95% CI 57.9–100) and 1-year overall survival 89.2% (95% CI 76.0–100, identical with 1-year melanoma-specific survival). Immune-related adverse events occurred in 50% of the patients (≥grade 3 in 15%). Our study confirms the feasibility of perioperative pembrolizumab in a real-world setting and shows promising efficacy and tolerability in melanoma. Pathological response may guide surgical and adjuvant strategies.

Background Chronic spontaneous urticaria (CSU) is characterized by recurrent wheals or angioedema lasting for more than 6 weeks and substantially affecting the quality of life. Given its fluctuating course, accurate symptom monitoring is essential. Mobile health apps (MHAs) offer promising tools for real-time symptom tracking, patient education, and communication. Systematic evaluation of existing MHAs for CSU is critical to inform the development of effective, patient-centered digital solutions. Objective This study aimed to identify and evaluate publicly available MHAs for patients with CSU, assessing their quality, usability, and alignment with the needs of both patients and physicians to guide the development of future patient-centered apps. Methods A systematic search of app stores and the internet was conducted to identify MHAs for CSU. Inclusion required German or English language support and patient-centered content. Apps were excluded if they contained advertisements; lacked patient-centered content, designed to assist patients in the self-management and care of their condition; or were focused on clinical trials or health care professional use. After screening, 1 app, CRUSE Control, met all criteria and was evaluated by 23 physicians and 16 patients with CSU using the German versions of the Mobile Application Rating Scale (MARS and end-user version of MARS) and the mHealth App Usability Questionnaire. Participants’ technical affinity was assessed using the affinity for technology interaction scale and the Mobile Device Proficiency Questionnaire. Additionally, they completed a custom questionnaire on their personal needs and expectations for CSU-specific MHAs. Results Fifteen MHAs were identified, with 12 available on both platforms. Eleven apps were excluded due to lack of specificity to CSU (n=10) or not being patient-centered (n=1). One app, CRUSE Control, met all inclusion criteria and was selected for final evaluation. CRUSE Control received similar mean (SD) quality ratings from physicians (MARS 4.03, SD 0.45) and patients (end-user version of MARS: 4.06, SD 0.40; P=.83). Among the MARS subcategories, functionality was rated significantly higher by patients than by physicians (4.75, SD 0.41 vs 4.47, SD 0.55; P=.04). Usability, measured using the German mHealth App Usability Questionnaire (assessing effectiveness, efficiency, and satisfaction), showed no significant difference between physicians (5.85, SD 0.71) and patients (5.76, SD 0.41; P=.64). Technology affinity was comparable between groups, with physicians scoring 3.50 (SD 0.66) and patients 4.00 (SD 0.88) on the affinity for technology interaction (P=.05). Proficiency with mobile devices, assessed via the Mobile Device Proficiency Questionnaire, also showed similar results (physicians: 4.81, SD 0.26; patients: 4.74, SD 0.45; P=.60). Conclusions Few high-quality MHAs for CSU are currently available, and only 1 met the inclusion criteria. Patients and physicians rated the app highly, though patients placed greater emphasis on functionality. High technology affinity in both groups supports adoption. Patients prioritized features that facilitate disease management. Although limited to a single app, these findings suggest that MHAs may support CSU care.

Cutaneous lupus erythematosus (CLE) comprises a heterogeneous spectrum of autoimmune dermatoses. Four main forms are distinguished: acute (ACLE), subacute (SCLE), intermediate (ICLE), and chronic CLE (CCLE). Epidemiological studies show that the overall risk of developing systemic lupus erythematosus (SLE) is highest within the first 3 years following diagnosis of CLE. Therefore, patients with newly diagnosed CLE should be closely monitored for systemic symptoms, especially in the first few years following CLE diagnosis. Therapy of CLE includes both topical and systemic approaches. Treatment of SLE with organ and cutaneous manifestation should ideally be treated in close cooperation with an internal medicine rheumatologist. The overall therapeutic landscape of lupus erythematosus in increasingly moving toward personalized approaches.

Kutane periphere T‐Zell‐Lymphome (PTCL) sind selten und zeigen einen aggressiven Verlauf mit limitiertem Therapieansprechen. Die Wirksamkeit von Brentuximab‐Vedotin bei kutanen PTCL wurde bisher nicht systematisch untersucht. In dieser retrospektiven Datenanalyse evaluierten wir die Therapie mit Brentuximab‐Vedotin als Mono‐ oder Kombinationstherapie bei kutanen CD30‐positiven PTCL (n = 9). Insgesamt zeigten sich gutes Ansprechen und akzeptable Verträglichkeit der Therapie. Ein Patient erzielte eine nahezu komplette Remission, bei fünf Patienten wurde eine partielle Remission und bei zwei Patienten ein gemischtes Ansprechen als bestes Ansprechen ( best overall response , BOR) beobachtet. Im Median vergingen 31,5 Tage (Interquartilabstand 12–53) bis zum Therapieansprechen. Die mediane Ansprechdauer war mit 4,3 Monaten kurz; das mediane Gesamtüberleben seit Einleitung der Brentuximab‐Vedotin‐Therapie betrug 15,2 Monate. Vier von neun Patienten verstarben an ihrer fortgeschrittenen Lymphomerkrankung, ein Patient verstarb aus anderer Ursache. Brentuximab‐Vedotin als Mono‐ oder Kombinationstherapie ist bei Patienten mit kutanem peripheren T‐Zell‐Lymphom eine rasch wirksame und verträgliche Therapieoption bei allerdings nur kurzer Ansprechdauer.

The immunosuppressive and immunomodulatory treatment of dermatological patients necessitates the regular review and updating of standard vaccinations and vaccines indicated for specific conditions. The German Standing Committee on Vaccination (STIKO) at the Robert Koch Institute regularly publishes evidence-based vaccination recommendations, which are adapted to the current epidemiological situation and availability of vaccines. Since 2020, several changes have been made that are relevant for patients with dermato(onco)logical diseases: (1) COVID-19 was defined as a new viral disease and several vaccines have been introduced; (2) in response to the global Mpox outbreak in 2022, a non-replicating live vaccine based on the modified Ankara vaccinia virus, which was approved in 2013 for the prevention of smallpox, was given an indication extension; (3) a new inactivated high-dose vaccine was approved for influenza vaccination of persons aged 60 years and older; (4) a new 20-valent conjugate vaccine is available for pneumococcal vaccination; (5) two recombinant vaccines against the respiratory syncytial virus (RSV) were recently approved. This article discusses the correspondingly adapted STIKO recommendations for adults, with particular emphasis on their implementation in immunocompromised patients in dermatology.

Der extramammäre Morbus Paget (EMP) ist ein seltenes, langsam wachsendes kutanes Adenokarzinom mit einer Inzidenz von 0,1–2,4 pro 1.000.000 Einwohner. Histomorphologisch sind typische Paget-Zellen zu erkennen, und es werden zwei pathogenetisch und prognostisch unterschiedliche Formen unterschieden: die primäre Form, die als Carcinoma in situ der apokrinen Schweißdrüsen klassifiziert wird, und die sekundäre Form, die durch die intraepitheliale Ausbreitung assoziierter apokrin differenzierter maligner Tumoren gekennzeichnet ist. Der EMP tritt vorwiegend bei Patienten im Alter von 50 bis 80 Jahren auf, wobei europäische Frauen und asiatische Männer am häufigsten betroffen sind. Sehr oft entsteht der EMP im Bereich der anogenitalen Region und seltener in den Axillen. Die Diagnose und Behandlung des EMP sind herausfordernd, da die Symptome oft zunächst unspezifisch sind und chronisch-entzündlichen Dermatosen ähneln, was zu Verzögerungen bei der Diagnosestellung führen kann. Die mikrographisch kontrollierte Exzision ist die bevorzugte Therapie für den primären EMP, jedoch bleibt die Rezidivrate mit bis zu 40

We present the case of a 22-year-old male who was first diagnosed with chronic recurrent multifocal osteomyelitis (CRMO) at the age of 16 years. During treatment with the tumor necrosis factor (TNF)-alpha inhibitor adalimumab, he developed severe palmoplantar psoriasis that affected his quality of life and necessitated discontinuation of the drug despite its efficacy against CRMO. Subsequent treatment with the interleukin (IL)-17a inhibitor secukinumab did not improve the psoriasis and led to a recurrence of the osteomyelitis. Therefore, the TYK-2 inhibitor deucravacitinib, approved in 2023 for the treatment of moderate to severe plaque psoriasis, was initiated. This resulted in clinical and morphological complete and sustained remission of CRMO within 12 weeks and a significant improvement of the psoriasis after six months of treatment with no occurrence of severe adverse events. To our knowledge, this is the first case report demonstrating complete and safe remission of CRMO associated with palmoplantar psoriasis treated with the TYK2 inhibitor deucravacitinib.