Background/Objectives: A "misnomer" is a term that is erroneous or inaccurate. Dermatology is replete with well-established misnomers such as "Mycosis fungoides", "keratoacanthoma", "actinomycosis", "granuloma pyogenicum", or "Kaposi sarcoma". Misnomers have originated from misconceptions or mistranslations that were passed down historically, and reflect the comparative-descriptive origin of terminology. We aimed to collect and categorize (non-)dermatological misnomers and to assess strategies for abandoning them. Methods: A questionnaire-based survey with 411 senior academic physicians of five university hospitals in Switzerland was conducted to evaluate the frequency of misnomers across dermatology and other specialties. In addition, a systematic review was conducted, complemented by manual searches to collect medical misnomers. Results: The survey and systematic review yielded 536 non-dermatological and 168 dermatological misnomers, pointing to a particular abundance of misnomers in dermatology, which could be categorized into seven categories. A wrong pathological concept was the most common origin of misnomers. Amongst dermatologists, 60.0% regarded misnomers as a relevant problem in their specialty compared to only 35.5% of non-dermatologists. Preferred strategies for abandoning misnomers were avoidance, consensus definitions, and information in teaching. Conclusions: Our results show that misnomers are particularly abundant in dermatology, indicating the need to modernize terminology.
Chronic spontaneous urticaria (CSU) substantially reduces patients' quality of life (QoL); therefore, it is crucial to include QoL-related patient-reported outcome measures when assessing treatment efficacy. To evaluate the impact of remibrutinib, an oral, highly selective Bruton's tyrosine kinase inhibitor, on disease control, sleep, and QoL in CSU. REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) were phase 3, double-blind, placebo-controlled studies in adults with CSU who remained symptomatic despite receiving second-generation H1-antihistamines. Patients were randomized 2:1 to oral remibrutinib 25 mg twice daily or placebo (24 weeks), followed by an open-label treatment period (28 weeks), and a treatment-free follow-up period (4 weeks); those on placebo transitioned to remibrutinib at week 24. Patients completed patient-reported outcome measures, including the Weekly Urticaria Control Test, Weekly Urticaria Activity Score, Weekly Sleep/Activity Interference Score, Dermatology Life Quality Index, EQ-5D-5L (EuroQol-5 dimensions-5 levels), and Work, Productivity, and Activity Impairment. The pooled analysis included 606 and 306 patients receiving remibrutinib and placebo, respectively. Within 1 week of starting remibrutinib, greater improvements in mean (SD) change from baseline (CFB) compared with placebo were noted in urticaria activity (CFB-Urticaria Activity Score: -11.8 [9.9] and -3.6 [7.6]) and sleep (CFB-Sleep Interference Score: -4.9 [4.9] and -1.9 [4.1]). Improvements with remibrutinib were also observed in Urticaria Control Test, Activity Interference Score, Dermatology Life Quality Index, EQ-5D-5L, and Work, Productivity, and Activity Impairment at the earliest time points collected. Across assessments, responses were sustained through week 52 with remibrutinib, and comparable improvements were observed in those who transitioned to remibrutinib. Remibrutinib exhibited fast improvements in disease control, sleep, and QoL in REMIX-1 and REMIX-2, supporting remibrutinib as a valuable therapeutic option for CSU. ClinicalTrials.gov identifiers: NCT05030311 (REMIX-1) and NCT05032157 (REMIX-2).
Inflammatory skin diseases and ocular disorders frequently coexist due to shared embryological origins, overlapping immune pathways, and common barrier functions. The increasing use of targeted systemic therapies in dermatology has further highlighted the skin-eye interface, introducing both therapeutic benefits and iatrogenic ocular complications. This review outlines the shared embryological and immunological mechanisms linking the skin and ocular surface, with emphasis on major inflammatory pathways, including TNF-α, Th17, and JAK-STAT signaling. We summarize the prevalence and spectrum of ocular involvement across common inflammatory skin diseases such as psoriasis, atopic dermatitis, rosacea, pemphigus vulgaris, and ocular mucous membrane pemphigoid. In addition, we evaluate ocular adverse effects associated with commonly used dermatologic therapies, highlighting the emerging phenomenon of iatrogenic and paradoxical inflammation. Ocular manifestations arising from both disease-associated and iatrogenic etiologies remain underrecognized in clinical practice. Early recognition, interdisciplinary collaboration, and risk-adapted strategies, including care accessibility and patient education, are essential to prevent vision-threatening complications. A shift from reactive care to proactive, risk-stratified screening based on individual patient risk profiles can improve clinical outcomes across the skin-eye axis.
In patients with moderate atopic dermatitis (AD), topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI) often do not sufficiently control AD signs/symptoms, and escalation to systemic therapy may be required. Report 8-week results of ruxolitinib cream in TRuE-AD4 (NCT06238817) in patients with moderate AD who had an inadequate response/intolerance/contraindication to TCS and TCI in the past 12 months (post-TCS and -TCI). Patients aged ≥18 years with AD, an Investigator's Global Assessment (IGA) of 3, Eczema Area and Severity Index (EASI) >7, itch numerical rating scale (NRS) ≥4, 10%-20% affected body surface area and Dermatology Life Quality Index score > 10 post-TCS and -TCI were randomized (2:1) to twice-daily 1.5% ruxolitinib cream or vehicle for 8 weeks. Coprimary endpoints at Week 8 were ≥75% improvement in EASI from baseline (EASI-75) and IGA score of 0/1 with a ≥ 2-point improvement from baseline (IGA treatment success [TS]). Of 241 randomized patients (mean age, 37.0 y; 54.4% female), mean EASI and itch NRS scores were 12.6 and 7.4, respectively, at baseline. At Week 8, significantly more patients who applied 1.5% ruxolitinib cream versus vehicle achieved IGA-TS (61.3% vs. 13.6%; p < 0.0001) and EASI-75 (70.0% vs. 18.5%; p < 0.0001). Significantly more patients achieved a ≥ 4-point improvement in itch NRS (itch NRS4) at Day 2 (29.8% vs. 13.7%; p = 0.0072); improvement in current itch (no recall) was observed in 15 min after the first application. No treatment-related adverse events were serious, and the most common adverse event occurring with ruxolitinib cream was application site acne (3.8%). In adults with moderate AD post-TCS and -TCI, who may otherwise be eligible for systemic therapy, 1.5% ruxolitinib cream significantly improved clinical signs of AD, rapidly improved itch and was well tolerated. Thus, ruxolitinib cream may represent an effective topical option before escalation to systemic therapy in patients with moderate AD. Atopic dermatitis (AD), also known as eczema, generally consists of red (inflamed), dry and itchy skin that affects about 2%–10% of adults worldwide. Patients with AD of moderate severity are usually treated with topical corticosteroid (TCS) and topical calcineurin inhibitor (TCI) creams/ointments. If these medicines are not effective, systemic treatments taken by mouth or injected are usually required. We investigated whether ruxolitinib cream is effective and safe in patients with moderate AD after failure of TCS and TCI. A total of 241 adults were recruited in Europe and North America and were asked to apply either ruxolitinib cream or nonmedicated comparator cream 2 times per day for 8 weeks. We found that patients who applied ruxolitinib cream experienced greater reductions in skin inflammation and itch than those who applied nonmedicated comparator cream over the first 8 weeks of treatment. Inflammation was reduced as early as 2 weeks (the first measurement), and itch was reduced 15 min after starting treatment. The most common side effect related to ruxolitinib cream was acne on the areas of skin where ruxolitinib cream was applied (3.8% of patients). No side effects considered related to ruxolitinib cream were serious. These study findings show that ruxolitinib cream is both effective and well‐tolerated in patients with moderate AD after failure of TCS and TCI. Therefore, ruxolitinib cream may be an alternative treatment option for patients before starting systemic treatments.
Tinea infections pose a significant therapeutic challenge in many African countries, exacerbated by limited diagnostic resources and increasing antifungal resistance. This survey aimed to evaluate treatment difficulties, laboratory access, and antifungal use patterns among healthcare providers across ten African countries. A survey was performed during the Continuing Medical Education (CME) meeting at the Regional Dermatology Training Centre (RDTC), Moshi, on 8th January 2025. The collected data included information on clinical response to antifungal treatment, access to laboratory diagnostics, antifungal agents used, and affected body sites. Descriptive analysis and cross-tabulations were performed to identify key trends. The response rate was 92.6%. Treatment difficulties were reported by 95.1% of respondents, more than half of those surveyed (54.3%) lacked access to laboratory services necessary for accurate diagnosis. Empirical use of multiple antifungal medications was common (77.2%), particularly in cases involving more than one body site (62%). This survey highlights critical gaps in the diagnosis and management of tinea infections across African countries, also this gap has been observed in the survey for lab access for dermatologists in Sub Saharan Africa.
Systemic treatment decisions for psoriasis are often initiated and guided depending on the severity of the disease, determined by the validated Psoriasis Area and Severity Index (PASI). Therefore, accurate evaluation of disease severity is crucial. However, exact and reproducible PASI assessment requires training. A virtual reality (VR)-PASI program could improve empowerment of healthcare providers and grading accuracy. The aim of this study was to compare the effectiveness of a VR-PASI training program to standard PASI teaching. In a randomised prospective trial, a classical lecture and a VR program were compared in 70 medical students (study participants) without previous knowledge and training in skin assessment. Effectiveness of training was measured by determining a PASI score in real patients and comparing the results to those of a trained assessor. Furthermore, the rating of quality and satisfaction of both training methods was measured in both educational groups. Both groups were equally interested in dermatology, all study participants had little to no experience with PASI, and both groups had similarly little to no experience in dealing with VR. VR-trained PASI raters achieved better results assessing correct PASI severity compared to those trained via classical lecture (U = 397.5, p = 0.011). The effect size, calculated using Rosenthal's method, was R = 0.302 (moderate effect). Median difference of PASI score was 1.5 (95% confidence interval [CI]: 0.3-2.4). Median difference scores of classical lecture group (PASI Δ: 2.7) was less accurate than in VR group (PASI Δ: 1.1), indicating a potentially clinically relevant effect for median difference (1.5 (95% CI: 0.3-2.4). VR group showed higher accuracy in the application of the PASI and reported both higher satisfaction with the learning unit and a better experience in implementing the teaching method. In untrained raters, PASI training via the VR program led to higher accuracy in severity assessment compared to a classical lecture.
Epithelial barrier disruption is a hallmark of allergic skin diseases. Sodium dodecyl sulfate (SDS), a surfactant in household cleaning products, is known to impair the barrier. We used a physiologically relevant ex vivo human skin combined with real-time electrical impedance spectroscopy (EIS) to monitor barrier integrity after SDS exposure. Multi-omics analyses, including RNA sequencing and proximity extension-based proteomics, characterized molecular responses. Barrier permeability and oxidative stress were evaluated in primary keratinocytes, and the protective effects of N-acetylcysteine (NAC) and nicotinamide (NAM) were assessed in both air-liquid interface keratinocyte cultures and ex vivo skins. Even a 1-min SDS exposure caused a rapid EIS decline, indicating immediate barrier compromise. 5-min exposures produced dose-dependent EIS decline with broad suppression of barrier and immune mediators (e.g., CXCL11, MCP4, and HNMT), 6-h exposure sustained skin barrier loss and associated inflammatory and remodeling programs. Proteomic signatures highlighted AREG, JUN, and ITGA6 can track skin damage, while CST5 and PRDX1 correlated with the preservation. Transcriptomics corroborated these changes, showing up-regulation of stress and repair programs-endoplasmic reticulum stress, oxidative stress, sphingolipid biosynthesis, and epidermal differentiation pathways. NAC/NAM reduced SDS-induced reactive oxygen species, cytotoxicity, and permeability in primary keratinocytes, and restored EIS values in ex vivo skin. Short-term SDS exposure rapidly disrupts human skin barrier integrity through oxidative stress-driven suppression of structural/immune mediators and activation of stress/remodeling pathways. NAC and NAM effectively mitigated damages, highlighting antioxidants as preventive interventions for surfactant-induced skin barrier dysfunction.
Mpox, caused by the monkeypox virus, emerged as a global public health concern following the 2022 outbreaks in non-endemic regions. Although classical presentations include a febrile prodrome and mucocutaneous lesions, atypical symptoms and stigma have complicated clinical recognition and containment. Smallpox-derived vaccines, such as ACAM2000 and modified vaccinia Ankara, have been deployed for prophylaxis; however, access, policy implementation, and public acceptance remain inconsistent across regions. Global mpox vaccination strategies demonstrate pronounced disparities in coverage, infrastructure, and public trust. High-income countries, including the United States and European nations, prioritized men who have sex with men, transgender individuals, and people living with HIV through targeted outreach in sexual health clinics and community-based programs. In contrast, many South-East Asian and African nations lacked coordinated vaccination campaigns due to limited resources, weak surveillance systems, and low awareness. Misinformation and sociocultural stigma further suppressed vaccine uptake, particularly in parts of the Eastern Mediterranean region. In settings such as Taiwan and the Netherlands, inclusive public health messaging and equitable access policies contributed to higher vaccination coverage. Healthcare worker knowledge significantly influenced vaccine delivery, though educational gaps persist. Despite demonstrated efficacy, vaccination coverage remains globally inequitable, with disparities shaped by structural and social determinants, including race, socioeconomic status, and geography. Dermatologists play a pivotal role in early detection, patient counseling, and vaccine advocacy. Strengthening coordinated, evidence-based vaccination strategies is essential to improving outbreak preparedness and advancing global health equity.
Epidermal growth factor receptor inhibitors (EGFRIs) are targeted therapies for solid cancers. Their use is associated with cutaneous adverse events (cAEs). This study aimed to investigate cAEs and changes in skin biophysics reflecting the skin barrier function, alterations in antimicrobial peptides (AMPs), and the skin microbiome in patients undergoing treatment with EGFRIs. A 2-year prospective cohort study was conducted involving patients receiving EGFRIs for solid cancers. cAEs and skin biophysical properties, including transepidermal water loss (TEWL), skin pH, elasticity, sebum, and pigmentation, were measured at baseline and follow-up visits up to 48 weeks. AMPs were assessed using a tape-stripping technique from the cheeks at months 0, 1, and 6, with protein assays and ELISA to determine the levels of human beta-defensin (hBD)-3 and ribonuclease (RNase)-7. Skin microbiome analysis was performed through 16S rRNA sequencing of cheek swabs collected at months 0, 1, and 6. Eighty-four patients were enrolled. The cumulative incidence of cAEs was 94.05%. Skin biophysical properties showed significantly increased TEWL and pH, decreased pigmentation, and no significant changes in elasticity and sebum. AMP analysis from 15 patients revealed significant reduction of RNase-7 levels after 6 months into EGFRIs, while hBD-3 level change was insignificant. A microbiome study from 18 patients showed statistically increased Corynebacterium kroppenstedtii at months 1 and 6, while Cutibacterium acnes, Corynebacterium aurimucosum, Staphylococcus epidermidis, and Staphylococcus aureus were not significantly different among groups. Treatment with EGFRIs compromises skin barrier function and AMP production, leading to skin microbiota changes.
Darier disease (DD) is a rare autosomal dominant genodermatosis. This comprehensive review, developed by the Darier Disease International Task Force (DDITF), consolidates current knowledge on the genetic basis, molecular pathophysiology, clinical presentation, diagnosis and management of DD, offering a global perspective that unites shared expertise. The disease arises from pathogenic variants in the ATP2A2 gene, which encodes sarco/endoplasmic reticulum Ca2+-ATPase isoform 2 (SERCA2), leading to disrupted calcium homeostasis and impaired desmosomal integrity. Clinically, DD is classified based on lesion type (classic vs. non-classic) and is often accompanied by significant extracutaneous manifestations. Management remains challenging and requires a multifaceted approach, including topical therapies, systemic retinoids and lifestyle modifications. Emerging treatments that target the underlying molecular mechanisms offer promise for improved outcomes. This review aims to provide an updated reference and practical guidance for clinicians involved in the care and study of DD.
Psoriasis is a common chronic inflammatory skin disease characterized by recurrent flares at previously affected locations. Although biologics targeting IL-17 or IL-23 effectively suppress active disease, they rarely result in long-term remission, suggesting that clinically resolved skin retains molecular changes predisposing to relapse. The STEPIn main study indicated that early intervention with secukinumab, an anti-IL-17A monoclonal antibody, may modify the course of psoriasis. This mechanistic substudy sought to define cellular and molecular changes in psoriatic skin lesions during treatment. Psoriatic skin was sampled at baseline and at up to 52 weeks of secukinumab treatment in new-onset (≤1 year) and long-standing (≥5 years) cohorts. Biopsy samples were evaluated histologically by immune profiling, global gene expression, and genome-wide DNA CpG methylation analyses. Treatment with secukinumab resulted in marked molecular differences between new-onset and long-standing psoriasis despite similar clinical improvement. Gene expression normalized faster in new-onset disease but ultimately resolved in both cohorts. In contrast, disease-associated CpG methylation detected at baseline persisted despite treatment, but only in long-standing psoriasis. Baseline methylation differences were enriched for AP-1 transcription factor binding sites in long-standing disease and persistent methylation changes mapped to genes enriched for small GTPase pathways. Notably, AP-1 components were found to amplify IL-17A and TNF-α responses in keratinocytes, and a subset of these persistent methylation sites overlapped with accessible chromatin regions in psoriatic keratinocytes. Early secukinumab intervention may prevent formation of an epigenetic scar that persists in long-standing psoriasis even after clinical resolution. NCT03020199.
Introduction Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a T cell mediated severe cutaneous adverse reaction (SCAR) to drugs. Due to its rarity, there are currently only a few studies which include a larger number of cases. We sought to analyze a larger number of DRESS cases to increase knowledge of clinical symptoms, causative agents, and potentially associated factors. Methods This is a non-interventional, retrospective, pharmacoepidemiological study analyzing descriptively DRESS reports in the EudraVigilance ADR database (EV) and DRESS cases in the registry of dZh/RegiSCAR. The two databases were analyzed separately, and the results were compared thereafter to identify both similarities and differences. Results 48 cases from EV and 84 registry cases were included for the in-depth analysis. The liver was the most frequently involved inner organ. Most of the reactions occurred within six weeks after initiating the suspected inducing agent. The percentage of cases with fatal outcome was similar in both datasets (EV: 4.2%, RegiSCAR: 3.6%). Antiseizure drugs - especially carbamazepine - were most frequently involved in both datasets. In 4 reports from EV and 5 cases from RegiSCAR sulfasalazine was identified as causative agent. Remarkably, all patients with sulfasalazine induced DRESS were females with arthritic disease who were clearly younger compared to patients of the whole dataset. Conclusion Our study confirms results obtained from other studies regarding the frequent involvement of the liver, the time to onset and DRESS-inducing drugs. Further studies are needed to investigate whether younger female with arthritic disease may carry a higher risk to develop DRESS or whether other factors might be responsible for this observation.
Lupus panniculitis (LP) is a neglected, often treatment-refractory subtype of cutaneous lupus erythematosus. It is characterized by inflammation of subcutaneous adipose tissue, and the pathomechanisms are poorly understood. We sought to explore the cellular and molecular signatures of LP and their relationship to systemic lupus erythematosus. We performed imaging mass cytometry (IMC; LP n = 8, Healthy Control (HC) n = 6) and targeted transcript profiling by NanoString nCounter (Human Immunology Panel, 579 genes; LP n = 9, HC n = 9). LP lesions showed extensive septal leukocyte infiltration. The infiltrate consisted predominantly of T cells (48%), followed by B cells (14%) and antigen-presenting cells (APCs). T cells exhibited a cytotoxic (CD8+, GranzymeB+) and skin-homing (CLA+) phenotype, with upregulation of Th1 markers. They closely interacted with M1 macrophages. B cells displayed strong spatial interactions with naïve T cells. NanoString analyses revealed upregulation of T- and B-cell receptor signaling pathway genes, antigen presentation-related genes (MHC-I/II), and Th1 associated programs (STAT1/IRF1), together with activation of innate immune, complement, and pattern-recognition receptor pathways. This was paralleled by strong upregulation of IDO1, a key enzyme in tryptophan metabolism, and inversely correlated, reduced AHR expression. Our data provide new pathomechanistic insights into LP, highlighting overlaps with systemic lupus, but also LP-specific features. This may pave the way for adopting more targeted treatment approaches for LP.
Background/Objectives: There is limited data on treatment outcomes under immune checkpoint inhibitor (ICI) administration in solid organ transplant recipients (sOTRs). This study aims to evaluate cancer outcome and allograft rejection risk in sOTRs receiving ICI. Methods: This is a retrospective multicenter study. The data had been collected within the Swiss Transplant Cohort Study (STCS) database. We searched for matching individuals from May 2008 up to the end of 2024. The primary outcomes were treatment response and survival; the secondary outcome was allograft rejection. Additional analyses included associated factors such as tumor, transplant, and treatment characteristics. Results: We identified ten patients, six of whom received a kidney allograft, while the remaining four received a liver, lung, pancreas, or combined kidney-pancreas transplant. Treatment response was achieved in half of the sOTRs, with a complete response (CR) in three and prolonged stable disease (SD) in two patients. CR was achieved in all three patients after only a few infusions. At the time of data analysis, four out of ten patients were still alive. Graft rejection occurred in six out of ten cases, five of which occurred after the first cycle of ICI administration. Conclusions: Data is limited and definitive conclusions from this study cannot be drawn given the limited sample size. However, ICI displays promising effects on cancer outcomes in sOTRs with advanced malignancies. The study's findings demonstrate an overall response in half of sOTRs, but with graft rejection occurring in a similar number of patients. We propose initiating immunotherapy as early as possible, given the promising results, particularly in patients with kidney transplants. We further suggest that in sOTRs, a few ICI infusions could potentially be a cautious option, pending further evidence.
Tumor-resident (TR) T cells, known as tissue-resident memory (TRM) T cells in mice, play a central role in melanoma immunosurveillance, yet their contribution to immune checkpoint inhibitor (ICI) therapy has not been comprehensively explored. We performed spatial and single-cell profiling on 32 metastatic melanoma lymph node samples, from treatment-naïve, ICI-resistant and ICI-responsive patients. Here we show that tumor areas in ICI-responders were enriched for both CD8+ and CD4+ TR. CD8+ TR cells were clonally expanded, and both CD8+ and CD4+ TR cells upregulated cytotoxicity-related gene expression, suggesting functional anti-tumor immunity. Conversely, ICI-resistant tumors displayed chronic IFN-γ response pathways, linked to T cell exhaustion. We further identified a spatially organized immune triad composed of CD8⁺ TR, CD4⁺ TR, and type-3 dendritic cells (DC3) that is exclusive to responding tumors. These findings define coordinated cellular interactions within the tumor microenvironment that underpin successful immunotherapy and provide a framework for spatial biomarkers of response.
Chronic spontaneous urticaria (CSU), characterized by recurring itchy wheals (hives) and/or angioedema lasting > 6 weeks without identifiable triggers, affects 1.29% of China's population. China ranks second globally in urticaria disability-adjusted life years (DALYs), thus understanding real-world outcomes is important. We hypothesized that, despite ongoing treatment, a substantial proportion of Chinese patients with CSU experience inadequate disease control and impaired quality of life (QoL), with gaps between their treatment expectations and perceived achievability of optimal control. This study assessed patient-reported burden, treatment patterns, and unmet needs in these patients. This was a cross-sectional study using 40-min online surveys. Patients were recruited through online panels. Eligibility included adults ≥ 18 years with physician-confirmed CSU diagnosis, actively treated. Descriptive analysis was stratified by disease control and treatment type. A total of 400 patients with CSU (mean age 35.09, [SD 7.24] years; 45% female) participated; 2% reported symptom onset < 1 year pre-study, 71% between 1 and 5 years, and 27% > 5 years (mean disease duration 5.31 [SD 4.89]). On the basis of the Urticaria Control Test (UCT), 35% of participants had inadequately controlled disease (UCT < 12), whereas Patient Global Impression of Severity (PGI-S) self-assessment suggested better perceived control (92% mild/no symptoms). Most diagnoses were made by dermatologists (94%); 57% of patients reported no fixed follow‑up schedule. Among inadequately controlled patients, 90% reported sleep disturbance during exacerbations. Most patients (82%) used second-generation antihistamines; one-third used Traditional Chinese Medicine. Complete symptom control was the top treatment goal (mean importance: 8.5/10), yet only 16% believed it achievable (9% of inadequately controlled). One-third of treated patients with CSU reported inadequate disease control impacting QoL. The disconnect between high priority for complete control and low perceived achievability, alongside irregular follow-ups, highlights limitations in current therapies and care delivery. These findings underscore the need for more effective treatments and structured, patient-centered management pathways to optimize CSU care in China.
Autoimmune bullous diseases (AIBDs), comprising pemphigoid and pemphigus diseases, have seen limited therapeutic advances beyond rituximab for pemphigus vulgaris. As novel therapies are evaluated in clinical trials, well-defined, uniform, and relevant outcomes with patient involvement are essential. To date, however, patient-reported outcomes remain underrepresented, leaving uncertainty about whether trial results genuinely reflect patients' expectations. This study examines perspectives of patients with AIBD on treatment outcomes and priorities to ensure that future research focuses on what matters most to them. A cross-sectional study was conducted among Dutch patients with AIBD between October 2023 and January 2024, using a self-developed questionnaire with both closed- and open-ended questions to assess patient perspectives on treatment outcomes and priorities, key factors in choosing a treatment, and indicators of treatment success. Regarding skin and/or mucous membrane complaints, "the formation of new blisters and wounds" emerged as the most important complaint a treatment should address for both pemphigoid (43%) and pemphigus (86%) patients. In open-ended questions, patients with pemphigoid most frequently prioritized "pruritus" (44%), while patients with pemphigus emphasized "pain" (39%). Most important concerns regarding physical and daily functioning were "vision problems" (20%), "sleep disturbances" (20%), and "self-care difficulties" (23%) for patients with pemphigoid, whereas patients with pemphigus most commonly cited "eating and/or swallowing difficulties" (57%) and "daily activity limitations" (41%). Regarding emotional/psychological functioning, both subgroups prioritized "anxiety and/or worry" as most important concern (pemphigoid: 28%, pemphigus: 43%). Side effects were identified as the most important factor in choosing a treatment (pemphigoid: 41%, pemphigus: 39%). The absence of one or more symptoms and clinical signs (i.e., "no blisters") was mentioned as the most important indicator of treatment success (pemphigoid: 88%, pemphigus: 91%), although minimal clinical signs (i.e., "minimal blisters") were also considered acceptable (pemphigoid: 25%, pemphigus: 13%). Patients with pemphigoid and pemphigus exhibit some distinct treatment priorities, reflecting their distinct pathomechanisms. Nonetheless, both subgroups consistently prioritize not only the resolution of disease-specific clinical signs but also preservation of physical and psychological well-being, underscoring the need for more holistic and patient-centered outcome measurement to ensure the establishment of meaningful, AIBD subgroup specific treatment outcomes.
Eczematized psoriasis is a clinical variant of psoriasis characterized by overlapping features of both psoriasis and eczema. Deucravacitinib is the first oral JAK inhibitor approved for the treatment of moderate to severe plaque psoriasis. The aim of this study was to investigate and compare the efficacy of deucravacitinib in patients with classical and eczematized psoriasis in real world. Patients with psoriasis who received deucravacitinib therapy in the dermatology department of two German University Medical Centers between 03/2023 and 03/2025 were included in this retrospective study. Treatment outcomes and drug survival of deucravacitinib was assessed with Ka¬plan-Meier analysis. A total of 38 patients were identified (19 with classical psoriasis, and 19 with eczematized psoriasis). Median drug survival of deucravacitinib was numerically higher in classical compared to eczematized psoriasis (21.0 vs. 6.0 months, p = 0.056). Partial or excellent response was more frequently observed in patients with classical psoriasis (68.4% vs. 47.4%). Relapses during treatment occurred significantly more frequently in eczematized than in classic psoriasis (57.9% vs. 26.3%, p = 0.033). The presence of an eczematous component in patients with psoriasis could adversely affect the treatment response to deucravacitinib and should be further investigated.
Peripheral nerves are emerging regulators of the tumor microenvironment, but how sensory innervation shapes breast cancer immunity remains poorly defined. Here we show that triple-negative breast cancers (TNBCs) co-opt nociceptor neurons to suppress antitumor immunity and promote disease progression. Across orthotopic TNBC models, we found that primary tumors and tumor-draining lymph nodes were densely innervated by CGRP+ sensory fibers. Tumor-derived cues directly activated dorsal root ganglion neurons, increased calcium responsiveness, induced Ngfr and Atf3, and triggered release of CGRP and substance P. Mechanistically, a tumor-derived proNGF-NGFR axis reprogrammed nociceptors and promoted neuropeptide secretion. Soluble mediators from activated nociceptors suppressed CD8+ T cell-mediated tumor-cell killing, whereas sensory-neuron silencing or ablation curtailed tumor growth and remodeled the immune microenvironment toward dendritic-cell activation, myeloid reprogramming, and enhanced CD8+ T cell and NK-cell effector states. Subset-specific analysis revealed nonredundant sensory control of immune states, with MrgD+ neurons selectively shaping macrophage-centered programs. Finally, blockade of CGRP signaling through RAMP1 reduced tumor growth and markedly enhanced PD-1 blockade, nearly eliminating primary tumor burden and lung metastasis in vivo. T cell-specific Ramp1 deletion similarly restrained tumor growth, and RAMP1+ CD8+ T cells in human TNBC displayed an exhaustion-associated phenotype. Together, these findings define a tumor-promoting proNGF-nociceptor-CGRP-RAMP1 axis and identify neuroimmune signaling as a therapeutically actionable vulnerability in TNBC.