This evidence- and consensus-based guideline for the treatment of acne was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. This guideline is an update of the 2016 version. This is a short summary of the full version of the EuroGuiDerm Evidence-based Guideline for the Treatment of Acne. For the complete guideline text, detailed methods report, and comprehensive evidence report, please refer to the online full version. In this targeted update, the guideline group prioritized three key clinical questions considered most relevant for current practice: (a) For which types of acne and patient groups should isotretinoin be recommended versus systemic antibiotics, and with what strength of recommendation? (b) What is the appropriate duration for systemic antibiotic therapy? For which types of acne and patient groups should hormonal treatments and spironolactone be recommended, and with what strength of recommendation? For which types of acne and patient groups should new topical treatments, including trifarotene and clascoterone, be recommended and with what strength of recommendation? Additionally, the updated guideline provides revised recommendations regarding: safety of benzoyl peroxide (BPO), selection of systemic antibiotic therapy, treatment considerations during pregnancy, isotretinoin dosing strategies, and the use of hormonal antiandrogenic contraceptives or other combined hormonal contraceptives, as well as spironolactone. All other aspects remain unchanged from the 2016 guideline.

INTRODUCTION:Dupilumab, a standard treatment for atopic dermatitis (AD), has been associated with cutaneous T-cell lymphomas (CTCL), particularly mycosis fungoides (MF) and Sézary syndrome (SS). Nevertheless, the available data remain heterogeneous. OBJECTIVES:To characterize the clinical features, timeline and outcomes of dupilumab-related CTCL emergence in order to develop consensus-based recommendations for dupilumab use in CTCL-related settings. METHODS:A systematic review was conducted involving 51 studies reporting cases of CTCL in patients treated with dupilumab, followed by a modified delphi process to generate expert consensus recommendations. RESULTS:Data were obtained from 547 patients (mean age: 58 years; SD: 11.5; range: 10-85). New or worsening skin lesions were reported after dupilumab initiation, occurring at a mean of 8.9 months (SD 5.1; range 0.5-27 months). These were diagnosed as MF in 72% of cases, SS in 11% and other CTCL subtypes in 19%, of which 53% were at an early stage (stage ≤IIA). Dupilumab was discontinued in 75% of cases, and 62% received CTCL-directed treatment. Clinical remission was achieved in 44 of the 63 patients with available follow-up. The expert panel reached broad consensus, agreeing that dupilumab may unmask or exacerbate pre-existing CTCL and should be avoided in cases of MF/SS and mogamulizumab-induced rashes. They emphasized the importance of diagnostic vigilance, providing recommendations for skin biopsy, histology and clonality testing before and during treatment, particularly for patients with AD onset after the age of 40 or with atypical features. Dupilumab should be discontinued once CTCL confirmed, and methotrexate or phototherapy considered as alternatives. Cyclosporine and JAK inhibitors are considered unsuitable, and switching to other Th2-targeting biologics is discouraged due to insufficient data. CONCLUSIONS:Dupilumab may unmask or exacerbate CTCL, particularly MF and SS. The consensus-based recommendations offer practical guidance for the safe management of patients.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare subset of diffuse large B-cell lymphoma (DLBCL) exhibiting genetic features shared with LBCL of immune-privileged sites (notably the MYD88L265P mutation) and enriched in tumor associated macrophages (TAM) expressing M2 markers. Using a unique PCDLBCL-LT cell line (ARSI cell line) developed in our institute, we sought to mechanistically decipher the interplay between lymphoma cells and macrophages. We demonstrate that ARSI cells induce phenotypic, transcriptional and functional changes in macrophages obtained from primary monocytes and THP-1 cell line. These changes do not require cell-cell contact, and proteome analysis of ARSI secretome reveals high concentration of several cytokines and chemokines known to affect macrophages, including IL-10. We then demonstrate that IL-10/IL-10RA interaction blockade inhibits macrophage polarization induced by tumor cells. These findings are reproduced when macrophages are co-cultured with PCDLBCL-LT cells from different patient-derived xenografts. However, among 4 other DLBCL cell lines only the MYD88-mutated OCI-Ly3 cell line exhibits similar effects, which highlights the variability of macrophage interplays and led us to hypothesize that macrophage shaping, beyond the cutaneous localization, may rely on specific genetics of tumor cells. Finally, we reveal that macrophages enhance tumor cell proliferation and promote resistance to doxorubicin in co-culture. In conclusion, these results confirm the robustness of this model to study lymphoma cell and macrophage interplays, underline the critical role of IL-10 in lymphoma microenvironment modeling, and may contribute to better define its specificities in an era of rising microenvironment-targeted therapies.

Abstract Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer associated with substantial morbidity and mortality in advanced stages. Despite its well-described stepwise progression from actinic keratosis to invasive disease, robust molecular markers for stage discrimination and clinical decision-making remain limited. We sought to define the transcriptional continuum underlying cSCC progression, identify stage-associated biomarkers, and assess the broader relevance of these programs across human malignancies. Bulk RNA sequencing (HTG EdgeSeq) and spatial transcriptomics (GeoMx) were performed on biopsies from eight patients, each presenting multiple disease stages (healthy skin, premalignant lesion, tumor core, and invasive front) within the same lesion field, enabling within-patient analysis of progression. Spatial transcriptomic analyses identified more than 2,000 differentially expressed genes whose expression varied across disease stages. These genes were organized into 18 coordinated expression programs reflecting progressive biological rewiring during tumor evolution. Proliferation, extracellular matrix remodeling, inflammation, and stress-response pathways were progressively upregulated, whereas epithelial differentiation and metabolic processes, including lipid and amino acid metabolism, were downregulated. Macrophages exhibited distinct metabolic reprogramming, with increased purine metabolism, glycolysis, and pyruvate metabolism across progression. To evaluate the broader clinical relevance of these progression-associated programs, we developed a reproducible Snakemake pipeline to systematically screen 32 solid and hematologic malignancies from The Cancer Genome Atlas (TCGA). A combined cSCC-progression signature was significantly associated with poor overall survival ( P < 0.05) in 10 additional cancer types. Finally, we identified 12 stage-informative biomarkers, whose spatially restricted expression patterns were validated using Visium HD. This study provides a spatially resolved and stage-aware transcriptomic map of cSCC progression, identifies coordinated gene programs underlying disease evolution, and defines progression-associated signatures with prognostic relevance across multiple cancers, highlighting their potential translational value.

BACKGROUND:Severe scabies, a rare parasitic skin disease characterized by abundant skin mites, may be life-threatening and poses public health concerns worldwide. A combination of standard-dose oral ivermectin and topical scabicides is recommended for treatment. However, data from randomized clinical trials are lacking, and the probability of cure is uncertain. Ivermectin at higher doses has been effective in the treatment of some parasitic diseases. METHODS:We conducted a blinded randomized trial involving adults with severe scabies (i.e., profuse or crusted), as confirmed by parasitologic or dermoscopic assessment. The patients were assigned in a 1:1 ratio to receive oral ivermectin (to be taken with food) at a dose of 400 μg per kilogram of body weight (higher-dose group) or 200 μg per kilogram (standard-dose group) on days 0, 7, and 14, combined with head-to-toe application of 5% permethrin cream on days 0 and 7 and daily application (as recommended) of an emollient cream. The primary end point was cure of severe scabies, which was defined as the absence of mites and mite-related products (i.e., eggs and feces), as confirmed by parasitologic or dermoscopic assessment on days 18 and 21, and the absence of active clinical lesions on physical examination on day 28. RESULTS:A total of 132 patients (66 in each group) were included in the main analysis. Cure was observed in 75% of the patients in the higher-dose group and in 82% of those in the standard-dose group (odds ratio for cure, 0.64; 95% confidence interval, 0.25 to 1.67). No safety issues were identified. CONCLUSIONS:Among adults, the 400-μg-per-kilogram dose of ivermectin plus 5% permethrin cream was not superior to the standard 200-μg-per-kilogram dose of ivermectin plus 5% permethrin cream in curing severe scabies. (Funded by the French Ministry of Health and French Society of Dermatology; ClinicalTrials.gov number, NCT02841215.).

Mogamulizumab (MOGA), an anti-CCR4 monoclonal antibody, improves progression-free survival (PFS) and overall survival in Sézary syndrome (SS). Recently, a multicentre retrospective study conducted by the French Cutaneous Lymphoma study group assessed PFS in 52 patients with SS (median age 73 years, 56% female sex, 75% stage IVA1) who discontinued MOGA for reasons other than disease progression (Moga-stop Study). We report data from an extended follow-up of this cohort, along with comparative PFS outcomes from a parallel SS cohort with continuous MOGA treatment until progression.

Abstract The PROspective Cutaneous Lymphoma International Prognostic Index Study ‘PROCLIPI’ (ClinicalTrials.Gov ID: NCT02848274) opened in 2015 at > 50 international expert centres for mycosis fungoides (MF) and Sézary syndrome (SS). The aim of the study was to determine a prognostic index to better stratify patients for survival. A prognostic index for advanced MF and SS has recently been published that stratifies patients with advanced MF/SS into risk groups with significantly different 5-year overall survival. A CLIPI for early-stage MF is urgently needed to allow dermatologists to identify patients at risk of progression to advanced stage and subsequently select treatments for improved survival, as PROCLIPI shows that 5-year overall survival varies between 72.4% and 95.4% in early-stage MF and SS. Prospectively collected predefined datasets were analysed, including clinical, pathological, genotypic, treatment and quality-of-life data, in patients with newly diagnosed MF or SS. In total, 2004 patients with early-stage disease (IA, n = 921; IB, n = 853; IIA, n = 154) were recruited across 52 sites, presenting at a median age of 57 years (interquartile range 43–68). In multivariate analysis, the presence of cutaneous plaques (P < 0.001), nodal enlargement (Nx–N2) (P < 0.001), age > 60 years (P = 0.02) and large cell transformation in skin (P < 0.001) were significant factors for progression and overall survival. Notably, plaques have a high correlation with disease progression and poor overall survival (83.2% 5-year survival) compared with patients with patch-only disease (94.9% 5-year survival). Early-stage MF is typically reported as a low-grade lymphoma, but data from PROCLIPI have found low 5-year survival rates coupled with a median age of diagnosis of 57 years. Thus there is a marked reduction in life expectancy for some patients. However, 5-year survival rates for patients with patch-only disease are comparable with those of the average 57-year-old individual in Europe. In addition to plaques, PROCLIPI has identified other significant factors associated with poor survival, enabling the identification of at-risk patients using markers such as nodal enlargement and large cell transformation in the skin. The data highlight the need for better stratification of patients with early-stage MF and SS to allow improved management.

T-cell–redirecting immunotherapies, including bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies, have rapidly become major treatment options of relapsed or refractory multiple myeloma but are associated with a distinctive spectrum of cutaneous toxicities. Dermatologic manifestations are particularly prominent with GPRC5D-targeting agents, reflecting on-target, off-tumor activity against hard-keratinizing tissues, whereas BCMA-targeted bispecific antibodies and anti-BCMA CAR T-cell therapies are associated with milder and less phenotypically distinct cutaneous adverse events. Despite their clinical relevance, these toxicities remain inconsistently reported, and standardized definitions and management strategies are lacking. This European Academy of Dermatology and Venereology (EADV) Task Force “Dermatology for Cancer Patients” position paper, developed in collaboration with hematology units experienced in multiple myeloma care, reviews the mechanistic basis, clinical spectrum, and grading of cutaneous toxicities associated with T-cell-redirecting therapies. We propose a phenotype-driven, stepwise management framework organized around four principal patterns - barrier dysfunction and hyperkeratotic disease, inflammatory cutaneous eruptions, nail toxicity, and injection-site reactions- incorporating preventive strategies, baseline dermatologic assessment, and grade-adapted treatment algorithms.

Abstract Brentuximab vedotin (BV), a CD30+ antibody conjugate, was approved for CD30+ cutaneous T-cell lymphoma in 2018. Mogamulizumab, an anti-CCR4 monoclonal antibody was approved for refractory mycosis fungoides and Sézary syndrome. The overall survival (OS) benefit and optimal sequencing of these therapies remain unclear in relation to traditional systemic therapies – bexarotene and extracorporeal photopheresis (ECP) – used in advanced-stage disease. The PROCLIPI study (NCT02848274) was interrogated for patients with advanced-stage disease (2015–2025) receiving mogamulizumab, BV, bexarotene or ECP. Of 593 patients, 566 had recorded systemic therapy. Treatment groups overlapped because most had more than one modality. Extracted data included stage, treatment line, OS and best response [either complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD)]. Mogamulizumab was given to 72 patients with 52 completed courses. Rates of CR, PR, SD and PD were 31%, 37%, 15% and 17%, respectively, and the median OS was 64 months. BV was given to 83 patients with 69 completed courses. The rates of CR, PR, SD and PD were 12%, 35%, 41%, and 13%, respectively, and the median OS was 28 months. Bexarotene was used in 178 patients (CR, PR, SD and PD in 8%, 37%, 42% and 13%; median OS 48.5 months) and ECP in 153 (CR, PR, SD and PD in 3%, 40%, 46% and 11%; median OS 41 months). In survival analyses (n = 370), OS improved if a patient received mogamulizumab for any line vs. those who received other systemic (P = 0.008). Data for BV did not reach statistical significance. Monoclonal exposure improved OS (P = 0.04). B2 stage favoured mogamulizumab (P = 0.001). Treatment groups were not mutually exclusive. Mogamulizumab demonstrated the highest objective response. Patients receiving mogamulizumab for any line had longer OS, favouring its use in blood-dominant Sézary syndrome. BV produced durable responses, supporting its role in CD30+ large-cell transformation. Shorter OS in BV any line may reflect inadequacies in current staging, as tumour disease (IIB) had worse outcomes than erythrodermic disease (stage III/IV). Bexarotene and ECP remain important systemic therapies. These data inform phenotype-directed sequencing and underscore the need for prospective comparative studies.

Cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and sometimes fatal diseases. Patients presenting with advanced-stage CTCL usually exhibit poor long-term survival outcomes. Only very few treatments have improved progression-free survival (PFS) in advanced CTCL, and no treatment has increased overall survival (OS). In 2023, the results of the CUTALLO trial supported the hypothesis that hematopoietic stem-cell transplantation (HSCT) was associated with significantly longer PFS as compared with standard-of-care treatment among advanced-stage patients although HSCT did not significantly affect OS. We provide herein the final OS data pertaining to the same patient population after a longer median follow-up of 38.9 months. Of the 99 patients included in the analysis, 55 (56%) were assigned to the HSCT group, whereas 44 (44%) were allocated to the non-HSCT group. The updated survival analysis reported that 16 of 55 patients (29%) in the HSCT group and 22 of 44 patients (50%) in the non-HSCT group died. The median OS was not reached in the HSCT group and 51.5 months (95% CI, 26.9 to 51.5) in the non-HSCT group (hazard ratio, 0.40 [95% CI, 0.20 to 0.80]). Compared with the standard of care for advanced CTCL, after extended follow-up, allogeneic HSCT was associated with significantly longer OS.

2522 Background: Sézary syndrome (SS) is a rare and aggressive cutaneous T-cell lymphoma, which commonly expresses KIR3DL2, a killer immunoglobulin-like receptor, reported in ≥ 85% of patients. SS is characterized by erythroderma, significant blood involvement, lymphadenopathy and poor prognosis (10-20% 5-year survival). Lacutamab is a first-in-class monoclonal antibody designed to specifically deplete KIR3DL2-expressing cells via antibody-dependent cell-cytotoxicity and phagocytosis. Methods: TELLOMAK is an international, Phase 2 trial with multiple cohorts (NCT03902184). We report here long term follow-up results from Cohort 1, evaluating lacutamab in patients with relapsed/refractory (R/R) SS after at least 2 prior systemic therapies including mogamulizumab. Lacutamab 750 mg is administered until progression or unacceptable toxicity. Primary endpoint was Objective Response Rate (ORR) based on the evaluation of 4 compartments: skin, blood, lymph nodes and viscera according to the International Consensus criteria Olsen 2011. Secondary endpoints included but were not limited to duration of response (DOR), progression free survival (PFS), safety, and quality of life assessments. Results: As of October 17, 2024, recruitment was completed with 63 SS patients enrolled. Median age was 69 years (range: 42-86), the median prior lines of systemic therapies were 5.0 (range: 2-13), 65.1% and 34.9 % patients had stage IVA1 and stage IVA2 at baseline respectively, all patients had blood involvement (B2), 63.5% had confluence of erythema covering ≥ 80% body surface area (T4), 34.9% had lymph node lymphoma involvement (N3). Median follow-up was 25.1 months (95% CI 21.0-29.4). Global confirmed ORR was 42.9% (CI 31.4-55.1) including 6 (9.5%) CRs who are all still in CR; with a median time to response of 2.8 months (range 1-10) and a median duration of response of 25.6 months (CI 11.0, NE). According to each compartment, ORR in skin was 52.4% (CI 40.3-64.2) including 9 (14.3%) CRs, ORR in blood was 50.8% (CI 38.8-62.7) including 21 (33.3) CRs, and ORR in lymph nodes was 28.8% (CI 18.3-42.3) including 9 (17.3) CRs. Median PFS was 8.3 months (CI 5.1-18.7). Grade ≥ 3 related Treatment-Emergent Adverse Events (TEAEs) were observed in 20.6% patients. Serious related TEAEs were observed in 9.5% patients and related TEAEs leading to study drug discontinuation in 6.3% patients. Data from additional key endpoints will be presented. Conclusions: The long term follow-up data from TELLOMAK study in a R/R SS population previously treated with 2 or more prior systemic therapies including mogamulizumab, confirm that lacutamab shows promising clinical activity with ORR 42.9% (95% CI 31.4-55.1) and median duration of response of 25.6 months (11.0, NE) and an overall favourable safety profile. These data support the further development of lacutamab in an effort to bring improved treatments to patients with SS. Clinical trial information: NCT03902184 // EU CT number: 2023-507777-18-00.

In recent classifications several cutaneous lymphomas were reclassified as lymphoproliferative disorder (LPDs). These include primary cutaneous CD4+ small/medium T-cell LPD (PCSM-TCLPD), primary cutaneous acral CD8+ T-cell LPD (acral CD8+ TCLPD) and primary cutaneous marginal zone lymphoma/LPD (PCMZL/LPD). The latter is still classified as primary cutaneous marginal zone lymphoma (PCMZL) in the 5th edition of the World Health Organization classification. A survey was previously carried out among 30 cutaneous lymphoma centres on the effects of this new terminology on clinical management. The results revealed considerable heterogeneity and emphasized the need to develop uniform recommendations for management and treatment of these disorders. Our objective was to develop consensus recommendations for staging, treatment and follow-up in PCSM-TCLPD, acral CD8+ TCLPD and PCMZL/LPD. Two surveys with questions regarding staging, treatment and follow-up of cutaneous LPDs were distributed among 30 cutaneous lymphoma expert centres collaborating within the EORTC-CLTG, USCLC and ISCL. Consensus recommendations were formulated based on these surveys, an extensive literature search, two rounds of feedback and a final consensus meeting. Important changes compared with current practice and literature are as follows. (i) Staging examinations, other than thorough clinical examination of skin and peripheral lymph nodes, are not required in typical cases of PCSM-TCLPD and acral CD8+ TCLPD. (ii) Low-dose radiotherapy (4-8 Gy) can be used rather than dose ≥ 20 Gy for PCSM-TCLPD and acral CD8+ TCLPD, and 4 Gy can be used for PCMZL/LPD. The dose can be escalated to 20-24 Gy in the case of local failure. (iii) Intralesional corticosteroids are also recommended as initial treatment in all three LPDs. (iv) A limited follow-up period (2 years) is acceptable in PCSM-TCLPD and acral CD8+ TCLPD LPD. These EORTC/USCLC/ISCL consensus recommendations reflect the state-of-the-art management and treatment as agreed upon by major cutaneous lymphoma centres. They may contribute to uniform staging, treatment and follow-up policy in patients with cutaneous LPDs.

9583 Background: Two hedgehog pathway inhibitors (HHIs) have been approved for the treatment of locally advanced basal cell carcinoma (laBCC): vismodegib and sonidegib. Efficacy of both seem similar, even though no head-to-head comparison has been performed. However, adverse events (AEs) in pivotal trials seemed less frequent with a later onset with sonidegib. CARADERM is a French national database created in 2013 to improve the management of rare skin tumors, including laBCC. The objective of our study was to compare the safety profile of HHIs in this real-life cohort. Methods: LaBCC patients from the CARADERM database were reviewed. Patients who started either vismodegib or sonidegib at least one year before analysis were included. Type and grade of AEs were collected when available. Cumulative incidence of the first occurrence of adverse events was estimated, with treatment discontinuation as a competing event. Results: In the total cohort of 452 laBCC patients, 330 met the inclusion criteria: 280 (85%) treated with vismodegib and 50 (15%) with sonidegib. The median follow-up was 22.3 months. Clinical characteristics (including age, gender, performance status, localization and tumor size) were similar for both groups. The cumulative incidence of the first AE was significantly lower with sonidegib (43.5%, 95% confidence interval (95%CI) = 29.0-57.2 at 12 months) than with vismodegib (63.5%, 95%CI = 57.5-68.9 at 12 months, p=0.0014) (Table 1). For vismodegib treated patients, 191 (68%) experienced at least one AE. The most frequent were cramps (n=123, 44%), dysgeusia (n=123, 44%) and alopecia (n=88, 31%). For sonidegib treated patients, 22 (44%) experienced at least one AE. The most frequent were cramps (n=8, 16%), alopecia (n=7, 14%) and dysgeusia (n=6, 12%). Major AEs seemed to be less frequent and to appear later with sonidegib, with a significant difference for cramps (p=0.007) and dysgeusia (p=0.001), but not significant for alopecia (p=0.059). Conclusions: We present here the largest real-life comparison of HHIs in a real-life cohort of laBCC patients. The cumulative incidence of the first AE was significantly lower with sonidegib. Even though the range of AEs was similar with both HHIs, dysgeusia and cramps were less frequent with sonidegib. These data highlight the difference in terms of tolerance of both HHIs, with a later onset and lower frequencies of AEs with sonidegib. However, though both groups were clinically comparable, vismodegib was overrepresented compared to current prescriptions of HHIs, and further analyses are mandatory to confirm these data. Cumulative incidence of first adverse event at 3, 6 and 12 months. 3 months [95CI] 6 months [95CI] 12 months [95CI] Sonidegib 16.3 % [7.5 ; 28.0] 26.8 % [15.2 ; 39.8] 43.5 % [29.0 ; 57.2] Vismodegib 31.6 % [26.2 ; 37.2] 55.5 % [49.5 ; 61.2] 63.5 % [57.5 ; 68.9] 95CI = 95% confidence interval.