Dermatitis herpetiformis (DH) is a dietary gluten -induced autoimmune blistering skin disease. It is hypothesized to be initiated by a small intestinal mucosal immune response. Gluten-free diet (GFD) is the primary treatment for DHdermatitis herpetiformis and effectively resolves skin lesions. Previous studies show that after gluten reintroduction, peripheral cell responses are detectable already in six6 days, and most patients relapse clinically within months. The relapse presentation may differ between patients, with some experiencing both rash and small intestinal mucosal damage and some only one of these. Here, RNA transcriptomics were utilized to characterize temporal systemic and small intestinal mucosal responses to gluten in DH,dermatitis herpetiformis and to identify transcriptomic profiles specific for rash or villous atrophy as relapse presentations. The cohort consisted of 19 DHdermatitis herpetiformis patients on GFDgluten-free diet who underwent a gluten challenge. Gluten challenge elicited pronounced gene expression changes related to inflammation in the small intestine. In patients relapsing with rash, DOCK8 expression was significantly upregulated, while IL10RB was downregulated at end of follow-up. These patients also had significantly increased frequency of intraepithelial lymphocytes. Our findings show that prolonged gluten exposure alters duodenal transcriptomic profiles considerably. Moreover, patterns related to rash could be detected and present interesting candidates for future studies.
Narrow-band TL-01 ultraviolet B phototherapy (TL-01) is generally considered a relatively safe treatment for skin diseases, although conflicting findings have also been reported. This study aimed to evaluate the association between TL-01 exposure and skin cancer risk using a nested case-control design within a Finnish cohort of 4,815 patients treated with TL-01 monotherapy, with subsequent 38 cases of basal cell carcinoma, 13 cases of cutaneous melanoma, and 9 cases of cutaneous squamous cell carcinoma. Four matched controls were selected for each skin cancer case. Personal TL-01 exposure data were obtained from hospital records. Conditional logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs). An increased risk for basal cell carcinoma was observed with higher TL-01 exposure (OR per 20 sessions 1.36, 95% CI 1.08–1.72), whereas no association was found for cutaneous melanoma or cutaneous squamous cell carcinoma. In a categorical analysis, with category of 1–29 TL-01 sessions as the reference, the risk of basal cell carcinoma was markedly elevated among patients who received ≥60 sessions (OR 4.16, 95% CI 1.49–11.6). Occupational outdoor work was considered a potential confounder, but it had no effect. Further studies with larger cohorts and longer follow-up are needed to confirm these findings.
Cutaneous sarcoidosis is a granulomatous skin disease associated with significant quality-of-life impairment. Evidence from randomized controlled trials (RCTs) guiding systemic or targeted therapy remains limited. To assess the efficacy and safety of pharmacological therapies for cutaneous sarcoidosis in randomized placebo-controlled trials PubMed, the Cochrane Library, and ClinicalTrials.gov were searched through January 2025. Eligible studies were RCTs including adults with cutaneous sarcoidosis randomized to pharmacological therapy versus placebo. Outcomes were clinical response, quality of life, and serious adverse events (SAEs). Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated using random-effects models. Six RCTs including 156 participants were analyzedanalysed. Pharmacological therapies did not significantly improve clinical response compared with placebo (OR 2.24; 95% CI, 0.73–6.90; p=0.16). A non-significant trend toward improved quality of life was observed (OR 2.23; 95% CI, 0.87–5.73; p=0.09). No significant difference in SAEsserious adverse events was found between groups (OR 0.97; 95% CI, 0.48–1.96; p=0.93). Risk of bias ranged from moderate to high, with low statistical heterogeneity. Pharmacological add-on therapies showed no significant efficacy beyond corticosteroids but may improve quality of life. Larger, well-designed RCTs are needed.
Skin damage from routine oronasal facemask use is common, but the early molecular changes and timing of inflammatory cytokine responses remain poorly characterized due to limitations in conventional detection methods. Early pressure ulcer formation involves a critical window where physiological changes occur before visible signs. This study addresses this gap, aiming to monitor the temporal inflammatory profile in skin sebumsurface after the standard use of oronasal facemasks. Sebum samples were collected from 11 patients at six6 timepoints up to 180 min post-mask removal. A panel of 71 inflammatory proteins was analysed using multivariate statistics, protein network analysis, and mathematical modelling. Two distinct cytokine response phases were identified: an early phase (0-20 min) and a delayed phase (40-180 min), with 17 cytokines driving this separation. Notably, the delayed phase showed sustained elevation despite the absence of visible erythema, indicating ongoing subclinical inflammation. Network analysis revealed activation of pathways related to angiogenesis, cell death regulation, and tissue remodelling - hallmarks of early wound healing and microvascular stress. These findings enhance understanding of early pressure ulcer pathophysiology, identify optimal biomarker sampling windows, and support the development of point-of-care biosensors for early detection and prevention of pressure-induced skin damage.
Keratinocyte carcinoma (KC) places a considerable and growing burden on healthcare systems. Given the KC population's heterogeneity, tailored clinical pathways are needed to accommodate diverse management needs. This study applied machine learning (ML)-based phenomapping to identify distinct real-world subgroups within a national KC population using demographic and medical history variables. The study included KC patients treated in publicly-funded, office-based dermatology practices and registered in the Danish Skin Cancer Registry (2014-2022). In 106,490 KC patients, 7 ML-derived clusters were identified. One cluster (22.2%; n=23,590) consisted primarily of young, well educated high-income medically noncomplex females presenting with low-risk basal cell carcinomas (BCCs). Four clusters (55.2%; n=58,736) comprised patients with a greater dermatological disease burden, characterized by facial BCCs, multiple BCCs, a greater proportion of squamous cell carcinomas (SCCs), a history of skin cancer or previous actinic keratosis-related treatment. The remaining 2 clusters (22.7%; n=24,164) comprised highly comorbid patients with a greater proportion of SCCs, a high number of KCs on the head and neck and high immunosuppressive drug exposure. ML-derived phenomapping of a national KC population identified distinct, clinically relevant KC subgroups, providing a basis for tailored clinical pathways with differentiated resource needs.
Atopic dermatitis (AD) is driven by type 2 inflammation, with interleukin-13 (IL-13) as one of the central operators. Lebrikizumab is a monoclonal antibody that inhibits IL-13 signalling. Adult patients with moderate-to-severe AD who received lebrikizumab in the TREATgermany registry until 12/2024 were selected, and patient characteristics as well as effectiveness and safety outcomes after 1, 3 and 6 months were evaluated. A total of 108 patients were initiated on lebrikizumab, with 80 having follow-up data available for this analysis (“registry cohort”). Forty-one patients were switched to lebrikizumab without a “washout period” from another advanced systemic therapy (“switchers”). The mean Eczema Area and Severity Index (EASI) decreased from 14.8 at baseline to 5.6 and 3.0 at month 3 and month 6 and was comparable between switchers and nonswitchers. Clinically meaningful improvements were also seen across all patient reported outcomes (PROs) equally in both groups, e.g. a decrease of the mean peak pruritus numeric rating scale (PP-NRS) from 6.6 to 3.8 and 3.4 and the Dermatology Life Quality Index (DLQI) from 11.9 to 4.9 and 4.8. Overall, adverse events (AEs) were reported for 26.6% of patients within the first 3. The most frequently reported AE was conjunctivitis or other ocular complications, reported in 13 patients (20.3%). 32 patients (40%) had an initial EASI≥16 and were comparable to patients in lebrikizumab phase 3 studies. In this “trial-like” cohort, EASI-75 and EASI-90 response rates were 60% and 26.7% at month 3 and 70% and 50% at month 6. Lebrikizumab shows effectiveness in routine care well comparable to observations made in randomized controlled trials.
Merkel cell carcinoma (MCC)is a rare but aggressive cutaneous malignancy with increasing incidence and poor prognosis. Host immune status is a key determinant of MCCmerkel cell carcinoma development and outcome. While the AEIOU criteria are widely used to facilitate clinical recognition, their value for prognostic assessment remains unclear. To evaluate the association between individual AEIOU presentation features and disease progression in patients with merkel cell carcinoma, with particular emphasis on immunosuppression. We performed a retrospective single-centre cohort study including 400 patients diagnosed with merkel cell carcinoma. Disease progression, defined as local recurrence, nodal involvement or distant metastasis, served as the primary endpoint. AEIOU criteria were assessed at diagnosis and analysed using logistic regression. Complete follow-up data were available for 241 patients, of whom 81 (33.6%) experienced disease progression. Patients with progression were significantly older and more frequently male. Among the AEIOU components, immunosuppression was the only criterion significantly associated with disease progression, conferring an increased risk compared with immunocompetent patients (p<0.001). Other AEIOU features showed no consistent prognostic association. Complete follow-up data were available for 241 patients, of whom 81 (33.6%) experienced disease progression. Patients with progression were significantly older and more frequently male. Among the AEIOU components, immunosuppression was the only criterion significantly associated with disease progression, conferring an increased risk compared with immunocompetent patients (p<0.001). Other AEIOU features showed no consistent prognostic association.
Treat-to-target strategies link predefined goals to regular assessment and treatment adaptation. In atopic dermatitis, recent initiatives have mainly defined thresholds using clinician- and patient-reported outcomes. This review and position paper critically examines current approaches and proposes priorities for a more clinically meaningful, patient-centred and globally applicable framework. It synthesizes recent consensus and outcome-harmonization initiatives with selected lessons from rheumatoid arthritis and asthma and was informed by multidisciplinary, patient-inclusive discussions at an International Society of Atopic Dermatitis-World Health Organization premeeting. The workshop was not a Delphi or formal consensus exercise; it was used to identify conceptual priorities and implementation challenges for future international consensus work. Current proposals converge partly around severity thresholds and symptom control but insufficiently capture disease instability, comorbidities, family burden, treatment burden and real-world constraints. We propose 4 complementary domains: disease activity; symptoms and function; global patient health and disease impact and longitudinal control and treatment adaptation. Some components are supported by validated measures, whereas others remain exploratory. Treat-to-target in atopic dermatitis should evolve beyond isolated thresholds towards an adaptable multidimensional strategy, followed by formal international consensus and prospective validation.
Basal cell naevus syndrome (BCNS) is a rare genetic disorder characteriszed by multiple basal cell carcinomas, as well as different extracutaneous tumours, cysts and abnormalities. Research on health-related quality of life (HRQoL) and mental health in BCNS is limited. This cross-sectional study included 62 individuals ≥18 years diagnosed with BCNS. Clinical and genetic data were collected, and five5 validated questionnaires were used to assess self-reported HRQoL, psychological distress, fatigue, pain and everyday executive functioning. Median regression analyses were conducted to identify factors associated with HRQoL. Independent samples t-tests and one proportion z-tests were conducted to compare the BCNS group with the general population. Individuals with BCNS reported lower HRQoL compared with the general population. Elevated anxiety symptoms were observed in 14 individuals (24%). The proportion of individuals reporting everyday executive deficits was higher in the BCNS group compared with the general population. Engagement in employment or higher education was associated with better physical and mental HRQoL, whereas symptoms of anxiety and everyday executive deficits were associated with reduced mental HRQoL. Findings highlight mental health challenges in BCNS. Routine screening for anxiety and executive functioning is suggested as essential steps in identifying those at risk and provideproviding timely psychological support.
Atopic dermatitis (AD) is characterized by substantial clinical heterogeneity. Global severity is typically assessed using scores such as the POEM; however, lesion localization —– particularly on the face –— may generate psychosocial consequences partly independent of overall disease severity. This cross-sectional observational study (VISEABLE) included 1,400 French adults with physician-confirmed AD. Severity was measured using the POEM (Clear/Almost Clear: 0–7 vs. Moderate–severe: ≥8) and facial involvement using the BoFA (0–109; threshold=36, population median). Six phenotypes were defined through a 2×3 combination. The POEM and BoFA correlation was moderate (r=0.365; ρ=0.389; p<0.001). Phenotype Ph3 (Clear/Almost Clear POEM / Severe facial involvement, n=58) exhibited stigmatization scores (PUSH-d=21.93) and life trajectory impact (DLLIM=14.76) not significantly different from Ph4 (Moderate–severe POEM / No facial involvement, n=527; p>0.25 for all comparisons). In multiple regression analysis restricted to patients with facial involvement, BoFA was the dominant independent predictor of stigmatization (β=11.44, p<0.001; partial R²=46.2 %; overall R²=0.532), superseding POEM (p=0.076, ns; partial R²=0.6%). Mild eczema with severe facial involvement generates a psychosocial burden comparable to that of moderate-to-severe eczema without facial involvement. Systematic BoFA assessment is essential in all patients with AD.
