Ignacio Garcia Doval

Background: Darier disease (DD) is caused by pathogenic ATP2A2 variants that impair calcium homeostasis and keratinocyte adhesion. Responses to MEK inhibition support investigating additional pathway-directed treatments. Phosphorylated ribosomal protein S6 (pS6) Ser240/244 provides a downstream readout of mTORC1-associated signalling. Objectives: To describe outcomes with topical sirolimus 1% in DD and quantify epidermal pS6 Ser240/244 in paired lesional and non-lesional skin and healthy controls. Methods: We retrospectively reviewed six patients treated with compounded sirolimus 1% cream, including three who received it as an add-on to ongoing systemic therapy. Treated areas were assessed using a retrospective Physician Global Assessment (PGA). Epidermal pS6 Ser240/244 immunofluorescence was quantified in nine pairs of lesional and non-lesional DD biopsies and nine healthy-control biopsies, using one aggregate value per biopsy. Results: All five evaluable patients showed symptomatic and/or clinical improvement at a median PGA assessment time of 1 month (range 10 days to 6 weeks). One patient discontinued treatment after three days because of local intolerance, precluding efficacy assessment. Mean (SD) corrected pS6 intensity was 10.3 (2.0) arbitrary units in controls, 60.0 (53.5) in non-lesional DD and 99.5 (41.2) in lesional DD. Both DD groups differed from controls (Holm-adjusted P = 0.00185 and P = 0.0000823, respectively). Non-lesional values were heterogeneous, and the paired lesional–non-lesional difference was not significant (P = 0.36). Conclusions: Topical sirolimus showed promise as a local treatment, including as an adjunct for persistent lesions during systemic therapy. Increased epidermal pS6 provides complementary biological support for investigating mTORC1 inhibition in DD.

Background: Current relevance of positive patch‐test reactions guides management in allergic contact dermatitis (ACD), yet its clinical predictors and the use of predictive models in clinical practice remain underused. Objectives: To identify demographic and clinical factors associated with current relevance in ACD and to develop overall and allergen‐specific predictive models. Methods: A multicentric REIDAC study included data from patch‐tested patients with the Spanish baseline series. Exposure history, anatomical sites, atopic status, and occupational data were recorded. Logistic regression (LR) models were trained and internally validated to predict current relevance overall and for top frequent allergens. Model discrimination was assessed with area under the receiver‐operating characteristic curve (AUC). Results: Among 17 005 patients, 4077 (24.0%) had at least one currently relevant reaction. The final overall LR model achieved an AUC for the validation sample of 0.679. Allergen‐specific AUC parameters (LR) varied among allergens but performed best for nickel (AUC = 0.770). The independent factors associated with current relevance were female gender, specific body sites (hand, neck, head, leg, feet) and two occupations (hairdresser and construction workers). The use of other models (LASSO, gradient boosting) revealed similar results. Conclusions: Prediction modelling may moderately predict current relevance in ACD and several clinical variables are associated with current relevance in ACD.

Darier disease (DD) is a rare autosomal-dominant genodermatosis caused by mutations in the ATP2A2 gene, which encodes sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2). This leads to impaired intercellular adhesion and epidermal blistering. We report the case of a 25-year-old man with severe DD who demonstrated a positive response to trametinib after multiple unsuccessful therapies.

Background: The lack of evidence from routine clinical settings has limited the widespread adoption of adalimumab biosimilars for the treatment of psoriasis. Objectives: To compare the drug survival and safety of adalimumab biosimilars with Humira® in psoriasis. Methods: We conducted a prevalent new-user cohort study using data from the French National Health Data System (SNDS), the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) and the Spanish Registry of Systemic Therapy in Psoriasis (BIOBADADERM). Adalimumab-naïve patients initiating adalimumab biosimilars (new users) were compared with Humira new users. Patients switching from Humira to biosimilars (switchers) were compared with those who continued Humira treatment. Patients were matched 1 : 1 based on previous adalimumab exposure time to create equal-sized cohorts of biosimilar and Humira users. Co-primary outcomes included drug discontinuation and serious adverse events (SAEs). Hazard ratios (HRs) were calculated using Cox proportional hazard models. Meta-analyses using random-effect models were performed to combine results from the three databases. Results: In total, 7387 biosimilar new users and 3654 switchers were matched and compared with Humira users. No differences in all-cause discontinuation were found between biosimilar and Humira new users [HR 0.99, 95% confidence interval (CI) 0.94–1.04]. Switching from Humira to biosimilars was associated with a higher discontinuation rate than remaining on Humira (HR 1.35, 95% CI 1.19–1.52). Similar results were observed for discontinuation due to ineffectiveness or adverse events. Risks of SAEs were similar between biosimilar new users and Humira new users [incidence rate ratio (IRR) 0.91, 95% CI 0.80–1.05] or between switchers and continuous Humira users (IRR 0.92, 95% CI 0.83–1.01). Conclusions: Adalimumab biosimilars can be considered viable alternatives to Humira for new patients, with comparable effectiveness and safety. However, owing to the higher likelihood of discontinuation, patients who switch from Humira to biosimilars may require closer monitoring and support.

Introduction: Patch test results may be influenced by age‐related factors. However, there is still discordant evidence between age and patch test results.Objectives: We aim to evaluate the patch test results reflecting skin sensitisation, their relevance and association with clinical features by age group.Methods: Prospective multicentric study of all patients patch tested with the Spanish baseline series in participating centres. Age groups were pre‐defined as children (0‐ to 11‐years), adolescents (12‐ to 18‐years), young adults (19‐ to 30‐years), middle‐aged adults (31‐ to 65‐years) and older adults (≥66‐years). Occurrence of sensitisation, relevance and clinical features were compared by age group. Factors associated with skin sensitisation were investigated with multivariate logistic regression.Results: A total of 13 368 patients were patch‐tested. Differences in positive patch test results and relevance by age were detected with the highest proportion in middle‐aged adults. Age‐related trend differences were found for nickel, potassium dichromate, caines, colophony, Myroxylon pereirae resin, 2‐hydroxyethyl methacrylate and limonene hydroperoxide. The multivariate logistic analysis (adjusted for sex, atopic dermatitis, body location and occupational dermatitis) showed an association between the age group of 31–65 (OR: 1.41, 95% CI: 1.26–1.58) and above 66‐years (OR: 1.15, 95% CI: 1.01–1.32) with a higher proportion of positive results, compared with young adults.Conclusions: Positive patch test results vary according to age, with the highest occurrence in middle‐aged adults. Most haptens did not present age‐related differences, reinforcing the use of baseline series regardless of age.

Spanish Autonomous Communities (ACs) are entitled to decide on the prescription requirements of their own territories, which can create inequalities in access to new drugs in the management of psoriasis. The objective of this study was to assess whether the level of restrictions in the access to new drugs for the management psoriasis was associated with the probability of achieving disease control measured using the Minimum Disease Activity (MDA) criteria. Therefore, we combined the results of 2 previous independent, cross-sectional studies: one that described the MDA in psoriasis by AC, and another that evaluated the level of restrictions to drug access by AC. We found that the higher the number of restrictions the lower the chances of achieving the MDA criteria (P=.013). Our results suggest that, in Spain, geographical differences in the access to new drugs may be creating health inequalities across the country.