Dimethyl fumarate as a safe and effective therapy for recalcitrant psoriasis in comorbid patients.

Psoriasis is a chronic condition for which multiple therapies are currently available. In particular, in cases of moderate- severe psoriasis, traditional systemic drugs or the new biological drugs can be administered. However, the treatment of patients who require systemic therapy and have multiple comorbidities can be particularly complex. Some treatment options may be in fact contraindicated or may lose effectiveness over time, reducing the options available to the dermatologists. In such circumstances, dimethyl fumarate may represent a safe and effective choice, also in patients who have already attempted biological therapies. In this regard, we report the case of a patient with moderate-severe psoriasis treated over time with various therapies (including topicals, phototherapy, traditional and biological drugs) that were discontinued due to ineffectiveness or incompatibility caused by the occurrence of concomitant diseases, who finally achieved clinical remission with dimethyl fumarate.

Italian expert-based recommendations on the use of photo(chemo)therapy in the management of mycosis fungoides: Results of an e-Delphi consensus.

BACKGROUND: Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule. AIMS: The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item. MATERIALS & METHODS: E-delphi study. Item-specific expert consensus was defined as the number of "Totally Agree" results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic. RESULTS: Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7). CONCLUSIONS: Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB-UVB and PUVA in MF.

Biological therapy in genital psoriasis in women.

Genital psoriasis (GenPs) is a frequent manifestation of psoriasis, causing distress, especially in women. We prospectively studied a population of 74 psoriatic women with severe and generalized psoriasis eligible to biologic therapy, to examine which biologic therapy is more effective on GenPs and to study possible associations between PASI severity and GenPs. Overall, 25/74 (34%) had GenPs: 6 received Ixekizumab, 7 Ustekinumab, 8 Adalimumab, 2 Secukinumab, 1 Etanercept, 1 Certolizumab. Therapies were administered based on PASI severity, independently from the presence of GenPs. Side effects, PASI score, sPGA-G scale for GenPs were recorded at time 0 and after 6 month of therapy. The mean sPGA-G scale value was 2.8 before treatment. After biologic therapy, all patients except one, improved of at least one point. Mostly, patients treated with anti-IL17 (Secukinumab, Ixekizumab) and anti-IL12/23 (Ustekinumab) improved. Mean PASI ranged from 10 to 16.3 before treatment. After 6 months of therapy, 4 anti-TNFα patients, 6 anti-IL17 and 1 anti-IL12/23, reached PASI 90. At time 0, no correlation between PASI and sPGA-G was visible (Pearson r = 0.10, p = .620). From our data, GenPs apparently responds favorably to IL17A inhibitors, but further studies, based on larger numbers of patients, are needed.

Serial biologic therapies in psoriasis patients: A 12-year, single-center, retrospective observational study.

BACKGROUND: Biologic therapy for psoriasis is effective but not always long-lasting and sometimes needs to be switched. OBJECTIVE: We aimed to evaluate the drug survival (ie, the time from initiation to discontinuation) of each biologic and the factors affecting survival to identify better switching strategies and improve drug survival. METHODS: In total, 195 psoriasis patients treated in our unit during 2006-2018 were retrospectively observed. Descriptive statistical analyses and logistic regression models were performed. Kaplan-Meier survival curves and multivariate Cox models adjusted for confounding variables were used to estimate and compare drug survival. RESULTS: Overall, 90.6% of patients achieved an ≥75% reduction in their baseline Psoriasis Area and Severity Index score. In 2018, the most frequently used biologic was ustekinumab (47/169, 27.8%). Patients with higher baseline Psoriasis Area and Severity Index scores were more likely to be switched (P = .0399, odds ratio 1.08). In naive patients, ustekinumab showed longer drug survival (>7.0 years), but in biologic-experienced patients, we found no significant differences in drug survival. Previous biologic therapies increased the need for switching (P = .014, hazard ratio 1.20). Switching between biologic classes yielded longer drug survival than switching within biologic classes (P = .003, hazard ratio 0.48). LIMITATIONS: As a single-center, retrospective real-life study, the data were not perfectly homogeneous. CONCLUSION: Switching between biologic classes might increase drug survival but retrospective studies designed ad hoc are needed to confirm this better switching strategy.

Atomic force microscopy for biomechanical and structural analysis of human dermis: A complementary tool for medical diagnosis and therapy monitoring.

Skin mechanical properties are usually measured considering the entire skin thickness and very little is known about the mechanical behaviour of individual skin layers. We propose atomic force microscopy (AFM) as a tool to quantify nanoscale changes in the biomechanical properties and ultrastructure of human papillary dermis exposed to different mechanical and physical stimuli. Samples from 3 human skin biopsies were studied: one stretched by obesity, one subjected to a high level of sun exposure and normal skin as control. Slices of the papillary dermis layer were harvested at controlled depths from each skin biopsy and 25 µm2 areas of each slice were imaged and D-periodicity of collagen fibres measured by AFM, together with their stiffness. Standard histological analysis was also carried out to correlate biochemical properties and their distribution with stiffness and topography. We obtained similar stiffness values between the sample affected by obesity and the control sample at any depth level into the dermis, while the sun-exposed sample presented a significantly lower stiffness. Additionally, all samples presented an increase in the stiffness at higher depths into the papillary dermis layer. Collagen fibres close to the epidermis of sample affected either by obesity and sun exposure-the former even more than the latter-are thicker and present a larger D-period than those in the control sample. Our results open the possibility to use structural and mechanical analysis based on AFM as a complementary tool for medical diagnosis and therapy monitoring.