Search

Abstract Introduction Since during the COVID-19 pandemic nail psoriasis was evaluated exclusively with teledermatology, dermatologists started to face the difficulty in rating it concurrent with other onycopathies (i.e., onychotillomania and onychophagy). Thus, we aimed to improve the existing severity scores and verify the value in different clinical settings (i.e., in person vs. teledermatology (video or picture)). Methods This multicenter prospective observational study evaluated patients with nail psoriasis and screened them for onychophagy or onychotillomania in telemedicine from May 2020 to January 2021. For therapeutic purposes patients with nail psoriasis were followed and rated with the Nijmegen-Nail psoriasis Activity Index tooL (N-NAIL) for 9 months; at the same time, N-NAIL and a new dedicated index that monitor also the changes in nail dimension (Galeazzi-(G) N-NAIL) were tested for accuracy. We assessed inter- and intraobserver agreement for the three different settings (in person, video, and pictures). Results In our cohort of 382 patients with nail psoriasis after a clinical and dermatoscopic assessment we found 20 (5.24%) patients with onychophagy and 17 (4.45%) patients with onychotillomania. Analysis of the impact of nail psoriasis on patients revealed that onycholysis and crumbing, followed by subungual hyperkeratosis, were the clinical signs that prevalently bothered patients. N-NAIL score displayed moderate intra- and interobserver agreement. Over the 9 months follow-up, N-NAIL vs. GN-NAIL displayed a solid correlation at all the examined time points, i.e., baseline and after 3, 6, and 9 months. Conclusion We created a new tool, the GN-NAIL capable of efficiently scoring nail psoriasis severity in complex cases, such as patients with onychotillomania and onychophagy, and monitor response to treatment during the COVID-19 pandemic.

Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA+ and extracutaneous/systemic CLA− memory T cells cocultured with autologous lesional epidermal cells from AD patients were activated with house dust mite (HDM) and staphylococcal enterotoxin B (SEB). Levels of AD-related mediators in response to both stimuli were measured in supernatants, and the cytokine response was associated with different clinical characteristics. Both HDM and SEB triggered heterogeneous IL-9 production by CLA+ and CLA− T cells in a clinically homogenous group of AD patients, which enabled patient stratification into IL-9 producers and non-producers, with the former group exhibiting heightened HDM-specific and total IgE levels. Upon allergen exposure, IL-9 production depended on the contribution of epidermal cells and class II-mediated presentation; it was the greatest cytokine produced and correlated with HDM-specific IgE levels, whereas SEB mildly induced its release. This study demonstrates that both skin-tropic and extracutaneous memory T cells produce IL-9 and suggests that the degree of allergen sensitization reflects the varied IL-9 responses in vitro, which may allow for patient stratification in a clinically homogenous population.

Abstract Introduction Interleukin-17 plays a pivotal role in both hidradenitis suppurativa (HS) and in maintaining oral homeostasis, but their potential link remains unknown. Thus, we aimed to evaluate and quantify the oral burden of patients with HS. Methods In this real-life, multicenter, cross-sectional study, patients with HS were clinically evaluated by two board-certified dermatologists and two board-certified dentists. Oral comorbidities were carefully collected with medical history and therapeutic information. Results A total of 102 patients (44.0 ± 0.9 years, body mass index 27.0 ± 2.2 kg/m2) were enrolled. Remarkably, 48% and 43% did not undergo at least an oral hygiene or a dental visit each year, respectively. Oral disorders were found in 55.9% of patients with HS, in particular 39.2% had caries and 46.7% reported at least one missing tooth. The main oral manifestations in patients with HS were recurrent aphthous stomatitis (N = 19, 19.2%), amalgam tattoo (N = 14, 14.1%), leukoplakia (N = 11, 11.1%), nicotinic stomatitis (N = 9, 9.1%), papilloma (N = 8, 8.1%), and geographic tongue (N = 8, 8.1%). Whilst the main predictor of oral pathological conditions was Hurley staging (P = 0.0276), multivariate regression analysis indicated that gender and International Hidradenitis Suppurativa Severity Score System (IHS4) were the main predictors for the presence of caries and number of missing teeth. Conclusion As a result of the relevant oral burden in patients with HS, dentists should be part of the multidisciplinary team and oral education should be promoted among patients with HS.

Abstract Introduction Minimal erythema dose (MED) remains a parameter of paramount importance to orient narrow-band (NB)-UVB phototherapy in psoriatic (PsO) patients. Recently, circadian rhythm and diet were recognized as potential MED modulators, but their mutual interaction remains understudied. Thus, we aimed to evaluate the potential diet modulation of MED circadian oscillations. Methods In the first phase, a cohort study was performed comparing potential MED oscillations (morning, afternoon, and evening) among omnivorous psoriatic patients before and after a phototherapy cycle and omnivorous healthy controls. The two groups were age-, gender-, skin-type-, MED-, and diet-matched. Then, in the second phase, another cohort study was carried out comparing MED oscillations 24 h after the last phototherapeutic session only in psoriatic patients cleared with NB-UVB and undergoing different diets (vegan, vegetarian, paleo , ketogenic, intermittent circadian fasting, and omnivore). Patients with different diets were age-, gender-, and skin-type matched. Results In the first phase, we enrolled only omnivores, specifically 54 PsO patients and 54 healthy individuals. Their MED before and after NB-UVB therapy changed significantly among the three different time-points (morning, afternoon, and evening) (p

Abstract Introduction Psoriasis (PsO) is currently regarded as a systemic inflammatory disease with a growing burden of post-diagnosis associated comorbidities. To determine the initial burden of comorbiditis we evaluated the comorbidome at PsO onset. Methods In a matched case–control study, we extracted data on 57,228 patients and 125 morbidities from the Clalit Health Services Israeli insurance database. PsO cases were matched with control individuals by sex and age at enrolment. As pre-existing comorbidities, we considered all conditions already present in controls at the same age as the matched PsO case at the time of their diagnosis. To test for differences in the odds of comorbidities between the case and control groups, logistic regression analyses were run to calculate the odds ratio (OR) for each comorbidity, after which the comorbidome was graphically represented. Results In this study we enrolled 28,614 PsO patients and 28,614 controls with an average age of 45.3 ± 19.6 years. At the time of diagnosis, PsO patients were more likely to be diagnosed with 2–4 comorbidities (28.8% vs 23.8%) and > 5 (19.6% vs 12.9%,). PsO patients’ specific comorbidomes evidenced several pathological cores: autoimmune and inflammatory systemic diseases [i.e., hidradenitis suppurativa (OR 3.55, 95% CI 1.88–7.28) or polymyalgia rheumatica (OR 3.01 95% CI 1.96–4.77)], inflammatory bowel diseases [i.e., Crohn’s disease (OR 2.99 95% CI 2.20–4.13)], pulmonary inflammatory diseases [i.e., chronic obstructive pulmonary disease (OR 1.81 95% CI 1.61–2.04)], hepatological diseases [i.e., cirrhosis (OR 2.00 95% CI 1.36–3.00)], endocrine diseases [dysthyroidisms (OR 1.82 95% CI 1.30–2.59)], mental disorders [i.e., depression (OR 1.72 95% CI 1.57–1.87)], and cardiovascular diseases (i.e., hypertension (OR 1.47 95% CI 1.41–1.53)]. Conclusion The PsO-onset comorbidome may help health professionals plan more comprehensive patient management. By screening for these common PsO-linked conditions, early diagnosis and treatment may become more frequent, thus greatly benefiting patients on their medical journey.

Abstract Introduction Randomized controlled trials (RCTs) suggested that liquid formulation of botulinum toxin type A (aboBoNT-A) is safe and effective, but data confirming these characteristics in a real-life heterogenous set of patients are currently lacking. This study aimed to assess the efficacy and safety of the ready-to-use aboBoNT-A solution in adults with moderate-to-severe glabellar wrinkles. Methods In this real-life, multicenter, retrospective, observational study, healthy adults were treated at baseline only with aboBoNT-A solution on the glabellar area and followed up for 24 weeks. Re-treatment after 20–24 weeks could also be combined with other aesthetic procedures. Family history of immune-mediated inflammatory diseases (IMIDs) was not an exclusion criterion. Patient-reported outcomes (patient’s satisfaction and injection-related pain) and physician-reported outcomes (Physician Global Assessment, PGA) were collected. Results Of the 542 patients enrolled in the study, 38 had IMID family history. Injection-related pain was reported in 128 (23.62%) as mild (pain VAS = 1.34 ± 0.87) mainly by non-botulinum toxin treatment-naïve women under 50 years of age. At 48 h, physicians rated the clinical result as “improved” in 64% of patients, conversely 264 patients (48.71%) self-evaluated as “satisfied”/”very satisfied”. At 4 weeks a touch-up (

IntroductionThe development of several effective biological drugs for moderate-to-severe plaque psoriasis has dramatically changed the lives of patients. Despite the wide use of interleukin (IL) inhibitors, limited data are available to date regarding long-term treatment persistence.MethodThis multicenter retrospective real-world study evaluated 5932 treatment courses across 5300 patients, all treated with interleukin inhibitors. Drug survival was expressed by using the Kaplan-Meier estimator for each biological drug at 6, 12, 24, 36 and 48 months. We also stratified by discontinuation associated with primary or secondary ineffectiveness.ResultsIn our study, the most prescribed drugs were secukinumab (1412), ixekizumab (1183), and risankizumab (977). After four years of follow-up, risankizumab emerged as the treatment with the highest drug survival overall, as 91.6% of patients were still on treatment. The overall probability of drug survival at four years was comparable for tildrakizumab (83.5%), ixekizumab (82.6%), guselkumab (82.4%) and brodalumab (81.8%). When evaluating only patients who discontinued the treatment because of ineffectiveness, once again risankizumab was the molecule with the highest drug survival at 4 years (93.4%), this time followed by ixekizumab (87%). Our study, in which all IL inhibitors were adequately represented, confirmed a slightly better treatment persistence for IL-23 inhibitors, consistent with other real-world studies.ConclusionOur experience showed that IL-23 inhibitors, and risankizumab in particular, had a higher probability of drug survival overall during a 4-year follow-up. Risankizumab and ixekizumab were less likely to be discontinued because of ineffectiveness after four years.

New evidence continues to accumulate regarding a significant association between excessive inflammation and dysregulated immunity (local and systemic) and the risk of cardiovascular events in different patient cohorts. Whilst research has sought to identify novel atheroprotective therapies targeting inflammation and immunity, several marketed drugs for rheumatological conditions may serve a similar purpose. One such drug, methotrexate, has been used since 1948 for treating cancer and, more recently, for a wide range of dysimmune conditions. Over the last 30 years, epidemiological and experimental studies have shown that methotrexate is independently associated with a reduced risk of cardiovascular disease, particularly in rheumatological patients, and exerts several beneficial effects on vascular homeostasis and blood pressure control. This review article discusses the current challenges with managing cardiovascular risk and the new frontiers offered by drug discovery and drug repurposing targeting inflammation and immunity with a focus on methotrexate. Specifically, the article critically appraises the results of observational, cross-sectional and intervention studies investigating the effects of methotrexate on overall cardiovascular risk and individual risk factors. It also discusses the putative molecular mechanisms underpinning the atheroprotective effects of methotrexate and the practical advantages of using methotrexate in cardiovascular prevention, and highlights future research directions in this area.

Abstract Background After decades of use, methotrexate displays an established safety and efficacy profile in both in-hospital and outpatient settings. Despite its widespread use, there is surprisingly little clinical evidence to guide daily practice with methotrexate in dermatology. Objectives To provide guidance for clinicians in daily practice for areas in which there is limited guidance. Methods A Delphi consensus exercise on 23 statements was carried out on the use of methotrexate in dermatological routine settings. Results Consensus was reached on statements that cover six main areas: (1) pre-screening exams and monitoring of therapy; (2) dosing and administration in patients naïve to methotrexate; (3) optimal strategy for patients in remission; (4) use of folic acid; (5) safety; and (6) predictors of toxicity and efficacy. Specific recommendations are provided for all 23 statements. Conclusions In order to optimize methotrexate efficacy, it is essential to optimize treatment using appropriate dosages, carrying out a rapid drug-based step-up on a treat-to-target strategy and preferably using the subcutaneous formulation. To manage safety aspects appropriately, it is essential to evaluate patients’ risk factors and carry out proper monitoring during the course of treatment.

Hidradenitis suppurativa (HS), or acne inversa, is a chronic inflammatory dermatological condition characterized by painful and recurrent nodules and purulent abscesses. HS can have a devastating impact on the quality of life of patients. This condition is commonly localized to the axilla, groin, perineal, and inframammary regions, and can develop fistulas and sinus tracts over time. Its pathogenesis remains elusive and is best characterized at the moment as multi-factorial. Additionally, questions remain about the role of cutaneous dysbiosis as a primary HS trigger or as a secondary perturbation due to HS inflammation. This article features works in relation to HS and its interplay with bacterial microflora. We address current treatment approaches and their impact on HS-related bacteria, as well as areas of therapeutic innovation. In the future, disease-modifying or remittive therapy will likely combine an advanced/targeted anti-inflammatory approach with one that effectively modulates cutaneous and deep tissue dysbiosis.

Background Psoriasis is nowadays regarded as a systemic inflammatory disorder. Among the topicals, vitamin D derivates are often applied on the skin for their anti-inflammatory and immune-modulatory properties. Vitamin D serum levels in psoriasis (PsO) patients are still debated and an eventual depletion may offer the rational to integrate anti-psoriatic therapies with oral vitamin D. Then, we aimed to perform a systematic review and meta-analysis on the current evidence towards serum vitamin D level in PsO. Methods We searched in PubMed, Scopus, Web of Sciences, ScienceDirect and Science Information Database (SID) using the terms “Vitamin D” and “Psoriasis” including manuscripts in English, Italian and Persian. Duplications were excluded using EndNote software and records were screened by title, abstract and full-text. Quality assessment of studies was assessed using Newcastle Ottawa Checklist (NOS). Psoriasis odds ratio (OR) and mean serum vitamin D levels were calculated and displayed in Forest-plots. Heterogeneity indexes were evaluated using I 2 and Q. Sensitivity analysis and publication biases were also considered. Results From 3006 records extracted, after removing duplicates and analyzing full texts we finally included 19 manuscripts involving a total of 1387 PsO cases and 6939 controls. PsO patients exhibited a substantial odds ratio (3.07, 95% CI: 1.56-6.04) for lower serum vitamin D levels compared to the control group. Standardized Mean Difference (SMD) of vitamin D in PsO versus controls was −0.92 (−1.33 to −0.51). Conclusion Psoriatic patients displayed higher risk to have a vitamin D deficiency. Interventional studies to verify the preventive value are mandatory.

Summary: Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38).

Abstract Background Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15–59 years across SSA. Methods We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. Results We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. Conclusions As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.

IntroductionBrodalumab is a monoclonal antibody that targets the subunit A of the interleukin-17A receptor (IL17RA), inhibiting the signaling of various isoforms of the IL-17 family. It has been approved for the treatment of moderate-to-severe plaque psoriasis after being evaluated in three Phase-3 trials. However, long-term data on brodalumab in a real-life setting are still limited.MethodsThe aim of this study was to evaluate the long-term effectiveness and safety of brodalumab in psoriasis. We also assessed the drug survival of brodalumab in a 3 years timespan. We conducted a retrospective multicenter study on 606 patients followed up at 14 Italian dermatology units, all treated with brodalumab according to Italian guidelines. Patients’ demographics and disease characteristics were retrieved from electronic databases. At baseline and weeks 12, 24, 52, 104 and 156, we evaluated the psoriasis area and severity index (PASI) score and investigated for adverse events. The proportions of patients reaching 75, 90 and 100% (PASI 75, PASI 90 and PASI 100, respectively) improvement in PASI, compared with baseline, were also recorded.ResultsAt week 12, 63.53% of the patients reached PASI 90 and 49.17% PASI 100. After 3 years of treatment, 65.22% of patients maintained a complete skin clearance, and 91.30% had an absolute PASI of 2 or less. Patients naïve to biological therapies had better clinical responses at weeks 12, 24 and 52. However, after 2 years of treatment, no significant differences were observed. Body mass index did not interfere with the effectiveness of brodalumab throughout the study. No new safety findings were recorded. After 36 months, 85.64% of our patients were still on treatment with brodalumab.ConclusionOur data confirm the effectiveness and the safety of brodalumab in the largest real-life cohort to date, up to 156 weeks.

Objectives: We explored temporal variations in disease burden of ambient particulate matter 2.5 μm or less in diameter (PM2.5) and ozone in Italy using estimates from the Global Burden of Disease Study 2019.Methods: We compared temporal changes and percent variations (95% Uncertainty Intervals [95% UI]) in rates of disability adjusted life years (DALYs), years of life lost, years lived with disability and mortality from 1990 to 2019, and variations in pollutant-attributable burden with those in the overall burden of each PM2.5- and ozone-related disease.Results: In 2019, 467,000 DALYs (95% UI: 371,000, 570,000) were attributable to PM2.5 and 39,600 (95% UI: 18,300, 61,500) to ozone. The crude DALY rate attributable to PM2.5 decreased by 47.9% (95% UI: 10.3, 65.4) from 1990 to 2019. For ozone, it declined by 37.0% (95% UI: 28.9, 44.5) during 1990–2010, but it increased by 44.8% (95% UI: 35.5, 56.3) during 2010–2019. Age-standardized rates declined more than crude ones.Conclusion: In Italy, the burden of ambient PM2.5 (but not of ozone) significantly decreased, even in concurrence with population ageing. Results suggest a positive impact of air quality regulations, fostering further regulatory efforts.

Abstract Background Injury remains a major concern to public health in the European region. Previous iterations of the Global Burden of Disease (GBD) study showed wide variation in injury death and disability adjusted life year (DALY) rates across Europe, indicating injury inequality gaps between sub-regions and countries. The objectives of this study were to: 1) compare GBD 2019 estimates on injury mortality and DALYs across European sub-regions and countries by cause-of-injury category and sex; 2) examine changes in injury DALY rates over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across the countries. Methods We performed a secondary database descriptive study using the GBD 2019 results on injuries in 44 European countries from 2000 to 2019. Inequality in DALY rates between these countries was assessed by calculating the DALY rate ratio between the highest-ranking country and lowest-ranking country in each year. Results In 2019, in Eastern Europe 80 [95% uncertainty interval (UI): 71 to 89] people per 100,000 died from injuries; twice as high compared to Central Europe (38 injury deaths per 100,000; 95% UI 34 to 42) and three times as high compared to Western Europe (27 injury deaths per 100,000; 95%UI 25 to 28). The injury DALY rates showed less pronounced differences between Eastern (5129 DALYs per 100,000; 95% UI: 4547 to 5864), Central (2940 DALYs per 100,000; 95% UI: 2452 to 3546) and Western Europe (1782 DALYs per 100,000; 95% UI: 1523 to 2115). Injury DALY rate was lowest in Italy (1489 DALYs per 100,000) and highest in Ukraine (5553 DALYs per 100,000). The difference in injury DALY rates by country was larger for males compared to females. The DALY rate ratio was highest in 2005, with DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest- and the highest-ranking country gradually decreased to 3.7 in 2019. Conclusions Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest- and lowest-ranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries.

The role of the skin–gut axis in atopic dermatitis (AD) remains a subject of debate, limiting non-pharmacological interventions such as probiotics and prebiotics. To improve understanding of their potential as a monotherapy for stable mild cases, we conducted a real-life, multicenter, retrospective observational study in Italy. We administered three selected bacteria (Bifidobacterium animalis subsp. lactis BS01, Lactiplantibacillus plantarum LP14, and Lacticaseibacillus rhamnosus LR05) orally to patients with mild atopic dermatitis without a placebo control group, following up for 12 weeks. Clinical assessments using the Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), and Three-Item Severity (TIS) score were conducted on 144 enrolled patients (average age: 25.1 ± 17.6 years). Notably, both pruritus and AD-related lesions (erythema, edema/papules, excoriation) exhibited significant clinical and statistical improvement (p < 0.001) after 12 weeks of exclusive probiotic and prebiotic use. These preliminary results suggest a potential link between the skin–gut microbiome and support the rationale for using specific probiotics and prebiotics in mild AD, even for maintenance, to reduce flares and dysbiosis.

Background and Objectives: Cutaneous lupus erythematosus (CLE) presents clinically heterogeneous manifestations, partially explained by the different expression of Toll-like receptors (TLRs) type 8 and 9, located to endosomal compartments where they are poised to recognize microbial nucleic acids. This disease is empirically treated with hydroxychloroquine (HCQ), which is hallmarked with a safe and effective profile, but induces a slow and sometimes clinically insufficient therapeutic response. Currently, no biomarkers predictive of response are validated or even proposed in the scientific literature. We aimed to evaluate endosomal TLR type 7, 8 and 9 as predictive biomarkers of HCQ efficacy. Materials and Methods: We conducted a case–control study comparing CLE patients retrospectively assigned to three subgroups based on 3–6-month Cutaneous LE Disease Area and Severity Index (CLASI) reduction upon treatment with HCQ (I = = 40–80% vs. III = >80%). Before HCQ, lesional skin specimens were collected in untreated CLE and through immunohistochemistry; TLR-7, -8 and -9 expression was evaluated in the epidermis and the lymphocytic infiltrate was evaluated in the dermis. Results: Sixty-six lesional skin biopsies were compared with healthy controls. CLE patients displayed lower epidermal expression of total TLR 8 and 9 as well as infiltrating TLR-8, TLR9 + lymphocytes compared to controls. High HCQ responders differed from low responders for TLR-9 positivity (high vs. low) and for the lymphocytic dermal infiltrate (high vs. low). Conclusions: TLR9 could be envisaged as a possible biomarker to predict HCQ response level and dosage in CLE patients.

Wound management represents a substantial clinical challenge due to the growing incidence of chronic skin wounds resulting from venous insufficiency, diabetes, and obesity, along with acute injuries and surgical wounds. The risk of infection, a key impediment to healing and a driver of increased morbidity and mortality, is a primary concern in wound care. Recently, antimicrobial dressings have emerged as a promising approach for bioburden control and wound healing. The selection of a suitable antimicrobial dressing depends on various parameters, including cost, wound type, local microbial burden and the location and condition of the wound. This review covers the different types of antimicrobial dressings, their modes of action, advantages, and drawbacks, thereby providing clinicians with the knowledge to optimize wound management.

Introduction: SARS-CoV-2 infection is associated with different cutaneous manifestations, including chilblain-like lesions (“COVID-19 toes”), more frequently observed in younger patients. During the current COVID-19 pandemic, pediatric teledermatology has increased considerably since it allows to assist even children quarantined or living in distant geographic locations, also reducing long waiting times. Nonetheless, the correct clinical interpretation of skin lesions suspicious for being related to COVID19 represent a challenge for the dermatologist; in fact, many cutaneous diseases of both infectious and non-infectious origin, like pool palms (also known as “juvenile palmar dermatitis of swimming pools”), can simulate COVID-19 toes. Objectives: to report a telemedicine-assisted experience on outpatient pediatric cases affected by acral dermatitis during the current COVID-19 outbreak, highlighting a possible underdiagnosed differential diagnosis. Methods: We included 6pediatric cases, affected by acral acute dermatitis, for which, due to the ongoing pandemic, it was impracticable to conduct a face-to-face visit. We collected clinical data and high resolution images of skin lesions, which were independently examined by three different dermatologists. Results: We described the first three pediatric cases of pool palms reported in the COVID-era, comparing the clinical characteristics of three other pediatric patients affected by COVID-19 toes. We also performed a literature review of all pool palms cases published to date. Conclusions: Our real-life experience highlights the crucial rule of teledermatology during the ongoing pandemic. Furthermore, the paper emphasizes its criticalities, mainly related to the difficult collection of anamnestic data.

BackgroundVestibular side effects such as dizziness and vertigo can be a limitation for some antibiotics commonly used to treat acne, rosacea, and other dermatology indications.ObjectiveUnlike minocycline, which is a second-generation tetracycline, sarecycline, a narrow-spectrum third-generation tetracycline-class agent approved to treat acne vulgaris, has demonstrated low rates of vestibular-related adverse events in clinical trials. In this work, we evaluate the brain-penetrative and lipophilic attributes of sarecycline in 2 non-clinical studies and discuss potential associations with vestibular adverse events.MethodsRats received either intravenous sarecycline or minocycline (1.0 mg/kg). Blood-brain penetrance was measured at 1, 3, and 6 h postdosing. In another analysis, the lipophilicity of sarecycline, minocycline, and doxycycline was measured via octanol/water and chloroform/water distribution coefficients (logD) at pH 3.5, 5.5, and 7.4.ResultsUnlike minocycline, sarecycline was not detected in brain samples postdosing. In the octanol/water solvent system, sarecycline had a numerically lower lipophilicity profile than minocycline and doxycycline at pH 5.5 and 7.4.ConclusionThe reduced blood-brain penetrance and lipophilicity of sarecycline compared with other tetracyclines may explain low rates of vestibular-related adverse events seen in clinical trials.

Atopic dermatitis (AD) is associated with cutaneous dysbiosis, barrier defects, and immune dysregulation, but the interplay between these factors needs further study. Early-onset barrier dysfunction may facilitate an innate immune response to commensal organisms and, consequently, the development of allergic sensitization. We aimed to compare the cutaneous microbiome in patients with active dermatitis with and without a history of childhood flexural dermatitis (atopic dermatitis). Next-gen Ion-Torrent deep-sequencing identified AD-associated changes in the skin bacterial microbiome (“bacteriome”) and fungal microbiome (“mycobiome”) of affected skin in swabs from areas of skin affected by dermatitis. Data were analyzed for diversity, abundance, and inter-kingdom correlations. Microbial interactions were assessed in biofilms using metabolic activity (XTT) assay and scanning electron microscopy (SEM), while host-pathogen interactions were determined in cultured primary keratinocytes exposed to biofilms. Increased richness and abundance of Staphylococcus, Lactococcus, and Alternaria were found in atopics. Staphylococcus and Alternaria formed robust mixed-species biofilms (based on XTT and SEM) that were resistant to antifungals/antimicrobials. Furthermore, their biofilm supernatant was capable of influencing keratinocytes biology (pro-inflammatory cytokines and structural proteins), suggesting an additive effect on AD-associated host response. In conclusion, microbial inter-kingdom and host-microbiome interactions may play a critical role in the modulation of atopic dermatitis to a greater extent than in non-atopic adults with allergic contact dermatitis.

Summary: Background: More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels. Methods: We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km × 5 km resolution in 98 LMICs based on 2·1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution. Findings: Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205 000 (95% uncertainty interval 147 000–257 000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution. Interpretation: Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Funding: Bill & Melinda Gates Foundation.

Despite the well-known cutaneous beneficial effect of thermal water on the skin, no data exist regarding the potential biological effect of orally consumed water on healthy skin. Thus, in this single-center, double-blind, randomized controlled clinical trial conducted on age and menstrual cycle timing-matched healthy female volunteers (24 + 24) consuming water A (oligo-mineral) or water B (medium-mineral) for 1 month (T1), the cutaneous lipidomics were compared. Interestingly, only water A consumers had a statistically significant (p < 0.001) change in cutaneous lipidomics, with 66 lipids different (8 decreased and 58 increased). The cutaneous lipidomics of consumers of water A vs. water B were statistically different (p < 0.05). Twenty cutaneous lipids were necessary to predict the water type previously consumed (AUC ~70). Our study suggests that drinking oligo-mineral water may change skin biology and may influence the cutaneous barrier, so future dermatological clinical trials should also account for the water type consumed to avoid potential confounders.

Background: Generalized pustular psoriasis (GPP) is a rare, severe inflammatory skin disease characterized by recurrent episodes of flares. Characteristics of patients experiencing a flare are hardly described in a real-life setting. The aim of the study is to investigate the clinical characteristics of patients experiencing a flare of GPP. Methods: Multicenter retrospective observational study on consecutive patients experiencing a flare of GPP between 2018 and 2022. Disease severity and quality of life were assessed by Generalized Pustular Psoriasis Area, Body Surface Area (BSA), and Severity Index (GPPASI), and Dermatology life quality index (DLQI) questionnaire, respectively. Visual analogue scale (VAS) of itch and pain, triggers, complications, comorbidities, pharmacological therapies, and outcome were collected. Results: A total of 66 patients, 45 (68.2%) females, mean age 58.1 ± 14.9 years, were included. The GPPASI, BSA, and DLQI were 22.9 ± 13.5 (mean ± standard deviation), 47.9 ± 29.1, and 21.0 ± 5.0, respectively. The VAS of itch and pain were 6.2 ± 3.3 and 6.2 ± 3.0, respectively. Fever (>38 °C) and leukocytosis (WBC > 12 × 109/L) were found in 26 (39.4%) and 39 (59.1%) patients, respectively. Precipitating triggers were identified in 24 (36.3%) and included infections (15.9%), drugs (10.6%), stressful life events (7.6%), and corticosteroids withdrawal (3.0%). Fourteen (21.2%) patients were hospitalized because of complications including infections in 9 (13.6%) leading to death in one case and hepatitis in 3 (4.5%). Conclusions: GPP flares can be severe and cause severe pain and itch with significant impact on the quality of life. In about one-third of patients the flare may have a persistent course and, with complications, lead to hospitalization.

In this single-arm clinical trial, the authors show that treatment of COVID-19 patients with bevacizumab, an anti-vascular endothelial growth factor drug, can improve PaO2/FiO2 ratios and oxygen-support status. Relative to an external control group, bevacizumab shows clinical efficacy by improving oxygenation.

Humorally associated autoimmune diseases generally show a female predominance whereas ankylosing spondylitis, a disease that overlaps with psoriatic arthritis (PsA), shows a male predominance. The present review ascertains the current knowledge of sex-specific differences related to psoriatic arthritis (PsA), a chronic, inflammatory condition associated with psoriasis. Sex differences may have important implications for clinical research in PsA and in terms of epidemiology (incidence, prevalence, lifetime risk, survival, and mortality), clinical, radiological, and laboratory features, and response to treatment. While nationwide surveys and large-scale databases and registries show no sex-specific differences, varying male/female ratios have been reported, ranging from 0.42 to 2.75 (comparable with those reported for psoriasis vulgaris: ranging from 0.28 to 2.38). This may reflect subtle, complex, nonlinear interactions between the biological make-up of the individual (genetic and epigenetic differences), hormonal components including menopausal status, environmental exposures including skeletal physical stressing, and psychological variables. There exists methodological heterogeneity and paucity of data concerning sex-specific differences, in terms of the specific population studied, study design, and the diagnostic criteria utilized. Harmonizing and reconciling these discrepancies would be of crucial importance in achieving the ambitious goals of personalized/individualized medicine and further standardized meta-data and Big Data could help disentangle and elucidate the precise mechanisms of underlying potential PsA sex-specific differences.

BackgroundRheumatological and dermatological disorders contribute to a significant portion of the global burden of disease. Big Data are increasingly having a more and more relevant role, being highly ubiquitous and pervasive in contemporary society and paving the way for new, unprecedented perspectives in biomedicine, including dermatology and rheumatology. Rheumatology and dermatology can potentially benefit from Big Data.MethodsA systematic review of the literature was conducted according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines, mining “Uno per tutti”, a highly integrated and automated tool/meta-database developed at the University of Genoa, Genoa, Italy, and consisting of 20 major scholarly electronic databases, including PubMed/MEDLINE. Big Data- or artificial intelligence-based studies were judged based on the modified Qiao’s critical appraisal tool for critical methodological quality assessment of Big Data/machine learning-based studies. Other studies designed as cross-sectional, longitudinal, or randomized investigations, reviews/overviews or expert opinions/commentaries were evaluated by means of the relevant “Joanna Briggs Institute” (JBI)’s critical appraisal tool for the critical methodological quality assessment.ResultsFourteen papers were included in the present systematic review of the literature. Most of the studies included concerned molecular applications of Big Data, especially in the fields of genomics and post-genomics. Other studies concerned epidemiological applications, with a practical dearth of studies assessing smart and digital applications for psoriatic arthritis patients.ConclusionsBig Data can be a real paradigm shift that revolutionizes rheumatological and dermatological practice and clinical research, helping to early intercept psoriatic arthritis patients. However, there are some methodological issues that should be properly addressed (like recording and association biases) and some ethical issues that should be considered (such as privacy). Therefore, further research in the field is warranted.Systematic Review RegistrationRegistration code 10.17605/OSF.IO/4KCU2.

IntroductionPromoting standardization and quality assurance (QA) in oncology on the strength of real-world data is essential to ensure better patient outcomes. Wide excision after primary tumor biopsy is a fundamental step in the therapeutic pathway for cutaneous malignant melanoma (CMM). The aim of this population-based cohort study is to assess adherence to wide local excision in a cohort of patients diagnosed with CMM and the impact of this recommended procedure on overall and disease-specific survival.Materials and MethodsThis retrospective cohort study concerns CMM patients diagnosed in the Veneto region (north-east Italy) in 2017, included in the high-resolution Veneto Cancer Registry, and followed up through linkage with the regional mortality registry up until February 29th, 2020. Using population-level real-world data, linking patient-level cancer registry data with administrative records of clinical procedures may shed light on the real-world treatment of CMM patients in accordance with current guidelines. After excluding TNM stage IV patients, a Cox regression analysis was performed to test whether the completion of a wide local excision was associated with a difference in melanoma-specific and overall survival, after adjusting for other covariates.ResultsNo wide excision after the initial biopsy was performed in 9.7% of cases in our cohort of 1,305 patients. After adjusting for other clinical prognostic characteristics, Cox regression revealed that failure to perform a wide local excision raised the hazard ratio of death in terms of overall survival (HR = 4.80, 95% CI: 2.05–11.22, p < 0.001) and melanoma-specific survival (HR = 2.84, 95% CI: 1.04–7.76, p = 0.042).ConclusionBy combining clinical and administrative data, this study on real-world clinical practice showed that almost one in ten CMM patients did not undergo wide local excision surgery. Monitoring how diagnostic-therapeutic protocols are actually implemented in the real world may contribute significantly to promoting quality improvements in the management of oncological patients.

Background and Objectives: The global spread of carbapenem resistance and the resulting increase in mortality forced the World Health Organization (WHO) to claim carbapenem-resistant enterobacteriaceae (CRE) as global priority pathogens. Our study aimed to determine the prevalence of carbapenemase-encoding genes and major plasmid incompatibility groups among Gram-negative hospital-based isolates in Egypt. Material and Methods: This cross-sectional study was carried out at Mansoura University Hospitals over 12 months, from January to December 2019. All the isolates were tested for carbapenem resistance. The selected isolates were screened by conventional polymerase chain reaction (PCR) for the presence of carbapenemase genes, namely blaKPC, blaIMP, blaVIM, and blaNDM-1. PCR-based plasmid replicon typing was performed using the commercial PBRT kit. Results: Out of 150 isolates, only 30 (20.0%) demonstrated carbapenem resistance. Klebsiella pneumoniae was the most resistant of all isolated bacteria, and blaNDM was the predominant carbapenemases gene, while the most prevalent plasmid replicons were the F replicon combination (FIA, FIB, and FII) and A/C. Plasmids were detected only in Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, and Pseudomonas aeruginosa. Remarkably, we found a statistically significant association between carbapenemase genes and plasmid replicons, including blaNDM, IncA/C, and IncX. Conclusions: Our study demonstrated an alarming rise of plasmid-mediated carbapenem-resistant bacteria in our locality. The coexistence of resistance genes and plasmids highlights the importance of a targeted antibiotic surveillance program and the development of alternative therapeutic options at the local and international levels. Based on our results, we suggest a large-scale study with more Enterobacteriaceae isolates, testing other carbapenemase-encoding genes, and comparing the replicon typing method with other plasmid detection methods. We also recommend a national action plan to control the irrational use of antibiotics in Egypt.

Atopic dermatitis is a chronic, relapsing, non-contiguous, exudative eczema/dermatitis, which represents a complex, multi-factorial disorder, due to an impairment of the stratum corneum barrier. Currently available drugs have a low skin bioavailability and may give rise to severe adverse events. Nanotechnologies, including nano-particles, liposomes, nano-gels, nano-mixtures, nano-emulsions and other nano-carriers, offer unprecedented solutions to these issues, enabling: i) the management of different clinical forms of atopic dermatitis, especially the recalcitrant ones, i) a better bio-availability and trans-dermal drug targeted delivery at the inflammation site, ii) dose control, iii) significant improvements both in clinical symptoms and immune responses, iv) with less adverse events being reported and a better safety profile. However, some nano-sized structures could amplify and even worsen symptoms in particularly susceptible individuals. Furthermore, most studies included in the present systematic review have been conducted in-vitro or in-vivo, with few randomized controlled clinical trials (RCTs). Future investigations should adopt this design in order to enable scholars achieving robust findings and evidence. Therefore, given the above-mentioned shortcomings, further research in the field is urgently warranted. Keywords: Nanodermatology, Nanobiotechnologies, Atopic dermatitis

Background: Psoriasis is a common, chronic, inflammatory, debilitating, systemic disease with a great impact on healthcare systems worldwide. As targeted therapies have transformed the therapeutic landscape, updated estimates of the Global Burden of Disease (GBD) imposed by psoriasis are necessary in order to evaluate the effects of past health care policies and to orient and inform new national and international healthcare strategies.Methods: Data were extracted from the GBD 2019 study, which collates a systematic review of relevant scientific literature, national surveys, claims data, and primary care sources on the prevalence of psoriasis. Prevalence data were combined with disability weight (DW) to yield years lived with disability (YLDs). Measures of burden at global, regional, and national levels were generated for incidence, prevalence, and YLDs, due to psoriatic disease. All measures were reported as absolute numbers, percentages, and crude and age-adjusted rates per 100,000 persons. In addition, psoriasis burden was assessed by socio-demographic index (SDI).Findings: According to the GBD 2019 methodology, there were 4,622,594 (95% uncertainty interval or UI 4,458,904–4,780,771) incident cases of psoriasis worldwide in 2019. The age-standardized incidence rate in 2019 was 57.8 (95% UI 55.8–59.7) per 100,000 people. With respect to 1990, this corresponded to a decrease of 20.0% (95% UI −20.2 to −19.8). By sex, the age-standardized incidence rate was similar between men [57.8 (95% UI 55.8–59.8) per 100,000 people] and women [(57.8 (95% UI 55.8–59.7) per 100,000 people]. With respect to 1990, this corresponded to a decrease by 19.5% (95% UI −19.8 to −19.2) and by 20.4% (95% UI −20.7 to −20.2) for men and women, respectively. The age-standardized incidence rate per 100,000 persons was found to vary widely across geographic locations. Regionally, high-income countries and territories had the highest age-standardized incidence rate of psoriasis [112.6 (95% UI 108.9–116.1)], followed by high-middle SDI countries [69.4 (95% UI 67.1–71.9)], while low SDI countries reported the lowest rate [38.1 (95% UI 36.8–39.5)]. Similar trends were detected for prevalence and YLDs.Conclusion: In general, psoriasis burden is greatest in the age group of 60–69 years, with a relatively similar burden among men and women. The burden is disproportionately greater in high-income and high SDI index countries of North America and Europe. With advances in psoriasis therapeutics, objective evaluation of psoriasis disease burden is critical to track the progress at the population level.

IntroductionAmong white people, the incidence of cutaneous malignant melanoma (CMM) has been increasing steadily for several decades. Meanwhile, there has also been a significant improvement in 5-year survival among patients with melanoma. This population-based cohort study investigates the five-year melanoma-specific survival (MSS) for all melanoma cases recorded in 2015 in the Veneto Tumor Registry (North-Est Italian Region), taking both demographic and clinical-pathological variables into consideration.MethodsThe cumulative melanoma-specific survival probabilities were calculated with the Kaplan-Meier method, applying different sociodemographic and clinical-pathological variables. Cox’s proportional hazards model was fitted to the data to assess the association between independent variables and MSS, and also overall survival (OS), calculating the hazard ratios (HR) relative to a reference condition, and adjusting for sex, age, site of tumor, histotype, melanoma ulceration, mitotic count, tumor-infiltrating lymphocytes (TIL), and stage at diagnosis.ResultsCompared with stage I melanoma, the risk of death was increased for stage II (HR 3.31, 95% CI: 0.94-11.76, p=0.064), almost ten times higher for stage III (HR 10.51, 95% CI: 3.16-35.02, p

Western diet may trigger sleep disorders and vice versa, but their single and mutual effects on systemic inflammatory diseases (i.e., psoriasis) are far from being fully elucidated. At the same time, psoriatic patients display a great burden of sleep disorders and dysmetabolisms related to an unhealthy lifestyle (i.e., diet). These patients are also affected by a chronic disorder deeply modulated by environmental factors (i.e., sleep and diet) capable to influence drug-response and disease progression. Thus, we aimed to summarize the evidence in the literature that may highlight a potential link among psoriasis–diet–sleep in order to further promote a multidisciplinary approach to psoriatic patients in the scientific community.

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify.

ObjectiveBacterial and viral infectious triggers are linked to spondyloarthritis (SpA) including psoriatic arthritis (PsA) development, likely via dendritic cell activation. We investigated spinal entheseal plasmacytoid dendritic cells (pDCs) toll-like receptor (TLR)-7 and 9 activation and therapeutic modulation, including JAK inhibition. We also investigated if COVID-19 infection, a potent TLR-7 stimulator triggered PsA flares.MethodsNormal entheseal pDCs were characterized and stimulated with imiquimod and CpG oligodeoxynucleotides (ODN) to evaluate TNF and IFNα production. NanoString gene expression assay of total pDCs RNA was performed pre- and post- ODN stimulation. Pharmacological inhibition of induced IFNα protein was performed with Tofacitinib and PDE4 inhibition. The impact of SARS-CoV2 viral infection on PsA flares was evaluated.ResultsCD45+HLA-DR+CD123+CD303+CD11c- entheseal pDCs were more numerous than blood pDCs (1.9 ± 0.8% vs 0.2 ± 0.07% of CD45+ cells, p=0.008) and showed inducible IFNα and TNF protein following ODN/imiquimod stimulation and were the sole entheseal IFNα producers. NanoString data identified 11 significantly upregulated differentially expressed genes (DEGs) including TNF in stimulated pDCs. Canonical pathway analysis revealed activation of dendritic cell maturation, NF-κB signaling, toll-like receptor signaling and JAK/STAT signaling pathways following ODN stimulation. Both tofacitinib and PDE4i strongly attenuated ODN induced IFNα. DAPSA scores elevations occurred in 18 PsA cases with SARS-CoV2 infection (9.7 ± 4 pre-infection and 35.3 ± 7.5 during infection).ConclusionEntheseal pDCs link microbes to TNF/IFNα production. SARS-CoV-2 infection is associated with PsA Flares and JAK inhibition suppressed activated entheseal plasmacytoid dendritic Type-1 interferon responses as pointers towards a novel mechanism of PsA and SpA-related arthropathy.

BackgroundCheckpoint inhibitors have revolutionized advanced melanoma care; however, their cutaneous side effects have not been definitively elucidated.ObjectiveTo identify the prevalence of cutaneous toxicity in patients with melanoma treated with immune checkpoint inhibitors as monotherapy and/or in combination with chemotherapy and/or radiotherapy.Materials and methodsWe performed a systematic review and meta-analysis, which encompassed both clinical trials and observational studies describing the dermatological toxicities in patients treated with immune checkpoint inhibitors. The protocol was registered in the International Prospective Register of Systematic Review under the number CRD42018091915. The searches were performed using the CINAHL, Cochrane CENTRAL, LILACS, LIVIVO, PubMed, Scopus, and Web of Science databases. The methodological quality of the studies was evaluated with the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data.ResultsA total of 9,802 articles were identified in the databases. The final sample comprised 39 studies. The evaluated drugs were ipilimumab, tremelimumab, pembrolizumab, and nivolumab. The results suggest that the most prevalent side effect was grade 1 and 2 pruritus (24%), followed by grade 1 and 2 rash (21%) and grade 1 and 2 vitiligo (10%).ConclusionThe most prevalent side effects in patients treated with checkpoint inhibitors are pruritus, rash, and vitiligo, and they are rated mostly as grades 1 and 2 adverse events. Remarkably, vitiligo is most commonly found in patients treated with PD-1 inhibitors.

Although pemphigus has recently been linked to psoriasis, the risk of emergence of pemphigus during the course of psoriasis is yet to be delineated. The aim of this study was to evaluate the risk of developing pemphigus during the course of psoriasis. A large-scale population-based longitudinal retrospective cohort study was performed to assess the hazard ratio (HR) of pemphigus among 68,836 patients with psoriasis relative to 68,836 age-, sex-, and ethnicity-matched controls. The incidence of pemphigus was 0.14 (95% confidence interval (95% CI) 0.10–0.19) and 0.04 (95% CI 0.02–0.07) per 1,000 person-years among psoriatic patients and controls, respectively. Patients with psoriasis were more than 3 times as likely to develop pemphigus (HR 3.25; 95% CI 1.70–6.21). The increased risk remained statistically significant following adjustment for several confounders (adjusted HR 3.19; 95% CI 1.67–6.11). To conclude, psoriasis is associated with an elevated risk of pemphigus. Further research is needed to explore the immunoserological profile of patients with a dual diagnosis.

The risk of developing psoriasis during the course of bullous pemphigoid (BP) is yet to be investigated. We aimed to assess the risk of psoriasis among patients with BP and the risk of BP in individuals with a history of psoriasis. A population-based retrospective cohort study was conducted comparing BP patients (n = 3,924) with age-, sex-, and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of psoriasis. A case-control design was additionally followed to estimate the risk of BP in those with a preceding diagnosis of psoriasis. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were estimated by Cox regression and logistic regression, respectively. The incidence of psoriasis was 1.78 (95% CI, 1.25–2.48) and 0.67 (95%CI, 0.53–0.83) per 1,000 person-years among patients with BP and controls, respectively. Patients with BP were 2.6-fold more likely to develop psoriasis (HR, 2.60; 95%CI, 1.59–4.27) compared to controls. Furthermore, the prevalence of preexisting psoriasis was higher in patients with BP than in control subjects (1.7 vs. 1.1%, respectively; P < 0.001). A history of psoriasis was associated with a 50% increase in the risk of BP (OR, 1.53; 95%CI, 1.17–2.02). Patients with a dual diagnosis of BP and psoriasis were younger, had higher prevalence of smoking and hypertension, and were treated more frequently with prolonged systemic and topical corticosteroids when compared to the remaining patients with BP. To conclude, a bidirectional association exists between BP and psoriasis. Awareness of this association may be of great importance for physicians managing patients with BP and psoriasis.

Summary: Background: Oral rehydration solution (ORS) is a form of oral rehydration therapy (ORT) for diarrhoea that has the potential to drastically reduce child mortality; yet, according to UNICEF estimates, less than half of children younger than 5 years with diarrhoea in low-income and middle-income countries (LMICs) received ORS in 2016. A variety of recommended home fluids (RHF) exist as alternative forms of ORT; however, it is unclear whether RHF prevent child mortality. Previous studies have shown considerable variation between countries in ORS and RHF use, but subnational variation is unknown. This study aims to produce high-resolution geospatial estimates of relative and absolute coverage of ORS, RHF, and ORT (use of either ORS or RHF) in LMICs. Methods: We used a Bayesian geostatistical model including 15 spatial covariates and data from 385 household surveys across 94 LMICs to estimate annual proportions of children younger than 5 years of age with diarrhoea who received ORS or RHF (or both) on continuous continent-wide surfaces in 2000–17, and aggregated results to policy-relevant administrative units. Additionally, we analysed geographical inequality in coverage across administrative units and estimated the number of diarrhoeal deaths averted by increased coverage over the study period. Uncertainty in the mean coverage estimates was calculated by taking 250 draws from the posterior joint distribution of the model and creating uncertainty intervals (UIs) with the 2·5th and 97·5th percentiles of those 250 draws. Findings: While ORS use among children with diarrhoea increased in some countries from 2000 to 2017, coverage remained below 50% in the majority (62·6%; 12 417 of 19 823) of second administrative-level units and an estimated 6 519 000 children (95% UI 5 254 000–7 733 000) with diarrhoea were not treated with any form of ORT in 2017. Increases in ORS use corresponded with declines in RHF in many locations, resulting in relatively constant overall ORT coverage from 2000 to 2017. Although ORS was uniformly distributed subnationally in some countries, within-country geographical inequalities persisted in others; 11 countries had at least a 50% difference in one of their units compared with the country mean. Increases in ORS use over time were correlated with declines in RHF use and in diarrhoeal mortality in many locations, and an estimated 52 230 diarrhoeal deaths (36 910–68 860) were averted by scaling up of ORS coverage between 2000 and 2017. Finally, we identified key subnational areas in Colombia, Nigeria, and Sudan as examples of where diarrhoeal mortality remains higher than average, while ORS coverage remains lower than average. Interpretation: To our knowledge, this study is the first to produce and map subnational estimates of ORS, RHF, and ORT coverage and attributable child diarrhoeal deaths across LMICs from 2000 to 2017, allowing for tracking progress over time. Our novel results, combined with detailed subnational estimates of diarrhoeal morbidity and mortality, can support subnational needs assessments aimed at furthering policy makers' understanding of within-country disparities. Over 50 years after the discovery that led to this simple, cheap, and life-saving therapy, large gains in reducing mortality could still be made by reducing geographical inequalities in ORS coverage. Funding: Bill & Melinda Gates Foundation.

BACKGROUND:Knowledge regarding differences in care for psoriatic patients is limited. The aim of this study was to investigate factors influencing prescription of systemic treatments for patients with psoriasis with a special focus on socioeconomic factors. METHODS AND FINDINGS:This was a non-interventional, cross-sectional study, conducted in 18 Italian University and/or hospital centers with psoriasis-specialized units. Questionnaires evaluating demographic and socioeconomic characteristics were administered to participants. Overall, 1880 consecutive patients affected by mild-to-severe psoriasis were recruited. Univariate and multivariable logistic regression analyses of systemic therapy prescription, with a special focus on biologics, accounting for the above mentioned characteristics were performed. Our analysis showed that all analyzed patients' characteristics were significantly associated with biological therapy compared to non-biological systemic one. Particularly, women were less likely to receive biologics than men (OR = 0.66; 95% CI, 0.57-0.77). Elderly patients (≥65 years) and subjects with a BMI ≥30 had lower odds to receive biologics respect to adults (≥35-64 years) (OR = 0.33; 95% CI, 0.25-0.40), and subjects with BMI≥25

Since psoriasis (PsO) is a chronic inflammatory disease, patients may experience a drug failure also with very effective drugs (i.e., secukinumab) and, consequently, dermatologists have two therapeutic options: switching or perform a combination therapy (rescue therapy) to save the drug that had decreased its efficacy. At the moment no studies focused on combination/rescue therapy of secukinumab, so we performed a 52-weeks multicenter retrospective observational study that involved 40 subjects with plaque psoriasis that experienced a secondary failure and were treated with combination therapy (ciclosporin (n = 11), MTX (n = 15), NB-UVB (n = 7) and apremilast (n = 7)). After 16 weeks of rescue/combination therapy, PASI and a DLQI varied respectively from 8 [7.0–9.0] and 13 [12.0–15.0], to 3 [2.8–4.0] and 3 [2.0–3.3]), suggesting a significant improvement of daily functionality and quality of life. Results were maintained at 52 weeks. No side effects were experienced during the study. Secukinumab remains a safety and effective drug for PsO patients also in the IL-23 and JAK inhibitors era. The rescue therapy is a valid therapeutic option in case of secukinumab secondary failure.

Summary: Background: Through a comprehensive analysis of Italy's estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we aimed to understand the patterns of health loss and response of the health-care system, and offer evidence-based policy indications in light of the demographic transition and government health spending in the country. Methods: Estimates for Italy were extracted from GBD 2017. Data on Italy are presented for 1990 and 2017, on prevalence, causes of death, years of life lost, years lived with disability, disability-adjusted life-years (DALYs), life expectancy at birth and at age 65 years, healthy life expectancy, and Healthcare Access and Quality (HAQ) Index. We compared the estimates for Italy with those of 15 other western European countries. Findings: The quality of the universal health system and healthy behaviours contribute to favourable overall health, even in comparison with other western European countries. In 2017, life expectancy and HAQ Index score in Italy were among the highest globally, with life expectancy at birth reaching 85·3 years for females and 80·8 for males in 2017, ranking Italy eighth globally for females and sixth for males, and an HAQ Index score of 94·9 in 2016 compared with 81·54 in 1990, keeping Italy ranked as ninth globally. Between 1990 and 2017 age-standardised death rates for cardiovascular diseases decreased by 53·7% (95% uncertainty interval −56·1 to −51·4), for neoplasms decreased by 28·2% (−32·3 to −24·6), and for transport injuries decreased by 62·1% (−64·6 to −59·2). However, population ageing is causing an increase in the burden of specific diseases, such as Alzheimer's disease and other dementias (DALYs increased by 77·9% [68·4 to 87·2]) and pancreatic (DALYs increased by 39·7% [28·4 to 51·7]) and uterine cancers (DALYs increased by 164·7% [129·7 to 202·5]). Behavioural risk factors, which are potentially modifiable, still have a strong effect, particularly on cardiovascular diseases and neoplasms. For instance, in 2017, 44 400 (41 200 to 47 800) cancer deaths were attributed to smoking, 12 000 (9600 to 14 800) to alcohol use, and 9500 (5400 to 14 200) to high body-mass index, while 47 000 (31 100 to 65 700) deaths due to cardiovascular diseases could be attributed to high LDL cholesterol, 28 700 (19 700 to 38 500) to diets low in whole grains, and 15 900 (8500 to 24 900) to low physical activity. Interpretation: Italy provides an interesting example of the results that can be achieved by a mix of relatively healthy lifestyles and a universal health system. Two main issues require attention, population ageing and gradual decrease of public health financing, which both pose several challenges to the future of Italy's health status. Our findings should be useful to Italy's policy makers and health system experts elsewhere. Funding: Bill & Melinda Gates Foundation.

Background and Objectives: Epidemiologic data show significant differences in melanoma incidence and outcomes between sexes. The role of hormonal receptors in the pathogenesis of melanocytic lesions remains unclear, thus we performed this study aiming to assess estrogen receptors expression in different melanocytic lesions. Materials and Methods: We performed a cross-sectional study that included 73 consecutively excised melanocytic lesions. Estrogen receptor alpha (ERα), beta (ERβ), and G-protein coupled estrogen receptor (GPER) expression was analyzed in melanocytes and keratinocytes of common nevi, dysplastic nevi, melanoma, healthy skin margin, and in sebaceous and sweat gland cells. Results: ERβ expression was higher in dysplastic nevi margin melanocytes compared to common nevi (p = 0.046) and in dysplastic nevi keratinocytes compared to melanoma keratinocytes (p = 0.021). ERβ expression was significantly higher in margin melanocytes compared to melanoma melanocytes (p = 0.009). No difference in ERβ expression was shown between melanocytes of three types of lesions. GPER expression was higher in nuclei and cytoplasm of dysplastic nevi (p = 0.02 and p = 0.036 respectively) and at the margin compared to melanoma. GPER expression was lower in sebaceous glands of tissue surrounding common nevi (p = 0.025) compared to dysplastic nevi. GPER expression was higher in skin margin tissue melanocytes (p = 0.016 nuclear, p = 0.029 cytoplasmic) compared to melanoma melanocytes. There were no differences in ERα expression between the melanocytic lesions. Conclusion: Further large-scale studies are warranted to investigate the potential role of ERβ and GPER in the pathogenesis of melanocytic lesions.

Vegans and vegetarians often consume foods containing photosensitizers capable of triggering phytophotodermatitis. The potential effect of vegan and vegetarian diets on the response of psoriatic patients undergoing phototherapy is not well characterized. We assessed clinical outcomes of vegan, vegetarian and omnivore adult psoriatic patients undergoing band ultraviolet B phototherapy (NB-UVB). In this multicenter prospective observational study, we enrolled 119 adult, psoriatic patients, of whom 40 were omnivores, 41 were vegetarians and 38 were vegans, with phototherapy indication. After determining the minimum erythemal dose (MED), we performed NB-UVB sessions for 8 weeks. The first irradiation dosage was 70.00% of the MED, then increased by 20.00% (no erythema) or by 10.00% (presence of erythema) until a maximum single dose of 3 J/cm2 was reached and constantly maintained. All the enrolled patients completed the 8 weeks of therapy. Severe erythema was present in 16 (42.11%) vegans, 7 (17.07%) vegetarians and 4 (10.00%) omnivores (p < 0.01). MED was lowest among vegans (21.18 ± 4.85 J/m2), followed by vegetarians (28.90 ± 6.66 J/m2) and omnivores (33.63 ± 4.53 J/m2, p < 0.01). Patients with severe erythema were more likely to have a high furocumarin intake (OR 5.67, 95% CI 3.74–8.61, p < 0.01). Vegans consumed the highest amount of furocumarin-rich foods. A model examining erythema, adjusted for gender, age, skin type, MED, phototherapy type, number of phototherapies and furocumarin intake, confirmed that vegans had a lower number of treatments. Vegans had more frequent severe erythema from NB-UVB, even after adjustment of the phototherapy protocol for their lower MED. Assessing diet information and adapting the protocol for vegan patients may be prudent.

Nutrigenomic DNA reprogramming in different chronic diseases and cancer has been assessed through the stimulation of gene expression and mRNA synthesis versus DNA silencing by CpG DNA modification (methylation); histone modification (acetylation, methylation) and expression of small noncoding RNAs, known as microRNAs (miRNAs). With regard to the specific nutrigenomic effects in psoriasis, the influence of specific diets on inflammatory cell signaling transcriptional factors such as nuclear factor (NF)-κB and Wnt signaling pathways, on disease-related specific cytokine expression, pro/antioxidant balance, keratinocyte proliferation/apoptosis and on proliferation/differentiation ratio have been documented; however, the influence of dietary compounds on the balance between ‘good and bad’ miRNA expression has not been considered. This review aims to summarize knowledge about aberrant microRNAs expression in psoriasis and to emphasize the potential impact of some dietary compounds on endogenous miRNA synthesis in experimental conditions in vivo and in vitro . Among the aberrantly expressed miRNAs in psoriasis, one of the most prominently upregulated seems to be miR-21. The beneficial effects of phenolic compounds (curcumin and resveratrol), vitamin D, methyl donors, and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) are discussed. Highly expressed miR-155 has been downregulated by flavonoids (through a quercetin-rich diet) and by vitamin D. Quercetin has been effective in modulating miR-146a. On the other hand, downregulated miR-125b expression was restored by vitamin D, Coenzyme Q10 and by microelement selenium. In conclusion, the miRNA profile, together with other ‘omics’, may constitute a multifaceted approach to explore the impact of diet on psoriasis prevention and treatment.

Methotrexate is a systemic immunosuppressant drug that is used for the treatment of psoriasis and psoriatic arthritis. Previous studies demonstrated a potential association between psoriasis and diabetes mellitus, obesity, atherosclerosis and hypertension. This study aimed at exploring the possible hyperglycaemic effects of methotrexate in psoriatic arthritis (PsA) patients. In this prospective cross-sectional study, 27 patients with PsA were evaluated. The status of PsA and presence of accompanying metabolic syndrome was determined by standard criteria and indexes. Blood indicators including, HbA1c, erythrocyte sedimentation rate, fasting blood sugar, total cholesterol, high-density lipoprotein, triglycerides, and C-reactive protein were examined before and 12 weeks after methotrexate therapy. There were no significant changes between HbA1c levels before and after methotrexate therapy in both genders (men: P=0.131, women: P=0.803). In addition, HbA1c levels in PsA patients with metabolic syndrome were not different before and after treatment (P=0.250). Finally, HbA1c levels did not change in PsA patients without metabolic syndrome before and after therapy (P=0.506). Methotrexate in PsA patients does not appear to have hyperglycaemic effects in the short-term and can be safely used in patients with metabolic syndrome and diabetes.