Alcohol consumption and risk of psoriasis: Results from observational and genetic analyses in more than 100,000 individuals from the Danish general population.

Background: Psoriasis is associated with high alcohol consumption, but the causality of this relationship is unclear. Objective: We aimed to use a Mendelian randomization approach to investigate the causal effects of alcohol on incident psoriasis. Methods: We included 102,655 adults from the prospective Copenhagen studies. All participants filled out a questionnaire on alcohol consumption, were physically examined, and had blood drawn for biochemical and genetic analyses. We created a genetic instrument based on the number of fast-metabolizing alleles in alcohol dehydrogenase 1B and alcohol dehydrogenase 1C, known to be associated with alcohol consumption, to test whether alcohol consumption was causally associated with psoriasis. Results: Observationally, we found an increased risk of incident psoriasis among individuals with high alcohol consumption compared to those with low alcohol consumption with a hazard ratio of 1.30 (95% confidence interval 1.05-1.60) in the fully adjusted model. Using genetic data to predict alcohol consumption to avoid confounding and reverse causation, we found no association between number of fast-metabolizing alleles and risk of psoriasis. Limitations: Alcohol consumption was self-reported and psoriasis was defined using the International Classification of Diseases 10th revision and 8th revision codes. Conclusion: Alcohol consumption is observationally but not causally associated with incident psoriasis.

Psoriasis and mental health in adolescents: A cross-sectional study within the Danish National Birth Cohort.

BACKGROUND: Psoriasis is a chronic skin disease associated with lower quality of life and higher risk of anxiety and depression in adults. We investigate whether adolescents with psoriasis also experience poorer mental health than their peers. METHODS: In this cross-sectional study, we included questionnaire data on psoriasis and mental health from the 18-year follow-up of the Danish National Birth Cohort. We estimated odds ratios (OR) and 95 % confidence intervals (CI) using a logistic regression with inverse probability weighting to account for potential selection bias, adjusted for potential confounders identified a priori. We estimated associations between self-reported psoriasis and multiple aspects of mental health (self-rated health, life satisfaction, mental well-being, loneliness, overall and internalizing behavioral difficulties, depressive symptoms, and anxiety symptoms). In sensitivity analyses, we examined doctor-diagnosed psoriasis and psoriasis with and without joint pain. RESULTS: Of the 44,838 included in this study, 1147 (2.6 %) reported psoriasis. Adolescents with psoriasis had a higher risk of nearly all outcomes, including depressive symptoms (OR 1.38; 1.19-1.58) and panic/agoraphobia among both males (OR 1.72; 1.33-2.19) and females (OR 1.60; 1.33-1.92). Associations attenuated when restricted to doctor-diagnosed psoriasis. Associations with poor mental health were mainly observed for adolescents with psoriasis also reporting joint pain. LIMITATIONS: We could not establish temporality and lacked data on joint pain in referents. CONCLUSION: Psoriasis is associated with poor mental health in adolescents. This appears to be driven by adolescents with psoriasis also reporting joint pain and is less evident in those with a doctor-confirmed diagnosis.

Adherence to general national dietary guidelines and risk of psoriasis: results from a general population study of 105,332 individuals.

BACKGROUND: It is unknown if an unhealthy diet can affect the risk of developing psoriasis. OBJECTIVES: We hypothesised that individuals with an unhealthy diet have increased risk of prevalent and incident psoriasis. METHODS: We included 105,332 adults from the Copenhagen General Population Study, who were invited between 2003 and 2015. Response-rate was 43%. An unhealthy versus healthy diet was defined according to adherence to general national dietary guidelines. The participants were grouped into low, intermediate, and high adherence to general national dietary guidelines based on information from a food frequency questionnaire. Identification of psoriasis was made using ICD codes. RESULTS: Of the 105,332 individuals, 580 had a diagnosis of psoriasis at the time of enrolment and 640 received a diagnosis during the median follow-up of 9 years. Risk of prevalent psoriasis increased according to non-adherence to general national dietary guidelines in a stepwise manner with an age and sex adjusted odds ratio of 1.70 (95% confidence interval 1.26-2.30) in individuals with low vs. high adherence to dietary guidelines. Results were similar in a multivariable adjusted model. Prospective analyses adjusted for age and sex showed a weak association between non-adherence to dietary guidelines and risk of incident psoriasis (P for trend 0.04). This association disappeared, when adjusting for multiple confounders (P for trend 0.50). CONCLUSIONS: Although individuals with psoriasis have an unhealthier diet, diet alone does not appear to independently increase the risk of developing psoriasis.

Effects of oral roflumilast therapy on body weight and cardiometabolic parameters in patients with psoriasis - results from a randomized controlled trial (PSORRO).

BACKGROUND: Weight loss is reported with oral roflumilast, which is approved for chronic obstructive pulmonary disease (COPD). Recently, the drug has shown efficacy in psoriasis, a disease strongly linked to overweight/obesity. OBJECTIVE: To describe the effects of oral roflumilast on body weight and cardio-metabolic parameters in patients with psoriasis. METHODS: Posthoc analyses from the PSORRO study, where patients with moderate-to-severe plaque psoriasis were randomized 1:1 to oral roflumilast 500 µg once-daily or placebo for 12 weeks, followed by active, open-label treatment through week 24 in both groups. Changes in body weight, blood pressure, gastrointestinal symptoms, and laboratory tests were registered. No lifestyle or dietary interventions were applied. RESULTS: Forty-six patients were randomized. Baseline characteristics across groups were comparable; mean weight was 103.6 kg. In patients receiving roflumilast, median weight change was -2.6% and -4% at week 12 and 24, respectively. Corresponding numbers were 0.0% and 1.3% in patients initially allocated to placebo. Reduced appetite was more frequent with active therapy. No changes in blood pressure or laboratory tests were observed. LIMITATIONS: Posthoc analyses and low numbers. CONCLUSION: Oral roflumilast induced weight loss and reduced appetite, which support the growing evidence of roflumilast as an attractive treatment alternative for patients with psoriasis.

Stratum Corneum Lipids in Non-Lesional Atopic and Healthy Skin following Moisturizer Application: A Randomized Clinical Experiment.

INTRODUCTION: It is an international standard to recommend patients with atopic dermatitis (AD) to use moisturizers; however, little is known about their effect on lipids in the stratum corneum (SC). METHODS: In this randomized clinical experiment of 30 Caucasian participants (15 with AD and 15 healthy controls), the superficial SC lipid profile was assessed through tape stripping non-lesional skin following treatment thrice daily for seven days with a moisturizer, and subsequently compared with untreated skin. RESULTS: No discernible disparity in superficial SC lipid quantity was evident between the AD group and the control group. However, the SC lipid composition diverged significantly, with the AD group exhibiting diminished levels of long-chain EO CERs (p = 0.024) and elevated levels of short-chain C34 CERs (p = 0.025) compared to healthy skin. Moisturizer application significantly reduced the total SC lipids and all lipid subgroups in both groups. Within the AD group, a non-significant inclination towards an augmentation in EO CERs (p = 0.053) and reduction in C34 CERs (p = 0.073) was observed. CONCLUSION: The recent identification of distinctions in SC lipid composition between AD and healthy skin was substantiated by our findings. Topical moisturizer application, despite reducing overall total lipids, indicated a potential tendency towards a healthier lipid constitution in AD skin.

Self-management Support for Patients with Atopic Dermatitis: A Qualitative Interview Study.

Patients with a chronic skin disease, eg, atopic dermatitis, need self-management skills to increase their quality of life. We explored patients' needs for self-management support from healthcare professionals and how these needs can be met in a dermatology setting. Interpretive description methodology was chosen for iterative data collection and analysis of qualitative interviews with patients with atopic dermatitis. Two mutually dependent themes were found to be supportive of patients' self-management. Personal and disease-related recognition was fundamental to successful support. However, guidance for agenda-setting from healthcare professionals was also needed on the wide range of topics that could be covered in the consultation based on individual needs. Patients need self-management support in addition to what can be found with family, friends, or peers. It is crucial that the support is delivered with an appreciative approach by healthcare professionals with profound knowledge of atopic dermatitis. Equally important is guidance towards agenda-setting, a way to co-construct the consultation with a clear focus on the specific patient's needs.

Defining disease severity in atopic dermatitis and psoriasis for the application to biomarker research- an inter-disciplinary perspective.

More severe atopic dermatitis (AD) and psoriasis are associated with a higher cumulative impact on quality of life, multimorbidity and healthcare costs. Proactive, early intervention in those most at risk of severe disease may reduce this cumulative burden and modify the disease trajectory to limit progression. The lack of reliable biomarkers for this at-risk group represents a barrier to such a paradigm shift in practice. To expedite discovery and validation, the BIOMAP consortium (Biomarkers in AD and Psoriasis, a large-scale European, inter-disciplinary research initiative) has curated clinical and molecular data across diverse study designs and sources including cross-sectional and cohort studies (small scale through to large multi-centre registries), clinical trials, electronic health records and large-scale population-based biobanks. We map all dataset disease severity instruments and measures to three key domains (symptoms, inflammatory activity and disease course), and describe important co-dependencies and relationships across variables and domains. We prioritise definitions for more severe disease with reference to international consensus, reference standards and/or expert opinion. Key factors to consider when analysing datasets across these diverse study types include explicit early consideration of biomarker purpose and clinical context, candidate biomarkers associated with disease severity at a point in time and over time and how they are related, taking the stage of biomarker development into account when selecting disease severity measures for analyses and, validating biomarker associations with disease severity outcomes using both physician- and patient-reported measures and across domains. The outputs from this exercise will ensure coherence and focus across the BIOMAP consortium so that mechanistic insights and biomarkers are clinically relevant, patient-centric and more generalisable to current and future research efforts.

BIOSKIN: A Protocol for the Copenhagen Translational Skin Immunology Biobank and Research Programme.

INTRODUCTION: Psoriasis, atopic dermatitis and contact dermatitis are common chronic inflammatory skin diseases that have a significant impact on individuals and society. METHODS AND ANALYSIS: The Copenhagen Translational Skin Immunology Biobank and Research Programme (BIOSKIN) is a translational biobank and research study that aims to prospectively collect high-quality biological samples and clinical data from 3000 patients with psoriasis, atopic dermatitis and contact dermatitis over a minimum period of 5 years. The longitudinal open design allows participants to enter and leave the study at different time points depending on their disease and treatment course. At every visit, the investigator collects biological samples, conducts interviews and assembles self-reported questionnaires on disease-specific and general health-related information. Clinical examination and biological sampling will be conducted at enrolment, during and after disease flare, before and after initiation of new treatment and at least once per year. The clinical examination includes dermatological verification of diagnosis, evaluation of disease severity and detailed information on phenotype. The biological samples include blood and when accessible and relevant, skin biopsies, tape strips and skin swabs. The data collected will undergo rigorous statistical analysis using appropriate analytical methods. As of December 2023, 825 patients have been enrolled in the study. ETHICS AND DISSEMINATION: The study is approved by the Scientific Ethical Committee of the Capital Region (H-21032986) and the Danish Data Protection Agency. Results will be published in peer-reviewed scientific journals and presented at national and international conferences.

Does Systemic Anti-Psoriatic Treatment Impact the Risk of Cardiovascular Disease? A Review Over Cardiovascular Imaging Studies.

Psoriasis is an immune-mediated inflammatory disease associated with an increased risk of cardiovascular disease (CVD). The risk of CVD increases with the severity of psoriasis, and exposure to systemic inflammation may partly explain the increased risk of CVD in these patients. This raises the question of whether anti-psoriatic treatment, in addition to treating the skin lesions, also lowers the risk of developing CVD. Different types of studies have examined the impact of systemic anti-psoriatic treatments on the risk of CVD in patients with psoriasis and epidemiological observational studies with, e.g., myocardial infarction and stroke as outcomes, and clinical studies investigating circulating inflammatory biomarkers in the blood indicate that anti-psoriatic therapy has a protective effect; however, no randomized controlled trial (RCT) has examined the impact of systemic anti-psoriatic treatment on future hard cardiovascular endpoints. This narrative review provides an overview of the clinical cardiovascular imaging studies examining the effect of systemic anti-psoriatic treatment on the risk of subclinical CVD in patients with psoriasis. We found a total of 24 clinical imaging studies, where 16 of these were observational cohort studies and eight were RCTs. The observational studies suggest an improvement in the risk of subclinical CVD based on different cardiovascular imaging biomarkers; however, the RCTs showed inconsistent results and mainly included vascular inflammation as the outcome. Future RCTs including other imaging biomarkers as surrogates for subclinical CVD, with longer follow-up and with hard cardiovascular endpoints are warranted to address whether systemic anti-psoriatic treatments reduce the risk of CVD.

In-Depth Proteomic Map of Innate Lymphoid Cells from Healthy Human Skin and Blood.

Innate lymphoid cells (ILCs) are essential players in the skin-associated immune system, nevertheless little is known about their proteomes and proteomic diversity. In this study, we describe about 6,600 proteins constitutively expressed by ILC2s and ILC3s from healthy human skin and blood using state-of-the-art proteomics. Although the vast majority of proteins was expressed by both ILC subsets and in both compartments, the skin ILC2s and ILC3s were more distinct than their counterparts in blood. Only skin ILC3s expressed uniquely detected proteins. Our in-depth proteomic dataset allowed us to define the cluster of differentiation marker profiles of the ILC subsets, explore distribution and abundance of proteins known to have immunological functions, as well as identify subset-specific proteins that have not previously been implicated in ILC biology. Taken together, our analyses substantially expand understanding of the protein expression signatures of ILC subsets. Going forward, these proteomic datasets will serve as valuable resources for future studies of ILC biology.

Proteins in the Skin and Blood in Patients with Psoriasis: A Systematic Review of Proteomic Studies.

BACKGROUND: Proteins play a central role in psoriasis as they are involved in the structural phenotypic changes and inflammation that characterize the disease. This systematic review aimed to assess which proteins have been consistently reported as upregulated or downregulated in the skin and blood from patients with psoriasis. METHODS: We included proteomic studies reporting differentially expressed proteins (DEPs) in at least one of four predefined comparisons using a standardized procedure to extract and align data. Network analysis of functional protein associations was made with StringApp in Cytoscape. A protocol for this review was registered in the PROSPERO database (ref:CRD42022363226). RESULTS: We identified and assessed 772 studies published between December 2, 1996, and April 28, 2023, among which 30 studies met the inclusion and data availability criteria for analysis that together reported a sum of 5,314 DEPs. The majority of consistently reported upregulated and downregulated proteins were found in lesional versus non-lesional skin (n = 313), followed by lesional versus healthy skin (n = 185), blood from patients with psoriasis versus blood from healthy individuals (n = 140), and non-lesional versus healthy skin (n = 1). Network analysis of upregulated proteins revealed different functional clusters with interleukin (IL)-6, IL-8, IL-17A, C-C motif chemokine (CCL) 20, signal transducer and activator of transcription (STAT) 3, and interferon (IFN)-γ along with less well-studied proteins playing central roles. Some of the reported changes are associated with anti-inflammatory effects. Additionally, the proteomic dysregulation also included antimicrobial peptides, alarmins, angiogenic factors, and proteins related to protein synthesis. CONCLUSION: Our findings generally support current understandings of the pathological mechanisms in psoriasis. Importantly, some consistent findings have not been discussed before and deserve attention in future research.

Oral glucose has little or no effect on appetite and satiety sensations despite a significant gastrointestinal response.

OBJECTIVE: The effect of oral glucose-induced release of gastrointestinal hormones on satiety and appetite independently of prevailing plasma glucose excursions is unknown. The objective is to investigate the effect of oral glucose on appetite and satiety sensations as compared to isoglycemic IV glucose infusion (IIGI) in healthy volunteers. DESIGN: A crossover study involving two study days for each participant. PARTICIPANTS: Nineteen healthy participants (6 women, mean age 55.1 [SD 14.2] years; mean body mass index 26.7 [SD 2.2] kg/m2). INTERVENTIONS: Each participant underwent a 3-h 50-g oral glucose tolerance test (OGTT) and, on a subsequent study day, an IIGI mimicking the glucose excursions from the OGTT. On both study days, appetite and satiety were indicated regularly on visual analog scale (VAS), and blood was drawn regularly for measurement of pancreatic and gut hormones. PRIMARY OUTCOMES: Difference in appetite and satiety sensations during OGTT and IIGI. RESULTS: Circulating concentrations of glucose-dependent insulinotropic polypeptide (P < .0001), glucagon-like peptide 1 (P < .0001), insulin (P < .0001), C-peptide (P < .0001), and neurotensin (P = .003) increased significantly during the OGTT as compared to the IIGI, whereas glucagon responses were similarly suppressed (P = .991). Visual analog scale-assessed ratings of hunger, satiety, fullness, thirst, well-being, and nausea, respectively, were similar during OGTT and IIGI whether assessed as mean 0-3-h values or area under the curves. For both groups, a similar, slow increase in appetite and decrease in satiation were observed. Area under the curve, for prospective food consumption (P = .049) and overall appetite score (P = .044) were slightly lower during OGTT compared to IIGI, whereas mean 0-3-h values were statistically similar for prospective food consumption (P = .053) and overall appetite score (P = .063). CONCLUSIONS: Despite eliciting robust responses of appetite-reducing and/or satiety-promoting gut hormones, we found that oral glucose administration has little or no effect on appetite and satiety as compared to an IIGI, not affecting the release of appetite-modulating hormones. TRIAL REGISTRY NO: ClinicalTrials.gov: NCT01492283 and NCT06064084.

Alopecia areata.

Alopecia areata (AA) is an autoimmune disease where inflammation around the lowest part of the hair follicle results in non-scarring hair loss. This review investigates the course of the disease, its unpredictability and variation from a single patch of scalp hair loss to the loss of all hair on the body. The first drug with AA indication was approved in 2022, the JAK-inhibitor baricitinib. This paves the way for future research that may lead to the development of new effective pathogenesis-specific treatments.

The importance of diet in psoriasis.

The impact of diet on psoriasis is not well studied but it is of interest to many patients. A hypocaloric diet with corresponding weight loss can reduce psoriasis severity in overweight or obese patients and should be considered an important supplement to conventional therapy, as argued in this review. Gluten-free diet might improve severity of psoriasis in patients with coeliac disease or merely presence of coeliac-specific antibodies. Mediterranean diet might also be beneficial. Overall, studies do not support a beneficial effect of micronutrient supplements (i.e., vitamin D, selenium, vitamin B12) in patients with normal serum levels.

Response to Interleukin-17A Inhibitors According to Prior Biologic Exposures: A Danish Nationwide Study.

Whether response to an interleukin (IL-17) inhibitor is different in patients with previous exposure to an IL-17 inhibitor compared with patients with exposure to biologics with other cytokine targets remains to be elucidated. Therefore, the aim of this study was to  assess whether previous exposure to an IL-17A inhibitor was associated with worse response than exposure to (an)other biologic(s). All patients in the DERMBIO register treated with an IL-17A inhibitor (secukinumab or ixekizumab) were included. With an absolute Psoriasis Area and Severity Index (PASI) ≤ 2 as response, the proportion of responders treated with IL-17A inhibitors was assessed in patients previously treated with another IL-17A inhibitor and compared with patients with previous exposure to (an)other biologic(s), using a χ2 test. In total, 100, 93 and 83 patients with  previous exposure to an IL-17A inhibitor and 414, 372 and 314 patients with previous exposure to (an) other biologic(s) were assessed after 3, 6 and 12 months, respectively. No differences in the proportion of  patients achieving PASI ≤ 2 were observed between the 2 groups after 3 months (54% vs 57%, p = 0.59), 6months (70% vs 66%, p = 0.42) and 12 months (69% vs 60%, p = 0.14). In conclusion, when treating patients with IL-17A inhibitors the cytokine target of the previous biologic does not appear to affect the  response.

Use of systemic and biological therapy in patients with moderate-to-severe psoriasis.

BACKGROUND: Patients with moderate-to-severe psoriasis are candidates for systemic treatment, but it is unknown how many receive such therapy at a national level in Denmark. OBJECTIVES: We aimed to determine the prevalence of conventional systemic therapy use in patients with moderate-to-severe psoriasis and, further, to investigate the time to discontinuation of conventional systemic therapy and initiation of biological therapy among biologic-naïve patients. METHODS: This registry-based study identified a cohort of patients with psoriasis in Denmark. We estimated the prevalence of moderate-to-severe psoriasis at a national level using registry data. Inverse probability weighting was used to mitigate potential selection bias in the prevalence estimate of moderate-to-severe psoriasis. Analyses were then performed on the weighted cohort. RESULTS: Of patients with psoriasis in Denmark, 10.9% were estimated to have moderate-to-severe psoriasis, of whom 62.3% received either conventional systemic or biological therapy, meaning 37.7% who were considered candidates for systemic therapy did not receive any systemic treatment. The study demonstrated that, comparing previous time periods with more recent years: (i) time on conventional systemic therapy for patients with moderate-to-severe psoriasis has become shorter, with a median (interquartile range) of 3.0 years (0.6-10.0) in 1985-1994 vs. 0.6 years (0.3-2.0) in 2014-2018; (ii) more patients initiated biologics as second-line therapy, with 69.5% in 2010-2013 vs. 71.2% in 2014-2018; and (iii) the median time from initiation of systemic therapy to initiation of biological therapy decreased from 13.3 years (11.5-16.8) in 2010-2013 to 1.9 years (1.7-2.4) in 2014-2018. CONCLUSIONS: This study found that nearly 37.7% of Danish patients with moderate-to-severe psoriasis do not receive systemic treatment even though they would qualify for this. Furthermore, for patients treated with conventional systemics, drug survival decreased during the observation period.

The association between Staphylococcus aureus colonization on cheek skin at 2†months and subsequent atopic dermatitis in a prospective birth cohort.

BACKGROUND: Staphylococcus aureus may worsen already established atopic dermatitis (AD), but its primary role in the aetiopathogenesis and severity of AD is unclear. OBJECTIVES: To compare the prevalence of S. aureus colonization in early infancy in children who developed AD during the first 2 years of life with children who did not. METHODS: In this prospective birth cohort study, which included 450 infants, we analysed bacterial swabs collected from cheek skin at 0 and 2 months of age. The development of AD, and its severity, was diagnosed by a physician and monitored prospectively for 2 years. Information on parental atopy, filaggrin gene mutation status and use of antibiotics and emollients was included in the analyses. RESULTS: At birth, the occurrence of S. aureus colonization was similar in infants who developed subsequent AD and those who did not. At 2 months of age, S. aureus colonization was more common in children who later developed AD (adjusted hazard ratio 1.97, 95% confidence interval 1.21-3.19; P = 0.006). No association was found between S. aureus colonization and AD severity or age at onset. CONCLUSIONS: It remains unknown whether colonization with S. aureus may directly increase the risk of AD, or whether it should be considered as secondary to skin barrier impairment or a skewed immune activity, but according to our findings, S. aureus colonization is more commonly increased at 2 months of age in children who later developed AD.