Characterization of patients with atopic dermatitis based on flare patterns and severity of disease: A Danish population-based study.

BACKGROUND: Flare patterns are not routinely considered in the severity classification or in clinical decision-making of atopic dermatitis (AD), but frequent or severe flares may contribute considerably to the disease burden. OBJECTIVES: To characterize patients with AD in relation to their flare pattern and compare flare patterns to disease severity, life quality and treatment satisfaction. METHODS: Patients with AD from the Danish Skin Cohort were included if they had active AD with and available data on number of flare-ups within the last 12 months. Categorical variables were presented as frequencies and percentages, whereas numerical variables were presented as median and interquartile ranges (IQR). Between-group differences were tested with chi-squared tests. RESULTS: A total of 1557 patients were included, with 57 reporting 0 flares, 698 (1-5 flares), 324 (6-10 flares) and 478 reporting >10 flares during the past 12 months. Both the severity measured by PO-SCORAD and the impairment of life quality measured by DLQI were higher among patients with more flares (median [IQR] PO-SCORAD: 13.0 [5.6-22.3], 29.7 [20.8-40.6], 36.3 [26.7-47.6]and 42.9 [30.7-55.6], respectively for the four flares strata, and median [IQR] DLQI: 1.0 [0.0-2.0], 3.0 [1.0-7.0], 4.0 [1.8-9.0] and 7.0 [3.0-11.0]). Satisfaction with the current treatment was generally higher among patients with no flares. However, 36.8%, 24.6% and 23.7% of patients with 1-5, 6-10 and >10 flares reported being extremely or very satisfied with their current treatment. CONCLUSIONS: Patients with many flares often report a higher severity and impairment of life quality compared to patients with fewer flares. Information on flaring could benefit treatment decisions, thereby decreasing undertreatment of patients with mild AD but severe flaring.

The association between psoriasis and chronic obstructive pulmonary disease: a systematic review and meta-analysis.

INTRODUCTION: Psoriasis is a chronic T-cell-mediated inflammatory and proliferative skin disease. Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the airways. COPD has been studied as a comorbidity of psoriasis, but the association needs further study, hence the objective of this study. EVIDENCE ACQUISITION: A systematic review was performed using the database PubMed and 155 records were found including the ones found through references. Seven records were found eligible for this study including six observational studies and one experimental study with a total of 229,075 participants. The odds ratio of COPD in patients with psoriasis and healthy subjects was analysed using a random effects model. EVIDENCE SYNTHESIS: The pooled data showed a significant association (OR=1.77, 95% CI [1.32; 2.39]) between psoriasis and COPD with high inter-study heterogeneity (I2=96%). Sub-analyses of the different types of studies (cohort study: OR=2.53 [2.43; 2.63], case-control study: OR=1.6 [0.03; 100.96] and cross-sectional study: OR=1.57 [0.58; 4.22]) and smoking status (OR=1.7 [0.69; 4.14]) were also performed to further examine the association. CONCLUSIONS: There is a significant association between psoriasis and COPD, but the underlying mechanism and how smoking status affects the results remain unclear and need further study. Physicians should be aware of the risk and its seriousness to provide better and more targeted treatment.

Artificial intelligence and allergic rhinitis: does ChatGPT increase or impair the knowledge?

BACKGROUND: Optimal management of allergic rhinitis requires patient education with easy access to accurate information. However, previous online platforms have provided misleading information. The demand for online medical information continues to grow, especially with the introduction of advanced chatbots like ChatGPT. METHODS: This study aimed to evaluate the quality of information provided by ChatGPT regarding allergic rhinitis. A Likert scale was used to assess the accuracy of responses, ranging from 1 to 5. Four authors independently rated the responses from a healthcare professional's perspective. RESULTS: A total of 20 questions covering various aspects of allergic rhinitis were asked. Among the answers, eight received a score of 5 (no inaccuracies), five received a score of 4 (minor non-harmful inaccuracies), six received a score of 3 (potentially misinterpretable inaccuracies) and one answer had a score of 2 (minor potentially harmful inaccuracies). CONCLUSIONS: The variability in accuracy scores highlights the need for caution when relying solely on chatbots like ChatGPT for medical advice. Patients should consult qualified healthcare professionals and use online sources as a supplement. While ChatGPT has advantages in medical information delivery, its use should be approached with caution. ChatGPT can be useful for patient education but cannot replace healthcare professionals.

Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis-a randomized controlled trial (PSORRO).

Background: Roflumilast is a targeted inhibitor of phosphodiesterase (PDE)-4 and has been approved for treatment of severe chronic obstructive pulmonary disease for more than a decade. Generic versions are available in the United States. PDE-4 is involved in the psoriasis pathogenesis, but the efficacy and safety of oral roflumilast in patients with psoriasis have not previously been studied. Methods: A company-independent, multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.govNCT04549870). Patients were randomized 1:1 to receive monotherapy with oral roflumilast 500 µg once daily or placebo. At week 12, placebo patients were switched to open-label roflumilast through week 24. The primary endpoint was a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI75) at week 12. Findings: In all, 46 patients were randomized (roflumilast, n = 23; placebo, n = 23). At week 12, significantly more patients in the active arm achieved PASI75 (8 of 23 patients [35%]) vs. placebo (0 of 23 patients [0%], with a difference vs. placebo of 8 [35%] patients, 95% CI: 3 [13%]-13 [57%] patients) (p = 0.014). At week 24, 15 (65%), 10 (44%), 5 (22%), and 2 (9%) of patients treated with roflumilast from week 0 had PASI50, PASI75, PASI90, and PASI100 responses (key secondary endpoints), respectively. The most prevalent, drug-related adverse events in both treatment groups were transient gastrointestinal symptoms, weight-loss, headache, and insomnia. A total of three patients (roflumilast n = 2; placebo, n = 1) discontinued therapy due to adverse events. Interpretation: Oral roflumilast was efficacious and safe in treating moderate-to-severe plaque psoriasis over 24 weeks. With generic versions available, this drug may represent an inexpensive and convenient alternative to established systemic psoriasis treatments. Funding: Financial support was received from Herlev and Gentofte Hospital, University of Copenhagen, and independent grants from private foundations in Denmark. No pharmaceutical company, including the market authorization holder of roflumilast, was involved in the study at any point.

Assessing anatomical distribution of atopic dermatitis identifies a cluster of patients with late onset and low risk of asthma and allergy: An observational study.

Background and Aims: A better understanding of distinct subgroups in atopic dermatitis (AD) is warranted. The aim was to identify and determine characteristics of clusters based on anatomical location of AD. Methods: In this 8-week, observational, decentralized study, patients with AD completed a baseline questionnaire about anatomical location and severity of AD, and a principal component analysis (PCA) was applied to identify clusters. The Patient-Oriented Eczema Measure (POEM) was completed weekly and photographs of affected body areas were captured by the participants' own smartphones. From the weekly photographs, the AD severity was evaluated using the intensity part of the SCORing Atopic Dermatitis. Results: Fifty-five participants were recruited, of which 53 completed the baseline questionnaire with a mean POEM of 14.5 (SD: 5.6). The PCA analysis revealed three clusters, with AD predominantly on the shins, knees, and genitals (Cluster 1), with involvement of the upper body (Cluster 2), and with AD on the hands and feet (Cluster 3). Cluster 1 had a lower mean POEM score (11.12, SD: 5.3) compared with Clusters 2 (12.64, SD: 4.5) and 3 (15.98, SD: 4.7), respectively (p = 0.007). Further, Cluster 1 had the highest age of AD onset (mean 9.5 vs. 2.5 and 4.7 years, p = 0.02) and the lowest proportion of asthma/allergy (47% vs. 82% and 90%, p = 0.01). Conclusion: Three clusters of patients with AD based on affected body areas were identified. The cluster with involvement of legs and genitals was characterized by the oldest age of AD onset and the lowest prevalence of asthma/allergy.

Reduced Skin Microbiome Diversity in Infancy Is Associated with Increased Risk of Atopic Dermatitis in High-Risk Children.

It is currently unknown whether alterations in the skin microbiome exist before development of atopic dermatitis (AD). In this prospective Danish birth cohort of 300 children, we examined whether skin microbiome alterations during the first 2 months of life were associated with an increased risk of AD in the first 2 years and its severity after adjustment for environmental factors and selected skin chemokine and natural moisturizing factor levels. We found no overall association between the skin microbiome at birth and age 2 months and AD during the first 2 years of life. However, when restricting the analysis to children with at least one parent with atopy, a lower alpha diversity at age 2 months was associated with an increased risk of AD (adjusted hazard ratio = 1.7, 95% confidence interval = 1.1-2.6). We observed a stronger association in children where both parents had atopy (adjusted hazard ratio = 4.4, 95% confidence interval = 1.1-18.2). The putative pathogenic role of changes in the skin microbiome on AD risk remains uncertain but may play a role in those with an atopic predisposition.

Association of homelessness and skin conditions: a Danish population-based cohort study.

BACKGROUND: Research has linked homelessness with an increased risk of skin conditions. However, representative studies of diagnosis-specific information on skin conditions in people experiencing homelessness are lacking. OBJECTIVES: To examine the association between homelessness and diagnosed skin conditions, prescribed medication and type of -consultation. METHODS: This cohort study included data from the Danish nationwide health, social and administrative registers from 1 January 1999 to 31 December 2018. All people of Danish origin living in Denmark and aged at least 15 years at some point during the study period were included. Homelessness, measured by homeless shelter contacts, was the exposure. The outcome was any diagnosis of a skin disorder and specific skin disorders recorded in the Danish National Patient Register. Information on diagnostic consultation type (i.e. dermatological, nondermatological and emergency room) and dermatological prescriptions was studied. We estimated adjusted incidence rate ratio (aIRR) (adjusted for sex, age and calendar year) and cumulative incidence. RESULTS: In total, 5 054 238 individuals (50.6% female) were included in the study population, accounting for 73 477 258 person-years at risk, with a start mean (SD) age of 39.4 (21.1) years. Of the total number of individuals, 759 991 (15.0%) received a skin diagnosis and 38 071 (0.7%) experienced homelessness. A 2.31-times [95% confidence interval (CI) 2.25-2.36] higher IRR of any diagnosed skin condition was associated with homelessness, higher for nondermatological and emergency room consultations. Homelessness was associated with a reduced IRR of a skin neoplasm diagnosis (aIRR 0.76, 95% CI 0.71-8.82) compared with no homelessness. By the end of follow-up, 2.8% (95% CI 2.5-3.0) of individuals experiencing homelessness had a skin neoplasm diagnosis vs. 5.1% (95% CI 4.9-5.3) of individuals not experiencing homelessness. Five or more shelter contacts during the first year from first contact was associated with the highest aIRR of any diagnosed skin condition (7.33, 95% CI 5.57-9.65) compared with no contacts. CONCLUSIONS: Individuals experiencing homelessness have high rates of most diagnosed skin conditions, but a lower occurrence of skin cancer diagnosis. Diagnostic and medical patterns for skin disorders differed clearly between people experiencing homelessness and individuals without these experiences. The time after first homeless shelter contact is an important window of opportunity for mitigating and preventing skin disorders.

The association between atopic dermatitis, cognitive function and school performance in children and young adults.

BACKGROUND: Children with atopic dermatitis (AD) may have disturbed sleep, affected self-esteem and decreased quality of life, likely interfering with performance in school. OBJECTIVES: To examine the association between hospital-managed paediatric AD, school performance and cognitive function. METHODS: In this cross-sectional study we linked data from the Danish national registers and identified three populations between 2001 and 2019. Population 1 comprised children with graduation grades registered from lower secondary school, population 2 comprised adolescents with registration of an upper secondary graduation mean, and population 3 comprised male conscripts with registration of an IQ test score. AD was defined as a hospital diagnostic code (inpatient or outpatient) prior to the exam or conscription date, and was stratified according to severity, activity and atopic comorbidity. Outcomes included graduation mean from lower and upper secondary school, special educational assistance in primary and lower secondary school, and IQ at conscription. RESULTS: In total, 770 611 (12 137 with AD), 394 193 (6261 with AD) and 366 182 (4539 with AD) children and adolescents were included in populations 1 (lower secondary graduation), 2 (upper secondary graduation) and 3 (conscription), respectively. In lower secondary school, children with severe AD had significantly lower overall, written and oral graduation grade means compared with children with mild AD: respectively, difference -0.29 [95% confidence interval (CI) -0.45 to -0.13, P < 0.001], difference -0.26 (95% CI -0.42 to -0.10, P = 0.0016) and difference -0.30 (95% CI -0.49 to -0.11, P = 0.0018). In upper secondary school, adolescents with AD performed similarly to their peers without AD. Young men with AD scored significantly lower IQ test means at conscription examination than male conscripts without AD: difference -0.60 (95% CI -0.87 to -0.32, P < 0.001). CONCLUSIONS: AD, in particular when severe, is associated with lower school performance in childhood and IQ in young men, which can interfere with academic achievements in life. Optimization of treatment of children with AD and specific educational support to children with severe AD could be needed.

Elevating the Standard of Care for Patients with Psoriasis: 'Calls to Action' from Epicensus, a Multistakeholder Pan-European Initiative.

INTRODUCTION: Despite advances in treatment options and the management of patients with psoriasis, considerable unmet needs remain. Our objective was to identify ways to elevate the standard of care for patients with psoriasis by combining the perspectives of three important stakeholders: patients, clinicians and payors, and define 'Calls to Action' designed to achieve the identified changes. METHODS: Eight themes relevant to elevating the standard of care were identified from an insights-gathering questionnaire completed by all three stakeholder groups. A modified Delphi exercise gained consensus on statements informed by the insights. Statements were then used to inspire 'Calls to Action' - practical steps that could be taken to realise the desired changes and elevate the standard of care. RESULTS: In total, 18 European experts (10 dermatologists, 3 payors and 5 patient representatives) took part in the Delphi process. Consensus was reached on statements relating to all eight themes: improve healthcare systems to better support multidisciplinary team working and digital services, real-world data generation and optimal use, improve patient access, elevate quality-of-life measures as the most important outcomes, involve patients in patient-centred and personalised approaches to care, improve the relevance and reach of guidelines, education, and multistakeholder engagement. 'Calls to Action' common to all three stakeholder groups recognised the need to capitalise on the shift to digital healthcare, the need for consistent input into registries to generate real-world evidence to support guideline development, and the necessity of educating patients on the benefits of reporting outcomes to generate real-world data. The enormous quality-of-life burden and psychological impact of psoriasis, as well as the clinical needs of patients must be better understood, including by healthcare commissioners, so that funding priorities are assessed appropriately. CONCLUSION: This unique initiative identified a practical 'Call-to-Action Framework' which, if implemented, could help improve the standard of care for patients with psoriasis.

Despite improvements in the management of psoriasis, there is room for the standard of care for patients to be improved further. The aim of the 'Epicensus' programme is to help realise improvements by bringing together three important stakeholder groups involved in the care of patients with psoriasis: dermatologists, payors and patient representatives. First, unmet needs were explored with these stakeholders and eight themes for change were identified: 1) improve healthcare systems to better support multidisciplinary team working and digital services; 2) optimise real-world data generation and use; 3) improve patient access; 4) elevate quality-of-life measures as the most important outcomes; 5) involve patients in people-centred and personalised approaches to care; 6) improve the relevance and reach of guidelines; 7) education; 8) multistakeholder engagement. Next, a panel of experts representing the three stakeholder groups took part in a consensus process (Delphi) to reach agreement on statements relating to each of the eight themes. The statements describe current problems and what needs to be changed to raise the standard of care for patients with psoriasis. Some of the problems identified are similar to those that existed a decade ago, showing that simply recognising what needs to change is not enough to bring about improvements: action must be taken. Therefore, the Epicensus participants met to produce specific 'Calls to Action'­ practical steps described in this publication that, if put into practice, should contribute to an improvement in the standard of care for patients with psoriasis.

Skin TARC/CCL17 increase precedes the development of childhood atopic dermatitis.

BACKGROUND: It is unknown whether skin biomarkers collected in infancy can predict the onset of atopic dermatitis (AD) and be used in future prevention trials to identify children at risk. OBJECTIVES: This study sought to examine whether skin biomarkers can predict AD during the first 2 years of life. METHODS: This study enrolled 300 term and 150 preterm children at birth and followed for AD until the age of 2 years. Skin tape strips were collected at 0 to 3 days and 2 months of age and analyzed for selected immune and barrier biomarkers. Hazard ratio (HR) with 95% confidence interval (CI) using Cox regression was calculated for the risk of AD. RESULTS: The 2-year prevalence of AD was 34.6% (99 of 286) and 21.2% (25 of 118) among term and preterm children, respectively. Skin biomarkers collected at birth did not predict AD. Elevated thymus- and activation-regulated chemokine/C-C motif chemokine ligand 17 -levels collected at 2 months of age increased the overall risk of AD (HR: 2.11; 95% CI: 1.36-3.26; P = .0008) and moderate-to-severe AD (HR: 4.97; 95% CI: 2.09-11.80; P = .0003). IL-8 and IL-18 predicted moderate-to-severe AD. Low filaggrin degradation product levels increased the risk of AD (HR: 2.04; 95% CI: 1.32-3.15; P = .001). Elevated biomarker levels at 2 months predicted AD at other skin sites and many months after collection. CONCLUSIONS: This study showed that noninvasively collected skin biomarkers of barrier and immune pathways can precede the onset of AD.

The road to biologics in patients with hidradenitis suppurativa: a nationwide drug utilization study.

BACKGROUND: Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's treatment journey leading to biologic therapy is unclear. OBJECTIVES: To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy. METHODS: We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients' treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables. RESULTS: A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214; 95·1%), dicloxacillin (n = 194; 86·2%), tetracycline (n = 145; 64·4%) and rifampicin/clindamycin (n = 111; 49·3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4·0 (SD 1·3) different systemic therapies, across a mean of 16·9 (SD 11·3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15·3 (SD 5·1) years [8·2 (SD 5·9) years when excluding penicillin and dicloxacillin]. CONCLUSIONS: Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression. What is already known about this topic? The treatment journey leading to biologic therapy in patients with HS has not previously been investigated. What does this study add? Our data from 225 patients with HS illustrate that patients who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS.

Assessment of Frequency of Rosacea Subtypes in Patients With Rosacea: A Systematic Review and Meta-analysis.

Importance: Four distinct rosacea subtypes have traditionally been recognized, but the frequency of these subtypes among patients with rosacea remains unknown. Objective: To assess the frequency of 4 rosacea subtypes. Data Sources: This systemic review and meta-analysis included a search of 2 databases, PubMed and Embase, from inception of the databases to November 2, 2021. The search was filtered to include only studies of human participants published in English, French, and German. Study Selection: Studies were screened independently by 2 of the authors and were included if they were original with a sample size of 25 or more patients and reported absolute numbers or frequency of patients affected by rosacea subtypes. Studies that did not report sufficient data to calculate the proportions of subtypes were excluded. Data Extraction and Synthesis: Data extraction was performed independently and in duplicate by 2 of the authors, using the search term rosacea, according to the Preferred Reporting items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search term, objectives, and study protocol methods were defined before the study was initiated. A total of 292 studies were included for full-text assessment. Owing to the heterogeneity of the included studies, a random-effects model was used. Main Outcome and Measures: The main outcome was the proportion of patients with rosacea in each of the 4 major subtype groups defined by the 2002 National Rosacea Society classification system. Measures were absolute numbers or frequency of patients affected by each of the 4 rosacea subtypes. Results: A total of 39 studies examining 9190 patients with rosacea were included. The pooled proportion of erythematotelangiectatic rosacea was 56.7% (95% CI, 51.4%-62.0%), of papulopustular rosacea was 43.2% (95% CI, 38.8%-47.6%), of phymatous rosacea was 7.4% (95% CI, 6.1%-8.9%), and of ocular rosacea was 11.1% (95% CI, 6.7%-16.3%). Subtype distribution occurred equally among men and women except for phymatous rosacea, which was more prevalent in men. Studies from Africa showed the lowest proportion of erythematotelangiectatic rosacea. Differences in frequency of subtypes were observed when stratification by publication year was performed. Conclusion and Relevance: In this systematic review and meta-analysis, differences were found in rosacea subtypes by patient sex and by continent of origin and publication year of included studies. Erythematotelangiectatic and papulopustular rosacea were the most prevalent subtypes, but data should be interpreted with caution. Future studies should use the phenotype-based rosacea approach.

Treatment Patterns and Clinical Outcomes of Chronic Urticaria: Two-year Follow-up Results from the Scandinavian AWARE Study.

The AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) study investigated outcomes in patients with chronic urticaria refractory to H1-antihistamine. The objective of the current study was to analyse the effects of treatment on patients' symptoms and quality of life for a period of up to 2 years. Over the 2 years, there was clear improvement in the high rates of disease burden from baseline, as evidenced by lower scores for disease severity scales, better quality of life, and a decreasing rate of medical resource utilization. However, this is the result of treatment adherence to the guidelines in highly specialized Scandinavian urticaria centres, and has its basis in the relatively low treatment intensity and control at enrolment. There is a need for greater adherence to the treatment guidelines and better management of antihistamine-refractory chronic urticaria.