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Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that has been shown to be associated with allergic comorbidities. However, studies examining comorbidities in patients with AD are incomplete, which may contribute to suboptimal care. Objectives: The objective was to compare the risk of developing different allergic and nonallergic comorbidities among adult patients with AD to that of a matched reference cohort in Sweden. Methods: This was a nationwide population-based cohort study using longitudinal data from primary and specialist care registers. AD patients were identified by confirmed diagnosis in primary or specialist care. A non-AD reference cohort was randomly drawn from the general population and matched 1:1 with the AD patients on age, gender, and geographical region. The risk of developing the following conditions was evaluated: asthma, food hypersensitivity, allergic rhinitis, neurological disorders, psychiatric disorders, infections, immunological & inflammatory disorders, type 1 diabetes (T1D), type 2 diabetes (T2D), endocrine & metabolic disorders, skeletal disorders, ocular disorders, cardiovascular diseases, and malignancies. Results: This study included 107,774 AD patients [mild-to-moderate (n = 92,413) and severe (n = 15,361)] and an equally-sized reference cohort. AD patients displayed a higher risk of developing comorbid conditions for all investigated categories, except for T1D, compared with the reference cohort. The highest risk compared with the reference cohort was observed for allergic comorbidities followed by immunological & inflammatory disorders (hazard ratio: 2.15) and infections (hazard ratio: 2.01). Patients with AD also had higher risk of developing multiple comorbidities (2 or more). The risk of comorbidity onset increased alongside AD severity and patients with active AD were associated with increased risk of comorbidity onset compared with patients in remission. Conclusions: AD patients are at a

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with allergic comorbidities. However, studies examining comorbidities in childhood AD are incomplete, which may contribute to suboptimal care. Objective: The objective was to compare the risk of developing different allergic and non-allergic comorbidities among children with AD to that of a matched non-AD reference cohort in Sweden. Methods: This was a nationwide population-based cohort study using longitudinal data from primary and specialist care registers. Patients with AD were identified by confirmed diagnosis in primary or specialist care. The non-AD reference cohort was randomly drawn from the general population and matched 1:1 with the AD patients. The risk of developing the following conditions was evaluated: hypersensitivity and allergic disorders, neurological disorders, psychiatric disorders, infections, immunological and inflammatory disorders, Type 1 diabetes (T1D), endocrine and metabolic disorders, skeletal disorders, ocular disorders and malignancies. Results: This study included 165,145 patients with AD (mild-to-moderate [n = 126,681] and severe [n = 38,464]) and an equally sized reference cohort. Patients with AD displayed a higher risk of developing comorbid conditions for all investigated categories, except for T1D and skeletal disorders, compared with the reference cohort. The highest risk compared with the reference cohort was observed for hypersensitivity and allergic disorders (hazard ratio [HR]: 3.87), followed by malignancies (HR: 2.53) and immunological and inflammatory disorders (HR: 2.36). Patients with AD also had higher risk of developing multiple comorbidities (≥2). The risk of comorbidity onset increased alongside AD severity and patients with active AD were associated with increased risk of comorbidity onset compared with patients in remission. Conclusions: The clinical burden of AD is substantial for children with AD and patients are at an

Treat-to-target (T2T) is a pragmatic therapeutic strategy being gradually introduced into dermatology after adoption in several other clinical areas. Atopic dermatitis (AD), one of the most common inflammatory skin diseases, may also benefit from this structured and practical therapeutic approach. We aimed to evaluate existing data regarding the T2T approach in dermatology, with a specific focus on AD, as well as the views of International Eczema Council (IEC) members on the potential application of a T2T approach to AD management. To do so, we systematically searched for peer-reviewed publications on the T2T approach for any skin disease in the PubMed and Scopus databases up to February 2022 and conducted a survey among IEC members regarding various components to potentially include in a T2T approach in AD. We identified 21 relevant T2T-related reports in dermatology, of which 14 were related to psoriasis, five to AD, one for juvenile dermatomyositis and one for urticaria. In the IEC member survey, respondents proposed treatable traits (with itch, disease severity and sleep problems getting the highest scores), relevant comorbidities (with asthma being selected most commonly, followed by anxiety and depression in adults), recommended specialists that should define the approach in AD (dermatologists, allergists and primary care physicians were most commonly selected in adults), and applicable assessment tools (both physician- and patient-reported), in both adult and paediatric patients, for potential future utilization of the T2T approach in AD. In conclusion, while the T2T approach may become a useful tool to simplify therapeutic goals and AD management, its foundation in AD is only starting to build. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to further define the essential components needed to utilize T2T in AD.

Atopic diseases such as atopic dermatitis, food allergy, allergic rhinoconjunctivitis, and/or asthma are common. In Denmark, however, there are multiple referral pathways for these diseases in the healthcare system and they are poorly understood. To describe how children with atopic diseases navigate their way through the Danish healthcare system, a questionnaire was distributed to children aged ≤ 17 years, who were being treated for atopic diseases between August 2020 and June 2021, either by a practising specialist or a hospital department, in the Capital Region of Denmark. A total of 279 children completed the questionnaire and most were referred to a specialist or to a hospital by their general practitioner. No “common track” to hospital existed for patients with ≥ 3 atopic diseases. These patients were more often referred to a hospital compared with children with 2 atopic diseases or fewer (odds ratio [OR] 3.79; 95% CI 2.07–7.24). The primary determinants for hospital treatment were food allergy (OR 4.69; 95% CI 2.07–10.61) and asthma (OR 2.58; 95% CI 1.18–5.63). In conclusion, children with multiple atopic diseases were more likely to be referred to hospital departments than to practising specialists, mainly due to food allergies., Atopic diseases such as atopic dermatitis, food allergy, allergic rhinoconjunctivitis, and/or asthma are common. In Denmark, however, there are multiple referral pathways for these diseases in the healthcare system and they are poorly understood. To describe how children with atopic diseases navigate their way through the Danish healthcare system, a questionnaire was distributed to children aged ≤ 17 years, who were being treated for atopic diseases between August 2020 and June 2021, either by a practising specialist or a hospital department, in the Capital Region of Denmark. A total of 279 children completed the questionnaire and most were referred to a specialist or to a hospital by their general practitioner. No "common track" to hospital existed for patients with ≥ 3 atopic diseases. These patients were more often referred to a hospital compared with children with 2 atopic diseases or fewer (odds ratio [OR] 3.79; 95% CI 2.07-7.24). The primary determinants for hospital treatment were food allergy (OR 4.69; 95% CI 2.07-10.61) and asthma (OR 2.58; 95% CI 1.18-5.63). In conclusion, children with multiple atopic diseases were more likely to be referred to hospital departments than to practising specialists, mainly due to food allergies.

The World Allergy Organization recommends probiotics in the prevention of atopic dermatitis in high-risk populations. Mutations in the filaggrin gene (FLG) result in an increased risk of atopic dermatitis through disruption of the skin keratin layer. This exploratory study investigated whether the preventive effect of maternal probiotics was evident in children with and without FLG mutations. DNA was collected from children (n = 228) from the Probiotic in the Prevention of Allergy among Children in Trondheim (ProPACT) study. Samples were analysed for 3 common FLG mutations (R501X, R2447X, and 2282del4). Overall, 7% of children had heterozygous FLG mutations; each child had only one of the 3 mutations. Mutation status had no association with atopic dermatitis (RR = 1.1; 95% CI 0.5 to 2.3). The risk ratio (RR) for having atopic dermatitis following maternal probiotics was 0.6 (95% CI 0.4 to 0.9) and RR was similar if the child expressed an FLG mutation (RR = 0.6; 95% CI 0.1 to 4.1) or wildtype FLG (RR = 0.6; 95% CI 0.4 to 0.9). The preventive effect of probiotics for atopic dermatitis was also evident in children without FLG mutation. Larger confirmatory studies are needed., The World Allergy Organization recommends probiotics in the prevention of atopic dermatitis in high-risk populations. Mutations in the filaggrin gene (FLG) result in an increased risk of atopic dermatitis through disruption of the skin keratin layer. This exploratory study investigated whether the preventive effect of maternal probiotics was evident in children with and without FLG mutations. DNA was collected from children (n = 228) from the Probiotic in the Prevention of Allergy among Children in Trondheim (ProPACT) study. Samples were analysed for 3 common FLG mutations (R501X, R2447X, and 2282del4). Overall, 7% of children had heterozygous FLG mutations; each child had only one of the 3 mutations. Mutation status had no association with atopic dermatitis (RR = 1.1; 95% CI 0.5 to 2.3). The risk ratio (RR) for having atopic dermatitis following maternal probiotics was 0.6 (95% CI 0.4 to 0.9) and RR was similar if the child expressed an FLG mutation (RR = 0.6; 95% CI 0.1 to 4.1) or wildtype FLG (RR = 0.6; 95% CI 0.4 to 0.9). The preventive effect of probiotics for atopic dermatitis was also evident in children without FLG mutation. Larger confirmatory studies are needed.

Background Psoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex-specific differences in the safety of systemic psoriasis therapies. Objectives To examine the real-world, long-term safety of systemic psoriasis therapies with sex stratification in drug-related adverse events (ADRs). Methods Ten-year data from adults with moderate-to-severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient-years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t-tests to compare treatment groups and sex. Results In total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2-fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0-fold higher drug-related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non-significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87–9.68) compared to CSTs (7.08, CI 5.39–9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8-fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0-fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug-related discontinuation rates for most CSTs in females. Conclusion Females were associated with a significantly, Background: Psoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex-specific differences in the safety of systemic psoriasis therapies. Objectives: To examine the real-world, long-term safety of systemic psoriasis therapies with sex stratification in drug-related adverse events (ADRs). Methods: Ten-year data from adults with moderate-to-severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient-years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t-tests to compare treatment groups and sex. Results: In total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2-fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0-fold higher drug-related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non-significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87–9.68) compared to CSTs (7.08, CI 5.39–9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8-fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0-fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug-related discontinuation rates for most CSTs in females. Conclusion: Females were associated with a significantly higher rate of ADRs and drug-related discontinua

Background: Chronic hand eczema (CHE) is a highly prevalent, heterogeneous, skin disease that encompasses different aetiological and clinical subtypes. Severe CHE without atopic dermatitis has been associated with systemic inflammation; yet it remains unknown if specific CHE subtypes leave distinct, systemic, molecular signatures. Objectives: To characterize the inflammatory plasma signature of different aetiological and clinical CHE subtypes. Methods: We assessed expression levels of 266 inflammatory and cardiovascular disease risk plasma proteins as well as filaggrin gene mutation status in 51 well-characterized CHE patients without concomitant atopic dermatitis and 40 healthy controls. Plasma protein expression was compared between aetiological and clinical CHE subgroups and controls both overall and according to clinical CHE severity. Correlation analyses for biomarkers, clinical and self-reported variables were performed. Results: Very severe, chronic allergic contact dermatitis (ACD) on the hands was associated with a mixed Type 1/Type 2 systemic immune activation as compared with controls. Circulating levels of Type 1/Type 2 inflammatory biomarkers correlated positively with clinical disease severity among CHE patients with ACD. No biomarkers were found, that could discriminate between aetiological subtypes, for example, between ACD and irritant contact dermatitis. Hyperkeratotic CHE showed a distinct, non-atopic dermatitis-like, systemic footprint with upregulation of markers associated with Type 1 inflammation and tumour necrosis factor alpha, but not Type 2 inflammation. Increased levels of CCL19 and CXCL9/10 could discriminate hyperkeratotic CHE from both vesicular and chronic fissured CHE, whereas no difference was found between the latter two subtypes. Conclusion: Profiling of systemic biomarkers showed potential for identifying certain CHE subtypes. Peripheral blood levels of inflammatory biomarkers were associated and correlated with the clinical d

Background Psoriatic arthritis (PsA) is a prevalent comorbidity among patients with psoriasis, heavily contributing to their burden of disease, usually diagnosed several years after the diagnosis of psoriasis. Objectives To investigate the predictability of psoriatic arthritis in patients with psoriasis and to identify important predictors. Methods Data from the Swiss Dermatology Network on Targeted Therapies (SDNTT) involving patients treated for psoriasis were utilized. A combination of gradient-boosted decision trees and mixed models was used to classify patients based on their diagnosis of PsA or its absence. The variables with the highest predictive power were identified. Time to PsA diagnosis was visualized with the Kaplan-Meier method and the relationship between severity of psoriasis and PsA was explored through quantile regression. Results A diagnosis of psoriatic arthritis was registered at baseline of 407 (29.5%) treatment series. 516 patients had no registration of PsA, 257 patients had PsA at inclusion, and 91 patients were diagnosed with PsA after inclusion. The model’s AUROCs was up to 73.7%, and variables with the highest discriminatory power were age, PASI, physical well-being, and severity of nail psoriasis. Among patients who developed PsA after inclusion, significantly more first treatment series were classified in the PsA-group, compared to those with no PsA registration. PASI was significantly correlated with the median burden/severity of PsA (P = .01). Conclusions Distinguishing between patients with and without PsA based on clinical characteristics is feasible and even predicting future diagnoses of PsA is possible. Patients at higher risk can be identified using important predictors of PsA., Background: Psoriatic arthritis (PsA) is a prevalent comorbidity among patients with psoriasis, heavily contributing to their burden of disease, usually diagnosed several years after the diagnosis of psoriasis. Objectives: To investigate the predictability of psoriatic arthritis in patients with psoriasis and to identify important predictors. Methods: Data from the Swiss Dermatology Network on Targeted Therapies (SDNTT) involving patients treated for psoriasis were utilized. A combination of gradient-boosted decision trees and mixed models was used to classify patients based on their diagnosis of PsA or its absence. The variables with the highest predictive power were identified. Time to PsA diagnosis was visualized with the Kaplan-Meier method and the relationship between severity of psoriasis and PsA was explored through quantile regression. Results: A diagnosis of psoriatic arthritis was registered at baseline of 407 (29.5%) treatment series. 516 patients had no registration of PsA, 257 patients had PsA at inclusion, and 91 patients were diagnosed with PsA after inclusion. The model’s AUROCs was up to 73.7%, and variables with the highest discriminatory power were age, PASI, physical well-being, and severity of nail psoriasis. Among patients who developed PsA after inclusion, significantly more first treatment series were classified in the PsA-group, compared to those with no PsA registration. PASI was significantly correlated with the median burden/severity of PsA (P =.01). Conclusions: Distinguishing between patients with and without PsA based on clinical characteristics is feasible and even predicting future diagnoses of PsA is possible. Patients at higher risk can be identified using important predictors of PsA.

Background Skin tape-strips and biopsies are widely used methods for investigating the skin in atopic dermatitis (AD). Biopsies are more commonly used but can cause scarring and pain, whereas tape-strips are noninvasive but sample less tissue. The study evaluated the performance of skin tape-strips and biopsies for studying AD. Methods Whole-transcriptome RNA-sequencing was performed on paired tape-strips and biopsies collected from lesional and non-lesional skin from AD patients (n = 7) and non-AD controls (n = 5). RNA yield, mapping efficiency, and differentially expressed genes (DEGs) for the two methods (tape-strip/biopsy) and presence of AD (AD/non-AD) were compared. Results Tape-strips demonstrated a lower RNA yield (22 vs. 4596 ng) and mapping efficiency to known genes (28% vs. 93%) than biopsies. Gene-expression profiles of paired tape-strips and biopsies demonstrated a medium correlation (R2 = 0.431). Tape-strips and biopsies demonstrated systematic differences in measured expression levels of 6483 genes across both AD and non-AD samples. Tape-strips preferentially detected many itch (CCL3/CCL4/OSM) and immune-response (CXCL8/IL4/IL5/IL22) genes as well as markers of epidermal dendritic cells (CD1a/CD207), while certain cytokines (IL18/IL37), skin-barrier genes (KRT2/FLG2), and dermal fibroblasts markers (COL1A/COL3A) were preferentially detected by biopsies. Tape-strips identified more DEGs between AD and non-AD (3157 DEGs) then biopsies (44 DEGs). Tape-strips also detected higher levels of bacterial mRNA than biopsies. Conclusions This study concludes that tape-strips and biopsies each demonstrate respective advantages for measuring gene-expression changes in AD. Thus, the specific skin layers and genes of interest should be considered before selecting either method., Background: Skin tape-strips and biopsies are widely used methods for investigating the skin in atopic dermatitis (AD). Biopsies are more commonly used but can cause scarring and pain, whereas tape-strips are noninvasive but sample less tissue. The study evaluated the performance of skin tape-strips and biopsies for studying AD. Methods: Whole-transcriptome RNA-sequencing was performed on paired tape-strips and biopsies collected from lesional and non-lesional skin from AD patients (n = 7) and non-AD controls (n = 5). RNA yield, mapping efficiency, and differentially expressed genes (DEGs) for the two methods (tape-strip/biopsy) and presence of AD (AD/non-AD) were compared. Results: Tape-strips demonstrated a lower RNA yield (22 vs. 4596 ng) and mapping efficiency to known genes (28% vs. 93%) than biopsies. Gene-expression profiles of paired tape-strips and biopsies demonstrated a medium correlation (R2 = 0.431). Tape-strips and biopsies demonstrated systematic differences in measured expression levels of 6483 genes across both AD and non-AD samples. Tape-strips preferentially detected many itch (CCL3/CCL4/OSM) and immune-response (CXCL8/IL4/IL5/IL22) genes as well as markers of epidermal dendritic cells (CD1a/CD207), while certain cytokines (IL18/IL37), skin-barrier genes (KRT2/FLG2), and dermal fibroblasts markers (COL1A/COL3A) were preferentially detected by biopsies. Tape-strips identified more DEGs between AD and non-AD (3157 DEGs) then biopsies (44 DEGs). Tape-strips also detected higher levels of bacterial mRNA than biopsies. Conclusions: This study concludes that tape-strips and biopsies each demonstrate respective advantages for measuring gene-expression changes in AD. Thus, the specific skin layers and genes of interest should be considered before selecting either method.