Chronic inflammatory diseases (CIDs) are systems disorders that affect diverse organs including the intestine, joints and skin. The essential amino acid tryptophan (Trp) can be broken down to various bioactive derivatives important for immune regulation. Increased Trp catabolism has been observed in some CIDs, so we aimed to characterise the specificity and extent of Trp degradation as a systems phenomenon across CIDs. We used high performance liquid chromatography and targeted mass spectrometry to assess the serum and stool levels of Trp and Trp derivatives. Our retrospective study incorporates both cross-sectional and longitudinal components, as we have included a healthy population as a reference and there are also multiple observations per patient over time. We found reduced serum Trp levels across the majority of CIDs, and a prevailing negative relationship between Trp and systemic inflammatory marker C-reactive protein (CRP). Notably, serum Trp was low in several CIDs even in the absence of measurable systemic inflammation. Increases in the kynurenine-to-Trp ratio (Kyn:Trp) suggest that these changes result from increased degradation along the kynurenine pathway. Increases in Kyn:Trp indicate the kynurenine pathway as a major route for CID-related Trp metabolism disruption and the specificity of the network changes indicates excessive Trp degradation relative to other proteogenic amino acids. Our results suggest that increased Trp catabolism is a common metabolic occurrence in CIDs that may directly affect systemic immunity. This work was supported by the DFG Cluster of Excellence 2167 "Precision medicine in chronic inflammation" (KA, SSchr, PR, BH, SWa), the BMBF (e:Med Juniorverbund "Try-IBD" 01ZX1915A and 01ZX2215, the e:Med Network iTREAT 01ZX2202A, and GUIDE-IBD 031L0188A), EKFS (2020_EKCS.11, KA), DFG RU5042 (PR, KA), and Innovative Medicines Initiative 2 Joint Undertakings ("Taxonomy, Treatments, Targets and Remission", 831434, "ImmUniverse", 853995, "BIOMAP", 821511).

Psoriasis is not optimally controlled in spite of newly developed treatments, possibly due to the difficulty of objectively quantifying the disease’s severity, considering the limitations of the clinical scores used in clinical practice. A major challenge addresses difficult-to-treat areas, especially in the absence of significant body surface involvement. It is controversial whether the severity evaluation of patients with several affected areas (having at least one difficult-to-treat area) should be done differently from current methods. Scores used for special areas (PSSI, NAPSI and ESIF) allow an accurate assessment of disease severity in difficult-to-treat areas, but the issue of whether to integrate these scores into PASI, BSA or DLQI remains. The review’s purpose resides in providing an overview of the main current issues in determining psoriasis severity in patients with psoriasis in difficult-to-treat areas and suggesting possible solutions for the optimal integration of the area assessment in current scores: severity can be either established according to the highest calculated score (PASI or PSSI or NAPSI or ESIF) or by adding a correction factor in the calculation of PASI for special areas.

Background: Psoriasis is associated with a significant comorbidity burden, especially cardiovascular and metabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, used to treat obesity and diabetes, could potentially reduce comorbidities in patients with psoriasis. Objectives: To investigate all-cause mortality, cardiovascular, inflammatory and psychiatric outcomes, and adverse events in patients with psoriasis treated with GLP-1RAs. Methods: This retrospective population-based cohort study used real-world data from the US TriNetX database. Patients with psoriasis who were treated for diabetes or obesity with a GLP-1RA during the follow-up period of 2 years were compared with those treated with other systemic antidiabetic or antiobesity drugs. After 1 : 1 propensity score matching for relevant risk factors, 3048 participants were included in each cohort. Primary outcomes included the risk of cardiometabolic, psychiatric and autoimmune sequelae of psoriasis, as well as all-cause mortality and potential adverse drug events. The analysis was repeated using cohorts without psoriasis and the results were further validated through two sensitivity analyses involving (i) later follow-up periods or (ii) the exclusion of patients with pustular psoriasis. Results: In the matched cohorts of 3048 patients with psoriasis treated with a GLP-1RA [60.4% women, mean (SD) age 56.94 (12.02) years] vs. other antidiabetic and antiobesity drugs [61.9% women, mean (SD) age 56.42 (14.16) years], GLP-1RA treatment was associated with significantly decreased all-cause mortality [hazard ratio (HR) 0.219, 95% confidence interval (CI) 0.123–0.391; P < 0.001] and reduced risk of major adverse cardiac events (HR 0.561, 95% CI 0.442–0.714; P < 0.001). Additionally, lower risks for alcohol (HR 0.346, 95% CI 0.174–0.685; P = 0.009) and substance abuse (HR 0.510, 95% CI 0.350–0.743; P = 0.002) were found. Typical adverse drug events were not more frequent in the GLP-1RA cohort. The risk reductions were more pronounced in the cohorts with psoriasis than in those with obesity or diabetes without psoriasis. The findings were consistent across all sensitivity analyses. Conclusions: GLP-1RA treatment was safe and associated with reduced risks of cardiovascular and psychiatric comorbidities, as well as lower mortality in patients with psoriasis, with risk reductions markedly higher than in cohorts without psoriasis. Physicians should consider this drug class for patients with psoriasis and comorbid obesity or diabetes.

Inflammatory skin diseases such as atopic dermatitis (AD), psoriasis and urticaria are associated with impaired mental health and sleep. In children the risk of developing these comorbidities is still poorly evaluated. Retrospective data analysis of a US Collaborative Network including children of 55 Health care providers was performed. Data from electronic health records of patients with a diagnosis of either AD, psoriasis, or urticaria, as well as a control cohort were retrieved in an anonymized batch format and propensity score matched. Children with psoriasis had a 3.2-fold higher risk for hypersomnia, 2.1-fold higher for sleep apnea, 1.8-fold higher for fatigue and 1.9-fold higher for depression. Children with urticaria (acute or chronic) and AD had a 1.7-fold higher risk for sleep disorders, 1.6 higher for anxiety disorders and 1.4-fold higher for insomnia. AD children had a 1.5-fold higher risk for anxiety disorders. Electronic health insurance data are not subject to random sampling of the general population and potential misdiagnosis is possible. Children with inflammatory skin diseases were at a higher risk for sleep psychological disorders. Thus, regularly performed screenings and appropriate treatment initiation might potentially prevent mental and physical health consequences and secure improved life quality.

Background: Type 2 chronic inflammatory diseases (T2IDs) are highly prevalent among women of reproductive age. Dupilumab, a monoclonal antibody, is increasingly used to treat T2IDs. While dupilumab is not approved during pregnancy, smaller studies suggest no increased risk of pregnancy complications (adverse pregnancy outcomes (APOs)). Additional data are required to better assess the drug's safety during pregnancy.Objectives: To retrospectively assess the risk of APOs in dupilumab‐treated pregnant women in a large real‐world database.Methods: Pregnant women with T2ID and dupilumab treatment during pregnancy were retrieved from the US Collaborative Network of TriNetX. Pregnant women with T2ID and without dupilumab treatment served as controls. Propensity score matching (PSM) for demographics, diagnoses, medications and putative APO risk factors was employed. Outcomes analysed included various maternal pregnancy complications, including premature obstetric labour, pregnancy‐induced hypertension, gestational diabetes, puerperal infections and spontaneous abortion. Survival analyses were assessed using the Kaplan–Meier method, outcome differences the log‐rank test and hazard ratios (HR) the Cox regression model.Results: During pregnancy, 293 women were exposed to dupilumab. Following PSM, no increased risks for APOs were noted. Of note, reduced risks for premature obstetric labour (HR: 0.11, confidence interval (CI): 0.03–0.45, p = 0.0002) and ‘any APO’ (HR: 0.53, CI: 0.33–0.84, p = 0.0067) in the dupilumab‐treated group were found. Furthermore, no difference in risks for any APO was noted between dupilumab‐treated and untreated women up to 6 months before pregnancy or during the postpartum period.Conclusions: This large‐scale propensity‐matched retrospective cohort study suggests a favourable safety profile of dupilumab during pregnancy. Given the difficulties of prospective studies during pregnancy, it provides valuable insights, though further studies are needed to confirm these findings and explore causal relationships.

Background: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease characterized by intense itch, and impacting heavily on patients’ and caregivers’ quality of life. Its clinical presentation is accompanied by a variety of comorbidities associated with type 2 inflammation, such as asthma, hay fever and food allergies. However, current data on cardiovascular comorbidities are inconsistent. Objectives: To identify the risk of cardiovascular diseases (CVDs) in patients with AD. Methods: Data from electronic health records of 1 070 965 patients with AD and equally distributed propensity-score matched controls were retrieved from the US Collaborative Network, part of the federated TriNetX network. Hazard ratios (HRs) for the risk of onset of CVDs with a prevalence of ≥ 1% in both cohorts within 20 years after diagnosis were determined. Results: In total, 55 CVDs belonging to 8 major cardiovascular groups were identified. Of those, 53 diagnoses displayed a significantly increased risk in patients with AD. Different diagnoses of heart failure and heart disease were found most often, followed by valve insufficiencies, arrhythmia, tachycardia, atrial fibrillation and flutter, but also major adverse cardiovascular events and venous thromboembolism. The highest HRs were displayed by the individual diagnoses of venous insufficiency, atherosclerosis of native arteries of the extremities, and unspecified diastolic (congestive) heart failure. Conclusions: AD is associated with an increased risk for multiple CVDs.