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Contains fulltext : 307088.pdf (Publisher’s version ) (Closed access), Radboud University, 04 juli 2024, Promotor : Jong, E.M.G.J. de Co-promotores : Wenink, M.H., Reek, J.M.P.A. van den, Vriezekolk, J.E., 310 p.

Contains fulltext : 304934.pdf (Publisher’s version ) (Closed access), INTRODUCTION: Psoriasis is a chronic inflammatory condition that can significantly impact the quality of life (QoL), regardless of the level of skin involvement. Apremilast is indicated for the treatment of moderate to severe psoriasis. Real-world data regarding the impact of apremilast on patient-reported outcomes in clinical practice in the Netherlands is lacking. METHODS: The prospective, multicenter observational Apremilast in Real-Life Psoriasis Treatment (APRIL) study enrolled patients ≥ 18 years old with moderate to severe plaque psoriasis receiving apremilast in clinical practice in the Netherlands. Patients were followed-up for 12 months, with assessments scheduled at 6 and 12 months. The primary outcome was Dermatology Life Quality Index (DLQI) response (score ≤ 5 or ≥ 5-point improvement from baseline) at 6 months. Secondary patient-reported outcomes included EQ-5D and skin-specific parameters; exploratory outcomes were Patient Benefit Index (PBI) and Work Productivity and Activity Impairment (WPAI). RESULTS: Of the 155 patients enrolled (February 2016-June 2019), 153 received apremilast; 69 (45%) and 39 (26%) continued treatment at 6 and 12 months, respectively. Psoriasis in special areas was common (scalp, 65%; nail, 51%; palmoplantar, 27%). Most patients (92%) had received prior systemic antipsoriatic therapies. Of the 151 patients with a baseline DLQI value, 56 (37%) achieved DLQI response at 6 months. Mean (standard deviation) PBI scores were 3.5 (1.2) and 3.8 (1.1) at 6 and 12 months, respectively. Improvements in DLQI, EQ-5D, and WPAI scores and disease signs and symptoms, including itch and special areas, were observed at 6 and 12 months. Adverse events were consistent with the known safety profile. CONCLUSIONS: In the Netherlands, patients with moderate to severe psoriasis receiving apremilast for up to 12 months reported improved disease-related QoL, skin involvement, and patient-reported outcomes. These data add to the growing body of evidence

01 december 2023, Item does not contain fulltext, BACKGROUND: Dose reduction (DR) of adalimumab, etanercept and ustekinumab has proven to be (cost-)effective in psoriasis patients with low disease activity. Further implementation is needed to establish application of DR for eligible patients. OBJECTIVES: To evaluate the implementation of protocolized biologic DR in daily practice. METHODS: A pilot implementation study was performed in 3 hospitals during 6 months. By combining education and protocol development, involved healthcare providers (HCPs) were directed toward the adoption of protocolized DR. DR of adalimumab, etanercept, and ustekinumab was achieved by stepwise injection interval prolongation. Implementation outcomes (fidelity, feasibility) were assessed. Factors for optimizing implementation were explored in interviews with HCPs. Uptake was measured in patients by chart review. RESULTS: The implementation strategy was executed as planned. Implementation fidelity was less than 100% as not all provided tools were used across study sites. HCPs indicated the feasibility of implementing protocolized DR, although time investment was needed. Identified additional factors for successful implementation included support for patients, uptake of DR into guidelines, and supportive electronic health record systems. During the 6 months intervention period, 52 patients were eligible for DR of whom 26 (50%) started DR. The proposed DR protocol was followed in 22/26 patients (85%) on DR. CONCLUSION: Additional staff for support, extra time during consultations, education on DR for HCPs and patients, and effective tools such as a feasible protocol can lead to more patients on biologic DR.

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Item does not contain fulltext, Patients with psoriasis are at risk of developing psoriatic arthritis, which can lead to joint damage. While screening questionnaires have been developed, their performance varies. The objective of this study was to develop a referral tool for dermatologists to identify psoriasis patients with concomitant psoriatic arthritis for rheumatological referral. This study used data from the DAPPER study, in which psoriasis patients were screened by a rheumatologist for the presence of concomitant psoriatic arthritis. Multivariable regression analysis was used to identify predictive variables for the presence of concomitant psoriatic arthritis: treatment history with conventional systemic drugs (odds ratio (OR) 2.97, 95% confidence interval (95% CI) 1.01-8.74, p = 0.04), treatment history with biologicals/small molecule inhibitors (OR 2.90, 95% CI 1.52-5.53, p = 0.01), patient-reported history of joint pain not caused by trauma (OR 4.23, 95% CI 1.21-14.79, p = 0.01), patient-reported history of swollen joints (OR 4.25, 95% CI 2.17-8.32, p < 0.001), and patient-reported history of sausage-like swollen digits (OR 2.38, 95% CI 1.25-4.55, p = 0.01). Based on these variables, a referral tool was created with an area under the curve of 0.82. This referral tool could be used to aid dermatologists to identify psoriasis patients with concomitant psoriatic arthritis, who may benefit from rheumatological referral.

01 juli 2023, Item does not contain fulltext

Radboud University, 05 september 2023, Promotores : Jong, E.M.G.J. de, Kerkhof, P.C.M. van de Co-promotores : Paller, A.S., Seyger, M.M.B., Item does not contain fulltext

01 augustus 2023, Item does not contain fulltext, Dose reduction of biologics for psoriasis could contribute to more efficient use of these expensive medicines. Evidence on opinions of patients with psoriasis regarding dose reduction is sparse. The objective of this study was therefore to explore patients' perspectives towards dose reduction of biologics for psoriasis. A qualitative study was conducted, comprising semi-structured interviews with 15 patients with psoriasis with different characteristics and treatment experiences. Interviews were analyzed by inductive thematic analysis. Perceived benefits of biologic dose reduction according to patients were minimizing medication use, lowering risks of adverse effects and lowering societal healthcare costs. Patients reported to have experienced a large impact of their psoriasis, and expressed concerns about loss of disease control due to dose reduction. Fast access to flare treatment and adequate monitoring of disease activity were among reported preconditions. According to patients, they should have confidence in dose reduction effects and should be willing to change their effective treatment. Moreover, addressing information needs and involvement in decision-making were deemed important among patients. In conclusion, addressing patients' concerns, fulfilling information needs, providing the possibility of resuming standard dose, and involving patients in decision-making are important according to patients with psoriasis when considering biologic dose reduction.

Radboud University, 23 november 2023, Promotor : Jong, E.M.G.J. de Co-promotor : Reek, J.M.P.A. van den, Item does not contain fulltext

Contains fulltext : 297081.pdf (Publisher’s version ) (Open Access), BACKGROUND: Anti-drug antibodies (ADA) are formed in patients treated with adalimumab (ADL). This might increase clearance of ADL, potentially causing a (secondary) non-response. Combination therapy of ADL and methotrexate (MTX) reduces ADA levels and has a clinical benefit in rheumatologic diseases. In psoriasis however, the long-term effectiveness and safety have not been studied. OBJECTIVES: To investigate the three-year follow-up data of ADL combined with MTX compared to ADL monotherapy in ADL-naive patients with moderate to severe plaque type psoriasis. METHODS: We conducted a multicentre RCT in the Netherlands and Belgium. Randomization was performed by a centralized online randomization service. Patients were seen every 12 weeks until week 145. Outcome assessors were blinded. We collected data on drug survival, effectiveness, safety, pharmacokinetics and immunogenicity of patients that started ADL combined with MTX compared to ADL monotherapy. We present descriptive analysis and patients were analysed according to the group initially randomized to. Patients becoming non-adherent to the biologic were excluded from analyses. RESULTS: Sixty-one patients were included and 37 patients (ADL group n = 17, ADL + MTX group n = 20) continued in the follow-up study after 1 year. After 109 weeks and 145 weeks, there was a trend towards longer drug survival in the ADL + MTX group compared to the ADL group (week 109: 54.8% vs. 41.4%; p = 0.326, week 145: 51.6% vs. 41.4%; p = 0.464). At week 145, 7/13 patients were treated with MTX. In the ADL group, 4/12 patients that completed the study developed ADA, and 3/13 in the ADL + MTX group. CONCLUSIONS: In this small study, there was no significant difference in ADL overall drug survival when it was initially combined with MTX, compared to ADL alone. Discontinuation due to adverse events was common in the combination group. To secure accessible healthcare, combination treatment of ADL and MTX can be considered in individual pati

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Contains fulltext : 299955.pdf (Publisher’s version ) (Closed access), 01 december 2023

Contains fulltext : 298930.pdf (Publisher’s version ) (Open Access)

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Item does not contain fulltext, BACKGROUND: The Psoriasis Area and Severity Index (PASI) score is commonly used in clinical practice and research to monitor disease severity and determine treatment efficacy. Automating the PASI score with deep learning algorithms, like Convolutional Neural Networks (CNNs), could enable objective and efficient PASI scoring. OBJECTIVES: To assess the performance of image-based automated PASI scoring in anatomical regions by CNNs and compare the performance of CNNs to image-based scoring by physicians. METHODS: Imaging series were matched to PASI subscores determined in real life by the treating physician. CNNs were trained using standardized imaging series of 576 trunk, 614 arm and 541 leg regions. CNNs were separately trained for each PASI subscore (erythema, desquamation, induration and area) in each anatomical region (trunk, arms and legs). The head region was excluded for anonymity. Additionally, PASI-trained physicians retrospectively determined image-based subscores on the test set images of the trunk. Agreement with the real-life scores was determined with the intraclass correlation coefficient (ICC) and compared between the CNNs and physicians. RESULTS: Intraclass correlation coefficients between the CNN and real-life scores of the trunk region were 0.616, 0.580, 0.580 and 0.793 for erythema, desquamation, induration and area, respectively, with similar results for the arms and legs region. PASI-trained physicians (N = 5) were in moderate-good agreement (ICCs 0.706-0.793) with each other for image-based PASI scoring of the trunk region. ICCs between the CNN and real-life scores were slightly higher for erythema (0.616 vs. 0.558), induration (0.580 vs. 0.573) and area scoring (0.793 vs. 0.694) than image-based scoring by physicians. Physicians slightly outperformed the CNN on desquamation scoring (0.580 vs. 0.589). CONCLUSIONS: Convolutional Neural Networks have the potential to automatically and objectively perform image-based PASI scoring at an anatomical r

Item does not contain fulltext, BACKGROUND: Reflectance confocal microscopy (RCM) enables noninvasive Demodex mite detection in rosacea. Objective scoring of rosacea severity is currently lacking. OBJECTIVES: To determine the value of RCM for monitoring Demodex, inflammation and vascular parameters in rosacea during treatment. METHODS: In 20 rosacea patients, clinical and RCM examination were performed before, during, and 12 weeks after a 16-week treatment course with topical ivermectin. Using RCM, number of mites and inflammatory cells, epidermal thickness, and vascular density and diameter were measured. RCM features were correlated with clinical assessment. RESULTS: Treatment resulted in clinical reduction of inflammatory lesions. Mites were detected in 80% of patients at baseline, 30% at week 16, and 63% at week 28. The number of mites reduced significantly during treatment, but no changes in inflammatory cells, epidermal thickness or vascular parameters were observed. Correlation between number of inflammatory lesions and mites was low. None of the RCM variables were significant predictors for clinical success. CONCLUSIONS: RCM enables anti-inflammatory effect monitoring of topical ivermectin by determining mite presence. Quantifying exact mite number, and inflammatory and vascular characteristics is challenging due to device limitations. In its current form, RCM seems of limited value for noninvasive follow-up of rosacea in clinical practice.

Item does not contain fulltext, BACKGROUND: Skin microvasculature changes are crucial in psoriasis development and correlate with perfusion. The noninvasive Handheld Perfusion Imager (HAPI) examines microvascular skin perfusion in large body areas using laser speckle contrast imaging (LSCI). OBJECTIVES: To (i) assess whether increased perilesional perfusion and perfusion inhomogeneity are predictors for expansion of psoriasis lesions and (ii) assess feasibility of the HAPI system in a mounted modality. METHODS: In this interventional pilot study in adults with unstable plaque psoriasis, HAPI measurements and color photographs were performed for lesions present on one body region at week 0, 2, 4, 6 and 8. The presence of increased perilesional perfusion and perfusion inhomogeneity was determined. Clinical outcome was categorized as increased, stable or decreased lesion surface between visits. Patient feedback was collected on a 10-point scale. RESULTS: In total, 110 lesions with a median follow-up of 6 (IQR 6.0) weeks were assessed in 6 patients with unstable plaque psoriasis. Perfusion data was matched to 281 clinical outcomes after two weeks. A mixed multinomial logistic regression model revealed a predictive value of perilesional increased perfusion (OR 9.90; p < 0.001) and perfusion inhomogeneity (OR 2.39; p = 0.027) on lesion expansion after two weeks compared to lesion stability. HAPI measurements were considered fast, patient-friendly and important by patients. CONCLUSION: Visualization of increased perilesional perfusion and perfusion inhomogeneity by noninvasive whole field LSCI holds potential for prediction of psoriatic lesion expansion. Furthermore, the HAPI is a feasible and patient-friendly tool.

Contains fulltext : 248288.pdf (Publisher’s version ) (Open Access)

Radboud University, 11 februari 2022, Promotor : Jong, E.M.G.J. de Co-promotores : Reek, J.M.P.A. van den, Coenen, M.J.H., Contains fulltext : 244740.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 282879.pdf (Publisher’s version ) (Open Access), BACKGROUND: Biologics for psoriasis are registered in standard dosages. In patients with low disease activity, reduction of the dose by interval prolongation can prevent overtreatment, and lower risks and costs. However, fear for increased anti-drug antibody (ADA) formation due to interval prolongation of biologics is an important barrier. OBJECTIVE: To investigate the course of serum drug concentrations, ADA levels, and predictors for successful dose reduction of adalimumab, ustekinumab, and etanercept for psoriasis. METHODS: Patients were randomized to dose reduction (DR) or usual care (UC) and followed for one year. The course and extent of detectable ADA levels were expressed as proportions/relative risks for DR vs. UC. Association of baseline characteristics with successful tapering was investigated with log-binomial regression analysis. RESULTS: In total, 118 patients were included. In adalimumab-treated patients, no significant difference in the proportion of patients with relevant ADA levels in DR vs. UC was seen. For ustekinumab, relevant ADA development was absent in both groups. Baseline trough levels were not predictive for successful DR. CONCLUSIONS: Immunogenicity may not increase by interval prolongation in psoriasis patients with low disease activity. This pilot provides important and reassuring insight into the pharmacological changes after dose tapering of adalimumab, etanercept, and ustekinumab.

Contains fulltext : 251837.pdf (Publisher’s version ) (Open Access), OBJECTIVE: To evaluate the effect of lifestyle changes on the severity of psoriasis and the quality of life in patients with psoriasis. METHODS: For this narrative review, PubMed, Embase and ClinicalTrials.gov were searched for lifestyle intervention studies with an intervention duration of at least 12 weeks. RESULTS: Thirty-four intervention studies were included. Most studies performed interventions in the diet of patients with psoriasis (n=9), or added supplements to the diet (n=18). Three studies comprised relaxation techniques and four studies combined relaxation or stress-reducing techniques with an educational program or exercise. No interventional studies were carried out regarding smoking, alcohol and sleep. Especially dietary and relaxation interventions showed promising results with respect to psoriasis severity and dermatology-related QoL, respectively. Regarding dietary supplements, the three largest studies investigating fish oil or vitamin D did not show significant effects. CONCLUSION: There is some evidence that dietary and relaxation interventions could be promising with respect to psoriasis severity and dermatology-related QoL, respectively. Furthermore, our review identified important gaps in psoriasis lifestyle research regarding study design and reporting of outcomes.

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Contains fulltext : 283291.pdf (Publisher’s version ) (Open Access), BACKGROUND: Treatment needs of young psoriasis patients and parents are not widely studied and could advance patient-centered care. OBJECTIVE: To explore treatment goals and preferences of pediatric psoriasis patients, young adults, and parents. METHODS: A web-based survey among Dutch psoriasis patients aged ≥6 to ≤30 years and parents included multiple-choice, open-ended, and 4-point Likert scale questions. Treatment goals and characteristic preferences of pediatric patients (≤17 years) were compared to young adults (≥18 years) and parents. RESULTS: 195 young patients (20.2 ± 6.3 years) and 45 parents were included. The most important treatment goals were 'preventing lesions', 'reducing lesions', 'no itch', and 'no lesions'. Regarding treatment characteristics, 'long-term safety', 'high effectiveness', and 'short-term safety' were most important. We found differences by age, gender, and current treatment. Pediatric patients rated 'not sticky', 'quick results', and 'no/few blood samples needed' higher than parents and/or young adults. Young adults rated 'feeling more confident' and 'better quality of sleep' higher than pediatric patients. Parents considered safety most important. Psychosocial goals were more important for women and patients on biologics. CONCLUSION: Young psoriasis patients and parents mainly strive to clear lesions and itch with effective and safe treatment. However, revealed differences underline the relevance of addressing individual needs.

Contains fulltext : 282872.pdf (Publisher’s version ) (Open Access), Patients with psoriasis are at risk of developing psoriatic arthritis, which can lead to irreversible joint damage. However, a proportion of patients with psoriasis and concomitant psoriatic arthritis remain undiscovered in practice. The aims of this study were: to prospectively determine prevalence, characteristics, and disease burden of psoriatic arthritis in a psoriasis population; and to determine the prevalence and characteristics of patients with active psoriatic arthritis, who were not under rheumatological care. Patients with psoriasis were screened by a rheumatologist at the dermatology outpatient clinic for psoriatic arthritis. Patients with suspected active psoriatic arthritis who were not seeing a rheumatologist were referred to a rheumatologist for confirmation. The total prevalence of psoriatic arthritis in this observational, prospective cohort (n = 303) was 24%. Patients with psoriasis with concomitant psoriatic arthritis had longer duration of skin disease and more often a treatment history with systemic therapies. In this academic, specialized, setting, 2.3% of patients (n = 7), were not receiving rheumatological care despite having active psoriatic arthritis. These patients were characterized by a combination of low (perceived) disease burden and low yield of screening questionnaires, making it difficult for dermatologists to discover psoriatic arthritis in these patients. Thus, screening for more subtle active arthritis in patients with psoriasis in a dermatology setting could be improved.

Radboud University, 26 oktober 2022, Promotores : Jong, E.M.G.J. de, Bogaard, E.H.J. van den Co-promotor : Seyger, M.M.B., Contains fulltext : 281496.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 286070.pdf (Publisher’s version ) (Open Access)

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Contains fulltext : 251762.pdf (Publisher’s version ) (Open Access), BACKGROUND/OBJECTIVES: Tightly-controlled dose reduction was possible during 1 year in psoriasis patients on adalimumab, etanercept or ustekinumab with low disease activity (CONDOR trial). Extended observation is needed to ensure long-term effectiveness and safety of the strategy. With prolonged follow-up, we investigated the clinical effects and safety of the strategy, the proportion of patients with successful dose reduction, and assessed if patients with a disease flare regained remission. METHODS: Two-year follow up of a subgroup of patients previously included in a randomized pragmatic study comparing usual care (UC) with stepwise dose reduction (DR). Effectiveness (Psoriasis Area and Severity Index, PASI), Dermatology Life Quality Index (DLQI), adverse events, proportion of patients with successful DR and proportion of persistent disease flares were analyzed. RESULTS: DR leads temporarily to a slightly increased PASI groupwise, but on the long-term patients regained low PASI. DLQI scores remained stable during follow-up. No serious adverse events due to DR were reported. Forty-one percent of patients remained on a low dose up to 2 years. The number of persistent flares was low in DR and UC. CONCLUSIONS: The proposed dose reduction strategy is effective for a significant part of patients and remains safe up to 2 years of follow-up.

Contains fulltext : 286659.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, Dose reduction (DR) of biologics, where possible, seems promising for more efficient use of expensive biologics. For implementation of DR strategies, it is essential to get insight in factors that influence implementation. The objective of this study was to evaluate the attitudes and behaviour regarding dose reduction of biologic therapies for psoriasis among psoriasis expert dermatologists worldwide. A 27-question e-survey was sent through the International Psoriasis Council (IPC) to its 114 dermatologist councilors worldwide. The survey assessed demographics, general and DR prescription behaviour, and motivations for and barriers against application of DR. Of 57 respondents, 53 respondents who prescribed biologics were included for analysis. Thirty-seven (69.8%) applied DR (i.e., 'DR dermatologists'), and 16 (30.2%) did not (i.e., 'Non-DR dermatologists'). DR strategies varied among respondents. Regarding criteria for starting DR, differences were reported in required treatment duration, and interpretation and duration of stable low disease activity. In addition, the prolongation of intervals between injections varied between respondents. For most 'DR dermatologists' (n = 32/37, 86.5%), cost savings were one of the main reasons to apply DR. Fifteen out of 16 'Non-DR dermatologists' (94%) did not apply DR due to lack of scientific evidence. In conclusion, DR of biologics for psoriasis is part of clinical practice in psoriasis experts globally. Barriers for applying DR included lack of evidence or guidelines, and uncertainty on DR effects and risks. Although growing evidence shows DR feasibility, future studies are needed to accumulate and broaden evidence, along with development of (inter)national guidelines on DR strategies.

Contains fulltext : 253351.pdf (Publisher’s version ) (Open Access)

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Radboud University, 23 september 2022, Promotores : Hoogen, F.H.J. van den, Jong, E.M.G.J. de Co-promotores : Wenink, M.H., Koenen, J.P.M., Contains fulltext : 253110.pdf (Publisher’s version ) (Open Access)

Radboud University, 11 oktober 2022, Co-promotores : Jong, E.M.G.J. de, Reek, J.M.P.A. van den, Contains fulltext : 277199.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 251743.pdf (Publisher’s version ) (Open Access), BACKGROUND: Incorporating patient-related factors associated with treatment outcomes could improve personalized care in older patients with basal cell carcinoma (BCC). OBJECTIVE: To evaluate and identify predictors of treatment burden, treatment outcomes, and overall survival in patients aged ≥70 years, surgically treated for BCC in the head and neck area. METHODS: The data from the prospective, multicenter Basal Cell Carcinoma Treatment in Older Adults (BATOA) cohort study were extracted to evaluate the experienced treatment burden (visual analog scale, 0-10 cm; lower scores indicating higher treatment burden), treatment outcomes, and mortality. RESULTS: A total of 539 patients were included (median age, 78 years). The patients experienced a low overall treatment burden (median, 8.6) and good cosmetic results. The predictors of higher treatment burden were instrumental activities of daily living (iADL) dependency, female sex, complications, larger tumor diameter, and polypharmacy. Thirty-five patients (6.5%) died (none of the deaths were due to BCC) within the follow-up period; the predictors of mortality were increasing comorbidity index and iADL dependency. No difference in these outcomes was seen between Mohs micrographic surgery and conventional excision after correction for covariates. Age was not significantly associated with any outcome. LIMITATIONS: A selection bias may exist owing to the observational design. CONCLUSION: BCC management decisions based on chronological age alone should be avoided, whereas more attention is recommended for patient-related factors. Based on these data, early BCC intervention is beneficial for robust and fit patients or those experiencing symptoms.

Contains fulltext : 283370.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND: Anti-TNFα is increasingly used as treatment for immune mediated inflammatory diseases (IMID), such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and psoriasis (PS). However, the impact of anti-TNFα during pregnancy on mother and newborn is under debate. This requires a sound knowledge of the effects of this treatment on pregnancy and neonatal outcomes. OBJECTIVES: To assess pregnancy and neonatal outcomes after anti-TNFα therapy during pregnancy in women with IMID, specifically IBD, RA and PS. METHODS: We performed a systematic review and meta-analysis of 39 studies assessing pregnancy and neonatal outcomes of women with IMID exposed to anti-TNFα agents during pregnancy. We used a random-effects model to determine pooled outcome measures. RESULTS: An increased risk of preterm births (OR 1.45, 95% CI = 1.16 to 1.82, p = 0.001) and infections in newborns (OR 1.12, 95% CI = 1.00 to 1.27, p = 0.05)) was seen for women in the combined group of IMID exposed to anti-TNFα compared to diseased controls. Specifically for IBD patients exposed to anti-TNFα, the risk was increased for preterm birth (OR 1.66, 95% CI = 1.14 to 2.42, p = 0.009), and low birth weight (OR 1.49, 95% CI = 1.01 to 2.20, p = 0.047) compared to diseased controls. Combined data from studies of women with RA and PS, showed no increased risk for adverse pregnancy outcome after exposure to anti-TNFα. Most children of mothers with IMID received vaccination according to national vaccination schemes and only minor adverse events were reported. CONCLUSION: Exposure to anti-TNFα agents during pregnancy is associated with increased risk of preterm birth and infections in newborns of women with IMID compared to diseased controls. The risk of preterm birth and low birth weight was increased in women with IBD specifically. The increased risk of infections in newborns underlines the importance of vaccination, which seems to be safe in children exposed to anti-TNFα. Delay of vaccination is t

Contains fulltext : 242597.pdf (Publisher’s version ) (Open Access), BACKGROUND: One in three patients with psoriasis will develop psoriatic arthritis (PsA). If left untreated, this can lead to pain, impaired function, and irreversible joint damage. Timely recognition and referral to a rheumatologist are therefore key. However, current methods used to screen patients with psoriasis for those who might benefit from referral to a rheumatologist are not performing well enough. OBJECTIVE: The Discovery of Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER) study is designed to determine the prevalence of PsA in a psoriasis population and to find parameters that can be used to develop a new or enhance an existing instrument for a rheumatological referral. METHODS: DAPPER is a longitudinal observational study with a 1-year follow-up. Patients with psoriasis (N=300) who are treated at an outpatient dermatological clinic will be screened extensively for signs and symptoms of PsA by a trained rheumatologist. If there is clinical suspicion of PsA and the patient is not yet treated by a rheumatologist, referral to the Department of Rheumatology will follow for confirmation of the diagnosis and further care. After 1 year, data on changes in quality of life and PsA and psoriasis disease activity will be collected from the referred patients. The screening visit will be used to gather demographical and medical data, which can later be used to develop the aforementioned screening instrument. RESULTS: Inclusion started in June 2019 and finished in June 2021. Follow-up with newly discovered patients with PsA is ongoing. CONCLUSIONS: The DAPPER study is specifically designed to improve the detection of existing PsA in a dermatologic outpatient setting. Although internal validity will be tested, external validity will have to be checked using a second validation cohort. To predict the development of PsA in the future, longitudinal/prospective data collection is required and will be performed in a follow-up study (DAPPER-i). TRIAL

Item does not contain fulltext, IMPORTANCE: Few studies have examined watchful waiting (WW) in patients with basal cell carcinoma (BCC), although this approach might be suitable in patients who might not live long enough to benefit from treatment. OBJECTIVE: To evaluate reasons for WW and to document the natural course of BCC in patients who chose WW and reasons to initiate later treatment. DESIGN, SETTING, AND PARTICIPANTS: An observational cohort study was performed at a single institution between January 2018 and November 2020 studying patients with 1 or more untreated BCC for 3 months or longer. EXPOSURES: Watchful waiting was chosen by patients and proxies regardless of this study. MAIN OUTCOME AND MEASURES: The reasons for WW and treatment were extracted from patient files and were categorized for analyses. Linear mixed models were used to estimate tumor growth and identify covariates associated with tumor growth. RESULTS: Watchful waiting was chosen for 280 BCCs in 89 patients (47 men [53%] and 42 women [47%]), with a median (interquartile range [IQR]) follow-up of 9 (4-15) months. The median (IQR) age of the included patients was 83 (73-88) years. Patient-related factors or preferences (ie, prioritizations of comorbidities, severe frailty, or limited life expectancy) were reasons to initiate WW in 74 (83%) patients, followed by tumor-related factors (n = 49; 55%). Treatment-related and circumstantial reasons were important for 35% and 46% of the patients, respectively. The minority of tumors increased in size (47%). Tumor growth was associated with BCC subtype (odds ratio, 3.35; 95% CI, 1.47-7.96; P = .005), but not with initial tumor size and location. The estimated tumor diameter increase was 4.46 mm (80% prediction interval, 1.42 to 7.46 mm) in 1 year for BCCs containing at least an infiltrative/micronodular component and 1.06 mm (80% prediction interval, -1.79 to 4.28 mm) for the remaining BCCs (only nodular/superficial component/clinical diagnosis). Most common reasons to initiate tre

Contains fulltext : 240688.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 239785.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND: Stratum corneum hydration (SCH) and transepidermal water loss (TEWL) provide useful information about skin barrier function. This study aimed to determine the value of GPSkin Pro, a new handheld device determining both SCH and TEWL, to measure skin barrier impairment and to monitor barrier function in rosacea in daily practice. MATERIALS AND METHODS: Two pilots were performed. Pilot 1: in 27 healthy participants, GPSkin SCH and TEWL were compared to Aquaflux(®) and Epsilon(®) values at the forearm before and after skin barrier perturbation via tapestripping. Moreover, GPSkin values were measured at both cheeks without intervention. Pilot 2: in 16 rosacea patients, GPSkin measurements were performed at the forearm, and at both cheeks before and during anti-inflammatory treatment. They were compared to clinical symptoms and to GPSkin values from pilot 1. RESULTS: Pilot 1: after merging data from before and after tapestripping, a strong correlation was observed between GPSkin TEWL and Aquaflux(®) (R(s) = 0.9256), and GPSkin SCH and Epsilon(®) (R(s) = 0.8798). Pilot 2: SCH was significantly lower at the cheeks of rosacea patients compared to controls, with a normalizing trend during successful treatment. TEWL was comparable among patients and controls and did not change during treatment at all locations. CONCLUSION: The GPSkin determines TEWL and SCH accurately in healthy and impaired skin barrier state and can monitor skin barrier function in rosacea during treatment. The GPSkin device is much more practical compared to previous skin barrier tools when used in clinical practice. Its further validation in other inflammatory skin diseases is recommended.

Contains fulltext : 235371.pdf (Publisher’s version ) (Open Access), BACKGROUND: Although solely topical treatment often suffices, patients with psoriasis may require more intensive treatment (phototherapy and/or systemic treatments) to control their disease. However, in paediatric, adolescent and young adult patients, little is known about persistence of topical treatment and time until switch to systemic treatment. OBJECTIVES: To determine the median time from psoriasis onset until (i) discontinuation of solely topical agents and (ii) switch to systemic treatment, and to identify patient characteristics associated with switching to systemic treatments. METHODS: Data were extracted from the Child-CAPTURE registry, a prospective, observational cohort of patients with paediatric-onset psoriasis followed into young adulthood from 2008 to 2018. Data prior to inclusion in the registry were collected retrospectively. Median times were determined through Kaplan-Meier survival analyses. Cox regression analysis was used to identify patient characteristics associated with switch to systemic treatment. RESULTS: Of 448 patients, 62·3% stayed on solely topical treatment until data lock; 14·3% switched from topicals to phototherapy, but not to systemic treatment; and 23·4% switched to systemic treatment. The median time from psoriasis onset until discontinuation of solely topical treatment was 7·3 years, and until switch to systemics was 10·8 years. Higher Psoriasis Area and Severity Index and (Children's) Dermatology Life Quality Index > 5 were independently associated with switching to systemic treatment. CONCLUSIONS: In a population of paediatric and adolescent patients with mild-to-severe psoriasis, one-third needed more intensive treatment than solely topical therapy to control their disease. We consider the median time until switching to systemics to be long.

Contains fulltext : 235078.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 235329.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, OBJECTIVES: Vasculopathy is an important hallmark of systemic chronic inflammatory connective tissue diseases (CICTD) and is associated with increased cardiovascular risk. We investigated disease-specific biomarker profiles associated with endothelial dysfunction, angiogenic homeostasis and (tissue) inflammation, and their relation to disease activity in rare CICTD. METHODS: A total of 38 serum proteins associated with endothelial (dys)function and inflammation were measured by multiplex-immunoassay in treatment-naive patients with localized scleroderma (LoS, 30), eosinophilic fasciitis (EF, 8) or (juvenile) dermatomyositis (34), 119 (follow-up) samples during treatment, and 65 controls. Data were analysed by unsupervised clustering, Spearman correlations, non-parametric t test and ANOVA. RESULTS: The systemic CICTD, EF and dermatomyositis, had distinct biomarker profiles, with 'signature' markers galectin-9 (dermatomyositis) and CCL4, CCL18, CXCL9, fetuin, fibronectin, galectin-1 and TSP-1 (EF). In LoS, CCL18, CXCL9 and CXCL10 were subtly increased. Furthermore, dermatomyositis and EF shared upregulation of markers related to interferon (CCL2, CXCL10), endothelial activation (VCAM-1), inhibition of angiogenesis (angiopoietin-2, sVEGFR-1) and inflammation/leucocyte chemo-attraction (CCL19, CXCL13, IL-18, YKL-40), as well as disturbance of the Angiopoietin-Tie receptor system and VEGF-VEGFR system. These profiles were related to disease activity, and largely normalized during treatment. However, a subgroup of CICTD patients showed continued elevation of CXCL10, CXCL13, galectin-9, IL-18, TNFR2, VCAM-1, and/or YKL-40 during clinically inactive disease, possibly indicating subclinical interferon-driven inflammation and/or endothelial dysfunction. CONCLUSION: CICTD-specific biomarker profiles revealed an anti-angiogenic, interferon-driven environment during active disease, with incomplete normalization under treatment. This warrants further investigation into monitoring