Challenges in Noninvasive Skin Biomarker Measurements in Daily Practice: A Longitudinal Study on Skin Surface Protein Detection by the Transdermal Analysis Patch in Pediatric Psoriasis.

INTRODUCTION: Skin surface proteins are potential biomarkers in psoriasis and can be measured noninvasively with the transdermal analysis patch (TAP). This study aimed to assess markers measured by TAP over time in daily clinical practice, explore their correlation with disease severity in pediatric psoriasis, and compare the TAP and tape stripping detection capability. METHODS: In this prospective observational daily clinical practice study, pediatric psoriasis patients (aged >5 to <18 years) were followed during 1 year. At each visit, TAPs were applied to lesional (n = 2), peri-lesional (n = 2), and non-lesional (n = 1) sites. Post-lesional skin was sampled if all lesions on the arms, legs, or trunk cleared. Treatment and psoriasis severity data were collected. IL-1RA, hBD-2, IL-1α, IL-8, VEGF, CXCL-1/2, CCL-27, IL-23, hBD-1, IL-22, IL-17A, KLK-5, and IL-4 levels were quantified by spot-ELISA. For the statistical analysis, Wilcoxon signed rank tests, Mann-Whitney U tests, and Spearman correlations were used. Detection capability of the TAP was compared to tape stripping in a separate cohort of adult psoriasis patients. RESULTS: 32 patients (median age 15.0 years, median Psoriasis Area and Severity Index [PASI] 5.2) were followed for a mean of 11.3 (±3.4) months with a total of 104 visits. In lesional skin (n = 197), significantly higher IL-1RA, hBD-2, IL-8, VEGF, CXCL-1/2, IL-23, hBD-1, IL-22, CCL-27, and IL-17A levels were found compared to non-lesional skin (n = 104), while IL-1α was higher in non-lesional skin. Marker levels were highly variable over time and did not correlate with disease severity measured by PASI or SUM scores. Comparison of the TAP and tape strip detection capability in adult psoriasis patients (n = 10) showed that lesional hBD-2, IL1-α, IL-8, and VEGF and non-lesional IL-1RA, hBD-2, IL-8, and VEGF were more frequently detected in tape extracts than TAPs. CONCLUSION: Due to the lack of correlation with clinical disease severity and the current detection capability of the markers measured by TAP in psoriasis, its use in regular practice is still a bridge too far.

Perfusion measured by laser speckle contrast imaging as a predictor for expansion of psoriasis lesions.

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.

Treatment goals and preferences of pediatric psoriasis patients, young adults, and parents.

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.

Handheld versus mounted laser speckle contrast perfusion imaging demonstrated in psoriasis lesions.

Enabling handheld perfusion imaging would drastically improve the feasibility of perfusion imaging in clinical practice. Therefore, we examine the performance of handheld laser speckle contrast imaging (LSCI) measurements compared to mounted measurements, demonstrated in psoriatic skin. A pipeline is introduced to process, analyze and compare data of 11 measurement pairs (mounted-handheld LSCI modes) operated on 5 patients and various skin locations. The on-surface speeds (i.e. speed of light beam movements on the surface) are quantified employing mean separation (MS) segmentation and enhanced correlation coefficient maximization (ECC). The average on-surface speeds are found to be 8.5 times greater in handheld mode compared to mounted mode. Frame alignment sharpens temporally averaged perfusion maps, especially in the handheld case. The results show that after proper post-processing, the handheld measurements are in agreement with the corresponding mounted measurements on a visual basis. The absolute movement-induced difference between mounted-handheld pairs after the background correction is [Formula: see text] (mean ± std, [Formula: see text]), with an absolute median difference of [Formula: see text]. Realization of handheld LSCI facilitates measurements on a wide range of skin areas bringing more convenience for both patients and medical staff.

Skin Surface Protein Detection by Transdermal Analysis Patches in Pediatric Psoriasis.

INTRODUCTION: Transdermal analysis patches (TAPs) noninvasively measure soluble proteins in the stratum corneum. Ultimately, such local protein profiles could benefit the search for biomarkers to improve personalized treatment in psoriasis. This study aimed to explore the patient friendliness and protein detection by TAP in pediatric psoriasis in daily clinical practice. METHODS: In this observational study, TAPs measuring CXC chemokine ligand (CXCL)-1/2, CC chemokine ligand (CCL)-27, interleukin (IL)-1RA, IL-23, IL-1α, IL-8, IL-4, IL-22, IL-17A, vascular endothelial growth factor (VEGF), human beta-defensin (hBD)-2, hBD-1, and kallikrein-related peptidase (KLK)-5 were applied on lesional, peri-lesional, and non-lesional skin sites of psoriasis patients aged >5 to <18 years. Discomfort during TAP removal as an indicator for patient friendliness was assessed by visual analogue scale (VAS; range 0-10). RESULTS: Thirty-two patients (median age 14.0 years) were included, of which 19 were treated with solely topical agents and 13 with systemic treatment. The median VAS of discomfort during TAP removal was 1.0 (interquartile range 1.0). Significantly higher levels in lesional versus non-lesional skin were found for IL-1RA, VEGF, CXCL-1/2, hBD-2, and IL-8, whereas lower levels were found for IL-1α. Skin surface proteins were measured in both treatment groups, with significant higher lesional levels of KLK-5, IL-1RA, hBD-2, IL-1α, IL-23, and CCL-27 in the systemic treatment group. CONCLUSION: The TAP platform holds the potential for patient-friendly and noninvasive monitoring of skin-derived proteins in pediatric psoriasis patients in daily clinical practice.

Persistent ventilation inhomogeneity after an acute exacerbation in preschool children with recurrent wheezing.

BACKGROUND: Preschool children with recurrent wheezing suffer high morbidity. It is unclear whether objective measures of asthma control, such as pulmonary function tests (PFTs), provide additional information to the clinical assessment. METHODS: We recruited children between 3 and 6 years old, with a history of recurrent wheezing in the preceding year and treated for acute wheezing exacerbation in the emergency department (ED) into an observational cohort study. Children attended two outpatient visits: the first study visit within five days of discharge from the ED and the second study visit 12 weeks after the ED visit. We performed standardized symptom score (test for respiratory and asthma control in kids (TRACK)), multiple breath washout (MBW), spirometry, and clinical assessment at both visits. RESULTS: Seventy-four children, mean (standard deviation (SD)) age of 4.32 years (0.84), attended both visits. Paired FEV0.75 and lung clearance index (LCI) measurements at both time points were obtained in 37 and 34 subjects, respectively. Feasibility for all tests improved at visit 2 and was not age-dependent. At the second study visit, a third had controlled asthma based on the TRACK score, and the mean lung clearance index (LCI) improved from 9.86 to 8.31 (P = .003); however, 46% had an LCI in the abnormal range. FEV0.75 z-score improved from -1.66 to -1.17 (P = .05) but remained in the abnormal range in 24%. LCI was abnormal in more than half of the children with "well-controlled" asthma based on the TRACK score. There was no correlation between PFT measures and TRACK scores at either visit. CONCLUSIONS: Lung clearance index demonstrates a persistent deficit post-exacerbation in a large proportion of preschoolers with recurrent wheezing, highlighting that symptom scores alone may not suffice for monitoring these children.

Representation of older adults in randomized controlled trials on systemic treatment in plaque psoriasis: A systematic review.

BACKGROUND: Psoriasis is frequently seen in older patients, and systemic treatment is often indicated. Randomized controlled trials (RCTs) generally maintain strict inclusion and exclusion criteria, which might lead to a disproportionally high exclusion rate of older adults. OBJECTIVE: To determine the representation of older adults (≥65 years) in RCTs studying systemic treatment in plaque psoriasis. METHODS: A systematic literature search was performed in PubMed/MEDLINE, Embase, and CENTRAL, including RCTs concerning systemic treatments in plaque psoriasis in the past 15 years. Direct exclusion (based on age limits) and indirect exclusion (other exclusion criteria) were assessed. Study selection and data extraction were performed by 2 independent reviewers. RESULTS: Of 162 trials reviewed in full, 54 (33.3%) maintained an upper age limit (55-85 years). Of the remaining 108 trials, 106 reported exclusion criteria and did not use an upper age limit. However, 96 (90.6%) of these trials used exclusion criteria that might unequally affect older adults. The exclusion criteria serious concurrent infection (n = 104, 66.7%) and malignancy (n = 100, 64.1%) were most commonly mentioned in the included RCTs. LIMITATIONS: Only published RCTs were included. CONCLUSION: Older adults might be poorly represented in RCTs studying systemic treatment in plaque psoriasis because of a high rate of direct and indirect exclusion.