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Background: Twin studies revealed that genetic effects play a role in hand eczema (HE), but the responsible genetic factors are unknown. Objectives: To identify and characterise genetic loci associated with HE and to provide insight into the genetic overlap between HE and atopic dermatitis (AD). Methods: We used questionnaire‐derived and genotype data from the European population‐based Lifelines cohort and biobank. We performed a discovery genome‐wide association study (GWAS) of HE (2879 cases and 16 249 controls) and of AD (1706 cases and 17 190 controls). We replicated our findings in an independent Lifelines sample for HE (1188 cases and 6431 controls) and AD (757 cases and 6747 controls). We conducted several post‐GWAS analyses and performed genetic correlation analyses between our HE results and independent AD data. Results: The two‐step GWAS of HE, regardless of adjusting for AD, identified one independent locus 20q13.33, likely driven by a number of causal single‐nucleotide polymorphisms. For the AD GWAS, we replicated a known stop‐gained rs61816761 at locus 1q21.3 (FLG, FLGAS1). We found a strong genetic correlation (p < 0.01) between HE and AD (rg = 0.65), regardless of adjusting for AD (rg = 0.63). Conclusions: Locus 20q13.33 is associated with HE, and there is a large genetic overlap between HE and AD. [ABSTRACT FROM AUTHOR]

Long-term daily practice data on patient-reported benefits of dupilumab for atopic dermatitis (AD) remains limited. To evaluate patient-reported outcome measures (PROMs) and the safety of dupilumab in patients with moderate-to-severe AD over a follow-up period of up to 5 years. Data were extracted from the prospective, multicenter BioDay registry (October 2017–2022) of patients with moderate-to-severe AD treated with dupilumab in daily practice. In total 1223 patients, 1108 adults and 115 pediatric patients were included. After ≥1 year of treatment, mean Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numeric rating scale (NRS)-pruritus ranged between 7.8 and 8.7, 3.5 and 4.2, and 2.9 and 3.1 in adults, respectively, whilst these patient-reported outcome measures (PROMs) ranged between 8.9 and 10.9, 4.4 and 6.4, and 3.0 and 3.7 in pediatric patients, respectively. At follow-up, overall work impairment decreased from 40.1% to 16.3% to 13.3% in adults. Furthermore, class I obesity and itch-dominant patients generally had less favorable treatment response. Of all patients, 66.8% reported ≥1 adverse event, with conjunctivitis being the most common (33.7%). The overall percentage of missing values for selected PROMs was 26% in adults and 46% in pediatric patients. In addition to favorable safety, dupilumab has demonstrated sustained effectiveness across various PROMs, underscoring the treatment benefits from patients' perspectives. [ABSTRACT FROM AUTHOR]

Background Limited data are available regarding patient-centred dosing of dupilumab for atopic dermatitis (AD) in daily practice. Objectives To evaluate our patient-centred dupilumab dosing regimen in daily practice, to assess prognostic factors for successful tapering and to estimate medication-related cost savings. Methods This prospective multicentre study included adult patients with AD, participating in the BioDay registry, treated with dupilumab for ≥ 1.3 years. Interval prolongation was considered in the case of dupilumab standard dose for ≥ 1 year and persistent controlled AD [Eczema Area and Severity Index (EASI) ≤ 7; ≥ 6 months]. Primary endpoints were the mean EASI and Numeric Rating Scale (NRS)-pruritus after the start of tapering. Prognostic factors for successful tapering were analysed with logistic regression and a cost-savings analysis was performed. Results A total of 595 patients were included, of whom 401 patients [mean EASI 2.5 (SD 2.3); NRS-pruritus of 2.4 (SD 1.9) at the start of tapering] prolonged their dupilumab interval. In 83.3% of these patients tapering was successful; most patients used dupilumab every 3 or 4 weeks (Q3W/Q4W). A significant small increase was observed for EASI (highest mean 3.5) and NRS-pruritus (highest mean 3.2) (P < 0.001); however, scores remained low. Predicting successful tapering showed nonsignificant odds ratios for all incorporated variables. The estimated cost savings was €3 977 033.98 for 401 patients between January 2019 and June 2022. Conclusions This study showed successful tapering of dupilumab in 83.3% of patients with AD who attempted tapering, while maintaining controlled disease and with the majority using Q3W/Q4W. Interval prolongation can be beneficial both for the patient and from a socio-economic perspective. [ABSTRACT FROM AUTHOR]

Background: Real‐world data on the effectiveness of upadacitinib on atopic dermatitis (AD), hand eczema (HE) and HE in the context of AD are limited. Objectives: To evaluate the effectiveness and safety of upadacitinib on AD and on HE in patients with AD. Methods: This prospective observational cohort study includes clinical outcomes: Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Hand Eczema Severity Index (HECSI), Photographic guide; and PROMs: average pruritus and pain Numeric Rating Scale (NRS) score of the past week, Patient‐Oriented Eczema Measure (POEM), Patient‐Oriented Eczema, Dermatology Life Quality Index (DLQI), Atopic Dermatitis Control Tool (ADCT), Patient Global Assessment of Disease (PGAD), Quality Of Life Hand Eczema Questionnaire (QOLHEQ) at baseline, Week 4, and Week 16 of upadacitinib‐treated patients. Adverse events were monitored during each visit. Results: Thirty‐eight patients were included, of which 32 patients had HE. At Week 16, EASI‐75 was achieved by 50.0%. Absolute cutoff score NRS‐pruritus ≤4 was reached by 62.5%, POEM ≤7 by 37.5%, DLQI ≤5 by 59.4%, ADCT <7 by 68.8%, and PGAD rating of at least 'good' by 53.1%. HECSI‐75 was achieved by 59.3% and (almost) clear on the Photographic guide by 74.1%. The minimally important change in QOLHEQ was achieved by 57.9%. Sub‐analysis in patients with concomitant irritant contact dermatitis showed no differences. Safety analysis showed no new findings compared to clinical trials. Conclusions: Upadacitinib can be an effective treatment for patients with AD and concomitant HE in daily practice. Future studies should focus on the effectiveness of upadacitinib on chronic HE, especially on the different etiological subtypes of HE, including HE in non‐atopic individuals. [ABSTRACT FROM AUTHOR]

There is a lack of knowledge concerning loneliness and psychiatric disorders other than anxiety and depression in patients with atopic dermatitis. This cross-sectional study was conducted within the Lifelines Cohort Study, in the Netherlands, by sending an atopic dermatitis questionnaire to adult participants (n=135,950) in 2020. Psychiatric disorders were measured with a self-reported question and validated instrument (Mini International Neuropsychiatric Interview; M.I.N.I.), and loneliness was assessed with the validated 6-item De Jong Gierveld Loneliness Scale. In total, 56,896 subjects (mean age 55.8 years, 39.7% males) were included. Atopic dermatitis showed positive associations with self-reported chronic fatigue syndrome, burnout, depression, social phobia, panic disorder, attention deficit hyperactivity disorder, and eating disorder in the participants’ lifetimes. Based on the M.I.N.I., atopic dermatitis was positively associated with panic disorder and at least 1 anxiety disorder. In addition, subjects with atopic dermatitis were more likely to experience loneliness compared with those without atopic dermatitis. These associations were observed only in the moderate-to-severe, but not mild, atopic dermatitis group. This study raises awareness that a significant proportion of adults with atopic dermatitis feel lonely and are affected by several psychiatric disorders, especially those severely affected by atopic dermatitis. Further studies are required to evaluate if interdisciplinary care, such as the collaboration between dermatologists and psychiatrists, could optimize medical care for this vulnerable patient group. [ABSTRACT FROM AUTHOR]

Background: Dupilumab has proven to be an effective and safe treatment for atopic dermatitis (AD) in pediatric patients in clinical trials. However, few daily practice studies are available. The aim of this study is to evaluate the effect of 28 weeks dupilumab treatment on effectiveness, safety, and serum biomarkers in pediatric patients with moderate‐to‐severe AD in daily practice. Methods: Patients visited the outpatient clinic at baseline, 4, 16, and 28 weeks of treatment. Disease severity was assessed by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), Numeric Rating Scale (NRS)‐pruritus and ‐pain, and the Patient‐Oriented Eczema Measure (POEM). Side effects were evaluated. Nineteen severity‐associated serum biomarkers were measured. Predicted‐EASI (p‐EASI) was calculated. Results: Sixty‐one patients were included. Respectively 75.4%, 49.2%, and 24.6% reached EASI‐50, EASI‐75, and EASI‐90 and 36.1% achieved an IGA‐score (almost) clear. Improvement of ≥4 points on POEM, NRS‐pruritus, and NRS‐pain was reached by 84.7%, 45.3%, and 77.4%, respectively. Most reported side effects were conjunctivitis (n = 10) and headache (n = 4). Biomarkers TARC, PARC, periostin, sIL‐2Ra, and eotaxin‐3 significantly decreased during treatment. The p‐EASI showed a significant correlation with disease severity. Conclusion: Dupilumab treatment significantly improved disease severity and disease‐associated symptoms and decreased severity‐associated serum biomarkers in pediatric AD patients in daily practice. [ABSTRACT FROM AUTHOR]

Background: At present, no real‐world studies are available on different dupilumab dosing regimens in controlled atopic dermatitis (AD). The aim of this study was to clinically evaluate a patient‐centered dupilumab dosing regimen in patients with controlled AD and to relate this to serum drug levels and serum biomarkers. Methods: Ninety adult AD patients from the prospective BioDay registry were included based on their dupilumab administration interval according to a predefined patient‐centered dosing regimen. Group A (n = 30) did not fulfill the criteria for interval prolongation and continued using the standard dupilumab dosage (300 mg/2 weeks), group B (n = 30) prolonged dupilumab interval with 50% (300 mg/4 weeks), and group C (n = 30) prolonged dupilumab interval with 66%–75% (300 mg/6–8 weeks). AD severity score, patient‐reported outcomes, serum dupilumab levels, and serum biomarkers were analyzed over time. Results: Disease severity scores did not significantly change over time during the tapering period in any of the groups. In groups B and C, the Numeric Rating Scale (NRS)‐pruritus temporarily significantly increased after interval prolongation but remained low (median NRS‐pruritus≤4). Median dupilumab levels remained stable in group A (standard dosage), but significantly decreased in groups B and C (24.1 mg/L (IQR = 17.1–45.6); 12.5 mg/L (IQR = 1.7–22.3)) compared with the levels during the standard dosage (88.2 mg/L [IQR = 67.1–123.0, p <.001]). Disease severity biomarker levels (CCL17/CCL18) remained low in all study groups during the whole observation period. Conclusions: This study showed that dose reduction was successful in a subgroup of patients with controlled AD by using a patient‐centered dosing regimen. These patients showed stable low disease activity and low severity biomarkers over time. [ABSTRACT FROM AUTHOR]

Background: Studies on the association between severity of atopic dermatitis (AD) and lifestyle factors in adults have not been conducted in the Netherlands to date. Aim: To explore the association between moderate to severe AD and lifestyle factors in adults in the Dutch general population. Methods: We conducted this cross‐sectional study within the Lifelines Cohort Study by sending a digital AD questionnaire to 135 950 adults in 2020. We extracted data on lifestyle factors from baseline, collected between 2006 and 2013. We analysed the association between lifestyle factors and presence of AD of any severity and of moderate to severe AD, using binary logistic regression and linear regression models. Results: We enrolled 56 896 participants (mean age 55.8 years, 39.7% males). The lifetime prevalence of self‐reported physician‐diagnosed AD was 9.1%, and the point prevalence of any AD and of moderate to severe AD was 3.3% and 2.3%, respectively. We found that moderate to severe AD was associated with smoking habit of > 15 pack‐years, alcohol consumption of > 2 drinks per day, chronic stress, Class I obesity, and both shorter and longer sleep duration. Moreover, we found dose–response associations with increases in smoking pack‐years and level of chronic stress. We observed no associations with abdominal obesity, physical activity, diet quality or a vegetarian/vegan diet. Conclusion: We found associations between moderate to severe AD and some modifiable lifestyle factors. Our findings indicate that more screening and counselling for lifestyle factors, particularly smoking, alcohol use, stress, obesity and sleep disturbances, appears warranted in patients with moderate to severe AD. Further longitudinal studies are required to better characterize the direction of these associations and to develop strategies for prevention. [ABSTRACT FROM AUTHOR]

Clinical trials have shown that baricitinib, an oral selective Janus kinase 1/2 inhibitor, is effective for the treatment of moderate-to-severe atopic dermatitis. However, daily practice data are limited. Therefore, this multicentre prospective study evaluated the effectiveness and safety of 16-weeks' treatment with baricitinib in adult patients with moderate-to-severe atopic dermatitis in daily practice. A total of 51 patients from the BioDay registry treated with baricitinib were included and evaluated at baseline and after 4, 8 and 16 weeks of treatment. Effectiveness was assessed using clinician- and patient-reported outcome measurements. Adverse events and laboratory assessments were evaluated at every visit. At week 16, the probability (95% confidence interval) of achieving Eczema Area and Severity Index ≤ 7 and numerical rating scale pruritus ≤ 4 was 29.4% (13.1-53.5) and 20.5% (8.8-40.9), respectively. No significant difference in effectiveness was found between dupilumab non-responders and responders. Twenty-two (43.2%) patients discontinued baricitinib treatment due to ineffectiveness, adverse events or both (31.4%, 9.8% and 2.0%, respectively). Most frequently reported adverse events were nausea (n = 6, 11.8%), urinary tract infection (n = 5, 9.8%) and herpes simplex infection (n = 4, 7.8%). In conclusion, baricitinib can be an effective treatment option for moderate-to-severe atopic dermatitis, including patients with non-responsiveness on dupilumab. However, effectiveness of baricitinib is heterogeneous, which is reflected by the high discontinuation rate in this difficult-to-treat cohort. [ABSTRACT FROM AUTHOR]

Keywords: dupilumab; hand dermatitis; hand eczema; hyperkeratotic hand eczema; treatment EN dupilumab hand dermatitis hand eczema hyperkeratotic hand eczema treatment 124 127 4 01/28/21 20210201 NES 210201 Dupilumab, a monoclonal antibody inhibiting interleukin (IL)-4 and IL-13 signaling, is currently approved for the treatment of atopic dermatitis (AD). Effective treatment of hand eczema with dupilumab has been reported previously in case series, two small retrospective cohorts, and one prospective observational study including atopic, irritant and vesicular hand eczema subgroups.1-4 However, the effect of dupilumab on isolated hyperkeratotic hand eczema (HHE) has not yet been described. Hand eczema guidelines based on the Danish guidelines for the diagnosis and treatment of hand eczema. [Extracted from the article]

Background: Hyperkeratotic hand eczema (HHE) is a typical clinical hand eczema subtype with a largely unknown pathophysiology. Objective: To investigate histopathology, expression of keratins (K), epidermal barrier proteins, and adhesion molecules in HHE. Methods: Palmar skin biopsies (lesional and perilesional) were obtained from seven HHE patients and two healthy controls. Moreover, 135 candidate genes associated with palmoplantar keratoderma were screened for mutations. Results: Immunofluorescence staining showed a significant reduction of K9 and K14 in lesional skin. Upregulation was found for K5, K6, K16, and K17 in lesional skin compared with perilesional and healthy palmar skin. Further, upregulation of involucrin and alternating loricrin staining, both in an extracellular staining pattern, was found. Filaggrin expression was similar in lesional, perilesional, and control skin. No monogenetic mutations were found. Conclusion: Currently, the phenotype of HHE is included in the hand eczema classification system; however, it can be argued whether this is justified. The evident expression of filaggrin and involucrin in lesional skin does not support a pathogenesis of atopic eczema. The upregulation of K6, K16, and K17 and reduction of K9 and K14 might contribute to the underlying pathogenesis. Unfortunately, comparison with hand eczema studies is not possible yet, because similar protein expression studies are lacking. [ABSTRACT FROM AUTHOR]