Exploring Two New, Validated Disease-Specific Outcome Measures to Assess Severity of Chronic Hand Eczema: Investigator Global Assessment of Chronic Hand Eczema (IGA-CHE) and Hand Eczema Symptom Diary (HESD)-A Podcast.

Self-assessment of general health status has a significant influence on patient-related outcomes. The aims of this study were to investigate and compare the level of agreement between patients’ and dermatologists’ assessments of the severity of chronic hand eczema. From the German registry “German Chronic Hand Eczema Patient Long-Term Management Registry” (CARPE), 1,281 pairs of patients with chronic hand eczema and their dermatologists were included. Of these, 788 pairs served as a comparison 2 years after baseline. Concordance analyses found that complete concordance between patients’ and dermatologists’ assessments were 16.62% at baseline and 11.47% at follow-up. Overall, patients assessed their chronic eczema at baseline as more severe than did the dermatologists; whereas, at follow-up, patients assessed their condition as less severe than the dermatologists’ assessment. Bangdiwala’s B showed lower values of concordance for womens’ and older patients’ self-assessment with the dermatologists’ assessments. In conclusion, dermatologists should consider the patient’s perspective and the individual’s assessment of their chronic hand eczema in order to provide effective care in clinical practice.SIGNIFICANCEDaily clinical practice shows that, for chronic hand eczema, self-reported and physician-reported severity may differ and may influence treatment success. This study found low levels of agreement between dermatologists’ and patients’ assessments of the severity of the condition. Statistical analysis showed that women and older people tended to assess the severity of their condition differently compared with the dermatologist’s perspective. At follow-up patients assessed their chronic hand eczema as less severe compared with their dermatologist. To ensure better treatment success, dermatologists should take into account the personal views of patients regarding their chronic hand eczema.

Baricitinib treatment of severe chronic hand eczema: Two case reports

Chronic hand eczema is a significant cause of morbidity. A number of treatments are traditionally used, and often useful, but in spite of this a sizeable group of patients develop chronic recalcitrant hand eczema. Retinoids are known to influence keratinization and inflammation, and acitretin has shown some effect in the treatment of chronic hand eczema. Alitretinoin (9-cis-retinoic acid) is a panagonist retinoid binding to all six known retinoid receptors (RAR-α, -β, -γ and RXR-α, -β, -γ). Several studies have been carried out with this new drug, and it has been shown to be effective in 28% to 89% of patients with previously intractable hand eczema. In addition, alitretinoin appears to have some potential in the treatment of AIDS-related Kaposi sarcoma. Attempts to use the drug in secondary prophylaxis has shown some promise in former tobacco smokers, whereas no effect was seen in patients with cervical intraepithelial neoplasia. Currently, the primary therapeutic potential of alitretinoin appears to be the treatment of chronic recalcitrant hand eczema, which also forms a large and hitherto neglected group of patients.

Physicians need a simple, disease-specific tool with which to assess disease severity and the effect of therapeutic intervention in patients with chronic hand eczema. The currently available clinical scoring systems include numerous items, which makes them laborious to complete and limit their use in daily practice. To develop a simple tool with which to assess disease severity of patients with chronic hand eczema. We evaluated two tools, the Hand Eczema Severity Index (HECSI) and the Hand Eczema Area and Severity score, to determine their ability to predict the Investigator's Global Assessment (IGA) of disease severity in patients with moderate to severe hand eczema. We used a stepwise reduction analysis to determine a minimal set of significantly contributing items for predicting IGA. A three-item score, based on the highest observed value of induration, fissuring, and scaling, predicted IGA with a correlation of 0.667. The HECSI predicted the IGA with a correlation of 0.675. On the basis of this analysis, we propose a simple tool for clinical decision-making and evaluation of therapeutic intervention in daily practice.

The impact of hand eczema (HE) on Health-Related Quality of Life (HRQoL) has only been sparsely studied in a general population setting, and never by use of the disease specific Quality Of Life in Hand eczema Questionnaire (QOLHEQ). To examine the HRQoL of unselected individuals with HE using the QOLHEQ. Further, to provide prevalence estimates of severe and chronic HE (CHE), and to contrast overall health related outcomes between individuals with and without HE. In this nationwide, cross-sectional study a questionnaire covering questions on HE related outcomes, and overall health was sent to a random sample of 100 000 Danish adults via a secure digital mailbox, linked to their unique civil registration numbers. Data on demographic characteristics were retrieved from the civil registration system. Individuals reporting HE, further answered the QOLHEQ and other disease specific questions. The response rate was 42.7% (n = 42 691). Total estimates of lifetime, 1-year and point prevalences of HE were 24.4%, 13.3% and 5.8%. Of individuals reporting a 1-year prevalence, 35.1% reported moderate-severe disease and 82.6% CHE. Individuals with HE were more likely to report less good or poor overall health, and sick leave (any reason), compared to those without. In the 2176 (92.5%) with current HE who completed the QOLHEQ, median QOLHEQ scores corresponded to a moderate impairment of the symptoms and treatment and prevention domains and a slight impairment overall and for the emotions and functioning domains. Factors that were strongly associated with moderate to severe HRQoL impairment included severe, chronic and occupational HE as well as female sex. HE is highly prevalent, bears a considerable burden on society and significantly affects the lives of impacted individuals. Our findings indicate a necessity for targeted prevention aimed at high-risk groups, and support and treatment for those most affected.

Patient-reported outcome measures (PROMs) provide an important complement to physician-assessed clinical outcome measures in dermatologic diseases such as atopic dermatitis (AD) and chronic hand eczema (CHE). AD and CHE are chronic and relapsing inflammatory skin conditions that often co-occur. While both diseases result in various signs and symptoms that are burdensome and can negatively affect patients’ lives, there may be distinct differences in the signs, symptoms, burden, and health-related quality of life (HRQOL) impact of these diseases. The objective of this study was to identify and evaluate PROMs used in studies of AD and CHE. The aim was to explore the assessment of key symptoms and impacts, and identify any gaps in the measures in use. A structured review of the PubMed database was conducted to identify PROMs used or developed for use in AD or CHE. The Dermatology Life Quality Index (DLQI), the Pruritus/Itch Numeric Rating Scale (NRS), the Patient-Oriented Eczema Measure (POEM), and the Quality of Life in Hand Eczema Questionnaire (QOLHEQ) were identified and reviewed in detail. With these measures, the AD and CHE symptoms and impacts most commonly evaluated in the literature include dermatology-related HRQOL in the domains of symptoms and feelings, daily activities, leisure, work and school, personal relationships, and adverse effects; pruritus; sleep disturbance; AD-specific symptoms (dryness, itching, flaking, cracking, bleeding, and weeping/oozing); and CHE-specific symptoms (pain, itch, fissuring, redness, bleeding, and dryness). A review of regulatory labels of drugs approved for AD by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) found that, among the four measures reviewed, the Pruritus NRS was included in the FDA and EMA labels for dupilumab, the DLQI was included in the EMA labels for dupilumab and tacrolimus, and the POEM was included in the EMA label for dupilumab. Key symptoms of AD (e.g. itching, flaking, cracking) and CHE (e.g. pain, itching, fissuring) are increasingly being assessed with PROMs; however, primary endpoints in clinical trials are often based on clinician-reported outcome measures. As therapeutic strategies in dermatology are targeted at specific dermatologic symptoms and diseases affecting specific sites (e.g. CHE), future research should explore patients’ experiences with these symptoms and sites and the changes with treatment that are most meaningful to them.Electronic supplementary materialThe online version of this article (10.1007/s40271-019-00373-y) contains supplementary material, which is available to authorized users.

Chronic hand eczema (CHE) is a chronic inflammatory skin condition that affects the hands and wrists causing itching, dryness, cracking, and pain. It often affects people with atopic dermatitis (AD) and can interfere with work and daily life. Topical therapies may have limited utility from ineffectiveness, poor adherence, or poor tolerability. Here, we evaluate oral upadacitinib (UPA) as a potential therapeutic alternative for patients with AD and refractory CHE. This narrative review analyzed studies from PubMed, SCOPUS, and EMBASE evaluating CHE treatments. Eligible studies utilized the Hand Eczema Severity Index (HECSI), a validated clinician-reported outcome measure assessing CHE severity. HECSI-75 is the proportion of patients achieving at least a 75% improvement in clinical severity. Cases of three CHE patients from diverse demographics are presented. In two phase 3 randomized controlled trials of UPA for moderate-to-severe AD, 94.8% (803/847) and 92.6% (774/836) of patients had CHE with HECSI assessments at baseline. Rapid improvement in CHE was observed in patients who received either dose of UPA (15 mg or 30 mg) as early as week 1 (P≤0.001 vs placebo). By week 8, up to 83% of UPA-treated patients achieved a statistically significant improvement in CHE (HECSI 75; P≤0.001 vs placebo). These benefits were sustained through week 16. Real-world clinical cases showed CHE patients experienced marked symptom relief within days of initiating UPA. UPA-treated patients experienced rapid and sustained relief from CHE lesions, making it a promising therapeutic option for CHE patients for whom topical therapies are ineffective.

The epidemiology of chronic hand eczema (CHE) remains poorly examined. To investigate the prevalence of CHE in a general adult population and describe the characteristics of affected individuals. We investigated the prevalence and characteristics of CHE using a random sample from the general Danish population (The Danish Skin Cohort). CHE was defined as eczema on the hands or wrists during a minimum of three consecutive months or reoccurrence of hand eczema at least twice within 12 months. Out of 11 166 adults, 1306 experienced hand eczema (HE) at some point in their lifetime. Within the last 12 months, 408 (3.7%) experienced HE, of which 332 (81.4%) reported CHE. The crude 1-year period prevalence of CHE was 3.0% (95% confidence interval (CI), 2.7%-3.3%) while the standardised prevalence was 3.5% (95% CI, 3.3%-3.6%). Among adults with CHE, 70.8% were female, and the mean age was 48.0 years (standard deviation 16.6 years). Most individuals with CHE had two relapses (n = 309, 93.1%), while n = 206, 61.1%, had HE for more than 3 months. Compared to HE, CHE was more likely diagnosed by a dermatologist and affect the fingers and back of the hand. The standardised prevalence was 3.5% (95% CI, 3.3%-3.6%) and 4.2% (95% CI, 4.0%-4.4%) for CHE and HE, respectively. We identified a large overlap between HE and CHE (81.4%) in adults from the general population, indicating that many individuals affected by eczema on the hands may experience a chronic course.

Data on chronic hand eczema and severity of hand eczema in the general population is scarce. In this cross-sectional study, a questionnaire was sent to 135,950 Lifelines Cohort Study participants, in order to investigate the prevalence and severity of hand eczema in the Dutch general population. In total, 57,798 subjects were included. The lifetime prevalence of hand eczema was 15.0% (95% confidence interval 14.7–15.3), the 1-year prevalence 7.3% (95% confidence interval 7.1–7.6), and the self-reported physician-diagnosed prevalence 6.1% (95% confidence interval 5.9–6.3). The 1-year prevalence of chronic hand eczema was 4.7% (95% confidence interval 4.5–4.9). The majority (56.9%) of the subjects with hand eczema had almost clear at worst ever and the prevalence of severe to very severe hand eczema at worst ever in the general population was 1.9% (95% confidence interval 1.8–2.1). Future epidemiological studies in the general population should include data about chronic hand eczema and severity of hand eczema, as this can provide perspective on the burden of hand eczema.

Management of chronic hand eczema (CHE) remains a challenge; effective topical treatment is limited to corticosteroids. To assess the efficacy and safety of a novel, pan-Janus kinase inhibitor (delgocitinib) in patients with CHE. In this randomized, double-blind, phase IIa study, patients with CHE received delgocitinib ointment 30mg g-1 or vehicle ointment for 8 weeks. The primary end point was the proportion of patients achieving treatment success ['clear'/'almost clear' skin with ≥ 2-point improvement in the Physician's Global Assessment of disease severity (PGA)] at week 8. Secondary end points included Hand Eczema Severity Index (HECSI) score changes and the proportion of patients achieving treatment success on the Patient's Global Assessment of disease severity (PaGA). Ninety-one patients were randomized. More patients receiving delgocitinib (46%) than vehicle (15%) [odds ratio 4·89, 95% confidence interval (CI) 1·49-16·09; P = 0·009] achieved treatment success (PGA). Adjusted mean HECSI score at week 8 was lower with delgocitinib (13·0) than with vehicle (25·8) (adjusted mean difference -12·88,95% CI -21·47 to -4·30; P = 0·003). More patients receiving delgocitinib than vehicle achieved treatment success by PaGA, but this did not reach statistical significance. The incidence of adverse events was similar with delgocitinib and vehicle; none led to discontinuation of delgocitinib. Delgocitinib ointment was efficacious and well tolerated. As a plateau of efficacy was not observed, a longer treatment period may lead to increased efficacy. Further clinical studies are warranted to confirm these findings in patients with CHE. What's already known about this topic? Chronic hand eczema (CHE) has a significant burden. Few randomized controlled studies have evaluated current treatments for CHE; only limited data are available to inform and guide clinical practice decisions. There is currently an unmet need for efficacious and well-tolerated topical treatment options for patients with CHE. What does this study add? Delgocitinib is a novel, pan-Janus kinase (JAK) inhibitor specific for JAK1, JAK2, JAK3 and tyrosine kinase 2. Topical use of delgocitinib ointment resulted in clearance of CHE after 8 weeks of treatment in a significantly greater number of patients than vehicle; delgocitinib was also well tolerated. Results from this proof-of-concept clinical study suggest that topical delgocitinib may provide therapeutic benefit to patients with CHE with inadequate responses to topical corticosteroids.

PSY52 PATIENT-REPORTED OUTCOME MEASURES IN ATOPIC DERMATITIS AND CHRONIC HAND ECZEMA IN ADULTS

The self-reported annual prevalence of hand eczema (HE) in adults is about 10%. Incidence and prevalence data for HE, chronic HE (CHE) and steroid-refractory CHE (SR-CHE) in physician-attended populations are lacking. To estimate the prevalences of HE, CHE and SR-CHE in a primary-care population using a cross-sectional design; and to estimate the incidence of each and describe initial therapy using a cohort approach. The population was all patients in the Clinical Practice Research Datalink for 2000-10, 2005-10 and 2010-11. HE was defined as any of 12 diagnoses (six specific to the hand, six for contact dermatitis). HE became CHE if any of these 12, or three additional diagnoses, occurred 90-365 days after the first HE, and if the patient was prescribed at least one course of potent topical steroids. A patient with CHE was classified as having SR-CHE if they were (i) referred to a dermatologist and/or (ii) prescribed phototherapy, systemic immunomodulators, oral corticosteroids, alitretinoin or acitretin. The 1-year adult prevalence of HE was 0·4%. The period prevalences of SR-CHE for 1, 5 and 10 years in adults were 0·008%, 0·036% and 0·072%, respectively; lifetime estimates were 0·071%, 0·080%, 0·098%. About one-half of cases of CHE were steroid refractory. All conditions were more common in female than in male patients. One-third of HE diagnoses were specific for the hand, the remainder were for contact dermatitis. The majority (62%) of newly diagnosed patients with HE were not prescribed treatment in the 12 months after diagnosis. Although the prevalence of HE could be 2-3 times higher than reported herein, the proportion of adults seeking medical care for HE is a fraction of those who self-report HE. SR-CHE is rare.

Measuring patient-reported outcomes is crucial to fully capture the burden of chronic hand eczema (CHE). To assess the effect of delgocitinib cream on itch, pain and nine additional key signs and symptoms reported by patients with CHE using the Hand Eczema Symptom Diary (HESD). In a double-blind, phase IIb dose-ranging trial (NCT03683719), 258 adults with mild to severe CHE were randomized to delgocitinib cream 1, 3, 8 or 20 mg/g or cream vehicle twice daily for 16 weeks. Patients assessed 11 signs and symptoms of CHE daily through the HESD using an 11-point numeric rating scale; this was an exploratory endpoint. Delgocitinib cream 20 mg/g was associated with an early and sustained reduction in itch and pain, along with clinically relevant reductions of ≥4 points from baseline to Week 16 in 48.4% and 63.6% of patients, respectively (17.9% and 5.9% with cream vehicle). There were improvements versus cream vehicle in all assessed CHE signs and symptoms (20 mg/g, p < 0.05). Delgocitinib cream reduced itch, pain and other signs and symptoms in patients with CHE. This data correlated with clinician-reported outcomes, indicating that the HESD may be a useful assessment tool for CHE management.

Hand eczema is a common condition that affects the hands and can have significant negative impacts on quality of life and socio-economic consequences. Unfortunately, treatment options are currently limited, with only alitretinoin approved for systemic treatment of severe chronic hand eczema. To identify new therapies, understanding the pathogenesis is crucial. Additionally, limited data is available on the prevalence and severity of chronic hand eczema in the general population. It was found that the lifetime prevalence of hand eczema in Dutch general population was 15.0%, with a one-year prevalence of 7.3%, and a majority of patients (56.9%) experiencing mild hand eczema. However, a significant portion of participants had severe to very severe hand eczema (1.9%). The majority of patients with hand eczema had chronic hand eczema, resulting in a one-year prevalence of 4.7%, and the severity of the condition was significantly higher in those with chronic complaints. A transcriptome (gene expression) and proteome (protein expression) analysis on vesicular hand eczema was conducted, in which it was found that the transcriptome of vesicular hand eczema overlaps largely with the transcriptome of eczema in patients with atopic dermatitis. Therefore, treatments for atopic dermatitis may also be effective in treating vesicular hand eczema. Finally, dupilumab, a biological treatment, showed promising results in hand eczema patients with atopic dermatitis in daily practice studies and in patients with severe hand eczema in a 16-week randomized, placebo-controlled clinical trial.

Chronic hand eczema is a common dermatological disorder of multifactorial aetiology. It affects physical, material, social and psychological aspects of life, thereby impairing health-related quality of life. The aim of the present study was to assess quality of life, anxiety, depression and obsessive-compulsive tendencies in patients with chronic hand eczema. Seventy-one patients with chronic hand eczema were included in the study. Quality of life was evaluated according to the Dermatology Life Quality Index (DLQI). Patients were also assessed for anxiety and depression with the Hospital Anxiety and Depression Scale (HADS), and for compulsive behaviour with the Leyton Trait Scale. The DLQI score was 11.11 ± 1.81 in patients with chronic hand eczema. Scores on the Leyton Trait Scale were significantly higher than those of healthy controls (p < 0.027). As concerns the HADS-Anxiety subscale, patients with hand dermatitis had statistically significantly higher scores than those of volunteers (p = 0.002). In contrast, no statistically significant difference was found between the two groups with regard to the HADS-Depression subscale score and total HADS score. Hand eczema treatment should address the severity of skin lesions as well as the psychological impact of hand eczema.