Dupilumab provides sustained effectiveness on patient-reported outcomes and favorable safety in patients with moderate-to-severe atopic dermatitis: Up to 5-year results from the daily practice BioDay registry.

BACKGROUND: Long-term daily practice data on patient-reported benefits of dupilumab for atopic dermatitis (AD) remains limited. OBJECTIVE: 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. METHODS: 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. RESULTS: 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%). LIMITATIONS: The overall percentage of missing values for selected PROMs was 26% in adults and 46% in pediatric patients. CONCLUSION: In addition to favorable safety, dupilumab has demonstrated sustained effectiveness across various PROMs, underscoring the treatment benefits from patients' perspectives.

Transcriptional differences between vesicular hand eczema and atopic dermatitis.

BACKGROUND: Transcriptome analyses of vesicular hand eczema (VHE) indicated a large overlap with atopic dermatitis (AD). However, differentially expressed genes (DEGs) that differentiate VHE from AD are unknown. OBJECTIVE: To identify distinctive transcriptional features of VHE in comparison to AD. METHODS: We re-analysed RNA sequencing data of 10 lesional palmar VHE epidermal biopsies and performed DEG analyses. We adjusted the obtained DEG results of 57 lesional whole AD skin biopsies of the upper extremities or trunk to our criteria. Up- and down-regulated DEGs in both skin diseases, VHE-only, AD-only, and opposite regulated DEGs were identified. Enrichment analyses and Chi-squared tests were conducted to test for differences in gene set enrichment between both skin diseases. RESULTS: Comparing 3028 DEGs in VHE (1645 up; 1383 down) with 5391 DEGs in AD (3842 up; 1549 down), revealed 1516 shared DEGs (1179 up; 337 down) and 1512 DEGs unique to VHE (466 up, 1046 down). Interferon signalling and necroptosis were significantly more prominent in VHE compared to AD. Downregulated genes identified only in VHE (like DNASE1L2, KRT2, KRT9 and KRT25) indicate an aberrant epidermal differentiation. CONCLUSION: Our study indicates a common pathophysiology between VHE and AD, but also reveals transcriptional differences between VHE and AD.

Successful tapering of dupilumab in patients with atopic dermatitis with low disease activity: a large pragmatic daily practice study from the BioDay registry.

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.

European patch test results with audit allergens as candidates for inclusion in the European Baseline Series, 2019/20: Joint results of the ESSCAA and the EBSB working groups of the ESCD, and the GEIDACC.

BACKGROUND: In 2019, a number of allergens (haptens), henceforth, "the audit allergens," were considered as potential additions to the European Baseline Series (EBS), namely, sodium metabisulfite, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, imidazolidinyl urea, Compositae mix II (2.5% or 5% pet), linalool hydroperoxides (lin-OOH), limonene hydroperoxides (lim-OOH), benzisothiazolinone (BIT), octylisothiazolinone (OIT), decyl glucoside, and lauryl glucoside; Evernia furfuracea (tree moss), was additionally tested by some departments as well. OBJECTIVES: To collect further data on patch test reactivity and clinical relevance of the audit allergens in consecutive patients across Europe. METHODS: Patch test data covering the audit allergens in 2019 and 2020 were collected by those departments of the European Surveillance System on Contact Allergies testing these, as well as further collaborators from the EBS working group of the European Society of Contact Dermatitis (ESCD), and the Spanish Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea. As patch test outcome, reactions between day (D) 3 and D5 were considered. RESULTS: Altogether n = 12 403 patients were tested with any of the audit allergen. Positive reactions were most common to lin-OOH 1% pet. (8.74% [95%CI: 8.14-9.37%]), followed by lin-OOH 0.5% pet., and lim-OOH 0.3% pet (5.41% [95% CI: 4.95-5.89%]). Beyond these terpene hydroperoxides, BIT 0.1% pet. was the second most common allergen with 4.72% (95% CI: 4.2-5.28%), followed by sodium metabisulfite 1% pet. (3.75% [95%CI: 3.32-4.23%]) and Compositae mix 5% pet. (2.31% [95% CI: 1.84-2.87%]). For some allergens, clinical relevance was frequently difficult to ascertain. CONCLUSIONS: Despite many positive patch test reactions, it remains controversial whether lin- and lim-OOH should be tested routinely, while at least the two preservatives BIT and sodium metabisulfite appear suitable. The present results are a basis for further discussion and ultimately decision on their implementation into routine testing among the ESCD members.

Prevalence of contact allergies in the population compared to a tertiary referral patch test clinic in Jena/Germany.

BACKGROUND: The contact allergy prevalences in patch-tested patients are usually higher than those in the population, owing to morbidity-driven selection. OBJECTIVES: To examine the differences between two samples, one from the population, one from the patch test clinic, in one area of Germany (Jena, Thuringia). METHODS: Between August 2008 and October 2011, a total of 519 participants of the population-based european dermato-epidemiology network (EDEN) fragrance study were patch tested in Jena using a TRUE Test baseline series extended with some pet.-based (fragrance) allergen preparations. Between 2007 and 2012 (inclusive), 1906 routine patients were patch tested for suspected allergic contact dermatitis (ACD) in the Jena University Hospital Department; of these 1694 (83.2%) with the German baseline series using pet./aq.-based, investigator-loaded allergens. RESULTS: In the population (clinical) sample, 19.6% (41.1%) were sensitized to at least one of the allergens considered. The most common baseline series allergens in the population/clinical sample were nickel (10.5%/13.2%), fragrance mix (FM) II (2.9%/6.7%), FM I (2.3%/8.3%), and cobalt (1.6%/5%). The clinical sample was slightly older (71.5% vs 55.9% age 40+) and included less males (36% vs 49.3%). CONCLUSIONS: Results are quite similar, although prevalences are usually higher in the clinical setting, with the exception of p-tert-butylphenol formaldehyde resin.

A survey of members of the European Surveillance System on Contact Allergy and the EU project "StanDerm" to identify allergens tested in cosmetic series across Europe.

BACKGROUND: There is currently no agreed cosmetic series for use across Europe. OBJECTIVES: To establish allergens currently tested in local and national cosmetic series. METHOD: Members of the European Surveillance System on Contact Allergy and the European Cooperation in Science and Technology project TD1206 ("StanDerm") were surveyed to establish their current practice. RESULTS: A wide range of allergens was tested but there was significant variation between centres on the allergens considered to be important in screening for allergy to cosmetics. The number of allergens tested in addition to the baseline series varied between 2 and 50. CONCLUSIONS: There is a need for further investigation to establish the frequency and relevance of reactions to cosmetic allergens to enable an agreed evidence-based cosmetic series to be produced. Criteria for inclusion need to be established.

Interventions for preventing occupational irritant hand dermatitis.

BACKGROUND: Occupational irritant hand dermatitis (OIHD) causes significant functional impairment, disruption of work, and discomfort in the working population. Different preventive measures such as protective gloves, barrier creams and moisturisers can be used, but it is not clear how effective these are. This is an update of a Cochrane review which was previously published in 2010. OBJECTIVES: To assess the effects of primary preventive interventions and strategies (physical and behavioural) for preventing OIHD in healthy people (who have no hand dermatitis) who work in occupations where the skin is at risk of damage due to contact with water, detergents, chemicals or other irritants, or from wearing gloves. SEARCH METHODS: We updated our searches of the following databases to January 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLlNE, and Embase. We also searched five trials registers and checked the bibliographies of included studies for further references to relevant trials. We handsearched two sets of conference proceedings. SELECTION CRITERIA: We included parallel and cross-over randomised controlled trials (RCTs) which examined the effectiveness of barrier creams, moisturisers, gloves, or educational interventions compared to no intervention for the primary prevention of OIHD under field conditions. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes were signs and symptoms of OIHD developed during the trials, and the frequency of treatment discontinuation due to adverse effects. MAIN RESULTS: We included nine RCTs involving 2888 participants without occupational irritant hand dermatitis (OIHD) at baseline. Six studies, including 1533 participants, investigated the effects of barrier creams, moisturisers, or both. Three studies, including 1355 participants, assessed the effectiveness of skin protection education on the prevention of OIHD. No studies were eligible that investigated the effects of protective gloves. Among each type of intervention, there was heterogeneity concerning the criteria for assessing signs and symptoms of OIHD, the products, and the occupations. Selection bias, performance bias, and reporting bias were generally unclear across all studies. The risk of detection bias was low in five studies and high in one study. The risk of other biases was low in four studies and high in two studies.The eligible trials involved a variety of participants, including: metal workers exposed to cutting fluids, dye and print factory workers, gut cleaners in swine slaughterhouses, cleaners and kitchen workers, nurse apprentices, hospital employees handling irritants, and hairdressing apprentices. All studies were undertaken at the respective work places. Study duration ranged from four weeks to three years. The participants' ages ranged from 16 to 67 years.Meta-analyses for barrier creams, moisturisers, a combination of both barrier creams and moisturisers, or skin protection education showed imprecise effects favouring the intervention. Twenty-nine per cent of participants who applied barrier creams developed signs of OIHD, compared to 33% of the controls, so the risk may be slightly reduced with this measure (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.72 to 1.06; 999 participants; 4 studies; low-quality evidence). However, this risk reduction may not be clinically important. There may be a clinically important protective effect with the use of moisturisers: in the intervention groups, 13% of participants developed symptoms of OIHD compared to 19% of the controls (RR 0.71, 95% CI 0.46 to 1.09; 507 participants; 3 studies; low-quality evidence). Likewise, there may be a clinically important protective effect from using a combination of barrier creams and moisturisers: 8% of participants in the intervention group developed signs of OIHD, compared to 13% of the controls (RR 0.68, 95% CI 0.33 to 1.42; 474 participants; 2 studies; low-quality evidence). We are uncertain whether skin protection education reduces the risk of developing signs of OIHD (RR 0.76, 95% CI 0.54 to 1.08; 1355 participants; 3 studies; very low-quality evidence). Twenty-one per cent of participants who received skin protection education developed signs of OIHD, compared to 28% of the controls.None of the studies addressed the frequency of treatment discontinuation due to adverse effects of the products directly. However, in three studies of barrier creams, the reasons for withdrawal from the studies were unrelated to adverse effects. Likewise, in one study of moisturisers plus barrier creams, and in one study of skin protection education, reasons for dropout were unrelated to adverse effects. The remaining studies (one to two in each comparison) reported dropouts without stating how many of them may have been due to adverse reactions to the interventions. We judged the quality of this evidence as moderate, due to the indirectness of the results. The investigated interventions to prevent OIHD probably cause few or no serious adverse effects. AUTHORS' CONCLUSIONS: Moisturisers used alone or in combination with barrier creams may result in a clinically important protective effect, either in the long- or short-term, for the primary prevention of OIHD. Barrier creams alone may have slight protective effect, but this does not appear to be clinically important. The results for all of these comparisons were imprecise, and the low quality of the evidence means that our confidence in the effect estimates is limited. For skin protection education, the results varied substantially across the trials, the effect was imprecise, and the pooled risk reduction was not large enough to be clinically important. The very low quality of the evidence means that we are unsure as to whether skin protection education reduces the risk of developing OIHD. The interventions probably cause few or no serious adverse effects.We conclude that at present there is insufficient evidence to confidently assess the effectiveness of interventions used in the primary prevention of OIHD. This does not necessarily mean that current measures are ineffective. Even though the update of this review included larger studies of reasonable quality, there is still a need for trials which apply standardised measures for the detection of OIHD in order to determine the effectiveness of the different prevention strategies.

Risk of Non-melanoma Skin Cancer in Patients with Atopic Dermatitis Treated with Oral Immunosuppressive Drugs.

There is uncertainty about the risk of developing non-melanoma skin cancer (NMSC), including basal cell carcinoma and squamous cell carcinoma (SCC), in patients with atopic dermatitis (AD) treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the University Medical Center Utrecht and Groningen, the Netherlands, were analysed. NMSC after oral immunosuppressive treatment was reported in 18 patients (3.2%). The standardized incidence ratio for developing SCC was 13.1 (95% confidence interval (95% CI) 6.5-19.7). Patients developing NMSC were older at the start of therapy (p<0.001) and data lock (p<0.001) compared with patients without NMSC. No significant differences were found in sex, cumulative days of oral immunosuppressive drugs and follow-up between these groups (p=0.42, p=0.88, and p=0.34, respectively). In interpreting these results it is important to include other factors, such as lack of association between treatment duration and tumour development and the long interval between treatment discontinuation and tumour development in some patients.

Two decades of p-phenylenediamine and toluene-2,5-diamine patch testing - focus on co-sensitizations in the European baseline series and cross-reactions with chemically related substances.

BACKGROUND: Cross-reactions and co-sensitizations are of great importance in understanding contact allergy and exposure sources. OBJECTIVES: To investigate common cross-reactions and co-sensitizations in p-phenylenediamine (PPD)-sensitized and toluene-2,5-diamine (TDA)-sensitized individuals. METHODS: From our patch test population, 8036 patients patch tested with the European baseline series were extracted. Readings had to be performed at least on day 3 according to ICDRG guidelines. RESULTS: Two hundred and fifty-one patients were sensitized to PPD and/or TDA; 231 patients were sensitized to PPD, and 109 to TDA. Significant differences were observed regarding the strengths of patch test reactions to PPD and number of cross-reactions. For TDA, a difference was found between all reaction strengths, except between + and ++ strengths. PPD-sensitized individuals were more likely to be sensitized to carba mix, cobalt chloride, colophonium, p-tert-butyl phenolformaldehyde resin, paraben mix, and methylisothiazolinone. TDA-sensitized individuals were more often sensitized to carba mix. CONCLUSIONS: Cross-reactivity was commonly found among individuals sensitized to PPD or TDA, and was strongly related to the strength of the patch test reaction. Regarding co-sensitizations, a frequently appearing or common exposure source could not be determined. However, modification of the allergen by, for example, the skin microbiota may have caused the formation of molecules that are, for the human immune system, indistinguishable from PPD.

Association of food allergy and atopic dermatitis exacerbations.

BACKGROUND: Atopic dermatitis (AD) and food allergy frequently coexist in children. OBJECTIVE: To examine the association between food allergy and AD. METHODS: Between 2001 and 2011, children referred to our tertiary care center underwent double-blind, placebo-controlled food challenges (DBPCFCs) for one or more suspected food allergies as part of regular care. Immediate reactions were observed and recorded by allergy nursing staff, whereas late reactions were ascertained by semistructured telephone interview 48 hours after challenge. To test to which degree specific IgE results were predictive in the outcome of DBPCFCs in children with and without (previous and current) AD, logistic regression analysis was performed. RESULTS: A total of 1186 DBPCFCs were studied. Sensitization to foods occurred significantly more often in children with previous AD. The association between specific IgE results and the outcome of DBPCFCs was significant for children with and without (previous and current) AD but stronger for children without current AD. The positivity rate of DBPCFCs in children with mild, moderate, and severe AD was 53.3%, 51.7%, and 100%, respectively. Children with AD and a history of worsening AD as their only symptom reacted as often to placebo as to challenge food. CONCLUSION: Children with current AD are more frequently asymptomatically sensitized to the foods in question than those without AD. In addition, children suspected of food allergy should be considered for testing, regardless of the severity of their AD. Our results suggest that children with exacerbation of AD in the absence of other allergic symptoms are unlikely to be food allergic.

Systematic review of cost-of-illness studies in hand eczema.

The individual burden of disease in hand eczema patients is considerable. However, little is known about the socio-economic impact of this disease. The aims of this review were to evaluate the literature on cost-of-illness in hand eczema, and to compose a checklist for future use. The literature was retrieved from the MEDLINE and EMBASE databases up to October 2015. Quality evaluation was based on seven relevant items in cost-of-illness studies. Cost data (direct and indirect) were extracted and converted into euros (2014 price level) by use of the Dutch Consumer Price Index. Six articles were included. The mean annual total cost per patient ranged from €1311 [corrected] to €9792 (direct cost per patient, €521 to €3722; [corrected] and indirect cost per patient, €100 to €6846). Occupational hand eczema patients showed indirect costs up to 70% of total costs, mainly because of absenteeism. A large diversity in hand eczema severity was found between studies. The socio-economic burden of hand eczema is considerable, especially for more severe and/or occupational hand eczema. Absenteeism from paid work leads to a high total cost-of-illness, although disregard of presenteeism often leads to underestimation of indirect costs. Differences in included cost components, the occupational status of patients and hand eczema severity make international comparison difficult. A checklist was added to standardize the approach to cost-of-illness studies in hand eczema.

The role of the antioxidant ascorbic acid in the elicitation of contact allergic reactions to p-phenylenediamine.

BACKGROUND: An allergic contact reaction is accompanied by high oxidative stress in the skin. Pretreatment of the skin with antioxidative substances could reduce the elicitation reaction. OBJECTIVES: To investigate, in a proof-of-principle study, whether pretreatment of the skin with the antioxidant ascorbic acid reduces the elicitation reaction to a p-phenylenediamine (PPD)-containing hair dye in sensitized subjects. METHODS: Twelve subjects with contact allergy to PPD, a documented skin reaction to a hair dye simulation exposure model and a history of hair dye-related skin complaints were included in this study. Skin areas on the forearms were, in a left versus right design, exposed to an emulsion with ascorbic acid and an emulsion without ascorbic acid, and then to a 2% PPD-containing hair dye testing formulation. In addition, control areas were exposed to the emulsions and to the PPD-containing hair dye formulation without pretreatment. Skin reactions were graded on day (D)2 and D3. RESULTS: Pretreatment with ascorbic acid emulsion resulted in a reduction in the elicitation reaction in 7 of 12 subjects at D3 (p = 0.046). No statistically significant difference was observed at D2. CONCLUSIONS: Pretreatment of the skin with the antioxidant ascorbic acid had an attenuating effect on the elicitation reaction to PPD in sensitized individuals.

ESSCA results with the baseline series, 2002-2012: p-phenylenediamine.

BACKGROUND: Allergic contact dermatitis caused by p-phenylenediamine (PPD) is common among all age groups and both sexes. Monitoring of prevalence and intensity of sensitization is important. OBJECTIVE: To evaluate contact allergy to PPD in Europe, and to compare reaction intensities in different European regions. METHODS: Data collected by the European Surveillance System on Contact Allergies (ESSCA) network between 2002 and 2012 from 12 European countries were analysed regarding prevalence, grading of positive reactions to PPD, and relevance. RESULTS: A total of 99 926 PPD-positive patients from 63 departments were included for analysis. The overall (2002-2012) prevalence of PPD sensitization in Europe is ∼4%. Stratified for country, the highest overall standardized prevalence was found in Lithuania, and the lowest in Slovenia. The prevalence of PPD sensitization did not decline over the years. In the southern European countries, higher numbers of strong and extremely strong reactions were registered. The clinical relevance of PPD sensitization varied from half to three-quarters. CONCLUSION: The prevalence of PPD sensitization has not changed over time. Strong and extremely strong patch test reactions are seen more often in the South, probably because of the higher number of PPD-containing hair dye products.

Patient Perception of Imiquimod Treatment for Actinic Keratosis and Superficial Basal Cell Carcinoma in 202 Patients.

OBJECTIVE: To document the impact on patient-reported outcomes and health-related quality of life (HRQoL) of treatment with imiquimod cream in patients with actinic keratosis (AK) and superficial basal cell carcinoma (sBCC). METHODS: This open-label, multicenter study included AK and sBCC patients eligible for treatment with imiquimod 5% cream. HRQoL was measured by the Skindex-17 and the Skin Cancer Index (SCI) and treatment satisfaction by the Treatment Satisfaction Questionnaire for Medication. RESULTS: 118 AK patients and 84 patients with sBCC were included. Low baseline HRQoL impairment was found on both questionnaires, which remained low after treatment, except for a small dip at the end of the application period. CONCLUSION: Imiquimod 5% cream treatment has no clinically relevant HRQoL impact in AK and sBCC patients according to the Skindex-17 and SCI. The effect of imiquimod treatment on HRQoL may be limited or these questionnaires do not fully capture relevant issues, such as fear of recurrence.

p-Phenylenediamine exposure in real life - a case-control study on sensitization rate, mode and elicitation reactions in the northern Netherlands.

BACKGROUND: The prevalence of p-phenylenediamine (PPD) sensitization is 4% in the patch tested population and varies between zero and 1.5% in the general population. Hair dye is a recognised sensitization source. OBJECTIVES: To define the prevalence rates of PPD sensitization in the general and patch tested populations of The Netherlands, and to gain insights into relationships between patch test strength and exposure sources. METHODS: Patch test database cases were matched with population-based controls. Analyses were performed based on demographic details, patch test reactions, and potential PPD exposure. RESULTS: PPD sensitization occurred in 3.3% of the patch tested population and in 1.3% of the general population. Hairdressers had a 4.4-fold increased chance of being sensitized to PPD (p = 0.041), and black henna tattoos showed a tendency for a 2.3-fold increased chance of sensitization (p = 0.081). Weak elicitation reactions were present in hairdressers and consumers. However, cases who had had black henna tattoos showed significantly more (extremely) strong patch test reactions upon elicitation (p = 0.015). CONCLUSIONS: The prevalence rates in the patch tested and general population of The Netherlands are comparable with the prevalence rates of other mid-European centres. PPD sensitization is often attributed to hair dye. However, this study shows that subjects sensitized by black henna tattoos present with very severe elicitation reactions, emphasizing the need for more strict policing the prohibition.

Patch test results with fragrance markers of the baseline series - analysis of the European Surveillance System on Contact Allergies (ESSCA) network 2009-2012.

BACKGROUND: Contact allergy to fragrances is common, and impairs quality of life, particularly in young women. OBJECTIVE: To provide current results on the prevalences of sensitization to fragrance allergens used as markers in the baseline series of most European countries. METHODS: Data of patients consecutively patch tested between 2009 and 2012 in 12 European countries with fragrance allergens contained in the baseline series were collected by the European Surveillance System on Contact Allergies network and descriptively analysed. Four departments used the TRUE Test(®) system. RESULTS: The 'basic markers' were tested on 51 477 [fragrance mix II (FM II)] to 57 123 [Myroxylon pereirae, balsam of Peru] patients, and yielded positive reactions as follows: fragrance mix I 6.9%, Myroxylon pereirae 5.4%, FM II 3.8%, colophonium 2.6%, and hydroxyisohexyl 3-cyclohexene carboxaldehyde 1.7%, with some regional differences. Prevalences with TRUE Test(®) allergens were lower. Additional fragrances were tested on 3643 (trimethylbenzenepropanol) to 14 071 (oil of turpentine) patients, and yielded between 2.6% (Cananga odorata) and 0.7% (trimethylbenzenepropanol) positive reactions. CONCLUSIONS: Contact allergy to fragrances is common throughout Europe, with regional variation probably being explained by patch test technique, and differences in exposure and referral patterns. The current basic markers of fragrance sensitivity in the baseline series should be supplemented with additional fragrance allergens.

Long-Term Effectiveness and Reasons for Discontinuation of Dupilumab in Patients With Atopic Dermatitis.

Importance: Limited data are available on the long-term effectiveness and safety of dupilumab for atopic dermatitis (AD) in daily practice. Objective: To evaluate clinical effectiveness and reasons for discontinuation of dupilumab treatment in children, adults, and older adults with AD with up to 5 years of treatment in daily practice. Design, Setting, and Participants: This prospective multicenter cohort study was conducted using the BioDay registry (4 academic and 10 nonacademic hospitals in the Netherlands) to identify patients with AD of all ages who were treated with dupilumab between October 2017 and December 2022. Main Outcomes and Measures: Clinical effectiveness was evaluated by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), and numeric rating scale (NRS) for pruritus, stratified by children (<18 years), adults (18-64 years), and older adults (≥65 years). In addition, time to response, treatment responders, EASI subscores, second treatment episodes, and thymus- and activation-related chemokine and eosinophil levels were assessed. For patients who discontinued dupilumab, the reason for discontinuation was evaluated. Results: In total, 1286 patients with AD (median [IQR] age, 38 [26-54] years; 726 [56.6%] male) were treated with dupilumab, including 130 children, 1025 adults, and 131 older adults. The median (IQR) follow-up time was 87.5 (32.0-157.0) weeks. Most patients maintained controlled AD, with EASI of 7 or lower and NRS for pruritus of 4 or lower varying between 78.6% and 92.3% and 72.2% and 88.2% for up to 5 years of treatment, respectively, while up to 70.5% of all patients prolonged the dosing interval to mostly 300 mg every 3 or 4 weeks. Mean EASI and NRS for pruritus were 2.7 (95% CI, 1.2-4.2) and 3.5 (95% CI, 2.7-4.3), respectively, after 5 years of treatment. Statistically significant differences between age groups were found over time for EASI and IGA; however, differences were rather small (week 52: EASI, 0.3-1.6; IGA, 0.12-0.26). No statistically significant differences between age groups were found for NRS for pruritus. Median thymus- and activation-related chemokine levels considerably decreased from 1751 pg/mL (95% CI, 1614-1900 pg/mL) to 390 pg/mL (95% CI, 368-413 pg/mL) after 6 months of treatment and remained low. Median eosinophil levels temporarily increased up to week 16, with a subsequently statistically significant decrease over time. In total, 306 patients (23.8%) discontinued dupilumab after a median (IQR) of 54.0 (29.0-110.00) weeks, with adverse events among 98 patients (7.6%) and ineffectiveness among 85 patients (6.6%) as the most frequently reported reasons. Forty-one patients (3.2%) restarted dupilumab, and most of these patients recaptured response. Conclusions and Relevance: In this cohort study with up to 5 years of follow-up, dupilumab maintained its clinical effectiveness, while two-thirds of patients tapered to a dosing interval of every 3 or 4 weeks. Treatment was discontinued in 23.8% of patients mainly due to adverse events and/or ineffectiveness.

Randomized controlled observer-blinded treatment of chronic foot eczema with iontophoresis and bath-PUVA.

The aim of this study was to investigate the effect of iontophoresis combined with local psoralen plus ultraviolet A (PUVA) therapy in chronic foot eczema. A randomized, observer-blinded, multi-centre study was conducted in 48 patients with chronic moderate-to-severe foot eczema randomized to one of 3 groups: In the iontophoresis group local bath-PUVA was preceded by iontophoresis. In the PUVA group only local PUVA was given. The corticosteroid group was treated with fluticasone. All treatments were given for 8 weeks, with an 8-week follow-up period. The primary efficacy parameter was eczema score described by Rosén et al. Secondary efficacy parameters were a global impression by the patient, and the Dermatology Life Quality Index (DLQI). The eczema score and the DLQI decreased significantly over time. There were no significant differences in the decrease in eczema score (p=0.053) and DLQI values (p=0.563) between the 3 treatments. The DLQI values in our chronic foot eczema patients were high. There was no obvious advantage of local bath-PUVA with or with-out iontophoresis over local steroid therapy.

Two decades of occupational (meth)acrylate patch test results and focus on isobornyl acrylate.

BACKGROUND: Acrylates constitute an important cause of occupational contact dermatitis. Isobornyl acrylate sensitization has been reported in only 2 cases. We encountered an industrial process operator with occupational contact dermatitis caused by isobornyl acrylate. OBJECTIVES: (i) To investigate whether it is relevant to add isobornyl acrylate to the (meth)acrylate test series. (ii) To report patients with (meth)acrylate contact allergy at an occupational dermatology clinic. PATIENTS/MATERIALS/METHODS: Our patch test database was screened for positive reactions to (meth)acrylates between 1993 and 2012. A selected group of 14 patients was tested with an isobornyl acrylate dilution series: 0.3%, 0.1%, 0.033%, and 0.01%. Readings were performed on D2, D3, and D7. RESULTS: One hundred and fifty-one patients were tested with our (meth)acrylate series; 24 had positive reactions. Most positive reactions were to 2-hydroxypropyl acrylate, 2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate, and diethyleneglycol diacrylate. Hypothetical screening with 2-hydroxypropyl acrylate, ethyleneglycol dimethacrylate, ethoxylated bisphenol A glycol dimethacrylate and trimethylolpropane triacrylate identified 91.7% of the 24 patients. No positive reactions were observed in 14 acrylate-positive patients tested with the isobornyl acrylate dilution series. The 0.3% isobornyl acrylate concentration induced irritant reactions in 3 patients. CONCLUSIONS: We report a rare case of allergic contact dermatitis caused by isobornyl acrylate. However, this study provides insufficient support for isobornyl acrylate to be added to a (meth)acrylate series.

Increase in vesicular hand eczema after house dust mite inhalation provocation: a double-blind, placebo-controlled, cross-over study.

BACKGROUND: It is unclear whether the respiratory tract is involved in eliciting or aggravating eczematous lesions in patients with vesicular hand eczema. Objectives. To investigate the effect of inhalation of house dust mite (HDM) on vesicular hand eczema. METHODS: Eighteen patients with vesicular hand eczema and HDM allergy received inhalation challenges with four concentrations of HDM in a randomized, double-blind, placebo-controlled, cross-over study. Early asthmatic reactions and late asthmatic reactions were defined as a placebo-corrected fall of 15% or more from baseline of forced expiratory volume in 1 second. Hand eczema was scored according to the Dyshidrotic Eczema Area and Severity Index (DASI) at baseline, and 1, 6, 24 and 48 hr. RESULTS: The median DASI increased significantly as compared with baseline at 6 and 48 hr after HDM inhalation. This increase was significantly different between the provocations at 6 hr. The median vesicles score increased significantly from baseline at 24 and 48 hr. Patients with a placebo-corrected increase in the number of vesicles at 24 hr and 48 hr had significantly more often late asthmatic reactions than those without an increase in the number of vesicles. Patients with a placebo-corrected increase of the DASI score at 24 hours had as a group a higher mean total IgE level than those without an increase of the DASI score. CONCLUSION: Hand eczema increased significantly more after HDM provocation than after placebo provocation. An increase in the number of vesicles was preceded by late asthmatic reactions. The group patients with an increase of hand eczema tended to have a higher mean total IgE level.