The epidemic of methylisothiazolinone contact allergy in Europe: follow-up on changing exposures.

BACKGROUND: Methylisothiazolinone (MI) has caused an unprecedented epidemic of contact allergy in Europe and elsewhere. Subsequently, regulatory action has been taken, at least in Europe, aiming at reducing risk of MI sensitization. OBJECTIVE: To follow-up on the prevalence of contact allergy to MI in consecutively patch tested patients and assess the spectrum of products containing MI or methylchloroisothiazolinone (MCI)/MI in patients positive to MI which elicited current allergic contact dermatitis. METHODS: A cross-sectional survey was performed in 2016 and 2017, including all adult patients patch tested with the baseline series (including MI 0.2% aq.) between 1 May and 31 October at 14 centres in 11 European countries. Patients with positive reactions (+ to +++) to MI were further examined regarding history, clinical characteristics and eliciting products, which were categorized into 34 types and 4 classes (leave-on, rinse-off, household, occupational). The results were compared with the reference year 2015. RESULTS: A total of 317 patients, n = 202 of 4278 tested in 2016 (4.72%) and n = 115 of 3879 tested in 2017 (2.96%), had positive reactions to MI; the previous result from 2015 was 5.97% (P < 0.0001). The share of currently relevant contact allergy among all positive reactions declined significantly as well (P = 0.0032). Concerning product classes, a relative decline of leave-on and a relative increase of rinse-off and household products was noted. CONCLUSION: The prevalence of MI contact allergy decreased by 50% from 2015 to 2017. As a consequence of regulation, the share of cosmetics products (leave-on in particular) eliciting allergic contact dermatitis is decreasing. The chosen method of analysing causative products in sensitized patients has proven useful to monitor effects of intervention.

Use of topical antipsoriatic drugs in Denmark: a nationwide drug utilization study.

BACKGROUND: The reported real-life use of prescribed topical antipsoriatic drugs is conflicting and based on heterogeneous data sources. OBJECTIVES: To describe the utilization of topical antipsoriatic drugs among patients with psoriasis in Denmark. METHODS: A drug utilization study was performed based on nationwide Danish health registry data. We identified patients who received a first-time hospital diagnosis of psoriasis and redeemed at least one topical drug prescription in the period 2005-2015 (n = 7743). Patients were followed for 3 years from the time of diagnosis. Use of topical and systemic antipsoriatic drugs was described, specified by the type of treatment. RESULTS: The total use of topical drugs was divided between corticosteroids with calcipotriol (31%), calcipotriol (6·5%), very potent corticosteroids (24%), potent corticosteroids (30%), moderate corticosteroids (7·2%) and corticosteroids with antimicrobials (1·6%). There was a 19% reduction in the overall use of topical drugs during the study period. Use increased around the time of diagnosis and the majority of patients redeemed more than two packages of topical drugs during the first year after being diagnosed. Regional differences in patients' use of topical drugs varied considerably. The distribution of use of topical drugs was uneven, with a minority of all patients (25%) using 70% of the total amount of topical treatment. There was a 70% increase in the use of methotrexate over the study period. Biologics were used by up to 6%. CONCLUSIONS: The study provides further evidence that the use of topical antipsoriatic drugs shows considerable heterogeneity over time and regional practices, and differences between patients.

A smartphone application supporting patients with psoriasis improves adherence to topical treatment: a randomized controlled trial.

BACKGROUND: Adherence to topical psoriasis treatments is low, which leads to unsatisfactory treatment results. Smartphone applications (apps) for patient support exist but their potential to improve adherence has not been systematically evaluated. OBJECTIVES: To evaluate whether a study-specific app improves adherence and reduces psoriasis symptoms compared with standard treatment. METHODS: We conducted a randomized controlled trial (RCT, clinicaltrials.gov registration: NCT02858713). Patients received once-daily medication [calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam] and were randomized to no app (n = 66) or app intervention (n = 68) groups. In total, 122 patients (91%) completed the 22-week follow-up. The primary outcome was adherence, which was defined as medication applied ≥ 80% of days during the treatment period and assessed by a chip integrated into the medication dispenser. Secondary outcomes were psoriasis severity measured by the Lattice System Physician's Global Assessment (LS-PGA) and quality of life, measured using the Dermatology Life Quality Index (DLQI) at all visits. RESULTS: Intention-to-treat analyses using regression was performed. More patients in the intervention group were adherent to Cal/BD cutaneous foam than those in the nonintervention group at week 4 (65% vs. 38%, P = 0·004). The intervention group showed a greater LS-PGA reduction than the nonintervention group at week 4 (mean 1·86 vs. 1·46, P = 0·047). A similar effect was seen at weeks 8 and 26, although it did not reach statistical significance. CONCLUSIONS: This RCT demonstrates that the app improved short-term adherence to Cal/BD cutaneous foam treatment and psoriasis severity.

Factors associated with combined hand and foot eczema.

BACKGROUND: As for hand eczema, the aetiology of foot eczema is multifactorial and not very well understood. The aim of the present study was to identify factors associated with foot eczema in a cohort of hand eczema patients being classified into different subgroups. METHODS: Associations between foot and hand eczema were studied in a cross-sectional design in a cohort of hand eczema patients. Consecutive patients were recruited from nine different European Centres during the period October 2011-September 2012. Data on demographic factors, presence of foot eczema, hand eczema duration and severity, and whether the hand eczema was work-related or not were available, as well as patch-test results. RESULTS: Of a total of 427 hand eczema patients identified, information on foot eczema was available in 419 patients who were included in the present study. A total of 125 patients (29.8%) had concomitant foot and hand eczema. It was found more often in association with hyperkeratotic hand eczema (P = 0.007) and was less often associated with irritant hand eczema (P < 0.001). However, foot eczema was nevertheless found in 18% of patient with irritant hand eczema and in 25% of patients with occupational hand eczema. Combined foot and hand eczema was associated with more severe and long-standing hand eczema (P < 0.001 and P = 0.004, respectively). Contact allergy was found in 51.8% with no difference between patients with combined foot and hand eczema and patients with hand eczema only. CONCLUSION: Occurrence of combined foot and hand eczema is a common finding and not restricted to endogenous hand eczema.

Classification of hand eczema.

BACKGROUND: Classification of hand eczema (HE) is mandatory in epidemiological and clinical studies, and also important in clinical work. OBJECTIVES: The aim was to test a recently proposed classification system of HE in clinical practice in a prospective multicentre study. METHODS: Patients were recruited from nine different tertiary referral centres. All patients underwent examination by specialists in dermatology and were checked using relevant allergy testing. Patients were classified into one of the six diagnostic subgroups of HE: allergic contact dermatitis, irritant contact dermatitis, atopic HE, protein contact dermatitis/contact urticaria, hyperkeratotic endogenous eczema and vesicular endogenous eczema, respectively. An additional diagnosis was given if symptoms indicated that factors additional to the main diagnosis were of importance for the disease. RESULTS: Four hundred and twenty-seven patients were included, 379 (89%) of the patients could be classified directly into one of the six diagnostic subgroups, with irritant and allergic contact dermatitis comprising 249 patients (58%). For 32 (7%) more than one of the six diagnostic subgroups had been formulated as a main diagnosis, and 16 (4%) could not be classified. 38% had one additional diagnosis and 26% had two or more additional diagnoses. Eczema on feet was found in 30% of the patients, statistically significantly more frequently associated with hyperkeratotic and vesicular endogenous eczema. CONCLUSION: We find that the classification system investigated in the present study was useful, being able to give an appropriate main diagnosis for 89% of HE patients, and for another 7% when using two main diagnoses. The fact that more than half of the patients had one or more additional diagnoses illustrates that HE is a multifactorial disease.

Atopic dermatitis from adolescence to adulthood in the TOACS cohort: prevalence, persistence and comorbidities.

BACKGROUND: While much is known about childhood atopic dermatitis, little is known about persistence of atopic dermatitis into adult life. We report, to our knowledge for the first time, the clinical course of atopic dermatitis in an unselected cohort of adolescents followed into adulthood. METHODS: The course of atopic dermatitis from adolescence to adulthood was studied prospectively in a cohort of unselected 8th-grade schoolchildren established in 1995 and followed up in 2010 with questionnaire and clinical examination. RESULTS: The lifetime prevalence of atopic dermatitis was high (34.1%), and a considerable number of adults still suffered from atopic dermatitis evaluated both by questionnaire (17.1%) and clinical examination (10.0%). Persistent atopic dermatitis was found in 50% of those diagnosed in school age, and persistent atopic dermatitis was significantly associated with early onset, childhood allergic rhinitis and hand eczema. A close association was also found with allergic contact dermatitis and increased specific IgE to Malassezia furfur, but not with filaggrin gene defect. CONCLUSION: Persistence of atopic dermatitis in adulthood is common and affects quality of life. Persistent atopic dermatitis is particularly prevalent in those with early onset, allergic rhinitis and hand eczema in childhood. It is important to recognizing atopic dermatitis as a common and disabling disease not only in children but also in adults.

Statin use and risk of nonmelanoma skin cancer: a nationwide study in Denmark.

BACKGROUND: Evidence is conflicting regarding statin use and risk of basal cell (BCC) and squamous cell skin cancer (SCC). METHODS: Using Danish nationwide registries, we identified all patients with incident BCC/SCC during 2005-2009 and matched them to population controls. We computed odds ratios (ORs) for BCC and SCC associated with statin use. RESULTS: We identified 38,484 cases of BCC and 3724 cases of SCC. Statin ever use was associated with ORs of 1.09 (CI: 1.06-1.13) for BCC and 1.01 (CI: 0.91-1.11) for SCC. CONCLUSIONS: Statin use was not associated with risk of SCC. Residual confounding plausibly explains the marginally increased risk of BCC.

Hand eczema in The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis (TOACS): prevalence, incidence and risk factors from adolescence to adulthood.

BACKGROUND: Several studies have evaluated the incidence and prevalence of hand eczema in unselected adults. However, no studies have followed unselected adolescents from primary school into adult life to evaluate the course and risk factors for hand eczema. OBJECTIVES: To estimate the incidence of hand eczema from adolescence to adulthood and the prevalence of hand eczema in young adults, together with risk factors for hand eczema. METHODS: A cohort of 1501 unselected eighth-grade schoolchildren (mean age 14 years) was established in 1995. In 2010, 1206 young adults from the cohort were asked to complete a questionnaire and participate in a clinical examination, including patch testing. RESULTS: The incidence of hand eczema was 8·8 per 1000 person-years. The 1-year-period prevalence of hand eczema in the young adults was 14·3% (127 of 891) and the point prevalence 7·1% (63 of 891), with significantly higher prevalence in females. At the clinical examination 6·4% (30 of 469) had hand eczema. Factors in childhood of importance for adult hand eczema were atopic dermatitis and hand eczema. Wet work in adulthood was a risk factor, as was taking care of small children at home. Interestingly, hand eczema among unselected young adults was associated with sick leave/pension/rehabilitation, indicating possible severe social consequences. Only 39·0% of patients participated in the clinical examination, while 75·0% answered the questionnaire. CONCLUSIONS: A high incidence and prevalence of hand eczema were found in 28-30-year-old adults, and were highly associated with childhood hand eczema and atopic dermatitis, along with wet work and taking care of small children in adulthood. There was no association with smoking, education level or nickel allergy in childhood.

Prevalence, incidence rates and persistence of contact allergy and allergic contact dermatitis in The Odense Adolescence Cohort Study: a 15-year follow-up.

BACKGROUND: A cohort of 1501 unselected 8th grade schoolchildren was established 15 years ago with the aim to follow the course of contact allergy and allergic contact dermatitis (ACD) from school age into adult life. To date no studies have evaluated incidence rates and persistence of contact allergy and ACD in an unselected population from adolescence to adulthood. OBJECTIVES: To estimate the incidence rates and persistence of contact allergy and ACD from adolescence to adulthood, and the point prevalence in adulthood. METHODS: In total, 1206 young adults from the cohort were contacted and asked to complete a questionnaire and participate in a clinical examination including patch testing with TRUE Test(®) . The questionnaire was answered by 899 (74.6%), however, only 442 (36·7%) of those invited participated in patch testing. RESULTS: Over the 15-year period the incidence rates of contact allergy and ACD were 13·4% and 7·8%, respectively. The point prevalence of contact allergy was 20·1%, and present or past ACD was found in 12·9% of those followed. Nickel was the most common contact allergen (11·8%), followed by cobalt (2·3%), colophony (2·0%), thiomersal (1·4%) and p-phenylenediamine (1·1%). Most nickel reactions were persistent, and a significant number of new nickel sensitizations were found. Fragrance mix I reactions from adolescence could not be reproduced. CONCLUSIONS: From adolescence to adulthood the incidence rates of contact allergy and ACD were high. Nickel was still the most common contact allergen, and new sensitizations occurred despite the European Union nickel regulation. Fragrance mix I was a poor marker for history of eczematous skin reaction to perfumed products.

Applicability of an exaggerated forearm wash test for efficacy testing of two corticosteroids, tacrolimus and glycerol, in topical formulations against skin irritation induced by two different irritants.

BACKGROUND/PURPOSE: Alternatives to corticosteroids in the treatment of irritant contact dermatitis (ICD) are needed and may include glycerol and topical immunomodulators like tacrolimus. Because the efficacy of different treatments in experimentally induced ICD may vary depending on the irritant applied, we tested the efficacy of four anti-irritant compounds using the two different irritants sodium lauryl sulfate (SLS) and nonanoic acid (NON). METHODS: In a randomized, double-blind, controlled trial, healthy volunteers were exposed to 5% SLS and 50% NON (the right and the left forearm, respectively) in a cumulative wash test. Induction of ICD was obtained by three daily washings for 7 days, followed by a maintenance phase with two daily washings for 12 days. Treatment (triamcinolone acetonide, clobetasol propionate, tacrolimus and glycerol ointment) was started at day 7 and applied immediately after washing. Vehicle and no treatment served as the control. Reactions were evaluated clinically and instrumentally. RESULTS: No treatments were significantly better than the other treatments and controls. There was a tendency toward a dose-dependent response to corticoid treatment, and a trend toward worsened irritancy by tacrolimus on SLS-irritated skin. Explained variance in the experiment by anova revealed a very small effect of treatments compared with an immense and significant subject effect. CONCLUSION: No claims of effective anti-irritant properties for any of the ointments can be maintained. Application of the present wash test as a tool for anti-irritant efficacy testing may be complicated by the small observed variance explained by treatment.

Sites of dermatitis in a patch test population: hand dermatitis is associated with polysensitization.

BACKGROUND: Sites of dermatitis in larger series of contact allergic patients are rarely reported. Increased risk of polysensitization has been linked only to stasis dermatitis and leg ulcers. However, a large proportion of polysensitized individuals may have dermatitis in other skin areas. OBJECTIVES: To examine the site of dermatitis at time of first appearance in contact allergic individuals with special focus on the distribution of dermatitis in polysensitized individuals and to examine if widespread dermatitis is more frequent in polysensitized than in single/double-sensitized patients. METHODS: A matched case-control study was carried out including 394 polysensitized and 726 single/double-sensitized patients who responded to a postal questionnaire. All subjects were recruited from a hospital patch test population. RESULTS: The hands were the most frequent and the anogenital region was the least frequent skin area affected with dermatitis. Dermatitis on the hands/wrists [odds ratio (OR) 1.58], in the armpits (OR 1.56) and on the back (OR 1.91) was positively associated with polysensitization. The hands were the only skin area with dermatitis which maintained the association to polysensitization in two subpopulations consisting of, respectively, individuals with and without atopic eczema. Dermatitis on the scalp was negatively associated with polysensitization (OR 0.66) primarily for individuals without atopic eczema. The dermatitis did not seem to be more widespread in polysensitized compared with single/double-sensitized patients. CONCLUSIONS: Special awareness in patients with hand dermatitis seems justified either to prevent development of multiple contact allergies or to document polysensitization as an aetiological factor.

The prevalence of food hypersensitivity in young adults.

rising prevalence of food hypersensitivity (FHS) and severe allergic reactions to foods have been reported in the last decade. However, little is known on the prevalence in young adults. This study estimated the prevalence of FHS to the most common allergenic foods in an unselected population of young adults. We investigated a cohort of 1272 young adults 22 years of age by questionnaire, skin prick test (SPT) and histamin release (HR) followed by oral challenge to the most common allergenic foods. FHS was divided into primary and secondary FHS. Primary FHS was defined as being independent of pollen sensitization, whereas secondary FHS was defined as reactions to pollen related fruits and vegetables in pollen allergic patients. The questionnaire was returned by 77.1%. Primary FHS was reported by 19.6% and secondary FHS by 16.7% of the participants. Confirmed primary FHS by oral challenge was 1.7% [1.1% - 2.95%]. In primary FHS, the most common allergenic food was peanut (0.6%) followed by additives (0.5%), shrimp (0.2%), codfish (0.1%), cow's milk (0.1%), octopus (0.1%) and soy (0.1%). In secondary FHS, kiwi allergy was reported by 7.8% of the participants followed by hazelnut (6.6%), pineapple (4.4%), apple (4.3%), orange (4.2%), tomato (3.8%), peach (3.0%) and brazil nut (2.7%). This study found a 1.7% [1.1% - 2.95%] prevalence of primary FHS confirmed by oral challenge to the most common allergenic foods in an unselected population of young adults.

Clinical severity and prognosis of hand eczema.

BACKGROUND: Hand eczema (HE) is a frequent, long-lasting disease with both personal and societal repercussions. Consequently, more information is needed on factors that maintain symptoms. OBJECTIVES: In this study, patients with HE were followed for 6 months from the first visit to a dermatologist to identify factors associated with severe disease and a poor prognosis. METHODS: Study participants were 799 patients with HE from nine dermatological clinics in Denmark. Severity assessment of the HE was done at baseline and at the 6-month follow-up using the Hand Eczema Severity Index (HECSI) and by patients using a self-administered photographic guide. Additional information was obtained from a baseline questionnaire. RESULTS: At baseline, 60.3% assessed their HE as moderate to very severe using the self-administered photographic guide compared with 36.1% at follow-up. The mean HECSI value decreased from 19.9 points at baseline to 11.2 points at follow-up (P < 0.001). In a multivariable logistic regression analysis, statistically significant associations with severe HE at baseline were older age (P < 0.001), atopic dermatitis (P = 0.01) and > or = 1 positive patch test (P < 0.001). Being an unskilled worker was a predictor for a poor prognosis at follow-up (P = 0.04), and the presence of frequent symptoms during the previous 12 months was associated with severe initial disease (P = 0.02) and a poor prognosis (P = 0.04). CONCLUSIONS: Overall, the disease had improved 6 months after the dermatological examination: nevertheless, many patients continued to have significant symptoms. Dermatologists should pay special attention to patients with frequent eruptions and to unskilled workers.

Food allergy and food sensitization in early childhood: results from the DARC cohort.

BACKGROUND: The prevalence of food hypersensitivity (FHS) and the relationship with atopic dermatitis (AD) is controversial. The aim of this study was to determine the development of FHS and to correlate this with AD in relation to sensitization and symptoms. METHODS: This study combines new data from birth to 18 months of age with previous published results from 3 and 6 years. The Danish Allergy Research Centre cohort, including 562 children, is a unique, population-based, prospective birth cohort, with clinical examinations at all follow-ups. All children were examined for the development of AD using Hanifin-Rajka criteria and for FHS using interviews, skin prick test (SPT), specific immunoglobulin E (IgE), and food challenge according to EAACI guidelines. RESULTS: Twenty children were confirmed with FHS to milk, egg, and peanut. FHS peaked at 18 months (3.6%) and then decreased to 1.2% at 72 months of age. No new cases were found after 3 years. Self-reporting could only be confirmed in 31% of cases. Among the 122 children with AD, 18 had FHS (14.8%). FHS was IgE-mediated in 95% of the cases but 16 of 20 children were additionally sensitized to other foods which they tolerated. Children with AD were neither more IgE-sensitized nor had higher levels of IgE when compared with healthy children but they were more persistently sensitized. CONCLUSIONS: Sensitization to foods in young children without food allergy seems to be a normal phenomenon. The discrepancy between sensitization, self-reported food-related symptoms and confirmed FHS illustrates the need to perform standardized oral challenges in order to confirm the diagnosis of FHS.

Hand eczema classification: a cross-sectional, multicentre study of the aetiology and morphology of hand eczema.

BACKGROUND: Hand eczema is a long-lasting disease with a high prevalence in the background population. The disease has severe, negative effects on quality of life and sometimes on social status. Epidemiological studies have identified risk factors for onset and prognosis, but treatment of the disease is rarely evidence based, and a classification system for different subdiagnoses of hand eczema is not agreed upon. Randomized controlled trials investigating the treatment of hand eczema are called for. For this, as well as for clinical purposes, a generally accepted classification system for hand eczema is needed. OBJECTIVES: The present study attempts to characterize subdiagnoses of hand eczema with respect to basic demographics, medical history and morphology. METHODS: Clinical data from 416 patients with hand eczema from 10 European patch test clinics were assessed. RESULTS: A classification system for hand eczema is proposed. CONCLUSIONS: It is suggested that this classification be used in clinical work and in clinical trials.

Management of irritant contact dermatitis: continuously a problem for patients and dermatologists.

Skin irritants may induce irritant contact dermatitis (ICD) in various ways but the end result remains the same: a clinical picture which in most cases is practically indistinguishable from allergic contact dermatitis (ACD). A treatment that works for ACD does not necessarily work for ICD. Management has to focus on preventive measures, education of people exposed to irritants and supportive topical treatment of varying nature depending on the clinical circumstances.