Prevalence of dermatitis including allergic contact dermatitis from medical devices used by children and adults with Type 1 diabetes mellitus: A systematic review and questionnaire study.

Use of medical devices (MDs), that is, glucose sensors and insulin pumps, in patients with Type 1 diabetes mellitus (T1D) has proven an enormous advantage for disease control. Adverse skin reactions from these MDs may however hamper compliance. The objective of this study was to systematically review and analyse studies assessing the prevalence and incidence of dermatitis, including allergic contact dermatitis (ACD) related to MDs used in patients with T1D and to compare referral routes and the clinical investigation routines between clinics being part of the European Environmental and Contact Dermatitis Research Group (EECDRG). A systematic search of PubMed, EMBASE, CINAHL and Cochrane databases of full-text studies reporting incidence and prevalence of dermatitis in persons with T1D using MDs was conducted until December 2021. The Newcastle-Ottawa Scale was used to assess study quality. The inventory performed at EECRDG clinics focused on referral routes, patient numbers and the diagnostic process. Among the 3145 screened abstracts, 39 studies fulfilled the inclusion criteria. Sixteen studies included data on children only, 14 studies were on adults and nine studies reported data on both children and adults. Participants were exposed to a broad range of devices. Skin reactions were rarely specified. It was found that both the diagnostic process and referral routes differ in different centres. Further data on the prevalence of skin reactions related to MDs in individuals with T1D is needed and particularly studies where the skin reactions are correctly diagnosed. A correct diagnosis is delayed or hampered by the fact that, at present, the actual substances within the MDs are not declared, are changed without notice and the commercially available test materials are not adequately updated. Within Europe, routines for referral should be made more standardized to improve the diagnostic procedure when investigating patients with possible ACD from MDs.

Chronic hand eczema in Europe: Patient experiences and perspectives (CHEPEP) in qualitative interviews.

BACKGROUND: Chronic hand eczema (CHE) is a very common skin disease among the European population. It causes itch and pain and, in more severe cases, seriously impairs hand functioning at work and in private life. OBJECTIVES: To explore perspectives of people with lived experience on CHE-related problems, wishes and goals. METHODS: Following a qualitative approach, we conducted topic-guided interviews in five European countries and applied template analysis to identify recurrent themes among patients with CHE. RESULTS: We interviewed 60 patients in seven outpatient dermatological and occupational medicine clinics in Croatia, Denmark, Germany, the Netherlands and Spain. Five main themes were identified: (1) knowledge about the disease and its course, (2) preventive behaviour, (3) hand eczema therapy, (4) impact on everyday life and (5) attitudes towards CHE and healthcare. Participants did not feel well informed about CHE, especially about causes, triggers and treatment options. Preventive measures were experienced as more or less effective but also cumbersome. Experiences with therapy were diverse. Treatment satisfaction depended on the results and on the perceived support from the treatment teams. Participants found it important to be taken seriously, to receive practical advice, to try out additional treatments or examinations, find new hope and have occupational perspectives. They wished that others could better understand the physical and emotional burden of CHE. Patient support groups were not mentioned. Participants found it important to learn to take care of themselves and accept life with CHE. CONCLUSIONS: Due to its annoying symptoms, high visibility and impaired functioning at work and in private life, CHE has a high emotional and social impact. Some people may require support to learn coping with CHE and its prevention. Patients wish for information about causes and triggers. They value physicians who listen to them and keep looking for solutions.

Systemic treatment of children and adolescents with atopic dermatitis aged ≥2 years: a Delphi consensus project mapping expert opinion in Northern Europe.

BACKGROUND: Paediatric atopic dermatitis (AD) can be burdensome, affecting mental health and impairing quality of life for children and caregivers. Comprehensive guidelines exist for managing paediatric AD, but practical guidance on using systemic therapy is limited, particularly for new therapies including biologics and Janus kinase (JAK) inhibitors, recently approved for various ages in this indication. OBJECTIVES: This expert consensus aimed to provide practical recommendations within this advancing field to enhance clinical decision-making on the use of these and other systemics for children and adolescents aged ≥2 years with moderate-to-severe AD. METHODS: Nineteen physicians from Northern Europe were selected for their expertise in managing childhood AD. Using a two-round Delphi process, they reached full or partial consensus on 37 statements. RESULTS: Systemic therapy is recommended for children aged ≥2 years with a clear clinical diagnosis of severe AD and persistent disease uncontrolled after optimizing non-systemic therapy. Systemic therapy should achieve long-term disease control and reduce short-term interventions. Recommended are cyclosporine A for short-term use (all ages) and dupilumab or methotrexate for long-term use (ages ≥6 years). Consensus was not reached on the best long-term systemics for children aged 2-6 years, although new systemic therapies will likely become favourable: New biologics and JAK inhibitors will soon be approved for this age group, and more trial and real-world data will become available. CONCLUSIONS: This article makes practical recommendations on the use of systemic AD treatments for children and adolescents, to supplement international and regional guidelines. It considers the systemic medication that was available for children and adolescents with moderate-to-severe AD at the time this consensus project was done: azathioprine, cyclosporine A, dupilumab, methotrexate, mycophenolate mofetil and oral glucocorticosteroids. We focus on the geographically similar Northern European countries, whose healthcare systems, local preferences for AD management and reimbursement structures nonetheless differ significantly.

Childhood atopic dermatitis is associated with a decreased chance of completing education later in life: a register-based cohort study.

BACKGROUND: Atopic dermatitis (AD) has far-reaching consequences in childhood and later in working life, but information on how it affects completion of education is sparse. OBJECTIVES: To compare the educational achievement of individuals with AD in childhood/adolescence and individuals without a history of AD. METHODS: The study population included patients diagnosed with AD prior to the age of 16 registered in the Danish National Patient Register (DNPR) born in the period 1977-1993 and a 23-fold matched control group from the background population. Cross-linkage of five different Danish registers from 1977 to 2015 allowed comparison of AD patients with controls regarding completion of education. RESULTS: In total, 10 173 individuals were registered with AD in the DNPR, while 234 683 individuals served as control group. Mild/moderate AD was associated with a decreased chance of completing basic compulsory education [hazard ratios (HR): 0.92, 95% CI: 0.90-0.95] and further academic education (HR: 0.96, 95% CI: 0.93-0.98). Severe AD was associated with a decreased chance of completing further academic education (HR: 0.86, 95% CI: 0.80-0.92), further vocational education (HR: 0.90, 95% CI: 0.84-0.97) and higher education: master's level (HR: 0.66, 95% CI: 0.53-0.81). CONCLUSION: Atopic dermatitis in childhood/adolescence is associated with a decreased chance of completing an education.

Disease severity and trigger factors in Danish children with atopic dermatitis: a nationwide study.

BACKGROUND: Atopic dermatitis (AD) is a prevalent chronically relapsing inflammatory skin disease of childhood. However, little is known about self-reported trigger factors, impact on daily life and factors associated with AD severity. METHODS: A nationwide questionnaire study of children in Denmark with hospital-diagnosed AD in the time period 2014-2018. The web-based questionnaire was completed by the legal parents. AD severity was assessed using Patient-Oriented Eczema Measure (POEM) tool. RESULTS: Of 3438 invited parents, 1343 (39%) completed the questionnaire. Factors associated with severe AD were onset during the first 6 months of life, onset of AD on multiple body regions, a history of hay fever, female sex and low maternal educational level. Staying home from daycare or school due to AD, concentration problems and sleep disturbances in the child were more frequently reported by parents to children with severe AD. Overall, 90% reported at least one AD trigger factor, and all were more frequently reported in children with severe AD. The three most commonly reported trigger factors were cold weather (51.9%), chlorinated water (35.7%) and warm weather (30.2%). CONCLUSIONS: We identified factors associated with severe AD in childhood, the impact on daily life, as well as the most common self-reported triggers of AD. These findings may be valuable in clinical practice to inform about prognosis and educate families about trigger avoidance.

Cytokine concentration across the stratum corneum in atopic dermatitis and healthy controls.

Tape stripping is a promising technique for assessment of epidermal biomarkers in inflammatory skin diseases. However, to facilitate its implementation in the clinical practice, a thorough validation regarding sampling strategy is needed. Knowledge of biomarkers variation in concentration across stratum corneum is scarce. Therefore, this study aimed to assess the variability of cytokines across stratum corneum using tape stripping technique by consecutive application of 21 adhesive tapes (D-squame) to lesional and non-lesional skin from 15 patients with atopic dermatitis (AD) and 16 healthy controls. Concentration of cytokines (IL-1α, IL-1b, IL-5, IL-18, IFN-γ, CCL17, CCL22, CCL27, CXCL8, CXCL10, TNF-α, TSLP, VEGFA) was determined in five different depths, using multiplex immunoassay. Comparing tape 4 with tape 21, no cytokine changed significantly in concentration in AD lesional skin. In AD non-lesional skin a small decrease was found for CCL17, CXCL8 and CXCL10. For healthy controls, a decrease was found for IL-1a, IL-1b, VEGFA and an increase for IL-18. Differences were found between AD skin and healthy control skin. Concentration of cytokines was stable across stratum corneum, indicating that sampling of only one tape from the stratum corneum is reliable in reflecting the overall cytokine milieu. Differences between AD and healthy skin confirm robustness of tape stripping for measuring cytokine levels.

Atopic dermatitis is associated with increased use of social benefits: a register-based cohort study.

BACKGROUND: The comprehensive consequences of atopic dermatitis (AD) include a negative influence on work life. However, data regarding use of social benefits in patients with AD are sparse. OBJECTIVE: To examine the association between AD and use of social benefits, with a specific focus on paid sick leave and disability pension. METHODS: The study cohort comprises citizens born in the period 1964-1999 with a diagnosis of AD registered in the Danish National Patient Registry (DNPR) and a 20-fold match control group from the background population. Cross-linkage of data from 1964 up to 2015 by four national registers (the DNPR; the Central Person Register; the Register of Medicinal Product Statistics; and the Danish Register for Evaluation of Marginalisation) enabled the comparison of AD patients and controls with respect to social benefits. Prescription of systemic medication served as a proxy for AD severity. Social benefits were analysed as a function of AD status using Cox regression. RESULTS: A total of 28 156 AD patients were registered in the DNPR, and the control group comprised 473 836 individuals not registered with AD in the DNPR. AD was found to be associated with increased risk of receiving social benefits, paid sick leave in particular, and most pronounced for younger patients with severe AD (OR = 1.37, 95% CI: 1.25-1.52). The use of disability pension was increased for all groups of AD patients compared to controls and most pronounced for older patients with severe AD [HR 1.67 (95% CI: 1.45-1.93)]. CONCLUSION: Our data emphasize that AD significantly impacts work life negatively for the patients and is a financial burden for the society.

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.

Hand eczema: epidemiology, prognosis and prevention.

Hand eczema (HE) is a heterogeneous and often chronic disease located to the hands and wrist, and frequently associated with eczema on the feet. The aetiology is diverse, and the eczema may present with a variety of clinical symptoms. Acute and chronic stages appear; severity varies from mild to moderate and severe, and flares may be frequently recurrent or rare. The divergent aetiology and varied morphology of HE is sometimes tricky and may be challenging to the dermatologist. This review has focus on epidemiology, prognosis and prevention of HE, and intends to point towards some practical advice on how to diagnose, inform and guide HE patients.

Hand eczema: treatment.

Hand eczema is a highly prevalent, multietiological disease with a wide spectrum of severity and chronicity. The treatment of hand eczema, especially in severe and chronic cases, is a challenge to the dermatologist requiring not only diagnostic and therapeutic, but also excellent patient communication skills. This review discusses the spectrum of therapeutic options for hand eczema, the evidence for their efficacy and safety, and proposes a stepwise approach of intensity of treatment depending on disease severity and chronicity. In the near future, hand eczema patients may benefit from new therapeutic principles such as biologics for the treatment of atopic eczema and topical Janus Kinase inhibitors.

Treatment of atopic dermatitis with dupilumab: experience from a tertiary referral centre.

BACKGROUND: Management of moderate-to-severe atopic dermatitis (AD) frequently requires treatment with systemic therapies. Dupilumab is the first biological agent approved for treatment of moderate-to-severe AD. Although promising results have appeared in clinical trials, real-life data on efficacy and safety are lacking. OBJECTIVES: To assess effectiveness and safety of treatment with dupilumab in the real-life clinical setting at a Danish tertiary referral centre. METHODS: All patients with AD treated with dupilumab from October 2017 to October 2018 at Bispebjerg Hospital, Denmark, were included in the study. Patients were evaluated three times: at treatment initiation and at 1 and 3 months after first dupilumab injection. At each visit, disease activity was assessed by severity score (Eczema Area and Severity Index, EASI), patient-reported outcomes (Dermatology Life Quality Index, DLQI, pruritus and sleep score) and serological markers [immunoglobulin (Ig)E, eosinophil count and lactate dehydrogenase (LDH)]. RESULTS: A total of 43 patients were included in the study. The mean reduction in EASI score from baseline was 19.6 points (72.4%) at 1-month and 22.6 points (76.7%) at 3-month follow-up. EASI, DLQI, pruritus score, sleep score, IgE and LDH were all statistically significantly reduced between baseline and 1- and 3-month follow-up. Mean reductions in EASI score and LDH at 3-month follow-up were significantly correlated (P = 0.003). One patient (2.3%) discontinued treatment due to side-effects, and seven patients (18.4%) developed conjunctivitis during the study period. CONCLUSION: The effectiveness and safety of dupilumab treatment in a real-life clinical setting are comparable to that of phase 3 clinical trials. LDH is suggested as a potential serological marker predictive of treatment response.

Factors influencing prognosis for occupational hand eczema: new trends.

BACKGROUND: Variables traditionally reported to influence the prognosis of occupational hand eczema (OHE) are atopic dermatitis (AD) and contact sensitization. However, recent studies indicate that lifestyle factors may be of major importance. OBJECTIVES: To identify factors influencing the prognosis in a cohort of patients with recognized OHE. METHODS: In this register-based cohort study, individuals with hand eczema recognized as occupational disease in the period January 2010-December 2011 were identified using files from Labor Market Insurance Denmark and included in the study. At baseline, information on sex, age, occupation, wet work, AD and contact sensitization was collected. In 2015 participants received a questionnaire with questions about lifestyle factors, current occupation and healing of OHE. RESULTS: In total, 2703 patients received the questionnaire; 1491 responded to the question about healing of OHE and were included in the study. Altogether, 19·3% of patients reported complete healing at follow-up. Current tobacco smoking and a high level of stress were factors inversely associated with healing of hand eczema (P < 0·001 and P = 0·030, respectively), while a high level of exercise was significantly related to healing of eczema (P = 0·011). Change of profession was a favourable prognostic factor, while age, sex, AD, contact sensitization and education did not significantly influence prognosis. CONCLUSIONS: Traditionally important risk factors such as AD and contact sensitization had no marked influence on prognosis, while lifestyle factors were of major importance. Our findings indicate that risk factors may vary over time, allowing for new perspectives on prevention. What's already known about this topic? Occupational hand eczema has a relapsing course and a poor overall prognosis. Atopic dermatitis and contact sensitization have previously been reported as risk factors for a poor prognosis. What does this study add? The results indicate that lifestyle factors are of importance for the prognosis of occupational hand eczema. Traditionally reported risk factors such as atopic dermatitis and contact sensitization do not currently influence prognosis.

Temporal variation of Staphylococcus aureus clonal complexes in atopic dermatitis: a follow-up study.

BACKGROUND: A strong link between disease severity and Staphylococcus aureus colonization of the skin has been reported in patients with atopic dermatitis (AD). OBJECTIVES: To examine temporal variations in S. aureus colonization and S. aureus CC type in patients with AD, and to investigate links to disease severity, skin barrier properties and filaggrin gene (FLG) mutations. METHODS: This was a follow-up study of a cohort of 101 adult patients with AD recruited from an outpatient clinic. Bacterial swabs were taken at baseline and follow-up from lesional skin, nonlesional skin and the nose. Swabs positive for S. aureus were characterized by spa and the respective clonal complex (CC) type was assigned. Patients were characterized with respect to disease severity [Scoring Atopic Dermatitis (SCORAD)], skin barrier properties [transepidermal water loss (TEWL), pH] and FLG mutations. RESULTS: In total, 63 patients participated in a follow-up visit. Twenty-seven patients (43%) were colonized at both visits, 27 were colonized at only one visit and nine (14%) were not colonized at either visit. Of patients colonized at both visits, 52% remained colonized with the same CC type at follow-up. Change in CC type was related to an increase in SCORAD of 10·7 points; patients who carried the same CC type had a reduction in SCORAD of 4·4 points. Significantly higher skin pH was found in patients colonized at both visits, while change in CC type was not related to TEWL, pH or FLG mutations. CONCLUSIONS: The data indicate that temporal variation in S. aureus CC type is linked to flares of the disease.

Is atopic dermatitis associated with obesity? A systematic review of observational studies.

Obesity has been associated with atopic dermatitis (AD); however, the results have been conflicting. Our aim was to provide an update on current knowledge from observational studies addressing the possible association between obesity and AD. Systematic literature review was performed by identifying studies addressing a possible link between AD and overweight/obesity from PubMed, EMBASE and the Cochrane Library in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. A total of 45 studies (comprising more than 90 000 individuals with AD) fulfilled the criteria and were included in the present review. The available studies revealed inconsistencies, but the majority indicated that obesity is associated with AD. Studies addressing obesity in infancy or early childhood (age < 2 years) and AD reported a positive association. From childhood into adulthood, there is a discrepancy in the observations, as the more recent prospective studies found a positive association, whereas this was not observed in older cross-sectional studies. The inconsistency might be explained by the difference in study design, the diagnostic criteria of AD, regional differences, and by the varied definitions of overweight and obesity used in the studies. In Conclusion, overweight/obesity is associated with an increased risk of AD. Large prospective cohort studies are required to confirm the association between AD and obesity and the possibility that weight control in childhood may help to mitigate or reverse AD symptoms.