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.

TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for a European safety study of dupilumab and other systemic therapies in patients with atopic eczema.

BACKGROUND: A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. OBJECTIVES: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting. METHODS: We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. CONCLUSIONS: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.

Defining and measuring 'eczema control': an international qualitative study to explore the views of those living with and treating atopic eczema.

BACKGROUND: Atopic eczema (also known as eczema) is a chronic, inflammatory skin condition that often afflicts patients' health and well-being. The Harmonising Outcome Measures for Eczema (HOME) initiative recommends that 'long-term control of eczema' is measured in all clinical trials 3 months or longer in duration. However, little has been published on what eczema control means to those living with or treating atopic eczema. OBJECTIVES: To (i) develop understanding of what eczema control means to patients, carers and clinicians and (ii) explore the feasibility and acceptability of different ways of measuring eczema control in the long term. METHODS: Online focus groups explored patients/carers experiences in the UK, the United States, the Netherlands, France, Sweden and Japan, and an international online survey gathered views of clinicians. The framework method was used to analyse the focus groups, and thematic analysis was used to analyse survey data. All findings were integrated into a theoretical framework to create overarching themes that cut across these diverse groups. RESULTS: Eight focus groups with patients (16 years+) and eight groups with carers of children took place (N = 97). Sixty-two people took part in the survey. Eczema control was described as a multifaceted construct involving changes in disease activity, the treatment and management of the condition and psychological, social and physical functioning. Patient/carer measurement allows personal accounts and frequent measurement, whilst clinician measurement was deemed less subjective. The burden on patients/carers and issues for analysing and interpreting data should be considered. CONCLUSIONS: This study formed the basis of judging the content validity and feasibility of measurement instruments/methods to assess control of eczema in clinical trials. This online approach to an international qualitative study is an example of how core outcome set developers with limited resources can engage with multiple stakeholder groups on an international basis to inform consensus meeting discussions.

Atopic dermatitis, educational attainment and psychological functioning: a national cohort study.

BACKGROUND: Atopic dermatitis (AD) might adversely affect academic performance, possibly through influences on psychological functioning such as stress resilience. OBJECTIVES: To investigate the association of atopic dermatitis with stress resilience, cognitive function and educational attainment. METHODS: We used data from a national cohort of men who underwent a military conscription examination at ages 17-20 years in Sweden between 1969 and 1976. All potential conscripts met a physician who assessed current or previous history of AD. Stress resilience was measured by a psychologist using a semistructured interview. The conscription assessment included a written cognitive function test. The highest level of education achieved was identified through record linkage. RESULTS: The study population included 234 715 men, 1673 (0·7%) of whom had a diagnosis of AD. AD was associated with a greater risk of low stress resilience [adjusted relative risk ratio (RRR) 1·60, 95% confidence interval (CI) 1·38-1·86]. AD was associated with higher cognitive function (ß-coefficient 0·15, 95% CI 0·05-0·24) and higher educational level (RRR 1·29, 95% CI 1·13-1·47). However, adjustment for socioeconomic characteristics of the family of origin attenuated the magnitude of the associations and eliminated the statistical significance (ß-coefficient 0·06, 95% CI -0·03 to 0·15; RRR 1·16, 95% CI 1·00-1·35). CONCLUSIONS: Swedish men with AD had lower stress resilience in late adolescence but did not have lower cognitive function or poorer educational attainment. The lower stress resilience associated with AD is consistent with an increased risk of possible long-term adverse health outcomes.

Evaluation of the measurement properties of symptom measurement instruments for atopic eczema: a systematic review.

BACKGROUND: Symptoms have been identified as a core outcome domain for atopic eczema (AE) trials. Various instruments exist to measure symptoms in AE, but they vary in quality and there is a lack of standardization between clinical trials. Our objective was to systematically evaluate the quality of the evidence on the measurement properties of AE symptom instruments, thereby informing consensus discussions within the Harmonising Outcome Measures for Eczema (HOME) initiative regarding the most appropriate instruments for the core outcome domain symptoms. METHODS: Using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist and predefined criteria for good measurement properties on identified development and validation studies of AE symptom instruments, a best evidence synthesis was performed to draw an overall conclusion on quality of the instruments and to provide recommendations. RESULTS: Eighteen instruments were identified and evaluated. When the quality and results of the studies were considered, only five of these instruments had sufficient validation data to consider them for the core outcome set for the core outcome domain symptoms. These were the paediatric Itch Severity Scale (ISS), Patient-Oriented Eczema Measure (POEM), Patient-Oriented SCOring Atopic Dermatitis (PO-SCORAD), Self-Administered Eczema Area and Severity Index (SA-EASI) and adapted SA-EASI. CONCLUSIONS: ISS (paediatric version), POEM, PO-SCORAD, SA-EASI and adapted SA-EASI are currently the most appropriate instruments and therefore have the potential to be recommended as core symptom instrument in future clinical trials. These findings will be utilized for the development of a core outcome set for AE.

Patient-Oriented Eczema Measure (POEM), a core instrument to measure symptoms in clinical trials: a Harmonising Outcome Measures for Eczema (HOME) statement.

BACKGROUND: The Harmonising Outcome Measures for Eczema (HOME) initiative has defined four core outcome domains for a core outcome set (COS) to be measured in all atopic eczema (AE) trials to ensure cross-trial comparison: clinical signs, symptoms, quality of life and long-term control. OBJECTIVES: The aim of this paper is to report on the consensus process that was used to select the core instrument to consistently assess symptoms in all future AE trials. METHODS: Following the HOME roadmap, two systematic reviews were performed which identified three instruments that had sufficient evidence of validity, reliability and feasibility to be considered for the final COS. RESULTS: At the fourth international HOME meeting, there was broad consensus among all stakeholders that the Patient-Oriented Eczema Measure (POEM) should be used as the core instrument (87·5% agreed, 9·4% unsure, 3·1% disagreed). CONCLUSIONS: All relevant stakeholders are encouraged to use POEM as the chosen instrument to measure the core domain of symptoms in all future AE clinical trials. Other instruments of interest can be used in addition to POEM.

Validation of a parental questionnaire to identify atopic dermatitis in a population-based sample of children up to 2 years of age.

BACKGROUND: Validated eczema questionnaires have been available for schoolchildren only, but the incidence of atopic dermatitis (AD) is highest during infancy. OBJECTIVE: To validate a parental questionnaire to identify AD in children up to 2 years of age. METHODS: Parents of 476 children answered a written questionnaire prior to an examination by a physician. Sensitivity, specificity, predictive values and test-retest reliability of the questionnaire were assessed. RESULTS: A total of 245 (51%) girls and 231 (49%) boys, aged 1-24 months, with and without physician-diagnosed AD participated. Seventy-one children (15%) had physician-diagnosed AD. Validation of the questionnaire by comparisons with physicians' diagnoses showed a sensitivity of 0.87 (95% confidence interval, CI, 0.77-0.94) and a specificity of 0.98 (95% CI, 0.96-0.99). The positive predictive value was 0.90 (95% CI, 0.80-0.96) and the negative predictive value was 0.98 (95% CI, 0.96-0.99). CONCLUSION: The questionnaire identified AD in children aged 0-2 years with high accuracy.