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.

Occupation and cutaneous melanoma: a 45-year historical cohort study of 14·9 million people in five Nordic countries.

BACKGROUND: The age-adjusted incidence of cutaneous melanoma (CM) in the Nordic countries has increased during the last 60 years. Few prospective population-based studies have estimated the occupational variation in CM risk over time. OBJECTIVES: To determine occupational variation in CM risk. METHODS: A historical prospective cohort study with a 45-year follow-up from 1961 to 2005 (Nordic Occupational Cancer Study, NOCCA) based on record linkages between census and cancer registry data for Nordic residents aged 30-64 years in Denmark, Finland, Iceland, Norway and Sweden. National occupational codes were converted to 53 occupational categories, and stratified into indoor, outdoor and mixed work, and into socioeconomic status. The standardized incidence ratios (SIRs) were estimated as observed number of CM cases divided by the expected number calculated from stratum-specific person-years and national CM incidence rates. RESULTS: During a follow-up of 385 million person-years, 83 898 incident cases of CM were identified. In all countries combined, men with outdoor work had a low SIR of 0·79 [95% confidence interval (CI) 0·77-0·81] and men with indoor work had a high SIR of 1·09 (95% CI 1·07-1·11). Differences in women pointed in the same direction. High socioeconomic status was associated with an excess risk: SIR 1·34 (95% CI 1·28-1·40) in men and SIR 1·31 (95% CI 1·26-1·36) in women. Technical, transport, military and public safety workers with potential skin exposure to carcinogens had excess risks. CONCLUSIONS: Occupational variation in CM risk may be partly explained by host, socioeconomic and skin exposure factors. Differences in CM risk across socioeconomic groups attenuated slightly over time.

Skin bioengineering in the diagnosis of occupational protein contact dermatitis.

Protein contact dermatitis (PCD) often presents as chronic hand eczema (CHE) with an immediate hypersensitivity to protein proved by a positive skin prick test or by the presence of specific immunoglobulin E. This is frequently induced by occupational exposure to proteins in food workers, farmers, animal breeders, veterinarians and healthcare professionals. While skin barrier impairment is crucial in the pathogenesis of PCD, methods to assess skin barrier function such as trans-epidermal water loss and stratum corneum hydration are not widely used in clinical settings. We describe the diagnostic workup of occupational PCD due to Argentinean shrimps and discuss how the use of skin bioengineering methods including assessment of corneocytes morphology by Scanning Electron Microscopy provides with insightful information on skin barrier function. Diagnosis of PCD is time-consuming and a multidisciplinary team contributes to early diagnosis and proper occupational rehabilitation.

Minimum standards on prevention, diagnosis and treatment of occupational and work-related skin diseases in Europe - position paper of the COST Action StanDerm (TD 1206).

BACKGROUND: Skin diseases constitute up to 40% of all notified occupational diseases in most European countries, predominantly comprising contact dermatitis, contact urticaria, and skin cancer. While insufficient prevention of work-related skin diseases (WRSD) is a top-priority problem in Europe, common standards for prevention of these conditions are lacking. OBJECTIVE: To develop common European standards on prevention and management of WRSD and occupational skin diseases (OSD). METHOD: Consensus amongst experts within occupational dermatology was achieved with regard to the definition of minimum evidence-based standards on prevention and management of WRSD/OSD. RESULTS: By definition, WRSDs/OSDs are (partially or fully) caused by occupational exposure. The definition of OSD sensu stricto additionally includes diverging national legal requirements, with an impact on registration, prevention, management, and compensation. With the implementation of the classification of WRSD/OSD in the International Classification of Diseases (ICD) 11th Revision in future, a valid surveillance and comparability across countries will be possible. Currently, WRDS and OSD are still under-reported. Depending on legislation and regulations, huge differences exist in notification procedures in Europe, although notification is crucial to prevent chronic and relapsing disease. Facilities for early diagnosis, essential for individual patient management, should be based on existing guidelines and include a multidisciplinary approach. Patch testing is essential if contact dermatitis persists or relapses. Workplace exposure assessment of WRSD/OSD requires full labelling of product ingredients on material safety data sheets helping to identify allergens, irritants and skin carcinogens. Comparable standards in primary, secondary and tertiary prevention must be established in Europe to reduce the burden of WRSD/OSD in Europe. CONCLUSION: The adoption of common European standards on prevention of WRSD/OSD will contribute to reduce the incidence of OSD and their socio-economic burden.

Occupational skin diseases: actual state analysis of patient management pathways in 28 European countries.

BACKGROUND: Work-related skin diseases (WSD) are caused or worsened by a professional activity. Occupational skin diseases (OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal diseases, neurologic diseases, lung diseases, diseases of the sensory organs, skin diseases) in Europe. OBJECTIVE: To retrieve information and compare the current state of national frameworks and pathways to manage patients with occupational skin disease with regard to prevention, diagnosis, treatment and rehabilitation in different European countries. METHODS: A questionnaire-based survey of the current situation regarding OSD patient management pathways was carried out with experts on occupational dermatology and/or occupational medicine from 28 European countries contributing to the European Cooperation in Science and Technology (COST) Action TD 1206 (StanDerm) (www.standerm.eu). RESULTS: Besides a national health service or a statutory health insurance, most European member states implemented a second insurance scheme specifically geared at occupational diseases [insurance against occupational risks (synonyms: insurance against work accidents and occupational injuries; statutory social accident insurance)]. Legal standards for the assessment of occupationally triggered diseases with a genetic background differ between different countries, however, in most European member states recognition as OSD is possible. In one-third of the countries UV light-induced tumours can be recognized as OSD under specific conditions. CONCLUSION: OSD definitions vary between European countries and are not directly comparable, which hampers comparisons between statistics collected in different countries. Awareness of this fact and further efforts for standardization are necessary.

Algunas características cinéticas de la beta galactosidasa recombinante libre y conjugada de E. coli empleada en ultramicroELISA / Some kinetic characteristics of recombinant beta galactosidase from E. coli used in ultramicroelisa

En este trabajo presentamos algunas de las características cinéticas de la ß galactosidasa de E. coli recombinante utilizada en la preparación de conjugados para los ensayos inmunoenzimáticos con la tecnología del Sistema Ultramicroanalítico (SUMA). Se estandarizó la técnica de determinación de la actividad enzimática empleando 4 metil-umberiferil- ß-D-galactopiranósido como sustrato y se calculó la correlación con la actividad específica determinada con el sustrato ortonitrofenil-ß-D-galactopiranósido. Se estudió la afinidad enzima-sustrato de la ß galactosidasa libre y conjugada a diferentes proteìnas y aptenos, utilizada en UltramicroELISA (UME) de tipo competitivo y sandwich. Las Km reales y aparentes fueron calculadas según el método de Lineweaver-Burk. La conjugación por el método del glutaraldehido no provocó grandes cambios en la afinidad enzima-sustrato, sin embargo las Km aparentes de los conjugados adsorbidos fueron diferentes en los distintos UME. Los resultados obtenidos pueden ser utilizados en la estandarización de la conjugación y en el montaje de los UME en la SUMA, así como en la interpretación de los fenómenos moleculares que ocurren en los ensayos inmunoenzimáticos