Systemic anti-inflammatory treatment of atopic dermatitis during conception, pregnancy and breastfeeding: Interdisciplinary expert consensus in Northern Europe.

Treating atopic dermatitis (AD) in pregnant or breastfeeding women, and in women and men with AD aspiring to be parents is difficult and characterized by uncertainty, as evidence to inform decision-making on systemic anti-inflammatory treatment is limited. This project mapped consensus across dermatologists, obstetricians and patients in Northwestern Europe to build practical advice for managing AD with systemic anti-inflammatory treatment in men and women of reproductive age. Twenty-one individuals (sixteen dermatologists, two obstetricians and three patients) participated in a two-round Delphi process. Full consensus was reached on 32 statements, partial consensus on four statements and no consensus on four statements. Cyclosporine A was the first-choice long-term systemic AD treatment for women preconception, during pregnancy and when breastfeeding, with short-course prednisolone for flare management. No consensus was reached on second-choice systemics preconception or during pregnancy, although during breastfeeding dupilumab and azathioprine were deemed suitable. It may be appropriate to discuss continuing an existing systemic AD medication with a woman if it provides good disease control and its benefits in pregnancy outweigh its risks. Janus kinase (JAK) inhibitors, methotrexate and mycophenolate mofetil should be avoided by women during preconception, pregnancy and breastfeeding, with medication-specific washout periods advised. For men preconception: cyclosporine A, azathioprine, dupilumab and corticosteroids are appropriate; a 3-month washout prior to conception is desirable for methotrexate and mycophenolate mofetil; there was no consensus on JAK inhibitors. Patient and clinician education on appropriate (and inappropriate) AD treatments for use in pregnancy is vital. A shared-care framework for interdisciplinary management of AD patients is advocated and outlined. This consensus provides interdisciplinary clinical guidance to clinicians who care for patients with AD before, during and after pregnancy. While systemic AD medications are used uncommonly in this patient group, considerations in this article may help patients with severe refractory AD.

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.

Comorbidities, mortality and survival in patients with pyoderma gangrenosum: a Danish nationwide registry-nested case-control study.

BACKGROUND: Pyoderma gangrenosum (PG) is an ulcerative skin disease associated with comorbidities and increased mortality; however, the literature on this topic is scarce. OBJECTIVES: To investigate the mortality, prevalence and risk of comorbidities in patients with PG. METHODS: This nationwide registry nested case-control study included all inpatients and outpatients diagnosed with PG in tertiary dermatology centres in Denmark between 1 January 1994 and 31 December 2016. Each case was matched on date of birth and sex with 10 unique controls. The Danish National Patient Registry was used to identify all patients and to gather information on comorbidity. Information on age, sex, vital status and emigration was obtained from the Danish Civil Registration System. The outcomes were 19 different comorbidities and all-cause mortality. Prevalence was assessed from odds ratios (ORs) for specific comorbidities at the time of PG diagnosis. The risk of developing specific comorbidities and death was assessed using hazard ratios (HRs) obtained using the Cox proportional-hazards model. RESULTS: A total of 1604 patients with PG were matched with 16 039 controls. Some associations were known, e.g. inflammatory bowel disease [OR 19·15 (15·27-24·02), HR 6·51 (4·24-10·01)], while others have not been described previously, e.g. osteoporosis [OR 1·57 (1·22-2·02), HR 2·59 (2·08-3·22)]. Mortality was significantly increased among patients with PG [HR 2·79 (2·57-3·03)]. CONCLUSIONS: Patients with PG have increased mortality and an increased prevalence and risk of both previously reported and novel comorbidities that may have severe consequences if left undiagnosed. Our findings are mainly related to moderate and severe PG.

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.

The European TREatment of ATopic eczema (TREAT) Registry Taskforce survey: prescribing practices in Europe for phototherapy and systemic therapy in adult patients with moderate-to-severe atopic eczema.

BACKGROUND: For many years dermatologists have had access to few therapies for patients with moderate-to-severe atopic eczema (AE). New promising therapies are entering the market but conventional phototherapies and systemic therapies have more well-known safety profiles, lower costs and wider availability. OBJECTIVES: To provide insight into current prescribing practices of conventional phototherapy and systemic immunomodulatory therapies for adults with chronic AE, and the factors influencing these prescribing practices, before biologics and other novel therapeutics become routine clinical practice. METHODS: In this exploratory study dermatologists were invited to participate in an online survey via a mailing list of the European Academy of Dermatology and Venereology and national societies. Data were collected on participant characteristics (including clinical practice data), the use of phototherapies and systemic therapies, and factors influencing their use. RESULTS: From 30 European countries, 238 out of 361 dermatologists willing to participate (65·9%) completed the survey, with 229 meeting the inclusion criteria. For phototherapy (prescribed by 84·7%), most preferred narrowband ultraviolet B as first line (80·9%) and psoralen plus ultraviolet A as second (21·6%). For systemic therapy (prescribed by 95·2%) ciclosporin (54·1%), oral corticosteroids (32·6%) and methotrexate (30·7%) were used first line. Dermatologists relied mostly on personal experience for prescribing phototherapy and systemic therapy. Azathioprine and mycophenolic acid were prescribed by only 135 (59·0%) and 85 (37·1%) participants in total, mostly due to a lack of personal experience. CONCLUSIONS: This study provides insight into prescribing practices for conventional phototherapy and systemic therapy in Europe and shows that off-label therapies are also preferred as first-line choice of systemic therapy.

The role of bacterial skin infections in atopic dermatitis: expert statement and review from the International Eczema Council Skin Infection Group.

Patients with atopic dermatitis (AD) have an increased risk of bacterial skin infections, which cause significant morbidity and, if untreated, may become systemic. Staphylococcus aureus colonizes the skin of most patients with AD and is the most common organism to cause infections. Overt bacterial infection is easily recognized by the appearance of weeping lesions, honey-coloured crusts and pustules. However, the wide variability in clinical presentation of bacterial infection in AD and the inherent features of AD - cutaneous erythema and warmth, oozing associated with oedema, and regional lymphadenopathy - overlap with those of infection, making clinical diagnosis challenging. Furthermore, some features may be masked because of anatomical site- and skin-type-specific features, and the high frequency of S. aureus colonization in AD makes positive skin swab culture of suspected infection unreliable as a diagnostic tool. The host mechanisms and microbial virulence factors that underlie S. aureus colonization and infection in AD are incompletely understood. The aim of this article is to present the latest evidence from animal and human studies, including recent microbiome research, to define the clinical features of bacterial infections in AD, and to summarize our current understanding of the host and bacterial factors that influence microbial colonization and virulence.

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.

ETFAD/EADV Eczema task force 2020 position paper on diagnosis and treatment of atopic dermatitis in adults and children.

Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier-stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti-inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid-potency corticosteroids are proven agents for proactive therapy, which is defined as the long-term intermittent anti-inflammatory therapy of frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit-risk ratio. The IL-4R-blocker dupilumab is a safe, effective and licensed, but expensive, treatment option with potential ocular side-effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) only have limited effects on AD-related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient-specific, and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. Efficacy-proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults.

Safety, efficiency and health-related quality of telephone triage conducted by general practitioners, nurses, or physicians in out-of-hours primary care: a quasi-experimental study using the Assessment of Quality in Telephone Triage (AQTT) to assess audio-recorded telephone calls.

BACKGROUND: To explore and compare safety, efficiency, and health-related quality of telephone triage in out-of-hours primary care (OOH-PC) services performed by general practitioners (GPs), nurses using a computerised decision support system (CDSS), or physicians with different medical specialities. METHODS: Natural quasi-experimental cross-sectional study conducted in November and December 2016. We randomly selected 1294 audio-recorded telephone triage calls from two Danish OOH-PC services triaged by GPs (n = 423), nurses using CDSS (n = 430), or physicians with different medical specialities (n = 441). An assessment panel of 24 physicians used a validated assessment tool (Assessment of Quality in Telephone Triage - AQTT) to assess all telephone triage calls and measured health-related quality, safety, and efficiency of triage. RESULTS: The relative risk (RR) of poor quality was significantly lower for nurses compared to GPs in four out of ten items regarding identifying and uncovering of problems. For most items, the quality tended to be lowest for physicians with different medical specialities. Compared to calls triaged by GPs (reference), the risk of clinically relevant undertriage was significantly lower for nurses, while physicians with different medical specialties had a similar risk (GP: 7.3%, nurse: 3.7%, physician: 6.1%). The risk of clinically relevant overtriage was significantly higher for nurses (9.1%) and physicians with different medical specialities (8.2%) compared to GPs (4.3%). GPs had significantly shorter calls (mean: 2 min 57 s, SD: 105 s) than nurses (mean: 4 min 44 s, SD: 168 s). CONCLUSIONS: Our explorative study indicated that nurses using CDSS performed better than GPs in telephone triage on a large number of health-related items, had a lower level of clinically relevant undertriage, but were perceived less efficient. Calls triaged by physicians with different medical specialities were perceived less safe and less efficient compared to GPs. Differences in the organisation of telephone triage may influence the distribution of workload in primary and secondary OOH services. Future research could compare the long-term outcomes following a telephone call to OOH-PC related to safety and efficiency.

TREatment of ATopic eczema (TREAT) Registry Taskforce: consensus on how and when to measure the core dataset for atopic eczema treatment research registries.

BACKGROUND: Comparative, real-life and long-term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate-to-severe atopic eczema (AE) is limited. Such data must come from well-designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling. OBJECTIVES: To reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE. METHODS: Proposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face-to-face consensus meetings, one teleconference and via e-mail. The frequency of follow-up visits was determined by an expert survey. RESULTS: A total of 16 experts from seven countries participated in the 'how to measure' consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow-up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined. CONCLUSIONS: This core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long-term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real-life and long-term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed. There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries. This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long-term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice. Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment-related adverse events that require large patient numbers).

TREatment of ATopic eczema (TREAT) Registry Taskforce: an international Delphi exercise to identify a core set of domains and domain items for national atopic eczema photo- and systemic therapy registries.

BACKGROUND: Evidence of immunomodulatory therapies to guide clinical management of atopic eczema (AE) is scarce, despite frequent and often off-label use. Patient registries provide valuable evidence for the effects of treatments under real-world conditions that can inform treatment guidelines, give the opportunity for health economic evaluation and the evaluation of quality of care, as well as pharmacogenetic and dynamic research, which cannot be adequately addressed in clinical trials. OBJECTIVES: The TREatment of ATopic eczema (TREAT) Registry Taskforce aims to seek international consensus on a core set of domains and items ('what to measure') for AE research registries, using a Delphi approach. METHODS: Participants from six stakeholder groups were included: doctors, nurses, nonclinical researchers, patients, industry and regulatory body representatives. The eDelphi comprised three sequential online rounds, requesting participants to rate the importance of each proposed domain item. Participants could add domain items to the proposed list in round 1. A final consensus meeting was held to ratify the core set. RESULTS: Participants (n = 479) from 36 countries accessed the eDelphi platform, of whom 86%, 79% and 74% completed rounds 1, 2 and 3, respectively. At the face-to-face consensus meeting attended by 42 participants the final core set was established containing 19 domains with 69 domain items (49 baseline and 20 follow-up items). CONCLUSIONS: This core set of domains and items to be captured by national AE systemic therapy registries will standardize data collection and thereby allow direct comparability across registries and facilitate data pooling between countries. Ultimately, it will provide greater insight into the effectiveness, safety and cost-effectiveness of photo- and systemic immunomodulatory therapies.

Conjunctivitis in atopic dermatitis patients with and without dupilumab therapy - international eczema council survey and opinion.

BACKGROUND: Conjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab. OBJECTIVE: To survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC). METHODS: Electronic survey and in-person discussion of management strategies. RESULTS: Forty-six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new-onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist. LIMITATIONS: The study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey. CONCLUSION: The IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab.

European task force on atopic dermatitis position paper: treatment of parental atopic dermatitis during preconception, pregnancy and lactation period.

Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up-to-date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine.

The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria.

This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Effects of a protein-free oat plantlet extract on microinflammation and skin barrier function in atopic dermatitis patients.

Atopic dermatitis (AD) is a common, highly pruritic, chronic inflammatory skin disease. Dysfunction of the epidermal barrier is witnessed by an increased transepidermal water loss in lesional and non-lesional AD skin. The inflammation in lesional AD skin is well characterized. Non-lesional skin of AD patients shows histological signs of a subclinical inflammation and a pro-inflammatory cytokine milieu. This microinflammation is present even in seemingly healed skin and must be taken into account regarding treatment of AD. Emollients provide a safe and effective method of skin barrier improvement, because they provide the skin with a source of exogenous lipids, thus improving its barrier function. The use of emollients is recommended for all AD patients irrespective of overall disease severity. Patients with moderate to severe AD should combine the emollients with a proactive therapy regimen of topical calcineurin inhibitors or topical corticosteroids. Skin areas affected by active eczema in flare should receive daily anti-inflammatory therapy first before introducing emollients, to induce rapid relief of skin lesions and pruritus. The microinflammation persisting in seemingly healed AD lesions should be addressed by a proactive treatment approach, consisting of minimal anti-inflammatory therapy and liberal, daily use of emollients. An emollient containing an extract of Rhealba oat plantlet has shown anti-inflammatory and barrier repairing properties, and was clinically tested in studies targeting the microinflammation in AD. All emollients based on Rhealba oat plantlet extract are free of oat protein, as the Rhealba extract is derived from the aerial parts of the oat plantlet and is unrelated to oatmeal proteins. The Rhealba oat plantlet extract is produced in a specific process, allowing the extraction of high levels of active principles such as flavonoids and saponins, whilst being virtually free of oat proteins to minimize the risk for allergic reactions.

Topical corticosteroid phobia in atopic dermatitis: International feasibility study of the TOPICOP score.

BACKGROUND: Adherence to topical corticosteroids (TCS) is essential for the effective treatment of atopic dermatitis but can be limited by concerns about their use. This study examined the feasibility of applying the validated TOPICOP score for assessing TCS phobia across different countries. METHODS: This was a prospective multicentre feasibility study conducted in 21 hospitals in 17 countries. Patients >3 months of age with atopic dermatitis or their parents or legal representatives completed a validated translation of the TOPICOP questionnaire in the country's native language. Respondents also completed questionnaires collecting opinions about the feasibility and acceptability of the TOPICOP questionnaire. RESULTS: A total of 1564 participants in 15 countries were included in the analysis. 81% of respondents considered the questions clear or very clear, and 79% reported that it took less than 5 minutes to complete. Each of the individual items in the TOPICOP questionnaire was considered to be not at all difficult to answer by 49% to 74% of participants. The mean global TOPICOP score was 44.7%±20.5. Mean TOPICOP subscores were 37.0±22.8% for knowledge and beliefs, 54.7±27.8% for fears and 50.1±29.1% for behaviours. Global scores and subscores differed between countries, although the subscores did not always vary in parallel, suggesting different levels of TCS phobia and different drivers for each country. CONCLUSIONS: The TOPICOP score can be feasibly applied across countries and may therefore be useful for obtaining qualitative and quantitative data from international studies and for adapting patient education and treatment.

Increased frequency of multiple sclerosis among patients with bullous pemphigoid: a population-based cohort study on comorbidities anchored around the diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is a disease of the elderly and may be associated with neurological and cardiovascular diseases and diabetes. Mortality rates strongly exceed those of the background population. OBJECTIVES: To investigate the frequency of comorbidities and their temporal relation to BP. METHODS: A register-based matched-cohort study on all Danish patients with a hospital-based diagnosis of BP (n = 3281). The main outcomes were multiple sclerosis (MS), Parkinson disease (PD), Alzheimer disease (AD), stroke, diabetes types 1 and 2, malignancies, ischaemic heart disease (IHD), hypertension and eventually death. RESULTS: At baseline, patients with BP had increased prevalences of MS [odds ratio (OR) 9·7, 95% confidence interval (CI) 6·0-15·6], PD (OR 4·2, 95% CI 3·1-5·8), AD (OR 2·6, 95% CI 1·8-3·5) and stroke (OR 2·7, 95% CI 2·4-2·9). Furthermore, malignancies, cardiovascular disease and diabetes were over-represented among patients with BP: type 1 diabetes (OR 3·1, 95% CI 2·5-3·8), type 2 diabetes (OR 2·3, 95% CI 2·0-2·6), malignancies (OR 1·3, 95% CI 1·1-1·4), IHD (OR 1·7, 95% CI 1·5-1·9) and hypertension (OR 2·0, 95% CI 1·8-2·2). During follow-up, the risk of MS was significantly higher among patients with BP [hazard ratio (HR) 9·4, 95% CI 4·9-18·0], even if events during the first year after diagnosis of BP were excluded (HR 5·1, 95% CI 2·3-11·3). Patients with BP had an average increased mortality rate of 2·04 (95% CI 1·96-2·13). CONCLUSIONS: We discovered a significantly increased frequency of MS among patients with BP. At the time of diagnosis, patients with BP had an excessive number of comorbidities and an increased mortality rate over the following years.

Chronic urticaria in the real-life clinical practice setting in Sweden, Norway and Denmark: baseline results from the non-interventional multicentre AWARE study.

BACKGROUND: Chronic urticaria (CU) is characterized by the recurrence of itchy hives and/or angioedema for more than 6 weeks. AWARE (A World-wide Antihistamine-Refractory Chronic Urticaria Patient Evaluation) is a multinational study designed to document the real-life treatment situation, burden of disease and clinical resource usage of H1-antihistamine-refractory CU patients. OBJECTIVE: To examine baseline data from Scandinavian AWARE patients. METHODS: AWARE is a prospective, non-interventional, multinational, umbrella design study, which includes adults (≥18 years) with a confirmed CU diagnosis (>2 months) that is refractory to H1-antihistamines. Baseline patient characteristics, disease activity (urticaria control test [UCT]), pharmacological treatment, comorbidities and healthcare usage were documented by the treating physician. Quality of life (QoL; dermatology life quality index [DLQI]; chronic urticaria quality of life questionnaire [CU-Q2 oL; Danish patients only]) and work productivity and activity impairment (WPAI) scores were also assessed. RESULTS: Overall, 158 CU patients from seven centres in Denmark (n = 80), Norway (n = 50) and Sweden (n = 28) were included in this baseline analysis. Mean age and BMI were 40.3 years and 26.5 kg/m2 , respectively. The majority of patients were female (69.6%), had uncontrolled CU (75.6%; UCT score <12) and had a 'spontaneous' component to their CU (61.4% CSU; 20.3% both CSU and chronic inducible urticaria). Common comorbidities included asthma (19.6%), allergic rhinitis (16.5%) and food allergies (8.2%). Overall, 60.1% of patients reported using treatments for CU including non-sedative H1-antihistamines (40.5%), corticosteroids (19%), montelukast (14.6%) and omalizumab (8.2%). Pharmacological treatment rates increased to 96.2% during the baseline visit. On average, patient QoL was moderately affected (mean DLQI score 7.7) and healthcare resource usage was high. CONCLUSION: Adult Scandinavian H1-antihistamine-refractory CU patients reported high rates of healthcare usage and QoL impairment. Rates of pharmacological treatment use were low before study enrolment but increased to almost 100% during the baseline visit.