Drug utilization among young adults with atopic dermatitis: Influence of sex, socio-economic status and disease severity.

BACKGROUND: Atopic dermatitis (AD) affects individuals of all ages, and the first-line treatment are emollients and topical corticosteroids. There is insufficient knowledge about factors possibly affecting the drug utilization of young adults with AD. OBJECTIVES: To describe the drug utilization of young adults with AD in relation to sex, socio-economic status and disease severity. METHODS: A cross-sectional study based on the 24-year follow-up from the population-based BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiology Survey) birth cohort linked with dispensing data from the National Drug Register (n = 2912). Self-reported AD and socio-economic status were defined from questionnaire data and disease severity was determined through the clinical examination and Patient-Oriented Eczema Measure questionnaire. RESULTS: The prevalence of AD in young adults was 17.7% (n = 516) and 45.5% of them were dispensed at least one drug for the treatment of AD during the study period (January 2016 to June 2019). Topical corticosteroids (TCS) were the most common drugs (32.9%) followed by emollients (21.7%). A larger proportion of men were dispensed TCS than women (39.0% vs. 29.1%: p-value = 0.020). A larger proportion of young adults with moderate-to-severe AD were dispensed TCS than those with mild AD (52.6% vs. 35.3%: p-value = 0.026). No one was dispensed the recommended amount of emollients and less than five individuals were dispensed the recommended amount of TCS for mild disease. Male sex (adj.OR 1.54, 95% CI 1.06-2.34) and moderate-to-severe AD (adj.OR 2.62, 95% CI 1.59-4.31) were associated with dispensation of TCS. CONCLUSIONS: A large proportion of young adults with AD was undertreated or untreated. Sex and disease severity did affect the dispensing patterns of investigated drugs.

Care pathways in atopic dermatitis: a retrospective population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) is a complex disease with variations in severity and healthcare utilization. Examining patient pathways through analyses of longitudinal patient data provides an opportunity to describe real-world clinical patient care and evaluate healthcare access and treatment. OBJECTIVE: To describe longitudinal care pathways including health care management, treatment patterns and disease progression (by proxy measures) in patients with AD. MATERIALS AND METHODS: This was a longitudinal observational study, which used linked data from national and regional healthcare registers in Sweden. Patients with AD were identified through diagnosis in primary or secondary care or by dispensed medications. Descriptive statistics for number of healthcare visits, type of dispensed drug class, rate of - and time to - referral to secondary care and treatment escalation were calculated. RESULTS: A total of 341 866 patients with AD distributed as 197 959 paediatric (age < 12), 36 133 adolescent (age ≥ 12- < 18) and 107 774 adult (age ≥ 18) patients were included in this study. Healthcare visits to primary and secondary care and dispensation of AD-indicated treatments were more common during the year in which managed AD care was initiated. Topical corticosteroids (TCSs) and emollients were the most frequently used treatments across all age cohorts while systemic treatment was uncommon in all age cohorts. Among patients who initiated treatment with TCSs, 18.2% escalated to TCSs with higher potency following the start of managed AD care. CONCLUSIONS: We found that healthcare contacts and use of AD-indicated treatments were concentrated in the year during which managed AD care was initiated and decreased significantly thereafter. Since a significant proportion of patients with AD have flares and persistent AD, our results suggest that patients with AD may be monitored infrequently and are undertreated. There is a need to inform practitioners about adequate treatment options to provide individualized care, in particular for patients with persistent severe AD.

Prevalence and characteristics of atopic dermatitis among young adult females and males-report from the Swedish population-based study BAMSE.

BACKGROUND: There is limited knowledge regarding prevalence and characteristics of atopic dermatitis (AD) among young adults in the general population. OBJECTIVES: To study AD among young adults in a Swedish population-based birth cohort, with a particular focus on prevalence, sex differences including risk for AD at different ages, disease course and characteristics of AD at 24 years. METHODS: The BAMSE cohort includes 4089 individuals who have been followed regularly from birth to age 24 years regarding AD and atopic diseases. For this study 3055 individuals who answered questions regarding AD at the 24-year follow-up were included. All were invited to a clinical examination including skin examination, evaluation by William's criteria and collection of blood for analysis of specific IgE, and 2264 individuals chose to participate. RESULTS: At 24 years, the 12-month prevalence of AD was 17.8% and more females than males had AD (20.5% vs. 14.8%), P < 0.0001. The point prevalence of ongoing AD at clinical examination was 8.0%. AD severity as assessed by Patient-Oriented Eczema Measure (POEM) did not differ between sexes. The proportion of adult onset of AD was 16.9% (92 of 543), females 17.3% vs. males 16.4%. More females than males with AD at 24 years reported disturbed sleep due to itch (26.1% vs. 15.5%, P < 0.003). IgE sensitization was less common among females with AD than males with AD (61.3% vs. 79.6%, P < 0.0001). In addition, male sex (female sex being the reference) was associated with increased odds for AD the first year of life (OR: 1.31, 95% CI; 1.10-1.56), and decreased odds of AD in adolescence and young adulthood (OR: 0.66, 95% CI; 0.55-0.80). CONCLUSIONS: Atopic dermatitis is a common disease among young adults, and even though more females than males have AD at 24 years, adult onset of AD seems to be equally prevalent among both sexes in young adulthood.

The asthma-rhinitis multimorbidity is associated with IgE polysensitization in adolescents and adults.

BACKGROUND: Children with multimorbid asthma and rhinitis show IgE polysensitization to several allergen sources. This association remains poorly studied in adolescents and adults using defined allergen molecules. We investigated IgE sensitization patterns towards a broad panel of aeroallergen components in adults and adolescents with a focus on individuals with asthma and rhinitis multimorbidity. METHODS: IgE reactivity to 64 micro-arrayed aeroallergen molecules was determined with the MeDALL-chip in samples from the French EGEA study (n = 840, age = 40.7 ± 17.1) and the Swedish population-based birth cohort BAMSE (n = 786, age = 16 ± 0.26). The age- and sex-adjusted associations between the number of IgE-reactive allergen molecules (≥0.3 ISU) and the asthma-rhinitis phenotypes were assessed using a negative binomial model. RESULTS: Groups representing 4 phenotypes were identified: no asthma-no rhinitis (A-R-; 30% in EGEA and 54% in BAMSE), asthma alone (A+R-; 11% and 8%), rhinitis alone (A-R+; 15% and 24%) and asthma-rhinitis (A+R+; 44% and 14%). The numbers of IgE-reactive aeroallergen molecules significantly differed between phenotypes (median in A-R-, A+R-, A-R+ and A+R+: 0, 1, 2 and 7 in EGEA and 0, 0, 3 and 5 in BAMSE). As compared to A-R- subjects, the adjusted ratio of the mean number of IgE-reactive molecules was higher in A+R+ than in A+R- or A-R+ (10.0, 5.4 and 5.0 in EGEA and 7.2, 0.7 and 4.8 in BAMSE). CONCLUSION: The A+R+ phenotype combined the sensitization pattern of both the A-R+ and A+R- phenotypes. This multimorbid polysensitized phenotype seems to be generalizable to various ages and allergenic environments and may be associated with specific mechanisms.

Cross-reactivity to fish and chicken meat - a new clinical syndrome.

BACKGROUND: Fish is one of the most allergenic foods. While clinical cross-reactivity among different fishes is a widely accepted feature of fish allergy, associations with other food allergies are not well understood. This study aims at analyzing the relevance of clinical cross-reactivity between fish and chicken meat in patients with allergy to chicken meat without sensitization to hen's eggs. METHODS: Patients with food allergy to fish and chicken meat (n = 29) or chicken meat only (n = 7) were recruited. IgE-reactive chicken proteins were identified (Edman, MS analysis) and quantified (ELISA). Allergens were used in IgE ELISA and skin testing. RESULTS: Chicken parvalbumin and two new allergens, aldolase and enolase, were identified at 12, 40, and 50 kDa, respectively. They were recognized by sIgE of 61%, 75%, and 83% of all patient sera which were in the majority of the cases positive for the fish homologues as well. Fish and chicken meat allergens were highly cross-reactive while high inhibition rates with fish or chicken allergens correlated with the patients' primary sensitization to fish or chicken. In cooked or roasted foods, enolase and aldolase were detectable in chicken breast while parvalbumin was detectable in chicken legs and wings. CONCLUSIONS: Fish and chicken meat are cross-reactive foods; both fish-allergic and chicken meat-allergic patients might be at risk of developing a food allergy to chicken meat or to fish, respectively. This clinical phenomenon is proposed to be termed 'fish-chicken syndrome' with cross-reactive allergens involved being parvalbumins, enolases, and aldolases.

Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015.

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

IgE antibodies in relation to prevalence and multimorbidity of eczema, asthma, and rhinitis from birth to adolescence.

BACKGROUND: Eczema, asthma, and rhinitis affect a large proportion of children, but their prevalence varies with age. IgE antibodies are also common in the pediatric population. However, the links between IgE, disease, and trajectories are unclear. OBJECTIVE: To better understand the links between sensitization and disease, we studied IgE sensitization ever in relation to eczema, asthma, and rhinitis, in children followed up to 16 years of age. METHODS: From the Swedish population-based birth cohort BAMSE, 2607 children were included. Parental reports from six time points between 1 and 16 years were used to identify children with eczema, asthma, and rhinitis. Blood was collected at 4, 8, and 16 years, and sensitization ever was defined as allergen-specific IgE ≥0.35 kUA /l to common food and/or inhalant allergens at any time point. Odds ratios for eczema, asthma, rhinitis, and multimorbidity in relation to sensitization ever were calculated using generalized estimating equations. RESULTS: Fifty-one percent were sensitized at least once up to 16 years. Almost a quarter of ever-sensitized children did not have any disease. After adjustment for potential confounders, sensitization ever was significantly associated with the following: (i) eczema throughout childhood, (ii) multimorbidity of eczema, asthma, and rhinitis from 1 to 16 years (OR for multimorbidity: 5.11, 95% CI: 3.99-6.55), (iii) asthma and rhinitis from 4 to 16 years of age. CONCLUSIONS: Specific IgE is strongly associated with eczema and allergic multimorbidity throughout childhood and with asthma and rhinitis from age 4 years. However, 23% of the children with IgE sensitization do not develop any disease in childhood.

Hand eczema and atopic dermatitis in adolescents: a prospective cohort study from the BAMSE project.

BACKGROUND: There is a well-known association between atopic dermatitis (AD) and hand eczema but less is known about how age at onset, persistence and severity of AD influence the risk of developing hand eczema. OBJECTIVES: To examine the role of AD in the occurrence of hand eczema in adolescence. In addition, associations between asthma and rhinoconjunctivitis, sensitization to common airborne and food allergens, and hand eczema were studied. METHODS: From the population-based birth cohort BAMSE, 2927 adolescents who had been followed up repeatedly concerning allergy-related disease were included. Questionnaires identified adolescents with hand eczema at 16 years, and their blood was analysed for specific IgE. RESULTS: A total of 152 (5·2%) adolescents had hand eczema at the age of 16 years. Many of these adolescents had a history of AD (n = 111; 73·0%) and asthma and/or rhinitis (n = 83; 54·6%), respectively. Children with AD (aged 0-16 years) had more than threefold increased odds ratios (OR) for having hand eczema; those with persistent or severe AD had a crude OR of 6·1 [95% confidence interval (CI) 4·0-9·1] and 5·3 (95% CI 2·9-9·6), respectively. CONCLUSIONS: We confirm a strong association between AD during childhood and hand eczema in adolescence. Children with persistent or more severe AD are at greater risk of developing hand eczema. Asthma and/or rhinoconjunctivitis, positive specific IgE or age at onset of AD are not associated with hand eczema in adolescence.

Atopic and nonatopic eczema in adolescence: is there a difference?

BACKGROUND: There is limited information on clinical manifestations of atopic eczema (AE) and non-AE in teenagers. OBJECTIVES: To describe the characteristics of adolescent eczema in the general population and to identify potential differences between AE and non-AE in teenagers. METHODS: Overall, 3108 teenagers were included from the population-based BAMSE cohort and 2529 of these teenagers provided blood samples for analysis of specific IgE. At age 16 years, the teenagers answered questionnaires regarding the symptoms of eczema, asthma and rhinitis for the previous year. RESULTS: The prevalence of eczema in adolescence was 9·6% (n = 297). More girls than boys had eczema (12·5% vs. 6·5%; P < 0·001). The age at onset was usually within the first 2 years of life (48·8%), but onset in adolescence was also common (25·6%). Eczema was mild in 72·7% of cases, moderate in 16·8% and severe in 10·4%. Body folds were most frequently affected (73·4%). More than half of the teenagers with eczema had AE (59%). The teenagers with AE had more severe and more chronic eczema. Onset in infancy was most common in AE and onset in adolescence was most common in non-AE. There were no major differences in location or seasonal variance between AE and non-AE in adolescence. CONCLUSIONS: AE is more common than non-AE among teenagers. More than one in four teenagers with eczema has moderate-to-severe disease. Onset in adolescence is common, especially for non-AE. AE in adolescence has an earlier onset and is more chronic and more severe than non-AE.

Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis.

Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen-specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono- and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention.

Allergy-related diseases and recurrent abdominal pain during childhood - a birth cohort study.

BACKGROUND: Allergy and immune dysregulation may have a role in the pathophysiology of recurrent abdominal pain of functional origin, but previous studies of allergy-related diseases and abdominal pain have contradictory results. AIM: To examine the association between allergy-related diseases or sensitisation during childhood and abdominal pain at age 12 years. METHODS: In this birth cohort study of 4089 children, parents answered questionnaires regarding asthma, allergic rhinitis, eczema and food hypersensitivity ('allergy-related diseases') at ages 0,1,2,4,8 and 12 years. Blood for analyses of allergen-specific IgE was sampled at 4 and 8 years. At 12 years, the children answered questions regarding abdominal pain. Children with coeliac disease or inflammatory bowel disease were excluded. Associations were examined using multivariable logistic regression. RESULTS: Among 2610 children with complete follow-up, 9% (n = 237) reported abdominal pain at 12 years. All allergy-related diseases were associated with concurrent abdominal pain at 12 years and the risk increased with increasing number of allergy-related diseases (P for trend <0.001). Asthma at 1 and 2 years and food hypersensitivity at 8 years were significantly associated with abdominal pain at 12 years. There was an increased risk of abdominal pain at 12 years in children sensitised to food allergens at 4 or 8 years, but in stratified analyses, this was confined to children whose parents had not reported food hypersensitivity at time of sensitisation. CONCLUSION: Allergy-related diseases as well as sensitisation to food allergens were associated with an elevated risk of abdominal pain, and the risk increased with the number of allergy-related diseases.

Eczema severity in preadolescent children and its relation to sex, filaggrin mutations, asthma, rhinitis, aggravating factors and topical treatment: a report from the BAMSE birth cohort.

BACKGROUND: Filaggrin (FLG) mutations are major genetic determinants for eczema, but their role in eczema severity needs further investigation. Children with eczema are at higher risk of having asthma and rhinitis but it is not known if this risk is associated with the severity of eczema. OBJECTIVES: To investigate eczema severity in relation to sex, FLG mutations, asthma, rhinitis and topical treatment among preadolescent children in a population-based cohort. METHODS: Parental questionnaires were used to obtain data on symptoms of eczema, asthma, and rhinitis among 3301 preadolescent children. Eczema severity was evaluated based on sleep disturbance, extent of disease and total time with eczema the previous year. Genotyping was performed in 1854 individuals for three common FLG mutations (R501X, R2447X and 2282del4). Results Eczema was more prevalent among girls (14·5%) than boys (9·4%). FLG mutations were detected in 13·1% of children with mild eczema and 12·5% with moderate-to-severe eczema. Of children with moderate-to-severe eczema, 45·1% had rhinitis and 22·0% had asthma compared with 32·7% and 13·8% of children with mild eczema, respectively. Children with moderate-to-severe eczema used moisturizers and topical glucocorticoids more frequently than children with mild eczema. Boys used moisturizers less frequently than girls. CONCLUSIONS: More preadolescent girls than boys had eczema. FLG mutations did not influence eczema severity in our population-based cohort. Prevalence of rhinitis and asthma was associated with eczema severity, with the highest prevalence among boys with moderate-to-severe eczema.

Development and comorbidity of eczema, asthma and rhinitis to age 12: data from the BAMSE birth cohort.

BACKGROUND: Allergy-related diseases are a public health issue, but knowledge on development and comorbidity among children is scarce. The aim was to study the development of eczema, asthma and rhinitis in relation to sex and parental allergy, in a population-based cohort, during childhood. METHODS: At 1, 2, 4, 8 and 12 years, parental questionnaires were used to obtain data on allergy-related diseases. Complete data for all five follow-up occasions were available from 2916 children. Odds ratios for the risk of any allergy-related disease in relation to heredity and sex were calculated using generalized estimating equations. RESULTS: At 12 years, 58% of the children had had eczema, asthma and/or rhinitis at some time. Disease turnover was high for all three diseases throughout the study. Comorbidity increased with age, and at 12 years, 7.5% of all the children were affected by at least two allergy-related diseases. Parental allergy was associated with increased comorbidity and more persistent disease and increased the risk of having any allergy-related disease (adjusted OR 1.76; 95% CI 1.57-1.97) up to 12 years. Male sex was associated with an increased risk throughout childhood. Boys and girls did not differ in disease persistence, and for comorbidity, the differences were minor. CONCLUSIONS: Allergy-related diseases may affect a majority of children. Eczema, asthma and rhinitis develop dynamically throughout childhood, and allergic comorbidity is common. These findings indicate that allergy-related diseases should be neither seen nor studied as isolated entities.

Enhanced expression of the antimicrobial peptide LL-37 in lesional skin of adults with atopic eczema.

BACKGROUND: Atopic eczema (AE) is a common multifactorial chronic skin disease associated with a defective skin barrier and increased susceptibility to skin infections. The human cathelicidin LL-37 plays a role in the host defence of skin. Studies have demonstrated deficient expression of LL-37 in skin of AE patients. OBJECTIVES: The aim of this study was to investigate the expression of LL-37 in lesional skin compared with nonlesional skin in patients with different severity of AE, patients with other eczema and healthy subjects. METHODS: Twenty patients with AE, four patients with other eczema and 10 healthy subjects were included. Severity of AE was graded using SCORing of atopic dermatitis (SCORAD). Skin biopsies were taken from lesional and nonlesional skin from all patients and from skin of healthy controls. The levels of LL-37 mRNA were analysed by quantitative reverse transcriptase-polymerase chain reaction. Evaluation of dermal and epidermal protein expression of LL-37 and the degree of inflammation was performed by immunohistochemical stainings. RESULTS: Patients with AE and patients with other eczema had significantly (P < 0.05) higher levels of LL-37 in lesional skin than in nonlesional skin. The expression of LL-37 was not statistically associated to severity of AE valued by SCORAD. Nonlesional skin from patients did not differ from skin of healthy subjects in terms of LL-37 expression. In the presence of epidermal injury or vesicles the LL-37 peptide was always detected. CONCLUSIONS: Patients with AE exhibit enhanced expression of LL-37 in lesional skin compared with nonlesional, suggesting a role of LL-37 in AE that might be associated with the process of re-epithelialization.

ImmunoCAP Phadiatop Infant--a new blood test for detecting IgE sensitisation in children at 2 years of age.

BACKGROUND: Correct diagnosis of immunoglobulin E (IgE)-mediated disease is the prerequisite for secondary allergy prevention during early childhood. OBJECTIVE: To evaluate the diagnostic efficacy of a new blood test, Phadiatop Infant, in detecting IgE sensitisation to food and inhalant allergens among children at 2 years of age. METHODS: Children (n = 239) were followed prospectively from birth to 2 years of age for the presence of IgE sensitisation and the development of atopic manifestations. Immunoglobulin E sensitisation was evaluated by skin prick test (SPT) and analysis of allergen-specific IgE antibodies in plasma to food and inhalant allergens. The children were classified into three groups: IgE-sensitised, non-IgE sensitised and inconclusive, depending on SPT and allergen-specific IgE results. RESULTS: Twenty-six (11%) of the children were classified as IgE-sensitised, 182 (76%) as non-IgE sensitised and 31 (13%) as inconclusive. Phadiatop Infant was positive in 50 (21%) of the children. Ten children (4%) with identified IgE antibodies against the selected food and inhalant allergens showed negative Phadiatop Infant. Three children showed positive Phadiatop Infant but were negative in the other tests performed. These results correspond to positive and negative predictive values for Phadiatop Infant of 89 and 99%, respectively. Children with clinical symptoms of atopic diseases had significantly increased levels for Phadiatop Infant (P < 0.01). CONCLUSION: Phadiatop Infant appears to be a reliable alternative to SPT and the measurement of allergen-specific IgE antibodies in plasma for detecting clinically important IgE sensitisation among children at 2 years of age.