Childhood atopic dermatitis is associated with cardiovascular risk factors in young adulthood-A population-based cohort study.

BACKGROUND: Studies have indicated that atopic dermatitis (AD) is associated with an increased risk of cardiovascular disease (CVD). However, data are conflicting. Furthermore, the longitudinal effect of childhood AD on cardiovascular risk factors in young adulthood is less investigated. OBJECTIVES: To assess associations between AD in childhood and CVD risk factors in young adulthood. METHODS: The study encompasses longitudinal data from a population-based birth cohort. Participants with data up to age 24 years were included (n = 2270). The primary outcomes were body mass index (BMI), waist circumference (WC), body fat per cent (BF%) and blood pressure (BP) at 24 years. The secondary outcome was blood lipids. Severe AD was defined as AD in combination with sleep disturbance due to itching. RESULTS: In total, 18.6% (n = 420) had AD at 24 years. Males with AD had higher BMI (ßAdj. 0.81, 95% CI 0.15-1.47), BF% (ßAdj. 1.19, 95% CI 0.09-2.29), systolic BP (ßAdj. 1.92, 95% CI 0.02-3.82), total cholesterol (ßAdj. 0.14, 95% CI 0.00-0.28) and LDL cholesterol (ßAdj. 0.15, 95% CI 0.02-0.27) compared with males without AD. No associations were seen in females. Current AD with prepubertal onset was associated with increased BMI in both males (ßAdj. 0.89, 95% CI 0.11-1.67) and females (ßAdj. 0.72, 95% CI 0.11-1.33). At 24 years, 23.1% (n = 97) of all with AD, had severe disease, which was significantly associated with overweight in both sexes, with BMI (ßAdj. 1.83, 95% CI 0.72-2.94), WC (ßAdj. 4.03, 95% CI 1.54-6.52) and BF% (ßAdj. 2.49, 95% CI 0.60-4.39) in females and with BF% (ßAdj. 2.96, 95% CI 0.23-5.69) in males, compared with peers with mild to moderate AD. CONCLUSION: AD in males appears to be associated with CVD risk factors in young adulthood. The duration and severity of AD seem to be of importance in both sexes.

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.

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.

Association between atopic dermatitis and autoimmune diseases: a population-based case-control study.

BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disorder and is well known to be associated with other atopic conditions. There is increasing evidence for an association also with nonatopic conditions, including autoimmune diseases, but data are limited about several autoimmune diagnoses. OBJECTIVES: To investigate the association between AD and autoimmune diseases. METHODS: This case-control study used Swedish national healthcare registers. The source population comprised the entire Swedish population aged ≥ 15 years from 1968 to 2016. Cases, including all those with an inpatient diagnosis of AD (from 1968) and/or a specialist outpatient diagnosis of AD (from 2001), were matched by sex and age to healthy controls (104 832 cases of AD, 1 022 435 controls). RESULTS: AD was significantly associated with one or more autoimmune diseases compared with controls - adjusted odds ratio (aOR) 1·97, 95% confidence interval (CI) 1·93-2·01 - and this association was significantly stronger in the presence of multiple autoimmune diseases compared with only one. The association was strongest for autoimmune disorders involving the skin (aOR 3·10, 95% CI 3·02-3·18), the gastrointestinal tract (aOR 1·75, 95% CI 1·69-1·82) or connective tissue (aOR 1·50, 95% CI 1·42-1·58). In the overall analysis, men with AD had a stronger association with rheumatoid arthritis and coeliac disease than did women with AD. In subanalyses, the findings remained stable in multivariable analyses after adjustment for smoking and parental autoimmune disease. CONCLUSIONS: This large population-based study indicates significant autoimmune comorbidity of adults with AD, especially between AD and autoimmune dermatological, gastrointestinal and rheumatological diseases. Having multiple autoimmune diseases resulted in a stronger association with AD than having only one autoimmune disease.

Use of emollients and topical glucocorticoids among adolescents with eczema: data from the population-based birth cohort BAMSE.

BACKGROUND: Knowledge regarding how adolescents treat their eczema is sparse. OBJECTIVES: To explore the use of emollients and topical glucocorticoids in adolescents with eczema in relation to sex and disease severity, and to study dispensing patterns of topical glucocorticoids. METHODS: Questionnaire-based data on symptoms of eczema, eczema severity and treatment with emollients and topical glucocorticoids were obtained from 3108 adolescents in the Swedish population-based birth cohort BAMSE. Severity of reported eczema was evaluated with the BAMSE Eczema Severity Score (BESS) in a questionnaire and with the Patient-Oriented Eczema Measure in clinically examined patients with current eczema (n = 247). Information on dispensed topical glucocorticoids was obtained from the Swedish Prescribed Drug Register. RESULTS: In all, 10% of the adolescents reported eczema in the preceding year: 73% mild, 17% moderate and 10% severe according to BESS. Almost all used emollients, whereas use of topical glucocorticoids was reported by 55%, with no significant difference between sexes. The likelihood of treatment with emollients and topical glucocorticoids increased when the adolescents had symptoms of current eczema [adjusted odds ratio (OR) 5·95, 95% confidence interval (CI) 1·90-18·8], but not if they had more severe eczema compared with mild eczema (adjusted OR 1·57, 95% CI 0·58-4·25). Among those with reported eczema, 24% had a topical glucocorticoid dispensed in the preceding year, and among those with moderate-to-severe current eczema 24% had a dispensed potent topical glucocorticoid. CONCLUSIONS: This population-based study indicates that adolescents with eczema are undertreated or completely untreated, even those with severe eczema.

Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey.

BACKGROUND: Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. OBJECTIVES: The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. METHODS: Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. RESULTS: The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg(-1) per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg(-1) vs. 2 mg kg(-1) vs. > 2 mg kg(-1) , the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33-1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04-5·46, P = 0·04, Ptrend < 0·001. CONCLUSIONS: The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.

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.

Functional and dispositional tolerance develops during continuous cocaine exposure.

Despite the fact that high doses of cocaine are abused chronically, relatively little is known regarding the development of tolerance and/or sensitization under these circumstances. Therefore, male Sprague-Dawley rats were infused continuously i.v. for 10 days, at a rate of 150 mg/kg/day (0.1 mg/kg/min) with cocaine hydrochloride. Body weight, food and water consumption, urine and fecal excretion, as well as blood pressure, heart rate and stereotypic behavior were monitored daily. Blood samples were also drawn daily so that plasma could be analyzed for cocaine and BEG by gas chromatography/mass spectrometry. Severe body weight loss on days 1 through 4 was followed by a gradual return to pre-drug levels. In addition, cocaine's effects on food and water consumption and urine and fecal excretion, which were maximal by day 2, were imperceptible by day 5. Complete tolerance developed rapidly to the remarkable rise in blood pressure noted on the first day. However, tolerance did not develop to the cocaine-induced increase in heart rate. A profound decrease in heart rate was noted in some animals which was interpreted to be cardiotoxicity since these animals subsequently died. On the other hand, sensitization or intensification of behavioral stereotypy occurred during the first 2 days followed by complete tolerance to this effect by day 5. No withdrawal phenomena were noted 24 h after cocaine was abruptly withdrawn. Plasma concentrations of cocaine rose rapidly during the first day and remained elevated at a constant level until day 5. Then, a sharp decline in plasma levels occurred at day 6 which remained depressed for the duration of the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adhesion of human myelomonocytic (HL-60) cells induced by 1,25-dihydroxyvitamin D3 and phorbol myristate acetate is dependent on osteopontin synthesis and the alpha v beta 3 integrin.

A key event in bone resorption is the attachment of osteoclasts on the bone surface. Accumulating data supports the notion that this interaction involves the matrix protein osteopontin on the bone surface interacting with a receptor of the integrin family (alpha v beta 3) at the osteoclast clear zone. Based on the recent observation that osteopontin phosphorylation appears to be required for this interaction, it is of considerable interest to delineate the structural requirements for osteopontin-mediated cell attachment. Although binding of isolated osteoclasts to osteopontin-coated surfaces involves the alpha v beta 3 integrin, this system suffers from considerable disadvantages to allow detailed studies in this respect. We have therefore turned to another cell system, HL-60 promyelocytic leukemia cells, to address these questions. In the presence of the phorbol ester TPA (10 nM) and 1,25-dihydroxyvitamin D3 (100 nM), 90% of the HL-60 cells became adherent within 24 hours and exhibited a macrophage-like appearance. Under these conditions, the osteopontin mRNA levels was elevated around 60-fold compared to the control, non-adherent cells. The absolute requirement of de novo osteopontin synthesis for the TPA and 1,25-vit D3-induced HL-60 cell adhesion was demonstrated by neutralisation of adhesion using an anti-osteopontin polyclonal antibody as well as following transfection of an antisense osteopontin phosphorothioate-modified oligonucleotide. Finally, inhibition of induced HL-60 cell adhesion by an RGD-containing peptide or by an antibody to the alpha v beta 3 integrin complex suggested that the cell-derived osteopontin interacts with this integrin. It is concluded that HL-60 cells induced to differentiate with the combination of TPA and 1,25-vit D3 can be utilised as a model system to delineate structural requirements involved in the interaction between osteopontin and the alpha v beta 3 integrin.

Urinary elimination half-life of delta-1-tetrahydrocannabinol-7-oic acid in heavy marijuana users after smoking.

The urinary excretion of delta 1-tetrahydrocannabinol-7-oic acid (delta 1-THC-7-oic acid), the major urinary metabolite of delta 1-THC, and the total amount of THC metabolites was studied in heavy marijuana users after smoking using high-performance liquid chromatography and the EMT-d.a.u. cannabinoid assay. An average elimination half-life (+/- SD) of 3.0 +/- 2.3 days was obtained for delta 1-THC-7-oic acid. The average ratio (+/- SD) of "EMIT readings"/delta 1-THC-7-oic acid concentrations was 1.23 +/- 1.03.

Low levels of essential fatty acids are related to impaired delayed skin hypersensitivity in malnourished chronically ill elderly people.

Essential fatty acid (FA) deficiency, which may accompany protein-energy malnutrition (PEM), has been associated with impaired inflammatory reactions. We evaluated this relationship by analysing FA profiles and delayed cutaneous hypersensitivity in 20 malnourished elderly non-cancer patients and in 20 age-matched control patients. As indicated by serum cholesterol and serum triglycerides, the lipid levels were decreased by about one-third in the subjects with PEM. In comparison with the controls, there was a reduction in the omega 3 FA (e.g. eicosapentanoate) in total serum lipids (mg l-1) and serum phospholipids (%) of 40% and 47%, respectively. Reductions in serum omega 6 FA (e.g. linoleate and arachidonate) levels corresponded to the drop in total FA concentrations (30%). The cutaneous hypersensitivity was impaired in 14 of the malnourished patients. The magnitude of the skin reaction was positively correlated (P < 0.05) to the concentrations of eicosapentanoate in serum lipids and serum phospholipids, as well as to the linoleate concentration in total serum lipids. Six of the malnourished patients took part in a nutritional intervention programme for 3 months. In parallel with an improvement in the nutritional status there was a 35% increase (P < 0.05) in the total omega 3 FA serum concentration. Negative skin tests became positive and the median skin induration enlarged threefold (P < 0.05). Thus, deficiency of omega 3 FA might be one factor contributing to cutaneous anergy in elderly malnourished patients.