The association between atopic dermatitis, cognitive function and school performance in children and young adults.

BACKGROUND: Children with atopic dermatitis (AD) may have disturbed sleep, affected self-esteem and decreased quality of life, likely interfering with performance in school. OBJECTIVES: To examine the association between hospital-managed paediatric AD, school performance and cognitive function. METHODS: In this cross-sectional study we linked data from the Danish national registers and identified three populations between 2001 and 2019. Population 1 comprised children with graduation grades registered from lower secondary school, population 2 comprised adolescents with registration of an upper secondary graduation mean, and population 3 comprised male conscripts with registration of an IQ test score. AD was defined as a hospital diagnostic code (inpatient or outpatient) prior to the exam or conscription date, and was stratified according to severity, activity and atopic comorbidity. Outcomes included graduation mean from lower and upper secondary school, special educational assistance in primary and lower secondary school, and IQ at conscription. RESULTS: In total, 770 611 (12 137 with AD), 394 193 (6261 with AD) and 366 182 (4539 with AD) children and adolescents were included in populations 1 (lower secondary graduation), 2 (upper secondary graduation) and 3 (conscription), respectively. In lower secondary school, children with severe AD had significantly lower overall, written and oral graduation grade means compared with children with mild AD: respectively, difference -0.29 [95% confidence interval (CI) -0.45 to -0.13, P < 0.001], difference -0.26 (95% CI -0.42 to -0.10, P = 0.0016) and difference -0.30 (95% CI -0.49 to -0.11, P = 0.0018). In upper secondary school, adolescents with AD performed similarly to their peers without AD. Young men with AD scored significantly lower IQ test means at conscription examination than male conscripts without AD: difference -0.60 (95% CI -0.87 to -0.32, P < 0.001). CONCLUSIONS: AD, in particular when severe, is associated with lower school performance in childhood and IQ in young men, which can interfere with academic achievements in life. Optimization of treatment of children with AD and specific educational support to children with severe AD could be needed.

Family burden of hospital-managed pediatric atopic dermatitis: A nationwide registry-based study.

BACKGROUND: Parents of children with atopic dermatitis (AD) report reduced quality of life and higher stress level, which could increase risk of psychiatric and pain disorders, and medication use. METHODS: By use of Danish national registries, we identified family members of all first-born Danish children born between 1 January 1995 and 31 December 2013 with a hospital diagnosis of AD, matched them 1:10 with family members of children without AD, and followed the cohorts over time. RESULTS: Mothers of children with hospital-managed AD had higher risk of filling a prescription for medications for depression, anxiety, pain and sleep problems, and of consulting a psychologist, but most associations disappeared after full adjustment. Siblings had higher risk of receiving a diagnosis for adjustment disorder, and fathers showed increased risk of filling a prescription for pain medication and of divorce, in crude but not adjusted models. CONCLUSIONS: The increased risk of study endpoints seen in mothers of children with hospital-managed AD was not explained by pediatric AD alone. Rather, the total burden in these families including parent and child morbidity and socioeconomic resources seems to explain these observations. The burden in families of children with AD may potentially affect the overall management of their child's AD.

Treatment of adult atopic dermatitis patients according to disease characteristics and demographics.

Little is currently known about possible associations between disease specific characteristics of atopic dermatitis (AD) and use of medical treatments. We explored the use of AD treatments within the past 12 months in Danish adults according to distinct patient characteristics. Patients who had received a diagnosis of AD in a hospital in- or outpatient setting as adults were surveyed and data cross-linked to a national prescription registry. AD severity was measured by the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD). A total of 3834 patients participated. Use of topical medication in the past 12 months increased with increasing AD severity, whereas no difference was observed for systemic medication use. Positive associations between AD in the face and neck, and use of mild and moderately potent topical corticosteroids were observed, while involvement of palms and chest was associated with use of more potent topical corticosteroids. The mean DLQI, skin pain, and itch severity scores were lower in patients managed only with topical corticosteroids (5.5, 3.2, and 4.3, respectively) compared to patients treated with both oral and topical medication (7.1, 3.8, and 5.0, respectively). Patients with frequent topical corticosteroid use tended to be older (50.7 vs 48.6 years), males (50.0% vs 33.6%), current daily smokers (17.3% vs 13.7%), and having asthma (59.1% vs 43.8%) compared with infrequent users of topical corticosteroids. We found a disconnect between the severity of AD signs and symptoms, and use of AD therapies. In particular, a very modest use of systemic immunosuppressants was seen even among patients with severe AD symptoms. However, the underlying clinical decisions and reasons behind this disconnect is not clear based on the current data.

Chronologic order of appearance of immune-mediated inflammatory diseases relative to diagnosis of psoriasis.

BACKGROUND: Psoriasis is a common inflammatory skin disease associated with several immune-mediated inflammatory diseases (IMIDs); however, little is known of the chronology of disease development. OBJECTIVE: To investigate the chronology of IMIDs relative to psoriasis. METHODS: We utilized routinely collected data from Danish nationwide administrative registries to examine the occurrence of IMIDs in patients with psoriasis (n = 10,923) and general population controls (n = 109,230). RESULTS: Approximately 20% of patients with psoriasis developed ≥1 IMID, with a 5-fold increased risk compared with the general population. Most IMIDs were diagnosed before psoriasis, except for psoriatic arthritis. Psoriasis was significantly associated with having multiple IMIDs (odds ratio 15.2, 95% confidence interval 11.6-20.0). Human leukocyte antigen B27 positivity was significantly more frequent among psoriasis patients. LIMITATIONS: Clinical measurements were unavailable. CONCLUSION: IMIDs occur frequently in patients with psoriasis and most are diagnosed before psoriasis. The observed chronology might represent important mechanisms of disease development.

Autoimmune diseases in adults with atopic dermatitis.

BACKGROUND: An increased susceptibility to autoimmune disease has been shown in patients with atopic dermatitis (AD), but data remain scarce and inconsistent. OBJECTIVE: We examined the co-occurrence of selected autoimmune diseases in adult patients with AD. METHODS: Nationwide health registers were used. Adult patients with a hospital diagnosis of AD in Denmark between 1997 and 2012 were included as cases (n = 8112) and matched with controls (n = 40,560). The occurrence of autoimmune diseases was compared in the 2 groups. Logistic regression was used to estimate odds ratios. RESULTS: AD was significantly associated with 11 of 22 examined autoimmune diseases. In addition, AD was associated with having multiple autoimmune comorbidities. Patients with a history of smoking had a significantly higher occurrence of autoimmune comorbidities compared to nonsmokers. LIMITATIONS: This study was limited to adult patients with AD. No information about AD severity or degree of tobacco consumption was available. Results from a hospital population of AD patients cannot be generalized to the general population. CONCLUSIONS: Our results suggest a susceptibility of autoimmune diseases in adult patients with AD, especially in smokers. While we cannot conclude on causality based on these data, an increased awareness of autoimmune comorbidities in patients with AD may be warranted.

Ten-year mortality is increased after hospitalization for atopic dermatitis compared with the general population, but reduced compared with psoriasis.

BACKGROUND: Psoriasis and atopic dermatitis (AD) are chronic inflammatory skin disorders. Mortality is increased in psoriasis, yet no studies on mortality in AD are currently available. OBJECTIVE: We investigated 10-year mortality after hospitalization for AD compared with psoriasis and the general population. METHODS: Between 1996 and 2002 all Danes aged 18 years or older with a first-time hospitalization as a result of AD or psoriasis and AD-matched healthy control subjects were examined in nationwide registers. Multivariable (adjusted for age, sex, socioeconomic status, Charlson Comorbidity Index score, smoking, and medication) hazard ratios were estimated by Cox regression. RESULTS: The study comprised 576 and 951 hospitalized patients with AD and psoriasis, respectively, with a maximum follow-up time of 10 years. During the study period, there were 65 and 286 deaths among patients with AD and psoriasis. Risk of death was decreased in patients with AD versus psoriasis (hazard ratio 0.75; 95% confidence interval 0.57-1.00), but higher than in general population control subjects (n = 5760) (hazard ratio 1.71; 95% confidence interval 1.20-2.44). Patients hospitalized with AD died on average 8.3 years younger than control subjects. LIMITATIONS: Lifestyle may have affected the risk. CONCLUSIONS: The 10-year mortality was significantly lower after hospitalization for AD compared with psoriasis, but increased when compared with the general population.

Gallstone Risk in Adult Patients with Atopic Dermatitis and Psoriasis: Possible Effect of Overweight and Obesity.

Adult atopic dermatitis (AD) is associated with overweight, obesity and cardiovascular diseases (CVD) in Americans, similarly to psoriasis, but no increased risk of CVD has been shown in European patients with AD. This study investigated the prevalence and risk of gallstones in adults with AD and in those with psoriasis as a proxy for obesity using nationwide data for all Danish citizens ≥ 30 years of age. Outcome was a diagnosis of gallstones. Odds ratios (ORs) were calculated by logistic regression (cross-sectional study) and hazard ratios (HRs) were estimated by Cox regression (cohort study). The study comprised 6,742 patients with AD, 53,810 patients with psoriasis, and 3,534,164 general population subjects. The prevalence of gallstones was 3.8%, 3.5% and 5.0% in the general population, AD and psoriasis patients, respectively. Adjusted ORs were 0.81 (0.71-0.92) for AD and 1.18 (1.14-1.23) for psoriasis. During follow-up, adjusted HRs were 0.72 (0.56-0.90) for AD and 1.10 (1.02-1.18) for psoriasis. The findings highlight important differences in obesity and lifestyle factors among patients with AD and those with psoriasis.

Prevalence of Cancer in Adult Patients with Atopic Dermatitis: A Nationwide Study.

is missing (Short communication).

Neonatal risk factors of atopic dermatitis in Denmark - Results from a nationwide register-based study.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin condition with a multifactorial etiopathogenesis. Studies have suggested that several perinatal factors may influence the risk of AD in early childhood. We investigated possible neonatal risk factors such as jaundice, blue light phototherapy, birthweight, gestational age at birth, and season of birth on the risk of developing AD in the first 5 years of life. MATERIALS & METHODS: Data were collected through Danish nationwide administrative registers. All newborn children between 1997 and 2007 (n = 673,614) were included in the cohort. Incidence rate ratios (IRRs) were estimated with 95% confidence intervals (95% CIs) by multivariate Poisson regression analyses. RESULTS: We identified a total of 85,743 children with AD in the first 5 years of life. The risk of AD was slightly increased in children with neonatal jaundice (IRR 1.13 [95% CI 1.06-1.21]). Preterm birth was inversely associated with the risk of AD (IRR 0.74, [95% CI 0.68-0.81]) as well as low birthweight (IRR 0.68, [95% CI 0.61-0.75]). Children born in fall and winter seasons had an increased risk of AD compared to spring and summer. No association between neonatal blue light therapy and the risk of AD was found. CONCLUSIONS: Low birthweight and preterm birth were inversely associated with AD, while neonatal jaundice and cold seasons of birth were associated with an increased risk of AD.

Patient characteristics and disease burden of alopecia areata in the Danish Skin Cohort.

PURPOSE: Alopecia areata (AA) is a common disorder of patchy hair loss which carries a substantial psychological burden for patients. The current understanding of AA prevalence, disease course and burden is limited, and further research is needed to improve patient care. This prospective cohort of AA patients within the Danish Skin Cohort was established to provide data that can serve as a tool in future studies of for example, AA epidemiology and disease burden. PARTICIPANTS: A total of 1494 patients with dermatologist-verified AA were included in the cohort. Patients were invited and included through electronic or phone-based questionnaires. Information regarding demographics, biometrics, lifestyle factors, skin type, AA onset and development, health-related quality of life and self-reported severity assessment was collected. FINDINGS TO DATE: The mean (SD) age of AA onset was 32.7 (17.6) years. The mean body mass index and history of cigarette smoking was comparable with the general population. The majority (92.5%) of participants were Caucasian. In total, 72.4% of patients received their diagnosis by a physician within a year after onset of symptoms, and 66.9% reported to still have symptoms of AA within the past year. A total of 12% reported to have a first-degree family member with AA. In total, 31.4% of patients were missing all or nearly all hairs on their scalp, 32.2% had no or barely no eyelashes and 36.2% had no or barely no eyebrow hairs. Overall, most patients (55.7%) did not experience irritated eyes, but 30% reported slight eye irritation and 47.2% reported no damage to finger nails or toenails. FUTURE PLANS: Observational studies regarding comorbidities, psychosocial burden of AA and efficacy of pharmacological interventions will be carried out and additional data will be linked from nationwide registries of routinely collected data. Furthermore, follow-up survey data will be added for longitudinal analyses.

Limitations of Using Questionnaires for Assessing the Prevalence of Psoriasis and Atopic Dermatitis Among Adults.

IMPORTANCE: Questionnaire studies are important for estimating the prevalence of psoriasis and atopic dermatitis; however, validity among the adult population remains an important concern. OBJECTIVE: To examine the test-retest accuracy of questionnaires for measuring psoriasis and atopic dermatitis prevalence in an adult population. DESIGN, SETTING, AND PARTICIPANTS: This nationwide population-based cohort study administered questionnaires on psoriasis and atopic dermatitis to the same 2333 and 2312 randomly selected adults (≥18 years) in Denmark, respectively, at 2 different time points from May 15, 2018, to November 20, 2020. Data were analyzed from January 10 to January 28, 2021. To reduce the risk of participation bias, potential respondents were given information on the research project only after agreeing to participate. EXPOSURES: Participants were asked identical questions on psoriasis and atopic dermatitis in 2018 and in 2020. Responses were linked at the individual-level. MAIN OUTCOMES AND MEASURES: The test-retest reliability (expressed by Cohen κ). RESULTS: The psoriasis questionnaire was completed by 2333 (mean [SD] age, 55.1 [16.2] years; 1338 [57.4%] women) participants in 2018 and in 2020. The atopic dermatitis questionnaire was completed by 2312 (mean [SD] age, 55.0 [16.2] years; 1326 [57.4%] women) participants in 2018 and in 2020. Among participants reporting a history of psoriasis, agreement between individual responses was high (κ = 0.7558); however, among those reporting a history of atopic dermatitis, agreement was low (κ = 0.4395). For psoriasis, prevalence changed from 7.8% to 8.0%; for atopic dermatitis, from 8.2% to 7.6%. Of participants who in 2018 reported dermatologist-diagnosed atopic dermatitis, 36.9% claimed in the 2020 questionnaire that they had never had atopic dermatitis. Analyses revealed substantial agreement for psoriasis responses across all age strata; for atopic dermatitis responses, the κ declined with increasing age, to 0.2613 for participants 65 or older. CONCLUSIONS AND RELEVANCE: This cohort study found considerable agreement between responses over time when participants were asked about a history of psoriasis. When asked about a history of atopic dermatitis, responses over time were inconsistent. This inconsistency suggests that questionnaires on a history of atopic dermatitis will confer considerable risk of bias and misclassification.

Association of Potent and Very Potent Topical Corticosteroids and the Risk of Osteoporosis and Major Osteoporotic Fractures.

Importance: Systemic and inhaled corticosteroids negatively affect bone remodeling and cause osteoporosis and bone fracture when given continuously or in high doses. However, risk of osteoporosis and major osteoporotic fracture (MOF) after application of topical corticosteroids (TCSs) is largely unexplored. Objective: To examine the association between cumulative exposure to potent and very potent TCSs and risk of osteoporosis and MOF. Design, Setting, and Participants: This nationwide retrospective cohort study included 723 251 Danish adults treated with potent or very potent TCSs from January 1, 2003, to December 31, 2017. Data were obtained from Danish nationwide registries. Filled prescription data were converted in equipotent doses to mometasone furoate (1 mg/g). Data were analyzed from June 1 to August 31, 2019. Exposures: Patients were considered exposed when they had filled prescriptions of cumulative amounts corresponding to the equivalent of at least 500 g of mometasone, using filled prescriptions of 200 to 499 g as the reference group. Main Outcomes and Measures: The co-primary outcomes were a diagnosis of osteoporosis or MOF. Hazard ratios (HRs) adjusted for age, sex, socioeconomic status, medication use, and comorbidity were calculated with 95% CIs using Cox proportional hazards regression models. Results: A total of 723 251 adults treated with the equivalent of at least 200 g of mometasone were included in the analysis (52.8% women; mean [SD] age, 52.8 [19.2] years). Dose-response associations were found between increased use of potent or very potent TCSs and the risk of osteoporosis and MOF. For example, HRs of MOF were 1.01 (95% CI, 0.99-1.03) for exposure to 500 to 999 g, 1.05 (95% CI, 1.02-1.08) for exposure to 1000 to 1999 g, 1.10 (95% CI, 1.07-1.13) for exposure to 2000 to 9999 g, and 1.27 (95% CI, 1.19-1.35) for exposure to at least 10 000 g. A 3% relative risk increase of osteoporosis and MOF was observed per doubling of the cumulative TCS dose (HR, 1.03 [95% CI, 1.02-1.04] for both). The overall population-attributable risk was 4.3% (95% CI, 2.7%-5.8%) for osteoporosis and 2.7% (95% CI, 1.7%-3.8%) for MOF. The lowest exposure needed for 1 additional patient to be harmed (454 person-years) was observed for MOF with exposure of at least 10 000 g. Conclusions and Relevance: These findings demonstrate that use of high cumulative amounts of potent or very potent TCSs was associated with an increased risk of osteoporosis and MOF.

Prevalence and characteristics of psoriasis in Denmark: findings from the Danish skin cohort.

BACKGROUND: Wide-ranging psoriasis prevalence estimates have been reported, possibly due to methodological differences. OBJECTIVES: To assess the prevalence of psoriasis in Denmark and to validate the use of questionnaire-based data to identify patients with psoriasis. METHODS: We used data from the Danish Skin Cohort, a prospective cohort comprising general population adults, as well as patients with dermatologist-verified psoriasis and atopic dermatitis, respectively. The general population cohort was interviewed to assess the psoriasis prevalence in Denmark, and validation of the questions was performed. RESULTS: From 3490 general population participants, 7.9% (n=275) were found to have self-reported psoriasis. Of these, 221 (prevalence 6.3%) had their disease diagnosed by a physician (the dermatologist-diagnosed prevalence was 4.3%), whereas 54 (prevalence 1.6%) were not diagnosed by a physician. A total of 176 (5%) had active psoriasis within the last 12 months. More than half of patients had at least one disease flare in the last 12 months, and 44.4% of patients with psoriasis had at least one family member with psoriasis, whereas this was only the case for 13.7% of non-psoriasis individuals. Validation of the psoriasis diagnosis yielded a high sensitivity and specificity, with little incremental value of limiting diagnoses to those diagnosed by a physician. CONCLUSION: The lifetime-prevalence of self-reported psoriasis was found to be 7.9%, whereas the 1-year prevalence (ie, currently active psoriasis) was 5.0%. If used appropriately, questionnaire-based data may accurately identify patients with psoriasis.

Association Between Topical Corticosteroid Use and Type 2 Diabetes in Two European Population-Based Adult Cohorts.

OBJECTIVE: Topical corticosteroids (CSs) are commonly used to treat inflammatory skin conditions including eczema and psoriasis. Although topical CS package inserts describe hyperglycemia and glycosuria as adverse drug reactions, it is unclear whether topical CS use in real life is also associated with an increased risk of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Two matched case-control studies and one cohort study were conducted using routinely collected health care data from Denmark and the U.K. A total of 115,218 and 54,944 adults were identified as case subjects with new-onset T2D in the Danish and U.K. case-control study, respectively. For the Danish cohort study, 2,689,473 adults were included. The main exposure was topical CSs, and the outcome was incident T2D. RESULTS: Topical CS was significantly associated with T2D in the Danish (adjusted odds ratio [OR] 1.25 [95% CI 1.23-1.28]) and U.K. (adjusted OR 1.27 [95% CI 1.23-1.31]) case-control studies. Individuals who were exposed to topical CSs had significantly increased risk of incident T2D (adjusted hazard ratio 1.27 [95% CI 1.26-1.29]). We observed significant dose-response relationships between T2D and increasing potency of topical CSs in the two Danish studies. The results were consistent across all sensitivity analyses. CONCLUSIONS: We found a positive association between topical CS prescribing and incident T2D in Danish and U.K. adult populations. Clinicians should be cognizant of possible diabetogenic effects of potent topical CSs.

Comorbidities of Atopic Dermatitis: Beyond Rhinitis and Asthma.

PURPOSE OF REVIEW: In this review article, we summarize the current evidence about atopic dermatitis (AD)-associated comorbidities, beyond the traditional atopic and allergic conditions. RECENT FINDINGS: Patients with AD may have an increased risk of cardiovascular diseases, certain malignancies, autoimmune diseases, and neuropsychiatric diseases. The causes of these associations are likely multifactorial and may include genetic predispositions, systemic low-grade inflammation, environmental exposures, medication, and lifestyle and behavioral risk factors. There appears to be geographical variations in prevalence of comorbidities in patients with AD, indicating that differences in ethnicity and lifestyle factors may significantly influence the risk of certain comorbidities. SUMMARY: The reported comorbidities in recent literature emphasize the burden of disease in patients with AD. Early appropriate AD therapy, in combination with reduction of risk factors, may help prevention of certain comorbidities. The reported observations may generate hypotheses for future investigations in underlying risk factors for AD-associated comorbidities.

Erratum to: Comorbidities of Atopic Dermatitis: Beyond Rhinitis and Asthma.

[This corrects the article DOI: 10.1007/s13671-017-0168-7.].