IMPORTANCE Atopic dermatitis (AD) is a common illness of childhood. OBJECTIVE To evaluate the natural history of AD and determine the persistence of symptoms over time. DESIGN, SETTING, AND ...PARTICIPANTS A cross-sectional and cohort study of a nation-wide long-term registry of children with AD enrolled in the Pediatric Eczema Elective Registry (PEER). MAIN OUTCOMES AND MEASURES Self-reported outcome of whether a child’s skin was AD symptom–free for 6 months at 6-month intervals. RESULTS A total of 7157 patients were enrolled in the PEER study for a total of 22 550 person-years. At least 2 years of follow-up were observed for 4248 children and at least 5 years of follow-up were observed for 2416 children. Multiple demographic and exposure variables were associated with more persistent AD. At every age (ie, 2-26 years), more than 80% of PEER participants had symptoms of AD and/or were using medication to treat their AD. It was not until age 20 years that 50% of patients had at least 1 lifetime 6-month symptom- and treatment-free period. CONCLUSIONS AND RELEVANCE Based on this large longitudinal cohort study, symptoms associated with AD seem to persist well into the second decade of a child’s life and likely longer. Atopic dermatitis is probably a life-long illness.
AbstractObjectiveTo investigate whether adults with atopic eczema are at an increased risk of cardiovascular disease and whether the risk varies by atopic eczema severity and condition activity over ...time.DesignPopulation based matched cohort study.SettingUK electronic health records from the Clinical Practice Research Datalink, Hospital Episode Statistics, and data from the Office for National Statistics, 1998–2015.ParticipantsAdults with a diagnosis of atopic eczema, matched (on age, sex, general practice, and calendar time) to up to five patients without atopic eczema.Main outcome measuresCardiovascular outcomes (myocardial infarction, unstable angina, heart failure, atrial fibrillation, stroke, and cardiovascular death).Results387 439 patients with atopic eczema were matched to 1 528 477 patients without atopic eczema. The median age was 43 at cohort entry and 66% were female. Median follow-up was 5.1 years. Evidence of a 10% to 20% increased hazard for the non-fatal primary outcomes for patients with atopic eczema was found by using Cox regression stratified by matched set. There was a strong dose-response relation with severity of atopic eczema. Patients with severe atopic eczema had a 20% increase in the risk of stroke (hazard ratio 1.22, 99% confidence interval 1.01 to 1.48), 40% to 50% increase in the risk of myocardial infarction, unstable angina, atrial fibrillation, and cardiovascular death, and 70% increase in the risk of heart failure (hazard ratio 1.69, 99% confidence interval 1.38 to 2.06). Patients with the most active atopic eczema (active >50% of follow-up) were also at a greater risk of cardiovascular outcomes. Additional adjustment for cardiovascular risk factors as potential mediators partially attenuated the point estimates, though associations persisted for severe atopic eczema.ConclusionsSevere and predominantly active atopic eczema are associated with an increased risk of cardiovascular outcomes. Targeting cardiovascular disease prevention strategies among these patients should be considered.
Atopic eczema is a common inflammatory skin disease. Various inflammatory conditions have been linked to cardiovascular disease, a major cause of global mortality and morbidity.
We sought to ...systematically review and meta-analyze population-based studies assessing associations between atopic eczema and specific cardiovascular outcomes.
MEDLINE, Embase, and Global Health were searched from inception to December 2017. We obtained pooled estimates using random-effects meta-analyses. We used a multivariate Bayesian meta-regression model to estimate the slope of effect of increasing atopic eczema severity on cardiovascular outcomes.
Nineteen relevant studies were included. The effects of atopic eczema reported in cross-sectional studies were heterogeneous, with no evidence for pooled associations with angina, myocardial infarction, heart failure, or stroke. In cohort studies atopic eczema was associated with increased risk of myocardial infarction (n = 4; relative risk RR, 1.12; 95% CI, 1.00-1.25), stroke (n = 4; RR, 1.10; 95% CI, 1.03-1.17), ischemic stroke n = 4; RR, 1.17; 95% CI, 1.14-1.20), angina (n = 2; RR, 1.18; 95% CI, 1.13-1.24), and heart failure (n = 2; RR, 1.26; 95% CI, 1.05-1.51). Prediction intervals were wide for myocardial infarction and stroke.
The risk of cardiovascular outcomes appeared to increase with increasing severity (mean RR increase between severity categories, 1.15; 95% credibility interval, 1.09-1.21; uncertainty interval, 1.04-1.28).
Significant associations with cardiovascular outcomes were more common in cohort studies but with considerable between-study heterogeneity. Increasing atopic eczema severity was associated with increased risk of cardiovascular outcomes. Improved awareness among stakeholders regarding this small but significant association is warranted.
IMPORTANCE: A black box warning describes a potential risk of malignancy associated with topical use of pimecrolimus to treat atopic dermatitis due to its similarity to oral calcineurin inhibitors ...used in solid-organ transplantation and spontaneous reporting of malignancies, including lymphomas and cutaneous malignancies. OBJECTIVE: To evaluate the risk of malignancy in a postmarketing study of children exposed to pimecrolimus. DESIGN, SETTING, AND PARTICIPANTS: A longitudinal cohort study among a nationwide ongoing long-term cohort of children enrolled in the Pediatric Eczema Elective Registry (PEER) who had a history of atopic dermatitis and pimecrolimus use with data available up through May 2014. MAIN OUTCOMES AND MEASURES: Reports of malignancy among those in the PEER compared with expected rates from the Surveillance, Epidemiology, and End Results (SEER) program. RESULTS: Overall, 7457 children were enrolled in the PEER, for a total of 26 792 person-years. Children used a mean (SD) of 793 (1356) g of pimecrolimus when enrolled in the study. As of May 2014, five malignancies had been reported. These include 2 leukemias, 1 osteosarcoma, and 2 lymphomas. No skin cancers were reported. The standardized incidence ratio for all malignancies (primary outcome) based on the age-standardized SEER population was 1.2 (95% CI, 0.5-2.8). As secondary analyses, the standardized incidence ratios (based on 2 cases for each) were 2.9 (95% CI, 0.7-11.7) for lymphoma and 2.0 (95% CI, 0.5-8.2) for leukemia. None of these findings were statistically significant. CONCLUSIONS AND RELEVANCE: Based on more than 25 000 person-years of follow-up, it seems unlikely that topical pimecrolimus as it was used in the PEER cohort to treat atopic dermatitis is associated with an increased risk of malignancy.
Limited evidence suggests increased fracture risk in people with atopic eczema. Any link could have substantial effect; atopic eczema is common, and fractures have associated morbidity and mortality.
...We sought to examine whether atopic eczema is associated with fracture and whether fracture risk varies with eczema severity.
We performed a matched cohort study set in primary care (Clinical Practice Research Datalink GOLD 1998-2016) and linked hospital admissions data (Hospital Episode Statistics), including adults (≥18 years old) with atopic eczema matched (by age, sex, general practice, and cohort entry date) with up to 5 individuals without eczema. We estimated hazard ratios (HRs) from stratified Cox regression comparing risk of major osteoporotic (hip, pelvis, spine, wrist, and proximal humerus) fractures individually and any fracture in those with and without atopic eczema.
We identified 526,808 people with atopic eczema and 2,569,030 people without atopic eczema. Those with eczema had increased risk of hip (HR, 1.10; 99% CI, 1.06-1.14), pelvic (HR, 1.10; 99% CI, 1.02-1.19), spinal (HR, 1.18; 99% CI, 1.10-1.27), and wrist (HR, 1.07; 99% CI, 1.03,-1.11) fractures. We found no evidence of increased proximal humeral (HR, 1.06; 99% CI, 0.97-1.15) fracture risk. Fracture risk increased with increasing eczema severity, with the strongest associations in people with severe eczema (compared with those without) for spinal (HR, 2.09; 99% CI, 1.66-2.65), pelvic (HR, 1.66; 99% CI, 1.26-2.20), and hip (HR, 1.50; 99% CI, 1.30-1.74) fractures. Associations persisted after oral glucocorticoid adjustment.
People with atopic eczema have increased fracture risk, particularly major osteoporotic fractures.
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Atopic dermatitis is known to be common among children, but there are few studies examining the epidemiology across the life course. In particular, there is a paucity of data on atopic dermatitis ...among older adults.
To evaluate participant characteristics, patterns of disease activity and severity, and calendar trends in older adult atopic dermatitis in comparison to other age groups in a large population-based cohort.
This was a cohort study of 9,154,936 individuals aged 0-99 years registered in The Health Improvement Network, a database comprised of electronic health records from general practices in the United Kingdom between 1994 and 2013. Atopic dermatitis was defined by a previously validated algorithm using a combination of at least one recorded atopic dermatitis diagnostic code in primary care and two atopic dermatitis therapies recorded on separate days. Cross-sectional analyses of disease prevalence were conducted at each age. Logistic mixed effect regression models were used to identify predictors of prevalent disease over time among children (0-17 years), adults (18-74 years), and older adults (75-99 years).
Physician-diagnosed atopic dermatitis was identified in 894,454 individuals with the following proportions in each age group: 18.3% of children, 7.7% of adults, and 11.6% of older adults. Additionally, atopic dermatitis prevalence increased across the 2-decade period (beta from linear regression test for trend in the change in proportion per year = 0.005, p = 0.044). In older adults, atopic dermatitis was 27% less common among females (adjusted OR 0.73, 95% CI 0.70-0.76) and was more likely to be active (59.7%, 95% CI 59.5-59.9%) and of higher severity (mean annual percentage with moderate and severe disease: 31.8% and 3.0%, respectively) than in other age groups.
In a large population-based cohort, the prevalence of physician-diagnosed atopic dermatitis has increased throughout adulthood and was most common among males age 75 years and above. Compared to children ages 0-17 and adults ages 18-74, older adult atopic dermatitis was more active and severe. Because the prevalence of atopic dermatitis among older adults has increased over time, additional characterization of disease triggers and mechanisms and targeted treatment recommendations are needed for this population.
IMPORTANCE: Associations between atopic eczema and cancer are unclear, with competing theories that increased immune surveillance decreases cancer risk and that immune stimulation increases cancer ...risk. Establishing baseline cancer risk in people with atopic eczema is important before exploring the association between new biologic drugs for atopic eczema and cancer risk. OBJECTIVE: To investigate whether atopic eczema is associated with cancer. DESIGN, SETTING, AND PARTICIPANTS: Matched cohort studies were conducted from January 2, 1998, to March 31, 2016, in England and from January 1, 1982, to June 30, 2016, in Denmark. We conducted our analyses between July 2018 and July 2019. The setting was English primary care and nationwide Danish data. Participants with atopic eczema (adults only in England and any age in Denmark) were matched on age, sex, and calendar period (as well as primary care practice in England only) to those without atopic eczema. EXPOSURE: Atopic eczema. MAIN OUTCOMES AND MEASURES: Overall cancer risk and risk of specific cancers were compared in people with and without atopic eczema. RESULTS: In England, matched cohorts included 471 970 individuals with atopic eczema (median IQR age, 41.1 24.9-60.7 years; 276 510 58.6% female) and 2 239 775 individuals without atopic eczema (median IQR age, 39.8 25.9-58.4 years; 1 301 074 58.1% female). In Denmark, matched cohorts included 44 945 individuals with atopic eczema (median IQR age, 13.7 1.7-21.1 years; 22 826 50.8% female) and 445 673 individuals without atopic eczema (median IQR age, 13.5 1.7-20.8 years; 226 323 50.8% female). Little evidence was found of associations between atopic eczema and overall cancer (adjusted hazard ratio HR, 1.04; 99% CI, 1.02-1.06 in England and 1.05; 99% CI, 0.95-1.16 in Denmark) or for most specific cancers. However, noncutaneous lymphoma risk was increased in people with atopic eczema in England (adjusted HR, 1.19; 99% CI, 1.07-1.34 for non-Hodgkin lymphoma NHL and 1.48; 99% CI, 1.07-2.04 for Hodgkin lymphoma). Lymphoma risk was increased in people with greater eczema severity vs those without atopic eczema (NHL adjusted HR, 1.06; 99% CI, 0.90-1.25 for mild eczema; 1.24; 99% CI, 1.04-1.48 for moderate eczema; and 2.08; 99% CI, 1.42-3.04 for severe eczema). Danish point estimates also showed increased lymphoma risk in people with moderate to severe eczema compared with those without atopic eczema (minimally adjusted HR, 1.31; 99% CI, 0.76-2.26 for NHL and 1.35; 99% CI, 0.65-2.82 for Hodgkin lymphoma), but the 99% CIs were wide. CONCLUSIONS AND RELEVANCE: The findings from 2 large population-based studies performed in different settings do not support associations between atopic eczema and most cancers. However, an association was observed between atopic eczema and lymphoma, particularly NHL, that increased with eczema severity. This finding warrants further study as new immunomodulatory systemic therapeutics are brought to market that may alter cancer risk.
Background There is a need to better understand the safety of tumor necrosis factor (TNF) inhibitors in patients with psoriatic disease in whom TNF inhibitors are frequently used as monotherapy. ...Objective We sought to examine the risks of infection and malignancy with the use of TNF antagonists in adult patients with psoriatic disease. Methods We conducted a systematic search for trials of TNF antagonists for adults with plaque psoriasis and psoriatic arthritis. We included randomized, placebo-controlled trials of etanercept, infliximab, adalimumab, golimumab, and certolizumab for the treatment of plaque psoriasis and psoriatic arthritis. Twenty of 820 identified studies with a total of 6810 patients were included. Results were calculated using fixed effects models and reported as pooled odds ratios. Results Odds ratios for overall infection and serious infection over a mean of 17.8 weeks were 1.18 (95% confidence interval CI 1.05-1.33) and 0.70 (95% CI 0.40-1.21), respectively. When adjusting for patient-years, the incidence rate ratio for overall infection was 1.01 (95% CI 0.92-1.11). The odds ratio for malignancy was 1.48 (95% CI 0.71-3.09) and 1.26 (95% CI 0.39-4.15) when nonmelanoma skin cancer was excluded. Limitations Short duration of follow-up and rarity of malignancies and serious infections are limitations. Conclusions There is a small increased risk of overall infection with the short-term use of TNF antagonists for psoriasis that may be attributable to differences in follow-up time between treatment and placebo groups. There was no evidence of an increased risk of serious infection and a statistically significant increased risk in cancer was not observed with short-term use of TNF inhibitors.
Individuals experience distinct patterns of atopic dermatitis disease control over time; female sex, lower income, non-white race, atopic history and earlier age of onset were highly predictive of ...persistently active disease into early adulthood.
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