Background
Adults with eczema are more likely to smoke cigarettes, consume alcohol, and have sedentary lifestyle. We sought to determine whether adult eczema is associated with increased ...cardiovascular and cerebrovascular disease.
Methods
Data from the 2005–2006 National Health and Nutrition Examination Survey (NHANES) (n = 4970) and 2010 (n = 27 157) and 2012 (n = 34 525) National Health Interview Survey (NHIS). History of coronary artery disease (CAD), angina, heart attack, stroke, and peripheral vascular disease (PVD) were determined.
Results
In NHANES, flexural eczema in the past year was associated with significantly higher odds of CAD (P ≤ 0.04), heart attack (P ≤ 0.01), and congestive heart failure (P ≤ 0.02), but not with stroke (P ≥ 0.37), in survey‐weighted multivariate logistic regression models that controlled for socio‐demographics, comorbid asthma, and hay fever. Similarly, in NHIS 2010 and 2012, 1‐year history of eczema was associated with significantly higher odds of CAD (P ≤ 0.02), angina (P ≤ 0.02), heart attack (P ≤ 0.047), other heart disease (P < 0.0001), stroke (P ≤ 0.02), and PVD (<0.0001) in multivariate models.
Conclusions
Adults with atopic dermatitis may have increased cardiovascular disease, heart attack, and stroke.
Summary
Background
Bullous pemphigoid (BP) is associated with significant disability and comorbid health disorders that may lead to or result from hospitalization. However, little is known about the ...inpatient burden and comorbidities of BP.
Objectives
To obtain data on the inpatient burden and comorbidities of BP in the U.S.A.
Methods
We analysed data from the 2002 to 2012 National Inpatient Sample, including a representative 20% sample of all hospitalizations in the U.S.A. (72 108 077 adults).
Results
The prevalence of hospitalization for BP increased from 25·84 to 32·60 cases per million inpatients from 2002 to 2012. In multivariate logistic regression models with stepwise selection, increasing age, nonwhite ethnicity, higher median household income, being insured with Medicare or Medicaid, and increasing number of chronic conditions were all associated with hospitalization for BP (P < 0·05 for all). The top three primary discharge diagnoses for patients with a secondary diagnosis of BP were septicaemia (prevalence 5·51%, 95% confidence interval 5·03–5·99), pneumonia (4·60%, 4·19–5·01) and urinary tract infection (3·52%, 3·15–3·89). Patients with BP also had numerous autoimmune, infectious, cardiovascular and other comorbidities. Interestingly, BP was associated with multiple neuropsychiatric disorders, including demyelinating disorders, dementias (presenile, senile, vascular and other), paralysis, neuropathy (diabetic, other polyneuropathy), Parkinson disease, epilepsy, psychoses and depression. The mean annual age‐ and sex‐adjusted in‐hospital mortality rate was significantly higher in patients with a secondary diagnosis of BP compared with no BP (2·9%, range 2·8–3·9% vs. 2·1%, range 1·9–2·2%). Significant predictors of mortality in patients with BP included increasing age, nonwhite ethnicity and insurance with Medicaid or other payment status (P < 0·05 for all).
Conclusions
Hospitalization for BP increased significantly between 2002 and 2012. Moreover, there were significant ethnic and healthcare disparities with respect to hospitalization and inpatient mortality from BP.
What's already known about this topic?
Bullous pemphigoid is associated with considerable morbidity.
The inpatient comorbidities and mortality of bullous pemphigoid have not been well described.
What does this study add?
The present study revealed novel associations between bullous pemphigoid and numerous neuropsychiatric, cardiovascular and infectious comorbidities in adults.
Mortality rates for adults with a secondary diagnosis of bullous pemphigoid were higher than for those without bullous pemphigoid.
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Summary
Background Obesity in early childhood is associated with increased risk for and severity of atopic dermatitis (AD).
Objective To determine whether obesity in adulthood is associated with ...risk of AD.
Methods This was a retrospective case–control study of 2090 adults using questionnaire, height and weight, and skin‐prick testing between January 1994 and December 2003.
Results Obesity in adults was associated with increased AD multinomial logistic regression: adjusted odds ratio (aOR) 1·43, 95% confidence interval (CI) 1·08–1·89; P = 0·01, but not nonatopic dermatitis (aOR 0·59, 95% CI 0·21–1·68; P = 0·32). Obesity was also associated with increased atopic asthma (aOR 1·98, 95% CI 1·47–2·66, P < 0·0001), but not associated with nonatopic asthma (P = 0·20), atopic or nonatopic rhinoconjunctivitis (P = 0·08 and 0·31, respectively), food allergies (P = 0·67 and 0·35, respectively) or atopy (P = 0·40). The association between obesity and AD remained significant even when controlling for history of asthma, rhinoconjunctivitis and food allergies (aOR 1·40, 95% CI 1·05–1·86; P = 0·02) or in subset analyses of subjects with AD alone (aOR 1·96, 95% CI 1·02–3·75; P = 0·04) and with comorbid asthma, rhinoconjunctivitis and/or food allergies (aOR 1·40, 95% CI 1·03–1·91; P = 0·03).
Conclusion Obesity in adulthood is associated with AD. Further studies are warranted to determine if weight loss may prevent or mitigate AD in adults.
Summary
Background
Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin‐13, a key driver of atopic dermatitis (AD).
Objectives
To evaluate the efficacy and ...safety of tralokinumab in combination with topical corticosteroids (TCS) in patients with moderate‐to‐severe AD who were candidates for systemic therapy.
Methods
This was a double‐blind, placebo plus TCS controlled phase III trial. Patients were randomized 2 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks (Q2W) with TCS as needed over 16 weeks. Patients who achieved an Investigator’s Global Assessment (IGA) score of 0/1 and/or 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16 with tralokinumab were rerandomized 1 : 1 to tralokinumab Q2W or every 4 weeks (Q4W), with TCS as needed, for another 16 weeks.
Results
At week 16, more patients treated with tralokinumab than with placebo achieved IGA 0/1: 38·9% vs. 26·2% difference (95% confidence interval): 12·4% (2·9–21·9); P = 0·015 and EASI 75: 56·0% vs. 35·7% 20·2% (9·8–30·6); P < 0·001. Of the patients who were tralokinumab responders at week 16, 89·6% and 92·5% of those treated with tralokinumab Q2W and 77·6% and 90·8% treated with tralokinumab Q4W maintained an IGA 0/1 and EASI 75 response at week 32, respectively. Among patients who did not achieve IGA 0/1 and EASI 75 with tralokinumab Q2W at 16 weeks, 30·5% and 55·8% achieved these endpoints, respectively, at week 32. The overall incidence of adverse events was similar across treatment groups.
Conclusions
Tralokinumab 300 mg in combination with TCS as needed was effective and well tolerated in patients with moderate‐to‐severe AD.
What is already known about this topic?
Atopic dermatitis (AD) is a chronic interleukin (IL)‐13‐mediated disease.
In clinical practice, biologics are commonly initiated as add‐on therapy to topical corticosteroids (TCS).
Tralokinumab is a fully human monoclonal antibody that binds specifically to the IL‐13 cytokine with high affinity, thereby preventing receptor interaction and subsequent downstream signalling.
Tralokinumab combined with TCS showed early and sustained efficacy and safety in a 12‐week, phase IIb trial in moderate‐to‐severe AD.
What does this study add?
This is the first phase III trial evaluating a targeted anti‐IL‐13 biologic in combination with TCS.
These data demonstrate that tralokinumab plus TCS can achieve significant improvements in AD signs and symptoms and quality of life, as well as exert a steroid‐sparing effect.
Response with tralokinumab in combination with TCS was maintained over 32 weeks.
Tralokinumab may be considered a targeted biological treatment option for patients with moderate‐to‐severe AD.
Linked Comment: Morra and Drucker. Br J Dermatol 2021; 184:386–387.
Plain language summary available online
Dupilumab, a first-in-class therapy targeting the two key cytokines involved in the persistent underlying inflammatory pathway in atopic dermatitis (AD), is approved for treatment of ...moderate-to-severe AD in Europe, USA, Japan and several other countries.
To assess dupilumab effects on SCORing Atopic Dermatitis (SCORAD) and component scores (objective and subjective SCORAD) over time in adults with moderate-to-severe AD.
This post hoc analysis included 2,444 patients in four placebo-controlled, double-blind, randomized, phase 3 trials. SOLO 1 and 2 (NCT02277743; NCT02277769) evaluated 16 weeks of dupilumab monotherapy against placebo. CAFÉ (NCT02755649) and CHRONOS (NCT02260986) evaluated dupilumab with concomitant topical corticosteroids (TCS) against TCS alone for 16 and 52 weeks, respectively.
2,444 patients randomized to treatment in SOLO 1 and 2 (N = 1,379), CAFÉ (N = 325) and CHRONOS (N = 740) were analyzed. Dupilumab treatment significantly improved overall SCORAD and individual components as early as Week 1 or 2, with significant and clinically meaningful differences vs. control through end of treatment (p < .0001). These results occurred irrespective of dupilumab regimen, 300 mg subcutaneously weekly or every 2 weeks.
In four large phase 3 trials in adults with moderate-to-severe AD, dupilumab treatment with or without concomitant TCS resulted in rapid and sustained improvements in all SCORAD outcomes vs. placebo or TCS alone.
Summary
Background
Little is known about the epidemiology of severe acne in the U.S.
Objectives
We sought to study the U.S. prevalence, determinants and comorbidities of severe acne in adolescence.
...Methods
We analysed data from the 2007 National Health Interview Survey, a cross‐sectional questionnaire‐based study of 9417 children ages 0–17 years. Prevalence of severe acne, demographics and comorbid disorders were determined.
Results
The U.S. prevalence of severe acne was virtually nil in the first decade of life, but increased in a linear fashion from 11 years 1·7% (95% confidence interval (CI) 0·4–3·0%) to 17 years of age 12·1% (95% CI 7·8–16·5%) (Rao‐Scott Chi‐square, P < 0·0001). Severe acne was more common in Whites compared with other racial groups at age 14–15 years (P = 0·0004) and girls at age 11–13 (P = 0·02). Severe acne was associated with a number of comorbid disorders. Sinopulmonary disease included sinus infection (P = 0·0003), sore throat other than strep infection (P = 0·0003), asthma (P = 0·03) and nonasthmatic lung disease (P = 0·03). Upper gastrointestinal comorbidities included reflux/heartburn (P = 0·0003), abdominal pain (P = 0·03), nausea/vomiting (P = 0·0001) and food/digestive allergy (P = 0·01). Psychological comorbidities included depression (P = 0·02), anxiety (P < 0·0001), attention deficit disorder/attention deficit hyperactivity disorder (P = 0·01) and insomnia (P = 0·02).
Conclusions
In conclusion, severe acne was more prevalent in older age, Whites, female sex and higher socioeconomic status. Future studies are needed to confirm the associations with sinopulmonary, upper gastrointestinal and psychological disorders in adolescents.
What's already known about this topic?
Little is known about racial, ethnic or socioeconomic differences of severe acne prevalence or about the medical comorbid disorders with severe acne.
What does this study add?
Severe acne is more prevalent in older age, Whites, female sex and higher socioeconomic status.
Severe acne was associated with higher prevalences of one or more sinopulmonary, gastrointestinal and psychological comorbid disorders.
The results of this study suggest that patients with severe acne are at higher risk for many comorbidities and warrant closer surveillance by dermatologists and primary care healthcare providers alike.
Summary
Background
The epidemiology of atopic dermatitis (AD) in the U.S.A. has been described largely via US population‐based questionnaire studies. However, the validity of the questions used for ...self‐ and caregiver‐reported eczema has not been previously demonstrated.
Objectives
To validate the assessment of self‐ and caregiver‐reported eczema.
Methods
We performed a prospective multicentre dermatology‐practice‐based study (three sites) to determine the validity of caregiver‐ and self‐reported ever having eczema and 1‐year history of eczema. Questionnaires were administered to unselected patients prior to their encounter. Patients (n = 782) were then evaluated by expert dermatologists trained in utilizing the Hanifin and Rajka criteria for AD. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value were determined.
Results
Caregiver‐reported 1‐year history of childhood eczema was found to have a sensitivity (95% confidence interval) of 0·70 (0·59–0·80), specificity of 0·96 (0·93–0·99) and PPV of 0·87 (0·78–0·96) when compared with a physician's diagnosis of AD at that visit. Similarly, self‐reported 1‐year history of adult eczema was found to have a sensitivity of 0·70 (0·59–0·80), specificity of 0·95 (0·93–0·97) and PPV of 0·76 (0·64–0·85). The specificities and PPVs of a history of ever having caregiver‐ (0·89, 0·82–0·96 and 0·81, 0·70–0·93) and self‐reported eczema (0·97, 0·95–0·99 and 0·91, 0·85–0·97) were high, with a high sensitivity in children (0·83, 0·72–0·95) but not in adults (0·43, 0·37–0·51).
Conclusions
Self‐ and caregiver‐reported diagnosis of eczema ever or in the past year based on a single question demonstrates sufficient validity for the epidemiological study of AD.
What's already known about this topic?
Questions about self‐reported eczema have been used in multiple epidemiological studies.
What does this study add?
A single question about self‐report and caregiver report of healthcare‐diagnosed eczema is valid to assess for atopic dermatitis.
Linked Comment: Ezzedine and Barbarot, Br J Dermatol 2015; 173: 1356–57.
Summary
Background
The relationship between atopic dermatitis (AD), anxiety and depression in the U.S. adult population is not well established.
Objectives
To determine the relationship of AD and its ...severity with symptoms and diagnosis of anxiety and depression in U.S. adults.
Methods
A cross‐sectional, population‐based study of 2893 adults was performed. AD was determined using modified U.K. Diagnostic Criteria.
Results
Adults with AD vs. those without AD had higher mean Hospital Anxiety and Depression Scale anxiety (HADS‐A) (7·7 vs. 5·6) and depression (HADS‐D) (6·0 vs. 4·3) scores and higher prevalences of abnormal (≥ 11) HADS‐A (28·6% vs. 15·5%) and HADS‐D (13·5% vs. 9·0%) scores. In multivariable linear and logistic regression models controlling for sociodemographics, AD was associated with significantly higher mean HADS‐A and HADS‐D scores (7·7 and 6·0) and higher odds of abnormal HADS‐A odds ratio (OR) 2·19, 95% confidence interval (CI) 1·65–2·91 and HADS‐D scores (OR 1·50, 95% CI 1·04–2·17) (P ≤ 0·03 for all). Mean and abnormal HADS‐A and HADS‐D scores were increased in moderate and severe/very severe self‐reported global AD severity, Patient‐Oriented Eczema Measure (POEM), Patient‐Oriented Scoring AD (PO‐SCORAD), PO‐SCORAD itch and sleep (P < 0·0001 for all). All respondents with severe PO‐SCORAD, POEM and PO‐SCORAD itch had borderline or abnormal HADS‐A and HADS‐D scores. Adults with AD vs. those without AD had higher prevalence of self‐reported healthcare‐diagnosed anxiety or depression in the past year (40·0% vs. 17·5%). Many adults with AD who had borderline and/or abnormal HADS‐A or HADS‐D scores reported no diagnosis of anxiety or depression.
Conclusions
AD is associated with significantly increased anxiety and depression, which may go undiagnosed.
What's already known about this topic?
Previous studies found higher rates of anxiety and depression in clinical cohorts of patients with atopic dermatitis.
What does this study add?
This study found dramatically higher rates of anxiety and depression among adults with atopic dermatitis in the U.S. population, which was primarily driven by atopic dermatitis severity.
Anxiety and depression often go undiagnosed in adults with atopic dermatitis.
Linked Comment: Nicholas and Drucker. Br J Dermatol 2019; 181:442–443.
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Summary
Background
Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced atopic dermatitis (AD) severity in a phase II study with concomitant topical corticosteroids.
...Objectives
To evaluate the efficacy and safety of baricitinib in patients with moderate‐to‐severe AD who had an inadequate response to topical therapies.
Methods
In two independent, multicentre, double‐blind, phase III monotherapy trials, BREEZE‐AD1 and BREEZE‐AD2, adults with moderate‐to‐severe AD were randomized 2 : 1 : 1 : 1 to once‐daily placebo, baricitinib 1 mg, 2 mg, or 4 mg for 16 weeks.
Results
At week 16, more patients achieved the primary end point of Validated Investigator's Global Assessment of AD (0, 1) on baricitinib 4 mg and 2 mg compared with placebo in BREEZE‐AD1 N = 624; baricitinib 4 mg 16·8% (P < 0·001), 2 mg 11·4% (P < 0·05), 1 mg 11·8% (P < 0·05), placebo 4·8%, and BREEZE‐AD2 N = 615; baricitinib 4 mg 13·8% (P = 0·001), 2 mg 10·6% (P < 0·05), 1 mg 8·8% (P = 0·085), placebo 4·5%. Improvement in itch was achieved as early as week 1 for 4 mg and week 2 for 2 mg. Improvements in night‐time awakenings, skin pain and quality‐of‐life measures were observed by week 1 for both 4 mg and 2 mg (P ≤ 0·05, all comparisons). The most common adverse events in patients treated with baricitinib were nasopharyngitis and headache. No cardiovascular events, venous thromboembolism, gastrointestinal perforation, significant haematological changes, or death were observed with any baricitinib dosage.
Conclusions
Baricitinib improved clinical signs and symptoms in patients with moderate‐to‐severe AD within 16 weeks of treatment and induced rapid reduction of itch. The safety profile remained consistent with prior findings from baricitinib clinical development in AD, with no new safety concerns.
What is already known about this topic?
Atopic dermatitis (AD) is a chronic heterogeneous inflammatory skin disease with few approved therapies for patients with moderate‐to‐severe disease.
What does this study add?
These two phase III trials show that baricitinib, an oral inhibitor of Janus kinase 1 and 2, significantly improved clinical signs and symptoms of AD compared with placebo within the first 16 weeks of treatment.
Baricitinib may represent a first‐in‐class oral treatment option for adult patients with moderate‐to‐severe AD.
Linked Comment: Drucker. Br J Dermatol 2020; 183:199–200.
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Summary
Background
Atopic dermatitis (AD) is associated with chronic itch, allergic disease and sleep disturbance, all of which might increase the risk of attention deficit (hyperactivity) disorder ...(ADD/ADHD). Previous analyses have found a consistent association between AD and ADD/ADHD, although the underlying factors contributing to such an association remain underexplored. Additionally, the relationship has been underexplored in adults.
Objectives
To determine if childhood and adult AD and AD severity are associated with ADD/ADHD and to delineate the factors contributing to such an association.
Methods
We analysed data on 354 416 children aged 2–17 years and 34 613 adults age 18+ years from 19 U.S. population‐based surveys, including the National Health Interview Survey 1997–2013 and the National Survey of Children's Health 2003/4 and 2007/8.
Results
In multivariate models adjusting for age, sex, sociodemographics, allergic disease and healthcare utilization, AD was associated with ADD/ADHD in both children adjusted odds ratio (95% confidence interval), 1·14 (1·03–1·26) and adults 1·61 (1·25–2·06). Children with both severe AD and only 0–3 nights of adequate sleep per week had much higher odds of ADD/ADHD 16·83 (7·02–40·33) than those with 0–3 nights of adequate sleep per week 1·83 (1·47–2·26) or mild–moderate AD alone 1·56 (1·22–1·99). AD was most strongly associated with severe ADHD. AD unaccompanied by other allergic disease was also associated with increased risk of ADD/ADHD in children. Among children with AD, history of anaemia, headaches and obesity were associated with even higher odds of ADD/ADHD. Asthma, insomnia and headaches increased the odds of ADHD in adults with AD, although underweight body mass index was protective.
Conclusions
Atopic dermatitis is associated with increased odds of ADD/ADHD in adults and children. Several factors increase the risk of ADHD in adults and children with AD.
What's already known about this topic?
Childhood atopic dermatitis (AD) is associated with increased risk of attention deficit hyperactivity disorder (ADHD); sleep disturbance and disease severity have been implicated as modifying factors.
What does this study add?
Severe AD and sleep disturbance independently and synergistically contribute to increased risk of ADHD.
AD unaccompanied by other allergic diseases is associated with increased risk of attention deficit disorder (ADD)/ADHD.
Obesity, headaches and anaemia further increase the risk of ADD/ADHD in children with AD.
Adult AD is associated with increased risk of ADHD. Asthma, headaches and insomnia increase the risk of ADHD in adult patients with AD, and underweight body mass index is protective.
Linked Comment: Genuneit. Br J Dermatol 2016; 175:863–864.
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