Association between hospital-diagnosed atopic dermatitis and psychiatric disorders and medication use in childhood.

BACKGROUND: While adult atopic dermatitis (AD) is associated with anxiety and depression, and paediatric AD is linked to attention deficit hyperactivity disorder (ADHD), the relationship between AD in childhood and other psychiatric disorders is largely unknown. OBJECTIVES: To determine the relationship between AD and diagnosis and treatment of psychiatric disorders in children. METHODS: All Danish children born between 1 January 1995 and 31 December 2012 with a hospital diagnosis of AD (n = 14 283) were matched 1 : 10 with children without a hospital diagnosis of AD. Endpoints were psychotropic medication use, hospital diagnoses of depression, anxiety, ADHD, or self-harming behaviour, accidental/suicidal death, and consultation with a psychiatrist or psychologist. RESULTS: Significant associations were observed between hospital-diagnosed AD and antidepressant [adjusted hazard ratio (aHR) 1·19, 95% confidence interval (CI) 1·04-1·36], anxiolytic (aHR 1·72, 95% CI 1·57-1·90), and centrally acting sympathomimetic (aHR 1·29, 95% CI 1·18-1·42) medication use. Consultation with a psychiatrist (aHR 1·33, 95% CI 1·16-1·52) or psychologist (aHR 1·25, 95% CI 1·11-1·41) was also associated with AD. No association with a hospital diagnosis of depression (aHR 0·58, 95% CI 0·21-1·56), anxiety (aHR 1·47, 95% CI 0·98-2·22) or self-harming behaviour (aHR 0·88, 95% CI 0·27-2·88) was observed, but a diagnosis of ADHD (aHR 1·91, 95% CI 1·56-2·32) was significantly associated with AD. The absolute risks were generally low. CONCLUSIONS: The increased risk of treatment, but not of a hospital diagnosis of psychiatric disorders in children with hospital-diagnosed AD, suggests that psychiatric issues in children with AD could be of a transient, reversible or mild-moderate nature.

Systematic review on rapidity of onset of action for interleukin-17 and interleukin-23 inhibitors for psoriasis.

Several novel biologics are available or in development for moderate-to-severe plaque psoriasis. These drugs may differ in time until Psoriasis Area and Severity Index (PASI) response is obtained. In this systematic review, we examined the time to onset of action for interleukin (IL)-17 and IL-23 agents in the treatment of psoriasis. The primary objective was the weighted mean time needed for 25% and 50% of patients with psoriasis to achieve PASI90. The medical databases PubMed, Web of Science and EMBASE were searched using the following terms: psoriasis AND (ixekizumab OR secukinumab OR brodalumab OR risankizumab OR guselkumab OR tildrakizumab). A total of 27 studies were included for data extraction and qualitative synthesis, and 26 of these were quantitatively analysed. The shortest time to 25% and 50% of patients to achieved PASI90 were seen with brodalumab 210 mg every 2 weeks (Q2W; 3.5 weeks and 6.2 weeks, respectively) followed by ixekizumab 80 mg Q2W (4.1 and 7.4 weeks, respectively) and ixekizumab 80 mg Q4W (4.6 and 8.1 weeks, respectively) dosages. In conclusion, clinical trials yielded shorter time to onset of action in studies assessing approved dosing ranges of IL-17 inhibitors compared with studies assessing IL-23 inhibitors.

Clinical characteristics, symptoms and burden of psoriasis and atopic dermatitis in adults.

BACKGROUND: There is debate as to whether psoriasis and atopic dermatitis (AD) belong to the same disease spectrum. OBJECTIVES: To describe and compare disease characteristics, lifestyle factors and disease burden in adult patients with psoriasis and AD. METHODS: We linked registry data with clinical and patient-reported outcomes from the Danish Skin Cohort, containing 3348 and 3834 adults with dermatologist-verified psoriasis or AD respectively, and 2946 adults from the general population. RESULTS: The participants were predominantly women and middle-aged. Patients with psoriasis mostly reported disease onset throughout adulthood, but with a distinct early incidence peak in those with a positive family history or severe disease. AD predominantly began in childhood, with only a very discrete incidence peak in adulthood. Scalp, extremity, chest and abdomen involvement was common to both diseases. Scalp/hairline, elbows, nails, intergluteal cleft, umbilicus, knees and legs were most frequently affected in patients with psoriasis. In AD, periocular, neck, antecubital fossae, back of the hands, interdigital areas and popliteal fossae were commonly affected. Patients with psoriasis (but not AD) were generally more overweight, obese and physically inactive, and had a positive smoking history, compared with the general population. Patients with both diseases experienced more frequent flares with increasing disease severity. Patients generally displayed uncontrolled disease despite being on systemic therapies. Itch and skin pain were much more severe in patients with AD, whereas joint pain was more common in patients with psoriasis. CONCLUSIONS: We identified important similarities and differences in the clinical characteristics of adults with psoriasis and AD; these should help clinicians to prioritize and improve patient management. What's already known about this topic? Psoriasis and atopic dermatitis in adults are increasingly being compared, and there is discussion as to whether they are part of the same disease spectrum. What does this study add? In this comparative study, patient-reported disease burden was markedly higher in atopic dermatitis than in psoriasis, whereas lifestyle-associated cardiometabolic risk factors were more frequent in psoriasis. In both disease groups, the condition in the majority of patients was uncontrolled even while they were on systemic therapy. The contrasting presentations highlight that these diseases are two distinct and different entities rather than belonging to the same spectrum.

Characteristics and prevalence of plaque psoriasis in patients with palmoplantar pustulosis.

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic pustular skin condition on the palms and soles. The disease is often seen in combination with plaque psoriasis, and whether PPP is a variant of psoriasis has been debated. The disease prevalence of PPP and co-occurring psoriasis is not yet established and the patient group remains understudied. OBJECTIVES: To estimate the prevalence of PPP and co-occurring psoriasis in three population-based cohorts and to provide information on patient demographics and characteristics. METHODS: Administrative healthcare registries and insurance databases from the U.S.A., Denmark and Germany were used as data sources. Patients with PPP were defined by a single International Classification of Diseases 10th Revision code for PPP during a 1-year period. Information regarding co-occurring plaque psoriasis and other comorbidities was extracted. Furthermore, use of antipsoriatic medication was identified. RESULTS: In total 1435, 751 and 1832 patients with PPP were identified in the U.S., Danish and German populations, with estimated 1-year prevalences of 0·009%, 0·005% and 0·08%, respectively. Plaque psoriasis was present in 14·2-61·3% of patients with PPP. Patients with co-occurring psoriasis had an overall higher prevalence of psoriatic arthritis. Similarly, medication use was more prevalent in patients with PPP with co-occurring psoriasis, and especially pronounced was the use of biologic therapies. CONCLUSIONS: This large observational study on patients with PPP provides detailed information regarding patient demographics, comorbidities and medication use. The 1-year prevalence of PPP varied in the three studied populations, possibly due to differences in diagnostics and recording practices. Psoriasis frequently co-occurred in patients with PPP. What's already known about this topic? Palmoplantar pustulosis (PPP) is a skin disease of the palms of the hands and soles of the feet and is known to be related to psoriasis. Whether PPP is a distinct disease or a variant of psoriasis is not yet established. The condition is understudied in terms of disease prevalence, disease predictors, patient characteristics and comorbidity. What does this study add? In this study using data from three large population-based cohorts we found low prevalence rates (< 0·1%) of PPP. The prevalence of psoriasis was estimated at between 14·2% and 61·3% in patients with psoriasis. Patients with PPP with co-occurring psoriasis have a higher prevalence of psoriatic arthritis and use of antipsoriatic drugs.

Demographics, healthcare utilization and drug use in children and adults with atopic dermatitis in Denmark: a population-based cross-sectional study.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin condition. While previous publications have examined healthcare expenses, large data regarding patient demographics, healthcare use and drug prescriptions are limited. OBJECTIVE: To examine demographics, healthcare use and drug prescriptions in children and adults with hospital-diagnosed AD. METHODS: Danish nationwide registries were cross-linked to access demographic, healthcare and drug prescription data on children and adults with hospital-diagnosed AD (ICD-10 code L20). The diagnostic code for AD used in this study was validated by reviewing medical charts. RESULTS: We identified 9704 children (time period 1997-2012) and 5558 adults (time period 1997-2007) with hospital-diagnosed AD. The diagnostic code L20 had a positive predictive value of 95%. Among children with AD, a larger proportion came from less resourceful families and had immigrant parents from non-European countries. In adults, we observed an opposite tendency. Topical and systemic antibiotics were used relatively frequent in both children and adults with AD. The use of prednisolone and other systemic anti-inflammatory therapy was substantially higher in adults with AD than in children. LIMITATIONS: We were unable to identify and describe patients treated by general and private practitioners. CONCLUSION: There exist significant differences in social predictors for AD and the use of AD medication between children and adults with hospital-diagnosed AD in Denmark. The diagnostic code for AD appears to be valid in Danish registries.

The effects of season and weather on healthcare utilization among patients with atopic dermatitis.

BACKGROUND: Patient-reported triggers for atopic dermatitis (AD) flares include changes in ultraviolet irradiation, humidity and temperature. OBJECTIVES: To identify the relationships between weather data and healthcare utilization in AD patients. METHODS: Using nationwide healthcare registries, clinic (1994-2012) and hospital visits (1977-2012) for AD treatment were calculated as well as monthly totals of topical corticosteroid (TCS) (1996-2012) and calcineurin inhibitor (TCI) prescriptions (2003-20012) filled by AD patients. We calculated monthly averages of temperature, atmospheric pressure, cloud cover and hours of bright sunlight and compared these variables to healthcare utilization endpoints, for the years 2000-2012 (n = 156 months), using linear regression models. RESULTS: In Denmark, between the year 2000 and 2012, mean monthly totals of AD emergency room visits were 6, AD hospitalizations 32, AD outpatient visits 170, TCS prescriptions filled by AD patients 3811 and TCI prescriptions 2552. Healthcare utilization among AD patients was highest in winter/spring. Temperature was the environmental variable that had the strongest association with healthcare utilization: per 1°C lower monthly temperature, 2 more (95% confidence interval [CI] 1-4) AD clinic/hospital visits hospitalizations were observed, 18 (95% CI 9-26) more TCS prescriptions and 53 (95% CI 36-70) more TCI prescriptions were filled by patients with AD. Environmental variables were highly correlated. Associations between AD healthcare utilization and hours of cloud cover were generally positive, while those with hours of bright sunlight were generally inverse. CONCLUSIONS: AD healthcare utilization markers changed significantly with season. A decline in temperature correlated well with AD patients' healthcare utilization, but a causative role could not be determined with certainty.

Loss-of-function mutations in filaggrin gene and malignant melanoma: a case-control study.

BACKGROUND: Loss-of-function mutations in filaggrin gene (FLG) have been suggested to increase the susceptibility of skin malignancies due to reduced levels of epidermal filaggrin and its degradation products, urocanic acid, which may be protective against ultraviolet irradiation. OBJECTIVE: We aimed to investigate the association between FLG mutation status and the occurrence of malignant melanoma (MM) in Danish adults. METHODS: The prevalence of FLG mutations in a sample of MM biopsies was compared with a FLG-genotyped cohort from two general population studies. Pearson's chi-squared and Fisher's exact tests were used to compare the two groups. RESULTS: A total of 867 MM biopsies and 9965 general population controls were genotyped, respectively. In the MM sample, two (0.23%) individuals were homozygous and 80 (9.4%) were heterozygous mutation carriers. In the general population controls, the prevalence of FLG mutations was 18 (0.18%) and 835 (8.4%) for homozygous and heterozygous mutations, respectively. Fisher's exact test and Pearson's chi-squared test yielded non-significant P-values when the groups were compared. CONCLUSION: FLG mutation was not associated with MM in the studied populations. This finding indicates that epidermal deficiency of filaggrin and its degradation products does not influence the risk of MM significantly.

The association with cardiovascular disease and type 2 diabetes in adults with atopic dermatitis: a systematic review and meta-analysis.

BACKGROUND: Recent studies examining the association between atopic dermatitis (AD) and cardiovascular disease (CVD) and type 2 diabetes have shown inconsistent results. OBJECTIVES: To carry out a systematic review and meta-analysis that examines the association with cardiovascular disease and type 2 diabetes in adults with AD. METHODS: We compared the risk of CVD and diabetes for adult patients with and without AD by searching the PubMed, Embase and Web of Science databases. Data extraction was carried out by two independent reviewers. We found a total of 2855 citations, of which 53 were considered relevant based on title and abstract. Overall, 16 publications were included in the qualitative analysis, of which 13 were also included in a quantitative meta-analysis of crude data. RESULTS: No association was observed between AD and unspecified but suspected type 2 diabetes [pooled odds ratio (OR) 1·11; 95% confidence interval (CI) 0·87-1·42], hypertension (pooled OR 1·16; 95% CI 0·98-1·37), stroke (pooled OR 1·15; 95% CI 0·95-1·39) or myocardial infarction (pooled OR 1·14; 95% CI 0·83-1·56), but a positive association was observed with angina pectoris (OR 1·73; 95% CI 1·27-2·37). Meta-analysis of adjusted data gave similar results. CONCLUSIONS: While adults with AD in some populations have an increased prevalence of cardiovascular risk factors, such as obesity and smoking, it is unlikely that AD represents an independent and clinically relevant risk factor for cardiometabolic disease.

Poor agreement in questionnaire-based diagnostic criteria for adult atopic dermatitis is a challenge when examining cardiovascular comorbidity.

BACKGROUND: The association between atopic dermatitis (AD) and cardio-metabolic risk factors is not yet established. Furthermore, no validated questionnaire-based method of identifying adults with AD is currently available. OBJECTIVES: To assess the cardio-metabolic risk in adults with a history of AD using 3 different questionnaire-based diagnostic criteria. METHODS: We utilized data from a general population study including questionnaire data and objective measurements of 9656 Danish adults. To identify adults with a history of AD, we used a question regarding physician-diagnosed AD and 2 versions of the UK Working Party Diagnostic Criteria. Associations between AD status and cardio-metabolic endpoints were estimated using survey weighted logistic and linear regression analysis. RESULTS: We identified 462 (4.8%) adults with self-reported physician-diagnosed AD, whereas 903 (9.4%) and 226 (2.3%) had AD according to the UK Working Party Criteria when at least 2 and 3of 4 minor criteria were fulfilled. The populations were not comparable in terms of occurrence of cardio-metabolic risk factors. For example, the prevalence of obesity was lower in participants with physician-diagnosed AD but overall higher in UK 2/4 and UK 3/4. CONCLUSION: Due to the heterogeneity in the captured study populations in terms of the studied outcomes and absence of a gold standard, no conclusions regarding the cardio-metabolic risk in adults with AD in a general population could be made. This study serves as an example of the challenges that are often encountered in questionnaire-based epidemiologic studies and highlights the need of better definitions for this patient group.

Filaggrin loss-of-function mutations, atopic dermatitis and risk of actinic keratosis: results from two cross-sectional studies.

BACKGROUND: Common loss-of-function mutations in filaggrin gene (FLG) represent a strong genetic risk factor for atopic dermatitis (AD). Homozygous mutation carriers typically display ichthyosis vulgaris (IV) and many have concomitant AD. Previously, homozygous, but not heterozygous, filaggrin gene mutations have been associated with squamous cell carcinomas. OBJECTIVE: The first objective was to examine the association between FLG mutations and actinic keratosis (AK). The second objective was to investigate the occurrence of AK in patients with IV and AD, respectively. METHODS: FLG mutation status in patients with AK was compared with controls from the general population. Furthermore, based on nationwide data from Danish registers, we compared the risk of AK in patients with IV, AD and psoriasis, respectively. RESULTS: The prevalence of homozygous FLG mutations was significantly higher in the AK group (n = 4, 0.8%) in comparison with the control group (n = 18, 0.2%), whereas the prevalence of heterozygous FLG mutations was lower. In hospital registry data, patients with AD exhibited an increased risk of AK than did psoriasis controls (adjusted OR 1.46; [95% CI 1.12-1.90]), whereas no difference in risk was observed between patients with IV and AD. CONCLUSIONS: This study indicates an increased susceptibility to AK in individuals with homozygous, but not heterozygous, FLG mutations and in patients with AD compared to psoriasis. Whether a reduction or absence of epidermal filaggrin could contribute to the susceptibility to AK in patients with IV and AD is unknown and additional research is needed to further explore this relationship.

Prevalence of comorbidity and associated risk factors in adults with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disorder, which may persist into adulthood; however, the prevalence of comorbidities in patients with AD is not well characterized. AD is considered a systemic disorder like psoriasis, which has raised a need for data on the comorbidity profile of patients with AD, to assess the potential risks, benefits, and complications in management of patients with AD. We described the occurrence of medical and psychiatric comorbidities and associated risk factors in adults with AD compared with psoriasis and the general population. METHODS: All Danish individuals aged ≥18 years with a hospital (inpatient or ambulatory) diagnosis of AD or psoriasis during the study period (January 1, 1995-December 31, 2012) were linked in administrative registers. RESULTS: Overall, prevalence of smoking and alcohol abuse was higher among patients with AD than the general population, but lower than psoriasis patients. Similarly, patients with AD had more risk factors and higher prevalence of comorbidity than the general population, but lower prevalence and reduced risk compared to psoriasis patients, except for use of anxiolytics, which was higher in severe AD. Prevalence of diabetes was lower in AD than psoriasis patients as well as general population controls. CONCLUSIONS: Despite an increased risk of various medical and psychiatric comorbidities compared to general population controls, adult patients with AD had markedly lower prevalence of cardiovascular disease than psoriasis patients. However, prevalence of psychiatric comorbidity and tobacco smoking was alarmingly high in severe patients with AD, which might be target for intervention in patient management.