Topical corticosteroid phobia among Danish pharmacy staff.

BACKGROUND: Topical corticosteroid (TCS) phobia may negatively impact treatment adherence. Currently, there are few studies exploring trust and knowledge of TCS use among pharmacy staff. OBJECTIVE: To examine TCS knowledge and possible phobia among Danish pharmacy staff. METHODS: A questionnaire, based on Topical Corticosteroid Phobia (TOPICOP©) questionnaire, was developed and rephrased to fit pharmacy staff. The questions were Likert scales and numerical rating scales (NRS) (0-10). In October/November 2021, 64 pharmacies were invited. If the pharma-cies agreed to participate, a researcher visited the pharmacies and distributed the questionnaires. RESULTS: A total of 244 pharmacy workers from 59 pharmacies participated. The majority (95.4%) responded that they were aware of side effects of TCS, however misconceptions regarding side ef-fects was found in up to 34% of participants. Regarding TCS use, 40% sometimes advised the pa-tients to wait as long as possible before initiating treatment with TCS. Confidence in dispensing TCS to patients was high with a mean of 8.45 (NRS). CONCLUSION: Danish pharmacy staff generally reported high confidence in TCS use. Misconcep-tions regarding side effects were common, and there was a tendency to giving advices on TCS treatment that may indicate low confidence in TCS. Thorough education of pharmacy staff is needed to improve the knowledge of TCS.

Demographics, characteristics and medical treatment among adults with hand eczema in Denmark. A cross-sectional validation and registry-based study.

BACKGROUND: The international classification of diseases, 10th revision (ICD-10) includes several unvalidated diagnostic codes for hand eczema (HE). Knowledge is sparse on HE patient characteristics. OBJECTIVES: To validate selected HE ICD-10 codes in the Danish National Patient Registry (DNPR) and describe disease characteristics, lifestyle factors and medication use in adult HE patients. METHODS: Nineteen HE ICD-10 codes were selected and validated based on patient charts. Five cohorts were constructed based on the diagnostic code, DL30.8H (HE unspecified), in the DNPR: (i) patients with DL30.8H code (n = 8386), (ii) patients with DL30.8H code, but without atopic dermatitis (AD) (n = 7406), (iii) sex- and age-matched general population (n = 8386) without HE. Two additional cohorts nested in the DNPR included participants from the Danish Skin Cohort, (iv) patients with DL30.8H code but without AD (n = 1340) and (v) general population cohort (n = 9876). RESULTS: ICD-10 codes revealed positive predictive values ≥90% except irritant contact dermatitis (unspecified) (79.7%) and hyperkeratotic hand and foot eczema (84.1%). HE patients were most often women, middle-aged or older, of Danish ethnicity, had an atopic medical history and were smokers. Topical corticosteroid prescriptions were almost doubled in HE cohorts compared to general populations. CONCLUSION: We validated several HE ICD-10 codes and identified important HE patient characteristics.

Effects of topical corticosteroid versus tacrolimus on insulin sensitivity and bone homeostasis in adults with atopic dermatitis-A randomized controlled study.

INTRODUCTION: Topical corticosteroids (TCS), used to treat atopic dermatitis (AD), have been associated with type 2 diabetes and osteoporosis in epidemiological studies, possibly explained by systemic absorption. OBJECTIVES: We examined whether intensive daily whole-body TCS treatment over 2 weeks followed by twice weekly application for 4 weeks could elicit insulin resistance and increase bone resorption in adults with AD. METHODS: A randomized parallel-group double-blind double-dummy non-corticosteroid-based active comparator study design was completed in Copenhagen, Denmark. Thirty-six non-obese, non-diabetic adults with moderate-to-severe AD were randomized to whole-body treatment with betamethasone 17-valerate 0.1% plus a vehicle once daily or tacrolimus 0.1% twice daily after washout. Insulin sensitivity assessed by the hyperinsulinemic-euglycemic clamp combined with tracer infusions and biomarkers of bone formation (P1NP) and resorption (CTX) were evaluated at baseline, after 2 weeks of daily treatment and after further 4 weeks of twice-weekly maintenance treatment. RESULTS: AD severity improved with both treatments and systemic inflammation was reduced. After 2 weeks, we observed similar increase in peripheral insulin sensitivity with use of betamethasone (n = 18) and tacrolimus (n = 18). Bone resorption biomarker, CTX, was unchanged, while bone formation marker, P1NP, decreased after betamethasone treatment after both 2 and 6 weeks but remained unchanged in the tacrolimus arm. CONCLUSIONS: Whole-body treatment with TCS leads to systemic exposure but appears not to compromise glucose metabolism during short-term use, which may be a result of reduced systemic inflammatory activity. The negative impact on bone formation could be regarded an adverse effect of TCS.

A nationwide 104 weeks real-world study of dupilumab in adults with atopic dermatitis: Ineffectiveness in head-and-neck dermatitis.

BACKGROUND: Evaluation of effectiveness and safety of new systemic treatments for atopic dermatitis (AD) after approval is important. There are few published data exceeding 52-week therapy with dupilumab. OBJECTIVES: To examine the safety, effectiveness and drug survival of dupilumab in a Danish nationwide cohort with moderate-to-severe AD up to 104 weeks exposure. METHODS: We included 347 adult patients with AD who were treated with dupilumab and registered in the SCRATCH registry during 2017-2022. RESULTS: At all visits, we observed improvement in AD severity measured by Eczema Area and Severity Index (EASI) [median (IQR)]. EASI score at baseline was 18.0 (10.6-25.2), at week 4: 6.5 (3.5-11.6), at week 16: 3.7 (1.2-6.2), at week 52: 2.0 (0.8-3.6), at week 104: 1.7 (0.8-3.8). While drug survival was high (week 52: 90%; week 104: 86%), AD in the head-and-neck area remained present in most patients at high levels; proportion with head-and-neck AD at baseline was 76% and 68% at week 104. 35% of patients reported any AE. Conjunctivitis was the most frequent (25% of all patients) and median time to first registration of conjunctivitis was 201 days. CONCLUSIONS: While 2-year drug survival was 86%, dupilumab was unable to effectively treat AD in the head-and-neck area, and conjunctivitis was found in 25% of patients.

Long-term efficacy (up to 68 weeks) of Baricitinib in combination with topical corticosteroids in adult patients with moderate-to-severe atopic dermatitis: Analysis of treatment responders, partial responders and nonresponders originating from study BREEZE-AD7.

BACKGROUND: Baricitinib demonstrated efficacy in treating adults with moderate-to-severe atopic dermatitis (AD) in Phase 3 clinical trials. OBJECTIVE: To examine long-term efficacy of baricitinib combined with topical corticosteroids (TCS) in adult patients from a Phase 3 study, BREEZE-AD7 (NCT03733301), enrolled in ongoing extension study, BREEZE-AD3 (NCT03334435). METHODS: Upon BREEZE-AD7 completion, responders or partial responders (RPR [vIGA-AD™ ≤2]) receiving baricitinib 2-mg or 4-mg + TCS maintained their original treatment doses in BREEZE-AD3. Nonresponders (NR; vIGA-AD 3,4) receiving baricitinib 2-mg were rerandomized 1:1 to baricitinib 2-mg or 4-mg; NR receiving baricitinib 4-mg remained on same dose. Integrated data from all patients (RPR + NR = baricitinib 4-mg intent-to-treat [ITT] cohort) receiving continuous baricitinib 4-mg in BREEZE-AD7 through BREEZE-AD3 were analysed, along with baricitinib 4-mg or 2-mg RPR cohorts. Primary endpoint was proportion of patients with vIGA-AD (0,1) at Weeks 16, 36 and 52 (Weeks 32, 52 and 68 of continuous therapy). Additional outcomes included improvement in EASI75 and Itch NRS (up to Week 32). Missing data were imputed by last observation carried forward. RESULTS: In baricitinib 4-mg ITT cohort (N = 102), proportions of patients achieving vIGA-AD (0,1) at Week 32, Week 52, and Week 68 were 21.6%, 26.5% and 23.5%; EASI75 were 46.1%, 40.2% and 43.1%, respectively. Itch NRS ≥4-point improvement (Itch ≥4) were 47.3% at Week 16 and 40.6% at Week 32. In baricitinib 4-mg RPR cohort (N = 63), proportions of patients achieving vIGA-AD (0,1) at Week 32, Week 52 and Week 68 were 31.7%, 33.3% 34.9%, respectively; EASI75 were 57.1%, 49.2% and 49.2%, respectively. Itch ≥4 were 53.6% at Week 16 and 46.4% at Week 32. Corresponding proportions for baricitinib 2-mg RPR cohort (N = 53) for vIGA-AD (0,1) were 39.6%, 45.3% and 30.2%; EASI75 were 77.4%, 69.8% and 58.5%, respectively. Itch ≥4 were 56.3% at Week 16 and 47.9% at Week 32. CONCLUSION: Baricitinib 4-mg and 2-mg combined with TCS maintained clinically meaningful sustained efficacy over 68 weeks of continuous treatment.

Occupational hand eczema reduces career length in hairdressers: a prospective cohort study of Danish hairdressers graduating from 1985 to 2007.

BACKGROUND: Occupational hand eczema (OHE) is common in hairdressers, and many leave the trade because of the disease. However, the exact impact of OHE on career length is unknown. OBJECTIVE: To assess the effect of OHE on career length and risk factors associated with leaving the trade because of OHE in hairdressers followed-up for up to 35 years. METHODS: A prospective cohort study of Danish hairdressers graduating between 1985 and 2007 (n=5219) was performed. A questionnaire was sent in 2009 and 2020. The Danish Labor Marked Supplementary Pension Scheme provided information on affiliation to the hairdressing profession. Career length was assessed by Kaplan-Meier analyses. RESULTS: The median survival time was 12.0 (95% CI 11.0 to 13.0) years in graduates with OHE and 14.0 (95% CI 12.6 to 15.4) years in graduates without OHE (p<0.001). Graduates with a frequency of hand eczema (HE) of 'once', 'several times' and 'almost all the time' had a median survival time of 20.0 (95% CI 14.6 to 25.4), 12.0 (95% CI 10.7 to 13.3) and 7.0 (95% CI 5.6 to 8.4) years, respectively. Graduates with OHE that left the trade (partly) because of HE constituted 11.7% of the study population. Factors associated with leaving the trade because of HE included a history of atopic dermatitis (adjusted OR (aOR) 2.2 (95% CI 1.2 to 4.0), a history of a positive patch test (aOR 5.1 (95% CI 2.3 to 11.0) and allergy to hair dyes (aOR 9.4 (95% CI 3.4 to 25.6). CONCLUSION: Career length is reduced in hairdressers with OHE, especially if frequently relapsing or caused by contact allergy, for example, to hair dyes.

Novel insights into contact dermatitis.

Contact dermatitis is a common disease that is caused by repeated skin contact with contact allergens or irritants, resulting in allergic contact dermatitis (ACD) and/or irritant contact dermatitis. Attempts have been made to identify biomarkers to distinguish irritant and allergic patch test reactions, which could aid diagnosis. Some promising candidates have recently been identified, but verification and validation in clinical cases still need to be done. New causes of ACD are constantly being recognized. In this review, 10 new contact allergens from recent years, several relating to anti-aging products, have been identified. Frequent allergens causing considerable morbidity in the population, such as the preservative methylisothiazolinone, have been regulated in the European Union. A significant drop in the number of cases has been seen, whereas high rates are still occurring in other areas such as North America. Other frequent causes are fragrance allergens, especially the widely used terpenes and acrylates found in medical devices for control of diabetes. These represent unsolved problems. Recent advances in immunology have opened the way for a better understanding of the complexity of contact dermatitis, especially ACD-a disease that may be more heterogenous that previous understood, with several subtypes. With the rapidly evolving molecular understanding of ACD, the potential for development of new drugs for personalized treatment of contact dermatitis is considerable.

Association of Childhood Atopic Dermatitis With a Higher Risk of Health Care Utilization and Drug Use for Asthma: A Nationwide Cohort Study.

BACKGROUND: Overwhelming evidence supports a causal relationship between occurrence of asthma and atopic dermatitis (AD). OBJECTIVE: The aims of the study were to determine the incidence of asthma in children with AD and to examine the health care utilization and drug use for asthma in children with AD. METHODS: Children with hospital-diagnosed AD (cases) were matched with individuals from the background population (controls) in a 1:4 ratio. RESULTS: In the final cohort (18,625 cases and 74,500 controls), the incident cases of asthma were 4203 among AD cases and 5298 in controls, corresponding to incidence rates of 34 and 9 in cases and controls per 1000 person-years, respectively (hazard ratio [HR] = 3.82, 95% confidence interval [CI] = 3.65-4.00). During the 1-year follow-up period from asthma diagnosis, children with concomitant AD had a significantly higher risk of hospital admission (HR = 1.97, 95% CI = 1.63-2.37), emergency department visits (HR = 1.62, 95% CI = 1.22-2.14), outpatient visits (HR = 1.97, 95% CI = 1.74-2.23), asthma medication (HR = 1.31, 95% CI = 1.27-1.35), and rescue course corticosteroids (HR = 1.74, 95% CI = 1.13-2.69) compared with children with asthma only. CONCLUSIONS: The risk of being diagnosed with asthma was higher in children with AD. Risk of health care utilization and drug use for asthma was higher in children with both AD and asthma compared with asthma only.

Assessment of biomarkers in pediatric atopic dermatitis by tape strips and skin biopsies.

BACKGROUND: The cytokine profile of atopic dermatitis (AD) depends on age, ethnicity, and disease severity. This study examined biomarkers in children with AD collected by tape strips and skin biopsies, and examined whether the levels differed with filaggrin genotype, disease severity, and food allergy. METHODS: Twenty-five children aged 2-14 years with AD were clinically examined. Skin biopsies were collected from lesional skin and tape strips were collected from lesional and non-lesional skin. We analyzed natural moisturizing factor (NMF) and 17 immune markers represented by mRNA levels in skin biopsies and protein levels in tape strips. Common filaggrin gene mutations were examined in all children. RESULTS: The cytokine profile in lesional skin was dominated by a T helper (Th) 2 response in skin biopsies, and by a general increase in innate inflammation markers (interleukin (IL)-1α, IL-1ß, IL-8, IL-18) along with TARC and CTACK in tape strips. The levels of TARC, CTACK, IL-8, IL-18 showed significant correlation with AD severity in both lesional and non-lesional tape stripped skin, while no significant correlations were observed in skin biopsy data. In tape strips from lesional and non-lesional skin, the levels of NMF and selected cytokines differed significantly between children with and without FLG mutations and food allergy. CONCLUSION: Sampling of the stratum corneum with non-invasive tape strips can be used to identify biomarkers that are associated with disease severity, food allergy and FLG mutations. Skin biopsies showed robust Th2 signature but was inferior for association analysis regarding severity.

Appraisal of Proactive Topical Therapy in Atopic Dermatitis: Pros and Cons.

Atopic dermatitis is a common inflammatory skin disease that can affect both children and adults. It is a chronic disease with recurrent, highly pruritic eczematous lesions. Topical treatment with anti-inflammatory agents is the mainstay of treatment for atopic dermatitis, either in a reactive or proactive approach according to severity of the disease and always in combination with daily application of an emollient cream. Several studies have shown that proactive therapy with either topical corticosteroids or topical calcineurin inhibitors is significantly superior at reducing the number of flares and increasing the interval between flares compared with reactive therapy in patients with moderate and severe disease. The risk of side effects is considered low, and there seem to be no extra economic costs related to this treatment approach. Proactive therapy is an advisable treatment option for patients with moderate and severe atopic dermatitis to gain prolonged disease control; however, long-term safety data and data on when to stop do not yet exist.

Increased all-cause mortality in concomitant atopic dermatitis and asthma: A nationwide registry-based study.

BACKGROUND: Excess mortality has been reported for adults with atopic dermatitis (AD) and asthma. OBJECTIVE: To assess the mortality rate in adults with concomitant AD and asthma. METHODS: Adults with hospital-diagnosed AD were matched (1:4) with non-AD individuals from the background population. RESULTS: The study cohort comprised 8,095 adults with AD (of which 1,201 (14.8%) had concomitant asthma) and 32,380 reference individuals without AD from the background population (of which 878 (2.7%) had asthma). A total of 1,057, 330, 55 and 99 deaths were observed among subjects with neither AD nor asthma, AD only, asthma only, and subjects with concomitant AD and asthma, respectively. The mortality rate per 1,000 person-years was 4.75 (95% CI 4.47-5.05) for subjects with neither AD nor asthma, 7.17 (95% CI 5.92-10.05) for asthma only, 7.09 (95% CI 6.37-7.90) for AD only and 10.87 (95% CI 8.92-13.23) for concomitant AD and asthma. Risk for all-cause mortality was increased in subjects with concomitant AD and asthma compared to asthma only (HR 1.52, 95% CI 1.07-2.15) and neither AD nor asthma (HR 2.27, 95% CI 1.83-2.81) but not compared to subjects with AD only (HR 1.10, 95% CI 0.87-1.39). However, compared to AD only subjects with AD and asthma had increased risk of death due to pulmonary disease (HR 1.81, 95% CI 1.04-3.15). CONCLUSION: Adults with AD, asthma or both conditions have increased risk of death, and further concomitant AD and asthma have increased risk of death compared with asthma alone.

Cohort profile: COpenhagen ROsacea COhort (COROCO) and COpenhagen MIgraine COhort (COMICO).

PURPOSE: Migraine has consistently been connected with rosacea. Commonalities in epidemiology, trigger factors and associated neuropeptides support shared aetiology and pathophysiological pathways, though underlying mechanisms remain unclear. We established two cohorts of patients diagnosed with either migraine and/or rosacea. All patients were phenotyped in regard to migraine and rosacea. In this article, we describe the baseline parameters of the cohorts. In the future, we expect that these cohorts will help uncover potential disease overlaps and allow for prolonged follow-up through national Danish health registers. PARTICIPANTS: COpenhagen ROsacea COhort (COROCO) and COpenhagen MIgraine COhort (COMICO) are prospective cohorts based in the Capital region of Denmark. Participants for COROCO were recruited primarily through two tertiary dermatology clinics in Copenhagen, Denmark and patients for COMICO were recruited through a tertiary neurology clinic in Copenhagen, Denmark. FINDINGS TO DATE: COROCO: 67.7% women (median age 51 years (interquartile range (IQR) 43.0-61.0)). Family history of migraine: 44.3%. Family history of rosacea: 45%. There were 13% who currently smoked, and 36.6% were former smokers. Regular intake of alcohol was present in 79.3% (median 4 items/week (IQR 1.0-9.0)). Median body mass index (BMI): 25.7 (IQR 23.1-29.0). Median Dermatology Life Quality Index (DLQI): 2 (IQR 1-5). COMICO: 88.5% women (median age 41 years (IQR 29.5-51.0)). Family history of migraine: 73.4%. Family history of rosacea: 18.4%. There were 17.1% who currently smoked, and 26.0% former smokers. Regular intake of alcohol was present in 62.2% (median intake: 2 item/week (IQR 1.0-3.0)). Median BMI was 24.6 (IQR 21.5-28.2). Median DLQI was 1 (IQR 0-2). FUTURE PLANS: COROCO and COMICO serve as strong data sources that will be used for future studies on rosacea and migraine with focus on risk factors, occurrence, treatment, natural history, complications, comorbidities and prognosis. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03872050).

The Association Between Season of Birth and Atopic Dermatitis in the Northern Hemisphere: A Systematic Review and Meta-Analysis.

BACKGROUND: Cold and dry climate negatively affects skin barrier functions. This could explain the higher incidence of atopic dermatitis (AD) in Northern countries distant from the equator, as well as the general worsening of AD in Northern European winter months. Although it has been suggested that fall and winter birth is associated with AD, this remains unknown. OBJECTIVES: To examine whether the prevalence of AD is associated with season of birth. METHODS: We conducted a systematic review and meta-analysis. Two reviewers independently searched 3 databases. Study quality was assessed using a Newcastle-Ottawa scale. Study heterogeneity was assessed with Cochrane Q and I2 statistics. Odds ratios with 95% CIs were calculated. Publication bias was assessed using funnel plots. RESULTS: The systematic review identified 23 relevant articles of which 9 articles were included in the meta-analysis. Among a total of 726,378 children aged 0 to 12 years, the overall pooled prevalence of AD was 12.9%. The pooled prevalence of AD was 15.4% (95% CI, 12.1%-19.1%), 14.9% (95% CI, 12.0%-18.1%), 12.7% (95% CI, 10.2%-15.4%), and 13.7% (95% CI, 10.8%-17.0%), among children born in the fall, winter, spring, and summer, respectively. AD was significantly associated with fall (odds ratio, 1.16; 95% CI, 1.06-1.28; P = .0018) and winter (odds ratio, 1.15; 95% CI, 1.04-1.27; P = .0076) birth compared with spring birth. CONCLUSIONS: Although a positive and significant association was observed between being born in fall and winter and developing AD on the Northern hemisphere, there is a need for additional and better-designed studies to understand the effect of seasonal changes on the risk of AD.

Increased Production of IL-17A-Producing γδ T Cells in the Thymus of Filaggrin-Deficient Mice.

Mutations in the filaggrin gene (Flg) are associated with increased systemic levels of Th17 cells and increased IL-17A production following antigen exposure in both humans and mice. In addition to Th17 cells, γδ T cells can produce IL-17A. The differentiation of γδ T cells to either IFNγ or IL-17A-producing (γδT17) cells is mainly determined in the thymus. Interestingly, it has been reported that filaggrin is expressed in the Hassall bodies in the human thymic medulla. However, whether filaggrin affects γδ T cell development is not known. Here, we show that filaggrin-deficient flaky tail (ft/ft) mice have an increased number of γδT17 cells in the spleen, epidermis, and thymus compared to wild-type (WT) mice. We demonstrate that filaggrin is expressed in the mouse thymic medulla and that blocking the egress of cells from the thymus results in accumulation of Vγ2+ γδT17 cells in the thymus of adult ft/ft mice. Finally, we find increased T cell receptor expression levels on γδ T cells and increased levels of IL-6 and IL-23 in the thymus of ft/ft mice. These findings demonstrate that filaggrin is expressed in the mouse thymic medulla and that production of Vγ2+ γδT17 cells is dysregulated in filaggrin-deficient ft/ft mice.

Electrochemical Screening Spot Test Method for Detection of Nickel and Cobalt Ion Release From Metal Surfaces.

BACKGROUND: Present screening methods to rapidly detect release of nickel and cobalt ions from metallic surfaces involve colorimetric dimethylglyoxime (DMG)- and disodium-1-nitroso-2-naphthol-3,6-disulfonate-based spot tests with a cotton bud. There is a risk of false-negative test reactions because test outcomes are dependent on the pressure, area, and duration of surface wiping. OBJECTIVE: The aim of the study was to develop a miniaturized electrochemical device that uses a voltage to accelerate nickel and cobalt release from the tested item and perform an initial validation. METHODS AND RESULTS: A device was built in plastic, and its performance was investigated using 0.5 mL of test solutions of, respectively, DMG and disodium-1-nitroso-2-naphthol-3,6-disulfonate. Cotton buds that had been wetted in test solution were pressed against different metal surfaces at various voltages (0-9 V) and a range of test durations (0-120 seconds). Duplicate testing for nickel and cobalt release was also performed on a sample of 163 jewelry items. CONCLUSIONS: This novel electrochemical device makes it possible to perform nickel and cobalt ion release testing without rubbing, thereby reducing interindividual differences in testing technique. The nickel testing with the device seemed to be superior to conventional DMG spot testing.

[Atopic dermatitis].

Atopic dermatitis is a chronic and relapsing inflammatory skin disease. The clinical features vary among different age and ethnic groups, but pruritus is a hallmark. The treatment of atopic dermatitis includes skin barrier restoration with daily application of moisturizers. Topical corticosteroids and calcineurin inhibitors are first-line treatment for acute flares. In severe cases, immunosuppressive drugs are indicated. Targeted biological drugs are being tested in clinical trials.

Filaggrin gene loss-of-function mutations explain discordance of atopic dermatitis within dizygotic twin pairs.

OBJECTIVES: This study was designed to examine the association between loss-of-function mutations in the filaggrin gene (FLG) and atopic dermatitis (AD) and asthma in adult twins. METHODS: A previously well-characterized cohort of 575 adult twins were genotyped for the loss-of-function mutations in FLG (R501X, 2282del4 and R2447X) most common among northern Europeans. Subjects were examined for symptoms of atopic diseases as well as for lung function, airway responsiveness, and atopy. RESULTS: In the whole population of twins, the risk for AD was significantly increased in individuals with FLG mutations in comparison with wild-type carriers (34.3% vs. 21.8%) after adjustment for possible confounders (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.07-3.41; P = 0.028). A significant association was also observed for persistent AD (OR 2.10, 95% CI 1.02-4.36; P = 0.046). There were no significant differences in risk for asthma by FLG mutation status in individuals with and without AD, respectively (P-value for interaction, 0.595). In 11 dizygotic twin pairs discordant for FLG mutation status, risk for AD was higher in the twin carrying the FLG mutation (five of 11 [45.5%] twins had developed AD) than in the non-carrier co-twin (two of 11 [18.2%] twins had developed AD) (OR 2.50, 95% CI 0.45-13.85; P = 0.293). FLG status did not explain a significant proportion of the variation in AD (P = 0.328) or asthma (P = 0.321). CONCLUSIONS: Filaggrin gene mutations are risk factors for the presence and persistence of AD and explain the discordance of AD within dizygotic twin pairs.