Adult-onset Atopic Dermatitis Research Articles

Safety and efficacy of dupilumab in adult atopic dermatitis in Singapore.

Dupilumab, a biologic approved for treatment of moderate-to-severe atopic dermatitis (AD), has been reported to be largely effective with minimal adverse effects. However, being a targeted therapy, its effectiveness and side effects are expected to be varied in a heterogeneous ethnic population. Currently, the majority of studies on dupilumab are based on Western populations. A retrospective cohort of 51 patients with moderate-to-severe AD treated with dupilumab at a tertiary skin institute from January 2018 to February 2020 was included. Outcome measures such as Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI) and Dermatology Quality of Life Index (DLQI) were analysed at baseline and after 16 weeks of treatment. Laboratory tests at the respective time points were also measured. Patients treated with dupilumab showed consistent reduction in body surface area (BSA) involved, SCORAD, EASI and DLQI scores. Concurrently, serum immunoglobulin E (IgE) and absolute eosinophil count showed a downward trend at 4 months of treatment. There was a transient increase in mean serum IgE at 1 month of dupilumab treatment. Also, 42.0% and 35.3% of patients developed eye symptoms, and head and neck dermatitis, respectively, but there were no major adverse events reported. Childhood-onset AD was more likely to have improved BSA scores compared to adult-onset AD. Our study confirms the efficacy of dupilumab with real-world data in an adult Asian population. Higher proportions of eye symptoms, and head and neck dermatitis were observed in our cohort compared to other Asian clinical cohort studies. Further studies are needed to evaluate these differences.

The Effects of Smoking on the Severity of Atopic Dermatitis in Saudi Arabia.

Background Atopic dermatitis (AD) is a well-known inflammatory skin disease that is associated with a family history of other atopic diseases. Tobacco smoking has been found to affect AD as well as several other inflammatory skin diseases. In this study, we aimed to investigate this association and to elucidate the link between dose-dependent tobacco exposure and symptom severity. Methods This cross-sectional study was conducted on individuals from the general population of Riyadh, Saudi Arabia. Data were collected using an online questionnaire. All statistical analyses were performed using RStudio, version 1.1.363 (RStudio, PBC, Boston, Massachusetts, United States). Questions about the participants' age, sex, and occupational status were included. The participants were asked to report their daily handwashing habits and history of atopic diseases. Data on the smoking duration, number of cigarettes smoked per day, and passive exposure were collected. Results A total of 510 participants (41.3 %) reported having AD. Smoking was significantly associated with an increased prevalence of AD. The odds of having AD were 1.78 and 2.27 times higher in occasional smokers (odds ratio (OR) = 1.78, p < 0.05) and daily smokers (OR = 2.27, p < 0.001) than in non-smokers. Neither smoking frequency (p = 0.19) nor duration (p = 0.73) was significantly associated with AD prevalence. Conclusion Smoking is significantly associated with an increased prevalence of AD. Adults should be discouraged from smoking in order to prevent adult-onset AD. The level of nicotine exposure should be measured objectively in future studies.

Dupilumab-associated mycosis fungoides: a cross-sectional study.

Treating atopic dermatitis (AD) with dupilumab, a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), may be associated with the progression of mycosis fungoides (MF).This study aimsto examine the associations between the length of dupilumab treatment, age and sex, and the onset of MF.An institutional data registry and literature search were used for a retrospective cross-sectional study. Only patients with a diagnosis of MF on dupilumab for the treatment of AD and eczematous dermatitis were included.The primary outcome was the length of dupilumab exposure, age, sex, and the onset of MF. Linear correlations (Pearson) and Cox regression analysis were used to assess the correlation and the risk.A total of 25 patients were included in this study. Five eligible patients were identified at our institution. In addition, a PubMed review identified an additional 20 patients. At the time of MF diagnosis, the median age was 58, with 42% female. Disease history was significant for adult-onset AD in most patients (n = 17, 65.4%) or recent flare of AD previously in remission (n = 3, 11.5%). All patients were diagnosed with MF, and one patient progressed to Sézary syndrome while on dupilumab, with an average duration of 13.5months of therapy prior to diagnosis. Tumor stage at diagnosis of MF was described in 19 of the cases and ranged from an early-stage disease (IA) to advanced disease (IV). Treatment strategies included narrow-band UVB therapy, topical corticosteroids, brentuximab, pralatrexate, and acitretin. Male gender, advanced-stage disease, and older age correlated significantly with the hazard of MF onset and a shorter time to onset during dupilumab treatment.Our results suggest a correlation between the duration of dupilumab treatment and the diagnosis of MF, the higher MF stage at diagnosis, and the shorter the duration of using dupilumab to MF onset. Furthermore, elderly male patients appeared to be more at risk as both male gender and older age correlated with a hazard of MF diagnosis. The results raise the question as to whether the patients had MF misdiagnosed as AD that was unmasked by dupilumab or if MF truly is an adverse effect of treatment with dupilumab. Close monitoring of these patients and further investigation of the relationship between dupilumab and MF can shed more light on this question .

Evaluating and comparing the clinical characteristics between adult-onset and childhood-onset atopic dermatitis in an Asian clinical cohort.

Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin conditions. We aimed to describe the clinical features of adult-onset and childhood-onset AD in a multi-ethnic Asian population. A retrospective study was performed of 188 patients with AD managed at a tertiary skin institution in Singapore. Patient demographics, clinical features and disease scores were analysed. Clinical features related to pigmentary changes, such as orbital darkening and Dennie-Morgan folds were more prevalent among childhood-onset AD patients than in adult-onset AD patients. Similarly, features related to prolonged scratching or friction, such as anterior neck folds, perifollicular accentuation and infra-auricular/infranasal fissuring were also more prevalent in childhood-onset AD patients. Disease scores such as SCORAD and EASI were not different between patients with childhood versus adult-onset disease. There were significant differences in clinical features between childhood-onset and adult-onset AD. Certain features are related to pigmentary changes and might be more accentuated in patients with skin of colour. Further studies are needed to understand how the different features might be clinically significant and related to the various AD endotypes and disease trajectories.

Age of onset defines two distinct profiles of atopic dermatitis in adults.

The incidence of adult-onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric-onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted-therapeutics for this growing population. We thus assessed the profile of AOAD in skin and blood compared to that of POAD. We collected skin biopsies and blood from adults with AOAD, POAD, and healthy controls (n = 15 in each group). Skin samples were analyzed by RNA sequencing, qRT-PCR, and immunohistochemistry, and Olink Proseek multiplex assay was used to identify the serum proteomic profile. Compared to healthy controls, both AOAD and POAD showed cutaneous immune and barrier dysregulations with a shared Th2/Th22 hyperactivation. Overall, POAD showed greater inflammation in lesional skin, with more prominent expression of Th2/Th17/Th22 markers (CCL17/22, S100A8/9, IL-36A, PI3/Elafin, DEFB4) in POAD compared to AOAD (p-value < .05). In contrast, higher Th1-(IFN-γ, IL-2, IL-15, CCL5) upregulation and Th1-skewing were seen in AOAD. The epidermal barrier was also more compromised in POAD, with greater epidermal hyperplasia and lower expression of markers related to terminal differentiation, lipids, and cell adhesion. In parallel with increased rates of cardiovascular comorbidities, AOAD demonstrated many more significantly dysregulated proteins in serum (n = 148) compared to POAD (n = 86), including pro-inflammatory and cardiovascular-risk markers. Th1-related products showed significant correlations between their skin and blood expressions only in AOAD subjects. Age-of-onset delineates two distinct endophenotypes in adult AD potentially suggesting the need for broader (beyond Th2) therapeutic targeting in AOAD.

Atopic dermatitis: Correlation of distinct risk factors with age of onset in adulthood compared to childhood.

Atopic dermatitis (AD) has long been regarded as a primarily pediatric disease. However, there is growing evidence for a high rate of adult-onset AD. We aimed to characterize factors associated with adult-onset versus childhood-onset AD and controls. We analyzed cross-sectional data of the CK-CARE-ProRaD cohorts Bonn, Augsburg, Davos, Zürich of 736 adult patients stratified by age of AD onset (childhood-onset <18 years: 76.4% (subsets: 0 to 2; ≥2 to 6; ≥7 to 11; ≥12 to 18); adult-onset ≥18 years: 23.6% (subsets: ≥18 to 40; ≥41 to 60; ≥61) and 167 controls (91 atopic, 76 non-atopic)). We identified active smoking to be associated with adult-onset AD versus controls (adjusted Odds Ratio (aOR) = 5.54 [95% Confidence Interval: 1.06-29.01] vs. controlsnon-atopic , aOR = 4.03 [1.20-13.45] vs. controlsatopic ). Conjunctivitis showed a negative association versus controlsatopic (aOR = 0.36 [0.14-0.91]). Food allergy (aOR = 2.93 [1.44-5.96]), maternal food allergy (aOR = 9.43 [1.10-80.95]), palmar hyperlinearity (aOR = 2.11 [1.05-4.25]), and academic background (aOR = 2.14 [1.00-4.54]) increased the odds of childhood-onset AD versus controlsatopic . Shared AD-associated factors were maternal AD (4-34x), increased IgE (2-20x), atopic stigmata (2-3x) with varying effect sizes depending on AD onset and control group. Patients with adult-compared to childhood-onset had doubled odds of allergic rhinitis (aOR = 2.15 [1.12-4.13]), but reduced odds to feature multiple (3-4) atopic comorbidities (aOR = 0.34 [0.14-0.84]). Adult-onset AD, particularly onset ≥61 years, grouped mainly in clusters with low contributions of personal and familial atopy and high frequencies of physical inactivity, childhood-onset AD, particularly infant-onset, mainly in "high-atopic"-clusters. The identified associated factors suggest partly varying endo- and exogeneous mechanisms underlying adult-onset versus childhood-onset AD. Our findings might contribute to better assessment of the individual risk to develop AD throughout life and encourage prevention by non-smoking and physical activity as modifiable lifestyle factors.

Treatment Strategies for Chronic Pruritus and Eczema/Dermatitis in Older Adults Under the Category of Chronic Eczematous Eruptions of Aging (CEEA)

Chronic eczematous eruptions of aging (CEEA) refers to a heterogenous group of longstanding, pruritic eczematous dermatoses with an unidentified etiology, or those which do not meet strict disease criteria. The literature has not yet established a single ubiquitous disease or term for these eruptions in adults over the age of 65years. Instead, CEEA is attributed various names, including immunologic eruption of aging, and eruption of immunosenescence. Atopic dermatitis in the elderly, eczema in the elderly, and late- or adult-onset atopic dermatitis or eczema likely also fall under the umbrella of CEEA, given that older patients often do not meet strict criteria for atopic dermatitis. As a reflection of such terminological heterogeneity, CEEA does not have a standardized workup algorithm. This lack of uniformity can obscure the ability to study and understand appropriate treatments for this condition. Yet, as providers become increasingly aware of CEEA and more comfortable in making this diagnosis in older adults, it is necessary that dermatologists understand the safety and efficacy of common CEEA treatments in this population. Here, we discuss special considerations, challenges, and recommendations for treating older adults with CEEA with topical and systemic therapeutics. We provide an overview of therapeutic strategies and potential barriers to treatment and discuss the essential role of shared decision making when caring for this patient population.

Prevalence and risk factors of atopic dermatitis in Chinese adults: a nationwide population-based cross-sectional study.

Atopic dermatitis (AD), also known as atopic eczema, eczema, endogenous eczema, and neurodermatitis, is a chronic inflammatory skin disease occurring in children, adolescents, and adults. Patients with AD often have severe itching and may have other atopic diseases (e.g., allergic rhinitis, asthma, or allergic conjunctivitis). AD has a profound impact on patients’ quality of life. The prevalence of AD in Chinese children has been reported.[1] However, no large-scale population-based study has focused on the prevalence of AD in Chinese adults. The present nationwide survey was conducted to investigate the prevalence and risk factors of AD in Chinese adults. This study received ethics approval of Peking University People's Hospital (No. 2017PHB074-01). Informed consent was obtained from all participants. This cross-sectional survey was conducted in 35 cities of 31 provinces in China from July to December 2017. The pre-estimated sample size was approximately 35,000. The estimated sample size in each region was calculated according to the geographic distribution in the National Census 2010. The cluster sampling method was adopted. Two to three communities in each city were randomly selected for this on-site investigation. Adult residents were invited to complete the questionnaires and undergo a dermatological examination. People with severe diseases or cognitive, linguistic, or mental disorders were not included. The investigators were dermatologists from Peking University People's Hospital and local medical college hospitals. All were trained for this investigation and required to pass an examination for qualification. AD was defined as a clinical diagnosis of AD, eczema, or neurodermatitis by dermatologists. The 1-year prevalence of AD was defined as having clinical manifestations of AD during the past 12 months. The point prevalence was defined as having AD upon dermatological examination. Current smokers were defined as having smoked daily during the past 12 months, ex-smokers as having stopped smoking for at least 1 year before the survey, and non-smokers as having never smoked. The severity of AD was determined by the Severity Scoring of Atopic Dermatitis (SCORAD) index. The age- and sex-adjusted prevalence of AD was calculated based on the China Population Composition in 2010. All data were input using EpiData 3.1 (EpiData Association, Odense, Denmark), and statistical analyses were performed with SPSS 22.0 (IBM Corp., Armonk, NY, USA). Quantitative data are presented as mean and standard deviation, whereas qualitative data are presented as number and/or percentage. Differences in the partici-pants’ characteristics between groups were evaluated using the student's t test for quantitative variables and the chi-squared test for categorical variables. Differences in the prevalence of AD between regions were compared by logistic regression models adjusted by age and sex. Logistic regression models that included significant variables identified in the chi-squared tests were constructed to identify risk factors for AD. Crude and adjusted odd ratios and 95% confidence intervals (CIs) were calculated. P values of <0.05 were considered significant. A total of 44,875 questionnaires were distributed and 40,573 were collected (response rate, 90.41%). After quality control selection, 36,700 valid questionnaires were finally included. The study population comprised 15,853 (43.20%) men and 20,847 (56.80%) women ranging from 18.0 to 99.0 years of age (mean, 35.58 ± 15.65 years). The 1-year prevalence of AD was 6.00% (95% CI, 5.76%–6.24%). After age- and sex-standardization, the prevalence was 6.13%. Women had a higher prevalence than men (6.38% vs. 5.50%, P < 0.001), with an adjusted prevalence of 6.48% and 5.80%, respectively. The prevalence of AD was similar across different age groups. The prevalence of AD in different regions ranged from 5.49% to 6.72%, as shown in [Supplementary Table 1, https://links.lww.com/CM9/B405]. The prevalence of AD was higher in urban areas than in rural areas (6.31% vs. 2.58%, P < 0.001). The point prevalence of AD was 2.17% (95% CI, 2.02%–2.32%) (2.13% in men and 2.20% in women, P = 0.664). After standardization, the point prevalence of AD was 2.42% (2.39% in men and 2.46% in women). The lesions of AD were most common on the hands (24.28%), followed by lower legs (21.51%), neck (21.38%), and face (14.97%). Mild, moderate, and severe AD was present in 73.33%, 24.78%, and 1.89% of patients, respectively, based on the SCORAD index. Of all patients, 66.08% experienced the first onset after 18 years of age. Self-reported food allergy and drug allergy were found in 10.54% and 9.99% of patients, respectively. Moreover, 20.48% of patients experienced over-reaction to insect bites. Allergic rhinitis, asthma, and allergic conjunctivitis were found in 20.71%, 2.68%, and 2.23% of patients, respectively. A history of atopic diseases in first-, second-, and third-degree relatives was found in 31.29%, 6.81%, and 2.68% of patients, respectively. Advanced age, female, living in urban areas, smoking, atopic comorbidities, and an atopic family history were associated with increased risk of AD [Table 1]. Table 1 - Characteristics, atopic comorbidities, and atopic family history in adult patients with atopic dermatitis and general population. Items Atopic dermatitis (N = 2202) General population (N = 34,498) P values Age (years) 37.09 ± 15.83 35.48 ± 15.64 < 0.001 Gender < 0.001 Male 872 (39.60) 14,981 (43.43) Female 1330 (60.40) 19,517 (56.57) Residence < 0.001 Rural 79 (3.59) 2979 (8.64) Urban 2123 (96.41) 31,519 (91.36) Smoking Current smoker 319 (14.49) 4935 (14.31) 0.004 Ex-smoker 134 (6.08) 1571 (4.55) Nonsmoker 1749 (79.43) 27,992 (81.14) Food allergy 232 (10.54) 1661 (4.81) < 0.001 Drug allergy 220 (9.99) 1891 (5.48) < 0.001 Over-reaction to insect bites 451 (20.48) 3375 (9.78) < 0.001 Allergic rhinitis 456 (20.71) 3249 (9.42) < 0.001 Asthma 59 (2.68) 369 (1.07) < 0.001 Allergic Conjunctivitis 49 (2.23) 302 (0.88) < 0.001 Atopy in first-degree relatives 689 (31.29) 4328 (12.55) < 0.001 Atopy in second-degree relatives 150 (6.81) 920 (2.67) < 0.001 Atopy in third-degree relatives 59 (2.68) 376 (1.09) < 0.001 Data are expressed as mean ± standard deviation or n (%). The logistic regression model including region, age, and sex showed no significant difference in the prevalence of AD among regions [Supplementary Table 1, https://links.lww.com/CM9/B405]. In the multivariate logistic regression model, female, advanced age (≥60 years), living in urban areas, and smoking were risk factors for AD. Other risk factors included food allergy, drug allergy, over-reaction to insect bites, allergic rhinitis, asthma, and atopy in first- and second-degree relatives [Supplementary Table 2, https://links.lww.com/CM9/B405]. Of all patients with AD, 65.67% had visited dermatolo-gists and 18.71% had visited traditional Chinese medicine (TCM) doctors. Self-treatment was found in 40.42% of patients, and 3.59% had left their AD untreated. Topical corticosteroids and calcineurin inhibi-tors were used in 64.85% and 4.50% of patients, respectively. Fewer patients used phototherapy (1.18%). Antihistamines, systemic steroids, and immunosuppressants were used in 35.51%, 2.18%, and 0.73% of patients, respectively. Moreover, 12.53% of patients used oral TCM and 11.81% used topical TCM. In this study, the 1-year prevalence of dermatologist-diagnosed AD in Chinese adults was 6.13%. In previous reports, the 1-year prevalence of physician-diagnosed AD in adults ranged from 1.2% to 17.1%.[2,3] The prevalence by clinical diagnosis is often higher than that by criteria-based diagnosis in these studies. For example, a study showed that the prevalence of childhood AD was 12.94% based on dermatologists’ diagnosis but was only 4.76% using the UK Working Party criteria.[1] In our study, the prevalence of AD was only 1.86% using the UK Working Party criteria. Patients who met the diagnostic criteria usually had typical AD, whereas those who did not often had atypical or mild AD. In this study, 66.08% of patients had adult-onset AD, suggesting that late-onset AD is common. Liu et al[4] also reported that 77.5% of adult and adolescent patients with AD experienced the first onset of disease after 12 years of age. The present study showed that the hands, lower legs, neck, and face were more commonly affected in adult AD, consistent with a previous study.[5] We found that most patients (73.33%) had mild AD, whereas moderate and severe AD were found in 24.78% and 1.89% of patients, respectively, similar to the findings in pediatric patients.[1] This study showed that AD was more in women than in men, consistent with most studies.[2] AD was also more common in urban than rural areas, which might be related to lifestyle. Food allergy, drug allergy, and over-reaction to insect bites were common in patients with AD. Allergic rhinitis, asthma, and allergic conjunctivitis were found in 20.71%, 2.68%, and 2.23% of patients with AD, respectively. An atopic family history was also commonly found in adult patients with AD. In this study, 18.71% of patients with AD went to TCM doctors and 40.42% patients chose self-treatment, suggesting high diversity of treatment options among Chinese adults with AD. A small number of patients (3.59%) chose not to treat their AD. These patients might have had mild AD. Topical corticosteroids (64.85%) were the most common topical treatment. Systemic steroids and immunosuppressants were used in only 2.18% and 0.73% of patients, respectively. Although this was a large-scale, nationwide, population-based survey, it has some limitations. The cross-sectional design restricted the exploration of cause-effect relationship. The sample size and the sex and age distributions were not balanced among provinces. Only a few comorbidities were studied. We hope that these limitations will be overcome in future studies. In conclusion, the 1-year prevalence of AD in Chinese adults was 6.13%. The point prevalence of AD was 2.42%. Female, living in urban areas, smoking, atopic comorbidities, and an atopic family history were associated with increased risk of AD. Acknowledgements Authors thank all investigators for their contributions to this study, and all participants for their substantial support. Funding This study was partly supported by grants from the National Natural Science Foundation of China (No. 81442005 and No. 82103750). Conflicts of interest None.

Study of The specificity of gut microbiota in adult patients with delayed-onset of atopic dermatitis.

Atopic dermatitis (AD) is a common and recurrent skin disease. The first onset of AD in adults is known as adult-onset atopic dermatitis (AOAD). Gut microbiota is closely associated with AD, and the "gut-skin" axis is considered as a novel target for prevention of AD. However, only a few studies have analyzed AOAD, particularly the studies that compared differences in intestinal flora between AOAD and persistent AD patients. To investigate main specificities of intestinal microbiota in AOAD patients, particularly comparing with persistent AD patients. A comprehensive taxonomic and functional analysis of gut microbiota in 10 healthy, 12 AOAD, and 10 persistent AD patients was done by using bacterial 16S ribosomal RNA (rRNA) gene analysis. Chao1 and Shannon diversity indices were measured to analyze alpha diversity, and the linear discriminant analysis (LDA) effect size (LEfSe) algorithm was applied to identify differences in genus. The alpha diversity of gut microbiota in AOAD patients was decreased, with Escherichia-shigella (15.8%) being the predominant genus of AOAD group. Agathobacter and Dorea in AOAD patients were significantly reduced, whereas the relative level of Bacteroides pectinophilus group was remarkably elevated compared with healthy volunteers and persistent AD patients. The present study revealed differences in intestinal flora between AOAD, healthy adults, and non-adult onset of AD, and explored differential dominant bacteria between AOAD and persistent AD patients.

Prevalence, Predictors, and Longitudinal Course of Sexual Dysfunction in Adults With Atopic Dermatitis.

Background: Little is known about the burden of sexual dysfunction (SD) in atopic dermatitis (AD). Objective: The objective of this study is to determine the prevalence and associations of SD in adults with AD. Methods: A prospective dermatology practice-based study of adult patients (N = 677) with AD was performed. Sexual dysfunction in the past 7 days was assessed by patient report (4-point Likert scale). Atopic dermatitis severity was assessed using multiple validated clinician-reported and patient-reported outcomes. Results: At baseline, SD was reported by 19.35% of patients and was associated with being married (adjusted odds ratio [95% confidence interval], 2.252 [1.226-4.136]) and younger age (3.363 [1.768-6.397]) but not race or gender in models controlling for sociodemographics and AD severity. Adult-onset versus childhood-onset AD (2.781 [1.211-6.383]) was associated with significant SD. Sexual dysfunction and SD severity were associated with total and objective scoring AD, Eczema Area and Severity Index, body surface area, Investigator's Global Assessment, and their cross-product, Patient-Oriented Eczema Measure and Patient Global Assessment of AD. Atopic dermatitis lesions on the genitals (3.255 [1.405-7.541]), neck (2.244 [1.066-4.723]), and lower extremities (2.236 [1.265-3.951]) were particularly associated with SD. Conclusions: Sexual dysfunction is commonly reported by adults with AD and is associated with marriage, adult-onset AD, AD severity, and lesions on the genitals.

Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets.

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% of children and 10% of adults in high-income countries. The prevalence and incidence of AD have increased in recent years. The onset of AD mostly occurs in childhood, although in some cases AD may persist in adult life or even manifest in middle age (adult-onset AD). AD pathophysiology is made of a complex net, in which genetic background, skin barrier dysfunction, innate and adaptive immune responses, as well as itch contribute to disease development, progression, and chronicization. One of the most important features of AD is skin dehydration, which is mainly caused by filaggrin mutations that determine trans-epidermal water loss, pH alterations, and antigen penetration. In accordance with the “outside-inside” theory of AD pathogenesis, in a context of an altered epidermal barrier, antigens encounter epidermal antigen presentation cells (APCs), such as epidermal Langerhans cells and inflammatory epidermal dendritic cells, leading to their maturation and Th-2 cell-mediated inflammation. APCs also bear trimeric high-affinity receptors for immunoglobulin E (IgE), which induce IgE-mediated sensitizations as part of pathogenic mechanisms leading to AD. In this review, we discuss the role of cytokines in the pathogenesis of AD, considering patients with various clinical AD phenotypes. Moreover, we describe the cytokine patterns in patients with AD at different phases of the disease evolution, as well as in relation to different phenotypes/endotypes, including age, race, and intrinsic/extrinsic subtypes. We also discuss the outcomes of current biologics for AD, which corroborate the presence of multiple cytokine axes involved in the background of AD. A deep insight into the correlation between cytokine patterns and the related clinical forms of AD is a crucial step towards increasingly personalized, and therefore more efficient therapy.

Is dupilumab effective in adult-onset atopic dermatitis: Real-life experience of 16 patients.

Dupilumab is approved for the treatment of atopic dermatitis (AD). However, there are few studies demonstrating its efficacy and safety, particularly in the treatment of adult-onset AD. The aim of this study is to evaluate the real-life experience regarding the efficacy and safety of dupilumab in the treatment of adult-onset AD. This study is a case series in retrospective design. Patients with the diagnosis of adult-onset AD, using dupilumab at a standard dose for at least 3months, were included in the study. Demographic and laboratory data of the cases, data regarding to dupilumab treatment, were recorded. The eczema area severity index (EASI) and the visual analog scale (VAS) for itch were used to evaluate treatment efficacy. A total of 16 patients, 6 female and 10male, were included. The median age was 41years, the median age of the disease onset was 37.5years, and the median duration of the disease was 90months. The median duration of the dupilumab treatment was 10.5months. The mean percent reduction from baseline in EASI score was 85.8±12.2 at 3months, 90.7±9.3 at 6months, and 93.1±5 at 12months. The mean percent reduction from baseline in VAS itch score was 82.2±8.6 at 3months. Acute vestibular neuritis was developed in one patient during the dupilumab therapy and resolved with anti-inflammatory therapy. Dupilumab seems to be highly effective and safe in the treatment of adult-onset AD. The present study is important as it is the first study to evaluate this patient group specifically.

Impairment of Quality of Life and Mental Health Status in Adult-Onset Atopic Dermatitis.

BackgroundPatients with atopic dermatitis (AD) have an impaired quality of life (QoL). To our knowledge, impairments in mental health status and health-related QoL (HRQoL) have not yet been evaluated in adult-onset and child-onset AD in a large-scale study.ObjectiveThis study compared the mental health status and HRQoL (using the EuroQoL [EQ] five-dimensional [5D] questionnaire) in child-onset AD and adult-onset AD to those in normal controls.MethodsWe used nationwide, population-based, cross-sectional data from the Korean National Health and Nutrition Examination Survey conducted from 2008 to 2013. We performed multiple logistic regression analyses with adjustments for age, sex, body mass index, income, education level, drinking status, current smoking, regular exercise, diabetes mellitus, hypertension, and dyslipidemia, and analyzed odds ratios (OR) for factors associated with impaired QoL.ResultsThe OR for strong psychological stress, depressed mood, and suicidal ideation were significantly increased in adult-onset AD patients compared to in normal controls. In addition, the OR (95% confidence interval [CI]) values for the EQ-5D questionnaire responses (for physical activity, self-control, daily activities, pain/discomfort, and anxiety/depression) were significantly high in adult-onset AD compared to in normal controls after adjustments for covariates. However, patients with child-onset AD showed a significantly increased OR (95% CI) only for problems in pain/discomfort in the EQ-5D questionnaire.ConclusionAdult-onset AD patients suffer from impaired HRQoL and significant mental problems compared to normal controls. Dermatologists should focus not only on the clinical phenotype but also patients’ psychological health status to ensure a better treatment outcome.

Unmet needs in atopic dermatitis management: an expert consensus

Introduction Atopic dermatitis (AD) has substantial negative impact on patients’ quality of life. Although considerable advances have been made in understanding the pathogenesis and its treatment, there is still limited transfer of this knowledge into daily management. Aiming to identify unmet needs in clinical management of patients with AD, we used a Delphi consensus process. Methods A set of statements regarding diagnosis, management, prognosis, and treatment was identified by five experts (Steering Committee). Then, the Steering Committee and a second group of four clinicians were involved in a Delphi process. Lastly, agreement was assessed in a larger panel of Italian clinicians. Results Overall, 37 clinicians participated to the process. 17 statements reached strong agreement and 2 reached weak agreement. Conclusions In general, the statements reflected the need for accurate and effective diagnostic criteria to support clinical experience, especially in the atypical forms of AD. Moreover, prognostic criteria are needed to predict the duration of adult-onset AD. The identification of biomarkers was considered to be useful for clinical management of AD at all stages of disease. Lastly, greater emphasis should be placed on patient education and development of effective tools that can aid informing patients about their disease and its treatment.

Adult late-onset atopic dermatitis presenting as cutaneous lupus in a male patient

BackgroundAdult-onset atopic dermatitis (AD) diagnosis is very challenging as it presents with clinical heterogeneity and can mimic a broad of differential diagnoses such as mycosis fungoid and psoriasis. Herein, we report a lupus-like presentation of adult-onset AD. Clinical caseA 32-year-old man with a history of asthma presented to our department with a – lupus like – malar rash. Cutaneous lupus was suspected, but neither clinical, nor paraclinical or immunological assessment were in favor of the disease, skin biopsy revealed epidermal spongiosis, and eosinophilic infiltrate which, together with the patient's personal history and laboratory abnormalities, allowed the diagnosis of late-onset AD. Treatment with topical corticosteroids on the body and tacrolimus on the face was started, with good improvement. ConclusionAdult AD can simulate cutaneous lupus. Recognition of the clinical mimickers of AD is crucial for an accurate diagnosis.

Topical therapy of atopic dermatitis with a focus on pimecrolimus.

Atopic dermatitis (AD) is a chronic and relapsing, inflammatory skin disease characterized by impaired skin barrier function and immune system dysregulation that results in dryness, skin microbiome dysbiosis and intense pruritus. It is highly heterogeneous, and its management is demanding. Patients with AD are at greater risk of comorbidities such as attention-deficit hyperactivity disorder as well as other atopic diseases. Early-onset AD cases typically improve or resolve in late childhood; however, it is proposed that the prevalence of persistent or adult-onset AD is higher than previously thought. Basic therapy consists of emollient application and trigger avoidance, and when insufficient, topical corticosteroids (TCS) are the first-line treatment. However, corticophobia/steroid aversion and TCS side-effects, particularly on sensitive skin areas, lead to low compliance and insufficient disease control. Several long- and short-term randomized controlled and daily practice studies have demonstrated that topical calcineurin inhibitors, such as pimecrolimus, have similar anti-inflammatory effects to low-to-medium strength TCS, reduce pruritus and improve the quality of life of patients. In addition, pimecrolimus does not cause skin atrophy, is steroid-sparing and has a good safety profile, with no evidence for an increased risk of malignancies or skin infections. In general, pimecrolimus cream is well-accepted and well-tolerated, encouraging patient adherence and leading to its use by many physicians as a preferred therapy for children and sensitive skin areas.

Efficacy of Dupilumab on Different Phenotypes of Atopic Dermatitis: One-Year Experience of 221 Patients.

Background: The clinical features of adult-onset atopic dermatitis (AD) are heterogeneous and the diagnosis can be a challenge. A new biologic drug (dupilumab) has been approved for moderate to severe AD in adult patients. The efficacy and safety have been demonstrated in clinical trials, but these studies do not reflect conditions in daily practice and do not consider the different clinical manifestations of AD. Objectives: Analyzing the dupilumab activity in a real-world setting and comparing its efficacy on different AD phenotypes. Methods: We retrospectively evaluated 221 AD patients treated with dupilumab, stratified into six clinical phenotypes: classic, generalized eczema inflammatory and lichenoid patterns, prurigo, nummular eczema, and erythroderma. At baseline and at weeks 4, 16, and 52, the disease severity was assessed through the Eczema Area and Severity Index (EASI) and the quality of life was assessed through the Dermatology Life Quality Index (DLQI) questionnaire, Peak Pruritus Numerical Rating Scale (itch NRS), and Peak Sleep NRS. Results: We found a significant improvement after 16 weeks of treatment (p < 0.0001) in all six phenotypes for all the assessed scores mentioned above, persisting up to week 52. The best improvement was seen in the more severe phenotypes, particularly the erythrodermic one. Conclusions: The present study confirmed the efficacy and safety of dupilumab in the treatment of severe AD. Its strength was in the stratification of AD patients in six different phenotypes based on their clinical presentation, all of whom markedly improved in terms of both clinically evident and reported symptoms, as well as their quality of life.

Smoking and risk of adult-onset atopic dermatitis in US women

To the Editor: Atopic dermatitis (AD) is common in adults, but few studies have examined risk factors for adult-onset AD.1Lee H.H. Patel K.R. Singam V. Rastogi S. Silverberg J.I. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis.J Am Acad Dermatol. 2019; 80: 1526-1532Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar Cross-sectional and case-control studies suggest that smoking is associated with AD, but there is insufficient data on the temporality of the association.2Kantor R. Kim A. Thyssen J.P. Silverberg J.I. Association of atopic dermatitis with smoking: a systematic review and meta-analysis.J Am Acad Dermatol. 2016; 75: 1119-1125Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar, 3Lee C.H. Chuang H.Y. Hong C.H. et al.Lifetime exposure to cigarette smoking and the development of adult-onset atopic dermatitis.Br J Dermatol. 2011; 164: 483-489PubMed Google Scholar, 4Kim S.Y. Sim S. Choi H.G. Atopic dermatitis is associated with active and passive cigarette smoking in adolescents.PLoS One. 2017; 12: e1087453Crossref Scopus (15) Google Scholar In this study, we examined the association between smoking and risk of incident AD in adult women in the Nurses' Health Study II cohort. Smoking status and AD were assessed by self-report. In 1989, participants were asked about their lifetime history of 20 or more packs of cigarettes. Smoking status (never, past, or current) was updated biennially. AD was assessed by self-report in 2013. Participants were asked if they ever received a diagnosis of “eczema (atopic dermatitis)” by a clinician and what year this occurred. In 2017, participants who reported a diagnosis of AD were sent a questionnaire to reaffirm their self-report. We excluded prevalent cases of AD at baseline (1995; n = 4575) and participants who had an unknown diagnosis date or reported having AD but did not confirm their report in 2017 (n = 42).5Drucker A.M. Cho E. Li W.Q. Camargo Jr., C.A. Li T. Qureshi A.A. Diagnosis validation and clinical characterization of atopic dermatitis in Nurses' Health Study 2.J Eur Acad Dermatol Venereol. 2019; 33: 588-594Crossref PubMed Scopus (8) Google Scholar We calculated person-years from the return date of the 1995 questionnaire to the first of the AD diagnosis date or the end of follow-up (June 2013). We used Cox proportional hazards models to calculate age- and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between smoking and AD. Covariates included age, race (white vs nonwhite), body mass index (kg/m2), physical activity (metabolic equivalent of task hours/week in quintiles), alcohol intake, asthma, and hay fever. All statistical tests were 2 tailed, and the significance level was set at P < .05. We used SAS, version 9.4 (SAS Institute, Inc, Cary, NC). We included 76,701 women in the analysis. Baseline characteristics of the participants according to smoking status are presented in Table I. Overall, 7,497 (9.8%) participants were current smokers, 17,847 (23.2%) were past smokers, and 51,357 (66.8%) had never smoked. During 1,357,932 person-years of follow-up, we identified 463 incident cases of AD. In our multivariable analysis, neither current (HR, 1.21; 95% CI, 0.86-1.68) nor past smoking (HR, 1.02; 95% CI, 0.82-1.26) were significantly associated with AD compared to never smoking (Table II). Among current smokers, there was no apparent dose-response relationship for the number of cigarettes smoked daily, neither smoking 1 to 14 (HR, 1.25; 95% CI, 0.81-1.94) nor 15 or more (HR, 1.15; 95% CI, 0.72-1.86) cigarettes daily was associated with AD. Among current smokers, risk for AD may have been slightly higher with 25 or more pack-years (HR, 1.25; 95% CI, 0.77-2.01) compared to less than 25 pack-years (HR, 1.18; 95% CI, 0.76-1.82) when both were compared to never smokers. We found no significant interaction between smoking and asthma on risk of AD (P = .45).Table IAge-standardized characteristics of study participants by smoking status in 1995: The Nurses' Health Study II∗Values are standardized to the age distribution of the study population.CharacteristicsSmoking statusNever (n = 51,357)Past (n = 17,847)Current (n = 7497)Age,†Values are not age adjusted. y, mean (SD)40.0 (4.7)41.2 (4.5)40.8 (4.5)Pack-years, mean (SD)0.0 (0.0)9.3 (7.3)18.6 (10.5)White, %94.897.497.1Body mass index, kg/m2, mean (SD)25.6 (5.8)25.8 (5.8)25.4 (5.4)Physical activity, metabolic equivalent hours/week, mean (SD)20.5 (26.3)22.2 (28.6)19.8 (27.6)Alcohol intake, g/day, mean (SD)2.7 (5.3)4.9 (7.9)5.6 (9.4)Personal history of asthma, %8.69.57.1Personal history of hay fever, %23.824.520.5SD, Standard deviation.∗ Values are standardized to the age distribution of the study population.† Values are not age adjusted. Open table in a new tab Table IIAge- and multivariable-adjusted HRs for atopic dermatitis by current cigarettes consumed daily, age at smoking initiation, and pack-years in the Nurses' Health Study II (1995-2013)Exposure variablesCase numberPerson-yearsAge-adjustedMultivariable, adjusted∗Adjusted for age (continuous variable), race (non-Hispanic white, African American, Asian, or other race), alcohol drinking (none, <4.9, 5.0-9.9, 10-14.9, 15-29.9, or ≥30.0 g/day), body mass index (continuous variable), physical activity (metabolic equivalent hours/week in quintiles), personal history of asthma, and personal history of hay fever.HR95% CIHR95% CISmoking status Never smoked301904,1221.00Referent1.00Referent Past smoker122349,3101.060.86-1.311.020.82-1.26 Current smoker40104,5001.210.87-1.681.210.86-1.68 Current smoker, 1-14 cigarettes daily2254,7681.260.82-1.951.250.81-1.94 Current smoker, 15+ cigarettes daily1849,1451.150.71-1.851.150.72-1.86Age, y, at smoking initiation Never smoked301904,1221.00Referent1.00Referent Ever smoked, initiated at ≤19105306,2881.040.84-1.310.900.66-1.23 Ever smoked, initiated at 20+55139,0231.240.93-1.661.130.81-1.57Smoking status, pack-years Never smoked301904,1221.00Referent1.00Referent Past, <1060190,7990.950.72-1.260.920.69-1.22 Past, 10-1944106,4781.270.92-1.741.210.88-1.67 Past, 20+1852,0331.050.65-1.691.000.62-1.63 Current, <252258,9561.190.77-1.841.180.76-1.82 Current, 25+1845,5451.240.77-1.991.250.77-2.01CI, Confidence interval; HR, hazard ratio.∗ Adjusted for age (continuous variable), race (non-Hispanic white, African American, Asian, or other race), alcohol drinking (none, <4.9, 5.0-9.9, 10-14.9, 15-29.9, or ≥30.0 g/day), body mass index (continuous variable), physical activity (metabolic equivalent hours/week in quintiles), personal history of asthma, and personal history of hay fever. Open table in a new tab SD, Standard deviation. CI, Confidence interval; HR, hazard ratio. In this large cohort of US women, we did not find a significant association between current smoking and incident AD. The positive direction of the association was consistent with previous observational studies. Our findings were imprecise, and future cohort studies in different populations are warranted.

Adult-Onset Atopic Dermatitis: Presentations and Progress.

Atopic dermatitis (AD) is a chronic skin disease characterized by barrier dysfunction and immune dysregulation that affects approximately 20% of children and 2-5% of adults worldwide. Traditionally, AD has been considered a disease of childhood with many cases resolving before adulthood. However, in recent years, the prevalence of adult AD is increasingly recognized to be substantial, but it is uncertain whether this increase is due to increased childhood-persistent or relapsed AD, or new adult-onset AD. This highlights a need for further investigation into the adult AD population and evaluation of phenotypes in the adult-onset cohort. In this literature review, we examine five studies focused on adult-onset AD phenotype, conducted between 2013 and 2017. The most commonly reported body regions affected in adult-onset AD were the hands, eyelids, neck, and flexural surfaces of the upper limbs. These vary from childhood-onset AD findings, which are less specific to body regions other than flexural areas. These findings have implications for diagnostic accuracy and treatment of AD, including considerations for therapeutic choices and inclusion and exclusion criteria in clinical trials.

Severe adult-onset atopic dermatitis mistaken for cutaneous T-cell lymphoma in a medically complex patient

A 45-year-old previously healthy man presented to the hospital with acute left foot pain with numbness, coldness, blue discoloration, a blackened third toe and chills for 4 days. Over the...