Atopic Dermatitis Disease Complications.

This chapter will describe infectious complications of atopic dermatitis, including bacterial, viral, and fungal infections and the evolving understanding of the relationship between atopic dermatitis and infectious disease. The underlying immunological dysregulation and poor skin barrier function associated with atopic dermatitis not only increase the likelihood of infectious complications but also lend atopic dermatitis skin vulnerable to flares induced by environmental triggers. Thus, this chapter will also highlight the impact of common external environmental agents on precipitating flares of disease. Lastly, this chapter will discuss complications that can arise from treatments and the association of atopic dermatitis with more serious conditions such as lymphoma.

Association between Outdoor and Indoor Air Pollution Sources and Atopic Eczema among Preschool Children in South Africa.

The objective of the study was to investigate the association between outdoor and indoor air pollution sources and atopic eczema among preschool children in South Africa. A cross-sectional design, following the International Study of Asthma and Allergies in Childhood (ISAAC) Phase III protocol, was applied. The study was conducted in Mabopane and Soshanguve Townships in the City of Tshwane Metropolitan Municipality in Gauteng, South Africa. A total population of 1844 preschool children aged 7 years and below participated in the study; 1840 were included in the final data analysis. Data were analyzed using multilevel logistic regression analysis. The prevalence of eczema ever (EE) and current eczema symptoms (ESs) was 11.9% and 13.3%, respectively. The use of open fires (paraffin, wood, or coal) for cooking and heating increased the likelihood of EE (OR = 1.63; 95% CI: 0.76-3.52) and current ESs (OR = 1.94; 95% CI: 1.00-3.74). Environmental tobacco smoke (ETS) exposure at home increased the likelihood of EE (OR = 1.66; 95% CI: 1.08-2.55) and current ESs (OR = 1.61; 95% CI: 1.07-2.43). Mothers or female guardians smoking cigarettes increased the likelihood of EE (OR = 1.50; 95% CI: 0.86-2.62) and current ESs (OR = 1.23; 95% CI: 0.71-2.13). The use of combined building materials in homes increased the likelihood of EE, and corrugated iron significantly increased the likelihood of current ESs. The frequency of trucks passing near the preschool children's residences on weekdays was found to be associated with EE and current ESs, with a significant association observed when trucks passed the children's residences almost all day on weekdays. Atopic eczema was positively associated with exposure to outdoor and indoor air pollution sources.

Smoke exposure and childhood atopic eczema and food allergy: A systematic review and meta-analysis.

BACKGROUND: There is no consensus on the effect of timing and type of smoke exposure on early allergy development. This study aimed to determine the relationship between early eczema or food allergy/hypersensitivity development in children by firstly investigating the effect of smoke exposure across critical development periods and secondly by analyzing effects of parental atcive or passive smoking. METHODS: Four databases (PubMed, Web of Science, Scopus and Embase) were searched in May 2022 and assessed by two independent reviewers. Case-control, cross-sectional or cohort studies reporting on smoke exposure from preconception to postnatal periods and atopic eczema, food allergy and/or hypersensitivity outcomes by age 3 years were included. The Newcastle-Ottawa Scale was used to assess study quality. Random effects model was used to estimate the pooled risk ratios. RESULTS: From 1689 identified records, 32 studies with nearly 190,000 subjects were included. Parental smoking during preconception, pregnancy and postnatal periods was generally not associated with the risk of eczema, food allergy and food sensitisation development by age 3 years. Maternal active smoking during pregnancy was negatively associated with self-reported doctor diagnosis of eczema (RR = 0.87, 95% CI 0.77-0.98; I2 = 50.56) and maternal passive smoking during pregnancy was positively associated with clinician assessment of eczema in one study (RR = 1.38; 95% CI 1.06-1.79). CONCLUSION: Our findings highlighted the importance of in utero programming in early-life allergy development. Despite the weak evidence, our results suggest pregnant women should minimise their contact with second-hand smoke to prevent offspring eczema development. There is a need for greater utilisation of objective allergy assessments in future studies.

Narrowband-ultraviolet B vs Broadband-ultraviolet B in Treatment of Chronic Pruritus: A Randomized, Single-blinded, Non-inferiority Study.

Narrowband-ultraviolet B has shown increased efficacy over broadband-ultraviolet B in pruritic skin diseases, such as psoriasis and atopic dermatitis. In patients with chronic pruritus, e.g. in end-stage renal disease, broadband-ultraviolet B is recommended, but narrowband-ultraviolet B has also shown efficacy in reducing pruritus. This randomized, single blinded, non-inferiority study investigated the effects of narrowband-ultraviolet B compared with broadband-ultraviolet B. Patients with chronic pruritus were treated with either broadband- or narrowband-UVB 3 times a week for 6 weeks and clinical response was monitored. Pruritus, sleep disturbance, and the patients' subjective overall response to treatment were evaluated by the patients on a visual analogue scale (0-10). Skin excoriations were evaluated by investigators on a 4-point scale (0-3). Both phototherapeutic modalities showed significant antipruritic activity (itch reduction 48% and 66.4%, respectively) by broadband-ultraviolet B and narrowband-ultraviolet B. Narrowband-ultraviolet B proved to be not inferior to broadband-ultraviolet B in treating pruritus in patients with chronic pruritus, assuming a 20% non-inferiority margin.

The Impact of Air Pollution on Atopic Dermatitis.

PURPOSE OF REVIEW: Atopic dermatitis (AD) remains a dermatological disease that imposes a significant burden on society. Air pollution has previously been linked to both the onset and severity of atopic dermatitis. As air pollution remains a critical environmental factor impacting human health, this review seeks to provide an overview of the relationship between different air pollutants and AD. RECENT FINDINGS: AD can develop from multiple causes that can be broadly grouped into epidermal barrier dysfunction and immune dysregulation. Air pollution imposes significant health risks and includes a wide variety of pollutant types. AD has been linked to outdoor air pollutants such as particulate matter (PM), volatile organic compounds (VOC), gaseous compounds, and heavy metals. Exposure to indoor pollutants such as tobacco smoke and fungal molds has also been associated with an increased incidence of AD. While different pollutants impact distinct molecular pathways in the cell, they mostly converge on ROS product, DNA damage, and dysregulated T-cell activity and cytokine production. The presented review suggests a strengthening tie between air pollution and AD. It points to opportunities for further studies to clarify, as well as potential therapeutic opportunities that leverage the mechanistic relationships between air pollution and AD.

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

BACKGROUND: 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. METHODS: 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)). RESULTS: 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. CONCLUSIONS: 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.

Nurturing Infants to Prevent Atopic Dermatitis and Food Allergies: A Longitudinal Study.

BACKGROUND: Atopic dermatitis (AD) at a young age often precedes the development of food allergies. Although AD affects millions of infants worldwide, prenatal and postnatal risk factors, and their association with the development of food allergies later on, are not fully elucidated. This study seeks to investigate AD epidemiology in infancy and its risk factors, examining early-life factors (both prenatal and postnatal) that could contribute to the later development of food allergies. METHODS: Between January 2019 and December 2019, 501 infants were included in this prospective cohort study. Longitudinal data collection was performed through maternal interviews, the first one conducted within three days after the delivery and the second within 24 to 36 months after the delivery, encompassing variables such as demographics, family history of atopy, maternal smoking, antibiotic use during pregnancy, the mode of delivery, breastfeeding history, food practices, and greenness exposure within 3 days from delivery, while they were still in the hospital. RESULTS: Maternal smoking during pregnancy (p = 0.001) and an older sibling atopy history (p = 0.03) was significantly linked to AD incidence. Cesarean section delivery (p = 0.04) was associated with a higher risk of food allergies in infants with AD. Having a garden at home correlated with a higher likelihood of AD (p = 0.01), and food elimination without medical guidance (p = 0.02) due to AD correlated with an elevated risk of food allergies. CONCLUSIONS: Encouraging timely allergenic food introduction while promoting dietary diversity, rich in plant-based foods, maternal smoking cessation, and professional dietary guidance may help minimize AD and food allergy risk. Future studies should address the role of greenness in the development of AD and food allergies.

Predictors of adherence to Narrowband ultraviolet B first-month treatment dosage plan.

BACKGROUND: The adherence to a narrowband ultraviolet B (NB-UVB) treatment plan is derived, in large part, from the patient's skin tolerance to the phototherapy dose. At present, the initial and first-month incremental phototherapy doses are determined prior to treatment initiation based on the patient's Fitzpatrick skin phototyping. OBJECTIVES: To identify variables that predict adherence to NB-UVB first-month treatment dosage plan. METHODS: Charts of 1000 consecutive patients receiving NB-UVB at a hospital-based phototherapy unit were retrospectively analyzed. We included patients receiving NB-UVB for atopic dermatitis, psoriasis, vitiligo, and mycosis fungoides. The first-month NB-UVB treatment plan was determined based on the patient's Fitzpatrick phototype. Adherence to treatment was defined as receiving at least 80% of the planned first-month cumulative dose. We compared adherent vs. non-adherent patient groups for age, sex, Fitzpatrick phototype, presence of freckles, nevus count category, and type of dermatological disease. RESULTS: The study included 817 eligible patients, mean age 40 (2-95) years; 54% men; 32% had Fitzpatrick phototype I-II. Distribution by diagnosis was atopic dermatitis (29%), psoriasis (27%), vitiligo (23%), and mycosis fungoides (21%). Adherence to NB-UVB treatment plan was observed in 71% of patients. Adherence decreased with age, with 7% decrease per year (P = 0.03) and was higher among mycosis fungoides patients (77.3%) compared to all other diagnoses (69.8%; P = 0.02). CONCLUSIONS: Adherence to NB-UVB treatment may be related to age and diagnosis. Fitzpatrick phototype-based first-month treatment plans should be modified accordingly.

Factors associated with allergy traits around the 2nd year of life: a brazilian cohort study.

BACKGROUND: Allergic status has been strongly influenced by early exposures; however, allergic diseases are hard to measure in early life. Thus, this study proposed a latent variable allergy traits around the second year of life and analyzed pre- and perinatal factors associated with this phenomenon. METHODS: The study used data from the BRISA birth cohort, Ribeirão Preto, Brazil (n = 3644). The theoretical model included: family allergy (history of allergic rhinitis, atopic dermatitis, and asthma); gestational period variables (socioeconomic status, mother's skin color, pregestational body mass index - BMI, smoking, gestational diabetes, and hypertension); birth variables (gestational age, 5-minute Apgar score, birth weight, type of delivery), and early life factor (exclusive breast feeding). The outcome was allergy traits around the 2nd year of life, a latent variable deduced from the shared variance among medical diagnosis of allergic rhinitis, atopic dermatitis, and food allergy. The model was analyzed by structural equation modeling. RESULTS: Higher socioeconomic status (SC = 0.256; p < 0.001) and higher family allergy values (SC = 1.224; p < 0.001) were associated with higher allergy trait values. Hypertension during pregnancy was associated with higher values (SC = 0.170; p = 0.022) and exclusive breast feeding (SC = -0.192; p < 0.001) with low allergy trait values. CONCLUSION: Although socioeconomic and environmental factors were associated with allergy traits around the 2nd year of life, the family component of allergy was the exposure that best explained this outcome.

Synergistic Effects between Ambient Air Pollution and Second-Hand Smoke on Inflammatory Skin Diseases in Chinese Adolescents.

Atopic dermatitis (AD), chronic hand eczema (CHE), and urticaria are common inflammatory skin diseases among adolescents and associated with air quality. However, the synergistic effects of ambient air pollution and second-hand smoke (SHS) have been unclear. We conducted a cross-sectional study including 20,138 Chinese college students where dermatological examinations and a questionnaire survey were carried out. A generalized linear mixed model was applied for the association between individualized exposure of O3, CO, NO2, SO2, PM2.5, and PM10 and the prevalence of inflammatory skin diseases. Interactions between air pollutants and SHS were analyzed. As a result, CO, NO2, SO2, PM2.5, and PM10 were positively correlated with the prevalence of AD, CHE, and urticaria. Higher frequency of SHS exposure contributed to increased probabilities of AD (p = 0.042), CHE (p < 0.001), and urticaria (p = 0.002). Of note, CO (OR: 2.57 (1.16−5.69) in third quartile) and NO2 (OR: 2.38 (1.07−5.27) in third quartile) had positive interactions with SHS for AD, and PM2.5 synergized with SHS for CHE (OR: 2.25 (1.22−4.15) for second quartile). Subgroup analyses agreed with the synergistic results. In conclusion, SHS and ambient air pollution are both associated with inflammatory skin diseases, and they have a synergistic effect on the prevalence of AD and CHE.

Risk factors of hand eczema: A population-based study among 900 subjects.

BACKGROUND: Many risk factors such as atopic dermatitis (AD) have shown to associate with hand eczema (HE). However, studies concerning other atopic diseases, parental or longitudinal risk factors of HE are scarce. OBJECTIVES: To examine the association between HE and atopic diseases, parental factors, environmental factors (keeping animals, exposure to moulds) and lifestyle factors (obesity, tobacco smoking, alcohol consumption and physical activity) at population level. METHODS: Subjects belonging to the Northern Finland Birth Cohort 1966 Study (NFBC1966) (n = 6830) answered a comprehensive health questionnaire. The data was completed with parental information. RESULTS: HE was reported in 900 (13.3%) individuals. All atopic diseases, parental allergy, female gender and obesity increased the risk of HE whereas physical activity decreased the risk of HE. A statistically significant association was not found between HE and tobacco smoking or alcohol consumption. CONCLUSIONS: All atopic diseases, not only AD, seem to have influence on the presence of HE. In addition, parental and environmental factors associated with HE.

Long-Term Narrowband UV-B Efficacy in Moderate to Severe Atopic Dermatitis.

BACKGROUND: Narrowband (NB) UV-B is known as an effective and safe treatment for atopic dermatitis (AD). However, there is a lack of studies regarding prognostic factors for favorable response and its duration. OBJECTIVE: The aim of the study was to evaluate the efficacy of NB-UV-B for AD, in a large cohort and "real-life" setting. METHODS: This is a retrospective cohort study based on the medical records of patients with moderate to severe AD treated with NB-UV-B therapy between 2000 and 2017 with a long-term follow-up (≥3 years) after completing therapy. RESULTS: A total of 390 of 555 AD patients who were scheduled for NB-UV-B were included; among them, 55.4% responded well to treatment. Facial involvement, presence of adverse effects, lower number of treatments, and pretreatment immunoglobulin E levels greater than 4000 were related to poorer response. There was an overall median response duration of 12 months with a greater relapse rate among the patients younger than 18 years. CONCLUSIONS: Narrowband UV-B phototherapy shows high and long-lasting efficacy in AD. Patients with facial involvement and patients with high immunoglobulin E levels respond less to treatment. Response duration seems to be shorter for patients younger than 18 years.

Indigo Pulverata Levis (Chung-Dae, Persicaria tinctoria) Alleviates Atopic Dermatitis-like Inflammatory Responses In Vivo and In Vitro.

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with a type 2 T helper cell (Th2) immune response. The IndigoPulverata Levis extract (CHD) is used in traditional Southeast Asian medicine; however, its beneficial effects on AD remain uninvestigated. Therefore, we investigated the therapeutic effects of CHD in 2,4-dinitrochlorobenzene (DNCB)-induced BALB/c mice and tumor necrosis factor (TNF)-α- and interferon gamma (IFN)-γ-stimulated HaCaT cells. We evaluated immune cell infiltration, skin thickness, and the serum IgE and TNF-α levels in DNCB-induced AD mice. Moreover, we measured the expression levels of pro-inflammatory cytokines, mitogen-activated protein kinase (MAPK), and the nuclear factor-kappa B (NF-κB) in the mice dorsal skin. We also studied the effect of CHD on the translocation of NF-κB p65 and inflammatory chemokines in HaCaT cells. Our in vivo results revealed that CHD reduced the dermis and epidermis thicknesses and inhibited immune cell infiltration. Furthermore, it suppressed the proinflammatory cytokine expression and MAPK and NF-κB phosphorylations in the skin tissue and decreased serum IgE and TNF-α levels. In vitro results indicated that CHD downregulated inflammatory chemokines and blocked NF-κB p65 translocation. Thus, we deduced that CHD is a potential drug candidate for AD treatment.

Associations of particulate matter with atopic dermatitis and chronic inflammatory skin diseases in South Korea.

BACKGROUND: Particulate matter (PM) is a mixture of solid and liquid particles suspended in air, which originates from industrial plants or vehicle emissions. Although the skin is the primary body area of contact with air pollutants, the associations between PM and chronic inflammatory skin diseases has not been well established. AIM: To investigate associations between PM and atopic dermatitis (AD) and between PM and other chronic inflammatory dermatoses, using data from the Korean Health Insurance Review and Assessment Service. METHODS: Monthly disease statistics from the seven largest cities in South Korea (Seoul, Busan, Daegu, Incheon, Gwangju, Daejeon, Ulsan) and from Jeju Island (in total, a population of 23 288 000 for all eight areas) were included. Based on daily air pollution level and weather forecast from 2015 to 2019, multivariate negative binomial regression analysis was conducted to estimate monthly visits of AD with respect to outdoor air pollutants: coarse PM with a diameter of ≤ 10 µm (PM10) and fine PM with a diameter of ≤ 2.5 µm (PM2.5) ozone (O3 ), nitrogen dioxide (NO2 ), sulphur dioxide (SO2 ) and carbon monoxide (CO). RESULTS: Increases in the levels of PM2.5, PM10, SO2 and CO were associated with significant increases in monthly patient visits for AD. Every 10 µg/m3 increase in PM2.5 and PM10 resulted in patient visit increases of 2.71% (95% CI 0.76-4.71; P < 0.01) and 2.01% (95% CI 0.92-3.11, P < 0.001), respectively, while every 1 part per billion (ppb) increase in SO2 and every 100 ppb increase in CO resulted in visit increases of 2.26% (95% CI 1.35-3.17; P < 0.001) and 2.86% (95% CI 1.35-4.40; P < 0.001), respectively. O3 and NO2 were not associated with increased patient visits for AD. Increases in PM2.5 and PM10 concentrations were also significantly associated with increases in patient visits for psoriasis, seborrhoeic dermatitis and rosacea. CONCLUSION: Our data suggest that PM is associated with AD and other chronic inflammatory skin diseases.

Does antioxidant-rich diet during pregnancy protect against atopic multimorbidity in children?

BACKGROUND: Genetics and prenatal environmental exposures are indicated in the complex etiopathogenesis and clinical expression of atopic diseases. This study examined the clinical features of infantile-onset atopic dermatitis (AD) in relation to maternal diet during pregnancy. METHODS: Maternal dietary habits were evaluated in terms of the frequency of intake of six different food categories rich in antioxidants or omega-3 fatty acids. RESULTS: One hundred mother-child pairs were recruited, 47 infants (<12 months) and 53 children aged 12-36 months. Forty-six of the children had mild, 41 moderate and 13 severe AD. The other atopic manifestations (alone or associated) included: asthma in 9 cases, allergic rhinitis in 22 cases and food allergy in 33 cases. The presence of asthma in children was significantly associated with a lower level of maternal dietary intake of fruits and vegetables as well as chocolate confectionery, while associations with whole grain breakfast cereals, nuts and seeds, non-alcoholic beverages (coffee, tea, fruit juices) and fish and fish products, were not statistically significant. The age of onset and severity of infantile-onset AD were not linked to any of the food categories considered for analyses. CONCLUSIONS: Healthy diet in pregnant women that is rich especially in antioxidants may provide protection against atopic comorbidities of AD. Further prospective reasearch on the role of maternal diet in primary prevention of atopic diseases is warranted.

Inhibitory Effects of Luteolin 7-Methyl Ether Isolated from Wikstroemia ganpi on Tnf-A/Ifn-Γ Mixture-Induced Inflammation in Human Keratinocyte.

Plants of the genus Wikstroemia are traditionally used in China to treat various inflammatory diseases. The purpose of this study was to isolate the components of Wikstroemia ganpi (Siebold & Zucc.) Maxim., to evaluate their anti-atopic activities and to identify candidates with anti-atopic therapeutics. A total of 24 compounds were isolated by bioassay-guided separation, including one novel compound, which was tilianin 5-methyl ether. The anti-atopic activities of the isolated compounds were determined using TNF-α-treated RBL-2H3 cells and HaCaT cells. The mRNA expressions of IL-4, IL-6, GM-CSF, G-CSF and TRPV1 were reduced by luteolin 7-methyl ether. The study shows that the luteolin 7-methyl ether isolated from W. ganpi is a potential therapeutic agent for the treatment of atopic dermatitis.

Angiogenesis in Chronic Inflammatory Skin Disorders.

Angiogenesis, the growth of new blood vessels from preexisting vessels, is associated with inflammation in various pathological conditions. Well-known angiogenetic factors include vascular endothelial growth factor (VEGF), angiopoietins, platelet-derived growth factor, transforming growth factor-ß, and basic fibroblast growth factor. Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) have recently been added to an important angiogenic factor. Accumulating evidence indicates associations between angiogenesis and chronic inflammatory skin diseases. Angiogenesis is deeply involved in the pathogenesis of psoriasis. VEGF, angiopoietins, tumor necrosis factor-a, interleukin-8, and interleukin-17 are unregulated in psoriasis and induce angiogenesis. Angiogenesis may be involved in the pathogenesis of atopic dermatitis, and in particular, mast cells are a major source of VEGF expression. Angiogenesis is an essential process in rosacea, which is induced by LL-37 from a signal cascade by microorganisms, VEGF, and MMP-3 from mast cells. In addition, angiogenesis by increased VEGF has been reported in chronic urticaria and hidradenitis suppurativa. The finding that VEGF is expressed in inflammatory skin lesions indicates that inhibition of angiogenesis is a useful strategy for treatment of chronic, inflammatory skin disorders.