Atopic Triad Research Articles

Risk factors and temporal associations of progression of the atopic march in children with early-onset atopic dermatitis

BackgroundRisk factors and the temporal relationship between atopic dermatitis (AD) and atopic march remain understudied. ObjectiveDetermine risk factors for atopic march in early-onset AD patients and the temporality between AD and atopic march. MethodsWe used the MarketScan Research Database for our retrospective cohort analysis from 2010-2018, comparing infants diagnosed with AD before age 1 with controls without early-onset AD. Primary outcomes were hazard ratios (HR) for development of asthma, allergic rhinitis and food allergy. ResultsCompared to 55,174 controls, higher proportions of the 27,228 AD patients developed asthma (19.21% vs 8.65%, p<0.001), allergic rhinitis (28.27% vs 12.62%, p<0.001), food allergy (16.00% vs 2.27%, p<0.001), and all atopic triad conditions (10.69% vs 0.71%, p<0.001). Among AD patients, higher proportions developed the atopic triad if they were male (HR 1.66, 95% confidence interval [1.45-1.90]), had severe disease (HR 3.16, [2.77-3.60]), or had family atopy history (HR>3.40, p<0.001 for all comparisons). Among AD patients, 20.1% developed allergic rhinitis. LimitationsOur study was based on health care claims data. ConclusionEarly-onset AD is associated with higher rates of developing atopic march conditions compared to controls. Particular attention should be paid towards risk factors and atopic march screening in early-onset AD patients.

54621 Applying Mendelian randomization to infer causality within the atopic triad

54621 Applying Mendelian randomization to infer causality within the atopic triad

Association Between Three Atopic Triad and Retinal Vein Occlusion Risk: A Nationwide Population-Based Study

ABSTRACT Purpose To evaluate the association between three allergic diseases (allergic dermatitis, allergic rhinitis, and asthma) and the development of retinal vein occlusion (RVO), a major retinal disease that causes visual impairment. Method This study used data obtained from the Korean National Health Insurance Claims database between 2009 and 2018. The association between the three atopic triads (allergic dermatitis, allergic rhinitis, and asthma) and the occurrence of sight-threatening RVO, as determined by diagnostic and treatment codes, were analyzed. Multivariate adjusted Cox regression analysis was used to determine the hazard ratios (HRs) and 95% confidence intervals for RVO development in the presence of allergic disease. Results In this population-based study, 2,160,195 (54.6%) individuals were male, 1,794,968 (45.4%) were female, and 620,938 (15.7%) were diagnosed with allergic diseases. Patients with either asthma or allergic rhinitis had a greater risk of RVO (adjusted hazard ratio (aHR) = 1.101, 95% confidence interval [CI] = 1.029–1.178 for asthma; aHR = 1.181, 95% CI = 1.147–1.215 for allergic rhinitis) compared to those without asthma or allergic rhinitis; however, patients with atopic dermatitis did not show a significant association with RVO (aHR = 1.071, 95% CI = 0.889–1.290), after adjusting for other risk factors. Conclusion Our study revealed that allergic rhinitis, asthma, and coexisting multiple allergic conditions were associated with an increased risk of RVO. Thus, it may be advisable to suggest an ophthalmological examination for patients with allergies due to the increased possibility of the occurrence of retinal vascular disease.

Evaluating the Impact of Perinatal Depression on Fetal and Childhood Development

Perinatal maternal depression leads to a variety of biochemical and behavioral changes in utero. These alterations are linked to impaired fetal development and may also be detrimental to future neonatal, pediatric, and adolescent health. There is a marked rise in the incidence of atopic triad conditions, such as dermatitis and asthmatic wheezing, in children of pregnant mothers with antepartum depression, possibly due to an aberrant TH2 immunologic response and increased fetal oxidative stress. Maternal antepartum depression may also contribute to small-for-gestational age birth status, anomalous fetal neurotransmitter levels, and depression throughout infancy and adolescence. Cortisol has been implicated as a common causative factor responsible for many of these negative offspring outcomes. Minimal research on untreated major depression in pregnancy has been conducted. However, current studies emphasize the importance of holistically evaluating the risks associated with untreated major depression in pregnancy in order to minimize harmful effects on children.

Comparative characteristics of the nasal mucosa microflora at different level of allergic inflammation in the respiratory tract

In the modern world, allergic respiratory diseases hold a huge place among all chronic diseases. The annual increase in the prevalence of allergic rhinitis and bronchial asthma among the global population makes relevant studies underlying their pathogenesis. Changes in the nasal mucosa alter its most important function protection from aggressive environmental factors allergens and pollutants. Inflammatory processes in the nasal cavity interfere with the normal mucosa functioning as a non-specific barrier, and facilitate their further penetration into the macroorganism. Objective of the study is to provide a comparative microbiological characteristic of the nasal mucosa of patients with respiratory allergies of various origin and level of respiratory tract damage. Patients with respiratory allergies aged 23 to 51 years old as well as sex- and age-matched apparently healthy subjects (n = 120) were examined. The study groups were as follows: atopic rhinosinusitis (AR, n = 28), atopic bronchial asthma (ABA, n = 28), polyposis rhinosinusitis (PRS, n = 68), and asthmatic triad (AT, n = 28). Diagnostics were carried out by an allergist-immunologist as well as an otorhinolaryngologist. Isolation of microorganisms was carried out by placing them on nutrient differential diagnostic media. Seeding was carried out by using the sector method. The culture media were incubated in a thermostat at 37C for 48 hours. Statistical processing was performed using the Statistica 7.0 software package. The study sample is described by calculating median as well as 25 and 75 percentiles. The normality distribution was checked by using the KolmogorovSmirnov method. The significance of differences between parameters of independent samples was assessed by using the nonparametric MannWhitney test. Dominance of opportunistic microorganisms in respiratory atopy (AR, ABA) relative to respiratory pseudoatopia (PRS, AT) was noted. The increased number of bacteria from the family Enterobacteriaceae and Enterococcus on the nasal mucosa characterizes dysbacteriosis, emphasizing the greatest importance of these families in the initiation of allergic pathology in the upper and lower respiratory tract during atopy. A distinctive intergroup feature is a high concentration of the Enterobacteriaceae family members in AR vs. PRS as well as microorganisms of the genus Enterococcus in ABA vs. AT. Thus, regardless of the cause of inflammation, allergic rhinosinusitis and bronchial asthma were featured with a pronounced dysbacteriosis due to rise in the opportunistic microflora on the nasal mucosa compared to the control group.

Epidemiology of alopecia areata in Black patients: A retrospective chart review

Epidemiology of alopecia areata in Black patients: A retrospective chart review

The association between urinary polycyclic aromatic hydrocarbon metabolites and atopic triad by age and body weight in the US population

Background Polycyclic aromatic hydrocarbons (PAHs) are generated during the incomplete combustion of coal/oil/gas and waste. The role of PAH exposure in the atopic triad remains poorly understood. Due to their lipophilic nature, PAHs deposit in adipocytes, potentially placing elderly and those who are overweight at higher risk. Objective To investigate the association between urinary PAHs and symptoms of atopic triad (chronic pruritus, sneezing, and wheezing). Methods Binary multivariable logistic regression was performed to estimate the association of nine urinary PAHs and atopic diseases followed by subgroup analyses by age (children 6–17, adults 18–49, elderly ≥50 years) and body mass index (BMI) (normal: BMI <25, overweight: BMI ≥ 25 kg/m2) among 2,242 participants of National Health and Nutrition Examination Survey 2005–2006 dataset. Results 1-hydroxynaphthalene (1-NAP) and hydroxyfluorenes (FLUs) were positively associated with wheezing. When stratified by age, positive associations were found between 1-NAP with wheezing in children/adults and 2-/3-FLU with wheezing in adults/elderly. 3-hydroxyphenanthrene (3-PHE) and 1-hydroxypyrene were positively associated with chronic pruritus in elderly. When stratified by BMI, positive associations were found between 2-PHE with chronic pruritus, 1-NAP and FLUs with wheezing in overweight. Conclusion Urinary PAH levels were positively associated with atopic triad and this connection was influenced by age and BMI.

28247 Pediatric hospitalizations for atopic dermatitis in the USA: Predictors for developing the atopic triad

Atopic dermatitis (AD) is one of the most common skin disorders in pediatric patients, with a prevalence of up to 18% in the US. It can lead to a greater risk of developing asthma and allergic rhinitis; when combined, these constitute the “atopic triad.” This study sought to characterize US pediatric patients hospitalized with a primary diagnosis of AD or Eczema (AD-E) from the 2012 to 2017 National Inpatient Sample. A multivariate logistic regression model was then created to determine independent characteristics predictive of developing additional diagnoses in the atopic triad.

26030 The impact of allergic sensitization and smoking on the association between urinary polycyclic aromatic hydrocarbons and the symptoms of atopic triad in the US population

Polycyclic aromatic hydrocarbons (PAHs) exposure is well known for its negative health effects. To investigate the relationship between PAHs and atopic triad as well as the impact of allergic sensitization and smoking on these connections, binary multivariable logistic regression was performed using National Heath and Nutritional Examination Survey 2005-2006 dataset. 2242 participants were included and nine urinary PAHs, 1-hydroxynaphthol (NAP), 2-NAP, 2-hydroxyfluorene (FLU), 3-FLU, 9-FLU, 1-hydroxylphenanthrene (PHE), 2-PHE, 3-PHE, 1-hydroxypyrene (PYR) levels were log transformed.

Interleukin-32 in Pathogenesis of Atopic Diseases: Proinflammatory or Anti-Inflammatory Role?

Atopic diseases, such as atopic dermatitis (AD), allergic asthma (AA), and allergic rhinitis (AR), are increasingly becoming a worldwide issue. This atopic triad originates at an early age and on a multifactorial basis, causing significant discomfort to susceptible individuals. The global case number is now reaching new highs, so exploring immune system regulation and its components is becoming critical. One cytokine, interleukin-32 (IL-32), is involved in inflammation and regulation of the immune system. It has nine isoforms that show varying degrees of expression, both intracellularly and extracellularly. IL-32 is secreted by immune cells, such as monocytes, macrophages, natural killer cells, and T cells, and by nonimmune cells, including fibroblasts, keratinocytes, and endothelial cells. Its production is regulated and augmented by microorganisms, mitogens, and other cytokines. Early studies demonstrated that IL-32 was an immune regulator that functioned to protect against inflammatory diseases, including AD, AA, and AR, and proposed a proinflammatory role for IL-32 in immune regulation and symptom exacerbation. However, several later reports suggested that IL-32 is downregulated in inflammatory diseases and exerts an anti-inflammatory effect. This review article focuses on recent findings regarding the detrimental and protective roles of IL-32 in development and management of inflammatory diseases. The exact role of IL-32 in AD, AA, and AR still remains to be elucidated. Future research should explore new avenues of IL-32 functionality in human inflammatory diseases.

Clinical characteristics and disease burden in prurigo nodularis.

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus, but information on patient experience and impact on quality of life (QoL) remains understudied. To characterize disease characteristics and QoL in a global sample of patients with PN. An anonymous survey was distributed via patient support groups for PN. In total, 231 members responded to the survey. The majority of respondents reported itch localized both to nodules and to intervening skin (67.0%). Associated symptoms included prickling, pain, stinging and burning. The extensor lower legs (69% right, 67.3% left) and flexor forearms (66.1% right, 62% left) were the most common sites of itch. Participants reported frequent healthcare utilization, with 36.3% visiting a doctor ≥10 times in the past year. Physician-diagnosed anxiety (45.4%), depression (16.4%) and the atopic triad (18.7%) were commonly reported. Patients with PN had mean scores of 16.4, 11.6 and 16.8 on the Dermatology Life Quality Index, Pittsburgh Sleep Quality Index and 5-Dimensions Itch, respectively. Severe pruritus with accompanying pain, stinging and burning is characteristic of PN, with the majority of patients experiencing itch in both nodular and interlesional skin. Patients further report decreased QoL scores and impaired sleep. Patient experiences should guide future management of PN.

Increased Risk of Atrial Fibrillation in Patients with Atopic Triad: A Nationwide Population-Based Study

Despite a sharp increase in the global prevalence of allergy over the past decade, the relation between multiple atopic conditions and atrial fibrillation (AF) has not been fully elucidated. To determine whether there is an association between atopic diseases and AF and to examine the effect of multiple atopic diseases on the incidence of AF. This retrospective population-based study used the database from the 2009 National Health Insurance Services-Health Screening Cohort in Korea. A total of 6,748,564‬ subjects without a previous history of AF were included in the final analysis and observed until 2017. The atopic triad included asthma, allergic rhinitis, and atopic dermatitis. A total of 1,168,196‬ subjects (17.3%) with at least one atopic disease were classified as the atopic group. The primary outcome was new-onset AF. During a median 7.2 ± 1.0 years of follow-up, 136,253‬ subjects were given the new diagnosis of AF (30,300 in the atopic group and 105,953 in the nonatopic group). The incidence of AF was 3.63/1000 person-years in the atopic group and 2.64/1000 person-years in the nonatopic group. The risk for AF showed a positive correlation with the number of diseases in the atopic triad (adjusted hazard ratio [aHR], 95% confidence interval [CI]: one disease: aHR= 1.15, CI, 1.14-1.17; two diseases: aHR= 1.34, CI, 1.31-1.38; and three diseases: aHR= 1.35, CI, 1.11-1.66; P for trend < .001). The atopic triad of asthma, allergic rhinitis, and atopic dermatitis was associated with an increased risk for AF. Moreover, multiple atopic conditions have a higher risk for AF.

Atopic triad (allergic rhinitis, eczema, and asthma) and eye rubbing as risk factors for keratoconus: a systematic review and meta-analysis

Keratoconus (KN), is an eye disorder, characterized by progressive thinning and protrusion of central cornea. A number of conditions such as such as allergy, asthma, eczema, and eye rubbing has been shown to be associated with the development of KN. However, there is a disagreement regarding some of risk factors and their strength so we conducted systematic review and meta-analysis to determine how strongly risk factors such as eye rubbing, and atopic triad associate with KN development and progression. We systematically searched the literature for related studies using specific keywords and key phrases. The studies were scrutinized based on inclusion and exclusion criteria. Finally, we extracted relevant qualitative and quantitate information from studies. For meta-analysis we used odds ratio (OR) and their 95% CI were used to draw forest plots. 35 studies were selected in final meta-analysis. Our meta-analysis yielded the combined effect of risk factors with OR of 2.20 and a 95% CI of 1.84–2.64. Furthermore, we found that eye rubbing-related studies had effect size of OR 2.09 with a 95% CI of 1.76–2.49 and a p value of 0.00001. For atopic triad (allergic rhinits, asthma and eczema) related studies, the meta-analysis yielded overall effect size of OR 2.34 with 95% CI of 2.06-2.66. Eye rubbing and atopic triad (allergic rhinitis, eczema, and asthma) are important risk factors for KC development with statistically strong association.

ОПЫТ ПРИМЕНЕНИЯ АЛЛЕРГЕНСПЕЦИФИЧЕСКОЙ ИММУНОТЕРАПИИ В ЛЕЧЕНИИ КРУГЛОГОДИЧНОГО АЛЛЕРГИЧЕСКОГО РИНИТА И СОПУТСТВУЮЩЕГО АТОПИЧЕСКОГО ДЕРМАТИТА

Allergen-specific immunotherapy (ASIT) is currently recognized as the only treatment that can affect all links in the pathological process of allergic diseases. Airway hyperresponsiveness is significantly reduced in case of allergy respiratory manifestations, which reduces symptoms severity and the need for drugs. The article describes a clinical observation of the ASIT positive effect in persistent atopic dermatitis (AtD) with concomitant respiratory allergy and complete atopic triad development. The authors propose to consider ASIT as a preventive therapy for bronchial asthma and allergic rhinitis if patient has AtD manifestations with confirmed sensitization to aeroallergens.

Clinical-epidemiological Profiles and Therapeutic Approaches of Atopic Dermatitis Patients.

Objectives: Atopic dermatitis, also known as atopic eczema, is a chronic inflammatory skin disease. The main objective of this study is to document atopic dermatitis patients’ clinical-epidemiological profiles and therapeutic approaches. Methods: The study is a retrospective cross-sectional study conducted at King Abdulaziz Medical City, Jeddah, Saudi Arabia, including records from 2016 to 2020. Results: Of the total 125 patients, 65 (52%) were males and 60 (48%) were females. Almost half (53%) of the study subjects reported a positive family history of at least one of the atopic triad diseases. 44 (35%) patients have another atopic disease, with bronchial asthma being the most common associated atopy. Multiple sites were affected in 63% of the patients, followed by the upper extremities (17.6%), lower extremities (11.2%), and finally the face (6.4%). Almost all patients (91%) received emollients and moisturizers as therapy. Topical steroids were the second most common treatment choice (82%). Most of the patients did not report aggravating factors, of those who reported, weather changes were the most common aggravating factor (12%). Conclusion: The clinical-epidemiological features of atopic dermatitis patients are consistent with global reports except for the affected sites, affected age group, and finally aggravating factors. This calls for the conduction of further studies in various centres across the Kingdom to provide more representative data on atopic dermatitis patients’ characteristics.

TSLP and IL-7R Variants Are Associated with Persistent Atopic Dermatitis

TSLP and IL-7R Variants Are Associated with Persistent Atopic Dermatitis

The risk of autoimmune connective tissue diseases in patients with atopy: A nationwide population-based cohort study.

The relationship between autoimmune connective tissue disease (ACTD) and atopy is controversial. To investigate the risks of ACTDs in patients with atopic triad diseases, including atopic dermatitis, allergic rhinitis, and asthma, by using a nationwide data base. A cohort of 155,311 patients newly diagnosed with atopic dermatitis, allergic rhinitis, or asthma in 2002-2011 was obtained from the Taiwan National Health Insurance Research Database. An age- and sex-matched control group was selected from the same data base. The association between atopy and ACTD was investigated by using Cox proportional hazards regression analyses. Atopic dermatitis, allergic rhinitis, and asthma were present in 12.1, 78.6, and 26.3%, respectively, of the patients with atopy. The presence of atopic diseases increased the overall risk of ACTDs (incidence rate ratio 1.85 [95% confidence interval {CI}, 1.52-2.25]). The hazard ratio (HR) for ACTDs remained higher after adjusting for age, sex, urbanization level, socioeconomic status, and comorbidities. Individual risks of systemic lupus erythematosus (HR 1.58 [95% CI, 1.06-2.37]), rheumatoid arthritis (HR 1.74 [95% CI, 1.31-2.33]), and Sjögren syndrome (HR 2.49 [95% CI, 1.71-3.63]) were also higher. The coexistence of atopic triad diseases increased the risk of ACTDs from 1.80 (95% CI, 1.48-2.21) for one atopic disease to 3.29 (95% CI, 1.22-8.88) for three atopic diseases. The presence of atopic triad diseases is significantly associated with risks of systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome, and their coexistence exacerbates this risk. To our knowledge, this was the first study that reported an increased risk of Sjögren syndrome among patients with atopy.

Multifactor-dimensionality reduction reveals interaction of important gene variants involved in allergy.

Elevated IgE levels in the atopic triad of asthma, allergic rhinitis and atopic dermatitis is a multifactorial condition whose genetic component involves interaction of several gene loci. One hundred and two matched pairs of allergic and nonallergic individuals were phenotyped for total serum IgE level using enzyme-linked immunosorbent assay (ELISA). Atopic status was defined by serum IgE concentration ≥100 IU mL(-1) . SNPs genotyped include the IL4 -590C>T (rs2243250), FCER1B E237G (rs569108), CD14 -159C>T (rs2569190), IL4RA Q551R (rs1801275) and ADRB2 R16G (rs1042713). Gene-gene interaction was analysed using multifactor-dimensionality reduction (MDR). Significant association between atopic allergy and the IL4 -590C>T polymorphism was confirmed in three genetic models. Interaction among the 5 gene variants was validated by MDR. The five-locus model was chosen as the best to describe the interaction of the SNPs within the context of atopy. The strongest interaction was between IL4 -590C>T and IL4RA Q551R and between FCER1B E237G and ADRB2 R16G. The IL4 variant also interacts synergistically with the FCER1B and ADRB2 coding variants. CD14 -159C>T, in general, interacts antagonistically with the rest of the SNPs. In conclusion, a five-locus interaction exists among IL4 -590C>T, FCER1B E237G, CD14 -159C>T, IL4RA Q551R and ADRB2 R16G in Filipino cases of atopic allergy.

Epidermal TSLP: a trigger factor for pathogenesis of atopic dermatitis

Atopic dermatitis (AD) is a common allergic inflammatory skin disease that affects 10–20% of infants, besides 3–5% of adults, and is often linked with family history of allergic disease [1]. It is characterized by strong itchy and inflamed skin and chronic lichenified, more scaly plaques. AD, asthma and allergic rhinitis forms an “atopic triad” and share a common pathogenesis, involving a T helper type 2 (Th2) cell–mediated allergic inflammation. This inflammation is characterized by secretion of cytokines (IL-4, IL-5, IL-13, and TNFα) by CD4+ T-cells, which trigger increased IgE antibody-production by B-cells; IgE binding to mast cells facilitates initiation of allergic reactions and drives infiltration of leucocytes into the skin dermis {[2], and refs therein}. Homing dendritic cells (DCs) control polarization of naive CD4+ T-cells to differentiate into Th2 lymphocytes. However, the initiating factor(s) that influence these important antigen-presenting cells to instruct T-helper cell polarization toward this inflammatory phenotype, and the mechanisms underlying the preferential activation of Th2-cells in atopic individuals by external allergens is poorly understood.

What Is Filaggrin?

FigureThis month’s continuing education article on page 231 is about the bacteria that make up the ecosystem of the skin. The article describes the various types of bacteria, virus, and fungi, and where they live and what predisposes them to protect or perturbate the protective skin barrier. As noted in the article, however, there are other mechanisms or lines of defense, including immunologic mechanisms, which protect the skin and serve as an early warning system. Some of our patients bring with them a barrier that is chronically less than prepared to serve its protective function. In this column, I’ll discuss a theoretical framework to stimulate our thinking about the commonalities of what we see, but may not know, or vice versa. The exemplar for this discussion is atopic dermatitis (AD). Atopic dermatitis is a prototype of alterations in the skin barrier and is a major problem in the patients we see and treat on a daily basis who happen to be at risk for the breakdown of the protective skin barrier. Atopic dermatitis affects 15% to 20% of children1; it is characterized as a complex trait in which genetic factors interact with the external environment to produce a chronicity of inflammation, which can lead to a break in the barrier of the skin. A systematic review estimated the annual direct and indirect costs of AD in the United States at $364 million to $3.8 billion.2 Approximately 10% of individuals from European populations are affected by AD.1–3 Consensus is building that the primary deficit in AD is a “barrier defect.”1 Filaggrin Filaggrin, like other genes, has been recently identified, thanks to the human genome project. Filaggrin or filament-aggregating protein (FLG) is thought to play a role, not only in AD, but in other diseases of the skin. A deficit or mutation of the FLG is thought to be responsible for the atopic triad, often occurring in association with asthma and allergic rhinitis. The FLG mutation carriers manifest a number of entities, including AD (which affects 42% of all mutation carriers), contact allergy, asthma, hay fever, and peanut allergy.2 These genetic variants also influence the severity of asthma and alopecia areata and the susceptibility to herpetic infections as well, all of which we see in our patients. As it relates to this month’s continuing education topic, “Skin Bacteria: Implications for Wound Care,” AD and its associated manifestations also give rise to the susceptibility to cutaneous bacterial colonization and infection (especially Staphylococcus aureus infection) and an elevation in the pH of the stratum corneum, which may lead to enhanced S aureus adhesion and multiplication.1–3 The exact function of FLG is complex; it is known, however, that its deficiency leads to a failure of the barrier function of the skin. Several serious skin diseases associated with FLG deficiency include ichthyosis vulgaris (characterized by dry scaly skin) and chronic eczema. Filaggrin is a natural moisturizer, containing several hydrophilic amino acids capable of increasing the water-holding capacity of the skin. The FLG discovery has brought about a new field of skin-barrier enhancement therapy (yet to be realized), which represents an exciting opportunity to tackle common diseases. The exploration of this model allowed us to consider the complexity of the skin barrier and the multifaceted factors that may explain its function. Using the model of FLG to explore deeper functions of the skin barrier enables us to “see what we know.” And finally, a dermatologist should be consulted if your wound patients manifest AD and skin infections that have not been diagnosed.Figure