Atopic March Research Articles

Barrier Impairment and Type 2 Inflammation in Allergic Diseases: The Pediatric Perspective.

Allergic diseases represent a global burden. Although the patho-physiological mechanisms are still poorly understood, epithelial barrier dysfunction and Th2 inflammatory response play a pivotal role. Barrier dysfunction, characterized by a loss of differentiation, reduced junctional integrity, and altered innate defence, underpins the pathogenesis of allergic diseases. Epithelial barrier impairment may be a potential therapeutic target for new treatment strategies Up now, monoclonal antibodies and new molecules targeting specific pathways of the immune response have been developed, and others are under investigation, both for adult and paediatric populations, which are affected by atopic dermatitis (AD), asthma, allergic rhinitis (AR), chronic rhinosinusitis with nasal polyps (CRSwNP), or eosinophilic esophagitis (EoE). In children affected by severe asthma biologics targeting IgE, IL-5 and against IL-4 and IL-13 receptors are already available, and they have also been applied in CRSwNP. In severe AD Dupilumab, a biologic which inhibits both IL-4 and IL-13, the most important cytokines involved in inflammation response, has been approved for treatment of patients over 12 years. While a biological approach has already shown great efficacy on the treatment of severe atopic conditions, early intervention to restore epithelial barrier integrity, and function may prevent the inflammatory response and the development of the atopic march.

No allergy left behind: The importance of food allergy in longitudinal cohorts

In recent years, the prevalence of immunoglobulin E (IgE)-mediated food allergy appears to be rising. Our ability to confirm this epidemiologic trend is limited. Over the past several decades, multiple cohorts have been established to investigate the etiologic risk factors and natural history of asthma and allergic diseases.1 The allergic (atopic) march includes the development of eczema, food allergy, allergic rhinitis, and asthma. One of the great tools of clinical epidemiology, the longitudinal cohort, has been successful in describing the allergic march, but this approach has been severely underutilized to study food allergy.

Deserters on the Atopic March: Risk Factors, Immune Profile and Clinical Outcomes of Food Sensitized-Tolerant Infants

To investigate the phenotypic features of infants who demonstrate immunoglobulin E sensitization to foods that they clinically tolerate. Such understanding may help elucidate strategies in the prevention of food allergies.A birth cohort of 1074 from southeastern Australia was composed of subjects <32 weeks’ gestation at time of enrollment and the mother planning to give birth at a local hospital. Participants were characterized as nonsensitized, sensitized-tolerant (ST), or food allergic (FA) on the basis of skin-prick testing and food challenge at 12 month of age.Environmental exposures were recorded throughout the study period of the cohort. Cord blood regulatory T-cell populations were measured at birth. Subsequent childhood allergic disease was assessed by parent report, clinical examination, and repeat skin-prick testing.Covariants were assessed among nonsensitized (n = 698), ST (n = 27), and FA (n = 61) groups and revealed that the ST group was more similar to the nonsensitized group than to the FA group in the following measures: family history of eczema (nonsensitized: 44.6%; ST: 44.6%; FA: 65.6%), pet ownership at 12 months (nonsensitized: 71.5%; ST: 81.5%; FA: 45.8%), eczema during the first 12 months (nonsensitized: 19%; ST: 32%; FA: 64%), and aeroallergen sensitivity at the age of 4 years (nonsensitized: 19.1%; ST 28.6%; FA 44.4%). At birth, a higher proportion of activated regulatory T cells was associated with the ST group.Infants who are sensitized but tolerant have similar pattern of exposures, immunity, and outcomes to nonsensitized infants. An elevated proportion of activated regulatory T cells at birth was specific to the ST infants and may be relevant to the clinical suppression of disease.Genetic and environmental factors are well known to play a role in the development of allergies. With this study, the authors compare prebirth cohorts to determine more specific factors that may put infants at higher risk for developing food allergies. A robust method of skin-prick testing plus an oral food challenge was used to confirm food allergies. The differences in proportion of cord blood naïve versus activated regulatory T cells in cohort groups provides insight into a mechanism for the prevention of food allergies.

The Impact of Formula Choice for the Management of Pediatric Cow’s Milk Allergy on the Occurrence of Other Allergic Manifestations: The Atopic March Cohort Study

To assess and compare the likelihood of developing other atopic conditions and time to achieve immune tolerance in individuals with cow’s milk allergy (CMA) on the basis of which formula (rice hydrolyzed formula, amino acid–based formula, soy formula, extensively hydrolyzed whey formula [EHWF], or extensively hydrolyzed casein formula [EHCF] containing the probiotic Lacticaseibacillus rhamnosus GG [LGG]) was consumed.A total of 365 infants (1 to 12 months) with oral food challenge-confirmed immunoglobulin E–mediated CMA were equally divided into 1 of 5 formula groups (rice hydrolyzed formula, amino acid–based formula, soy formula, EHWF, or EHCF + LGG), resulting in 73 infants per group.In this prospective cohort study, the research team evaluated each patient 3 times per year for a total of 36 months. At each visit, growth, clinical state, incidence of allergic conditions (eczema, urticaria, asthma, and rhinoconjunctivitis), avoidance of cow’s milk protein (CMP), compliance with prescribed formula, and skin-prick testing to cow’s milk protein and fresh milk were assessed. Oral food challenges were used to assess for tolerance. In the instance that any allergic symptoms developed, families were instructed to notify the research team to further evaluate and diagnose these conditions. Binomial regression was used to calculate the incidence of at least 1 atopic event in 36 months (primary outcome) as well as development of tolerance to CMP at 36 months (secondary outcome).Of the 5 cohorts, the incidence of the primary outcome was lowest in the EHCF + LGG cohort. The cohorts who consumed rice hydrolyzed formula, amino acid–based formula, soy formula, and EHWF all had higher incidences of the primary outcome that were greater than the prespecified absolute difference of 0.25, at the prespecified α level of 0.0125. In comparison with EHCF + LGG, the risk ratios of each cohort were as follows: 2.37 (1.46–3.86; P < .001) for rice hydrolyzed formula; 2.62 (1.63–4.22; P < .001) for soy formula; 2.31 (1.42–3.77; P < .001) for EHWF; and 3.50 (2.23–5.49, P < .001) for amino acid–based formula. Individuals who consumed EHCF + LGG also had the highest incidence of immune tolerance to CMP over the 36-month time period.Patients in the EHCF + LGG cohort had a lower incidence of certain allergic manifestations and a higher incidence of developing immune tolerance to CMP by 36 months, when compared with that of the cohorts who consumed rice hydrolyzed formula, amino acid–based formula, soy formula, and EHWF.In agreement with previous studies, in this study, the authors propose that EHCF + LGG is an excellent option for patients with CMA. With the incidence of food allergy on the rise, it is helpful to have an option for patients which has potential prognostic benefits, including preventing the atopic march and a quicker induction of tolerance to CMP. The limitations such as not including patients with a history of milk-protein anaphylaxis, conclusion of the study after 3 years, and lack of blinded randomization indicate a need for more studies. In addition, it would be interesting to compare the use of EHCF + LGG with the commonly used recommendation of consuming baked milk to accelerate the development of tolerance to CMP.

Current Insights into Atopic March.

The incidence of allergic diseases is increasing, and research on their epidemiology, pathophysiology, and the prevention of onset is urgently needed. The onset of allergic disease begins in infancy with atopic dermatitis and food allergy and develops into allergic asthma and allergic rhinitis in childhood; the process is defined as “atopic march”. Atopic march is caused by multiple immunological pathways, including allergen exposure, environmental pollutants, skin barrier dysfunction, type 2 inflammation, and oxidative stress, which promote the progression of atopic march. Using recent evidence, herein, we explain the involvement of allergic inflammatory conditions and oxidative stress in the process of atopic march, its epidemiology, and methods for prevention of onset.

Клинические и иммуногенетические особенности течения атопического дерматита

Актуальность. Атопическим дерматитом (АД) страдает 10-20% педиатрического и 1-3% взрослого населения. Распространенность АД в течение последних 30 лет выросла во всем мире, включая около пятой части населения развитых стран. Атопический дерматит или атопическая экзема является хроническим воспалительным заболеванием кожи, представляет серьезную проблему общественного здоровья во всем мире. Эта болезнь имеет существенный социально-экономическое бремя частично из-за отсутствия эффективного лечения, способного контролировать болезнь в долгосрочной перспективе. Целью исследования стал анализ современных представлений патогенеза и особенностей течения атопического дерматита. Материалы и методы. В процессе исследования были использованы методы семантического оценивания научных документов, а также методы структурного и логического анализа. В исследовании использованы материалы планирования и выполнения диссертационной работы по специальности 14.01.20 - кожные и венерические болезни и 14.03.08 - иммунология и аллергология. Результаты. В статье представлены результаты анализа обзора современных научных исследований патогенеза и особенностей течения атопического дерматита. Проанализированы последние направления научного поиска, научная новизна, теоретическое и практическое значение достижений научных исследований в практическом здравоохранении. Освещены подходы к современной профилактики и лечения атопического дерматита. Выводы. Наше настоящее понимание о АД резко изменилось на протяжении последних годов, главным образом, из-за значительного прогресса в эпидемиологии и генетике, огромный прорыв в понимании концепции атопического марша, а также раскрытия новых аспектов анамнеза болезни и изучения форм АД, которые персистируют в течение всей жизни. Четкое определение различных клинических фенотипов, с одной стороны, и потенциальных биомаркеров с другой являются ключевыми элементами для успешного развития новых и персонализированных терапевтических подходов у больных АД.

Longitudinal atopic dermatitis endotypes: An atopic march paradigm that includes Black children

The atopic march has been studied mostly in White populations, biasing our current paradigms. We sought to define the atopic march in Black and White children and explore mechanisms for racial differences. Utilizing the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort (n= 601), we assessed longitudinal sensitization, food allergy (FA), allergic rhinitis, risk of asthma development (through the Pediatric Asthma Risk Score), Scoring for Atopic Dermatitis (SCORAD), transepidermal water loss, skin filaggrin (FLG) expression, exposures, and genetic heritability to define AD progression endotypes in Black and White children. White MPAACH children were more likely to be sensitized to aero and food allergens (P= .0001) and over 3 times more likely to develop FA and/or allergic rhinitis (AR) without asthma risk (P< .0001). In contrast, Black children were over 6 times more likely to proceed to high asthma risk without FA, sensitization, or AR (P< .0001). White children had higher lesional and nonlesional transepidermal water loss (both P< .001) as well as decreased nonlesional keratinocyte FLG expression (P= .02). Black children had increased genetic heritability for asthma risk and higher rates of exposures to secondhand smoke and traffic-related air pollution. Black and White children with AD have distinct allergic trajectories defined by different longitudinal endotypes. Black children exhibit higher asthma risk despite a more intact skin barrier and less sensitization, FA, and AR. White children have less asthma risk, despite a more dysfunctional skin barrier, and more FA, AR, and sensitization. The observed racial differences are likely due in part to increased genetic heritability for asthma risk and harmful environmental exposures in Black children. Collectively, our findings provide a new paradigm for an atopic march that is inclusive of Black children.

Epidermal Barrier Dysfunction in Atopic Dermatitis

Impaired skin barrier is one of the hallmarks of atopic dermatitis (AD), with abnormalities in the cornified envelope, lipid lamellae, tight junctions and cutaneous microbiome. These findings are also present in nonlesional skin of AD individuals, suggesting that epidermal barrier defects may be the initial step towards the development of AD and eventually other atopic diseases (atopic march). It is currently known that pathophysiology of AD involves an interplay between this dysfunctional skin barrier and a predominantly type 2 skewed innate and adaptive immune responses, which further disrupt the skin barrier through type 2 cytokines. In this setting, there is enhanced penetration of environmental and food allergens through a deficient barrier, leading to an increased susceptibility to sensitization. During the sensitization process, thymic stromal lymphopoietin (TSLP) polarizes skin dendritic cells to a T-helper 2 response, and TSLP seems to be a key cytokine in the sensitization of food allergy, allergic asthma and rhinitis. In this review, the authors describe the current knowledge of the pathophysiology of the epidermal barrier, its disruption in AD and how it may be involved in the development of atopic comorbidities and the role of barrier repair therapy on the prevention of the atopic march progression.&#x0D;

Type 2 immunity-driven diseases: Towards a multidisciplinary approach.

Asthma, atopic dermatitis and chronic rhinoconjunctivitis are highly heterogeneous. However, epidemiologic associations exist between phenotypic groups of patients. Atopic march is one such association but is not the only common point. Indeed, beyond such phenotypes, hallmarks of type 2 immunity have been found in these diseases involving immune dysregulation as well as environmental triggers and epithelial dysfunction. From the canonical Th2 cytokines (IL‐4, IL‐5, IL‐13), new cellular and molecular actors arise, from the epithelium's alarmins to new innate immune cells. Their interactions are now better understood across the different environmental barriers, and slight differences appeared. In parallel, the development of type 2‐targeting biotherapies not only raised hope to treat those diseases but also raised new questions regarding their true pathophysiological involvement. Here, we review the place of type 2 immunity in the different phenotypes of asthma, chronic rhinitis, chronic rhinosinusitis and atopic dermatitis, highlighting nuances between them. New hypotheses rising from the use of biotherapies will be discussed along with the uncertainties and unmet needs of this field.

Anti-Interleukin Biologics for the treatment of the Atopic March Diseases

The atopic march refers to the natural history of allergic disorders as they develop from infancy to childhood. Classically, the atopic march begins with atopic dermatitis (AD), followed by food allergy, advancing to asthma, allergic rhinitis (AR), and finally to the fifth member eosinophilic esophagitis. The pathogenesis of the atopic march is complex, and involves genetic, immunological, and environmental factors. T helper type 2 (Th2) lymphocytes, and epithelial cells play a key role in the pathogenesis of the diseases in the atopic march. Th2 cells secrete cytokines, such as interleukin-5 (IL-5), IL-4, and IL-13, whereas, epithelial cell injury release alarmin cytokines, including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). Th2 cells and alarmin cytokines play an important role in the development of eczematous skin lesions, airway inflammation and remodeling, and oesophageal mucosal inflammation. Treatment of eosinophilic asthma and associated comorbid disorders is challenging, and requires a precision targeted approach with biologics. Dupilumab is a fully humanized IgG4 monoclonal antibody to the IL-4Rα, which mediates signaling to both IL-4 and IL-13, and blocks their immunopathological effects. Dupilumab is the only biologic that has been approved for the treatment of eosinophilic asthma, AD, and eosinophilic esophagitis. In patients with eosinophilic asthma treatment with dupilumab has been shown to improve asthma control, reduce exacerbations, and improve lung function. In patients with atopic dermatitis dupilumab has been demonstrated to improve the Eczema Area Severity Index (EASI) score, Investigator’s Global Assessment (IGA) response, SCORing Atopic Dermatitis (SCORAD) score, and the Peak Pruritus Numerical Rating (PNR) scale. Lebrikizumab and Tralokinumab (anti-IL-13) failed to show the expected results for the treatment of asthma, astoundingly, in several clinical trials they have been shown to significantly improvement EASI score, IGA response, SCORAD score, PNR scale, sleep architecture, and Dermatology Life Quality Index (DLQI). They have been granted First Tract Designation, and European Commission regulatory approval, respectively. Tezepelumab (anti-TSLP) is approved for the treatment of eosinophilic asthma, and has been shown to significantly reduce exacerbations, and improve asthma control, lung function, and HLQoL. However, tezepelumab did not meet the endpoints in phase II for the treatment of AD. Keywords: Atopic March; Atopic Dermatitis; Eosinophilic Asthma; Interleukin; Dupilumab; Tralokinumab

The main aspects of the immunopathogenesis of atopic dermatitis in children

Research objective &#x0D; Atopic dermatitis (AtD) is the earliest and most frequent manifestation of the body’s hypersensitivity reaction to environmental allergens. Often manifested in severe form, affecting the skin, can occur in early infancy, childhood. The disease is genetically determined and is chronic. AtD is one of the most common skin diseases (from 20 to 40% in the structure of skin diseases), which occurs in all countries in people of both sexes. In recent years, there has been an increase in the incidence of AtD throughout the world. The disease is more common in highly developed countries and cities (less commonly in rural areas).&#x0D; AtD significantly reduces the quality of life of children, causing psychological discomfort and disrupting their social adaptation. AtD in children is a risk factor for the «atopic march» — the further sequential development of other allergic diseases: allergic rhinitis, pollinosis, allergic conjunctivitis, bronchial asthma. With a reduced immune response of the body, AtD in children can be complicated by the addition of a secondary infection (bacterial, viral, fungal). Such a high incidence rate, a debut in early childhood, a frequently recurring course of the pathological process, and a tendency towards an increase in the forms of the disease resistant to traditional therapy make the details of the pathogenesis of AtD particularly relevant. One of the main roles in the pathogenesis of AtD belongs to the cells of the immune system. &#x0D; The purpose of this article: to systematize the information available today on the immunopathogenesis of atopic dermatitis.

Atopic Manifestations in Children Born Preterm: A Long-Term Observational Study.

(1) Background: Preterm birth exposes the infant to the known risk factors for atopic diseases. We aimed to study the neonatal risk factors and to describe the clinical manifestations of atopy, including the march of symptoms, in a cohort of preschool children born preterm. (2) Methods: We enrolled neonates with gestational age < 32 weeks or birth weight < 1500 g. We classified patients in cases and controls according to the presence of at least one atopic manifestation. (3) Results: We observed 72 cases and 93 controls. Multivariate models showed that the administration of more than one cycle of antibiotics (B 0.902, p = 0.026) and gestational diabetes (B 1.207, p = 0.035) influence the risk of atopy in babies born preterm. In addition, risk of atopic dermatitis was influenced by gestational age < 29 weeks (B −1.710, p = 0.025) and gestational diabetes (B 1.275, p = 0.027). The risk of wheeze was associated with familiarity for asthma (B 1.392, p = 0.022) and the administration of more than one cycle of antibiotics (B 0.969, p = 0.025). We observed a significant reduction in the rate of atopic manifestation after 2 years of life (33.9% vs. 23.8%, p < 0.05). (4) Conclusions: Modifiable (gestational diabetes, antibiotics use) and unmodifiable (familiarity for asthma) conditions influence the risk of atopy in babies born preterm. Extreme prematurity reduces the risk of atopic dermatitis. Preterm babies showed a peculiar atopic march.

Melatonin prevents allergic airway inflammation in epicutaneously sensitized mice.

Purpose: The pathological process of atopic dermatitis (AD) progressing into other types of allergic diseases such as asthma and allergic rhinitis during the first several years of life is often referred to as the atopic march. Although the phenomenon of atopic march has been recognized for decades, how asthma stems from AD is still not fully understood, confounding a universal strategy to effectively protect people from the atopic march. Methods: We established experimental atopic march mice by first inducing allergic dermatitis with 0.5% fluorescein isothiocyante (FITC) applied to the skin, followed by an ovalbumin (OVA) airway challenge. In addition, by examining serum immunoglobulin (Ig) concentrations, airway cytokines, the levels of oxidative stress markers, histopathological changes in lung tissue and airway hyperresponsiveness (AHR), we were able to validate the successful establishment of the model. Furthermore, by detecting the attenuating effects of melatonin (MT) and the levels of oxidative stress in the atopic march mice, we explored the potential molecular mechanisms involved in the development of atopic march. Results: By successfully establishing an experimental atopic march mouse model, we were able to demonstrate that overproduction of oxidative stress in the lung significantly up-regulated the activation of nuclear factor-κB (NF-κB) signaling pathways causing thymic stromal lymphopoietin (TSLP) release, which further promotes the development of atopic march. Conclusions: To mitigate the development of the atopic march, antioxidants such as MT may be imperative to inhibit NF-κB activation in the lung, especially after the onset of AD.

Однонуклеотидний поліморфізм rs510432 гена автофагії 5 та розвиток «атопічного маршу» у дітей

Мета: визначити зв’язок між однонуклеотидним поліморфізмом rs510432 гена автофагії 5 (ATG5) та розвитком «атопічного маршу» у дітей, з’ясувати ймовірність маніфестації клінічних проявів та особливості клінічного перебігу атопічних захворювань в осіб із різними алельними варіантами поліморфізму. Методи. Генотипування поліморфізму rs510432 гена ATG5 у дітей з атопічними захворюваннями та практично здорових дітей із застосуванням методики полімеразної ланцюгової реакції в реальному часі. Результати. Мінорна алель Т rs510432 гена ATG5 вірогідно частіше виявляється у пацієнтів з атопічними захворюваннями, ніж у практично здорових дітей (χ2 = 6,36; р &lt; 0,05). За результатами логістичної регресії ризик розвитку атопічних захворювань у дітей із мінорним генотипом у 2,4 раза вищий, ніж у дітей із мажорним генотипом. Середні значення об’єму форсованого видиху за 1 секунду (ОФВ1) у хворих на бронхіальну астму з мінорним генотипом вірогідно нижчі, ніж з мажорним генотипом (Q = 2,71; р &lt; 0,05). Не виявлено статистично значущих відмінностей у розподілі алельних варіантів поліморфізму rs510432 гена ATG5 залежно від тяжкості бронхіальної астми, атопічного дерматиту та алергічного риніту у дітей. Висновки. У дітей з мінорним генотипом ТТ поліморфізму гена ATG5 виявлено підвищений ризик розвитку атопічних захворювань, що становить 72 %. У хворих на бронхіальну астму мінорний генотип ТТ поліморфізму гена ATG5 асоційований зі зниженим показником ОФВ1. Поліморфізм rs510432 гена ATG5 доцільно використовувати з метою прогнозування розвитку атопічних захворювань у дітей.

Значення однонуклеотидного поліморфізму rs4769628 гена РОМР у розвитку атопічних захворювань у дітей

Метою даного дослідження було визначити зв’язок між наявністю однонуклеотидного поліморфізму rs4769628 гена РОМР та розвитком алергічних захворювань у дітей. Методи: генотипування поліморфізму rs4769628 гена POMP у дітей з маніфестацією атопічного маршу та практично здорових дітей із застосуванням методики ПЛР в реальному часі. Результати. У 62,26 % дітей, хворих на атопічні захворювання, і 53,06 % здорових дітей зустрічається мажорна алель rs4769628 гена РОМР. 33,67 % і 37,76 % дітей відповідно мають гетерозиготний варіант АG. Мінорний генотип GG у дітей, хворих на атопічні захворювання, не зустрічається, 9,18 % здорових осіб є носіями мінорної алелі (р &lt; 0,05). Висновки. Мінорна алель G rs4769628 гена РОМР асоційована зі зниженим ризиком розвитку атопічних захворювань у дітей. Поліморфізм rs4769628 гена РОМР може використовуватись як важливий прогностичний маркер розвитку атопічних захворювань у дітей.

ДЗ «Дніпропетровська медична академія МОЗ України», м. Дніпро, Україна

В огляді наведені дані досліджень за останні 10 років у популяціях різних країн щодо асоціацій атопічних хвороб, що становлять атопічний марш у дітей (атопічного дерматиту, алергічного риніту, алергічного ринокон’юнктивіту та бронхіальної астми), і патологічних мутацій генів (однонуклеотидних поліморфізмів, single nucleotid polymorphysms — SNP), які кодують синтез молекул, що беруть участь в алергічному запаленні на шкірі та слизових оболонках. Як пошукову систему використано PubMed. Наданий аналіз досліджень вивчених SNP — філагрину, тол-подібних рецепторів, висвітлено перспективний каскад запалення при бронхіальній астмі — інтерлейкін-1-подібний рецептор 1 та інтерлейкін-33. Запропоновано проведення досліджень наведених SNP на українській педіатричній популяції для розробки персоналізованого генотип-асоційованого підходу до діагностики та лікування атопічних хвороб у дитячого населення України.

Dysregulation of the epithelial barrier by environmental and other exogenous factors.

The “epithelial barrier hypothesis” proposes that the exposure to various epithelial barrier–damaging agents linked to industrialization and urbanization underlies the increase in allergic diseases. The epithelial barrier constitutes the first line of physical, chemical, and immunological defense against environmental factors. Recent reports have shown that industrial products disrupt the epithelial barriers. Innate and adaptive immune responses play an important role in epithelial barrier damage. In addition, recent studies suggest that epithelial barrier dysfunction plays an essential role in the pathogenesis of the atopic march by allergen sensitization through the transcutaneous route. It is evident that external factors interact with the immune system, triggering a cascade of complex reactions that damage the epithelial barrier. Epigenetic and microbiome changes modulate the integrity of the epithelial barrier. Robust and simple measurements of the skin barrier dysfunction at the point‐of‐care are of significant value as a biomarker, as recently reported using electrical impedance spectroscopy to directly measure barrier defects. Understanding epithelial barrier dysfunction and its mechanism is key to developing novel strategies for the prevention and treatment of allergic diseases. The aim of this review is to summarize recent studies on the pathophysiological mechanisms triggered by environmental factors that contribute to the dysregulation of epithelial barrier function.

A new era of atopic eczema research: Advances and highlights.

Atopic eczema (AE) is an inflammatory skin disease with involvement of genetic, immunological and environmental factors. One hallmark of AE is a skin barrier disruption on multiple, highly interconnected levels: filaggrin mutations, increased skin pH and a microbiome dysbiosis towards Staphylococcus aureus overgrowth are observed in addition to an abnormal type 2 immune response. Extrinsic factors seem to play a major role in the development of AE. As AE is a first step in the atopic march, its prevention and appropriate treatment are essential. Although standard therapy remains topical treatment, powerful systemic treatment options emerged in the last years. However, thorough endotyping of the individual patients is still required for ideal precision medicine approaches in future. Therefore, novel microbial and immunological biomarkers were described recently for the prediction of disease development and treatment response. This review summarizes the current state of the art in AE research.

Relationship Between Concomitant Atopic Diseases With Atopic Dermatitis Severity And Persistence.

Introduction: The atopic march consists of atopic dermatitis (AD), allergic rhinitis or sinusitis (AR), allergic conjunctivitis (AC) and bronchial asthma (BA). The influence of concomitant atopic diseases on AD is under-explored. We determined the relationship between personal and family history of atopic diseases with AD severity and persistence. Methods: A cross sectional study involving AD patients was performed at dermatology clinics of two tertiary hospitals. Inclusion criterion was all patients diagnosed with AD. Demographic data, personal and family history of atopy (BA, AR and AC) were obtained by face-to-face interview. AD severity was evaluated using Investigator’s Global Assessment (IGA). AD was considered persistent if continued beyond age 12 years. Results: Sixty patients aged 21.6±17.2 participated. There were 25(41.7%) with concomitant AR, 16(26.7%) BA and 12(20%) AC. Forty seven (78.3%) patients had family history of atopy, 25(41.7%) had eczema, 24(40%) AR, 19(31.7%) BA and 2(3.3%) AC. Patients with BA [OR=3.8, 95%CI 1.04 to 14.4)], BA and AR [OR=9.74, 95%CI 1.13 to 83.67) and family history of BA [OR= 4.00, 95%CI 1.20 to 13.27) were more likely to exhibit moderate-severe AD. Personal AR, AC and family history of AD and BA were significantly more prevalent in patients with persistent AD. Conclusions: AR was the most common atopic disease associated with AD. Family history of eczema and AR were common. Personal BA, BA with AR and family history of BA were predictors of severe AD. Personal AR, AC and family history of AD and BA were associated with AD persistence.

Atopic Dermatitis-Beyond the Skin.

Atopic dermatitis is a chronic inflammatory disease that can arise during the first months of life or at maturity and have a significant negative impact on the quality of life. The main pathogenic mechanism is the breakdown of cutaneous barrier integrity, which is associated with systemic inflammatory immunologic disorders. Atopic dermatitis involves numerous immunologic, allergic, respiratory, and ophthalmologic comorbidities that develop through similar intricate pathogenic phenomena. The atopic march represents the evolution in time of various allergic diseases, of which food allergies often cause the first manifestations of atopy, even from a very young age. Chronic inflammation translated through specific markers, next to increased immunoglobulin E (IgE) serum levels and heterogenous clinical manifestations, argue for the inclusion of atopic dermatitis in the systemic disease category.