Atopic March Research Articles

Принципы введения прикорма при атопическом дерматите

Atopic dermatitis (AD) is one of the most common inflammatory skin disorders. In most patients, AD is a starting point for developing other atopic diseases, e.g., food allergy, allergic diseases of the gastrointestinal tract, allergic rhinitis, and asthma known under the umbrella of "atopic march". In addition to genetic predisposition, various environmental factors are essential for the development of this dermatosis. In young children, food is the most relevant factor. This paper discusses principles of the selection of complementary food, techniques, and terms of its introduction. Prolonging of breastfeeding, the adequate introduction of complementary food, and personified nutrition program prevent the atopic march. The authors highlight that there is no special diet for atopic dermatitis. Meanwhile, food should be safe, low allergy, and balanced to provide a child with essential macro-and micronutrients. In addition, the paper addresses the utility and validity of an elimination diet which should be prescribed only in established food sensitization and used under the control o f a specialist. KEYWORDS: atopic dermatitis, atopic march, infancy, early childhood, nutrition, complementary foods, prevention. FOR CITATION: Botkina A.S., Dubrovskaya M.I. Principles of complementary food introduction in atopic dermatitis. Russian Medical Inquiry. 2021;5(6):421–426 (in Russ.). DOI: 10.32364/2587-6821-2021-5-6-421-426.

Update on management of pediatric atopic dermatitis

Atopic dermatitis is the most common chronic inflammatory skin disease in children. It usually develops in infancy and early child hood and is an entry point of ‘atopic march’, which may progress to other allergic diseases, including allergic rhinitis and asthma. Al though there is no disagreement on the importance of early treatment of atopic dermatitis, it is difficult to treat children with mod erate to severe atopic dermatitis due to concerns about treatment-related side effects and age restrictions for effective drugs in real world. As recent researches have extend our understanding of pathogenesis, new agents targeted key pathologic mechanisms have been developed. Therefore, it is time to establish a new paradigm of treatment for children with atopic dermatitis since new biologics have been demonstrated to be effective and safe in children. The objective of this article is to review the clinical character istics, severity classification, pathogenesis, and treatment, in particular, biologics already approved/undergoing clinical trials for chil dren with atopic dermatitis. (Allergy Asthma Respir Dis 2021;9:59-68)

Atopic dermatitis and atopic march: which link?

There is a long standing debate on the atopic march in childhood. The natural progression of allergic manifestations may be considered as comorbidities, which occur more frequently in a specific evolutive age. On the other hand, the natural history of allergies in children may follow trajectories that may be heterogeneous. The effects of atopic march in clinical practice have also been reported. (www.actabiomedica.it)

Allergy - Patients with Atopic Dermatitis Express Themselves Through a Questionnaire.

IntroductionAllergies are becoming more prevalent across the globe and can be linked to several skin diseases, particularly atopic dermatitis (AD). Disruption of the immune system in the skin can lead to inflammatory diseases such as atopic and contact dermatitis, skin infections, and allergies. This is especially evident in processes such as “atopic march”, where in childhood, the development of atopic dermatitis can later lead to food allergies, allergic rhinitis and asthma.ObjectiveThe aim of this international online survey is to study the link between self-reported doctor-diagnosed AD and allergy prevalence.MethodologyOur survey queried a representative sample of the general population over the age of 18 from five countries (Brazil, China, Russia, the USA and France).ResultsA total of 9399 participants answered the entire online questionnaire. Among them, 2483 (26.4%) had an allergy diagnosed by a doctor (1243 with food allergies (13.2%), 1564 with respiratory allergies (16.6%) and 1669 with skin allergies (17.7%)). There were 794 (31.9%) participants with current AD in the allergy group and 640 (9.25%) in the group without allergies (p<0.001), and there were 1299 (52.3%) participants with CAD in the allergy group versus 1368 (19.8%) in the group without allergies (p<0.001). Multivariate analysis showed ORs of 3.24 [2.98, 3.63] (p<0.001) for current AD and 2.4 [2.09, 2.74] (p<0.001) for CAD. There was no significant interaction between AD and CAD (p=0.6).ConclusionA total of 26.4% of survey respondents reported having doctor-diagnosed allergies. Among these patients, half reported having AD during childhood, and 1/3 reported having a current AD. CAD and AD patients clearly have a higher risk of having an allergy than patients without CAD or AD.

Atopic March Will Be Implemented from Skin Sensitization

Atopic March Will Be Implemented from Skin Sensitization

Persistan Atopik Dermatit'li İnfantlarda Beklenmeyen Kedi Alerjisi

Atopic dermatitis is a chronic, recurrent inflammatory skin disease usually caused by genetic predisposition, immune dysregulation, epidermal barrier dysfunction and interaction of environmental factors. Atopic dermatitis is part of atopic march and is often accompanied by food allergy. Aeroallergenic sensitization at early age is not an expected finding. Here, we present five cases with moderate-severe atopic dermatitis during infancy, in whom food allergy was detected and the symptoms improved only partially despite elimination and treatment. Sensitization was investigated in patients with a history of intense exposure to cats by specific IgE and skin prick test in infants with atopic dermatitis who had food allergy and persistant findings. Egg allergy was detected in four of the cases, wheat allergy in one. Cat allergy was present in all. Elimination diet was started in all cases. When exposure to cats was reduced, a marked improvement in the findings of atopic dermatitis was observed in all cases. Allergic diseases are increasing day by day. Unexpected aeroallergenic sensitization is now more common in the early stages of life. Allergic patients, regardless of age, should be questioned in detail for aeroallergen exposure. If it is detected; necessary preventive measures should be taken.

Modern Outlooks on «Atopic March» Secondary Prevention Capabilities in Children with Atopic Dermatitis

Atopic dermatitis (AD) is one of the most common inflammatory diseases of childhood, and it is the first one in gradual development of allergic diseases, also known as «atopic march». Sensitization establishment during the AD uncontrolled course is associated with the high risk of developing of serious allergic pathologies, increase in the severity of the disease course, and patients’ quality of life reduction. Thereby, it is crucial to achieve quick jugulation of the inflammatory process in case of severe AD with early onset of disease. This article shows modern therapeutic approaches to disease control in children.

Eosinophil microRNAs Play a Regulatory Role in Allergic Diseases Included in the Atopic March.

(1) Background: The atopic march is defined by the increased prevalence of allergic diseases after atopic dermatitis onset. In fact, atopic dermatitis is believed to play an important role in allergen sensitization via the damaged skin barrier, leading to allergic diseases such as allergic asthma and allergic rhinitis. The eosinophil, a pro-inflammatory cell that contributes to epithelial damage, is one of the various cells recruited in the inflammatory reactions characterizing these diseases. Few studies were conducted on the transcriptome of this cell type and even less on their specific microRNA (miRNA) profile, which could modulate pathogenesis of allergic diseases and clinical manifestations post-transcriptionally. Actually, their implication in allergic diseases is not fully understood, but they are believed to play a role in inflammation-related patterns and epithelial cell proliferation. (2) Methods: Next-generation sequencing was performed on RNA samples from eosinophils of individuals with atopic dermatitis, atopy, allergic rhinitis and asthma to obtain differential counts of primary miRNA (pri-miRNA); these were also analyzed for asthma-related phenotypes such as forced expiratory volume in one second (FEV1), immunoglobulin E (IgE) and provocative concentration of methacholine inducing a 20% fall in forced expiratory volume in 1 s (PC20) levels, as well as FEV1 to forced vital capacity (FEV1/FVC) ratio. (3) Results: Eighteen miRNAs from eosinophils were identified to be significantly different between affected individuals and unaffected ones. Based on counts from these miRNAs, individuals were then clustered into groups using Ward’s method on Euclidian distances. Groups were found to be explained by asthma diagnosis, familial history of respiratory diseases and allergic rhinitis as well as neutrophil counts. (4) Conclusions: The 18 differential miRNA counts for the studying phenotypes allow a better understanding of the epigenetic mechanisms underlying the development of the allergic diseases included in the atopic march.

Physiopathologie de la dermatite atopique et des autres maladies atopiques : une approche globale est-elle possible ?: Pathophysiology of atopic dermatitis and other atopic diseases: is a global approach possible?

Atopy is defined by the propensity to develop an exaggerated type-2 inflammatory response to environmental molecules. Clinically, atopy is diagnosed when atopic disease occurs: atopic dermatitis, food allergy, atopic asthma and allergic rhinitis and conjunctivitis. Whereas the classical "atopic march" is increasingly challenged through epidemiological studies, type-2 cellular inflammation is a characteristic shared by the atopic diseases. This inflammation can be innate (non-specific: eosinophils, mast cells, dendritic cells, innate lymphoid cells [ILC]), or adaptive (antigen-specific, involving T cells). Interleukins (IL-)4, 5 and 13 are major actors of type-2 inflammation and are mainly produced by ILC and T cells. The efficacy of treatments targeting these type-2 cytokines highlight the importance of type-2 inflammation in atopic diseases. However, several patients do not respond to type-2 targeting treatments, highlighting the presence of other actors in pathophysiology of atopic diseases: alteration of epithelial barrier, IgE-mediated allergic responses, type-17 inflammation. Thus, the term "endotype" can illustrate this diversity in pathophysiology. Finally, a global approach of atopic diseases, as type-2 inflammatory diseases, is fundamental, but not sufficient. An approach by endotype is advisable, in a personalized medicine perspective. © 2020 Elsevier Masson SAS. All rights reserved.

Prenatal Exposure to Cadmium and Risk of Allergic Diseases in Pre-school Children

Background/Aim: The prevalence of child’s allergic disease has been increased worldwide. Atopic dermatitis is considered to be the first clinical characteristic and the beginning of the atopic march that followed by asthma and allergic rhinitis during the first several years of life. Exposure to metals (such as chromium, cadmium and lead) was reported to associate with immune biomarkers and allergy. Our aim is to investigate the association between prenatal exposure to metals and allergic diseases in children. Methods: A total of 243 pairs of pregnant women and newborns were recruited in central Taiwan during 2012 to 2013, and the questionnaires and specimens were collected from pregnant women. Children were follow-up during 2016 to 2017 to identify their allergic disease by International Study of Asthma and Allergies in Childhood (ISAAC). Metal concentration (cadmium, Cd; lead, Pb) in maternal urine was measured by inductively coupled plasma mass spectrometry (ICP-MS), and child’s blood IgE was quantified using ImmunoCAP total IgE assay system. A few cigarette smokers at pregnancy were excluded from the beginning. Child's sex, allergic status in parents, environmental tobacco smoke at pregnancy, and child’s blood total IgE were adjusted in statistical model. Results: The mean age of children is 3.95 years (SD = 0.56), and approximate 60% is boy. In these children, 30.45% were identified with atopic dermatitis, 3.70% with asthma, and 20.99% with allergic rhinitis. Per doubling increase of prenatal Cd exposure was significantly associated with elevated risk of allergic rhinitis in children (OR = 1.59; 95% CI 1.07, 2.36) even Pb was included in full-adjusted model. Conclusions: Prenatal exposure to cadmium has increased risk of allergic rhinitis in early childhood. Therefore, it is suggested to identify pregnant women at risk of metal exposure and avoid the exposure sources thus might reduce the risk of allergic disease on their children.

The efficacy and safety of local therapy of atopic dermatitis in infants and school-age children

Atopic dermatitis is a multifactorial genetic inflammatory skin disease associated with disturbances of skin barrier function affected by predisposition to IgE-mediated hypersensitivity, which is characterized by itching, chronic recurrent course of the disease, age-related features of localization and lesion morphology, and requires the long-term and permanent treatment.Treatment is based on the continuous use of emollients, topical calcineurin inhibitors, topical glucocorticoids, and hygienic skin care.The mechanisms of the atopic dermatitis development are primarily based on a genetic predisposition to allergies, failure of the normal development of congenital and acquired factors of the immune system, as well as the influence of environmental factors and various trigger factors, such as allergenic (food, indoor, epidermal, fungal allergens, etc.). and non-allergenic (tobacco smoke, pollutants, psycho-emotional stress, concomitant chronic and acute diseases, mainly ARVI, etc.).It has been established that atopic dermatitis is characterized by the epidermal barrier dysfunction leading to excessive tran-sepidermal water loss, increased permeability of the epidermis, the penetration of allergens and microbial agents via the skin and eventually to sensitization to allergens and the development of specific allergic skin inflammation and atopic march with the sequential development of other atopic diseases.Modern therapeutic strategies are actively aimed at repairing the epidermal barrier, preventing sensitization and atopic march development. This article describes the features of the epidermal barrier dysfunction in atopic dermatitis, lists the methods of its restoration and ways to prevent subsequent exacerbations using local therapy and emollients, and presents 3 clinical cases.

IgE Autoreactivity in Atopic Dermatitis: Paving the Road for Autoimmune Diseases?

Atopic dermatitis (AD) is a common skin disease affecting 20% of the population beginning usually before one year of age. It is associated with the emergence of allergen-specific IgE, but also with autoreactive IgE, whose function remain elusive. This review discusses current knowledge relevant to the mechanisms, which leads to the secretion of autoreactive IgE and to the potential function of these antibodies in AD. Multiple autoantigens have been described to elicit an IgE-dependent response in this context. This IgE autoimmunity starts in infancy and is associated with disease severity. Furthermore, the overall prevalence of autoreactive IgE to multiple auto-antigens is high in AD patients. IgE-antigen complexes can promote a facilitated antigen presentation, a skewing of the adaptive response toward type 2 immunity, and a chronic skin barrier dysfunction and inflammation in patients or AD models. In AD, skin barrier defects and the atopic immune environment facilitate allergen sensitization and the development of other IgE-mediated allergic diseases in a process called the atopic march. AD is also associated epidemiologically with several autoimmune diseases showing autoreactive IgE secretion. Thus, a potential outcome of IgE autoreactivity in AD could be the development of further autoimmune diseases.

Research Progress in Atopic March.

The incidence of allergic diseases continues to rise. Cross-sectional and longitudinal studies have indicated that allergic diseases occur in a time-based order: from atopic dermatitis and food allergy in infancy to gradual development into allergic asthma and allergic rhinitis in childhood. This phenomenon is defined as the “atopic march”. Some scholars have suggested that the atopic march does not progress completely in a temporal pattern with genetic and environmental factors. Also, the mechanisms underlying the atopic march are incompletely understood. Nevertheless, the concept of the atopic march provides a new perspective for the mechanistic research, prediction, prevention, and treatment of atopic diseases. Here, we review the epidemiology, related diseases, mechanistic studies, and treatment strategies for the atopic march.

Dietary Prevention of Atopic March in Pediatric Subjects With Cow's Milk Allergy.

Cow's milk allergy (CMA) is one of the most prevalent food allergies and the most expensive allergic diseases in the pediatric age. There is no cure for CMA, and actual disease management is based on strict avoidance of cow milk protein-containing foods, access to rescue medication, and use of substitutive formulas. Early-life CMA could be one of the first steps of the “allergic march” (AM), leading to the occurrence of other atopic manifestations later in the life, including asthma and oculorhinitis, with subsequent further increase of costs for health care systems and families of affected children. In the last years, diet is emerged as a relevant strategy to prevent allergic diseases through, at least in part, epigenetic modulation of immune system. We provide an overview of studies that investigate the potential role of different dietary strategies in preventing the AM in pediatric patients with CMA.

Food Allergies.

Food allergy is 1 of the 4 manifestations of the "atopic march," along with eczema, allergic rhinitis, and asthma. Depending on the pathophysiologic immune mechanisms behind a food allergy, it can be classified as immunoglobulin E-mediated, non-immunoglobulin E-mediated, or mixed. The prevalence of food allergies has risen worldwide during the past few decades, becoming a significant global health concern. Patients experiencing food allergies and their caregivers are heavily burdened personally, socially, emotionally, and financially. The health-care system is also considerably affected. Pediatricians, as primary health-care providers, are often challenged with these patients, becoming the first-line for the recognition and management of food allergies. The purpose of this review is to provide a comprehensive summary of food allergies, including the most up-to-date information, recent guidelines, and recommendations.

Assessment of asthma risk in patients with allergic rhinitis

The evolution from allergic rhinitis to asthma was reported in numerous studies referred as “atopic march”. Often those two diseases coexist and represent a single disease of an allergic patient, so named “the united airways disease”. The question “Which patients with allergic rhinitis will develop asthma?” is important for all the physicians which are taking care of allergies. Genetic studies showed a number of genes which are involved in allergic diseases occurrence, but it is also important the influence of the environment. The aim of this study was to evaluate if some inflammatory markers may predict the occurrence of asthma in patients with allergic rhinitis. We studied a group of 75 patients with persistent allergic rhinitis. The initial clinical evaluation was done at the beginning of the study, referring to disease severity and sensitization. The FENO measurement was performed to all patients with allergic rhinitis. The serum levels of ICAM-1, E-selectine and VCAM-1, IL-6, IL-8 and TNF-α were determined using ELISA method. The same group was clinically evaluated after one year, in order to determine the presence of asthma symptoms and to establish diagnose of bronchial asthma. The markers of allergic inflammation, total IgE and eosinophils were higher in patients who developed asthma after 1 year, compared to patients with allergic rhinitis without asthma, but the differences were not statistically significant (p>0.05). We noticed similar results for adhesion molecules (ICAM, VCAM and E-selectin) and IL-6, but not for TNF-α and IL-8. Only FeNO was significantly higher in patients with allergic rhinitis and asthma compared to those without asthma (p<0.001). FENO and some proinflammatory cytokines may predict the occurrence of asthma in patients with allergic rhinitis. This study also underlines the importance for asthma evaluation in patients with allergic rhinitis.

A case of atopic dermatitis with a severe resistant course in adult patient with atopic march

Introduction. The atopic march is the natural course of development of atopy symptoms. It is characterized by a typical sequence of development of clinical symptoms of atopic disease, when some symptoms become more significant, others are recede. Timely allergological diagnostics with the identification of causal allergens allows to preventor suspend the atopic march.&#x0D; Purpose of the study was to demonstrate the stages of the atopic march formation and clinical manifestations of atopy, the importance of on timely detection of causal allergens, the capability of modern diagnostics and treatment of severe resistant forms of allergic diseases.

FABP5 as a possible biomarker in atopic march: FABP5-induced Th17 polarization, both in mouse model and human samples.

BackgroundWhile the incidence of patients with atopic dermatitis (AD) with atopic march (AM) showing respiratory allergy is steadily rising, the pathomechanism is still unknown. There are currently no biomarkers to predict progression of AM.MethodsTo explore the mechanism of AM, patients with AD and AM and healthy controls were recruited and RNA microarray, flow cytometry, quantitative real-time polymerase chain reaction, and immunofluorescence staining were performed. We also co-cultured dendritic cells and CD4+T cells with various Dermatophagoides farinae allergen fractions. Cytokine levels were evaluated using enzyme-linked immunosorbent assay.FindingsBoth fatty-acid-binding protein 5 (FABP5) and Th17-related genes were more highly expressed in AM. FABP5 knockdown significantly decreased Th17-inducing cytokines in keratinocytes and IL-17A in T cells from AM patients. Further confirmation was obtained using an AM mice model compared to mice without AM. Der f 1, a major D. farinae allergen, increased FABP5 and IL-17A expression in T cells from AM patients. Higher serum FABP5 levels from AM patients were positively correlated with serum IL-17A levels.InterpretationFABP5 expression, possibly enhanced by higher epicutaneous and respiratory sensitization to Der f 1, may directly promote Th17 responses in AD patients with AM. Thus, AM progression can be explained by Th17 reaction induced by FABP5. FABP5 was identified as a potential biomarker in AM.FundingThis study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT; No. NRF-2017R1A2B4009568), grants of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, and the Republic of Korea (HI13C0010, HI14C1324, HI14C1799).

223 Skin barrier, inflammation, and metabolism– connections through Ovol1/Ovol2

Skin barrier dysfunction contributes to inflammatory diseases such as psoriasis and atopic dermatitis, which can lead to systemic defects (e.g. atopic march). The cellular and molecular events that regulate barrier-induced inflammation and its connection to whole-body physiology remain to be fully understood. SNPs in human OVOL1, which encodes a transcriptional repressor, are associated with many skin inflammatory diseases. Germline deletion of Ovol1 leads to epidermal hyperproliferation and a transient delay in embryonic skin barrier acquisition. However, the function of Ovol1 and its homolog Ovol2 in adult skin homeostasis and inflammation is unknown. Here we show that skin epithelia-specific deletion of Ovol1 results in radically aggravated barrier disruption and psoriasis-like inflammation upon stimulation with imiquimod. Using ChIP-seq we found that Ovol1 protein in epidermal cells directly binds to the promoters of not only genes involved in controlling proliferation and differentiation (e.g. Id1) but also genes involved in inflammation (e.g. Cxcl1 and Nfkb2). We generated mice with both Ovol1 and Ovol2 inducibly deleted in adulthood specifically in epidermal cells and found the mice to rapidly develop skin barrier defects. Subsequently, they developed oversized paws with elongated and reddish toenails, and lower bodyweight and reduced fat deposits. Preliminary analysis using metabolic cages shows that these mice eat more and are metabolically more active than their control littermates. Additionally, they release more heat while maintaining a normal body temperature. Current experiments focus on characterizing potential inflammation in mutant mice and analyzing gene expression changes in skin and metabolic tissues such as brown adipose tissue of these mice. Our goal is to elucidate the mechanism by which Ovol1 and Ovol2 regulate skin barrier function and inflammation, and how cutaneous defects are linked to alterations in whole-body physiology and metabolism.

DIAGNOSTIC CRITERIA FOR ALLERGIC RHINITIS IN CHILDREN WITH ATOPIC DERMATITIS

Summary . This article substantiates that the timely diagnosis of atopy and adequate treatment of AtD and AR help prevent the development of severe forms of the disease and the progression of the atopic march. It also analyzes the modern possibilities of solving problems related to the complexity of diagnosis, differential diagnosis, false-positive and false-negative results of clinical and laboratory studies of allergic diseases, genetic characteristics of patients and many other parameters; We are considering the possibility of integrating bioinformatics and systemic biomedicine approaches, based, on the one hand, on massive databases of experimental studies, and on the other, on advanced technologies for genotyping and marker identification. It is concluded that further improvement of modern methods for the diagnosis of atopic dermatitis associated with allergic rhinitis is an actual scientific direction at the junction of allergology, genetics and immunology.