From atopic dermatitis to asthma: The atopic march

Division of Allergy and Immunology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology (Impact Factor: 2.6). 08/2010; 105(2):99-106; quiz 107-9, 117. DOI: 10.1016/j.anai.2009.10.002
Source: PubMed


To examine the mechanisms whereby allergen exposure through the epidermis could initiate systemic allergy and predispose individuals to the development of 1 or more atopic diseases via the so-called atopic march.
PubMed databases from 1950 to the present were searched for relevant articles pertaining to epidemiologic and genetic evidence of the progression of the atopic march.
Articles concerning pathophysiologic conditions that link atopic dermatitis, allergic rhinitis, and asthma were examined.
The data suggest that a sequence of atopic manifestations occurs, typically atopic dermatitis in infancy followed by allergic rhinitis and/or asthma in later stages. Reduced filaggrin expression is implicated as a major predisposing factor for atopy in multiple lines of evidence, including genome-wide analysis and microarray investigations. Other gene products have an important role. Cross-sectional and longitudinal studies provide preliminary epidemiologic support for the sequential development of allergic diseases.
The mechanisms by which allergen exposure through the epidermis can initiate systemic allergy and predispose individuals to atopic dermatitis, allergic rhinitis, and asthma have become clearer in recent years. Longitudinal studies of individuals carrying loss-of-function filaggrin gene mutations are needed to further define the risks associated with epidermal barrier dysfunction and potentially identify specific targets for barrier repair and prevention of atopic dermatitis and other atopic disease. The effects of preventive and treatment strategies have been inconsistent across studies, and further research is warranted before any definitive recommendations can be made.

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    • "William found that prevalence of AD increases with improvement in socio-economic condition.[4] Similar finding was reported by Spergel et al. who found that the prevalence of AD had increased two to three folds during past three decades in industrialized countries due to improvement of socio-economic condition and improved life style.[13] In contrast to our study, 46.2% patients came from middle class, 28% from lower socio-economic class, and only 25.8% from upper socio-economic class, which was comparable with Indian study carried out by Sarkar and Kanwar, in which they found that majority belonged to middle class families (53.8% for up to 1 year and 57.57% onwards) whereas minority of patients was from low strata 15.55% for up to 1 year and 23.23% above 1 year.[8] "
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    ABSTRACT: To study the clinical features, absolute eosinophil count, and total immunoglobulin E (IgE) level and their association with severity of atopic dermatitis in Eastern Indian children (Bihar). Prospective hospital-based study. Pediatrics out-patient Department (OPD) and Dermatology OPD of a Tertiary Care Teaching Hospital located in Rohtas District of Bihar. The study was carried out over a period of 2 years during January 2010 to December 2011. One hundred and thirty two children aged 0 month to 15 years were diagnosed with atopic dermatitis. Demographic profile, common clinical features, absolute eosinophil count, and total IgE level and their correlation with severity of atopic dermatitis in Eastern Indian children. Out of a total 1829 pediatric patients aged 0 month to 15 years with some pediatric dermatoses, 132 (7.21%) had atopic dermatitis. Of 132 patients, 57 (43.2%) were boys and 75 (56.8%) were girls, with a male to female ratio 1:1.3. Of these 29 were infants and 103 were children. Two (62.1%) patients belonged to rural area whereas 50 (37.9%) belonged to urban area. Personal history, family history (up to third degree relatives), and both personal and family history of atopy were present in 43.18%, 33.34%, and 12.1% of the subjects respectively. Majority (89.4%) of patients had onset before 5 years of age. In infantile Atopic dermatitis (AD), mean age ± SD at onset was 5.2 months ± 3.01 months. In infantile group, 8 (27.6%) had mild, 14 (48.3%) moderate, and 7 (24.1%) had severe atopic dermatitis. Infantile AD had statistically significant higher SCORing Atopic Dermatitis (SCORAD) index score in all three grades of severity of the disease. One hundred and three patients had childhood AD, out of which 40 (38.8%) were boys and 63 (61.2%) were girls, with a male to female ratio 1:1.57. In childhood AD, mean age ± SD at onset of the disease was 3.47 years ± 3.02 years. Sixty three (61.1%) belonged to rural area whereas 40 (38.9%) were from urban area. One hundred and thirty (98%) patients presented with itching. Ninety two (69.7%) patients had high absolute eosinophils count (AEC) with mean ± SD of 1004.1 ± 596.2 (range 325-2510). Eighty seven (65.9%) patients had increased total serum immunoglobulin E (TsIgE) with mean ± SD value of 1127.11 IU/ml ± 731.69 IU/ml (range: 125-2680 IU/ml). Epidemiological data on atopic dermatitis in India are mainly hospital-based, true-point prevalence in community is still scanty. Although the prevalence of AD is considered to be increasing, it still remains low in comparison to developed countries. In Indian children, the disease is relatively milder than children of developed countries. This study identified that both AEC and TsIgE increased significantly in about 66% patient and directly correlated with the severity of the AD.
    03/2014; 5(1):95-100. DOI:10.4103/0976-9668.127296
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    • "The hallmarks of atopic dermatitis (AD), also termed atopic eczema, include chronic, pruritic, relapsing form of skin inflammation, disturbance of epidermal-barrier function that culminates in dry skin, and IgE-mediated sensitization to environmental allergens [1]. AD is considered an entry point of the atopic march, the progression of atopic disorder from AD in infants to allergic rhinitis and finally to asthma in children and adults and underlying atopy is considered the thread linking these disorders [2], [3], [4], [5], [6], [7]. The concept of a progressive atopic march is supported by multiple lines of genetic, epidemiological and experimental evidence. "
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    ABSTRACT: Atopic dermatitis (AD) is the initial step of the atopic march: the progression from AD to allergic rhinitis and asthma. There is a close association between skin barrier abnormalities and the development of AD and the atopic march. One of cardinal features of AD is that the lesional skin of the majority of AD patients is chronically colonized with Staphylococcus aureus with half isolates producing superantigen enterotoxin B (SEB). Although diverse roles of SEB in the pathogenesis and severity of AD have been recognized, whether SEB contributes to the dermal inflammation that drives lung inflammation and airway hyperresponsiveness (AHR) has not been examined. Here we show a novel role of S. aureus superantigen SEB in augmenting allergen ovalbumin (Ova) induced atopic march through an IL-17A dependent mechanism. When mice epicutaneously (EC) sensitized with allergen Ova, addition of topical SEB led to not only augmented systemic Th2 responses but also a markedly exaggerated systemic Th17/IL-17 immune environment. The ability of SEB in enhancing Th17/IL-17 was mediated through stimulating lymphocytes in spleen and draining lymph nodes to promote IL-6 production. Epicutaneous sensitization of mice with a combination of Ova and SEB significantly enhanced Ova-induced AHR and granulocytic lung inflammation than Ova allergen alone. When IL-17A was deleted genetically, the effects of SEB on augmenting lung inflammation and AHR were markedly diminished. These findings suggest that chronic heavy colonization of enterotoxin producing S. aureus in the skin of patients with atopic dermatitis may have an important role in the development of atopic march via an IL-17A dependent mechanism.
    PLoS ONE 07/2012; 7(7):e39032. DOI:10.1371/journal.pone.0039032 · 3.23 Impact Factor
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    • "Many Asian patients would think that western medicine cannot offer a cure, and that topical steroids and associated treatment have significant side effects [13]. These principles all favor the concept that eczema is more like a systemic disease (atopy) with early skin manifestations (dermatitis) than a skin disease with systemic associations [5]. Recent research suggested that neutrophils, lymphocytes, eosinophils, immunoglobulins and complements are all important players in the pathophysiology of eczema [25]. "
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    ABSTRACT: Atopic eczema is a common and distressing disease. This study aims to review PubMed indexed research statistics on atopic eczema over a-10 year period to investigate the clinical relevance and research interest about this disease. PubMed (a service of the U.S. National Library of Medicine) was searched for the terms "atopic dermatitis" and "eczema", with limits activated (Humans, Clinical Trial, Meta-Analysis, Randomized Controlled Trial, English, published in the last 10 years), and editorials, letters, practice guidelines, reviews, and animal studies excluded. Journal impact factor (IF) is in accordance with Journal Citation Report (JCR) 2009, a product of Thomson ISI (Institute for Scientific Information). A total of 890 articles were retrieved. Taking out publications that were irrelevant and those without an impact factor, 729 articles were obtained. These articles were grouped into dermatology (n = 337, mean IF: 3.01), allergy/immunology (n = 215, mean IF: 4.89), pediatrics (n = 118, mean IF: 2.53) and miscellaneous subject categories (n = 142, mean IF: 5.10). The impact factors were highest in the miscellaneous category (p = 0.0001), which includes such prestigious journals as the New England journal of Medicine (n = 1, IF: 47.05), the Lancet (n = 4, IF: 30.76) and BMJ (n = 6, IF: 13.66). There was no publication in any family medicine or general practice journal. The British Journal of Dermatology (n = 78), Pediatric Allergy and Immunology (n = 49) and Journal of Allergy and Clinical Immunology (n = 46) had the highest number of publications on the subject. Atopic eczema ranked higher in impact factors in allergy/immunology although more publications appeared in the dermatology category. Atopic eczema is a multidisciplinary disease. Its clinical relevance and research interests are definitely beyond that of a mere cutaneous disease. Investigators may consider allergy/immunology and miscellaneous journal categories for higher impact of their research.
    Italian Journal of Pediatrics 06/2012; 38(1):26. DOI:10.1186/1824-7288-38-26 · 1.52 Impact Factor
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