A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: Possible immunological state of the intrinsic type

Kabashima-Kubo, Rieko; Nakamura, Motonobu; Sakabe, Jun‐ichi; Sugita, Kazunari; Hino, Ryosuke; Mori, Tomoko; Miwa, Koichi; Bito, Toshinori; Kabashima, Kenji; Ogasawara, Kunio; Nomura, Yukiko; Nomura, Toshifumi; Akiyama, Masashi; Shimizu, Hiroshi; Tokura, Y.

doi:10.1016/j.jdermsci.2012.04.004

Cited by 93 publications

(83 citation statements)

References 41 publications

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“…Total IgE seems to be more increased in patients with FLG mutations (95). In contrast, a subgroup of children as well as most of the late-onset patients (about 30% of all patients with AD) will never be sensitized although displaying typical eczematous lesions.…”

Section: Total and Specific Igementioning

confidence: 87%

Atopic dermatitis 2.0: from the clinical phenotype to the molecular taxonomy and stratified medicine

Bieber

2012

Allergy

166

125

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Atopic dermatitis (AD) is a paradigmatic inflammatory chronic skin disease. As for other chronic skin diseases, (i) the spectrum of the clinical phenotype and severity as well as (ii) the genetic background and (iii) the underlying mechanisms strongly suggest a high degree of pathophysiological heterogeneity yet leading to a similar clinical pattern, that is, the eczematous skin lesion, but showing distinct progression patterns. This review suggests to exploit the recent knowledge about AD for a novel approach proposing a tentative first molecular taxonomy of this disease based on the genotype and endophenotype. The consequences in terms of personalized prevention and management are delineated.As an evolution of the biomedical research and our genetic and pathophysiological understanding of complex diseases, we are currently experiencing a new trend in the classification of diseases moving from the purely phenotypic definition to a molecular taxonomy. It is expected that in future medicine, every disease will be characterized by three main groups of information: (i) the genotype, including epigenotypic information, (ii) the endophenotype (1) that comprises all available biomarkers (BMs), and (iii) the clinical phenotype (Fig. 1). Among all chronic inflammatory diseases, atopic dermatitis (AD) represents a paradigmatic condition because of its genetic and pathophysiological complexity (2) and finally the result thereof: the wide spectrum of clinical phenotype (3). This wide spectrum includes at one end the very minor forms such as atopic stigmata or simply dry skin with minimal itching and the erythrodermic and most severe form of AD at the other end. Due to the recent progress in the research of genetic, immunologic, and environmental factors (the so-called exposome) leading to AD, we are just starting to understand the complexity of the mechanisms underlying the variety in the clinical phenotype and to make first attempts to link the genotype and endophenotype to distinct clinical forms and courses of this disease such as the atopic march. After exposing a brief update of the clinical phenotype and pathophysiological aspects, this review introduces the concept of molecular taxonomy for AD and the consequences for its future management in the context of stratified or personalized medicine.

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Section: Total and Specific Igementioning

confidence: 87%

Atopic dermatitis 2.0: from the clinical phenotype to the molecular taxonomy and stratified medicine

Bieber

2012

Allergy

166

125

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“…Powszechnie jednak w piśmiennictwie medycznym stosuje się określenie atopic dermatitis. Dzieli się go na 2 podtypy: extrinsic (eAD) (80% przypadków), związany z podwyższonym stężeniem całkowitego IgE, obecnością swoistych przeciwciał IgE skierowanych przeciwko alergenom pokarmowym i/lub powietrznopochodnym i towarzyszącymi chorobami atopowymi dróg oddechowych, oraz podtyp intrinsic (iAD) (20% przypadków), w którym nie stwierdza się opisanych cech [4,5].…”

Section: Wprowadzenieunclassified

“…Nevertheless, they are both universally referred to as "atopic dermatitis" in the medical literature. Two types of AD can be distinguished: extrinsic AD (eAD) (80% of AD cases), associated with increased total IgE levels, presence of specific IgE directed against food and/or aero-allergens, and concomitant atopic diseases affecting the airways; and intrinsic AD (iAD) (20% of AD cases), in which these characteristics are not present [4,5].…”

Section: Introductionmentioning

confidence: 99%

Contact hypersensitivity to nickel in patients with atopic dermatitis

Rożalski¹,

Blicharz²,

Samochocki³

2017

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Atopic dermatitis is a chronic, recurrent inflammatory dermatosis with a complex and not fully explained pathogenesis. Recent years' research points to a significant percentage of patients with atopic eczema in whom hapten patch test results are positive, especially with respect to nickel. These observations undermine suggestions that contact allergy (type IV hypersensitivity) is rare in this group due to the dominance of the Th2-type cellular response characteristic for type I allergic reactions. In this review we aimed to systematize current knowledge regarding the pathomechanisms of contact hypersensitivity to nickel in patients with atopic dermatitis and the potential influence of this hapten on the clinical course of the disease. STRESZCZENIEAtopowe zapalenie skóry jest przewlekłą, nawrotową dermatozą zapalną o złożonej, nie w pełni wyjaśnionej etiopatogenezie. Badania z ostatnich lat wskazują na istotny odsetek chorych na wyprysk atopowy, u których stwierdza się dodatnie wyniki płatkowych testów kontaktowych z haptenami, głównie z niklem. Obserwacje te przeczą sugestii, że w tej grupie pacjentów alergia kontaktowa (IV mechanizm nadwrażliwości) jest rzadkim zjawiskiem ze względu na przewagę odpowiedzi komórkowej typu Th2, typowej dla I mechanizmu nadwraż-liwości. W poniższej pracy autorzy podjęli próbę usystematyzowania dotychczasowej wiedzy o patomechanizmie rozwoju nadwrażliwości kontaktowej na nikiel u chorych na atopowe zapalenie skóry i ewentualnym wpływie tego haptenu na kliniczny przebieg schorzenia.

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“…The intrinsic type has normal tIgE levels, no elevations in allergen-specific IgE, and negative skin-prick tests for common aeroallergens or food allergens [24,25]. The outside-in or barrier hypothesis may be more important in patients with extrinsic AD, who have a higher incidence of FLG mutations, lower frequency of interferon (IFN)-c producing Th1 and IL-17A-producing Th17 cells, but similar levels of Th2 cells in lesional skin (however, in blood, the frequency of Th17 cells appears similar between the intrinsic and extrinsic subtypes) [26,27]. Ultimately, it may be impossible to determine the primary pathology in AD (immune or epithelial), as both processes may be critical for the development of the disease and their relative importance within an individual may explain some of the clinical heterogeneity observed in this disease.…”

Section: Atopic Dermatitis (Ad) Pathogenesismentioning

confidence: 99%

Immunologic Targets in Atopic Dermatitis and Emerging Therapies: An Update

Wang

Beck

2016

Am J Clin Dermatol

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Atopic dermatitis is one of the most common chronic inflammatory skin diseases. It usually begins in childhood, has a considerable impact on patients' quality of life, and incurs substantial healthcare costs. The standard-of-care treatments for patients with moderate to severe disease are very limited and have variable and typically insufficient efficacy and many side effects, some of which are quite serious. However, over the last decade, considerable advances in our understanding of the pathogenesis of atopic dermatitis have paved the way for a number of new treatments. Most notable are the drugs that target the Th2-polarized immune system, which is thought to play a key role in many of the signs and symptoms characteristic of this disease. In this article, we briefly review the pathophysiology of atopic dermatitis, while noting that each patient's disease phenotype is likely due to a unique interplay of several disease-specific dysregulated pathways. Lastly, we cover emerging therapies for atopic dermatitis, focusing on those that target specific components of the immune system, which are altered in atopic dermatitis. The hope is that these new biologics or small-molecule antagonists, which have high specificity for their target molecules, will decrease the undesirable side effects caused by off-target effects commonly observed with current immunosuppressive agents that are characterized by broad biological actions.

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A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: Possible immunological state of the intrinsic type

Cited by 93 publications

References 41 publications

Atopic dermatitis 2.0: from the clinical phenotype to the molecular taxonomy and stratified medicine

Atopic dermatitis 2.0: from the clinical phenotype to the molecular taxonomy and stratified medicine

Contact hypersensitivity to nickel in patients with atopic dermatitis

Immunologic Targets in Atopic Dermatitis and Emerging Therapies: An Update

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