Atopic Dermatitis

Boguniewicz, Mark; Leung, Donald Y.M.

doi:10.1001/archderm.134.7.870

Cited by 31 publications

(25 citation statements)

References 17 publications

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“…This physical barrier is significantly compromised in the skin of AD patients; resulting in increased allergen sensitization, as well as viral and bacterial infections [24,25]. Previous studies have shown that increased penetration of allergens and human pathogens augment the atopic inflammatory response which can exacerbate the disease [6,26].…”

Section: Discussionmentioning

confidence: 99%

Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6

Kim

Leung

Boguniewicz

et al. 2008

Clinical Immunology

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451

206

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Atopic dermatitis (AD) is characterized by a defective skin barrier which allows increased allergen and pathogen penetration. Loricrin (LOR) and involucrin (IVL) are proteins important for skin barrier formation and integrity. In this study, we demonstrate that the gene and protein expression of LOR and IVL is significantly decreased in acute (LOR: p<0.001; IVL: p<0.001) and non-lesional (LOR: p<0.001; IVL: p<0.001) skin of AD subjects, as compared to skin from healthy subjects. Using primary keratinocytes, we further demonstrate the down-regulatory effect of IL-4 and IL-13 -which are over-expressed in the skin of AD patients -on LOR and IVL expression in keratinocytes. Additionally, skin biopsies from signal transducer and activator of transcription (STAT)-6 transgenic mice were deficient in the expression and production of LOR and IVL. This study suggests that Th2 cytokines inhibit expression of LOR and IVL through a STAT-6 dependent mechanism.

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Section: Discussionmentioning

confidence: 99%

Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6

Kim

Leung

Boguniewicz

et al. 2008

Clinical Immunology

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451

206

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“…19 In addition, patients with AD are also susceptible to widespread cutaneous viral infections, including molluscum contagiosum, herpes simplex (Kaposi's varicelliform eruption), and lifethreatening vaccinia. 22 Widespread dermatophytosis (tinea corporis) and Malassezia species infections also occur in AD, and the latter, such as S aureus, can stimulate specific IgE production. 22,23 Taken together, these observations point to loss of a competent antimicrobial barrier in AD.…”

Section: Broad Barrier Failure In Admentioning

confidence: 99%

Basis for the barrier abnormality in atopic dermatitis: Outside-inside-outside pathogenic mechanisms

Elias

Hatano

Williams

2008

Journal of Allergy and Clinical Immunology

412

364

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Until quite recently, the pathogenesis of atopic dermatitis (AD) has been attributed to primary abnormalities of the immune system. Intensive study revealed the key roles played by T H 1/T H 2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling in the evolution of the chronic, pruritic, inflammatory dermatosis that characterizes AD. Accordingly, current therapy has been largely directed toward ameliorating T H 2-mediated inflammation and pruritus. In this review we will assess emerging evidence that inflammation in AD results from inherited and acquired insults to the barrier and the therapeutic implications of this paradigm. KeywordsAntimicrobial peptides; atopic dermatitis; barrier function; barrier repair; cytokines; filaggrin; pH; psychologic stress; Staphylococcus aureus; serine proteases; T H 2 cells Until recently, atopic dermatitis (AD) has been viewed largely as a disease of immunologic etiology. 1-5 Yet, the epidermis generates a set of protective/defensive functions (Table I) mediated by its unique differentiation end product, the stratum corneum (SC). 6,7 These functions include the permeability barrier, which retards transcutaneous evaporative water loss, allowing survival in a potentially desiccating external environment, and an antimicrobial barrier, which simultaneously encourages colonization by nonpathogenic ''normal'' flora while resisting growth of microbial pathogens. 8 Although both a defective epidermal permeability 9-13 and a propensity to secondary infection 14,15 are well-recognized features of AD, these abnormalities have been widely assumed to reflect downstream consequences of a primary immunologic abnormality (the historical inside-outside view of AD pathogenesis). We and others have long proposed that the permeability barrier abnormality inADis not merely an epiphenomenon but rather the ''driver'' of disease activity (ie, the reverse outside-inside view of disease pathogenesis) 16-19 for the following reasons: (1) the extent of the permeability barrier abnormality parallels the severity of the disease phenotype in AD 9,10,12 ; (2) both clinically uninvolved skin sites and skin cleared of inflammation for as long as 5 years continue to display significant barrier abnormalities 10,13 ; (3) emollient therapy comprises effective ancillary therapy 20 ; and most importantly, (4) specific replacement therapy, which targets the NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript prominent lipid abnormalities that account for the barrier abnormality in AD (see below), corrects both the permeability barrier abnormality and comprises effective anti-inflammatory therapy for AD (see the Therapeutic implications section below). BROAD BARRIER FAILURE IN ADLike permeability barrier dysfunction, the antimicrobial barrier is also compromised in patients with AD. Colonization by Staphylococcus aureus is a common feature of AD, 21 and although colonization is highest on lesional skin, colony counts often are high on the clinically no...

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“…16,[48][49][50] Approximately, 90% of AD patients demonstrate the presence of Staphylococcus aureus in the lesions. 51 The Staphylococcal exotoxins can activate skin Langerhans cells and macrophages to produce keratinocyte inflammatory mediators including IL-1 and TNF-α.…”

Section: B Infectious Triggersmentioning

confidence: 99%

Clinical correlations of recent developments in the pathogenesis of atopic dermatitis

Sehra

Tuana

Holbreich

et al. 2008

An. Bras. Dermatol.

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Atopic dermatitis is a chronic inflammatory skin disease with a steadily increasing prevalence affecting 10-20 % of infants and 1-3% of adults globally. It is often the first clinical manifestation of atopic disease preceding asthma and allergic rhinitis. Probably half of the children with atopic dermatitis develop some other form of atopic disease later in life. The pathogenesis involves a complex interplay of factors including genetic predisposition due to altered immune or skin barrier function, interactions with the environment such as food and allergen exposures, and infectious triggers of inflammation. In this review, we summarize the recent advances in understanding the contribution of different factors in the pathophysiology of atopic dermatitis and how insights provide new therapeutic potential for its treatment. Keywords: Asthma; Atopic Dermatitis, Eczema; Eosinophils; Genetics; Immunoglobulin E; Keratinocytes; Rhinitis, T-Lymphocytes Resumo: A dermatite atópica é uma doença cutânea inflamatória crônica cuja prevalência tem aumentado de forma constante, afetando 10-20% dos lactentes e 1-3% dos adultos em todo o mundo. Ela é freqüentemente a primeira manifestação clínica de doença atópica, precedendo a asma e a rinite alérgica. Provavelmente metade das crianças com dermatite atópica desenvolvem alguma

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Atopic Dermatitis

Cited by 31 publications

References 17 publications

Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6

Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6

Basis for the barrier abnormality in atopic dermatitis: Outside-inside-outside pathogenic mechanisms

Clinical correlations of recent developments in the pathogenesis of atopic dermatitis

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