Donald Y M Leung

..ADEH+ subjects are also more likely to have a history of food allergy or asthma, early onset of AD and a history of other cutaneous infections with Staphylococcus aureus or molluscum contagiosum...

..Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance...

..The basis for increased susceptibility of patients with atopic dermatitis (AD) to develop disseminated viral skin infections such as eczema herpeticum (AD with a history of eczema herpeticum, ADEH(+)) is poorly understood...

..These data indicate that combination IL-2/IL-4 inhibits GCRalpha nuclear translocation in human T cells, and this effect is reversed by IFN-gamma via inhibition of p38 MAPK activation...

..CLINICAL IMPLICATIONS: The atopic immune response contributes to the skin barrier defect in AD; therefore, neutralization of IL-4 and IL-13 could improve skin barrier integrity...

..S100/A11 and p21 gene expression was also found to be significantly lower in acute and chronic AD skin. This study demonstrates an important role for S100/A11 and p21 in regulating skin barrier integrity and the innate immune response...

..The current study demonstrates that Th2 cytokines enhance VV replication in AD skin by subverting the innate immune response against VV in a STAT-6-dependent manner...

..We have demonstrated that expression of S100A11, a calcium-binding protein involved in keratinocyte differentiation, is downregulated in AD...

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..Eczema herpeticum (ADEH) develops in a subset of patients with atopic dermatitis (AD) because of disseminated infection with herpes simplex virus (HSV)...

..The data indicate refractory steroid-induced transactivation but similar steroid-induced transrepression of CD8(+) cells compared with CD4(+) cells caused by decreased levels of the histone acetyltransferase ATF2...

..The cause of corticosteroid-resistant (CR) asthma is unknown...

..These studies suggest that neutralizing the Th2 cytokine milieu in AD skin may augment the innate immune response against bacterial and viral pathogens...

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..There is little knowledge about clinical variables associated with vitamin D (VitD) insufficiency in asthmatic children...

..These data suggest that IL-4 plays an important role in regulating epidermal homeostasis and innate barrier function...

..Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with increased susceptibility to recurrent skin infections...

..We utilized an hypothesis-free cluster analytical approach to define the contribution of obesity and related variables to asthma phenotype...

..These observations could explain the increased susceptibility of AD skin to microorganisms, and suggest a new fundamental rule that may explain the mechanism for frequent infection in other Th2 cytokine-mediated diseases...

..Patients with atopic dermatitis (AD) with a history of eczema herpeticum have increased staphylococcal colonization and infections. However, whether Staphylococcus aureus alters the outcome of skin viral infection has not been determined...

..Previous studies have found specificity protein (Sp) 1 transcription factor in the viral replication machinery and postulated that Sp1 was required for viral replication in host cells...

..Additionally, treatment of AD skin explants with anti-IL-10 augmented the expression of both HBD-2 and LL-37. Thus, increased levels of IL-10 may contribute to the AMP deficiency in both IAD and EAD by reducing cytokines that induce AMP...

..Immune features of infants with food allergy have not been delineated...

..Individuals with atopic dermatitis (AD) have frequent colonization and infection with Staphylococcus aureus. Rapid elimination of S. aureus depends on constitutive synthesis and mobilization of human beta-defensin-3 (HBD-3)...

..Our data suggest that GCRbeta contributes to variation in the GC responses of monocytes versus T cells...

..aureus were exposed to human skin explants. Blocking peptide binding of HBD3 inhibited killing of the bacteria, indicating an essential role for beta-defensin 3 in the constitutive killing of bacteria by normal keratinocytes...

..In conclusion, this study identified the upregulation of MKP-1 by vitamin D as a novel pathway by which vitamin D inhibits LPS-induced p38 activation and cytokine production in monocytes/macrophages...

..Macrophage inflammatory protein 3alpha (MIP-3alpha) is a C-C chemokine expressed by keratinocytes that exhibits antimicrobial activity against bacteria and fungi; however, its role in antiviral innate immunity is unknown...

..Such observations may contribute to a characteristic "signature" for these two skin diseases...

..Cross-talk between glucocorticoid receptors and histone deacetylases (HDACs) under steroid-insensitive conditions has not been explored...

..Patients with asthma exhibit variable response to inhaled corticosteroids (ICS). Vitamin D is hypothesized to exert effects on phenotype and glucocorticoid (GC) response in asthma...

..This study demonstrates cross-talk between estrogen-induced PP5 and GR action. It also reveals that PP5 inhibition may antagonize estrogen-promoted events in response to corticosteroid therapy...

..01). These data support a role for cathelicidins in the inhibition of orthopox virus (vaccinia) replication both in vitro and in vivo. Susceptibility of patients with AD to eczema vaccinatum may be due to a deficiency of cathelicidin...

..New therapeutic approaches to AD, urticaria, and angioedema have been reported including use of probiotics, biologics, vitamin D, and skin barrier creams...

..Glucocorticoids (GCs) are highly effective in the treatment of asthma. However, some individuals have GC-insensitive asthma...

..CLINICAL IMPLICATIONS: Prevention of GITR-L induction on monocytes by SEB may be a novel target for control of inflammation in superantigen-driven diseases such as atopic dermatitis...

..Microbial superantigens induce human T-cell resistance to corticosteroids...

..Our current study suggests that ADM-expressing monocytes that infiltrate the coronary vascular wall may be the cause of coronary dilation in the acute phase of KD...

..The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation...

..The effects of serum vitamin D status on atopy, steroid requirement, and functional responsiveness to corticosteroids in children versus adults with asthma have not been studied systematically...

..Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by a defective skin barrier function. Recent studies have reported mutations of the skin barrier gene encoding filaggrin in a subset of patients with AD...

..This study suggests that Th2 cytokines inhibit expression of LOR and IVL through a STAT-6 dependent mechanism...

..These results indicate that Sp1 expression deficiency leads to abnormally increased KLK protease activity in keratinocytes and may contribute to T(H)2 immune responses in the skin by inducing TSLP...

..Blood tests are needed to identify steroid-resistant (SR) asthmatic patients early so that they can be managed with alternative anti-inflammatory therapy...

..Obesity may alter glucocorticoid response in asthma...

..This suggests that treatment with CSA-13 may be an intervention for individuals with a disseminated VV skin infection...

..Progress in our understanding of the immunology of atopic dermatitis and autoimmune urticaria has also been made. These observations will likely contribute toward optimizing management of these common allergic disorders...

..Steroid-resistant (SR) asthma is characterized by airway inflammation that fails to resolve despite treatment with corticosteroids, raising concerns that resistance to steroid therapy in asthma could lead to airway remodeling...

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..These exciting advances reported in the Journal can improve patient care today and provide insights on how we can improve the diagnosis and treatment of these allergic diseases in the future...

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..New therapeutic approaches to control chronic urticaria have also been identified during the past year...

..Augmentation of the skin barrier with reduction in skin inflammatory responses will likely lead to the most effective intervention in patients with this common skin disease...

..Our current study suggests that TNF inhibits barrier protein expression, and TNF-α antagonists may contribute to clinical improvement in patients with psoriasis by improving barrier protein expression...

..aureus. CONCLUSIONS: A deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S. aureus...

..Understanding these pathomechanisms may improve our current therapies for atopic dermatitis...

..The relationship between sleep quality and disease severity in patients with atopic dermatitis has not been clearly defined...

..New treatment approaches include use of topical steroids as maintenance therapy and use of topical calcineurin inhibitors for early intervention with topical steroids used as rescue therapy...

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..However, after SAg stimulation, Treg cells lose their immunosuppressive activity. These data suggest a novel mechanism by which SAgs could augment T-cell activation in patients with AD...

..New therapeutic approaches to AD, urticaria, and angioedema have been reported, including use of sublingual immunotherapy, anti-IgE, and a kallikrein inhibitor...

..Patients with atopic dermatitis (AD) exposed to the vaccinia virus (VV) smallpox vaccine have an increased risk of developing eczema vaccinatum...

..This review summarizes recent progress in our understanding of the pathophysiology of atopic dermatitis and the implications for new management strategies...

..A multipronged approach directed at healing or protecting the skin barrier and addressing the immune dysregulation is necessary to improve the likelihood of successful outcomes...

..This study demonstrates a novel role for STAT5 in IL-2-induced steroid insensitivity...

..Understanding the events that control suppressive function of nTreg cells will allow manipulation of these cells to inhibit or enhance their functions in the development of novel therapies for autoimmune and allergic diseases...

..Asthma morbidity and mortality is increased in blacks...

..The introduction of a new class of topical anti-inflammatory medications, topical calcineurin inhibitors, has significantly increased our treatment options and led to a rethinking of potential management approaches in atopic dermatitis...

..In addition, IL-15 was found to suppress IgE synthesis (p < 0.01) by the PBMC of AD patients. These data support the concept that reduced IL-15 expression may contribute to the pathogenesis of AD...

..New management approaches have evolved from advances in our understanding of the pathobiology of this common skin disorder...

..However, future studies should further examine the potential role of Vbeta2-stimulatory superantigens (TSST-1 and SPEB/SPEC) in KD...

..This study demonstrates that B cells develop steroid resistance in the presence of CD56(+) cells after IL-15 stimulation. Furthermore, IL-15 and IL-4 have the capacity to induce B cell insensitivity to steroids...

..Lastly, there are new recommendations for patients with convincing insect sting reaction histories but negative skin test responses to venom...

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..The actigraph is an objective, unobtrusive measure of sleep at home in patients with skin disease and can provide an important outcome measure in clinical trials...

..The treatment of these patients requires a systematic approach to rule out underlying conditions that lead to steroid resistance or treatment failure, as well as the use of alternative strategies to inhibit tissue inflammation...

..An increased prevalence of atopic dermatitis has generated increased interest and research into each of these areas, and new treatment strategies are being developed based upon an increased understanding of these issues...

..A multidisciplinary approach is needed to comprehensively evaluate triggers and response to treatment, address confounding factors including sleep disruption, and educate patients and caregivers...

..Furthermore, in such cells GCRalpha is complexed with GCRbeta. Such heterodimer formation may account for the reduced effectiveness of GC action in cells overexpressing GCRbeta...

..The introduction of a new class of topical anti-inflammatory medications, topical calcineurin inhibitors, has significantly increased our treatment options and led to the rethinking of potential management approaches in AD...

..This skin disease is often triggered by bacterial, fungal, or viral skin infections. The mechanisms resulting in this increased propensity for skin infections have been an area of active investigation...