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The article discusses anaphylaxis in the consumption of hydrolyzed fish collagen and its effects on patients suffering from atopic dermatitis also reporting the nutritional value of products including moisturizer, gelatin and histamine.

Background Following vaccination with traditional smallpox vaccines or after exposure to vaccinated individuals, subjects with atopic dermatitis (AD) can develop eczema vaccinatum, a severe disease with disseminated eruption of pustular contagious lesions. Alternative smallpox vaccines with an improved safety profile would address this unmet medical need. Methods An open-label controlled Phase I clinical trial was conducted to investigate the safety and immunogenicity of modified vaccinia Ankara (MVA) in 15 healthy subjects compared to 45 subjects with either mild allergic rhinitis, a history of AD or presenting with mild active AD. MVA was given (Week 0 and 4) by a subcutaneous injection during a 28-week observation period. Results No serious adverse event was reported and vaccinations with MVA did not lead to any clinically relevant skin reactions in AD subjects. Unsolicited administration site reactions did not show any trends compared to the healthy subject group. The majority of adverse reactions were mild to moderate, and all reactions were transient and resolved without intervention. The majority of vaccinees had seroconverted by ELISA (80–93%) and PRNT (69–79%) already two weeks after the first vaccination, increasing to 100% after the second immunization, with peak GMT above 1000 and 145 for ELISA and PRNT, respectively. Conclusions MVA was equally well tolerated and immunogenic in all enrolled subjects with mild to moderate pain and redness at the injection site being the most frequent adverse reactions. There were no differences in the safety or immunogenicity profile of MVA in healthy subjects or those with AD or allergic rhinitis. The study has confirmed MVA as a promising smallpox vaccine candidate and demonstrated in a small study population that the vaccine has a similar safety and immunogenicity profile in healthy subjects and people with active AD. Clinical trials registration: NCT00189917 . [ABSTRACT FROM AUTHOR]

Ceramides(Cer) are the central molecules in sphingolipid metabolismthat participate in cellular signaling and also prevent excessivewater loss by the skin. Previous studies showed that sphingosine-basedCer with a long 16C chain (CerNS16) and very long 24C-chain ceramides(CerNS24) differ in their biological actions. Increased levels oflong CerNS16 at the expense of the very long CerNS24 have been foundin atopic dermatitis patients, and this change correlated with theskin barrier properties. To probe the membrane behavior of the longCerNS16 and the very long chain CerNS24, we studied their interactionswith fatty acids and cholesterol in model stratum corneum membranesusing infrared spectroscopy. Using Cer with deuterated acyls and/ordeuterated fatty acids, we showed differences in lipid mixing, packing,and thermotropic phase behavior between long and very long Cer. Thesedifferences were observed in the presence of lignoceric acid or aheterogeneous fatty acid mixture (C16–C24), in the presenceor absence of cholesterol sulfate, and at 5–95% humidity. Inthese membranes, very long CerNS24 prefers an extended (splayed-chain)conformation in which the fatty acid is associated with the very longCer chain. In contrast, the shorter CerNS16 and fatty acids are mostlyphase separated. [ABSTRACT FROM AUTHOR]

Abstract: Among allergic skin diseases, atopic dermatitis is the most difficult to cure. In the majority of patients, atopic dermatitis can be easily controlled by treatment based on three therapeutic approaches: avoidance of precipitating factors, skin care, and medication. In some adult patients, however, severe atopic dermatitis is refractory to treatment, and no fundamental effective treatment modality has yet been established for such cases. Chronic contact dermatitis without an identified causative hapten is also considered an allergic skin disease that is difficult to cure. Topical nucleic acid-based medications are currently being applied clinically, and an ointment containing nuclear factor-κB decoy oligodeoxynucleotides (hereafter referred to as Decoy) has reached clinical trials. In addition, synthetic double-stranded DNA with high affinity for signal transducers and activators of transcription 6 (STAT6) introduced in vivo as a decoy cis element to bind the transcriptional factor and block the activated gene that contributes to the onset and progression of atopic dermatitis functions as an effective therapeutic agent. We also introduce another STAT1 decoy treatment, cytosine-phosphate-guanine-ODN or STAT6 small interfering RNA therapy, for allergic skin diseases. [Copyright &y& Elsevier]

Background Th17/Treg imbalance is involved in several autoimmune, inflammatory and allergic reactions. Nevertheless, the possible contribution of Th17/Treg imbalance in atopic dermatitis (AD) remains unknown. Objective To explore the possible role of Th17/Treg imbalance in AD. Methods Th17 and Treg cells percentage in peripheral blood mononuclear cells (PBMCs) and skin specimens, specific transcription factor retinoic acid-related orphan receptor (ROR)ct and Foxp3 mRNA levels in PBMCs, as well as Th17- and Treg-related cytokines mRNA levels in PBMCs, serum concentrations, and expression levels in PBMCs culture supernatant after recombinant Dermatophagoides pteronyssinus antigen stimulation were detected in AD patients. Controls included patients with psoriasis, allergic contact dermatitis (ACD) and healthy donors. Results Th17 cells percentage, RORγt, IL-17 and IL-23 levels in peripheral circulation of AD patients were significantly higher than those in ACD patients and healthy controls, but lower than those of psoriasis patients. Treg cells percentage, Foxp3 and TGF-β mRNA levels were reduced in AD patients compared with healthy controls, while there were no significant differences among AD, ACD and psoriasis patients. Th17 cells percentage, IL-17 and IL-23 levels were increased, while Treg cells percentage and TGF-β level were decreased in AD lesion and PBMCs culture supernatant respectively. There was a negative association between Th17 and Treg cells percentage in AD patients. AD severity score positively correlated with Th17 cells percentage and Th17/Treg ratio, while negatively correlated with Treg cells percentage. Serum IgE levels positively correlated with Th17/Treg ratio. Conclusion In AD, there exists an immune imbalance in Th17 and Treg cells, which may contribute to its pathogenesis and development. [ABSTRACT FROM AUTHOR]

Histamine is thought to have a critical role in the synthesis of extracellular matrix in skin and may be involved in tissue remodeling of allergic diseases. Recent studies revealed that periostin, a matricelluar protein, contributed to tissue remodeling; however, a link between periostin and histamine remains unproven. We investigated whether periostin was involved in histamine-induced collagen production. Cultured dermal fibroblasts derived from wild-type (WT) or periostin knockout (PN−/−) mice were stimulated with histamine, and then collagen and periostin production was evaluated. Histamine induced collagen gene expression in WT fibroblasts in the late phase but not in the early phase, whereas no effect on collagen expression was observed in histamine-stimulated PN−/− fibroblasts. In WT fibroblasts, histamine directly induced periostin expression in a dose-dependent manner, and an H1 receptor antagonist blocked both periostin and collagen expression. Histamine activated extracellular signal-regulated kinase 1/2 (ERK1/2) through the H1 receptor. Periostin induction was inhibited by either H1 antagonist or ERK1/2 inhibitor treatment in vitro and was attenuated in H1R−/− mice. Elevated expression of periostin was found in lesional skin from atopic dermatitis patients. These results suggest that histamine mediates periostin induction and collagen production through activation of the H1 receptor-mediated ERK1/2 pathway; furthermore, histamine may accelerate the chronicity of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis ( AD) and ichthyosis vulgaris ( IV) are two common disorders of epidermal homeostasis resulting in dry skin. The profilaggrin gene, located on chromosome 1q22, encodes a keratin filament aggregating protein (filaggrin) that is essential to forming the epidermal barrier and maintaining hydration. Null mutations in filaggrin have been found to underlie IV and are common in patients with AD, but the minority of African Americans with AD or IV show these mutations in filaggrin. We have selectively studied African Americans with both AD and IV to maximize the possibility of finding filaggrin null mutations in this population. DNA was collected using buccal swabs from 18 African American children with both AD and IV and 17 African American controls without either of these diseases. Purified genomic DNA was amplified using polymerase chain reaction from three regions of the filaggrin gene, exon 3, including R501X, 2282del4, E2554X, R2447X, 1249insG, R826X, 2767insT, and E2422X. Of the African American children with both AD and IV, 22.2% were heterozygous for filaggrin null mutations. Out of the control group, one carried a null mutation and was later discovered to have a history of asthma. Null mutations found in this population included R501X ( n = 1), 2282del4 ( n = 2), and R826X ( n = 2, including the control patient). Our data demonstrate a prevalence of filaggrin mutations in the African American population that exceeds previously published data, although the overall prevalence is still lower than in other populations. It is likely that factors other than known FLG mutations are involved in African American patients. [ABSTRACT FROM AUTHOR]

Background The successful treatment of atopic eczema ( AE) should result in the improvement of both physical symptoms and patient′s quality of life (QoL). This study was conducted using a sample of dermatologists throughout Germany. This is due to dermatologists being the main health care providers of AE. Objectives Obtaining reliable data on quality of care of AE from both the patient's and the physician's perspective. Methods This cross-sectional study assessed: the individual clinical history; dermatology-specific QoL ( DLQI); state of health ( EQ-5d- VAS); treatments; burden caused by disease and treatment; patient-defined treatment benefit ( PBI). Results Data from 1678 adult patients (60.5% female, mean age: 38.4 ± 15.9) were analysed. The most frequently used treatments during the last five years were emollients (90.4%) and topical corticosteroids (85.5%). In this study, 75.8% of the patients felt only moderately or not at all impaired by their treatment. The mean DLQI (0 = minimum-30 = maximum QoL impairment) was 8.5 ± 6.5. The EQ-5d- VAS (100 = best possible) was 63.6 ± 22.0 on average. 26.6% reported suffering 'often' or 'every night' from sleeplessness due to severe itching. Mean PBI was 2.4 ± 1.1 (4 = maximum benefit). Conclusions This study provides first data on the health care of adults with AE in Germany at a national level and reveals the need for a more effective care. Whereas most patients consider their treatment-related burden as low, the daily burden of the disease seems to be high: one third reports sleeplessness due to itching which indicates insufficient therapeutic regimes in these cases. A better implementation of the German national guideline for AE and a systematic analysis of the difficulties causing its limited effects is needed. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by pruritic and eczematous skin lesions and dermatitis that worsens under stressful conditions. However, the relation of these symptoms to an individual's stress sensitivity is not well understood. On the other hand, expression of the translocator protein (18 kDa) (TSPO), formerly known as the peripheral-type benzodiazepine receptor, has been used as a biological marker of trait anxiety and stress sensitivity. The present study was designed to address this issue by examining TSPO in patients with AD. Fifty-two patients with AD (30 male and 22 female) and 163 healthy volunteers (89 male and 74 female) participated in this study. State-Trait Anxiety Inventory (STAI) scores were significantly higher in patients with AD, especially male patients, than in healthy subjects. The expression of platelet TSPO, as determined with a binding assay with [³H] PK11195, was also significantly higher in patients with AD, indicating that AD is a stress-responsive disease. In genomic analysis using lymphocytes, a singlenucleotide polymorphism of the human TSPO gene at exon 4 (485G>A), which is presumably associated with an individual's stress sensitivity, showed significantly lower frequencies of G/G and higher frequencies of G/A in patients with AD than in healthy subjects. The severity of AD, as determined with the Scoring of Atopic Dermatitis index, was correlated with TSPO expression in male patients with the G/A phenotype. In conclusion, the present study provides new evidence that variation in the TSPO gene affects susceptibility to AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis ( AD) usually begins during infancy. In its classical form infantile AD involves the scalp, the face and the extensor surfaces of the extremities. However, it may present as erythroderma, which should exclude other differential diagnoses including metabolic and immunodeficiency disorders. In the management we have to consider the high ratio of body surface to body weight, which is associated with high absorption of topically applied drugs. Especially in early childhood off-label use is a common practice. This requires intensive educational work with parents. [ABSTRACT FROM AUTHOR]

Abstract: Atopic dermatitis (AD) is a chronic inflammatory disease that seriously affects the quality of life of these patients. Both immune deviations and epidermal barrier deficiency have been defined as pathophysiologic mechanisms in the disease development. The atopic march, or the natural progression form atopic dermatitis in infancy to asthma and allergic rhinitis, is a classic example for the multiorgan involvement in atopy. It has been hypothesized that epidermal barrier impairment is the primary pathologic condition responsible for the atopic march. In recent decades, a growing body of evidence has accumulated that AD can be accompanied by a variety of systemic diseases, such as autoimmune disorders, ophthalmologic involvement, eosinophilic gastroenteritis, inflammatory bowel disease, nephritic syndrome, and metabolic diseases. This contribution reviews these associations and focuses on the possible common underlying mechanisms of AD and the associated syndromes. We present a concept on AD as a multiorgan systemic disease. [Copyright &y& Elsevier]

The purpose of this investigation was to compare the genotypic profiles of Staphylococcus aureus isolated from atopic dermatitis (AD) patients and from control subjects, and to study the relationship between clinical severity, immune response, and genomic pattern of S. aureus isolated from AD patients. We selected 32 patients with AD and S. aureus skin colonization and 31 atopic controls with no history of AD who where asymptomatic carriers of S. aureus. Microarray-based genotyping was performed on S. aureus isolates. In AD patients, clinical severity was assessed using the Scoring Atopic Dermatitis index and total IgE levels and staphylococcal superantigen-specific IgE levels (SEA, SEB, SEC, TSST1) were determined. The genes lukE, lukD, splA, splB, ssl8, and sasG were more frequent in isolates from AD patients. CC30 was more common in isolates from atopic controls than in AD patients. There was a correlation between total IgE and clinical severity, but an association between clinical severity, immune response, and the presence of S. aureus superantigen genes, including enterotoxin genes, could not be demonstrated. Finally, a correlation was found between AD severity and other S. aureus genes, such as sasG and scn. S. aureus factors besides superantigens could be related to the worsening and onset of AD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Staphylococcus aureus (S. aureus) is found on the skin of approximately 90% of patients with atopic dermatitis and approximately 20% of apparently healthy subjects. S. aureus induces keratinocytes and immune cells to secrete immunoregulatory factors that cause epidermal barrier dysfunction in atopic skin. Objective: This study examined factors that cause epidermal permeability barrier dysfunction in skin colonized by S. aureus. Methods: We examined the effect of S. aureus on keratinocyte differentiation in the stratum corneum (SC) of in vivo skin, normal human keratinocytes (NHKs) and a reconstructed human epidermis (RHE) model. The fold change in expression of the terminal differentiation markers and the level of secreted cytokines were investigated. Results: The SC displayed decreased expression of keratin 10 (KRT 10). NHKs treated with S. aureus extracts increased expression of interleukin (IL)-6 and significantly reduced expression of the terminal differentiation markers KRT 1, KRT 10, loricrin (LOR), and filaggrin (FLG); however, the expression of basal layer markers (KRT 5, KRT 14) remained unchanged. Treatment of NHKs with an anti-IL-6 antibody in combination with IL-6 or the S. aureus extracts inhibited the decrease in KRT 10 mRNA or protein expression. After the RHEs were exposed to the S. aureus extracts, KRT 1 and KRT 10 protein levels decreased. Conclusions: These findings suggest that S. aureus inhibits the terminal differentiation of keratinocytes by stimulating IL-6 secretion. [Copyright &y& Elsevier]

Atopic dermatitis (AD) is a frequent and burdensome disease. The objectives of this study were (1) to assess the willingness to pay (WTP) and quality of life (Qol) in AD patients and (2) to compare the results with data on other chronic skin diseases. To collect data, a non-interventional, cross-sectional nationwide postal survey on adult patients with clinically diagnosed AD was performed; socio-demographic data, clinical features/symptoms, WTP and QoL were recorded. WTP was assessed in three different approaches, including relative and absolute figures. Data from n = 384 AD patients (mean age 42.0, range 18-92, 69.8 % female) were analyzed. WTP for complete healing was on median €1,000 (average €11,884) and exceeded WTP in rosacea (median €500) but not in vitiligo (median €3,000). Mean Dermatology Life Quality Index (DLQI) was 8.5 (vitiligo 7.0; psoriasis 6.7; rosacea 4.3) and correlated with pruritus, xerosis and disturbed sleep. WTP and DLQI correlated only marginally ( r = 0.134, p = 0.01). In conclusion, AD patients show high WTP and markedly reduced QoL compared to other chronic skin diseases. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of pimecrolimus cream 1% in the treatment of AD in the pediatric population. Methods: PubMed, EMBASE, Web of Science and Cochrane library databases were searched till July 2013. The randomized and nonrandomized blinded studies of pimecrolimus cream 1% applied twice daily with Jaded score ≥3 in pediatric patients with AD were included. The efficacy outcomes included investigator global assessment (IGA), eczema area and severity index (EASI) scores, pruritus and care giver's assessments and flares free period. Adverse events were reviewed to assess the safety. Results: Out of 81 studies, 7 were selected that enrolled 2,170 pediatric patients. The pooled analysis reported that pimecrolimus was no better to vehicle reducing eczema at day-8, day-26 and six weeks (OR 4.95, 95% CI 2.79–8.80), (OR 9.69, 95% CI 4.12–22.83) and (OR 3.83. 95% CI 1.94–7.56), respectively in children. Similarly, pimecrolimus did not show beneficial effects when analyzed for mild or absent pruritus at day 4 (OR 8.29, 95% CI 3.88–17.72 favoring vehicle), day 43 (OR 1.81 95% CI 1.13–2.89 favoring vehicle) and 1 week (OR 2.29, 95%CI 1.45 to 3.60 favoring vehicle) as compared with vehicle. One study comparing pimecrolimus with tacrolimus found no significant difference in achieving mild or absent pruritus (OR 0.94, 95% CI 0.44–1.99). More patients showed an improvement in overall disease in vehicle group at day 8 (OR 3.30, 95% CI 2.03–5.35), day 29 (OR 14.14, 95% CI 6.87–29.13) and day 43 (OR 4.11, 95% CI 2.59–6.52) as compared with pimecrolimus 1% group, as assessed by caregivers. No significant difference was seen between the total AEs in both groups (pimecrolimus vs vehicle/tacrolimus) (OR 1.19, 95% CI 0.85, 1.65) Conclusion: The results of the present meta-analysis showed that pimecrolimus cream 1% was not significantly better to vehicle for AD in pediatrics population. [ABSTRACT FROM AUTHOR]

ABSTRACT In this study, peptidoglycan (PEG) from Staphylococcus aureus-stimulated, but not muramyldipeptide (MDP)-stimulated, Langerhans cells (LCs) induced a dose-dependent Th2-prone immune response. However, when LCs were stimulated with PEG in combination with MDP, the strength of Th2 immune responses was synergistically augmented by MDP. Furthermore, it was found that production of IL-10, but not of IL-12 p40, by PEG-stimulated LCs was also enhanced in the presence of MDP. These results suggest that MDP enhances Th2 cell development through up-regulation of IL-10 production from PEG-stimulated LCs, increase the importance of S. aureus colonization in patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background/objectives Environmental exposure and personal susceptibility both contribute to the development of hand eczema. In this study, we investigated the effect of loss-of-function mutations in the filaggrin gene ( FLG), atopic dermatitis and wet work exposure on the development of hand eczema in apprentice nurses. Methods Dutch apprentice nurses were genotyped for the four most common FLG mutations; atopic dermatitis and hand eczema history were assessed by questionnaire. Exposure and hand eczema during traineeships were assessed with diary cards. Results The prevalence of hand eczema during traineeships was higher among subjects with a history of hand eczema reported at inclusion. Hand washing during traineeships and at home increased the risk of hand eczema. After adjustment for the effects of exposure and FLG mutations, an odds ratio of 2.5 (90% confidence interval 1.7-3.7) was found for a history of atopic dermatitis. In this study, an increased risk of hand eczema conferred by FLG mutations could not be shown, but subjects with concomitant FLG mutations and atopic dermatitis showed the highest risk of hand eczema during traineeships. Conclusion A history of atopic dermatitis, a history of hand eczema and wet work exposure were the most important factors increasing the risk of hand eczema during traineeships. [ABSTRACT FROM AUTHOR]

Background The Malassezia yeasts which belong to the physiological microflora of human skin have also been implicated in several dermatological disorders, including pityriasis versicolor (PV), atopic dermatitis (AD), and psoriasis (PS). The Malassezia genus has repeatedly been revised and it now accommodates 14 species, all but one being lipid-dependent species. The traditional, phenotype-based identification schemes of Malassezia species are fraught with interpretative ambiguities and inconsistencies, and are thus increasingly being supplemented or replaced by DNA typing methods. The aim of this study was to explore the species composition of Malassezia microflora on the skin of healthy volunteers and patients with AD and PS. Methods Species characterization was performed by conventional, culture-based methods and subsequently molecular techniques: PCR-RFLP and sequencing of the internal transcribed spacer (ITS) 1/2 regions and the D1/D2 domains of the 26S rRNA gene. The Chi-square test and Fisher's exact test were used for statistical analysis. Results Malassezia sympodialis was the predominant species, having been cultured from 29 (82.9%) skin samples collected from 17 out of 18 subjects under the study. Whereas AD patients yielded exclusively M. sympodialis isolates, M. furfur isolates were observed only in PS patients. The isolation of M. sympodialis was statistically more frequent among AD patients and healthy volunteers than among PS patients (P < 0.03). Whether this mirrors any predilection of particular Malassezia species for certain clinical conditions needs to be further evaluated. The overall concordance between phenotypic and molecular methods was quite high (65%), with the discordant results being rather due to the presence of multiple species in a single culture (co-colonization) than true misidentification. All Malassezia isolates were susceptible to cyclopiroxolamine and azole drugs, with M. furfur isolates being somewhat more drug tolerant than other Malassezia species. Conclusions This study provides an important insight into the species composition of Malassezia microbiota in human skin. The predominance of M. sympodialis in both normal and pathologic skin, contrasts with other European countries, reporting M. globosa and M. restricta as the most frequently isolated Malassezia species. [ABSTRACT FROM AUTHOR]

Background IL-33 enhances Fcε RI-induced mediator release in human basophils without inducing degranulation itself. In contrast, studies in mice suggested that in the presence of high Ig E levels, IL-33 triggers degranulation and anaphylaxis of similar severity as specific allergen. Consistent with this view, sera of atopic patients contain elevated levels of IL-33 after anaphylaxis. In this study, we determined whether IL-33 is potentially anaphylactogenic in humans with high Ig E levels by regulating exocytosis independent of Fcε RI cross-linking. Furthermore, we investigated whether IL-33 is released upon allergen provocation in vivo. Methods In subjects with high serum Ig E levels, we measured IL-33-induced histamine/ LTC4 in vitro, CD63 translocation ex vivo, and responsiveness of mast cells in vivo by skin prick test ( SPT). In asthma patients, release of IL-33 and its correlation with early (tryptase)- and late-phase markers ( IL-13 levels, eosinophil numbers) of the allergic response were assessed in bronchoalveolar lavage fluids ( BALFs) after allergen challenge. Results IL-33 itself does not trigger basophil degranulation in vitro and ex vivo, even in subjects with high serum Ig E levels, and negative SPTs demonstrate that skin mast cells do not degranulate in response to IL-33. However, in response to allergen challenge, IL-33 is rapidly released into BALFs at levels that do not correlate with other immediate- and late-phase parameters. Conclusion IL-33 is unlikely an independent trigger of anaphylaxis even in subjects with high Ig E levels. However, the rapid release of IL-33 upon allergen provocation in vivo supports its role as a mediator of immediate allergic responses. [ABSTRACT FROM AUTHOR]

T helper type 9 (Th9) cells are a novel identified subset of CD4+ T helper cells, which could partly contribute to allergic inflammation, while the precise contribution of Th9 cells in atopic dermatitis ( AD) remains unknown. We aimed to explore the possible role of Th9 cells in AD pathogenesis. The Th9 cell percentage, transcription factor PU.1 and cytokine interleukin ( IL)-9 mRNA levels, as well as IL-9 serum concentration in peripheral circulation, were measured in AD patients, psoriasis patients and healthy controls. The Th9 cell percentage, PU.1 and IL-9 expression levels of AD patients were all increased significantly compared with the other two control groups ( P < 0·01), and correlated positively with SCORing Atopic Dermatitis index, serum immunoglobulin ( Ig)E and thymus- and activation-regulated chemokine ( TARC) levels ( P < 0·05). In simple AD patients and AD patients complicated by allergic rhinitis or asthma, there were no significant differences in the Th9 cell percentage, PU.1 and IL-9 expression levels between them. At the same time, IL-9 and vascular endothelial growth factor ( VEGF) mRNA levels were detected in AD lesions and normal skin samples, which were both distinctly elevated in AD lesions, and there was a positive association between them ( P < 0·01). Keratinocytes were cultured with IL-9 stimulation and the secretion of VEGF was detected. IL-9 can promote the secretion of VEGF by keratinocytes in a time- and dose-dependent manner. In conclusion, the expansion of the Th9 cell subset, up-regulation of the PU.1 transcription factor and increased secretion of the IL-9 cytokine may contribute to the pathogenesis of AD, which may be supported by the increased release of VEGF by keratinocyes after IL-9 stimulation. [ABSTRACT FROM AUTHOR]

Omalizumab, a monoclonal antibody targeting Ig E, is an established therapy for severe allergic asthma and has shown efficacy in chronic spontaneous urticaria. Small-scale studies indicated some beneficial effect also in atopic dermatitis ( AD). To evaluate the efficacy of omalizumab in AD and to identify markers associated with treatment response, we conducted a prospective 28-week open-label trial on 20 adults with moderate-to-severe AD. Our results confirm previous observations of a positive response in a subgroup of patients and suggest that responders are characterized by the absence of filaggrin mutations and altered lipid metabolite profiles with high levels of various glycerophospholipids. [ABSTRACT FROM AUTHOR]

Systemic therapy for atopic dermatitis ( AD) is indicated in patients with severe disease refractory to adequate topical treatment. Currently available drugs aim to decrease inflammation by suppressing and/or modulating immune responses and thus may indirectly improve skin barrier function, resulting in a decrease in clinical signs and symptoms in particular pruritus. Before considering systemic treatment, patient adherence to topical treatment including skin care has to be ensured. The selection of the drug depends on the disease severity, localization, complications, concomitant diseases, and age of the patient, but also on their availability and costs as well as the doctor's experience. Bearing in mind the potential risk of resistance, systemic therapy with antibiotics should be exclusively considered in clinically manifest infections such as in children. Here, we review recently published clinical trials and case reports on systemic therapy of pediatric and adult patients with AD to draw conclusions for clinical practice. Although AD is a common disease, controlled clinical studies investigating the efficacy of systemic drugs are scarce, except for cyclosporine, which has been approved for the therapy of severe AD. [ABSTRACT FROM AUTHOR]

Background The most intriguing function attributed to interleukin-31 ( IL-31) is its ability to induce pruritus in pathologic conditions, such as atopic dermatitis ( AD). As of today, this feature of IL-31 was tested in vivo only in animal models. Methods Ten patients with AD and 10 healthy controls were challenged with IL-31 and NaCl (negative control) by skin prick testing. Twenty additional healthy controls were subjected to skin prick testing with histamine. Itch and local inflammatory responses of the skin were assessed for up to 72 h. Results All of the histamine-challenged subjects developed immediate pruritus (i.e. within the first 5 min). In contrast, only one IL-31- and two of the NaCl-challenged subjects reported immediate itch at the provocation site (short lasting, for 2-6 min). Nine subjects (five patients with AD) reported late itch responses to IL-31 challenges with a mean delay of 143 min. No subject reported late itch responses to histamine or NaCl testing. There was no significant difference in IL-31-induced itch start time, duration and intensity between patients with AD and healthy volunteers. Conclusion IL-31 does not induce immediate itch responses in humans. The late onset of IL-31-induced itch supports the notion that IL-31 exerts its pruritic effect indirectly via keratinocytes and secondary mediators, rather than through its receptors on cutaneous nerves. [ABSTRACT FROM AUTHOR]

Background: Filaggrin is expressed in the epidermis and is essential for the maintenance of the epidermal barrier. Null mutations within the filaggrin gene (FLG) lead to a disturbed epidermal barrier and are associated with a significantly increased risk of atopic dermatitis (AD). The association of AD with ocular surface disorders prompted us to speculate that common FLG mutations may be particularly prevalent in AD patients with ocular comorbidities. Methods: Corneal buttons and biopsies from AD patients with ocular involvement (n = 11) and from non-atopic patients (n = 9) with a histological diagnosis of keratitis were included in the study. DNA samples obtained from paraffin-embedded corneal specimens were genotyped for the two most common FLG mutations (R501X and 2282del4). Filaggrin protein expression was analysed by immunohistochemistry. Results: Normal skin and corneal specimens (n = 6) were positive for filaggrin, which could be detected in the stratum corneum of the skin and in the basal epithelial layer of the cornea. Interestingly, all AD corneal specimens as well as the specimens from keratitis patients without AD were negative for filaggrin expression. Genotyping of the FLG mutations R501X and 2282del4 revealed wild-type alleles in all analysed samples. Conclusions: The lack of filaggrin expression observed in the analysed corneal specimens from AD patients is not due to the two most common FLG mutations (R501X, 2282del4) but is most likely secondary to inflammation, as all keratitis specimens of non-AD patients showed lack of filaggrin expression as well. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The beneficial effects of nonpathogenic bacteria are increasingly being recognized. We reported in a placebo-controlled study with atopic dermatitis (AD) patients that cutaneous exposure to lysates of nonpathogenic bacteria alleviates skin inflammation. To now unravel underlying mechanisms, immune consequences of sensing nonpathogenic bacterium Vitreoscilla filiformis lysate (Vf) were characterized analyzing (1) differentiation of dendritic cells (DCs) and, consecutively, (2) effector functions of DCs and T helper (Th) cells in vitro and in a murine model of AD in NC/Nga mice in vivo. Topical treatment with Vf significantly reduced AD-like inflammation in NC/Nga mice. Importantly, cutaneous exposure to Vf in combination with the allergen FITC significantly also reduced subsequent allergen-induced dermatitis indicating active immune modulation. Indeed, innate sensing of Vf predominantly induced IL-10-producing DCs, which was dependent on Toll-like receptor 2 (TLR2) activation. Vf-induced IL-10+ DCs primed naive CD4+ T helper cells to become regulatory IFN-γlow IL-10high Tr1 (type 1 regulatory T) cells. These IL-10high Tr1 cells were also induced by Vf in vivo and strongly suppressed T effector cells and inflammation. In conclusion, we show that innate sensing of nonpathogenic bacteria by TLR2 induces tolerogenic DCs and regulatory Tr1 cells suppressing T effector cells and cutaneous inflammation. These findings indicate a promising therapeutic strategy for inflammatory skin diseases like AD. [ABSTRACT FROM AUTHOR]

Highlights: [•] Pro-inflammatory lipid mediators from LOX and COX pathways are lower in PBMCs of AD patients. [•] Expression of LOX and COX pathway are lower in PBMCs of AD patients. [•] PBMCs counteract the inflammatory status by reducing eicosanoid synthetic pathways. [ABSTRACT FROM AUTHOR]

Background: Pruritus ani (PA) is defined as intense chronic itching affecting perianal skin. Objective: We aimed to determine the efficacy of topical tacrolimus treatment in atopic dermatitis (AD) patients who have PA. Methods: The study included 32 patients with AD who were suffering PA. Patients were randomized into two groups. In total, 16 patients used 0.03% tacrolimus ointment and 16 patients used vaseline as placebo. All groups applied topical treatments to their perianal area twice daily for 4 weeks. The treatments were then reversed for 4 weeks after a 2 weeks wash out period. Results: In total, 32 patients with AD who had refractory anal itching were enrolled in this study. None of the patients had obtained successful results with previous treatments. There was a statistically significant decrease in the recorded EASI, DLQI and itching scores for the tacrolimus group compared to the placebo group at weeks 4 and 6 of treatment ( p < 0.05). Conclusion: Topical tacrolimus treatment was well tolerated and effective in controlling persistent PA in AD patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Atopic dermatitis (AD) is classified into extrinsic AD with high serum IgE levels and impaired barrier, and intrinsic AD with low serum IgE levels and unimpaired barrier. Intrinsic AD has a lower frequency of FLG mutations and a higher frequency of circulating Th1 cells, implying that non-protein antigens, represented by metals, may be an exacerbation factor in intrinsic AD. Objective: To investigate metal allergy in intrinsic AD. Methods: Enrolled in this study were 86 Japanese AD patients seen in three university hospitals, consisting of 55 extrinsic and 31 intrinsic AD patients. Patch testing was performed, focusing on nickel, cobalt, and chrome, in parallel with other 14 metals. FLG mutations were analyzed in 49 patients (extrinsic, 29; intrinsic, 20). In 17 patients (extrinsic, 12; intrinsic, 5), sweat was collected from the forearms by exercise, and the concentration of nickel was fluorometrically measured. Results: Nickel, cobalt, and chrome were the major positive metals. Intrinsic AD showed significantly higher percentages of positive reactions than extrinsic AD to nickel (intrinsic 41.9% vs extrinsic 16.4%, P =0.019) and cobalt (38.7% vs 10.9%, P =0.005). There was no significant difference between FLG mutation-bearing and non-bearing patients. The concentration of nickel was higher in the sweat of intrinsic AD than extrinsic AD patients (333.8 vs 89.4ng/g, P =0.0005) and inversely correlated with serum IgE levels. Conclusions: Nickel and cobalt allergy may be involved in intrinsic AD. Given that the metals are excreted through sweat, intrinsic AD might be exaggerated by highly metal-containing sweat. [Copyright &y& Elsevier]

In atopic dermatitis ( AD), the skin barrier is disturbed, and the expression of calcium-dependent S100 proteins and the calcium gradient is also altered in the epidermis. The calmodulin-like skin protein ( CLSP), which is expressed in the differentiated epidermis, is believed to modulate the function of calcium-dependent proteins involved in barrier formation and is significantly increased in the epidermis of psoriatic patients. We, therefore, investigated the CLSP level in skin biopsies taken from patients with acute exacerbated and non-exacerbated AD as well as from healthy control subjects. Immunohistochemical, Western blot and ELISA analyses showed significant increases ( P < 0.03) in CLSP level in the epidermis from patients with acute exacerbated AD as compared to that from patients with non-exacerbated AD and from control subjects. Such increased expression of CLSP may help re-establish a functional epidermal barrier in acute AD. [ABSTRACT FROM AUTHOR]

The transient receptor potential channel vanilloid subfamily V member 3 ( TRPV3), which functions as a thermosensor in keratinocytes, plays an important role in the development of allergic and itchy dermatitis in rodents. Although real-time PCR analysis using lesional and non-lesional skin samples from patients with atopic dermatitis showed that TRPV3 was expressed in lesional skin, the role that TRPV3 plays in patients with dermatitis is still relatively obscure. Here, we determined whether TRPV3 was a dendritic cell ( DC) modulator using DS-Nh mice with a gain-of-function mutation in TRPV3 ( TRPV3Gly573Ser), because increasing skin temperature is associated with the modulation of dermal dendritic cells ( DCs). Interestingly, increased responses to haptens by skin and DCs were observed in DS- Nh mice compared with those from DS mice with wild-type TRPV3. Increased thymic stromal lymphopoietin ( TSLP) responses were also observed in keratinocytes from DS- Nh mice compared with those from DS mice. Taken together, we propose that the DS- Nh mouse is a good model to use in order to better understand the role of this orphan channel and that TRPV3 may represent a new therapeutic target in certain types of dermatitis through the control of DCs. [ABSTRACT FROM AUTHOR]

Background Photodermatoses are characterized by an abnormal cutaneous response to 'ordinary' light exposure. Aim To study the spectrum of photodermatoses in populations with dark skin (skin types IV- VI) at a tertiary referral centre. Methods Consecutive patients with skin lesions confined to or predominantly located on photoexposed parts of the body and/or with photosensitivity were enrolled in the study, and their clinical details were recorded. Diagnosis was made on clinical grounds, and relevant investigations were carried out if required. Patch and photopatch testing were carried out in patients with chronic actinic dermatitis ( CAD). Selected patients with CAD also underwent phototesting with UV (ultraviolet) A and broadband UVB light. Results We enrolled 362 patients (146 men, 216 women; mean age 35.6 ± 13.6 years), with mean disease duration of 3.4 years. The Fitzpatrick skin types were IV and V (52.8% and 47.2% of patients, respectively). Polymorphic light eruption ( PMLE) was the commonest photodermatosis seen, affecting 59.7% of patients, followed by CAD (13.8%), collagen vascular disorders (7.7%), photoaggravated atopic dermatitis (6.1%), actinic lichen planus ( ALP; 2.2%) and lichen planus pigmentosus ( LPP; 1.6%). The majority (84.5%) of patients were involved in indoor work. Papular PMLE (37%) was the most common variant of PMLE, followed by pinpoint (31%), eczematous (22.2%), lichenoid (5.5%) and plaque-type (4.1%) PMLE. Conclusions The spectrum of photodermatoses in Indian patients with dark skin phototypes ( IV and V), is similar to that reported from other parts of the world. PMLE was the commonest photodermatosis seen, with the pinpoint and lichenoid variants accounting for over one-third of the PMLE cases. ALP and LPP were also not uncommon in our dark-skinned population. [ABSTRACT FROM AUTHOR]

The effects of particulate pollutants on lung function in children with atopic dermatitis (AD) remain to be determined. The authors investigated the short-term effects of ambient particles on peak expiratory flow rate (PEFR) in 84 children with and without AD. Daily particulates less than 10, 2.5, and 1 μm (PM10, PM2.5, and PM1) and number concentrations of submicron particles were measured. The authors observed elevated levels of PM10, PM2.5, and PM1, and accumulation-mode particles were associated with decreased PEFR in children with AD. The PEFR decrements were −2.89 L/min (95% confidence interval [CI], −4.93 to −0.89) for an interquartile-range increase of previous-day PM10, −2.79 L/min (95% CI, −4.89 to −0.69) for PM2.5, and −2.71 L/min (95% CI, −4.81 to −0.61) for PM1. These results suggest that ambient fine particles may affect the pulmonary function in children with AD. The respiratory health of children with atopic skin disorders renders them more vulnerable to ambient particles than healthy subjects. [ABSTRACT FROM AUTHOR]

Background: The fear of using topical corticosteroids, usually called topical corticophobia, is a frequent concern for atopic dermatitis patients and/or their parents. Assessing patients’ atopic dermatitis and their parents’ topical corticosteroid phobia is an essential step to improving adherence to treatment. Because topical corticophobia appears to be a complex phenomenon, its evaluation by binary responses (yes/no) is too simplistic. Thus, a scale is needed, which is capable of identifying the subtleties of topical corticosteroid phobia. Objectives: To develop and validate a scale, TOPICOP©, measuring worries and beliefs about topical corticosteroids among atopic dermatitis outpatients and their parents. Methods: An initial statistical validation of TOPICOP was carried out, collecting qualitative data about patients’ topical corticophobia behaviors and beliefs using focus-group methodology. Then, 208 outpatients or their parents from five French centers completed a self-administered questionnaire built from focus-group results. The scale-development process comprised an explanatory principal component analysis, Cronbach’s α-coefficients and structural equation modeling. Results: The validated questionnaire comprised 12 items, covering two important dimensions relative to “worries” (6 items) and “beliefs” (6 items). Psychometric properties showed that items had very good communality (>0.60) within their own dimension. The final two-factor solution accounted for 47.3% of the variance. Cronbach’s α-coefficients were, respectively, 0.79 and 0.78. Structural equation modeling strongly supported the possibility of calculating a global score. Conclusions: TOPICOP© is the first scale aimed at assessing topical corticophobia in adult patients and parents of children with eczema. TOPICOP® has excellent psychometric properties and should be easy to use in everyday clinical practice for clinicians and researchers. Further studies are needed to confirm our results and validate TOPICOP© in other cultures. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is an inflammatory, chronically relapsing, pruritic skin disease and lesions associated with AD are frequently colonized with Staphylococcus aureus (S. aureus). Activation of T cells by staphylococcal enterotoxins (SE) plays a crucial role in the pathogenesis of AD. Previous studies have demonstrated that lidocaine could attenuate allergen-induced T cell proliferation and cytokine production in peripheral blood mononuclear cells (PBMCs) from asthma patients. The purpose of this study was to investigate the effects of lidocaine on SE-stimulated activation of PBMCs from AD patients. PBMCs were isolated from ten AD patients and stimulated by staphylococcal enterotoxin A (SEA) or staphylococcal enterotoxin B (SEB) in the presence or absence of lidocaine in various concentrations. Cellular proliferation and the release of representative T1- and T2-type cytokines were measured. The effect of lidocaine on filaggrin (FLG) expression in HaCaT cells co-cultured with SE-activated PBMCs was also examined. Our results demonstrated that lidocaine dose-dependently inhibited the proliferative response and the release of IL-4, IL-5, IL-13, TNF-α, and IFN-γ from SEA- and SEB-stimulated PBMCs and also blocked the down-regulation of FLG expression in HaCaT cells co-cultured with SEA- and SEB-activated PBMCs. These results indicate that lidocaine inhibited SEA- and SEB-stimulated activation of PBMCs from patients with AD. Our findings encourage the use of lidocaine in the treatment of AD. [ABSTRACT FROM AUTHOR]

Background: Atopic allergy is among the immune tolerance-related disorders resulting from a failure of the regulatory network. Regulatory T cells (Tregs) play a leading role in the development of homeostasis in the immune system. The aim of this study was to determine the role of Tregs in the pathogenesis of atopic diseases in children by exploring the relationship between Treg frequency, activation markers and the clinical manifestations of the disease. Methods: Twenty allergic and 50 healthy children were enrolled to the study. Peripheral blood mononuclear cells were stained with monoclonal antibodies (anti-CD25-CD4-CD127-FoxP3-CD69-CD71) and evaluated using flow cytometry. Tregs were identified as CD4+CD25+/highFoxP3+CD127- T cells. Results: The percentage of Tregs in allergic patients (2.3%) was significantly decreased in comparison to healthy controls (4.6%, p = 0.003). The frequency of Tregs in patients with symptoms of atopic dermatitis and/or food allergy (1.7%) was significantly lower than in patients without these symptoms (2.9%, p = 0.04). A significant correlation between the percentage of Tregs and the sIgE serum concentration was observed (p = 0.037). Relative fluorescence intensities of FoxP3 expression in allergic patients were higher than in healthy controls (p = 0.00004). The frequency of CD4+CD25highCD127-CD71+ cells did not differ between the groups. Conclusions: Tregs display substantial deficiencies in atopic children, especially in children with multiorgan involvement, compared to patients with single organ manifestations. Additionally, there is an association between Tregs and the sIgE serum concentration. Better identification and characterization of Tregs in allergy is needed as they limit responses to foreign antigens, thereby minimizing T cell-mediated immunopathology in allergic diseases. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. An association between Compositae sensitization and atopic dermatitis has been suggested on the basis of case reports and clinical studies. Objectives. To describe the characteristics of sensitization in Compositae-allergic patients with current and/or past atopic dermatitis. Patients/materials/methods. Consecutive Compositae-sensitive patients were selected for analysis if they had a history of (i) present and/or past atopic dermatitis or (ii) childhood flexural eczema or (iii) childhood eczema of any kind and a positive prick test result. Results. Fifty-one persons (35 females and 16 males) were included. The mean age was lower and the percentage of males was slightly higher than in non-atopics. Testing with sesquiterpene lactone mix, parthenolide and Compositae mix 6% or 5% detected 96% of the patients. Occupational sensitization occurred in 22%. The sensitizing pattern did not differ much from that of non-atopics, except that dandelion was an important allergen in children. Cobalt allergy was the most frequent other contact allergy, occurring in 37%. Conclusions. Persons with current or past atopic dermatitis may become sensitized to Compositae at any age, both occupationally and non-occupationally. They should be screened for Compositae allergy on equal terms with non-atopics, except that dandelion extract should always be tested in children. Co-sensitization to cobalt was frequent, but probably not related to the plant allergy. [ABSTRACT FROM AUTHOR]

Background. Occupational contact dermatitis is frequent, and further understanding of the epidemiology will improve the basis of its prevention. Objectives. To identify occupations at risk for severe occupational contact dermatitis. Methods. The last 1000 cases of severe occupational contact dermatitis seen at our department were identified. Results. The study population comprised 618 females and 382 males. The mean age at onset of irritant contact dermatitis was significantly lower than the mean age at onset of allergic contact dermatitis for both sexes, irrespective of the presence of atopic dermatitis. Females at high riskwere cooks, butchers, beauticians, bakers, and hairdressers, ranging from 23.3 to 96.8 cases per 10 000 workers per year. Males at high risk were painters, cooks, mechanics, locksmiths, and bakers, ranging from 16.5 to 32.3 cases per 10000 workers per year. Conclusions. Occupational contact dermatitis remains frequent, even if only severe cases are considered. It is a concern that no effective, systematic interventions and prevention schemes have been launched in Europe, despite documentation of a significant problem overmany years, and knowledge of risk occupations and risk factors. This study suggests new approaches for general and specific prevention of occupational contact dermatitis. [ABSTRACT FROM AUTHOR]

Pentaherb formula (PHF) has been proven to improve the quality of life of children with atopic dermatitis without side effects. The aim of this study was to elucidate the potential anti-inflammatory and anti-allergic activities of PHF, Moutan Cortex (Danpi/DP) and gallic acid (GA) using human basophils (KU812 cells), which are crucial effector cells in allergic inflammation. PHF, DP and GA could significantly suppress the expression of allergic inflammatory cytokine IL-33-upregulated intercellular adhesion molecule (ICAM)-1, and the release of chemokines CCL2, CCL5, CXCL8 and inflammatory cytokine IL-6 from KU812 cells (all p < 0.05). With the combined use of dexamethasone (0.01 μg/mL) and GA (10 μg/mL), the suppression of ICAM-1 expression and CCL5 and IL-6 release of IL-33-activated KU812 cells were significantly greater than the use of GA alone (all p < 0.05). The suppression of the IL-33-induced activation of intracellular signalling molecules p38 mitogen activated protein kinase, nuclear factor-kB and c-Jun amino-terminal kinase in GA-treated KU812 cells could be the underlying mechanism for the suppression on ICAM-1, chemokines and cytokines. The combined use of dexamethasone with the natural products PHF or DP or GA might therefore enhance the development of a novel therapeutic modality for allergic inflammatory diseases with high potency and fewer side effects. [ABSTRACT FROM AUTHOR]

Purpose: To determine the prevalence and severity of psychological comorbidity in patients with chronic tinnitus in comparison with other chronic illnesses, namely chronic pain, chronic asthma and atopic dermatitis. Methods: Psychological diagnoses were done according to ICD-10 Chapter V(F). Subjective impairment was evaluated using 5 psychometric questionnaires: tinnitus questionnaire, Berlin mood questionnaire, sense of coherence (SOC-L9) and perceived stress questionnaire. Sleep disturbance was measured by the subdomain 'exhaustion' of the Giessen physical complaints inventory. Results: Somatoform or affective disorders were most frequent in all disease groups. Patients with chronic tinnitus had a stronger SOC and better subjective mood, stronger commitment, and less anger and anxious depression than the patients with chronic pain, chronic asthma or atopic dermatitis. However, in patients with higher tinnitus annoyance, psychological comorbidity was similar to that found in patients with other chronic diseases. Conclusions: Besides collecting medical and social history, special psychometric instruments should be used for the diagnosis of tinnitus patients. Based on relative high frequency of psychological comorbidity, we recommend interdisciplinary cooperation between otorhinolaryngologists and other specialists (psychosomatic medicine, psychology or psychiatry) during the treatment of tinnitus patients, especially when high degree of tinnitus annoyance is involved. [ABSTRACT FROM AUTHOR]

Background: Atopic eczema or dermatitis (AD) is associated with atopy and is characterized by reduced skin hydration and an impaired skin barrier in the epidermis. We investigated the patient acceptability and efficacy of an emollient containing ceramide-precursor lipids and moisturizing factors (LMF) in AD. Methods: Consecutive AD patients were recruited. Swabs and cultures were obtained from the right antecubital fossa and the worst-affected eczematous area, and disease severity [according to the SCORing Atopic Dermatitis (SCORAD) Index], skin hydration, and transepidermal water loss (TEWL) were measured prior to and after 2 weeks' use of the LMF moisturizer. The general acceptability of treatment was documented as being 'very good', 'good', 'fair', or 'poor'. Results: Twenty-four AD patients [mean age 13.8 (standard deviation 5.7) years] were recruited. Two thirds of the patients reported very good or good acceptability of the LMF moisturizer, whereas one third reported fair or poor acceptability. There were no inter-group differences in the pre-use clinical parameters of age, objective SCORAD score, pruritus score, sleep disturbance score, skin hydration, TEWL, topical corticosteroid use, oral antihistamine use, or acceptability of previously used proprietary emollients. However, patients in the fair/poor acceptability group were more likely to have Staphylococcus aureus colonization and to be female (odds ratio 13, 95 % confidence interval 1.7-99.4; p = 0.021). Following use of the LMF moisturizer, the objective SCORAD score, pruritus score, and sleep disturbance score were lower in the very good/good acceptability group than in the fair/poor acceptability group. The mean objective SCORAD score improved (from 31.5 to 25.7; p = 0.039) and skin hydration improved [from 30.7 arbitrary units (a.u.) to 36.0 a.u.; p = 0.021] in the very good/good acceptability group. When the data were analyzed for the strength of the agreement of the rating of acceptability, the κ values were 0.338 (fair) for use of body wash and 0.118 (poor) for use of emollients before and after the trial. Conclusion: The LMF moisturizer was considered acceptable by two thirds of the patients with AD. It seems that patients who found the moisturizer acceptable were less likely to be female or to be colonized by S. aureus before switching to the product, and they had less severe eczema, less pruritus, and less sleep disturbance after its use than patients who did not find the product acceptable. Gender and S. aureus colonization may have influenced the patient acceptability and clinical efficacy of the LMF moisturizer. The lack of agreement with regard to the acceptability of the moisturizer implies that there is room for parent/patient education to improve compliance. [ABSTRACT FROM AUTHOR]

Atopic dermatitis ( AD) is a chronic inflammatory skin disease with a large impact on quality of life of the patients and their families. In most cases, the diagnosis of AD can easily be made based on (family) history and clinical examination. If necessary, a practical set of diagnostic criteria such as the UK diagnostic criteria can be used. During the diagnostic phase, it is important to pay attention to atopic comorbidity, such as allergic airway disease (allergic asthma and/or rhinitis), allergic eye disease (atopic (kerato) conjunctivitis) and immediate-type food allergy. This will not have direct consequences for the treatment of AD, but may be important for the overall well-being of the patient. Psychological factors, such as family circumstances, work/school performance and lifestyle factors should also be explored. Severity scoring using properly validated scoring lists may not be necessary for the diagnosis, however, is recommended for monitoring therapy. Simple scoring systems, such as TIS and IGA are easy to perform in daily practice. Several flare factors in AD, such as exposure to irritants or UV light, can be identified by history and clinical examination: in individual cases, additional diagnostic tests may sometimes be useful to confirm clinical suspicion. There is only limited evidence that allergen exposure to aeroallergens and/or food allergens influences AD severity. Therefore, routine allergen testing is not necessary for diagnosis and treatment of AD. The decision to perform allergen tests mainly depends on atopic comorbidity. [ABSTRACT FROM AUTHOR]

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Background Recently, we have reported filaggrin mutations ( FLG) of atopic dermatitis in southern China. However, there have been few detailed reports of FLG mutations of patients with AD in northern China by now. Objectives The present aim was to establish the mutation spectrum of FLG gene in AD patients in northern China. Methods A total of 339 cases met Hanifin and Rajka diagnostic criteria of AD were recruited. A comprehensive sequencing of the entire FLG coding region in these patients was conducted. All detected FLG null mutations were screened in a cohort of 301 normal controls. Results Seven novel mutations (478insA, Q1070X, 4026delT, Q1712X, Q2397X, 7145del4 and 8001del4) and eleven reported mutations (3222del4, 3321delA, 4271delAA, S1515X, Q1790X, 5757del4, 6834del5, Q2417X, E2422X, 7945delA and K4671X) in AD were identified. Mutations 3321delA and K4671X were two of the most common mutations in AD. FLG null mutations were present in 26.0% of AD patients. FLG null alleles (compound genotypes) were significantly higher in AD ( P < 0.001) than in the controls. The compound genotypes for all FLG variants were significantly associated with IV ( P < 0.001) and palmar hyperlinearity ( P < 0.001). The common mutation, K4671X, was significantly associated with AD-coexistent allergic rhinitis ( P = 0.005). Conclusions Our study increases the total number of FLG mutations. We clearly demonstrated that FLG loss-of-function mutations were significantly associated with AD in northern China. The FLG null mutations in the Chinese population differed not only from that in the European population but also from that in sub-populations of Asians outside of the Chinese mainland. [ABSTRACT FROM AUTHOR]

Background Itching is a cardinal symptom of atopic dermatitis (AD). Objective The study aim was to evaluate the relationships between pruritus and stress, health-related quality of life (HRQoL) and depression in adult patients with AD. Methods Eight-nine patients (30 men and 59 women) with AD were included. Demographic and clinical data were collected. The intensity of pruritus was assessed according to the 10-point Visual Analogue Scale (VAS) and the 4-Item Itch Questionnaire, HRQoL according to Dermatology Life Quality Index, and depression symptoms with Beck's Depression Inventory (BDI). Stress experienced by patients was evaluated with Social Readjustment Rating Scale and Stress Self-assessment Scale. Results The mean intensity of pruritus according to VAS was 7.9 ± 2.2 points, and according to 4-Item Itch Questionnaire 14.0 ± 4.4 points. The intensity of pruritus was related to the stress experienced by the patients prior to disease exacerbation (ρ = 0.37, P < 0.001). A significant correlation between pruritus and HRQoL was also found (VAS: ρ = 0.5, P < 0.001, 4-Item Itch Questionnaire: ρ = 0.5, P < 0.001) as well as between pruritus and BDI (VAS: ρ = 0.44, P < 0.001, 4-Item Itch Questionnaire: ρ = 0.51, P < 0.001). Patients with symptoms suggesting depression had more intense pruritus compared with the rest of patients (VAS: 9.1 ± 1.6 vs. 7.6 ± 2.2 points, P = 0.004; 4-Item Itch Questionnaire: 17.3 ± 2.5 vs. 13.1 ± 4.4 points, P < 0.001). Conclusions Itching intensity in AD plays an important role in determining patients' psychosocial well-being. Patients with atopic dermatitis require an effective, long-term antipruritic therapy to improve their QoL and reduce the potential risk of depression. [ABSTRACT FROM AUTHOR]

Orchestrating when and how the cutaneous innate immune system should respond to commensal or pathogenic microbes is a critical function of the epithelium. The cutaneous innate immune system is a key determinant of the physical, chemical, microbial, and immunologic barrier functions of the epidermis. A malfunction in this system can lead to an inadequate host response to a pathogen or a persistent inflammatory state. Atopic dermatitis is the most common inflammatory skin disorder and characterized by abnormalities in both skin barrier structures (stratum corneum and tight junctions), a robust TH2 response to environmental antigens, defects in innate immunity, and an altered microbiome. Many of these abnormalities may occur as the consequence of epidermal dysfunction. The epidermis directly interfaces with the environment and, not surprisingly, expresses many pattern recognition receptors that make it a key player in cutaneous innate immune responses to skin infections and injury. This review will discuss the role epidermal innate receptors play in regulation of skin barriers and, where possible, discuss the relevance of these findings for patients with atopic dermatitis. [Copyright &y& Elsevier]

Introduction: Atopic dermatitis (AD) is a disease that mainly affects the pediatric population involving chronic and repetitive inflammatory skin manifestations. Its evolution is known as atopic march, which is characterized by the occurrence of respiratory and food allergies. Aim: To carry out a classical review of the state-of-the-art scientific literature regarding the effect of probiotics on the treatment of children with AD. Methods: Searches were conducted in Medline and Lilacs through the portals PubMed (http://www.ncbi.nlm. nih.gov/pubmed/) and SciELO (http://www.scielo.br). There was a selection of the available publications in the period from 2001 to 2011, using the keywords atopic dermatitis and probiotics (in English and in Portuguese). Results: After applying the inclusion and exclusion criterias, we selected 12 case-control studies which were conducted in four European countries and Australia. The methodological quality of the studies was assessed according to the STROBE recommendations. Assessment of agreement among researches in classifying the quality of the articles showed excellent agreement (k = 1.00, 95%) with a total of 9 papers at B level. The majority of the studies (75%) indicated a beneficial biological effect of probioties on AD, including protection against infections, enhancement of the immune response, inflammation reduction and changes in gut the flora. The remaining studies showed no beneficial effects according to the outcomes of interest. Conclusion: The majority of the studies in the scientific literature in this review showed improvements in some inflammatory parameters and in intestinal microbiota and not exactly, changes in clinical parameters. However, the biological effects observed in most of them suggest the possibility of benefits of the use of probiotics as an adjunvant in the treatment of AD. [ABSTRACT FROM AUTHOR]

Background: Overproduction of vascular endothelial growth factor (VEGF) in atopic dermatitis (AD) lesions has previously been observed. It is also known that platelet is an important source of VEGF and platelet factor 4 (PF-4), a potential marker of AD severity. Aim: To evaluate concentrations of VEGF and its soluble receptors (sVEGF-R1 and sVEGF-R2) in the plasma of AD patients and to examine its possible correlation with disease severity and plasma concentrations of PF-4, a platelet activation marker. Methods: Plasma concentrations of VEGF and its receptors and levels of PF-4 were measured by an immunoenzymatic assay in 51 AD patients and in 35 healthy non-atopic controls. The severity of the disease was evaluated using the eczema area and severity index. Results: AD patients showed significantly increased VEGF and PF-4 plasma concentrations as compared with the controls. Plasma concentrations of sVEGF-R1 and sVEGF-R2 did not differ between the groups. There were no remarkable correlations between plasma VEGF concentration and disease severity or between VEGF and PF-4 concentration. Conclusions: This study shows that plasma concentration of VEGF may be increased in patients suffering from AD. It seems that plasma VEGF concentration is not a useful marker of disease severity and, apart from platelets, other cells might also release the cytokine. [ABSTRACT FROM AUTHOR]