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Objective: Numerous studies have reported that various environmental factors during early life are key determinants for developing allergic disease. Herein, we aimed to investigate the impact of environmental factors on allergic rhinitis.Methods: This cross-sectional study was conducted in a single university in Japan (from April to June, in 2015 and 2016). Students voluntarily answered online questionnaires regarding their allergic rhinitis symptoms and their exposure to various environmental factors during preschool-age.Results: Overall, 3075 students participated the questionnaire. After excluding those with incomplete datasets, 3016 students were eligible. Of these, 49% had allergic rhinitis symptoms. Female sex was associated with a lower risk of allergic rhinitis symptoms (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.68-0.99). Comorbidity of asthma or atopic dermatitis and a family history of allergy (asthma, atopic dermatitis, or allergic rhinitis) were associated with higher risks of allergic rhinitis symptoms. Regarding the number of household members, compared with subjects with <3 people, those with 5 (OR, 0.74; 95% CI, 0.57-0.97) and ≥6 people (OR, 0.66; 95% CI, 0.49-0.88) in their household showed lower incidences of allergic rhinitis symptoms. No other environmental factors, including birth order, number of siblings, living environment, passive smoking, furry pet ownership, housing, bedding, breastfeeding, dairy product intake, preschool setting, and starting age of preschool, was associated with the incidence of allergic rhinitis symptoms.Conclusion: Sex, current asthma and atopic dermatitis symptoms, family history of allergies, and the number of people in the household at preschool-age were associated with the incidence of allergic rhinitis symptoms. [ABSTRACT FROM AUTHOR]

Abstract: Background: Barrier dysfunction is an important feature of atopic dermatitis (AD) in which IL‐4 and IL‐13, signature type 2 cytokines, are involved. Periostin, a matricellular protein induced by IL‐4 or IL‐13, plays a crucial role in the onset of allergic skin inflammation, including barrier dysfunction. However, it remains elusive how periostin causes barrier dysfunction downstream of the IL‐13 signal. Methods: We systematically identified periostin‐dependent expression profile using DNA microarrays. We then investigated whether IL‐24 downregulates filaggrin expression downstream of the IL‐13 signals and whether IL‐13‐induced IL‐24 expression and IL‐24‐induced downregulation of filaggrin expression are dependent on the JAK/STAT pathway. To build on the significance of in vitro findings, we investigated expression of IL‐24 and activation of STAT3 in mite‐treated mice and in AD patients. Results: We identified IL‐24 as an IL‐13‐induced molecule in a periostin‐dependent manner. Keratinocytes are the main IL‐24‐producing tissue‐resident cells stimulated by IL‐13 in a periostin‐dependent manner via STAT6. IL‐24 significantly downregulated filaggrin expression via STAT3, contributing to barrier dysfunction downstream of the IL‐13/periostin pathway. Wild‐type mite‐treated mice showed significantly enhanced expression of IL‐24 and activation of STAT3 in the epidermis, which disappeared in both STAT6‐deficient and periostin‐deficient mice, suggesting that these events are downstream of both STAT6 and periostin. Moreover, IL‐24 expression was enhanced in the epidermis of skin tissues taken from AD patients. Conclusions: The IL‐13/periostin pathway induces IL‐24 production in keratinocytes, playing an important role in barrier dysfunction in AD. [ABSTRACT FROM AUTHOR]

Summary: Background : JTE‐052 is a novel Janus kinase inhibitor presently under clinical development for the topical treatment of atopic dermatitis (AD). Objectives : To evaluate the efficacy and safety of JTE‐052 ointment in Japanese adult patients with AD. Methods : Patients with moderate‐to‐severe AD were randomized (2: 2: 2: 2: 1: 1) to receive JTE‐052 ointment at 0·25%, 0·5%, 1% or 3%, the vehicle ointment or tacrolimus 0·1% ointment (reference) twice daily for 4 weeks. The primary efficacy end point was the percentage change in modified Eczema Area Severity Index (mEASI) score from baseline at the end of treatment (EOT). Secondary efficacy end points included change from baseline in the pruritus numerical rating scale (NRS) score. Results : In total, 327 patients were enrolled. At EOT, the least‐squares mean percentage changes from baseline in mEASI score for JTE‐052 at 0·25%, 0·5%, 1% and 3% and the vehicle ointment were −41·7%, −57·1%, −54·9%, −72·9% and −12·2%, respectively. All JTE‐052 groups showed significant reductions of mEASI score vs. the vehicle group (P < 0·001 for all). In the tacrolimus group, the mean percentage change in mEASI score was −62·0%. The JTE‐052 groups also showed significant improvement in other parameters; notably, the pruritus NRS score was reduced as early as day 1 night‐time. JTE‐052 ointment at doses up to 3% was safe and well tolerated. Conclusions : Topical JTE‐052 markedly and rapidly improved clinical signs and symptoms in Japanese adult patients with moderate‐to‐severe AD, with a favourable safety profile. The study results indicate that topical JTE‐052 is a promising therapeutic option for AD. The trial registration number is JapicCTI‐152887. [ABSTRACT FROM AUTHOR]

Abstract: Background: Therapeutic patient education is a continuous, systematic, patient‐centered learning process to help patients and their families acquire and maintain the skills they need to manage their lives with a chronic disease. It has been proven effective in increasing treatment adherence and improving quality of life for patients with atopic dermatitis (AD) in Western countries. We introduce the first multicenter, randomized controlled clinical trial of therapeutic patient education in Chinese children with AD. Objectives: To evaluate the effects of therapeutic patient education on the severity of AD, quality of life, and understanding and successful use of emollients in Chinese children with eczema. Methods: We recruited 580 children, ages 2‐14 years, with moderate to severe AD from six hospitals in China. Participants were randomized (1:1) to an intervention (n = 293) or control (n = 249) group. In addition to the severity of AD, data on quality of life and a questionnaire on family and patient knowledge of emollients were evaluated at the 6‐month follow‐up. Results: On study completion, we found that the intervention group showed a significantly greater reduction in mean SCORing Atopic Dermatitis (P < .001) and Infant's Dermatology Life Quality Index (P = .030) scores than the control group. In addition, knowledge about the use of emollients improved significantly in the intervention group. There was no significant difference between groups in Children's Dermatology Life Quality Index scores. Conclusions: The first randomized controlled trial of a therapeutic patient education program in China had positive long‐term effects on decreasing eczema severity and improvement of quality of life in children 2‐4 years of age with AD, as well as in promoting greater understanding of the use of emollients. [ABSTRACT FROM AUTHOR]

Wet wrap therapy ( WWT) consists of topical steroids administered under a layer of wet cotton bandages or garments. Several trials with WWT have reported promising results in atopic dermatitis ( AD). However, no systematic review and meta-analysis on its efficacy and safety has been published. Our objective was to conduct a systematic review of the literature on WWT in AD to assess its efficacy and safety. We included randomized controlled trials among patients of all ages with a diagnosis of AD based on predefined criteria or made by a dermatologist. Electronic searches were performed from 1970 to 30 March 2016 in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase and the World Health Organization International Clinical Trials Registry. Selection of studies and data extraction were performed independently by two researchers, and discrepancies were resolved by consensus. Six trials comparing WWT with topical steroids in children or adults with AD were included. Sample sizes ranged from 19 to 51 patients. Results on clinical severity and quality of life were reported incompletely and proved heterogeneous across studies. A nonsignificant tendency to increased risk of mild skin infections was observed in those treated with WWT (pooled relative risk 6·35, 95% confidence interval 0·83-48·55). The overall grade of quality of evidence for the efficacy and safety outcomes was low. In conclusion, the evidence that WWT is more effective than conventional treatment with topical steroids in AD is of low quality. Further clinical trials should establish the efficacy of WWT in AD. [ABSTRACT FROM AUTHOR]

Adult atopic dermatitis (AD) is associated with overweight, obesity and cardiovascular diseases (CVD) in Americans, similarly to psoriasis, but no increased risk of CVD has been shown in European patients with AD. This study investigated the prevalence and risk of gallstones in adults with AD and in those with psoriasis as a proxy for obesity using nationwide data for all Danish citizens ≥ 30 years of age. Outcome was a diagnosis of gallstones. Odds ratios (ORs) were calculated by logistic regression (cross-sectional study) and hazard ratios (HRs) were estimated by Cox regression (cohort study). The study comprised 6,742 patients with AD, 53,810 patients with psoriasis, and 3,534,164 general population subjects. The prevalence of gallstones was 3.8%, 3.5% and 5.0% in the general population, AD and psoriasis patients, respectively. Adjusted ORs were 0.81 (0.71-0.92) for AD and 1.18 (1.14-1.23) for psoriasis. During follow-up, adjusted HRs were 0.72 (0.56-0.90) for AD and 1.10 (1.02-1.18) for psoriasis. The findings highlight important differences in obesity and lifestyle factors among patients with AD and those with psoriasis. [ABSTRACT FROM AUTHOR]

The aim of this study is the evaluation of the specificity and sensitivity of the skin prick tests (SPTs), specific IgE and atopy patch tests (APTs) in atopic dermatitis patients suffering from food allergy. A total of 301 patients were examined, complete dermatological and allergological examination was performed in all patients. The food allergy was confirmed to peanuts in 62 patients (20%), to egg in 16 patients (5%), to soy in 9 patients (3%), to wheat in 12 patients (4%) and to cow milk in 6 patients (2%). The specificity of SPT, specific IgE and APT is considered as good; the sensitivity of APT is low. The positive results in isolation cannot confirm the food allergy; however, together with other diagnostic methods, such as clinical history and open exposure test, these tests are valuable tool in examination of food allergy. [ABSTRACT FROM AUTHOR]

Background A topic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by skin barrier dysfunction, allergic inflammation and intractable pruritus resistant to conventional antipruritic treatments, including H 1 -antihistamines. Granzymes (Gzms) are a family of serine proteases expressed by cytotoxic T lymphocytes and natural killer cells that have been shown to modulate inflammation. However, the relationship between Gzms and pathology in AD remains unclear. Objective This study assessed the correlation between plasma GzmB levels and severity of pruritus and dermatitis, in AD patients. Methods Plasma was collected from 46 patients with AD, 24 patients with psoriasis, and 30 healthy controls. AD severity was assessed with the scoring atopic dermatitis (SCORAD) index, psoriasis severity with the psoriasis area and severity index (PASI), and degree of pruritus by visual analogue scale (VAS) score. GzmA, GzmB and gastrin releasing peptide (GRP) levels were measured by enzyme-linked immunosorbent assays. Results Plasma GzmB concentrations were significantly higher in patients with AD and psoriasis than in healthy controls. Correlation analyses showed that plasma GzmB concentrations positively correlated with SCORAD and serum levels of severity markers such as thymus and activation-regulated chemokine, and lactate dehydrogenase in AD patients. Moreover, plasma levels of GRP, an itch-related peptide, were higher in patients with AD, positively correlating with VAS score and plasma GzmB level. In addition, plasma GzmB concentration was significantly lower in the treatment group than the untreated group with AD. Meanwhile, there were no correlations among GzmB levels, VAS score and PASI score in patients with psoriasis. In contrast to the results of plasma GzmB, plasma GzmA levels were unchanged among AD, psoriasis and healthy groups, and showed no correlations with VAS score and SCORAD index in patients with AD. Conclusion Plasma GzmB levels may reflect the degree of pruritus and dermatitis in patients with AD. [ABSTRACT FROM AUTHOR]

Introduction: Phosphodiesterase type 4 (PDE4) inhibition is a well-known anti-inflammatory mechanism. However, the clinical use of PDE4 inhibitors has been compromised by the occurrence of mechanism-associated adverse reactions, which often limit the maximum tolerated dose. To minimize systemic exposure, a topically active PDE4 inhibitor with low transdermal bioavailability could be clinically useful. The purpose of this study was to evaluate the efficacy of a novel topical PDE4 inhibitor, E6005, in patients with atopic dermatitis.Methods: This randomized, investigator-blinded, vehicle-controlled, multiple ascending dose study included 40 adult male patients with atopic dermatitis, who were randomly assigned to 10 days of treatment with either E6005 ointment (0.01, 0.03, 0.1 or 0.2%) or vehicle ointment.Results: Of 81 patients screened, 40 who had typical lesions on their posterior trunk were randomized into the study. One patient receiving 0.03% E6005 treatment discontinued because of acute gout and one receiving vehicle treatment discontinued because of progression of atopic dermatitis. The targeted lesion severity scores decreased in a concentration-dependent manner in patients treated with E6005. This drop was significant in the 0.2% E6005 ointment treatment group (mean percent change: −54.30%,p = 0.007).Conclusion: E6005 ointment showed anti-inflammatory efficacy in adult patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Inflammatory cytokines can impair the skin barrier, but the question as to whether barrier alterations affect keratinocyte immune responses remains unanswered. The aim of this study was to investigate whether immune-mediated skin inflammation differs between severe atopic dermatitis patients with or without filaggrin mutation. The levels of filaggrin, inflammatory T helper 2 polarizing cytokines (thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL-33)) and chemokine (C-C motif) ligand 27 (CCL27), histological severity markers, T-cell and dendritic cell counts in biopsies from lesional skin of severe atopic dermatitis patients with and without filaggrin mutation and healthy skin were quantified by immunohistochemistry. The results were confirmed by quantitative PCR analyses. No significant differences were found between the 2 patient groups. Expression of atopic dermatitis-specific cytokines showed significant correlation with histological severity. These findings suggest that the immune-mediated skin inflammation (represented by keratinocyte-derived factors, T-cell and dendritic cell counts) is similar in the 2 patient groups with severe atopic dermatitis, and that immune activation is connected to the severity of the disease rather than to the origin of barrier alterations. [ABSTRACT FROM AUTHOR]

Recent studies have shown that pollen proteins can penetrate the impaired skin barrier of atopic patients and exacerbate their disease. In the presented study the effect of a topically applied barrier-enhancing formulation was investigated for its preventive effect on the uptake of pollen allergens into CD1c+ epidermal cells. The pollen proteins were fluorescence labelled and applied on barrier-disrupted excised human skin. CD1c+ cells were selected after magnetic cell sorting and analysed using laser scanning microscopy. In untreated disrupted skin, 81% of the CD1c+ cells contained the fluorescence-labelled pollen allergens. In formulation-pretreated skin only 12% of the CD1c+ cells showed an uptake of pollen allergens. These results encourage the treatment of atopic patients with barrier-enhancing formulations to reduce the impact of pollen on air-exposed skin areas and hence the exacerbation of cutaneous symptoms. [ABSTRACT FROM AUTHOR]

Atopic dermatitis ( AD) is a distressing dermatological disease, which is highly prevalent during infancy, can persist into later life and requires long-term management with anti-inflammatory compounds. The introduction of the topical calcineurin inhibitors ( TCIs), tacrolimus and pimecrolimus, more than 10 yr ago was a major breakthrough for the topical anti-inflammatory treatment of AD. Pimecrolimus 1% is approved for second-line use in children (≥2 yr old) and adults with mild-to-moderate AD. The age restriction was emphasized in a boxed warning added by the FDA in January 2006, which also highlights the lack of long-term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short- and long-term studies including over 4000 infants (<2 yr old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long-term intermittent use. Unlike topical corticosteroids, long-term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post-marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered. [ABSTRACT FROM AUTHOR]

Background The tight junction (TJ) barrier is located in the granular layer of the epidermis. Filaggrin deficiency predisposes patients to atopic dermatitis (AD) by impairing stratum corneum (SC) barrier function. Altered TJ barrier function has been observed in the skin of patients with AD; however, it remains unclear whether TJ function is influenced by filaggrin deficiency directly or secondarily via skin inflammation. Objective To investigate the in vivo effects of filaggrin deficiency and skin inflammation on epidermal TJ function. Methods Morphological changes in the TJ were investigated in filaggrin knockout mice and mice with hapten-induced dermatitis using en face visualization of epidermal sheets, and functional changes in the TJ were assessed with an in vivo permeation assay using tracers of various sizes. Results In filaggrin knockout mice, there was no apparent change in the honeycomb morphology of the TJ, TJ component mRNA expression, or TJ barrier function in neonates and adults, indicating that filaggrin-deficiency had no direct effects on the TJ. By contrast, in mice with hapten-induced dermatitis, the mRNA expression of TJ components was decreased markedly and the TJ barrier function was size-dependently impaired: the TJ leaked small tracers (<5 kDa), but not large tracers (>30 kDa). Conclusion Filaggrin deficiency did not affect the epidermal TJ barrier directly, but once dermatitis occurred, the skin inflammation induced TJ dysfunction. Since TJ dysfunction induces the SC barrier impairment, skin inflammation will enhance skin permeability to external antigens and result in a vicious cycle of barrier dysfunction and skin inflammation. [ABSTRACT FROM AUTHOR]

Background Data on the epidemiological impact and clinical characteristics of chronic hand eczema in Southern Europe are lacking. Objectives To estimate the prevalence of chronic hand eczema in its different stages of severity and refractoriness to standard therapy in patients accessing Italian dermatological reference centres, and to evaluate sociodemographic and clinical factors associated with each stage. Methods A cross-sectional multicentre study was conducted. Adult patients with hand eczema, consecutively accessing 14 centres over a 6-month period, were enrolled. Patients were classified according to disease duration, severity and response to standard therapy with potent topical corticosteroids. Logistical regression was performed to investigate the relationship between sociodemographic and clinical data with different stages of eczema. Results The total number of participants was 981. Hand eczema was chronic in 83·5% of patients; 21·3% had severe eczema, with 62·0% of these patients refractory to standard therapy. Food processing and related work, the health professions, craft and related trade works (building, plumbing, electrical), hairdressing/beauty and handicraft work were most frequently associated with chronic hand eczema. Severe chronic hand eczema was more likely to be seen in men, older patients and those with less education. Severe and refractory hand eczema was also more likely among the unemployed and patients with allergic rhinitis and/or atopic dermatitis. Conclusions Chronic hand eczema is frequent among patients with hand eczema accessing dermatology centres. Many patients were severe and refractory to standard therapy. The appropriate identification of hand eczema is the first step in implementing effective and efficient treatments. [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]

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 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]

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]

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]

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]

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]

Individuals with one atopic disease are far more likely to develop a second. Approximately half of all atopic dermatitis (AD) patients subsequently develop asthma, particularly those with severe AD. This association, suggesting a role for AD as an entry point for subsequent allergic disease, is a phenomenon known as the 'atopic march.' Although the underlying cause of the atopic march remains unknown, recent evidence suggests a role for the cytokine thymic stromal lymphopoietin (TSLP). We have established a mouse model to determine whether TSLP plays a role in this phenomenon, and in this study show that mice exposed to the antigen ovalbumin (OVA) in the skin in the presence of TSLP develop severe airway inflammation when later challenged with the same antigen in the lung. Interestingly, neither TSLP production in the lung nor circulating TSLP is required to aggravate the asthma that was induced upon subsequent antigen challenge. However, CD4 T cells are required in the challenge phase of the response, as was challenge with the sensitizing antigen, demonstrating that the response was antigen specific. This study, which provides a clean mouse model to study human atopic march, indicates that skin-derived TSLP may represent an important factor that triggers progression from AD to asthma. [ABSTRACT FROM AUTHOR]

Background About 8-10% of the general population in Europe carry a null mutation in the filaggrin gene which is associated with early onset of atopic dermatitis as well as persistence into adulthood. No studies have investigated whether individuals with the homozygous filaggrin null genotype always develop dermatitis. Objectives The aim of this study was to describe the natural history of individuals with no filaggrin expression. Materials Three study populations were included: (i) a random sample of 3335 subjects aged 18-69 years from the general population in Copenhagen who underwent general health examination; (ii) a total of 499 patients seen in our dermatitis clinic since 2009 and who were filaggrin genotyped as a part of the routine diagnostic work up; and (iii) a prospective, longitudinal, birth cohort study of 411 children born to mothers with a history of asthma. Filaggrin genotyping was performed for the 2282del4 and R501X mutations. Results Filaggrin homozygous/compound heterozygous individuals accounted for 0.3% of adults, 3% of dermatitis patients and 0.7% of children. Respectively, one of nine adults and one of three children never experienced dermatitis until now. All hospital patients had atopic dermatitis with onset during (early) childhood. Year-long complete remission was observed in half of patients. Conclusions The natural history of individuals with the filaggrin null genotype is fairly good in the sense that they may not develop dermatitis at all, and if they do, they may experience complete remission. [ABSTRACT FROM AUTHOR]

Severe cases of atopic dermatitis (AD) may require systemic immunosuppression to achieve disease control. Unfortunately, some cases continue to be refractory to management or develop unacceptable adverse effects. There are limited reports of the use of intravenous immunoglobulin (IVIg) in the treatment of severe AD, but results are inconsistent. In a retrospective study, we report 10 children with severe AD refractory to systemic immunosuppression and maximal topical therapy who were treated using IVIg. The children received monthly IVIg for an average of 24 months. This resulted in a significant improvement in symptoms, with fewer infection-related exacerbations and hospitalizations, allowing systemic immunosuppression to be tapered. The effect was associated with a significant decrease in serum immunoglobulin E and was sustained after cessation of IVIg in 50% of cases. No significant side effects attributable to the IVIg infusions were noted. In this cohort of children with severe AD and recurrent cutaneous infections, IVIg provided an effective treatment with minimal side effects and significant benefits in school attendance and quality of life. [ABSTRACT FROM AUTHOR]

Loss-of-function variants within the filaggrin gene (FLG) increase the risk of atopic dermatitis. FLG also demonstrates intragenic copy number variation (CNV), with alleles encoding 10, 11, or 12 filaggrin monomers; hence, CNV may affect the amount of filaggrin expressed in the epidermis. A total of 876 Irish pediatric atopic dermatitis cases were compared with 928 population controls to test the hypothesis that CNV within FLG affects the risk of atopic dermatitis independently of FLG-null mutations. Cases and controls were screened for CNV and common FLG-null mutations. In this population the 11-repeat allele was most prevalent (allele frequency 51.5%); the 10-repeat allele frequency was 33.9% and the 12-repeat allele frequency was 14.6%. Having excluded FLG mutation carriers, the control group had a significantly higher number of repeats than cases (χ2 P=0.043), and the odds ratio of disease was reduced by a factor of 0.88 (95% confidence interval 0.78-0.98, P=0.025) for each additional unit of copy number. Breakdown products of filaggrin were quantified in tape-stripped stratum corneum from 31 atopic dermatitis patients and urocanic acid showed a positive correlation with total copy number. CNV within FLG makes a significant, dose-dependent contribution to atopic dermatitis risk, and therefore treatments to increase filaggrin expression may have therapeutic utility. [ABSTRACT FROM AUTHOR]

We sought to describe the clinical outcomes of eight pediatric patients diagnosed with atopic dermatitis (AD) and hypogammaglobulinemia through retrospective review of medical records. All patients presented with severe facial AD. The mean and median ages of diagnosis of hypogammaglobulinemia were 6.2 months and 6.5 months, respectively, with a mean immunoglobulin G (IgG) level of 156 mg/dL. Seven of the eight patients identified in our search demonstrated simultaneous improvement in AD and serum IgG levels within 2 years of initial presentation, suggesting a diagnosis of transient hypogammaglobulinemia. The remaining patient demonstrated normalization by age 6, but no IgG levels had been measured between initial presentation and age 6. The five patients who were tested for specific antibody response to tetanus and Haemophilus influenzae type b vaccination all produced protective responses. All eight patients initially presented with high serum IgE levels. On initial evaluation, three patients had leukocytosis (white blood cell count >18,000 cells/μL), and six had peripheral blood eosinophilia. Three patients outgrew their AD by age 5, and five had clinically good to excellent control of their AD at their last visit, coincident with normalization of IgG levels. Although severe AD and immunoglobulin deficiency may rarely be associated with complex immunodeficiency disorders, our observations suggest that, with careful immunologic monitoring and diligent skin care, most children who present with severe AD and hypogammaglobulinemia exhibit improvement in dermatitis and serum IgG levels within 2 years of onset without major complications. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common skin disease that has a formidable impact on the quality of life of the suffering individual. By correctly diagnosing and treating AD this situation may be ameliorated. This overview aims to provide practising clinicians with guidelines to achieve optimisation of the management of patients with AD. [ABSTRACT FROM AUTHOR]

Phototherapy has proven to be one of the most versatile and effective treatment options for a variety of inflammatory and pigmentary skin diseases. However, the use of these treatment modalities in patients of color requires some special considerations. The modality chosen, the dosing of the treatment and duration of treatment are all issues to be considered for patients of color treated with ultraviolet phototherapy. In addition, there are some diseases which are more commonly seen in patients of color. These diseases may have better treatment outcomes using newer phototherapeutic options such as the long pulsed Nd:YAG laser or UVA1. As our population in the United States becomes more diverse it would behoove all dermatologists to acquaint themselves with the special circumstances of treating ethnic patients with phototherapy. [ABSTRACT FROM AUTHOR]

Background: Interleukin (IL)-16 has been characterized as an immunomodulatory cytokine. Besides its chemotactic properties, IL-16 amplifies inflammatory processes and possesses immunoregulatory functions. Our aim was to investigate the association between serum IL-16 levels and the degree of allergic sensitization in patients with atopic dermatitis (AD). Methods: The serum level of IL-16 was measured by immunoenzymatic assays. Eosinophil cell count, serum total and specific IgE levels were assessed; prick tests were also carried out. Based on specific IgE levels and prick tests, AD patients were divided into sensitized and nonsensitized subgroups, and correlations among serum IL-16, total IgE levels and eosinophil cell counts were measured in the total patient group and in subgroups. Results: In the total patient group, significantly higher levels of IL-16 were found in the sera of patients with AD, compared to healthy individuals and patients with psoriasis. A significant correlation was detected between serum levels of IL-16 and total IgE, total IgE and eosinophil counts, but not between IL-16 and eosinophils. When sensitized and nonsensitized subgroups were compared, IL-16 levels showed a significant difference in subgroups that were divided based on specific IgE measurements, but not in those subgroups which were divided based on prick tests. On the other hand, serum total IgE levels showed a significant difference between sensitized and nonsensitized subgroups, assessed by the specific IgE method and also by prick test. Conclusion: Serum IL-16 levels of AD patients correlate to some extent with sensitization. This correlation is not as strong as the correlation between total IgE levels and allergic sensitization. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a multifaceted disease resulting from a complex interaction between environmental and genetic factors. Both of these factors can shape skin barrier function and the immunological response of predisposed patients. There is increasing evidence that an impaired skin barrier plays a role in both human and canine AD. Although many primary skin barrier defects had already been documented in the past in humans, the recent identification of the filaggrin mutations and the fact that such mutations are now considered the most important risk factor for development of AD have further emphasized the relevance of epidermal dysfunction in human AD. Much less is known in veterinary medicine, but evidence is rapidly building to support a role for skin barrier dysfunction in canine AD. Canine AD shares many clinical and immunological similarities with its human counterpart. The similar distribution of clinical lesions and the importance of the epicutaneous route of allergen exposure provided the incentive to investigate the role of skin barrier impairments in canine AD. The purpose of this comparative review is to present the current evidence of barrier dysfunction in both human and canine AD. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency could be associated with the prevalence of atopic dermatitis (AD). We carried out a study to see whether deficient/insufficient levels of vitamin D correlate with the severity of atopic skin disease. Using the SCORAD index, we evaluated the severity of disease in 37 children (17 girls and 20 boys) aged between 8 months and 12 years with AD, consecutively enrolled in the study. Serum levels of 25-hydroxyvitamin D [25(OH)D] were determined by a chemiluminescent method. Specific IgE (sIgE) to Staphylococcus aureus enterotoxins and sIgE to Malassezia furfur were assayed by the ImmunoCAP system. and the Pearson correlation test were used for statistical evaluation. We found severe, moderate and mild AD in nine (24%), 13 (35%) and 15 (41%) children, respectively. Mean ± SD serum levels of 25(OH)D were significantly higher ( P < 0·05) in patients with mild disease (36·9 ± 15·7 ng mL) compared with those with moderate (27·5 ± 8·3 ng mL) or severe AD (20·5 ± 5·9 ng mL). The prevalence of patients with sIgE to microbial antigens increased in relation to vitamin D deficiency and AD severity. These data suggest that vitamin D deficiency may be related to the severity of AD and advocate the need for studies evaluating the use of vitamin D as a potential treatment in patients with this disease. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that occurs in persons of all ages but is more common in children. Objective To determine the effect of breast feeding on atopic dermatitis. Methods A descriptive study carried on pediatric patients visiting asthma and allergy center and pediatrics out patient in Tikrit Teaching Hospital from March 2007 to August 2007. This study included 100 patients with AD; 58 cases (58%) were males and 42 cases (42%) were females, they all underwent full history, clinical examination and blood sampling for total WBC count, eosinophil cells count, and total serum IgE. Results Statistical analysis was done by using (ANOVA, Chi-square test). There was significant association between severity of AD according to scorad index (S.I) and type of infant feeding, the mean severity score (S.S) for the breast fed (B.F) children was 21.48±4.96, while the mean S.S for the formula fed (F.F) children was 35.70±9.79, p value = 0.05. There was a significant association between the hematological parameters of disease activity (total serum IgE level, eosinophil count) and type of infants feeding; the mean total serum IgE level for the B.F children was 211±178.7 IU/ml, was lower than mean total serum IgE level for F.F children (638.2±355.8 IU/ml). The mean eosinophil cells count for the B.F children (355.7±193.1) cell/μl was lower than the mean eosinophil cells count for the F.F children (654.8±236.3) cell/μl. Conclusions There is significant association between the type of feeding and the level of hematological parameters (IgE and eosinophil count), and that breast feeding is protective against development of severe AD. [ABSTRACT FROM AUTHOR]

Background: Recently, we found that Staphylococcus aureus produces extracellular vesicles (EV) that contain pathogenic proteins. Although S. aureus infection has been linked with atopic dermatitis (AD), the identities of the causative agents from S. aureus are controversial. We evaluated whether S. aureus-derived EV are causally related to the pathogenesis of AD. Methods: Extracellular vesicles were isolated by the ultracentrifugation of S. aureus culture media. The EV were applied three times per week to tape-stripped mouse skin. Inflammation and immune dysfunction were evaluated 48 h after the final application in hairless mice. Extracellular vesicles-specific IgE levels were measured by ELISA in AD patients and healthy subjects. Results: The in vitro application of S. aureus EV increased the production of proinflammatory mediators (IL-6, thymic stromal lymphopoietin, macrophage inflammatory protein-1α, and eotaxin) by dermal fibroblasts. The in vivo application of S. aureus EV after tape stripping caused epidermal thickening with infiltration of the dermis by mast cells and eosinophils in mice. These changes were associated with the enhanced cutaneous production of IL-4, IL-5, IFN-γ, and IL-17. Interestingly, the serum levels of S. aureus EV-specific IgE were significantly increased in AD patients relative to healthy subjects. Conclusion: These results indicate that S. aureus EV induce AD-like inflammation in the skin and that S. aureus-derived EV are a novel diagnostic and therapeutic target for the control of AD. [ABSTRACT FROM AUTHOR]

Emotional factors and a recurrent psychosomatic environment, have been implicated in the evolution of atopic dermatitis. These, in turn, affect the disease. This study was under taken to evaluate the functioning of families with a child that has atopic dermatitis without skin symptoms and the parents' perceptions of their child's disease. Semi-quantitative and cross-sectional study in which questionnaires were applied: one to study family functioning (Espejel et al. scale) and the second to determine aspects of parental perception of their child's atopic dermatitis. Pearson's correlation was used to analyze the correlation between the categories of the Family Function Scale. The most affected categories of family functioning were authority, handling of disruptive conduct, communication, and negative affect. The most significant positive correlations between the categories of family functioning were: authority and support, =0.867, <.001; disruptive conduct and communication, =0.798, <.001; and support and communication, =0.731, <.001. Of the parents, 66.4% thought that the pharmacotherapy used for their child's atopic dermatitis was not effective, and 33.3% of parents stated that the disease had affected their child's daily activities. In families of children with atopic dermatitis, various family environment factors facilitate the recurrence of symptoms even when no cutaneous lesions have been found on the child. The identification and use of family resources to face this disease are aspects that should be taken into consideration during the psychotherapeutic management of these families, putting emphasis on the most affected functional categories of these families in a strategy that should be implanted in a multi-disciplinary context. [ABSTRACT FROM AUTHOR]

Background: Hanifin and Rajka's criteria (HRC) are the gold standard for the diagnosis of atopic dermatitis (AD). Apart from the age-related distribution and typical morphology of the lesions as defined in one of the major criteria of HRC, patients may also show nontypical morphology and localization. Aim: The aim of this study was to find the frequency of nontypical morphology and localization in Turkish AD patients with onset before the age of 18 years, who were diagnosed according to HRC. Methods: This was a methodological study based on the analysis of patients' data derived from the checklists of HRC and precise clinical documentation of each patient. A total of 321 Turkish patients diagnosed between 1996 and 2004 with the onset of AD before the age of 18 years were allocated to the study group. Results: 49.5% of patients had nontypical localization of AD, the majority being infants or children who had flexural involvement rather than the typical cheek or extremity lesions. Lichenified/exudative eczematous pattern was the most frequent morphologic type (45.5%); however, 54.5% of the patients showed combined or isolated variants, e.g. nummular and seborrheic patterns, in particular. Conclusions: A considerable amount of Turkish patients with AD before the age of 18 years presented with nontypical morphology and/or localization according to their age group. The confirmation of our findings in a multicentric prospective study would further allow a completion and correction of the diagnostic criteria of AD for age groups. [ABSTRACT FROM AUTHOR]

We review the particular characteristics of atopic dermatitis (AD) in adult life, and compare findings with those of AD in childhood. AD affects 1-3% of adults world-wide, and can present as adult-onset AD, or as infantile/childhood AD that persists, or recurs after many years. Eczema in adults usually exists for years, compromising quality of life, sex life and occupational choices. The flexural areas, shoulders, head-and-neck, and hands are typically affected. In elderly adults, eczematous erythroderma is common. The intrinsic (non-IgE-allergic) eczema subtype affects 5-15% of cases. Classical food allergy has a low importance, although non-IgE-mediated and pseudoallergic reactions can cause eczema. Sensitivity to aeroallergens, especially dust mite, is demonstrated in the majority of adult AD patients, including elderly adults, by immunoglobulin E-mediated tests and/or atopy patch tests. Occupational allergic and irritant contact dermatitis is increased. In adults, as in children, Staphylococcus aureus colonization is very high, whereas adult skin is more heavily colonized with Malassezia yeasts. Immediate and delayed sensitization to Malassezia sympodialis is specific for intrinsic and extrinsic AD, occurring especially in head-and-neck eczema. Concerning therapy, older patients are prone to certain adverse drug effects. In conclusion, differences exist between childhood and adult disease. As we should be seeing more adults with AD in the future, there is a need for more clinical and immunological studies in older patients. [ABSTRACT FROM AUTHOR]

Background There is a vast literature describing the association between psoriasis, atopic dermatitis (AD) and psychological distress. Some of these studies were uncontrolled and others used non-dermatological diseases as control, but only a few used chronic skin diseases as controls. Objective To compare well being, psychopathology and coping strategies of psoriatic, AD and healthy controls in a prospective case-control study. Methods Thirty-seven psoriatic patients and 31 AD patients were recruited from the Hadassah Ein Karem Hospital, Jerusalem, Israel, outpatient and inward clinic. The participants in the control group were 31 healthy workers and volunteers with no dermatological diseases from Kaplan Hospital, Rehovot, Israel. We used self-report questionnaires [Mental Health Inventory (MHI) and Adjustment to Chronic Skin Diseases Questionnaire (ACSD)], a projective technique (Hand Test) and assessment tools (Clinical Global Impression). Results Psoriatic patients experienced reduced well being ( P = 0.007) and more anxiety and depression ( P = 0.018) than normal controls. Psoriatic patients also displayed more severe psychopathology ( P = 0.039) a more passive attitude towards life, and loss of meaning in life ( P = 0.001) as measured by the projective technique compared with AD patients and normal controls. Conclusions We propose two explanations, derived from the psychological and the psycho-neuro-immunological domains. First, greater mental distress in psoriasis is because of the greater stigma it bears compared with AD. Alternatively, we hypothesize that the psoriatic inflammatory process may possibly have a direct central nervous system effect. [ABSTRACT FROM AUTHOR]

Background: Filaggrin null (FLG) mutations lead to skin barrier disruption with a reduced resistance towards exogenous agents and also influence the course of disease in atopic dermatitis. Objectives: To examine the association between FLG mutations and contact allergy, polysensitization, hand eczema at first appearance of disease, occurrence, and course of dermatitis. Methods: A venous blood sample from 430 individuals was genotyped for FLG mutations R501X and 2282del4 with polymerase chain reaction followed by typing through hybridization to paramagnetic polystyrene beads and analysis on a BioPlex 200. All individuals had a minimum of one positive patch test reaction. Results: In all, 3.5% were 2282del4 heterozygote and 5.1% were R501X heterozygote. An odds ratio (OR) of 1.49 [95% confidence interval (CI) 0.74–3.00] was found for nickel allergy, OR 0.84 (95% CI 0.41–1.74) for polysensitization, OR 0.78 (95% CI 0.25–2.43) for dermatitis, OR 0.96 (95% CI 0.48–1.92) for hand eczema at debut, OR 1.25 (95% CI 0.99–1.57) for duration of disease, and OR 0.76 (95% CI 0.59–0.97) for age at onset. Conclusions: No association between nickel allergy, polysensitization, hand eczema at first appearance or occurrence of dermatitis, and FLG mutations was found. However, patients with FLG mutations had an earlier age of onset compared with the wild-type genotype and a trend towards longer duration of disease. [ABSTRACT FROM AUTHOR]

Background. B cell-activating factor (BAFF) is a tumour necrosis factor superfamily member best known for its role in the survival and maturation of B cells. BAFF activity is seen in naïve and effector/memory T cells. Aim. To investigate the level and role of BAFF in serum of patients with atopic dermatitis (AD). Methods. Levels of serum BAFF, a proliferation-inducing ligand (APRIL) and total serum IgE level, and total eosinophil count were measured in 245 children. Results. Patients were characterized as having atopic eczema (AE) ( n = 90) or non-AE ( n = 77); the remainder were healthy control subjects ( n = 78). Serum BAFF level in children with AE (1625.04 ± 708.32 pg/mL) was significantly higher than in non-AE children (1194.69 ± 448.44 pg/mL, P < 0.0001) or healthy controls (1062.89 ± 444.74 pg/mL, P < 0.0001). Serum APRIL level was not different between the three groups. Serum BAFF level significantly correlated with total serum IgE level (γ = 0.42, P < 0.0001) and total eosinophil count. It was also positively correlated with serum BAFF and egg-specific IgE level (γ = 0.252, P = 0.045) in AE. Conclusions. Serum BAFF level is high in AE and might be a useful marker for AE. [ABSTRACT FROM AUTHOR]

The true prevalence of allergic contact dermatitis (ACD) in children remains unknown. Our aim was to compare the results of patch tests in children with suspected ACD between two different periods of time and identify possible changes in emerging allergens. We compared contact allergens, gender, age distribution, and personal history of atopic dermatitis (AD), in correlation with the positivity of patch tests, between two equal periods of time (232 children tested during 1980–1993, period A, and 255 children during 1994–2007, period B) in the same region and in the same institution. Patch test positivity was 47.8% in period A, and 60% in period B (p = 0.083). The most common allergens in period A were: nickel sulfate (16.3%), cobalt chloride (8.6%), fragrance mix (7.3%), potassium dichromate (4.3%), and thimerosal only (1.7%). In period B, the allergen distribution was as follows: nickel sulfate (21.56%), thimerosal (18.03%), cobalt chloride (12.9%), potassium dichromate (9.4%), and fragrance mix (4.7%). Girls were more likely to have a positive patch test compared with boys, with reactions in 53% of girls and 39% of boys in period A (p = 0.003), and 61% of girls and 58% of boys in period B (p = 0.691). Twenty-nine per cent of patients with positive results had a personal history of AD in period A and 44% in period B (p = 0.015). Differences in the positivity of allergens between different time periods reflect changes in habits, of allergens exposure or preventive measures. [ABSTRACT FROM AUTHOR]

Background The dermatological becoming of children presenting with atopic dermatitis (AD) is not well known. Objective We performed a study on the presence of AD and other dermatological diseases in subjects with a previous history of AD. Methods An opinion poll was conducted in eight countries through a telephone interview: Belgium, France, Germany, Greece, Italy, Portugal, Spain and Switzerland. Results Among 4369 interviewees, 12.25% declared a history of AD in infancy and 12.4% declared to suffer from a dermatological disease (27% of patients had a history of AD and 10.3% did not have it). Current declared cases of atopic eczema or contact eczema were more frequent in patients with previous history of AD (39.3% vs. 21.5%), whereas these patients appeared less affected by rosacea (2.9% vs. 7.9%). Some differences were observed between different countries. Conclusion The main interests of this study are the large number of subjects, originating from eight different countries, and its focus on the dermatological future of patients with AD, which is not limited to AD itself. [ABSTRACT FROM AUTHOR]

Managing atopic eczema and other dry and itchy skin conditions is a skill required in all nursing specialties. Nurses need to assess and address their patients' skin-care needs. Atopic eczema and all dry and itchy skin conditions require emollient therapy to restore the skin barrier. Nurses are ideally placed to educate patients in the importance of emollient therapy and provide practical information on the individual selection of bath additives, soap substitutes and moisturizers, as well as education on application and self-management. Nurse prescribers will benefit from understanding specific individual patient needs and individual emollient properties to enable them to make informed prescribing decisions and foster patient choice in selecting the best emollient therapy for the individual. This will restore the skin barrier function, reduce itch and suit the patient. [ABSTRACT FROM AUTHOR]

Background Neuropeptides (NPs) may play an important role in the pathogenesis of atopic dermatitis (AD) by regulating immune responses and contributing to the cross-talk between the immune and nervous systems. Objectives To assess the ability of NPs to influence interleukin (IL)-13 and interferon (IFN)-γ production and the expression of the activation marker HLA-DR in skin memory T cells [cutaneous lymphocyte-associated antigen (CLA)+ T cells] from patients with AD with severe, chronic lesions and intense pruritus, and from nonatopic controls. Methods Cells were cultured in the presence and absence of different NPs, calcitonin gene-related peptide (CGRP), somatostatin (SOM) and substance P (SP). IL-13 and IFN-γ production and HLA-DR expression were measured in both CLA+ and CLA− T-cell subsets by flow cytometry. Results CGRP increased IL-13 production in peripheral blood mononuclear cells from patients with AD ( P < 0·05), with no changes detected in the presence of SOM or SP. These patients with AD had a lower expression of CGRP receptor compared with controls ( P < 0·05). Memory T cells incubated with CGRP also showed an increase in IL-13 ( P < 0·05) and HLA-DR ( P < 0·05) in CLA+ T cells from patients with AD compared with controls, but not in CLA− T cells. Patients with a higher production of IL-13 were those with higher total IgE and percentage of skin area involved. Furthermore, the IL-13/IFN-γ ratio was increased in patients with AD after cells were cultured with CGRP ( P < 0·05). Conclusions Our results suggest an immunomodulatory role of CGRP towards a Th2 pattern in CLA+ T cells, which may contribute to exacerbating clinical symptoms in patients with AD. [ABSTRACT FROM AUTHOR]

The filaggrin ( FLG) gene is one of the most widely replicated susceptibility genes for atopic dermatitis (AD) so far. Yet, FLG mutations cannot fully account for the original linkage peak on chromosome 1q21, a region comprising the so-called epidermal differentiation complex (EDC). Since the EDC contains numerous genes relevant for epidermal differentiation, we sought to evaluate variation in other genes located in this region in a German AD case–control cohort. Thirty-two single nucleotide polymorphisms (SNPs) in 21 genes across the EDC were genotyped in 402 unrelated AD patients and 325 non-atopic controls by means of restriction enzyme digestion or TaqMan assays. Allele and genotype frequencies were tested for differences between patients and controls by logistic regression. Haplotype frequencies were evaluated using thefamhap software. Except for the already known association with FLG, we did not identify any additional significant associations of EDC genes with AD. Thus, in this German cohort, there is no evidence that additional genes in the EDC region apart from FLG contribute substantially to AD pathogenesis. [ABSTRACT FROM AUTHOR]

This review considers randomized trials of topical calcineurin inhibitors in atopic dermatitis that have included quality-of-life (QOL) data. Relatively few trials were identified and several different QOL measures have been used, partly because trial subjects included adults, children, and the parents of affected infants. Tacrolimus 0.1% and 0.03% ointment and pimecrolimus 1% cream were found to be superior to vehicle treatment in terms of QOL for active AD. In adults, tacrolimus 0.1% ointment provided a greater improvement in QOL than the 0.03% strength. Pimecrolimus 1% cream was superior to vehicle treatment for flare prevention in the studies that contained QOL outcomes but no data are available for tacrolimus ointment in this regard. QOL data comparing topical calcineurin inhibitors with other active treatments such as topical corticosteroids are sparse and it would be useful for future randomized trials to include QOL measures as a primary outcome. [ABSTRACT FROM AUTHOR]

Abstract: Patients with atopic dermatitis (AD) have significantly reduced plasma cAMP levels, and the cAMP level is correlated with the immunopathogenesis of AD. The production of thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) in keratinocytes is significantly enhanced in patients with AD. In the present study, we investigated the in vitro effects of the adenylyl cyclase-cAMP system on IFN-γ and TNF-α-stimulated production of TARC and MDC in human HaCaT keratinocytes. Both forskolin (a direct activator of adenylyl cyclase) and dibutyryl-cAMP (DBcAMP, a permeable analog of cAMP) suppressed production of TARC and MDC in parallel with the activation of NF-κB in IFN-γ and TNF-α-stimulated HaCaT cells. Moreover, inhibition of NF-κB suppressed TARC and MDC production induced by IFN-γ plus TNF-α. However, dideoxyforskolin, a forskolin derivative that does not activate cAMP, failed to suppress the secretion of these chemokines. An inhibitor of p38 MAPK suppressed the production of TARC and MDC in parallel to the activation of NF-κB in HaCaT cells. Of note, the IFN-γ plus TNF-α-stimulated activation of p38 MAPK was suppressed following incubation with forskolin or DBcAMP alone. These results indicate that the adenylyl cyclase-cAMP system has an inhibitory role in IFN-γ plus TNF-α-stimulated production of TARC and MDC in HaCaT keratinocytes by inhibiting NF-κB activation through p38 MAPK pathway, implying that the adenylyl cyclase-cAMP system could be a candidate therapeutic target of Th2-skewed skin inflammation such as AD. [Copyright &y& Elsevier]

Atopic dermatitis (AD) has been sub-classified into extrinsic and intrinsic types according to the presence or not of allergen-specific IgE antibodies. Although total serum IgE levels are frequently elevated in AD, their potential to predict allergen-specific IgE (asIgE) has rarely been studied. We investigated 103 children with AD and suspected allergen-specific sensitization. A thorough clinical examination, a structured medical history and total serum IgE and asIgE measurements were performed. Fifty-three male and 50 female patients, median age 35 months (range 3 months to 17 years), were recruited. Sixty-three percent of patients were aslgE positive, while 37% did not reveal such IgE antibodies; median total serum IgE levels were 224.0 kU/I (14-12,013 kU/I) and 25.2 kU/I (0-4352 kU/I), respectively. Associations of asIgE status with atopic co-morbidity and total serum IgE levels were statistically significant. At a cut-off total serum IgE level of 106 kU/I (sensitivity 68.7%; specificity 92.3%), positive and negative predicted values (93.6% and 64.3%, respectively) were determined. Clinical decision points predictive of positive asIgE results were identified in 90%, 95% and 99% of patients, respectively. Total serum IgE values were significantly associated with the aslgE status of investigated patients. However, these preliminary data warrant further large-scale investigations before total serum IgE levels can be regarded as a clinically useful parameter between patients with extrinsic atopic dermatitis and intrinsic atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Photosensitivity in atopic dermatitis (AD) is a well known but ill-defined phenomenon. Objectives: To determine the prevalence of photosensitivity in patients with AD, define its clinical characteristics, and analyze the photo provocation test (phototest) results. Methods: A retrospective study of patients with AD who were phototested because of suspected photosensitivity at our department during the period 1994-2004, Results: The total number of patients with AD seen in our department between 1994 and 2004 was 3804, of whom 145 patients (45 men and 100 women) were phototested, Photosensitivity was confirmed in 108 (74%) of these 145 patients (33 men and 75 women). The minimal erythema dose (MED) for UVB was decreased in eight of these 108 patients (7%) and the MED for UVA in five patients (5%). Two major clinical reaction patterns were observed: a polymorphic light eruption-type reaction in 51 patients (47%) and an eczematous reaction in 44 patients (41%). Seventy-two of the 108 patients (67%) had a pathologic reaction to UVA and UVB, 18 patients (17%) were only UVB sensitive, and 18 patients (17%) were only UVA sensitive, Photopatch tests were performed in 125 patients (86%). Twenty-nine patients (23%) had a positive photocontact reaction to one or more substances. Conclusion: Photosensitivity is found in approximately 3% of patients with AD and the majority are female. Photosensitivity in patients with AD consists of two clinical reaction patterns distinguishable by phototesting. Patients were diagnosed with either AD and co-existing polymorphic light eruption or photosensitive AD. [ABSTRACT FROM AUTHOR]

Background: Previous studies have extensively documented antimicrobial and chemotactic activities of beta-defensins. Human beta-defensin-2 (hBD-2) is strongly expressed in lesional psoriatic epidermis, and recently we have shown that high beta-defensin genomic copy number is associated with psoriasis susceptibility. It is not known, however, if biologically and pathophysiologically relevant concentrations of hBD-2 protein are present in vivo, which could support an antimicrobial and proinflammatory role of beta-defensins in lesional psoriatic epidermis. Methodology/Principal Findings: We found that systemic levels of hBD-2 showed a weak but significant correlation with beta defensin copy number in healthy controls but not in psoriasis patients with active disease. In psoriasis patients but not in atopic dermatitis patients, we found high systemic hBD-2 levels that strongly correlated with disease activity as assessed by the PASI score. Our findings suggest that systemic levels in psoriasis are largely determined by secretion from involved skin and not by genomic copy number. Modelling of the in vivo epidermal hBD-2 concentration based on the secretion rate in a reconstructed skin model for psoriatic epidermis provides evidence that epidermal hBD-2 levels in vivo are probably well above the concentrations required for in vitro antimicrobial and chemokine-like effects. Conclusions/Significance: Serum hBD-2 appears to be a useful surrogate marker for disease activity in psoriasis. The discrepancy between hBD-2 levels in psoriasis and atopic dermatitis could explain the well known differences in infection rate between these two diseases. [ABSTRACT FROM AUTHOR]