ResearchPad - eczema https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Likely questionnaire-diagnosed food allergy in 78, 890 adults from the northern Netherlands]]> https://www.researchpad.co/article/elastic_article_13854 It is challenging to define likely food allergy (FA) in large populations which limited the number of large studies regarding risk factors for FA.ObjectiveWe studied the prevalence and characteristics of self-reported FA (s-rFA) in the large, population-based Dutch Lifelines cohort and identified associated risk factors.MethodsLikely food allergic cases (LikelyFA) were classified based on questionnaire reported characteristics consistent with FA. Subjects with atypical characteristics were classified as Indeterminate. We investigated 13 potential risk factors for LikelyFA such as birth mode and living on a farm and addressed health-related quality of life (H-RQOL).ResultsOf the 78, 890 subjects, 12.1% had s-rFA of which 4.0% and 8.1% were classified as LikelyFA and Indeterminate, respectively. Younger age, female sex, asthma, eczema and nasal allergy increased the risk of LikelyFA (p-value range <1.00*10−250–1.29*10−7). Living in a small city/large village or suburb during childhood was associated with a higher risk of LikelyFA than living on a farm (p-value = 7.81*10−4 and p = 4.84*10−4, respectively). Subjects classified as Indeterminate more often reported depression and burn-out compared to those without FA (p-value = 1.46*10−4 and p = 8.39*10−13, respectively). No association was found with ethnicity, (duration of) breastfeeding, birth mode and reported eating disorder. Mental and physical component scores measuring H-RQOL were lower in both those classified as LikelyFA and Indeterminate compared to those without FA.ConclusionThe prevalence of s-rFA among adults is considerable and one-third reports characteristics consistent with LikelyFA. Living on a farm decreased the risk of LikelyFA. The association of poorer H-RQOL as well as depression and burn-out with questionable self-perceived FA is striking and a priority for future study. ]]> <![CDATA[Topical antifungals for seborrhoeic dermatitis]]> https://www.researchpad.co/article/Nfc71b64a-3351-42f6-962d-7c7d1405796f

Abstract

Background

Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy.

Objectives

To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults.

A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS.

Search methods

We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials.

Selection criteria

Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life.

Data collection and analysis

Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed‐effect meta‐analysis for studies with low statistical heterogeneity and used a random‐effects model when heterogeneity was high.

Main results

We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies.

Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141), two bifonazole trials (N = 136) and one clotrimazole trial (N = 126) that compared the effectiveness of these treatments versus placebo or vehicle. Nine ketoconazole trials (N = 632) and one miconazole trial (N = 47) compared these treatments versus steroids. Fourteen studies (N = 1541) compared one antifungal versus another or compared different doses or schedules of administration of the same agent versus one another.

Ketoconazole

Topical ketoconazole 2% treatment showed a 31% lower risk of failed clearance of rashes compared with placebo (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.59 to 0.81, eight studies, low‐quality evidence) at four weeks of follow‐up, but the effect on side effects was uncertain because evidence was of very low quality (RR 0.97, 95% CI 0.58 to 1.64, six studies); heterogeneity between studies was substantial (I² = 74%). The median proportion of those who did not have clearance in the placebo groups was 69%.

Ketoconazole treatment resulted in a remission rate similar to that of steroids (RR 1.17, 95% CI 0.95 to 1.44, six studies, low‐quality evidence), but occurrence of side effects was 44% lower in the ketoconazole group than in the steroid group (RR 0.56, 95% CI 0.32 to 0.96, eight studies, moderate‐quality evidence).

Ketoconozale yielded a similar remission failure rate as ciclopirox (RR 1.09, 95% CI 0.95 to 1.26, three studies, low‐quality evidence). Most comparisons between ketoconazole and other antifungals were based on single studies that showed comparability of treatment effects.

Ciclopirox

Ciclopirox 1% led to a lower failed remission rate than placebo at four weeks of follow‐up (RR 0.79, 95% CI 0.67 to 0.94, eight studies, moderate‐quality evidence) with similar rates of side effects (RR 0.9, 95% CI 0.72 to 1.11, four studies, moderate‐quality evidence).

Other antifungals

Clotrimazole and miconazole efficacies were comparable with those of steroids on short‐term assessment in single studies.

Treatment effects on individual symptoms were less clear and were inconsistent, possibly because of difficulties encountered in measuring these symptoms.

Evidence was insufficient to conclude that dose or mode of delivery influenced treatment outcome. Only one study reported on treatment compliance. No study assessed quality of life. One study assessed the maximum rash‐free period but provided insufficient data for analysis. One small study in patients with HIV compared the effect of lithium versus placebo on seborrhoeic dermatitis of the face, but treatment outcomes were similar.

Authors' conclusions

Ketoconazole and ciclopirox are more effective than placebo, but limited evidence suggests that either of these agents is more effective than any other agent within the same class. Very few studies have assessed symptom clearance for longer periods than four weeks. Ketoconazole produced findings similar to those of steroids, but side effects were fewer. Treatment effect on overall quality of life remains unknown. Better outcome measures, studies of better quality and better reporting are all needed to improve the evidence base for antifungals for seborrhoeic dermatitis.

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<![CDATA[A retrospective analysis omalizumab treatment patterns in patients with chronic spontaneous urticaria: a real‐world study in Belgium]]> https://www.researchpad.co/article/N314df29f-596b-4d98-bdd9-59c4606335c2

Abstract

Background

Chronic spontaneous urticaria (CSU) is characterized by the repeated occurrence of persistent hives and/or angioedema for ≥6 weeks, without specific external stimuli. H1‐antihistamines have long been the standard of care of CSU, but many patients remain uncontrolled even at 4× the approved dose. Add‐on therapy with omalizumab has proven effective in clinical trials, but little is known about omalizumab treatment in Belgium.

Objective

To collect real‐world clinical data on omalizumab treatment in adults with CSU in Belgium.

Methods

This was an observational, retrospective chart review of adults with CSU, who initiated omalizumab treatment between August 2014 and December 2016 (maximum 28 months follow‐up).

Results

In total, 235 patients were included (median time from symptom onset to diagnosis, 5.4 months; median time from diagnosis to commencing omalizumab, 6.7 months). Treatments used before/after commencing omalizumab did not always adhere to guidelines; many patients (26.4%/11.1%) received first‐generation H1‐antihistamines, while 20.4% used omalizumab monotherapy after initiating treatment. The mean interval between omalizumab administrations was 4.8 (SD 1.7) weeks; 67.8% of patients had ≥1 interval prolongation and/or shortening. Mean baseline 7‐day Urticaria Activity Score (UAS7) was 32.0 (SD 6.05); this improved to 12.6 (SD 11.2) after 1 month of omalizumab. About 67.2% of patients reached UAS7 ≤ 6 (well controlled) during the study. A total of 87 patients stopped omalizumab and never restarted before the end of the observation period; the most prevalent reason was remission of symptoms (49.4% of patients), followed by lack of effect (12.6%), lost to follow‐up (6.9%) and adverse events (3.4%). Headache was the most common adverse event (n = 8/82). No anaphylaxis was reported.

Conclusions

This study revealed that patients initiated on omalizumab in Belgium had severe CSU at baseline, and showed substantial improvements after 1 month of treatment. Greater adherence to the prescription of guideline‐recommended medications is needed for the treatment of CSU.

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<![CDATA[Real-world utilization patterns of systemic immunosuppressants among US adult patients with atopic dermatitis]]> https://www.researchpad.co/article/5c644930d5eed0c484c2f855

At the time of this study, prior to the introduction of biologics in the US, systemic therapies used for the treatment of moderate-to-severe atopic dermatitis included off-label immunosuppressants and corticosteroids. Immunosuppressant therapy is associated with a substantial risk of side-effects, therefore needing clinical monitoring, and is likely to incur a significant healthcare burden for patients and payers. This retrospective cohort study based on claims data measured immunosuppressant use and its associated burden among US adult patients with atopic dermatitis covered under commercial or Medicare Supplemental insurance from January 01, 2010, to September 30, 2015. Overall, based on age, gender, region, and index year, 4201 control patients with atopic dermatitis without immunosuppressant use were matched with 4204 patients treated with immunosuppressants. The majority (68.5%) of patients using immunosuppressants were non-persistent with immunosuppressant treatment during the 12-month follow-up period after a mean (standard deviation) of 88.1 (70.7) days of immunosuppressant use; 72.3% required systemic steroid rescue treatment. Immunosuppressant users had higher incidence of immunosuppressant-related clinical events than controls; in addition, a larger proportion of immunosuppressant users versus controls developed cancer (0.28% vs 0.14%, respectively; P < 0.0001). Healthcare utilization and costs associated with clinical events and monitoring were also higher for immunosuppressant users compared with controls (total costs, $9516 vs $1630, respectively; P < 0.0001; monitoring costs, $363 vs $54, respectively; P < 0.0001). This study revealed that patients treated with systemic immunosuppressants often require systemic steroids or changes to treatment. The increase in immunosuppressant-related clinical events, including the need for increased monitoring with immunosuppressant treatment, compared with controls demonstrates a substantial treatment burden and highlights the unmet need for more effective long-term therapies for atopic dermatitis with improved safety profiles and reduced monitoring requirements.

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<![CDATA[Allergic rhinitis, atopic dermatitis, and asthma are associated with differences in school performance among Korean adolescents]]> https://www.researchpad.co/article/5989db51ab0ee8fa60bdc2e8

Several studies have reported negative relations between allergic diseases and school performance but have not simultaneously considered various allergic diseases, including allergic rhinitis, asthma, and atopic dermatitis, and only examined a limited number of participants. The present study investigated the associations of allergic rhinitis, asthma, and atopic dermatitis with school performance in a large, representative Korean adolescent population. A total of 299,695 7th through 12th grade students participated in the Korea Youth Risk Behaviour Web-based Survey (KYRBWS) from 2009 to 2013. The subjects’ history of allergic rhinitis, asthma, and atopic dermatitis and number of school absences due to these diseases in the previous 12 months were examined and compared. School performance was classified into 5 levels. The relations between allergic disorders and school performance were analyzed using multiple logistic regressions with complex sampling and adjusted for the subjects’ durations of sleep, days of physical activity, body mass indexes (BMIs), regions of residence, economic levels, parents’ education levels, stress levels, smoking status, and alcohol use. A subgroup analysis of the economic groups was performed. Allergic rhinitis was positively correlated with better school performance in a dose-dependent manner (adjusted odds ratios, AOR, [95% confidence interval, CI] = 1.50 [1.43–1.56 > 1.33 [1.28–1.38] > 1.17 [1.13–1.22] > 1.09 [1.05–1.14] for grades A > B > C > D; P < 0.001). Asthma was negatively correlated with better school performance (AOR [95% CI] = 0.74 [0.66–0.83], 0.87 [0.79–0.96], 0.83 [0.75–0.91], 0.93 [0.85–1.02] for performance A, B, C, and D, respectively; P < 0.001). Atopic dermatitis was not significantly correlated with school performance. The subgroup analysis of the students’ economic levels revealed associations between allergic diseases and school performance. Compared to other allergic disorders, the asthma group had more school absences due to their symptoms (P < 0.001). School performance was positively correlated with allergic rhinitis and negatively correlated with asthma in Korean adolescents, even after adjusting for other variables. The asthma group had an increased number of school absence days, which presumably contributes to these students’ poor school performance.

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<![CDATA[Nitrile versus Latex for Glove Juice Sampling]]> https://www.researchpad.co/article/5989da66ab0ee8fa60b91ffb

The objective of this study was to explore the utility of nitrile gloves as a replacement for latex surgical gloves in recovering bacteria from the hands. Two types of nitrile gloves were compared to latex gloves using the parallel streak method. Streaks of Klebsiella pneumoniae and Staphylococcus aureus were made on tryptic soy agar plates, and the zones of inhibition were measured around pieces of glove material placed on the plates. Latex gloves produced a mean zone of inhibition of 0.28 mm, compared to 0.002 mm for nitrile gloves (p<.001). While the parallel streak method is not intended as a quantitative estimate of antimicrobial properties, these results suggest that nitrile may be a viable alternative to latex in glove juice sampling methods, since nitrile avoids the risk of latex exposure.

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<![CDATA[Genetically Programmed Differences in Epidermal Host Defense between Psoriasis and Atopic Dermatitis Patients]]> https://www.researchpad.co/article/5989da38ab0ee8fa60b870e0

In the past decades, chronic inflammatory diseases such as psoriasis, atopic dermatitis, asthma, Crohn’s disease and celiac disease were generally regarded as immune-mediated conditions involving activated T-cells and proinflammatory cytokines produced by these cells. This paradigm has recently been challenged by the finding that mutations and polymorphisms in epithelium-expressed genes involved in physical barrier function or innate immunity, are risk factors of these conditions. We used a functional genomics approach to analyze cultured keratinocytes from patients with psoriasis or atopic dermatitis and healthy controls. First passage primary cells derived from non-lesional skin were stimulated with pro-inflammatory cytokines, and expression of a panel of 55 genes associated with epidermal differentiation and cutaneous inflammation was measured by quantitative PCR. A subset of these genes was analyzed at the protein level. Using cluster analysis and multivariate analysis of variance we identified groups of genes that were differentially expressed, and could, depending on the stimulus, provide a disease-specific gene expression signature. We found particularly large differences in expression levels of innate immunity genes between keratinocytes from psoriasis patients and atopic dermatitis patients. Our findings indicate that cell-autonomous differences exist between cultured keratinocytes of psoriasis and atopic dermatitis patients, which we interpret to be genetically determined. We hypothesize that polymorphisms of innate immunity genes both with signaling and effector functions are coadapted, each with balancing advantages and disadvantages. In the case of psoriasis, high expression levels of antimicrobial proteins genes putatively confer increased protection against microbial infection, but the biological cost could be a beneficial system gone awry, leading to overt inflammatory disease.

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<![CDATA[Childhood chronic conditions and health-related quality of life: Findings from a large population-based study]]> https://www.researchpad.co/article/5989db5cab0ee8fa60be0269

The objective of this study was to assess the impact of health-related quality of life (HRQOL) across prevalent chronic conditions, individually and comorbid, in school-aged children in the Netherlands. 5301 children aged 4–11 years from the Dutch Health Interview Survey were included. Parents completed questionnaires regarding child and parental characteristics. HRQOL of children was measured using the Child Health Questionnaire Parent Form 28 (CHQ-PF28). Independent-t tests were used to assess differences in the mean scores of the CHQ-PF28 summary scales and profile scales between children with a prevalent chronic condition (excluding or including children with multiple chronic conditions) and children without a chronic condition. Cohen’s effect sizes (d) were calculated to assess the clinical significance of difference. The mean age of children was 7.55 (SD 2.30) years; 50.0% were boys. In children without any chronic condition, the mean score of physical summary scale (PhS) was 58.53 (SD 4.28) and mean score of the psychosocial summary scale (PsS) was 53.86 (SD 5.87). Generally, PhS and/or PsS scores in children with only one condition were lower (p<0.05) than for children without chronic conditions. When children with multiple conditions were included, mean scores of CHQ-PF28 summary and profile scales were generally lower than when they were excluded. The present study shows important information regarding the impact of prevalent chronic conditions on HRQOL in a representative population-based sample of school-aged children in the Netherlands. The information could be used for developing a more holistic approach to patient care and a surveillance framework for health promotion.

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<![CDATA[Plasma Lipid Profiling of Patients with Chronic Ocular Complications Caused by Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis]]> https://www.researchpad.co/article/5989da49ab0ee8fa60b8c760

Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are drug-induced acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface. Even after recovery from skin symptoms, some SJS/TEN patients continue to suffer with severe ocular complications (SOCs). Therefore, this study aims to understand the pathophysiology of chronic SOCs. Because plasma lipid profiling has emerged as a useful tool to understand pathophysiological alterations in the body, we performed plasma lipid profiling of 17 patients who suffered from SJS/TEN-associated chronic SOCs. A lipidomics approach yielded 386 lipid molecules and demonstrated that plasma levels of inflammatory oxylipins increased in patients with SJS/TEN-associated chronic SOCs. In addition, oxidized phosphatidylcholines and ether-type diacylglycerols increased in the patients with chronic SOCs, while phosphoglycerolipids decreased. When we compared these lipidomic profiles with those of patients with atopic dermatitis, we found that patients with chronic SOCs, specifically, had decreased levels of ether-type phosphatidylcholines (ePCs) containing arachidonic acid (AA), such as PC(18:0e/20:4) and PC(20:0e/20:4). To confirm our finding, we recruited additional patients, who suffered from SOC associated with SJS/TEN (up to 51 patients), and validated the decreased plasma levels of AA-containing ePCs. Our study provides insight into the alterations of plasma lipidomic profiles in chronic SOCs and into the pathophysiology of SJS/TEN-associated chronic SOCs.

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<![CDATA[High-Fat and Low-Carbohydrate Diets Are Associated with Allergic Rhinitis But Not Asthma or Atopic Dermatitis in Children]]> https://www.researchpad.co/article/5989dae6ab0ee8fa60bbd6c8

Background

Numerous studies have suggested that nutritional intake is related to allergic diseases. Although conflicting results exist, fat intake is often associated with allergic diseases. We investigated the relationship between allergic diseases and nutritional intake after adjusting for various demographic and socioeconomic factors in a large, representative sample of Korean children.

Methods

A total of 3,040 participants, aged 4 to 13 years old, were enrolled in the present study from the Korean National Health and Nutrition Examination Survey (KNHANES), 2010–2012. Nutritional intake data, including total calories, protein, fat, carbohydrate, vitamin A, vitamin C, thiamine, riboflavin, and niacin, were retrieved from the survey using the complete 24-hour recall method. The associations between each nutritional factor and allergic rhinitis/asthma/atopic dermatitis were analyzed using simple and multiple logistic regression analyses with complex sampling. Age, sex, body mass index (BMI), number of household members, income level, and region of residence were adjusted for as covariates.

Results

Of the participants, 22.1%, 6.0%, and 15.5% suffered from allergic rhinitis, asthma, and atopic dermatitis, respectively. Allergic rhinitis was significantly correlated with high-fat and low-carbohydrate diets. The adjusted odds ratio (AOR) was 1.25 (95% CIs = 1.06–1.46, P = 0.007) for fat intake, denoting a 10% increase. Carbohydrate intake (10% increase) was negatively related to allergic rhinitis with an AOR of 0.84 (95% CIs = 0.74–0.95, P = 0.004). No other significant relationships were found between the retrieved nutritional factors and either asthma or atopic dermatitis.

Conclusion

Allergic rhinitis was related to high-fat and low-carbohydrate diets. Although the underlying mechanisms and causal relationships remain elusive, the present study provides reliable evidence regarding the associations between nutritional factors and allergic rhinitis by considering numerous factors within a large and representative population.

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<![CDATA[Adjuvant treatment with the bacterial lysate (OM-85) improves management of atopic dermatitis: A randomized study]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdc1d8

Background

Environmental factors play a major role on atopic dermatitis (AD) which shows a constant rise in prevalence in western countries over the last decades. The Hygiene Hypothesis suggesting an inverse relationship between incidence of infections and the increase in atopic diseases in these countries, is one of the working hypothesis proposed to explain this trend.

Objective

This study tested the efficacy and safety of oral administration of the bacterial lysate OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®), in the treatment of established AD in children.

Methods

Children aged 6 months to 7 years, with confirmed AD diagnosis, were randomized in a double-blind, placebo-controlled trial to receive, in addition to conventional treatment with emollients and topical corticosteroids, 3.5mg of the bacterial extract OM-85 or placebo daily for 9 months. The primary end-point was the difference between groups in the occurrence of new flares (NF) during the study period, evaluated by Hazard Ratio (HR) derived from conditional Cox proportional hazard regression models accounting for repeated events.

Results

Among the 179 randomized children, 170 were analysed, 88 in the OM-85 and 82 in the placebo group. As expected most children in both treatment groups experienced at least 1 NF during the study period (75 (85%) patients in the OM-85 group and 72 (88%) in the placebo group). Patients treated with OM-85 as adjuvant therapy had significantly fewer and delayed NFs (HR of repeated flares = 0.80; 95% confidence interval (CI): 0.67–0.96), also when potential confounding factors, as family history of atopy and corticosteroids use, were taken into account (HR = 0.82; 95% CI: 0.69–0.98). No major side effect was reported, with comparable and good tolerability for OM-85 and placebo.

Conclusions

Results show an adjuvant therapeutic effect of a well standardized bacterial lysate OM-85 on established AD.

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<![CDATA[Prevention of Diabetes in NOD Mice by Repeated Exposures to a Contact Allergen Inducing a Sub-Clinical Dermatitis]]> https://www.researchpad.co/article/5989dad0ab0ee8fa60bb5fc8

Background

Type 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutanous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT) cells, since involvement of NKT cells could suggest an innate connection between the two diseases.

Method

NOD mice 4 weeks of age were exposed, on the ears, to two allergens, p-phenylenediamine and 2,4-dinitrochlorobenzene respectively, to investigate the diabetes development. The mice were followed for a maximum of 32 weeks, and they were either repeatedly exposed to the allergens or only sensitized a week after arrival. The stimulation of NKT cells by the two allergens were additionally studied in C57BL/6 mice. The mice were sensitized and two weeks later provocated with the allergens. The mice were subsequently euthanized at different time points after the provocation.

Results

It was found that repeated application of p-phenylenediamine reduced the incidence of diabetes compared to application with water (47% vs. 93%, P = 0.004). Moreover it was shown that in C57BL/6 mice both allergens resulted in a slight increment in the quantity of NKT cells in the liver. Application of the allergens at the same time resulted in an increased number of NKT cells in the draining auricular lymph node, and the increase appeared to be somewhat allergen specific as the accumulation was stronger for p-phenylenediamine.

Conclusion

The study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in NOD mice. The contact allergens gave a non-visible, sub-clinical dermatitis on the application site.

The preventive effect on diabetes may be due to stimulation of peripheral NKT cells, as shown for provocation with p-phenylenediamine in the C57BL/6 mouse. This epicutanous procedure may lead to new strategies in prevention of type 1 diabetes in humans.

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<![CDATA[IgE Sensitization Profiles Differ between Adult Patients with Severe and Moderate Atopic Dermatitis]]> https://www.researchpad.co/article/5989da78ab0ee8fa60b976ab

Background

Atopic dermatitis (AD) is a complex chronic inflammatory disease where allergens can act as specific triggering factors.

Aim

To characterize the specificities of IgE-reactivity in patients with AD to a broad panel of exogenous allergens including microbial and human antigens.

Methodology

Adult patients with AD were grouped according to the SCORAD index, into severe (n = 53) and moderate AD (n = 126). As controls 43 patients were included with seborrhoeic eczema and 97 individuals without history of allergy or skin diseases. Specific IgE reactivity was assessed in plasma using Phadiatop®, ImmunoCap, micro-arrayed allergens, dot-blotted recombinant Malassezia sympodialis allergens, and immune-blotted microbial and human proteins.

Results

IgE reactivity was detected in 92% of patients with severe and 83% of patients with moderate AD. Sensitization to cat allergens occurred most frequently, followed by sensitization to birch pollen, grass pollen, and to the skin commensal yeast M. sympodialis. Patients with severe AD showed a significantly higher frequency of IgE reactivity to allergens like cat (rFel d 1) and house dust mite (rDer p 4 and 10), to Staphylococcus aureus, M. sympodialis, and to human antigens. In contrast, there were no significant differences in the frequencies of IgE reactivity to the grass pollen allergens rPhl p 1, 2, 5b, and 6 between the two AD groups. Furthermore the IgE reactivity profile of patients with severe AD was more spread towards several different allergen molecules as compared to patients with moderate AD.

Conclusion

We have revealed a hitherto unknown difference regarding the molecular sensitization profile in patients with severe and moderate AD. Molecular profiling towards allergen components may provide a basis for future investigations aiming to explore the environmental, genetic and epigenetic factors which could be responsible for the different appearance and severity of disease phenotypes in AD.

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<![CDATA[JAK3 as an Emerging Target for Topical Treatment of Inflammatory Skin Diseases]]> https://www.researchpad.co/article/5989db23ab0ee8fa60bcfd49

The recent interest and elucidation of the JAK/STAT signaling pathway created new targets for the treatment of inflammatory skin diseases (ISDs). JAK inhibitors in oral and topical formulations have shown beneficial results in psoriasis and alopecia areata. Patients suffering from other ISDs might also benefit from JAK inhibition. Given the development of specific JAK inhibitors, the expression patterns of JAKs in different ISDs needs to be clarified. We aimed to analyze the expression of JAK/STAT family members in a set of prevalent ISDs: psoriasis, lichen planus (LP), cutaneous lupus erythematosus (CLE), atopic dermatitis (AD), pyoderma gangrenosum (PG) and alopecia areata (AA) versus healthy controls for (p)JAK1, (p)JAK2, (p)JAK3, (p)TYK2, pSTAT1, pSTAT2 and pSTAT3. The epidermis carried in all ISDs, except for CLE, a strong JAK3 signature. The dermal infiltrate showed a more diverse expression pattern. JAK1, JAK2 and JAK3 were significantly overexpressed in PG and AD suggesting the need for pan-JAK inhibitors. In contrast, psoriasis and LP showed only JAK1 and JAK3 upregulation, while AA and CLE were characterized by a single dermal JAK signal (pJAK3 and pJAK1, respectively). This indicates that the latter diseases may benefit from more targeted JAK inhibitors. Our in vitro keratinocyte psoriasis model displayed reversal of the psoriatic JAK profile following tofacitinib treatment. This direct interaction with keratinocytes may decrease the need for deep skin penetration of topical JAK inhibitors in order to exert its effects on dermal immune cells. In conclusion, these results point to the important contribution of the JAK/STAT pathway in several ISDs. Considering the epidermal JAK3 expression levels, great interest should go to the investigation of topical JAK3 inhibitors as therapeutic option of ISDs.

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<![CDATA[Association of Polymorphisms of the CHI3L1 Gene with Asthma and Atopy: A Populations-Based Study of 6514 Danish Adults]]> https://www.researchpad.co/article/5989da23ab0ee8fa60b7fc9c

Background

YKL-40 is a chitinase-like glycoprotein encoded by the chitinase 3-like 1 gene, CHI3L1, localized at chromosome 1q32.1. Increased levels of serum YKL-40 have been reported to be a biomarker for asthma and a reduced lung function. Interestingly, the C-allele of the -131 C→G (rs4950928) polymorphism of CHI3L1 has been shown to associate with bronchial hyperresponsiveness and reduced lung function suggesting that variations in CHI3L1 may influence risk of asthma. The objective of the present study was to investigate the association of common variation in the CHI3L1 locus with asthma, atopy and lung function in a large population-based sample of adults.

Methods/Principal Findings

Eleven single nucleotide polymorphisms (SNPs) of CHI3L1 including rs4950928 were genotyped in 6514 individuals. Asthma was defined as self-reported history of physician-diagnosed asthma. Total IgE and specific IgE to inhalant allergens were measured on serum samples. Lung function was measured by spirometry. Homozygosity of the rs4950928 G allele as compared to homozygosity of the C allele was associated with self-reported physician diagnosed asthma (OR 1.5 (95% CI, 1.00–2.26)) and with prevalence of atopic asthma (OR 1.93 (95% CI, 1.21–3.07)) after adjustment for age, sex, smoking status, socio-economic class and BMI. Carriers of rs883125 G allele had a significantly lower prevalence of atopy (OR 0.82 (CI, 0.72; 0.94)) as compared to homozygosity of the C allele. None of the SNPs examined were significantly associated with FEV1. However, two SNPs (rs10399931and rs4950930) appeared to be significantly associated with FEV1/FVC-ratio. Subgroup analyses of never-smokers did not consistently influence the associations in an either positively og negatively way.

Conclusions

In contrast to previous studies, the rs4950928 G allele, and not the C allele, was found to be associated with asthma. A few other SNPs of the CHI3L1 was found to be significantly associated with atopy and FEV1/FVC ratio, respectively. Thus, more studies seem warranted to establish the role of CHI3L1 gene in asthma and atopy.

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<![CDATA[Food-Related Symptoms and Food Allergy in Swedish Children from Early Life to Adolescence]]> https://www.researchpad.co/article/5989da10ab0ee8fa60b795bb

Background

Risk factors for persistence of food-related symptoms (FRS) and food allergy (FA) from early life to adolescence are incompletely understood. The aim of this study was to identify risk factors for FRS and FA in adolescence amongst children with FRS or FA in the first four years of life (early life).

Methods

In children enrolled in a Swedish birth cohort and followed to 16 years (n = 2572), we defined children with early life FRS in the absence of FA, and FA. Corresponding phenotypes were defined at 16 years. Associations between potential risk factors at 4 years and FRS and FA at 16 years were investigated using logistic regression.

Results

Early life FRS and FA prevalences were 12.2% and 6.8%, respectively. Amongst children with early life FRS, 35.7% had FRS or FA at 16 years, whereas 74.3% of the children with early life FA had FA at 16 years. For each of the early life phenotypes, parental allergy, early life allergic multimorbidity, early life reactions to peanuts/tree nuts and IgE reactivity at 4 years were statistically significantly associated with FRS or FA at 16 years. In contrast, male sex was associated with an increased risk of FA at 16 years among children with early life FA only.

Conclusions

In early life, food-related symptoms are twice as common as food allergy. Unlike food allergy, food-related symptoms often remit by adolescence. Yet, these phenotypes have many common risk factors for persistence to adolescence.

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<![CDATA[Risk of Allergic Rhinitis, Allergic Conjunctivitis, and Eczema in Children Born to Mothers with Gum Inflammation during Pregnancy]]> https://www.researchpad.co/article/5989db45ab0ee8fa60bd8256

Purpose

Despite links between maternal and child health status, evidence on the association between gum infection in pregnant mothers and childhood allergies is scarce. We aim to evaluate the risk of developing allergy in children born to periodontal mothers in a nationwide study.

Methods

We conducted a 9-year population-based, retrospective cohort study using Taiwan’s National Health Insurance database. A study cohort of 42,217 newborns born to mothers with periodontal disease during pregnancy was identified in 2001 and matched with 42,334 babies born to mothers without any infection (control) by mother’s age at delivery and baby sex. With a follow-up period from 2001 to 2010, we observed the incidence of allergic rhinitis (AR), allergic conjunctivitis (AC), and eczema in these children. Cox proportional hazards regression models were performed with premature deaths as competing risk for the estimation of allergic disease risks.

Results

Nine-year cumulative incidences were the highest among children born to periodontal mothers; they reached 46.8%, 24.2%, and 40.4% (vs. 39.5%, 18.3% and 34.8% in control) for AR, AC, and eczema, respectively. Our results showed moderately increased risks for the allergies in children born to periodontal mothers relative to their matched non-inflammatory control (adjusted HRs: 1.17, 95% CI: 1.15–1.20; 1.27, 1.24–1.31; 1.14, 1.12–1.17, respectively). Because the impact of food consumption and living environment cannot be considered using insurance data, we attempted to control it by adjusting for parental income and mother’s residential area.

Conclusions

Overall cumulative incidence and risks of children born to periodontal mothers for AR, AC, and eczema are significantly higher than those born to non-inflammatory mothers. Gum infection in women during pregnancy is an independent risk factor for allergic diseases in children, thus its intergenerational consequences should be considered in gestational care.

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<![CDATA[Oral Administration of p-Hydroxycinnamic Acid Attenuates Atopic Dermatitis by Downregulating Th1 and Th2 Cytokine Production and Keratinocyte Activation]]> https://www.researchpad.co/article/5989da92ab0ee8fa60ba050b

Atopic dermatitis (AD) is a complex disease that is caused by various factors, including environmental change, genetic defects, and immune imbalance. We previously showed that p-hydroxycinnamic acid (HCA) isolated from the roots of Curcuma longa inhibits T-cell activation without inducing cell death. Here, we demonstrated that oral administration of HCA in a mouse model of ear AD attenuates the following local and systemic AD manifestations: ear thickening, immune-cell infiltration, production of AD-promoting immunoregulatory cytokines in ear tissues, increased spleen and draining lymph node size and weight, increased pro-inflammatory cytokine production by draining lymph nodes, and elevated serum immunoglobulin production. HCA treatment of CD4+ T cells in vitro suppressed their proliferation and differentiation into Th1 or Th2 and their Th1 and Th2 cytokine production. HCA treatment of keratinocytes lowered their production of the pro-inflammatory cytokines that drive either Th1 or Th2 responses in AD. Thus, HCA may be of therapeutic potential for AD as it acts by suppressing keratinocyte activation and downregulating T-cell differentiation and cytokine production.

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<![CDATA[Exposure to secondhand smoke and asthma severity among children in Connecticut]]> https://www.researchpad.co/article/5989db51ab0ee8fa60bdc26d

Objective

To determine whether secondhand smoke (SHS) exposure is associated with greater asthma severity in children with physician-diagnosed asthma living in CT, and to examine whether area of residence, race/ethnicity or poverty moderate the association.

Methods

A large childhood asthma database in CT (Easy Breathing) was linked by participant zip code to census data to classify participants by area of residence. Multinomial logistic regression models, adjusted for enrollment date, sex, age, race/ethnicity, area of residence, insurance type, family history of asthma, eczema, and exposure to dogs, cats, gas stove, rodents and cockroaches were used to examine the association between self-reported exposure to SHS and clinician-determined asthma severity (mild, moderate, and severe persistent vs. intermittent asthma).

Results

Of the 30,163 children with asthma enrolled in Easy Breathing, between 6 months and 18 years old, living in 161 different towns in CT, exposure to SHS was associated with greater asthma severity (adjusted relative risk ratio (aRRR): 1.07 [1.00, 1.15] and aRRR: 1.11 [1.02, 1.22] for mild and moderate persistent asthma, respectively). The odds of Black and Puerto Rican/Hispanic children with asthma being exposed to SHS were twice that of Caucasian children. Though the odds of SHS exposure for publicly insured children with asthma were three times greater than the odds for privately insured children (OR: 3.02 [2.84,3,21]), SHS exposure was associated with persistent asthma only among privately insured children (adjusted odds ratio (aOR): 1.23 [1.11,1.37]).

Conclusion

This is the first large-scale pragmatic study to demonstrate that children exposed to SHS in Connecticut have greater asthma severity, clinically determined using a systematic approach, and varies by insurance status.

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<![CDATA[Age-Related Cataract Is Associated with Elevated Serum Immunoglobulin E Levels in the South Korean Population: A Cross-Sectional Study]]> https://www.researchpad.co/article/5989da3fab0ee8fa60b89765

Background

Previous research has suggested that immunoglobulin E (IgE)-mediated events lead to several chronic diseases. We investigated the association between allergic conditions and age-related cataracts in the South Korean adult population.

Methods

A cross-sectional study was performed using data obtained from 1,170 participants aged 40 years or older who were enrolled in the Korean National Health and Nutrition Examination Survey 2010. Multivariable logistic regression was used to examine the relationship between age-related cataracts and allergic conditions, including total serum IgE and allergen-specific serum IgE levels, after adjustment for potential confounders (age, sex, alcohol consumption, smoking, sun exposure, blood pressure, plasma glucose and cholesterol levels, as well as histories of asthma, atopic dermatitis, and rheumatoid arthritis).

Results

After adjusting for potential confounders, the odds ratio (OR) for age-related cataract was greater in participants with higher total serum IgE levels (OR = 1.37; P = 0.044). In particular, increased IgE levels were significantly associated with nuclear cataract (OR = 1.42; P = 0.032). However, allergen-specific serum IgE levels did not differ significantly between groups. In the trend analysis, no significant relationship was observed between serum IgE and any type of age-related cataract.

Conclusion

Increased total serum IgE level is independently associated with age-related cataracts after adjustment for confounding factors.

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