Natural killer T cells expressing IFN-γ and IL-4 in lesional skin of atopic eczema

Background:  The inflammation of atopic eczema (AE) is orchestrated not only by T cells predominantly but also B cells, eosinophils and dendritic cells. Recently, a role of invariant natural killer T (NKT) cells has been reported in bronchial asthma and allergy. Natural killer T cells express a restricted repertoire of T-cell receptor α/β and produce interferon (IFN)-γ and/or interleukin (IL)-4 upon activation.
Aim of the study:  To determine the presence of NKT cells in lesional AE skin in comparison with other eczematous disorders and to analyse their cytokine expression.
Methods:  Immunofluorescence stainings were carried out using antibodies recognizing NKT cells, CD3+ and CD4+ cells, IFN-γ and IL-4.
Results:  Natural killer T cells have been detected in small numbers in the majority of AE specimens as well as in atopy patch test (APT) reactions, allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). In AE, the proportion of NKT cells among CD3+ cells was approximately 5%. NKT cells expressed both IFN-γ and IL-4 in AE, APT and ACD but predominantly IFN-γ in ICD.
Conclusion:  Natural killer T cells are part of the inflammatory infiltrate of AE as well as APT, ACD and ICD, suggesting a pathogenic role of NKT cells in eczematous skin disorders. The pattern of IFN-γ and IL-4 cytokine expression by NKT cells varied depending on the type of eczematous disease.     

Molluscum contagiosum and associations with atopic eczema in children: a retrospective longitudinal study in primary care

Background

Molluscum contagiosum (MC) is a common skin condition in children. Consultation rates and current management in primary care, and how these have changed over time, are poorly described. An association between the presence of atopic eczema (AE) and MC has been shown, but the subsequent risk of developing MC in children with a diagnosis of AE is not known.

Aim

To describe the consultation rate and management of MC in general practice in the UK over time, and test the hypothesis that a history of AE increases the risk of developing MC in childhood.

Design and setting

Two studies are reported: a retrospective longitudinal study of MC cases and an age–sex matched case-cohort study of AE cases, both datasets being held in the UK Clinical Practice Research Datalink from 2004 to 2013.

Method

Data of all recorded MC and AE primary care consultations for children aged 0 to 14 years were collected and two main analyses were conducted using these data: a retrospective longitudinal analysis and an age–sex matched case-cohort analysis.

Results

The rate of MC consultations in primary care for children aged 0 to 14 years is 9.5 per 1000 (95% CI = 9.4 to 9.6). The greatest rate of consultations for both sexes is in children aged 1–4 years and 5–9 years (13.1 to 13.0 (males) and 13.0 to 13.9 (females) per 1000 respectively). Consultation rates for MC have declined by 50% from 2004 to 2013. Children were found to be more likely to have an MC consultation if they had previously consulted a GP with AE (OR 1.13; 95% CI = 1.11 to 1.16; P<0.005).

Conclusion

Consultations for MC in primary care are common, especially in 1–9-year-olds, but they declined significantly during the decade under study. A primary care diagnosis of AE is associated with an increased risk of a subsequent primary care diagnosis of MC.     

Atopy patch test in patients with atopic eczema/dermatitis syndrome: comparison of petrolatum and aqueous solution as a vehicle

BACKGROUND: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens. This study was designed to compare two commonly used APT methods. METHODS: In the first method, the allergen is dissolved in aqueous solution, which is applied on tape-stripped skin. In the second method, the allergen is dissolved in petrolatum and applied without tape stripping. Thirteen patients with atopic dermatitis sensitized to inhalant allergens were patch tested using both methods. Reactions were evaluated macroscopically and microscopically after 48 h. RESULTS: Nine out of 13 patients displayed a positive reaction for both methods. One patient had a positive APT for the aqueous method alone and three for the petrolatum method alone. Reactions were significantly stronger when using the petrolatum method. Histological evaluation of the nine patients positive for both methods showed no significant differences in number of eosinophils, T-cells and neutrophils. CONCLUSION: The APT using the petrolatum vehicle induces a higher number of positive reactions and is significantly stronger relative to the APT using allergen in aqueous vehicle. The cellular influx in both test methods is comparable. Both methods can be used to study the mechanisms in the induction of eczema by inhalant allergens.     

Atopic eczema and other manifestations of atopy: results of a study in East and West Germany

Within an environmental health study, dermatologic examination of 1273 pre-school-age children (5–7 years old) was carried out in selected areas of East (n= 287) and West (n= 987) Germany in spring 1991. On the basis of comparable genetic background, the influence of a different exposure to air pollutants on the manifestation of atopic diseases was investigated. Halle an der Saale (East Germany) and Duisburg (North/South) as well as Essen (West Germany) were chosen as polluted study areas, whereas the countryside town of Borken (West Germany) served as a control region. Outdoor pollution with particles and SO₂ was significantly higher in Halle an der Saale. Of the total study group. 12.9% suffered from atopic eczema at the time of examination. The prevalence was highest in East Germany (17.5%; adjusted odds ratio [OR] 1.39, confidence intervals [CI] 0.77–2.52, compared to Borken). The reported frequencies of hay fever and asthma in the total study population were 2% and 1.3%, respectively, without significant differences between study sites. Some 34.7% of the children showed at least one positive skin prick test reaction; significantly (P< 0.001) higher sensitization rates were obtained in western regions (Essen, Duisburg-South) than in the control region (Borken) and East Germany. Multivariate analysis of the prevalence of atopic eczema showed associations with parental predisposition (OR 1.52, CI 1.03–2.25), sex (for boys, OR 0.63, CI 0.43–0.92), location (Duisburg-South vs Borken OR 0.52, CI 0.30–0.96). month of investigation (May vs April, and March vs February OR 0.55, CI 0.37–0.81), contact with rabbits (for girls, OR 2.90, CI 1.36–6.19), animal fur in bedrooms (2.17, 1.01–4.67), indoor use of gas without hood (1.68, 1.11–2.56), and distance of homes from a busy road (<50 m 1.71, 1.07–2.73). Nonsignificant associations were observed for history of helminthic infections (OR 1.61, CI 0.98–2.64) and high parental education level (OR 1.83, CI 0.83–4.02). In East and West Germany, atopic eczema seems to follow a course different from that of respiratory allergic diseases and specific sensitization, a fact which underlines the need for a differentiated analysis.     

The prevalence of positive reactions in the atopy patch test with aeroallergens and food allergens in subjects with atopic eczema: a European multicenter study

BACKGROUND: The atopy patch test (APT) was proposed to evaluate IgE-mediated sensitizations in patients with atopic eczema (AE). OBJECTIVE: The prevalence and agreement with clinical history and specific IgE (sIgE) of positive APT reactions was investigated in six European countries using a standardized method. METHODS: A total of 314 patients with AE in remission were tested in 12 study centers on clinically uninvolved, non-abraded back skin with 200 index of reactivity (IR)/g of house dust mite Dermatophagoides pteronyssinus, cat dander, grass, and birch pollen allergen extracts with defined major allergen contents in petrolatum. Extracts of egg white, celery and wheat flour with defined protein content were also patch tested. APT values were evaluated at 24, 48, and 72 h according to the European Task Force on Atopic Dermatitis (ETFAD) guidelines. In addition, skin-prick test (SPT) and sIgE and a detailed history on allergen-induced eczema flares were obtained. RESULTS: Previous eczema flares, after contact with specific allergens, were reported in 1% (celery) to 34% (D. pteronyssinus) of patients. The frequency of clear-cut positive APT reactions ranged from 39% with D. pteronyssinus to 9% with celery. All ETFAD intensities occured after 48 and 72 h. Positive SPT (16-57%) and elevated sIgE (19-59%) results were more frequent. Clear-cut positive APT with all SPT and sIgE testing negative was seen in 7% of the patients, whereas a positive APT without SPT or sIgE for the respective allergen was seen in 17% of the patients. APT, SPT and sIgE results showed significant agreement with history for grass pollen and egg white (two-sided Pr > /Z/ < or = 0.01). In addition, SPT and sIgE showed significant agreement with history for the other aeroallergens. With regard to clinical history, the APT had a higher specificity (64-91% depending on the allergen) than SPT (50-85%) or sIgE (52-85%). Positive APT were associated with longer duration of eczema flares and showed regional differences. In 10 non-atopic controls, no positive APT reaction was seen. CONCLUSION: Aeroallergens and food allergens are able to elicit eczematous skin reactions after epicutaneous application. As no gold standard for aeroallergen provocation in AE exists, the relevance of aeroallergens for AE flares may be evaluated by APT in addition to SPT and sIgE. The data may contribute to the international standardization of the APT.     

Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study

BACKGROUND: The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi-centre, randomized dose-response trial, double-blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed. METHODS: Eighty-nine adults with a chronic course of atopic dermatitis, SCORAD >or=40 and allergic sensitization to house dust mites [CAP-FEIA >or=3] were included, of whom 51 completed the study. Subcutaneous SIT with a house dust mite preparation (Dermatophagoides pteronyssinus/D. farinae) applying maintenance doses of 20, 2,000 and 20,000 SQ-U in weekly intervals for 1 year. The main outcome measures addressed the change of the SCORAD as average of the values after 9 and 12 months of SIT in comparison with the value at baseline. RESULTS: The SCORAD declined in the three dose groups in a dose-dependent manner (P = 0.0368, Jonckheere-Terpstra test) and was significantly lower in the two high-dose groups (2,000, 20,000 SQ-U) compared with the low-dose group of 20 SQ-U (P = 0.0379, U-test) after 1 year of SIT. The use of topical corticosteroids was significantly reduced with higher doses (P = 0.0007, Mantel-Haenszel chi-square test). CONCLUSIONS: Allergen-SIT for 1 year with a house dust mite preparation is able to improve the eczema in patients with atopic dermatitis who are sensitized to house dust mite allergens and reduces the need for topical corticosteroids. SIT may be valuable in the treatment of this chronic skin disease.     

Altered cortical and subcortical local coherence in obstructive sleep apnea: a functional magnetic resonance imaging study

Obstructive sleep apnea (OSA) syndrome is the most common sleep‐related breathing disorder, characterized by excessive snoring and repetitive apneas and arousals, which leads to fragmented sleep and, most importantly, to intermittent nocturnal hypoxaemia during apneas. Considering previous studies about morphovolumetric alterations in sleep apnea, in this study we aimed to investigate for the first time the functional connectivity profile of OSA patients and age–gender–matched healthy controls, using resting‐state functional magnetic resonance imaging (fMRI). Twenty severe OSA patients (mean age 43.2 ± 8 years; mean apnea–hypopnea index, 36.3 h^?1) and 20 non‐apneic age–gender–body mass index (BMI)‐matched controls underwent fMRI and polysomnographic (PSG) registration, as well as mood and sleepiness evaluation. Cerebro‐cerebellar regional homogeneity (ReHo) values were calculated from fMRI acquisition, in order to identify pathology‐related alterations in the local coherence of low‐frequency signal (<0.1 Hz). Multivariate pattern classification was also performed using ReHo values as features. We found a significant pattern of cortical and subcortical abnormal local connectivity in OSA patients, suggesting an overall rearrangement of hemispheric connectivity balance, with a decrease of local coherence observed in right temporal, parietal and frontal lobe regions. Moreover, an increase in bilateral thalamic and somatosensory/motor cortices coherence have been found, a finding due possibly to an aberrant adaptation to incomplete sleep–wake transitions during nocturnal apneic episodes, induced by repetitive choke sensation and physical efforts attempting to restore breathing. Different hemispheric roles into sleep processes and a possible thalamus key role in OSA neurophysiopathology are intriguing issues that future studies should attempt to clarify.     

针刺中风患者阳陵泉后度中心性及动态度中心性变异系数变化的fMRI研究

目的:借助功能磁共振成像技术探索中风偏瘫患者度中心性(DC)及动态度中心性(DDC)变异系数针刺前后的差异。方法:选取发病1个月内右侧梗死的中风患者,共18例,进行基本资料的获取及Fugl-Meyer运动功能评分法(FMA)、Brunnstrom评价法的评估,采集静息态、针刺态的功能磁共振图像,进行全脑DC、DDC变异系数的比较。采用偏相关分析方法对DC、DDC变异系数和临床数据、评分进行分析。结果:针刺态与静息态的DC在左侧顶下小叶存在统计学差异(P<0.05),针刺态与静息态的DDC变异系数在右侧额上回、右侧额中回存在统计学差异(P<0.05)。纠偏后,年龄和左侧顶下小叶针刺态DDC变异系数具有相关性,病程和左侧顶下小叶静息态DDC变异系数具有相关性,下肢Brunnstrom评分和右侧额上回、右侧额中回针刺态DC具有相关性。结论:DC及DDC变异系数在针刺态中存在不同于静息态的变化,且DDC变异系数与病程、年龄和运动功能均具有相关性,表明针刺对中风患者脑功能,尤其是运动相关脑功能的调整功能,并反映出针刺态脑功能的持续变化,为针刺留针提供证据支持。     

Altered metabolites of the rat hippocampus after mild and moderate traumatic brain injury – a combined in vivo and in vitro 1H–MRS study

Traumatic brain injury (TBI) has been shown to affect hippocampus‐associated learning, memory and higher cognitive functions, which may be a consequence of metabolic alterations. Hippocampus‐associated disorders may vary depending on the severity of injury [mild TBI (miTBI) and moderate TBI (moTBI)] and time since injury. The underlying hippocampal metabolic irregularities may provide an insight into the pathological process following TBI. In this study, in vivo and in vitro proton magnetic resonance spectroscopy (¹H–MRS) data were acquired from the hippocampus region of controls and TBI groups (miTBI and moTBI) at D0 (pre‐injury), 4 h, Day 1 and Day 5 post‐injury (PI). In vitro MRS results indicated trauma‐induced changes in both miTBI and moTBI; however, in vivo MRS showed metabolic alterations in moTBI only. miTBI and moTBI showed elevated levels of osmolytes indicating injury‐induced edema. Altered levels of citric acid cycle intermediates, glutamine/glutamate and amino acid metabolism indicated injury‐induced aberrant bioenergetics, excitotoxicity and oxidative stress. An overall similar pattern of pathological process was observed in both miTBI and moTBI, with the distinction of depleted N‐acetylaspartate levels (indicating neuronal loss) at 4 h and Day 1 and enhanced lactate production (indicating heightened energy depletion leading to the commencement of the anaerobic pathway) at Day 5 in moTBI. To the best of our knowledge, this is the first study to investigate the hippocampus metabolic profile in miTBI and moTBI simultaneously using in vivo and in vitro MRS.     

The neurobiology of depression in later-life: clinical, neuropsychological, neuroimaging and pathophysiological features

As the population ages, the economic and societal impacts of neurodegenerative and neuropsychiatric disorders are expected to rise sharply. Like dementia, late-life depressive disorders are common and are linked to increased disability, high healthcare utilisation, cognitive decline and premature mortality. Considerable heterogeneity in the clinical presentation of major depression across the life cycle may reflect unique pathophysiological pathways to illness; differentiating those with earlier onset who have grown older (early-onset depression), from those with illness onset after the age of 50 or 60 years (late-onset depression). The last two decades have witnessed significant advances in our understanding of the neurobiology of early- and late-onset depression, and has shown that disturbances of fronto-subcortical functioning are implicated. New biomedical models extend well beyond perturbations of traditional monoamine systems to include altered neurotrophins, endocrinologic and immunologic system dysfunction, inflammatory processes and gene expression alterations. This more recent research has highlighted that a range of illness-specific, neurodegenerative and vascular factors appear to contribute to the various phenotypic presentations. This review highlights the major features of late-life depression, with specific reference to its associated aetiological, clinical, cognitive, neuroimaging, neuropathological, inflammatory and genetic correlates. Data examining the efficacy of pharmacological, non-pharmacological and novel treatments for depression are discussed. Ultimately, future research must aim to evaluate whether basic biomedical knowledge can be successfully translated into enhanced health outcomes via the implementation of early intervention paradigms.