Prevalence of comorbidities in atopic dermatitis and psoriasis in the French population

BackgroundAtopic dermatitis (AD) and psoriasis (Pso) are highly prevalent chronic inflammatory skin diseases. They share similarities regarding severity and impact on quality of life but display differences regarding risk factors, comorbidities, and pathogenesis.ObjectiveThis study sought to assess the prevalence of AD and Pso among the French population, along with associated comorbidities, and to compare these data with those of the age- and gender-adjusted French population with neither AD nor Pso.MethodsThe survey was conducted by a polling institute between September 1 and November 30, 2016, with proportional quota sampling being applied to render the study population representative of the French population. In all, 20 012 individuals were selected from among 900,000 internet users aged ≥ 15 years.ResultsOverall, 20,012 adults (48.8% men; 51.2% women) completed a digital questionnaire. The prevalence of AD was 4.65% [95% confidence interval (CI) 4.36%–4.94%] and that of Pso was 4.42% [95% CI: 4.14%–4.71%]. More AD patients presented ≥ 1 comorbidity compared to subjects without AD (57.04% vs. 49.2%, P < 0.0001) and more Pso patients presented ≥ 1 comorbidity compared to subjects without Pso (60.68% vs. 49.05%, P < 0.0001). After adjustment for gender and age, hypertension and dyslipidemia, a greater prevalence of osteoarticular, respiratory and psychiatric diseases was noted in both AD and Pso patients, whereas increased prevalence of obesity was seen only in Pso patients. The prevalence of components of metabolic syndrome was higher among Pso than AD patients.ConclusionFurther studies are required to consolidate these findings, to better characterize the entire spectrum of AD and Pso comorbidities, and to better identify determinants and risk factors, along with targeted therapies.     

Enhanced procoagulant acticity of mononuclear leukocytes in patients with atopic dermatitis and psoriasis

Fibrin deposition is an important histopathological feature of inflammatory skin lesions and is mediated in part, by procoagulants generated by mononuclear leucocytes (MNL). We examined whether MNL from patients with atopic dermatitis or psoriasis generate enhanced procoagulant activity (PCA). MNL isolated from the peripheral blood of 15 healthy control individuals, 15 patients with atopic dermatitis and 15 patients with psoriasis were incubated for 24 h in the presence or absence of bacterial lipopolysaccharide (LPS). MNL or the cell culture supernatants were then added to recalcified human plasma to determine the clotting time. We found that in both atopic dermatitis and psoriasis MNL cultured in the presence or absence of LPS expressed greatly enhanced PCA (p<0.01 to <0.002). Supernatants from MNL cultures from patients with psoriasis, but not those from patients with atopic dermatitis, also generated augmented PCA (p<0.002). In psoriasis, PCA normalized after successful topical treatment with anthralin. We conclude that enhanced PCA is a characteristic feature of MNL in both atopic dermatitis and psoriasis. In psoriasis the enhanced PCA is directly related to disease activity.This paper contains data from the doctoral thesis of H. W.     

The role of ceramides in skin homeostasis and inflammatory skin diseases

Ceramides, members of sphingolipid family, are not only the building blocks of epidermal barrier structure, but also bioactive metabolites involved in epidermal self-renewal and immune regulation. Hence, abnormal ceramide expression profile is recognized to defect extracellular lipid organization, disturb epidermal self-renewal, exacerbate skin immune response and actively participate in progression of several inflammatory dermatoses, exemplifying by psoriasis and atopic dermatitis. Here, we discuss recent advances in understanding skin ceramides and their regulatory roles in skin homeostasis and pathogenic roles of altered ceramide metabolism in inflammatory skin diseases. These insights provide new opportunities for therapeutic intervention in inflammatory dermatoses.     

Mast cells of psoriatic and atopic dermatitis skin are positive for TNF-α and their degranulation is associated with expression of ICAM-1 in the epidermis

Abstract The release of cytokines from cutaneous cells may be of major importance in the initiation and development of many inflammatory skin disorders. For example, tumor necrosis factor-alpha (TNF-α), which in healthy skin is found preformed only in mast cells, is able to induce the expression of several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1). Increased expression of ICAM-1 occurs in keratinocytes in lesional skin of psoriasis and atopic dermatitis (AD) and it is considered to be an important initiator of leucocyte/keratinocyte interactions in skin inflammation. We counted the mast cells showing TNF-α immunoreactivity using a double-staining method in nonlesional and lesional skin sections from 12 patients with AD and 12 patients with psoriasis. The percentage of TNF-α⁺ mast cells in lesional and nonlesional AD skin was 36 ± 22% and 21 ± 15% (P < 0.018, paired t-test), respectively, and in psoriatic skin was 16 ± 25% and 15 ± 15%, respectively (P < 0.89, paired t-test). We also cultured whole skin biopsies taken from the healthy-looking skin of psoriatic and AD patients in the presence of mast cell degranulator compound 48/80, which resulted in focal expression of ICAM-1 in the epidermis. In cultured keratinocytes, both histamine and an extract of a human mast-cell line (HMC-1) induced ICAM-1 immunostaining only in occasional cells, but the combination of histamine and the HMC-1 extract resulted in intense ICAM-1 staining in numerous cells. This enhancement of ICAM-1 staining was abolished by preincubation of the HMC-1 extract with anti-TNF-α antibody. These results suggest that the degranulation of mast cells induces the expression of ICAM-1 in keratinocytes probably via TNF-α and histamine. Received: 8 August 1997     

特应性皮炎光疗进展

特应性皮炎(atopic dermatitis,AD)是一种具有家族遗传倾向的慢性、复发性、炎症性皮肤病.光疗法在AD的治疗中一直占有较为重要的地位.近年来随着对AD病因学和发病机制的深入了解,以及光疗法在皮肤科应用研究的进展,AD的光治疗法有了一些新策略,现将其作一概述.     

Mast cells and atopic dermatitis. Stereological quantification of mast cells in atopic dermatitis and normal human skin

Stereological quantification of mast cell numbers was applied to sections of punch biopsies from lesional and nonlesional skin of atopic dermatitis patients and skin of healthy volunteers. We also investigated whether the method of staining and/or the fixative influenced the results of the determination of the mast cell profile numbers. The punch biopsies were taken from the same four locations in both atopic dermatitis patients and normal individuals. The locations were the scalp, neck and flexure of the elbow (lesional skin), and nates (nonlesional skin). Clinical scoring was carried out at the site of each biopsy. After fixation and plastic embedding, the biopsies were cut into 2 μm serial sections. Ten sections, 30 μm apart, from each biopsy were examined and stained alternately with either toluidine blue or Giemsa stain and mast cell profile numbers were determined. The study yielded the following results: (1) in atopic dermatitis lesional skin an increased number of mast cell profiles was found as compared with nonlesional skin, (2) comparing atopic dermatitis skin with normal skin, a significantly increased number of mast cell profiles per millimetre squared was found in specimens from the neck, (3) staining with toluidine blue yielded a lower number of mast cell profiles than Giemsa staining, (4) the use of Carnoy’s fixative resulted in a lower mast cell profile count than the use of formaldehyde, and (5) there was no statistically significant correlation between the clinical score and the number of mast cell profiles per millimetre squared. Using stereological techniques, this study indicated that mast cells might participate in the inflammatory process in skin leading to atopic dermatitis. Received: 17 April 1996     

特应性皮炎患者瘙痒性皮损中神经形态变化及蛋白酶活化受体2的表达

目的 探讨皮肤神经及蛋白酶活化受体2（PAR2）在特应性皮炎瘙痒发生中的作用。方法 取特应性皮炎患者（7例）慢性期瘙痒性皮损及正常人（7例）皮肤,用真皮单片制备技术,免疫荧光双染标记,比较皮损与正常皮肤中神经形态变化及PAR2表达。结果 特应性皮炎患者皮损及正常人皮肤蛋白基因产物9.5（PGP9.5）/PAR2及P物质（SP）/PAR2免疫荧光双染均呈阳性表达,阳性部分基本重叠。与正常皮肤比较,瘙痒性皮损中PGP9.5阳性神经纤维总长度增加,直径增大（P ＜ 0.05）,SP阳性神经纤维总长度没有明显变化（P > 0.05）,但直径增大（P ＜ 0.05）;瘙痒性皮损中PAR2和SP免疫荧光的累积光密度值增加（P ＜ 0.05）。结论 特应性皮炎慢性期瘙痒性皮损中出现神经纤维明显增生,PAR2及SP在神经上的表达上调,提示蛋白酶-PAR2通路的信号增强可能与特应性皮炎患者皮肤瘙痒的机制有关。     

特应性皮炎与皮肤微生物态的关系

特应性皮炎是一种慢性、周期性、瘙痒性皮肤病。近年来,我国患病人数迅速上升,尽管越来越多的人深受其困扰,但目前病因尚不清楚,近年来发现皮肤微生物态对全身免疫功能及局部皮肤免疫功能有影响,皮肤屏障完整性的改变会导致皮肤微生物多样性的改变和皮肤菌群的紊乱,诱发并加重特应性皮炎。特应性皮炎的患者与健康人相比,发生皮肤感染的风险也更高。因此,特应性皮炎与皮肤微生物态的关系也成为近年来研究的热点。     

Mast cell chymase is increased in chronic atopic dermatitis but not in psoriasis

Mast cell chymase is a chymotrypsin-like serine proteinase primarily stored in secretory mast cell granules. Mast cell chymase has various effects on angiotensin, metalloproteases, lipoproteins, procollagen, neuropeptides and cytokines. Recent studies have demonstrated that chymase inhibitors inhibit skin inflammation. In this study we sought to determine the role of mast cell chymase in atopic dermatitis (AD) in comparison with its role in psoriasis and normal skin. Skin biopsy specimens were obtained from non-lesional and lesional skin of patients with chronic AD and psoriasis and from normal skin of non-atopic and non-psoriatic controls. The number of mast cells containing chymase was determined by immunohistochemistry using a chymase-specific monoclonal antibody. A significantly (P<0.05) enhanced number of chymase-positive cells was found in lesional AD skin as compared to normal skin as well as to lesional and non-lesional skin of patients with psoriasis. A significant (P<0.05) increase in the number of chymase-positive cells was also found in non-lesional AD skin in comparison to psoriasis. An enhanced, albeit not statistically significant difference was noted in non-lesional AD skin as compared to normal skin. In conclusion, these results suggest that mast cell chymase may play an integral part in eliciting and maintaining cutaneous inflammation in AD but not in psoriasis. The increased proteinase activity of mast cell chymase may also be involved in promoting a skin barrier defect in AD, which subsequently enhances the skins permeability to allergens and microbes and thereby aggravates the eczema.     

中国特应性皮炎诊断和治疗指南

本指南是中华医学会皮肤性病学分会免疫学组在参考国内外文献的基础上共同讨论制定的,制订过程中邀请了部分儿科专家参与.本指南供国内皮肤科同行在诊疗中参考,并将在今后进一步修订.     

Urinary histamine in severe atopic dermatitis

Summary Urinary histamine was studied in 11 patients with severe atopic dermatitis and 17 controls, as well as in seven atopics prior to and 6 months following hyposensitization. No statistically significant differences were found between the groups. Urinary histamine seems to be of no value as an indicator of disease activity in atopic dermatitis.     

Mometasone furoate in the treatment of atopic dermatitis in children

Background Efforts are being made to find a non-fluorinated topical corticosteroid with higher anti-inflammatory activity for use in chronic dermatoses. Patients and methods In a third-party blind evaluation study we compared Mometasone cream, 0.1% once a day, with Clobetasone cream, 0.05% twice daily, in 60 children with atopic dermatitis treated for 3 weeks. At each visit carried out at days 0, 7, 14. 21 we evaluated signs and symptoms, therapeutic response and skin atrophy. Further visits were carried out at days 2, 3, 4 to evaluate the onset of action. During the first and last visit we also carried out laboratory tests including blood cortisol. Results Mometasone was more effective and rapid in reducing signs and symptoms than Clobetasone. The difference between the two drugs was statistically significant (P < 0.05) from the fourth day of treatment for pruritus, and from days 7 and 14 for induration and eythema, respectively. At the end of the study 50% of the patients treated with Mometasone showed no symptoms vs 6.7% of those treated with Clobetasone. Topical and systemic tolerability were very good and laboratory tests were not significantly affected by either drug. Conclusions Monometasone cream seems to represent an interesting therapeutic approach to chronic dermatoses, i.e., atopic dermatitis.     

特应性皮炎治疗中的患者教育和管理

特应性皮炎传统的治疗方法虽能起到缓解症状、恢复皮肤屏障功能的作用,但不能达到根本控制和处理疾病的目的.以社会学习理论为基础,针对慢性病自我处理的教育,从医学、营养学及心理学等方面,开展如教育课堂、湿疹工作室、网络咨询平台等形式多样的教育计划,可显著减轻疾病严重程度、促进患者应对行为及家庭生活质量的改善.在各种教育模式中,“多学科年龄相关结构性的患者教育计划”已被证实是特应性皮炎传统治疗基础上最有效的辅助治疗手段.     

Treatment of severe atopic dermatitis with extracorporeal photopheresis

Extracorporeal photopheresis using UVA irradiation of enriched lymphocytes in the presence of 8-methoxypsoralen (8-MOP) as a photoactivatable substrate has been employed for the treatment of several immunologically mediated disorders. We report on the first three patients subjected to extracorporeal photopheresis for severe atopic dermatitis. All patients had a lifelong history of atopic skin inflammation, and their disease had finally become resistant to well-established therapeutic regimes. Extracorporeal photopheresis resulted in a marked clinical improvement in the skin lesions of all patients. The decrease in cutaneous inflammatory activity became evident by the end of the second photopheresis cycle. In two patients skin lesions had virtually disappeared after the fifth treatment cycle, while in the third patient a lasting and substantial improvement in pruritus and erythema was achieved. Clinical remission was stable under maintenance therapy with prolonged intervals between photopheresis sessions. Therapeutic efficacy was reflected by a marked reduction in IgE serum levels in all three patients, while serum concentration of IgG, IgM and IgA as well as the profile of circulating lymphocytes remained essentially unchanged. No clinical signs of immunosuppression or other severe adverse events became evident. Collectively, our preliminary results indicate that extracorporeal photopheresis may interfere with the pathomechanisms leading to atopic dermatitis and therefore should be considered as a treatment modality for severe forms of this recalcitrant disorder.     

Involvement of complement in psoriasis and atopic dermatitis — Measurement of C3a and C5a,C3, C4 and C1 inactivator

Summary Normal complement components and activation products were determined in the peripheral blood of 35 patients with atopic dermatitis (AD) and 24 patients with psoriasis at a mild to intermediate stage. None of the patients had received systemic or local steroid therapy 6 weeks prior to blood collection. Levels of C3, C4 and C1 inactivator (C1 INA) were determined in serum by radial immunodiffusion, whereas C3a and C5a levels were measured by radioimmunoassay. In comparison to healthy non-atopic controls, the levels of C3, C4 and C1 INA were found to be significantly increased in both diseases. No substantial differences were detected between patients with psoriasis vulgaris and psoriasis guttata, which suggests that the dissimilarities found were not due to preceding or concomitant infections. In AD, there was a tendency towards increased C3a levels, whereas in psoriasis, C3a levels were significantly increased. In both diseases, no measurable amounts of C5a could be detected. The results indicate that, in both AD and psoriasis, the complement participates in the inflammatory process. Elevated levels of C3a suggest that there is a continuous activation of the complement system leading to the generation of inflammatory mediators.     

中外特应性皮炎诊疗指南比较

特应性皮炎是一种炎症性、瘙痒性和慢性复发性皮肤病,其治疗强调根据病情制定长期的综合方案。i治疗方案的重要内容包括基础治疗、药物治疗和健康教育。以循证医学文献、专家讨论意见为基础的诊断和治疗指南是制定治疗方案的最佳依据。本文概述目前国内外重要的6项指南中关于特应性皮炎诊断和治疗意见的异同和强调的理念。     

特应性皮炎的转录组学研究进展

【摘要】 随着基因芯片技术、RNA测序技术等转录组学技术发展,特应性皮炎（AD）发病中重要的相关影响因素逐渐被揭示,如不同T辅助（Th）细胞的亚型以及其他免疫相关细胞如巨噬细胞、朗格汉斯细胞;在AD的瘙痒及皮肤屏障破坏方面,相关免疫细胞如Th2细胞及角质形成细胞等所释放白细胞介素4、白细胞介素13、聚丝蛋白、兜甲蛋白等活性物质的异常变化起着主要作用。同时,转录组技术已被用于分析患者治疗前后转录谱的变化从而对患者的病情和治疗效果进行评估等。本文总结近年来在AD转录组学方面的研究进展。     

Therapy of atopic dermatitis

Background Appropriate management of patients with atopic dermatitis must depend primarily on early, accurate diagnosis and allergen avoidance in infants. Patients with less typical lesions, such as extensor involvement, may be misdiagnosed. Aim Dermatologists should try to ensure that correct management is initiated in the primary care setting and maintained by patients and parents. Guidelines for the management of both paediatric and adult patients with atopic dermatitis have been drawn up by an international panel of dermatologists. For patients with mild disease, elaborate investigations to identify the trigger factors are unnecessary. Management should include general measures (skin hydration, irritant and allergen avoidance), provision of information to parents and intermittent use of low potency topical corticosteroids when necessary. For patients with mild to moderate disease, investigations may require assessment of food allergies in paediatric cases and of contact allergens and irritants in adult cases. Identification of Staphylococcus aureus and herpes simplex virus secondary infection is also important. Conclusions General measures remain important in mild to moderate atopic dermatitis, with appropriate education and support for parents. Topical corticosteroids play an important role, possibly with antihistamines to help alleviate the pruritus. In certain situations, systemic treatment with antibiotics, corticosteroids and other agents may be indicated.