慢性自发性荨麻疹的严重程度及预后影响因素研究进展

 慢性自发性荨麻疹是临床上常见的疾病,与肥大细胞激活有关,慢性自发性荨麻疹的不可预测性及病程迁延给患者带来了很大的困扰,并严重影响患者的身心健康。一些临床相关因素（如年龄、病程、早期使用激素治疗、是否合并可诱导荨麻疹、自身免疫性疾病）以及实验室生物学相关因素（如凝血功能异常,血清中维生素D、白介素-24等的水平）对于慢性自发性荨麻疹的病情评估、治疗管理及预后判断具有十分重要的意义。本文综述慢性自发性荨麻疹的严重程度及预后影响因素。     

荨麻疹

慢性特发性荨麻疹患单一核细胞IL-2、4、10受体mRNA的表达，慢性荨麻疹患外周血单一核细胞CC型趋化因子的表达，慢性荨麻疹患过敏原检测结果分析，肥大细胞及嗜碱性粒细胞在慢性尊麻疹发病机制中的作用（综述），依巴斯汀治疗慢性荨麻疹临床疗效及治疗前后患血清sCD23和白介素-4水平检测……     

慢性自身免疫性荨麻疹研究进展

慢性自身免疫性荨麻疹发病以自身免疫反应为基础.这类有自身抗体参与的慢性自身免疫性荨麻疹在预后和治疗上均有其特殊性,常规的抗组胺药物治疗很难奏效.研究发现,慢性自身免疫性荨麻疹的发病原因与抗IgE及其受体的自身抗体、自身免疫性甲状腺疾病以及幽门螺杆菌感染、遗传因素、精神因素等诸多因素有关.慢性自身免疫性荨麻疹患者体内B淋巴细胞刺激因子水平增高,刺激产生抗IgE的高亲和力受体抗体和抗IgE抗体,与肥大细胞结合后诱发自身免疫性荨麻疹.     

生物制剂在慢性自发性荨麻疹治疗中的应用进展

慢性自发性荨麻疹(CSU)是一种临床常见的免疫反应性皮肤病,其发病的关键效应细胞是肥大细胞。随着近年来对CSU发病机制的不断认识,不少新型生物制剂被应用于CSU患者的治疗。生物制剂可通过靶向作用于肥大细胞的活化过程的不同阶段,阻断肥大细胞的活化、脱颗粒,从而有效治疗CSU;根据作用靶点和作用机制,可分为抑制肥大细胞激活、抑制胞内信号转导、激活抑制性受体的药物。本文对生物制剂在CSU治疗中的应用展开综述。     

慢性特发性荨麻疹的发病机理

慢性特发性荨麻疹发病机理目前尚不清楚,但主要的效应细胞是肥大细胞。大约1/3的患者具有循环功能性组胺释放自身抗体,此抗体与高亲合力IgE受体或IgE相结合。该病的治疗主要用抗组胺治疗,血浆去除法等对重症难治患者可能有效。对免疫调节起反应以及最近发现与HLA-DR4有关均为某些患者的慢性特发性荨麻疹自身免疫基础提供了进一步支持。     

维生素D与慢性荨麻疹

慢性荨麻疹是皮肤科的常见病,持久的病程给患者的生理和心理造成极大的影响,其发病机制尚未被完全阐明。近年来,维生素D在治疗慢性荨麻疹中发挥的作用受到了越来越多的关注。该文将对国外文献报道的关于维生素D治疗慢性荨麻疹的理论依据进行综述。     

慢性特发性荨麻疹的发病机理

慢性特发性荨麻疹发病机理目前尚不清楚，但主要的效应细胞是肥大细胞。大约１／３的患者具有循环功能性组胺释放自身抗体，此抗体与高亲合力ＩｇＥ相结合。该病的治疗主要用抗组胺治疗，血浆去除法等对重症难治患者可能有效。对免疫调节起反应以最近发现与ＨＬＡ－ＤＲ４有关均为某些患者的慢性荨麻疹自身免疫基础提供了一步支持。     

类胰蛋白酶在慢性荨麻疹发病中的作用

慢性荨麻疹是皮肤科常见病,主要由变态反应引起,但临床上大多数患者难以找到明确的过敏原,有关其发病机制尚不完全清楚.近年来,有文献报道由激活的肥大细胞脱颗粒所释放的类胰蛋白酶在慢性荨麻疹患者中常增高.类胰蛋白酶作为肥大细胞分泌的一种中性蛋白酶,与其他递质一起,参与炎症特别是过敏性炎症过程.这些递质一方面引起过敏反应的临床症状,另一方面又可作为肥大细胞被激活的证据.该文就类胰蛋白酶在慢性荨麻疹发病过程中的作用进行综述.     

卡介菌多糖核酸治疗慢性荨麻疹疗效及对Th1/Th2平衡和IgE的影响

慢性荨麻疹是皮肤科的常见病,病因复杂,目前研究认为,Th1/Th2细胞亚群失衡在慢性荨麻疹的发生与发展中起重要作用.近年来研究发现卡介菌多糖核酸作为非特异性免疫增强治疗慢性荨麻疹患者的疗效确切,但作用机制目前尚不明确.本研究通过观察卡介菌多糖核酸对慢性荨麻疹患者外周血白介素-4(IL-4)、γ-干扰素(IFN-γ)和IgE水平的影响,探讨其对慢性荨麻疹的可能作用机制.     

肥大细胞在特应性皮炎发病中的研究进展

特应性皮炎是一种与遗传过敏素质有关的慢性、复发性、瘙痒性、炎症性皮肤疾病，其病因复杂，发病机制尚未明确。近年来，随着对特应性皮炎直接相关的效应细胞及效应分子，特别是肥大细胞及其表达的细胞因子的深入研究，逐步明确肥大细胞在特应性皮炎炎症过程中迁移、聚集、局部数量增多的机制，以及肥大细胞与嗜酸粒细胞、T细胞之间相互作用的关系。其结果将有助于进一步理解特应性皮炎皮肤炎症的细胞基础，并可能为临床治疗提供新的靶点。     

Vitamin D as a Marker for Disease Severity in Chronic Urticaria and Its Possible Role in Pathogenesis

Background

Chronic urticaria is defined as repeated episodes of wheals lasting for 6 weeks or longer. Nowadays, the role of vitamin D in various chronic diseases is a matter of great interest, but limited data is available on the vitamin D status in patients with chronic urticaria.

Objective

The goal of this study was to investigate the relationship between vitamin D status and clinical characteristics of chronic urticaria.

Methods

The clinical records of 72 patients with chronic urticaria, 26 with acute urticaria and 26 with atopic dermatitis, along with 72 healthy controls, were retrospectively reviewed.

Results

The serum 25-(OH)D₃ level was found to be significantly reduced in patients with chronic urticaria compared to those in the other groups. In particular, the proportion of patients with critically low vitamin D levels (<10 ng/ml) was significantly higher in the chronic urticaria group than in the other groups. The serum vitamin D levels showed significant negative associations with urticaria activity score and disease duration. In addition, serum vitamin D levels were significantly lower in subjects with a positive autologous serum skin test than in subjects with a negative result.

Conclusion

In conclusion, the serum vitamin D level was more likely to be critically low in patients with chronic urticaria, and an inverse relationship with disease severity and disease duration was observed. These findings may open up the possibility of the clinical use of vitamin D as a contributing factor in the pathogenesis of chronic urticaria and a predictive marker for disease activity in chronic urticaria.     

Four cases of acute infectious urticaria showing significant elevation of plasma D‐dimer level

D‐dimer, a fibrinolytic end‐product, has been regarded as a biomarker indicating the severity of urticaria, especially in chronic urticaria. Regarding acute urticaria, D‐dimer level is also suggested to be elevated, which may be significant in comparison with chronic urticaria. However, the clinical features of acute urticaria with concomitant significant elevation of D‐dimer level have not been investigated in detail so far. We present four cases of acute urticaria fulfilling the proposed diagnostic criterion of acute infectious urticaria, in which significant elevation of D‐dimer level and rapid spontaneous normalization in parallel with the resolution of fever and urticaria occurs. No cases had deep vein thrombosis, disseminated intravascular coagulation and malignancy. All cases responded well to antihistaminic treatment in combination with antibiotics, and their fever and urticaria resolved within 10 days. All cases showed severe wheals persistent for several days resolving with hyperpigmentation. Histologically, infiltration into blood vessel walls and interstitial infiltration of lymphocytes and polymorphonuclear cells were marked in the dermis. In our cases, clinical features accorded with acute infectious urticaria, and their histological features were similar to those of neutrophilic urticaria as described previously. In conclusion, there is a certain group of acute urticaria associated with significant elevation of D‐dimer level. These common features of our cases may be characteristic in acute urticaria showing the coagulative and fibrinolytic abnormalities.     

Urticaria associated with thyrotoxicosis

We report a patient with chronic urticaria which was closely associated with elevated levels of thyroxine. The urticaria responded poorly to antihistamines and only partially to systemic steroids, but resolved consistently when the thyroxine level was reduced to normal. The mechanism for the association may involve modulation of the cyclic AMP levels within mast cells. The association between thyrotoxicosis and urticaria was reported as early as 1966. More recent reports have concentrated on the increased frequency of chronic urticaria in those with thyroid autoantibodies.^1–3 These cases were unrelated to abnormal levels of thyroid hormones. We report a case showing a close association between urticaria and hyperthyroidism, and discuss the possible mechanisms contributing to the relationship between thyroid disease and urticaria.     

Infektfokus und chronische spontane Urtikaria

Urticaria represents a common skin reaction pattern that can be induced by different factors. Triggering by infections has been discussed for many years but the exact role and mechanism of mast cell activation by infectious processes is unclear. In acute spontaneous urticaria, there is no doubt about a causal relationship to infections and all chronic urticaria must start as acute. Remission of annoying spontaneous chronic urticaria has been reported after successful treatment of persistent infections. Summarizing available studies evaluating the course after proven Helicobacter eradication demonstrates a statistically significant benefit compared to not-eradicated or Helicobacter-negative patients. The licensed treatment with a standard dose of H1-antihistamines is not effective in a significant number of patients and infections can be easily treated. Therefore, appropriate diagnostic procedures should be included in the routine work-up, especially the search for Helicobacter pylori.     

Nutrition and urticaria

Urticaria is a distressing dermatologic condition for many. Although the wheals of urticaria are characteristically evanescent, lasting less than 24 hours, patients tend to have recurrent episodes. Hives that last less than 6 weeks are considered acute urticaria. Acute urticaria does not routinely require supplementary work-up because the history often identifies a convincing, inciting allergen. Chronic urticaria is defined as episodes that occur for longer than 6 weeks, and there is often not an easily identifiable trigger. For both acute and chronic urticaria, patients frequently report food as a precipitating cause. For acute urticaria, the foods that are associated with true allergies, such as nuts and shellfish, are the most frequent offenders. The relationship between diet and chronic urticaria is not as firmly defined. Many patients unnecessarily restrict their diets, so it becomes the role of dermatologists to help patients identify if there is a reproducible link between their symptoms and their dietary exposures. The literature suggests that diets free from pseudoallergens and histamine-releasing foods may attenuate urticaria. Supplements such as fats, vitamin D, iron, and flavonoids have also been studied and may diminish symptoms.     

Increased expression of endothelial cell adhesion molecules due to mediator release from human foreskin mast cells stimulated by autoantibodies in chronic urticaria sera

Histamine-releasing antibodies that act against the epitope of the alpha chain of Fc(epsilon)RI (anti-Fc(epsilon)RI(alpha) antibody) that may affect pathogenesis in serum of patients with chronic urticaria. We assessed the capability of anti-Fc(epsilon)RI(alpha) antibody in sera from patients with chronic urticaria to release histamine and cytokines, and to induce the expression of endothelial cell adhesion molecules. We also assessed the release of inflammatory mediators from cultured foreskin mast cells, and expression of endothelial cell adhesion molecules on human dermal microvascular endothelial cells. Cells were pretreated with mast cell-conditioned media: culture media of mast cells treated with sera from chronic urticaria patients containing anti-Fc(epsilon)RI(alpha) antibody. Histamine release from human foreskin mast cells challenged with sera, increased after both 20 min and 16 h intervals. Leukotriene D4 release also increased at both 20 min and 16 h. Tumor necrosis factor-alpha increased significantly in foreskin mast cell culture challenged with sera of chronic urticaria patients. After the stimulation of human dermal microvascular endothelial cells with the conditioned media, the expression of intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin increased significantly. Treatment of the conditioned media with anti-tumor necrosis factor-alpha monoclonal antibody partially inhibited the expression of intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. The data suggest that sera from patients with chronic urticaria containing anti-Fc(epsilon)RI(alpha) antibody release mediators and tumor necrosis factor-alpha by activating human foreskin mast cells. This release can play a pathogenic role in chronic urticaria by activating endothelial cells, in part due to the actions of tumor necrosis factor-alpha from mast cells.     

CHRONIC AUTOIMMUNE URTICARIA: WHERE WE STAND?

It is well-recognized that 30-40% of chronic idiopathic urticaria is autoimmune in nature. Chronic autoimmune urticaria is caused by anti-FcεRI and less frequently, by anti-IgE autoantibodies that lead to mast cell and basophil activation, thereby giving rise to the release of histamine and other proinflammatory mediators. Activation of the classical complement pathway and formation of C5a are important in dermal mast cell activation. C5a is also a neutrophil and eosinophil chemoattractant. Chronic autoimmune urticaria has been found to be associated with autoimmune thyroid disease. The autologous serum skin test is used as a screening test for chronic autoimmune urticaria and has a sensitivity and specificity of about 70 and 80%, respectively. The current gold standard diagnostic test is the basophil histamine release assay. The treatment of chronic autoimmune urticaria, as in chronic idiopathic urticaria, is with H1 antihistamines. Oral corticosteroids may be used during acute flares. Refractory cases have been shown to respond to cyclosporine and other immunomodulators. The prevalence of chronic autoimmune urticaria in Singapore is similar to that reported in Western countries at about 42%. The presence of thyroid autoimmunity appears to be higher than reported, with 22.5% of patients with chronic idiopathic urticaria here, exhibiting presence of thyroid autoantibodies.     

Physikalische Urtikaria

The different types of physical urticaria are triggered by mechanical and thermal stimuli, as well as electromagnetic waves. Localized forms restricted to the skin and mucous membranes are most common, but generalized urticaria with variable extracutaneous manifestations can also occur. Physical urticaria is usually sporadic but may rarely have a familial form; it is often associated with chronic urticaria. In most instances, the short time interval between the physical stimulus and reaction points to a causal relationship, but in delayed types the exact diagnosis may be missed without provocation tests. The clinical implication of physical urticaria is demonstrated by investigations showing a greater degree of disability in affected patients as compared to other types of urticaria. There is still an incomplete understanding of the crucial pathophysiological aspects; most likely inflammatory reactions involving leukocytes, endothelial cells and nerves stimulated by various mediators play an important role in this form of urticaria.     

Association of insertion/deletion polymorphism of the angiotensin-converting enzyme gene with angio-oedema accompanying chronic urticaria but not chronic urticaria without angio-oedema or the autologous serum skin test response

Background Chronic urticaria is defined as the daily or almost daily occurrence of weals for more than 6 weeks. The underlying pathophysiology is reported to be mast cell activation, with release of mast cell mediators, predominantly histamine. Substance P is a neuropeptide and has the capacity to provoke histamine release from skin mast cells. Angiotensin‐converting enzyme (ACE), widely expressed in skin, is one of the major peptidase for the degradation of substance P. An insertion/deletion polymorphism (I/D) in the ACE gene has been reported to be related to the levels of enzyme. Objective An increase in substance P levels due to a polymorphism in ACE gene might be related to the pathology. Thus, we aimed to investigate whether there is an association between ACE I/D polymorphism and chronic ordinary urticaria. Methods Ninety‐five patients with chronic ordinary urticaria were recruited and divided into two groups according to autologous serum skin test status and accompanying angio‐oedema. One hundred and sixty‐one healthy subjects were enrolled as control group. All participants were genotyped for I/D polymorphism in intron 16 of the ACE gene by polymerase chain reaction. Results A statistically significant association was not found between ACE I/D polymorphism and chronic ordinary urticaria. Further analyses of chronic ordinary urticaria patients showed that ACE I/D polymorphism was not associated with autologous serum skin test status of patients. However, the frequencies of II genotype and I allele were statistically significantly higher in chronic ordinary urticaria patients with accompanying angio‐oedema with regard to angio‐oedema‐negative patients (II genotype: 24% vs. 9%, P = 0.0002; I allele: 58% vs. 27%, P = 0.0001) and control group (II genotype: 24% vs. 19%, P = 0.01; I allele: 58% vs. 41%, P = 0.03). Conclusion The results of this study suggest no evidence of an association between ACE I/D polymorphism and risk of developing chronic ordinary urticaria. However, it can be a contributing factor to susceptibility of angio‐oedema in chronic ordinary urticaria.     

凝血机制参与慢性荨麻疹发病的研究进展

凝血机制与慢性荨麻疹有关.内外凝血途径均参与其发病,同时被激活产生凝血酶.凝血酶不仅可以直接作用于血管内皮细胞,增加血管通透性,还可以间接使肥大细胞脱颗粒释放组胺,从而诱发荨麻疹.慢性荨麻疹患者检测出的一些凝血标记物也间接证明凝血机制参与其发病.在慢性荨麻疹发病过程中,凝血机制与炎症反应机制、自身免疫机制和血管机制密切相关.对于抗组胺治疗无效的顽固性荨麻疹患者,抗凝血治疗提供了新的思路和方向.