自体全血注射对自体血清皮肤试验阳性的难治性慢性自发性荨麻疹患者嗜碱性粒细胞FcεRⅠ与CD63表达的影响

【摘要】 目的 评估自体全血注射（AWBI）联合抗组胺药治疗对自体血清皮肤试验（ASST）阳性的难治性慢性自发性荨麻疹患者的临床疗效,并检测其对嗜碱性粒细胞高亲和力IgE受体（FcεRⅠ）以及CD63表达水平的影响,探讨AWBI治疗ASST阳性慢性荨麻疹的机制。方法 2017年11月至2018年6月在陆军军医大学第一附属医院皮肤科门诊收集ASST阳性的慢性难治性荨麻疹患者80例,随机数字表法分成AWBI组（40例）及对照组（40例）,两组均常规口服氯雷他定和依巴斯汀治疗,AWBI组同时接受AWBI治疗每周1次,共12次。治疗前及12周后评估两组周荨麻疹活动程度评分（UAS7）以及皮肤病生活质量指数（DLQI）。AWBI组30例在治疗前及第4、8、12周用流式细胞仪检测外周血嗜碱性粒细胞FcεRⅠ、CD63表达水平。采用GraphPad Prism7.00软件进行统计分析,两组UAS7和DLQI比较采用t检验,FcεRⅠα表达水平比较采用Mann-Whitney U检验,不同时点指标两两比较采用Wilcoxon′s配对秩和检验,指标相关性采用Spearman相关分析。结果 AWBI组在治疗前及治疗后第12周UAS7分别为27.15 ± 4.53、14.25 ± 7.56,DLQI分别为16.88 ± 6.01、8.48 ± 4.15;对照组UAS7分别为26.90 ± 5.22、19.93 ± 6.32,DLQI分别为17.08 ± 6.79、13.93 ± 5.43。两组治疗前UAS7与DLQI评分差异均无统计学意义;治疗后两组UAS7与DLQI均较治疗前明显降低（均P < 0.01）,且AWBI组UAS7及DLQI评分显著低于对照组（均P < 0.01）。AWBI组患者治疗前和第4、8、12周时嗜碱性粒细胞FcεRⅠα荧光强度中位数（P25,P75）分别为22 532（16 740,29 220）、16 911（10 240,21 816）、13 282（7 600,16 848）与11 466（7 161,14 578）,ASST阳性血清诱导的CD63阳性嗜碱性粒细胞比例中位数（P25,P75）分别为35.25%（26.75%,49.13%）、25.95%（19.37%,37.54%）、13.57%（7.79%,19.57%）与9.87%（6.43%,16.52%）,治疗第4周时嗜碱性粒细胞FcεRⅠα与CD63表达水平均较基线显著降低,且第8周较第4周亦显著降低（均P < 0.01）。AWBI治疗前至第4周、第4 ~ 8周以及第8 ~ 12周FcεRⅠα的变化值与ASST阳性血清诱导的CD63变化值均呈不同程度正相关,r值分别为0.364、0.422、0.455,均P < 0.05。结论 AWBI联合抗组胺药有助于改善ASST阳性难治性慢性自发性荨麻疹的临床症状,并且可能通过影响嗜碱性粒细胞FcεRⅠ以及CD63表达水平发挥作用。     

42例脂溢性角化病的临床与病理分析

脂溢性角化病可分为6型；角化型，棘层肥厚型，菌落型，腺样型，刺激型与黑棘皮瘤。     

儿童皮下脂膜炎样T细胞淋巴瘤临床病理特点及其与EB病毒关系的研究

目的：研究儿童皮下脂膜炎样T细胞淋巴瘤（SPTCL）的临床和病理特点及与EB病毒感染的关系。方法：选用CD20、CD5RO．CD68．CD30、CD56、TIA—1等抗体作免疫组织化学ABC法染色；应用EBER1／2原位杂交检测EB病毒，结果：13例SPTCL占同期观察的皮肤非何杰金淋巴瘤的36．1％，其中男8例，女5例；发病年龄平均4．8岁；主要表现为下肢、躯干无症状性结节或肿块，常伴发热和肝脾肿大。组织学特点为肿瘤花皮下脂肪内呈脂膜炎样浸润，瘤细胞大小不等、形态各异，瘤内可见上皮样肉芽肿、多核巨细胞、豆袋细胞、小片坏死。免疫表型：TIA—1抗体表达12例，13例CD5RO均为阳性，CD20、CD30、CD56均为阴性；EB病毒EBER1／2原位杂交阳性率38．5％。13例中随访10例，死亡5例，其中4例合并噬血细胞综合征（HPS），4例中EBER阳性3例。结论：SPTCL在儿童皮肤非何杰金淋巴瘤中并不少见．儿童SPICL可能与EB病毒潜伏感染有一定的相关性。与EB病毒相关的SPTCL具有更大的侵袭性，常伴有HPS．预后较差。     

Pathophysiology and clinical aspects of the venous low-pressure system]

The pathophysiology especially of the venous low-pressure system, the venous muscle pump, and the pressure-volume relation is represented. The clinical manifestations--varicous veins-varicophlebitis, phlebothrombosis, and chronic venous insufficiency--are described. Consecutively, the ways of possible therapy are shown.     

Etiologic aspects of chronic urticaria

Background Urticaria is a common disease that is always a challenge to the dermatologist due to its evasive etiology. Patients and methods One hundred and seven chronic urticaria patients were studied. Routine laboratory investigations were performed and Helicobacter pylori (H. pylori) immunoglobulin G (IgG) antibody determinations, autoimmune reactivity, infections, allergies, and hyperreactivities were investigated. Results Pathologic findings were seen in 92 patients. Concomitant diseases suggesting autoimmune reactivity were detected in nine patients and, in 16 patients, infections including maxillary sinusitis, streptococcal tonsillitis, and tooth infection were found. Elevated total IgE level was detected in 37 out of 75 patients and positive skin prick test results in 47 out of 91 patients. Fifty-five patients had a history of recent dyspeptic symptoms. A diagnosis of adult celiac disease was made in two patients and, additionally, IgA antigliadin antibodies were seen in four patients. H. pylori IgG antibodies were found in 40 out of 107 patients. Active gastritis was verified by esophagogastroduodenoscopy in 30 out of 32 patients with positive Helicobacter staining in 24 samples. An elevated IgE level was detected in 64% of H. pylori-positive and in 39% of H. pylori-negative patients. Conclusions In this study, several findings suggesting aberrant immunologic activation were detected in chronic urticaria patients. Inflammation in the gastrointestinal tract, e.g. caused by H. pylori infection, may have an important role in the etiology of chronic urticaria.     

Clinical and aetiological aspects in urticaria and angio-oedema

BACKGROUND: Urticaria is a common disorder that affects as many as 20% of all people at some time during their lifetime. OBJECTIVES: To analyse the prevalence of various forms of urticaria according to an aetiological and clinical classification, we carried out a 4-year study in an outpatient clinic. METHODS: The study was carried out on 562 consecutive patients (178 males and 384 females; mean age 35.4 +/- 16), who had been referred to our unit for the study of urticaria and angio-oedema. Baseline investigations included: the patient's family and personal history of allergy; duration of symptoms, presence of associated symptoms and objective signs of the current episode; clinical, laboratory and instrumental investigations; assessment of response to antihistamine treatment. RESULTS: A family history of atopy was present in 35% of patients and a personal history of allergy in 24%. We subdivided urticaria and angio-oedema into several groups on the basis of their clinical and aetiological aspects. Of the 562 patients, 424 (76%) presented with ordinary urticaria (43 acute urticaria, 311 chronic urticaria, 70 episodic urticaria), 80 (14%) physical urticaria, 49 (9%) angio-oedema without weals, six (1%) IgE-mediated contact urticaria and three (0.5%) urticarial vasculitis. In 64 cases (11%) urticaria/angio-oedema was associated with one or more symptoms. We identified 394 cases (82%) of idiopathic urticaria, 42 (9%) of immunological urticaria, 29 (6%) of non-immunological urticaria and 17 (3%) of urticaria secondary to infections. Of the treated subjects, 54% showed a good response to treatment with antihistamines. CONCLUSIONS: Our data provide an overview of urticaria/angio-oedema in a large series of patients, based on clinical-aetiological aspects, and related to recent diagnostic guidelines.     

Combined cold urticaria and cholinergic urticaria clinical characterization and laboratory findings

Thirteen patients with both cold and cholinergic urticaria are reported. There was considerable variability, particularly in the cold urticaria which was of the common cold contact type in seven patients, of the generalized cold induced cholinergic type in two and in four patients the lesions induced by direct contact with ice were morphologically like cholinergic urticaria, but appeared despite prior application of an acetyl choline antagonist. The natural history, laboratory findings and the effects of therapy are discussed.     

Clinical, pharmacological and immunological aspects of delayed pressure urticaria

We studied the clinical features of thirty-two patients with delayed pressure urticaria, and special laboratory tests were performed in seven patients. Striking clinical features included a long duration of the disease (mean 6 years) and an elevated erythrocyte sedimentation rate in 71%, dermographism in 63% and a leukocytosis in 33% of the patients. There was prolongation of weals in response to histamine, compound 48/80, concanavalin A and NaCl. In some patients, histamine and chemotactic factor levels were increased in suction blisters over skin test and delayed pressure sites. In extracts from pressure weals, chemotactic activity was found for leukotriene B₄, its 20-ω-oxidation products and mono-HETEs. Studies of peripheral blood leukocytes revealed significantly increased intracellular histamine levels and increased release of histamine, and a trend to increased release of chemotactic activity from stimulated patient cells. The response of leukocytes to mitogens was normal.
We conclude that histamine plays a major role in the pathogenesis of PU. Arachidonate-derived chemotactic factors might account for the variably observed leukocytosis and the cellular infiltrate in lesions of pressure urticaria. Additional mediators must be involved in PU in order to explain the unique prolonged wealing response.     

Cholinergic urticaria. A clinical and histologic study

We studied the natural history, the prevalence of atopy, and the frequency of systemic symptoms during attacks in 35 patients with cholinergic urticaria, the histologic condition of the eruption in seven patients (20%), and the response to intradermal injections of acetylcholine, histamine, and methacholine in 18 patients (51%). In most patients symptoms began between the ages of 10 and 30 years, persisted for many years, and caused them to modify their activities to avoid the provoking factors of exercise, emotion, and heat. The condition usually improved with time, and five patients (14%) had a spontaneous remission. Atopy, present in about 12 (34%) of the patients, was more frequent than in the general population. Systemic symptoms were uncommon during attacks, and patients had no greater responses than controls to the intradermal tests. The histologic study revealed neutrophils in and around the walls of superficial subpapillary dermal vessels.     

Chronic idiopathic urticaria: prevalence and clinical course

The purpose of our study was to assess the prevalence and clinical course of patients with chronic idiopathic urticaria (CIU), as well as possible causes or associated findings, laboratory findings and the duration of the disease in patients with chronic urticaria (CU). We retrospectively reviewed the 450 case record forms of patients with CU and/or angioedema who attended the Department of Dermatology, Siriraj Hospital, during the period 2000-2004. Of 450 patients with CU, 337 patients (75%) were diagnosed as CIU. Forty-three patients (9.5%) had physical urticaria, while 17 patients (3.8%) had infectious causes. Other possible causes were food, thyroid diseases, atopy, drugs, dyspepsia and collagen vascular diseases. In eighty-nine percent of patients, no abnormalities were detected at the time of physical examination. The most common abnormal laboratory finding was minimal elevation of the erythrocyte sedimentary rate (42%). In 61 patients, autologous serum skin tests had been done. Fifteen patients (24.5%) had positive results i.e. autoimmune urticaria. Anti-thyroglobulin and anti-microsomal antibodies were positive in 16 % and 12% of CIU patients respectively. After 1 year from the onset of the symptoms, 34.5% of CIU patients were free of symptoms and after 1.2 years from the onset of the symptoms, 56.5% of autoimmune urticaria patients were free of symptoms. The median disease duration of CIU and autoimmune urticaria were 390 days and 450 days respectively. Our study provided an overview of CU and CIU in a large series of Thai patients, based on etiological aspects and clinical courses.