丙基硫氧嘧啶诱发的抗中性粒细胞胞质抗体阳性甲状腺功能亢进患者的临床研究

目的研究丙基硫氧嘧啶（PTU）诱发的抗中性粒细胞胞质抗体（ANCA）阳性的甲状腺功能亢进症（甲亢）患者的临床和预后特点。方法对45例PTU诱发的ANCA阳性的甲亢患者进行长期随访（3～60个月,中位数27个月）,观察其甲状腺功能和ANCA百分结合率的变化,对其中17例有小血管炎临床表现的患者进一步观察血管炎的病情变化。结果（1）血管炎组17例患者中13例（76．5％）肾脏受累,表现为血尿、蛋白尿及不同程度的肾功能受损,7例（41．2％）肺脏受累,多表现为肺出血。核周型ANCA（p-ANCA）阳性率为100％,其中16例（94．1％）髓过氧化物酶（MPO）-ANCA抗体阳性。所有患者均停用PTU,6例改用他巴唑治疗甲亢,13例内脏受累较重的患者应用免疫抑制剂治疗6～12个月。除2例诊治较晚的患者发展至终末期肾衰竭外,其余患者临床症状均得到缓解,随访期间（8～60个月,中位数30个月）未发现小血管炎复发。（2）无血管炎临床表现组28例患者中有27例（96．4％）为p-ANCA阳性,14例（50．0％）的MPO—ANCA阳性。24例患者停用PTU,其中15例改用他巴唑;4例患者继续应用小剂量PTU。随访期间（3～36个月,中位数20个月）均未发生小血管炎临床表现。但血管炎组及无血管炎组多数患者ANCA百分结合率下降较慢。结论PTU诱发的ANCA阳性甲亢患者应及时停用PTU,必要时改用他巴唑治疗甲亢;血管炎病情严重者应用免疫抑制治疗。停用PTU后未发现小血管炎复发,但ANCA可较长时间维持阳性。     

Recurrent episodes of arthritis in a hyperthyroid patient

Antineutrophil cytoplasmic antibody (ANCA)- associated vasculitis is a potentially life-threatening adverse effect of antithyroid medications. We present a 22-year-old woman with Graves' disease who developed recurrent episodes of arthritis while on treatment with propylthiouracil. A diagnosis of propylthiouracil-induced ANCA-associated vasculitis was established only after exhaustive rheumatological investigations failed to establish a cause for her arthritis. Anti-myeloperoxidase antibody (anti-MPO) titres were grossly elevated at 172.7 RU/mL (0-20). Her arthritis resolved promptly following the withdrawal of propylthiouracil and the anti-MPO titres declined over 16 months to 66.8 RU/mL. While she did not develop the life-threatening renal or respiratory tract complications, there was a delay in establishing the correct diagnosis with its attendant morbidity. This case highlights the need for greater awareness of this relatively rare adverse effect of antithyroid medications so as to allow its early detection, leading to the prompt cessation of the offending medication.     

丙基硫氧嘧啶致抗中性粒细胞胞浆抗体阳性患者的临床特点

目的探讨丙基硫氧嘧啶(PTU)导致抗中性粒细胞胞浆抗体(ANCA)阳性病例的临床特点,以提高对PTU导致ANCA阳性血管炎(APV)的认识。方法分析北京协和医院自2000年以来9例因应用PTU导致的ANCA阳性病例临床资料,并进行相关文献复习。结果(1)9例患者发病年龄16—51岁(平均33．1岁),服用PTU时间3—84个月(平均32．4个月);(2)6例进行了ANCA靶抗原谱的测定,除抗髓过氧化物酶(MPO)外,均同时存在识别其他抗原的抗体,包括：抗蛋白酶3(PR3)、抗人白细胞弹力蛋白酶(HLE)、抗杀菌／通透性增高蛋白(BPI)和抗乳铁蛋白(LF);(3)6例核周型ANCA(pANCA)高滴度阳性(≥1：1280)的病例临床确诊为APV(均有肾脏受累,其中5例为肾穿刺病理证实),另外3例pANCA低滴度阳性(≤1：320)的病例无明确血管炎表现;(4)8例患者被发现ANCA阳性后停用PTU,其中1例APV仅停用PTU后病情缓解,另外4例APV同时予糖皮质激素和免疫抑制剂后病情逐渐缓解,而1例继续服用PTU随诊18个月pANCA滴度未升高。结论PTU可引起ANCA阳性,而高滴度pANCA阳性提示APV,其病情与抗体滴度相关;及时停用PTU,根据肾穿刺病理的病变程度确定治疗方案,对改善预后意义重大。     

糖尿病高危人群尽早筛查胰岛自身抗体的价值

胰岛自身抗体是一组针对胰岛细胞本身及其成分的血清自身抗体的总称,它常作为区分1型糖尿病（T1DM）与2型糖尿病（T2DM）的标志,特别是在成人迟发型自身免疫性糖尿病（LADA）的诊断中意义重大,胰岛自身抗体阳性人群随访数月或数年后可发展为糖尿病。因此针对糖尿病高危人群及早行胰岛自身抗体等的筛查,对糖尿病的早期防治意义深远。     

Human amnion in the treatment of chronic ulceration of the legs

A prospective study to evaluate the efficacy of human amniotic membrane dressings in the treatment of chronic leg ulcers was conducted on 15 patients. Patients with two ulcers were selected. One ulcer was treated with human amnion and the other, treated with standard dressings, served as a control. The rate of healing of the two ulcers was observed and compared. Chronic ulcers of post-phlebitic, post-irradiation and post-burn origin responded to treatment with human amnion and healed more rapidly than the control ulcer. Ulcers associated with rheumatoid arthritis and vasculitis showed no improvement. It was observed that all ulcers treated with human amnion quickly became pain-free.     

抗内皮细胞抗体与丙硫氧嘧啶引起的抗中性粒细胞胞浆抗体阳性小血管炎病变活动相关

目的:在丙硫氧嘧啶(propylthiouracil,PTU)引起的抗中性粒细胞胞浆抗体(antineutrophil cytoplasmic antibody,ANCA)相关小血管炎患者血清中检测抗内皮细胞抗体(anti-endothelial cell antibody,AECA),探讨其在该类疾病发病中的作用.方法:选取11例PTU引起的ANCA相关小血管炎患者及10例临床上使用PTU治疗甲亢,无系统性血管炎症状而ANCA阳性的患者,应用体外原代培养的脐静脉血管内皮细胞制备可溶性抗原,采用蛋白免疫印迹法检测其血清中的AECA.结果:PTU相关ANCA阳性小血管炎组患者疾病活动期共有10(91%,10/11)例病人血清可检出AECA,有6种不同的蛋白可以被识别.对以上10例AECA阳性患者同时测定了其缓解期血清的AECA,发现其中7例AECA转为阴性,3例出现的条带与活动期比较无差别.使用PTU治疗甲亢,无系统性血管炎症状而ANCA阳性患者组中未检出AECA.结论:PTU相关的ANCA阳性小血管炎中存在着不同分子质量大小的AECA,AECA在该类疾病的发病中可能具有比ANCA更为重要的意义.     

Disseminated histoplasmosis and necrotizing vasculitis.

A 74-year-old man with congestive heart failure was found to have Histoplasma capsulatum in a lesion of the right nasal septum. His initial treatment with amphotericin B was inadequate because of severe intolerance to the drug. Three months after initial presentation H. capsulatum was detected in his blood and bone marrow. Slightly elevated purpuric lesions on the arms, lower legs and trunk showed the typical features of necrotizing vasculitis. Cutaneous anergy was reversed after treatment with transfer factor. Skin involvement in disseminated histoplasmosis is unusual and there are no previous reports of vasculitis associated with this infection.     

Adverse immunologic effects of antithyroid drugs.

Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful.     

抗髓过氧化物酶抗体IgG亚型在丙基硫氧嘧啶引起的小血管炎中的分布及其意义

目的观察丙基硫氧嘧啶(PTU)引起的抗中性粒细胞胞浆抗体(ANCA)相关小血管炎患者活动期和缓解期血清中抗MPO抗体IgG亚型的分布并探讨其意义。方法以12例PTU引起的ANCA相关小血管炎患者为研究对象,收集患者未治疗的活动期血清,其中10例同时具有缓解期的血清,应用抗原特异性ELISA法检测抗MPO抗体总IgG及各IgG亚型的滴度,比较其与原发性小血管炎中抗MPO抗体IgG亚型分布的异同。结果与原发性血管炎不同,所有PTU引起的ANCA相关小血管炎患者血清中均未检测到IgG3亚型。其他亚型在活动期的检测结果分别为IgG1(12／12例,100％),IgG2(8／12例,66、7％),IgG4(7／12例,58．3％);缓解期各亚型的检测结果分别为IgG1(9／10例,90％),IgG2(4／10例,40％),IgG4(2／10例,20％)。与原发性小血管炎缓解期中IgG4仍保持较高水平的现象不同,经停用PTU及应用免疫抑制治疗病情缓解后,IgG4亚型的滴度显著下降甚至转阴。结论PTU引起的抗MPO抗体IgG亚型的分布与原发性小血管炎并不一致。高滴度的ANCA可能与PTU的反复抗原刺激有关。     

Infective endocarditis from Enterococcus faecalis complicating colonoscopy in Heyde's syndrome

A case of infective endocarditis from Enterococcus faecalis after colonoscopy in a patient with aortic stenoinsufficiency and bleeding intestinal angiodysplasia (Heyde's syndrome) is reported.A 77 year old man with aortic stenoinsufficiency presented with enterorrhagia and underwent a colonoscopy, which showed normal findings. Fifteen days later he developed a moderate degree of fever. Blood cultures were positive for E faecalis. An echocardiogram showed aortic valve vegetations, and infective endocarditis was diagnosed and successfully treated by antibiotics. Some months later, intestinal bleeding recurred and intestinal resection was performed. Histopathology showed angiodysplasia. In patients with Heyde's syndrome antibiotic prophylaxis should be considered before colonoscopy.     

Severe Pulmonary Embolism,Thrombosis of Lower Extremity,Unexpected Mild Renal Disorder in MPO-ANCA Associated Vasculitis:A Case Report

Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis is an autoimmune disease usually with severe multiple dysfunction syndrome,especially prominent acute renal failure.A 65-year-old woman was admitted with progressive dyspnoea for six months and fever,sputum with blood,pain of the lower extremities and intermittent claudication for two days,indicating multiple organ involvement(respiratory system,blood vessels).The renal involvement was relatively mild,presenting with microscopic haematuria.The chest computed tomography demonstrated multiple pulmonary embolisms.Ultrasound and computed tomography angiography for the lower extremity vessels showed venous and arterial thrombosis.Exclusion of other diseases that can cause multiple organ damage and thrombosis,the positive perinuclear ANCA and MPO-ANCA strongly support the diagnosis of MPO-ANAC-associated vasculitis.The patient's physical condition has been greatly improved by treatment with corticosteroids and anticoagulation.     

抗甲状腺药物诱发ANCA相关血管炎研究

目的了解抗甲状腺药物在治疗甲状腺功能亢进症(甲亢)过程中是否诱发抗中性粒细胞胞浆抗体(ANCA)相关血管炎。方法对60例初诊Graves病甲亢患者进行研究,分为两组,每组各30例,分别予以他巴唑(MMI)及丙基硫氧嘧啶(PTU)治疗。检测研究对象初诊与药物治疗后第24个月的血清ANCA水平,以及TT4、TT3、FT4、FT3、TSH、TPOAb、TGAb、小便常规、血常规、肝功能、肾功能等临床指标。结果治疗组各25例完成2年追踪观察,失访率16.7%。两组在性别、年龄分布上无差别(性别:25%vs 40%,χ2=3.57,P=0.61;年龄(31.6±9.3)岁vs(33.8±10.8)岁,t=0.79,P=0.42。研究对象初诊时均无血管炎。药物治疗2年过程中,PTU组6/25例(24%)和MMI组5/25例(20%)患者发生小血管炎(24%vs 20%,χ2=0.17,P=0.70),其中PTU组4/6(66.7%)例与MMI组0/5(0%)例ANCA阳性(66.7%vs 0%,χ2=2.75,P=0.06)。结论在内科药物治疗过程中,丙基硫氧嘧啶(PTU)可以诱发ANCA及ANCA相关血管炎,而他巴唑(MMI)可能诱发与ANCA无关血管炎。     

白塞病合并8号染色体三体22例分析及文献复习

目的 探讨分析8号染色体三体异常白塞病(Behcet's disease,BD)患者的临床特点.方法 分析2012年10月至2020年7月复旦大学附属华东医院收治的22例8号染色体三体BD的住院患者,并检索中英文文献库中BD合并8号染色体三体的患者共46例,对临床特点进行比较分析.结果 22例8号染色体三体的BD患者中...     

幽门螺杆菌细胞毒素相关蛋白A与溃疡病的关系

目的　探讨幽门螺杆菌 (Hp)细胞毒素相关蛋白A(CagA)与溃疡病的关系。方法　采用ELISA方法对 98例溃疡病患者进行血清CagA -Hp -IgG抗体检测 ,治疗后半年再次检测。结果　 5 0例十二指肠球部溃疡 (DU)阳性率为10 0 % ,4 8例胃溃疡 (GU)阳性率为 83.3% ;半年后复检DU阳性率为 10 % ,GU阳性率为 7.5 % ,治疗前后两者阳性率具有显著性差别 (P <0 .0 1)。结论　CagA与溃疡病密切相关。     

Importance of checking anti-glomerular basement membrane antibody status in patients with anti-neutrophil cytoplasmic antibody-positive vasculitis

The case is reported of a 68-year-old man with perinuclear anti-neutrophil cytoplasmic antibody (pANCA)-associated glomerulonephritis who developed antibodies to glomerular basement membrane (anti-GBM) resulting in end stage renal failure. His pANCA titre on admission was 1:1024 IgG and he was anti-myeloperoxidase positive. A renal biopsy showed advanced sclerosing necrotising glomerulonephritis consistent with a pauci-immune ANCA-positive glomerulonephritis. He was treated with steroids and cyclophosphamide. His serum creatinine profile improved. He had a relapse of disease 16 months later, which was successfully treated. After a further 16 months, he presented with acute renal failure (creatinine 1060 micromol/l). His pANCA titre on admission was 1:64 IgG. This was treated as a further relapse of ANCA-positive vasculitis. He became oliguric and his haemoglobin concentration fell. Eight days after admission, he was found to be strongly positive for anti-GBM (138 U/ml). Despite receiving cyclophosphamide, steroids and plasma exchange, he remained dialysis-dependent.     

Scleroderma and repeated spontaneous abortions treated with vitamin E--a case report--

A 33-year-old woman was referred to our hospital due to repeated spontaneous abortions and positive autoantibodies. She had noticed Raynaud's phenomenon 13 years earlier. We diagnosed scleroderma based on the presence of Raynaud's phenomenon, proximal scleroderma, presence of anti-centromere antibodies, and histological findings on skin biopsy. Neither lupus anticoagulant nor anti-cardiolipin-beta2-glycoprotein 1 antibody was detected. We administered tocopherol nicotinate. Five months after the initiation of the treatment, she became pregnant and later delivered a healthy baby.     

术前MRV联合多普勒超声在活动性下肢静脉性溃疡诊断及治疗中的作用

目的 探讨术前磁共振静脉造影(magnetic resonance venography, MRV)检查在活动性下肢静脉性溃疡诊断及治疗中的作用。方法 回顾性分析60例慢性下肢静脉性溃疡患者资料,根据术前进行MRV联合多普勒超声检查(35例)和单纯多普勒超声检查(25例),分别设定为A组和B组。患者行腔内激光治疗技术(endovenous laser ablation, EVLT)联合隐股静脉结扎术,应用Kaplan-Meier生存分析方法对两组患者术后6个月的溃疡愈合率及术后36个月的溃疡复发率进行统计学分析。结果 随访36个月,随访率93.33%。两组患者的性别、年龄、溃疡直径和溃疡持续时间差异无统计学意义。术后6个月,两组患者的累积溃疡愈合率差异没有统计学意义(88.6% vs 92%, P=0.642)。36个月的随访期中,A组累积溃疡复发率明显低于B组(5.7% vs 24%, P=0.037)。结论 术前MRV联合多普勒超声检查对活动性下肢静脉性溃疡的诊断和治疗具有重要的指导价值。     

胶囊内镜在小肠疾病诊断中的应用

目的：探讨胶囊内镜在小肠疾病诊断中的应用价值和安全性。方法：对81例不明原因的消化道出血和腹痛患者行Given M2A胶囊内镜检查,分析其临床资料。结果：81例患者中9例胶囊内镜检查未发现明显异常,1例胶囊内镜未进入小肠,其余71例共发现小肠病变132处,小肠病变检出率88.75%。这些小肠病变包括炎症36例,血管病变24例,隆起性病变16例,息肉15例,小肠内血液覆盖12例,溃疡11例,小肠蛔虫6例,憩室5例,克罗恩病5例,钩虫病1例,小肠发育不良畸形并内瘘1例。胶囊内镜诊断的5例间质细胞瘤均经手术后病理证实,而克罗恩病、淋巴瘤、血管瘤等隆起性病变在胶囊内镜均未能正确诊断。胶囊内镜获取的图像质量良好。患者无明显并发症发生。结论：胶囊内镜对小肠疾病检出率较高、安全性好,但定性诊断能力有限,是一种安全有效的小肠疾病诊断的筛查方法。     

筋膜皮瓣治疗小腿顽固溃疡9例报告

本文报道应用小腿后侧筋膜皮瓣治疗9例胫前区顽固性溃疡的经验,一期治愈者8例,二次皮瓣转移治愈者1例。随诊6个月至2年,未见溃疡复发。     

扶脾抑肝汤治疗糖尿病性腹泻临床研究

目的:观察扶脾抑肝汤治疗糖尿病性腹泻的临床疗效。方法:将100例糖尿病性腹泻患者随机分为对照组和观察组各50例,对照组给予整肠生胶囊,口服,每次3粒,每日3次,观察组给予扶脾抑肝汤,每日2次,分早晚口服。两组患者均连续治疗3个月,在治疗1个月和3个月时统计两组患者临床疗效。结果:治疗1个月后,对照组有效率为80.00%,观察组有效率为88.00%,两组有效率比较,差异无统计学意义(P0.05);治疗3个月后,对照组有效率为50.00%,观察组有效率为90.00%,两组有效率比较,差异有统计学意义(P0.05)。两组患者治疗后部分中医症状积分较治疗前降低,治疗前后比较,差异有统计学意义(P0.05),两组治疗后比较,差异有统计学意义(P0.05);两组患者治疗后空腹血糖(fasting plasma glucose,FPG)、餐后2小时血糖(2-hour postprandial blood glucose,2h PG)水平较治疗前降低,治疗前后比较,差异有统计学意义(P0.05);观察组治疗后FPG、2h PG水平与对照组治疗后比较,差异有统计学意义(P0.05)。两组患者治疗后肠道菌群计数与治疗前比较,差异有统计学意义(P0.05);观察组治疗后肠道菌群计数与对照组治疗后比较,差异有统计学意义(P0.05)。结论:扶脾抑肝汤可以提高糖尿病性腹泻患者的临床疗效,可以改善糖尿病性腹泻患者中医症状积分,降低FPG、2h PG水平,改善肠道菌群。