系统性红斑狼疮生物疗药物浅谈

近年来,生物靶向治疗越来越多地应用于自身免疫性疾病患者的治疗,并取得了较好的疗效。系统性红斑狼疮(SLE)是一种多系统受累的自身免疫病,患者体内存在多种免疫紊乱。目前治疗SLE的生物制剂包括去除B细胞、抑制T-B细胞间相互作用以及拮抗炎性细胞因子和B细胞活化因子等方面的药物。本文简要介绍已经上市和正在进行临床试验的SLE生物靶向治疗药物。     

系统性红斑狼疮合并淋巴瘤临床特征

目的探讨系统性红斑狼疮(SLE)合并恶性淋巴瘤(ML)的临床特点。方法回顾1998年1月至2012年2月北京协和医院收治的9例SLE合并ML患者的临床资料,分析其临床表现、实验室检查指标、淋巴瘤病理分型、治疗及预后。结果 SLE合并ML患者共9例,占同期SLE入院患者的0.18%;其中女性患者7例,男性患者2例;SLE平均发病年龄43.1岁(24～57岁),SLE平均确诊年龄为44.7岁(29～57岁),淋巴瘤平均确诊年龄为48.7岁(39～63岁),SLE发病到合并淋巴瘤病程均数为3.8年(1～15年)。淋巴瘤病理类型以非霍奇金淋巴瘤(NHL)为主,共7例,占77.8%(7/9),且淋巴瘤结外受累多见,共7例,占77.8%(7/9)。淋巴瘤在消化系统、呼吸系统、骨髓等部位均可发生,其中胃肠道受累3例,支气管和肺受累2例,骨髓受累2例。SLE合并ML患者中100%出现关节痛、淋巴结肿大及发热。实验室检查结果发现9例患者中6例补体减低,9例乳酸脱氢酶升高,5例红细胞沉降率(ESR)升高大于100mm/h。SLE合并ML的患者6例对化疗敏感,4例死亡,2例死因均为淋巴瘤消化道受累;2例诊断淋巴瘤放弃治疗后死亡。结论当SLE患者出现不明原因持续发热、淋巴结肿大、ESR持续大于100mm/h,乳酸脱氢酶持续偏高者需警惕SLE合并淋巴瘤的可能。当SLE合并淋巴瘤时结外受累多见,SLE合并ML多数对化疗敏感,但消化道受累时预后差。     

Ibuprofen-induced Meningitis in a Male with Systemic Lupus Erythematosus

ABSTRACT. Jensen S, Glud TK, Bacher T, Ersgaard H (Departments of Endocrinology, Clinical Immunology and Anaesthetics, Aalborg Hospital, Aalborg, Denmark). Ibuprofen-induced meningitis in a male with systemic lupus erythematosus. Acta Med Scand 1987; 221:509–11. A 36-year-old male with systemic lupus erythematosus developed aseptic meningitis after in-gestion of ibuprofen. He was unconscious, had a universal rash, high fever and a pathological CSF. Being severely ill he was treated with high doses of corticosteroids and plasmapheresis and recovered within a week. Ibuprofen, a non-steroidal anti-inflammatory drug of the propionic acid group, is frequently used in patients with connective tissue disorders. Within the past eight years a few reports have been published on aseptic meningitis following ingestion of ibuprofen in patients with systemic lupus erythematosus (SLE) (1–5) and mixed connective tissue disease (6–8). All of these patients were women. We report a serious case of aseptic meningitis in a male subject with SLE.     

Lymphocytic Enterocolitis in Systemic Lupus Erythematosus

Microscopic colitis (MC) is a recognized cause of chronic watery diarrhea. It is characterized by subepithelial collagen deposition or intraepithelial lymphocytic infiltration of the colonic mucosa which, however, appears grossly normal on endoscopy. The term microscopic enterocolitis is applied when MC is associated with similar microscopic affection of the ileum and/or proximal small intestine. MC is reported to be associated with a variety of autoimmune conditions. Systemic lupus erythematosus (SLE) is rarely reported in association with MC. We report a female patient with microscopic enterocolitis as one of the presenting manifestations of SLE.     

系统性红斑狼疮并发蛛网膜下腔出血的临床特点

目的探讨系统性红斑狼疮(systemic lupus erythematosus,SLE)并发蛛网膜下腔出血(subarachnoid hemorrhage,SAH)患者的临床特点及预后。方法总结分析1983年1月至2012年1月就诊于北京协和医院的12例SLE并发SAH患者的临床资料。结果 SLE并发SAH患者住院期间的病死率高达42%(5/12)。SLE并发SAH的症状以头痛为主(75%)。系统性红斑狼疮疾病活动指数平均为(17.5±4.5)分。死亡患者在SAH发生早期即出现意识障碍者占80%(4/5),合并严重感染者占60%(3/5)。结论 SAH是SLE的少见且致命的并发症。对于出现意识障碍或合并感染的SLE患者,应当提高警惕,积极治疗SLE原发病及SAH,提高生存率。     

系统性红斑狼疮合并Evans综合征临床特点

目的总结系统性红斑狼疮(systemic lupus erythematosus,SLE)合并Evans综合征患者的临床特点。方法回顾性分析北京协和医院2004年1月至2012年7月SLE合并Evans患者的临床表现及实验室特点及治疗和预后。结果 SLE并发Evans综合征患者22例,占同期SLE住院患者3400例的0.65%。其中男3例,女19例,平均35.1岁(16~53岁)。22例患者中以血液系统受累[特发性血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)或自身免疫性溶血性贫血(autoimmune hemolytic anemia,AIHA)]为首发表现的11例(50%),确诊SLE后诊断Evans综合征者6例,二者同时诊断的5例。SLE并发Evans综合征时,患者往往有多系统受累,表现为肾脏受累13例(59.1%),皮肤黏膜受累、关节炎各9例(40.9%),神经系统受累4例(18.2%),胃肠道、肺部受累各2例等。Evans综合征多发生于SLE活动期,患者平均狼疮活动指数评分(11.45±7.6)分(3~30分)。伴发其他结缔组织病5例(22.7%)。经激素联合免疫抑制剂治疗后,20例好转,2例无效者应用利妥昔单抗后好转。结论 SLE合并Evans综合征罕见,发生于SLE多系统受累及活动期。部分患者以ITP或AIHA为SLE首发表现,应及时筛查多种自身抗体,并定期随访密切观察,以期早期诊治。     

系统性红斑狼疮男性患者临床及免疫学特征

目的 分析142例男性系统性红斑狼疮(SLE)患者起病时首发及发病过程中临床表现特征、自身抗体分布以及其他实验室指标改变特征,探讨SLE男性患者的临床及免疫学特征.方法 收集1994年4月至2010年4月于本院风湿免疫科住院的男性SLE患者142例,年龄12 ～ 68岁,平均年龄31.9岁;同期住院女性SLE患者320...     

43例系统性红斑狼疮病人的心电图分析

目的 分析系统性红斑狼疮病人的心电图表现。方法 对汕头大学医学院第一附属医院收治的107例系统性红斑狼疮病人，应用心电图仪行常规心电图检查，并分类统计。结果 107例系统性红斑狼疮病人中心电图异常43例，其中窦性心动过速24例（22．4％）．ST-T改变11例（10．3％）其他8例；期前收缩1例（0．9％）；低电压9例（8．4％）；左室高电压2例（1．9％）；房室传导阻滞3例（2．8％）。结论 系统性红斑狼疮的心电图改变常见。提示临床可将心电图作为系统性红斑狼疮心脏损害的常规检查。     

51例系统性红斑狼疮患者妊娠结局

目的研究系统性红斑狼疮(systemic lupus erythematosus,SLE)患者妊娠不良结局的发生率及引起不良结局的相关因素。方法回顾性分析51例在本院风湿免疫科规律随访并最终在本院产科分娩的SLE患者的病历资料,总结患者的妊娠结局、新生儿情况以及妊娠期间服用药物、分娩前SLE疾病活动度评分(systemic lupus erythomatosus disease activity index,SLEDAI)。比较不同疾病活动度组患者在药物治疗、不良妊娠结局发生率方面的不同,并比较不良妊娠结局组(妊娠胎儿丢失、新生儿死亡)与活产组患者药物治疗及疾病活动情况。结果 51例SLE患者的平均年龄(28.0±3.9)岁,平均病程(4.7±4.5)年,妊娠期间26例(51.0%)应用羟氯喹治疗,31例(60.8%)应用糖皮质激素治疗,平均剂量为泼尼松5 mgd(0~30 mgd)。分娩(或引产)前51例患者的SLEDAI为(11.8±10.3)分,其中SLE中-重度活动组患者20例(39.2%),8例(15.7%)引产;病情缓解-轻度活动组患者31例,无1例引产。共出生新生儿45例(其中2对双胎),新生儿死亡2例(4.4%);活产43例新生儿中2例(4.7%)发生新生儿狼疮。与疾病缓解-轻度活动组患者相比,中-重度活动组患者的平均住院时间[(25.5±14.0)vs.(13.5±8.5)]、胎儿丢失率[10(50.0%)vs.0(0.0)]及早产率[9(63.6%)vs.9(21.4%)]均显著高于前者,差异有统计学意义(均P0.05);而应用糖皮质激素比例[8(40.0%)vs.23(60.7%)]及用药剂量[0(0,30)mg vs.6(0,20)mg]更低,但差异无统计学意义(P0.05)。不良妊娠结局(胎儿丢失及新生儿死亡)组分娩(或引产)前SLEDAI明显高于活产组[(21.3±8.9)vs.(7.1±7.9),P0.01],而妊娠期糖皮质激素应用比例少于活产组(30.0%vs.68.3%,P=0.032),但两组在羟氯喹应用剂量上无明显差别[0(0,20)mg vs.6(0,30)mg,P=0.096]。结论分娩前SLE活动度与妊娠不良结局(如胎儿丢失、早产及新生儿死亡)有关,疾病活动度高是发生妊娠不良结局的危险因素。     

系统性红斑狼疮患者血清基质金属蛋白酶水平变化

目的探讨系统性红斑狼疮(systemic lupus erythematosus,SLE)患者血清基质金属蛋白酶(matrix metalloproteinase,MMP)-3及MMP-9水平变化与疾病的关系和意义。方法测定SLE患者及健康对照者血清MMP-3,MMP-9水平,将SLE患者分为SLE活动期组与SLE非活动期组,且根据有无累及神经系统、肾脏及关节分为不同病损组,将同时无神经系统、肾脏及关节炎者定义为无器官损害组。结果共纳入SLE组患者85例,将其中临床资料相对充分的59例患者分为SLE活动期组22例,SLE非活动期组37例。SLE患者血清MMP-3水平明显高于对照组(P0.01),SLE活动期和非活动期患者之间无明显差异(P0.05);SLE活动期患者血清MMP-9水平低于SLE非活动期患者和对照组,差异有统计学意义(P0.05,P0.01)。神经系统损害组、肾损害组及关节炎组患者血清MMP-9水平明显低于无器官损害组(P0.05)。结论血清MMP-3可能参与了SLE的发病,其水平下降可能与狼疮病情改善有关,可作为治疗后病情好转的信号。血清MMP-9水平和疾病活动或进行性脏器损害有关,有望作为评判SLE疾病活动和预后的指标。     

Lupus Band Test in Uninvolved Oral Mucosa in Systemic Lupus Erythematosus

ABSTRACT In 42 patients with systemic lupus erythematosus, clinically normal oral mucosa was investigated with direct immunofluorescence technique for the presence of immunoglobulins G, A and M and complement factor C3 in the mucosal basement membrane zone (the lupus band test, LBT). Punch biopsies were performed in the posterior part of the hard palate (n = 39) or the lower labial mucosa (n = 3). The immunopathological observations were compared with clinical and serological data. The LBT was positive for IgM in 45% of the patients and trace amounts of IgM were found in another 19%. In 7 cases (17%) either IgG, IgA or C3 were found in addition to IgM and these patients all had a severe form of the disease, while the presence of IgM only was not correlated to clinical parameters.     

The Dissociation of Arterial Hypertension and Lupus Glomerulonephritis in Systemic Lupus Erythematosus

In spite of several articles questioning the general opinion that arterial hypertension in patients with systemic lupus erythematosus (SLE) is only the consequence of lupus glomerulonephritis (LGN), this still remains the usual pathophysiologic explanation. The purpose of this study was to explore the correlations between hypertension and LGN and to assess the importance of hypertension control for the prognosis of patients. A retrospective analysis of 173 patients with SLE over a period of 14 years was performed. For most of the patients, data were available from regular follow-up visits over an average of 6 years. Our results show a dissociation of hypertension and LGN and an association of hypertension and renal dysfunction. Severe hypertensive renal vascular lesions correlated well with a decrease of renal function. Successful treatment of hypertension is therefore essential in order to prevent deterioration of renal function in patients with LGN.     

Haemophilus influenzae type b conjugate vaccine is highly effective in the Ugandan routine immunization program: a case-control study

Objective To study the effectiveness of the Haemophilus influenzae type b (Hib) vaccination program in Uganda. Methods Case–control study of Hib vaccine effectiveness against Hib meningitis. Cases were children hospitalized with Hib meningitis confirmed by culture and/or latex agglutination. Cases were identified retrospectively from July 2002 to July 2004, and prospectively from July 2004 to July 2005. Each case‐patient was matched by age to three neighbourhood and three hospital controls; all children were eligible to receive Hib vaccine through the routine schedule. Vaccine effectiveness was evaluated by conditional logistic regression, controlling for confounding variables. Results We enrolled 41 cases; their median age was 6 months. Only six (15%) cases, all HIV‐negative, had received ≥2 doses of Hib vaccine, compared with 64% of neighbourhood controls and 70% of hospital controls. Controlling for maternal education, the only variable which remained in the multivariable model, vaccine effectiveness for two or three doses vs. no dose was 99% [95% confidence intervals (CI) 92–100%] and 96% (95% CI 80–100%) when cases were compared with neighbourhood and hospital controls, respectively. Conclusion In Uganda, Hib vaccine was highly effective in the context of the routine immunization schedule. Sustained routine use of Hib vaccine will contribute to the prevention of childhood morbidity and mortality.     

Risk Factors in Cardiovascular Disease in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic and multisystemic autoimmune disorder which predominantly affecting women. The most common cause of death in SLE patients affected by disease for more than 5 years is cardiovascular disease (CVD). Epidemiological observations suggest that, together with classical conventional risk factors, other mechanisms (non-conventional/disease-specific factors) promote accelerated atherosclerosis in inflammatory diseases like SLE. Traditional CVD risk factors included age, hypertension, diabetes mellitus, dyslipidemia, previous vascular event defined as previous history of cerebrovascular accidents or ischemic heart disease, menopause and smoking. The non-traditional factors presents in SLE are disease-specific like renal disease manifestation as Lupus nephritis (LN), presence of pro-inflammatory cytokines, some of inflammatory mediators, antiphospholipid antibodies, anti-oxLDL antibodies, corticosteroid uses and cumulative dose of glucocorticoids. We will review traditional and non-traditional risk factors associated with CVD in SLE patients.     

Therapeutic Plasma Exchange Improved Pregnancy-associated Thrombotic Microangiopathy but not the Pregnancy Outcome in Patient with Systemic Lupus Erythematosus

Thrombotic microangiopathy (TMA) is a rare but life-threatening complication of systemic lupus erythematosus (SLE) and is associated with adverse pregnancy outcomes. We herein report a 30-year-old pregnant woman with SLE complicated by TMA. Because her condition was unresponsive to initial corticosteroid and fresh-frozen plasma infusion treatment, we attempted plasma exchange (PE). Although thrombocytopenia and microangiopathic hemolytic anemia gradually improved, fetal death was confirmed at 23 weeks of gestation. This case suggests that PE is an effective therapeutic option but might be insufficient to maintain pregnancy in patients with SLE complicated by TMA.     

Increase in invasive disease caused by Haemophilus influenzae b,the Netherlands, 2020 to 2021

The incidence of most respiratory-transmitted diseases decreased during the COVID-19 pandemic as a result of containment measures. In contrast, in the Netherlands we noted an increase in invasive disease caused by Haemophilus influenzae b (Hib) (from < 0.3/100,000 before 2019 to 0.39 and 0.33/100,000 in 2020 and 2021) in vaccinated and unvaccinated age groups. We did not find a change in vaccine effectiveness against Hib invasive disease (effectiveness > 90%). We discuss factors that may have contributed to this rise.     

Bone Marrow Megakaryocytes and Platelet Kinetics in Systemic Lupus Erythematosus

ABSTRACT. The megakaryocyte number and mean megakaryocyte area were determined in histological sections of sternal bone marrow from 26 patients with systemic lupus erythematosus (SLE). Also 20 platelet survival studies were carried out in these patients. The results were analyzed with respect to corticosteroid (CS) and CS+azathioprine (AT) therapy. The mean bone marrow megakaryocyte number was highest in untreated SLE patients, slightly lower in patients receiving CSs and lowest in those receiving CSs + AT. The difference was, however, not significant. The mean megakaryocyte areas were smallest in untreated SLE patients, slightly larger in those treated with CSs and significantly (p<0.05) larger in patients who received CSs + AT than in untreated patients. Platelet production rate was normal in all 3 groups of SLE patients. The results suggest that CS and AT therapy in SLE intervenes with the bone marrow megakaryopoiesis without affecting the production rate of platelets.