妊娠期狼疮危象的早期识别和规范化救治

系统性红斑狼疮(systemic lupus erythematosus, SLE)是一种好发于育龄期女性的慢性自身免疫性疾病,狼疮危象是指急性的危及生命的重症SLE。妊娠可使SLE患者病情加重,甚至诱发狼疮危象。早期识别和规范化治疗妊娠期狼疮危象,是抢救患者生命的关键。     

妊娠合并系统性红斑狼疮180例临床分析

目的:探讨孕期新发狼疮、狼疮肾炎对妊娠合并系统性红斑狼疮(SLE)患者母婴结局的影响。方法:回顾分析2009年1月至2018年12月广州医科大学附属第三医院收治的180例妊娠合并SLE患者的临床资料。依据SLE发生时间分为孕前SLE组和孕期新发SLE组;依据肾脏是否受累,将孕前SLE组分为狼疮肾炎组和非狼疮肾炎组。结果:相比活产产妇,胚胎丢失产妇的高血压、低补体血症、尿蛋白、贫血、狼疮肾炎发生率显著升高(P0.05)。相比孕前SLE组,孕期新发SLE组的母婴结局更差。孕前SLE组中,相比非狼疮肾炎组,狼疮肾炎组的母体结局更差。结论:孕期新发SLE的母婴结局更差,孕前SLE狼疮肾炎组的母体结局更差。     

妊娠合并系统性红斑狼疮与不良妊娠结局

系统性红斑狼疮（SLE）是好发于育龄期女性的自身免疫性结缔组织病。系统性红斑狼疮患者发生不良妊娠结局的风险高达19.0%～70%。妊娠合并SLE常见的不良妊娠结局包括狼疮复燃、流产、早产、子痫前期、胎儿生长受限、新生儿狼疮等。当SLE同时伴有特异性抗体如抗磷脂抗体时,不良妊娠结局的发生风险上升28.4%;伴有Ro/La抗体时,胎儿、新生儿先天性心脏传导阻滞发生率为1%～2%。SLE缓解期在医生指导下计划妊娠、孕期严密监测、个体化及多学科管理是改善不良妊娠结局的关键。     

妊娠合并系统性红斑狼疮77例临床分析

目的:探讨妊娠时机及孕期狼疮活动对妊娠合并系统性红斑狼疮(SLE)患者的妊娠并发症及妊娠结局的影响。方法:回顾分析77例妊娠合并SLE患者的临床资料,根据妊娠前SLE病情将患者分为妊娠前SLE病情稳定≥6月组(25例)、SLE病情稳定4~6月组(19例)、SLE病情稳定4月组(16例)和妊娠前SLE活动组(17例)。根据妊娠期SLE病情是否活动分为SLE稳定组(49例)和SLE活动组(28例)。比较各组的妊娠并发症和妊娠结局情况。结果:(1)妊娠前SLE病情稳定≥6个月组的子痫前期、胎儿宫内生长迟缓(IUGR)、胎儿宫内窘迫、胎儿丢失、早产及新生儿低出生体重的发生率显著低于妊娠前SLE病情活动组,其IUGR、胎儿宫内窘迫、胎儿丢失及新生儿低出生体重的发生率显著低于妊娠前SLE病情稳定4个月组。(2)妊娠期SLE稳定组的子痫前期、IUGR、PROM、胎儿丢失率、早产率和新生儿低出生体重率均显著低于SLE活动组。(3)妊娠前SLE病情稳定≥6月组的妊娠期SLE活动率低于妊娠前SLE病情稳定4个月组,差异有统计学意义(P0.05);妊娠前SLE病情稳定≥6月组和稳定4~6月组的妊娠期SLE活动率比较,差异无统计学意义(P0.05)。结论:妊娠前SLE病情应至少稳定4个月,同时孕期控制狼疮活动,以减少妊娠期并发症及改善妊娠结局。     

妊娠时机对妊娠合并系统性红斑狼疮病情及妊娠结局的影响

目的:探讨妊娠时机对妊娠合并系统性红斑狼疮(SLE)患者孕期病情及妊娠结局的影响.方法:对46例妊娠合并SLE孕妇的临床资料进行回顾性分析,按妊娠时机的不同分为两组:SLE控制期和缓解期达6个月以上怀孕者为指导性妊娠组(32例);SLE活动期怀孕者以及孕期新发SLE的病例为非指导性妊娠组(14例),比较两组患者孕期SLE的病情和妊娠结局的不同.结果:①指导性妊娠组孕期SLE的活动率和泼尼松用量分别为15.6％和9.6±1.1 mg/d明显低于非指导性妊娠组100％和24.1±18.2 mg/d(P =0.000,P=0.012).②指导性妊娠组24小时尿蛋白定量、肌酐、抗dsDNA抗体等指标的异常率均较非指导性妊娠组明显降低(P=0.003,P=0.004,P=0.021).③指导性妊娠组无一例母婴死亡;非指导性妊娠组产妇死亡1例,胎儿丢失5例.指导性妊娠组的活产率(100％)较非指导性妊娠组(64.3％)明显升高(P=0.001);胎儿丢失和胎儿生长受限发生率分别为0和18.8％,较非指导性妊娠组35.7％和50.0％明显降低(P=0.001,P=0.030).结论:妊娠时机对妊娠合并SLE患者孕期是否出现狼疮活动以及妊娠结局,尤其是胎儿结局影响较大,选择在SLE病情稳定半年以上计划怀孕,妊娠结局较好.     

妊娠合并系统性红斑狼疮7例临床分析

目的:明确妊娠与系统性红斑狼疮(SLE)间的相互影响,探讨对妊娠合并高血压或蛋白尿患者中SLE的早期识别、诊断与治疗方法.方法:对近8年来我院7例妊娠合并SLE的高危患者进行回顾分析,观察其病情演变与治疗间的关系.结果:4例妊娠后初发SLE患者均伴有血压升高及尿蛋白阳性,其中3例患者病情危重(死亡1例),足月分娩1例,早产3例(死亡1例).3例妊娠前确诊患者,其中1例控制期患者合并有高血压;2例缓解期患者中1例合并有蛋白尿,但病情均平稳,3例均足月分娩,1例为小于胎龄儿.结论:妊娠可诱发或加重SLE.妊娠后初发的患者妊娠结局差,合并高血压及蛋白尿预后较差;SLE控制期和缓解期妊娠预后较好.应加强妊娠合并高血压或蛋白尿患者中SLE的早期识别、诊断及相应治疗.     

系统性红斑狼疮患者妊娠及终止妊娠时机的探讨

目的 探讨系统性红斑狼疮(SLE)患者适宜的妊娠时机及终止妊娠的时机。方法 回顾性分析我院1998～2003年共29例SLE患者妊娠和妊娠结局,选择出适宜的妊娠时机及终止妊娠的时机。结果29例SLE患者均在至少6个月内未服用细胞毒药物的情况下妊娠。其中23例患者在病情控制1年以上(缓解期)妊娠(为选择性妊娠组);2例患者在病情活动期未经医生同意自行妊娠,4例患者妊娠期首发SLE(为非选择性妊娠组)。两组患者在妊娠期均发生病情变化,根据个体情况选择不同剂量的糖皮质激素(泼尼松)予以适当治疗。其中选择性妊娠组妊娠评分4～9分(以中度高危为主),分娩孕周为34—38周;非选择性妊娠组妊娠评分9-15分(全部为重度高危),平均分娩孕周为32周。两组患者共分娩活婴29个,其中早产儿8个,胎儿生长受限(FGR)3个,严重先天性心脏病患儿1个,因早产并发症致早期新生儿死亡2个,未发现新生儿狼疮。结论 SLE患者妊娠期给予适当合理的糖皮质激素治疗,加强监护,在病情缓解期选择性妊娠,其安全性明显提高。在药物治疗无好转威胁母婴安全情况下,或胎儿已成熟时,应适时终止妊娠(孕34—38周终止妊娠较为适宜),可以减少并发症的发生,提高妊娠成功率及围产儿存活率。     

妊娠合并系统性红斑狼疮的诊治

系统性红斑狼疮(SLE)患者合并妊娠时,可使SLE病情复发或恶化,同时SLE亦会增加妊娠合并症,并对胎儿产生不良影响。因此,对于有生育要求的SLE患者须选择适当的妊娠时机,孕期接受严密的监护和适当的治疗,方能获得良好的妊娠结局。现本文就妊娠合并系统性红斑狼疮的诊断及治疗方法做一阐述。     

妊娠合并系统性红斑狼疮患者孕期并发症及妊娠结局的临床分析

目的分析并探讨系统性红斑狼疮(SLE)患者的孕期并发症情况及妊娠结局。方法回顾性分析2000年1月至2010年3月北京大学人民医院收治的19例妊娠合并SLE患者的临床资料,对影响SLE合并妊娠并发症的相关因素和SLE不同妊娠时机的妊娠结局进行分析。结果 19例患者中11例(11/19,57.9%)出现了母儿并发症,4例重度子痫前期,1例流产,2例死胎,2例足月低出生体重,4例早产。无并发症组8例,两组患者的孕产次及孕前病程、分娩方式无明显差异,但无并发症组患者的年龄小于并发症组,分娩孕周明显延长,新生儿体重明显增加,两组差异有统计学意义(P=0.006);孕前病情的稳定程度对孕期母儿并发症的影响差异无统计学意义(P=0.633);但妊娠前病情稳定大于6个月的患者出现并发症的比例较低(6/12,50.0%vs5/7,71.4%)。3例妊娠期间诊断SLE的患者均在孕期或产后出现了严重的并发症,1例(1/3,33.3%)新生儿诊断为SLE;与孕前病情控制平稳6个月的患者相比,分娩孕周较小,新生儿体重较低(P0.05)。结论 SLE患者即使孕前病情控制平稳,妊娠后仍有可能出现严重的母儿并发症。在病情控制平稳后妊娠,孕期在产科和风湿科医师的共同严密监测下,坚持治疗,适时终止妊娠是改善母婴结局的关键。同时应注意提高对妊娠期SLE的诊断。     

自身抗体与系统性红斑狼疮孕妇的妊娠结局

系统性红斑狼疮( SLE)是自身免疫介导的、以免疫性炎症为突出表现的弥漫性结缔组织病,好发于生育年龄段女性.妊娠状态有可能使SLE病情活动、恶化,同时SLE病情又能影响母胎结局.20％ ～ 35％的SLE患者会继发抗心磷脂抗体综合征,抗磷脂抗体综合征(APS)与复发性流产、胎儿生长受限、早产、死产、子痫前期的发生密切相关.抗磷脂抗体(aPL)是APS的特征性抗体,包括狼疮抗凝抗体、抗心磷脂抗体、抗β2球蛋白1抗体.抗SSA/Ro、SSB/La抗体与新生儿先天性心脏传导阻滞的发病有关.本文旨在总结这些自身抗体与SLE孕妇的妊娠结局的关系,以便指导临床.     

Comparison of different diagnostic methods for lupus pleuritis and pericarditis: a prospective three-year study.

BACKGROUND AND PURPOSE: Pleural or pericardial effusions, or both, are commonly encountered, but the differential diagnosis is sometimes difficult. We evaluated the diagnostic value of effusion immunofluorescent antinuclear antibody (ANA) titer, systemic lupus erythematosus (SLE) latex agglutination slide test, and cytologic LE cell examination in patients with pleural and/or pericardial effusions of various etiologies. METHODS: A total of 153 pleural and/or pericardial effusion specimens were collected by aspiration from 152 patients (14 SLE and 138 non-SLE patients). All specimens were sent for routine biochemistry testing, determination of ANA titer, SLE latex agglutination slide test, and LE cell examination. RESULTS: Ten of the 14 SLE patients had lupus serositis and all of them had high ANA titers (> or = 1:160) in their effusions. SLE latex and LE cell tests were positive in seven and eight patients with lupus serositis, respectively. The remaining four SLE patients with effusion of etiologies other than lupus serositis had low or negative effusion ANA titers. Among the non-SLE patients, 29 of 112 patients (26%) with pleural effusion and six of 26 patients (23%) with pericardial effusion had positive ANA tests (> or = 1:40). None of them had a positive SLE latex or LE cell test result. Thirteen of the 138 non-SLE patients (11%) had high effusion ANA titers (> or = 1:160). Effusion in 11 of 13 non-SLE patients (85%) was due to malignancy. CONCLUSIONS: Effusion ANA titer detection is a very sensitive but nonspecific test for the diagnosis of lupus serositis. SLE latex and cytologic LE cell tests can aid in the differential diagnosis as complementary tools. The specificity, positive and negative predictive values of these two tests are excellent for the diagnosis of lupus serositis.     

Retrospective evaluation of pregnancy in women suffering from systemic lupus erythematosus (SLE)

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease predominantly affecting women of childbearing age, which may negatively influence the pregnancy course and outcomes. The objective of the study was to estimate the risk of fetal loss and prematurity in lupus patients. These data seem to be an important component of family counselling in lupus patients. DESIGN: The pregnancies' course and outcomes in lupus patients and in healthy controls were compared. MATERIAL AND METHODS: 47 lupus patients with pregnancies occurring after the diagnosis of SLE and 108 healthy controls were included in this study. The pregnancies were analysed in terms of delivery term and outcomes (live births/ miscarriage/ neonatal deaths/ congenital defects). The structured review and case histories analysis were used to gather the data. RESULTS: The percentage of spontaneous abortions (24.1%) and preterm deliveries (24.1%) were significantly higher in lupus patients when compared with healthy controls (9.3% and 5.3% respectively). CONCLUSIONS: The caution in pregnancy planning in lupus patients is necessary and the role of physicians' information in patients' awareness of fetal loss and prematurity is vital.     

Pregnancy in patients with systemic lupus erythematosus

We reviewed the obstetrical performance and outcome of 15 pregnancies in patients with systemic lupus erythematosus (SLE) (study group) and compared them with 45 age and parity-matched normal pregnancies (control group). Eleven women (73.8%) were in remission phase and 4 (26.7%) had active disease at the time of conception. The time interval between disease diagnosis and the index pregnancy was 4.2 +/- 2.5 years. Two patients with renal involvement had lupus flare-up during the antenatal period. There was no case of lupus flare-up in the postpartum period. Gestational age at delivery was significantly lower in SLE patients (35.9 +/- 2.5 weeks) compared to the control group (37.4 +/- 2.2 weeks). The incidence of intrauterine growth retardation was significantly higher in the SLE patients (40%). There was no case of neonatal lupus or congenital heart block.     

Abnormal cervicovaginal cytology in women with lupus: a retrospective cohort study.

OBJECTIVE: The aim of this study was to review Pap smear reports in women with systemic lupus erythematosus and compare them to a large control population. METHODS: Pap smear results of 29 women with a diagnosis of lupus seen consecutively were compared to those of a control population of 747 women attending the gynecology clinic at the same medical center during the same year. Records of lupus patients were reviewed to obtain clinical data. Fisher's exact test and chi(2) analysis were used to determine statistical significance, as appropriate. RESULTS: Of 29 women with lupus, 1/29 had high-grade squamous intraepithelial lesions (HGSIL) and 6/29 had low-grade squamous intraepithelial lesions (LGSIL). The control population of 747 women had 9/747 with HGSIL and 63/747 with LGSIL. chi(2) and Fisher's exact tests showed that the lupus population had a statistically significant increase in Pap smear reports of dysplasia compared to the control group (P < 0.021 for HGSIL/LGSIL combined, P < 0.036 for LGSIL alone). Examination of serial Pap smear results revealed that 45% of the lupus patients had cervical dysplasia at some time. CONCLUSION: Women with lupus have an increased prevalence of cervical dysplasia. Serial observation revealed dysplastic cytologies in nearly half of the patients, suggesting that this may be a more common problem than previously reported. Serial prospective studies are needed to assess better the risk of premalignant cervical lesions in lupus.     

Sjögren syndrome in Obstetric and Gynecology: literature review

Sjogren syndrome (SS) is an immune disease characterized by a progressive degeneration of exocrine glands. It leads to dryness of mucosa and conjunctivitis. Gynecologists and obstetricians may encounter this disease in women at any age, including during pregnancy. Knowledge of the main characteristics is required for early diagnosis and multidisciplinary program. In the event of secondary Sj?gren syndrome occurring during pregnancy, treatment focuses on the associated disease, mainly systemic lupus erythematosus. In primary Sj?gren syndrome, pregnancy does not appear to influence disease course. However, patients with both primary and secondary Sj?gren syndrome must be monitored carefully. There is a risk of neonatal lupus and congenital atrioventricular bloc associated with high morbidity and mortality. These patients should benefit from multidisciplinary care in a hospital with a neonatal intensive care unit.     

Early recurrent spontaneous abortion: How to take care in 2006?

More than 1% of the couples whishing children suffer from recurrent miscarriage, but investigations and treatment are not consensual. Most patients have several risk factors, and a minimum investigation of known factors has to be undertaken: karyotyping of the couple, hysteroscopy for searching uterine anatomic anomalies, evaluation for thrombophilias (anticardiolipin antibodies, lupus anticoagulant, protein C activity, Proteine S activity, factor V Leiden and factor II mutations, activated protein C resistance), antinuclear antibodies. Systemic diseases (like lupus) and endocrine abnormalities (like thyroid diseases and diabetes mellitus) have to be detected by clinical examination and questioning. No endocrine investigation is recommended, unless irregular menstruations or sterility. Research in recurrent pregnancy loss are conducted in new associated factors, such as skewed-X-chromosome inactivation, maternal HLA types, modifications in specific immune molecules and cells regulation. Therapeutic proposals are preimplantation genetic diagnosis in case of abnormal karyotiping, hysteroscopic surgery for septate uterus, aspirin plus heparin in antiphospholipid-positive patients, and aspirin plus corticosteroids in systemic lupus. Heparin seems to improve obstetrical prognosis for patients with congenital or acquired thrombophilias, but there are only few studies carried out on the subject. This new therapeutic approach should incite the patients with a negative medical appraisal to be referred to specialized consultations in order to include them in eventual clinical tests. Finally, empathic listening and psychological support are necessary in a pathology with multiple etiological factors.     

Lupus anticoagulant in pregnancy

In a group of 10 women with circulating lupus anticoagulant 25 intrauterine deaths were previously documented in the nine multigravidae. The presence of lupus anticoagulant activity was confirmed by showing prolongation of the activated partial thromboplastin time and kaolin clotting time with failure of correction of the prolongation on incubation with normal plasma. A clinical diagnosis of systemic lupus erythematosus (SLE) was made in four women. Three had deep vein thrombosis in pregnancy, one chorea gravidarum while two had only recurrent fetal losses. All the women had positive antinuclear antibody tests and blood platelet counts less than 175 X 10(9)/l. Anti-smooth muscle antibody and VDRL tests were each positive in half the patients; anti-DNA antibody was present in two patients with clinically active SLE. In six pregnancies correction of the activated partial thromboplastin and kaolin clotting time was attempted using prednisone (40-60 mg/day); aspirin, 75 mg/day, was added. Five live infants were obtained, four by spontaneous delivery, when the restoration of the clotting abnormalities to normal was achieved. In one woman presenting with extensive deep vein thrombosis a live infant was delivered following therapeutic doses of heparin and low dose aspirin. Maternal lupus anticoagulant activity has major implications for pregnancy and should be excluded in women with a clinical suspicion of SLE, a positive antinuclear antibody test, thrombotic episodes, biologically false-positive VDRL and unexplained late or repetitive early fetal losses.     

Anticardiolipin antibodies and complement in ninety-nine women with habitual abortion

Immunologic investigations were performed on sera from 99 women with habitual abortion (three or more consecutive miscarriages). All were considered healthy and clinical investigations had not revealed any cause for the miscarriages. Sixty-eight were considered to have primary habitual abortion whereas 31 had secondary habitual abortion. Increased anticardiolipin antibody levels were found in 42 patients. None had a primary diagnosis of systemic lupus erythematosus, but at follow-up studies one of them fulfilled the diagnostic criteria of systemic lupus erythematosus. Ten sera, all from patients with primary habitual abortion, showed high anticardiolipin antibody values (greater than or equal to 10 units) concomitant with significantly lower levels of complement factor C4 than those found in sera with moderate or normal anticardiolipin antibody levels. There was no indication of genetic defects explaining the low C4 values, which could be explained at least in part by an activation of complement by the classical pathway.     

Serum urate, complement 3 and pre-eclampsia in patients with systemic lupus erythematosus

Pre-eclampsia (PE) is a frequent complication of pregnancies in women with systemic lupus erythematosus (SLE). The diagnosis of PE is usually based on clinical features such as hypertension and proteinuria, which could also be features of SLE disease exacerbation. As the management of these conditions is different, tests that could confirm the diagnosis of pre-eclampsia would be helpful. Previous studies have shown that serum urate is elevated in PE, while a fall in serum complement 3 occurs in exacerbation of SLE. In this study we looked at the serum urate and complement 3 levels in a group of SLE patients who were in remission before pregnancy. Patients who developed PE had a significantly higher serum urate level while their serum complement 3 level was similar to patients without PE. Our results suggest that measurement of serum urate together with serum complement 3 would help to diagnose PE, and delivery should not be delayed, especially if intra-uterine growth retardation is suspected, in order to avoid intra-uterine death.     

Hormonal life in systemic lupus and other connective tissue diseases

Among connective tissue diseases, systemic lupus erythematosus is the illness that is most concerned by hormonal life events. The sex ratio is 9/1, and symptoms begin mostly during the third decade, sometimes during birth pill contraception or during pregnancy. As soon as systemic lupus is under control of an efficient treatment, pregnancy is no longer contra-indicated. A medical multidisciplinary surveillance is required. Complicated pregnancy concerns mother and baby. Lupus flares are more frequent during the second and third trimesters as well as during the post-partum period. Usually the intensity is moderate. Severe flares concern patients with renal involvement, hypertension and renal insufficiency and are mostly seen in patients with unplanified pregnancy and yet with still active lupus. Foetal death occurs in 10-30% of the cases, depending on the lupus activity and severity (renal lupus). Prematurity remains an important cause of morbidity (30% of live births). Foetal deaths and prematurity are even more frequent if the patient has an antiphospholipid syndrome. Neonatal cutaneous lupus and auriculo-ventricular congenital heart block is infrequent (1% of SLE patients with anti-Ro/SSA antibodies). Among other connective tissue diseases, polymyositis has a very severe obstetrical prognosis for both mother and foetus. Among primary vasculitis, polyarteritis nodosa, as found during pregnancy, can herald a very bad prognosis.