Pancytopenia in systemic lupus erythematosus related to azathioprine

A patient with systemic lupus erythematosus (SLE) developed pancytopenia when azathioprine (first 2.0 mg kg-1 day-1, then 2.5 mg kg-1 day-1) was added to prednisone for active SLE. This unusual toxic effect of azathioprine occurred during the reduction of corticosteroid dosage. After discontinuation of azathioprine, clinical and haematological recovery occurred.     

Immunosuppressive therapy. Guidelines for drug dosage. Depression of bone marrow granulocyte reserves in systemic lupus erythematosus

Marrow granulocyte reserves, when estimated by the granulocyte response to etiocholanolone (GRE), are smaller in patients with systemic lupus erythematosus (SLE) than in a comparable group of patients with chronic glomerulonephritis (CGN). Consequently, the dose of azathioprine tolerated by patients with SLE was only one-half that tolerated by patients with CGN. Use of the GRE as a guide to therapy may permit individualization of dosage so that maximum tolerated doses of immunosuppressive drugs can be given to each patient.     

The functional p53 codon 72 polymorphism is associated with systemic lupus erythematosus

The aim of the study is to investigate whether the functional p53 codon 72 polymorphism is associated with susceptibility to SLE and its clinical features. A polymerase chain reaction of genomic DNA-restriction fragment length polymorphism was used to determine genotypes of the p53 codon 72 in 90 SLE patients and 114 healthy controls. Clinical/serological manifestations were analysed in each patient and correlated with the genotypes. The OR of the association of the Pro allele with SLE was 1.70 (95% CI, 1.15-2.53, P = 0.0079) and the OR of the Pro/Pro (a recessive model) was significantly increased (OR = 2.58, 95% CI = 1.24-5.39, P = 0.0093). The Armitage's trend test indicated a significant dosage effect of the Pro allele for SLE (OR = 1.73, chi-square = 7.08, P = 0.0078). However, there was no significant association of the polymorphism with clinical/serological manifestations studied here. In conclusion, our finding suggests the functional p53 codon 72 polymorphism may be associated with SLE susceptibility, suggesting individuals who carry the Pro allele may have a higher risk to SLE susceptibility than those with the Arg allele. Further studies for replications are needed to confirm that the p53 polymorphism contributes to SLE.     

系统性红斑狼疮并发无菌性股骨头坏死的临床研究

目的 探讨系统性红斑狼疮(SLE)并发无菌性股骨头坏死(ONFH)的临床特点.方法 回顾分析卫生部中日友好医院住院治疗的SLE合并ONFH患者的临床资料.结果 461例SLE住院患者中ONFH的发病率为6.94%(32/461),在SLE病程3年之内发生ONFH的病例占65.63%(21/32);SEE合并ONFH者与SLE未合并ONFH者间年龄、性别、病程差异无统计学意义(P>0.05);具有皮肤血管炎、血小板升高、血清纤维蛋白原(Fib)升高、LDL-C升高、骨密度低表现的患者在SLE并发ONFH者所占的比例较SLE未合并ONFH者高,平均初始口服糖皮质激素量和1个月、半年、总糖皮质激素累积量亦较SLE未合并ONFH者高,两者比较差异有统计学意义(P<0.05);而雷诺现象、口腔溃疡、肾脏受累、高血压、贫血、抗心磷脂抗体阳性、有无行糖皮质激素冲击和免疫抑制剂治疗等方面两者比较差异无统计学意义(P>0.05).结论 在SLE病程3年之内发生ONFH的危险性相对较高,SLE并发ONFH患者多数具有皮肤溃疡、坏疽等皮肤血管炎以及血小板、Fib、LDL-C升高和骨密度低的表现,且多数患者经过大剂量糖皮质激素治疗.     

Systemic lupus erythematosus and pregnancy: a prospective study.

We have prospectively followed 25 pregnancies in 21 patients: 20 were affected by systemic lupus erythematosus (SLE) and 1 by subacute cutaneous lupus erythematosus (SCLE). A flexible treatment schedule was applied to the follow-up of all the pregnancies, and included low dose aspirin, steroids at medium-low dosage and, if needed, azathioprine (AZA) after 20 weeks of gestation. There were 4 spontaneous first trimester abortions and 21 live-born neonates without major problems related to the treatment or to the maternal disease. The relapse rate of the disease recorded during the observation period was 0.07 patient/month, not different from that already reported in SLE patients (pregnant or nonpregnant). Obstetrical complications were relatively frequent, but careful monitoring allowed us to avoid late fetal wastage. We conclude that in SLE patients a successful pregnancy outcome, without worsening of the disease, can be obtained with a careful multidisciplinary follow-up.     

Prevalence and associations of an abnormal ankle-brachial index in systemic lupus erythematosus: a pilot study

BACKGROUND: Accelerated atheroma is a well recognised complication of systemic lupus erythematosus (SLE). Its aetiology is multifactorial and several methods may be used to detect early signs of atheroma. METHODS: Patients aged 相似文献   

Analysis of cognitive and psychological deficits in systemic lupus erythematosus patients without overt central nervous system disease

Objective. To examine cognitive and psychological functioning in relation to antiribosomal P protein autoantibodies in patients with systemic lupus erythematosus (SLE) who had no previous history of central nervous system disease (non-CNS SLE). Methods. Comprehensive neuropsychological and psychological tests were administered to 51 non-CNS SLE patients, 29 rheumatoid arthritis (RA) patients, and 27 healthy controls. Results. Twenty-nine percent of the non-CNS SLE patients, 31% of the RA patients, and 11% of the control subjects were classified as cognitively impaired. Similar reductions in intelligence, attention, and fluency were detected in the non-CNS SLE and RA patients compared with controls. The non-CNS SLE patients showed a distinct deficit in learning compared with the RA and control groups. Forty-two percent of the non-CNS SLE patients demonstrated psychological distress, compared with 7% of the RA patients and 6% of the controls. In the patient groups, neither cognitive dysfunction nor psychological distress was associated with disease activity or prednisone dosage. Elevated serum levels of autoantibodies to ribosomal P protein were not associated with either psychological or cognitive abnormalities. Conclusion. These results suggest that certain cognitive deficits in non-CNS SLE patients may not be specific to the immunopathology of SLE. In contrast, it is possible that deficits in learning, as well as psychological distress without major psychiatric pathology, may be subtle manifestations of CNS lupus.     

A case of lupus nephritis improved after appropriately adjusting the dosage of mizoribine

Abstract

A 29-year-old male presenting nephrotic syndrome and facial skin erythema was admitted to our hospital in September of 2000. We diagnosed him as having systemic lupus erythematosus (SLE) accompanied by lupus nephritis (WHO class V). The disease activity had decreased after treatment with methylprednisolone (m-PSL) pulse therapy, which was followed by oral PSL. Thereafter, when tapering the dosage from 60 to 30 mg/day, the lupus nephritis flared up and he was re-hospitalized in February of 2001. After successful retreatment with m-PSL pulse therapy followed by the tapering of the dosage from 60 to 30 mg/day, we used mizoribine (MZR) as a combination therapy. The lupus nephritis flared up again after tapering down to 17.5 mg/day of PSL. Then, we changed the MZR dosage from 150 mg/day in three divided daily doses to 200 mg/day in two divided daily doses. This modification increased the peak blood concentration (Cmax) of MZR from 0.63 to 1.55 μg/ml. At present, we have been able to successfully taper the dosage to 7.5 mg/day of oral PSL and the patient has achieved a state of remission without any side effects. Monitoring of the serum concentration of MZR is thus considered to be important for achieving effective therapy of SLE, especially for steroid-resistant lupus nephritis. If the serum concentration of MZR does not reach an effective level, then the dosage of MZR should be adjusted appropriately in order to maintain an adequate serum concentration of MZR.     

A case of lupus nephritis improved after appropriately adjusting the dosage of mizoribine

A 29-year-old male presenting nephrotic syndrome and facial skin erythema was admitted to our hospital in September of 2000. We diagnosed him as having systemic lupus erythematosus (SLE) accompanied by lupus nephritis (WHO class V). The disease activity had decreased after treatment with methylprednisolone (m-PSL) pulse therapy, which was followed by oral PSL. Thereafter, when tapering the dosage from 60 to 30 mg/day, the lupus nephritis flared up and he was re-hospitalized in February of 2001. After successful retreatment with m-PSL pulse therapy followed by the tapering of the dosage from 60 to 30 mg/day, we used mizoribine (MZR) as a combination therapy. The lupus nephritis flared up again after tapering down to 17.5 mg/day of PSL. Then, we changed the MZR dosage from 150 mg/day in three divided daily doses to 200 mg/day in two divided daily doses. This modification increased the peak blood concentration (Cmax) of MZR from 0.63 to 1.55 μg/ml. At present, we have been able to successfully taper the dosage to 7.5 mg/day of oral PSL and the patient has achieved a state of remission without any side effects. Monitoring of the serum concentration of MZR is thus considered to be important for achieving effective therapy of SLE, especially for steroid-resistant lupus nephritis. If the serum concentration of MZR does not reach an effective level, then the dosage of MZR should be adjusted appropriately in order to maintain an adequate serum concentration of MZR.     

糖皮质激素受体α与激素量化治疗的初步研究

目的探讨31例系统性红斑狼疮（SLE）患者激素治疗前、后外周血单个核细胞（PBMCs）糖皮质激素受体α（GRet）的蛋白质水平、mRNA表达及其与疾病活动性的关系，分析GRot与SLE患者激素治疗疗效和剂量的关系。方法采用蛋白印迹（Western—blotting）和反转录-聚合酶链反应（RT-PCR）检测激素治疗前、后SLE患者和正常人外周血PBMCs中GRα蛋白质水平和GRαmRNA的表达，并将其与疾病活动性及激素剂量作相关分析。结果27例SLE患者激素敏感，4例激素耐药。激素敏感组PBMCs中GRα蛋白质水平和mRNA表达用药前高于用药后（P〈0．05），且与疾病活动性及激素剂量呈负相关。结论测定GRα的表达可能为激素的量化治疗提供依据。     

Aseptic necrosis and glucocorticosteroids in systemic lupus erythematosus: a reevaluation

To reassess predisposing factors in patients with systemic lupus erythematosus (SLE) who develop aseptic necrosis of bone, we studied 172 patients with SLE seen at our institution between 1975 and 1987 followed for longer than 1 year. Twenty-eight (16.3%) of these patients developed clinically apparent aseptic necrosis. In 12 of these 28 the continuous glucocorticosteroid dose was known. These 12 patients were compared to 15 controls with SLE followed for a minimum of 4.5 years for whom continuous glucocorticosteroid dosage was also known. We were unable to find any significant differences between patients with aseptic necrosis and controls in prevalence of specific lupus organ system involvement, Raynaud's phenomenon, or abnormal serological or hematological variables. Overall disease activity at the time of maximal glucocorticosteroid dosage did not differ significantly between the 2 groups but was slightly greater at the time SLE was diagnosed in the group with aseptic necrosis. Glucocorticosteroid intake during the first 1.5 years after diagnosis of SLE and during the third year after diagnosis was significantly greater for the patients with aseptic necrosis than for the control patients, as was glucocorticosteroid intake during the maximal 1, 3 and 6 months of therapy. We conclude that glucocorticosteroid intake is the major factor predisposing to aseptic necrosis in patients with SLE.     

Presentation and prognosis of the shrinking lung syndrome in systemic lupus erythematosus

BACKGROUND AND OBJECTIVES: Systemic lupus erythematosus (SLE) may affect all the components of the respiratory system, including upper airways, lung parenchyma, pulmonary vasculature, pleura, and respiratory muscles. The shrinking lung syndrome (SLS) is a rare complication of SLE. This study describes the presenting features, investigation findings, treatment measures, and outcome of 7 patients with SLE and SLS. METHODS: Five patients with SLE/SLE were chosen retrospectively by examination of patient records, and 2 patients were chosen prospectively. All patients attended St. Thomas' Hospital or the Royal London Hospital between 1984 and 2001, with a total population of 2650 patients with SLE. RESULTS: Clinical features included dyspnea and pleuritic chest pain. Chest x-ray films showed small but clear lung fields, or basal atelectasis, with diaphragmatic elevation. No evidence of major parenchymal lung or pleural disease was found on the computerized tomography scan. Lung volumes were reduced on pulmonary function testing (PFT) in a restrictive pattern. Treatment of SLS included theophylline, increase in corticosteroid dosage, and intensification of immunosuppressive medication to include methotrexate or cyclophosphamide. During follow-up, 5 of 7 patients showed objective evidence on PFT of stabilization or improvement. CONCLUSIONS: The long-term prognosis of our SLS patients was reasonable, highlighting the importance of establishing a correct diagnosis and in particular differentiating it from fibrosing lung disease. Immunosuppressive therapy was helpful in stabilizing SLS and improving respiratory symptoms and PFT in some cases. RELEVANCE: SLS represents a rare complication of SLE, and it is important to be aware of its presenting features and prognosis.     

Changes in body composition after glucocorticoid therapy in patients with systemic lupus erythematosus

The aim of this study was to evaluate the changes in body composition after glucocorticoid treatment in patients with systemic lupus erythematosus (SLE). Consecutive SLE patients were recruited for serial measurements (baseline, months 2 and 6) of bone mineral density (BMD) and body composition [bone mineral content (BMC), fat and lean mass] by dual energy X-ray absorptiometry scan after high-dose oral glucocorticoid therapy. Factors correlated with changes in body composition were evaluated. 29 SLE patients were studied (age 39.7 +/- 11.5 years; 83% women with 29% postmenopausal; SLE duration 80.1 +/- 80 months). Fourteen patients (48%) were glucocorticoid-naive. The mean maximum daily dosage of prednisolone was 32.9 +/- 6.5 mg and the cumulative prednisolone dosage in 6 months was 2.7 +/- 0.7 g. At 6 months, a significant drop in BMC of the trunk (-5.0 +/- 2.2%; P = 0.04) and whole body (-1.2 +/- 0.4%; P = 0.002) compared with baseline was observed, and so was the BMD of the hip (-1.7 +/- 0.6%; P = 0.006) and whole body (-0.7 +/- 0.3%; P = 0.01). A significant increase in the fat mass of the trunk (+14.5 +/- 4.1%; P = 0.001) and limbs (+10.0 +/- 3.2%; P = 0.004), but a non-significant drop in lean mass of the trunk (-3.3 +/- 1.8%; P = 0.08) and limbs (-0.8 +/- 2.4%; P = 0.75) also occurred. The changes in whole body BMC correlated significantly with age (rho = -0.51; P = 0.02) and changes in total fat mass (rho = 0.44; P = 0.02) but not with lean mass (rho = -0.21; P = 0.27), gender, body mass index, smoking, prednisolone dosages or changes in BMD. In SLE patients, high-dose glucocorticoids lead to an early and rapid drop in bone mass, which is more serious in older patients and correlates with an increase in body fat.     

Prevalence of conventional and lupus-specific risk factors for cardiovascular disease in patients with systemic lupus erythematosus: A case-control study

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are significantly more likely to experience a myocardial infarction or a stroke than age-matched controls. We compared the prevalence of conventional and lupus-specific risk factors in patients with SLE just before a cardiovascular event and in matched controls with SLE but no cardiovascular disease (CVD). METHODS: Twenty-nine patients with SLE and CVD were enrolled. For each patient, 2 ethnically- and sex-matched controls were obtained, 1 matched for age and 1 for SLE duration. Data regarding risk factors were collected for the time immediately preceding the relevant cardiovascular event, or at an equivalent time for controls. RESULTS: Patients' median age at event was 49 years (interquartile range 43-54 years) and mean disease duration was 12.0 +/- 7.1 years. Patients with SLE and CVD were more likely than both age and duration controls to be treated for hypertension (P = 0.01 and P = 0.001, respectively) and to have elevated triglyceride levels (P = 0.05 and P = 0.01, respectively). Compared with duration controls, CVD patients were more likely to have lupus anticoagulant (P = 0.03), but less likely to be receiving treatment with hydroxychloroquine (P = 0.003). Compared with age controls, patients were more likely to be current smokers (P = 0.03), to have taken a mean dosage >7.5 mg/day of prednisolone (P = 0.04), and to have been treated with pulsed methylprednisolone (P = 0.03). In multivariable analysis, only hypertension treatment was an independent risk factor for CVD. CONCLUSION: We identified significantly increased prevalence of some conventional and lupus-specific risk factors in patients with SLE immediately before a CVD event compared with controls matched for age or disease duration.     

系统性红斑狼疮合并妊娠145例次母婴结局及临床预测因素

目的 总结系统性红斑狼疮(SEE)合并妊娠的母婴结局,分析妊娠期问SLE病情恶化、胎儿丢失、不良胎儿结局的预测因素.方法 回顾性分析1990年1月至2007年12月在北京协和医院和深圳市人民医院住院的SEE合并妊娠临床资料.结果 120例SEE合并妊娠145例次,妊娠时年龄18～4I岁,平均(28±4)岁,SEE病程0.5～18年,平均(5±4)年.共有46例次(31.7%)妊娠期间SLE病情恶化,主要在妊娠中、晚期,常累及皮肤黏膜及关节肌肉系统.妊娠期间SEE病情恶化与妊娠前病情活动及低补体血症有关(P＜0.05).妊娠前病情活动组子痫前期及子痫的发生率明显高于病情稳定组(P＜0.01).共成功分娩104例次(71.7%,其中双胞胎2例),18例次自然流产(12.4%),10例次死产(6.9%),13例次治疗性流产(9.0%).早产36例次(34.6%),新生儿出现宫内生长迟缓(IUGR)37例次(35.6%).胎儿丢失(包括自然流产及死产)的危险因素有合并抗磷脂综合征(APS)、妊娠前病情活动(P＜0.05);引起不良胎儿结局(包括早产或IUGR)的危险因素有妊娠前抗dsDNA抗体阳性、泼尼松剂量≥10 mg/d及妊娠期间SLE病情恶化(P＜0.05).21例患者行胎盘病理学检查,其中13例发现胎盘组织血管壁纤维素样坏死、梗死表现,该组患者抗磷脂抗体阳性率明显高于胎盘病理基本健康组(P＜0.05).结论 妊娠前SEE病情活动、低补体血症与SEE妊娠期间SEE病情恶化相关.合并APS、妊娠前病情活动使胎儿丢失的危险性增加,而妊娠前抗dsDNA抗体阳性、泼尼松剂量≥10 mg/d及妊娠期间SLE病情恶化使不良胎儿结局的危险性增加.     

Outcome of protein-losing gastroenteropathy in systemic lupus erythematosus treated with prednisolone and azathioprine

OBJECTIVES: To report the efficacy of prednisolone and azathioprine (AZA) in the treatment of systemic lupus erythematosus (SLE)-related protein-losing gastroenteropathy (PLGE). METHODS: Between 1995 and 2002, 16 consecutive patients with SLE-related PLGE were treated with a regimen consisting of high-dose prednisolone (0.8-1 mg/kg/day for 6 weeks, then tapered to < or =10 mg/day) and AZA (2 mg/kg/day). Protein leakage from the gastrointestinal tract was confirmed by 99mTc-labelled human serum albumin scintigraphy and significant urinary loss of protein was excluded. Clinical response at 6 months of therapy was assessed and patients were followed for relapse of PLGE. RESULTS: Clinical characteristics of our patients at the time of PLGE were: age 36.2 +/- 8.7 (s.d.) yr; female:male ratio 15 : 1; mean SLE duration 29.6 +/- 65 months. Twelve patients had PLGE as the initial presentation of SLE. Fifteen (94%) patients had concomitant activity in other organs. All patients presented with oedema and eight patients (50%) had non-bloody diarrhoea. The mean serum albumin level was 22.8 +/- 5.7 g/dl. Protein leakage was at the small bowel in 11 (69%) patients and the large bowel in 5 (31%) patients. At 6 months of therapy, 14 (88%) patients had complete clinical response, 1 (6%) patient responded partially and 1 patient (6%) was treatment-refractory. Patients who responded were maintained on low-dose prednisolone (7.8 +/- 6.1 mg/day) and AZA (56.3 +/- 37 mg/day). Over a mean follow-up of 57.5 months, 1 (6%) patient had relapse of PLGE which responded to augmentation of prednisolone dosage. No patients developed alternative gastrointestinal diagnoses. Corticosteroid-induced psychosis, AZA-induced pancytopenia and herpes zoster occurred in three patients. CONCLUSION: PLGE is an uncommon manifestation of SLE. Treatment with a combination of prednisolone and AZA is effective and well tolerated.     

Infection and disease activity in systemic lupus erythematosus: a review of hospitalized patients

Infection is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). A review of all SLE admissions to our hospital during a 5-year period was conducted to determine the rate and nature of infection, and its association with overall disease activity, measured by the SLE Disease Activity Index (SLEDAI). Eighty-one patients (79 women, 2 men) were admitted for a total of 2,738 days (176 admissions). There were 53 proven infections, giving an infection rate of 1.94/100 hospital days. Twenty-three (43.4%) of these were major infections (requiring IV antibiotics). Two of 3 deaths were due to septicemia. By logistic regression analysis, infection was significantly associated with disease activity (p = 0.005), but not with disease duration or prednisone dosage. Our data confirm that infection is common in hospitalized patients with SLE, is associated with overall disease activity independent of prednisone dose, and causes significant mortality. These facts should be borne in mind when hospitalization is considered for patients with SLE.     

Renal cortical necrosis at presentation in a patient with systemic lupus erythematosus: an autopsy case report

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disorder. Renal involvement has the worst prognosis. However, renal cortical necrosis is extremely unusual in SLE. In this case report, we describe the autopsy findings in a young female patient with SLE presenting with renal failure. At autopsy, there was Libmann–Sacks endocarditis with multiorgan infarcts and renal cortical necrosis. Secondary antiphospholipid antibodies contribute to the cardiac and renal manifestations in SLE. We discuss the incidence and pathogenesis of endocarditis with differential diagnosis for cortical necrosis in a patient of SLE.     

重症监护病房系统性红斑狼疮患者预后因素分析

目的 了解重症监护病房(ICU)危重症系统性红斑狼疮(SLE)患者的预后及其影响因素.方法 1993年6月至2007年6月所有第1次入住ICU的SLE患者纳入组,除外入住ICU后确诊为SLE患者.对在单蹦素相关分析中提示对SLE患者死亡有明显相关性的临床指标进一步采用多因素回归模型分析.结果 符合SLE分类标准的患者共101例,总体病死率为48.6%.入住ICU最常见原因是肺部病变并发急性呼吸窘迫综合征(ARDS).多因素回归分析提示SLE疾病慢性损伤指数(SLICC/ACR DI)>7.7、急性生理和慢性健康评估指数(APACHE Ⅲ)≥21、肺部病变并发ARDS、败血症休克、颅内出血、血细胞减少、近1个月平均等效泼尼松剂量>25 mg/d和气管插管时间>4 d与ICU危重症SLE患者死亡明显相关.而性别、年龄、SLE疾病活动指数(SLEDAI)>27、上消化道出血、甲泼尼龙冲击和末月使用环磷酰胺>1.0 g与死亡结果无明显相关性.结论 人住ICU危重症SLE患者病死率很高,死亡第1位原因是感染.与其死亡明显相关的因素主要有SLICC/ACR DI>7.7、APACHE Ⅲ>121、肺部病变并发ARDS、败血症休克、颅内出血、血细胞减少、近1个月平均等效泼尼松剂量>25 mg/a和气管插管时间>4 d.     

系统性红斑狼疮患者合并重症感染的危险因素分析

目的　了解系统性红斑狼疮 (SLE)患者发生重症感染的危险因素。方法　合并重症感染的SLE患者 (88例 ,重症感染组 )和无感染的SLE患者 (70例 ,无感染组 ) ,对两组年龄、病程、免疫抑制剂和激素的使用、受累脏器数、血白细胞以及白蛋白水平进行分析 ,并行SLE DAI评分。结果　 (1)重症感染组和无感染组间SLE DAI评分、激素用量、受累脏器数、白细胞减少和血浆白蛋白水平比较差异有显著性 (P <0 .0 5 )。 (2 )SLE病情活动、低白蛋白、血WBC下降、激素冲击和免疫抑制剂使用合并严重感染的相对危险性分别为 4、4.3 7、3 .5 1、2 .74和 0 .87。 (4 )真菌感染与甲基强的松龙冲击相关性最强。结论　SLE患者合并重症感染主要与病情活动性和轻重以及激素用量有关 ,免疫抑制剂的使用不增加感染危险性