硫唑嘌呤与羟氯喹联合糖皮质激素治疗轻中度系统性红斑狼疮的临床观察

目的探讨硫唑嘌呤(azathioprine,AZA)、羟氯喹(hydroxychloroquine,HCQ)联合糖皮质激素(简称ACP方案)治疗轻中度系统性红斑狼疮(systemic lupus erythematosus,SLE)的疗效。方法采用自身对照研究对甲氨蝶呤(methotrexate,MTX)、HCQ联合糖皮质激素(简称MCP方案)治疗6个月以上,因为没原因停用MTX、HCQ的37例轻中度SLE患者,换用ACP方案治疗6个月,观察其补体、血管炎样皮疹、尿蛋白等指标的变化。结果治疗前后dsDNA阳性率、血管炎表现、补体特别是补体C3及SLE活动性指数(SLE disease active index,SLEDAI)差异有统计学意义(P<0.05);狼疮肾炎患者尿蛋白明显降低(P<0.01)。结论病情活跃的轻中度SLE患者可以较早采用AZA、HCQ联合糖皮质激素治疗方案。     

Monocyte procoagulant activity in glomerulonephritis associated with systemic lupus erythematosus.

Monocyte infiltration and activation of the coagulation system have been implicated in the pathophysiology of glomerulonephritis. In this study, spontaneous procoagulant activity (PCA) was measured in circulating mononuclear cells to determine whether elevated PCA correlated with the presence of proliferative glomerulonephritis in patients with systemic lupus erythematosus (SLE). No increase in PCA was found in 20 patients with end-stage renal failure, 8 patients with glomerulonephritis without SLE, and 10 patients undergoing abdominal surgical or orthopedic procedures as compared with 20 normal controls. In eight patients with SLE but with no apparent active renal disease, PCA was not elevated above normal basal levels. Seven additional patients with SLE who had only mesangial proliferation on biopsy also had no increase in PCA. In contrast, eight patients with focal or diffuse proliferative lupus nephritis, and one patient with membranous nephritis who ultimately developed a proliferative lesion, had a marked increase in PCA with greater than 100 times the base-line levels. The activity was shown to originate in the monocyte fraction of the mononuclear cells and was shown to be capable of cleaving prothrombin directly. The prothrombinase activity was not Factor Xa, because it was not neutralized by anti-Factor X serum and was not inhibited by an established panel of Factor Xa inhibitors. Monocyte plasminogen activator determinations did not correlate with renal disease activity. We conclude that monocyte procoagulant activity, a direct prothrombinase, seems to correlate with endocapillary proliferation in lupus nephritis and could be a mediator of tissue injury.     

Hereditary C1q deficiency and systemic lupus erythematosus

We describe a 27-year-old woman with systemic lupus erythematosus,C1q deficiency and cytomega-lovirus retinitis. She sufferedfrom severe SLE, with cutaneous and CNS involvement, and diedof CNS disease aged 28. Review of 29 other published cases ofC1q deficiency shows that SLE in these patients is often severe(five with CNS disease, ten with glomerulonephritis). The resultsof autoantibody studies in this and another patient with C1qdeficiency and SLE are presented—both patients had autoantibodiesto the extractable nuclear antigens, Sm, RNP and Ro, and onepatient had high titres of antibodies to dsDNA. One of the patientshad previously been treated with fresh frozen plasma, and antibodiesto C1q were present in his serum. Homozygous C1q deficiencyis associated with a very high prevalence of severe SLE withthe full panoply of autoantibodies characteristic of this disease.     

Lupus and pregnancy: integrating clues from the bench and bedside

Adequate pregnancy care of women with systemic lupus erythematosus (SLE) rests on three pillars: a coordinated medical-obstetrical care, an agreed and well-defined management protocol and a good neonatal unit. Pregnancy should be planned following a preconceptional visit for counselling. Women with severe active disease or a high degree of irreversible damage, such as those with symptomatic pulmonary hypertension, heart failure, severe restrictive pulmonary disease or severe chronic renal failure should best avoid pregnancy. Treatment is based on hydroxychloroquine, low-dose steroids and azathioprine. Patients with antiphospholipid antibodies/syndrome should receive low-dose aspirin +/- low molecular weight heparin. The addition and the dose of heparin depend on the clinical profile of the patient, i.e. a previous history of miscarriage, foetal loss, placental insufficiency or thrombosis. A close surveillance, with monitoring of blood pressure, proteinuria and placental blood flow by Doppler studies helps the early diagnosis and treatment of complications such as preeclampsia and foetal distress. Postpartum follow-up is important.     

系统性红斑狼疮25例死亡原因分析

目的分析系统性红斑狼疮（systemic lupus erythematosus,SLE）患者的主要死亡原因,以提高SLE患者生存率。方法收集2000年1月～2011年1月我院确诊的610例SLE中死亡25例的临床资料,对其病程、死亡原因为存活时间、肾脏病理活检情况、疾病活动度及患者治疗依从性等进行回顾性分析。结果本组病死率为4.09%（25/610）,前三位死因为感染12例（48%）,神经精神性狼疮5例（20%）,心脏猝死3例（12%）,平均病程4.9年。死亡因素分析,处于中、重度疾病活动期19例（76%）,治疗依从性差19例（76%）。结论增强SLE患者治疗依从性,定期评估疾病活动度,积极防治感染、神经系统和心血管系统并发症,保持病情稳定,是提高患者生存率的关键。     

Systemic diseases with renal manifestations

This article discusses the epidemiology, recognition, screening, and management of six systemic diseases that commonly present with renal manifestations: diabetic nephropathy, lupus nephritis, congestive heart failure, HIV, liver disease, and dysproteinemias. Diabetic nephropathy remains the leading cause of end-stage renal disease in the United States. The outlook for patients who have lupus nephritis and HIV-associated nephropathy has improved in the last decade. Kidney disease is common in patients who have advanced liver disease, and creatinine-based methods do not provide an accurate estimation of renal function in this population. Dysproteinemias are associated with protean renal manifestations, and renal disease may be the presenting manifestation.     

The problem of cytomegalovirus infection in renal allograft recipients

A prospective study of the effects of cytomegalovirus (CMV) infection on 145 recipients of 155 renal allografts is reported. Immunosuppression was either with azathioprine and low-dose prednisolone (103 transplants) or with Cyclosporin A (52 transplants). Sixty-one cases of CMV infection were diagnosed; of those 21 were primary (i.e. in CMV sero-negative recipients) and 40 were secondary (i.e. in previously sero-positive recipients). The infection rate in patients treated with azathioprine and low-dose prednisolone did not differ from the rate in those treated with Cyclosporin A. Eighteen of the 21 primary CMV infections were clinically overt; several of these patients became seriously ill, and one of them died. Only four of the 40 secondary infections were overt, and these were all mild. Graft and patient survival were not adversely affected by CMV infection. Indeed the group with secondary CMV had significantly better survival rates than the uninfected sero-positive or sero-negative patient groups. Recommendations to minimise the effects of primary CMV infections are given.     

Long-term control of CMV retinitis in a patient with idiopathic CD4+ T lymphocytopenia

Cytomegalovirus (CMV) retinitis with idiopathic CD4⁺ T lymphocytopenia (ICL) is rare and difficult to control. We report a first case for long-term control of CMV retinitis with ICL using interleukin-2 (IL-2) therapy and succeeded in discontinuation of anti-CMV therapy. A 49-year-old Japanese woman was diagnosed with ICL based on low CD4⁺ count (72/μl), negative for HIV-1 and -2 antibodies, and absence of any defined immunodeficiency diseases or immunosuppressive therapy. PCR test of the aqueous humor in the right eye was suggestive of CMV retinitis. She was treated with systemic ganciclovir, but after several relapses of CMV retinitis, rhegmatogenous retinal detachment appeared in the right eye and she became blind in that eye. Three years later, she developed CMV retinitis in the left eye. Although she received systemic and focal anti-CMV treatments, the retinitis showed no improvement. Finally, retinal detachment occurred, and she underwent vitrectomy. IL-2 was injected to increase CD4⁺ counts. Because of hyperpyrexia, blepharedema, central scotoma, and color anomaly, we changed to low-dose IL-2 therapy with no side effects. Finally, we succeeded in increasing the CD4⁺ count to more than 200/μl after discontinuation of low-dose IL-2 therapy. CMV retinitis never recurred after discontinuation of anti-CMV therapy, with good visual acuity of 20/20 in the left eye. She developed blindness of the first affected right eye, whereas the visual acuity of the left eye remains excellent more than 12 years after the onset of CMV retinitis through the combined use of anti-CMV therapy, IL-2 therapy, and vitrectomy.     

A PRESing case of visual changes and confusion

Visual disturbances are an uncommon pediatric chief complaint. Usually, after a complete ocular exam including visual acuity, most causes are benign and not life-threatening. Children with abnormal visual complaints who have underlying medical conditions, such as SLE or other autoimmune conditions, a recipient of a transplant, renal disease, and even eclampsia require closer scrutiny. We report a 10-year-old female with a history of systemic lupus erythematosus complicated by hypertension and cardiomyopathy secondary to lupus who presented to the emergency department with a history of vision loss and headache. Head computer tomography demonstrated findings of posterior reversible encephalopathy syndrome (PRES). PRES is a clinical disease associated with cranial radiological findings of heterogenous etiologies that is often reversible. Prompt recognition and treatment are important in preventing permanent damage, long term morbidity and even death.     

SLE with diffuse alveolar hemorrhage,microangiopathic hemolytic anemia and acute renal failure

In SLE patients with diffuse alveolar hemorrhage (DAH) and acute renal failure (ARF), the most common associated renal injury is proliferative lupus nephritis. We report a case of a young SLE patient with DAH and ARF who was successfully treated with a course of therapeutic plasma exchange (TPE) plus pulse IV cyclophosphamide. Kidney biopsy revealed an alternative diagnosis. J. Clin. Apheresis 27:263–264, 2012. © 2012 Wiley Periodicals, Inc.     

The clinical and renal biopsy predictors of long-term outcome in lupus nephritis: a study of 87 patients and review of the literature

The prognostic markers in 87 consecutive patients with lupus nephritis who underwent renal biopsy are reported for five clinically relevant long-term outcomes--renal insufficiency, renal failure, death due to renal systemic lupus erythematosus, death due to non-renal SLE and death due to SLE, both renal and non-renal. We have demonstrated that a number of previously neglected or rarely studied predictors were important prognostic markers. These included the duration of renal disease before biopsy, overall severity of SLE, as well as the presence of vasculitis, hypertension or a comorbid ailment. Furthermore, the study confirms the predictive importance of serum creatinine, 24-h urinary excretion of protein, C3, and of the activity and chronicity indices on biopsy. However, overall a simple measure of tubulointerstitial disease was the best predictor obtained from biopsy. Prognostic models based on clinical data alone were developed for each of the five outcomes. The models amplify our clinical understanding of lupus nephritis. Markers of renal severity were most important in predicting renal outcomes such as renal insufficiency and renal failure. Prognostic factors less directly related to renal disease (comorbidity and vasculitis) were important predictors of fatality. A marker of immunologic disease activity (C3) was a valuable predictor for many of the outcomes. Thus markers of disease severity reflecting organ damage due to SLE and other comorbid conditions could be combined with markers of immunologic activity to predict a variety of outcomes of relevance to a clinician. When biopsy data obtained by light or electron microscopy were evaluated for their ability to add new predictive information to the clinical models, only a limited value for biopsy was noted. It is likely that this reflected the close correlational relationships between clinical and biopsy variables, the strong clinical models generated, and the inclusion in the clinical models of the previously neglected clinical variables, duration of renal disease before biopsy and the presence of vasculitis or comorbid disease.     

Negative anti-C1q antibody titers may influence therapeutic decisions and reduce the number of renal biopsies in systemic lupus erythematosus

In a cross-sectional study involving 62 patients with systemic lupus erythematosus (SLE), we found that patients with biopsy-proven lupus nephritis (LN) had higher titers of anti-C1q antibodies than active SLE without nephritis patients. Anti-C1q was associated with a negative predictive value of 94.59%, a positive predictive value of 52%, a sensitivity of 86.66% and a specificity of 74.47% for the diagnosis of LN. We conclude that high titers of anti-C1q antibodies are strongly associated with the presence of active LN, and the negative predictive value of this test for diagnosing LN is very high; therefore, it can influence therapeutic decisions and reduce the number of renal biopsies in patients with SLE.     

Renal hemodynamics in patients with systemic lupus erythematosus as shown by renal scintigraphy

Dynamic scintigraphy (DS) provides qualitative and quantitative assessment of renal circulation in patients with different diseases. Few data are still available on application of DS of the kidneys in patients with systemic lupus erythematosus (SLE). Renal hemodynamics studies with DS are not described in SLE patients with disturbances of renal metabolism and/or antiphospholipid syndrome (APS). We examined renal hemodynamics in SLE patients with renal disease, arterial hypertension, impaired lipid metabolism, APS. We examined 65 patients with confirmed diagnosis of SLE with 99mTc DS and estimated effective renal blood flow. The latter was damaged more in SLE patients with symptoms of renal disorders. Arterial hypertension deteriorated renal hemodynamics. In hypertensive patients with affected kidneys angionephroscintigraphic parameters changed most significantly. Renal hemodynamics in disturbed lipid metabolism was worse than in normal one but the difference was not significant. Angionephroscintigraphy findings were worse in patients with APS than in those with renal lesion and arterial hypertension but free of APS.     

Longitudinal analysis of gray and white matter loss in patients with systemic lupus erythematosus

Cerebral atrophy has been described to occur in systemic lupus erythematosus (SLE) with variable frequency. The aim of this study was to determine white and gray matter abnormalities in brain magnetic resonance imaging (MRI) of patients with SLE and to determine if these abnormalities progress over a one-year period. Seventy-five patients with SLE and 44 healthy age and sex-matched controls were enrolled in this study. T1-weighted volumetric images were used for voxel based morphometry (VBM) analyses. SLE patients exhibited a significant reduction in white matter and gray matter volume compared to controls (p=0.001). Follow-up images, after an average interval of 19 months, revealed a progressive white matter and gray matter atrophy (p=0.001). Reduced white and gray matter volume was associated with disease duration and the presence of antiphospholipid antibodies. Patients with severe cognitive impairment had a more pronounced white and gray matter reduction than patients with moderate cognitive impairment. Total corticosteroid dose was associated with gray matter reduction and not with white matter loss in SLE patients. We concluded that brain tissue loss associated with SLE is significant and progresses over a relatively short period of time. Disease duration, the presence of antiphospholipid antibodies and cognitive impairment were associated with white and gray matter loss. Corticosteroid was associated only with gray matter atrophy.     

Clinical and morphological characteristics of lupus nephritis in systemic lupus erythematosus with antiphospholipid syndrome

AIM: To ascertain clinical and morphological features of lupus nephritis (LN) in systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome (APS). MATERIAL AND METHODS: Immunological markers of SLE and APS, clinical picture, urine indices were examined in 138 patients with SLE, APS and renal dysfunction. RESULTS: LN associated with APS is characterized with marked arterial hypertension, such patients had arterial thromboses more frequently than patients with isolated LN. Patients with anticardiolipin antibodies have arteriolosclerosis, in APS - diffuse interstitial sclerosis. CONCLUSION: Renal impairment in SLE may run not only with LN but also with thrombotic microangiopathy modifying clinical symptoms and course of the disease.     

Association of autoantibodies to different nuclear antigens with clinical patterns of rheumatic disease and responsiveness to therapy

Using a hemagglutination test which can detect antibodies to (a) native and denatured deoxyribonucleic acid (DNA) and (b) an extractable nuclear antigen (ENA), a comparative study of patterns of autoantibody formation has been done in systemic lupus erythematosus (SLE) and related rheumatic diseases. Antibody to native DNA was present in the serum in 96% of patients with active SLE and disappeared during remissions. Antibody to ENA was found in 86% of those patients with SLE nephritis who responded to treatment but in only 8% of those who did not. The highest titers of antibody to ENA were found in patients having a mixed connective tissue disease syndrome with features of SLE, scleroderma, and myositis. The latter syndrome was notable for the absence of renal disease and for a striking responsiveness to corticosteroid therapy. Hemagglutination testing of 277 sera from normal persons and patients with a wide variety of acute diseases other than SLE revealed the presence of antibody to native DNA in only 1.4% and antibody to ENA in only 0.4%.These results yield significant correlations among the pattern of autoimmune reactivity, the clinical form of the rheumatic disease, and responsiveness to treatment. They implicate the qualitative nature of the patient's immune response as a conditioning factor in the type of disease. Together with other correlations they may allow classification of rheumatic diseases into more biologically meaningful groups and lead to more selective methods of therapy.     

Lupus nephritis: efficacy of monthly pulse therapy with intravenous methylprednisolone

Fourteen patients with severe systemic lupus erythematosus and nephritis were treated with high-dose intravenous methylprednisolone (IVMP) pulse therapy. Six patients (group 1) received one or two courses of 1 gm of IVMP when they were acutely ill with rapidly progressive renal failure or with multisystemic disease. All patients had a poor outcome; three died and three had end-stage renal disease. Eight patients (group 2) were treated with repeated pulses of 1 gm of IVMP for four to 21 months. Six of the eight patients had a favorable outcome, with four in complete remission and two in partial remission. One of the eight patients had partial response with stable renal disease at 16 months after pulse therapy. Only one patient had no response, with gradual worsening of renal function. All patients in both groups had rapid improvement of levels of anti-DNA and CH50 after pulse therapy was started. Patients in group 2 were compared to 21 randomized patients (group 3) with comparable severity of disease. Renal function deteriorated in group 3, with a mean duration of disease of 82.5 +/- 56.4 months. Renal function improved in group 2, with a mean duration of disease of 87.8 +/- 46.8 months. We conclude that repeated monthly pulse therapy with IVMP in severe SLE was effective and that major side effects can be avoided with proper timing of pulsing.     

以红斑肢痛为首发表现的系统性红斑狼疮1例

患者,女,44岁。双足疼痛2年,伴颜面浮肿半年,加重1天。患者于2年前无明显诱因出现双足疼痛,以双足底疼痛,伴烧灼感,疼痛以夜间为甚,疼痛时轻时重,严重时伴有血压升高,自觉遇冷时疼痛可缓解,但运动及保暖时疼痛加重,伴口干、视物模糊,无晨僵,无畏寒发热,无夜间盗汗、午后低热,无口腔溃疡、蝶形红斑、颜面部皮疹,     

Systemic lupus erythematosus: obstetric and neonatal implications

Systemic lupus erythematosus (SLE) is a collagen vascular disease that may have a tremendous impact on pregnancy. The pregnant patient with SLE is at increased risk for fetal wastage, intrauterine growth retardation (IUGR), intrauterine fetal demise (IUFD), pregnancy-induced hypertension (PIH), and exacerbations of the lupus process. SLE is an autoimmune disease with tremendous implications for pregnancy. The diagnosis of SLE is based on criteria developed by The American Rheumatism Association. The recent identification of circulating antibodies associated with women who have lupus has led to some confusion. The circulating antibodies are associated with an increased risk of fetal wastage. However, those antibodies have been documented in women who do not have lupus. The diagnosis of SLE and pregnancy requires intensive obstetrical care. SLE may also affect the neonate, from skin lesions to complete heart block. This article describes the effects of SLE on the mother, pregnancy, and the neonate.     

Prevalence of migraine in patients with systemic lupus erythematosus

OBJECTIVE: To determine the prevalence of migraine in patients with systemic lupus erythematosus (SLE), and to examine the relationships between headache type and other clinical, serologic, and treatment features of the disease. BACKGROUND: Headaches are common in SLE and are a significant source of patient disability. The exact prevalence of headaches in patients with SLE is unknown. The classification of headache syndromes in SLE is also unclear. Previous studies were based on small numbers of patients and the headache types and criteria to define headache types varied widely. METHODS: Four hundred fourteen patients meeting American College of Rheumatology criteria for the diagnosis of SLE were sent the University of California, San Diego Migraine Questionnaire. Patients who completed the questionnaire had their medical records reviewed for constitutional, respiratory, cardiac, vascular, skin, musculoskeletal, other neuropsychiatric, hematologic, renal, and immunologic manifestations of the disease. Recent corticosteroid, nonsteroidal anti-inflammatory drug, antimalarial, and immunosuppressive medications were also recorded. RESULTS: One hundred eighty-six patients completed the questionnaire. Sixty-two percent of patients reported headaches: 39% met diagnostic criteria for migraine and 23% met criteria for nonmigrainous headache. Of the patients with migraine, 56% met criteria for migraine without aura and 44% met criteria for migraine with aura. There were no significant associations between headache type and other clinical, serologic, or treatment features of the disease. CONCLUSIONS: There is a high prevalence of migraine in patients with SLE, and patients should be routinely evaluated for migraine symptoms.