Successful delivery in a pregnant woman with lupus anticoagulant positive systemic lupus erythematosus treated with double filtration plasmapheresis.

The case was a 29 year old female who has suffered from systemic lupus erythematosus (SLE) since 15 years of age. The activity of SLE was low, and she took prednisolone orally. Her first pregnancy failed after 14 weeks. In the second pregnancy, she had thrombocytopenia, prolonged activated partial thromboplastin time (APTT), positive lupus anticoagulant (LAC) and thus was diagnosed with antiphospholipid antibody syndrome (APS). Combination therapy with steroids and aspirin was started, and she underwent treatment of double filtration plasmapheresis (DFPP) in the early stage of pregnancy. Her platelet count increased, and the value of APTT has normalized with DFPP treatment. She delivered successfully on the 32nd week of pregnancy. We think that DFPP is an effective and safe treatment in patients with an LAC positive pregnancy.     

Sequential plasmapheresis and intravenous immunoglobulin therapy for refractory myasthenia gravis: case report.

Immunotherapy is currently the standard therapy for myasthenia gravis (MG) although some patients may be refractory to treatment. We describe the use of sequential plasmapheresis and intravenous immunoglobulin (IVIG) therapy for treatment of advanced MG in a patient refractory to all forms of medical treatment including corticosteroids, immunosuppressants, and intermittent plasmapheresis. The patient, a 37-year-old woman with systemic lupus erythematosus (SLE), had initially responded well to treatment with high dose corticosteroids and intermittent plasmapheresis, with the duration of response ranging from 3 to 4 months. However, after 18 months of therapy, the duration of response had gradually decreased to 1 month. She responded well to a 5 day trial of plasmapheresis followed by high dose IVIG, and the duration of response increased to 6 months. The SLE activity was relatively silent during each relapse. This report indicates the potential usefulness of sequential plasmapheresis and IVIG in the treatment of patients with refractory MG and SLE.     

Catastrophic antiphospholipid syndrome: diagnosis and treatment

AIM: To analyse data on patients who developed catastrophic antiphospholipid syndrome (CAPS) in primary and secondary APS, to assess outcomes of CAPS. MATERIAL AND METHODS: We analysed retrospectively the data on 164 patients with systemic lupus erythematosus (SLE) and APS, on 76 patients with primary APS (PAPS) treated in the Institute of Rheumatology from 1989. Verification of vascular complications was made using ultrasonic dopplerography (UDG) of peripheral vessels, echocardiography of the heart, CT of the brain, abdominal organs. Anticardiolipin antibodies (ACLab) and lupus anticoagulant (LA) served as serological markers of APS. RESULTS: In the observation period of 9.4 +/- 4.2 years, 33 patients (23 females and 10 males) out of 164 patients with SLE+APS developed CAPS, 8 of them survived while 25 died. CAPS patients had no differences by age, duration of the disease, its activity and symptoms from patients who had no CAPS. Ten out of 76 patients with PAPS developed CAPS, 7 of them died. The analysis of the concomitant factors which may initiate PAPS showed that in SLE and APS these factors consisted of initial menopause (n = 2), infection (n = 12), including pneumonia (n = 7), acute respiratory disease (n = 3), food poisoning (n = 1), abscess (n = 1). Cancer was in one patient, trauma after road accident in one patient. Trigger factor was not determined in 13 patients. In PAPS provoking factors were pneumonia (n = 2) and abscess (n = 1), in 7 patients these factors were not detected. CONCLUSION: Any infection in SLE patients should be adequately treated with antibiotics; APS patients treated surgically should receive parenteral anticoagulants instead of oral ones; puerperas with APS must receive adequate parenteral anticoagulant therapy for at least 6 weeks; in exacerbation of SLE, APS patients should receive parenteral anticoagulants with following hypocoagulation with oral anticoagulants.     

Osteonecroses in systemic lupus erythematosus and antiphospholipid syndrome

The purpose of the study was to analyze the incidence of osteonecroses (ON) in systemic lupus erythematosus (SLE) patients with and without antiphospholipid syndrome (APS), primary APS (PAPS) and to define a relationship of the development of ON to some risk factors for vascular diseases. The study included 369 patients, including 293 with SLE, 160 with secondary APS, 76 with PAPS. The patients aged 14 to 63 years (mean 31.9+/-10.9 years). The history of disease was 0.6 to 30 years (mean 9.1+/-7.5 years). Among them 32 (8.7%) patients with aseptic necroses of different bones were selected in accordance with the data of X-ray studies. ON was detected in 8.7 patients with SLE and APS. The X-ray signs corresponded to third-to-sixth-degree ON. The most common site of ON was the head of the femur, although another site of ON was observed and multiple ON was typical. Leukopenia, creatininemia, fibrinogen levels were associated with ON (p < 0.05 by the Mann-Whitney test). The activity of SLE was significantly associated with SLEDAI scale scores (p < 0.05 by the Wald-Wolfovitz test). Six patients with SLE and ON had high scores by this scale--more than 40 scores of the maximum 150 possible scores. APS was diagnosed in 87.5 of the patients with ON (28 of the 32 patients) and only in 61.7% of the patients without ON (in 208 of the 337 patients) (chi2 = 8.4; p = 0.004). The development of ON in the examinees was significantly associated with the presence of APS. The activity of SLE, particularly nephritis, arthritis, positive tests for phospholipid antibodies, the presence of arterial thromboses, thrombocytopenia at the height of disease, therapy with large doses of glucocorticoids.     

SLE继发抗磷脂抗体综合征合并Libman-Sacks心内膜炎一例

临床部分SLE患者可继发抗磷脂抗体综合征（APS）,但同时合并非细菌性心内膜炎的患者则较为罕见。该文报道1例SLE继发APS合并Libman-Sacks心内膜炎患者的诊治过程。该患者入院前有发热、关节痛、咽痛和皮疹,入院后UCG示二尖瓣前叶赘生物形成,查狼疮抗体、抗磷脂抗体、狼疮样抗凝物试验阳性,经抗感染治疗后病情未缓解,后患者突发头晕、口周麻木、构音不清、吞咽困难,查头颅MRI见一新发的延髓梗死灶。结合患者临床表现、体征及辅助检查,诊断为APS,Libman-Sacks心内膜炎,延髓梗死,SLE。予免疫抑制、免疫调节、低分子肝素抗凝等治疗后患者病情好转出院。该例的诊治提示,在UCG发现赘生物时,不仅要考虑感染性心内膜炎,同时需要考虑SLE继发APS可能,尤其是对于既往无明确心瓣膜病病史的年轻女性,早期诊断APS合并Libman-Sacks心内膜炎,并给予个体化抗凝治疗,可取得良好疗效。     

Complement inhibition with eculizumab for thrombotic microangiopathy rescues a living-donor kidney transplant in a patient with antiphospholipid antibody syndrome

Antiphospholipid antibody syndrome (APS) is an enigmatic heterogeneous disorder despite several revelations in its pathobiology. Renal transplantation in patients with APS has been notoriously difficult due to the high risk of development of thrombotic microangiopathy (TMA), which is often refractory to conventional treatment modalities such as aggressive anticoagulation and plasmapheresis. We describe a case of a 58-year-old male with secondary APS undergoing living unrelated renal transplantation for end-stage renal disease from lupus nephritis. Shortly after transplantation, he developed graft dysfunction from APS related TMA that was refractory to systemic anticoagulation and plasmapheresis. After becoming hemodialysis dependent, the patient was started on eculizumab, a humanized monoclonal antibody against complement factor 5, as salvage therapy. We show that this intervention successfully rescued his renal allograft and that the patient has remained dialysis free for over 20 months. Our experience adds to the limited body of literature suggesting the role of complement inhibition in facilitating renal transplantation in patients with APS spectrum of disorders, thus adding a new tool to the therapeutic armamentarium for this difficult disease. The optimal treatment schedule and long term safety data for eculizumab in complement mediated TMA is still unclear. The search for an optimal biomarker to help guide treatment duration is an area of active research.     

Microcirculatory disorders in systemic lupus erythematosus

AIM: To examine microcirculation in patients with systemic lupus erythematosus (SLE) showing clinical signs which may deteriorate hemodynamic indices: arterial hypertension (AH), atherosclerosis, antiphospholipid syndrome (APS). MATERIAL AND METHODS: Microcirculatory changes were studied in 63 patients with SLE using biomicroscopy of bulbar conjunctival vessels (Zeiss slit-lamp, 32 times magnification). The following conjunctival indices were estimated: general (GCI), vascular (VCI), intravascular (IVCI), extravascular or perivascular. RESULTS: Microcirculatory changes in SLE patients covered disturbances of microvascular architectonics, microvascular blood flow. VCI, IVCI, GCI were significantly higher than in control subjects: 6.16 +/- 0.31, 3.69 +/- 0.36 and 9.87 +/- 0.57 scores vs 3.20 +/- 0.50; 120 +/- 0.20 and 4.20 +/- 0.50 scores, respectively. The degree of structural changes in the vessels depended on the disease duration while intravascular changes depended on the activity of lupus process. In patients with AH and atherosclerosis microcirculatory disturbances were similar and related to vascular architectonics. In APS there were marked intravascular disorders (IVCI was 7.50 +/- 0.59 scores, GCI was 16.13 +/- 1.41 scores). CONCLUSION: In SLE patients with AH and/or atherosclerosis microcirculatory changes involved primarily structure of the vascular wall and may be brought about by compensatory-adaptive mechanisms of the microcirculatory bed in high hemodynamic load. Intravascular microcirculatory changes were most pronounced, first of all as sludge-phenomenon, in APS and high SLE activity.     

Immunoadsorption in systemic connective tissue diseases and primary vasculitis.

Immunoadsorption offers some advantages over plasmapheresis; until recently the primary advantage has been avoidance of substitution fluids. In collagen vascular disorders, immunoadsorption is performed for the same indications as plasma exchange; most often adsorbers with binding capacities for IgG and circulating immune complexes are used. Tested ligands are protein A, anti-IgG antibodies, Clq, phenylalanine, and tryptophan. Human IgG was utilized to adsorb rheumatoid factor and dextran sulfate, DNA, or specific anti-idiotypes for anti-DNA antibodies in systemic lupus erythematous (SLE). Most applications have used immunoadsorbent columns in pretransplantation treatment of patients with high panel reactivity and in patients with idiopathic thrombocytopenic purpura (ITP). For these indications, as for systemic connective tissue diseases, randomized trials have yet to be conducted. SLE controlled trials have been completed for IMPH-350 and Ig-Therasorb. Results indicated excellent biocompatibility and good clinical responses. Using protein A in primary systemic vasculitis, histologically proven inactivation of renal involvement was demonstrated, but the patients were also treated with immunosuppressive drugs. Randomized controlled trials are mandatory to provide continued support to the therapeutical opportunities offered only by immunoadsorption.     

Clinical importance of antibodies against platelet activating factor in antiphospholipid syndrome manifestations

BACKGROUND: We assessed whether antibodies against platelet activating factor (PAF) are related to the presence of antiphospholipid syndrome (APS) clinical manifestations, in particular thrombosis, in patients with connective tissue diseases. MATERIALS AND METHODS: Anti-PAF, anticardiolipin (aCL), antibeta2 glycoprotein I (antibeta2GPI) and antiphosphatidylcholine (anti-PC) antibodies were determined in 52 patients with APS, 29 patients with systemic lupus erythematosus (SLE) aCL but without APS, 30 patients with SLE without aCL, and 30 patients with scleroderma. A new enzyme-linked immunosorbent assay (ELISA) was developed for determining anti-PAF antibodies in a bovine serum-free fashion. RESULTS: The ELISA showed high specificity. Homologous inhibition experiments showed 60-70% inhibition. Anti-PAF antibodies were found in 18/52 APS patients, 10/29 SLE/aCL+ patients, 9/30 SLE/aCL- patients and 3/30 scleroderma patients. Anti-PAF antibodies were significantly associated with anti-PC antibodies (odds ratio [OR] 12. 7, P < 0.01), and there was a modest association with immunoglobulin G (IgG) aCL (OR 3.1, P > 0.10), but not with IgM aCL or antibeta2GPI. Three SLE/aCL+ patients and five SLE/aCL- patients had clinical manifestations characteristic of APS. All these patients had anti-PAF antibodies, while none had high titres of aCL or antibeta2GPI antibodies and only one had anti-PC antibodies. Among the combined APS and SLE groups, the presence of anti-PAF antibodies was significantly associated with clinical manifestations which are characteristic of APS (OR 2.6, P = 0.02). The effect was independent of IgG aCL and antibeta2GPI antibodies. CONCLUSIONS: Anti-PAF antibodies are common in APS and SLE and comprise an independent factor for the development of thrombosis. Several patients experiencing thromboses have anti-PAF antibodies without other antiphospholipid specificities.     

Fatal tumor thrombosis due to an inferior vena cava leiomyosarcoma in a patient with antiphospholipid antibody syndrome

We describe a patient with antiphospholipid antibody syndrome (APS) who died because of relentless inferior vena cava (IVC) tumor thrombosis due to an unsuspected leiomyosarcoma. Laboratory confirmation for APS was provided by functional identification of a lupus anticoagulant and anticardiolipin IgG and anti-beta2-glycoprotein I IgM antibodies. Although sensitive for detecting vascular obstruction, radiocontrast venography and magnetic resonance imaging and angiography detected the IVC thrombosis but failed to distinguish its malignant nature. Concomitant refractory thrombocytopenia prevented further invasive diagnostic and therapeutic maneuvers for progressive, severe IVC thrombosis unresponsive to aggressive treatment of APS. Deep venous thrombosis refractory to anticoagulant and immunomodulatory therapies in a patient with APS may be due to a concomitant underlying malignancy, such as a leiomyosarcoma, causing vascular obstruction.     

Antiphospholipid syndrome and exogenic risk factors in thromboses

AIM: To examine relationships between incidence rate of thromboses in antiphospholipid syndrome and exogenic risk factors (RF) of thrombosis. MATERIAL AND METHODS: The trial enrolled 131 patients (105 females and 26 males). They were divided into three groups: 23 patients with systemic lupus erythematosus (SLE, group 1), 63 patients with SLE and antiphospholipid syndrome (APS, group 2), 45 patients with primary APS (PAPS, group 3). Thrombosis RF questionnaire survey was made. Effects of corticosteroids and cyclophosphamide on occurrence of thrombosis were assessed. RESULTS: Such exogenic RF as intake of coffee, fat food, alcohol were not related to thromboses. Hypodynamia was more typical for APS patients (21.3%) than for SLE patients free of APS (8.7%). Overweight for was characteristic for APS patients (49 and 34.7%, respectively). The proportion of smokers was higher in APS patients, though smoking did not provoke thrombotic complications. A direct correlation was found between occlusion and corticosteroids administration, while occlusion and cyclophosphamide treatment correlated inversely. CONCLUSION: Venous thrombosis RF in patients with APS and PAPS are obesity and treatment with glucocorticosteroids.     

Recovery of both acute massive pulmonary hemorrhage and acute renal failure in a systemic lupus erythematosus patient with lupus anticoagulant by the combined therapy of plasmapheresis plus cyclophosphamide

Acute massive pulmonary hemorrhage (AMPH) is a rare and highly fatal complication in systemic lupus erythematosus (SLE). We report here survival in a case of AMPH in a SLE patient with both rapidly progressive glomerulonephritis and lupus anticoagulant. The AMPH occurred while the nephritis was refractory to 2 courses of pulse methylprednisolone therapy. After combined therapy with plasmapheresis plus cyclophosphamide, circulating immune complex levels declined, AMPH recovered, and serum creatinine levels returned to normal. In conclusion, the combined therapy of plasmapheresis plus cyclophosphamide should be considered for treating AMPH especially in those SLE patients with rapidly progressive glomerulonephritis.     

Soluble adhesion molecules in antiphospholipid syndrome associated with systemic lupus erythematosus and in primary antiphospholipid syndrome

AIM: To evaluate clinical implications of measurements of the level of soluble cell molecules of adhesion (sCMA) in systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS) and primary APS (PAPS). MATERIAL AND METHODS: Serum levels of sP-selectine, sE-selectine, sVCAM-1 were determined with enzyme immunoassay (R&D, USA) in 23 SLE with APS, 15 SLE patients free of APS and 19 patients with PAPS. RESULTS: Mean levels of sE-selectine and sVCAM-1 in SLE patients with APS, PAPS and SLE was higher than in donors. Elevated mean levels of sP-selectine were observed only in SLE patients free of APS. These patients also showed a correlation between sVCAM-1 level and the disease activity (p < 0.01). CONCLUSION: The development of immunopathological process in APS is associated with increased concentration of sCMA.     

Thrombotic thrombocytopenic purpura and systemic lupus erythematosus - distinct entities or overlapping syndromes?

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening syndrome characterized by platelet aggregation leading to occlusive microangiopathy. TTP has been rarely reported to simultaneously present with systemic lupus erythematosus (SLE). CASE: A 61-year-old male presenting with TTP was also concurrently diagnosed with SLE. The patient recovered only after combined treatments with plasmapheresis and immunosuppressive therapy. CONCLUSION: This case is the first to describe the simultaneous presentation of TTP and SLE in an elderly gentleman. While it is important to distinguish between the two diseases because of therapeutic implications, cases of concurrent TTP and SLE help to elucidate the pathophysiology that underlies each condition.     

Survival and prognostic factors of death risk in antiphospholipid syndrome: results of 8-year follow-up

AIM: To evaluate survival and mortality in antiphospholipid syndrome (APS) as well as prognostic factors of APS deterioration. MATERIAL AND METHODS: We retrospectively studied 248 case histories of patients admitted to the Institute of Rheumatology for 8 years. Primary APS was diagnosed in 35 patients, SLE + APS (according to criteria of ACR, 1982)--in 122 patients and SLE without APS--in 91 patients. Mean age was 31.2 +/- 15.0 years (range from 14 to 63), median length of follow-up from the time of diagnosis was 11.9 +/- 5.4 years. During 8 year period all the patients annually and the latest 5 years at least twice a year were examined for the presence of IgG and IgM-anticardiolipin antibodies (aCL) and lupus anticoagulant (LA). Thrombotic events were verified with special techniques. RESULTS: Thirty-eight patients (15%) died during the follow-up period. Mean age of the decreased was 35.4 +/- 12.2 years (range 21-52 years) and the disease duration 8.6 +/- 8.2 years (range 0.6-20), the median length of the survival from the time of the diagnosis was 6.2 +/- 4.3 years. The 8-year survival for SLE patients without APS was 98%, for those with SLE + APS-75% and for patients with primary APS-83%. The presence of APS in SLE patients was significantly associated with high mortality (chi 2 = 12.3, freedom = 4, p = 0.006). Cox regression analysis revealed that the activity of the disease at onset, arterial thrombosis, especially recurrent, thrombocytopenia, valvular disease of the heart, capillaritis, digital necrosis and nephritis were independent risk factors for mortality (p < 0.05). CONCLUSION: Thus, long-term follow-up is necessary for patients with antiphospholipid antibodies especially with APS which lowers survival of SLE patients. Such patients need early corrective therapy to prevent thrombotic events.     

Plasma exchange for thrombocytopenia in antiphospholipid syndrome: a case report.

The remarkable effect of plasma exchange (PE) was observed on thrombocytopenia in a patient with antiphospholipid syndrome (APS) associated with systemic lupus erythematosus. Three times PE led to recovery from severe thrombocytopenia refractory to treatment with corticosteroid, anticoagulant, and antiplatelet drugs accompanied by a decrease in the serum cardiolipin beta2 glycoprotein I antibody level. This result suggests that PE is a valuable therapeutic tool for refractory thrombocytopenia in APS.     

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.     

贝利尤单抗联合环孢素治疗难治性系统性红斑狼疮继发免疫性血小板减少1例并文献复习

目的 探讨贝利尤单抗治疗难治性系统性红斑狼疮(systemic lupus erythematosus, SLE)合并顽固性血液系统损害的疗效。方法 回顾性分析贵州省人民医院收治的1例以顽固性血液系统损害为主要表现的SLE病例的诊治过程。结果 患者为青年女性,SLE病史1年余,因皮下瘀斑伴腹痛10天入院,住院后明确诊断SLE合并难治性血液系统损害,在环孢素等基础治疗上加用贝利尤单抗维持治疗后,患者病情明显改善,且未见不良反应。随访1年余,患者激素用量已减至最低维持量,无复发。结论 贝利尤单抗联合环孢素治疗为难治性SLE继发免疫性血小板减少的治疗提供了新选择,更多的临床应用证据有待长期的大样本病例研究观察、评估。     

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.     

Risk factors for central nervous system involvement in systemic lupus erythematosus

We investigated risk factors for central nervous system (CNS) involvement in systemic lupus erythematosus (SLE), in 32 such patients individually matched 1 : 3 to 96 control SLE patients without CNS events. Univariate analysis showed that CNS involvement was significantly associated with the antiphospholipid syndrome (APS) as well as its features: arterial thrombosis, recurrent fetal loss, livedo reticularis and IgG anticardiolipin (aCL) antibodies in high titres. Other potential associations included cutaneous vasculitic lesions, thrombocytopenia, positive ANA, anti-SS-B/La and low serum levels of C(3) and C(4) complement components, while articular manifestations and discoid rash were significantly less common in patients with neuropsychiatric (NP) disease. In multivariate modeling, CNS involvement was strongly associated with cutaneous vasculitic lesions OR 33, 95% CI 1.5-720) and arterial thromboses (OR 13, 95%CI 0.82-220), and negatively related to the presence of articular manifestations (OR 0.015, 95%CI 0.00-0.17) and discoid rash (OR 0.004, 95%CI 0.00-0.35). Associations with APS-related arterial thromboses and vasculitis point to the importance of arterial vascular pathophysiology in the pathogenesis of NP disease in SLE. Patients with articular manifestations and discoid rash are at very low risk of NP events. Patients with an adverse SLE disease profile may require closer observation and may be the target group for studying pre-emptive interventions.