Treatment of isolated severe immune hemolytic anaemia associated with systemic lupus erythematosus: 26 cases

The aim of this study was to evaluate the response to treatment and the long-term outcome in a cohort of patients in whom severe autoimmune hemolytic anaemia (AHA) was the leading manifestation of systemic lupus erythematosus (SLE). Twenty-six women with severe isolated AHA were included. Corticosteroids were used as the initial treatment for all patients in our study. An initial response was obtained in all but one patient (96%). The overall recurrence rate was three per 100 person-years, with an expected recurrence-free proportion of 73% with a 180 months median follow-up. Seven patients (27%) experienced a relapse of AHA. We found a higher proportion of pleuritis in relapsing patients. Only three patients experienced multiple relapses despite splenectomy and several immunosuppressants. Steroid-sparing effect of hydroxychloroquine and azathioprine could not be assessed because most of the patients received these treatments for other reasons than AHA. Intravenous immunoglobulins induced transient response in three cases. Splenectomy was efficient to definitively control AHA in one patient but two patients quickly experienced relapses while one patient did not benefit. Five patients received immunosuppressants that induced only transient responses. Rituximab was long-term efficient in one case. In conclusion, severe AHA is a serious complication of SLE that warrants appropriate management. On the basis of our experience, the ideal treatment of isolated AHA should be oral corticosteroids in first-line treatment. Our study does not support an important role for splenectomy. Patients refractory to conventional therapy should be treated either with few toxic immunosuppressive drugs, danazol or rituximab.     

系统性红斑狼疮合并重症血小板减少的临床特征

目的　研究系统性红斑狼疮 (SLE)并发重症血小板减少的临床特征 ,并与慢性特发性血小板减少性紫癜 (CITP)急性发作进行对比。方法　比较SLE并发重症血小板减少组 (SLE组 )和CITP组病人的出血情况、血小板相关抗体、骨髓巨核细胞成熟障碍程度、对泼尼松(≥ 1mg·kg-1·d-1)联合长春新碱近期治疗效果等的差异。结果　SLE组出血程度轻 ,以皮肤、黏膜出血为主 ,而CITP组出血程度重 ,以黏膜和脏器出血为主 ;两组间血小板相关抗体差异无显著性 (P>0 0 5 ) ;SLE组骨髓巨核细胞总数显著低于CITP组 (P <0 0 5 ) ,巨核细胞成熟被阻碍在颗粒巨核细胞阶段的程度低于CITP组 ;SLE组泼尼松 (≥ 1mg·kg-1·d-1)联合长春新碱的近期疗效明显低于CITP组 (P <0 0 5 )。结论　SLE并发重症血小板减少在骨髓巨核细胞成熟障碍的程度、出血程度及对治疗的反应等方面与CITP均有显著不同之处     

Cell-mediated amegakaryocytic thrombocytopenia associated with systemic lupus erythematosus

We studied a patient with a rare complication of amegakaryocytic thrombocytopenia (AMT) associated with systemic lupus erythematosus (SLE). To investigate the underlying pathogenesis of AMT, the effects of peripheral blood T cells and serum on human megakaryocyte progenitor cells were studied using in vitro coculture techniques. Mononuclear bone marrow cells (2 X 10(5) from normal donors produced 33.6 +/- 8.8 (n = 10) colony-forming unit-megakaryocytes (CFU-M) in our plasma clot system. When 2 X 10(5) of the patient's T cells were added to the culture system, the number of CFU-M decreased to only 3.5 +/- 0.6/2 X 10(5) bone marrow cells. No evidence of inhibitory effects was found by the addition of the patient's serum and complement to the culture system. The T cells stored at -80 degrees C on admission were also capable of suppressing autologous CFU-M after recovery from AMT. These results indicate that in vitro suppression of CFU-M from allogenic and autologous bone marrow cells by this patient's T cells provides an explanation for the pathogenesis of AMT associated with SLE.     

Treatment of severe thrombocytopenia in systemic lupus erythematosus with intravenous gammaglobulin.

Three patients with lupus with severe auto-immune thrombocytopenia were treated with high doses of intravenous gammaglobulin. In the patient with active disease a prolonged but partial response with respect to platelet counts was observed. In the two other patients who had no disease activity other than thrombocytopenia at the time of intravenous gammaglobulin treatment a minor (and only transient) increase in platelet counts was seen after treatment. No change in the state of disease activity nor in the levels of antinuclear antibodies, circulating immune complexes, nor complement C3/4 was observed in these three patients after treatment with intravenous gammaglobulin.     

Lupus mastitis associated with severe systemic erythematosus lupus

We report a 46-year-old woman with a systemic lupus erythematosus complicated with a lupus panniculitis. The patient developed initial deep breast nodules secondarily completed by superficial erythematosus and keratotic cutaneous lesions. Neoplasia was ruled out by X-ray and echographic investigations. Both subcutaneous and skin biopsies were consistent with the diagnosis of lupus mastitis. Lupus mastitis is a form of lupus panniculitis seldom associated with systemic lupus. A breast neoplasia should be ruled out by appropriate investigations and deep biopsies. The first-line treatment is based on antimalarial drugs.     

Treatment with rituximab for thrombocytopenia due to systemic lupus erythematosus

Some patients with thrombocytopenia due SLE fail to respond to conventional therapies. Rituximab has been reported to be an alternative for patient treatment.ObjectiveTo evaluate the response of thrombocytopenia due to Systemic Lupus Erythematosus to the use of Rituximab and patient relapse time at our hospital.Patients and methodsWe analyzed patients with SLE than received a 2 gram rituximab treatment for thrombocytopenia. We analyzed the rate of patients that achieved complete remission (CR), defined as a platelet count over 100 mil/mm³, partial remission (PR) described as platelets within 50–100 mil/mm³ and no response (NR) if platelets remained unchanged and the time the remission was sustained.Results16 treatments were applied to 13 patients, aged 28±9 years of age and SLE mean duration time of 68±44 months with a mean platelet count of 38±29 mil. In 14 treatments (87%) remission was achieved after 5±2 weeks where 2 patients (12.5%) were non respondent. One of them died due to a massive hemorrhage. The mean response time without relapse was 15.6±6 months. Follow up of three patients was not possible and 3 other died due to infections.ConclusionsRituximab is an alternative for treatment of thrombocytopenia due to Systemic Lupus Erythematosus.     

Refractory immune thrombocytopenia in systemic lupus erythematosus: response to mycophenolate mofetil

Immune thrombocytopenia (IT) is a common manifestation of systemic lupus erythematosus (SLE). Although severe IT (<20 x 10(9)/L) occurs in about 5-10% of patients, usually in the context of active disease, the absence of randomized controlled trials has not allowed the development of evidence-based guidelines for managing this condition. Conventionally, high-dose glucocorticoids are considered first-line therapy. Adjunctive medical and surgical treatments for patients with an absent or partial response to glucocorticoids have met with varying degrees of success. We describe an SLE patient with IT refractory to high-dose corticosteroids, pulse methylprednisolone and intravenous immunoglobulin therapy, whose platelet counts normalized during therapy with mycophenolate mofetil (MMF). Pending further controlled studies to confirm this observation, we suggest that MMF may be considered as a therapeutic option in the treatment of glucocorticoid-refractory immune thrombocytopenia in SLE.     

Splenectomy for thrombocytopenia associated with systemic lupus erythematosus in 11 Chinese patients

Since the role of splenectomy in treating thrombocytopenia associated with systemic lupus erythematosus has been controversial, the study was focused on determining the efficacy of splenectomy in the SLE-associated thrombocytopenia. Between 1980 and 2008, 11 patients with SLE underwent splenectomy for treating their thrombocytopenia. Surgical indications, operative mortality and morbidity, and haematological outcomes were followed in both short term (first 30 days) and long term (last recorded platelet count, last contact, or death). Indications for splenectomy included: thrombocytopenia refractory to (63.7%), dependent on (27.3%), or patient intolerance of (9%) medical treatments. Perioperative mortality and morbidity was 0%. The overall rate of early partial or complete response rate to splenectomy was 100%. After a median follow-up of 36 months, 9 (81.9%) patients had sustained complete or partial response without relapse. Eight (72.8%) of these patients required adjunctive medical therapy, whereas the other 1 (9%) did not. The remaining 2 (18.2%) patients relapsed, could not been subsequently salvaged to at least partial response with further treatments. The overall PR or CR to splenectomy combined with medical therapy was 81.8%. Splenectomy should be considered as a safe and efficacious therapy for the severe thrombocytopenia associated with SLE in some selected patients.     

抗血小板生成素抗体与系统性红斑狼疮伴血小板减少的相关性研究

目的 分析抗血小板生成素(TPO)抗体在系统性红斑狼疮(SLE)中的作用,并探讨其与SLE伴血小板减少及病情的相关性.方法 应用酶联免疫吸附试验(ELISA)检测56例SLE患者中的抗TPO抗体,并与20例免疫性血小板减少性紫癜(ITP)及20名健康人对照.同时分析SLE患者临床特点.正态分布的计数资料采用x2检验或Fisher精确检验,计量资料采用t检验,非正态分布采用M(Q)表示及Wilcoxon's rank检验.结果 抗TPO抗体在SLE组中阳性率为39％,35％的免疫性血小板减少患者抗TPO抗体阳性,而健康对照中未能检测到抗TPO抗体(x2=11.058,P=0.001).26例伴发血小板减少的SLE患者中,15例(58％)抗TPO抗体阳性,而30例无血小板减少患者中仅有7例(23％,x2=6.894,P=0.009);进一步分析发现抗TPO体抗体阳性患者其血小板下降程度重(t=3.010,P=0.004).对照抗TPO抗体阳性与阴性患者的临床资料显示,关节炎(x2=5.959,P=0.015)、抗双链DNA(dsDNA)抗体阳性(x2=5.959,P=0.015)的SLE患者更易产生抗TPO抗体.结论 在伴发血小板减少的SLE患者中检测出较高阳性率的抗TPO抗体表明该抗体可能在SLE发生血小板减少的过程中起重要作用.在伴发血小板减少的SLE患者中检测该抗体具有一定的临床价值.     

Narcolepsy associated with systemic lupus erythematosus

Many neurologic and psychiatric manifestations have been associated with systemic lupus erythematosus. Narcolepsy, currently hypothesized as related to an autoimmune process, has been rarely associated with systemic lupus erythematosus. We report a 36-year-old woman who presented with narcolepsy and who subsequently developed systemic lupus erythematosus. Excessive daytime sleepiness resolved after the administration of four intravenous bolus of cyclophosphamide and methylprednisolone followed by maintenance therapy with hydroxychloroquine, aspirine and prednisone. Narcolepsy should be included in the neuropsychiatric manifestations of systemic lupus erythematosus and it may have a parallel clinical course to the activity of the lupus.     

Treatment of severe and difficult cases of systemic lupus erythematosus with tacrolimus. A report of three cases

OBJECTIVES—An analysis of the efficacy of tacrolimus treatment in three patients with difficult and severe systemic lupus erythematosus (SLE) whose active disease had been previously poorly controlled by cyclosporine and cyclophosphamide.
METHODS—A review of patient notes.
RESULTS—Two patients are well controlled after six and nine months of treatment with tacrolimus 0.06 mg/kg/day and 0.18 mg/kg/day. Previous persistent vasculitis had resolved and other features of active disease were controlled. The third patient's vasculitis had not improved significantly after two months of treatment and tacrolimus 0.17 mg/kg/day was discontinued because of nephrotoxicity.
CONCLUSION—Tacrolimus may be a useful additional immunosuppressive agent in some patients whose SLE is not well controlled by conventional treatments.

     

Efficacy of cyclosporin-A in the long-term management of thrombocytopenia associated with systemic lupus erythematosus

Thrombocytopenia frequently complicates systemic lupus erythematosus (SLE), and its long-term management may be problematic. Intravenous immunoglobulins and high doses of steroids are often effective as induction therapy, but thrombocytopenia frequently relapses during steroid tapering. Several immunosuppressive agents have been evaluated as induction or maintenance therapy in small series or in case reports. We describe six consecutive unselected SLE patients where cyclosporin-A (CyA) was effective and safe in the long-term management of thrombocytopenia and allowed steroid tapering. One relapse occurred during CyA reduction and responded to CyA dose adjustment. Steroids could be stopped in three out of six patients, and were maintained at very low doses in the remaining patients. CyA was stopped in one patient after one year of treatment, without relapse at month 11+ from discontinuation. No severe side effects were documented. Overall, these data suggest that CyA may prove to be an effective and safe therapeutic option for SLE-related thrombocytopenia.     

A case of systemic lupus erythematosus associated with severe acute pancreatitis]

A 22-year-old woman began to have the symptoms of anorexia, high fever, cough and general fatigue from June of 1997. She was admitted in our hospital on Aug. 8th, 1997 for the further detail examination because of pancytopenia and positive antinuclear antibody (ANA). Her laboratory findings and clinical symptoms were compatible with systemic lupus erythematosus (SLE) such as leukopenia, proteinuria, hypocomplementemia, positive ANA, elevated titer of autoantibodies including anti-DNA, anti-Sm, anti-RNP antibodies, polyarthralgia and photosensitivity. The administration of oral prednisolone (40 mg/day) was started on Aug. 15th, 1997 under the diagnosis of SLE. However, she had severe abdominal pain in epigastrium with elevated serum amylase, ascites and dull shape of pancreas tail by CT scan compatible with acute pancreatitis. On Aug. 18th, her general condition was worsening with fever, epigastralgia, abdominal distension, anemia, weak palpation of radial artery, hypotension, tachycardia, shallow breathing and cold sensation on both extremities as shock. In spite of steroid pulse therapy with nafamostat mesilate intraarterial infusion, her condition was not improved. The dose of 50 mg/day of cyclophosphamide was added to the regimen on Aug. 22nd. Then, gradually her condition started to be restored. Anemia, leukopenia, hypocomplementemia continued. Second steroid pulse therapy was done on Sep. 5th. After then, she became better in her clinical symptoms and laboratory data. The dose of PSL was tapered to 15 mg/day and 7.5 mg/day update of Oct. 1998 without the pseudcysts found after pancreatitis. She is a rare case who recovered from severe acute pancreatitis due to SLE itself.     

Effect of splenectomy for management of thrombocytopenia associated with systemic lupus erythematosus: a case report

A 51-year-old female with systemic lupus erythematosus (SLE) was admitted in November 1987 because of general fatigue and muscular weakness. She was treated with prednisolone (PSL) 30 mg and azathioprine (AZP) 50 mg after failure in the management of thrombocytopenia by PSL 15 mg. She exhibited no splenomegaly. Muscular atrophy and weakness were seen in the proximal muscles. Her platelet count was 44,000/microliters. A bone marrow aspiration revealed an increase in megakaryocytes. The blood chemistry revealed a normal CPK level and an elevated LDH level, indicating a presence of steroid myopathy. A splenectomy was performed after an increase of platelet count by giving gamma-globulin 400 mg/kg for 5 days. The platelet count rose to 368,000/microliters on the 46th postoperative day. She was treated with PSL 5 mg and AZP 50 mg as postsplenectomy therapy. The splenectomy did not adversely affect other aspects of SLE, in particular, renal function. She had no major complications in the postoperative period. Her platelet count reached a plateau 4 months later and revealed 115,000/microliters 18 months postoperatively.     

Autoimmune hemolytic anemia in systemic lupus erythematosus: association with thrombocytopenia

Hematological disturbances are common in systemic lupus erythematous (SLE). Specifically, autoimmune hemolytic anemia (AHA) may manifest in SLE patients at the time of diagnosis or within the first year of the disease. AHA is often associated with thrombocytopenia, lupus nephritis, and central nervous system activity. In this study we investigated these associations in Brazilian patients with SLE. Forty-four consecutive SLE patients who had a history of AHA were age, gender, and disease duration matched with 318 SLE patients without AHA who formed the control group. All patients fulfilled the revised American College of Rheumatology criteria for SLE and were followed-up within our Service. Clinical and laboratorial manifestations were similar in both groups, except for the predominance of leukopenia, thrombocytopenia, and anti-dsDNA on univariate analysis in the AHA group. The multivariate logistic regression model revealed risk only for thrombocytopenia in the AHA group compared to the control group (odds ratio, 2.70; 95% confidence interval, 1.32–5.50). Our results corroborate previous data that AHA in SLE increases the risk of thrombocytopenia in individuals with SLE. This association suggests a common mechanism in AHA and SLE pathophysiologies.     

The significance of thrombocytopenia in systemic lupus erythematosus

The significance of thrombocytopenia in systemic lupus erythematosus (SLE) is unclear. Some researchers have found it associated with severe disease, others with mild disease. Thrombocytopenia (platelets < 100,000) occurred in 21 patients seen at an SLE clinic over 18 months. Prospective assessment of 19 (non-SLE causes excluded) revealed 2 distinct subgroups. Seven were thrombocytopenic only during severe multisystem flares. Twelve had chronic thrombocytopenia with intermittent mild flares in other systems. Serious bleeding was rare in both subgroups. It was concluded that thrombocytopenia clearly is not a prognostic indicator.