Interferon-alpha: a key cytokine in systemic lupus erythematosus pathogenesis

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by a chronic inflammation affecting multiple tissues and the production of antibodies directed against nuclear antigens. Leading observations in patients suggested years ago that interferon-alpha (IFNα) was involved in SLE pathogenesis. These observations have now been confirmed in SLE-prone mice. New promising therapeutic strategies, aiming at neutralizing IFNα or its effects, are currently under development.     

Pregnancy in systemic lupus erythematosus

Issues concerning contraception, fertility, and pregnancy usually arise during a typical lupus patient's disease course. Pregnancy superimposed on established lupus may alter the course of the disease, and, conversely, lupus may affect the natural history of pregnancy. Two recently described autoantibody markers, anti-SSA (Ro) and anticardiolipin, have provided new insights concerning fetal risks in these patients. Furthermore, they should lead to improved understanding of mechanisms of tissue injury and to new ideas about therapeutic interventions and/or prevention of pregnancy complications.     

系统性红斑狼疮与高同型半胱氨酸血症的临床研究

目的　观察系统性红斑狼疮 (SLE)患者血浆中同型半胱氨酸 (Hcy)水平 ,分析影响Hcy的因素和某些心血管因素的变化。 方法　测定 2 7例SLE和 31名正常对照的Hcy、维生素B12 、叶酸、C反应蛋白 (CRP)、氧化低密度脂蛋白 (oxLDL)、一氧化氮 (NO)、丙二醛 (MDA)的水平和亚甲基四氢叶酸还原酶 (MTHFR)基因 6 77位的多态性。结果　①SLE组Hcy水平明显较对照组高 ,其差异有显著性 [SLE组 (19± 7) μmol/L ,对照组 (12± 4 ) μmol/L ,P <0 0 0 1];②Hcy与维生素B12 、叶酸呈负相关 ,相关系数分别为 - 0 76 7和 - 0 6 7,P <0 0 0 0 1;③MTHFR基因 6 77位CT的突变使Hcy水平升高 [CC型 (12 8± 6 2 ) μmol/L ,CT型 (16 0± 2 1) μmol/L ,TT型 (18 9± 5 7) μmol/L ,P<0 0 0 1];TT基因型是高Hcy血症的易感基因 ,相对危险度 (RR) =31 4 9,P <0 0 5 ;TT基因型是SLE的易感基因 ,RR =6 913,P <0 0 5 ;④Hcy水平与NO、MDA、oxLDL呈正相关 ,并与CRP呈正相关。结论　①SLE患者普遍有高Hcy血症。②导致高Hcy血症的原因包括叶酸、维生素B12 的水平降低和MTHFR基因的突变 ,TT型基因是Hcy异常升高的易感基因。③TT型基因也是SLE的易感基因。④高Hcy血症可能通过损伤血管内皮 ,大量产生氧自由基 ,加速低密度     

Dehydroepiandrosterone in systemic lupus erythematosus

Objective. To determine if dehydroepiandrosterone (DHEA) is beneficial in the treatment of systemic lupus erythematosus (SLE). Methods. In a double-blind, placebo-controlled, randomized trial, 28 female patients with mild to moderate SLE were given DHEA 200 mg/day or placebo for 3 months. Outcomes included the SLE Disease Activity Index (SLEDAI) score, patient's and physician's overall assessments of disease activity, and concurrent corticosteroid dosages (which were adjusted as clinically indicated). Results. In the patients who were receiving DHEA, the SLEDAI score, patient's and physician's overall assessment of disease activity, and concurrent prednisone dosage decreased, while in the patients taking placebo, small increases were seen. The difference in patient's assessment between the groups was statistically significant (P = 0.022, adjusted). Lupus flares occurred more frequently in the placebo group (P = 0.053). Mild acne was a frequent side effect of DHEA. Conclusion. DHEA may be useful as a therapeutic agent for the treatment of mild to moderate SLE. Further studies of DHEA in the treatment of SLE are warranted.     

Immunoadsorption in systemic lupus erythematosus

Plasmapheresis and immunoadsorption (IA) have been introduced into the therapeutic strategy of patients with systemic lupus erythematosus (SLE) and severe organ involvement. Despite numerous reports about the clinical efficacy of extracorporeal treatments controlled studies have failed to show significant advantages compared with standard immunosuppressive treatment. We describe the historical development of plasmapheresis‐based IA‐techniques with special comments on substitution fluids and especially immunoglobuline (Ig) specific adsorption columns. In addition, an overview is given of our clinical experience with different columns and a new strategy of aggressive Ig lowering combined with standard cyclophosphamide pulse therapy in SLE patients with severe organ involvement.     

Malignancy in systemic lupus erythematosus

Objective. To estimate the risk of cancer in patients with systemic lupus erythematosus (SLE). Methods. Patients with SLE (n = 724) have been followed prospectively, for 24 years, at the University of Toronto Lupus Clinic. The diagnosis of cancer was confirmed by histologic or autopsy reports. Standardized rates of cancer and standardized incidence rates (SIR) (ratio of observed-to-expected cancers) were used to estimate the risk for cancers. Results. Twenty-four cancers were identified in 23 SLE patients (3.2%) during 7,233 patient-years of followup. Compared with the Ontario population, the overall estimated risk for all cancers was not increased in the lupus cohort (SIR 1.08, 95% confidence interval 0.70–1.62). A 4.1-fold increased risk for hematologic cancers was observed, due mainly to an increased risk of non-Hodgkin's lymphoma. The risk for cancer was significantly lower in the SLE cohort compared with patients with rheumatoid arthritis (RA) and systemic sclerosis (SSc). Conclusion. SLE is associated with a lower risk of all cancers compared with RA and SSc, but an increased risk for non-Hodgkin's lymphoma compared with the general population.     

Hypercalcaemia in systemic lupus erythematosus

Hypercalcaemia is found in more than 90% of the cases of primitive hyperparathyroidism and malignancies. Rarely, D hypervitaminosis, sarcoidosis, other granulomatous diseases, some drugs, and endocrine diseases may be responsible. Nine patients with systemic lupus erythematosus (SLE) and hypercalcaemia, without evidence of primary hyperparathyroidism, have been previously described. Here we report the 10th patient with SLE and hypercalcaemia, along with a brief review of the literature.     

Hypoparathyroidism in systemic lupus erythematosus

We present the case of a man diagnosed with lupus and hypoparathyroidism. This combined diagnosis has very rarely been reported, which is surprising given the evidence that idiopathic hypoparathyroidism can be due to autoimmunity, the multiplicity of organ systems that lupus can affect and the evidence that other endocrinopathies such as hypothyroidism do occur at increased rates in patients with lupus. Hypoparathyroidism does not always cause overt clinical symptoms but the resultant hypocalcemia be a significant health risk. In addition to presenting the case, we review the relevant literature and offer a discussion.     

Mucormycosis in systemic lupus erythematosus

OBJECTIVE: To describe a case of mucormycosis in systemic lupus erythematosus (SLE) and to review other patients reported in the English literature. METHOD: A Medline search for articles about mucormycosis in SLE published between 1970 and 2002 was performed by using the key words "lupus," "mucormycosis," "zygomycosis," "Mucorales," "Rhizopus," and "Mucor." Cases were pooled for analysis, and the mycology, diagnosis, treatment, and outcome of mucormycosis in SLE was reviewed. RESULTS: Eight cases of mucormycosis in SLE were identified (female:male = 7:1). The mean age at the time of infection was 31.8 +/- 7.6 years and the mean duration of SLE was 6.3 +/- 3.9 years. All except 1 patient had active lupus and all were receiving high-dose corticosteroids. Concomitant cytotoxic agents were used in 4 patients. Additional predisposing factors for opportunistic infection included hypocomplementemia, nephrotic syndrome, uremia, leukopenia, and diabetes mellitus. The disseminated form of mucormycosis was the most common presentation and the diagnosis often was made only at autopsy (63%). For cases with positive culture results, Rhizopus was the causative species. In 4 patients, manifestations of the fungal infection mimicked those of active SLE. The overall mortality of mucormycosis was very high (88%) and, in most cases, was probably a function of delayed diagnosis and treatment. The cutaneous form appeared to have the best prognosis with combined medical and surgical treatment. CONCLUSIONS: Mucormycosis is a rare but usually fatal fungal infection in SLE. Judicious use of immunosuppressive agents, a high index of suspicion, early diagnosis, and combination treatment with amphotericin B and surgical debridement may improve the prognosis of this serious infection.     

Myocarditis in systemic lupus erythematosus

Although clinical manifestations of myocarditis in systemic lupus erythematosus are uncommon, noninvasive cardiac testing may detect subclinical cases. The pathogenesis of myocarditis in systemic lupus erythematosus has been ascribed to many factors, including autoimmunity, medications, and coexisting diseases. Lupus myocarditis merits urgent clinical attention because of the likely progression to arrhythmias, conduction disturbances and heart block, dilated cardiomyopathy, and heart failure. Endomyocardial biopsy can be used to identify the underlying inflammatory histopathology. Usual therapy includes high-dose corticosteroids, in addition to standard cardiac medications.     

Prognosis in systemic lupus erythematosus

To assess the impact of demographic and clinical factors on prognosis in patients with systemic lupus erythematosus (SLE), we examined survivorship by life-table analysis in 389 patients. There were approximately equal numbers of Caucasian patients and American black patients in this study group. On both univariate and multivariate analyses, we found that both American black race and increasing age at SLE onset independently worsened the probability of survival. Of all the clinical factors we analyzed, thrombocytopenia emerged as the only independent risk factor for a worse prognosis in SLE. In all clinical and demographic groups considered, the leading cause of death was infection.     

Minoxidil-induced systemic lupus erythematosus

A patient treated for two months with the antihypertensive agent minoxidil developed pleural and pericardial effusions in association with a positive antinuclear antibody titer. No evidence of central nervous system or renal involvement was present, and results of specific tests for idiopathic systemic lupus erythematosus, including anti-double-stranded DNA and anti-Smith antibodies, were negative. Complement levels were normal. The patient's clinical picture improved and titers of antinuclear antibody decreased after discontinuation of minoxidil therapy, suggesting that minoxidil induced a lupus-like syndrome in this patient.