bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographical variation in mortality from systemic lupus erythematosus in the United States
Authors: Walsh S J , Dechello L M
Published: November 2003

The aim was to identify demographic and environmental factors that affect the incidence and course of systemic lupus erythematosus (SLE) by studying geographical variation in mortality from the disease.

Counts of SLE deaths during a 10-y period were determined for each of the 3111 counties in the United States. The counts were subjected to statistical techniques for detecting spatial clusters with significantly higher or lower mortality than expected. Census data were used to compare attributes of the resulting clusters.

Four clusters with significantly elevated SLE mortality were identified. They were centered in Alabama, Arkansas, Louisiana and New Mexico and had 41–65% more SLE deaths than expected. Four other clusters with significantly low mortality were centered in Minnesota, Vermont, Virginia and Washington and had 32 ± 44% fewer deaths than expected. Comparison of SLE mortality rates between the New Mexico and Vermont clusters yielded relative risks of 3.2, 3.4 and 5.9 for white, black and other race women, respectively, and of 2.1, 5.2 and ‘undefined’ for white, black and other race men. Census data showed that the clusters with elevated mortality had higher poverty rates and/or greater concentrations of ethnic Hispanics than those with lower mortality.

SLE mortality rates show great regional variation within the United States. The variation appears to reflect, in part, geographical patterns in socioeconomic status and in the distribution of persons of Hispanic origin.
Vertigo and Parinaud's syndrome as presentation of Churg–Strauss syndrome
Authors: Plaza G , Yangüela J , López-Lafuente J , Linares M J
Published: November 2003

Intracranial complications are rare in Churg–Strauss syndrome (CSS). Cerebral infarctions are the most common intracranial presentation, usually after the clinical diagnosis of CSS had been established. We present a case of vertigo and Parinaud's syndrome as presentation of CSS in an asthmatic patient. Clinical examination revealed upward gaze limitation and bilateral midriasis. A cranial computed tomography scan showed a small round hypoattenuating lesion located in the right thalamic–mesencephalic region, which was later confirmed by magnetic resonance imaging. There was eosinophilia of more than 50%, and p-ANCA were positive. After steroid treatment was started, vertigo and diplopia resolved, and eosinophilia was reduced. After 24 months follow-up, the patient remains stable, with negative p-ANCA, taking 20 mg prednisone daily. Further magnetic resonance exams have shown findings that were similar to those of previous studies. This case shows how vertigo and transient diplopia may be the first symptoms of neurological complications in patients with CSS. Lupus (2001) 10, 653–655.
Renal crisis in asclerodermic scleroderma—lupus overlap syndrome
Authors: Horn H C , Ottosen P , Junker P
Published: November 2003

A 24-year-old woman with overlappingfeatures of sclerodermia sine scleroderma and systemic lupus erythematosus (SLE) presented with rapidly acceleratinghypertension accompanied by neuropsychological deficits and tonic—clonic seizures. Kidney biopsy showed severe intimal hyperplasia of small renal arteries but no glomerulonephritis. Following treatment with ACE inhibitor, prednisolone and cyclophosphamide complete remission was achieved with minimal brain damage and normal kidney function. Anti-RNA polymerase I, II and III antibodies have remained positive during follow-up for 2 years, suggesting a linkage with the underlying pathogenetic pathway.
Systemic lupus erythematosus and B-cell hematologic neoplasm
Authors: Xu Y , Wiernik P H
Published: November 2003

The association of systemic lupus erythematosus (SLE) and B-cell malignancy is widely reported in the literature. Here we report nine cases of concurrent of SLE or discoid lupus erythematosus (DLE) and lymphoma or plasma cell disorder. A MEDLINE search was done using the keywords, ‘SLE’ and ‘lymphoma’ and the characteristics of all identified cases were summarized and analyzed, along with data from our own cases. Numerous variants of B-cell malignancies were encountered in these patients. B-cell malignancy occurs after the diagnosis and treatment of SLE in most reported cases, although it may precede SLE, or occur synchronously with it. The age at onset of the B-cell neoplasm in SLE patients is similar to that in the general population. Mortality in patients with both diseases is associated with progressive B-cell neoplasm, sepsis secondary to either disease, or both. B-cell malignancy and SLE seem to run independent clinical courses rather than being affected by each other. The use of immunosuppressive drugs is common in patients with SLE diagnosed prior to B-cell lymphoma, arguing that the effect of immunosuppression on the pathogenesis of lymphoma can not be excluded. Three areas worthy of study regarding the probable mechanisms for the occurrence of SLE and B-cell malignancies are discussed. A tumor suppressor gene PTEN may link the two disorders via a defective apoptosis pathway to eliminate hyperactive B and T cells in SLE. The accumulation of clonally expanded hyperactive B-cells that recognize self-antigens in the lymph nodes of SLE may predispose these B-cells to DNA breaks, facilitating tumorigenesis. Lastly, EBV infection, found to have a high prevalence in SLE patients, may serve as a common etiological factor in both disorders.
Longitudinal myelitis associated with systemic lupus erythematosus: clinical features and magnetic resonance imaging of six cases
Authors: Téllez-Zenteno J F , Remes-Troche J M , Negrete-Pulido R O , Dávila-Maldonado L
Published: November 2003

Myelopathy is a rare central nervous system (CNS) complication associated with systemic lupus erythematosus (SLE). Acute transverse myelitis (ATM) is the most frequent form of SLE-related myelopathy. Magnetic resonance imaging (MRI) typically shows increased signal intensity in T2-weighted images and cord swelling. In the present paper, we describe six cases of SLE-related myelopathy with multiple increased signals in the T2-weighted images involving continuous levels of the cervical and thoracic spinal cord, a distinctive feature recently named ‘longitudinal myelitis’. The clinical and laboratory findings are similar to those presented by ATM patients, including paraparesis, sensory level and sphincter disturbances. Four patients had positive antiphospholipid antibodies (aPL) suggesting that this could be a characteristic of longitudinal myelitis. Treatment in all cases included high doses of corticosteroids and immunosuppressive agents (intravenous (i.v.) cyclophosphamide). Anticoagulation therapy was given to one patient and two others received low doses of aspirin. The outcome was mainly unfavorable with slow improvement in only one case, no improvement in two and relapse of the myelopathy in the remaining three. In conclusion, longitudinal myelitis is an unusual form of SLE-related myelopathy, it might be associated with aPL and it has a poor prognosis.
Severe pulmonary hemorrhage as the initial manifestation in systemic lupus erythematosus with active nephritis
Authors: Wu C -Y , Chiou Y -H , Chiu P -C , Hsieh K -S
Published: November 2003

Pulmonary hemorrhage (PH) is an uncommon clinical manifestation of patients with systemic lupus erythematosus (SLE). In this report, we describe a 14-year-old male with PH as the sole clinical manifestation of his SLE. Kidney biopsy was performed and the report revealed lupus nephritis class IVb. He demonstrated a rapid clinical response to the therapy of intravenous pulse methylprednisolone. Awareness of the possibility of PH as a sole clinical presentation of SLE may aid in the diagnosis and early aggressive management of this condition.
Foetal loss, liver necrosis and acute lupus erythematosus in a patient with antiphospholipid antibody syndrome
Authors: Fehr T , Cathomas G , Weber C , Fontana A , Schaffner A
Published: November 2003

The antiphospholipid antibody syndrome (APS) is characterized by arterial or venous thromboses and recurrent foetal loss. It occurs as primary disease, but also in the context of systemic lupus erythematosus (SLE). Whereas primary APS induces a thrombotic microangiopathy without significant inflammatory reaction, secondary APS in SLE is usually associated with vasculitis. Here we report a patient with APS who presented with acute diarrhoea and then developed a HELLP-like syndrome characterized by a spontaneous abortion, multifocal hepatic necroses and thrombocytopenia. Thereafter an acute flare of SLE with arthralgias, pleuritis, skin rash and glomerulitis occurred. Clinical amelioration was only achieved by combining curettage, antic-oagulation and immunosuppression, a treatment taking into account the pathogenesis of HELLPlike disease, APS and SLE. To our knowledge this is the first reported case of APS associated with combined acute manifestations of these three syndromes triggered by a presumable intestinal infection.
Pre-treatment affinity for LJP 394 influences pharmacodynamic response in lupus patients
Authors: Mcneeley P A , Iverson G M , Furie R A , Cash J M , Cronin M E , Katz R S , Weisman M H , Aranow C , Linnik M D
Published: November 2003

Five prospective clinical studies in lupus patients have shown that LJP 394 can reduce circulating anti-dsDNA antibody levels without causing generalized immunosuppression. The compound is currently being evaluated in a phase III clinical trial for the prevention of renal flares in patients with high-affinity antibodies to LJP 394 and a history of lupus nephritis. The current study analyzed the affinity of patient IgG for LJP 394 prior to and following 4 months of treatment with LJP 394 to determine if pretreatment affinity influenced pharmacodynamic response. Patient serum samples from a multicenter, double-blind, placebo-controlled trial were evaluated prior to and following 4 months of weekly, biweekly or monthly treatment with placebo (n=9) or weekly treatment with 10 mg LJP 394 (n=6) or 50 mg LJP 394 (n=4). After treatment there was a dose-dependent reduction in affinity in the 10 mg/week and 50 mg/week groups (P < 0.05 and P < 0.01, respectively), whereas the placebo group was unchanged. This study demonstrates that weekly treatment with LJP 394 produces a dose-dependent reduction in titer-weighted average affinity. These results suggest it may be possible to use an affinity assay to define prospectively patients that are most likely to exhibit the desired pharmacodynamic response to LJP 394.
Enhanced serum prolactin (PRL) in patients with systemic lupus erythematosus: PRL levels are related to the disease activity
Authors: Jacobi A M , Rohde W , Ventz M , Riemekasten G , Burmester G-R , Hiepe F
Published: November 2003

Recent accumulated evidence suggests that prolactin (PRL) is an important immunomodulator and plays a part in the pathogenesis of systemic lupus erythematosus (SLE). The current study assessed the frequency of hyperprolactinaemia in patients with SLE and its association with defined clinical manifestations or serological abnormalities.

PRL levels were analysed in 60 patients with SLE including a follow-up of 20 patients, 18 patients with rheumatic autoimmune diseases other than SLE (AID) and in 47 normal healthy subjects (NHS) using ELISA. Clinical manifestations and disease activity (ECLAM) were recorded. Autoantibodies (anti-dsDNA, anti-CL) were determined by standard techniques.

In all, 28.3% of the patients with SLE had raised serum PRL. Their PRL levels (17.4 15.1 ng =ml, P < 0.0001) and those of patients with AID (13.1 10.3 ng/ml, P < 0.001) were significantly higher compared to NHS (6.3 3.2 ng =ml). Anti-dsDNA (rs=0.3, P=0.04) and anti-CL antibody titres (IgG; rs=0.3, P=0.03) correlated with PRL level. Furthermore, elevated erythrocyte sedimentation rate (ESR), anaemia, decrease in C3, fatigue, fever and renal involvement were associated with hyperprolactinaemia. These results were confirmed by follow-up examinations.

Moderate hyperprolactinaemia is present in a subset of patients with SLE and serum PRL correlates with clinical and serological disease activity.
Pituitary production of prolactin and prolactin-suppressing drugs
Authors: Tansey M J , Schlechte J A
Published: November 2003

Prolactin secretion from the anterior pituitary is mediated via dopaminergic pathways. Any process that alters dopamine production or transport in the central nervous system may lead to hyperprolactinemia. Most cases of hyperprolactinemia are due to prolactin secreting pituitary tumors or to medications which alter dopamine production. Prolactinomas cause amenorrhea, galactorrhea and infertility in women and impotence and neurological deficits in men. Dopamine receptor agonists are the mainstay of therapy for hyperprolactinemia as they rapidly lower serum prolactin and cause tumor shrinkage. In this paper we review the regulation of prolactin secretion, the clinical features and causes of hyperprolactinemia, and the use of dopamine agonists.
Prolactin production by immune cells
Authors: Montgomery D W
Published: November 2003

Prolactin (PRL) is a pituitary hormone and a cytokine that plays an important role in rodent and human immune responses, including autoimmune diseases. However, many cells and tissues other than the pituitary make PRL, including immune cells. Here, we will present the evidence demonstrating PRL synthesis by different subtypes of immune cells from humans, mice and rats, describe the regulation of PRL gene expression in human lymphocytes, and discuss the functions of PRL made by immune cells. Finally, we will present evidence for involvement of immune cell PRL in human autoimmune disease and suggest how it might play a unique immunoregulatory role.
Stimulation of interferon regulatory factor-1 by prolactin
Authors: Yu-Lee Li-yuan
Published: November 2003

Prolactin (PRL), a pituitary peptide hormone, is known to regulate diverse cellular functions including proliferation, differentiation, angiogenesis and protection against apoptosis and inflammation. To understand the mechanism of PRL signaling in T cells, we have cloned both PRL and its receptor (PRL-R), one potent mediator of PRL signaling, Stat5b, and a panel of PRL-inducible immediate early genes from T cells. We are employing these genes as tools with which to understand how PRL regulates the expression of one target gene, the transcription factor interferon regulatory factor-1 (IRF-1), which is a multifunctional immune regulator gene. In investigating regulatory events along the PRL-R/JAK/Stat/IRF-1 signaling pathway, we show that Stat factors can activate as well as inhibit IRF-1 promoter activity and that cross-talk between Stat and NFkB signaling pathways also regulates IRF-1 promoter activity. These findings have much broader implications not only for T lymphocytes but also for other PRL responsive target cells and tissues.
Unmodified and phosphorylated prolactin and gamma delta T cell development and function
Authors: Walker A M
Published: November 2003

This manuscript discusses our studies to date concerning the effects of unmodified prolactin (PRL) and phosphorylated PRL on immune function. Most of the discussion refers to effects of changing the ratio of these two forms in maternal PRL on gd T cell development in rat pups in utero, but limited experiments where adult animals have been directly treated are also discussed. The manuscript begins with some general background on gd T cells and the different forms of PRL and then proceeds to a discussion of experimental findings. Results demonstrate that the ratio of unmodified to phosphorylated PRL during rat pregnancy is crucial to normal epidermal gd T cell development in the pup thymus. Elevation of phosphorylated PRL in the dams, by administration of a recombinant molecular mimic of phosphorylated PRL, produces a defect in epidermal gd T cell seeding and subsequent function in the offspring. In contrast, a functional defect is not seen for uterine gd T cells in the offspring, a finding likely reflective of the continued availability of precursors to these cells after the fetal period. Preliminary results from treatment of the NZB/NZW mouse model of lupus with the two forms of PRL suggest opposing effects of unmodified and phosphorylated PRL on one measure of the disease.
Prolactin in murine systemic lupus erythematosus
Authors: McMurray R W
Published: November 2003

Murine systemic lupus erythematosus (SLE) manifests several autoimmune perturbations that resemble human SLE, including cytokine aberrations, lymphoproliferation, hypergammaglobulinemia, autoantibody formation, and immune complex glomerulonephritis. In multiple studies, elevated serum prolactin concentrations (hyperprolactinemia) stimulated appearance or progression of murine lupus. Autoimmune disease acceleration by prolactin appears to be accentuated by estrogen stimulation of prolactin secretion and independent of immunosuppressive effects of androgens such as testosterone. Conversely, suppression of serum prolactin concentrations by bromocriptine inhibits development of murine SLE. These data clearly support the concept that prolactin is immunostimulatory in autoimmune disease and that the therapeutic goal of lowering serum prolactin concentrations may be beneficial to patients. Further utilization of murine SLE models will facilitate dissection of the actions and interactions of prolactin with estrogen, progesterone and testosterone and lead to a better understanding of hormonal immunomodulation and therapy of autoimmune disease.
Prolactin in human systemic lupus erythematosus
Authors: Jara L J , Vera-Lastra O , Miranda J M , Alcala M , Alvarez-Nemegyci J
Published: November 2003

In the last decade, evidence has accumulated to support the hypothesis that both mild and moderate elevations of serum prolactin (PRL) participate in the clinical expression and pathogenesis of systemic lupus erythematosus (SLE). Hyperprolactinemia (HPRL) has been found in 20–30% of patients with SLE. HPRL seems to be associated with clinical activity of SLE during pregnancy. Although the relationship between HPRL and active SLE in non-pregnant patients is controversial, recent clinical and experimental studies support the potential role of prolactin (PRL) as a promoter of clinical activity and severity of SLE. Mild elevations of serum PRL secondary to microadenoma could trigger the onset of SLE in a subset of patients.

Elevated PRL and interleukin (IL)-6 have been found in the urine of patients with active lupus nephritis and in cerebrospinal fluid (CSF) of patients with active central nervous system (CNS) SLE. PRL may therefore participate in the pathogenesis of lupus nephritis and cerebritis, and the presence of PRL may reflect an abnormal communication between the immune system and the neuroendocrine system in active SLE. Lymphocytes from patients with active SLE produce increased amounts of PRL, and this extrapituitary PRL may participate in aberrant immune processes in SLE. There is exciting new evidence that HPRL in SLE may be explained by stimulation of pituitary PRL secretion by cytokines. In addition, defects in peptidergic modulators and dopamine metabolism have been described in patients with SLE. The interactions between PRL, cytoquines, autoantibodies and organ involvement suggest that PRL participates in local and generalized immune and inflammatory processes and acts as a bridge between the neuroendocrine and immune systems in SLE. Understanding the interactions between these systems in SLE will help us to understand and treat this important autoimmune disease.
Analysis of anti-prolactin autoantibodies in systemic lupus erythematosus
Authors: Blanco-Favela F , Chavez-Rueda K , Leaños-Miranda A
Published: November 2003

Evidence has shown that prolactin is an essential component of an effective immune response. In systemic lupus erythematosus, clinical trials have produced controversial information about the role of PRL. Some results find association between serum PRL levels and disease activity. In contrast, other authors did not find this. Recently, autoantibodies against prolactin in SLE patients have been described. One hundred percent of SLE patients with anti-PRL autoantibodies had hyperprolactinemia (hPRL) and 31.7% of the SLE patients classified with idiopathic hPRL had anti-prolactin antibodies. A similar result was found in 103 pediatric SLE patients. The patients with idiopathic hyperprolactinemia and anti-PRL autoantibodies had less clinical and serological lupus activity than the SLE patients with idiopathic hyperprolactinemia, but without anti-PRL autoantibodies.

This evidence suggests that anti-PRL autoantibodies or the complex with any other molecule, like macroprolactinemia (big-big PRL) could have attenuated biological activity and this could explain why some clinical studies did not find any association between serum PRL levels and disease activity in SLE patients. However, studies in vitro have shown normal or elevated biological activity in Nb2 cell lines using PRL from serum with anti-PRL autoantibodies from patients with or without autoimmune diseases.

Several conclusions could be drawn. One is that while a set of hyperprolactinemic SLE patients display autoantibodies against PRL, it is not clear what role these autoantibodies play in the whole system. However, until now, we knew that the patients with antibodies to PRL lacked the clinical symptoms of hyperprolactinemia such as menstrual disturbances and/or galactorrhea and show less clinical and serological lupus activity.
Bromocriptine treatment of systemic lupus erythematosus
Authors: Walker S E
Published: November 2003

Prolactin, a peptide hormone, acts as a cytokine. It has been hypothesized that bromocriptine, a dopamine analog that suppresses pituitary secretion of prolactin, suppresses circulating prolactin and, through this mechanism, has the potential to suppress autoimmune disease. This rationale has been applied to the treatment of systemic lupus erythematosus (SLE), a prototype autoimmune illness that occurs spontaneously in animal models such as the F1 hybrid NZB NZW mouse, and in humans. Treatment with bromocriptine was effective in treating some induced and spontaneous autoimmune disease in experimental models. Bromocriptine did slow the course of SLE in NZB NZW mice when treatment was started before the appearance of clinical disease. In addition, bromocriptine was effective in treating established disease in this model. In three separate clinical trials, bromocriptine showed evidence that it had a therapeutic effect in treating human lupus. Bromocriptine is currently considered an unproven therapy for SLE. Its use is entirely experimental. The fact that bromocriptine was effective in treating NZB-NZW mice, the beneficial therapeutic effects in human trials, and the low toxicity of the drug form a solid rationale for undertaking further therapeutic trials.
Can the weighted criteria improve our ability to capture a larger number of lupus patients into observational and interventional studies? A comparison with the American College of Rheumatology Criteria
Authors: Sanchez M L , Alarcón G S , McGwin G , Fessler B J , Kimberly R P
Published: November 2003

The objective of this study was to determine if the modified weighted criteria have better psychometric properties than the ACR criteria for the classification of patients with systemic lupus erythematosus (SLE). A computerized list of all patients with the diagnosis of SLE (ICD9 code 710.0) attending an outpatient rheumatology clinic was generated and their medical records reviewed. The attending rheumatologists validated the diagnosis of SLE; this assessment was used as the gold standard to compute the sensitivity, specificity and accuracy of both the American College of Rheumatology (ACR) and the modified weighted criteria. A total of 363 patients were identified and included in the study. Ninety percent were women; the mean age was 44.0 (14.4) years, and 51% were Caucasians. The modified weighted criteria had a sensitivity of 90.3% and specificity of 60.4%. The ACR criteria had a sensitivity of 86.5% and specificity of 71.9%. Both methods had comparable positive and negativepredictivevalues as well as similar overall accuracy. The modified weighted criteria allow the identification of more lupus patients for clinical or interventional studies; some of these patients, however, may not have SLE according to experienced rheumatologists.
Effects of liposteroid on the hemophagocytic syndrome in systemic lupus erythematosus
Authors: Funauchi M , Ohno M , Yamagata T , Nozaki Y , Kinoshita K , Kanamaru A
Published: November 2003

Hemophagocytic syndrome (HPS) is a life-threatening disorder characterized by pancytopenia and activation of macrophages. Recently, corticosteroid incorporated in lipid microspheres (liposteroid) has been reported to be taken up by macrophages and to suppress their functions. Here we present a case of systemic lupus erythematosus complicated by HPS that was successfully treated with liposteroid in addition to an oral corticosteroidand intravenoushigh-dose cyclophosphamidetherapy. The serum levels of tumor necrosis factor-a and ferritin that have been reported to be associated with activity of macrophages remarkably reduced after liposteroid administration. This case suggests that liposteroid is useful for the treatment of HPS.
Reversal of brain dysfunction with UV-A1 irradiation in a patient with systemic lupus
Authors: Menon Y , McCarthy K , McGrath H
Published: November 2003

Low-dose ultraviolet A-1 (UV-A1; 340-400nm) bodily irradiation significantly reduces clinical manifestations of systemic lupus erythematosus (SLE). As neuropsychiatric-likesymptoms respond prominently, a single patient was selected to undergo positron emission tomography (PET) before and after therapy to determine the effects of the therapy on the brain. The functional changes in 18F-deoxyglucose uptake as determined by PET imaging in this SLE patient indicated that improvement in brain function paralleled the reversal of cognitive deficits noted after the administration 160kJ of bodily UV-A1 irradiationadministeredthree times a week. Also of interest is that the UV-A1 irradiation, for the first time, ameliorated discoid lupus rashes, presumably due to a systemic action, as the lesions were for the first time covered during therapy.
Outcome of primary antiphospholipid syndrome in childhood
Authors: Gattorno M , Falcini F , Ravelli A , Zulian F , Buoncompagni A , Martini G , Resti M , Picco P , Martini A
Published: November 2003

The objective of this paper is to investigate the long-term outcome of primary antiphospholipid syndrome (APS) in the paediatric age. The features of unselected patients with primary APS who had disease onset before the age of 16 years were retrospectivelyanalysed in three Italian referral centres. Clinical and laboratory manifestationswere assessed to establish whether, at the end of follow-up, the final diagnosis was still primary APS or whether they had developed definite SLE or lupus-like syndrome.Fourteen patients, nine boys and five girls, who had the presentingclinical manifestationof APS between three and 13 years of age (median nine years) and were followed for two to 16 years (median six years). Six patients presented with deep vein thrombosis, five with cerebral stroke, two with peripheral artery occlusion and one with myocardial infarction. During follow-up, four patients had one or more recurrences of vascular thrombosis. At last observation, 10 patients could still be classified as having primary APS, two had developed SLE, one lupus-like syndrome and one Hodgkin’s lymphoma. In conclusion; our analysis suggests that some children who present with the features of primary APS may progress to develop SLE or lupus-like syndrome.
EBER-1 positive diffuse large cell lymphoma presenting as lupus nephritis
Authors: Lin Ming-Hsien , Huang Jeng-Jong , Chen Tsai-Yun , Chen Fen-Fen , Chang Kong-Chao , Liu Ming-Fei , Huang Wen-Tsung , Su Wu-Chou , Tsao Chao-Jung
Published: November 2003

Approximately one-third of membranous glomerulonephritis (MGN) cases in adults are associated with systemic diseases, including systemic lupus erythematosus(SLE) or malignancies. Malignancy-associated glomerulonephritis is rarely found in non-Hodgkin’s lymphoma (NHL). Epstein-Barr virus (EBV) has been postulated to contribute to the pathogenesis of both SLE and NHL. We described a 37-year-oldwoman with nephrotic syndrome who presented with clinical features of SLE and renal-biopsy revealed lupus MGN. The patient also suffered from concomitant progressive lymphadenopathyand NHL (diffuse large B-cell type) was demonstratedby neck lymph node biopsy. Serologic studies demonstratedEBV infection and specific EBV antigenswere present on lymph node and metastatic sites. We offer a discussion regarding the complex relationships between SLE, NHL, MGN and EBV.
Refractory immune thrombocytopenia in systemic lupus erythematosus: response to mycophenolate mofetil
Authors: Vasoo S , Thumboo J , Fong K-Y
Published: November 2003

Immune thrombocytopenia(IT) is a common manifestation of systemic lupus erythematosus (SLE). Although severe IT (< 20 ×109/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-basedguidelinesfor managing this condition.Conventionally, high-doseglucocorticoidsare consideredfirst-line therapy. Adjunctivemedical 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.
Mycophenolate mofetil as a treatment for autoimmune haemolytic anaemia in patients with systemic lupus erythematosus and antiphospholipid syndrome
Authors: Alba P , Karim M Y , Hunt B J
Published: November 2003

Unresponsive autoimmune haemolytic anaemia (AIHA) may require therapy with second-line drugs. There is no consensusthat any one of these agents is more effectivethan another. Mycophenolatemofetil (MMF) is an immunosuppressivedrug proven to be effectivein reducing renal allograftrejectionas well as being used in autoimmune diseases including systemic lupus erythematosus (SLE). We describe its use in two patients who were treated with MMF for AIHA in the context of underlying SLE and antiphospholipid syndrome (APS). The patients showed a good response to treatment with MMF, suggesting a possible role in the treatment of AIHA.
Increased expression of insulin-like growth factors in progressive glomerulonephritis of the MRL lpr mouse
Authors: Mohammed J A , Mok A YP , Parbtani A , Matsell D G
Published: November 2003

Glomerulonephritisis an important complication of systemic lupus erythematosus (SLE). The tissue distribution and exact role of the insulin-like growth factors (IGFs) in the development of lupus nephritis in the MRL/lpr mouse model have not been established. The present study was undertaken to evaluate the changes over time in mRNA and peptide expression of IGF-I and IGFBP-2 in the MRL/lpr mouse. Using in situ hybridizationand immunocytochemistrytechniques, the expressionof IGF-I and IGFBP-2 in MRL/lpr mouse was examined and compared to their congenic normal MRL- mouse counterparts from nine to 24 weeks of age. In the MRL- and MRL/lpr mouse kidneys, IGF-I and IGFBP-2 mRNA expression was limited to the cortical and medullary collecting ducts, while their immunoreactivity (IR) was localized to the cortical and medullary collecting ducts, loop of Henle, glomeruli and proximal tubules. Over time, and with progression of disease, the MRL/lpr mice displayed a significant increase in IGF-I IR and a modest increase in IGFBP-2 IR within the outer cortical glomeruli, which was associated with a significant increase in glomerulosclerosis and glomerular cell proliferation and with a significant decrease in renal function. In conclusion, this overexpression of IGF-I and IGFBP-2 within the glomeruli of the MRL/lpr mouse kidney supports their potential role in the alterations in renal function and morphology that accompany lupus nephritis.
Apoptosis of CD34 cells after incubation with sera of leukopenic patients with systemic lupus erythematosus
Authors: Tiefenthaler M , Bacher N , Linert H , Mühlmann O , Hofer S , Sepp N , Amberger A , Geisen F , Obermoser G , Konwalinka G
Published: November 2003

Leukopenia and anaemia are observed in about a fifth of all patients with systemic lupus erythematosus (SLE) and may be due either to the destruction of blood cells or their decreased production. The former may be humoral or cell-mediatedor result from apoptosis of peripheral blood cells. Several observations suggest the occurrence of the latter: reduced in vitro proliferation of pluripotentbone marrow progenitorsfrom the bone marrow aspirates of SLE patients, reduced counts of CD34 cells in bone marrow aspiratesin SLE patients, apoptosisof lymphopoieticprogenitorsand apoptosis of bone marrow cells. The aim of our study was to investigatewhether humoral factors may induce suppression of haematopoiesis by increased apoptosis of CD34 cells. For this purpose, we incubated allogeneic CD34 -enriched cells with sera of 18 leukopenic SLE patients. Apoptosis was induced by four of 18 sera. This effect was independentof complement-inhibitionand FAS-blockade. Although reduced proliferationof autologouspluripotentbone marrow progenitorshas been attributed to an IgG serum inhibitor, removal of IgG from these four proapoptoticsera had no effect on apoptosis of allogeneic CD34 cells. The proapoptotic effect was associated with high titres of anti-dsDNA antibodies and low haemoglobin concentrations, but not with high titres of antinuclear antibodies, TNF-a and IFN-a of the sera tested.
Telomerase activity and telomere length of peripheral blood mononuclear cells in SLE patients
Authors: Kurosaka Daitaro , Yasuda Jun , Yoshida Ken , Yokoyama Toru , Ozawa Yoshinori , Obayashi Yutaka , Kingetsu Isamu , Saito Saburo , Yamada Akio
Published: November 2003

We evaluated the clinical significance of the telomerase activity and telomere length of peripheral blood mononuclearcells (PBMC) in systemic lupus erythematosus (SLE). PBMC were isolated from 55 patients with SLE and the telomerase activity was measured by TRAP assay. The telomere length of PBMC was also measured in 30 of these subjects. As a control group, 45 healthy adults with no particular clinical history were studied. The results were compared with clinical data. In patients with active SLE, the telomerase activity of PBMC was significantly increased compared with the control group. In patients with inactive SLE, the PBMC telomerase activity was not different compared with the controls in their 20s, 30s and 40s, but it was significantly increased compared with the controls in their 50s. In SLE patients, the telomerase activity of PBMC was significantly correlatedwith modified SLEDAI. The telomere length of PBMC in younger SLE patients tended to be shorter than that in the controls, but no difference was observed in older patients. The correlation coefficient between the telomerase activity and telomere length of PBMC in SLE patients was not significant. Abnormalities in the telomeraseactivity and telomere length observedin SLE patients are consideredto be important findings for evaluation of the pathology of SLE.
Therapy with statins in patients with refractory rheumatic diseases: a preliminary study
Authors: Abud-Mendoza C , de la Fuente H , Cuevas-Orta E , Baranda L , Cruz-Rizo J , González-Amaro R
Published: November 2003

We have explored the therapeuticpotentialof statins in patients with differentinflammatory rheumatic diseases refractory to conventional therapy. We found that simvastatin (80mg o.d. for eight days) induced a rapid and significant reduction in proteinuria levels in three systemic lupus erythematosus (SLE) patients. A similar kind of therapy had a marked beneficial effect in a patient with Wegener’s granulomatosis and a patient with erythema nodosum. On the other hand, five patients with rheumatoid arthritis (RA) who received atorvastatin for eight days (20mg/day) showed reduction in C-reactive protein levels and a clinical improvement that was classified as an ACR20 response. Prior to the administrationof statins, all these patients had receivedaggressiveconventionaltherapy with no satisfactory response. A significant reduction in spontaneous apoptosis of peripheral blood lymphocytes and expression of CD69 and HLA-DR was observed in SLE patients after simvastatin therapy. These results prompted us to perform a pilot short-time comparative (simvastatin versus chloroquine) open clinical trial in 15 patients with RA who were receiving methotrexate as a single disease modifying antirheumatic drug with no satisfactory response. Most patients (9/10) who received simvastatin (40mg/day) showed an ACR50 or better response after eight weeks, whereas such a response was not observed in any patient (0/5) treated with chloroquine. Our preliminary results indicate that statins may be an important therapeutic tool for the treatment of inflammatory rheumatic diseases.
Severity of systemic lupus erythematosus with diffuse proliferative glomerulonephritis and the ineffectiveness of standard pulse intravenous cyclophosphamide therapy in Jamaican patients
Authors: Williams W , Bhagwandass A , Sargeant L A , Shah D
Published: November 2003

The majority of patients seen at the renal clinic of the University Hospital of the West Indies (UHWI) are of African descent. The case notes of patients with systemic lupus erythematosus(SLE) with class 4 nephritis and who were given standard pulse intravenous cyclophosphamide therapy during the period 1990-2000 were retrospectively reviewed. Primary outcomes were doubling of serum creatinine and development of end stage renal disease (ESRD). Secondary outcomes were return of proteinuriato normal and renal remission. A total of 117 patients had a renal biopsy for SLE nephritis at the UHWI between 1990 and 2000. Of the patients, 34 (29%) had diffuse proliferative glomerulonephritis(WHO class 4), of which 29 were reviewed. Twenty-two patients of 24 in whom it was measured (92%) had significant proteinuria at presentation. The 24-hour proteinuria was measured at final review in 16 patients and in 10 patients it went into complete remission. At the beginning of therapy, 24 patients (83%) had renal impairment. Of the 18 who had final creatinine values, the renal function returned to normal in eight patients (44%) and an additional six patients showed a significant improvement in renal function at final review. Six patients developed end stage renal disease (ESRD). The risk (95% confidence interval)of developingESRD at one year was 16.2% (CI, 6.4-37.6) and at two years was 23.2% (CI, 10.0-48.5). There were three deaths, two from sepsis and one from heart failure. The one-year mortality (95% CI) was 8% (CI, 2.0-28.5), the two-year mortality was 15.6% (CI, 4.9-43.5) and the five-year mortality was also 15.6% (CI, 4.9-43.5). Intravenous pulse cyclophosphamide for Jamaican patients with SLE and diffuse proliferative glomerulonephritisis an ineffective form of treatment.
The two hit hypothesis in the antiphospholipid syndrome: acute ischaemic heart involvement after valvular replacement despite anticoagulation in a patient with secondary APS
Authors: Bordin G , Boldorini R , Meroni P L
Published: November 2003

A patient with the antiphospholipid syndrome (APS), in whom a nonfatal myocardial infarction ensued after valvular heart replacement despite anticoagulation, is described. The report further stresses the role of concomitant risk co-factors in inducing thrombotic events and points out that cardiosurgery might represent a potential major risk for myocardial ischaemic damage in APS.
The molecular basis of antiphospholipid syndrome
Authors: Gharavi A E , Wilson W , Pierangeli S
Published: November 2003

We herein review evidence that the phospholipid-binding protein β2 glycoprotein-1 (β2 GPI) is a causativeautoantigenin APS. Recent work suggeststhat the molecular regions in β2 GPI that facilitate autoimmunization are those that promote binding to negatively charged phospholipids by means of strong positive (anionic) charge and hydrophobicity. Although many common infections can cause antiphospholipidantibodies to be produced in humans, such postinfectious aPL are rarely associated with thromboses or pregnancy morbidity, the central features of antiphospholipid syndrome (APS). We propose that the causes of APS include those infectious agents that mimic the above molecular domains in β2 GPI. In peoplewho are susceptibleto APS, tolerance to self-β2 GPI and phospholipidsis likely to be broken by foreign bacterial or viral proteins that contain such β2 GPI-like epitopes.
Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy
Authors: Weide R , Heymanns J , Pandorf A , Köppler H
Published: November 2003

Systemic lupus erythematosus(SLE) is a chronic, inflammatory autoimmune disease that may involve multiple organ systems. Treatment consists of immunosuppression, cytotoxic treatment, plasmapheresis and immunoglobuline therapy. Treatment of patients refractory to standard treatment approaches is difficult and results are poor. We describe a 39-year old patient with SLE sufferingfrom grand mal epilepsy due to cerebralvasculopathywith positivelupus anticoagulant, who was refractory to standard treatment modalities. The patient was treated with the anti-CD20 monoclonal antibody rituximab (375 mg/m2 ×4, repeated at weekly intervals). Rituximab applications were delivered in October 2000, March 2001 and October 2001. Since March 2002 she has received maintenance therapy with rituximab 375 mg/m2 every three months. A second female with refractory SLE was treated successfully in April 2002 and receives maintenance therapy every three months. Both patients responded well to rituximab therapy. The first patient showed a major improvement of her clinical condition, and 30 months after the beginning of the rituximab therapy she is free of any symptoms. inflammation parameters, ANA and lupus anticoagulantdeclined significantly after the treatment. The clinical conditionof the second patient improved dramatically, all inflammation parameters normalized and her circulating immunocomplexes disappeared. In conclusion, rituximab maintenance treatment may be a new effective therapy in SLE.
Familial autoimmunity as a risk factor for systemic lupus erythematosus and vice versa: a case-control study
Authors: Priori R , Medda E , Conti F , Cassara E AM , Danieli M G , Gerli R , Giacomelli R , Franceschini F , Manfredi A , Pietrogrande M , Stazi M A , Valesini G
Published: November 2003

The objective of this multicentric case-control study was to investigate if a history of autoimmune disease (AD) in first-degree relatives (FDR) is a risk factor for systemic lupus erythematosus (SLE) and to evaluate the risk of AD among FDR of SLE patients. Cases were Italian SLE patients consecutively enrolled. Controls were orthopaedic inpatients without any autoimmune diseases.The strength of the association between family history of AD and SLE was measured as an odds ratio (OR) calculated from the coefficient of an unconditional regression model. To calculate the risk of AD among FDR of SLE patients, the extended generalized estimating equation technique was used. In total, 154 SLE cases and 140 controls were enrolled. A family history of AD was reported by 22.7% of SLE patients and by 5.7% of the controls. The risk of SLE increased with the number of FDR with AD (one FDR affected, OR 4.1; two or more, OR 11.3). The probability of having AD was higher among FDR of SLE cases in comparison to FDR of controls (RR 4.6; 95%CI 1.9-11.1). A female SLE patient conferred an increased risk of AD to her FDR; this risk is doubled in females (OR 10.3; 95% CI 3.1-34.4).
Thromboembolism in paediatric lupus patients
Authors: Levy D M , Massicotte M P , Harvey E , Hebert D , Silverman E D
Published: November 2003

Paediatric patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPL), specifically lupus anticoagulants(LAC) are at high risk of developingthromboembolicevents (TE). Our objectiveswere to determine the prevalenceof TE in paediatricSLE patientswith LAC and to determine if anticoagulation was effective to decrease morbidity, and prevent recurrent TE. We reviewed data on 149 paediatric SLE patients treated over 10 years. In all, 24 patients (16%) were LAC positive, and 21 TE occurred in 13 of these LAC positive patients (54% incidence of TE in LAC positive patients). The events were cerebral venous thrombosis (9), arterial stroke (3), deep venous thrombosis (4), pulmonary embolism (2), other venous event (1) and other arterial events (2). The median duration between SLE diagnosis and first TE was 15.2 months (range 0-62), and the median age at first TE was 15.1 years (range11.4-18.4). Long-termanticoagulationwas prescribed, and eight patients (62%) were transferred to adult care on lifelong oral warfarin; four (31%) remain under our care on lifelong warfarin, and one patient died of causes unrelated to her TE. No patient has been identified with deficiencies of protein C, protein S or antithrombinIII. One patient is heterozygousfor Factor V Leiden, and one is heterozygous for both the Prothrombin 20210A mutation and the MTHFR (methylene tetrahydrofolate reductase) mutation. Four patients had recurrent TE (31%), and three were not anticoagulated at the time of their second event. One patient had two recurrences on therapeuticanticoagulation.Thromboembolic events are prevalent in the LAC positive paediatric SLE population, and consideration for lifelong anticoagulation must occur after an initial TE.
Assessment of strategies for identifying diagnosed cases of systemic lupus erythematosus through self-report
Authors: McAlindon T E , Formica M , Palmer J R , Lafyatis R , Rosenberg L
Published: November 2003

The objective of this work was to assess the optimal way to identify potential systemic lupus erythematosus (SLE) cases in large epidemiologic studies through self-reported information about diagnosis of SLE, symptoms and medications, and to investigate the utility of a criteria checklist sent directly to participants’physicians.We used data collected in 1997 from 53322 participantsin a study of African-American women, the Black Women’s Health Study, including a lupus screening questionnaire(LSQ) and questionsabout SLE diagnosisand medications.We confirmed self-reported SLE through medical records and criteria checklists sent to participants’physicians.Among those for whom we received medical records and/or criteria checklists, we compared the predictive value and proportion of missed cases of several algorithms using combinations of self-reported SLE diagnosis, LSQ score and medication use to self-reported SLE diagnosis alone. We obtained a physician checklist or medical chart for 251 individuals who reported SLE, of whom 212 (84%) fulfilled ACR criteria for definite or probable SLE, or had clinical lupus (SLE diagnosis recorded in medical charts plus appropriatemedication use). The use of LSQ score or medication use in addition to self-report of SLE tended to decrease the false positiverate but also to reduce the proportionof true cases identified. Checklists of ACR criteria completed by subjects’ physicians documented more criteria than medical records. In conclusion, among participants who consented to medical record review, SLE prediction algorithms using questions about lupus symptoms and medications offered slightly higher predictive value for detecting cases than self-reporteddiagnosis alone, but at the cost of case detection.SLE case confirmation strategies can be complemented by the use of criteria checklists sent directly to participants’ physicians.