bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychiatric and psychosocial disorders in patients with systemic lupus erythematosus: a longitudinal study of active and inactive stages of the disease
Authors: Seguí J , Ramos-Casals M , García-Carrasco M , de Flores T , Cervera R , Valdeés M , Font J , Ingelmo M
Published: November 2003

The objective was to analyze psychiatric disorders and psychosocial dysfunction in patients with systemic lupus erythematosus (SLE), studied longitudinally during active and subsequent inactive stage of their disease.

During a 6 month period of study, we selected 20 consecutive patients with SLE who presented with a SLE flare. All patients fulfilled the 1982 revised criteria of the American College of Rheumatology for the classification of SLE. When patients entered the study, we performed psychiatric (CIS, RDC, STAI, HD, BDI, GHQ and MMS) psychosocial (GAS and VAS-P) scores assessment. One year later, we repeated the psychiatric and psychosocial assessment when patients showed inactive disease.

The 20 patients evaluated were women, with a mean age of 34 y (SE 14.4, range 20-57). According to CIS evaluation, we diagnosed 8 (40%) psychiatric cases in the acute episode of SLE. The RDC diagnosis showed generalized anxiety in 5 patients, panic disorders in 2 patients and generalized anxiety plus depressive symptoms in one patient. One year later, when patients did not show disease activity, we diagnosed 2 (10%) psychiatric cases (P < 0.05). When SLE patients were clinically inactive, they showed lower levels of psychological distress (GHQ scale, 1.8 vs 5.6, P < 0.001), with a lower grade of anxiety measured by both HA (3.2 vs 8.2, P < 0.01) and STAI-S (7.95 vs 20.90, P < 0.001) scales. We also found a lower score in pain perception (VAS-P) (2.80 vs 4.25, P < 0.01) and higher occupational activity (VAS-P) (83.9 vs 66.2, P < 0.01) and general functioning (GAS) (93.75 vs 83.50, P < 0.05) during the inactive stage. No significant differences were found when we compared cognitive impairment, grade of depression and physical disability between inactive and active stages.

We conclude that in SLE patients, psychiatric and psychosocial disorders during acute episodes are usually mild and seem to be related to the psychological impact of disease activity on patients. This type of psychiatric pathology is similar to that which would be expected in other groups coping with a stressful event, indicating that our patients did not react in a way specifically determined by their systemic disease.
Increased serum soluble CD14, ICAM-1 and E-selectin correlate with disease activity and prognosis in systemic lupus erythematosus
Authors: Egerer K , Feist E , Rohr U , Pruss A , Burmester G-R , Dörner T
Published: November 2003

To improve monitoring of immunological and disease activity, we determined soluble markers of activity of the monocyte/macrophage system (sCD14) and the vascular endothelium (sE-selectin, sICAM-1) in patients with systemic lupus erythematosus (SLE) and primary Sjögren' syndrome (pSS) in comparison to patients with infections or sepsis.

Concentrations of sCD14, sICAM-1 and sE-selectin (soluble CD14, ICAM-1 and E-selectin, respectively) were measured in serum samples from patients with SLE and pSS, patients with sepsis, different infectious diseases and healthy controls using ELISA systems.

Elevated levels of sE-selectin and sICAM-1 were detected in patients with SLE as well as sepsis, in contrast to patients with a localized infection (SLE and sepsis, respectively, versus infection P < 0.001; Kruskal–Wallis test). Levels of sCD14 were persistently elevated in sera from patients with SLE, whereas these values decreased rapidly after effective therapy in patients with sepsis or infection. A continuous elevation of all of these three parameters was associated with a fatal outcome in patients with sepsis as well as in patients with SLE.

Combined elevation of sCD14, sICAM-1 and sE-selectin correlates with the prognosis in patients with active SLE and indicates a remarkable immune activation involving the monocyte/macrophage system and the endothelium comparable to an activation found only in patients with sepsis.
Antibodies to human myeloperoxidase in glomerular immune deposits of systemic lupus erythematosus
Authors: Mannik M , Merrill C E , Wener M H
Published: November 2003

Antibodies to human myeloperoxidase and cathepsin G have been detected in the serum of some patients with systemic lupus erythematosus. Therefore, the presence of antibodies to human myeloperoxidase and cathepsin G was examined in glomerular immune deposits. Glomerular basement membrane fragments were prepared from renal tissues obtained at autopsy from 19 patients with systemic lupus erythematosus. IgG was extracted from the glomerular basement membrane fragments and tested with sensitive immunoassays for antibodies to myeloperoxidase and cathepsin G. Antibodies to cathepsin G were not detected in the extracts but antibodies to human myeloperoxidase were found in extracts of one specimen. In the extract with 6M guanidine hydrochloride these antibodies were enriched 103-fold, compared to the initial supernatant of glomeruli, which served as a serum surrogate. The recovered antibodies to myeloperoxidase accounted for 12% of the recovered IgG. These findings add autoantibodies to human myeloperoxidase to the list of antibodies that have been shown to be present in glomerular immune deposits of patients with lupus glomerulonephritis.
Erythema nodosum associated with antiphospholipid antibodies: a report of three cases
Authors: Nekhlyudov L , Gradzka M , Conti-Kelly A M , Greco T P
Published: November 2003

Erythema nodosum is a dermatologic condition characterized by painful, erythematous nodules on the anterior surfaces of the lower extremities. Its association with a variety of conditions has been previously described. We present three cases of erythema nodosum in patients with elevated anticardiolipin antibodies. In one patient, a temporal relationship was seen in the simultaneous detection of antibodies and skin lesions. We propose an association between erythema nodosum and the antiphospholipid antibody syndrome (APS).
Lupus patients in an emergency unit. Causes of consultation, hospitalization and outcome. A cohort study
Authors: Rojas-Serrano J , Cardiel M H
Published: November 2003

The objectives were to determine causes of consultation, hospitalization and outcome in a cohort of lupus patients in an emergency unit.

Patients with systemic lupus erythematosus (SLE) who visited the emergency department for consultation from 1 September 1996 to 17 May 1997 were included in the study. They were evaluated during the visit by looking at 100 variables such as demographic, socioeconomic, clinical, therapeutical, behavioral, (compliance), emotional (Beck depression inventory), disease activity, (Mex-SLEDAI), disease severity (Lupus SDI), chronic damage (SLICC-ACR), and physician' and patient' global assessments of severity. All causes of consultation, hospitalization and outcome were registered. Descriptive statistics, univariate analysis and multiple logistic regression were used for analysis. Significance was set at the 0.05 level.

180 patients were included. 164 were female, mean age 31.7=11.39 y, mean Mex SLEDAI score 3.8, mean SLICC-ACR 1.3. Fever, poliarthralgia and abdominal pain were the main causes of consultation with 26, 25 and 18 cases each. 49 patients were hospitalized and these were statistically different than non-hospitalized patients in level of formal education (10.2 vs 11.8, P ‘ 0.03); compliance (7.6 vs 9, P ‘ 0.0001); malar rash (57% vs 82%, OR, 95% CI ‘ 0.28, 0.13–0.62, P ‘ 0.0008), chloroquine daily dose intake (45 vs 77 mg, P ‘ 0.04); disease severity in physician' global assessments (5.6 vs 2.1, P ‘ 0.0001) and Beck depression inventory (21 vs 16, P ‘ 0.01). Multiple logistic regression identified physician' global assessment, fewer ACR criteria and higher SLICC-ACR scores as the main variables associated with hospitalization. Five patients died; two with community acquired pneumonia, one with pancreatitis, multiple thromboses, and sepsis, one with pulmonary hemorrhage; and one with pulmonary thromboembolism.

In conclusion, poor compliance, low level of formal education, severity, depression, lower ACR criteria and higher SLICC-ACR scores were important variables identified with hospitalization. Chloroquine use seemed to have a protective effect. Causes of death were related to infections and antiphospholipid syndrome.
Red ear(s) syndrome associated with child neuropsychiatric systemic lupus erythematosus
Authors: Lee H-S , Bae S-C , Uhm W-S , Jun J-B , Lee I-H , Kim S Y
Published: November 2003

This case illustrates that a child having severe neuropsychiatric systemic lupus erythematosus (NPSLE) with seizure and cerebral vascular disease showed excellent clinical outcome in response to intravenous methylprednisolone and cyclophosphamide pulse, and presented unexplained red ears phenomenon.
Nocardia infection of a joint prosthesis complicating systemic lupus erythematosus
Authors: Arnal C , Man H , Delisle F , M'Bappe P , Cocheton J-J
Published: November 2003

The authors report the case of a 43-year-old woman suffering from severe systemic lupus erythematosus treated with long-term prednisone, who developed Nocardia nova infection on a hip prosthesis. Sepsis occurred about two years after an episode of pulmonary nocardiosis with the same Nocardia species, that was successfully treated by 12 months of antibiotics. A good outcome of the joint infection was observed in response to antibiotics and removal of the prosthesis.

Nocardiosis is a rare infection, acting as an opportunisticinfection, facilitated in the present case by systemic lupus erythematosus and chronic corticosteroid therapy. Nocardia infections mainly affect the lungs, skin and central nervous system; these last two sites are mostly due to haematogenous spread, a frequent event. Treatment is based on antibiotics, usually continued for 3 ‐ 12 months, especially because of the risk of relapse. The imipenem ‐ amikacin combination appears to be more effective than trimethoprim ‐ sulfamethoxazole. To our knowledge, this is the first case report of Nocardia nova joint prosthesis infection also presenting as late septic spread of pulmonary nocardiosis, complicating corticosteroid-treated systemic lupus erythematosus.
Cyclosporine for lupus membranous nephritis:experience with ten patients and review of the literature
Authors: Hallegua D , Wallace D J , Metzger A L , Rinaldi R Z , Klinenberg J R
Published: November 2003

Objectives: The treatment of lupus membranous nephritis (LMN), a lupus subset that carries a high morbidity, is unsatisfactory. We report our experience in treating LMN with the immunosuppressive drug cyclosporine (CYS).

Methods: We treated 10 patients with systemic lupus erythematosus fulfilling ACR criteria with CYS for at least 12 months and followed renal function, serologic activity and SLEDAI scores. Patient characteristics:8 females, 2 males, 50% Caucasian, mean age 37.3 y (range 22–48), disease duration 108.7 months (range 16–216), nephritis duration 35.5 months (range 12–59), date of biopsy to date of starting treatment 10.7 months (range 0–90). The patients were started on CYS with a mean dose of 3.8 mg/kg (range 2.2–6) and followed for a mean duration of 24.8 months (range 12–59). A Medline search identified all patients with lupus who were given CYS or had LMN in articles from 1966–1999.

Results: Proteinuria improved from a baseline mean of 5588 mg/24 h (range 2712–11 055) to 1404 mg/24 h (range < 150–2652). Serum albumin increased from a baseline mean of 2.8 g=100 ml (range 1.31–3.8) to a mean of 3.9 g/100 ml (range 3–4.5) at last follow-up. There was no significant change in lupus activity as measured by SLEDAI. Nephrotoxicity was common as evidenced by an increase in serum creatinine but it returned to baseline with adjustment of the dose of CYS (20% decrease in the dose of CYS for a 20% increase in serum creatinine). More antihypertensive medications were required to control the blood pressure in these ten patients at the end of the study compared to the onset (total number = 13 versus 6).

Conclusion: Proteinuria and serum albumin improved in all patients on CYS. A literature review is consistent with this. Controlled studies of the use of CYS for membranous lupus nephritis would be useful.
Acute optic neuropathy and transverse myelopathy in patients with antiphospholipid antibody syndrome: Favorable outcome after treatment with anticoagulants and glucocorticoids
Authors: Aziz A , Conway M D , Robertson H J , Espinoza L R , Wilson W A
Published: November 2003

We describe two patients with established antiphospholipidsyndrome, who during periods of subtheraputic anticoagulation, developed acute optic neuropathy and transverse myelopathy. Treatment with optimal anticoagulation and high dose glucocorticoids was followed by resolution of the neurologic deficits.
Autoimmune antiphospholipid antibodies and cryoglobulinemia
Authors: Hanly J G , Smith S A
Published: November 2003

In addition to their role in the thrombotic manifestations of the antiphospholipid syndrome (APS), autoimmune antiphospholipid (aPL) antibodies may also be responsible for direct injury to the blood vessel wall, although the mechanism is unclear. Cryoglobulinemia has been reported infrequently in patients with APS and is one potential means of blood vessel injury. The aim of the present study was to determine if autoimmune aPL antibodies and their target antigens contribute to the formation of cryoprecipitates. Cryoglobulins were identified and isolated from 5 of 8 patients with autoimmune aPL antibodies. Using identical concentrations of immunoglobulins isolated from matched sera and washed cryoprecipitates there was a significant enrichment (at least 100%) of aCL antibodies in the cryoprecipitates from 4 of 5 patients. This involved IgG, IgM and IgA isotypes with specificity for both b2-glycoprotein I (GPI) and prothrombin (PT). The target antigens were detected in cryoprecipitates from all 5 aPL positive patients and in cryoprecipitates from 3 controls. These results suggest that anti-b2-GPI and anti-PT antibodies in association with their target antigens are integrally involved in the formation of cryoprecipitates in patients with autoimmune aPL antibodies and provide insight into a potential mechanism for blood vessel injury.
Altered bone marrow cell sensitivity in the lupus-prone NZB/W mouse: regulation of CFU-GM colony formation by estrogen, tamoxifen and thrombopoietin
Authors: Aronica S M , Dozier A , Fanti P , Nazareth M
Published: November 2003

Estrogen is thought to contribute to the onset of systemic lupus erythematosus (SLE) in women through mechanisms that are not completely understood. Although estrogen serves as a negative regulator in normal hematopoietic development, little research has been conducted examining alteration in hematopoietic development triggered by estrogen in lupus-susceptible individuals. We examined whether estrogen and other factors could influence colony formation of bone marrow cells obtained from normal and lupus-susceptible mice. Bone marrow cells isolated from New Zealand Black (NZB) and lupus-prone New Zealand Black and New Zealand White cross (NZB/W) mice were cultured in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) alone or in combination with estrogen, thrombopoietin (TPO), tamoxifen, estrogen and TPO, or estrogen and tamoxifen, and plated in methylcellulose culture medium. Plates were scored for the number of CFU-GM (colony forming unit granulocyte-macrophage) colonies after 6 d in culture. For females of both mouse strains, estrogen significantly decreased (P < 0.05) the number of GM colonies. Co-treatment of NZB/W cells, but not NZB cells, with TPO or tamoxifen reversed the suppressive action of estrogen (P < 0.05). In contrast, while estrogen did suppress colony formation from cells of NZB/W males (P < 0.05), neither TPO nor tamoxifen reversed this effect. Our results indicate that the sensitivity of bone marrow cells isolated from both female and male NZB/W lupus-prone mice to hormones/growth factors is qualitatively different from cells of NZB mice, and suggest that hematopoietic alterations at the level of the bone marrow may be related to the pathogenesis of SLE.
Paraoxonase activity is dramatically decreased in patients positive for anticardiolipin antibodies
Authors: Lambert M , Boullier A , Hachulla E , Fruchart J-C , Teissier E , Hatron P-Y , Duriez P
Published: November 2003

It has been reported that paraoxonase 1 (PON1) activity inhibits low-density lipoprotein (LDL) oxidation and modulates the risk of coronary heart disease. This study shows that autoantibodies (IgG) directed against modified LDL were increased in 71 patients positive for anticardiolipin antibodies. In a representative subgroup of these patients (n ‘ 36) PON1 activity was dramatically decreased and the prevalence of the RR genotype of this enzyme tended to be increased in patients who had developed arterial thrombosis. This study suggests that PON1 abnormalities play a role in the antiphospholipid syndrome.
Toxic effects of SLE serum on normal monocytes in vitro: cell death induced by apoptosis related to complement dysfunction
Authors: Klint C , Truedsson L , Andreasson A , Johansson I , Sturfelt G
Published: November 2003

The aim of this study was to assess toxic effects of systemic lupus erythematosus (SLE) serum on blood peripheral mononuclear cells from healthy donors and to evaluate if complement activation was involved. Monocytes from a healthy donor were incubated with 20 sera from ten SLE patients in both high and low disease activity states. After incubation non-adherent cells were analysed by flow cytometry. Serum from six SLE patients induced an increased cell death, four in active disease only, one in the inactive state and one in the active and the inactive state. Five of these sera, three with high and two with low disease activity, induced an increased apoptosis in the monocytes. Proportion of apoptotic cells correlated inversely with C1q and C3 concentration in the active disease sera, but not with disease activity as evaluated by SLEDAI. Apoptosis could be induced by addition of active C1s or antigen/antibody complexes to normal serum before incubation. Serum with complexes added induced increased tumour necrosis factor-a secretion from mononuclear cells, but SLE patient sera did not.

The results demonstrate that the toxic effect of serum from SLE patients on healthy monocytes is explained by induction of apoptosis. The induction process is suggested to be connected with complement activation in the serum.
Grand Rounds from International Lupus Centres Cardiac abnormalities in SLE: pancarditis
Authors: Bijl M , Brouwer J , Kallenberg G GM
Published: November 2003

Many patients with systemic lupus erythematosus (SLE) develop cardiac manifestations during the course of their disease. Pericarditis is most commonly seen, with a reported prevalence of 60%. Myocardial involvement is present in only a minority of patients. In recent years, due to better non invasive diagnostic techniques, valvular abnormalities can be demonstrated in an increasing number of patients. Depending on the technique used, valvulopathy can be demonstrated in up to 77% of SLE patients. Although most of the valvular lesions will be present without any symptoms, valve incompetence can result in congestive heart failure. Valvular lesions are associated with IgG anticardiolipin antibodies (aCL) and disease duration. We present a patient with SLE and secondary antiphospholipid syndrome (APS) who developed acute congestive heart failure due to pancarditis. Endocarditis, together with left ventricular dysfunction and pericardial effusion, were present. The endocarditis caused hemodynamically significant mitral valve insufficiency due to thickening of the mitral cusps. Just two weeks prior to the occurrence of congestive heart failure echocardiography had been normal. Treatment with high dose corticosteroids resulted in a gradual, almost complete recovery. Literature concerning cardiac manifestations in lupus is reviewed.
Choroidopathy of systemic lupus erythematosus
Authors: Nguyen Q D , Uy H S , Akpek E K , Harper S L , Zacks D N , Foster C S
Published: November 2003

Purpose: To describe the ocular and systemic manifestations associated with systemic lupus erythematosus (SLE) choroidopathy.

Methods: Three new cases of choroidopathy in patients with active SLE were described. Twentyfive published cases of lupus choroidopathy were summarized.

Results: There have been 28 cases of lupus choroidopathy (47 involved eyes) that have been reported in the English literature since 1968, including the three current cases. Only two of the patients were male. The choroidopathy was bilateral in 19 patients (68%). All 28 patients (100%) had active systemic vascular disease at the onset of their choroidopathy; 18 (64%) had nephropathy and 10 (36%) had central nervous system (CNS) lupus vasculitis. All but one of the patients had a known diagnosis of SLE at the onset of choroidopathy. 30 of the 47 involved eyes had presenting visual acuity of 20=40 or better; 14 eyes showed improvement in visual acuity with therapy. 23 patients (82%) had resolution of their choroidopathy when their systemic disease was brought under control. Despite treatment, 4 of the 28 patients (14%) died from complications of SLE.

Conclusions: Although less known than retinopathy, lupus choroidopathy may be more common than generally appreciated. It usually serves as a sensitive indicator of lupus activity. The presence of SLE choroidopathy is generally indicative of coexistent (although sometimes occult) nephropathy, CNS vasculitis, and other SLE visceral lesions. Immunomodulation of the systemic disease can lead to improvement and resolution of the systemic vasculitis as well as the choroidopathy.
Lipid-lowering drugs in lupus: an unexplored therapeutic intervention
Authors: Wierzbicki A S
Published: November 2003

Lipid-lowering drugs have been shown to have profound actions beyond modulation of lipid profiles. Statins have been shown to reduce the levels of pro-inflammatory cytokines and markers of acute phase response including C-reactive protein and serum amyloid A. Fibrates have also shown to reduce interlukin-6 levels. Both groups of drugs seem to act through a peroxisomal proliferating activating receptor alpha mechanism to achieve these actions. In lupus, there is profound activation of cytokine production and the acute phase response and a markedly increased risk for the development of atherosclerosis. The role of lipid-lowering drugs in the management of both the acute and chronic sequelae of lupus needs to be explored.
Systemic lupus erythematosus. Disease outcome in patients with a disease duration of at least 10 years: second evaluation
Authors: Swaak A JG , van den Brink H G , Smeenk R JT , Manger K , Kalden J R , Tosi S , Domljan Z , Rozman B , Logar D , Pokorny G , Kovacs L , Kovacs A , Vlachoyiannopoulos P G , Moutsopoulos H M , Chwalinska-Sadowska H , Kiss E , Cikes N , Anic B , Schneider M , Fischer R , Bombardieri S , Mosca M , Graninger W , Smolen J S
Published: November 2003

Data related to the disease course of patients with systemic lupus erythematosus (SLE) with special attention tothepersistence of disease activity in the long term are scarce. At this moment reliable figures are only knownabout the survival rate as a measure of outcome. The aim of this multicenter study was to describe the outcome ofSLE patients with a disease duration of greater than 10 y.Outcome parameters were two disease activity-scoring systems (SLEDAI and ECLAM), the end organ damage (SLICC/ACR damage index) and treatment. Our results are derived from 187SLE patients followed at 10 different centres in Europe over a period of 1 y. Serious clinical signs or exacerbations, defined by the occurrence or detoriation of already existing symptoms of renal and cerebral nervous systems were observed in 2 ‐ 11% of the patients,seizures and psychosis in 3%, proteinuria in 11% and an increase in serum creatinine in 5% of the patients. No change took place in the overall damage index. Yet, the diseasecourse in most patients was characterized by periods of tiredness (42 ‐ 60%), arthritis (20 ‐ 25%), skin involvement such as malar rash (32 ‐ 40%), migraine (15 ‐ 20%), anaemia(15%) and leucopenia (17 ‐ 19%). Summarizing these results it is shown that patients, still under care after such a long time of having this disease, do have a disease that is far from extinguished.
Immunologic and hematologic properties of antibodies to prothrombin and plasminogen in a mouse model
Authors: Puurunen M , Palosuo T , Lassila R , Anttila M , Vaarala O
Published: November 2003

Antibodies to prothrombin have been associated with venous and arterial thrombosis, and they cross-react with a structurally closely related protein plasminogen. We immunised 16 mice with human prothrombin and 15 mice with human plasminogen. Mice immunised with prothrombin developed cross-reactive antibodies to plasminogen (12/16), b2-glycoprotein I (4/16), tissue-type plasminogen activator (6/16) and cardiolipin (11/16). Mice immunised with plasminogen developed cross-reactive antibodies to prothrombin (8/15), tissue-type plasminogen activator (2/12) and cardiolipin (5/12). Functional effects of antibodies were examined. Immunisation with prothrombin induced lupus anticoagulant activity in 9/14 mice. In mice immunised with plasminogen, radial fibrinolysis was inhibited in 8/10 and plasminogen activation in the chromogenic assay was inhibited in 9/11. No cross-functionality was observed. In conclusion, antibodies to prothrombin and plasminogen cross-react in vivo. Antibodies to prothrombin and plasminogen have different functional profiles, immunisation with prothrombin leads to prolonged blood clotting time, and immunisation with plasminogen induces antibodies interfering with fibrinolysis.
Anti-oxidized low-density-lipoprotein (OxLDL) antibodies in systemic lupus erythematosus with and without antiphospholipid syndrome
Authors: Hayem G , Nicaise-Roland P , Palazzo E , de Bandt M , Tubach F , Weber M , Meyer O
Published: November 2003

The aim of this study was to examine potential links between antiOxLDL antibodies and the clinical and biological features of secondary antiphospholipid syndrome (II APLS) associated with systemic lupus erythematosus (SLE).

A cohort study was done of 98 SLE patients followed-up for 1 y, including 18 with definite II APLS and 13 patients with definite primary APLS (I APLS). IgG anticardiolipin, IgG antib2 GPI, lupus anticoagulant, VDRL and IgG antiOxLDL were measured in all 98 study subjects.

High antiOxLDL titers were found in seven (39%) of the 18 patients with II APLS vs 10 (12.5%) of the 80 patients without APLS (P < 0.01; OR ‘ 4.45; 95% CI = 1.4–14.1) and none of the 13 patients with I APLS (P < 0.02). The mean antiOxLDL titer was not significantly higher in the SLE patients with than without II APLS (P > 0.05). A high antiOxLDL titer was correlated with deep venous thrombosis (P < 0.01; OR = 5.77; 95% CI = 0.54–61) but not with arterial thrombosis (P > 0.05; OR = 1; 95% CI = 0.29–3.09), thrombocytopenia, central nervous system involvement, livedo reticularis, or a positive Coombs test. The antiOxLDL antibody titer was correlated with the IgG anticardiolipin antibody titer (r = 0.235; P = 0.02) and with the IgG anti-b2 GPI antibody titer (r = 0.224; P = 0.026).

AntiOxLDL elevation was found in 17% of SLE patients and was significantly associated with II APLS and venous thrombosis. We found no evidence suggesting that antiOxLDL may be associated with atherosclerosis.
Placentation, antiphospholipid syndrome and pregnancy outcome
Authors: Stone S , Khamashta M A , Poston L
Published: November 2003

The antiphospholipid antibodies (aPLs) are a diverse group of autoantibodies associated with a pattern of disease known as antiphospholipid syndrome (APS). Pregnancy complications secondary to placental insufflciency are key features of this disease. The mechanisms underlying the placental pathology remain unclear. In this article the process of placentation in healthy and pathological pregnancies is reviewed. The evidence for defective placentation in APS pregnancies and involvement of aPLs in this process is summarized. Finally hypotheses based on the interpretation of these studies are discussed.
Local therapy for cutaneous and systemic lupus erythematosus: practical and theoretical considerations
Authors: Ting W W , Sontheimer R D
Published: November 2003

Local therapeutic measures should be maximized in the management of lupus erythematosus (LE), particularly for patients with forms of LE-specific skin disease such as SCLE and CCLE. Local therapy consists of sun protection and locally-applied pharmacologic agents, eg topical/intralesional corticosteroids. Patients should be advised to avoid direct sun exposure, wear lightweight tightly woven clothing and broad-brimmed hats, and use broad-spectrum, water-resistant sunscreens. There are several modalities that enhance permeability of local therapeutics through the stratum corneum that could be applied to topical therapy of cutaneous LE, eg polar solvent, liposomal encapsulation, ethosomal system, iontophoresis, electroporation and sonophoresis. As novel and more effective modalities to deliver pharmacologic agents across the stratum corneum become available, therapeutics that have been experimental and untested thus far may become part of the local armamentarium in the near future. In addition, physical/contact therapy as well as dermatosurgical methods can be invaluable in enhancing self-image and quality of life of patients with disfiguring cutaneous LE lesions.
Antiaggregant and anticoagulant therapy in systemic lupus erythematosus and Hughes' syndrome
Authors: Ruiz-Irastorza G , Khamashta M A , Hughes G RV
Published: November 2003

Antiaggregant and anticoagulant drugs are essential in the management of the manifestations due to antiphospholipid syndrome (APS) in patients with primary Hughes' syndrome or systemic lupus erythematosus. Coumadin derivatives (warfarin and acenocumarol), heparin and aspirin are used for secondary thromboprophylaxis and treatment of recurrent miscarriage. The available evidence for each indication is reviewed in this paper. There is still debate regarding the optimal intensity of oral anticoagulation, the best drug combination for pregnancy failure in APS and the management of asymptomatic patients with antiphospholipid antibodies.
High-dose intravenous immunoglobulins for lupus nephritis — a salvage immunomodulation
Authors: Rauova L , Lukac J , Levy Y , Rovensky J , Shoenfeld Y
Published: November 2003

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with a great diversity of clinical manifestations which is difficult to manage. IVIGs represent promising immunoregulatory agents with the ability to control SLE without subsequent predisposition to infectious complications. Despite the implied risk of developing renal failure due to IVIG, considerable beneficial effects on lupus nephritis are reported. In this review, the clinical and adverse effects, and machanism of action, with special emphasis on modulation, of idiotypic network is discussed.
Long-term anti-CD154 dosing in nephritic mice is required to maintain survival and inhibit mediators of renal fibrosis
Authors: Kalled S L , Cutler A H , Ferrant J L
Published: November 2003

The CD154=CD40 pathway is required for the development and progression of disease in a variety of autoimmune model systems. We have demonstrated previously that long-term anti-CD154 treatment of nephritic (SWR×NZB)F1 mice prolonged survival and preserved kidney function. Herein we ask if long-term treatment is required and further characterize the protective effect on renal pathology by examining a-smooth muscle actin, collagen and TGF-b1 expression in renal tissue. The effects of anti-CD154 on brain and heart inflammation are also examined. Three dosing strategies of anti-CD154 mAb were compared in SNF1 mice that exhibited moderate or severe nephritis: (1) weekly for 6 weeks; (2) monthly; (3) weekly for 6-12 weeks followed by monthly dosing. Proteinuria, serum anti-DNA, anti-CD154 pharmacokinetics and serum soluble CD154 analyses were performed. Anti-CD154 treatment of moderate disease increased survival across all regimens, although weekly followed by monthly maintenance dosing proved most efficacious. This regime also inhibited renal a-smooth muscle actin and collagen deposition. Only the most aggressive anti-CD154 treatment protocol increased survival in severely nephritic mice.

Long-term anti-CD154 treatment significantly inhibits key mediators of kidney fibrosis and is required to maximize survival and renal function. Potential reasons for differential therapeutic efficacy in moderately vs severely nephritic mice are discussed.
Anti-insulin antibodies and the natural autoimmune response in systemic lupus erythematosus
Authors: Lidar M , Braf A , Givol N , Langevitz P , Pauzner R , Many A , Livneh A
Published: November 2003

Systemic lupus erythematosus (SLE) is characterized by the finding of ample serum autoantibodies. The role and the origin of many of these antibodies are still obscure. The aim of this work was to study the occurrence of anti-insulin antibodies (AIA) in SLE, and to postulate, based on AIA determination, on the mechanisms involved in the production of some autoantibodies in SLE. IgG and IgM AIA, anti-DNA antibodies (ADA) and anti-tetanus toxoid antibodies (ATA) were determined using ELISA in sera and B-lymphocytes culture media of 24 SLE patients, 10 healthy controls and 19 insulin-dependent diabetes mellitus (IDDM) patients. B and T-lymphocytes were isolated using Ficoll gradient, depleted of T-cells using cyclosporin A, EBV infected and grown in medium. The frequencies of IgM-AIA and IgG-ADA were higher in SLE patients than in healthy controls (P<0.02 and P<0.05, respectively). The rate of IgM-AIA in SLE and IDDM was comparable, while IgG-AIA was significantly less common in SLE than in IDDM (P<0.05). The prevalence of ATA in SLE patients and healthy controls was similar. These findings increase the spectrum of the humoral autoimmune response in SLE and suggest that part of it (natural autoantibodies) is independent of antigen driven response.
Antimalarial therapy: a panacea for mild lupus?
Authors: D'Cruz D
Published: November 2003

Antimalarial therapy has a long and successful track record in the management of patirents with mild SLE. Medium to long term use of hydroxychloroquine, alone or in combination with mepacrine, ameliorates lupus and may reduce the relapse rate. Recent guidelines for monitoring hydroxychloroquine have reduced the need for frequent visual checks. Antimalarials have other beneficial effects on lipid and glucose metabolism as well as having weak anticoagulant activity. They should be considered for most patients with mild lupus.
Monoclonal antibodies and other biologic therapies
Authors: Strand V
Published: November 2003

The treatment of systemic lupus erythematosus (SLE) presents a significant therapeutic challenge: multi-organ involvement and a variable disease course characterized by clinical exacerbations and remissions make it difficult to predict outcome. Few products have been specifically developed in this clinical indication and most accepted therapies have not been tested in randomized controlled trials in SLE. A variety of biologic agents under investigation as potential treatments for SLE are designed to interfere with specific immunologic responses, hopefully avoiding gneralized immunosuppression. These include therapies to downregulate IL-10 and/or upregulate TGFb production. Agents which interfere with T cell activation and T cell–B cell collaboration, such as CTLA4-Ig and anti-CD40 ligand monoclonal antibodies, may result in long term therapeutic benefit; alone or in combination, even following brief treatment courses. Products designed to decrease production of anti-dsDNA antibodies or inhibit complement activation may prevent immune complex deposition and amerliorate organ-specific manifestations such as renal disease. More aggressive interventions include gene therapy and stem cell transplantation. As these agents enter clinical trials, efforts to develop international consensus regarding trial methodology and outcome measures will be crucial to their successful development.
Early damage as measured by the SLICC/ACR damage index is a predictor of mortality in systemic lupus erythematosus
Authors: Rahman P , Gladman D D , Urowitz M B , Hallett D , Tam L S
Published: November 2003

The aim of this study was to determine whether early damage accrued in SLE as measured by the SLICC/ACR Damage Index predicts mortality in an inception cohort of lupus patients that have been followed prospectively in a single centre. SLE patients from the University of Toronto Lupus Clinic presenting within 1 y of their diagnosis prior to 1988 were included. This enabled all patients to be potentially followed for at least 10 y. Yearly SLICC/ACR Damage Index scores were determined for each patient. Early damage was defined as a score 1 and no damage as a score of 0 at the initial assessment. Log rank test was used to compare the survival experience between those with and without damage, with all patients being censored at 10 y. Two-hundred and sixty-three patients were identified in this inception cohort who were followed for 10 y. One-hundred and ninety patients (72%) had a SLICC/ACR Damage Index score of 0 (no damage) while 73 patients (28%) had at least one SLICC/ACR Damage Index item scored (early damage). Twenty-five percent of lupus patients who exhibited damage at their first SLICC/ACR Damage Index assessment died within 10 y of their illness as compared to only 7.3% who had no early damage (log rank P-value = 0.0002). SLE patients who died within 10 y were more likely to have renal damage (P = 0.013), and a trend toward more cardiovascular disease (P = 0.056), compared to patients who were alive. Early damage as reflected by the initial SLICC/ACR Damage Index is associated with a higher rate of mortality.
CD4 positive peripheral T cells from patients with systemic lupus erythematosus (SLE) are clonally expanded
Authors: Kolowos W , Gaipl U S , Voll R E , Frank C , Haas J P , Beyer T D , Kalden J R , Herrmann M
Published: November 2003

T cell activation was analysed in peripheral CD4/ T cells from both systemic lupus erythematosus (SLE) patients with active and inactive disease as well as in normal healthy donors (NHD) to investigate the involvement of CD4/ T cells in the etiopathogenesis of SLE. CD4/ T cell receptor (TCR) b-chain transcripts, containing the complementarity determining region 3 (CDR3), were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and analysed by highresolution polyacrylamide gel electrophoresis. In addition the CDR3 of both clonally activated as well as heterogeneous Vb families from SLE patients were analysed at the molecular level.

We observed a restricted CDR3 length polymorphism in peripheral CD4/ T cells from SLE patients compared with NHD, more pronounced in patients with high disease activity. Furthermore, in some Vb families single peaks in the histogram indicated nearly monoclonal T cell expansion. Sequencing of selected TCR b-chains revealed a increased content of acidic amino acids in the CDR3 encoded by either proximal Jb elements or N nucleotides.

We conclude that CD4/ T cells from peripheral blood of SLE patients display features of a secondary antigen driven immune response. The bias of the CDR3 towards acidic amino acids suggests the involvement of positively charged antigens.
Cyclophosphamide for the treatment of systemic lupus erythematosus
Authors: Takada K , Illei G G , Boumpas D T
Published: November 2003

Aggressive immunosuppressive therapy with cyclophosphamidehas improved the outcome of major organ disease in lupus patients. Controlled trials have shown that pulse cyclophosphamide is the treatment of choice for patients with moderate to severe proliferative nephritis. Long-term follow-upof patients participating in these controlled trials suggests that combining pulse cyclophoshamide with pulse methylprednisolone increases efficacy but not toxicity.Retrospective case series have also shown that pulse cyclophosphamide therapy may be effective for the managementofsevere or refractory to standard therapy neuropsychiatric,pulmonary, cardiovascular and hematologic disease. Pulsecyclophosphamide is associated with an increased risk for herpes zoster infections in the short term and with sustained amenorrhea in the long-term. Recent studies have also drawn attention to the lack of response (or incomplete response) and flare of lupus after an initial response. In an effort to circumvent these limitations, current investigations explore the therapeutic potential of high-dose, immunoablative cyclophosphamide therapy or low-dose cyclophosphamide in combination with nucleoside analogs or biologic response modifiers.
Osteoporosis in systemic lupus erythematosus: prevention and treatment
Authors: Sen D , Keen R W
Published: November 2003

The patient with systemic lupus erythematosus (SLE) is at risk of osteoporosis through several factors: the inflammatory disease itself, disease-related co-morbidity, and its treatment. Bone loss is apparent early in the disease and this may be confounded primarily by treatment with corticosteroids. Patients should be assessed for additional risk factors for osteoporosis and general lifestyle measures adopted. Bone mineral density measurement should be considered in SLE patients at high risk of osteoporosis, particularly those starting corticosteroids and in postmenopausal women. Calcium and vitamin D supplementation provide general prophylaxis and are a suitable first-line option. Hormone replacement should be used in hypogondal subjects unless contra-indicated. In subjects at high fracture risk, particularly in postmenopausal women, bisphosphonate therapy should be considered as these agents have been shown to significantly reduce vertebral fracture risk. These measures should reduce the burden of osteoporosis and fracture in patients with lupus.
Apheresis for lupus erythematosus: state of the art
Authors: Wallace D J
Published: November 2003

PP is a safe, expensive, labor-intensive procedure. Its absolute SLE indications include hyperviscosity, cryoglobulinemia, pulmonary hemorrhage and TTP. PP may be useful in cyclophosphamide-resistant, serious, organ-threatening disease. It may be potentially useful in the antiphospholipid syndrome or mothers or children at risk for congenital heart block. Refinements in apheresis technology may expand the indications for PP.
No constitutive defect in phagocytosis of apoptotic cells by resident peritoneal macrophages from pre-morbid lupus mice
Authors: Licht R , Jacobs C WM , Tax W JM , Berden J HM
Published: November 2003

Antibodies against nucleosomes are a hallmark of systemic lupus erythematosus (SLE). Nucleosomes are uniquely formed during apoptosis, through cleavage of chromatin by nucleases. Increased exposure of nucleosomes to the immune system could play a role in the induction of the autoimmune repertoire in SLE. To determine whether there exists a constitutive defect in the clearance of apoptotic cells, resident peritoneal macrophages from pre-morbid SLE-prone MRL and New Zealand (NZ) mice were analysed for their efficacy to phagocytose apoptotic cells in vitro. Although differences in phagocytic efficacy of up to 50% between different strains of mice were found, these were not related to SLE development. To evaluate whether macrophages from SLE-prone mice are more susceptible to phagocytic ‘exhaustion’, resident peritoneal macrophages were challenged by 20 h of additional culture in the presence of apoptotic cells. In both lupus and control strains this led to an increased capacity to phagocytose fresh apoptotic cells (increase between 15 and 92%). As a control, macrophages from all strains were also exposed to 20 h of additional culture without apoptotic cells. Under this condition resident peritoneal macrophages from all SLE-prone strains, and of the SLE-parental strain NZB, displayed a significant decrease in their efficacy to phagocytose apoptotic cells (decrease between 16 and 55%). Together, these findings do not support the hypothesis that a constitutive defect in the clearance of apoptotic cells, as evaluated by testing resident peritoneal macrophages, plays an important role in the induction of SLE.
Detection of macroprolactinemia with the polyethylene glycol precipitation test in systemic lupus erythematosus patients with hyperprolactinemia
Authors: Leaños-Miranda A , Pascoe-Lira D , Chávez-Rueda K A , Blanco-Favela F
Published: November 2003

The objective of this study was to determine the diagnostic performance of the percentage of serum prolactin (PRL) precipitated with polyethylene glycol (PEG) for the detection of macroprolactinemia in systemic lupus erythematosus (SLE) patients with hyperprolactinemia.

Serum samples from SLE patients were examined. Serum PRL was measured by immunoradio-metric assay (IRMA) and samples with hyperprolactinemia (>20 ng/ml) were submitted to PEG precipitation, gel filtration chromatography and affinity chromatography with protein-G sepharose. A comparative survey was used. Among 259 consecutive serum samples from SLE patients, PRL was >20.1 ng/ml in 43 samples (16.6%). Gel filtration showed a predominant pattern of macroprolactinemia (>100 kDa) in 14 (32.6%), a predominant pattern of monomeric PRL (23 kDa) in 27 (62.7%), and a variable pattern in two (4.7%). All sera with a predominant pattern of macroprolactinemia displayed anti-PRL autoantibodies by affinity chromatography for IgG. The best cut-off point for percentage of serum PRL precipitated with PEG for detection of macro-prolactinemia was ≥58.4%. Sensitivity and specificity were 100 and 96.6%, respectively.

We can conclude that PEG precipitation is a convenient and simple procedure to screen for the presence of macroprolactinemia in sera from SLE patients. Precipitations ≥58.4% are indicative of the presence of, and those <50% the absence of, macroprolactinemia. However, samples with precipitations between 50 and 58.3% require gel filtration chromatography to characterize the predominant molecular form of PRL. Therefore, it is important to take these findings into account in future studies that aim to establish a relationship between PRL and disease activity in SLE.
The treatment of lupus with cyclosporin A
Authors: Griffiths B , Emery P
Published: November 2003

Cyclosporin is a potent immunosuppressive drug and is frequently used in the therapy of auto-immune diseases, including systemic lupus erythematosus (SLE). Few large studies have been performed using this drug in SLE patients. However, small uncontrolled studies of patients with SLE have shown favourable results with a significant improvement in disease activity, a fall in anti ds DNA titres and proteinuria and an improvement in complement levels,leucopaenia and thrombocytopaenia. Interestingly, a consistent reduction in corticosteroid dosage often by as much as 50% is seen. Toxicity, especially with hypertension and renal impairment, occurs but usually reverses on dose reduction or the addition of an anti-hypertensive agent and isminimised by adherence to the strict monitoring guidelines.Large multi-centre randomised-controlled trials of the use of cyclosporin in SLE patients are underway and the results are eagerly awaited.