bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete heart block in an adult with systemic lupus erythematosus and recent onset of hydroxychloroquine therapy
Authors: Comí-Colet J , Sánchez-Corral M A , Alegre-Sancho J J , Valverde J , López-Gómez D , Sabaté X , Juan-Mas A , Esplugas E
Published: November 2003

Complete heart block (CHB) is a rare complication of systemic lupus erythematosus (SLE), mainly seen during an acute flare-up of the disease or after high-dose long-term treatment with antimalarial drugs, although anti-Ro and anti-RNP antibodies have also been implied by some authors.

A 40-y-old woman developed CHB in the context of an acute flare-up of SLE, first diagnosed three years ago, having recently commenced hydroxychloroquine (HCQ) treatment. Anti-Ro and anti-RNP antibodies were also positive. No features of myocarditis were found. A temporary pacemaker was required and complete resolution was achieved on steroid therapy with withdrawal of antimalarial therapy. The characteristics of previous cases are well publicised and discussion focuses on the possible aetiology and pathogenesis of the present case.
Therapeutic response and long-term follow-up in a systemic lupus erythematosus patient presenting with Kikuchi's disease
Authors: Vilá L M , Mayor A M , Silvestrini I E
Published: November 2003

Kikuchi's disease (KD) can occur in association with systemic lupus erythematosus (SLE). The treatment of concomitant diseases, however, is unclear. We describe a case of a 45-y-old man who presented with generalized histiocytic necrotizing lymphadenitis, fever, malaise and weight loss. Ten months later he also developed arthritis, serositis, anemia, leukopenia and lymphopenia. ANA, anti-Smith, anti-snRNP and anti-Ro antibodies were positive. He responded rapidly and favorably to mid-dose prednisone. Hydroxychloroquine, added 5 months later, allowed tapering down and discontinuation of prednisone treatment. He has remained in complete remission for 5 years.
Treatment of systemic lupus erythematosus with mycophenolate mofetil
Authors: Adu D , Cross J , Jayne D RW
Published: November 2003

Mycophenolate mofetil is an immunosuppressive drug that is of established efficacy in renal transplantation. It inhibits the de novo pathway of purine synthesis and therefore lymphocyte proliferation. Mycophenylate mofetil has been shown to ameliorate the severity of renal injury in murine models of lupus nephritis. Recent studies suggest that it may also be effective in the treatment of patients with lupus nephritis when used in conjunction with steroids. These observations need to be confirmed in adequately sized randomised-controlled studies.
Disassociation of sex hormone levels and cytokine production in SLE patients
Authors: Verthelyi D , Petri M , Ylamus M , Klinman D M
Published: November 2003

This study examines whether changes in the cytokine milieu of patients with systemic lupus erythematosus (SLE) are associated with abnormal levels of sex hormone levels in serum. The concentration of 17b-estradiol (E2), progesterone (Pg) and dehydroepiandrosterone-sulphate (DHEAS) was monitored in sera from 128 lupus patients and 96 controls, and correlated with the activity of their cytokine secreting cells.

Results indicate that SLE patients have (i) significantly fewer cells secreting IFNg, (ii) increased serum E2 and Pg levels, and (iii) reduced serum DHEAS levels compared to normal controls. However, the observed abnormalities in the cytokine milieu of SLE patients did not correlate with abnormalities in serum sex hormone levels. Instead, the association between IFNg production and DHEAS levels evident in healthy controls is absent in SLE patients, suggesting that cells from lupus patients are defective in their ability to produce IFNg in response to physiologic stimuli. Similarly, the normal correlation between IL-4 production and E2 levels was lost in patients with severe disease. Thus, while it remains possible that increased E2 and reduced DHEAS levels in lupus patients may help induce cytokine abnormalities early in disease, the subsequent cytokine imbalance does not correlate with sex hormone levels.
Diet and lupus
Authors: Leiba A , Amital H , Gershwin M E , Shoenfeld Y
Published: November 2003

The effect of dietary modifications has been extensively studied in lupus animal models. Calorie, protein, and especially fat restriction, caused a significant reduction in immune-complex deposition in the kidney, reduced proteinuria and prolongation of the mice's life span.

The addition of polyunsaturated fatty acids (PUFAs), such as fish oil or linseed oil, was also related to decreased mice morbidity and mortality in animal models of lupus and of antiphospholipid syndrome. PUFAs such as eicosapetaenoic acid (EPA) and docosahexaenoic acid (DHA) competitively inhibit arachidonic acid with a resultant decrease in inflammmatory eicosanoids and cytokines.

Human studies support the effect of a PUFAs-enriched diet, both scrologically and clinically. Large scale clinical studies are needed to confirm the primary results.
Treatment of lupus with corticosteroids
Authors: Chatham W W , Kimberly R P
Published: November 2003

Through direct signals to the nucleus mediated by the glucocorticoid receptor, exogenous glucocorticoids impact a broad array of cellular functions. DNA binding of the glucocorticoid receptor, depending upon the specific promoter to which the receptor binds, affects gene expression by recruiting transcription factors to the promoter or by interfering with the function of co-factors required for gene transcription. Steroid effects on the adhesion functions and release of products by phagocytic cells are prompt, occurring within hours of administration. Administration of corticosteroids results in rapid depletion of circulating T-cells due to a combination of effects including enhanced circulatory emigration, induction of apoptosis, inhibition of T-cell growth factors, and impaired release of cells from lymphoid tissues. Corticosteroid effects on B-cell function and immunoglobulin production are more delayed. The broad, generally suppressive effects of corticosteroids on the immune response render them useful for the management of most organ system manifestations of lupus. Corticosteroid toxicity in lupus is notable for greater susceptibility to infections, osteoporosis, osteonecrosis and accelerated atherogenesis. Although use of corticosteroids for patients with severe disease manifestations is associated with higher numbers of deaths from infections, overall survival appears to be improved.
Immunoablation and haemopoietic stem cell transplantation for severe autoimmune disease with special reference to systemic lupus erythematosus
Authors: Tyndall A
Published: November 2003

Internationally 397 patients (310 in Europe/Austalasia and 87 in North America) with severe autoimmune disease (AD) have received an autologous haemopoietic stem cell transplant (HSCT) following immunoablation, 32 with systemic lupus erythematosus (SLE). The 23 in the EBMT= EULAR database mostly received cyclophosphamide (Cy) and G-CSF as mobilisation followed by Cy and antithymocyte globulin (ATG) conditioning. Nineteen improved with five relapses (mostly mild to moderate) and there were three procedure-related mortalities. In the Chicago series, nine patients were entered, seven improved, one died following mobilisation and one from active disease 3 months after mobilisation. Randomised, prospective controlled phase III trials are desired, but by consensus, more phase I and II data is required to plan the optimal protocol.
Skin lesions - an indicator of disease activity in systemic lupus erythematosus?
Authors: Zeĉević R D , Vojvodić D , Ristić B , Pavlović M D , Stefanović D , Karadaglić D
Published: November 2003

Cutaneous manifestations have great diagnostic value for systemic lupus erythematosus (SLE). In this study we tried to establish a correlation between lupus erythematosus LE-specific and LE-nonspecific cutaneous lesions and disease activity measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Sixty-six patients with SLE were evaluated. They were divided into three groups having: (1) only LE-specific lesions (38 or 58.46%); (2) only LE-nonspecific lesions (4 or 6.15%); and (3) both types of lesions (23 or 35.38%). Results were analyzed using the Student t-test.

Patients with LE-nonspecific skin manifestations had significantly increased disease activity compared to those with only LE-specific lesions. The number of different skin lesion types also correlated with disease activity. It was significantly increased in a group with three different types of lesion, either specific or nonspecific. Patients with only one type of lesion had mild disease. An intermediate disease activity was found in the group with two different lesion types.

Lupus-specific skin manifestations serve primarily as an important diagnostic clue. In conclusion, patients with LE-nonspecific lesions have significantly more active SLE than those with LE-specific lesions and may therefore require more intensive therapy and disease monitoring.
Non-thyphoidal salmonellosis in patients with systemic lupus erythematosus. A study of fifty patients and a review of the literature
Authors: Lim E , Koh W-H , Loh S-F , Lam M-S , Howe H-S
Published: November 2003

The objective of this study was to characterize the clinical profile of lupus patients with nontyphoidal salmonellosis. A retrospective review of the clinical charts of lupus patients diagnosed with bacteriologically proven non-typhoidal salmonellosis over the last 20 y was undertaken, paying special attention to risk factors, clinical presentation and treatment outcome. Most episodes were bacteraemic without a localizing focus; and some patients were afebrile. They usually occurred in patients prone to opportunistic infections, and at times of increased immunosuppression given for lupus flares (especially nephritis). However, salmonellosis also occurred in some patients presenting with lupus. The C-reactive protein level was found to be significantly higher during the infective episodes compared to episodes of non-infective febrile lupus flare. All isolates were sensitive to the usual first-line antibiotics and eminently treatable with 3 weeks of appropriate antibiotics without recurrence/persistence or significant morbidity/mortality, the exceptions being spinal osteomyelitis and septic arthritis involving deformed joints requiring surgical debridement and prolonged antibiotic therapy for eradication. Mortality occurred in the setting of septic shock from mixed-microbial sepsis and major organ failure from active lupus. There is a high association of non-epidemic, non-typhoidal salmonellosis with SLE, especially in patients with active disease on intensified immunosuppression. The C-reactive protein value may be helpful in distinguishing between fever from a pure lupus flare and one complicated by infection.
xAzathioprine therapy for patients with systemic lupus erythematosus
Authors: Abu-Shakra M , Shoenfeld Y
Published: November 2003

Azathioprine is the only purine analog that is widely used for the management of systemic lupus erythematosus (SLE). For SLE patients without renal involvement, it is given to those patients who require a maintenance dose of 15 mg or higher of prednisone and for those who experience recurrent flares. Azathioprine in combination with steroids may be given to a large number of patients with lupus nephritis. It is also effective for patients with skin lesions, pneumonitis, thrombocytopenia or hemolytic anemia. Azathioprine may be used during pregnancy but not during lactation. It has not been shown to increase the risk for the development of malignancies among patients with SLE.
Exogenous estrogen in systemic lupus erythematosus: oral contraceptives and hormone replacement therapy
Authors: Petri M
Published: November 2003

The role of exogenous estrogen in the initiation and maintenance of human SLE remains very controversial. Although cohort studies suggest an increase in the incidence of SLE with both oral contraceptives and hormone replacement therapy, recent retrospective studies suggest that the risk of flare is not increased with hormone replacement therapy. However, exogenous estrogen does increase hypercoagulability, an issue in SLE patients with antiphospholipid antibodies. The prospective SELENA study will ultimately address whether exogenous estrogen increases severe flares in SLE.
Lupus in the family—analysis of a cohort followed from 1978 to 1999
Authors: Giles I , Isenberg D
Published: November 2003

Familial lupus is recognised but rarely described in mother-daughter case pairs. We describe the prevalence of lupus occurring in the first degree relatives of a cohort of 300 lupus patients under long-term follow-up at a specialised lupus clinic. Three instances of mothers and their daughters who both developed the disease are described in detail to try and ascertain whether there are any particular clinical/serological/genetic factors in common which might explain the phenomenon.
FcγRIIa polymorphism in Japanese patients with systemic lupus erythematosus
Authors: Sato H , Iwano M , Akai Y , Nishino T , Fujimoto T , Shiiki H , Dohi K
Published: November 2003

Systemic lupus erythematosus (SLE) is an immune complex-mediated disease and organ damage is caused by the deposition of immune complex. Receptors which recognize the Fc portion of immunoglobulin G (FcgR) play a key role in the phagocytosis of immune complexes. As the gene encoding for FcgR of class IIa (FcγRIIa) has two allelic forms, H131 and R131, which differ in their affinity to IgG2, this polymorphism might have implications in handling immune complex. We studied the distribution of the FcγRIIa polymorphism in 90 Japanese patients with SLE. We also examined the association between FcγRIIa polymorphism and the disease activity of SLE and the histopathological findings of lupus nephritis. FcγRIIa polymorphism was determined by PCR and dot blot analysis. The allelic frequency of H131 in patients with SLE was significantly lower (H131/R131 ‘ 0.44/0.56) than that of normal controls (H131/R131 ‘ 0.62/0.38; P < 0.05). No significant association was observed between FcγRIIa polymorphism and the clinical parameters for the activity of SLE. There was no association between FcγRIIa polymorphism and the histological findings in lupus nephritis. The difference in the distribution of FcγRIIa alleles between patients with SLE and normal subjects indicates that this polymorphism is a candidate of susceptibility gene for SLE in Japanese.
Counter-proliferative effects of nucleosomal antigens in cultures from lupus patients
Authors: Salaman M R , Mawer D PC , Hogarth M B , Seifert M H , Isenberg D A
Published: November 2003

Blood mononuclear cells from 20 lupus patients were cultured in the presence of nucleosomal antigens to determine whether they induce lymphocyte proliferation. The predominant effect seen, however, was one of inhibition of the background proliferation. Such inhibition was rare with cells from female or male controls. Nucleohistone (NH), crude histone and enriched preparations of histones H2A/H4, H2B and H3 showed this effect in approximately one-third of patients, but H1 and single-stranded (ss) DNA had no such activity. Double-stranded (ds) DNA may show this inhibitory action, but further tests are required. ssDNA was the only antigen that showed evidence (two patients) of disease-related stimulation of proliferation. Histones and NH induced proliferation in many subjects but the strongest responders were controls. Patients responded poorly to tuberculin PPD but gave an exceptionally strong proliferative response to pokeweed mitogen. It is suggested that the inhibition of background proliferation in patients is a consequence of the interaction of nucleosomal antigens with sensitised T cells. If T cell sensitisation to histones is an important factor in the development of lupus, the disease may be preventable in those at risk by inducing tolerance to the appropriate peptides.
International classification criteria for antiphospholipid syndrome: synopsis of a post-conference workshop held at the Ninth International (Tours) aPL Symposium
Authors: Wilson W A , Gharavi A E , Piette J C
Published: November 2003

An international workshop on classification criteria for antiphospholipid syndrome (APS) was held on 16 September 2000 in Tours, France, following the Ninth International APS Symposium. The workshop addressed issues that were not resolved by the previous (1998) international workshop on the classification criteria. Participants at the workshop agreed that no changes should be made to the international (Sapporo) criteria at the present time. However, to improve the criteria, future efforts should be focused on the following: (1) further evaluation of the international (Sapporo) criteria for definite APS; (2) definition of other categories of APS such as ‘probable’ and ‘possible’ APS; (3) guidelines for the clinical diagnosis as distinct from classification of APS; (4) strategies to improve the compliance of laboratories worldwide, with recommended procedures for Lupus anticoagulant (LA) and anticardiolipin (aCL) assays; (5) development of monoclonal antibody standard reagents for aCL and LA assays; and (6) refinement and subsequent evaluation of antib2GPI assays for use in idenfitication of APS.
Subacute abdominal pain requiring hospitalization in a systemic lupus erythematosus patient: a retrospective analysis and review of the literature
Authors: Buck A C , Serebro L H , Quinet R J
Published: November 2003

In the systemic lupus erythematosus (SLE) patient, abdominal pain is a common problem. Intraabdominal vasculitis must be excluded as the source because of its potentially high mortality rate. We retrospectively reviewed the charts of 56 SLE patients with 75 admissions for predominantly subacute abdominal pain (abdominal pain without peritoneal signs) severe enough to require hospital admission, comparing the diagnostic modalities used, ultimate diagnoses, and use of corticosteroids before admission with 56 age-and sex-matched patients without SLE admitted for abdominal pain during the same time interval. SLE patients were further subdivided by disease activity at presentation using the SELENA SLEDAI score. The in-hospital mortality for all patients in this review was 0%. There were no statistically significant differences in the use of computed tomography between SLE and control patients. Intestinal vasculitis was diagnosed in 5.4% of SLE patients compared with 0% of control patients (P = 0.0433). Only patients with SLEDAI scores >8 developed vasculitis (P < 0.001). We recommend the routine use of computed tomography to diagnose vasculitis only in patients with SLEDAI scores >8 and subacute abdominal pain. All SLE patients with SLEDAI scores ≤8 and subacute abdominal pain should be evaluated for a cause of abdominal pain other than vasculitis.
Malignancies during follow-up in an epidemiologically defined systemic lupus erythematosus inception cohort in southern Sweden
Authors: Nived O , Bengtsson A , Jönsen A , Sturfelt G , Olsson H
Published: November 2003

The objective of this study was to identify all malignancies in an inception cohort of SLE patients in southern Sweden and compare with the observed frequencies and spectrum of malignancies in the general population. All adult incidence cases of SLE in a defined population during the period 1981–1996 were retrieved from a prospective database and the cases were followed to endpoint or through 1998. The SLE cohort registry was aggregated with the National Cancer Registry to identify all malignancies by date, type and outcome. Standardized morbidity rates (SMR) were calculated based on the sex-and age-matched general population of the region.

Sixteen malignancies occurred in 13 patients out of a total of 116 SLE patients observed for 1086 patient-years. The SMR for all cancers detected was 2.24 (confidence interval 0.6–5.7) for males and 1.02 (confidence interval 0.4–2.1) for females and thus indicative of no general increase in malignancies. However, the SMR for non-Hodgkin lymphoma was 11.63 (confidence interval 1.4–42.0), for pulmonary cancer 5.55 (confidence interval 0.7–20.1) and prostatic cancer 6.41 (confidence interval 1.3–18.7) all significantly increased. The increase in prostatic carcinoma disappeared when only cases occurring after a latency period of 3 y after SLE diagnosis were included.

In this comprehensive inception cohort of SLE no increase in relative risk of malignancy overall was found, but the frequencies of non-Hodgkin lymphoma and pulmonary cancer were increased, possibly also the frequency of prostatic carcinoma.
Infections in outpatients with systemic lupus erythematosus: a prospective study
Authors: Zonana-Nacach A , Camargo-Coronel A , Yañez P , Sánchez L , Jimenez-Balderas F J , Fraga A
Published: November 2003

The objective of this study was to assess the incidence and risk factors of infections in 200 SLE outpatients. All outpatients with active or inactive SLE without infections in the previous month were included. They were assessed every 3 months. Major infections were those requiring hospitalization and parental antibiotic therapy; minor infections required oral or topical therapy. Sociodemographic, disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), therapy and laboratory variables were evaluated.

After a follow-up of 22 7 months, 65 (32%) patients had infections; 35% of those were major. The most common sites for infection were urinary (26%), skin (23%), systemic (12%), and vaginal (9%). At infection onset, 50 of 65 patients (77%) had disease activity, with a mean SLEDAI score of 6.1. The variables signifycantly associated with infection in the univariate analyses were the presence of disease activity, SLEDAI score, renal activity, prednisone dose, and IV cyclophosphamide. The only variable associated with infection in the multivariate analyses was a SLEDAI score of 4 or higher.

Most infections in SLE outpatients were single, minor, non-life threatening, and associated with disease activity independently of sociodemographic and therapeutic factors.
Two and three-dimensional echocardiography in primary antiphospholipid syndrome: misdiagnosis as rheumatic valve disease
Authors: Espinola-Zavaleta N , Amigo M C , Vargas-Barrón J , Keirns C , Cárdenas A Romero , Vidal M , Roldán J
Published: November 2003

This is a report of a woman in the fyfth decade of life with primary antiphospholipid syndrome and involvement of a heart valve. Diagnosis was reached with echocardiography and serological studies.
Systemic lupus erythematosus and the risk of malignancy
Authors: Cibere J , Sibley J , Haga M
Published: November 2003

The objective of this study was to determine the relative risks of malignancy and of site-specific malignancies in patients with systemic lupus erythematosus (SLE).

A cohort of 297 patients (91% Caucasian) with SLE were seen between 1975 and 1994 and followed for a mean of 12 years at the University of Saskatchewan Rheumatic Disease Unit. Expected cancer incidence rates were determined based on Province of Saskatchewan population statistics matched to each study patient for age, sex and calendar year of follow-up. Standardized incidence ratios (SIRs) of observed to expected cancers and 95% confidence intervals (95% CI) were calculated.

A total of 27 cases of cancer were observed, whereas only 16.9 were expected (SIR 1.59 (95% CI 1.05–2.32)). For site-specific malignancies, an excess of cancer of the cervix (SIR 8.15 (95% CI 1.63–23.81)) as well as hemopoietic malignancy (SIR 4.9 (95% CI 1.57–11.43)) was found. The hemopoietic cancers were predominantly non-Hodgkin's lymphoma (SIR 7.01 (95% CI 1.88–17.96)). We did not find an association of malignancy with known risk factors, including use of cytotoxic agents.

Increased risk of malignancy, notably non-Hodgkin's lymphoma and perhaps cervical cancer, should be regarded as a complication of SLE.
Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study
Authors: Levy R A , Vilela V S , Cataldo M J , Ramos R C , Duarte J LMB , Tura B R , Albuquerque E MN , Jesús N R
Published: November 2003

We conducted a randomized, controlled study to assess the need for hydroxychloroquine (HCQ) during lupus pregnancy and to assess safety. Twenty consecutive pregnant patients with similar characteristics were enrolled. The HCQ group included eight patients with systemic lupus erythematosus (SLE) and two with discoid lupus erythematosus (DLE). The placebo (PL) group included nine patients with SLE and one with DLE. The HCQ group had no flare-ups. SLEPDAI scores were similar at study entry, and at conclusion the placebo group had significantly higher scores. One patient had improvement of skin lesions and another of arthritis, allowing a decrease of prednisone dose. There were no retinal effects. Three patients in the PL group flared up, two with skin rashes, one also with arthritis and uveitis, and one (previously in remission on HCQ) with hemolytic anemia, polyserositis and anti-dsDNA antibody. Toxemia was diagnosed in only three patients in the PL group (one fetal death). Comparing prednisone dosage change, we noted a decrease in the HCQ and an increase in the PL group. Delivery age and Apgar scores were higher in the HCQ group. Neonatal examination did not reveal congenital abnormalities, nor did a neuroophthalmological and auditory evaluation at 1.5–3 y of age. In spite of the small number of patients studied, we noted beneficial effects of HCQ during lupus pregnancy, as measured by SLEPDAI and decrease in prednisone dose with no detriment to patients' health.
Reliability and validity of systemic lupus activity measure-revised (SLAM-R) for measuring clinical disease activity in systemic lupus erythematosus
Authors: Bae S-C , Koh H-K , Chang D-K , Kim M-H , Park J-K , Kim S Y
Published: November 2003

New clinical scales for semiquantitating disease activity in systemic lupus erythematosus (SLE) are widely used in research. They are reliable and valid measures. One of the original scales, the Systemic Lupus Activity Measure (SLAM), has been modified based on experience with it in multiobserver studies and training of individuals in its use. We tested the psychometric properties of the revised SLAM (SLAM-R).

SLAM-R was tested on 30 SLE patients, who fulfilled 1997 revised ACR criteria and were selected to represent a range of disease activity. The patients were evaluated independently by two physicians, who studied the instruction booklet and who had never used SLAM-R, on two occasions 2–4 weeks apart. At the first visit, the physician's global assessment of activity using visual analog scale, anti-dsDNA Ab, C3 and C4 were checked for construct validity. The psychometric properties were analyzed with nested analysis of variance and Pearson's correlation coefficient using SAS.

All patients were female, the median age was 31 (15–52) y, and the mean score of SLAM-R was 10.5±5.3 (3–26). Estimates of reliability were 0.78 of inter-rater, 0.61 of inter-visit, 0.76 of physician 1 between visits, and 0.56 of physician 2 between visits. Among subcategories except ‘Eye,’ the ‘Gastrointestinal’ category had the highest (0.96) and the ‘Neuromotor’ category had the lowest inter-rater reliability (0.50). With respect to construct validity, the correlation of SLAM-R scores with the disease activity variables except C4 was high and statistically significant.

In conclusion, the SLAM-R is reliable and valid for measuring clinical disease activity in SLE.
Circulating antibodies to guanosine in systemic lupus erythematosus: correlation with nephritis and polyserositis by acute and longitudinal analyses
Authors: Colburn K K , Green L M , Wong A K
Published: November 2003

Systemic lupus erythematosus (SLE) is characterized by autoantibodies, including antibodies to the nucleosides of DNA. Guanosine is the most immunogenic nucleoside. In this study serum antiguanosine antibody levels were compared with disease activity, determined by their SLEDI score, in 86 patients with SLE. Sera from these patients were tested, by ELISA, for autoantibodies to guanosine, single-stranded DNA (ssDNA), and double-stranded DNA (dsDNA). Anti-doublestranded DNA levels were also measured by RIA. Resultant values from these assays were correlated with SLE disease activity, and compared with specific features of SLE. The strongest correlation was higher levels of antiguanosine antibodies in patients with active lupus nephritis and polyserositis compared to patients with inactive disease (P < 0.0001). Antiguanosine levels also correlated with arthritis (P < 0.006), CNS lupus (P < 0.005), and hematologic manifestations of SLE (P < 0.002). To test the validity of this association in chronic SLE, serum antiguanosine antibodies were measured in patients with SLE at various phases of disease activity. Twelve patients with SLE had serum samples drawn at active, active-improved, and inactive phases over a 3–7 y period. Differences were significant for serum antiguanosine antibodies in the active group compared to the inactive group (P < 0.05) and the active vs the active-improved group (P < 0.02), unlike those for dsDNA and ssDNA by ELISA or RIA. Antiguanosine antibodies correlated more closely with disease activity in SLE patients in this longitudinal study than either anti-dsDNA or ssDNA antibodies. Thus, antibodies to guanosine correlated as well or better with disease activity than the other anti-DNA antibodies measured and should be considered to contribute to the pathology of SLE, especially lupus nephritis.
Significance of isolated hematuria and isolated pyuria in systemic lupus erythematosus
Authors: Rahman P , Gladman D D , Ibanez D , Urowitz M B
Published: November 2003

Hematuria or sterile pyuria as isolated urinary findings present a clinical dilemma for the treating physician. Our objective was to determine whether isolated hematuria and isolated sterile pyuria are associated with active systemic lupus erythematosus (SLE) with respect to renal and non-renal disease activity.

This is a descriptive study from a large SLE cohort followed prospectively at the University of Toronto Lupus Clinic. All episodes of isolated hematuria and isolated pyuria between 1970 and 2000 were identified from our database. Isolated hematuria was defined as >5 red blood cells per high power field; isolated sterile pyuria was defined as >5 white blood cells per high power field in the absence of urinary infection and other renal manifestations. Non-renal disease activity (defined as nrSLEDAI >1) was determined at first episode of isolated hematuria and pyuria. Renal disease activity was assessed by scoring renal biopsies within 3 months of detecting isolated hematuria or sterile pyuria.

Thirty-four percent (323=946) of our cohort had at least one episode of isolated hematuria. Seventy-seven percent of these patients had concurrent non-renal disease activity. Of the 22 biopsies scored with isolated hematuria, 96% were abnormal (WHO >class I), including 52% with active nephritis. Twenty-three percent (215=946) had at least one episode of isolated sterile pyuria. Seventy-eight percent of these patients had concurrent non-renal disease activity. All 12 biopsies scored with isolated pyuria were abnormal (WHO Class >1), including 75% with active nephritis. The appearance of isolated hematuria and isolated pyuria is associated with active renal and non-renal disease activity.

An ongoing debate has emerged regarding the significance of isolated hematuria and isolated pyuria with respect to SLE disease activity. The results of this study suggest that isolated hematuria and isolated pyuria is associated with active renal and non-renal disease activity. Thus isolated hematuria and isolated sterile pyuria should be considered manifestations of active SLE.
Osteoporosis in murine systemic lupus erythematosus - a laboratory model
Authors: Schapira D , Kabala A , Raz B , Israeli E
Published: November 2003

The aim of this study was to assess the skeletal metabolism in a murine model of systemic lupus erythematosus (SLE). MRL/n and MRL/l mice (respectively representing a benign and a malignant form of the disease) were observed from 1.5 to 6.5 months of life. The monthly follow-up included: biochemical and histomorphometrical studies of the femoral bone, serum biochemistry, immunoglobulins and osteocalcin, and histological evaluation of the kidney tissue. The results showed a higher femoral weight (/ 11.5%), calcium (/ 4.4%) and protein bone content (/ 11.4%) and a significantly higher (/ 77%) phosphorus bone content in the MRL =n group; significantly lower (748.9%) bone alkaline phosphatase enzymatic activity, lower bone alkaline/acid phosphatase enzymatic activities ratio (740.8%) and lower (738.4%) serum osteocalcin values in the MRL/l group (which might suggest reduced bone formation in these animals); markedly smaller trabecular bone volume (BV/TV) in the femoral head (736.2%) and femoral neck (739.8%), and smaller cortical and femoral areas in the mid-femoral shaft (738.8% and 738.1% respectively) in the MRL/l group; higher serum immunoglobulins, increased serum blood urea nitrogen (BUN) and creatinine and a higher index of activity in the kidney histology in the MRL/l group, indicating increased activity of the disease in this substrain. The MRL mice, through their two substrains, may serve as a valuable laboratory animal model for study of the skeletal changes in SLE and of the influence of the disease activity on the skeletal metabolism.
Systemic lupus erythematosus with polyglandular autoimmune syndrome type II: report of an unusual case
Authors: Al-Mutairy M , Malaviya A N
Published: November 2003

A patient with systemic lupus erythematosus (SLE) is described who had associated autoimmune thyroiditis with subclinical hypothyroidism and idiopathic Addison's disease. The presence of autoimmune thyroid disease and Addison's disease could classify her as having polyglandular autoimmune syndrome (PGAS) type II, which is the commonest of the three types of this syndrome. However, the additional presence of SLE in PGAS type II has not been described earlier. This patient appears to be the first such case.
Therapy with pulse methylprednisolone and short course pulse cyclophosphamide for diffuse proliferative glomerulonephritis
Authors: Mosca M , Neri R , Giannessi S , Pasquariello A , Puccini R , Bencivelli W , Bombardieri S
Published: November 2003

The incidence of renal flares and the long-term outcome in a group of 33 systemic lupus erythematosus (SLE) patients with diffuse proliferative glomerulonephritis (DPGN) treated with pulse steroids and a short course of pulse cyclophosphamide (CYC) are evaluated. Fifteen patients (45%) experienced a flare of renal disease at some time after the discontinuation of the immunosuppressive (IS) therapy; among these half (24%) were ‘early’ flares occurring shortly after the discontinuation of therapy, and the other half (21%) were ‘late’ flares occurring more than 2 y after the discontinuation of the treatment. Nine patients (27%) showed a poor renal outcome at the end of follow-up. On multiple regression analysis, a younger age and a high activity index (AI) on renal histology were found to be correlated with the occurrence of renal flares. Our results suggest that the combination of pulse steroids with a short course of pulse CYC (six to nine pulses) is effective in both controlling disease activity and in preventing the occurrence of renal flares in DPGN. However, short term IS therapy might not be sufficient to maintain disease control in younger patients with active lesions on renal histology. Such patients might be candidates to receive more prolonged IS treatment.
Antioxidants suppress mortality in the female NZB × NZW F1 mouse model of systemic lupus erythematosus (SLE)
Authors: Suwannaroj S , Lagoo A , Keisler D , McMurray R W
Published: November 2003

Inflammation produces reactive oxygen intermediates (ROI) that cause vascular damage and activate T lymphocytes. Conversely, antioxidants not only protect tissue from oxidative damage but also suppress immune reactivity. The objective of this study was to examine immunomodulatory effects of the non-enzymatic antioxidants, N-acetylcysteine (NAC) and cysteamine (CYST), on autoimmune disease, glomerulonephritis, and mortality in the female B/W mouse model of human systemic lupus erythematosus (SLE). The development of murine lupus was assessed during the lifespan of female B/W mice given NAC or CYST. Morbidity and mortality were assessed daily. At 6 week intervals mice were examined for weight change, albuminuria, serum BUN, antibodies to DNA, and IgG immunoglobulin levels. Serum prolactin, estrogen and progesterone were measured at 18 weeks of age. In a parallel study, NAC-and CYST-treated and control B/W mice were examined at 24 weeks of age for interval renal histopathology, lymphocyte adhesion molecule expression, and antibody titers and in vitro cytokine production in response to immunization with DNP-KLH. CYST significantly suppressed development of albuminuria and azotemia at 36 and 42 weeks of age compared to control and NAC-treated mice. NAC significantly suppressed anti-DNA antibody levels at 24 weeks. In contrast CYST significantly increased anti-DNA antibody levels at 18 weeks of age (P < 0.001 CYST vs control and NAC-treated mice). Kidneys of CYST-treated mice also had accelerated inflammatory histologic changes despite their lower incidence of albuminuria and azotemia. Mean (± s.e.m.) survival of control mice was 33±2 weeks compared to 38±2 weeks in NAC-treated mice (P < 0.05 vs control), and 48±2 weeks in the CYST-treated group (P < 0.01 vs control mice). The antioxidants, NAC and CYST, significantly improved mortality in the female B/W mouse model of SLE. NAC suppressed autoantibody formation and modestly prolonged survival. CYST, despite its augmentation of anti-DNA levels and renal inflammatory changes, inhibited the development of renal insufficiency and markedly improved survival. These findings suggest that ROIs play a role in the pathogenesis of lupus nephritis and that antioxidants reduce the damage causing renal insufficiency. Antioxidants may be a beneficial adjunctive therapy in the treatment of human SLE.
In vitro ultraviolet irradiation induces pro-inflammatory responses in cells from premorbid SLE mice
Authors: Foltyn V N , Golan T D
Published: November 2003

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, in which sunlight (especiallyits ultraviolet radiation (UVR)) is known to induce exacerbation of cutaneous lesions as well as systemic manifestations of the disease. The aim of this in vitro study was toinvestigate whether UVR (UVA, UVB) amplifies pro-inflammatory factors in cultured dermal fibroblasts (DF) or lymph node cells derived from premorbid or morbid mice from the murine SLE strains (MRL-1pr=1pr, (NZB/NZW)F1), in comparison to cells derived from normalmice from the non-SLE strains (C57BL=6, BALB/c). Our results demonstrate the following. Dermal fibroblast of premorbid SLE mice showed increased susceptibility toUVA and UVB irradiation, determined by viability assay, incomparison to those of normal mice. UVB irradiation inducedan enhanced expression of ICAM-1 in such SLE derived cells,in comparison to cells of normal mice. UVA and UVB increased functional activity of LFA-1 in lymph node cells of premorbid SLE mice and not in normal controls. UVB irradiation induced increased production and secretion of pro-inflammaory cytokines (IL-1, IL-6, TNF-a) in DF o premorbid SLE mice, in comparison to normal controls. Theenhanced pro-inflammatory responses to UVR werealsoobserved in experiments conducted with cells derivedfrom morbid SLE mice.

In conclusion, the pro-inflammatory pronenessdetected in the premorbid stage of murine SLE could be ofmajor importance in SLE pathogenesis. Furthermore, it suggests that the autoimmine inflammatory process in vivo, triggered initially by immune complex deposition, could be further amplified by UVR.
Lues and lupus: syphilis mimicking systemic lupus erythematosus (SLE)
Authors: Shatley M J , Walker B L , McMurray R W
Published: November 2003

Malar rash and photosensitivity are common findings in systemic lupus erythematosus (SLE). However, a number of inflammatory, dermatologic, infectious or drug-induced conditions may mimic cutaneous findings of SLE. These typically include seborrheic dermatitis, contact dermatitis, rosacea, polymorphous light eruption, syphilis and dermatomyositis sine myositis. Herein we describe a patient with fever, malar rash, alopecia, photosensitivity, arthralgias and lymphadenopathy who was subsequently diagnosed with secondary syphilis. In this case report we review clinical and histopathological findings in the differential diagnosis of malar rash and photosensitivity and discuss the overlapping features of syphilis and SLE.
Life-threatening angioedema in systemic lupus erythematosus
Authors: Thong B YH , Thumboo J , Howe H S , Feng P H
Published: November 2003

Life-threatening angioedema involving the upper respiratory tract is an uncommon manifestation in systemic lupus erythematosus (SLE). We report three patients in their late adolescence who had laryngeal oedema causing airway obstruction and requiring mechanical ventilation during active disease following symptoms of a respiratory tract infection. All of them had major organ involvement from lupus and none had a family history of hereditary angioedema (HAE). The mechanisms of angioedema in SLE are heterogeneous. There has been little evidence so far of antiCl inhibitor (Cl INH) autoantibody in SLE patients with angioedema. These are the first three cases reported in the literature of life-threatening angioedema following respiratory tract infection in SLE.
Polymorphisms of the CTLA-4 exon 1 and promoter gene in systemic lupus erythematosus
Authors: Lee Y H , Kim Y R , Ji J D , Sohn J , Song G G
Published: November 2003

The objective of this study was to determine whether the polymorphisms of the CTLA-4 exon 1 (/49) and promoter (7318) are associated with susceptibility to systemic lupus erythematosus (SLE) and its clinical features. Polymerase chain reaction of genomic DNA-restriction fragment length polymorphism was used to determine genotypes of the CTLA-4 exon 1 (/49) and promoter (7318) in 80 SLE patients and 86 healthy control subjects. The genotype distribution of the CTLA-4 exon 1 (/49) differed between SLE patients and controls (w2 = 6.74, 2 degrees of freedom (d.f.), P = 0.03). The CTLA-4 AG genotype occurred more frequently in patients with SLE (46.3% vs 33.7% controls). On the other hand, the CTLA-4 AA genotype as well as the CTLA-4 GG genotype was less frequent among SLE patients than among control subjects (1.3% vs 9.3% and 52.5% vs 57.0%, respectively). The genotype distribution of the CTLA-4 promoter (-318) different between SLE patients and control subjects (CT, TT, CC; genotype 27.5%, 0%, 72.5% vs 16.3%, 4.7%, 79.1% controls respectively, w2 = 6.36 2 d.f., P = 0.04). However, Fisher's exact or w2 P-values for each genotypes of the CTLA-4 exon l (+49) and promoter (-318) between SLE and control group < 0.05. Clinically, in the lupus patients there was no significant difference according to the CTLA-4 polymorphism.

In conclusion, no correlation was found between CTLA-4 exon 1 (+49) and promoter (-318) polymorphisms and SLE in our study.
The safety and efficacy of MMF in lupus nephritis: a pilot study
Authors: Kingdon E J , McLean A G , Psimenou E , Davenport A , Powis S H , Sweny P , Burns A
Published: November 2003

Inducing and maintaining remission in patients with lupus nephritis may be difficult. Current treatments have significant toxicity. Mycophenolate mofetil (MMF) limits damage in murine models of lupus nephritis. We have assessed the efficacy and tolerability of MMF in the treatment of patients with long-standing or resistant lupus nephritis. We have treated 13 patients with biopsy proven lupus nephritis (two membranous nephropathy, four membranous nephropathy with super-imposed proliferative changes, seven with proliferative glomerulonephritis). All patients had relapsed on conventional treatment or there were pressing indications to minimise steroid dosage or avoid alkylating agents. Nine out of 13 were treated with MMF and prednisolone, 3=10 with MMF alone and 1=10 with MMF, prednisolone and cyclosporine. Thirteen patients were treated with MMF for up to 37 months (median 25 months). Three patients were withdrawn from MMF during the first 8 months of treatment. The remainder tolerated MMF (median dose 1 g/day). Serological improvements were observed in 9=13 and steroid dosage was reduced in 8=10 patients. Infections occurred in 3=13. One patient relapsed. MMF significantly reduced the rate of decline of renal function. MMF should be considered in the treatment of long-standing or resistant lupus nephritis. Controlled clinical trials are required to confirm these findings.
Antiribosomal P protein antibody in human systemic lupus erythematosus reacts specifically with activated T cells
Authors: Hirohata S , Nakanishi K
Published: November 2003

We examined the presence of the epitope recognized by antiribosomal P protein antibody (anti-P) on the cell surface of human immunocompetent cells. Highly purified CD4/ and CD8/ T cells, and B cells from normal healthy individuals were reacted with affinity-purified IgG anti-P, and were stained with FITC-conjugated F(ab0)2, fragment goat anti-human IgG, followed by analysis on flow cytometry with gating for viable cells by propidium iodide staining. The presence of an epitope that is antigenically related to the carboxyl-terminal 22-amino-acid sequence of ribosomal P protein was not demonstrated on the surface of fresh CD4/ and CD8/ T cells, or fresh B cells. However, the expression of the ribosomal P epitope was induced on CD4/ and CD8/ T cells after activation with immobilized anti-CD3, whereas the epitope was not expressed on activated B cells. These results indicate that anti-P is an antilymphocyte antibody, which reacts specifically with activated T cells but not with resting T cells or B cells, suggesting possible direct effects of anti-P on the immune dysregulation in systemic lupus erythematosus.
AVEMAR (a new benzoquinone-containing natural product) administration interferes with the Th2 response in experimental SLE and promotes amelioration of the disease
Authors: Ehrenfeld M , Blank M , Shoenfeld Y , Hidvegi M
Published: November 2003

The potential of oral treatment with AVEMAR (AVEMAR), a new benzoquinone-containing fermentation product of wheat germ, on features of experimental systemic lupus erythematosus (SLE) in naive mice, induced by idiotypic manipulation, was studied. We assessed the effect of AVEMAR on the profile of autoantibody production and the response of Th1=Th2 related cytokines as well as the clinical picture of experimental SLE in the SLE-induced mice.

When the product was given in the pre-immunization period, down-regulation of autoantibody production (anti-dsDNA, mouse 16=6 Id, and anti-histones) following treatment with AVEMAR was noted (eg anti-dsDNA decreased from 0.898 0.097 OD at 405 nm to 0.519 0.103 OD following treatment). This effect was sustained for at least 4 weeks after discontinuation of the therapy. Serological manifestations associated with a delay in Th2 response (IL-4 and IL-10) were recorded (eg IL-4 decreased from 91.7 8.11 to 59.55 7.78 ng =ml in splenocyte condition media). The mice showed normal ESR, WBC and less than 100 mg/dl of protein in the urine in comparison to > 300 mg/dl protein in the SLE non-treated mice.

In conclusion, oral intake of AVEMAR can ameliorate the clinical manifestations of experimental SLE, via affecting the Th1=Th2 network inhibiting Th2 response.