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PubMed1994

Safety of hormone replacement therapy (HRT) in systemic lupus erythematosus (SLE).

Despite its obvious benefits, many physicians are reluctant to prescribe HRT to patients with SLE. We have performed a retrospective study in 60 postmenopausal women with SLE including 30 HRT users and 30 never users. The patients were studied for 12 months after the initiation of HRT. The two groups were well matched for disease characteristics. The HRT users experienced significant improvements in general well being, libido and depression. There was no significant difference in any other parameter measured. There was no increase in the number of thrombo-embolic events in the user group despite 7 patients having a positive thrombophilia screen. In conclusion, in stable postmenopausal SLE HRT appears well tolerated and safe.

Adult↗

PubMed1994

SLE anti-DNA autoantibodies binding estradiol-albumin-DNA conjugate.

The present study was designed to study the possible role of the female sex hormone, estradiol in conjugation with DNA, in the pathogenesis of systemic lupus erythematosus (SLE). Calf thymus DNA fragments (average size 200 bp) were covalently linked to estradiol-albumin (E2-BSA) by treatment with glutaraldehyde. The conjugate was separated from free DNA by gel exclusion chromatography. It was characterized by UV spectroscopy and thermal denaturation studies. The conjugate (E2-BSA-DNA) induced high titer antibodies which were highly specific towards their immunogen. These antibodies also recognize estradiol-albumin and beta-estradiol but not native DNA (B-form), brominated DNA (Z-form) or poly(rG).poly(dC) (A-form). The E2-BSA-DNA conjugate showed significant binding with SLE sera known to have a high level of anti-native DNA antibodies. The results indicated the recognition of unique conformation of estradiol-BSA-DNA conjugate by naturally occurring SLE anti-DNA autoantibodies.

Animals↗

PubMed1994

Solar ultraviolet radiation induces enhanced accumulation of oxygen radicals in murine SLE-derived splenocytes in vitro.

Although sunlight is known to induce generalized manifestation in systemic lupus erythematosus (SLE) patients, its underlying mechanism remains obscure. In the present study we have investigated whether UVA (320-400 nm), the most predominant UV component in solar radiation, induces enhanced accumulation of reactive oxygen species in murine SLE-derived cells (MRL/l) in comparison to normal cells (Balb/c), as measured by oxygen (O2) consumption, by means of a Clark-type electrode. Our data show enhanced O2 consumption by MRL/1 cells (which correlates with the formation of reactive oxygen species), accompanied by decreased viability, in comparison to irradiated normal cells. This finding suggests that increased accumulation of reactive oxygen species contributes to the enhanced photosensitivity observed in SLE patients.

Animals↗

PubMed1994

SLE in Indian men: analysis of the clinical and laboratory features with a review of the literature.

Data on the clinical and laboratory profile of 39 male lupus patients has been analysed. An attempt has been made to (1) delineate the pattern of SLE in Indian males, (2) compare it with that reported in the world literature, (3) find out differences, if any, between male children and adults with the disease, and (4) compare it with our previously published data on Indian females with SLE. Several important points were brought out in this study. First, SLE in Indian males has an earlier age of disease onset, a higher incidence of mucocutaneous and renal involvement and a lower incidence of neuropsychiatric, gastrointestinal and hematological disease in comparison to those published from the developed countries. Second, leucopenia and lymphopenia, a reflection of disease severity, occur significantly more in male children compared with adults. Thrombocytopenia is exclusively noted in adult males and virtually non-existent in children. Third, male patients overall have a less severe form of the disease in comparison with their female counterpart, as was evident by significantly less patients with hypocomplementemia, diffuse proliferative lupus nephritis and psychosis. Finally, a higher frequency of infection, particularly tuberculosis, was seen in male patients, which was the cause of death in some.

Adolescent↗

PubMed1995

A new endocrinological and immunological syndrome in SLE: elevation of human chorionic gonadotropin and of antibodies directed against ovary and endometrium antigens.

We have analysed the levels of gonadotropins in male and female patients with systemic lupus erythematosus (SLE). Human chorionic gonadotropin hCG was elevated in 23.8% of patients compared with 12.7% of controls. hCG isolated from the serum of SLE patients was bioactive in vitro. Levels of hCG were significantly correlated with those of its beta-subunit but not with the levels of follicle stimulating hormone, luteinizing hormone, prolactin alphafetoprotein or carcino embryonic antigen. A high percentage of patients presented an organ-specific humoral immune response against ovarian (26.7%) and endometrial (40%) antigens compared with controls (8% and 7.6%, respectively). Endometrial antibodies were significantly correlated to the levels of prolactin. The ovarian tumour marker CA-125 was elevated in 32.5% of patients, including two males. As a whole, these elements delineate a new endocrine and immunological syndrome in SLE in which the elevation of hCG could provide a central physiological explanation for a series of endocrine alterations that characterize this disease.

Adolescent↗

PubMed1996

A comparison of five health status instruments in patients with systemic lupus erythematosus (SLE).

The aim of the present investigation was to assess and compare health status instruments in SLE. One hundred and twenty-five patients completed five health status instruments: the Health Assessment Questionnaire (HAQ), Functional Ability Index, the Fatigue Severity Scale (FSS), the Disability Days Measure (DDM), the Centre for Epidemiological Studies-Depression Scale (CES-D), and the Medical Outcomes Study (MOS) Short Form Health Survey during their Clinic visit. Disease activity was measured using the SLE Disease Activity Index (SLEDAI). All instruments described a spectrum of quality of life outcomes in these patients. An inter-instrument correlation analysis revealed that components of the MOS correlated significantly with each of the other instruments used. There was no correlation between any of the instruments used and the SLEDAI. We conclude that health status assessment as measured by the MOS short form is a valid independent outcome measure in patients with SLE.

Adolescent↗

PubMed1997

Hepatitis B and C viruses serology in patients with SLE.

Sera of 95 patients with SLE were tested for the presence of hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibodies. The results show that HBsAg was not detected in the sera of all of the SLE patients. Only one patient was confirmed to have anti-HCV antibodies, suggesting that chronic infection with hepatitis B and C is not increased in patients with SLE compared with the general population.

Adolescent↗

PubMed1997

Fatal amoebic colitis in a patient with SLE: a case report and review of the literature.

Colitis in systemic lupus erythematosus (SLE) poses a diagnostic challenge as clinical, radiological and laboratory findings are often non-specific. Fulminant amoebic colitis is a rare cause of death in SLE. Early diagnosis coupled with timely surgery can reduce the mortality. The demonstration of haematophagous trophozoites in the stool is diagnostic but insensitive. Early endoscopy with adequate specimen collection is an important part of the diagnosis. Serology is both sensitive and specific but can take up to 2-4 weeks for seroconversion making it less useful in a disease that takes a rapid downhill course if treated inappropriately. We report a fatal case of colitis in a patient with SLE due to invasive amoebiasis which was complicated by Salmonella bacteraemia, disseminated intravascular coagulation, acute oliguric renal failure and adult respiratory syndrome. We also reviewed the literature on the clinical features and diagnosis of fulminant amoebic colitis. Amoebic colitis, although rare, should be considered in the differential diagnosis of lupus patients with colitis.

Adult↗

PubMed1997

Elevated soluble fas production in SLE correlates with HLA status not with disease activity.

Evidence from animal models of lupus suggests that disruption of Fas-mediated apoptotic events may play a role in systemic lupus erythematosus (SLE). The recently described secreted from of Fas (sFas) could interfere with apoptotic events by blockading Fas/Fas ligand interactions. We describe elevated secreted Fas protein in sera from 60 patients with SLE compared with controls but neither sFas protein nor sFas mRNA levels correlated with disease activity. At the mRNA level there is strong evidence that individuals with human leucocyte antigens common in SLE patients have a genetic predisposition for increased secreted Fas production.

Adult↗

PubMed2003

SLE - Rituximab in lupus.

B cells are essential to the development of systemic lupus erythematosus (SLE). The chimeric monoclonal antibody rituximab depletes B cells by targeting the pan-B-cell surface marker CD20. Preliminary experience with this agent in SLE and other autoimmune diseases has been encouraging. Controlled trials in SLE will be necessary to determine whether rituximab is useful therapy in this disease, and will teach us more about the roles of B cells in its pathogenesis.

Animals↗

PubMed2003

SLE - Practical and theoretical barriers to the prevention of accelerated atherosclerosis in systemic lupus erythematosus.

Accelerated atherosclerotic vascular disease (ASVD) is a major cause of death in systemic lupus erythematosus (SLE). Although many authorities are calling for aggressive assessment and management of cardiac risk factors in patients with SLE, both theoretical and practical barriers to this approach exist. It seems that SLE and/or its treatment are themselves strong risk factors for the development of ASVD and it is unclear how much this risk can be decreased by the control of traditional risk factors. Studies from several centers have shown that suboptimal risk factor management and barriers to acceptance of these measures must also be studied further.

Arteriosclerosis↗

PubMed2000

Cardiac abnormalities in SLE: pancarditis.

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 noninvasive 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.

Adult↗

PubMed2001

Prevalence and isotype distribution of antiphospholipid antibodies in Chilean patients with systemic lupus erythematosus (SLE).

Previous studies have demonstrated that ethnicity plays a role in the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-beta2 glycoprotein I (abeta2-GPI) antibodies in systemic lupus erythematosus (SLE) patients. Few studies have been done in Latin American populations. Serum samples from 129 Chilean SLE patients were tested for IgG, IgM and IgA aCL and abeta2-GPI by ELISA. Clinical data were reviewed with the focus on clinical manifestations of antiphospholipid syndrome (APS). Positivity for at least one isotype of aCL was found in 30% of patients, while only 10% were positive for at least one isotype of abeta2-GPI. IgG was the most prevalent isotype for aCL (16%), and the isotype distribution was similar (4%) for abeta2-GPI. In general, the presence of aCL was significantly associated with the presence of abeta2-GPI, but a number of samples were positive for only one antibody, some of them associated with clinical manifestations of APS. ACL antibodies at medium-high titers were significantly correlated with thrombosis (P = 0.0007) and fetal loss (P = 0.009); however, the sensitivity of abeta2-GPI for detecting thrombosis and fetal loss was lower than aCL (19 and 17% vs 56 and 50%, respectively), and the specificity slightly higher (91 and 90% vs 84 and 82%). In Chilean SLE patients, aCL and abeta2-GPI antibodies are important in the evaluation of patients with APS. However, the utility of abeta2-GPI antibodies was limited by the low prevalence of these antibodies in comparison with other ethnic groups. Further studies are needed to define the basis of the observed differences among ethnic groups.

Antibodies, Antiphospholipid↗

PubMed2001

Antioxidants suppress mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus (SLE).

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.

Acetylcysteine↗

PubMed2001

Lues and lupus: syphilis mimicking systemic lupus erythematosus (SLE).

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.

Adult↗

PubMed2001

Chorioretinopathy and discoid plaque-like lesions of the eyelids as useful indicators of systemic lupus erythematosus (SLE) progression.

Choroidal involvement in systemic lupus erythematosus (SLE) occurs infrequently. We report a 45-y-old woman with bilateral chorioretinopathy associated with SLE. Diagnosis was performed using indirect ophthalmoscopy, retinal fluorescein angiography (FA) and green indocianin angiography (ICG). In this patient chorioretinopathy and discoid-like plaque of the lids represented the only signs of SLE progression after 15 y of apparent remission of systemic disease.

Chorioretinitis↗

PubMed2002

Mycobacterium haemophilum infection in an SLE patient on mycophenolate mofetil.

We describe a case of Mycobacterium haemophilum in an immunocompromised patient with systemic lupus erythematosus (SLE). Mycobacterium haemophilum is a recently described pathogen which has not been previously described either in SLE patients or patients on Mycophenolate Mofetil. Mycobacterium haemophilum can be difficult to diagnose, as it may not have the granulomas characteristic of atypical mycobacterial infections. Combination therapy with at least two drugs for several months is required and the outcome depends on the patient's underlying immunocompromised state. Our report highlights the need for early diagnosis and treatment of Mycobacterium haemophilum in immunocompromised patients with SLE.

Adult↗

PubMed2002

Triggers for anti-chromatin autoantibody production in SLE.

The formation of autoantibodies against chromatin is the main feature of systemic lupus erythematosis (SLE), an autoimmune disease, which is T-cell dependent and autoantigen-driven. Historically, antibodies against dsDNA, one of the components of chromatin, are considered as a hallmark of SLE. However, dsDNA is poorly immunogenic. Nucleosome-specific T helper cells have been identified. These T cells propagate not only nucleosome-specific antibodies, but also anti-dsDNA antibodies. Nucleosomes are formed during apoptosis by cleavage of chromatin, and evidence of disturbed apoptosis has been found especially in certain murine models of lupus. In addition to an increased rate of apoptosis, autoimmunity against chromatin might also result from an impaired phagocytosis of apoptotic material, for which strong evidence has been provided by studies in certain knock-out mice (C1q, SAP, Dnase I). The induction of an immune response to nucleosomes could be enhanced by modifications of histones or DNA during apoptosis, altered presentation by antigen presenting cells or a viral infection. The release of nucleosomes and the formation of anti-chromatin autoantibodies result in formation of complexes, which bind to the glomerular basement membrane via heparan sulfate. This deposition incites glomerulonephritis, the most serious manifestation of SLE.

Autoantibodies↗