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Lack of association between slow acetylator status and spontaneous lupus erythematosus.

The Chinese in Southeast Asia are recognized as a population group that has a relatively high prevalence of rapid "acetylators" and a relatively high incidence of systemic lupus erythematosus. This study was designed to evaluate the possibility that there were environmental lupus erythematosus provocative substances eliminated by acetylation that resulted in a preponderance of slow acetylators among patients with the disease. We compared acetylator status in 36 Chinese women with mild, stable, and confirmed lupus erythematosus and 36 healthy control subjects matched for age, sex, and ethnic origin. Acetylator status was determined by use of HPLC to assay 5-acetylamino-6-formylamino-3-methyluracil/methylxanthine (AFMU/MX) and AFMU/(AFMU + MX) ratios in urine 1 to 4 hours after drinking a strong cup of coffee (caffeine). By use of parametric and nonparametric methods of analysis, the frequency distribution of AFMU/MX and AFMU/(AFMU + MX) ratios in both the patients and control subjects were determined to be very similar. Thus there was no association between slow acetylator status and lupus erythematosus in the study subjects.

Acetylation↗

[Panniculitis and macrophage activation syndrome in a child with lupus erythematosus].

INTRODUCTION: Panniculitis is rarely presented in the course of systemic lupus erythematosus. When it occurs, it is mainly related to lupus profundus. However, when panniculitis is associated with a reactive hemophagocytic syndrome, panniculitis could be linked to this hemophagocytosis reaction. CASE REPORT: We report a case of an 11-year-old girl treated for several years for systemic lupus erythematosus, who simultaneously presented panniculitis and an hemophagocytic syndrome. The reality of both diagnoses was based on the analysis of biological and histological data. Therapy with immunosuppressive drugs led to relief of the symptoms. DISCUSSION: We emphasize our discussion on the pathophysiology of lupus profundus and hemophagocytosis with regards to the role of cytokines and circulating immune complexes in both diseases. They may enhance the hypodermal necrosis observed in lupus profundus and induce macrophage cell dysregulation through cytotoxic cells known in hemophagocytosis. The immunomodulative action of immunosuppressive therapy with inhibition of cells involved in immune response, may explain its efficacy.

Antigen-Antibody Complex↗

Bullous systemic lupus erythematosus.

Two patients with bullous systemic lupus erythematosus are reported. In one, the disease appears to have been caused by hydralazine. The cutaneous lesions of bullous SLE have not been previously reported in drug-induced lupus.

Adult↗

Antiphospholipid antibodies in paediatric systemic lupus erythematosus, juvenile chronic arthritis and overlap syndromes: SLE patients with both lupus anticoagulant and high-titre anticardiolipin antibodies are at risk for clinical manifestations related to the antiphospholipid syndrome.

Antiphospholipid antibodies (APA) are often associated with severe clinical manifestations, especially in the setting of systemic lupus erythematosus (SLE). Here we have investigated the prevalence of anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) in paediatric patients affected with SLE, JCA and overlap syndromes (OS) and correlated the presence of aCL and LA with clinical features. aCL were assayed by enzyme-limited immunoassay; LA was determined by activated partial thromboplastin time and the kaolin clotting time test. aCL and LA assays were performed in parallel on at least two occasions over a 7-30-month follow-up. Fifteen out of nineteen (79%) SLE patients had aCL and 8/19 (42%) had LA. Six SLE patients displayed manifestations that were APA-related: deep venous thromboses, autoimmune haemolytic anaemia, pulmonary hypertension, neurological alterations. Five out of six symptomatic patients had both LA and high-titre aCL. In contrast, JCA and OS patients had usually low-titre aCL, no detectable LA and no APA-related manifestations. aCL persisted at high titre over time in SLE patients, but was only transiently detected in JCA and OS patients. This study shows that the simultaneous positivity for LA and high-titre aCL allows the identification of paediatric SLE patients who are at risk not only for thrombosis, but also for other APA-related clinical features.

Adolescent↗

Neonatal lupus erythematosus: clinical findings and pathogenesis.

Neonatal lupus erythematosus is an uncommon disease associated with maternal autoantibodies to proteins of the Ro/La (SSA/SSB) family. The clinical findings most often reported are third-degree heart block and cutaneous lupus lesions, but a significant number of children have cardiomyopathy, hepatobiliary disease, or hematologic cytopenias. The consistent presence of maternal autoantibodies and the transient nature of the disease implicate maternal autoantibodies as the cause of the disease, and developing animal models support the concept that the autoantibodies are pathogenic. Only a minority of babies exposed to the autoantibodies develop disease, however, and mothers and their babies have different disease manifestations. Thus, additional factors are likely to be important in determining disease expression.

Autoantibodies↗

Accurately describing changes in disease activity in Systemic Lupus Erythematosus.

OBJECTIVE: To determine whether Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores correlate with the clinician's impression of level of disease activity. METHODS: In total, 230 patients with SLE followed at the University of Toronto Lupus Clinic who had 5 visits 3 months apart in 1992-93 were studied. At each visit a standard protocol was completed. A clinician who did not know the patients or their SLEDAI scores evaluated each patient record and assigned a clinical activity level. "Flare" was defined by new or increased therapy for active disease, an expression of concern, or use of the term "flare" in the physician's notes. The SLEDAI score was calculated from the database. RESULTS: SLEDAI scores described a range of clinical activity as recognized by the clinician. Median SLEDAI scores ranged from 2 (inactive disease) to 8 (persistently active or flare). When the clinician assessed the patient to be improved, the median SLEDAI score decreased by 2. When the clinician assessed that the patient was experiencing a flare, the SLEDAI score increased by a median of 4. CONCLUSION: Based on our data we propose the following outcomes for patients with SLE: flare, an increase in SLEDAI > 3; improvement is a reduction in SLEDAI of > 3; persistently active disease is change in SLEDAI +/- 3; and remission a SLEDAI of 0. These outcomes will allow a more complete description of a patient's response to therapeutic intervention in a responder index.

Adolescent↗

Presence of antibodies to ubiquitin during the autoimmune response associated with systemic lupus erythematosus.

Sera from patients with systemic lupus erythematosus (SLE) were shown to react with both ubiquitin and a synthetic fragment of it (residues 22-45) in an ELISA and with ubiquitin in immunoblotting experiments. Close to 80% of lupus patients possessed ubiquitin antibodies, whereas only 55% of them possessed native DNA antibodies, a marker of SLE. Less than 16% of patients with other rheumatic autoimmune diseases possessed antibodies to ubiquitin. Our results indicate that the combined measurement of antibodies to native DNA and to ubiquitin could appreciably increase the detection of SLE cases (up to 85% in our study). It is suggested that ubiquitin, a heat shock protein, could be involved in antibody formation against ubiquitin-protein conjugates present during cellular injury and that this represents a major characteristic of the autoimmune response in SLE.

Antibodies, Antinuclear↗

Lupus band test in uninvolved oral mucosa in systemic lupus erythematosus.

In 42 patients with systemic lupus erythematosus, clinically normal oral mucosa was investigated with direct immunofluorescence technique for the presence of immunoglobulins G, A and M and complement factor C3 in the mucosal basement membrane zone (the lupus band test, LBT). Punch biopsies were performed in the posterior part of the hard palate (n = 39) or the lower labial mucosa (n = 3). The immunopathological observations were compared with clinical and serological data. The LBT was positive for IgM in 45% of the patients and trace amounts of IgM were found in another 19%. In 7 cases (17%) either IgG, IgA or C3 were found in addition to IgM and these patients all had a severe form of the disease, while the presence of IgM only was not correlated to clinical parameters.

Adult↗

Molecular aspects of systemic lupus erythematosus: murine endogenous retroviral expression.

Systemic lupus erythematosus is an immune-mediated disease in which the etiology is unknown. Full-length (8.4 kb), type C, modified polytropic (Mpmv) retroviral transcripts from the thymus are characteristic of murine lupus. Reciprocal bone marrow transplantation studies determined that this thymic expression maps to the pre-T bone marrow stem cell. In vitro and in vivo oligonucleotide antisense work suggest that type C retroviruses play a role in immune activation. This paper summarizes our studies of endogenous retroviruses in murine lupus.

Animals↗

The emerging role of interferon in human systemic lupus erythematosus.

Recent studies of patients with systemic lupus erythematosus, together with data from lupus-prone mice, suggest that inappropriate activation of type I interferon might have a role in disease pathogenesis. Serum levels of IFN-alpha are elevated in SLE patients, and gene expression profiling of peripheral blood cells shows that most lupus cases demonstrate an upregulation of IFN-responsive genes. Of interest, the IFN gene 'signature' correlates with more severe disease. The available data support a model whereby chromatin-containing immune complexes circulating in the blood of lupus patients stimulate leukocytes to produce IFN, which perpetuates disease. These emerging insights into the connection between IFN and lupus provide a host of new diagnostic and therapeutic opportunities.

Animals↗

Distribution and clinical significance of lupus anticoagulant and anticardiolipin antibody in 349 patients with systemic lupus erythematosus.

Samples from 349 patients with systemic lupus erythematosus (SLE) were tested simultaneously for lupus anticoagulant (LAC) and anticardiolipin antibodies (ACL). LAC was detected in 27.2% of 349 SLE patients by a modified mixing kaolin clotting time. ACL was detected in 34.7% by enzyme-linked immunosorbent assay. Only half of the patients who had LAC or ACL were positive for both of them. In addition, isotypes of ACL in these patients were studied. The IgG isotype was detected in 81.8% of 121 patients, and more than half had only the IgG isotype. When clinical features of patients with LAC or ACL were studied, the incidence of thrombosis, fetal loss, and thrombocytopenia were significantly higher in both groups compared with patients without LAC or ACL. In particular, the patients with both LAC and ACL showed the highest risk of fetal loss (89%) during pregnancy. These results indicate that LAC and ACL are detected in partly different groups of SLE patients, but both of these groups are clinically similar.

Antiphospholipid Syndrome↗

Is there a relationship between lupus erythematosus and lichen planus?

Three patients showing features of both lupus erythematosus and lichen planus are described together with their histological, immunofluorescence and other investigative findings. The similarities between lupus erythematosus and lichen planus are discussed and it is suggested that these may be the result of common pathophysiological pathways.

Adult↗

Asplenia in systemic lupus erythematosus: a simple coincidence?

Two patients with asplenia and systemic lupus erythematosus are described. Both patients presented with unusual symptoms of the disease. The possible association of asplenia, presumably congenital, and systemic lupus erythematosus is discussed.

Antibodies, Antinuclear↗

Systemic lupus erythematosus presenting initially as hydrogen ATPase pump defects of distal renal tubular acidosis.

Tubulointerstitial involvement is well recognized in systemic lupus erythematosus. The tubular dysfunction is usually latent and usually presents after diagnosis of systemic lupus erythematosus. We report a case presenting that she is well previously and initially diagnosed as periodic paralysis of hypokalemia at emergency room and final diagnosis is systemic lupus erythematosus with H+-ATPase pump defect of distal type renal tubular acidosis. Kidney biopsy showed lupus nephritis classified as mesangial proliferative glomerulonephritis WHO class II B. Her renal tubular acidosis was subsided after steroid therapy was administered.

Acidosis, Renal Tubular↗

Cyclosporine-A plus steroids versus steroids alone in the 12-month treatment of systemic lupus erythematosus.

The positive results obtained with cyclosporine-A both in an experimental model and in selected patients with advanced systemic lupus erythematosus support the hypothesis that the drug could be used as a steroid sparer in the earliest stages of active disease. To determine the 12-month clinical efficacy (disease control and steroid sparing), safety, and tolerability of low-dose cyclosporine-A plus steroids versus steroids alone, we designed a multicenter, open, prospective, randomized, pilot study, controlled for parallel groups. The patients were then followed up to month 24. A total of 18 consenting patients with recently diagnosed systemic lupus erythematosus of moderate severity indicated for the use of steroids in acute boluses and subsequently per os were enrolled at two university hospital medical centers. The protocol was based on three 1-g boluses of 6-methylprednisolone followed by cyclosporine-A (<5 mg/kg per day) plus prednisone 0.5-1 mg/kg per day per os, reduced by 5 mg/day every 2 weeks following clinical remission, versus the same doses of oral prednisone alone. The efficacy evaluation was based on a four-point scale (from absent/none to severe) for signs and symptoms of systemic lupus erythematosus and immunoserological parameters. The disease activity index and cumulative prednisone dose per patient were analyzed. Any adverse events were reported. All patients showed a reduction in disease activity index within the 1st month. The results were significantly better in the group with cyclosporine-A plus prednisone throughout month 12 (baseline and 12-month disease activity indexes: 21.3+/-8.6 and 5.0+/-2.5 versus 20.4+/-7.1 and 8.8+/-6.0 in the prednisone group, P<0.05). The 12-month cumulative mean dose of prednisone was significantly lower in the group with both cyclosporine-A plus prednisone (179.4+/-40.1 versus 231.8+/-97.1 mg/kg, P<0.005). No unusual adverse events related to the study drugs have been reported. In particular, renal function and blood pressure monitoring revealed no significant changes from mean baseline values in either group. No disease flares were reported in the group treated with cyclosporine-A plus prednisone during the 12- to 24-month period. Thus cyclosporine-A represents a useful corticosteroid sparer in the maintenance of clinical remission in patients with an early-stage, active systemic lupus erythematosus.

Adolescent↗

Histocompatibility antigens in discoid and systemic lupus erythematosus.

A study of histocompatibility (HLA) antigens in 69 patients with discoid lupus erythematosus (DLE) showed an increased incidence of HLA-B7 and HLA-B8 related to the age at onset and sex of the patient. Young females and males aged 15-39 years at onset were associated with HLA-B7 and females aged over 40 years with HLA-B8. This supports previous studies concerning sex and age specific onset rates in DLE which suggests that there is more than one genotype in this disorder. Female patients with systemic lupus erythematosus (SLE) at all ages of onset showed a significant association with HLA-B8. Female patients, with onset 15-39 years, with either SLE or DLE which has transformed to SLE, show a significant increase in HLA-B8 compared with the females in the same age onset group who have the discoid disease. The presence of HLA-B8 in a young female with DLE may represent a risk factor for the development of the systemic disease.

Adolescent↗

Pregnancy outcome and anti-cardiolipin antibody in women with systemic lupus erythematosus.

Pregnancies in women with systemic lupus erythematosus are recognized to result in excessive fetal morbidity and mortality. Maternal autoantibody status may explain some of these problems. Anti-cardiolipin antibody has been associated with recurrent pregnancy losses in some women with lupus, but the risk of these losses has not been defined. At the University of Pittsburgh between January 1, 1979, and December 31, 1989, an unmatched case-control study design was used to determine whether patients with lupus and anti-cardiolipin antibody (81 cases) were at increased risk for adverse pregnancy outcomes in comparison with lupus patients without the antibody (174 controls). Cases had 98 of 192 (51%) pregnancies with an adverse outcome, while controls had 212 of 494 (43%). The odds ratio for having any adverse pregnancy outcome was 1.40 (95% confidence interval (CI) 0.98-1.98). When pregnancies were classified according to specific adverse outcome types, the frequency of late miscarriages (14-20 weeks gestation) in cases and controls was 8% and 3%, respectively. The odds ratio for late miscarriage was 2.94 (95% CI 1.31-6.60). When pregnancies were stratified by birth number and by occurrence of pregnancy before or after diagnosis, the increased frequency of late miscarriages in cases was noted only in the first pregnancy when the pregnancy occurred before recognized disease. Preterm births (before 38 weeks gestation) were increased in cases compared with controls in pregnancies that occurred after diagnosis for second and third pregnancies. If a case had one previous adverse outcome, the odds ratio for another adverse outcome was 3.00 (95% CI 1.62-5.57). If a case had two previous adverse outcomes, the odds ratio for a third adverse pregnancy outcome was 4.14 (95% CI 1.62-10.58). Thus, a previous adverse pregnancy outcome was the most important risk factor for an adverse outcome in a subsequent pregnancy.

Adult↗