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PubMed1994

Nodular cutaneous lupus mucinosis associated with atrophie blanche-like lesions in a patient with systemic lupus erythematosus.

BACKGROUND: Multiple, pale, atrophic depressions surrounded by erythema developed on nodular cutaneous mucinosis lesions in a patient with systemic lupus erythematosus. OBSERVATIONS: A 22-year-old man developed multiple nodular erythematous lesions on the upper arms, back, and chest during the course of systemic lupus erythematosus. Histologically, these nodular lesions were diagnosed as lupus mucinosis. Three years later, the patient began to have atrophic depressed lesions on several nodular mucinosis lesions. These lesions did not develop on normal appearing skin. A biopsy specimen from one of these lesions showed occlusion of blood vessels with thickening of their walls and perivascular dense lymphocytic infiltration. No leukocytoclastic vasculitis was found. Hyaline degeneration was present in some parts of the fatty tissue. CONCLUSION: The atrophic depressed lesions were atrophie blanche-like and induced by the vascular occlusion. Since these lesions developed only on the lupus mucinosis lesions, mucin deposition and vascular changes may be closely related.

Adult↗

PubMed1990

Platelet autoantibodies detected by immunoblotting in systemic lupus erythematosus: association with the lupus anticoagulant, and with history of thrombosis and thrombocytopenia.

71 patients with systemic lupus erythematosus (SLE) were studied for the occurrence of platelet antibodies by immunoblotting. Binding of IgG antibodies to platelet protein antigens was observed in 39 of the 71 patients. The most frequently detected and exceptionally strongly reacting antibodies were directed against platelet protein antigens with an approximate molecular weight of 65 kDa under nonreducing conditions. These antibodies were autoreactive and, when followed, they usually persisted. Interestingly, in this group of well-defined SLE patients, platelet antibodies against the most common targets (65 kDa) were significantly associated with the lupus anticoagulant, a history of thrombocytopenia and thrombosis, particularly with arterial occlusions. The lupus anticoagulant, on the other hand, correlated significantly only with venous thrombosis. In addition to the lupus anticoagulant, platelet antibodies against this unknown platelet protein may thus be a marker of a higher risk of thrombosis in SLE patients.

Adolescent↗

PubMed1983

Gangrene developing after minor surgery in a patient with undiagnosed systemic lupus erythematosus and lupus anticoagulant.

We report a case of progressive peripheral ischaemia and gangrene as a presenting feature of systemic lupus erythematosus. It developed in a previously asymptomatic 40-year-old woman following minor surgery to her toe. Eventually she required a below-knee amputation and despite systemic corticosteroids continued to deteriorate, presenting later with signs of systemic intravascular thromboses. Histopathology and immunofluorescence on vessels repeatedly failed to demonstrate any evidence for vasculitis. A full coagulation screen confirmed the presence of 'lupus' anticoagulant. A plasma exchange was performed to remove circulating immunoglobins and she made a rapid and sustained recovery. Peripheral gangrene has not previously been described in association with lupus anticoagulant. We would suggest that in all cases of systemic thrombosis or unexplained peripheral vascular ischaemia lupus anticoagulant should be considered.

Adult↗

PubMed1992

Prospective study of fluctuations of lupus anticoagulant activity and anticardiolipin antibody titre in patients with systemic lupus erythematosus.

Fluctuations of lupus anticoagulant activity and anticardiolipin antibody titres were studied in 53 patients with systemic lupus erythematosus (SLE). The median study time was 26 months with a median number of 12 samples. Lupus anticoagulant was measured by the kaolin clotting time (KCT) and dilute Russell viper venom time (dRVVT) assays; anticardiolipin antibodies were assayed by an enzyme linked immunosorbent assay (ELISA). Normal and increased KCTs or dRVVTs were seen during follow up in 13 and 12 patients, respectively. IgG anticardiolipin antibodies changed from negative to positive or positive to negative in 26 patients and IgM anticardiolipin antibodies in 16 patients. Disease activity and treatment with prednisone could account for these fluctuations in the kaolin clotting time (KCT) in 7 of 13 patients and in the dRVVT in 2 of 12 patients. Whole group analysis showed that the KCT, dRVVT, and IgM anticardiolipin antibodies were not associated with disease activity, in contrast with IgG anticardiolipin antibodies. During treatment with prednisone normal KCT and dRVVT results were obtained more easily than normal anticardiolipin antibody levels. It is recommended that lupus patients should not be classified as antiphospholipid antibody positive or negative on the basis of only one sample.

Adolescent↗

PubMed1992

Methods for detecting lupus anticoagulants and their relation to thrombosis and miscarriage in patients with systemic lupus erythematosus.

AIMS: To examine the sensitivity and specificity to past thrombotic events of four different coagulation tests, which screen for lupus anticoagulant (LA), and of anticardiolipin antibodies in patients with systemic lupus erythematosus. METHODS: Fifty three consecutive patients with systemic lupus erythematosus were studied of whom three males and 21 females, aged 21-60 years, had a history of venous and arterial thrombosis, or miscarriage, or both. Activated partial thromboplastin time (aPTT), dilute Russell's viper venom time (dRVVT), kaolin clotting time (KCT), dilute aPTT and the circulating titre of anticardiolipin antibodies were investigated in the two groups of patients and in 20 healthy control subjects. RESULTS: The prolonged dilute aPTT was more sensitive to thromboses or miscarriages, or both than dRVVT (p less than 0.05), KCT (p less than 0.01), and aPTT (p less than 0.001). No significant differences in specificity were found among aPTT (100%), dRVVT (93%), KCT (93%) and dilute aPTT (86.2%); but aPTT and dRVVT were significantly more specific (p less than 0.01, p less than 0.05, respectively) than anticardiolipin antibodies. CONCLUSIONS: The study shows a strong association between lupus anticoagulant and thrombosis when a very sensitive test such as the dilute aPTT is used. The combination of this assay with a very specific test such as dRVVT might enable patients with SLE at high risk of thrombosis to be identified.

Abortion, Spontaneous↗

PubMed2006

Transforming growth factor beta 1 in children with systemic lupus erythematosus: a possible relation with clinical presentation of lupus nephritis.

Plasma and urinary (latent and active) TGF-beta1 levels were assessed in 32 children with active lupus and compared to 15 healthy controls of matched age and sex. Plasma latent and active TGF-beta1 levels in children with active disease were significantly lower than controls (P = 0.004 and P < 0.001 respectively). Plasma active TGF-beta1 correlated negatively with Systemic Lupus Erythematosus Disease Activity Index (r = -0.38, P = 0.03). On the contrary, urinary latent and active TGF-beta1 levels in children with active disease were significantly higher than controls (P < 0.001 and P = 0.003 respectively). Urinary active TGF-beta1 levels correlated positively with Anti-ds DNA titre (r = 0.42, P = 0.015) and negatively with serum C3 levels (r = -0.48, P = 0.005). Patients with symptomatic nephritis had significantly elevated urinary active TGF-beta1 levels in comparison to those with silent nephritis (P = 0.008). From this data we conclude that lowered plasma TGF-beta1 levels may be a feature of systemic immune dysfunction in children with active lupus while increased renal production of active TGF-beta1 seems to have a role in the clinical presentation of lupus nephritis.

Adolescent↗

PubMed1993

Disseminated intravascular coagulation in a patient with systemic lupus erythematosus with lupus anticoagulant.

A 19-year-old female patient with systemic lupus erythematosus (SLE) who had lupus anticoagulant (LA) and concurrently developed disseminated intravascular coagulation (DIC) during an exacerbation of "central nervous system (CNS) lupus". Since no other indications or causes for DIC could be demonstrated, she was treated with prednisolone and anticoagulants, which rapidly alleviated her DIC condition as well as "CNS lupus". Although abnormalities of coagulation are frequently reported in SLE patients, DIC rarely occurs in patients with SLE without associated complications. A review of the pathogenesis of DIC in patients with SLE is discussed.

Adolescent↗

PubMed1995

Pulmonary thromboembolic hypertension in systemic lupus erythematosus with lupus anticoagulant: histopathological analysis of localization and distribution of thromboemboli in pulmonary vasculature.

We report a systemic lupus erythematosus patient with lupus anticoagulant accompanied by pulmonary thromboembolic hypertension possibly due to large vegetation of the tricuspid valve of the heart. Histopathological analysis of localization and distribution of thromboemboli in pulmonary vasculature revealed that the organized thromboembolic occlusion of multiple blood vessels (99 out of 222 arteries), might be responsible for the pulmonary hypertension both in quality and quantity. The contribution of lupus anticoagulant to the pathogenesis of Libman-Sacks endocarditis in systemic lupus erythematosus, and its possible relationship to pulmonary thromboembolic hypertension are discussed.

Adult↗

PubMed2003

Cytomegalovirus colitis following immunosuppressive therapy for lupus peritonitis and lupus nephritis.

We report a woman with lupus nephritis complicated with lupus peritonitis and cytomegalovirus (CMV) colitis. Diagnosis of lupus peritonitis was made by abdominal computed tomography scan, colonoscopy, and ascitic fluid analysis. Steroid and cyclophosphamide therapy resulted in the improvement of severe lupus nephritis and peritonitis. Thereafter, she developed multiple colonic ulcers as diagnosed by colonoscopy and positive CMV antigenemia assay. Treatment with ganciclovir resulted in the disappearance of colonic lesions. The low cluster of differentiation (CD)4+ lymphocyte count (41/mm3) suggested that the cell-mediated immunity of this patient was comparable to that seen in patients with acquired immunodeficiency syndrome (AIDS).

Adult↗

PubMed2005

Genetic dissection of the murine lupus susceptibility locus Sle2: contributions to increased peritoneal B-1a cells and lupus nephritis map to different loci.

Lupus pathogenesis in the NZM2410 mouse model results from the expression of multiple interacting susceptibility loci. Sle2 on chromosome 4 was significantly linked to glomerulonephritis in a linkage analysis of a NZM2410 x B6 cross. Yet, Sle2 expression alone on a C57BL/6 background did not result in any clinical manifestation, but in an abnormal B cell development, including the accumulation of B-1a cells in the peritoneal cavity and spleen. Analysis of B6.Sle2 congenic recombinants showed that at least three independent loci, New Zealand White-derived Sle2a and Sle2b, and New Zealand Black-derived Sle2c, contribute to an elevated number of B-1a cells, with Sle2c contribution being the strongest of the three. To determine the contribution of these three Sle2 loci to lupus pathogenesis, we used a mapping by genetic interaction strategy, in which we bred them to B6.Sle1.Sle3 mice. We then compared the phenotypes of these triple congenic mice with that of previously characterized B6.Sle1.Sle2.Sle3, which express the entire Sle2 interval in combination with Sle1 and Sle3. Sle2a and Sle2b, but not Sle2c, contributed significantly to lupus pathogenesis in terms of survival rate, lymphocytic expansion, and kidney pathology. These results show that the Sle2 locus contains several loci affecting B cell development, with only the two NZW-derived loci having the least effect of B-1a cell accumulation significantly contributing to lupus pathogenesis.

Animals↗

PubMed2001

Calcifying lupus panniculitis in a patient with subacute cutaneous lupus erythematosus: response to diltiazem and chloroquine.

Lupus panniculitis has been reported to occur with a frequency of 2-3% in patients with lupus erythematosus (LE). It is most often reported in association with lesions of discoid LE. We describe a patient with subacute cutaneous LE who developed calcified nodules that were histopathologically consistent with lupus panniculitis. She was treated with a combination of chloroquine and diltiazem with a good therapeutic response. The addition of diltiazem may be beneficial in patients with calcified nodules of lupus panniculitis.

Adult↗

PubMed1988

Successful pregnancy in systemic lupus erythematosus with an untreated lupus anticoagulant.

A lupus anticoagulant in pregnancy has almost always been associated with an adverse outcome. In previous reports of successful pregnancy in patients with a lupus anticoagulant, whether treated or untreated, all were complicated by premature delivery, and many were complicated by preeclampsia or placental insufficiency. Four patients with systemic lupus erythematosus and an untreated lupus anticoagulant, had an uncomplicated pregnancy that resulted in a live birth at term. The circulating anticoagulant persisted throughout the pregnancy in three patients, and disappeared spontaneously during pregnancy in the fourth patient. As pregnancy outcome is unpredictable, the best treatment of these patients remains to be determined by controlled studies.

Adult↗

PubMed1995

[Lupus pregnancy, its effect on the course of lupus nephritis and the evaluation of fetal loss frequency].

The subject of analysis were data concerning the 101 pregnancies in 43 patients with systemic lupus erythematodes observed in years 1965-1990. The evaluation proved that pregnancy does not deteriorate the course of lupus nephritis that is in the remission before the conception. In lupus patients the risk of fetal loss and stillbirth is high, especially in the presence of anticardiolipin antibodies. The course of active lupus occurring during pregnancy is frequently severe and its effect on the pregnancy is very harmful.

Antibodies, Anticardiolipin↗

PubMed1989

Synovial fluid characteristics and the lupus erythematosus cell phenomenon in drug-induced lupus. Findings in three patients and review of pertinent literature.

The characteristics of synovial fluid obtained from 3 patients with drug-induced lupus erythematosus are described. Two patients had "inflammatory" counts of synovial leukocytes, in the range of 2,500-39,000/mm3, with mononuclear predominance in 1 patient and neutrophil predominance in the other. The third patient had "noninflammatory" fluid, with mononuclear predominance. Lupus erythematosus cells formed in vivo were observed in the synovial fluid of 2 of the patients. Biopsy of the synovium of 1 patient showed nonspecific chronic inflammatory changes. Our findings in these patients with drug-induced lupus are indistinguishable from those previously described in patients with idiopathic lupus erythematosus.

Adult↗

PubMed2003

European Consensus Lupus Activity Measurement is sensitive to change in disease activity in childhood-onset systemic lupus erythematosus.

OBJECTIVES: To evaluate the European Consensus Lupus Activity Measurement (ECLAM) for responsiveness to change in disease activity when used in childhood-onset systemic lupus erythematosus (cSLE). To confirm the construct validity and to characterize the measurement properties of the ECLAM by assessing its ability to predict damage and steroid requirements. METHODS: The disease courses of 66 newly diagnosed cSLE patients were reviewed. The ECLAM and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were scored for all clinic visits and hospitalizations. Damage was assessed at the end of the followup period using the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index. Disease activity at the time of diagnosis, 6 months after diagnosis, at the time of first flare, and 6 months after first flare was used to estimate responsiveness of the measures. Responsiveness was measured by the effect size, the effect size index, the standardized response mean, and the relative efficiency index (REI). The measurement properties of the ECLAM and SLEDAI over time were examined by comparing the ability of both measures to predict damage and oral steroid requirement. RESULTS: The ECLAM and SLEDAI are both responsive to change in disease activity irrespective of the statistic used. The ECLAM is more sensitive than the SLEDAI using the REI (all >1.9). Cumulative disease activity as measured by the SLEDAI or the ECLAM are important predictors of damage. There are no statistically important differences between the 2 measures with regard to their ability to predict steroid requirements. CONCLUSIONS: The ECLAM has construct validity in cSLE and, like the SLEDAI, is highly sensitive to clinically important change in disease activity. The ECLAM may be more responsive. The quantitative properties of the 2 measures are very similar. The SLEDAI likely remains the preferable disease activity measure for cSLE given its overall measurement properties and ease of use.

Administration, Oral↗

PubMed2004

The lupus anticoagulant is a risk factor for myocardial infarction (but not atherosclerosis): Hopkins Lupus Cohort.

UNLABELLED: Antiphospholipid antibodies, both anticardiolipin and lupus anticoagulant, are common in SLE. We asked, in a prospective cohort, whether these antibodies are predictive of atherosclerosis and/or coronary artery disease. METHODS: Three hundred eighty patients, 92% female, 49% Caucasian, 51% African-American, mean age 46.4+/-12.3 years are followed quarterly, with assessment of both anticardiolipin and lupus anticoagulant (dRVVT). These patients underwent both helical CT and carotid duplex. RESULTS: Both the lupus anticoagulant and anticardiolipin are predictive of later venous or arterial thrombosis. Twenty years after diagnosis, SLE patients with the lupus anticoagulant (LA) have a 50% chance of a venous thrombotic event. Myocardial infarction occurs significantly more often in those with LA 22% vs. 9%, p=0.04. Neither anticardiolipin nor LA are associated with carotid IMT, carotid plaque, nor coronary calcium by helical CT. In aCL positive patients carotid IMT was 0.57+/-0.01 vs. 0.58+/-0.01 in aCL negative patients (p=NS); carotid plaque 0.47+/-0.13 vs. 0.32+/-0.10 (p=NS); and coronary calcium 65.4+/-37.4 vs. 65.4+/-30.2 (p=NS). In LA positive patients, carotid IMT was 0.59+/-0.03 vs. 0.59+/-0.02 in LA negative patients (p=NS); carotid plaque 0.07+/-0.02 (SE) vs. 0.80+/-0.02 (SE) (p=0.06); and coronary calcium 28.1+/-3.7 (SE) vs. 85.7+/-2.6 (SE) (p=NS). CONCLUSION: Antiphospholipid antibodies are not associated with subclinical atherosclerosis (carotid IMR, carotid plaque, helical CT coronary calcium), but are associated with actual thrombotic sequelae (myocardial infarction).

Adult↗

PubMed2003

Health-related quality of life in patients with systemic lupus erythematosus: development and validation of a lupus specific symptom checklist.

Reliable and sensitive measures are needed to evaluate the quality of life (QoL) in patients with systemic lupus erythematosus (SLE). No lupus specific questionnaires are available. This study describes the development and validation of a disease-specific questionnaire for lupus patients, which assesses the presence and burden of 38 disease- and treatment-related symptoms: the SLE Symptom Checklist (SSC). Reliability and reproducibility were tested in respectively 87 and 28 stable SLE patients. The internal consistency (Cronbach's alpha coefficients 0.89) and test-retest reliability (Pearson product-moment correlation coefficient between 0.67 and 0.87) were satisfactory. Concurrent validity was supported by significant, but moderate correlations with other measures of subjective well-being and functional status. Responsiveness was measured in 17 patients with lupus nephritis treated with cyclophosphamide, at start of therapy and 1 year thereafter. A significant change in number of symptoms and total distress level was found. It is concluded that the SSC has satisfactory psychometric properties and appears suitable for both clinical and research purposes.

Female↗

PubMed2003

X-linked immunodeficient mice spontaneously produce lupus-related anti-RNA helicase A autoantibodies, but are resistant to pristane-induced lupus.

Murine lupus can occur spontaneously or be induced by hydrocarbons, such as pristane. Spontaneous disease in MRL and NZB/W F1 mice is suppressed by the xid (X-linked immunodeficiency) mutation, which greatly diminishes T cell-independent type 2 responses as well as the number of peritoneal B1 cells. The present study asked whether lupus induced by i.p. injection of pristane likewise is inhibited by the xid defect. Male CBA/N (xid) mice were refractory to the induction of autoantibodies by pristane, whereas 23% of pristane-treated male CBA/CaJ controls produced anti-nRNP/Sm, -Su and/or -OJ (isoleucyl tRNA synthetase) antibodies. Unexpectedly, 43% (12 of 28) of the xid mice spontaneously produced anti-nuclear antibodies that proved highly specific for the lupus antigen RNA helicase A (RHA). Strikingly, this specificity was absent in CBA/CaJ mice (none of 51). Moreover, pristane treatment suppressed the production of anti-RHA antibodies when administered prior to the onset of autoantibody production, but enhanced anti-RHA levels when given after the onset of autoantibody production, suggesting that pristane interferes with anti-RHA production at an early stage. Large amounts of IgG1 anti-RHA autoantibodies were detected in the sera of xid mice, whereas pristane-induced anti-nRNP/Sm and -Su autoantibodies were almost exclusively IgG2a. Cytokine production within the peritoneal cavity reflected the predominant isotypes: IL-12 and IFN-gamma predominated in pristane-treated mice, whereas IL-4 and IL-6 were more predominant in untreated xid mice. The spontaneous production of anti-RHA by xid mice and its suppression by pristane treatment at the level of autoantibody induction supports the idea that lupus autoantibodies may be generated through a variety of mechanisms.

Agammaglobulinemia↗