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Background and Purpose: Systemic lupus erythematosus (SLE) is an autoimmune disease in which almost all the organs are involved. Neuropsychiatric SLE is of one of the major concerns in the clinical evaluation of this disease. Routine magnetic resonance imaging (MRI) findings are often nonspecific or negative. In this study, we explored the use of diffusion tensor imaging in assisting with the diagnosis of SLE., Methods: Data from 34 SLE patients (age range, 18-73 years) and 29 age-matched volunteers (age range, 29-64 years) were analyzed. MRI was performed on a 1.5-T clinical MR scanner with a quadrature head coil. The average diffusion constant (D(av)) and diffusion anisotropy maps [fractional anisotropy (FA)] were determined on a pixel-by-pixel basis. Regional diffusion measurements were made by region of interest in the genu and splenium of the corpus callosum (CC), anterior and posterior limb of the internal capsule (IC) and frontal lobe and thalamus. The diffusion distribution was fitted to a triple-Gaussian model. The mean of the brain tissue distribution was determined as a mean diffusion constant for the whole brain (BD(av)). Student's t test was used to determine the diffusion difference between SLE patients and control subjects. The SLE patients were separated into two groups according to their MRI results. A P value lower than .05 was considered to be statistically significant., Results: Twenty of the 34 SLE patients with abnormal MRI results showed findings dominated by nonspecific white matter disease. The BD(av) and D(av) values of the frontal lobe, splenium CC and anterior IC were significantly higher in all SLE patients as compared with the control subjects. The SLE patients with normal MRI results also showed higher BD(av) and D(av) values in the frontal lobe, splenium and anterior and posterior limbs of the IC as compared with the control subjects. There was no significant difference in the D(av) values of the thalamus between the SLE patients and the control subjects. The BD(av) value in the SLE patient group was robustly correlated with the D(av) values of the frontal lobe, splenium and thalamus. These correlations were found to be similarly significant for the SLE patients with normal MRI findings. The diffusion anisotropy measurements showed that splenium CC had the highest FA value in both the control subjects and SLE patients. Overall, SLE patients had lower FA values in the genu and splenium CC as compared with the control subjects. In the group of patients with normal MRI findings, the FA values of the genu and splenium CC as well as the anterior IC were also lower than those in the control subjects. Pearson's correlation statistics revealed robust correlations between the measurements of D(av) and FA values in the SLE patient group., Conclusion: Quantitative diffusion imaging and diffusion anisotropy showed early changes in the brains of the SLE patients. Increased BD(av) and D(av) values of the frontal lobe as well as decreased anisotropy in the genu CC and anterior IC may represent preclinical signs of central nervous system involvement of SLE even when the routine MRI findings are negative or nonspecific. Quantitative diffusion analysis may prove to be useful in detecting the initial brain involvement of SLE and may enable monitoring of early disease progression and treatment efficacy.

New clinical, laboratory and experimental insights, since the 1999 publication of the Sapporo preliminary classification criteria for antiphospholipid syndrome (APS), had been addressed at a workshop in Sydney, Australia, before the Eleventh International Congress on antiphospholipid antibodies. In this document, we appraise the existing evidence on clinical and laboratory features of APS addressed during the forum. Based on this, we propose amendments to the Sapporo criteria. We also provide definitions on features of APS that were not included in the updated criteria.

The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving > or =50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.

Objectives: Systemic lupus erythematosus and antiphospholipid antibody, often identified in patients with systemic lupus erythematosus, are associated with poor pregnancy outcome. This study distinguishes between the effect of each of these factors on gestational outcome and placental pathologic conditions in pregnant patients with systemic lupus erythematosus., Study Design: Thirty-seven pregnancies and 40 placentas from 33 women with systemic lupus erythematosus were studied prospectively., Results: Systemic lupus erythematosus alone, but not systemic lupus erythematosus activity, was associated with increased spontaneous abortions, preterm gestations, and fetal growth restriction. Placental correlates were ischemic-hypoxic change, decidual vasculopathy, decidual and fetal thrombi, chronic villitis, and decreased placental weight. Extensive infarction and fetal death were important antiphospholipid antibody-related findings., Conclusions: Decidual vasculopathy/coagulopathy appears to mediate the antiphospholipid antibody-related and much of the systemic lupus erythematosus-related deleterious effect on the placenta and gestational outcome. The presence of antiphospholipid antibody largely, but not invariably, predicts fetal death. Antiphospholipid antibody-independent chronic villitis may represent a second mechanism of systemic lupus erythematosus-related change.

The antiphospholipid syndrome is now well recognized and is separable from SLE, but better quantitation of both the clinical elements and the serologic definitions is still needed. It is likely for autoimmune but not for infection-induced aPL that the antigen is not phospholipid itself but a complex formed by phospholipid and beta 2 glycoprotein I. There are few treatment trials yet published. Those that are available suggest that antiplatelet therapy or anticoagulant therapy are more valuable than is immunosuppression.

Antibodies directed against phospholipids are highly associated with venous and arterial thrombotic episodes, which are often recurrent. There seems to be a skewed frequency of cerebral and ocular events when the arterial circulation is affected. Other neurologic syndromes, including dementia, migraine, chorea, transverse myelopathy, Guillain Barré syndrome, transient global amnesia, seizures, motor neuron disease, myasthenia gravis, and depression, have also been described in association with aPL. Although some of them (for example, dementia, chorea, seizures, and transient global amnesia) could well be the result of aPL-related cerebrovascular disease, the relationship of aPL to the underlying pathophysiology of these syndromes is less clear. Clues that should lead one to consider evaluating for these antibodies include recurrent thrombosis (especially in young people), recurrent fetal loss, and thrombocytopenia. Associated laboratory abnormalities may include a biologically false-positive VDRL test, abnormal ANA or anti-DNA titers, and a high ESR. If the APTT is positive on routine screening and does not correct with mixing studies, a LA should be highly suspected. More sensitive and specific tests are usually necessary to detect aPL, however. Many in vitro and, more recently, in vivo systems strongly suggest that aPL may be directly implicated in the pathogenesis of thrombosis, as opposed to being markers of a procoagulant state. The management of patients with aPL-associated thrombosis can be difficult. Prospective studies are needed to determine the optimal treatment strategies for this group of patients.

The tests for antiphospholipid antibody are relatively crude but usable. Asymptomatic persons with incidentally discovered antiphospholipid antibody do not need treatment. Those with symptoms are best treated with anticoagulation, but data specifically supporting aspirin, heparin, or warfarin or combinations thereof remain to be generated. High-dose corticosteroid therapy has at best equivocal efficacy and much toxicity and should be used only for lupus activity and not for phenomena of the antiphospholipid antibody syndrome. The roles of low-dose corticosteroid therapy, immunosuppressive agents, and other treatments are unknown.

Antepartum fetal monitoring was initiated at 19 to 26 weeks' gestation in 15 pregnancies: six (five with systemic lupus erythematosus, one with circulating anticoagulant) with a complicated antepartum course (group 1); three, all systemic lupus erythematosus, with a normal antepartum course (group 2); and six normal control pregnancies (group 3). Group 1 all exhibited nonperiodic fetal heart rate decelerations, without the classical appearance of early, late, or variable decelerations, and four of the six had fetal bradycardia. In three group 1 cases, there was no active intervention because of early gestational age, and fetal death occurred at 23, 27, and 27 weeks, respectively. The other three patients in group 1 received betamethasone and were delivered by cesarean section at 28 to 30 weeks. There were no cases of respiratory distress syndrome or neonatal death. Five of the six infants in group 1 were small for gestational age. The nonperiodic fetal heart rate decelerations were absent in both groups 2 and 3 who all had normal fetal outcomes at term. The abnormal finding of women with nonperiodic fetal heart rate decelerations at 20 to 28 weeks may detect the fetus at risk for intrauterine death in pregnancies complicated by systemic lupus erythematosus or circulating anticoagulant. Continued surveillance, steroid induction of lung maturity, and delivery should be considered in these cases.

Effects of therapy, antibody titer, and pregnancy history on pregnancy outcome were evaluated in pregnancies of women with antiphospholipid antibody. Prior fetal death and a high antiphospholipid antibody titer (greater than 40 IgG phospholipid units) contributed independently, in an additive manner, to current fetal loss. Twenty-one pregnancies occurred in asymptomatic women who had both prior fetal death and a high IgG antiphospholipid antibody titer. In this very high-risk group, 9 of 11 (82%) of pregnancies treated with prednisone, 10 to 60 mg/day, ended in fetal death, compared with 5 of 10 (50%) not treated with prednisone (p approximately 0.01, life-table analysis). Of pregnancies treated with aspirin, 80 mg/day, 9 of 14 (64%) treated and 5 of 7 (71%) not treated with prednisone had a fetal death (difference not significant). Prednisone does not improve, and may worsen, current fetal outcome in asymptomatic pregnant women with a high antiphospholipid antibody titer and prior fetal death.

Abnormal SLE mononuclear cell responses to PHA can be corrected by removal of adherent mononuclear cells. The present study demonstrates that cell-free supernatants from allogeneic adherent cell cultures inhibit lymphocyte response and that addition of indomethacin to cultures partly blocks the inhibitory effect of the resulting supernatant. Supernatants from SLE monocyte cultures suppressed allogeneic normal T cell responses by 36% (response in supernatant 33,515 +/- 3814 cpm, media control 51,947 +/- 3173 cpm) but normal monocyte culture supernatants did not suppress (48,384 +/- 4172 vs. 47,477 +/- 3221 cpm). Early (less than 24 hr) addition of indomethacin to monocyte cultures prevented elaboration of inhibitory material. In normals, indomethacin-treated supernatants were strikingly stimulatory (response 178% +/- 24 of control), whereas similarly treated supernatants of SLE monocyte cultures were not stimulatory (response 103% +/- 8 of control). The data indicate that a soluble inhibitor of lymphocyte blastogenesis is produced by SLE monocytes.