Lupus

The objective of this study was to retrospectively evaluate the clinical and immunological effects of anti-B cell treatment in patients with systemic lupus erythematosus (SLE) and mixed connective-tissue disease (MCTD) with autoimmune thrombocytopenia (AITP) refractory to conventional immunosuppressive treatment.

Rituximab (RTX) was added to the ongoing treatment of 16 patients (median age 36 years, range 17–84, all female) with treatment-resistant AITP. Thirteen patients had SLE and three had MCTD. RTX was given intravenously on four occasions during four consecutive weeks at a dose of 375 mg/m². Clinical and laboratory disease activity variables recorded at every follow-up visit were analyzed.

The median disease duration before RTX treatment was nine years (range 0.2–27) and the median post-treatment follow-up time was 28 months (range 3 to 92). Ten patients (63%) were treated repeatedly with RTX during the follow-up period. Complete depletion of B cells was achieved in 94% of cases one month after RTX treatment. A significant increase (p = 0.0001) of platelet counts was seen already after one month (median 58 × 10⁹/ml vs 110 × 10⁹/ml) whereas within three months platelet counts normalized in 10 patients (median 223 × 10⁹/ml). Three patients did not respond to RTX treatment (median platelet count 69 × 10⁹/ml). High titers of anti-platelet antibodies were detected in seven patients before RTX treatment, and the autoantibody titers decreased significantly (p < 0.03) after RTX treatment in six of these patients who also achieved complete remission. A review of the literature revealed 24 articles including 18 case reports, one retrospective cohort study and five prospective studies documenting the outcomes of 65 RTX-treated patients with SLE- or MCTD-related thrombocytopenia with an overall treatment response rate of 80%. In conclusion, these findings indicate that RTX is an additional potent therapeutic treatment option for SLE patients with AITP refractory to conventional immunosuppressive treatment whereas best response may be expected in patients with high titers of anti-platelet antibodies at baseline.

The objective of this paper is to investigate conventional and nonconventional brain magnetic resonance imaging (MRI) findings in systemic lupus erythematosus (SLE) patients with diffuse neuropsychiatric involvement (dNPSLE) compared to healthy controls (HCs).

Twenty-six (26) SLE patients with one or more diffuse NP syndromes related to the central nervous system (CNS) (dNPSLE) and 36 age- and sex-matched HCs were scanned on a 3T MRI using a multimodal imaging approach. Univariate and multivariate analyses were used to determine MRI-specific measure differences between dNPSLE and HCs for lesion burden, tissue-specific atrophy, magnetization transfer ratio (MTR) and diffusion-tensor imaging (DTI) outcomes.

In univariate analyses, dNPSLE patients showed significantly increased T1 lesion number (p = .001) and T1-lesion volume (LV, p = .008) compared to HCs. dNPSLE patients showed decreased whole brain volume (p < .0001), gray matter volume (p < .0001), cortical volume (p < .0001) and increased lateral ventricle volume (p = .004) compared to HCs. dNPSLE patients had increased axial diffusivity (AD) of NAWM (p = .008) and NA brain tissue (p = .017) compared to HCs. In the multivariate regression analysis, decreased cortical volume was associated with SLE (R²= 0.59, p < .0001).

This study shows that cortical and central atrophy are associated with SLE patients with diffuse CNS syndromes. Microscopic tissue injury in the NAWM on AD DTI measures in SLE patients indicates a predominant reduction of axonal density.

One-hundred and twenty-five adult Caucasian and Hispanic lupus patients participated in this study. Demographic data, patient- and physician-reported disease activity, as well as psychological functioning, were collected. Fatigue, pain, and vitality were measured using visual analogue scales as well as a subscale of the SF-36 questionnaire. Linear and hierarchical regression analyses were conducted. In the regression analysis, ethnicity was entered at the first step, followed by age, income and education at step 2, pain and disease activity measures at step 3, and psychological measurements at step 4.

In the linear regression analysis, Caucasians reported more fatigue. Fatigue positively correlated with income, education, pain, patient-reported disease activity, helplessness, and depression, and negatively with internality, and the energy analysis mirrored the results of the fatigue analysis. In the first regression analysis, fatigue was the dependent variable. At step 1, Caucasians reported more fatigue. At step 2, no other demographic variables were significant. At step 3, pain and disease activity measures were significant when entered as a block; however, pain independently explained a large amount of variance. At step 4, psychological factors were significant as a block, with depression being the strongest predictor. In the second analysis, energy was the dependent variable. At step 1, Hispanics reported more energy. At step 2, demographic variables were not significant. At step 3, pain and disease activity were significant when entered as a block; however, only pain uniquely predicted energy. At step 4, psychological factors were significant as a block, with depression as the major contributor.

Both pain and depression were found to be strong predictors of fatigue, and negatively correlated with energy. Disease activity did not appear to play a significant role in lupus fatigue. These findings support the importance of managing depression and pain in order to reduce fatigue in patients with systemic lupus erythematosus.

The objective of this article is to investigate clinical presentations and outcomes of systemic lupus erythematosus (SLE) patients with infection admitted to the intensive care unit (ICU).

SLE patients with infection, SLE patients with noninfectious causes, and non-SLE patients with infection were identified from the Cooper University Hospital Project IMPACT database between 2002 and 2010. We examined demographic data, APACHE II scores, physiologic data, laboratory data, length of stay in the ICU and hospital, and mortality of the three groups.

Twenty-five SLE patients with infection, 45 SLE patients with noninfectious causes, and 1466 non-SLE patients with infection were included in the study. SLE patients with infection had higher APACHE II scores, higher maximum temperature, higher minimum and maximum heart rate (HR), lower minimum and maximum systolic blood pressure (SBP), and longer ICU length of stay in comparison to SLE patients with noninfectious causes. There were no statistical differences in white blood cell (WBC) count. SLE patients with infection had a higher mortality compared to SLE patients with noninfectious causes. There was no difference in mortality between SLE patients with infection and non-SLE patients with infection.

SLE patients with infection in the ICU had a higher mortality and a higher APACHE II score compared to SLE patients with noninfectious causes in the ICU. Their physiologic signs including temperature, HR, and SBP were more reflective of infection than their WBC count.

Organ damage in systemic lupus erythematosus (SLE) patients is highly associated with the use of corticosteroids. Doses of prednisone below 6 mg daily are associated with reduced organ damage. We now report on the largest prospective cohort study of predictors of prednisone tapering in SLE patients.

A total of 866 SLE patients (91% female, 50% Caucasian, 43% African-American, mean age 43 years) who consented for the Hopkins Lupus Cohort from 1987 through 2009 were included. The analysis was based on patient visits in which the previously prescribed dose of prednisone was 5 mg/day. We then examined the proportion of times the patient’s dose was reduced to below 5 mg/day (“tapering”). Among those patients who tapered and were followed for at least one year thereafter, we examined the proportion whose prednisone dose remained below 5 mg/day for at least one year (“Successful tapering”). Rates of tapering and successful tapering were calculated for patient subsets based on demographic and clinical characteristics.

The analyses showed that Caucasians, younger patients, patients with a higher level of education, lower disease activity, or absence of urine protein were more likely to have a prednisone taper. However, successful tapering was not dependent on age, ethnicity, or education. As expected, successful tapering was more frequent in those with lower disease activity. Successful tapering was achieved more often after the year 2000.

Our study suggests that successful tapering of prednisone below 5 mg has increased since the year 2000, which may reflect the greater knowledge of the long-term harm of even low-dose chronic corticosteroid use. Caucasians, younger age, higher level of education, and absence of proteinuria predicted tapering, but not successful tapering. Ongoing cutaneous or arthritis activity were associated with unsuccessful tapering. Lack of disease activity, as expected, was the only major clinical variable that significantly predicted successful tapering.

Depressive symptoms are common in adolescence and young adulthood; however, their prevalence in childhood-onset systemic lupus erythematosus (cSLE) is unknown.

The objective of this study was to examine the prevalence of depressive symptoms and their association with disease characteristics in children, adolescents, and young adults with cSLE.

A cross-sectional sample of patients with cSLE between 10 to 24 years old completed standardized depression inventories. Demographics and disease characteristics were collected.

Total depression inventory scores reported were below standard cut-off values for depression. However, 26% (10/38) of children and adolescents, and 44% (seven of 16) of young adults had scores at or above established cut-offs for elevated depression symptoms. Physical symptoms of depression were endorsed most frequently. There were no differences in depressive symptoms by disease characteristics including disease duration, health-related quality of life inventory scores, antiphospholipid antibody status, and a history of renal involvement or neuropsychiatric SLE (NPSLE). However, two patients had a history of depression as an NPSLE manifestation of their SLE. In the children and adolescents, prednisone dose was associated with negative self-esteem (r = 0.37, p = 0.04) and somatic depressive symptoms (r = 0.39, p = 0.02), but we did not observe a significant association in the young adults.

Depressive symptoms in cSLE are frequent, although similar to the high prevalence rates in the general population. Physical symptoms are most frequently endorsed. Further study will determine if serial evaluations are recommended for early detection in this at-risk population.

Plasma mycophenolic acid (MPA) concentrations may predict therapeutic response in active lupus nephritis (LN). We determined the efficacy and safety of a concentration-controlled MPA regime in the treatment of severely active LN.

In this prospective study, 19 biopsy-proven class III/IV LN patients were treated with mycophenolate mofetil (MMF) for 48 weeks. The MMF dosage was based on maximal plasma MPA concentration at 1-hour post dose (MPA-C1). All patients had plasma MPA-C1 levels monitored weekly until achieving the targeted level of >13 mg/L. A low-dose steroid protocol was started at 0.5 mg/kg/day and rapidly tapered to 5 mg/day. Therapeutic response was evaluated at week 24 and week 48. MPA area-under-the curve (MPA-AUC_0–12h) was measured at week 12 to verify the optimum dosage.

No death or end-stage kidney disease occurred in this study. Seventeen patients (89%) responded to therapy at week 24 with four (21%) patients having complete response. There was no renal relapse at week 48 and four more patients had converted from partial response to complete response. Seventy eight percent of patients achieved the recommended MPA-AUC_0–12h level. No association between plasma MPA concentrations and adverse reactions or infections was found.

MPA-C1 may be a practical monitoring of MPA levels in patients with LN. It is convenient to monitor and may facilitate an optimum estimate of MPA exposure.