Lupus

The association of isolated congenital heart block (CHB) with maternal autoantibodies to SSA/Ro and SSB/La ribonucleoproteins is approaching the predictable, even in mothers who are completely asymptomatic. Indeed, this model of passively acquired autoimmunity offers an exceptional opportunity to examine the effector arm of immunity and define the pathogenicity of an autoantibody in mediating tissue injury. The study of CHB exemplifies not only translational research, which inherently draws upon clinical observations and explores them in the laboratory, but “integrational” research which attempts to fit critical clinical and basic observations together, even those seemingly at odds. The spectrum of conduction abnormalities includes second and third-degree block, but injury can extend to the myocardium and endocardium, in rare cases without AV nodal dysfunction. The rarity of disease continues to drive the search for factors (fetal and environmental) that might amplify the effects of the maternal autoantibodies. The identification of exaggerated apoptosis, macrophage/myfibroblast crosstalk, TGFβ expression, and extensive fibrosis in the conducting system and in some cases surrounding myocardium in fetuses dying with CHB, provide in vivo support for several parallel lines of in vitro investigation. Specifically, the consideration of exaggerated apoptosis as the initial link between maternal antibody and tissue injury led to the observation that cardiocytes are capable of phagocytosing autologous apoptotic cardiocytes and anti-Ro/La antibodies inhibit this function. Recognizing that this perturbation of physiologic efferocytosis might divert uptake to professional FcγR-bearing phagocytes fits well with experiments demonstrating macrophage secretion of pro-inflammatory and fibrosing cytokines when coincubated with apoptotic cardiocytes bound by Ro/La antibodies. While CHB is rare, its study should set precedent for defining the role of autoantibodies in driving end organ disease. Lupus (2008) 17, 86—90.

The outcome, quality of life and prognosis of lupus patients can be enhanced with close follow up and coordination between the individual's primary care physician and rheumatologist. Rheumatologists usually do not act as primary care physicians and leave health care maintenance to practitioners who need to be reminded to screen for various co-morbidities associated with inflammation and complications of medication. Rheumatologists need to take the responsibility to ensure that their lupus patients have optimal primary care access which includes a working relationship with them. Lupus (2008) 17, 91—92.

Neuropsychiatric (NP) events are severe manifestations of systemic lupus erythematosus (SLE) and relate to poor outcome. The aims of this study are to investigate the NP manifestations of SLE and to identify the predictive factors for clinical outcome. There was a retrospective review of 240 hospital patients with primary NP events of SLE (NPSLE) from 1990 to 2004. Neuropsychiatric manifestations, SLE disease activity index (SLEDAI) score, System lupus International Collaborating Clinic/American College of Rheumatology Damage Index (SLICC/ACR-DI) score, magnetic resonance imaging (MRI) findings, treatment and mortality rate were included for analysis. From this group of patients, 15 NP syndromes were identified. The most frequent manifestation was headache, followed by seizure. The mean SLEDAI and SLICC/ACR-DI scores were 19.9 ± 6.9 and 3.5 ± 1.6, respectively. Abnormal MRI features were found in 67% (61/91) patients. At least one intrathecal (IT) injection of methotrexate (MTX) plus dexamethasone (DXM) was administered to 109 (45.4%) patients. High dose (1 g) intravenous methylprednisolone pulse therapy (IVMP) was administered to 167 (69.5%) patients. Multifactor analysis revealed that high SLICC/ACR-DI scores and sets of concurrent NP symptoms were independently associated with poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM were protective factors against poor outcome. From our data, NPSLE is heterogeneous and is usually associated with high disease activity and organ damage scores. High SLICC/ACR-DI score and having more than two sets of NP symptoms are the predictors for poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM can improve the prognosis. Lupus (2008) 17, 93—99.

The present aim is to investigate the relationships between aerobic capacity and disease activity, organ damage, health-related quality of life (HRQL) and physical activity in 34 women with systemic lupus erythematosus (SLE) with low-to-moderate disease activity and organ damage. Mean age was 51 (SD 10) years, disease duration 17 (SD 11) years. Aerobic capacity (maximal oxygen uptake/VO₂ max) was measured with a bicycle ergometer exercise test. Overall disease activity was assessed with Systemic Lupus Activity Measure (SLAM) and the modified Systemic Lupus Erythematosus-Disease Activity Index (modified SLE-DAI), overall organ damage with the Systemic Lupus International Collaboration Clinics/American College of Rheumatology-Damage Index, [SLICC/(ACR)-DI], HRQL with the 36-item Short-form health-survey (SF-36) and physical activity with a self-assessed question. The women who were low-to-moderately physically active had 89—92% (P ≤ 0.001) of VO₂ max predicted for sedentary women. Maximal oxygen uptake (L/min, mL/min/kg) correlated to SF-36 physical function (r_s = 0.49, r_s = 0.72) (P ≤ 0.01), but not (r_s ≤ 0.25) to other HRQL scales, overall disease activity or organ damage or physical activity. The correlation between aerobic capacity and physical function and the absence of correlation between aerobic capacity and physical activity, suggest a possible disease-related factor behind the low aerobic capacity. However, with no correlation between aerobic capacity and overall disease activity and organ damage, low physical activity may contribute to the low aerobic capacity in our sample. Lupus (2008) 17, 100—104.

To determine the frequency of carotid plaque and intima-media thickness (IMT) in patients with systemic lupus erythematosus (SLE) and their association with risk factors in a Brazilian university setting. Carotid plaque and IMT were identified and measured by ultrasonography. Traditional risk factors and lupus-related factors were analysed. One hundred and seventy-two patients (women = 96%, age = 38 ± 11 years) were evaluated. The frequency of carotid plaque was 9.3%. The median (IR) IMT was 0.60 mm (0.54—0.71 mm). Age, family history (FH) of premature coronary disease, low-density cholesterol (LDL-c) >100 mg/dL, hypertriglyceridemia, diabetes, hypertension, smoking, postmenopause, number of risk factors, Framingham risk score, age at diagnosis, duration of lupus, mucocutaneous manifestations and duration of prednisone use were associated with plaque (P < 0.05), univariate analysis. Nephritis, immunosuppressive therapy, intravenous methylprednisolone and a higher average daily dose of prednisone were associated with the absence of plaque. Independent predictors of plaque were smoking (P = 0.004), LDL-c >100 mg/dL (P = 0.044), Framingham score (P = 0.006) and absence of immunosuppressive therapy (P = 0.032). There was an independent correlation between IMT and age (P < 0.001) and duration of prednisone use (P = 0.020). Subclinical atherosclerosis was associated with traditional risk and SLE-related factors, especially the absence of immunosuppressive therapy. The present study suggests that the levels of LDL-c should be kept under 100mg/dL in lupus. Lupus (2008) 17, 105—113.

Despite the increased prevalence of cardiovascular disease in patients with systemic lupus erythematosus (SLE), little is known about the role of high sensitivity C-reactive protein (hsCRP) or whether ethnicity, gender, anthropometric measures and treatment can alter hsCRP levels. We evaluated the effects of treatment and demographic, anthropometric and socio-economic variables on hsCRP levels in SLE. High sensitivity C-reactive protein levels were measured using an immunoturbidimetric assay in 610 patients from the Hopkins Lupus Cohort, who were followed-up regularly. In stepwise multiple regression analyses, body mass index (BMI) [odds ratio (OR) 1.72, 95% confidence interval (CI) 1.34—2.20, P < 0.001], African-American ethnicity (OR 1.97, 95% CI 1.22—3.19, P < 0.01), education (OR 0.60, 95% CI 0.42—0.86, P < 0.01), statin use (OR 0.38, 95% CI 0.18—0.82, P < 0.05), estrogen use (OR 3.65, 95% CI 1.19—11.22, P < 0.05), SLE Disease Activity Index score (OR 1.76, 95% CI 1.09—2.87, P < 0.05) and cumulative prednisone dose (OR 1.27, 95% CI 1.01—1.60, P < 0.05) were significant predictors of hsCRP levels. These findings suggest that hsCRP levels should be adjusted for BMI, ethnicity, education level, disease activity and medications when conducting cardiovascular risk assessment in patients with lupus. Lupus (2008) 17, 114—123.

Interleukin-18 (IL-18) is associated with chronic inflammation, autoimmune diseases and various cancers and infectious diseases. An IL-18 genetic A/C polymorphism at coding position 105 (rs549908) has been linked with asthma and rheumatoid arthritis. We tested a hypothesis that the IL-18 genetic polymorphism confers systemic lupus erythematosus (SLE) susceptibility. Study participants were Taiwanese SLE patients and a healthy control group. Our results indicate (1) a significantly higher A allele frequency in SLE patients (P = 0.003; OR = 1.97; 95% CI = 1.26—3.08) and (2) a significantly higher A allele frequency in SLE patients with a central nervous system disorder (P = 0.027; OR = 7.18; 95% CI = 0.95—54.28). Our results suggest that the A/C polymorphism contributes to SLE pathogenesis. Lupus (2008) 17, 124—127.

It is widely acknowledged that genetic factors play a significant role in the pathogenesis of systemic lupus erythematosus (SLE). However, the female preponderance remains unexplained. We hypothesized that the female preponderance in childhood SLE results from selection early in the course of conception against male fetuses bearing genetic material predisposing to SLE. If this hypothesis is accurate, there should be a decreased number of male children in families with a child with SLE. Alternatively, children with SLE would have fewer male siblings. Further, this hypothesis may apply to other diseases with a female predominance such as pauciarticular onset juvenile rheumatoid arthritis (PaJRA), and not apply to diseases without female preponderance such as systemic onset juvenile rheumatoid arthritis (SoJRA). Chart review of patients with childhood onset SLE and PaJRA revealed a greater number of female children in these families compared with families of patients with SoJRA. Large-scale epidemiologic studies with precise counting of miscarriages and abortions could help to confirm these findings. Detailed studies of genetic and maternal intrauterine factors are required to conclusively prove this hypothesis. Lupus (2008) 17, 128—131.

Azathioprine (AZA) is a commonly used immunosuppressant for systemic lupus erythematosus (SLE). Myelosuppression is a serious adverse reaction due to AZA and its metabolites. Thiopurine S-methyltransferase (TPMT) is the rate-limiting enzyme. Variations of TPMT enzyme activity may be responsible for myelosuppression. However, a correlation between certain mutant alleles of low TPMT enzyme activity and myelotoxicity has also been suggested as a factor. We describe herein a case of AZA-induced severe myelosuppression associated with TPMT*3C heterozygous mutant allele in a SLE patient. The patient presented with pancytopenia, sepsis, typhlitis and disseminated intravascular coagulopathy after a short period of AZA therapy. The patient had low TPMT activity and TPMT*3C genotype. Measurement of TPMT activity and determination of TPMT variant allele may identify patients at risk for AZA-induced myelosuppression. Lupus (2008) 17, 132—134.

Patients with systemic lupus erythematosus (SLE) are prone to infection. Immunomodulation treatment increases the susceptibility. Salmonella infections in SLE patients may present with various clinical pictures, like pneumonia, septic arthritis, osteomyelitis, peritonitis, abscess and so on. The vascular complications commonly seen in the general population with salmonella infection are rarely encountered in SLE patients. Here we report an SLE patient who presented with spontaneous rupture of salmonella mycotic aneurysm involving the left renal artery. The 54 year-old woman had a stable premorbid condition and had 30 mg prednisolone per day. Acute abdomen and hypotensive shock developed suddenly without warning signs in advance. Image and tissue culture confirmed the diagnosis. The patient had an uneventful recovery. The rare clinical scenario is reported. Lupus (2008) 17, 135—138.

Posterior reversible encephalopathy syndrome (PRES) associates various neurological manifestations (headaches, seizures, altered mental status, cortical blindness, focal neurological deficits, vomiting) and transient changes on neuroimaging consistent with cerebral edema. Posterior reversible encephalopathy syndrome mainly occurs in the setting of hypertension, eclampsia, renal failure and/or use of immunosuppressive drugs.

We report four cases of PRES complicating systemic lupus erythematosus (SLE). In all our cases, renal involvement and hypertension were present. Neurological symptoms were typical. Magnetic resonance imaging showed posterior cerebral edema and in one case hemorrhagic complication. With symptomatic treatment and immunosuppressor withdrawal when they were previously used, symptoms fully resolved within 15 days in all cases, but one who had only partial regression related to cerebral hemorrhage.

Including our cases, we reviewed a total of 46 patients with SLE and PRES. Their clinical and radiological presentation was not specific. The peculiar role of SLE itself in the occurrence of PRES was not clear, since hypertension (95%), renal involvement (91%), recent onset of immunosuppressive drugs (54%) and/or recent treatment with high intravenous dose of steroids (43%) were often present. The hypertension and other worsening factors should be treated. Finally, the evolution of this clinical and radiological spectacular syndrome is generally rapidly favorable. Lupus (2008) 17, 139—147.

The contribution of the p53 Arg72Pro polymorphism in the development of systemic lupus erythematosus (SLE) remains controversial. We investigated the frequency of the p53 Arg72Pro genotype in patients with SLE (n = 155) and in controls (n = 150) in Poland. We found a weak contribution of the Arg/Arg genotype to the morbidity of SLE. Odds ratio (OR) for patients with SLE and p53 Arg/Arg genotype was 1.875 [95% CI = 1.180—2.979], P = 0.0075 and OR of the Arg/Arg and Arg/Pro genotypes was 1.549 [95% CI = 0.752—3.195], P = 0.2328.

Since the p53Arg variant supports apoptosis better than the p53Pro variant, our findings can be linked to an increase in the number of apoptotic leucocytes in SLE patients. The distinction between various populations may be because of differences in racial composition and/or exposure to distinct environmental factors that have a different impact on SLE incidence along with the changed Argp53Pro genotype. Lupus (2008) 17, 148—151.