Lisabeth V. Scalzi

Sleep and Periodic Limb Movement in Sleep in Juvenile Fibromyalgia

Objectives. Fibromyalgia has been recently recognized in children and adolescents as juvenile fibromyalgia (JF). In adult fibromyalgia, subjective complaints of nonrestorative sleep and fatigue are supported by altered polysomnographic findings including a primary sleep disorder known as periodic limb movements in sleep (PLMS) in some subjects. Although poor sleep is a diagnostic criterion for JF, few reports in the literature have evaluated specific sleep disturbances. Our objectives were to evaluate in a controlled study the polysomnographic findings of children and adolescents with JF for alterations in sleep architecture as well as possible PLMS not previously noted in this age group. Methods. Sixteen consecutive children and adolescents (15.0 ± 2.6 years of age) diagnosed with JF underwent overnight polysomnography. Polysomnography was also performed on 14 controls (14.0 ± 2.2 years of age) with no history of an underlying medical condition that could impact on sleep architecture. Respiratory variables, sleep stages, and limb movements were measured during sleep in all subjects. Results. JF subjects differed significantly from controls in sleep architecture. JF subjects presented with prolonged sleep latency, shortened total sleep time, decreased sleep efficiency, and increased wakefulness during sleep. In addition, JF subjects exhibited excessive movement activity during sleep. Six of the JF subjects (38%) were noted to have an abnormally elevated PLMS index (>5/hour), indicating PLMS in these subjects. Conclusion. Our study demonstrated abnormalities in sleep architecture in children with JF. We also noted PLMS in a significant number of subjects. This has not been reported previously in children with this disorder. We recommend that children who are evaluated for JF undergo polysomnography including PLMS assessment. juvenile fibromyalgia; periodic limb movement in sleep; restless legs syndrome.

Commissural size in neonatal rats: Effects of sex and prenatal alcohol exposure

Sex differences have been reported in the size of the adult corpus callosum in both humans and rodents. This experiment investigated whether sex and/or different prenatal treatment conditions would influence commissural size at birth. Male and female 3‐day‐old Long Evans rats were selected from one of three prenatal treatment histories: prenatal alcohol‐exposed (35% ethanol‐derived calories, 35% EDC), nutritional control (0% ethanol‐derived calories, 0% EDC) or standard control (lab chow). Midline sagittal areas of the corpus callosum and the anterior commissure were determined for these subjects. Male control subjects had significantly larger callosal areas than females. Prenatal alcohol exposure significantly abolished this sexual dimorphism, with 35% EDC males having a significantly smaller callosal area than males from both control groups. This effect was independent of prenatal treatment differences in body or brain size. There were no significant sex differences in the midline sagittal area of the anterior commissure, nor were there any apparent effects of prenatal treatment on this measure. These results indicate that sex differences in the size of the corpus callosum are present at birth. Since a difference in myelination cannot account for this difference in area, there may be a sex difference in the number of fibers or in the average fiber size. Additionally, the effects of prenatal alcohol exposure on male, but not female, offspring suggest that this alcohol‐related birth defect is hormonally mediated.

Racial disparities in age at time of cardiovascular events and cardiovascular-related death in patients with systemic lupus erythematosus

OBJECTIVE To determine whether racial disparities exist with regard to the age at which patients with systemic lupus erythematosus (SLE) experience cardiovascular disease (CVD) and CVD-associated death. METHODS Using the 2003-2006 Nationwide Inpatient Sample, we calculated the age difference between patients with SLE and their race- and sex-matched controls at the time of hospitalization for a cardiovascular event and for CVD-associated death. In addition, we calculated the age difference between white patients with SLE and sex-matched controls for each minority group for the same outcomes. RESULTS The mean age difference between women with and those without SLE at the time of admission for a CVD event was 10.5 years. All age differences between women with SLE (n = 3,627) and women without SLE admitted for CVD were significant (P < 0.0001). Among different racial groups with SLE, black women were the youngest to be admitted with CVD (53.9 years) and to have a CVD-associated in-hospital death (52.8 years; n = 218). Black women with SLE were 19.8 years younger than race- and sex-matched controls at the time of CVD-associated death. Admission trends for CVD were reversed for black women, such that the highest proportions of these patients were admitted before age 55 years, and then the proportions steadily decreased across age categories. Among the 805 men with SLE who were admitted with a CVD event, those who were black or Hispanic were youngest. CONCLUSION There are significant racial disparities with regard to age at the time of hospital admission for CVD events and CVD-related hospitalization resulting in death in patients with SLE.

Prolonged expression of CD154 on CD4 T cells from pediatric lupus patients correlates with increased CD154 transcription, increased nuclear factor of activated T cell activity, and glomerulonephritis.

OBJECTIVE To assess CD154 expression in patients with pediatric systemic lupus erythematosus (SLE) and to explore a transcriptional mechanism that may explain dysregulated expression of CD154. METHODS Cell surface CD154 expression (pre- and postactivation) in peripheral blood CD4 T cells from 29 children with lupus and 29 controls matched for age, sex, and ethnicity was examined by flow cytometry. CD154 expression was correlated with clinical features, laboratory parameters, and treatments received. Increased CD154 expression on CD4 T cells from the SLE patients was correlated with CD154 message and transcription rates by real-time reverse transcription-polymerase chain reaction (RT-PCR) and nuclear run-on assays, respectively. Nuclear factor of activated T cell (NF-AT) transcription activity and mRNA levels in CD4 T cells from SLE patients were explored by reporter gene analysis and real-time RT-PCR, respectively. RESULTS CD154 surface protein levels were increased 1.44-fold in CD4 T cells from SLE patients as compared with controls in cells evaluated 1 day postactivation ex vivo. This increase correlated clinically with the presence of nephritis and an elevated erythrocyte sedimentation rate. Increased CD154 protein levels also correlated with increased CD154 mRNA levels and with CD154 transcription rates, particularly at later time points following T cell activation. Reporter gene analyses revealed a trend for increased NF-AT, but decreased activator protein 1 and similar NF-kappaB, activity in CD4 T cells from SLE patients as compared with controls. Moreover, NF-AT1 and, in particular, NF-AT2 mRNA levels were notably increased in CD4 T cells from SLE patients as compared with controls. CONCLUSION Following activation, cell surface CD154 is increased on CD4 T cells from pediatric lupus patients as compared with controls, and this increase correlates with the presence of nephritis, increased CD154 transcription rates, and increased NF-AT activity. These results suggest that NF-AT/calcineurin inhibitors, such as tacrolimus and cyclosporine, may be beneficial in the treatment of lupus nephritis.

The relationship between race, cigarette smoking and carotid intimal medial thickness in systemic lupus erythematosus

Racial differences are known to account for a higher incidence of systemic lupus erythematosus (SLE), as well as increased disease severity and mortality. The purpose of this study was to determine whether there are any race-specific risk factors that affect measures of subclinical atherosclerosis in SLE patients. Traditional and SLE-related cardiovascular disease (CVD) risk factors were assessed in 106 female SLE patients. Carotid medial intimal medial thickness (mIMT) and coronary artery calcification (CAC) were measured on all subjects. Differences were evaluated between races for all clinical, serologic, and CVD risk factors and the racial interactions with all covariables. Outcomes included mIMT and CAC. There were no significant differences between races with regard to mIMT or CAC. Significant covariables in the final model for mIMT included age, triglycerides, glucose, and race—age and race—smoking interactions. A prediction model with fixed significant covariables demonstrated that Black subjects with a smoking history had a significantly higher mIMT than Blacks who had never smoked, an effect not seen in Whites. There were no differences between having CAC or with the CAC scores between the races. In the final model for CAC, age and SLE disease duration were significant covariables impacting CAC. When controlling for other significant CVD covariables and interactions, Black women, but not White, with SLE with a history of smoking have higher mIMT measurements than those who have never smoked. This is the first report documenting the race-specific effect of smoking on subclinical measures of CVD in SLE. Lupus (2009) 18, 1289—1297.

Short-Term Perioperative All-Cause Mortality and Cardiovascular Events in Women With Systemic Lupus Erythematosus

Persons with systemic lupus erythematosus (SLE) are at an increased risk of cardiovascular disease (CVD) events, but this excess CVD burden in the perioperative setting is yet to be determined. We aimed to determine the risk of perioperative short‐term all‐cause mortality and CVD events among women with SLE compared to those without SLE.

Peripheral vascular disease in systemic lupus patients.

BackgroundSystemic lupus erythematosus (SLE) is an independent risk factor for cardiovascular disease (CVD). Ankle-brachial index (ABI) is a measure of peripheral vascular disease (PVD), low values of which are associated with CVD. ObjectivesObjectives were to identify the prevalence of PVD in SLE, to identify risk factors associated with PVD in SLE, and to determine whether SLE is an independent risk factor for PVD as assessed by ABI. MethodsIn a cross-sectional analysis of SLE subjects and control subjects, free of known CVD, SLE-related variables and cardiovascular risk factors were measured. Peripheral vascular disease was assessed using ABI. The prevalence of PVD (ABI ⩽1.0) and comparisons of mean ABI, between SLE and control subjects, were examined. Systemic lupus erythematosus was examined as an independent risk for PVD in the cohort using propensity score matching. Logistic regression was performed to identify independent risk factors for PVD in SLE. ResultsAnkle-brachial index was lower in the 134 SLE subjects compared with 77 control subjects: 1.05 versus 1.09 (P = 0.003), and the prevalence of PVD was higher in SLE than in control subjects (33% vs 20%; P = 0.037). Systemic lupus erythematosus was not an independent risk for PVD. In the SLE subjects, the only significant risk factor for PVD was smoking. ConclusionsAnkle-brachial index, a marker of subclinical CVD, is an inexpensive and easy method in which to assess PVD. There was a 33% prevalence of PVD in SLE, which was independently associated with smoking. As PVD is a coronary artery disease risk equivalent, screening and diagnosis may change lipid management in preventive cardiovascular risk assessment in patients with SLE. The combination of SLE and a smoking history may identify individuals for whom checking an ABI makes particular sense.

Remittive agents in pediatric rheumatology

Purpose of review Children with rheumatic diseases frequently require therapy with disease-modifying antirheumatic drugs and/or biologic agents. Therapies that have been prospectively tested in adults are often used in children before full evaluation of their safety and efficacy. Published experience that may report “off-label” usage can be helpful in decision making, although such reports do not reduce the need for prospective clinical trials in children. The purpose of this review is to summarize the recent published evidence regarding efficacy (and safety, when available) of standard and novel agents used in pediatric rheumatic disease. Recent findings Etanercept, one of three currently available tumor necrosis factor-α inhibitors has a juvenile idiopathic arthritis indication. Novel “off-label” uses in children for interleukin-1 receptor agonist (Anakinra), antiinterleukin-6 receptor antibody (MRA), and rituximab (anti-CD20 monoclonal antibody) are discussed. Summary This review summarizes the published evidence that supports the use of selected disease-modifying antirheumatic drugs and novel biologic agents in children with rheumatic diseases.

An assessment of variables affecting transition readiness in pediatric rheumatology patients.

BackgroundWe sought to identify which adolescent patient characteristics might lead to subjective reported independence in accessing medical care when patients transition from pediatric to adult medicine.MethodsPediatric and adult rheumatologists were asked which pediatric patient characteristics they believed would improve transition to adult medical care. Based on these responses, a questionnaire was created and administered to 76 teenage/young adult patients in a pediatric rheumatology clinic. The first set of questions included demographic, disease features, and life skills questions. The second set of questions pertained to self-reported independence in managing medical care. Data was analyzed to see if there were any significant associations between an individual’s response to demographic, disease feature, or life skills questions and the independence outcome questions.ResultsIn our study, older age correlated with self-reported independence in almost all questions asked regarding accessing medical care. Other patient characteristics that were associated with increased self-perceived autonomy included having a younger parent, having a family member with a similar disease, longer disease duration, having a comorbid non-rheumatic diagnosis, and having had a summer job.ConclusionsThe patient characteristics that we found associated with self-reported independence in obtaining medical care should be considered when determining which patients might be more likely to make a successful transition.

Evaluation of the reliability of the Cutaneous Dermatomyositis Disease Area and Severity Index and the Cutaneous Assessment Tool-Binary Method in juvenile dermatomyositis among paediatric dermatologists, rheumatologists and neurologists

The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and Cutaneous Assessment Tool–Binary Method (CAT‐BM) have been shown to be reliable and valid outcome measures to assess cutaneous disease in adult dermatomyositis (DM) and juvenile DM (JDM), respectively.