Obesity is Independently Associated With Worse Patient-Reported Outcomes in Women with Systemic Lupus Erythematosus.

OBJECTIVE: To determine whether obesity in women with systemic lupus erythematosus (SLE) is independently associated with worse patient-reported outcomes (PROs). METHODS: Data were derived from a prospective study of adult women with a diagnosis of SLE that was verified by medical record review. Two established definitions for obesity were used: fat mass index (FMI) ≥13 kg/m2 and body mass index (BMI) ≥30 kg/m2 . Dependent variables included 4 validated PROs: disease activity as assessed by the Systemic Lupus Activity Questionnaire (SLAQ), depressive symptoms as assessed by the Center for Epidemiologic Studies Depression Scale (CES-D), pain as assessed by the Short Form 36 (SF-36) pain subscale, and fatigue as assessed by the SF-36 vitality subscale. We used multivariable linear regression to evaluate the associations of obesity with PROs, while controlling for potential confounders (age, race, education, income, smoking, disease duration, disease damage, and prednisone use). RESULTS: The analysis included 148 participants, 32% of whom were obese. In the multivariate regression model, obesity was associated with worse scores for each PRO. Mean adjusted scores for the SLAQ and CES-D comparing obese versus non-obese participants were 14.8 versus 11.5 (P = 0.01) and 19.8 versus 13.1 (P < 0.01), respectively. The obese group also reported worse mean adjusted scores for pain (38.7 versus 44.2; P < 0.01) and fatigue (39.6 versus 45.2; P = 0.01). CONCLUSION: In a representative sample of women with SLE, obesity (as defined by both FMI and BMI) was independently associated with worse PROs, including disease activity, depressive symptoms, and symptoms of pain and fatigue. Obesity may represent a modifiable target for improving outcomes among obese women with SLE.

Pneumocystis jirovecii pneumonia (PJP) prophylaxis patterns among patients with rheumatic diseases receiving high-risk immunosuppressant drugs.

INTRODUCTION/OBJECTIVES: Pneumocystis jirovecii pneumonia (PJP) is a rare but potentially fatal opportunistic infection; however, consensus varies around which conditions or medications confer a level of risk sufficient to justify antibiotic prophylaxis for PJP. We used electronic health record (EHR) data to assess the current patterns of PJP prophylaxis, PJP outcomes, and prophylaxis-related adverse events among patients with rheumatic diseases who were receiving high-risk immunosuppressant drugs. METHODS: Data derive from the EHR of a large health system. We included new immunosuppressant users with diagnoses of vasculitis, myositis, or systemic lupus erythematosus. We calculated the proportion of patients who received PJP prophylaxis for each diagnosis and drug combination. We also calculated the number of PJP infections and the number of antibiotic adverse drug events (ADEs) per patient-year of exposure. RESULTS: We followed 316 patients for 23.2 + /- 14.2 months. Overall, 124 (39%) of patients received prophylactic antibiotics for PJP. At least 25% of patients with the highest risk conditions (e.g. vasculitis) or highest risk immunosuppressants (e.g. cyclophosphamide) did not receive PJP prophylaxis. We found no cases of PJP infection over 640 patient-years of follow up, including among those not receiving prophylaxis, and an overall incidence rate of ADEs of 2.2% per patient-year. CONCLUSIONS: PJP prophylaxis for patients with rheumatic conditions is inconsistent, with one quarter of patients who have high risk conditions or high risk immunosuppressants not receiving prophylaxis. However, given extremely low rates of PJP infection, but detectable ADEs to prophylactic antibiotics, our findings suggest that evidence to guide more personalized risk assessments are needed to inform PJP prophylaxis.

Correction to: Hydroxychloroquine dosing in immune-mediated diseases: implications for patient safety.

The given and family name of a co-author R. Adams Dudley was swapped in the published article. The correct given name is R. Adams and the family name is Dudley.

Discordance of the Framingham cardiovascular risk score and the 2013 American College of Cardiology/American Heart Association risk score in systemic lupus erythematosus and rheumatoid arthritis.

Despite the increasing use of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cardiovascular (CV) risk score in clinical practice, few studies have compared this score to the Framingham risk score among rheumatologic patients. We calculated Framingham and 2013 ACC/AHA risk scores in subjects with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and assessed demographic, CV, and rheumatologic characteristics associated with discordant scores (high-risk ACC/AHA scores but low-risk Framingham scores). SLE and RA subjects drawn from two population-based cohort studies were assessed during in-person study visits. We used chi-squared tests and t tests to examine the association of discordant CV risk scores with baseline characteristics. Eleven (7.0%) of 157 SLE subjects and 11 (11.5%) of 96 RA subjects had discordant CV risk scores with high ACC/AHA scores and low Framingham scores. These findings did not significantly change when a 1.5 multiplier was applied to the Framingham score. Rheumatologic disease duration, high-sensitivity CRP levels, African-American race, diabetes, current use of anti-hypertensive medication, higher age, and higher systolic blood pressure were each significantly associated with discordant risk scores. Approximately 10% of SLE and RA subjects had discordant 10-year CV risk scores. Our findings suggest that the use of the 2013 ACC/AHA risk score could result in changes to lipid-lowering therapy recommendations in a significant number of rheumatologic patients. Prospective studies are needed to compare which score better predicts CV events in rheumatologic patients, especially those with risk factors associated with discordant risk scores.

Central Nervous System Manifestations of Systemic Lupus Erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) encompasses a variety of phenomena. Manifestations are focal or diffuse, and correlate with disease mechanisms. Recent understanding of the contribution of blood-brain barrier dysfunction to the passage of circulating antineuronal antibodies into the brain parenchyma has shed light on pathogenesis. Correct attribution of neuropsychiatric manifestations to SLE remains a challenge, but validated attribution models will help. Diagnosis relies on characteristic clinical manifestations, SLE disease activity, antibody measurements, cerebrospinal fluid findings, specific neuroimaging findings, and exclusion of alternative etiologies. Current treatment encompasses the identification and management of the inciting event, symptomatic treatment, and anticoagulation or immunosuppression.

Hydroxychloroquine dosing in immune-mediated diseases: implications for patient safety.

Evidence suggests that hydroxychloroquine (HCQ) retinal toxicity is more common than previously thought. Adhering to careful weight-based dosing can significantly reduce the risk of this adverse event and is recommended in recent guidelines. We used electronic health record data from a large health system to examine HCQ dosing over a 5-year period and identify risk factors associated with higher dosage of HCQ. We constructed a longitudinal, retrospective cohort of patients with HCQ prescriptions (1681 patients with 3490 prescribing events) between 2012 and 2016. We measured HCQ dosing patterns relative to guidelines (<6.5 and <5.0 mg/kg) over time and used longitudinal multivariate mixed effects logistic regression to identify sociodemographic, clinical and health system factors associated with receiving higher than recommended doses of HCQ. The proportion of patients receiving doses above 6.5 mg/kg decreased from 12% in 2012 to 7% by 2016. Similarly, the proportion of patients with doses above 5.0 mg/kg fell from 38% in 2012 to 30% in 2016. Low body weight (<68 kg) was strongly associated with receiving doses of HCQ above 6.5 mg/kg across all time points, even after adjusting for other factors (odds ratios ranging from 13.2 to 21.0). Although the proportion of patients receiving higher than recommended HCQ doses has declined over a period of 5 years, a substantial number of individuals remain at increased risk for toxicity. Given the widespread use of HCQ in immune-mediated diseases, our study suggests that interventions aimed to ensure appropriate dosing are warranted to improve patient safety.

Antimalarial myopathy in a systemic lupus erythematosus patient with quadriparesis and seizures: a case-based review.

Weakness, seizures, and encephalopathy have a broad differential diagnosis in patients with systemic lupus erythematosus (SLE). We present a case of a 26-year-old female with a recent diagnosis of SLE who experienced a clinical deterioration with quadriparesis, seizures, and encephalopathy. Her quadriparesis was found to be secondary to biopsy-proven hydroxychloroquine-induced myopathy with concomitant inflammatory myopathy. Her seizures and encephalopathy were suspected to be multifactorial in the setting of sepsis and critical illness with possible contributions from neuropsychiatric manifestations of SLE and macrophage activation syndrome. She experienced a dramatic clinical recovery with discontinuation of hydroxychloroquine, treatment of lupus disease activity with mycophenolate mofetil and prednisone, and antibiotic treatment for methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. This case-based review provides a systematic approach to quadriparesis, seizures, and encephalopathy in patients with SLE and an evidence-based discussion of antimalarial myopathy, which is of critical importance given the widespread use of antimalarial medications for rheumatologic diseases.

Incidence and Management of Cardiovascular Risk Factors in Psoriatic Arthritis and Rheumatoid Arthritis: A Population-Based Study.

OBJECTIVE: To examine the prevalence and incidence of cardiovascular (CV) risk factors, including hypertension, hyperlipidemia, diabetes mellitus (DM), and obesity among patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) compared to the general population, and to examine the treatment of incident CV risk factors in PsA and RA compared to controls. METHODS: A cohort study was conducted within The Health Improvement Network, a medical record database in the UK, using data from 1994 to 2014. Patients ages 18-89 years with PsA or RA were matched to controls on practice and start date. The prevalence and incidence of CV risk factors identified by diagnostic codes were calculated. Cox proportional hazards models were used to examine the relative incidence of these CV risk factors. Finally, pharmacologic therapies for incident CV risk factors were examined. RESULTS: Study subjects included patients with PsA (n = 12,548), RA (n = 53,215), and controls (n = 389,269). The prevalence of all CV risk factors was significantly elevated in PsA. Only the prevalence of DM and obesity was increased in RA. Incidence of hypertension, hyperlipidemia, and DM was elevated in PsA and RA. Receipt of therapy within 1 year following incident diagnosis of CV risk factors was not substantially different between the groups; approximately 85%, 65%, and 45% of patients received prescriptions for hypertension, hyperlipidemia, and DM, respectively. CONCLUSION: Patients with PsA have an increased prevalence of CV risk factors, and both patients with PsA and patients with RA have increased incidence of a new diagnosis of CV risk factors. Pharmacologic treatment of CV risk factors in patients with PsA and RA was similar to controls in the UK.

Management of hyperlipidemia among patients with rheumatoid arthritis in the primary care setting.

BACKGROUND: Rheumatoid arthritis (RA) has been associated with an increased risk of cardiovascular morbidity and mortality but this has not translated to optimal management of traditional cardiovascular risk factors such as hyperlipidemia. The objectives of this study were to 1) determine the prevalence of screening for hyperlipidemia in patients with RA followed by primary care practitioners (PCP); 2) examine initiation of lipid-lowering therapy in patients with an indication, and 3) assess whether proposed modifications to cardiovascular risk calculations change the percentage of RA patients with an indication for therapy. METHODS: We performed a retrospective cohort study using an academic medical center-based medical record database in the United States. Patients with RA defined by the presence of at least one ICD-9 code between 2005-2010 and followed by a PCP within the health care system were included. The positive predictive value of ICD-9 codes for accurately identifying patients with RA was 96.7%. Descriptive statistics were used to report the prevalence of screening and use of lipid-lowering therapy among those with an indication. Factors associated with not receiving lipid screening were examined using logistic regression models. Indication for and receipt of therapy were then assessed before and after the application of the European Union League Against Rheumatism (EULAR) recommended multiplier to the Framingham risk score. RESULTS: Among 1,056 patients with RA followed by PCPs and eligible for lipid screening, lipid screening was ordered for 539 (51%) within the 3-year follow-up period. Patients with diabetes, hypertension, chronic kidney disease, obesity or age >50 were more likely to be screened. Of those with lipid results (N = 290), 25 (9%) patients had an indication for lipid-lowering therapy based on Adult Treatment Panel III guidelines. Ten (40%) patients with an indication for lipid-lowering therapy received therapy did not receive therapy. Applying the EULAR multiplier only changed the indication for lipid-lowering therapy in two patients. CONCLUSIONS: Screening and management of traditional cardiovascular risk factors, including hyperlipidemia, need to be optimized.

Immune reconstitution inflammatory syndrome associated with biologic therapy.

The use of biologics in the treatment of autoimmune disease, cancer, and other immune conditions has revolutionized medical care in these areas. However, there are drawbacks to the use of these medications including increased susceptibility to opportunistic infections. One unforeseen risk once opportunistic infection has occurred with biologic use is the onset of immune reconstitution inflammatory syndrome (IRIS) upon drug withdrawal. Although originally described in human immunodeficiency virus (HIV) patients receiving highly active antiretroviral therapy, it has become clear that IRIS may occur when recovery of immune function follows opportunistic infection in the setting of previous immune compromise/suppression. In this review, we draw attention to this potential pitfall on the use of biologic drugs.

The anti-oxidative capacity of high-density lipoprotein is reduced in acute coronary syndrome but not in stable coronary artery disease.

OBJECTIVES: This study examined an anti-inflammatory property of high-density lipoprotein (HDL) in subjects with acute coronary syndrome (ACS) and stable coronary artery disease (CAD) compared with control subjects. BACKGROUND: HDL has anti-inflammatory properties in vitro, but its relationship to coronary disease in humans is unclear. The high-density lipoprotein inflammatory index (HII) measures the ability of HDL to mitigate oxidation of low-density lipoprotein; this function may be impaired in ACS and/or CAD. METHODS: We measured HII in 193 patients undergoing angiography for symptoms of CAD. Control subjects (n = 99) had no angiographic CAD, chronic CAD subjects (n = 51) had ≥ 70% vessel stenosis, and ACS subjects (n = 43) had ≥ 20% vessel stenosis and ischemia or infarction. We also examined HII in a cohort of healthy subjects randomly assigned to a statin or placebo. RESULTS: Subjects who had ACS had higher HII (less antioxidative capacity) compared with controls (1.57 vs. 1.17, p = 0.005) or those with chronic CAD (1.57 vs. 1.11, p = 0.006). HII was not different in subjects with stable CAD compared with controls. Furthermore, those subjects with higher HII were more likely to have ACS than no CAD (quartile 4 vs. 1, odds ratio [OR]: 1.74, p = 0.008). In a multivariate logistic regression model, HII was associated with ACS after adjusting for traditional cardiac risk factors (OR: 3.8, p = 0.003). There was a small improvement in HII after statin therapy compared with placebo (-14%, p = 0.03). CONCLUSIONS: HDL has less anti-inflammatory capacity as assessed by HII in the setting of ACS compared with controls or subjects with chronic CAD.

Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis.

BACKGROUND: High-density lipoprotein (HDL) may provide cardiovascular protection by promoting reverse cholesterol transport from macrophages. We hypothesized that the capacity of HDL to accept cholesterol from macrophages would serve as a predictor of atherosclerotic burden. METHODS: We measured cholesterol efflux capacity in 203 healthy volunteers who underwent assessment of carotid artery intima-media thickness, 442 patients with angiographically confirmed coronary artery disease, and 351 patients without such angiographically confirmed disease. We quantified efflux capacity by using a validated ex vivo system that involved incubation of macrophages with apolipoprotein B-depleted serum from the study participants. RESULTS: The levels of HDL cholesterol and apolipoprotein A-I were significant determinants of cholesterol efflux capacity but accounted for less than 40% of the observed variation. An inverse relationship was noted between efflux capacity and carotid intima-media thickness both before and after adjustment for the HDL cholesterol level. Furthermore, efflux capacity was a strong inverse predictor of coronary disease status (adjusted odds ratio for coronary disease per 1-SD increase in efflux capacity, 0.70; 95% confidence interval [CI], 0.59 to 0.83; P<0.001). This relationship was attenuated, but remained significant, after additional adjustment for the HDL cholesterol level (odds ratio per 1-SD increase, 0.75; 95% CI, 0.63 to 0.90; P=0.002) or apolipoprotein A-I level (odds ratio per 1-SD increase, 0.74; 95% CI, 0.61 to 0.89; P=0.002). Additional studies showed enhanced efflux capacity in patients with the metabolic syndrome and low HDL cholesterol levels who were treated with pioglitazone, but not in patients with hypercholesterolemia who were treated with statins. CONCLUSIONS: Cholesterol efflux capacity from macrophages, a metric of HDL function, has a strong inverse association with both carotid intima-media thickness and the likelihood of angiographic coronary artery disease, independently of the HDL cholesterol level. (Funded by the National Heart, Lung, and Blood Institute and others.).