Peripheral vascular disease in systemic lupus patients.

BACKGROUND: Systemic 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. OBJECTIVES: Objectives 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. METHODS: In 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. RESULTS: Ankle-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. CONCLUSIONS: Ankle-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.

Prolonged Thrombocytopenia in a Case of MIS-C in a Vaccinated Child.

Multisystem inflammatory syndrome in children (MIS-C) has been extensively described in patients following severe acute respiratory syndrome coronavirus 2 infection. There are now questions about what MIS-C may look like in vaccinated children. Multisystem inflammatory syndrome in children has many clinical and laboratory features in common with other inflammatory disorders including Kawasaki disease and toxic shock syndrome. Rheumatologic conditions can present with similar musculoskeletal complaints and elevated inflammatory markers. Laboratory markers and clinical symptoms of MIS-C usually improve once therapy is begun. We describe a child with persistent thrombocytopenia as an example of variable presentation of MIS-C in vaccinated children. This case report discusses an atypical progression of MIS-C in a vaccinated child with a known prior positive COVID-19 polymerase chain reaction (PCR) test. She presented with nonspecific abdominal pain and fever and was found to have elevated inflammatory markers, lymphopenia, and thrombocytopenia. Intravenous immunoglobulin and steroid treatment failed to induce rapid recovery in her clinical condition or thrombocytopenia. Rheumatologic, hematologic, oncologic, and infectious causes were considered and worked up due to the uncertainty of her case and persistence of pancytopenia but ultimately were ruled out with extensive testing and monitoring. It was key to include a broad differential including viral-induced bone marrow suppression, idiopathic thrombocytopenic purpura, secondary hemophagocytic lymphohistiocytosis, systemic juvenile idiopathic arthritis, and malignancy. The spectrum of MIS-C and response to treatment continues to evolve, and prior vaccination in this child's case complicated the clinical picture further. Additional evaluation of MIS-C in vaccinated cases will permit characterization of the range of MIS-C presentation and response to standard therapy.

Intraarticular steroids as DMARD-sparing agents for juvenile idiopathic arthritis flares: Analysis of the Childhood Arthritis and Rheumatology Research Alliance Registry

BACKGROUND: Children with juvenile idiopathic arthritis (JIA) who achieve a drug free remission often experience a flare of their disease requiring either intraarticular steroids (IAS) or systemic treatment with disease modifying anti-rheumatic drugs (DMARDs). IAS offer an opportunity to recapture disease control and avoid exposure to side effects from systemic immunosuppression. We examined a cohort of patients treated with IAS after drug free remission and report the probability of restarting systemic treatment within 12 months. METHODS: We analyzed a cohort of patients from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry who received IAS for a flare after a period of drug free remission. Historical factors and clinical characteristics and of the patients including data obtained at the time of treatment were analyzed. RESULTS: We identified 46 patients who met the inclusion criteria. Of those with follow up data available 49% had restarted systemic treatment 6 months after IAS injection and 70% had restarted systemic treatment at 12 months. The proportion of patients with prior use of a biologic DMARD was the only factor that differed between patients who restarted systemic treatment those who did not, both at 6 months (79% vs 35%, p < 0.01) and 12 months (81% vs 33%, p < 0.05). CONCLUSION: While IAS are an option for all patients who flare after drug free remission, it may not prevent the need to restart systemic treatment. Prior use of a biologic DMARD may predict lack of success for IAS. Those who previously received methotrexate only, on the other hand, are excellent candidates for IAS.

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.

Exercise-Induced Purpura in Children.

Exercise-induced purpura, which has also been called "golfer's purpura," is a phenomenon that has been rarely reported in the pediatric literature. This is the first case series in which this benign vasculopathy, which is most often associated with warm weather and high-impact activity, is described. In this series, we describe 5 patients, most of whom had an erythematous purpuric rash above the sock line that extended to the knees and was associated with warm weather and prolonged activity. Exercise-induced purpura may be mistaken for Henoch-Schönlein purpura or as a manifestation of a possible systemic vasculitis. Recognition of this benign condition is vital to avoid an unnecessary workup and a costly evaluation with accompanying anxiety.

Improvement of medication adherence in adolescents and young adults with SLE using web-based education with and without a social media intervention, a pilot study.

BACKGROUND: Self-management skills, including medication management, are vital to the health of adolescents and young adults with systemic lupus erythematosus (SLE). The purpose of this study was to assess the feasibility and preliminary effects of an online educational program in a cohort of adolescent and young adults with SLE with and without a social media (SM) experience. METHODS: Adolescents and young adults with SLE participated weekly for 8 sessions on a web-based educational program about SLE created specifically for this project. Subjects were randomized to respond to questions at the end of each weekly module in a journal or on a SM forum with other SLE subjects. Patients were surveyed prior to initiating the study, (T0) and 6 weeks after completion of the sessions (T1). Medication adherence for hydroxychloroquine, utilizing the medication possession ratio (MPR), was compared for the 3 months preceding T0 and for the 3 months following T1. RESULTS: Twenty-seven of the 37 subjects (73%) enrolled completed the study, including the two required sets of surveys. Reasons for being lost to follow up included being too busy, forgetting, and/or not seeing email reminders. Medication adherence improved in all subjects (p < 0.001). The percentage of the SM intervention group that was adherent (MPR ≥ 80%) significantly improved from 50% to 92% (p = 0.03), while the control group did not. Secondary outcome measures that improved, only in the SM group, included self-efficacy, sense of agency (SOA), sense of community (SOC), and empowerment. There was a strong correlation between empowerment with SOA and SOC and in turn a strong correlation with SOA and SOC with MPR, providing a possible explanation for why social media participation helped to improve medication adherence. Subjective reporting of medication adherence was not reliably correlated to MPR. CONCLUSIONS: This pilot study has demonstrated feasibility for the use of an online educational SLE website, recruitment, and measurement of chosen outcome measures. This study provides evidence for a larger multi-site trial which has the potential to address an important service gap by delivering self-management education and peer interactions in a format that is accessible, and engaging to young people with SLE. TRIAL REGISTRATION: Trial registration: NCT03218033 . Retrospectively registered 14 July 2017.

Nonclassic neurologic features in cryopyrin-associated periodic syndromes.

Neurologic manifestations in early childhood occur in the cryopyrin-associated periodic syndromes, especially in the chronic infantile neurological, cutaneous, and articular syndrome (CINCA) and the Muckle-Wells syndrome. Cryopyrin-associated periodic syndromes are commonly linked to mutations in the cold-induced autoinflammatory syndrome gene CIAS1 (current symbol, NLRP3) on chromosome 1. We describe three children with atypical cryopyrin-associated periodic syndromes, neurologic symptoms, and a Q705K mutation. Cryopyrin-associated periodic syndrome screening should be considered for children with neurologic and other periodic symptoms with elevated inflammatory markers. This syndrome is treatable with anakinra.

Lean intervention improves patient discharge times, improves emergency department throughput and reduces congestion.

OBJECTIVE: To determine if a lean intervention improved emergency department (ED) throughput and reduced ED boarding by improving patient discharge efficiency from a tertiary care children's hospital. METHODS: The study was conducted at a tertiary care children's hospital to study the impact lean that changes made to an inpatient pediatric service line had on ED efficiency. Discharge times from the general pediatrics' service were compared to patients discharged from all other pediatric subspecialty services. The intervention was multifaceted. First, team staffing reconfiguration permitted all discharge work to be done at the patient's bedside using a new discharge checklist. The intervention also incorporated an afternoon interdisciplinary huddle to work on the following day's discharges. Retrospectively, we determined the impact this had on median times of discharge order entry, patient discharge, and percent of patients discharged before noon. As a marker of ED throughput, we determined median hour of day that admitted patients left the ED to move to their hospital bed. As marker of ED congestion we determined median boarding times. RESULTS: For the general pediatrics service line, the median discharge order entry time decreased from 1:43pm to 11:28am (p < 0.0001) and the median time of discharge decreased from 3:25pm to 2:25pm (p < 0.0001). The percent of patients discharged before noon increased from 14.0% to 26.0% (p < 0.0001). The discharge metrics remained unchanged for the pediatric subspecialty services group. Median ED boarding time decreased by 49 minutes (p < 0.0001). As a result, the median time of day admitted patients were discharged from the ED was advanced from 5 PM to 4 PM. CONCLUSION: Lean principles implemented by one hospital service line improved patient discharge times enhanced patient ED throughput, and reduced ED boarding times.

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

BACKGROUND: We 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. METHODS: Pediatric 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. RESULTS: In 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. CONCLUSIONS: The 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.

Patient preferences and satisfaction in a multispecialty infusion center.

PURPOSE: Direct feedback from patients about their preferred modes of medication administration has been increasingly sought by providers to develop care programs that best match patient goals. Multispecialty infusion centers generally provide care to hematology-oncology (HO) and non-HO patients in one unit, with the same nursing staff. Our staff perceived that this was dissatisfying to our non-HO patients. We assessed patient satisfaction, as well as nursing and physician perceptions of patient preference/satisfaction with our infusion center, to determine whether a separate unit should be recommended when designing our new Cancer Institute Infusion Center. PATIENTS AND METHODS: A seven-question Likert scale satisfaction survey for patients, and a separate survey to assess nurses' and physicians' perception of patient satisfaction, were developed. The survey was administered to non-HO patients receiving infusions, doctors prescribing infusions, and nurses administering infusions. Results of the survey were compared between groups to assess differences in responses. RESULTS: Responses were received from 52 non-HO patients, 18 physicians, and 13 nurses. Patients had more satisfaction, on all survey items, with the multispecialty infusion center than had been realized by physicians and nurses. Analysis demonstrated that patients were satisfied with care in a multispecialty infusion unit and were in favor of continuing their care in this combined center. Total scores of patient surveys were significantly different (P<0.001) from those of physicians and nurses, who had assumed patients would prefer to have their care in a non-HO infusion setting. CONCLUSION: Understanding patient preferences is an important step in deciding the structure of infusion centers. Based on these survey conclusions, a combined multispecialty infusion center has been continued at our institution, thus improving quality by including patients in decision-making affecting their care.

Short-term perioperative all-cause mortality and cardiovascular events in women with systemic lupus erythematosus.

OBJECTIVE: 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. METHODS: We conducted a cross-sectional analysis of pooled hospital discharge data of the Nationwide Inpatient Sample from 1998-2002. We abstracted diseases and procedures using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The principal procedure was categorized into either a low, intermediate, or high risk level. Survey logistic regression adjusting for potential confounders provided estimates for stratum-specific odds of adverse events in women with SLE relative to those without SLE for each procedure risk level. RESULTS: All-cause mortality was significantly greater among women with SLE having a low- (odds ratio [OR] 1.54, 95% confidence interval [95% CI] 1.00-2.37) or a high-risk principal procedure (OR 2.52, 95% CI 1.34-4.75) relative to women without SLE, but did not differ significantly among persons with intermediate-risk procedures. Women with SLE with a low-risk procedure were also more likely to experience a composite CVD event relative to women without SLE (OR 1.40, 95% CI 1.04-1.87). CONCLUSION: Women with SLE are at an increased risk for short-term perioperative adverse events. These results highlight a need for greater scrutiny during perioperative evaluation and management of women with SLE.

NOD2-associated pediatric granulomatous arthritis, an expanding phenotype: study of an international registry and a national cohort in Spain.

OBJECTIVE: To study the phenotype characteristics of the largest to date cohort of patients with pediatric granulomatous arthritis (PGA) and documented mutations in the NOD2 gene. METHODS: We analyzed merged data from 2 prospective cohorts of PGA patients, the International PGA Registry and a Spanish cohort. A systematic review of the medical records of interest was performed to identify phenotype characteristics. RESULTS: Forty-five patients with PGA (23 sporadic cases and 22 from familial pedigrees) and documented NOD2 mutations were identified and formed the basis of the study. Of these 45 patients, 18 had the R334W-encoding mutation, 18 had R334Q, 4 had E383K, 3 had R587C, 1 had C495Y, and 1 had W490L. The majority of patients manifested the typical triad of dermatitis, uveitis, and arthritis. In contrast, in 13 patients, the following "atypical" manifestations were noted: fever, sialadenitis, lymphadenopathy, erythema nodosum, leukocytoclastic vasculitis, transient neuropathy, granulomatous glomerular and interstitial nephritis, interstitial lung disease, arterial hypertension, hypertrophic cardiomyopathy, pericarditis, pulmonary embolism, hepatic granulomatous infiltration, splenic involvement, and chronic renal failure. In addition, 4 individuals who were asymptomatic carriers of a disease-causing mutation were documented. CONCLUSION: NOD2-associated PGA can be a multisystem disorder with significant visceral involvement. Treating physicians should be aware of the systemic nature of this condition, since some of these manifestations may entail long-term morbidity.

Cardiovascular disease risk awareness in systemic lupus erythematosus patients.

OBJECTIVE: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. The aim of this study was to identify factors associated with patients' recognition of SLE as an independent risk factor for CVD and their perception of their personal CVD risk. METHODS: SLE patients were sent questionnaires that assessed demographic characteristics, any CVD risk factors, and information regarding the CVD counseling they had received from their physicians. Variables significantly associated with the outcomes were analyzed using logistic regression models. RESULTS: Information obtained from 226 questionnaires was analyzed. Fifty-eight percent of the respondents reported receiving no CVD counseling from a physician. Patients who recalled receiving counseling from a physician were 2.3 times more likely (P = 0.02) to recognize SLE as a CVD risk factor and 3.2 times more likely (P = 0.02) to perceive themselves as being at risk of CVD compared with those patients who did not receive physician counseling. Receiving physician CVD counseling was the strongest predictor of a patient's self-perception of CVD risk. Those patients at intermediate to high risk (n = 167) who reported having received counseling were 5.3 times as likely (P = 0.007) to perceive themselves to be at higher risk of CVD compared with similar patients who did not receive counseling. Younger patients were 4.2 times as likely (P = 0.002) as older patients to recognize SLE as a CVD risk factor. Other variables associated with patients' self-perceptions of CVD risk included family history of CVD and hypertension. CONCLUSION: Physician counseling regarding CVD in SLE patients has an important impact on patients' awareness of SLE as a CVD risk factor and their self-perception of CVD risk.

Homocysteine levels and disease duration independently correlate with coronary artery calcification in patients with systemic lupus erythematosus.

OBJECTIVE: To compare the incidence and extent of coronary artery calcification (CAC) as measured by electron beam computed tomography (EBCT) in patients with systemic lupus erythematosus (SLE) and controls, and to identify variables associated with CAC in patients with SLE. METHODS: Female patients with SLE and matched controls were recruited; EBCT of the coronary arteries was performed, and laboratory values (including the homocysteine concentration, the lipid level, the high-sensitivity C-reactive protein [hsCRP] concentration, the glomerular filtration rate [GFR], and the level of soluble CD154 [sCD154]) were determined. For patients, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index and the SLE Disease Activity Index scores were recorded. Tests of association between the CAC score and the above-mentioned variables were performed. RESULTS: The incidence of CAC was higher in patients with SLE than in controls (P = 0.009), and patients had a higher mean raw CAC (rCAC) score (87.9 versus 9.6 in controls; P = 0.02). In particular, more CAC-positive patients than CAC-positive controls had rCAC scores above the 75th percentile (P = 0.003). Among both patients and controls, those with CAC were approximately 10 years older than those without CAC. In addition to age, a significant determinant of positive CAC status in both groups was the number of cardiovascular risk factors. In patients with SLE, CAC was associated with a higher homocysteine concentration, a lower GFR, and longer disease duration. In controls, the total cholesterol level correlated positively with CAC. When multivariate logistic regression methods were applied to candidate explanatory variables, homocysteine concentration, age, and disease duration (but not the levels of sCD154 or hsCRP) contributed significantly to CAC status. The methylenetetrahydrofolate reductase C677T genotype was not a predictor of hyperhomocysteinemia or CAC status. CONCLUSION: Among patients with SLE, the homocysteine concentration, the GFR, age, and disease duration were associated with CAC. CAC occurred more frequently and was more extensive in patients with SLE than in controls, suggesting that EBCT could be used to detect premature atherosclerosis in the former group. An elevated homocysteine concentration might identify patients with SLE who are likely to have premature atherosclerosis and who would benefit from evaluation of CAC by EBCT.

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-alpha 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.