Fulfilling 6 Domains of Health Care Quality: A Qualitative Parental Caregiver Study of Pediatric Telehealth During a Pandemic.

Using qualitative methods, we examine telehealth care quality from the perspective of parents of pediatric patients during a pandemic. We fill a gap in the literature essential for measuring effectiveness of pediatric telehealth. A total of 22 participants (n = 21 female; n = 1 male) enrolled in 1 of 9 interviews and focus groups conducted in 2021. Transcribed data were thematically analyzed and organized based on the 6 domains of quality health care by the Institute of Medicine (IOM). Analyzed data revealed 7 themes and 52 codes. Pediatric telehealth visits were perceived as efficient, timely, safe, and generally effective by parents for their child's health care. Participants experienced equal or greater time with their child's care provider via telehealth than through in-person visits. Qualitative results directly align with IOM domains of quality health care and contribute to the growing literature and evidence that may lead to improved telehealth outcomes and better preparedness for emergent public health events.

Understanding Drivers of Telemedicine in Pediatric Medical Care.

Purpose: As the demand for telemedicine services continues, greater knowledge about health care delivery preferences can inform high quality, efficient care. The present study sought to evaluate patient and family characteristics that may influence telemedicine utilization, particularly the choice between telephone and video telemedicine visits. Methods: This is a single-site cross-sectional, mixed methods study aimed at identifying factors associated with use of telephone and video telemedicine visits with pediatric patients and their families. Results: Seven hundred seventy-five (n = 775) caregivers completed a survey and 22 caregivers participated in follow-up focus groups and interviews. Findings indicate that female caregivers, those with higher education levels, and those with experience with technology were more likely to choose video telemedicine visits. Qualitative feedback provided several valuable recommendations based on patient/family experiences, which fell into four categories, including scheduling, accessibility, treatment resources, and care coordination. Conclusion: Findings demonstrate that previous experience, familiarity, and technology access may be important drivers in health care modality preference. Key elements that emerged relevant to user satisfaction and overall quality of the telemedicine experience: caregiver choice on visit type (telemedicine vs. in-person), child health care needs, and telemedicine education/training. As society moves toward pay-per-performance and value-based reimbursement, it is imperative that we focus on experience, health care needs, and training to improve patient experience and lower health care costs.

Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti-Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy.

OBJECTIVE: To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti-tumor necrosis factor (anti-TNF) therapy and the occurrence of disease flare following withdrawal of anti-TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA). METHODS: In this prospective, multicenter study, 137 patients with polyarticular-course JIA whose disease was clinically inactive while receiving anti-TNF therapy were enrolled. Patients were observed for an initial 6-month phase during which anti-TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti-TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti-TNF withdrawal. Spearman's rank correlation test, Mann-Whitney U test, Kruskal-Wallis test, receiver operating characteristic (ROC) curve, and Kaplan-Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti-TNF withdrawal. RESULTS: Over the 6-month initial phase with anti-TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular-course JIA; following anti-TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti-TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti-TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti-TNF withdrawal were inversely correlated with the time to disease flare (r = -0.36). CONCLUSION: Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular-course JIA, and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare.

Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease.

OBJECTIVE: To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease. METHODS: In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare. RESULTS: Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05). CONCLUSION: Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified.

High Levels of DEK Autoantibodies in Sera of Patients With Polyarticular Juvenile Idiopathic Arthritis and With Early Disease Flares Following Cessation of Anti-Tumor Necrosis Factor Therapy.

OBJECTIVE: The nuclear oncoprotein DEK is an autoantigen associated with juvenile idiopathic arthritis (JIA), especially the oligoarticular subtype. DEK is a secreted chemotactic factor. Abundant levels of DEK and DEK autoantibodies are found in inflamed synovium in JIA. We undertook this study to further characterize the nature of DEK autoantibodies in screening serum samples from 2 different cohorts that consisted mostly of patients with JIA. METHODS: DEK autoantibody levels were analyzed in sera from 33 JIA patients, 13 patients with other inflammatory conditions, and 11 healthy controls, as well as in 89 serum samples from JIA patients receiving anti-tumor necrosis factor (anti-TNF) therapy. Recombinant His-tagged full-length DEK protein (1-375 amino acids [aa]) and the 187-375-aa and 1-350-aa His-tagged DEK fragments made in a baculovirus system were used for enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The C-terminal 25-aa fragment of DEK was expressed in a glutathione S-transferase-tagged vector. ELISA results were calculated as area under the curve by the trapezoidal rule. RESULTS: DEK autoantibody levels were significantly higher in patients with polyarticular JIA than in those with oligoarticular JIA, and were higher in patients with polyarticular JIA who had more active disease after cessation of anti-TNF therapy. Immunoblotting against the C-terminal 25-aa fragment of DEK confirmed that this section of the DEK molecule is the most immunogenic domain. CONCLUSION: DEK autoantibody levels are higher in patients with polyarticular JIA than in those with oligoarticular JIA, and higher in patients who have disease flares after cessation of anti-TNF therapy. The C-terminal 25-aa fragment is the most immunogenic portion of DEK. These findings are significant with respect to the nature of DEK autoantibodies, their contribution to JIA pathogenesis, and their implications for JIA management.

Screening for Behavioral Risks: A Precision Healthcare Driven Approach for Chronic Pain Evaluation in Pediatric Specialty Care.

We previously described an informatics tool (PROBE) to automate screening for behavioral risks for pain in children and adolescents. PROBE was deployed for a one year pilot study in our pediatric specialty care practice. Here we describe evaluation of this tool to assess self-report of pain, chronic disease activity and behavioral risks in 109 patients who sought routine care in the busy outpatient pediatric rheumatology practice of our large healthcare system. Results show that patients who self-report poorer self-efficacy and coping skills and night-time awakenings have significantly higher odds (8 and 5 times higher respectively) of reporting chronic pain even after accounting for their chronic disease activity. Our results show that automating screening in specialty care waiting rooms can not only inform the clinicians of patient's unknown risks but may even help drive the judicious use of precision healthcare resources such as cognitive behavioral therapy.

Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's): An ARChiVe Cohort Study.

OBJECTIVE: To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons. RESULTS: In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n = 48) or GPA (n = 183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil. CONCLUSION: Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding.

HDL function and subclinical atherosclerosis in juvenile idiopathic arthritis.

BACKGROUND: Increasing evidence suggests that inflammation adversely impacts the protective properties of high-density lipoproteins (HDL) and progression of atherosclerosis. The impact of early chronic inflammatory conditions on HDL function and vascular risk has not been well investigated. METHODS: We compared measures of HDL particle distribution and functionality, in addition to measures of carotid intima-medial thickness (cIMT) in patients with juvenile idiopathic arthritis (JIA) and age matched controls. RESULTS: JIA patients demonstrated lower levels of HDL cholesterol [47.0 (40.0, 56.0) vs. 56.0 (53.0, 61.0) mg/dL, P=0.04], total HDL [29.5 (27.9, 32.3) vs. 32.9 (31.6, 36.3) mg/dL, P=0.05] and large HDL [5.1 (3.7, 7.3) vs. 8.0 (6.7, 9.7) mg/dL, P=0.04] particles. In association JIA patients demonstrated greater cholesterol efflux mediated via ATP binding cassette A1 (ABCA1) [17.3% (12.8, 19.7) vs. 10.0% (5.8, 16.0), P=0.05] and less efflux mediated via ATP binding cassette G-1 (ABCG1) [3.2% (2.0, 3.9) vs. 4.8% (3.5, 5.8), P=0.01] and SR-B1 [6.9% (6.0, 8.4) vs. 9.1% (8.6, 10.2), P=0.002] compared with controls. Exposure of macrophages to serum from JIA patients resulted in a smaller increase in mRNA expression of ABCA1 (2.0±0.95 vs. 7.1±5.7 fold increase, P=0.01) and greater increases in expression of ABCG1 [1.4 (0.9, 1.5) vs. 0.8 (0.7, 1.1) fold increase, P=0.04] and SR-B1 (1.3±0.47 vs. 0.7±0.3 fold increase, P=0.001) compared with controls. Arylesterase (128.9±27.6 vs. 152.0±45.2 umoles/min/mL, P=0.04) activity and endothelial cell migration (491.2±68.9 vs. 634.2±227.4 cells/field, P=0.01) were less in JIA patients. No differences in cIMT were observed between JIA patients and controls. CONCLUSIONS: The presence of JIA was associated with alterations in HDL particle distribution, cholesterol efflux and non-lipid transporting activities. The ultimate implication of these findings for cardiovascular risk requires further investigation.

Leveraging Electronic Tablets and a Readily Available Data Capture Platform to Assess Chronic Pain in Children: The PROBE system.

The Patient Risks Outcomes and Barriers Evaluation (PROBE) system is developed using a readily available data capture platform (REDCap) and iPads. PROBE performs complete and consistent assessment of pain at every patient visit in pediatric rheumatology practices of our very large healthcare system. Using evidence based clinical guidelines, it combines the following essential elements for care: 1) screening for behavioral risks for chronic pain such as anxiety, sleep deprivation, or painful conditions affecting a caregiver living in child's home, 2) capturing disease activity related measures and enabling 3) clinical decision support. In this demonstration project we describe PROBE and evaluate it for usability in practice. Using PROBE, we observed significant differences for behavioral risk factors in children with juvenile idiopathic arthritis in those who report chronic pain vs. not.

Novel method to collect medication adverse events in juvenile arthritis: results from the childhood arthritis and rheumatology research alliance enhanced drug safety surveillance project.

OBJECTIVE: Few data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product-based registries and clinical trials for juvenile idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4-year (2008-2012) EDSSP. METHODS: Participating physicians were surveyed monthly to ascertain whether their JIA patients experienced an SAE or IME. Sites were surveyed every 6 months to determine the number of unique JIA patients seen at each site during that 6-month period. Reporting rates were calculated per 100 person-years and 95% confidence intervals (95% CIs) were calculated based on a Poisson distribution. RESULTS: Thirty-seven Childhood Arthritis and Rheumatology Research Alliance sites with 115 physicians participated. The mean response rate to the monthly surveys was 65%. There were 147 total SAEs and 145 total IMEs. The largest proportion of SAEs and IMEs occurred in children with polyarticular JIA (39% and 37%, respectively). The majority of SAEs and IMEs were reported for patients receiving therapy with biologic agents (76% and 69%, respectively). The total event rate for SAEs and IMEs combined was 1.07 events per 100 person-years (95% CI 0.95-1.19). The rates for SAEs and IMEs were 0.54 per 100 person-years (95% CI 0.45-0.63) and 0.53 per 100 person-years (95% CI 0.49-0.62), respectively. CONCLUSION: The EDSSP provided a simple tool for SAE/IME reporting within an established research network and resulted in a similar range of reported events as captured by a traditional product-based registry.

Extension study of participants from the trial of early aggressive therapy in juvenile idiopathic arthritis.

OBJECTIVE: To follow children with juvenile idiopathic arthritis (JIA) who had completed at least 6 months of the TRial of Early Aggressive Therapy (TREAT) clinical study for an additional 2 years, describing safety of early aggressive treatment, disease activity, function, and duration of clinical inactive disease (CID) during followup. METHODS: Children were treated as per provider's discretion. Physician, patient/parent, and laboratory measures of disease status as well as safety information were collected at clinic visits every 3 months for up to 2 years. RESULTS: Forty-eight children were followed for a mean of 28 months (range 12-42) beyond the end of the TREAT study. Half of patients were in CID for > 50% of their followup time. Overall, 88% of patients achieved CID at > 1 study visit and 54% achieved clinical remission while taking medication. Six patients were in CID for the duration of the study, and, of those, 2 achieved a full year of clinical remission while not taking medication. Active disease was mild: mean physician's global assessment 2.4, active joint count 3.5, parent global evaluation 2.4, Childhood Health Assessment Questionnaire 0.32, erythrocyte sedimentation rate 19 mm/h, and morning stiffness 23 min. There were no serious adverse events or adverse events reported at grade 3 or higher of Common Terminology Criteria for Adverse Events. CONCLUSION: Early aggressive therapy in this cohort of patients with polyarticular JIA who had high initial disease activity was associated with prolonged periods of CID in the majority of patients during followup. Those not in CID had low levels of disease activity.

The effect of rilonacept versus placebo on health-related quality of life in patients with poorly controlled familial Mediterranean fever.

OBJECTIVE: To examine the effect of rilonacept on the health-related quality of life (HRQoL) in patients with poorly controlled familial Mediterranean fever (FMF). METHODS: As part of a randomized, double-blinded trial comparing rilonacept and placebo for the treatment of FMF, patients/parents completed the modified Child Health Questionnaire (CHQ) at baseline, and at the start and end of each of 4 treatment courses, 2 each with rilonacept and placebo. RESULTS: Fourteen subjects were randomized; mean age was 24.4 ± 11.8 years. At baseline the physical HRQoL score was significantly less (24.2 ± 49.5) but the psychosocial score was similar to the population norm (49.5 ± 10.0). There were significant improvements in most HRQoL concepts after rilonacept but not placebo. Significant differences between rilonacept and placebo were found in the physical (33.7 ± 16.4 versus 23.7 ± 14.5, P = 0.021) but not psychosocial scores (51.4 ± 10.3 versus 49.8 ± 12.4, P = 0.42). The physical HRQoL was significantly impacted by the treatment effect and patient global assessment. CONCLUSION: Treatment with rilonacept had a beneficial effect on the physical HRQoL in patients with poorly controlled FMF and was also significantly related to the patient global assessment. This trial is registered with ClinicalTrials.gov Identifier NCT00582907.

Intestinal obstruction secondary to infantile polyarteritis nodosa.

Polyarteritis Nodosa (PAN) is a rare systemic necrotising vasculitis of medium and small-sized arteries. Patients typically present with systemic symptoms. Obstructive intestinal symptoms are described but usually resolve with treatment of the underlying vascular disease. We report a case of a one year old boy with multiple ischemic small bowel strictures secondary to infantile PAN, who was treated with resection of the affected segments by single port laparoscopy.

Takayasu Arteritis in the pediatric population: a contemporary United States-based single center cohort.

BACKGROUND: Takayasu Arteritis is an idiopathic, chronic, large vessel vasculitis involving the aorta and its primary branches. Few studies have been done in pediatric patients to date with the largest case series of US patients published in 2003 consisting of only 6 patients. METHODS: A retrospective chart review was performed on all patients seen at Cleveland Clinic Children's up until 2012 who met EULAR/PRINTO/PRES classification criteria for childhood Takayasu Arteritis. RESULTS: Twenty-one patients with a mean follow up of 2.3 years were studied. Weight loss, fatigue, and anorexia were the most common presenting complaints. 57.1% of patients were hypertensive at first visit. The most common examintation finding was diminished pulses (61.9%), followed by bruits, and then murmurs. Thoracic aorta stenosis was the most common vascular abnormality. Seven of twenty-one patients responded well to methotrexate and prednisone alone. Ten of twenty-one patients required an additional medication for symptom and disease control (infliximab most commonly). About two-thirds of patients required at least one anti-hypertensive medication. Eight of the twenty-one patients required surgical intervention for severe disease refractory to medications (renal artery stenosis being the most common indication). Almost all patients reported symptomatic improvement after surgical intervention. Two of the eight patients required a second surgery for return of symptoms. Disease sequelae included arterial aneurysms, resolved heart failure, and hypertensive emergencies. CONCLUSION: Our study emphasizes that constitutional symptoms coupled with objective findings of diminished pulses, bruits, and hypertension should raise clinical suspicion for Takayasu Arteritis in pediatric patients. Pharmacologic therapy alone can be successful in controlling disease progression, however surgery was successful in minimizing symptoms when medical therapies failed.

Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis.

OBJECTIVE: To assess the efficacy and safety of rilonacept, an interleukin-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. METHODS: An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multicenter design, followed by an open-label phase. Seventy-one children who had active arthritis in ≥2 joints were randomized (1:1) to the 2 arms of the study. Patients in the rilonacept arm received rilonacept (loading dose 4.4 mg/kg followed by 2.2 mg/kg weekly, subcutaneously) beginning on day 0. Patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary end point was time to response, using the adapted American College of Rheumatology Pediatric 30 criteria coupled with the absence of fever and taper of the dosage of systemic corticosteroids, using prespecified criteria. RESULTS: The time to response was shorter in the rilonacept arm than in the placebo arm (χ(2) = 7.235, P = 0.007). The secondary analysis, which used the same response criteria, showed that 20 (57%) of 35 patients in the rilonacept arm had a response at week 4 compared with 9 (27%) of 33 patients in the placebo arm (P = 0.016). Exacerbation of systemic juvenile idiopathic arthritis (JIA) was the most common severe adverse event. More patients in the rilonacept arm had elevated liver transaminase levels (including levels more than 3 times the upper limit of normal) compared with those in the placebo arm. Adverse events were similar in the 2 arms of the study. CONCLUSION: Rilonacept was generally well tolerated and demonstrated efficacy in active systemic JIA.

Clinically inactive disease in a cohort of children with new-onset polyarticular juvenile idiopathic arthritis treated with early aggressive therapy: time to achievement, total duration, and predictors.

OBJECTIVE: To determine the elapsed time while receiving aggressive therapy to the first observation of clinically inactive disease (CID), total duration of CID and potential predictors of this response in a cohort of children with recent onset of polyarticular juvenile idiopathic arthritis (poly-JIA). METHODS: Eighty-five children were randomized blindly to methotrexate (MTX), etanercept, and rapidly tapered prednisolone (MEP) or MTX monotherapy and assessed for CID over 1 year of treatment. Patients who failed to achieve intermediary endpoints were switched to open-label MEP treatment. RESULTS: Fifty-eight (68.2%) of the 85 patients achieved CID at 1 or more visits including 18 who received blinded MEP, 11 while receiving MTX monotherapy, and 29 while receiving open-label MEP. Patients starting on MEP achieved CID earlier and had more study days in CID compared to those starting MTX, but the differences were not significantly different. Patients given MEP (more aggressive therapy) earlier in the disease course were statistically more likely to have a higher proportion of followup visits in CID than those with longer disease course at baseline. Those who achieved American College of Rheumatology Pediatric 70 response at 4 months had a significantly greater proportion of followup visits in CID, compared to those who failed to achieve this improvement (p < 0.0001). Of the 32 patients who met criteria for CID and then lost CID status, only 3 fulfilled the definition of disease flare. CONCLUSION: Shorter disease duration prior to treatment, a robust response at 4 months, and more aggressive therapy result in a higher likelihood and longer duration of CID in patients with poly-JIA. The original trial from which data for this analysis were obtained is registered on www.clinicaltrials.gov NCT 00443430.

Childhood-onset eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome): a contemporary single-center cohort.

OBJECTIVE: To date only 38 cases of childhood-onset eosinophilic granulomatosis with polyangiitis (cEGPA; formerly Churg-Strauss syndrome) have been reported. Additional patients with cEGPA could enhance the understanding of this rare and life-threatening condition. Our objectives were (1) to determine the frequency of specific organ system involvement; (2) to examine initial therapeutic regimen; and (3) to document disease and therapy-related morbidity in a contemporary cohort of patients with cEGPA. METHODS: Retrospective review of patients evaluated at the Cleveland Clinic between 2003 and 2011 who met either American College of Rheumatology or Lanham criteria for EGPA and whose age was < 18 years at symptom onset. RESULTS: Nine patients (8 female; 7 white) were identified. Median age at onset of rhinitis/asthma symptom was 13 years and median age at diagnosis of cEGPA was 15 years. All patients demonstrated eosinophilia, upper airway disease (allergic rhinitis, chronic sinusitis, and/or nasal polyps), and pulmonary involvement. Other frequently involved organ systems included musculoskeletal (67%), gastrointestinal (67%), cutaneous (67%), neurologic (56%), and cardiac (44%). Antineutrophil cytoplasmic antibody (ANCA) serologies were negative in all patients. The medications used most frequently for initial therapy included oral (44%) or intravenous corticosteroids (56%) and azathioprine (67%). Disease or therapeutic complications occurred in half of the cohort and included heart failure, stroke, and sequela from longterm, high-dose steroids. CONCLUSION: Eosinophilia, in combination with upper airway, pulmonary, musculoskeletal, neurologic, and cardiac manifestations, is frequently observed in cEGPA. ANCA titers are often negative. Steroids are the mainstay of initial therapy but steroid-related side effects occur regularly.

Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever: a randomized trial.

BACKGROUND: Currently, there is no proven alternative therapy for patients with familial Mediterranean fever (FMF) that is resistant to or intolerant of colchicine. Interleukin-1 is a key proinflammatory cytokine in FMF. OBJECTIVE: To assess the efficacy and safety of rilonacept, an interleukin-1 decoy receptor, in treating patients with colchicine-resistant or -intolerant FMF. DESIGN: Randomized, double-blind, single-participant alternating treatment study. (ClinicalTrials.gov number: NCT00582907). SETTING: 6 U.S. sites. PATIENTS: Patients with FMF aged 4 years or older with 1 or more attacks per month. INTERVENTION: One of 4 treatment sequences that each included two 3-month courses of rilonacept, 2.2 mg/kg (maximum, 160 mg) by weekly subcutaneous injection, and two 3-month courses of placebo. MEASUREMENTS: Differences in the frequency of FMF attacks and adverse events between rilonacept and placebo. RESULTS: 8 males and 6 females with a mean age of 24.4 years (SD, 11.8) were randomly assigned. Among 12 participants who completed 2 or more treatment courses, the rilonacept-placebo attack risk ratio was 0.59 (SD, 0.12) (equal-tail 95% credible interval, 0.39 to 0.85). The median number of attacks per month was 0.77 (0.18 and 1.20 attacks in the first and third quartiles, respectively) with rilonacept versus 2.00 (0.90 and 2.40, respectively) with placebo (median difference, -1.74 [95% CI, -3.4 to -0.1]; P = 0.027). There were more treatment courses of rilonacept without attacks (29% vs. 0%; P = 0.004) and with a decrease in attacks of greater than 50% compared with the baseline rate during screening (75% vs. 35%; P = 0.006) than with placebo. However, the duration of attacks did not differ between placebo and rilonacept (median difference, 1.2 days [-0.5 and 2.4 days in the first and third quartiles, respectively]; P = 0.32). Injection site reactions were more frequent with rilonacept (median difference, 0 events per patient treatment month [medians of -4 and 0 in the first and third quartiles, respectively]; P = 0.047), but no differences were seen in other adverse events. LIMITATION: Small sample size, heterogeneity of FMF mutations, age, and participant indication (colchicine resistance or intolerance) were study limitations. CONCLUSION: Rilonacept reduces the frequency of FMF attacks and seems to be a treatment option for patients with colchicine-resistant or -intolerant FMF. PRIMARY FUNDING SOURCE: U.S. Food and Drug Administration, Office of Orphan Products Development.

Autoinflammatory syndromes: fever is not always a sign of infection.

Autoinflammatory syndromes are a newly understood group of conditions characterized by recurrent episodes of fever, rash, and serositis. Generalists and specialists should know about and consider these syndromes in the differential diagnosis of recurrent fever. This article reviews the genetics, pathophysiology, clinical presentation, and treatment of several of these relatively recently discovered diseases.

The role of benign joint hypermobility in the pain experience in Juvenile Fibromyalgia: an observational study.

BACKGROUND: Juvenile Fibromyalgia (JFM) is characterized by chronic widespread musculoskeletal pain and approximately 40% of children and adolescents with JFM also suffer from benign joint hypermobility (HM). It is not currently known if the presence of HM affects the pain experience of adolescents with JFM. The objective of this study was to examine whether there were any differences in self-reported pain intensity and physiologic pain sensitivity between JFM patients with and without joint HM. METHODS: One hundred thirty-one adolescent patients with JFM recruited from four pediatric rheumatology clinics completed a daily visual analogue scale (VAS) pain rating for one week and underwent a standardized 18-count tender point (TP) dolorimeter assessment. Medical records were reviewed for the presence of joint HM. Average pain VAS ratings, tender point count and tender point sensitivity were compared between JFM patients with and without hypermobility (HM+ and HM-). RESULTS: Nearly half (48%) the sample of JFM patients were found to be HM+. HM+ and HM- patients did not differ in their self-reported pain intensity. However, HM + patients had significantly greater pain sensitivity, with lower TP thresholds (p = 0.002) and a greater number of painful TPs (p = 0.003) compared to HM- patients. CONCLUSION: The presence of HM among adolescent patients with JFM appears to be associated with enhanced physiologic pain sensitivity, but not self-report of clinical pain. Further examination of the mechanisms for increased pain sensitivity associated with HM, especially in adolescents with widespread pain conditions such as JFM is warranted.