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 For those patients who maintained clinically inactive disease over the 6 months, anti-TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare.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.

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.

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.

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.

Decreased use of non-steroidal anti-inflammatory drugs for the treatment of juvenile idiopathic arthritis in the era of modern aggressive treatment.

We examined whether the use of non-steroidal anti-inflammatory drugs has decreased for the treatment of juvenile idiopathic arthritis in a cohort treated with aggressive modern therapy as well as potential factors influencing their use. We randomly sampled 100 of 377 patients with juvenile idiopathic arthritis treated by pediatric rheumatologists at our center between 2003 and 2008. We used electronic health records and detailed chart review to examine the trends of non-steroidal anti-inflammatory drug use and factors impacting use, including disease subtype, disease activity, adverse effects, and other medication use. Data were analyzed longitudinally using a non-linear mixed effects regression model. Ninety-two percent used non-steroidal anti-inflammatory drugs at some point and 70% at anti-inflammatory doses. At patients' last visit within the study time frame, 52% were using non-steroidal anti-inflammatory drugs and only 28% at anti-inflammatory doses, decreased from 79 and 56%, respectively, at their first visit. In 2003, 53% used an anti-inflammatory dose compared to 35% in 2008. Active joint count was significantly associated with non-steroidal anti-inflammatory drug use at anti-inflammatory doses, while methotrexate and biologic modifiers use, later calendar year, the presence of uveitis, and positive anti-nuclear antibody status were significant negative predictors. The use of non-steroidal anti-inflammatory drugs decreased significantly over time, with decreasing numbers of active joints, and when methotrexate or biologic modifiers were used. The number of patients currently using non-steroidal anti-inflammatory drugs is less than reported in series from the 1990s.

Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis.

OBJECTIVE: To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months. METHODS: Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2-16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks (arm 1), or MTX (same dosage as arm 1), etanercept placebo, and prednisolone placebo (arm 2). The primary outcome measure was clinical inactive disease at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous clinical inactive disease) at 12 months. RESULTS: By 6 months, clinical inactive disease had been achieved in 17 (40%) of 42 patients in arm 1 and 10 (23%) of 43 patients in arm 2 (χ(2) = 2.91, P = 0.088). After 12 months, clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 (P = 0.053). There were no significant interarm differences in adverse events. CONCLUSION: Although this study did not meet its primary end point, early aggressive therapy in this cohort of children with recent-onset polyarticular JIA resulted in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms.

Airway manifestations in childhood granulomatosis with polyangiitis (Wegener's).

OBJECTIVE: Granulomatosis with polyangiitis (Wegener's) (GPA) is a necrotizing granulomatous vasculitis affecting the upper and lower respiratory tract, kidneys, and other small vessels throughout multiple organ systems. Recently, classification criteria for childhood GPA have been proposed and include the addition of airway stenosis. Airway inflammation occurs more frequently in children than adults and often proves difficult to diagnose and treat. Our objectives were to 1) determine the frequency of airway involvement in a cohort of children with GPA as defined by the European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Pediatric Rheumatology European Society (EULAR/PRINTO/PRES) criteria, 2) document the frequency of specific airway findings, and 3) review our treatment approach to children with GPA-related airway disease. METHODS: A retrospective chart review was performed on patients ages <18 years with a diagnosis of vasculitis evaluated at the Cleveland Clinic between 2004 and 2010. RESULTS: Twenty-eight patients fulfilling the EULAR/PRINTO/PRES classification criteria for the diagnosis of childhood GPA were included in the analysis. There was a mean followup time of 3.1 years. The overall prevalence of any airway disease was 86%, with upper airway involvement in 86% and laryngotracheobronchial (LTB) disease in 50% of patients. LTB disease was present at diagnosis in 36%, while in the remaining 14% it developed on immunosuppressive therapy. Ten patients underwent a successful endoscopic intervention. CONCLUSION: Airway manifestations frequently occur in childhood GPA. Inflammatory changes can occur at any point in the disease course, necessitating diligent surveillance. Endoscopic interventions for LTB stenotic lesions represent a safe and effective therapeutic option.

Orbital inflammation in IgG4-related sclerosing disease.

IgG4-related sclerosing disease is a recently described systemic inflammatory disease that should be considered when evaluating patients with nonspecific orbital inflammation (pseudotumor). Orbital biopsy is necessary to establish a diagnosis and demonstrates lymphoplasmacytic infiltration, fibrosis, obliterative phlebitis of medium and small veins, and variable degrees of eosinophilia. We report the clinical and histopathological findings of 2 patients who developed chronic orbital inflammation as a manifestation of IgG4-related sclerosing disease. The 2 cases illustrate the widely varying clinical characteristics of this elusive disease.

Parent satisfaction with the electronic medical record in an academic pediatric rheumatology practice.

BACKGROUND: Patient satisfaction has not been widely studied with respect to implementation of the electronic medical record (EMR). There are few reports of the impact of the EMR in pediatrics. OBJECTIVE: The objective of this study was to assess the impact of implementation of an electronic medical record system on families in an academic pediatric rheumatology practice. METHODS: Families were surveyed 1 month pre-EMR implementation and 3 months post-EMR implementation. RESULTS: Overall, EMR was well received by families. Compared with the paper chart, parents agreed the EMR improved the quality of doctor care (55% or 59/107 vs 26% or 26/99, P < .001). More parents indicated they would prefer their pediatric physicians to use an EMR (68% or 73/107 vs 51% or 50/99, P = .01). CONCLUSIONS: Transitioning an academic pediatric rheumatology practice to an EMR can increase family satisfaction with the office visit.

The localized scleroderma skin severity index and physician global assessment of disease activity: a work in progress toward development of localized scleroderma outcome measures.

OBJECTIVE: To develop and evaluate a Localized Scleroderma (LS) Skin Severity Index (LoSSI) and global assessments' clinimetric property and effect on quality of life (QOL). METHODS: A 3-phase study was conducted. The first phase involved 15 patients with LS and 14 examiners who assessed LoSSI [surface area (SA), erythema (ER), skin thickness (ST), and new lesion/extension (N/E)] twice for inter/intrarater reliability. Patient global assessment of disease severity (PtGA-S) and Children's Dermatology Life Quality Index (CDLQI) were collected for intrarater reliability evaluation. The second phase was aimed to develop clinical determinants for physician global assessment of disease activity (PhysGA-A) and to assess its content validity. The third phase involved 2 examiners assessing LoSSI and PhysGA-A on 27 patients. Effect of training on improving reliability/validity and sensitivity to change of the LoSSI and PhysGA-A was determined. RESULTS: Interrater reliability was excellent for ER [intraclass correlation coefficient (ICC) 0.71], ST (ICC 0.70), LoSSI (ICC 0.80), and PhysGA-A (ICC 0.90) but poor for SA (ICC 0.35); thus, LoSSI was modified to mLoSSI. Examiners' experience did not affect the scores, but training/practice improved reliability. Intrarater reliability was excellent for ER, ST, and LoSSI (Spearman's rho = 0.71-0.89) and moderate for SA. PtGA-S and CDLQI showed good intrarater agreement (ICC 0.63 and 0.80). mLoSSI correlated moderately with PhysGA-A and PtGA-S. Both mLoSSI and PhysGA-A were sensitive to change following therapy. CONCLUSION: mLoSSI and PhysGA-A are reliable and valid tools for assessing LS disease severity and show high sensitivity to detect change over time. These tools are feasible for use in routine clinical practice. They should be considered for inclusion in a core set of LS outcome measures for clinical trials.