Comprehensive and reliable sonographic assessment and scoring system for inflammatory lesions of the paediatric ankle.

OBJECTIVE: The clinical decision-making process in paediatric arthritis lacks an objective, reliable bedside imaging tool. The aim of this study was to develop a US scanning protocol and assess the reliability of B-mode and Doppler scoring systems for inflammatory lesions of the paediatric ankle. METHODS: As part of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) US group, 19 paediatric rheumatologists through a comprehensive literature review developed a set of standardized views and scoring systems to assess inflammatory lesions of the synovial recesses as well as tendons of the paediatric ankle. Three rounds of scoring of still images were followed by one practical exercise. Agreement among raters was assessed using two-way single score intraclass correlation coefficients (ICC). RESULTS: Of the 37 initially identified views to assess the presence of ankle synovitis and tenosynovitis, nine views were chosen for each B-mode and Doppler mode semi-quantitative evaluation. Several scoring exercises and iterative modifications resulted in a final highly reliable scoring system: anterior tibiotalar joint ICC: 0.93 (95% CI 0.92, 0.94), talonavicular joint ICC: 0.86 (95% CI 0.81, 0.90), subtalar joint ICC: 0.91 (95% CI 0.88, 0.93) and tendons ICC: 0.96 (95% CI 0.95, 0.97). CONCLUSION: A comprehensive and reliable paediatric ankle US scanning protocol and scoring system for the assessment of synovitis and tenosynovitis were successfully developed. Further validation of this scoring system may allow its use as an outcome measure for both clinical and research applications.

Reliability of the Pediatric Specific Musculoskeletal Ultrasound Scoring Systems for the Elbow, Wrist, and Finger Joints.

OBJECTIVE: Musculoskeletal ultrasound (MSUS) is increasingly being used in the evaluation of pediatric musculoskeletal diseases. In order to provide objective assessments of arthritis, reliable MSUS scoring systems are needed. Recently, joint-specific scoring systems for arthritis of the pediatric elbow, wrist, and finger joints were proposed by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) MSUS workgroup. This study aimed to assess the reliability of these scoring systems when used by sonographers with different levels of expertise. METHODS: Members of the CARRA MSUS workgroup attended training sessions for scoring the elbow, wrist, and finger. Subsequently, scoring exercises of B mode and power Doppler (PD) mode still images for each joint were performed. Interreader reliability was determined using 2-way single-score intraclass correlation coefficients (ICCs) for synovitis and Cohen [Formula: see text] for tenosynovitis. RESULTS: Seventeen pediatric rheumatologists with different levels of MSUS expertise (1-15 yrs) completed a 2-hour training session and calibration exercise for each joint. Excellent reliability (ICC > 0.75) was found after the first scoring exercise for all the finger and elbow views evaluated on B mode and PD mode, and for all of the wrist views on B mode. After a second training session and a scoring exercise, the wrist PD mode views reached excellent reliability as well. CONCLUSION: The preliminary CARRA MSUS scoring systems for assessing arthritis of the pediatric elbow, wrist, and finger joints demonstrate excellent reliability among pediatric MSUS sonographers with different levels of expertise. With further validation, this reliable joint-specific scoring system could serve as a clinical tool and scientific outcome measure.

The Systemic Juvenile Idiopathic Arthritis Cohort of the Childhood Arthritis and Rheumatology Research Alliance Registry: 2010-2013.

OBJECTIVE: We aimed to identify the (1) demographic/clinical characteristics, (2) medication usage trends, (3) variables associated with worse disease activity, and (4) characteristics of patients with persistent chronic arthritis in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry's systemic juvenile idiopathic arthritis (sJIA) cohort. METHODS: Demographics, disease activity measures, and medications at enrollment of patients with sJIA in the CARRA Registry were analyzed using descriptive statistics. Multivariate analyses were conducted to identify associations with increased disease activity. Medication usage frequencies were calculated by year. RESULTS: There were 528 patients with sJIA enrolled in the registry (2010-2013). There were 435 patients who had a complete dataset; of these, 372 met the International League of Associations for Rheumatology criteria and were included in the analysis. At enrollment, median disease duration and joint count were 3.7 years and 0, respectively; 16.4% had a rash and 6.7% had a fever. Twenty-six percent were taking interleukin 1 (IL-1) inhibitors and 29% glucocorticoids. Disease-modifying antirheumatic drugs and tumor necrosis factor inhibitors use decreased, while IL-6 inhibitor use increased between 2010 and 2013. African American patients had worse joint counts (p = 0.003), functional status (p = 0.01), and physician's global assessment (p = 0.008). Of the 255 subjects with > 2 years of disease duration, 56% had no arthritis or systemic symptoms, while 32% had persistent arthritis only. CONCLUSION: Most patients in the largest sJIA cohort reported to date had low disease activity. Practice patterns for choice of biologic agents appeared to change over the study period. Nearly one-third had persistent arthritis without systemic symptoms > 2 years after onset. African Americans were associated with worse disease activity. Strategies are needed to improve outcomes in subgroups with poor prognosis.

Autoimmune response to transthyretin in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatological condition. Although it has been proposed that JIA has an autoimmune component, the autoantigens are still unknown. Using biochemical and proteomic approaches, we identified the molecular chaperone transthyretin (TTR) as an antigenic target for B and T cell immune responses. TTR was eluted from IgG complexes and affinity purified from 3 JIA patients, and a statistically significant increase in TTR autoantibodies was observed in a group of 43 JIA patients. Three cryptic, HLA-DR1-restricted TTR peptides, which induced CD4+ T cell expansion and IFN-γ and TNF-α production in 3 out of 17 analyzed patients, were also identified. Misfolding, aggregation and oxidation of TTR, as observed in the synovial fluid of all JIA patients, enhanced its immunogenicity in HLA-DR1 transgenic mice. Our data point to TTR as an autoantigen potentially involved in the pathogenesis of JIA and to oxidation and aggregation as a mechanism facilitating TTR autoimmunity.

Normal epiphyseal cartilage measurements in the knee in children: an alternative sonographic approach.

OBJECTIVES: The purpose of this study was to validate previously reported distal femoral cartilage measurements in healthy children of different ages using an alternative sonographic imaging plane and patient position than previously reported and to provide preliminary proximal tibial epiphyseal cartilage measurements in healthy children. METHODS: Distal femoral and proximal tibial epiphyseal cartilage thickness was measured using sonography in a cohort of healthy children based on a coronal image at the medial aspect of the femorotibial joint with the knee in 30° of flexion. The average of 3 measurements of femoral and tibial epiphyseal cartilage was obtained and correlated with age and sex. Femoral epiphyseal cartilage measurements were compared to recently reported measurements at the patellofemoral joint. RESULTS: Sixty children (31 boys and 29 girls; newborn to 21 years; mean, 9 years; median, 7 years 11 months) were imaged. Seventy-four percent of distal femoral cartilage epiphyseal measurements fell into the 95% confidence intervals predicted by previously published reports. At age ranges outside those previously reported, there was less concordance between measured cartilage thickness values and those predicted. CONCLUSIONS: Values of distal femoral epiphyseal cartilage thickness measured by sonography of the femorotibial joint are similar to those reported at the patellofemoral joint. We propose that femoral epiphyseal cartilage thickness be measured on the basis of a coronal image at the medial femorotibial joint. This technique requires less knee flexion, which may prove advantageous when evaluating cartilage in patients with joint inflammation and a limited range of motion. It also allows concurrent measurement of tibial epiphyseal cartilage and thus provides another parameter for assessing cartilage loss.

Humoral and cell-mediated immune responses to monovalent 2009 influenza A/H1N1 and seasonal trivalent influenza vaccines in high-risk children.

OBJECTIVE: Humoral and cell-mediated immune responses to monovalent 2009 pandemic influenza A (H1N1/2009) and seasonal trivalent influenza (TIV) vaccines were evaluated in healthy children and children with asthma, sickle cell disease (SCD), systemic lupus erythematosus (SLE), and solid organ transplantation (SOT). STUDY DESIGN: Blood was collected from 112 subjects at the time of H1N1/2009 vaccination and 46 ± 15 days later for hemagglutination inhibition titers and γ-interferon ELISPOT responses to H1N1/2009 vaccine and TIV; unvaccinated children also received TIV at enrollment. RESULTS: A significant increase in the percentage of subjects with seroprotective hemagglutination inhibition titers to both vaccines was observed in all high-risk groups. Children with asthma and SCD were most likely to achieve seroprotective titers to H1N1/2009, whereas <50% of subjects with SOT and SLE had a seroprotective response. Subjects with SOT and SLE also had lower rates of seroprotection after TIV, and subjects with SLE had the lowest ELISPOT responses to both vaccines. Overall, 73% of healthy children exhibited protective responses to TIV; only 35% achieved seroprotection for H1N1/2009. CONCLUSIONS: This evaluation of immune responses to H1N1/2009 in high-risk children suggests suboptimal responses for SOT and SLE subjects, but not for subjects with SCD or asthma. Higher antigen dose, additional dose regimens, or both for immunocompromised children warrant further investigation.

The heart of the matter: an atypical presentation of Takayasu arteritis in the Pediatric Emergency Department.

Takayasu arteritis (TA) is a rare chronic large-vessel vasculitis of unknown etiology. Although commonly thought of as an adult disease, initial manifestations frequently appear during adolescence. This is a case discussion of an 11-year-old boy with a recent history of fever who presented with shortness of breath, sore throat, chest pain, hypertension, and a new murmur. He had a markedly elevated antistreptolysin O titer, had a prolonged PR interval, and was initially evaluated with acute rheumatic fever. After admission, he had persistent hypertension, proteinuria, and hemoptysis, which prompted a magnetic resonance angiography that revealed aortic enhancement and thickening, and he was evaluated with TA. To our knowledge, this is the first case report in the pediatric literature of TA presenting with heart block. This case highlights the recondite nature of the systemic vasculitides and emphasizes the importance of keeping a broad differential diagnosis when seeing patients who present with common complaints.

Detection of active disease in juvenile idiopathic arthritis: sensitivity and specificity of the physical examination vs ultrasound.

OBJECTIVE: To determine sensitivity and specificity of the physical examination (PE) for identifying synovitis in the knee and ankle joints of children with juvenile idiopathic arthritis (JIA), and to identify cases in which ultrasound (US) screening augments the PE. METHODS: Nineteen patients with JIA were referred for US. Both knees and ankles were examined using US with and without power Doppler. Active arthritis on PE was defined as (1) non-bony swelling or (2) limitation of motion with either pain on motion or tenderness to palpation. Active arthritis on US was defined as synovial hyperplasia, effusion, or increased vascularity on power Doppler scan. RESULTS: There was agreement between US and PE in 75% of cases. PE was 64% sensitive and 86% specific for identifying active arthritis. PE was 100% specific if (1) the patient was positive for both PE criteria or (2) if arthritis was present on PE in the knees. When the PE was negative and the US was positive, 21.4% developed active disease on PE within 6 months. In cases where the PE was positive and US was negative, the joint involved was most often the ankle and frequently the subtalar joint. CONCLUSION: PE is neither highly sensitive nor specific for identifying active synovitis when compared to US, and screening with US can identify subclinical disease. In joints with both non-bony swelling and limitation of motion with pain on motion or tenderness, and in the knee joint, little additional information is gained by US. This has implications for classification and treatment of JIA.

Wasabi nose: an underreported complication of cyclophosphamide infusions.

Wasabi nose, a term used to describe the nasopharyngeal discomfort experienced during cyclophosphamide infusions, is a rare phenomenon, previously described in case reports of adult oncology patients typically receiving high-dose chemotherapy regimens. The underlying mechanism by which this phenomenon occurs is unknown. We report four cases of children with rheumatic diseases afflicted by profound nasopharyngeal discomfort secondary to low-dose cyclophosphamide infusions. We additionally review the literature regarding potential medical management of these complications and describe our experience using these interventions.

Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series.

OBJECTIVE: To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA). METHODS: Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome. RESULTS: Among 46 patients meeting inclusion criteria, anakinra monotherapy was used in 10 patients (22%), while 67% received corticosteroids and 33% received additional DMARDs. Outcomes were evaluated at a median followup interval of 14.5 months. Fever and rash resolved within 1 month in >95% of patients, while C-reactive protein and ferritin normalized within this interval in >80% of patients. Active arthritis persisted at 1 month in 39% of patients, at 3 months in 27%, and at >6 months of followup in 11%. Approximately 60% of patients, including 8 of 10 receiving anakinra monotherapy, attained a complete response without escalation of therapy. Disease characteristics and treatment were similar in partial and complete responders, except that partial responders were markedly younger at onset (median age 5.2 years versus 10.2 years; P = 0.004). Associated adverse events included documented bacterial infection in 2 patients and hepatitis in 1 patient. Tachyphylaxis was not observed. CONCLUSION: Anakinra as first-line therapy for systemic JIA was associated with rapid resolution of systemic symptoms and prevention of refractory arthritis in almost 90% of patients during the interval examined. These results justify further study of IL-1 inhibition as first-line, rather than rescue, therapy in systemic JIA.

Leuconostoc septicemia in a preterm neonate on vancomycin therapy: case report and literature review.

We report the case of a 26-day-old premature infant born at 24 weeks' gestation who developed septicemia while receiving vancomycin therapy. The blood isolate initially identified as a vancomycin-resistant Streptococcous viridans was found to be Leuconostoc spp. Her condition improved with parenteral ampicillin and gentamicin therapy and removal of the intravenous central catheter. Prematurity is a recognized risk factor for Leuconostoc disease. Clinicians need to consider Leuconostoc spp. when vancomycin-resistant pathogens are identified and provide appropriate therapy.