Kelly Rouster-Stevens

Lactobacillus Sepsis Associated With Probiotic Therapy

Probiotic strains of lactobacilli are increasingly being used in clinical practice because of their many health benefits. Infections associated with probiotic strains of lactobacilli are extremely rare. We describe 2 patients who received probiotic lactobacilli and subsequently developed bacteremia and sepsis attributable to Lactobacillus species. Molecular DNA fingerprinting analysis showed that the Lactobacillus strain isolated from blood samples was indistinguishable from the probiotic strain ingested by the patients. This report indicates, for the first time, that invasive disease can be associated with probiotic lactobacilli. This report should not discourage the appropriate use of Lactobacillus or other probiotic agents but should serve as a reminder that these agents can cause invasive disease in certain populations.

Pharmacokinetic study of oral prednisolone compared with intravenous methylprednisolone in patients with juvenile dermatomyositis

OBJECTIVE To determine areas under the curve (AUCs) of oral prednisolone (OP) and intravenous methylprednisolone (IVMP) in patients with juvenile dermatomyositis (DM) and assess the association with nailfold end-row loops (ERLs). Patients with active disease have fewer ERLs that possibly occur in the gastrointestinal tract, impairing absorption of oral medications. METHODS Six patients with juvenile DM received 50 mg/m(2) of OP (day 1) and IVMP (day 2). Blood was drawn at baseline and at 5, 15, 30, 45, 60, and 90 minutes, and hourly (hours 2-8) after each dose. Samples were analyzed by reverse-phase high-performance liquid chromatography for levels of prednisolone and methylprednisolone. AUCs of OP and IVMP were determined by the trapezoid method; pharmacokinetic parameters were obtained using noncompartmental and compartmental analysis. ERLs were determined from freeze-frame video microscopy and nailfold capillaroscopy. RESULTS There was a trend toward significance in difference in mean AUC of IVMP (116.72 microg x ml/hour) compared with OP (65.16 microg x ml/hour; P = 0.059). Mean peak concentration was higher for IVMP (34.49 microg/ml) than OP (7.08 microg/ml); mean half-life was shorter for IVMP (1.90 hours) than OP (2.36 hours). There was an inverse association between DeltaAUCs (IVMP AUC - OP AUC) and ERLs (R = -0.68, P = 0.044). CONCLUSION Patients with juvenile DM and ERL loss may have decreased bioavailability of OP compared with IVMP. This can provide the rationale for greater efficacy of IVMP in patients with active vasculopathy of juvenile DM. Further studies investigating the pharmacokinetics and pharmacodynamics of high-dose IVMP need to be performed in patients with juvenile DM.

Mycophenolate Mofetil: A Possible Therapeutic Agent for Children With Juvenile Dermatomyositis

To determine if mycophenolate mofetil (MMF) diminishes skin and muscle disease activity in children with juvenile dermatomyositis (DM), thereby permitting a decrease in corticosteroid dose.

Risk Markers of Juvenile Idiopathic Arthritis-associated Uveitis in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry

Objective. To characterize the epidemiology and clinical course of children with juvenile idiopathic arthritis-associated uveitis (JIA-U) in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and explore differences between African American (AA) and non-Hispanic white (NHW) children. Methods. There were 4983 children with JIA enrolled in the CARRA Registry. Of those, 3967 NHW and AA children were included in this study. Demographic and disease-related data were collected from diagnosis to enrollment. Children with JIA were compared to those with JIA-U. Children with JIA-U were also compared by race. Results. There were 459/3967 children (11.6%) with JIA-U in our cohort with a mean age (SD) of 11.4 years (± 4.5) at enrollment. Compared to children with JIA, they were younger at arthritis onset, more likely to be female, had < 5 joints involved, had oligoarticular JIA, and were antinuclear antibody (ANA)-positive, rheumatoid factor (RF)-negative, and anticitrullinated protein antibody-negative. Predictors of uveitis development included female sex, early age of arthritis onset, and oligoarticular JIA. Polyarticular RF-positive JIA subtype was protective. Nearly 3% of children with JIA-U were AA. However, of the 220 AA children with JIA, 6% had uveitis; in contrast, 12% of the 3721 NHW children with JIA had uveitis. Conclusion. In the CARRA registry, the prevalence of JIA-U in AA and NHW children is 11.6%. We confirmed known uveitis risk markers (ANA positivity, younger age at arthritis onset, and oligoarticular JIA). We describe a decreased likelihood of uveitis in AA children and recommend further exploration of race as a risk factor in a larger population of AA children.

Pilot study of etanercept in patients with refractory juvenile dermatomyositis

To evaluate the efficacy of etanercept in patients with juvenile dermatomyositis (DM) refractory to standard treatment.

Development of a Novel Renal Activity Index of Lupus Nephritis in Children and Young Adults

Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histologic LN activity.

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative

To develop response criteria for juvenile dermatomyositis (DM).

Meta-analysis confirms association between TNFA-G238A variant and JIA, and between PTPN22-C1858T variant and oligoarticular, RF-polyarticular and RF-positive polyarticular JIA

BackgroundAlthough more than 100 non-HLA variants have been tested for associations with juvenile idiopathic arthritis (JIA) in candidate gene studies, only a few have been replicated. We sought to replicate reported associations of single nucleotide polymorphisms (SNPs) in the PTPN22, TNFA and MIF genes in a well-characterized cohort of children with JIA.MethodsWe genotyped and analyzed 4 SNPs in 3 genes: PTPN22 C1858T (rs2476601), TNFA G-308A, G-238A (rs1800629, rs361525) and MIF G-173C (rs755622) in 647 JIA cases and 751 healthy controls. We tested for association between each variant and JIA as well as JIA subtypes. We adjusted for multiple testing using permutation procedures. We also performed a meta-analysis that combined our results with published results from JIA association studies.ResultsWhile the PTPN22 variant showed only modest association with JIA (OR = 1.29, p = 0.0309), it demonstrated a stronger association with the RF-positive polyarticular JIA subtype (OR = 2.12, p = 0.0041). The MIF variant was not associated with the JIA as a whole or with any subtype. The TNFA-238A variant was associated with JIA as a whole (OR 0.66, p = 0.0265), and demonstrated a stronger association with oligoarticular JIA (OR 0.33, p = 0.0006) that was significant after correction for multiple testing. TNFA-308A was not associated with JIA, but was nominally associated with systemic JIA (OR = 0.33, p = 0.0089) and enthesitis-related JIA (OR = 0.40, p = 0.0144). Meta-analyses confirmed significant associations between JIA and PTPN22 (OR 1.44, p <0.0001) and TNFA-238A (OR 0.69, p < 0.0086) variants. Subtype meta-analyses of the PTPN22 variant revealed associations between RF-positive, RF-negative, and oligoarticular JIA, that remained significant after multiple hypothesis correction (p < 0.0005, p = 0.0007, and p < 0.0005, respectively).ConclusionsWe have confirmed associations between JIA and PTPN22 and TNFA G-308A. By performing subtype analyses, we discovered a statistically-significant association between the TNFA-238A variant and oligoarticular JIA. Our meta-analyses confirm the associations between TNFA-238A and JIA, and show that PTPN22 C1858T is associated with JIA as well as with RF-positive, RF-negative and oligoarticular JIA.

Catheter-related bacteremia due to Roseomonas species in pediatric hematology/oncology patients

Roseomonas is a newly described genus of pink‐pigmented, gram‐negative bacteria. Human infections caused by Roseomonas species are very rare. We report two cases of central venous catheter‐related bacteremia associated with Roseomonas species (one case with R. gilardii and one with R. fauriae), and review the clinical spectrum of previously reported cases in the literature. Clinicals should be aware that Roseomonas species may cause serious infections in children. Pediatr Blood Cancer 2006, 46:514–516.

Limitations in the Classification of Childhood-onset Rheumatoid Arthritis

Objective. Rheumatoid factor-positive polyarthritis (RF+ poly) is the juvenile idiopathic arthritis (JIA) category that resembles adult seropositive rheumatoid arthritis (RA). We studied children with RF+ and/or anticyclic citrullinated peptide antibody (anti-CCP)+ JIA to determine what proportion of those children meet International League of Associations for Rheumatology (ILAR) criteria for RF+ poly JIA and to assess for significant differences between children who meet RF+ poly criteria and those who are classified in other categories. Methods. Charts of children with JIA who were RF+ and/or anti-CCP+ were reviewed. Children with RF+ poly JIA were compared to children in other categories. Statistical analysis was performed using chi-square, Fisher’s exact test, and the Student’s t-test. Results. Of 56 children with RF+ and/or anti-CCP+ JIA, 34 (61%) met ILAR criteria for RF+ poly JIA. Twelve children had RF–/anti-CCP+ JIA with low anti-CCP titers. When these 12 children were excluded, there were few significant differences between children who met criteria for RF+ poly and those who were classified in other categories. The American College of Rheumatology/European League Against Rheumatism criteria for RA identified more RF+ children than did the ILAR RF+ poly classification (100% vs 77%). Conclusion. A number of children with RF+ arthritis were excluded from the RF+ poly JIA classification, though many demographic features and disease measures were similar to those of children who met criteria for RF+ poly JIA. We propose prioritization of RF/anti-CCP positivity over specific exclusions, along with inclusion of anti-CCP, in future revisions of the JIA classification criteria, to improve the sensitivity of diagnosing childhood-onset RA.