Search

Objective. To examine the usefulness of ultrasonography (USG) for monitoring paediatric localized scleroderma (LS). Methods. A retrospective chart review of six paediatric patients who had USG of their LS. Results. USG detected several abnormalities in active lesions including increased blood flow, increased echogenicity and loss of subcutaneous fat. USG findings corresponded with clinical assessment, and documented regeneration of subcutaneous fat and reduction in lesion size during treatment. In one patient, USG was more sensitive than magnetic resonance evaluation. Conclusion. USG was found to be a sensitive tool for assessing the activity and extent of LS lesions in paediatric patients. Further studies are needed to assess its general applicability for monitoring these patients.

1. Danielle Magrini, DO* 2. Suzanne C. Li, MD, PhD† 3. Vikram Bhise, MD* 4. Pamela F. Weiss, MD, MSCE‡ 5. Lakshmi N. Moorthy, MD, MS* 1. *Department of Pediatrics, Rutgers-RWJ Medical School, New Brunswick, NJ; 2. †Department of Pediatrics, Joseph M Sanzari Children’s Hospital, Hackensack University Medical Center, Hackensack, NJ; 3. ‡Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA. A 9-year-old girl presents to the dermatology clinic for right-sided scalp hair loss. The hair loss started as a small spot on the right frontal scalp but has increased in size over the last few months. She has no history of shortness of breath, chest pain, weight loss, fevers, seizures, headaches, learning disabilities, vision problems, musculoskeletal complaints, or recurrent infections. She denies trichotillomania or risks for traction alopecia. The hair throughout the remainder of the scalp, eyebrows, and eyelashes appears normal. On physical examination, her temperature is 36.3°C (97.4°F), pulse is 77 beats/min, respiratory rate is 20 breaths/min, and blood pressure is 101/65 mm Hg. Her weight, height, and body mass index are at the 50th percentile. She has a solitary patch of alopecia over the right frontal hairline extending about 10 cm into the parietal scalp region but not overtly appearing …

OBJECTIVE. Systemic sclerosis (SSc) is a rare disease that is particularly uncommon in children. Specific HLA alleles have been associated with SSc in adults. This study was undertaken to investigate HLA class II alleles in juvenile-onset SSc. METHODS. DRB1, DQA1, and DQB1 alleles were determined by DNA-based HLA typing. Analyses were conducted comparing Caucasian patients with juvenileonset SSc (n = 76) to healthy Caucasian controls (n = 581). RESULTS. Initial analyses focused on HLA class II associations previously reported in adult Caucasian patients with SSc. The frequency of DRB1*11 was not significantly increased in juvenile-onset SSc (22.4% of patients with juvenile-onset SSc versus 17.6% of controls; odds ratio [OR] 1.35, P = 0.34), nor were the specific DRB1*11:01 or *11:04 alleles. DQA1*05, a risk factor previously identified in adult men with SSc, was increased in patients with juvenile-onset SSc versus controls (57.9% versus 44.1%; OR 1.76, P = 0.027), as was DRB1*03 (34.2% versus 22.5%; OR 1.79, P = 0.031). Secondary analyses of all DRB1 allele groups revealed an association with DRB1*10 (10.5% of patients with juvenile-onset SSc versus 1.5% of controls; OR 7.48, P = 0.0002). As this is a new observation, correction was made for multiple comparisons of 13 different DRB1 allele groups; results nevertheless remained significant (P = 0.003). Also, a lower frequency of DRB1*01 was observed in patients with juvenile-onset SSc who were younger at disease onset (OR 0.06, P = 0.01) and in those with antibodies to topoisomerase (OR 0.14, P = 0.024). CONCLUSION. Associations of HLA alleles with juvenile-onset SSc differed from associations with SSc in women, but were similar to associations with SSc in men. Additionally, a novel association with DRB1*10 was observed in children. The greatest proportion of genetic risk of SSc is contributed by the HLA complex, and the current study reveals the importance of the association of HLA class II genes in juvenile-onset SSc.

In animals with binocular vision, retinal ganglion cell (RGC) axons from each eye sort in the developing ventral diencephalon to project to ipsi- or contralateral targets, thereby forming the optic chiasm. Ipsilaterally projecting axons arise from the ventrotemporal (VT) retina and contralaterally projecting axons primarily from the other retinal quadrants. The winged helix transcription factor Foxd1 (previously known as BF-2, Brain Factor 2) is expressed in VT retina, as well as in the ventral diencephalon during the formation of the optic chiasm. We report here that in embryos lacking Foxd1,both retinal development and chiasm morphogenesis are disrupted. In the Foxd1 deficient retina, proteins designating the ipsilateral projection, such as Zic2 and EphB1, are missing, and the domain of Foxg1 (BF-1) expands from nasal retina into the VT crescent. In retina-chiasm co-cultures, VT RGCs from Foxd1 deficient retina are not repulsed by chiasm cells, and in vivo many VT RGCs aberrantly project contralaterally. However, even though the ipsilateral program is lost in the retina, a larger than normal uncrossed component develops in Foxd1 deficient embryos. Chiasm defects include axon stalling in the chiasm and a reduction in the total number of RGCs projecting to the optic tract. In addition, in the Foxd1 deficient ventral diencephalon, Foxg1 invades the Foxd1 domain, Zic2 and Islet1 expression are minimized, and Slit2 prematurely expands, changes that could contribute to axon projection errors. Thus, Foxd1 plays a dual role in the establishment of the binocular visual pathways: first, in specification of the VT retina, acting upstream of proteins directing the ipsilateral pathway; and second, in the patterning of the developing ventral diencephalon where the optic chiasm forms.

During mammalian cerebral corticogenesis, progenitor cells become progressively restricted in the types of neurons they can produce. The molecular mechanism that determines earlier versus later born neuron fate is unknown. We demonstrate here that the generation of the earliest born neurons, the Cajal-Retzius cells, is suppressed by the telencephalic transcription factor Foxg1. In Foxg1 null mutants, we observed an excess of Cajal-Retzius neuron production in the cortex. By conditionally inactivating Foxg1 in cortical progenitors that normally produce deep-layer cortical neurons, we demonstrate that Foxg1 is constitutively required to suppress Cajal-Retzius cell fate. Hence, the competence to generate the earliest born neurons during later cortical development is actively suppressed but not lost.

The winged helix gene Brain factor-1 (BF1) has a pleiotropic role in the development of the cerebral hemispheres of the brain. Mice lacking BF1 have defects in the morphogenesis of the structures of the dorsal telencephalon (e.g., neocortex) and the ventral telencephalon (e.g., the basal ganglia). This study focuses on the functions of BF1 in the dorsal telencephalon. We showed previously that telencephalic progenitor cells lacking BF1 differentiate into neurons prematurely. Here, we demonstrate that the loss of BF1 also results in an early lengthening of the cell cycle in neocortical progenitors. To investigate the mechanisms by which BF1 regulates progenitor cell proliferation and differentiation in the developing brain, we have replaced the endogenous BF1 protein with a DNA binding defective form of BF1 in mice, BF1(NHAA). The BF1(NHAA) protein restores the growth of the dorsal telencephalon, by improving the proliferation of progenitor cells. However, the BF1(NHAA) protein does not correct the early neuronal differentiation associated with the loss of BF1. In contrast, replacement of endogenous BF1 with wild-type BF1 corrects the defects in both the proliferation and differentiation of neocortical progenitors. These results demonstrate that BF1 controls progenitor cell proliferation and differentiation in the neocortex through distinct DNA binding-independent and binding-dependent mechanisms.

Thymocyte winged helix (TWH) is a putative transcription factor expressed in the developing neural tube. At midgestation, TWH expression identifies subsets of spinal cord motor neurons and interneurons. TWH-expressing motor neurons were restricted to specific spinal cord levels, distinguishing motor neurons at lumbar from those at cervical levels. To understand the developmental role of TWH, we replaced the TWH gene with the lacZ reporter gene and generated mice with a homozygous disruption of the TWH gene. TWH(−/−) mutant mice had increased perinatal mortality, retarded postnatal growth, and motor weakness. The TWH(−/−) mutation resulted in alterations in the sizes and position of different neuronal populations. Our results demonstrate that TWH plays a critical role in neuronal development and suggest that TWH regulates the early differentiation of neural progenitors.

Objective.To determine whether adult disease severity subclassification systems for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are concordant with the decision to treat pediatric patients with cyclophosphamide (CYC).Methods.We applied the European Vasculitis Study (EUVAS) and Wegener’s Granulomatosis Etanercept Trial (WGET) disease severity subclassification systems to pediatric patients with AAV in A Registry for Childhood Vasculitis (ARChiVe). Modifications were made to the EUVAS and WGET systems to enable their application to this cohort of children. Treatment was categorized into 2 groups, “cyclophosphamide” and “no cyclophosphamide.” Pearson’s chi-square and Kendall’s rank correlation coefficient statistical analyses were used to determine the relationship between disease severity subgroup and treatment at the time of diagnosis.Results.In total, 125 children with AAV were studied. Severity subgroup was associated with treatment group in both the EUVAS (chi-square 45.14, p < 0.001, Kendall’s tau-b 0.601, p < 0.001) and WGET (chi-square 59.33, p < 0.001, Kendall’s tau-b 0.689, p < 0.001) systems; however, 7 children classified by both systems as having less severe disease received CYC, and 6 children classified as having severe disease by both systems did not receive CYC.Conclusion.In this pediatric AAV cohort, the EUVAS and WGET adult severity subclassification systems had strong correlation with physician choice of treatment. However, a proportion of patients received treatment that was not concordant with their assigned severity subclass.

Objective. Juvenile localized scleroderma (LS) is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although a wide range of therapeutic strategies has been reported in the literature, a lack of agreement on treatment specifics and accepted methods for clinical assessment has made it difficult to compare approaches and identify optimal therapy. Our objective was to develop standardized treatment plans, clinical assessments, and response criteria for active, moderate to high severity juvenile LS. Methods. A core group of pediatric rheumatologists, dermatologists, and a lay advisor was engaged by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) to develop standardized treatment plans and assessment parameters for juvenile LS using consensus methods/nominal group techniques. Recommendations were validated in 2 face-to-face conferences with a larger group of practitioners with expertise in juvenile LS and with the full membership of CARRA, which encompasses the majority of pediatric rheumatologists in the US and Canada. Results. Consensus was achieved on standardized treatment plans that reflect the prevailing treatment practices of CARRA members. Standardized clinical assessment methods and provisional treatment response criteria were also developed. Greater than 90% of pediatric rheumatologists responding to a survey (66% of CARRA membership) affirmed the final recommendations and agreed to utilize these consensus plans to treat patients with juvenile LS. Conclusion. Using consensus methodology, we have developed standardized treatment plans and assessment methods for juvenile LS. The high level of support among pediatric rheumatologists will support future comparative effectiveness studies and enable the development of evidence-based guidelines for the treatment of juvenile LS.

In two children ages 8 months and 4 years, tuberculous synovitis of the knee was suggested by pathologic examination of synovial tissue obtained through needle biopsy. Culture of the biopsy material was positive for Mycobacterium tuberculosis in one case. In this child, the tuberculin test was negative, in the absence of anergy, at the time the child was first evaluated, and the primary lung lesion was not identified by the radiologist.Tuberculous synovitis has not previously been recognized as part of primary tuberculosis during the early weeks when the tuberculin skin test may be negative. Magnetic resonance imaging (MRI) is a sensitive modality for demonstrating joint fluid, synovial hypertrophy, and associated osteomyelitis, if present. With the increasing frequency of cases of tuberculosis in the population, greater awareness of the risk of tuberculous arthritis in childhood is important in order to recognize this unusual presentation. If negative early on, the tuberculin skin test should be repeated after 6 weeks of arthritis. A needle biopsy of the synovium is helpful and appropriate in all children with monoarticular arthritis who have a positive tuberculin skin test.

Recent work has shown that the ability of cytokines to direct immunoglobulin heavy chain class-switch recombination to particular heavy chain constant (C) region (CH) genes correlates with the induction of specific germ-line CH transcripts. To test the role of germ-line transcripts in class switching, we have used homologous recombination to mutate the immunoglobulin heavy chain locus of the 18.81A20 murine pre-B-cell line. In the parent cell line, the combination of interleukin-4 (IL-4) and lipopolysaccharide (LPS) induces germ-line epsilon locus transcription prior to class switching to epsilon. The heavy chain locus of the mutated cell line contains the immunoglobulin heavy chain enhancer and variable region gene promoter in place of the LPS/IL-4-responsive germ-line epsilon promoter. The mutant cell line constitutively transcribes the epsilon locus in the absence of IL-4. Strikingly, the mutant cell line also switches to epsilon in the absence of IL-4. This result demonstrates that, at least in the 18.81A20 cell line, germ-line epsilon transcription plays a direct role in class switching to the epsilon locus. In addition, the ability to change the pattern of class switching by altering transcriptional activity indicates that transcription of germ-line CH is mechanistically important in regulation of class switching.

Background/Purpose: Localized scleroderma (LS) is a chronic inflammatory and fibrosing skin disease. We present baseline data on the juvenile LS (jLS) cohort from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry, a multicenter observational pediatric rheumatic disease registry. Methods: Descriptive statistics were used for demographic, clinical and laboratory features. Data analysis included the two-sample t-test, chi-square test, Fisher's exact test, and analysis of variance as appropriate. Results: Of 259 children in the database, 78% were female and 81% were Caucasian. Mean age at onset was 8.3 yr (± 4.2). Mean age at first pediatric rheumatology (PRH) evaluation was 9.5 yr (± 4.2), yet 37% had ≥5 yr delay from onset to first PRH visit. Linear scleroderma (LiS) was the most common subtype (54%), followed by circumscribed morphea (CM) (15%), generalized morphea (GM) (8%), eosinophilic fasciitis (2%), and pansclerotic morphea (1%). 20% of children had mixed subtype, and LiS-CM was the most frequent combination (60%). Among LiS patients with face-scalp localization (40%), neurologic and ocular diseases were reported in 7% and 4%, respectively. ANA positivity was found in 50% tested and was not associated with subtype, age at onset, extracutaneous manifestations, or features of disease damage. Children with new lesions were more likely to have an elevated creatine kinase (CK) (p=0.02) or aldolase (p=0.02); muscle atrophy (p=0.04) and extremity shortening (p=0.02) were also associated with an elevated CK. Children with any functional limitation (baseline worst ever ACR functional class II, III, and IV) (28%) had earlier first PRH visit (mean 0.88 yr ± 0.89) compared to those without limitation (class I) (mean 1.4 yr ± 1.8, p=0.03). The association was also significant when evaluating ≥1 yr (p=0.04), ≥2 yr (p=0.02), and ≥5 yr delay (p=0.02) in first PRH visit. Poorer function also correlated with presence of muscle atrophy, joint contracture, and extremity shortening (all p

Background/Purpose: Localized scleroderma (LS) is an autoimmune, inflammatory disease of the skin and subdermal tissues, resulting in fibrosis and atrophy. Outcomes are monitored by scoring signs of inflammation and damage to compose the LS cutaneous assessment tool (LoSCAT). The utility of skin scoring is limited by the need for training and ongoing practice and its inherent subjectiveness. Establishing an objective, simple, measure of skin disease would facilitate standardized outcomes for multicenter studies. One component of the LoSCAT is skin thickness (ST), graded by the clinician using the Rodnan Skin Score (0–3 ST). A surrogate for ST is skin hardness, which can be measured by a tool called a durometer, in durometer units. Among adults with systemic sclerosis, the durometer is a valid measure of skin hardness with high intra– and inter–rater reliability, correlation to skin scores, and sensitivity to change over time. This study was undertaken to examine the validity of the durometer as a measure of disease in pediatric LS. Methods: Patients from two separate clinics who attended regular appointments for LS were eligible to participate. After consent, durometer measures were taken of a single LS lesion, the “study lesion,” as well as an area of normal skin, typically in a contralateral location. Measures were taken in triplicate on either edge of the study lesion and normal skin and at approximately 1cm intervals from edge to edge. Durometer readings were repeated at up to 5 follow–up visits. The highest durometer reading from the study lesion and corresponding normal skin at each patient's initial visit was used for statistical analysis. Affected and unaffected skin was compared using a paired sample t–test. At each visit concurrent standardized clinic outcome measures were obtained, including the LoSCAT. Results: Seventeen patients were included in the analysis; most were female (76%) and Caucasian (88%) with a linear subtype of LS (41%). Mean age was 13.5 yrs old during the study and 9.0 yrs old at the onset of disease. Seven patients had study lesions on the chest or back, 2 on the abdomen, and 8 on the limbs. Analysis revealed a significant difference between durometer measures of affected and unaffected skin with a p–value of

Treatment of splenic B lymphocytes and certain B-lineage cell lines with the mitogen lipopolysaccharide (LPS) and the lymphokine interleukin-4 (IL-4) induces expression of germ line immunoglobulin C epsilon transcripts and class switching to the C epsilon gene. We show that LPS-plus-IL-4 induction of germ line epsilon transcripts (termed I epsilon transcripts) occurs at the transcriptional level in an Abelson murine leukemia virus-transformed pre-B-cell line. A 1.1-kb region of DNA surrounding the I epsilon promoter endows inducible transcription to a heterologous reporter gene stably transfected into these cells; such inducible expression depends on combined treatment with LPS and IL-4. Analyses of constructs transiently introduced into a B-cell lymphoma line demonstrated that LPS-plus-IL-4-inducible expression can be conferred by a 179-bp segment of DNA spanning the I epsilon transcriptional initiation site. Mutational analyses demonstrated that this expression depended on DNA sequences within a conserved region directly upstream from the I epsilon transcriptional initiation region. One nuclear protein that is constitutively expressed in normal B cells binds to the downstream end of the conserved sequence; its binding specificity correlates with the functional effect of several mutations. Two additional proteins, which are induced by IL-4 treatment of splenic B cells, bind to the transcription initiation sites of I epsilon. These proteins are indistinguishable in binding assays from proteins previously shown to bind an enhancer region of the class II major histocompatibility complex gene A alpha.

Brain factor 1 (BF-1) is a winged-helix transcription factor with restricted expression in the anterior optic vesicle and in the telencephalic neuroepithelium of the neural tube. We have previously found that targeted disruption of the BF-1 gene results in hypoplasia of the cerebral hemispheres, which is more severe in structures derived from the ventral telencephalon. Here we show that the loss of BF-1 leads to multiple developmental anomalies of the eyes. The most ventral structure arising from the optic vesicle, the optic stalk, is missing and is replaced by an expanded retina. Ventral closure of the optic cup and choroid fissure does not occur. These dorsal–ventral patterning defects are not limited to the BF-1-expressing (anterior) cells, but also involve the cells of the posterior optic vesicle. Sonic hedgehog (shh) expression within the ventral telencephalic neuroepithelium is specifically lost in the BF-1(−/−) mutant. Taken together, these findings suggest that shh produced at this site plays a role in patterning the developing eye. This localized deficit in shh expression may also contribute to the prominence of the ventral defects in the telencephalon of the BF-1(−/−) mutant.

Purpose Although ultrasound shows great potential for aiding assessment of LS disease activity, its use has been limited because both image acquisition and interpretation are operator dependent. To facilitate evaluating and to standardize interpretation of jLS ultrasound scans, we generated a scoring measure for evaluating echogenicity and vascularity differences (U-DA, Ped Rheum 2010;8:14). Objective: To assess the reliability of an ultrasound scoring measure (U-DA) for jLS.

Methods A retrospective chart review was conducted of all JIA patients who received IACI from 6/05 to 3/10, and had at least six months of follow-up. Data collected included demographic information, JIA subtype, date of injection and arthritis flare, type of joint injected and concomitant medications. Any joint that did not flare by the study end date in 9/10 was censored. Time to flare of arthritis was calculated based on the Kaplan-Meier product limit estimator. Two-sided log-rank test was conducted to compare the time to flare within each characteristic group: joints, diagnosis, medications. All analysis in this study was performed using SAS 9.2 (SAS Institute Inc, Cary, NC).

Germline CH transcripts initiate from a non-coding I exon and terminate downstream of the associated CH exons. Ig heavy chain class switch recombination from the VDJ-C mu gene to particular downstream CH genes appears to be regulated by a process that involves mitogen and/or cytokine induction of germline CH transcripts from the downstream genes. We have examined the expression of germline C mu transcripts (I mu-C mu transcripts) in splenic B cells and pre-B cell lines after cytokine and mitogen stimulation. In contrast to the expression of the germline transcripts from downstream CH genes, expression of germline C mu transcripts was constitutive and unaffected by mitogen and cytokine treatment. After a primary switch recombination event, the germline I mu promoter, which is now associated with a downstream CH gene, continues to be active--leading to the generation of a novel germline transcript consisting of the I mu exon spliced to the CH exons of the switched CH gene. We discuss the potential role of the expression of hybrid I mu-containing transcripts in the class switch process. We also describe a novel and sensitive assay, based on the detection of the hybrid I mu-containing transcripts, that allows detection of class switch recombination events even in heterogeneous populations of cells.

We have used a plasmid antitermination test system to examine the response of an Escherichia coli rRNA operon antiterminator to transcription through Rho-dependent and Pho-independent terminator-containing fragments. We also monitored transcription through multiple copies of a terminator to explore the mechanism of rrn antitermination. Four principal observations were made about antitermination and transcriptional terminators. (1) The rrn antiterminator mediated efficient transcription through Rho-dependent terminators. (2) Under the influence of the rrn antiterminator, RNA polymerase transcribed through two and three copies of the Rho-dependent 16 S ⇐ terminator with nearly the same efficiency as through one. (3) The antiterminator had less effect on fragments containing Rho-independent terminators; the rpoC t fragment and three fragments derived from the rrnB terminator region stopped antiterminated transcription. Four other Rho-independent terminator fragments were weakly antiterminated in our test system. (4) Surprisingly, the strength of these terminator fragments was not strongly related to properties such as the −Δ G or number of trailing uridine residues of their canonical Rho-independent structures, but appears to be related to additional downstream terminators. We have drawn the following conclusions from these experiments. First, that ribosomal antitermination primarily reverses Rho-dependent termination by modifying the RNA polymerase elongation complex. Transcription through a 1700 nucleotide, multiple terminator sequence showed that the antiterminator caused persistent changes in the transcription process. Second, that fragments derived from the Rho-independent rrnB and rpoBC terminator regions can effectively stop antiterminated transcription. Third, that efficient in vivo termination may often involve regions with complex multiple terminators.

We have localized the antitermination system involved in E. coli ribosomal RNA transcription and compared it with antitermination in the lamboid bacteriophages. In vivo experiments with gene-fusion plasmids were used to examine the ability of specific areas of the rrnG control region to convert an ordinary transcription complex into antitermination transcription complex. A 67 bp restriction fragment immediately following the rrnG P2 promoter decreased transcription termination about 50%. This fragment contains box A-, box B-, and box C-like sequences similar to those in lambda nut loci. It also caused transcripts from lac and hybrid trp-lac promoters to read through a transcription terminator. Translation through the 67 bp segment or reversal of its orientation resulted in complete loss of antitermination activity. We conclude that the E. coli ribosomal RNA operons possess an antitermination system similar to that used by the bacteriophage lambda.

We describe two retroviral vector-based recombination substrate systems designed to assay for lymphoid VDJ recombinase activity in cultured cells. Both incorporate a constitutive dominant marker gene (the simian virus promoter driven neo gene) to allow selection of cells that stably integrate the substrate. A second marker gene is included in the substrates that can undergo transcriptional activation when inverted by a site-specific recombination event between flanking immunoglobulin variable region gene segments. In the first vector, the activatible gene is the bacterial guanine-xanthine phosphoribosyl transferase gene (gpt); detection of inversion (VDJ recombinase activity) involves drug selection and Southern blotting analyses. We have used this vector to assay VDJ recombinase activity in a panel of cell lines representing various stages of the B cell differentiation pathway and compared the results to those of other studies that employ transient recombination substrates. In the second vector, the activatible gene is the bacterial beta-galactosidase gene (lacZ). Detection for inversional activation of this gene is achieved by a fluorogenic assay that detects beta-galactosidase activity in viable cells. The latter assay has the unique advantage of rapidly detecting cells that undergo recombination and also allows viable sorting of cells based on the presence or absence of VDJ recombinase activity. We discuss the potential applications of this vector for obtaining variant cell lines expressing differing levels of recombinase activity and for assaying VDJ recombinase activity in cells of transgenic mice.

Background Intra-articular corticosteroid injections (IACI) are routinely used by pediatric rheumatologists in the treatment of chronic arthritis. Frequently, topical anesthetics are used to control procedural pain, but their relative efficacy has not been reported. In this study, we evaluated the level of pain associated with different anesthetic methods, Numby® 900 Iontophoretic Drug Delivery System, or EMLA® cream, with or without subcutaneous buffered lidocaine (SQBL), during IACI of the knee in children with arthritis. Methods We conducted a prospective study of patients, ages 4 to 21 years old, followed at three pediatric rheumatology centers who were undergoing IACI of a knee joint. Patients were randomized into two treatment groups: 1) topical anesthetic only (EMLA® or Numby® (E/N)), or 2) topical anesthetic (E/N) and SQBL. Pain was assessed at baseline, during topical anesthetic placement, and following the IACI (post-procedure). The Faces Pain Scale-Revised (FPS-R), the Face, Leg, Activity, Cry, Consolability (FLACC) behavioral scale and the parental global assessment (PGA) (0 = best experience, 10 = worst experience) were determined. Results Sixty-three patients (44 females) with a median [IQR] age of 10.8 [IQR = (8.2–14.4)] years (range 4.7–20 years) with active knee arthritis were consented. FPS-R post-procedure (P = 0.03), FLACC (P = 0.02) and PGA (P = 0.01) scores were significantly lower in females treated with E/N plus SQBL compared to patients treated with E/N only. Females in the E/N only group had a significant worsening of their baseline pain (p

Purpose LS can cause significant morbidity in the growing child, including joint contractures and facial and extremity hemiatrophy. Optimal therapy is not known, and few randomized clinical trials have been carried out. A prior survey of Childhood Arthritis and Rheumatology Research Alliance (CARRA) members identified methotrexate (MTX) and corticosteroids (CS) as the most commonly used medications to treat serious jLS. However, there was no consensus on dose, route of administration, or duration of treatment for these medications. Objective: To develop standardized consensus treatment regimens and disease assessments tools for jLS.