Unmet Needs in Spondyloarthritis: Pathogenesis, Clinical Trial Design, and Nonpharmacologic Therapy.

A program focused on pathogenesis, clinical trial design, and nonpharmacologic mind-body therapy for of spondyloarthritis (SpA) was presented at the Spondylitis Association of America Unmet Needs Conference IV. SpA pathogenesis is incompletely understood but involves a complex set of drivers, including genetics, biomechanical stress, and microbial factors. Affected tissues may include axial and peripheral joints, entheses, skin, uvea, and intestines. The specific role of key cytokines like interleukin (IL)-23, IL-17, and tumor necrosis factor in the phases of this inflammatory process remains unclear. New insights into pathogenesis will continue to generate targets for novel therapeutics. How to optimally evaluate those therapeutics in clinical trials, and for the various manifestations of SpA, remains less clear. Future trials need better generalizability, robust subgroup analyses to assess differential responses for distinct disease manifestations, a focus on comparative efficacy, and outcomes relevant to the clinician and the patient. Additionally, study designs need to leverage available technology to facilitate subject participation in trials. In view of the interplay between biologic, physical, and psychological aspects of disease, there is increasing attention to nonpharmacologic agents, with the aim of maximizing long-term health-related quality of life through the control of symptoms and inflammation. Recent studies provide encouraging evidence that mind-body interventions such as tai chi, qigong, yoga, and meditation have benefits for patients with SpA, particularly those with pain. The advances in our understanding of pathogenesis, novel therapeutics, and nonpharmacologic interventions have revolutionized the management of SpA, but numerous questions around optimal management remain.

Association of Infant Breastfeeding and Juvenile Spondyloarthritis: A Case-Control Study.

OBJECTIVE: Given the multifactorial pathogenesis of juvenile spondyloarthritis (JSpA) and evidence of a protective effect in phenotypically similar diseases, we aimed to test whether breastfeeding is associated with the development and disease activity of JSpA. METHODS: This single-center retrospective case-control study included children with JSpA and age- and sex-matched controls with a 1:1 ratio. Univariable and multivariable conditional logistic regression modeling for matched pairs was used to test the association of infant factors with the development of JSpA, including infant nutrition and form of delivery. Linear regression was used to assess the association of JSpA disease activity (JSpA Disease Activity Index with 6 elements [JSpADA6]) at presentation with breastfeeding exposure, form of delivery, and antibiotic exposure. RESULTS: For the 195 case-control matched pairs, the mean age was 13.0 years and 47.7% were female. For breastfeeding, 88.7% of controls and 69.2% of JSpA cases were exposed to breastfeeding of any duration, respectively (P < 0.001). In the multivariable model, exclusive breastfeeding > 6 months was independently and significantly associated with a lower chance of JSpA development (odds ratio 0.47, 95% CI 0.30-0.72; P < 0.001). The median JSpADA6 was not significantly associated with breastfeeding for > 6 months. However, vaginal delivery was significantly associated with a lower JSpADA6 (B = -0.65, 95% CI -1.13 to -0.17; P = 0.008). CONCLUSION: This study suggests that infant factors that affect the microbiome may be associated with the occurrence and disease activity of JSpA at presentation.

Prologue: Spondyloarthritis Unmet Research Needs Conference IV.

The Spondylitis Association of America (SAA) and the National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) convened a conference on the campus of the National Institutes of Health (NIH) on September 28 and 29, 2023, to identify unmet needs in spondyloarthritis (SpA) research. The conference featured presentations by experts in areas of disease endotypes, pain, innovative imaging in SpA, health disparities in rheumatic diseases, and therapeutics. Members of the conference planning committee moderated the sessions and led the development of manuscripts summarizing recommendations to address unmet research needs. Early career investigators were invited to submit abstracts, which were presented at a networking session during the conference. Here, we highlight each of the sessions comprising the conference in the form of manuscripts published together as a conference summary.

When to stop medication in juvenile idiopathic arthritis.

PURPOSE OF REVIEW: Disease-modifying antirheumatic drugs (DMARDs) have dramatically improved patient outcomes in juvenile idiopathic arthritis (JIA). However, these medications may also result in physical, psychologic, and economic burden, which must be balanced with risk of flare off treatment. Although some children remain in remission after medication discontinuation, evidence is sparse for if, when, and how medications should be de-escalated once achieving clinically inactive disease (CID). We review the data on medication discontinuation and the role of serologic and imaging biomarkers in JIA. RECENT FINDINGS: The literature uniformly supports early biologic DMARD initiation, although the optimal timing and strategy for medication withdrawal in patients with sustained CID remains unclear. In this review, we present the current data on flare frequency and time to flare, clinical factors associated with flare, and recapture data for each JIA category. We also summarize the current knowledge on the role of imaging and serologic biomarkers in guiding these treatment decisions. SUMMARY: JIA is a heterogenous disease for which prospective clinical trials are needed to address the question of when, how, and in whom to withdraw medication. Research investigating the roles of serologic and imaging biomarkers may help improve the ability to ascertain which children can successfully de-escalate medications.

Imaging in pediatric spondyloarthritis.

PURPOSE OF REVIEW: Imaging is used in the diagnosis of peripheral and axial disease in juvenile spondyloarthritis (JSpA). Imaging of the joints and entheses in children and adolescents can be challenging for those unfamiliar with the appearance of the maturing skeleton. These differences are key for rheumatologists and radiologists to be aware of. RECENT FINDINGS: In youth, skeletal variation during maturation makes the identification of arthritis, enthesitis, and sacroiliitis difficult. A great effort has been put forward to define imaging characteristics seen in healthy children in order to more accurately identify disease. Additionally, there are novel imaging modalities on the horizon that are promising to further differentiate normal physiologic changes versus disease. SUMMARY: This review describes the current state of imaging, limitations, and future imaging modalities in youth, with key attention to differences in imaging interpretation of the peripheral joints, entheses, and sacroiliac joint in youth and adults.

Modified Juvenile Spondyloarthritis Disease Activity Index in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.

OBJECTIVE: To validate the Juvenile Spondyloarthritis Disease Activity Index (JSpADA), and modified versions thereof, in a North American cohort of patients with enthesitis-related arthritis (ERA). METHODS: We utilized the Childhood Arthritis and Rheumatology Research Alliance Registry database ERA cohort to validate the JSpADA and its modifications (JSpADA6-no Schober, no C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR]; JSpADA7-no Schober; and JSpADA7-no CRP/ESR) using the Outcome Measures in Rheumatology principles of face validity, discriminative validity, and responsiveness to change. RESULTS: There were 51 subjects (64 visits) with complete JSpADA data with a mean age of 13.7 years and disease duration of 30.9 months. Subjects were predominantly White (84.3%), and 56.9% were male and 50% were HLA-B27 positive. The JSpADA showed high correlation with the clinical 10-joint Juvenile Arthritis Disease Activity Score (cJADAS10; r = 0.81), moderate-to-high correlation with physician global assessment (PGA; r = 0.69), and low-to-fair correlation with Childhood Health Assessment Questionnaire (CHAQ; r = 0.22). The modifications of the JSpADA (JSpADA7-no Schober; JSpADA7-no CRP/ESR; and JSpADA6-no Schober, no CRP/ESR) performed similarly with high correlation with cJADAS10 (r = 0.81, 0.79, and 0.80, respectively), moderate-to-high correlation with PGA (r = 0.65, 0.67, 0.64, respectively), and low-to-fair correlation with CHAQ (r = 0.35, 0.34, 0.39, respectively). All modified versions of JSpADA had good responsiveness to change. All versions of JSpADA had excellent discriminative validity. CONCLUSION: We propose the term modified JSpADA for the modification of JSpADA with 6 elements (JSpADA6-no Schober, no CRP/ESR). This shorter disease activity index may improve implementation of JSpADA in both clinical practice and research trials.

Opioid use in children with inflammatory bowel disease-related arthritis.

OBJECTIVES: Concomitant arthritis may increase risk of chronic opioid use in youngsters with IBD. We aimed to assess trends and clinical features associated with opioid use in children with IBD-related arthritis. METHODS: Adolescents under 18 years of age with IBD-related arthritis, at least 1 year of continuous enrolment, and at least 1 pharmacy claim in the Truven Health MarketScan Claims and Encounter Database were included. Subjects were identified using previously validated algorithms consisting of ICD codes, pharmacy claims and procedure codes. The primary outcome was chronic opioid exposure. Temporal trends in opioid exposure were tested using the Cuzick-Wilcoxon test. The association of chronic opioid use and baseline covariates in the IBD and IBD-arthritis cohorts were examined using multivariable logistic regression models. RESULTS: 14,943 adolescents with IBD, 480 of whom had arthritis, were included. Chronic opioid use was non-trivial in youngsters with IBD-related arthritis, higher than that of total IBD cohort (12.3% vs. 5%) and remained stable over the years of study. Using multivariable regression, joint pain and arthritis were significantly associated with chronic opioid exposure in young people with IBD. Among IBD-related arthritis patients older age, public insurance, gastrointestinal surgery, hospitalisation and psychiatric comorbidities were significantly associated with chronic opioid use. CONCLUSIONS: Chronic opioid use in adolescents with IBD-related arthritis was higher than that of total IBD cohort but stable over the years of study. Future study is needed to explore ways to optimise non-narcotic pain management strategies and ensuring appropriate use of opioids when necessary.

Stakeholder outcome prioritization in the Biologic Abatement and Capturing Kids' Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA) trial.

BACKGROUND: The Biologic Abatement and Capturing Kids' Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA) study is a randomized, pragmatic trial investigating different tumour necrosis factor inhibitor de-escalation strategies for children with sustained inactive disease. In this project, we elicited concept rankings that aided in the selection of the patient-reported outcome (PRO) measures that should be examined as part of the BACK-OFF JSpA trial. METHODS: We conducted a discrete choice experiment to evaluate individuals' preferences regarding PROs. Stakeholders assessed a discrete list of 21 outcome concepts, each of which had a Patient-Reported Outcome Measurement Information System (PROMIS) measure associated with it. PROMIS measures are self- or proxy-reported instruments that are universally applicable to the general population and all chronic conditions. Stakeholders were required to make choices instead of expressing the strength of a preference. RESULTS: Fourteen caregivers, 12 patients (9-22 years old), 16 rheumatologists and three executives from health insurance companies completed the exercise, which took approximately 10 min. The discrete choice experiment resulted in an estimate of the relative importance of each outcome and rank. All stakeholder groups agreed that the primary PRO should be 'Pain Interference', a measure that evaluates the effect of pain on a child's everyday activities, including its impact on social, emotional, mental and physical functioning. Patients and caregivers were mostly aligned in their top priorities, with patients valuing physical health (50% of the top 10) whereas caregivers were more interested in mental health (60% of the top 10). Rheumatologists and health insurance executives were most interested in physical health outcomes, which were ranked 80% and 60% of their top 10 PROs, respectively. Overall, the patients had the most diverse set of prioritized outcomes, including at least one of each category in their top 10 rank order of importance. Patients were also the only stakeholders to prioritize 'social' health. CONCLUSIONS: Patients and caregivers were mostly aligned in their outcome priority rankings. The rank-order list directly informed the creation of a profile of PRO measures for our upcoming trial. PATIENT OR PUBLIC CONTRIBUTION: Stakeholder partners helped with acquisition of data and lead parent partners helped interpret data.

Use of renin angiotensin aldosterone system inhibitors in children with lupus and time to glucocorticoid discontinuation.

There is little data to inform use of renin angiotensin aldosterone system (RAAS) inhibitors in pediatric patients with systemic lupus erythematosus (SLE). Here, we sought to characterize RAAS inhibitor use in pediatric SLE and determine whether early RAAS inhibitor initiation among children with incident lupus nephritis is associated with decreased duration of chronic glucocorticoid exposure. A retrospective cohort study was performed of children (ages 5-18) with SLE and/or lupus nephritis in the Truven MarketScan™ Medicaid and Commercial databases (2013-2018) and estimated RAAS inhibitor use. Among incident nephritis cases, we used competing risk hazard models with inverse probability of treatment weighting to estimate the association between RAAS inhibitor initiation less than 180 days after diagnosis and time to glucocorticoid discontinuation with kidney failure as a competing event. Among 592 children with nephritis and 1407 children with non-kidney SLE, 67% and 15% ever received RAAS inhibitors, respectively. Median duration of RAAS inhibitor use among 323 incident users was 14 and 9 months in children with and without nephritis, respectively. Medicaid enrollment was independently associated with greater likelihood of RAAS inhibitor use, irrespective of nephritis. Among 158 incident nephritis cases, early RAAS inhibitor initiation was significantly associated with a faster rate of glucocorticoid discontinuation (adjusted sub-distribution hazard ratio 1.81, 95% confidence interval [1.09 - 3.00]). Thus, early initiation of RAAS inhibitors may have a role in children newly diagnosed with lupus nephritis; not only those with refractory proteinuria after induction therapy. Hence, integrated health systems data could be leveraged to confirm these findings and optimize adjunctive therapies in pediatric lupus.

Survey of current practices in the management of anti-TNF failure in juvenile spondyloarthritis.

OBJECTIVES: To evaluate the current practices in management of patients with juvenile spondyloarthritis (JSpA) who failed anti-tumour necrosis factor agents (anti-TNF). METHODS: An online survey was distributed to Childhood Arthritis and Rheumatology Research Alliance (CARRA) members of the JIA workgroup. Data collection included estimated number of JSpA patients who have failed anti-TNF therapy over two-year period, reasons for discontinuing anti-TNF therapy and other medications used afterward. The JSpA population was de ned as the following subtypes: enthesitis-related arthritis, psoriatic arthritis, undifferentiated spondyloarthritis, juvenile ankylosing spondylitis (AS) i.e. meeting modi ed NY criteria for AS before age 16, and reactive arthritis. Findings were summarised using descriptive statistics. RESULTS: The survey response rate was 36% (n= 60/169). The majority of participants were paediatric rheumatologists (93%). Many physicians have JSpA patients who failed anti-TNF therapy (63%). The most common reason for changing anti-TNF therapy was secondary non-response (72%). Sacroiliitis was the most important factor considered when assessing response to an anti-TNF agent and the most common reason for primary non-response (45%). When assessing anti-TNF failure for sacroiliitis, many (65%) felt imaging of the sacroiliac joints was the most important aspect in their decision making. The majority try a second anti-TNF agent after initial anti-TNF failure (87%) and switch to another medication class after 2 anti-TNF agents have failed (62%). CONCLUSIONS: More than half of paediatric rheumatologists surveyed have at least one JSpA patient who failed anti-TNF therapy. The majority failed because of secondary non-response. Sacroiliitis is an important but challenging aspect to manage for patients with JSpA.

Clinical features, treatment patterns and short-term outcomes of children with inflammatory bowel disease evaluated in rheumatology clinic.

OBJECTIVES: This study evaluated the clinical features, treatment patterns, and short-term outcomes of children with inflammatory bowel disease (IBD)-associated musculoskeletal manifestations. METHODS: This was a retrospective cohort study of children with IBD evaluated for joint complaints in a paediatric rheumatology clinic from 2015 to 2020. The index visit was the date of initial rheumatology evaluation. Clinical features were evaluated using standard descriptive statistics. Differences in outcomes over time were compared using rank-sum tests. Univariate logistic regression was used to test associations between clinical features and persistent arthritis or enthesitis. RESULTS: Seventy-five patients met inclusion criteria. 61% had active arthritis or enthesitis at initial evaluation, 1/3 of whom were not yet diagnosed with IBD. Of those with known IBD, over half with joint complaints had arthritis or enthesitis. Active joint disease was common even among patients already receiving tumour necrosis factor (TNF) inhibitors or other immunomodulatory medications for IBD and despite inactive gastrointestinal disease. Treatment escalation was often needed to control articular disease, which included changes in immunomodulatory therapy and NSAIDs. Treatment outcomes for arthritis were good and significant improvements in functional mobility were observed (p<0.01), while enthesitis often persisted at follow-up (11/28, 39%). Moreover, a significant proportion of patients with pain at the index visit reported persistent pain at follow-up (29/44, 65%). CONCLUSIONS: This study provides several findings relevant to the multidisciplinary care of children with IBD, including high rates of active arthritis and enthesitis despite ongoing use of immunomodulatory medications for the management of IBD, responses to treatment, and pain management.

Echocardiographic strain analysis reflects impaired ventricular function in youth with pediatric-onset systemic lupus erythematosus.

BACKGROUND: Strain analysis with speckle-tracking echocardiography shows promise as a screening tool for silent myocardial dysfunction in pediatric-onset systemic lupus erythematosus (pSLE). We compared left ventricular (LV) systolic deformation (measured by strain) in children and adolescents with pSLE to controls, and assessed the relationship between strain, disease activity, and other noninvasive measures of cardiovascular health. METHODS: Twenty pSLE subjects ages 9-21 underwent comprehensive cardiovascular testing, including 2D speckle-tracking echocardiography, ambulatory blood pressure monitoring (ABPM), peripheral endothelial function testing, pulse wave velocity and analysis, and carotid ultrasound. Longitudinal apical-4 chamber (LSA4C ) and midpoint circumferential strain (CSmid ) were compared to that of 70 healthy controls using multivariable linear regression. Among pSLE subjects, Pearson correlation coefficients were calculated to evaluate relationships between global longitudinal or circumferential strain and other measures of cardiovascular health. RESULTS: Average SLE disease duration was 3.2 years (standard deviation [SD] 2.1). 2/20 pSLE subjects had persistent disease activity, and only one met criteria for hypertension by ABPM. LSA4C was significantly reduced in pSLE subjects compared to controls (mean -18.3 [SD 3.2] vs -21.8% [SD 2.2], P-value <.001). There was no significant difference in CSmid (-24.8 [SD 3.7] vs -25.7% [SD 3.4], P = .29). Among pSLE subjects, decreased nocturnal blood pressure dipping on ABPM was associated with reduced global circumferential strain (r -0.59, P = .01). CONCLUSIONS: Longitudinal myocardial deformation is impaired in pSLE patients despite clinical remission and may represent early myocardial damage. Strain analysis should be considered in addition to standard echocardiographic assessment during follow-up of patients with pSLE.

Normal hip joint fluid volumes in healthy children of different ages, based on MRI volumetric quantitative measurement.

BACKGROUND: While magnetic resonance imaging (MRI) of the pelvis and hips is common in pediatric patients, to date there are no data on the quantification of normal hip joint fluid volume in this patient population. OBJECTIVE: We sought to assess the feasibility and reliability of quantitative hip joint fluid measurement in the pediatric population to estimate the normal volume of fluid in a pediatric hip joint. MATERIALS AND METHODS: Seventy healthy children ages 8-17 years underwent a pelvic MRI including a large field of view coronal T2 fat-saturated sequence where hips were entirely imaged. Following 3 training sessions, 2 readers with experience in musculoskeletal imaging performed volumetric quantitative measurements of hip fluid (140 hips) using semiautomated pixel-based thresholding on custom MATLAB software. RESULTS: The mean processing time per hip was 2 min, 41 s. The mean volume of fluid in a hip joint was 2.1 mL (range: 0.38-5.41 mL), increasing slightly with age. Volumes were also greater in boys than in girls (P=0.004). Intra-observer and interobserver agreement were high (intra-class correlation coefficients 0.93 and 0.98, respectively), with mean volume differences of 0.04 mL for intra-observer and 0.09 mL for interobserver. CONCLUSION: A semiautomated pixel-based thresholding approach was feasible and reliable for measuring joint fluid in pediatric hip MRI. The average fluid volume of 2.1 mL can represent a visually substantial quantity of fluid per MRI slice, particularly in small children, and should not be misinterpreted as a joint effusion.

Erythema Ab Igne in an Adolescent With Chronic Pain: An Alarming Cutaneous Eruption From Heat Exposure.

Erythema ab igne (EAI) is a cutaneous finding caused by prolonged heat exposure and is characterized by a reticular, brownish-pigmented, often telangiectatic dermatosis. The eruption is reminiscent of livedo reticularis, which is typically seen in the setting of a number of rheumatologic conditions, most prominently vasculitis. Identification of key features distinguishing EAI from livedo reticularis can aid in the diagnosis of EAI and correct elucidation of the underlying etiology. Our patient presented with heating pad-induced EAI in the setting of chronic pain. Only 6 other pediatric cases of EAI associated with heat sources for chronic pain are reported (Acta Derm Venereol. 2014;94:365-367, J Pediatr. 2013;163:1789, Int J Eat Disord. 2013;46:381-383, Arch Dis Child. 2008;93:389, Arch Pediatr Adolesc Med. 2012;166:185-186, Br J Clin Pract. 1990;44:248-251). Our case highlights the need for awareness of this pathognomonic skin eruption in children with chronic pain conditions to help avoid an extensive workup for vasculitis.

Akkermansia muciniphila is permissive to arthritis in the K/BxN mouse model of arthritis.

Studies have identified abnormalities in the microbiota of patients with arthritis. To evaluate the pathogenicity of human microbiota, we performed fecal microbial transplantation from children with spondyloarthritis and controls to germ-free KRN/B6xNOD mice. Ankle swelling was equivalent in those that received patient vs. control microbiota. Principal coordinates analysis revealed incomplete uptake of the human microbiota with over-representation of two genera (Bacteroides and Akkermansia) among the transplanted mice. The microbiota predicted the extent of ankle swelling (R2 = 0.185, p = 0.018). The abundances of Bacteroides (r = -0.510, p = 0.010) inversely and Akkermansia (r = 0.367, p = 0.078) directly correlated with ankle swelling. Addition of Akkermansia muciniphila to Altered Schaedler's Flora (ASF) resulted in small but statistically significant increased ankle swelling as compared to mice that received ASF alone (4.0 mm, 3.9-4.1 vs. 3.9 mm, IQR 3.6-4.0, p = 0.041), as did addition of A. muciniphila cultures to transplanted human microbiota as compared to mice that received transplanted human microbiota alone (4.5 mm, IQR 4.3-5.5 vs. 4.1 mm, IQR 3.9-4.3, p = 0.019). This study supports previous findings of an association between A. muciniphila and arthritis.

The Role of Patient and Parental Resilience in Adolescents with Chronic Musculoskeletal Pain.

OBJECTIVES: To assess the level of resilience among patients with chronic musculoskeletal pain and their parents and to determine factors associated with patient and parental resilience. STUDY DESIGN: Cross-sectional cohort study of children aged 13-17 years diagnosed with chronic musculoskeletal pain and their parents. Patient-parent pairs were seen for initial consultation in the pediatric rheumatology pain clinic at Children's Hospital of Philadelphia between March and May 2018 and were administered a series of questionnaires including measures of resilience (Connor-Davidson Resilience Scale 10 item, The 14-item Resilience Scale, and the 7Cs of Resilience Tool). We calculated Pearson correlation coefficients to examine the relationship between the variables of interest and resilience. RESULTS: According to all resilience measures, patients and parents had low to moderate levels of resilience. These levels were lower than those previously reported among healthy populations, as well as those with chronic medical conditions. According to the Connor-Davidson Resilience Scale 10 item, patient-level resilience was negatively correlated with pain level (r = -0.48), physical disability (r = -0.54), and symptom severity (r = -0.53). The level of resilience among patients was positively correlated with energy level (r = 0.57) and health-related quality of life (r = 0.64). Parental resilience was positively correlated with parental mental health (r = 0.61). CONCLUSIONS: Higher patient resilience was correlated with reduced disease severity among adolescents with chronic musculoskeletal pain. Future research should explore whether fostering resilience in adolescents with chronic musculoskeletal pain via the application of resilience-training interventions mitigates disease burden in this vulnerable patient population.

MRI of the Sacroiliac Joint in Healthy Children.

To listen to the podcast associated with this article, please select one of the following: iTunes, Google Play, or direct download. OBJECTIVE. Increasing reliance on MRI for the evaluation of sacroiliitis requires that radiologists be familiar with the normal appearance of the developing sacroiliac joint. We describe age-related MRI features of the sacroiliac joints in healthy children. SUBJECTS AND METHODS. Seventy healthy children from three age groups-prepubertal (8-10 years), peripubertal (11-13 years), and approaching skeletal maturity (14-17 years)-completed questionnaires and underwent sacroiliac joint MRI. Imaging studies were evaluated by three experienced pediatric radiologists. Metaphyseal-equivalent signal intensity, nonperiarticular osteitis, cartilage volume, joint fluid, enthesitis, and surface cortex irregularities were evaluated. Metaphyseal-equivalent signal intensity was evaluated using an ordinal grading system (types I-IV). Intraclass correlation coefficients were calculated to assess interrater reliability. RESULTS. Increased metaphyseal-equivalent signal intensity (types I and II) was present in most prepubertal children and in less than 10% of the group approaching skeletal maturity. More prepubertal girls had type I signal than boys, but signal progressed to type IV signal faster in girls than in boys. None of the subjects had subchondral marrow edema, but four subjects had nonperiarticular osteitis. Cartilage volumes decreased with advancing age in girls and, on average, were lower in girls than in boys of the same age. One subject had measurable joint fluid. Cortex irregularities were common (57.1%), most frequently seen along the iliac bone (51.4% ilium vs 11.4% sacrum, p < 0.01) and in the upper quadrants (42.8% upper vs 27.1% lower, p = 0.01). CONCLUSION. We provide valuable reference MRI descriptions of the healthy pediatric sacroiliac joint that should improve our ability to distinguish between normal and pathologic findings.

Opioid Prescribing and Polypharmacy in Children with Chronic Musculoskeletal Pain.

OBJECTIVE: Thirty percent of adults with fibromyalgia receive an opioid, but the prevalence of opioid prescribing in pediatric chronic musculoskeletal pain is unknown. The aims of this study were to determine the prevalence of and factors associated with opioid exposure and polypharmacy among children with chronic musculoskeletal pain. METHODS: In this retrospective cohort study using health care claims data from 2000 to 2013, the index date was the first ICD-9 code 729.1. Included subjects were ≥ 2 and < 18 years old at the index date with two or more codes within 12 months and 18 months of continuous enrollment. Subjects with burns, sickle cell disease, or malignancy were excluded. Opioid exposure was defined as one or more prescriptions within six months before or any time after the index date. Polypharmacy was considered minor (2-4 medications) or major (≥5 medications). RESULTS: Of 25,321 included subjects, 20% received an opioid and 26% experienced minor polypharmacy. Opioid exposure was associated with female sex (odds ratio [OR] = 1.27, P < 0.01), Caucasian race (OR = 1.27, P < 0.01), hospitalization (OR = 1.20, P < 0.01), and visit with anesthesiology (OR = 1.97, P < 0.01) or orthopedics (OR = 1.09, P < 0.05). Mental health codes were associated with decreased odds of opioid exposure (all P < 0.05). Children seen by a chiropractor or physiatrist had a reduced odds of receipt of an opioid (OR = 0.42 and 0.84, respectively, both P < 0.01). CONCLUSIONS: Twenty percent of children with chronic musculoskeletal pain received an opioid. Twenty-six percent experienced polypharmacy, with the majority receiving 2-4 medications. Increased availability of psychological and nonpharmacologic services are potential strategies to reduce opioid exposure.

Tumor necrosis factor-α inhibitor-induced psoriasis in juvenile idiopathic arthritis patients.

BACKGROUND/OBJECTIVES: The development of psoriasis while on tumor necrosis factor inhibitors (TNFi) is a paradoxical effect of agents that treat psoriasis. There is a paucity of data available on this entity in juvenile idiopathic arthritis (JIA). Our objectives were to determine the prevalence of TNFi-induced psoriasis in patients with JIA at two pediatric centers, and psoriasis response to therapeutic modifications. METHODS: We performed retrospective chart review on patients with JIA treated with TNFi (adalimumab, etanercept, infliximab) who developed psoriasis. TNFi-induced psoriasis was defined as an incident diagnosis of psoriasis after starting a TNFi. Patients with personal histories of psoriasis prior to TNFi therapy were excluded. Following diagnosis, responses to medication changes were defined based on physician assessments. RESULTS: Nine of 166 (5.4%) patients on TNFi for JIA were diagnosed with TNFi-induced psoriasis. All cases were female. One had a family history of psoriasis. The median age was 10 (range 2-16) years. Five (55%) patients experienced scalp psoriasis, including four (44%) with alopecia. Two (22%) patients achieved significant improvement after switching to different classes of biologic agents, while three (33%) patients had significant improvement following discontinuation of biologic therapy. One of five patients who switched to a different TNFi had complete resolution, while four had worsening symptoms or partial improvement. CONCLUSIONS: Our findings demonstrate the prevalence of TNFi-induced psoriasis in JIA at two centers. Though larger studies are needed, our data suggest discontinuation of TNFi or biologic class switching should be considered as treatment strategies in select patients.

Echocardiographic Assessment of Diastolic Function in Children with Incident Systemic Lupus Erythematosus.

The timing and etiology of diastolic impairment in pediatric-onset systemic lupus erythematosus (SLE) are poorly understood. We compared echocardiographic metrics of left ventricular diastolic function in children at SLE diagnosis to controls and identified factors associated with diastolic indices. Echocardiograms of children aged 5-18 years within 1 year of SLE diagnosis and age-/sex-matched controls were retrospectively read by blinded cardiologists. Clinical characteristics were abstracted separately. Z-scores for diastolic indices (E/A, e', E/e', and isovolumetric relaxation time (IVRT)) were calculated using published normative data and study controls, and compared using linear mixed-effects models adjusted for blood pressure. Pericardial effusions and valvular disease were also evaluated. Linear regression was used to identify factors associated with diastolic measures. 85 children with incident SLE had echocardiograms performed a median of 6 days after diagnosis (interquartile range (IQR) 1-70). Prior cumulative prednisone exposure was minimal (median 60 mg, IQR 0-1652). SLE cases had lower E/A, lower e', higher E/e', and longer IVRT compared to controls. Though none met criteria for Grade I diastolic dysfunction, Z-scores for e', E/e', and IVRT were abnormal in 30%, 25%, and 6% of SLE cases, respectively. Greater disease activity was associated with lower septal e' (p < 0.01), higher E/e' (p = 0.02), and longer IVRT (p < 0.01). Children with incident SLE have worse diastolic indices at diagnosis compared to peers without SLE, independent of blood pressure and prior to significant prednisone exposure. Longitudinal studies will determine whether diastolic dysfunction develops in this population over time.