[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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 < 0.0004) and a greater magnitude of change in their baseline FPS-R scores (p < 0.001) from the procedure compared to females in the E/N plus SQBL group who had no worsening of their baseline pain. No significant change in pain level or PGA score was found among males in either treatment group. Pain scores overall were similar to the oligoarthritis patients, a more homogeneous group of patients. Both EMLA® (n = 33) and Numby® (n = 29) were equally well tolerated with no significant difference in median FPS-R administration scores overall.
Our results suggest that a topical anesthetic plus SQBL is more effective for injection pain control than topical anesthesia only. Further studies addressing pain and anxiety will help determine the optimal method of pain control for IACI.
Preview · Article · Aug 2015 · Pediatric Rheumatology
[Show abstract][Hide abstract] ABSTRACT: Objective: Epidemiological associations suggest that vitamin D status may play a role in inflammation and progression of atherosclerosis. Using frozen serum, carotid intima medial thickness (CIMT) measurements and other existing data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed interactions between serum 25-hydroxyvitamin D (25(OH)D), atorvastatin randomisation and CIMT progression rate. Methods: Participants in the 3-year APPLE trial were randomised to placebo or atorvastatin and CIMT progression rate was measured. Baseline frozen serum was used to measure 25(OH)D concentrations. Mixed effect longitudinal models for CIMT progression at 3 years were used to evaluate interaction between vitamin D deficiency (serum 25(OH)D <20 ng/mL) at baseline and atorvastatin or placebo treatment, adjusting for key systemic lupus erythematosus disease variables and cardiovascular risk factors. Results: 201/221 APPLE participants had available samples and were included in this analysis; 61/201 (30%) had vitamin D deficiency at baseline. In adjusted longitudinal modelling, there was significant interaction between baseline vitamin D deficiency and atorvastatin randomisation in 3-year progression of mean-max CIMT. In four out of six carotid segments, there was a greater decrease in mean-max CIMT progression rate in subjects who were treated with atorvastatin compared with placebo if they had baseline serum 25(OH)D levels ≥20 ng/mL. Conclusions: Subjects with serum 25(OH)D ≥20 ng/mL had less mean-max CIMT progression following 3 years of atorvastatin treatment. Results from secondary analyses must be interpreted cautiously, but findings suggest that underlying vitamin D deficiency may be involved in response to atorvastatin in atherosclerosis prevention.
[Show abstract][Hide abstract] ABSTRACT: Objective Epidemiological associations suggest vitamin D may play a role in inflammation and atherosclerosis. Using frozen serum and data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed associations between 25-hydroxyvitamin D [25(OH)D] and measures of systemic lupus erythematosus (SLE) disease activity and cardiovascular risk.
Methods Baseline APPLE serum samples were used to measure 25(OH)D levels. Logistic regression models for vitamin D deficiency [25(OH)D levels <20 ng/mL] were constructed using baseline variables collected as part of the trial, including race, season, latitude, disease duration, disease activity, high-sensitivity C-reactive protein (hsCRP), proteinuria, fasting lipids and carotid intima medial thickness (CIMT).
Results Samples were available from 201 of 221 APPLE subjects; 61/201 (30%) had vitamin D deficiency at baseline. In univariable analysis, baseline vitamin D deficiency was associated with season (p<0.01), minority status (p<0.01), body mass index (p=0.04), duration of SLE (p<0.01), SLICC damage index (p=0.04), hsCRP (p<0.01), mean–max CIMT (p=0.01), LDL-cholesterol (p=0.03) and timed urine protein (p=0.03). In multivariable modelling, vitamin D deficiency was associated with age, latitude, season, minority status, proteinuria and hsCRP.
Conclusions Vitamin D deficiency is common in paediatric lupus and is independently associated with elevated hsCRP, a marker of inflammation that predicts cardiovascular disease risk. Although association is not proof of causation, this association is novel in the paediatric SLE population and suggests that vitamin D deficiency may contribute to heightened inflammation and cardiovascular risk in this population.
Trial register number NCT00065806.
[Show abstract][Hide abstract] ABSTRACT: 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<0.001). Medications used are listed below. 1Table 1. LiSCMGMPanscleroticEosinophilic FasciitisMixedTotalOral methotrexate (MTX) Current Use43 (33%)13 (37%)8 (44%)0 (0%)1 (25%)14 (29%)79 (33%)Past Use34 (26%)6 (17%)4 (22%)0 (0%)2 (50%)21 (44%)67 (28%)Subcutaneous MTX Current Use54 (42%)12 (34%)7 (39%)2 (100%)2 (50%)23 (48%)100 (42%)Past Use49 (38%)13 (37%)4 (22%)0 (0%)2 (50%)12 (25%)80 (34%)Mycophenolate mofetil (MMF) Current Use17 (13%)3 (9%)4 (22%)2 (100%)0 (0%)6 (13%)32 (14%)Past Use4 (3%)0 (0%)0 (0%)0 (0%)0 (0%)3 (6%)7 (3%)Intravenous corticosteroids Current Use13 (12%)2 (10%)1 (6%)2 (100%)2 (50%)7 (17%)27 (14%)Past Use41 (38%)2 (10%)7 (41%)0 (0%)1 (25%)15 (36%)66 (34%)Long-term daily corticosteroids Current Use24 (23%)5 (24%)4 (24%)1 (50%)1 (25%)13 (31%)48 (25%)Past Use47 (45%)12 (57%)10 (59%)1 (50%)3 (75%)18 (43%)91 (48%)Conclusion:In the CARRA registry, jLS occurred more frequently in females and Caucasians. LiS was the most common subtype. More than 1/3 of children had a ≥ 5 yr delay from symptom onset to PRH referral. Children without limitation are referred later, highlighting the insidious onset and need for educating referring providers. There is significant morbidity, with 28% of children reporting functional limitations. Poorer function correlated with disease damage, specifically muscle atrophy, joint contracture, and limb shortening. An elevated CK or aldolase was associated with new lesions, suggesting possible use as disease activity markers. CK elevation, associated with muscle atrophy and limb shortening, may also predict muscle involvement. Subcutaneous and oral MTX and pulse and long-term daily corticosteroids are the most commonly used medications, followed by MMF.
No preview · Article · Mar 2014 · Arthritis and Rheumatology
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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 <0.001. The median durometer reading was 40 (IQR: 25-48) for study lesions and 19.5 (IQR: 12.75-29) for normal skin. An upward trend was seen for durometer measures of study lesions with increasing ST scores (see figure)
Among pediatric patients with LS the durometer serves as an objective measure of skin hardness, discriminating affected versus unaffected skin on the trunk and limbs. This tool may serve as a surrogate for ST, though further analysis is needed to examine its sensitivity to change over time. A larger study would be helpful to further correlate durometer ranges with ST scores.
No preview · Article · Mar 2014 · Arthritis and Rheumatology
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Aug 2012 · The Journal of Rheumatology
[Show abstract][Hide abstract] ABSTRACT: Granulomatosis with polyangiitis (Wegener's; GPA) and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare in childhood and are sometimes difficult to discriminate. We compared use of adult-derived classification schemes for GPA against validated pediatric criteria in the ARChiVe (A Registry for Childhood Vasculitis e-entry) cohort, a Childhood Arthritis and Rheumatology Research Alliance initiative.
Time-of-diagnosis data for children with physician (MD) diagnosis of AAV and unclassified vasculitis (UCV) from 33 US/Canadian centers were analyzed. The European Medicines Agency (EMA) classification algorithm and European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) and American College of Rheumatology (ACR) criteria for GPA were applied to all patients. Sensitivity and specificity were calculated (MD-diagnosis as reference).
MD-diagnoses for 155 children were 100 GPA, 25 microscopic polyangiitis (MPA), 6 ANCA-positive pauciimmune glomerulonephritis, 3 Churg-Strauss syndrome, and 21 UCV. Of these, 114 had GPA as defined by EMA, 98 by EULAR/PRINTO/PRES, and 87 by ACR. Fourteen patients were identified as GPA by EULAR/PRINTO/PRES but not by ACR; 3 were identified as GPA by ACR but not EULAR/PRINTO/PRES. Using the EMA algorithm, 135 (87%) children were classifiable. The sensitivity of the EMA algorithm, the EULAR/PRINTO/PRES, and ACR criteria for classifying GPA was 90%, 77%, and 69%, respectively, with specificities of 56%, 62%, and 67%. The relatively poor sensitivity of the 2 criteria related to their inability to discriminate patients with MPA.
EULAR/PRINTO/PRES was more sensitive than ACR criteria in classifying pediatric GPA. Neither classification system has criteria for MPA; therefore usefulness in discriminating patients in ARChiVe was limited. Even when using the most sensitive EMA algorithm, many children remained unclassified.
No preview · Article · May 2012 · The Journal of Rheumatology
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: There are no validated tools for measuring disease activity in pediatric vasculitis. The Birmingham Vasculitis Activity Score (BVAS) is a valid disease activity tool in adult vasculitis. Version 3 (BVAS v.3) correlates well with physician's global assessment (PGA), treatment decision, and C-reactive protein in adults. The utility of BVAS v.3 in pediatric vasculitis is not known. We assessed the association of BVAS v.3 scores with PGA, treatment decision, and erythrocyte sedimentation rate (ESR) at diagnosis in pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV).
Children with AAV diagnosed between 2004 and 2010 at all ARChiVe centers were eligible. BVAS v.3 scores were calculated with a standardized online tool (www.vasculitis.org). Spearman's rank correlation coefficient (r(s)) was used to test the strength of association between BVAS v.3 and PGA, treatment decision, and ESR.
A total of 152 patients were included. The physician diagnosis of these patients was predominantly granulomatosis with polyangiitis (n = 99). The median BVAS v.3 score was 18.0 (range 0-40). The BVAS v.3 correlations were r(s) = 0.379 (95% CI 0.233 to 0.509) with PGA, r(s) = 0.521 (95% CI 0.393 to 0.629) with treatment decision, and r(s) = 0.403 (95% CI 0.253 to 0.533) with ESR.
Applied to children with AAV, BVAS v.3 had a weak correlation with PGA and moderate correlation with both ESR and treatment decision. Prospective evaluation of BVAS v.3 and/or pediatric-specific modifications to BVAS v.3 may be required before it can be formalized as a disease activity assessment tool in pediatric AAV.
No preview · Article · Feb 2012 · The Journal of Rheumatology
[Show abstract][Hide abstract] ABSTRACT: Our earlier work in the ultrasonograpy of localized scleroderma (LS) suggests that altered levels of echogenicity and vascularity can be associated with disease activity. Utrasound is clinically benign and readily available, but can be limited by operator dependence. We present our efforts to standardize image acquisition and interpretation of pediatric LS to better evaluate the correlation between specific sonographic findings and disease activity.
Several meetings have been held among our multi-center group (LOCUS) to work towards standardizing sonographic technique and image interpretation. Demonstration and experience in image acquisition were conducted at workshop meetings. Following meetings in 2007, an ultrasound measure was developed to standardize evaluation of differences in echogenicity and vascularity. Based upon our initial observations, we have labeled this an ultrasound disease activity measure. This preliminary measure was subsequently evaluated on over 180 scans of pediatric LS lesions. This review suggested that scoring levels should be expanded to better capture the range of observed differences. The revised levels and their definitions were formulated at a February 2009 workshop meeting. We have also developed assessments for scoring changes in tissue thickness and lesion size to better determine if these parameters aid evaluation of disease state.
We have standardized our protocol for acquiring ultrasound images of pediatric LS lesions. A wide range of sonographic differences has been seen in the dermis, hypodermis, and deep tissue layers of active lesions. Preliminary ultrasound assessments have been generated. The disease activity measure scores for altered levels of echogenicity and vascularity in the lesion, and other assessments score for differences in lesion tissue layer thickness and changes in lesion size.
We describe the range of sonographic differences found in pediatric LS, and present our efforts to standardize ultrasound acquisition and image interpretation for this disease. We present ultrasound measures that may aid evaluation of disease state. These assessments should be considered a work in progress, whose purpose is to facilitate further study in this area. More studies are needed to assess their validity and reliability.
[Show abstract][Hide abstract] ABSTRACT: To compare the criteria for Wegener's granulomatosis (WG) of the American College of Rheumatology (ACR) with those of the European League Against Rheumatism/Pediatric Rheumatology European Society (EULAR/PRES) in a cohort of children with WG and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs), and to describe the interval to diagnosis, presenting features, and initial treatment for WG.
Eligible patients had been diagnosed by site rheumatologists (termed the "MD diagnosis") since 2004. This diagnosis was used as a reference standard for sensitivity and specificity testing of the 2 WG classification criteria. Descriptive analyses were confined to ACR-classified WG patients.
MD diagnoses of 117 patients (82 of whom were female) were WG (n = 76), microscopic polyangiitis (n = 17), ANCA-positive pauci-immune glomerulonephritis (n = 5), Churg-Strauss syndrome (n = 2), and unclassified vasculitis (n = 17). The sensitivities of the ACR and EULAR/PRES classification criteria for WG among the spectrum of AAVs were 68.4% and 73.6%, respectively, and the specificities were 68.3% and 73.2%, respectively. Two more children were identified as having WG by the EULAR/PRES criteria than by the ACR criteria. For the 65 ACR-classified WG patients, the median age at diagnosis was 14.2 years (range 4-17 years), and the median interval from symptom onset to diagnosis was 2.7 months (range 0-49 months). The most frequent presenting features by organ system were constitutional (89.2%), pulmonary (80.0%), ear, nose, and throat (80.0%), and renal (75.4%). Fifty-four patients (83.1%) commenced treatment with the combination of corticosteroids and cyclophosphamide, with widely varying regimens; the remainder received methotrexate alone (n = 1), corticosteroids alone (n = 4), or a combination (n = 6).
The EULAR/PRES criteria minimally improved diagnostic sensitivity and specificity for WG among a narrow spectrum of children with AAVs. Diagnostic delays may result from poor characterization of childhood WG. Initial therapy varied considerably among participating centers.
Full-text · Article · Nov 2009 · Arthritis & Rheumatology
[Show abstract][Hide abstract] ABSTRACT: We surveyed pediatric rheumatologists (PR) in North America to learn how they treat pediatric localized scleroderma (LS), a disease associated with significant morbidity for the growing child.
A Web-based survey was sent to the 195 PR members of the pediatric rheumatology research alliance CARRA (Childhood Arthritis and Rheumatology Research Alliance). Members were asked which medications they use to treat LS and which factors modify their treatment strategies. Clinical vignettes were provided to learn the specific treatment regimens used.
A total of 158 PR from over 70 clinical centers in the United States and Canada participated in the survey, representing 81% of the CARRA membership. These PR saw over 650 patients with LS in the prior year. Nearly all respondents treated LS with methotrexate (MTX) and corticosteroids; most of them intensify treatment for lesions located on the face or near a joint, and about half intensify treatment for recent disease onset (< 6 months). Most PR reserve topical medications for limited treatment situations. Clinical vignettes showed that PR use a broad range of treatment doses and durations for MTX and corticosteroids.
Most PR in North America treat localized scleroderma with a combination of MTX and corticosteroids. However, there is no consensus on specific treatment regimens. There is a need for controlled treatment trials to better determine optimal therapy for this potentially disabling disease.
No preview · Article · Nov 2009 · The Journal of Rheumatology
[Show abstract][Hide abstract] ABSTRACT: Doppler ultrasound shows great promise for the evaluation of localized scleroderma (LS). Disease-related structural changes, such as tissue thickening, atrophy, and architectural alterations, can be readily detected using ultrasound. High spatial resolution enables monitoring of changes in tissue thickness over the course of disease and treatment. Doppler ultrasound may also aid assessment of disease activity. Both abnormal tissue echogenicity and vascularity levels can represent disease activity in some patients. Because tissue thickness, echogenicity, and vascularity vary with body site and age, accurate ultrasound evaluation of the LS lesion requires comparison to a control site, ideally the contralateral side. Evaluation of deeper tissues is important, as disease involvement may reside primarily below the dermis. Further study is needed to determine the validity, sensitivity, and reliability of ultrasound for LS.
Preview · Article · Aug 2009 · Current Rheumatology Reports