CURRENT ABSTRACTS

Serum Soluble Receptor for Advanced Glycation End Prod-ucts Levels and Aortic Augmentation Index in Early Rheu-matoid Arthritis—A Prospective Study . . . By Lai-ShanTam, Qing Shang, Edmund K. Li, Shang Wong, Rui-Jie Li,Ka-Lai Lee, Ying-Ying Leung, King-Yee Ying, Cheuk-Wan Yim,Emily W. Kun, Moon-Ho Leung, Martin Li, Tena K. Li, Tracy Y.Zhu, Ricky K. Chui, Lorraine Tseung, Shui-Lian Yu, Woon-PangKuan, and Cheuk-Man Yu

Objective: We assessed whether a serum soluble receptor foradvanced glycation end product (sRAGE) levels were associatedwith a progression of carotid atherosclerosis and arterial stiff-ness indexes in a cohort of early rheumatoid arthritis (RA)patients.Methods: RA patients with symptoms onset �2 years wererecruited. Vascular assessments and serum sRAGE levels weremeasured at baseline and 1 year later. Arterial stiffness wasdetermined by pulse wave velocity and aortic augmentationindex (AIx). Carotid intima-media thickness was measured us-ing high-resolution ultrasound.Results: Ninety-four patients completed the 1-year study. Fifty-three (56.4%) achieved disease remission [28-joint disease ac-tivity score (DAS28 � 2.6)] at 12 months. Improvement inarterial stiffness was observed as reflected by the significantreductions in AIx and pulse wave velocity. At 12 months, thesRAGE levels increased significantly compared with baseline(939.8 � 517.7 pg/ml to 1272.1 � 567.3 pg/ml, P � 0.001).Changes in sRAGE levels were significantly higher in mencompared to women (768 � 510 pg/ml versus 271 � 490pg/ml, P � 0.05) and was negatively associated with the changein AIx (r � �0.259, P � 0.023). Changes in sRAGE level werenot associated with other demographic, clinical, cardiovascularrisk factors or treatment. Using multivariate analysis, thechange in sRAGE levels and baseline high-density lipoproteinwere independent predictors associated with the change in AIx.Conclusions: Arterial stiffness improved significantly in pa-tients with early RA after effective control of inflammation.Increase in sRAGE level was associated with a decrease in AIx,suggesting that sRAGE may play an important role in theligand–soluble receptor for advanced glycation end productinteraction propagated inflammation and vascular stiffness inthese patients.Semin Arthritis Rheum 42:333-345. © 2013 Elsevier Inc. Allrights reserved.

Barriers to Participant Retention in Knee OsteoarthritisClinical Trials: A Systematic Review . . . By Yun Hyung Koog,Munsoo Gil, Seo Ryang We, Hyungsun Wi, and Byung-Il Min

Objective: We investigated the reasons and rates of attrition inknee osteoarthritis trials through a systematic review of ran-domized, placebo-controlled, clinical trials.Methods: Randomized trials were identified by searches con-ducted in MEDLINE, SCOPUS, and the Cochrane CentralRegister of Controlled Trials. We then attempted to identifyand describe the reasons for attrition and their associatedthemes. For each theme, we calculated the rate of patients whodiscontinued a trial from the total number of dropouts in eachtrial. The rates obtained with different trials were combinedusing a random effects model. We also performed a randomeffects meta-regression analysis to identify sources associatedwith the rates.Results: Overall, 259 studies consisting of 266 trials and 13,593patients were included in the analysis. From these, we short-listed 54 attrition reasons and identified 21 key themes. “Inef-fectiveness” and “adverse event” were the reasons frequentlyreported by �5% of the dropouts. On further investigation ofthe theme ineffectiveness, the attrition rate was associated withdelivery routes of treatment, trial duration, flare design, prohi-bition of usual analgesics, and allowing the use of escape med-ication. In cases of adverse events, we found that the treatmenttype and delivery route affected the attrition rate.Conclusions: Our findings not only support the importance ofthe intention-to-treat analysis, but also suggest the possibility ofcontrolling the attrition at the study level.Semin Arthritis Rheum 42:346-354. © 2013 Elsevier Inc. Allrights reserved.

Premature Osteoarthritis as Presenting Sign of Type II Col-lagenopathy: A Case Report and Literature Review . . . ByEmma Husar-Memmer, Arif Ekici, Ali Al Kaissi, Heinrich Sticht,Bernhard Manger, Georg Schett, and Jochen Zwerina

Objectives: Osteoarthritis (OA) is a frequent, chronic, and of-ten disabling disease. Early-onset OA should prompt rheuma-tologists to search for underlying causes. We describe the clin-ical presentation and diagnosis of a patient with severepremature OA.Methods: We report a patient with severe polyarticular OAstarting in young adulthood due to a heterozygous mutation in

Seminars in

Arthritis and RheumatismVOL 42, NO 4 FEBRUARY 2013

the COL2A1 gene. We discuss the clinical features, diagnosis,and known mutations of previously reported cases identifiedthrough a PubMed literature review.Results: A 43-year-old Caucasian woman of normal staturepresented with a 24-year history of symmetrical polyarticularOA involving both large and small joints. At the time of pre-sentation, the patient already underwent 6 joint replacementsurgeries. Family history was unremarkable. Clinical, serologic,radiographic, and histologic studies did not reveal any specificcause for this unusual clinical presentation. Genetic analysisrevealed a heterozygous COL2A1 mutation (R519C) consis-tent with the clinical phenotype. Reviewing the literature, wediscuss the clinical spectrum of type II collagenopathies empha-sizing premature OA as the sole clinical manifestation.Conclusions: Unusual clinical presentations of OA shouldprompt investigations to search for an underlying cause. Type IIcollagenopathy should be considered in young adults with se-vere symmetrical OA even in the absence of other clinical fea-tures. A correct diagnosis allows classification and genetic coun-seling of the patient.Semin Arthritis Rheum 42:355-360. © 2013 Elsevier Inc. Allrights reserved.

Fatigue in Ankylosing Spondylitis: Treatment ShouldFocus on Pain Management . . . By Sinead Brophy, HelenDavies, Michael S. Dennis, Roxanne Cooksey, Muhammad J.Husain, Elizabeth Irvine, and Stefan Siebert

Objectives: Fatigue is an important symptom associated withankylosing spondylitis (AS). This study examines patients’ per-spectives and clinical associations of fatigue to help informpotential strategies to alleviate fatigue in AS.Methods: A mixed methods approach was taken to examinefatigue in a cohort of people with AS. Fatigue levels were eval-uated from 3 consecutive monthly questionnaires. Open-endedquestions on fatigue were analyzed using thematic analysis andlogistic regression was used to examine quantitative data. Inaddition, fatigue levels were examined before and after treat-ment with anti-tumor necrosis factor (TNF) compared to non-treated controls.Results: Three hundred forty-eight of 385 participants com-pleted a fatigue questionnaire. Fatigue was reported to havesignificant physical, social, and psychological effects. A third ofthe participants reported that there was nothing they could doto reduce their fatigue, whereas other participants reported thatmedication, exercise, and resting helped. The main factor asso-ciated with fatigue was pain [�-coefficient: 0.74 (95% CI: 0.66to 0.81)], whereas depression was much less strongly associated.However, these factors only explained 40% of the variation infatigue levels. Starting anti-TNF therapy reduced fatigue andpain levels compared to the period of time before taking anti-TNF [difference: 14.4 (95% CI: 5.3 to 23.5) on a scale of0-100] and this reduction was not seen in controls over thesame period.Conclusions: Fatigue is not strongly associated with anxiety,motivation, and depression; instead the factor most associatedwith fatigue is pain. This suggests that in addition to treatmentsto reduce disease activity, strategies for alleviating fatigue in AS

should focus on pain management techniques and activelytreating inflammation.Semin Arthritis Rheum 42:361-367. © 2013 Elsevier Inc. Allrights reserved.

The Role of Ectopic Germinal Centers in the Immunopa-thology of Primary Sjogren’s Syndrome: A Systematic Re-view . . . By Anna P. Risselada, Marjolein F. Looije, Aike A.Kruize, Johannes W.J. Bijlsma, and Joel A.G. van Roon

Objectives: To determine whether the presence of germinalcenters (GCs) in salivary glands of patients with primarySjogren’s syndrome (pSS) is related to the severity of diseasecourse and distinct immunopathology features.Methods: A systematic search was performed in September2011 for terms and synonyms of Sjogren’s syndrome and ger-minal centers. A total of 80 articles were retrieved, of which 16were included for (meta-) analysis.Results: GC morphology was present in a mean � SD 25.1 �5.0% of pSS patients. Mean lymphocyte focus scores were 1.25points higher in patients with GCs as compared to those with-out GCs. Saliva production was reduced in patients with GCs,although this did not reach statistical significance. Percentagesof patients positive for rheumatoid factor, anti-Sjogren’s syn-drome A (SSA), and anti-Sjogren’s syndrome B (SSB) antibod-ies were significantly higher in patients with GCs (mean in-crease, 15%, 18%, and 18%, respectively). Additionally,patients with GCs were characterized by enhanced levels oflocal and systemic proinflammatory mediators. Importantly,these patients have a higher risk of lymphoma development(14% versus 1%).Conclusions: Patients with GCs are characterized by more se-vere disease, although the small number of studies and theirdesign hamper generalizability of results. The precise mecha-nisms that contribute to the development and persistence ofgerminal centers in pSS are largely unknown. This and thestrongly increased risk of lymphoma development warrant in-tensive studies for the role of germinal centers in the immuno-pathology of pSS.Semin Arthritis Rheum 42:368-376. © 2013 Elsevier Inc. Allrights reserved.

Therapeutic Inhibition of Tyrosine Kinases in SystemicSclerosis: A Review of Published Experience on the First108 Patients Treated with Imatinib . . . By Vasiliki-KalliopiBournia, Konstantinos Evangelou, and Petros P. Sfikakis

Objective: Experimental and clinical evidence suggest a thera-peutic role for the tyrosine kinase inhibitor imatinib in fibrosingconditions. We evaluated published data on the safety andefficacy of imatinib for patients with systemic sclerosis (SSc), asevere autoimmune disease with significant morbidity and mor-tality.Methods: A careful search for all original articles and abstractson the use of imatinib in SSc published in English from 2008through February 2012 was performed. Two additional pa-tients from our center are also described.Results: Five small observational clinical trials on the use ofimatinib in severe SSc have been conducted and case reports

and small series of refractory to current approaches patientshave been reported, adding to a total of 108 patients havingreceived this drug to date. In most of these patients imatinib wasgiven for skin or pulmonary fibrosis. Encouraging results werereported in 3 of 4 studies, whereas the fifth study was prema-turely terminated for safety reasons. Overall, clinical results arehighly variable, ranging from ineffective or toxic responses toextremely encouraging clinical improvements in some severelyill patients. These discrepancies could partly reflect imatinib-related safety issues, in particular, SSc patients or idiosyncraticresistance to imatinib, as happens in chronic myelogenous leu-kemia and gastrointestinal stromal tumors, the drug’s approvedindications.Conclusions: The limited available experience suggests thatimatinib could be considered as an individualized treatmentapproach in severe SSc and underscores the need to identifymarkers for selecting particular patients, who will safely respondto therapeutic inhibition of tyrosine kinases.Semin Arthritis Rheum 42:377-390. © 2013 Elsevier Inc. Allrights reserved.

Pulmonary Hemorrhage in Henoch-Schonlein Purpura:Case Report and Systematic Review of the English Litera-ture . . . By Srinivas Rajagopala, Vineeta Shobha, Uma Devaraj,George D’Souza, and Isha Garg

Background: Diffuse alveolar hemorrhage (DAH) is a rare com-plication of Henoch-Schonlein purpura (HSP) and data on itsprevalence, management, and outcomes are scant.Objectives: To enable evidence-based management of DAH inHSP.Methods: A case report and a systematic review were conductedof all reported cases of DAH complicating HSP in the Englishliterature.Results: DAH predominantly affects older male children andadults with HSP. The occurrence of DAH in HSP is rare andthe reported prevalence ranged from 0.8% to 5%. DAH oc-curred variably after the diagnosis of HSP, ranging from 2 daysto 18 years. Hemoptysis (75%), drop in hemoglobin (74%),and chest infiltrates (94%) were the most common clinicalfindings. Lung biopsy showed leukocytoclastic vasculitis withalveolar hemorrhage (69.2%) or only alveolar hemorrhage(31.8%) with variable IgA staining by immunofluorescence.DAH was frequently severe and 50% of the patients requiredmechanical ventilation. Cyclophosphamide and pulse methyl-prednisolone for DAH was associated with better outcomes,particularly in patients who were already receiving steroids atthe time of DAH. Steroids and immunosuppressants were ad-ministered for a median duration of 9 and 4.5 months, respec-tively. Systemic recurrences (27.7%) and recurrences of DAH(8.3%) were frequent. DAH was associated with high mortality(27.6%) and morbidity (persistent urinary abnormalities, 12%;chronic renal failure, 9%; complications of therapy, 27%).Conclusions: DAH is a life-threatening complication in HSP.Current protocols use pulse methylprednisolone and cyclo-phosphamide for 6 months.Semin Arthritis Rheum 42:391-400. © 2013 Elsevier Inc. Allrights reserved.

The Role of Multimodality Imaging in the Evaluation ofTakayasu Arteritis . . . By Sophie Mavrogeni, Theodoros Dim-itroulas, Sofia N. Chatziioannou, and George Kitas

Objectives: Takayasu arteritis is a rare large vessel vasculitis ofunknown etiology, in which both early diagnosis and follow-uppresent very significant challenges. The high incidence of dis-ease-associated morbidity and significant risk of prematuredeath—particularly in young adults—mandate the need to fa-cilitate early diagnosis and aggressive treatment where appro-priate. The aim of this review is to summarize the current levelof knowledge regarding the usefulness of evolving imaging mo-dalities in the diagnostic workup and management of patientssuffering with Takayasu arteritis. We also propose an imagingalgorithm for the evaluation of this population.Methods: A MEDLINE search for articles published betweenJanuary 1999 and December 2011 was conducted using thefollowing keywords: Takayasu arteritis, imaging modalities,echocardiogram, cardiac magnetic resonance, positron emis-sion tomography scan, diagnosis.Results: Imaging studies—particularly cardiac magnetic reso-nance—can assist early diagnosis by demonstrating vascularlesions even when angiography is negative, by identifying thepresence of vascular inflammation and/or wall thickening; theyare also useful for monitoring purposes. However, availability,expertise, high cost, and radiation are considerable limitations.Magnetic resonance imaging, although it can detect both ana-tomic and pathophysiologic changes without radiation, is time-consuming, needs high expertise, and still remains an expensivetool, not widely available.Conclusions: Knowledge of the advantages and limitations ofthe various imaging procedures can complement the physicians’clinical assessment and, along with nonspecific serologic tests,can aid them in diagnosing active arteritis and commence rele-vant treatment early on, as well as monitor activity and tailortherapy subsequently.Semin Arthritis Rheum 42:401-412. © 2013 Elsevier Inc. Allrights reserved.

Canakinumab in Schnitzler Syndrome . . . By Steven Vander-schueren and Daniel Knockaert

Objectives: Daily injections of anakinra, an interleukin-1-receptorantagonist, have been reported to control effectively the symptomsand signs of Schnitzler syndrome, a rare acquired autoinflamma-tory disorder, presenting in adulthood by intermittent fever, urti-carial rash, and paraproteinemia, usually IgM. Canakinumab, afully human interleukin-1� monoclonal antibody, approved forthe cryoporin-associated periodic syndrome, may offer a practicaladvantage because its half-life of �28 days may allow less frequentdosing. The present trial was designed to test canakinumab inpatients with Schnitzler syndrome.Methods: A patient with Schnitzler syndrome was treated withcanakinumab, 150 mg subcutaneously injection every 8 weeksfor 6 consecutive months. Injections were resumed in case of aflare following discontinuation.Results: Canakinumab induced a swift and sustained clinical re-sponse, with disappearance of fever and arthralgias, near abolish-ment of fatigue and rash, and substantial reduction of C-reactive

protein levels. Interruption of canakinumab after four 8-weeklyinjections led to a flare 10 weeks after the last administration,which was countered as soon as canakinumab injections were re-sumed. The patient remained in complete remission. Canaki-numab was well tolerated. No injection site reactions, other adverseevents, or laboratory abnormalities were observed.Conclusions: Canakinumab has potential for the treatment ofSchnitzler syndrome (ClinicalTrials. gov.number, NCT01245127).Semin Arthritis Rheum 42:413-416. © 2013 Elsevier Inc. Allrights reserved.

Relapsing Catastrophic Antiphospholipid Syndrome Poten-tial Role of Microangiopathic Hemolytic Anemia in DiseaseRelapses . . . By Gerard Espinosa, Ignasi Rodrıguez-Pinto, Jose A.Gomez-Puerta, Guillermo Pons-Estel, and Ricard Cervera, for theCatastrophic Antiphospholipid Syndrome (CAPS) Registry ProjectGroup (European Forum on Antiphospholipid Antibodies)

Objective: To analyze the clinical and laboratory characteristicsof patients with catastrophic antiphospholipid syndrome (APS)who suffer relapses.Methods: We analyzed the Web site--based international regis-try of patients with catastrophic APS (“CAPS Registry”) http://infmed.fcrb.es/es/web/caps and selected those cases that re-lapsed.Results: Relapses were reported in 9 of 282 (3.2%) patientswith catastrophic APS. A total of 35 episodes of catastrophicAPS were found: 6 patients presented 2 relapses, 2 patientssuffered 3 relapses, and 1 patient developed 17 relapses.However, the last patient was not included in the statisticalanalysis because his clinical and immunologic characteristicswere not fully described. Therefore, a total of 18 episodeswere analyzed. In 9 (50%) episodes, a precipitating factorwas identified. The most frequent precipitating factor,found in 5 (28%) episodes, was infection. Brain, kidney,heart, and lung were the most common organs involved.Laboratory features of microangiopathic hemolytic anemia(MHA) were present in 13 of 18 (72%) episodes (definitivein 9, corresponding to 4 patients, and probable in 4, corre-sponding to 2 patients). Three relapses did not present withfeatures of MHA and in the remaining 2 these data were notreported. The mortality rate was 38%.Conclusions: Although relapses are rare in patients with cata-strophic APS, these results support the hypothesis that an asso-ciation between MHA and relapsing of catastrophic APS couldbe present.Semin Arthritis Rheum 42:417-423. © 2013 Elsevier Inc. Allrights reserved.

Factors Influencing Discrepancies Between the Quanti-FERON-TB Gold in Tube Test and the Tuberculin SkinTest in Korean Patients with Rheumatic Diseases . . . ByJae-Hoon Kim, Soo-Kyung Cho, Minkyung Han, Chan-BumChoi, Tae-Hwan Kim, Jae-Bum Jun, Sang-Cheol Bae, Dae-HyunYoo, and Yoon-Kyoung Sung

Objectives: To estimate the positivity and agreement betweenQuantiFERON-tuberculosis (TB) gold in tube test (QFT-

GIT) and tuberculin skin test (TST) according to underlyingrheumatic diseases and to identify the influencing factors ondiscrepancies between the 2 tests.Methods: Among the 757 patients who underwent both QFT-GIT and TST simultaneously from September 2008 to No-vember 2010, patients with indeterminate QFT-GIT results(n � 21), with active (n � 11) or suspicious (n � 1) findings fortuberculosis on a chest radiograph, were excluded. Finally, 724patients were recruited for this study: 497 patients with rheu-matoid arthritis (RA), 198 with ankylosing spondylitis (AS),and 29 with juvenile rheumatoid arthritis (JRA). The agree-ment between the 2 tests was estimated by Cohen’s � andfactors influencing discrepancies were identified using multi-variate analysis.Results: The positivity of QFT-GIT was higher in RA than ASor JRA (30.2%, 16.2%, and 3.4%, respectively). In contrast,TST positivity was highest in AS compared to RA and JRA(45.5%, 28.2%, and 17.2%, respectively). The agreement be-tween the 2 tests was low in all patients (� � 0.285). The onlypredictor of a discrepancy between the 2 tests was older age.Factors associated with discordant QFT-GIT-negative/TST-positive results were female [odds ratio (OR) � 2.33, confi-dence interval (CI) 1.11 to 4.89] and AS (OR � 3.12, CI 1.44to 6.79), whereas a discordant QFT-GIT-positive/TST-nega-tive result was associated with glucocorticoid use (OR � 2.44,CI 1.24 to 4.81).Conclusions: The agreement between the 2 tests is low; there-fore, it would be better to perform both tests than to use any 1test alone for the detection of LTBI in TB-endemic regions.Female and underlying AS are related to being QFT-GIT-negative/TST-positive, and the use of glucocorticoid is associ-ated with being QFT-GIT-positive/TST-negative.Semin Arthritis Rheum 42:424-432. © 2013 Elsevier Inc. Allrights reserved.

Proceedings from the 5th Annual International Societyfor Musculoskeletal Imaging in Rheumatology AnnualConference . . . By Philip Conaghan, Mikkel Ostergaard, MariaAntonietta D’Agostino, Norman Gaylis, Orrin Troum, WilliamArnold, Ewa Olech, Alvin Wells, Charles Peterfy, and Judy L.Seraphine

Since its inception, ISEMIR has held an annual educationmeeting highlighting the changes in the utilization of imagingtools for the management of rheumatic diseases. ISEMIR’sinternational faculty and world-renowned experts have dis-cussed these topics at a very high scientific level. The evolutionof the content demonstrates the rapidly changing environmentin the field of rheumatology. Advances in treatment have led tothe increased use of magnetic resonance imaging (MRI) andultrasound (US). This publication is based upon the proceed-ings from the 2012 ISEMIR educational meeting that tookplace on April 26th in Chicago, Illinois. Presentations from thelive proceedings can be viewed at www.isemir.org.Semin Arthritis Rheum 42:436-449. © 2013 Elsevier Inc. Allrights reserved.