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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ESj\u00f6gren\u0027s syndrome (SS) is characterized by chronic inflammation occurring primarily in the exocrine glands. Better ways of defining and diagnosing patients with SS, monitoring patients and their disease activity, understanding the pathogenesis of the disease, and addressing the lack of effective evidence-based treatment are some of the challenges currently facing clinicians and patients. This is a very active field of research, with more than 800 articles published from 2013 to 2014. This article presents an overview of the latest SS research findings.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatological Autoimmune Disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatological Autoimmune Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ESjogren\u0027s syndrome (SS) is characterized by chronic inflammation occurring primarily in the exocrine glands. First described in the 1930s by Henrik Sjogren, SS is most commonly characterized by dry eyes and mouth, severe fatigue, arthralgia, and myalgia. Better ways of defining and diagnosing patients with SS, monitoring patients and their disease activity, understanding the pathogenesis of the disease, and addressing the lack of effective evidence-based treatment are some of the challenges currently facing clinicians and patients. This is a very active field of research, with more than 800 articles published from 2013 to 2014. Marie Wahren-Herlenius, MD, PhD, Karolinska Institutet, Stockholm, Sweden, presented an overview of the latest SS research findings.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EWomen are much more likely than men to develop SS, with a peak incidence at 40 to 50 years of age. The clinical manifestations of SS are divided into glandular and extraglandular, and extraglandular features can affect nearly every organ in the body. The immune phenotype of SS includes increased memory B cells, hypergammaglobulinemia, anti-SSA\/SSB antibodies, antinuclear antibodies, rheumatoid factor, the interferon (IFN) signature, lymphocytic infiltrates in salivary glands with germinal center formation, and increased levels of tumor necrosis factor, B-cell activating factor (BAFF), and IFN-a. The risk of lymphoma is 16 times higher in patients with SS, predominantly non-Hodgkin lymphoma B-cell type [Theander E et al. \u003Cem\u003EAnn Rheum Dis\u003C\/em\u003E 2006].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EClassification criteria for SS continue to evolve. The American-European Consensus Group (AECG) revised its criteria in 2002 [Vitali C et al. \u003Cem\u003EAnn Rheum Dis\u003C\/em\u003E 2002], and the American College of Rheumatology (ACR) criteria were published in 2012 [Shiboski SC et al. \u003Cem\u003EArthr Care Res (Hoboken)\u003C\/em\u003E 2012]. There are differences between the 2 groups (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). The ACR criteria are more complicated because they require evaluation in a specialized setting for the biopsy and ocular staining score. While most studies have demonstrated concordance between the 2 sets of criteria, there are cases that are overlooked by either set. Collaboration between the European League Against Rheumatism (EULAR) and the ACR is ongoing to develop universal validated consensus criteria.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/17\/27\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Comparison of AECG and ACR Criteria\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1418043501\u0022 data-figure-caption=\u0022Comparison of AECG and ACR Criteria\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/17\/27\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/17\/27\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/17\/27\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14609\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003EComparison of AECG and ACR Criteria\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EACR=American College of Rheumatology; AECG=American-European Consensus Group; ANA=antinuclear antibodies; RF=rheumatoid factor;\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003ESS=Sjogren\u0027s syndrome.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-6\u0022\u003ELacrimal gland involvement in SS is evaluated by using tear flow via Schirmer\u0027s test and ocular surface stain and scoring. Salivary gland involvement is assessed by measuring unstimulated and stimulated salivary flow and salivary gland biopsy. The salivary gland biopsy is an invasive method that can lead to complications, so alternative methods are being studied. In parotid gland ultrasonography, ultrasound analysis of the parenchyma can detect the SS-associated appearance. Abnormal parotid ultrasonography has been shown to correlate with antibody-positive disease, hypergammaglobulinemia, clinical scores, and systemic disease. This method also appears to correlate with markers for lymphoma development [Theander E, Mandi T. \u003Cem\u003EArthritis Res Care (Hoboken)\u003C\/em\u003E 2014].\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003ETwo scales have been developed to assess disease activity in SS. The EULAR SS Patient Reported Index (ESSPRI) is rated by the patient and includes symptomatic features such as dryness, fatigue, and pain [Seror R et al. \u003Cem\u003EAnn Rheum Dis\u003C\/em\u003E 2011]. Systemic features are rated by physicians in the EULAR SS Disease Activity Index (ESSDAI) [Seror R et al. \u003Cem\u003EAnn Rheum Dis\u003C\/em\u003E 2010]. Validations studies of both assessments have been recently conducted. The ESSPRI was compared with the Sicca Symptoms Inventory and Profile of Fatigue and Discomfort, and the ESSDAI was compared with the SS Disease Activity Index and Sjogren\u0027s Systemic Clinical Activity Index. Analyses indicated that all scores had good to excellent reliability. The physician scores had greater sensitivity to change, with the ESSDAI having better construct and face validity and better discriminating power. The patients\u0027 scores had a smaller sensitivity to change, but the ESSPRI had better construct validity and sensitivity to change [Seror R et al. \u003Cem\u003EAnn Rheum Dis\u003C\/em\u003E 2014]. \u201cThese scores have been very valuable to the field. We are now able to assess patient disease activity and compare between studies,\u201d said Prof. Wahren-Herlenius.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EProf. Wahren-Herlenius also reviewed 4 recent clinical studies of the treatment of SS. In a randomized, double-blind, placebo-controlled trial, 26 patients with SS were treated for 4 weeks with placebo or the interleukin-1 receptor antagonist anakinra [Norheim KB et al. \u003Cem\u003EPLoS One\u003C\/em\u003E 2012]. The primary outcome measure was a group-wise comparison of fatigue scores at Week 4 adjusted for baseline values. The study did not meet the primary outcome measure, as no significant differences were seen between the treatment groups. However, at 4 weeks, 6 of 12 (50%) anakinra-treated patients reported a 50% reduction in fatigue versus 1 of 13 (8%) patients taking placebo (p=0.03).\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EIn another randomized, double-blind controlled trial, rituximab was tested against placebo in 120 patients with SS at 14 centers in France [Devauchelle-Pensec V et al. \u003Cem\u003EAnn Intern Med\u003C\/em\u003E 2014]. Improvement at Week 24 of at least 30 mm in 2 of 4 visual analog scales (VAS) for fatigue, pain, dryness, and global disease was the primary outcome measure. While the study did not meet its primary end point, some significant alleviation of fatigue was seen at earlier time points.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EIn the prospective BELISS [Mariette X et al. \u003Cem\u003EAnn Rheum Dis\u003C\/em\u003E 2013] Phase 2 open-label trial, 30 patients were treated with the anti-BAFF\/BlyS drug belimumab. Patients with SS received belimumab 10 mg\/kg at Weeks 0, 2, and 4 and then every 4 weeks to Week 24. The primary end point was measured at Week 28 and consisted of improvement in 2 of the following 4 items: 30% or more reduction in dryness, 30% or higher improvement in fatigue or pain VAS score, 30% or higher improvement in systemic activity VAS score, and\/or greater than 25% improvement in B-cell activation biomarkers. Sixty percent of patients met the primary outcome measure.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EThe prospective open-label ASAP study [Meiners PM et al. \u003Cem\u003EAnn Rheum Dis\u003C\/em\u003E 2014] was conducted in 15 patients who received intravenous abatacept infusions (10 mg\/kg) on Days 1, 15, and 29 and every 4 weeks thereafter up to 24 weeks and were followed to Week 48. Disease activity was assessed with the ESSDAI and ESSPRI. The results were promising: Improvement in ESSDAI and ESSPRI scores was seen, with stable or slight increase in salivary gland function. In addition, most patients had a clinically relevant improvement in their well-being. While these trials were encouraging, concluded Prof. Wahren-Herlenius, the optimal drug remains to be found, which underscores the importance of defining pathogenic mechanisms.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/17\/27.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzp3uq\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzp3uq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}