An early view of the International Sjögren's Syndrome Registry

Oral Pathology, University of California at San Francisco, Box 0422, San Francisco, California 94143, USA.
Arthritis & Rheumatology (Impact Factor: 7.76). 05/2009; 61(5):711-4. DOI: 10.1002/art.24397
Source: PubMed


In the process of developing new classification criteria for SS, we use area-proportional Venn diagrams to visualize the interrelationship between various phenotypic characteristics of SS (14). Figure 1 illustrates the overlapping relationships of 3 objective SS signs in the cohort (72% exhibit positive ocular staining for KCS, 42% positive LSG biopsy specimen, 39% positive serum anti-SSA and/or anti-SSB, and 20% none of these). Interestingly, 3% of the participants had only an abnormal focus score, 2% had only a positive serology to anti-SSA or anti-SSB, whereas 28% had only an abnormal ocular staining score. The high proportion of participants with only abnormal ocular staining led us to compare this subgroup (termed KCS-only; n = 323) with those having KCS and at least 1 of the 2 other main phenotypic features of SS, specifically focal lymphocytic sialadenitis with a focus score >1 and/or anti-SSA or anti-SSB antibodies (termed SS-KCS; n = 510). KCS-only participants had significantly lower levels of serum autoantibodies (RF, ANA titer, IgG), better ocular physiologic tests (Schirmer's test, tear break-up time), more frequent use of anticholinergic drugs and/or cigarettes (P < 0.0001 for all), and were older (P = 0.001) compared with SS-KCS participants. This suggests that KCS-only cases may represent a distinct entity of seronegative KCS that is significantly less severe than SS-KCS. Additional recall data will allow us to explore if KCS-only subjects progress into SS-KCS or whether KCS-only is a disease entity distinct from SS.

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    • "The need for better diagnostic criteria for SS is reflected in the establishment and funding of SICCA from 2003 to 2013. One of the goals of this multinational study was to develop standardized, universally accepted classification criteria for SS [124]. The study is now complete, and the clinical criteria recommended for SS diagnosis are under review by the American College of Rheumatology [3]. "
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    ABSTRACT: Sjögren's Syndrome (SS) is a debilitating autoimmune disease that primarily affects women. Patients with SS experience dry eyes and dry mouth in addition to systemic disease manifestations, including arthritis, peripheral neuropathy and pulmonary fibrosis. As in many autoimmune diseases, the inciting factors that precipitate SS are poorly understood. Patients with SS have periductal and perivascular lymphocytic infiltration of salivary and lacrimal tissue, and this is a hallmark of disease. While this infiltration is well characterized, the pathologic events that precede and cause this inflammatory cell recruitment are unknown. Although few studies have examined SS salivary tissue prior to disease onset, there is strong evidence for innate immune hyperactivity. Accordingly, processes such as apoptosis of glandular tissue, heightened inflammatory cytokine and chemokine production, and toll-like receptor (TLR) activation are described in early disease and are each linked to innate immune activation in murine models of disease and SS patients. This review will explore the relationship between innate immunity and SS pathogenesis prior to overt disease onset and discuss therapeutic strategies to mitigate disease progression in SS patients.
    Cytokine 03/2014; 67(2). DOI:10.1016/j.cyto.2014.02.009 · 2.66 Impact Factor
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    • "Recently, the American College of Rheumatology [59] proposed new classification criteria for Sjögren’s syndrome. These criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sjögren’s International Collaborative Clinical Alliance [60]. The proposed criteria are: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer ≥1:320), 2) ocular staining score ≥3, or 3) presence of focal lymphocytic sialadenitis with a focus score ≥1 focus/4 mm2 in salivary gland biopsy samples. "
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    ABSTRACT: Background: The most advocated clinical method for diagnosing salivary dysfunction is to quantitate unstimulated and stimulated whole saliva (sialometry). Since there is an expected and wide variation in salivary flow rates among individuals, the assessment of dysfunction can be difficult. The aim of this systematic review is to evaluate the quality of the evidence for the efficacy of diagnostic methods used to identify oral dryness. Methods: A literature search, with specific indexing terms and a hand search, was conducted for publications that described a method to diagnose oral dryness. The electronic databases of PubMed, Cochrane Library, and Web of Science were used as data sources. Four reviewers selected publications on the basis of predetermined inclusion and exclusion criteria. Data were extracted from the selected publications using a protocol. Original studies were interpreted with the aid of Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Results: The database searches resulted in 224 titles and abstracts. Of these abstracts, 80 publications were judged to meet the inclusion criteria and read in full. A total of 18 original studies were judged relevant and interpreted for this review. In all studies, the results of the test method were compared to those of a reference method.Based on the interpretation (with the aid of the QUADAS tool) it can be reported that the patient selection criteria were not clearly described and the test or reference methods were not described in sufficient detail for it to be reproduced. None of the included studies reported information on uninterpretable/intermediate results nor data on observer or instrument variation. Seven of the studies presented their results as a percentage of correct diagnoses. Conclusions: The evidence for the efficacy of clinical methods to assess oral dryness is sparse and it can be stated that improved standards for the reporting of diagnostic accuracy are needed in order to assure the methodological quality of studies. There is need for effective diagnostic criteria and functional tests in order to detect those individuals with oral dryness who may require oral treatment, such as alleviation of discomfort and/or prevention of diseases.
    BMC Oral Health 08/2012; 12(1):29. DOI:10.1186/1472-6831-12-29 · 1.13 Impact Factor
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    ABSTRACT: Das nach den AECG-Kriterien diagnostizierte primäre Sjögren-Syndrom (pSS) ist mit einer Prävalenz von rund 0,2% in der erwachsenen Normalbevölkerung und einer Jahresinzidenz von 4/100.000 Gesamtbevölkerung deutlich seltener als bisher angenommen. Auch der wiederkehrend berichtete Anteil von einem Mann auf 9Frauen dürfte eher bei etwa 1:20 liegen. An pSS erkrankte Männer haben seltener immunologische, histopathologische oder sialographische Befunde und Organbeteiligungen. Das Erkrankungsalter liegt in jüngeren Untersuchungen mit rund 45Jahren um rund 10Jahre niedriger als in solchen des letzten Jahrzehnts. Im jüngeren Alter erkrankte Patienten sind häufiger Rheumafaktor- und/oder Anti-Ro/SS-A-positiv und leiden häufiger an Hypokomplementämie oder Lymphadenopathien. Mit der Einführung der spezifischeren AECG-Kriterien finden sich weniger Männer, mehr jüngere und mehr schwer erkrankte Patienten in pSS-Kohorten. Etwa 5–10% der pSS-Patienten spezialisierter Zentren leiden an schwerwiegenden extraglandulären Manifestationen. Diese zeigen sich zumeist früh im Krankheitsverlauf und gehen z.T. mit erhöhter Mortalität einher. Betroffene ohne früh auftretende Organbeteiligungen können mehrheitlich mit einem leichten bis mäßig schweren Verlauf rechnen. In Deutschland wird nur rund ein Zehntel der Sjögren-Kranken rheumatologisch betreut. Zusammen mit den nach AECG-Kriterien nicht berücksichtigten Anti-Ro/La-negativen Sjögren-Kranken und den Patienten mit sekundärem Sjögren-Syndrom dürften mindestens 0,4% der erwachsenen Bevölkerung unter stark beeinträchtigender immunpathologischer Sicca-Symptomatik leiden. According to the classification criteria of the American-European Consensus Group (AECG), the prevalence of primary Sjögren’s syndrome (pSS) of about 0.2% in the adult population and a yearly incidence of 4/100.000 in the general population are far lower than previously assumed. Moreover, the repeatedly reported male/female ratio of 1:9 seems to lie more in the range of 1:20. Male pSS patients show fewer immunological, histopathological or sialographic findings and organ involvement. Information on age at disease onset has also changed over the last decade. Recent studies indicate an onset age of approximately 45 years as compared to 56 in earlier studies of the last decade. Patients with an early disease onset are more frequently positive for rheumatoid factor (RF) and/or anti-Ro/SS-A. These patients also seem to have a higher risk of developing hypocomplementemia or lymphadenopathy. As compared to earlier cohorts, the introduction of the rather specific AECG criteria will probably result in the participation of fewer men, younger patients in general and of more seriously ill patients in future cohorts. The change in the spectrum of pSS patients obviously reflects the altered classification criteria since the AECG criteria require anti-Ro/La positivity and therefore exclude a high number of patients with other immunological markers who also show severe sicca symptoms and organ involvements. About 5%–10% of pSS patients in rheumatological care suffer from severe extraglandular manifestations, which generally occur soon after disease onset. In particular, palpable purpura, hypocomplementemia, cryoglobulinemia and lymphoma are associated with increased mortality. In Germany, approximately one tenth of Sjögren syndrome patients receive specialized rheumatological care. There is still insufficient knowledge about the vast majority of pSS patients who are not treated by rheumatologists. These patients, as well as all those who, according to the AECG criteria, are not classified as having pSS either due to anti-Ro/La negativity or having secondary Sjögren’s syndrome, probably add up to at least 0.4% of the adult population which, at present, suffers from considerable immunopathologic sicca symptoms.
    Zeitschrift für Rheumatologie 02/2009; 69(1):41-49. DOI:10.1007/s00393-009-0518-3 · 0.61 Impact Factor
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