title: Fatigue in Primary Sjögren's Syndrome: Clinical, Laboratory, Psychometric, and Biologic Associations.
abstract: OBJECTIVE
  To identify independent contributors of fatigue in primary Sjögren's syndrome (SS) patients, taking into account clinical, laboratory, and psychological features, and to explore the potential role of interferon (IFN)-induced gene indoleamine 2,3-dioxygenase (IDO-1), anti-21-hydroxylase (anti-21[OH]) antibodies, and soluble BAFF.
  
  
  METHODS
  Detailed clinical and laboratory characteristics were recorded for 106 primary SS patients. The Functional Assessment of Chronic Illness Therapy-Fatigue, Zung Depression Scale, State-Trait Anxiety Inventory, Eysenck Personality Questionnaire Scale, and Athens Insomnia Scale were adopted to assess fatigue, depression, anxiety, and sleep disturbances, respectively. Peripheral whole blood expression levels of IDO-1, as well as type I and II IFN-induced genes were calculated using quantitative reverse transcriptase-polymerase chain reaction. Serum anti-21(OH) antibodies and soluble BAFF levels were determined by a radioimmunoassay and an enzyme-linked immunosorbent assay, respectively. Univariate and multivariate models were performed to identify determinants of fatigue.
  
  
  RESULTS
  Fatigue was detected in 32 of 106 (30.2%) primary SS patients. In univariate analysis, fatigue was associated with arthralgias/myalgias, fibromyalgia hydroxychloroquine therapy, both state and trait anxiety scores, depression, and neuroticism, as well as impaired sleep patterns. Multivariate analysis revealed neuroticism (odds ratio [OR] 6.9, [95% confidence interval (95% CI) 1.7-28.0]), depression (OR 3.0 [95% CI 0.8-11.0]), and fibromyalgia (OR 5.5 [95% CI 1.1-27.7]) as independent fatigue contributors. Soluble BAFF levels, anti-21(OH) autoantibodies, and IDO-1 messenger RNA expression did not significantly differ between fatigued and nonfatigued primary SS patients.
  
  
  CONCLUSIONS
  Depression, neuroticism, and fibromyalgia play a major role in primary SS-associated fatigue and should be addressed in clinical practice, with active collaboration between rheumatologists and mental health professionals. Further studies are warranted in order to explore underlying pathophysiologic pathways that might explain fatigue in the setting of primary SS.
authors: National and Kapodistrian University of Athens, Athens, Greece.
authors: Theofanis
authors: T
authors: Karageorgas
authors: National and Kapodistrian University of Athens, Athens, Greece.
authors: Sofia
authors: S
authors: Fragioudaki
authors: National and Kapodistrian University of Athens, Athens, Greece.
authors: Adrianos
authors: A
authors: Nezos
authors: National and Kapodistrian University of Athens, Athens, Greece.
authors: Dimitrios
authors: D
authors: Karaiskos
authors: National and Kapodistrian University of Athens, Athens, Greece.
authors: Haralampos M
authors: HM
authors: Moutsopoulos
authors: National and Kapodistrian University of Athens, Athens, Greece.
authors: Clio P
authors: CP
authors: Mavragani
mesh_terms: D000368:Aged; D001008:Anxiety Disorders / Q000175:diagnosis / Q000523:psychology; D001323:Autoantibodies / Q000097:blood; D053264:B-Cell Activating Factor / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003863:Depression / Q000175:diagnosis / Q000523:psychology; D005221:Fatigue / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000523:psychology; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000075384:Neuroticism; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011594:Psychometrics; D060888:Real-Time Polymerase Chain Reaction; D012698:Serologic Tests; D012859:Sjogren's Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000523:psychology; D013255:Steroid 21-Hydroxylase / Q000276:immunology; D011795:Surveys and Questionnaires
chemical_list: D001323:Autoantibodies; D053264:B-Cell Activating Factor; D015415:Biomarkers; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C505719:TNFSF13B protein, human; D013255:Steroid 21-Hydroxylase