title: Elucidating the role of hyposalivation and autoimmunity in oral candidiasis.
abstract: BACKGROUND
  Oral candidiasis (OC) is a potential oral complication in Sjögren's syndrome (SS). Some studies indicate that the low stimulated salivary flow and not low unstimulated salivary flow is associated with OC in SS, while others report that the underlying autoimmune disorders contribute to OC, based solely on correlation coefficients. Given the conflicting and limited existing evidence, we purposed to ascertain the role of both salivary gland dysfunction (hyposalivation based on unstimulated and stimulated flow rates) and autoimmunity (SS, other autoimmune disorders) in OC among those with SS, other salivary gland dysfunction, and non-salivary gland dysfunction controls (NSGD).
  
  
  METHODS
  A nested case-control study was designed within a larger NIH/NIDCR cohort. Descriptive analyses, nonparametric tests, comparative analyses, and multivariate logistic regression analyses were undertaken.
  
  
  RESULTS
  Data on 1526 subjects (701 SS, 247 ISS, 355 Sicca, and 223 NSGD) were obtained from the source cohort of 2046 and analyzed for this study. The median whole unstimulated salivary flow rate (WUS, ml 15 min-1) was lower in SS (0.8, interquartile range (IQR) 1.8) compared to ISS (5.5, IQR: 5.2, P < 0.001) and NSGD (3.8, IQR: 3.8, P < 0.001) but comparable with that of Sicca (1.0, IQR: 1.5, P = 0.777) participants. The median total stimulated salivary flow rate (TSS, ml 15 min-1) was lowest in SS (7.0, IQR: 12.4, P < 0.001) compared to other groups. Of the 45 OC cases in this cohort, 71.1% (n = 32) were from the SS group. The prevalence of OC was highest in the SS group (4.6%, P = 0.008). SS group had twice the risk of OC than NSGD (OR = 2.2, 95%CI: 1.1-4.2, P = 0.02) and Sicca (OR = 2.2, 95% CI: 1.0-4.8, P = 0.03), adjusting for confounders; hyposalivation [WUS (OR = 5.1, 95%CI: 2.5-10.4, P < 0.001), TSS (OR = 1.9, 95%CI: 1.0-3.5, P = 0.04)], history of other autoimmune disorders (OR = 4.4, 95%CI: 1.7-11.3, P = 0.002), medications for extraglandular manifestations (OR = 2.3, 95%CI: 1.1-4.9, P = 0.03), and diabetes mellitus (4.2, 95%CI: 1.2-15.2, P = 0.02) were independent predictors of OC; females had a lower risk than males (OR = 0.29, 95%CI: 0.13-0.67, P = 0.004). Age, race, anti-SSA/SSB autoantibodies, focus score, other medications, anxiety, fatigue, cigarette smoking, alcohol, and caffeine use were not associated with oral candidiasis.
  
  
  CONCLUSIONS
  Salivary gland dysfunction (hyposalivation with WUS being a stronger predictor than TSS) and autoimmunity (SS, other autoimmune disorders, medications, i.e., DMARDS) are both independent predictors of OC. Diabetes mellitus is an independent predictor of OC among those with salivary gland dysfunction. Our findings suggest that these independent predictors should be considered in the prevention and management of OC in this population.
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institutes of Health, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Billings
authors.affiliation: Program Analysis and Reporting Branch, National Institutes of Health, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Dye
authors.affiliation: Program Analysis and Reporting Branch, National Institutes of Health, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: Iafolla
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institutes of Health, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Grisius
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institutes of Health, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA.
authors.forename: I
authors.identifier: http://orcid.org/0000-0001-5331-1652
authors.initials: I
authors.lastname: Alevizos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000453:epidemiology; D015551:Autoimmunity; D002180:Candidiasis, Oral / Q000453:epidemiology* / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors; D012463:Saliva; D012737:Sex Factors; D012859:Sjogren's Syndrome / Q000453:epidemiology* / Q000503:physiopathology*; D014987:Xerostomia / Q000453:epidemiology* / Q000503:physiopathology; D055815:Young Adult
keywords: Sjogren's syndrome; autoimmunity; hyposalivation; oral Candidiasis