title: The use of Western blotting as the confirmatory test for syphilis in patients with rheumatic disease.
abstract: OBJECTIVE
  As a direct or indirect result of antiphospholipid antibody production, subjective laboratory interpretation, and false positive results, the common serologic tests for syphilis have been inherently inaccurate diagnostic tests in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases. We assessed the diagnostic accuracy of syphilis testing in patients with SLE and other autoimmune diseases using the treponemal Western blot (TWB) as the gold standard.
  
  
  METHODS
  A prospective cohort study carried out at a tertiary care medical center. We studied 107 patients with autoimmune disease, 50 with at least one positive serologic test for syphilis and 57 disease matched controls. Prior to enrollment all eligible patients underwent a clinical assessment performed by at least 2 rheumatologists to confirm a diagnosis of rheumatic disease. All subjects underwent serologic testing, in blinded fashion, for syphilis using the rapid plasma reagin test (RPR), Venereal Disease Research Laboratory test (VDRL), fluorescent treponemal antibody absorption test (FTA-ABS), and the TWB.
  
  
  RESULTS
  Eighty-seven percent of the patients studied were female, the mean age was 46.5 years, and the most common diagnosis at the time of enrollment was SLE. Using the TWB as the gold standard diagnostic test for syphilis, the sensitivity, specificity, and positive predictive values for each syphilis test were calculated. The sensitivity and specificity for the RPR in patients with rheumatic disease was 62.5% (95% confidence interval 24.5 to 91.5%) and 91.9% (95% CI 84.2 to 96.2%), respectively. The sensitivity and specificity for the VDRL were 37.5% (95% CI 8.5 to 75.5%) and 89.9% (95% CI 81.8 to 94.8%), respectively. Confirmatory syphilis testing using the FTA-ABS showed a sensitivity of 100% (95% CI 68.6 to 100%) and a specificity of 67.7% (95% CI 57.4 to 76.5%). Eight patients tested positive for syphilis by Western blotting. For the FTA-ABS test, there was a significantly higher number of false positive results (n = 32) compared to false negative results (n = 0), p < 0.0005.
  
  
  CONCLUSIONS
  The FTA-ABS is not an accurate confirmatory test for syphilis in patients with SLE and other autoimmune diseases. While a negative FTA-ABS may exclude syphilis infection in the majority of cases, a positive FTA-ABS test result cannot assuredly confirm syphilis infection in this population. Western blotting is an accurate confirmatory test for syphilis and may be necessary to unequivocally discern the immunological response of syphilis from that of an underlying autoimmune disease.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, Walter Reed Army Medical Center, Washington, DC, USA.
authors.forename: F T
authors.initials: FT
authors.lastname: Murphy
authors.forename: R
authors.initials: R
authors.lastname: George
authors.forename: K
authors.initials: K
authors.lastname: Kubota
authors.forename: M
authors.initials: M
authors.lastname: Fears
authors.forename: V
authors.initials: V
authors.lastname: Pope
authors.forename: R S
authors.initials: RS
authors.lastname: Howard
authors.forename: G J
authors.initials: GJ
authors.lastname: Dennis
mesh_terms: D015153:Blotting, Western / Q000379:methods*; D015331:Cohort Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012216:Rheumatic Diseases / Q000150:complications*; D012680:Sensitivity and Specificity; D013587:Syphilis / Q000150:complications / Q000175:diagnosis*; D013588:Syphilis Serodiagnosis