Syphilis IgG with Reflex Confirmation
Label Mnemonic: SYPHG
Epic Lab Code: LAB7824
Downtime Form: A-1a General Laboratory Requisition
Chemistry
6240 RCP
356-3527
Specimen(s):
Serum
Specimen Instructions:
3.0 mL whole blood from red top tube or TWO microtainers
Collection Medium:
Red top tube 5 mL (Clot Activator)
Testing Schedule:
24 hrs/day, 7 days a week, including holidays.
Turn Around Time:
3 hours (upon receipt in laboratory)
Reference Range:
Negative: 0.8 AI (antibody index) or less
Equivocal: 0.9-1.0 AI
Weak Positive: 1.1-2.0 AI
Moderate Positive: 2.1-8.0 AI
Strong Positive: > 8.0

Syphilis IgG results with low reactivity (especially in the 0.9-2.0 AI range) are more likely to be false positives (see below).
Interpretive Data:
The syphilis IgG screen is an entirely new method relative to the RPR (rapid plasma reagin). The RPR detects non-treponemal antibodies (cardiolipin, cholesterol, and lecithin), whereas the new test detects IgG antibodies to T. pallidum proteins (15 kDa, 17 kDa, 47 kDa). The new approach to syphilis is termed 'reverse algorithm' in that RPR is not done as first test (traditional algorithm) but as the confirmation (i.e., reverse of the traditional algorithm). A negative syphilis IgG means that past and present syphilis infection is unlikely. A positive syphilis IgG can indicate a past or present infection. Specimens showing positive syphilis IgG will be reflexed automatically to RPR. If there is discrepancy between syphilis IgG and RPR, TPPA (T. pallidum particle agglutination) is additionally performed. A negative syphilis IgG means that past or present syphilis infection is unlikely. A positive syphilis IgG can indicate a past or present infection. Specimens showing positive syphilis IgG will be reflexed automatically to RPR. If there is discrepancy between syphilis IgG and RPR, TPPA (T.pallidum particle agglutination) is additionally performed. For patients who have been treated for syphilis, RPR titers should be followed (orderable as Syphilis Treatment Follow-up (RPR with Titer) in Epic). Successful treatment is generally indicated by a 4-fold or more reduction in RPR titer (e.g., 1:32 to 1:8). From retrospective analysis, the syphilis IgG value (measured in antibody index, AI) correlates with likelihood that specimen will confirm with additional testing. Equivocal (0.9-1.0 AI) and weak positive (1.1-2.0 AI) syphilis IgG values have low likelihood (< 20%) of confirming. Historically, about 50% of specimens with moderate positive (2.1-8.0 AI) syphilis IgG values show a positive RPR or TPPA. Over 95% of specimens of specimen with strong positive (> 8.0) syphilis IgG values confirm positive. As mentioned above, a positive syphilis IgG (even high values) can occur with past or present infection. The interpretation is as follows using CDC guidelines: Syphilis IgG RPR TPPA Interpretation Negative (Not done) (Not done) Syphilis infection unlikely Positive Positive (Not done) Syphilis - recent infection likely Positive Negative Positive Syphilis - past or present infection Positive Negative Negative Infection unlikely - false positive syphilis IgG There are several advantages of the reverse algorithm: • Rapid turnaround time for syphilis IgG • Avoids the false positives seen with RPR in autoimmune disease (e.g., lupus), infectious mononucleosis, viral pneumonia, and non- syphilis treponemal diseases (e.g., yaws) • Detects early primary and latent infection that may be missed with traditional RPR screening Some key points to remember with the reverse algorithm: • Syphilis IgG can persist for many years. A positive result does not necessarily indicate active disease. In patients with positive syphilis IgG, the RPR provides information on active versus past infection. • For assessing treatment efficacy in patients who have been treated for syphilis, "Syphilis Treatment Follow-up (RPR with Titer)" should be ordered. Successful treatment is generally indicated by a 4-fold reduction in RPR titer (e.g., 1:32 to 1:8). • The syphilis IgG can have false positives. These will be indicated by negative RPR and TPPA confirmation. Given the generally low prevalence of syphilis in Iowa, false positives will be a significant fraction of positive screening test results regardless of testing method used. • Iowa Department of Public Health will investigate positive syphilis IgG results only after confirmatory testing results are available. The full set of results guides investigation and follow-up.
Comments:
New assay and syphilis testing algorithm introduced February 25, 2013.

Positive syphilis IgG results are reflex automatically to RPR. If syphilis IgG and RPR results are discrepant, TPPA is additionally performed.
Methodology:
Multiplex flow immunoassay
CPT Code:
86780 (Syphilis IgG)
86592 (RPR - if performed as reflex)
86593 (RPR titer - if performed as reflex)
86780 (TPPA - if performed as reflex)