{"id":9512,"date":"2020-01-13T06:58:33","date_gmt":"2020-01-13T11:58:33","guid":{"rendered":"https:\/\/blogs.nejm.org\/hiv-id-observations\/?p=9512"},"modified":"2020-01-13T07:15:04","modified_gmt":"2020-01-13T12:15:04","slug":"diagnostic-tests-for-syphilis-continue-to-perplex-even-the-experts-an-unanswerable-question-in-infectious-diseases","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/diagnostic-tests-for-syphilis-continue-to-perplex-even-the-experts-an-unanswerable-question-in-infectious-diseases\/2020\/01\/13\/","title":{"rendered":"Diagnostic Tests for Syphilis Continue to Perplex Even the Experts: An Unanswerable Question in Infectious Diseases"},"content":{"rendered":"

\"\"<\/a>Here’s a tricky clinical scenario:<\/p>\n

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  1. An elderly person with cognitive decline or some other non-specific neurologic symptom sees a clinician.<\/li>\n
  2. Clinician sends a syphilis screen with a T. pallidum<\/em> enzyme immunoassay (TP-EIA), which returns positive.<\/em><\/li>\n
  3. Lab runs a confirmatory test — a T. pallidum<\/em> particle agglutination test (TP-PA), or similar, which also returns positive.<\/em><\/li>\n
  4. The lab then runs a rapid plasma reagin (RPR) test, which returns negative<\/em>.<\/li>\n
  5. There is no known prior clinical or lab history of syphilis exposure, diagnosis, or treatment.<\/li>\n<\/ol>\n

    Now what are we supposed to do?<\/p>\n

    I bring this up because Dr. Thomas Fekete raised just this issue on the IDSA’s ID Exchange message board, generating a spirited discussion.<\/p>\n

    (I’m citing this discussion and quoting with his permission.)<\/p>\n

    And every card-carrying ID doctor has been asked what to do in just this setting numerous times since labs started using TP-EIA — and not RPR — for syphilis screening a bit over a decade ago. In one study, this pattern (two positive treponemal tests and a negative RPR) occurred in approximately 3% of individuals undergoing testing.<\/a><\/p>\n

    Here’s why the next step is so controversial:\u00a0 This exact<\/em> pattern describes three separate clinical scenarios, each of them requiring very different next steps. Here are the potential interpretations:<\/p>\n

      \n
    1. The result is consistent with, but not diagnostic of, neurosyphilis.<\/strong> Recommendation:<\/em> Perform a CSF exam to rule out neurosyphilis. This is hardly a trivial undertaking, especially in the elderly. Further complicating this next step is that the CSF exam is notoriously poor at either ruling in or ruling out neurosyphilis. Plenty of false-positives and false-negatives.<\/li>\n
    2. The result suggests late-latent syphilis with an RPR that has reverted spontaneously to negative.<\/strong> Recommendation:<\/em>\u00a0 Treat with benzathine penicillin 2.4 million units by intramuscular injection, weekly for 3 doses. In this interpretation, clinicians must consider the likelihood of clinical neurosyphilis to be sufficiently low that this result is unrelated to the neurologic symptoms — which begs the question, why was the test ordered in the first place?<\/li>\n
    3. The result demonstrates prior treated syphilis, with an adequate serologic response. <\/strong>Recommendation:<\/em>\u00a0 No treatment or further testing necessary. Lots of antibiotics have activity against T. pallidum,<\/em> so antibiotics administered for other indications over the years have inadvertently provided sufficient treatment.<\/li>\n<\/ol>\n

      Let’s add to the quandary by quoting Dr. Fekete on two key points:<\/p>\n

      I cannot find modern information about the incidence of true tertiary or neurosyphilis in elderly patients with this [testing] profile … These patients would not have come to our attention in the old system for syphilis screening.<\/p><\/blockquote>\n

      Where are the prospective clinical series outlining either actual clinical neurosyphilis — or even CSF abnormalities — in those who have this serologic profile?<\/p>\n

      Plus, in the pre-TP-EIA era, when we used RPR for screening, neurosyphilis would have been considered “ruled out” unless there was a strong<\/em> prior probability of this disease (which there hardly ever is).<\/p>\n

      Sometimes ignorance is bliss!<\/p>\n

      Want a further wrinkle? Some believe that the recommended treatment for latent syphilis — benzathine penicillin, with its long half-life but low CSF concentrations — adequately treats neurosyphilis as well. The thought here is that the immune system plays a role in clearing the infection<\/a>, so no need for high CNS concentrations of penicillin — except perhaps in people with immunosuppression, as is seen in untreated HIV.<\/p>\n

      The data supporting this view (like many other aspects of clinical syphilis) are largely uncontrolled and somewhat dated — but strongly endorsed and frequently cited by advocates nonetheless.<\/p>\n

      But this position is vociferously challenged by others — again with largely anecdotal and outdated data. This group, now in the majority, inform the current CDC guidelines for treatment of neurosyphilis<\/a>, which recommend high-dose intravenous penicillin G for 10-14 days — a burdensome treatment not easily (or cheaply!) administered to the\u00a0 elderly, especially those with cognitive impairment.<\/p>\n

      It’s not as if this neurosyphilis quagmire were a new problem; indeed, the diagnosis of neurosyphilis has been fraught for decades. Often the leading strategy adopted by a hospital or a practice is the one endorsed the most passionately (or most loudly, in case conference) by the local expert or experts.<\/p>\n

      All this controversy makes this case scenario a classic Unanswerable Question in Infectious Diseases.<\/em> And perfect for a poll!<\/p>\n

      So have it at — and educate us by using the comments section to justify your vote.<\/p>\n

      A 78-year-old man with no known prior history of syphilis or other sexually transmitted infections is evaluated for mild cognitive decline. As part of the work-up, he has the following blood test results:\u00a0 TP-EIA positive, TP-PA positive, RPR negative.<\/em><\/p>\n

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      <\/p>\n\t\t

      <\/p>\n\t\t

      What would you recommend next?<\/strong><\/p>