Transcript: Syphilis Laboratory Diagnosis for New Nurse Practitioners

​Liz Rohr:
Well, hey there. It's Liz Rohr from Real World NP, and you're watching NP Practice Made Simple. The weekly video is to help save you time/frustration and help you learn faster so you can take the best care of your patients. In this week's video, I'm going to be talking about syphilis. I'm going to actually be talking about a very specific scenario that I see all the time in primary care.

We learn about syphilis in school. We learn about primary, the secondary, tertiary, all that stuff. Most of the time, when I am encountering syphilis... And specifically, I'm talking about lab interpretation in this video. The main scenario that I'm seeing has something to do with the labs being abnormal, but they never had symptoms in the first place. I'm really going to focus on that, touching a little bit on when patients are symptomatic and you're proactively concerned about them having syphilis versus when you're screening them for whatever reason.

I want to talk about the labs. When it comes to diagnosing syphilis, and you're doing a screening test, whether or not they have symptoms... I guess either way. But if they have no symptoms, sometimes you can get a positive test back. Then, you're left with like, "Oh, gosh. I didn't expect that. What do I do with it?"

There's two main categories of tests. There are the non-treponemal and the treponemal. Non-treponemal are the screening tests that we usually start with that are less complicated/more cost-effective. We start there. If those are positive, then it will reflexively go to the treponemal tests. The non-treponemal tests are typically RPR. I can't remember it off the top of my head. My notes are a little convoluted. But RPR and VDRL are the two main ones. Sorry about that. 

Then, when that is reported back, it's actually a dilution. Without getting into too much of the details, it's basically a ratio of how much they had to dilute it to how much was detected. The ratio is one to two, one to 4, 32, 64, 120. It keeps going up and up: 1000, 2000. The higher the second number, the more likely it is to be an acute infection versus a false positive versus a latent infection.

The RPR is usually the one that our lab does. I'm more familiar with that. The RPR, for example, is positive... It will be either non-reactive, or it will be reactive. Then, it has a titer... associated with an antibody titer in that one-to-whatever ratio. When that becomes positive, the workflow is typically that the laboratory you're ordering from will add on the treponemal test automatically, and the Department of Public Health will likely be notified. That's how at least it works in the state I live, which is Massachusetts. I would check with your supervisor on that. But that's the general workflow of what happens. You automatically get a test added on, or they call you. They ask you to add it on, that kind of thing.

The treponemal test, the more specific, a little bit more complicated test... There's a whole bunch of them. I have my notes here so I don't forget. FTA-ABS, FTA antibody... That is the main one that I see. Fluorescent treponemal antibody absorption... There's a whole bunch of other ones. I'm not as familiar with MHA-TP. TPPA... I have seen that one. TPEIA... So those are treponemal pallidum particle agglutination assay and T. pallidum enzyme immunoassay. I guess what I've read is that the TPEIA is recommended. But most of the time, like I said, I see the FTA antibody. But basically, it's like a confirmatory test.

Any of those will come back as reactive or not reactive or positive or negative. Once those are positive, they will be positive for life. That doesn't necessarily tell you if it's an active infection right now. It just suggests very sensitively and specifically that it is likely an infection at some point. Where you go from there depends on a couple of different things. One, if you have a positive RPR and a positive FTA-ABS or whatever it is, the treponemal test of your choice or of your lab's choice... If those are both positive... There are some rare cases of them being both false positive, but that's pretty uncommon. The more likely scenario is that the RPR is going to be false positive, and then the FTA-ABS or whatever the treponemal test is going to be negative, which is suggestive of a false positive.

The reasons behind that are a little bit obscure to me. But they're not very common. They can be a reactive thing. I've seen it in some people with autoimmune conditions, stuff like that. But when it comes to the actual interpretation, if you have both the positive RPR that has a titer and then you have the positive antibody of some kind or the treponemal test of some kind, you can take it from there.

The places that you take it from there are, did they have symptoms at the time of presentation? I'll only briefly touch on that because it's a little bit more involved. I think we got a little bit more of that in school, honestly, versus this other scenario, which you just have to figure out. For the symptomatic patients, it's important to investigate. What are we dealing with here? Is it secondary/tertiary? What were the initial presenting symptoms? Do they need to see infectious disease? I would tag in somebody if I found that to be the case.

Then, the second scenario is if they have no symptoms, then where are we from there? Then, that's getting into the history because it doesn't necessarily mean that they have an infection now, but they have at some point. I say that for a couple of reasons. Just stick with me for a second. But the main thing you want to ask is, if they have no symptoms, "Do you have any records?" Or do they have any history of treatment? Because what can happen is that they expected actions after that happens... For example, say, if somebody has a one-to-four titer on their RPR, and they have a positive FDA antibody, and they have no idea if they've ever been treated before... Basically, you're getting into... "What type of syphilis are we talking about?"

You have to presume that if they don't know that it's been treated, that you have to presume that it's never been treated. Then, if you can try to compare it to their previous labs, is this from the last 12 months, or is it just unknown completely? I have to say the most common scenario is unknown completely: no records, no idea about treatment, that whole thing.

Doing your best to elicit if it's in the last 12 months or not because that helps to differentiate what type of syphilis we're talking about, if it's latent syphilis or if it's late latent syphilis. Late latent syphilis is... You have no idea. It's greater than 12 months since they possibly got that infection. They have no symptoms. That's the key here. If they have any symptoms, I'm definitely consulting with either ID or my supervisor and doing more digging and research. It just doesn't come up that often.

But for those people who are asymptomatic... Well, someone with an RPR of one to four, positive antibody, no history on record, no idea if they've ever been treated, no idea if it happened in the last 12 months. We're assuming that it's a late latent syphilis. Then, we're going to treat them as such. The main treatment is Bicillin, penicillin G... I'm not going to say it right. Bicillin is the brand name. I'm not affiliated with them 2.4 million units IM once a week for three weeks. We just have to presume.

I mean, there are alternatives if there's a penicillin allergy, of course. But that's the main treatment. Then, what your follow-up monitoring is... I have my notes here. That's why I'm looking over there. The main thing for follow-up is you're checking their labs again. Again, FTA antibody or whatever treponemal test you've already done is going to stay positive. But the RPR, theoretically, will decrease fourfold, four times below, to show that it's getting better. That's a sign of treatment success: versus, a treatment failure is the next time you check it, and there's a fourfold increase, four times increase of what your initial lab was. If it's a one-to-four, hopefully, it will go down either to one-to-one, or it will say non-reactive because that's a possibility too.

There's two possibilities. Hold on a sec for that, though. But six months, 12 months, and 24 months is the monitoring parameters after the initial treatment of wherever you've dropped in. Then, you're checking to see if it's a fourfold decrease, a fourfold increase, or no change.

Two caveats I want to add in here. One, there's something called serofast. Some patients, especially with those low-level RPRs reactive... Those patients may not ever get... It might not go back down to normal. It might stay at one-to-one. It might stay at one to four. As long as it hasn't increased over time and they don't have symptoms, then you can continue to check those labs: versus, if they have any symptoms or you have concern of there being neurologic things, especially like neurosyphilis, those patients need to be referred to infectious disease to have a conversation about... "Do we need a CSF sampling? Do we need a lumbar spine... a lumbar puncture rather, to obtain CSF for evaluation?" I'm not going to make that decision as primary care. But if they have no symptoms, we're just rechecking the RPR titers at six months, 12 months, and 24 months and, hopefully, a fourfold decrease.

One caveat I did want to add about symptomatic patients. Again, I didn't talk a ton about symptomatic patients in this video because there's a lot more to pack in there. But for those patients, there's something called a hook effect. Real fancy. It's not unique to syphilis RPR testing. However, it can happen with other labs too. But basically, it's just so high that it almost over-saturates the machine, or they don't get to the point of dilution enough to show a result. It can come back as a false negative. If somebody's presenting to you, and you're like, "Oh, my gosh, this is classic textbook syphilis. I'm so worried about it," you order an RPR, and it's like, "Oh, non-reactive," it could be that hook effect of it's almost too high for them to even measure it.
You don't necessarily have to remember that name. But the action step you would take in that case is obviously consulting with somebody. I do recommend that. Active syphilis consulting. Then, the other one is to call the lab and ask them about... Is there a way to address that?

I mean, you can remember that it's called a hook effect, or you can just say, "I'm worried it's not measured because it was too high. Is there a way that you can run that?" I'm sure they'll know what you're talking about because they work in the lab, or, hopefully, they will, or your supervisor will. Somebody will.

But hopefully, that's helpful. That's the most common scenario that I see. I guess one other pearl to think about... It comes to the neurosyphilis thing. One specific time I'm thinking about. I had an older woman in her seventies had some cognitive impairment. Part of the workup for that is syphilis, doing an RPR, HIV, some other labs. Her RPR came back reactive. A low-level reactive. I think it was like a one-to-four or one-to-eight. She had cognitive impairment.

What I ended up doing was having a consultation with... by cold calling, an infectious disease physician that actually I had developed a relationship with, related to our HIV treatment program that I was a part of. But I also just did some cold calling. I have a whole video about that. If you are nervous about that prospect, you can totally do it. It's amazing. But anyway, having a conversation with him of... "Is this an appropriate referral? Do you recommend this person get a CSF sampling to test for syphilis?" What he ended up recommending is her having an appointment to discuss.

I think that, ultimately, they determined that it wasn't necessary: that she and the family decided that it wasn't because it wouldn't necessarily affect her quality of life going forward because she had very likely a late latent syphilis that we treated. It was a risk/benefit discussion that they ultimately decided not to do that. But anyway, just as a general pearl of practice is to get other people involved when it comes to syphilis. But this main approach will be helpful for the vast majority of the RPR positives that you're seeing.

If you struggle with labs, we'd love to have you in the lab interpretation crash course for new nurse practitioners. It's open all the time now. 8.7 hours of continuing education. It covers CBC, CMP, TSH, lipids, urinalysis, and the main endocrine labs and primary care. Head on over to realworldnp.com/labs if you're on the struggle bus with labs because it's bomb. It will help you feel so much better. They're just glowing reviews. But anyway, if you have questions about that, definitely let me or the team know.

But thank you so much for watching. Let us know what questions you have. Hang in there. I'll talk to you soon.