[Question #5265] Following up on #5232

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76 months ago
Following up from #5232. I'm trying to convince myself not to test again, per the advice of Dr. Handsfield. The main issue I'm having is pain around my groin area (basically on both sides of where the penis joins the base of the torso). It feels inflamed and if I sit forward for a period of time the pain is more pronounced. Dr. H said with no typical chancre, no lymph inflammation, and negative RPR at 6 weeks it's not syphilis, but I guess I'm still wondering about that possibility. I did have a 10-day penile ulcer of some description which is otherwise unexplained and I'm feeling pain that seems to me possibly consistent with lymph inflammation in the groin. If we conceded possible chancre, and possible lymph inflammation, would you still consider a 6-week RPR conclusive just a week after a chancre appeared, or would you advise testing again?

I've been researching and I came across the finding that "lesions develop more rapidly when the inoculum size is larger." Could my unusual exposure (oral) be associated with a smaller inoculum size and hence a longer time (5 wks) to appearance of a chancre? A smaller inoculum size would presumably also take longer to be detected by the immune system and delay production (and detection in blood tests) of antibodies? I've also read research that the clearance of a chancre is a DTH rather than an antibody response so wouldn't it be possible to clear a chancre entirely before antibodies are detectable?


Finally, Dr. H said that even if syphilis is ruled out there's an unexplained penile ulcer to account for with a description that’s also not typical for herpes. I believe I’ve described all of my symptoms so is there anything else I should be looking for to make an accurate diagnosis? Thank you.

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Edward W. Hook M.D.
76 months ago
Welcome back to the Forum.  Per chance, on this occasion I happened to pick up your new question and so now you will get my assessment as well.  As an FYI, while both of us are experts on STIs of all sorts, syphilis in particular is an interest of mine. I do syphilis research, write text book chapters on the infection and interact with other health care professionals on the topic.  And I agree with Dr. Handsfield's assessment- this is not syphilis. the epidemiology of your lesion is not consistent with syphilis - as Dr. Handsfield indicated, over 80% of syphilis in the U.S. currently occurs in males, the majority of whom are men with other sex partners.  Further, oral syphilis is extraordinarily rare.  Once lesions are present antibody production is well underway so the idea that an RPR test would be negative more than a week after a syphilitic chancre appeared is a non-starter. Further, resolution of syphilis chancres occurs as a result of the immune response - thus your test AFTER the lesion has resolved pretty much rules out syphilis.  Despite the fact that chancre resolution correlates strongly with DTH responses, antibody production occurs in parallel.  

IF your lesion was an STI (something that may is somewhat doubtful), herpes is a possibility and there is little to do about that (if you got HSV from oral sex it would be HSV-1 which rarely occurs and is rarely transmitted through genital contact.

My assessment and sincere advice. 
1.  This is not syphilis.  Your test results at the time you were tested effectively prove this.
2.  You may never know what caused this.  In my opinion, it is relatively unlikely that it was an STI at all.  This is more common than any of us would like.
3.  The bilateral groin discomfort deserves further evaluation.  Your description makes it difficult to assess and it is unlikely to be STI-related but it is worth seeking evaluation by your own doctor.

I hope these comments are helpful to you.  EWH
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76 months ago
Thank you Dr. Hook. It's great to get such advice from you and the other Dr. H! So to clarify, do you believe I need a further test or are my results conclusive already? I'm guessing you think conclusive already but I just want to be clear. If you think I should test again, when should I do this? (How far from my exposure?)  

And irrespective of your answers above, why is 90 days from exposure such a commonly-stated time to get a "conclusive" result? It's a lot longer than what you and Dr. Handsfield appear to endorse and that certainly creates a lot of anxiety for people like me! Waiting another month or so would be hell if I really have to wait that long. I wonder if you could just explain that 90 day thing to me a bit? Is it because in very rare cases it can take that long for symptoms to manifest and hence for a test to become positive (in which case for someone like me where "symptoms" have already appeared and tested negative it's essentially an irrelevant marker)? But I don't want to put words into you mouth, so please just explain it to me as you see it! Thank you.

Oh and I take it there isn't anything to my smaller inoculum size notion that I put in my first question to you? I promise no additional research after this!

Thank you again and have a Happy Easter.
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Edward W. Hook M.D.
76 months ago
Correct.  I see no medical need whatsoever for additional testing for syphilis.  Your test results prove that you did not get syphilis.

The origin of the 90 day figure, which is based on assumptions made more than 30 or 40 years ago, is that, because persons may not notice signs of syphilis, if there is evidence that they may have been exposed to the disease within the past 90 days, it is worthwhile to test them to determine if they were infected or not. This is a conservative estimate designed to not miss infection.  If the history of syphilis exposure is more than 90 days in the past, there is no benefit to testing exposed persons.  On the other hand, the presence of signs of syphilis, such as a chancre, changes the calculation and lead to the assessments that Dr. Handsfield and I have both made independently related to your case.  If you had signs of infection, blood tests would certainly be positive within a few days of the appearance of lesions

And yes, you are correct, the small inoculum hypothesis you suggest does not work.  

Hope this helps.  EWH
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76 months ago
Okay thank you, Dr.   So I understand you are certain that a negative RPR at 6 weeks just as a 10 day "chancre" was healed has ruled out syphilis.

I really appreciate your expert insight.  It's hard to get a straight answer anywhere else and the clinic's recommendation to get tested again has me a little antsy about it. 

Almost every source I can find talks about tests like RPR being only 75% to 85% percent accurate for detecting primary syphilis and that it only rises to 100% accurate in secondary syphilis. Indeed, every research paper talks about those levels of sensitivity in primary syphilis for RPR and most other blood tests (although the treponemal ones seem somewhat more sensitive, but still none reaches 100% in the primary stage). Statements like this are ubiquitous: "Sensitivity of the RPR and VDRL tests are estimated to be 78% to 86% for detecting primary syphilis infection, 100% for detecting secondary syphilis infection."  I'm sure you're familiar with these data (indeed you are cited in many of these papers!) I just want to be sure that it's not possible for me to be in the 15-25% of people that aren't picked up on the RPR in the primary stage. Who would fall into that category? 

It's also possible, even on this forum, to find people who test negative at 6 weeks and then subsequently test positive (for e.g. post #4685, where he tested negative at 1.5 months, which Dr. Handsfield mistook for 2.5 months, and then tested positive at 4.5 months, and post #2957 where initial test at 6 weeks in presence of chancre was negative and subsequent test a month later was positive). I only highlight these examples to explain my concern and because I think the answers are interesting and useful to people in my situation.

Finally, can you elaborate on why the small inoculum size concept doesn't work? Logically, a smaller size seems like it would take longer to develop a chancre (because this is based on replication of the bacteria), longer to be detected by the immune system, and therefore longer to develop a reactive blood test. What's the science behind why this is flawed logic?

Thank you for all that you do here. It's a great service.
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Edward W. Hook M.D.
76 months ago
Final responses:
1.So I understand you are certain that a negative RPR at 6 weeks just as a 10 day "chancre" was healed has ruled out syphilis.
Correct

2.  Accuracy of the RPR VDRL.  You missed the remainder of the statements you were reading.  These tests are typically 80-85% sensitive at the time of presentation, i.e. at the time lesions have appeared.  You were tested a week AFTER your lesion appeared and were still negative.  AT that time the sensitivity of the test is far, far higher. 

3.  I went back and re-read 2957 which I answered.  My assessment has not changed.  It is unlikely that the signs and symptoms that that person reported were due to syphilis. the issue was not sorted out in later exchanges and may well have been related to a false positive result or other circumstance.  I did not review 4685.

4.  You are mixing up the incubation time (i.e. time to go from inoculation to chancre formation) which may be prolonged if the number of organisms in the initial exposure is low and the amount of antigen needed to stimulate and immune response which is independent of lesion development.

This is my 3rd and therefore final response as part of this thread.  The thread will be closed shortly without further responses.  Further, I must point out that while you may be having trouble accepting that you do not have syphilis, our assessments will not change without proof.  You asked for expert assessment and got it (twice).  Further questions related to these events without new data may not be answered and may be deleted without return of your posting fee.  I hope that you will be able to move forward soon.  EWH
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76 months ago
Thank you Dr. 

Unfortunately I will not be able to move on until I get a positive blood result that shows what I already know. I suffered a penile sore and inflamed lymph nodes after the events described. Both for the first time ever. The chances of this being coincidental are remote, to put it mildly. Further, all the research just indicates those levels of RPR VDRL sensitivity during primary syphilis. I don't see a single one that says "at time of presentation." It is just a matter of time until mine turns positive.

I am sorry for this reply. I am frustrated at myself for being reckless when I should have known better. I sincerely thank you and appreciate you interacting with me on this. You provide a great service and a great deal of reassurance to a great many people, and with only limited information to go on in most cases. I will let you know if I get a positive test, but otherwise will of course respect your request not to interact on this again.

Thank you.