T.R. Eckler (2): I don't think There's anything quite as cool as the term
dark field microscopy in terms of like what's on your resume as the lab tech.
Like what do you do?
I handle the dark field.
Sam : Hi everyone, and welcome to another episode of EMPlify
I'm your host, Sam Ashoo.
Before we dive into this month's episode, I want to say thank you for joining us.
I sincerely hope that you find it to be helpful and informative for your
clinical practice, and I want to remind you that you can go to ebmedicine.net
where you will find our three journals, Emergency Medicine Practice, Pediatric
Emergency Medicine Practice, and Evidence Based Urgent Care, and a multitude of
other resources, like the EKG course, the laceration course, interactive
clinical pathways, just tons of information to support your practice
and help you in your patient care.
And now, let's jump into this month's episode.
Sam: All right, ladies and gentlemen, welcome back to
another episode of EMPlify.
I am one of your hosts, Sam Ashoo, and on the other end of the microphone,
T.R. Eckler: Dr. TR Eckler could not be more excited to be here.
I'm sick, it's my birthday and I wanna talk about syphilis, and that just seems
like a really great summary of my life.
Sam: Happy birthday.
Today is the day and I can't think of celebrating it in a better
way than talking about syphilis.
T.R. Eckler: Let's, let's go.
Sam: We are discussing the January 2026.
This is the inaugural episode of the podcast for the year 2026.
T.R. Eckler: I was like
podcast did.
Sam: no, no, no, no.
Sponsored by, no.
Today we're talking about the emergency medicine practice article by Dr.
Beason and Dr. He.
This was published in January of this year on the emergency department diagnosis
and management of patients with syphilis.
And I think if you have read the article or are going to read the article, the
best summary would be everything you see is syphilis and everyone should just be
drinking penicillin on a daily basis.
T.R. Eckler: I feel especially qualified to celebrate and appreciate
this article because Dr. Chen, he was my chief when I was an intern in
Sam: No way.
That's awesome.
T.R. Eckler: What it's now.
Mount Sinai, St. Luke's and Roosevelt, they've changed all the
names, but it's still an incredible emergency residency program.
And then Dr. Dan Egan was my assistant program director when I was there, so
this is just a homecoming podcast for me.
Sam: Fantastic.
All right.
Well, let's talk about syphilis then.
So, syphilis, the great masquerader as it's called for a good reason because
it has a multitude of presentations and all of them look different and
all of them look like other diseases can, and so it can be exceptionally
hard to make this diagnosis and.
Just because the US has published data from the CDC saying that cases are
going up, especially congenital syphilis cases and cases have dramatically
increased in specific populations.
And before we go on, if you're listening to this podcast and you have like,
I dunno, children in the vehicle or you're blasting it at home and there's
children around, we're gonna talk about.
Syphilis, which is a transmitted disease, and we're gonna talk
about how it's transmitted.
And so now would be a good time to pop in your headphones or to take
the little ears out of the room.
The rest of the podcast will not be appropriate for children.
Having said that,
T.R. Eckler: pictures though.
Great pictures in the article.
No pictures in the podcast.
Sam: no pictures in the podcast.
But I tell you what, this issue is packed with a multitude of pictures and
some of these things you really need to see to understand how easy it would
be to confuse this for something else.
And.
on the epidemiology note, I was going to say that there's been a 42%
increase in cases, especially in the most vulnerable population, and this
is the men who have sex with other men identify as gay or bisexual.
Those with HIV.
Those on HIV pre-exposure prophylaxis or living with a partner with HIV
that's the highest risk population.
And that's where there's been a significant rise.
But there also has been a large rise in congenital syphilis, so that's cases
going underdiagnosed in pregnant women.
And that's a sad note really because that is a disease that we screen
for with adequate, prenatal care.
But if patients do not have access to prenatal care, then this is where one
of those processes could get missed and where you might be able to catch it in
the ED when they present with their rash,
T.R. Eckler: I'll tell you having, trained in New York City where I
saw a lot of HIV patients, I never saw syphilis in my residency, and I
really have never seen it for years.
But since moving to the South, I've seen more and more of this.
In both primary syphilis, tertiary syphilis, neurosyphilis.
And then just in the last month I've gotten a chance to be a part of a case
where one of my partners diagnosed ocular syphilis, which counts as neurosyphilis.
Sam: Hmm.
T.R. Eckler: And then I just the other day diagnosed a patient with PJP pneumonia
from HIV that was progressing to aids.
And I would tell you that as primary care gets harder to access, and as public
health gets more and more deprioritized I think at a lot of levels of government.
I think as emergency physicians and urgent care physicians, we need to basically
look at this as our time as providers to step up and get more aggressive with
our screening, because more of this is gonna start slipping through the cracks
and it's gonna be, an opportunity for us to catch it and save these patients from
a really nasty progression of disease.
Sam: Absolutely.
I could not have said it better myself.
That was a, fantastic public service announcement for our
public health colleagues, really.
But also for anyone working in the emergency department or really even
an urgent care center where you might see some of these present.
The highest risk population now really everyone is at risk.
So we talk about highest risk.
This is based purely on numbers, and this is going to be people who
are younger adults, those who have multiple sex partners or engage in
drug use, especially IV drug use.
Those who are incarcerated, those who are homeless or those
who exchange money for sex.
And then there is the population I just mentioned who's had the
largest increase in the us and that's men who have sex with other men.
And then there is the population who live with HIV and are immunosuppressed.
And so as you add up all of these populations, including those who are
pregnant or who don't have access to good prenatal care or infants
who are born outside of the hospital and did not get infant screening,
now we're just starting encompass pretty much the entire population.
So your, threshold for testing should be exceptionally low for everyone really.
T.R. Eckler: I, I would tell you our protocol in-house right now is
to screen all of our psychiatric patients that come in for both
thyroid dysfunction and syphilis.
And I think at first I'd just never seen syphilis, so I was like,
oh, I'm not sure we really need to be doing this for everybody.
But I've seen enough positives come of that process
Sam: Hmm.
T.R. Eckler: that I'm realizing how much more it's starting to
become a bigger and bigger problem.
Sam: Yeah.
All right.
Well, let's talk about what causes syphilis.
So syphilis is caused by Treponema pallidum.
It's a spirochete, it's a bacterium and it's found only in humans.
We are the reservoir for this bacterium, for this disease.
So we can't blame this on anything else.
It basically lives and thrives off of us, and it has no expressed surface
based proteins, which is if you're into the molecular biology of diseases,
these are the things that allow us to, you know, make antibodies and attack
diseases early, and maybe even make it an ideal vaccine for a disease.
It doesn't display any of those.
And that allows it to slip into the central nervous system pretty
easily, which unfortunately is going to be one of those, phases
we're gonna talk about here soon.
And so it's a nasty little bug.
It's transmitted through contact.
That can be oral, vaginal, anal, or skin to skin from lesions.
And it can be from mother to fetus in utero.
And so that basically covers all gamut of types of transmissions
for pretty much any disease.
Uh, It's not respiratory.
And it can't be transmitted through surfaces.
So as long as you're wearing appropriate PPE and gloves, you are
protected as a healthcare provider.
Interestingly, it has been shown, at least there are some cases of
it being transmitted through blood transfusions and through dialysis.
And so that's just another method that the disease can be passed on.
And unfortunately, previous infection doesn't give you any kind of immunity.
And if anything, becoming reinfected patients are less likely to be
symptomatic, so it just makes it even more challenging if you're
dealing with a repeat infection.
T.R. Eckler: I'm trying to understand how to read these titers is a really important
thing to look at, and it's worth exploring as we talk about this because you're gonna
see more of these patients that have been treated before and have been positive,
and now you need to interpret whether this is a new positive or an old positive.
Sam: Yes.
Yes.
And if there's not a protocol in your department, then hey, pull out this
article, find those clinical pathways and make that your department protocol.
'cause it's already spelled out by the authors very nicely
here as a step-by-step process.
Okay, so syphilis occurs.
Really in, in multiple stages, there's the primary syphilis, which is when they first
get infected, it's somewhere around three to six weeks after the initial infection,
and they have a painless skin lesion.
It's classically described as the chancre, which is supposed to be
initially this papule that then becomes ulcerated and then resolves by itself.
Unfortunately.
It's painless.
And so unless the patient happens to see it, they're not gonna know.
And if it's in an area where they don't usually look because it's sexually
transmitted, then they're gonna be completely unaware this thing is present.
And we as emergency clinicians might have the opportunity to
stumble upon it completely by accident during an examination.
So if you see this thing and it's inconsistent with what you're looking
for, then you just have to have a really low threshold for saying, oh.
You know, maybe we should get you tested.
But that appears somewhere around three to six weeks after initial infection.
And just like any other disease process, there's the classic lesion
and then there's what can also occur.
And if their patient has HIV or a very high spirochete load, they can
get multiple lesions, not just one.
And they can be atypical looking So.
It can be difficult to make the diagnosis, but there is a
good picture in the article.
I encourage you to go take a look at that, figure one.
And that one's actually intraoral, so it's a good picture to go take a peek at.
Secondary syphilis is the rash and it's associated with a prodrome fever,
headache, fatigue, and lymph adenopathy.
And the most common rash that you see is this red, red, brown, kind
of flat and scaly and diffuse, and again, it's classically described
as being on the hands and feet.
So you see a rash on the hands and the feet, you're thinking
like hand, foot, mouth.
You should also think syphilis because this is one of those diseases that is
supposed to classically present this way.
But unfortunately it can also be more diffused so it's not
isolated to the hands and feet.
It can be generalized all over their body.
Sometimes the lesions can be vesicular, sometimes they can be pustular.
And these are considered like the less typical presentations,
but they're possible and they can occur about four to eight weeks.
After the appearance of the chancre, so the chancre was coming three
to six weeks after the infection.
Now four to eight weeks later, we've got secondary syphilis with
the prodrome of those symptoms.
And if it's untreated, it's going to resolve on its own within a few
weeks to a month and then go away.
And now we're in that problem stage where the patient once again has no awareness
of the disease that they're carrying.
And that brings us to tertiary syphilis.
This is the late stage infection, and this can occur as late as 50
years after the initial infection, which is a ridiculous timeframe, but.
Tertiary infection includes all kinds of things.
Cardiac manifestations like aortic aneurysms, aortic valve insufficiency,
coronary stenosis or myocarditis.
Vaso-occlusive complications like strokes can also occur.
You can get gummatous lesions.
These things are like necrotic, large granulomas with immune
cells and bacteria inside them.
They can be internal, like around the liver.
They can be external and be on the skin.
And patients will sometimes present with altered augmentation like depression
which can occur in neurosyphilis, and we'll get to that in one second.
But before we get to that, there is also a latent stage of syphilis.
So in that up to 50 year gap between secondary and tertiary syphilis you
can get this latent syphilis period where you're completely asymptomatic.
And if it's pretty close to the time of your infection, it's considered early.
If we don't know the time of your infection, or it's been maybe
years, it's considered late.
But that's what we define as the latent syphilis stage.
And then come the interesting ones.
Neurosyphilis is one of those.
So neurosyphilis can cause syphilitic meningitis, which
presents like meningitis, does fever, headache, neck pain.
Patients with HIV, especially those with lower CD four counts have
particular predilection to this disease process, but it can affect
anyone who has untreated syphilis.
And it can also present with headaches and cranial nerve deficits.
So if you're examining somebody who's got cranial nerves six, seven, or eight
as a primary deficit and an isolated symptom, you should also think about
syphilis and it can present as what's called meningo vascular syphilis.
Which occurs early and has this kind of stuttering findings
that lead to a stroke, right?
So this is one of those stroke complications.
It can also present with spinal cord disease, which results in lower
extremity pain and ataxia and this kind of foot slapping gait that they get.
And then you can get seizures and general paresis as well.
And unfortunately you make the diagnosis, you do the lumbar puncture,
you get the CSF, you treat them you might clear the infection, but the
neurological symptoms are permanent.
That's not going to get rid of those.
Then there's congenital syphilis.
Again this is passed from mom to child In utero comes with a
12% higher risk of miscarriage, preterm labor, and stillbirths.
If the fetus survives, they can present with low birth weight, with
rashes, with condylomas, with just rhinorrhea and hepatomegaly or anemias.
And then that can progress to neurological symptoms like seizures, cranial nerve
deficits, hearing loss or blindness.
And this is something that is screened for at birth in most hospitals.
This is part of that TORCH testing so that it can be caught early
and treated before it leads to permanent neurological deficits.
And if not, then as a pediatrician or primary care physician, you
might see it present later.
And interestingly, one of the ways that it presents is by notching the teeth
in the child giving them an appearance of something called Hutchinson teeth.
There's a picture of that in the article.
And so it can cause deformities in the nose, in the frontal bones , it can
cause otic and ocular abnormalities.
And so some of these may be picked up very, very late by
primary care pediatricians.
And then the diagnosis is made unfortunately way, way later than we want.
And then, as you mentioned, one of your partners made the
diagnosis of ocular syphilis.
This is again, considered a neurosyphilis variant.
Tell me how we pick this up.
T.R. Eckler: Basically a patient that had come in with this known uveitis that
everyone was having trouble figuring out and just with a careful history and, a
high enough, concern for the potential for this being sexually associated.
He ran the RPR test and managed to catch it, and I thought it was just a
really great piece of diagnostic work, that usually it doesn't come from, your
emergency room visits where you've only got a few minutes with the patients.
I thought it was just a really great case of, detective work and also it was
just really interesting to learn how serious this is because it's treated
like neurosyphilis and you've gotta admit 'em for full on IV penicillin,
which we'll kind of talk about as we move into the treatment phase of this.
Sam: Yeah, and ocular syphilis is you know, if you're talking with
your ophthalmology colleagues, this is gonna be panuveitis.
So not just in one location.
They might have disc edema, they might have retinitis, they might
have an occlusive vasculitis.
So this is kind of the same vascular problem you would get from a
stroke except involving the eye.
And the patients may describe floaters and flashers and even vision loss.
Interestingly, they can get otosyphilis as well, and so this is
syphilis that affects your hearing mechanisms, giving you hearing loss,
both conductive or sensory neural and ringing or tinnitus in your ear.
And ocular syphilis and otosyphilis can be seen with or independent
of classic neurosyphilis.
So this may be their only presentation just to make it
even more difficult to diagnose.
T.R. Eckler: Yep.
And I, just wanna make one case, just as one of the biggest areas they talked
about for being of concern is the increase in newborn diagnosed syphilis.
And I thought that the figures and figure four, the rashes showing like
kind of a non-specific desquamating rash, kind of a pustular rash on a newborn.
Then the more classic macular , copper colored rashes that you can see.
I thought those were helpful because I think if I saw that on a
newborn I, I wouldn't immediately jump to syphilis in my head.
But now I think my pretest concern is significantly higher from that.
Sam: Yeah, yeah.
I really can't stress enough the fantastic figures in this issue.
Like figure six shows the cutaneous and mucosal lesions.
And some of these I could easily see myself glancing
over in physical examination.
Figure seven shows some of the mucosal lesions on the tongue and the lips.
Figure eight shows the skin ulcerations of malignant syphilis.
And these are multiple ulcerated lesions all over the back and
chest in that particular instance.
So I highly recommend you just go take a peek of these and
add them to your armamentarium.
There is a section about differential diagnosis, and really this just
depends on which stage they're in and what it's mimicking.
So, you know, if they're in their primary stage, it's very easy to
just dismiss the rash as primary alopecia, condyloma, psoriasis,
drug eruptions, viral exanthems.
But you just gotta really have that high suspicion, especially in the highest
risk patients that we discussed earlier.
And if you're seeing them in the secondary stage, they've got the rash.
If you're seeing 'em in the tertiary stage then they may present with
that tabes dorsalis that drop foot.
They may have a stroke, they may have multiple sclerosis type symptoms.
They may have neuro deficits or cranial nerve abnormalities.
You're thinking vitamin B12 deficiencies.
And there's lots of other things on the differential that syphilis
mimics and they may have cardiac abnormalities, come in with chest pain.
They may have a new murmur.
You're thinking they've got aortic valve insufficiency or some kind of
coronary stenosis or they present with myocarditis and they don't
have a specific reason to have it.
And, you know, most of those are idiopathic or viral, but you gotta
test them for syphilis to make sure.
So.
There's lots and lots of disease processes on the differential.
Table one has a good one for the skin lesions because if you see the chancre
you gotta think to yourself, okay, is it a painless lesion, you know,
is this person at risk for syphilis.
Should I just go ahead and treat them while we're waiting for testing?
Chancroid, herpes, genital warts initial primary HIV infection, mpox, molluscum.
All of these are on the differential for cutaneous lesions, so just,
be very careful and have a low suspicion and send the testing.
For pre-hospital personnel, there's not a whole lot you're gonna do in
the way of diagnosis for this, but you just gotta make sure you're
wearing your PPE and reduce your chance of exposure because when the
patient is found to have secondary syphilis, that rash is contagious.
Those skin lesions are contagious, so just make sure if they have a
rash, you're wearing your PPE so you don't get yourself exposed.
And then when they're in the ED and we're trying to get a history all
of those risk factors are important.
They're not diagnostic, but they're important and they come into play later
when you're deciding, am I gonna test this person and wait for the results,
or am I just gonna go ahead and treat this person and send the testing and
then somebody else can follow up on it?
So the highest risk features are the ones like men who have sex with other
men, HIV positive patients, those on pre-exposure prophylaxis therapy, those
who trade sex for money and those who are IV drug users, recurrent sexual
transmitted infections, or if you're seeing somebody for a sexually transmitted
infection, you should consider screening them for syphilis as well, because
it can be a concomitant infection.
And if you're seeing somebody who's pregnant and has no prenatal care.
That's another good time to test them as well.
You might be saving two lives in that scenario.
So those are the kinds of things you wanna pull out in the history.
When it comes to examination again, depending on which stage they're in,
you're looking for specific symptoms.
You're looking for the chancre, you're looking for
the rash on the hands and feet.
You're looking for hair loss, especially if it's on the scalp.
If it's tertiary, you're looking for those new onset murmurs or aortic
regurgitation, or in your case, maybe some ocular symptoms that are not
resolved and are kind of been a little bit mysterious and difficult to diagnose.
Hearing loss if they have the otosyphilis.
And then if you're considering things like meningitis or
neurosyphilis, do they have fever?
Do they have a stiff neck?
Do they have headache?
Have you noticed any kind of neurological deficits?
Maybe they're ataxic.
You gotta get 'em up and walk 'em to get that slapping feet gait
and test them for mental status to see, do they have confusion?
Do they have dementia symptoms?
Have they been having seizures?
Is there any history of dementia?
So lots of information you need to extract from the history and physical
before you can make this diagnosis.
But a lot of it will support your suspicion.
T.R. Eckler: The thing that really, I think, pushed me in a couple of cases
that I've seen was just a patient with a horrible rash that had, bad,
tertiary syphilis neurosyphilis that both times the patients were just really
unconcerned about how severe their rash was through their whole body.
you know, there was just such a disconnect between how ill and
sick appearing they looked and how they perceived their health to be.
So I think that that's something to consider if you'd notice kind of a
disconnect between your estimation of the patient's, wellbeing and their appearance.
I think that should also make you stop and think syphilis.
Sam: Mm-hmm.
Mm-hmm.
Okay.
Let's talk about making the diagnosis.
So before we start, just know that every state, that's all 50 states
have rules for mandatory reporting of syphilis to your state or local public
health agency because they'll track these and hopefully track down people
who live with them and partners and do their diligence to try and contain it.
So just know that whatever state you're in, you should have access to that.
But those are mandatory reporting guidelines.
There are multiple types of tests.
And a specific sequence you want to perform them in there are non
treponemal tests, meaning these tests don't detect the bacteria themselves.
They detect antibodies and usually they're antibodies to the
tissue that's being destructive.
It's not an antibody specifically to the bacterium.
That's your VDRL or RPR test, and that's usually the one that's
available to us to order from the ED.
oftentimes it's not going to come back while they're in their ED stay.
Just kind of depends on how long it is or whether or not
they're going to observation.
But it's a test that may result and it's a titer.
So you gotta know what's abnormal and normal.
Usually that's in your reference ranges.
You gotta look back and see if they've ever tested positive before.
And then if it's positive, move on to a more definitive test.
If it's negative, then they are lower risk.
But just know that there are gonna be scenarios where you get false
negatives and false positives.
The authors mentioned that false negative results can be seen early in infection.
So if they're newly infected, they might not have the antibodies yet.
So your VDRL and RPR are gonna be negative.
So if you highly suspect it, just treat them and then you can retest them later.
Or you can get false positives in patients who don't have syphilis if they
were previously treated for syphilis.
And that's why I say you look back and you see what their prior test results were.
And that doesn't make the tests completely useless.
You can follow titers.
Generally it's a fourfold monitoring.
So if their titer has gone down by fourfold, they're considered to
have been treated and disease free.
And if you repeat it and now the titer has gone up by fourfold, then now you're
considered reinfected and you need to undergo antibiotic therapy again.
So that doesn't make the test useless, but just know it's a titer, you're
gonna get a number, like one to eight, one to four, one to two, one to 64.
And so expect to have to do a little bit of math if they've had previous testing.
T.R. Eckler: It's also worth noting that patients coming from other countries may
test positive in some of these tests, but they have been exposed to other treponemal
infections, not necessarily syphilis.
So again, like you said, it's just keep following the testing,
keep, working the patient up.
Try to make sure that they land with the health department or
with their primary care doctor to, keep interpreting these things.
But more and more of this is gonna kind of land in our lap, so it's
good to understand what the date is that you're looking at, and then
what is the next step that you need?
If you need more clarification from the test.
Sam: Yeah.
And then if that initial test is positive, you're gonna move on to a
next level test, which is typically going to be the antibody test.
And if that's positive, that's considered diagnostic, and then
you're into the treatment section.
There are some PCR tests that are available as well, and those can
take the place of some of that , RPR or VDRL initial testing and can
be a little bit more sensitive.
And so if you're at a facility that has those, just check
whatever your in-house protocol is.
But , the antibody test is considered the treponemal test.
So it's specific for the antibody to Treponema pallidum and it comes
after a initial non treponemal test has been performed and is positive.
And again, that's something that's not going to come back during your ED stay,
so someone's gonna have to follow up on that test, call the patient and give
them that result, and then call them back for treatment if it's positive.
There are, interestingly, a couple of point of care tests
that are now FDA approved that are mentioned by the authors.
The Health Check and DPPV are both tests that can be performed at the point of care
and have shown similar sensitivity and specificity to the non treponemal testing.
So that's.
That's a possibility.
And the patient may have had one at an outpatient clinic already.
And then there's dark field microscopy, so this is where you swab the
lesion and then send it to the lab.
The authors did a good job of, asserting that it's difficult to do
so even the person in your lab might get this wrong, might misinterpret
it but it is a test that can be sent and they're looking specifically
for the, spirochetes on a slide.
And so if you have someone who has a primary chancre you can swab with a
saline moistened cotton tip applicator.
You can swab that lesion and send it to the lab and they can slide
it and try and look if that's positive, that is diagnostic.
And then you can begin treatment,
T.R. Eckler (2): I don't think There's anything quite as cool as the term
dark field microscopy in terms of like what's on your resume as the lab tech.
Like what do you do?
I handle the dark field.
T.R. Eckler: come on, that's, that sounds awesome.
Sam: Oh, my job is dark field microscopy.
T.R. Eckler: Like, like, like I run the gas spectometer, like not, not as cool.
Just not as good.
Like that's gotta be the guy that everybody's like, yo,
that guy does dark field.
Don't mess with him.
Sam: Dark field.
That's right.
The proud, the few, the dark field microscopists.
All right.
You can test other body fluids.
So if you're thinking they have syphilitic meningitis, you need a lumbar puncture,
you take that CSF and you test it.
If you're, diagnosing ocular syphilis.
There really isn't a tissue sample here that you're gonna be able to get.
Same with the o kind of treated based on examination and suspicion
and maybe a positive RPR and VDRL.
Alright, let's get into treatment.
So treatment gets a little complicated and I'll say a little
because there is historically one treatment and that's penicillin.
And if you are practicing in an ED or urgent care anywhere in the United States
right now, you know that there continues to be a shortage of that medication.
And so even though the US government and the FDA have approved purchasing
of the drug from other countries like France and Spain, we're still short.
And so even though we used to give this out, like it was water, just
based on suspicion, you may have more stringent criteria for administering
this medication in your ED.
You may have to actually have a positive test.
So just be aware that we've been using penicillin since it was
discovered back in the 1920s.
And in about the 1940s is when it was thought, oh, okay.
Somebody discovered, Hey, we can use this for syphilis.
And it keeps people from bouncing back.
The IM route is superior to the IV route, so you actually do not want to give
this IV unless you absolutely have to.
You're treating like Neurosyphilis for an extended period of time on a daily
basis, and they're getting multiple doses.
But the preferred method is IM.
The efficacy there is way better.
And it's a single dose, 2.4 million units for an adult.
Intramuscularly.
Covers you for syphilis.
It does not treat neurosyphilis right?
And it doesn't treat the neurosyphilis related disorders
like the oto or ocular involvement.
But it will treat primary and secondary.
There are first line agents.
Those are penicillin G or benzathine penicillin, or Bicillin L-A
that comes by multiple names.
That's the one that's in the shortage and that the FDA is still
trying to procure samples from France and Portugal and elsewhere.
So if you have access to it, that's great.
It's 2.4 million units IM.
There is a similar preparation, penicillin g procaine, and other
formulations that are oral are not considered sufficient for treatment.
So you might be in the untenable position of trying to figure out, okay, what do
I have at my disposal to treat this?
And a couple of caveats there.
So there's a great table on page 12 that goes through the
medications and dosages for syphilis.
Know that if they're pregnant, there are no other options.
It's penicillin or penicillin or penicillin.
And if they're penicillin allergic, they have to go through desensitization therapy
and then get the full dose while pregnant.
And I cannot think of anything more terrible than having to do that.
But just know that if they're pregnant, it's that.
If they're not pregnant, there are some second line agents.
Thankfully, there is limited evidence that doxycycline a hundred milligrams
orally twice a day for 14 days or tetracycline may actually work.
And when I say may, like the evidence says that one study showed it was about 82.9%
efficacious versus 97% for penicillin.
So it's pretty close.
It's not a hundred percent, but it's pretty close.
There is also some evidence that Ceftriaxone given daily as an IM injection
is also efficacious, has a cure rate of somewhere between 65 and a hundred percent
depending on which study you look at.
And so the CDC lists it as an alternative to IM penicillin
if there's none available.
So those are your only two other options you get.
IM penicillin, 2.4 million units or doxycycline or maybe
ceftriaxone, as an alternative.
and that's all for primary and secondary and early latent.
If you've got late stage latent syphilis it's, IM or doxycycline.
If you've got tertiary syphilis, it's, again, IM penicillin.
No other choices.
If you've got Neurosyphilis, now we're into the IV therapy extended course.
And.
If they're pregnant, of course you're treating that with just penicillin.
The little ones, if they've got congenital syphilis, again, it's
penicillin, no secondary options.
So really, your, alternative drugs exist for primary and secondary
and maybe early, late in syphilis.
When you are treating patients with syphilis you gotta be aware of the
Jarisch–Herxheimer reaction, which is, you know, especially if they're in secondary
syphilis and they've got a high treponemal load and you give them that penicillin,
all that bacterium dies and they can present with something that looks like
anaphylaxis or acute allergic reaction.
And you just gotta recognize that it is not an allergic
reaction to the penicillin.
uh, Headache, myalgias, and even fever can occur.
You gotta caution the patient that this may occur and this is all of that
bacterium in their body dying and it is not a life-threatening allergic reaction.
T.R. Eckler: I actually have the other version of this where I diagnosed
someone with syphilis because someone gave them penicillin for a dental
infection and they got a rash and flu-like symptoms, and I said.
Boy, this doesn't seem like allergic reaction.
It kind of seems more like, you know something's working on something here.
And I remember the term Jarisch–Herxheimer and I looked it up and said, I'm
just gonna send some tests off, but I just wanna make sure this isn't
some other kind of an infection.
And God bless it.
We caught a syphilis case there from just a, a dental infection and a rash.
Sam: Great news.
You don't have a dental infection.
T.R. Eckler: You're not allergic to penicillin like everybody
Sam: That's right.
T.R. Eckler: other news, you have syphilis and you're
Sam: Even better news, your dentist cured your syphilis.
T.R. Eckler: Well, they, I think they, they did not cure it
'cause the oral penicillin is not enough, but they at least gave us
the opportunity to diagnose it.
Sam: There you go.
There you go.
Well said.
Wow.
T.R. Eckler: free toothpaste to that dentist.
Free toothpaste.
Sam: That's right.
Nine out of 10 dentists recommend penicillin for syphilis.
That's fantastic.
Okay, let's talk about treatment.
When, when we're talking about treatment, obviously if you have a high
suspicion and you have access to the medication treatment is recommended.
Treatment of sexual partners is highly recommended.
So, you know, all sexual partners in the last 90 days
should be screened and treated.
Any sexual partner beyond 90 days should at the very least be tested.
If they're exceptionally high risk in that category we discussed
before they should just be treated.
Period.
And if they have had a sexual encounter within three months of somebody with
primary syphilis within six months of somebody with secondary syphilis, or
within a year of somebody with latent syphilis, they just need to be tested and
then treated depending on what that shows.
So testing at the very least.
And if they're high risk, just go ahead and treat with whatever
you have available to you.
I wanna pause for one second and just say there's an excellent discussion in
the article in the controversy section about the Tuskegee study, we really, we
can't talk about syphilis without talking about the Tuskegee study because it's
kind of a dark moment in the history of medicine and it really brings to light
some of the, issues around informed consent that we have today in studies and
some of the challenges we have today in studies because we've gone back, looked
at this dark moment in our own history.
We admit it was a terrible thing to do.
And if you've never heard of it, the Tuskegee study occurred.
In the United States by the Public Health Service between 1932 and 1972.
So this is really not that long ago.
And although at the time that they started the study, there was some evidence already
about the natural course of syphilis.
The study continued.
It enrolled 600 black men in Macon County, Alabama, really not far
from where I'm sitting right now.
And 412 of them had syphilis and the rest were considered controls,
and despite the existence of a known treatment, penicillin, for the syphilis,
these enrollees were left untreated.
They were given vitamins and aspirin as placebos, and were led to believe that
this treatment was for their infection.
But actually what the authors were doing was just observing the natural
history of syphilis infection.
And then they were subjected to procedures like lumbar punctures under the guise
that this was part of their therapy, when again, all that was being done was samples
were being collected and tested to look at the natural progression of neurosyphilis.
The study was started just prior to penicillin therapy becoming widely
available, but continued long after, into the 1970s long after penicillin
treatment had become widely accepted.
The results of the study were exactly what we expected and what we already
knew before the study started about the morbidity and mortality associated
with syphilis and about how the disease progresses into later stages and
unfortunately, although the Tuskegee study is the most well-known, really
controversial, the most well-known, controversial study of syphilis there was
another one, another group of researchers between 1946 and 1948 that that same group
infected a large population in Guatemala, 5,500 people with syphilis gonorrhea.
And or Chancroid, and again, watched them for the natural history.
They were selected from vulnerable populations, prisoners,
orphanages, mental health centers, health clinics, sex workers.
They were inoculated with diseases in order to evaluate whether penicillin
was effective as a pretreatment to prevent syphilis and to evaluate
whether the patients who were previously treated with penicillin
could get repeat syphilis infections.
That study was actually never formally published, but came to
light when the journals of Dr. John Charles Cutler were published.
And he was a participant in both of those experiments, the
Tuskegee and the Guatemala studies.
So a very, very dark period in medicine, but a very important historical note
about what we know and what we know we're not supposed to be doing in
medicine and about the Hippocratic Oath we take and why informed consent is
such an important thing in medicine.
And about the, just really the tragedy that those 600 men in
Macon County underwent as they were just watched, really dying
from their syphilis infections.
So a very, very important historical point.
T.R. Eckler: Can I make one positive,
Sam: yeah.
T.R. Eckler: note on this,
so I can't agree with you more that it's really important to understand
that especially as we, are entering again, a time of deemphasis on public
health and on the scientific process.
I think this is a really important lesson to make sure everyone remembers as to
the slippery slope of how you start off trying to help people and then eventually
end up in, in a very dark place.
But I think a positive other side of this coin is the book Miracle Cure by William
Rosen about basically like the history of how penicillin came to be a treatment and
how it was, you know, discovered years before it was ever considered that it
could be employed for treating people.
And then the interesting period after that where we were mixing all kinds
of antibiotics together and selling them to the public as like, a miracle
cure that, could fix everything.
And kind of the recommitment multiple times in that process to the scientific
process and trying to go through and see exactly what actually did work to
help people and what did treat disease.
It's a great thing to look at in the history of medicine and to look at just
how incredible it is because that is still the treatment we're using today
for syphilis, and it's still enormously effective and really doing a ton to
save lives that before this we were giving mercury and arsenic and all
kinds of horrible, poisonous things
Sam: Mm-hmm.
T.R. Eckler: I think it's a cool thing when you get frustrated by some of the
challenges in medicine today to look at a process like that and realize that
we're still having an incredible time where we can cure disease when before
you could just kind of watch it and offer some things that might have a
chance of making it a little better.
Sam: Yeah.
Yeah.
Well said.
And there is a section at the very end of the article on
kind of cutting edge therapies.
One of them is whether or not we have alternative treatments
coming down the pipeline.
And there is some published data about oral cefixime, which
I thought was pretty positive.
Uh, Published in studies with men and non-pregnant women.
Showing some pretty decent promises, about a 87% efficacy in treating syphilis.
That's in the, anywhere from the primary, through the early latent
stages which is pretty close really to what you get from doxycycline.
So it is probably an option.
There is limited evidence 'cause the studies are small, but hopefully
that's something that will get studied more and we'll be able
to use that as an option as well.
And then there's a discussion about post-exposure prophylaxis.
So again, limited evidence, but suggesting that a one-time 200 milligram oral dose
of doxycycline, ideally within 24 hours, but up to 72 hours after exposure reduces
the combined risk of gonorrhea, chlamydia, and syphilis by two thirds, which I
thought was pretty amazing, honestly.
T.R. Eckler: So this, immediately entered into something that I would
think about offering to patients because I think that there's not much
downside, and I think that I'm usually basically giving ceftriaxone and then
writing a prescription for the doxy.
But I would now think of changing that to, Hey, here's your ceftriaxone
and here's a dose of doxy here.
With the idea being, I'm not sure you'll ever pick up this prescription, but at
least I know that if I gave you one shot and a pill, I'm really reducing your
chance of developing gonorrhea, syphilis, or chlamydia with just one shot, one pill.
Sam: Yeah.
T.R. Eckler: and just again, let's put something in the
Hall of Fame for study titling.
In the era of so many complicated, silly titles for studies, doxy Pep
is beautiful, clear, and explains exactly what the study looked at and
exactly how much of a great idea it is.
So first of all, just round of applause for those authors and that study.
And I would like to personally offer to fund their follow-up study that's
gonna make this standard of care.
'cause it sounds like they're really close to getting there.
Sam: That's right.
That's right.
It's gonna be called the Eckler STI study or the Eckler protocol.
It's gonna be just one tablet of doxy.
T.R. Eckler: Uh, No.
The Eckler protocol remains Suboxone for patients that get Narcan and
want to immediately be discharged.
And I say, Hey if you wanna go right now, you can, but you've
gotta take this suboxone.
And I really wouldn't recommend that.
Sam: all right, ladies and gentlemen, well that brings us to the end.
Things to remember, five things that will change your practice.
Syphilis is very prevalent and unfortunately on the rise, especially
in those high risk populations.
So keep that in the forefront of your mind.
Patients on pre-exposure prophylaxis are at the highest
risk for syphilis infection.
There is a national shortage of IM benzathine, penicillin G. So if your
hospital doesn't already have a protocol for it, maybe consider doxycycline
as a possible second line agent.
Remember the chancre three to six weeks after infection and then secondary
syphilis four to eight weeks later.
And it's often missed in those high risk populations.
And go and claim your CME.
So if you are a subscriber, know that each one of these issues comes with
four hours of CME for the amount of time that you spend reading, digesting,
and learning about the topic and reviewing those clinical pathways.
So two clinical pathways in the back of this article are great for your
hospital and for your personal practice.
And the link to the CME test will be in the show notes.
So after listening to this episode, you can go and take
that test and get your credit.
T.R. Eckler: could not more strongly recommend how easy it is to get
a lot of CME from these articles.
I think it's the best value in terms of time put in for information that
you actually learn and how fast you get the credit for the CME that you earn..
Sam: There you go, ladies and gentlemen, from the mouth of Dr. Eckler himself.
And that brings us to the end January, 2026, emergency Medicine Practice
article from Dr. Beason and Dr. He, emergency department diagnosis and
management of patients with syphilis.
And until next time, everyone, be careful wear your PPE and be safe.
T.R. Eckler (2): Penicillin Shots for Everybody.
Sam: Just put it in your drinks
T.R. Eckler: Everybody shots all the time.
Sam: all the time.
All right.
Bye-bye everyone.
Sam : And that's a wrap for this month's episode.
I hope you found it educational and informative.
Don't forget to go to ebmedicine.net to read the article and claim your CME.
And of course, check out all three of the journals and the multitude of
resources available to you, both for emergency medicine, pediatric emergency
medicine, and evidence based urgent care.
Until next time, everyone be safe.