A complex case of a woman presenting with neurological and sensory symptoms, initially misdiagnosed, ultimately reveals a widespread syphilis outbreak linked to a common partner, highlighting evolving strains and the challenges in diagnosis and public health response.
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PC is a 43 year old woman, presenting to the emergency room with headache, bilateral hearing
loss. Bi from Latin meaning 2 and lateral meaning sides. And she had diplopia. Diplo
from Greek meaning double, and opia referring to a visual disorder. She had double vision, in both
eyes. 2 months ago, something was wrong. She had a unilateral headache. Uni meaning one. It was just
on her left side. But, it was a pain that she had experienced before, she thought. 15 years earlier,
when she was 28, she had an episode of shingles. This is a time when chicken pox is reactivated.
PC is 43 right now. This is happening in year 2022. Meaning she was born in the late 1970s,
a time when 99% of children got chicken pox. Varicella zoster virus causes chickenpox,
which later in life can reactivate to Shingles, also known as Herpes Zoster. And it gets into the
nerves causing very painful symptoms. One of which is a particular feeling headache. At the urgent
care, given this history, and her symptoms at that time, they gave her a 1 week course of antiviral
medicine. And the headache went away. So they tried that medicine again for this presumed SECOND
shingles episode, 15 years later. And it resolved the headache at the time. But something else was
wrong. One month after the headache, which is one month before she’s presenting to the emergency
room now, PC started having tinnitus, a ringing in her right ear. She just woke up one morning
with the horrible sound blasting on that one side. But then her left ear started ringing too.
And both her eyes became bloodshot red. At the Otolaryngology, Ears Nose Throat doctor’s office,
PC was found to have something going on, but nothing was conclusive. Her auricles and her
external auditory canals were normal. Hearing tests confirmed she had hearing loss. But reasons
why were NOT found. An MRI of her head showed nothing wrong. PC was diagnosed with Sudden
Idiopathic Hearing Loss. Idiopathic meaning of an unknown cause. She was given a 12 day course
of steroids, because many times, this could be inflammation related. And things seemed to be fine
at first. But 4 weeks later, it was only getting worse. The ears help maintain balance. They do
this through fluid-filled semicircular canals that contain sensory cells. This is called the
vestibular system. It relays signals to the brain. One of the first things the doctor noticed, was
that PC’s balance was totally off. And a repeat hearing test found that her hearing got much worse
over the last few weeks. Given that balance is ear related, and that her hearing has gotten worse,
then it means something very terrible is happening. It could be wrong with her nerves. It
could be something wrong with her brain. She was given an urgent referral to a rheumatology clinic,
one who specializes in autoimmune diseases. And they set the schedule to see her in just 3 days.
But she wasn’t going to make it to 3 days. Hey, have you learned something from this video so far?
If you have, and you aren’t subscribed yet, I’d really appreciate it if you did subscribe,
and come back to see the video I publish next month too. I’ve made, on average, 1 video a month,
every month, since 2017. I do these videos for fun, and they are to teach medicine by showing
cases, and their associated stories. Your time is one of the most valuable things you have,
so I want to make sure that it’s worth your time to watch, everytime. And I always enjoy making
these. Thanks so much. Appreciate you. PC had polyarthalgia. Poly meaning many,
and arthr referring to joint. -algia meaning pain. Her entire body hurt. She started seeing spots in
her field of view. Her head was pounding so hard, she wasn’t going to make it to the rheumatology
visit. She drives herself to the emergency room where we are now. At examination, PC physically
looked fine. A blood test finds she has some kind of inflammation happening. Every other
everyday vital sign was fine. Her blood pressure, heart rate, breathing, all normal. No fever.
Looking at her eyes, doctors found inflammation there. At this hospital, they did the tests again
and confirmed: PC did have hearing loss. One ear was worse than the other. And she couldn’t
balance herself. But it was just these four problems. Given her headache, polyarthralgia,
asymmetric sensorineural hearing loss with vestibular hypofunction, and ocular inflammation,
doctors have some clues as to what’s happening. They write a list of problems that can cause all
of these together, and they need to rule out each one to figure out exactly what’s happening. PC’s
problem started 8 weeks ago with a headache that may have been shingles. 4 weeks if you only count
the hearing loss. This pace is important. If these problems came up in 8 seconds instead of 8 weeks,
then you would think that the problem is vascular. Blood vessel. So, with a headache,
you’d think stroke. If it was 8 years, you would think of cancer. That a tumor has grown somewhere
in her body and has finally manifested its symptoms in a way perceivable, obvious and rapidly
degrading her quality of life. But despite her current problems coming up in just weeks, she did
have a SUSPECTED shingles reactivation 15 years ago. What if that wasn’t Shingles? Leukemia can
create blood cells that infiltrate nerve tissue causing sudden hearing loss. Tiny little tumors
that have spread throughout the body can also get in and do the same thing. But there’s a very easy
way to find out if this is happening. Tumors would be in the brain. That means we can see that on the
MRI. And when doctors did a brain MRI, it looked normal, so she doesn’t have cancer. But if we know
her problem is inflammation, what else could this be? It could be autoimmune. Auto meaning self.
But which disease affects the eyes and the ears simultaneously, like this? Lupus actually can do
this. But it typically affects eye blood vessels, when it does. And she doesn’t have that. She also
doesn’t have other symptoms of Lupus. There’s a disease where the immune system inflames the spine
completely disabling a person known as ankylosing spondylitis. In the immune overreaction,
this can cause permanent hearing loss, but when it affects the eye, it typically only affects one at
a time. And she doesn’t have anything wrong with her spine. Every single autoimmune problem that PC
could have, would exhibit hearing and vision loss in ways different than what she has. And she also
doesn’t have any of the disease defining problems of any of these, except for one, so this is marked
as a maybe. The only way it could be this is if it isn’t anything else. Which brings doctors to
the final inflammation category. Infection. Lyme disease. It’s caused by a bacteria named Borrelia
burgdorferi that comes from a tick bite. PC is in Michigan. Michigan has ticks. Lyme Disease causes
polyarthralgia, vision loss, hearing loss and vertigo. Borrelia is spiral shaped bacteria called
a spirochete. Doctors sent PC’s blood samples to test for this. But a different spirochete,
that also causes all her symptoms but forms an entirely different disease is Treponema pallidum,
the bacteria that causes syphilis. Because PC is having neurological signs and symptoms,
doctors stick a needle into her back to draw some of the fluid that cushions the spine and the brain
called cerebrospinal fluid CSF. If her problem is syphilis, then it means that the bacteria
has gotten in to her brain. And when the tests returned, they found out, PC has syphilis. But,
something was wrong. When doctors found syphilis, they reported it to the Michigan
Disease Surveillance System. And when the Michigan Department of Health and Human Services got the
report, they immediately opened an investigation, because there was much more to this case. 5 weeks
earlier, a 50-year-old woman presented to the emergency room with blurred vision. She was in
a panic because she was scared that she was going blind. There were multiple sores between her legs.
Her primary care doctor believed this to be a herpes simplex virus reactivation. But in the
hospital, they found out. That wasn’t herpes, she had syphilis. When they asked her about intimate
partners, she gave the name of a man that she had met on the internet 2 months earlier. And she
didn’t have any close contact with anyone else for more than 12 months prior. 2 weeks later, in the
same emergency room. A third person, a 60-year-old woman, presented to the emergency room with
hearing loss, blurry vision and double vision. But she had trouble moving her eyes. Her face was
drooping. They thought she was having a stroke, but physical exam found… lesions between her legs.
And when they tested further, they found out this woman also had syphilis. When they asked her about
intimate partners, she gave the name of a man she met on the internet 2 months earlier. And she also
didn’t have any close contact with anyone else for years prior. The reason why Michigan Department of
Health and Human Services opened an investigation, is because the name of the man given by these 3
women, was the same. All 3 women had met him with close contact, in just the timespan of a couple
of weeks. Public health officials called this man. He picked up. But he didn’t have much to say. They
scheduled a visit for him to come in and see one of their public health doctors. And he agreed to a
set time and day. But he didn’t show up. A couple weeks pass. At an emergency room, in another
southwest Michigan county, a 45 year old woman presents to the emergency room with blurred vision
and a rash on her hands. The inflammation in her eye looked very particular. When they tested her,
they found syphilis. She had had close contact with 3 people in the last 6 months. 2 of the
men tested negative for syphilis. And when she gave the name of the most recent person,
it was the same name as given by PC and the 2 other women. And it still wasn’t finished. At yet
another emergency room in a neighboring county, still in Michigan. A 51 year old woman presented
with visual floaters, seeing flashing lights, and worsening vision. These came 3 months earlier when
she had cataract surgery. So they thought that that was responsible. But not even a few weeks
later, when this woman came in with headache, confusion, and stiff neck, they found out that
she had syphilis. And when they asked her about recent intimate contact, she listed a few names,
one of which, was the same name given by PC, and the 3 other women. All of these cases tracing back
to the same person. Syphilis, as we know it today, was first documented clinically in the
late 1400s. But, humans didn’t know that bacteria caused it until 1905. And 92 years after that,
Treponema pallidum’s entire genome was sequenced. So we happen to know a lot about this particular
bacteria. Which means when health officials finally got to meet the common intimate partner
of these 5 women, they noticed something weird. A local public health physician reviewed this man’s
medical records around the time PC’s case was reported to the state. They found out, he had gone
to the same emergency room as one of the other women, 2 months before he met PC. The medical
record logged that he had ulcerative lesions on not only the part between his legs, but he
also had a rectal lesion too. He had told doctors here, that he had had intimate contact with a 60
year old woman just a day earlier. This would turn out to be the same 60 year old woman who
presented to the emergency room 3 weeks before PC. When doctors asked further, he stated that he had
multiple female partners in the last 12 months. And all of them were women. Typically, early
syphilis for men presents as 1 lesion. It’s called a chancre. And that chancre doesn’t usually show
up the immediately the day after. What can show up as multiple lesions, much quicker, is herpes. And
so this man was tested for herpes. But it was negative. Sometimes the test isn’t right. And
he was discharged with medicines for herpes. No syphilis was testing done, therefore the Michigan
Disease Surveillance System didn’t get the report. And it was from here, where he continued to have
intimate contact with local women in neighboring counties, all along the southwest Michigan region.
But this wasn’t the weird thing that public health officials noticed. All 5 women had blurred vision,
and thus, ocular syphilis. And this happened just weeks after their initial infection.
Syphilis that has systemic symptoms like this, this quickly, should be rare. If it does happen,
it’s most recorded with HIV co-infection, and with male to male contact. People who misuse substances
by injection are also at risk of getting more severe syphilitic disease. But none of these
5 women fit any of this criteria. All of this, stemming from a single common intimate partner,
suggests that an unidentified strain of Treponema pallidum was transmitted here.
Data typically hasn’t logged majority women to experience this kind of disease. And this is
where some connections need to be made. In 2015, Seattle. 4 men were reported by local hospitals to
have come in with vision loss. They were diagnosed with uveitis. Itis meaning inflammation of the
uvea, the middle layer of the eye’s outer wall. Further testing found all 4 had syphilis. They
were men who had intimate contact with men, and 2 of them, knew each other, they were partners.
3 of these patients recovered some eyesight after syphilis treatment, but one was permanently blind.
2 months later, in San Francisco, 8 patients with ocular syphilis were reported to the CDC. 1 was a
woman, 7 were men of which 6 had intimate contact with other men, and only the straight man did not
have HIV. 7 patients recovered some vision after syphilis treatment and one was permanently blind
in one eye. In 2015, syphilis cases in the United States had been rising for 15 years. It would go
higher, too. Before 2015, CDC didn’t have a good way to record ocular syphilis. In fact,
PC’s situation where her hearing loss was diagnosed as Idiopathic. That there was no
known reason for the hearing loss. Well, there was an ocular version of that that was happening
to syphilis patients at the time. An eye doctor would just treat the uveitis without finding the
patient’s underlying syphilis, or, the patient, just under the notion that they might have an eye
infection, could have just taken treatment that did nothing for the syphilis. And then gone on to
have intimate contact with more people, passing on the Treponema before becoming permanently blind.
So in 2016 following these reports, CDC issued a clinical advisory and an easier way to report
ocular syphilis. And this is where we will start hypothesizing. Do you remember that we sequenced
Treponema pallidum’s genome in 1998? Well, since then, we have a decent idea of what strains are
around in different regions in the United States. In 2016, 63 patients with syphilis in Seattle gave
samples, where Treponema genome was sequenced. They wanted to see if ocular symptoms were being
caused by a specific strain. 18 of them had ocular syphilis. And from them, at least 5 distinct
strains of Treponema were identified, of which, one unusual strain was detected. Different from
the other ones with and without ocular syphilis. On its own, this study didn’t find clear evidence
that this increased incidence of ocular syphilis was absolutely, 100% because of an unknown strain.
But newer evidence since then, suggests that the bacteria is changing in a way that we’ve
never seen before. In 2023, a 32 year old man in Seattle came into the emergency room with fever
and purulent urethral discharge. Purulent meaning that there was pus. He told the admitting nurse
that he had an intense pain between his legs. And all of this came a few days after intimately
interacting with a woman, different from the woman who he lived with and normally interacted
with. And he said that that woman he lived with was newly diagnosed with HIV 4 weeks earlier.
This particular man was newly diagnosed, at this emergency room visit, with acute HIV. They found
a single chancre between his legs, and unlike the 5 women from Michigan, he was tested for syphilis
right then and there. And it came out positive. He was given antibiotics in the emergency room,
and given additional antibiotics to take at home. These would clear out the Treponema and
prevent syphilis from progressing further. And he was scheduled for an appointment to
start HIV treatment. But he never showed up for that appointment. Over the next 15 months, this
man would be in and out of urgent care and the emergency room. He’d have severe abdominal pain,
blurred vision, and a shooting pain up his leg. But every time, just before they’d treat him,
he would leave. 18 months after his initial diagnosis, the symptoms were so severe that
this man presented to the emergency room. By this point, he had lost 40 pounds, lost most of
his hair, and he had become blind in his left eye. When doctors sent a camera down his throat to look
in his stomach, they found multiple ulcers. They took samples from these to test, and they found
Treponema pallidum. Doctors sent another camera through his other end and found inflammation. And
they took even more samples. And this is where further evidence that Treponema is changing,
appears. When the Treponema genome from this man’s ulcers were sequenced, doctors found there were
2 distinct strains present. This man had told doctors that he only ever had intimate contact
with women. But he hadn’t for several months at this point because he had become so sick.
Meaning, at the time of infection, he may have been infected more than once,
simultaneously. But also found, was that both strains’ DNA featured mutations not yet observed,
meaning that the bacteria may have undergone intrahost evolution. This might have been from
the fact that he discontinued treatment shortly after his initial diagnosis 18 months earlier
and possibly with his HIV coinfection. But all of this led to the most unique finding. Some specific
genes were discovered that were a combination of both strains together. You can’t get these
specific genes without putting these two strains together. Meaning that both bacterial strains had
gathered together, and were creating a brand new strain of syphilis through genetic recombination.
Given that this man had extreme ocular symptoms to the point of becoming blind in one eye, and
that this is happening about 8 years after the CDC issued the clinical advisory on ocular syphilis,
this is another signal for us to consider, that syphilis is changing in a way that we’ve never
seen before. And this brings us back to PC’s case. When she was found to have ocular and
neurosyphilis, she was given intravenous penicillin. When syphilis is found early,
and there aren’t that many Treponema bacteria floating around, it’s usually one dose,
intramuscularly. When syphilis is in the brain, and the nerves, like in PC’s case, the
intramuscular dose can’t get into the brain. Cant get into the nerves. But Intravenous Penicillin
can get in, so it was given every 4 hours for 2 weeks. There’s several things that are true,
that may or may not be connected here. First, syphilis cases in the US have been going up since
year 2000. Second, HIV co-infection makes syphilis disease worse because of immune deficiency. Third,
the prevalence of ocular syphilis cases appears to be increasing. This may have been happening before
the CDC advisory in 2016, however, the increase could also be attributed to the fact that we are
paying more attention to ocular syphilis. Fourth, Treponema pallidum is changing through genetic
recombination. We have documentation going back decades that this particular bacteria changes
slowly. But we’ve now been able to directly observe that different strains can and will
recombine genetically to create new strains. It’s not to say that this has never happened before,
it’s just that we now have evidence of seeing it first-hand. These 4 things are not an exhaustive
list, there’s probably a lot more. But if we just look at these 4, a few questions come up.
If the cases have been increasing, and there’s a situation whereby the bacteria can cause a
different-looking illness in humans, and given that the bacteria can and has changed in ways we
haven’t seen before, is it possible that certain new strains are causing more cases of, and more
severe, ocular syphilis? Will these changes in the bacteria create a different syphilis with
different signs and symptoms? And maybe the worst question that we could think of right now: from
these changes, can an antibiotic-resistant strain of Treponema emerge? We saw it happen in the early
2000s. Another antibiotic called azithromycin was able to treat syphilis. This was for the patients
who were allergic to penicillin. But since around 2002, we can’t use it anymore, because the
bacteria is completely resistant to it now. But that recombination paper from Seattle says that
that particular recombined strain didnt feature penicillin resistance. And the question that we
might not ever know, because doctors weren’t able to take samples from PC or the 4 other women,
or from the 1 common partner they interacted with, is did they have an unusual, undocumented
bacterial strain passed among them? One that caused their ocular syphilis of this severity,
in such a short amount of time? No matter what, we have this case now to refer to going forward.
Syphilis isn’t going anywhere anytime soon. Public health campaigns have been raising awareness about
it. Which by the way, please see a medical professional if you believe you may have been
infected. And don’t wait. And don’t pass it on to others. And with research and application of
past experience, we should be able to soon answer some of the questions about Treponema pallidum,
and the disease. With the right treatment finally, after the right diagnosis, PC was
able to make A recovery. The other women and the common partner did receive some treatment. And
presumably they did recover some. Thanks so much for watching. Take care of yourself. And be well.
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