Ocular Syphilis: Keep an Eye Out for Syphilis

Hi, I’m Dr. Sharon Adler from the
California Prevention Training Center and I’m going to be talking to you about
ocular syphilis and emphasizing why ocular syphilis is so important for all
providers to be aware of. If you’re a primary care provider working in an STD clinic or if
you’re an ophthalmologist, everyone should be keeping an eye out for syphilis. First I want to start by sharing some
data from the California Department of Public Health. This is data from the
years 1996 to 2014 looking at our early cases of syphilis, and as you can see
here, our cases among men have been on the rise since about the year 2000, and
we have data that demonstrates that most of these men are men who have sex with
men, and so that is where the vast majority of our epidemic is within
California. Now this data is consistent with our national data, so this slide
here from the CDC looks at national data from 33 areas nationally for the
years 2007 to 2013, looking at primary and secondary syphilis cases. And again here
highlighted in red we can see that the vast majority of cases are among men who
have sex with men, so that is where we’re seeing syphilis nationally. Very
importantly we also have information in terms of syphilis and HIV, and we have
data nationally that demonstrates that a good proportion, anywhere between fifty
to seventy percent of our syphilis cases for primary and secondary are
co-infected with HIV. And why this is so important is is the natural history of
syphilis infection in someone who’s got HIV disease is going to be a little bit
different than the natural history in someone who doesn’t have HIV disease, and
that person may be more likely to have serious sequelae such as ocular
syphilis or neurosyphilis. So let’s review now the natural history
of syphilis. This slide shows you the stages of
syphilis. Syphilis untreated will pass from primary to secondary then to a
period of latency and then a small proportion of people, about thirty
percent, will go on and have tertiary complications. So this demonstrates that syphilis is a disease that has periods of active
disease manifested by clinical manifestations primary, secondary and
tertiary, and also a disease that has periods of latent disease, and in latency
the only way to make a diagnosis of syphilis would be by doing a serologic
blood test. But what I really want to highlight is down here in the yellow on
the slide, is that ocular syphilis and neurosyphilis can occur at any stage of
syphilis. And CDC has been following cases of ocular syphilis and these are
being reported in many patients who have primary infection and secondary
infection. So early on in their syphilis course of disease they’re being
diagnosed with ocular manifestations. And it may be that the ocular manifestations
are the presenting manifestation of their syphilis disease. So back in April
of 2015 the CDC came out with a clinical advisory because they were
seeing more cases of ocular syphilis and there were two cities, two large
cities in the United States, Seattle and San Francisco, which suddenly had 12
cases of ocular syphilis which is something that many providers had not
seen for awhile. And so CDC has been following this and what they found in
the past two years from 20 states, they have seen 200 cases of ocular syphilis.
The vast majority of these have been among HIV-infected men who have sex with
men. A few have been among heterosexual men and women who are HIV negative or
HIV positive, but very importantly, many of these patients have been left
with serious sequelae, including blindness in a few of them. And there have
also been diagnostic delays because as a patient who’s being diagnosed with an
STD that patient may not be aware to talk to their provider about ocular
manifestations and so it’s upon us as clinical providers to make the
connection and be aware that syphilis can manifest with ocular symptoms. The other thing that came out in this
clinical advisory was that at this point it’s really not known if there is a
particular strain of treponema pallidum, so treponema pallidum is the bacteria
that causes syphilis, is there a strain of treponema pallidum that is ocular tropic.
That is not known, but there is precedent for this. There are strains of treponema
pallidum that are neurotropic and we know this and so the CDC is trying to
investigate to see if the reason that we’re seeing more cases of ocular
syphilis, is it because we’re just seeing lots of
syphilis and so we’re seeing more ocular syphilis or is there a specific strain
that likes to go to…that manifests with ocular disease. So let’s
talk about ocular syphilis and what the symptoms are in patients, and they are a
whole host of symptoms. So patients may present, as in this picture, with
redness and irritation, they may present with eye pain, they may present with
floaters, flashing lights or changes in their vision and actual blindness may be
a presenting manifestation of ocular syphilis. So a clinical provider needs to query
their patient about these ocular symptoms because the patient may not
reveal those if those are not asked of them in terms of their medical history.
In terms of ophthalmologic manifestations syphilis has always been called the great
masquerader, it can mimic many other conditions, and in terms of its
ophthamologic manifestations there is not one specific manifestation that is
pathognomonic for ocular syphilis, there’s a whole host of them. And in the
200 cases that the CDC recently reported, many of these cases presented with ocular
manifestations as uveitis, bilateral uveitis, posterior uveitis, anterior
uveitis and pan uveitis, but there’s a whole host of other possible
manifestations ranging from conjunctivitis, scleritis, episcleritis,
keratitis, chorioretinitis to vasculitis. And so an ophthalmologist needs to be
aware that syphilis is a possible etiology for all these manifestations.
Now I want to move on and talk about a case, and this case really demonstrates
some important points relating to ocular syphilis. And so the case patient
is a male who’s got male partners and he presents, he’s 31 years of age, and he
presents to his provider because he’s got a new rash. This rash is symmetric,
it’s on his trunk, it’s a macular configuration, and he also has a rash on his palms. And I know
in my medical school training I learned that if you see a rash on the palms you
got to be thinking about syphilis, and so this provider is definitely thinking
about syphilis. In addition the patient has other risks for syphilis: he’s a male
who’s got male partners and he has methamphetamine use, which has been linked to syphilis
as well. Interesting this patient also has some visual complaints, he complains of
one month of blurry vision and he has general malaise, he just does not feel
well at all. So this provider is thinking about
syphilis, he sends off an RPR, which turns out to be negative. He also sends off testing for HIV and it
turns out this is acute HIV, this patient has a rapid HIV test that’s positive and
he’s referred to an ophthalmologist and the opthamologist makes the diagnosis of
retinitis. But what’s going on here, what might actually bring this case together,
what might explain this patient’s rash and ocular manifestations. Turns out what
explains all of this is that it actually is syphilis and that the RPR test was
a false negative RPR. So all providers need to be aware of something called the
prozone. It’s a false negative, it can occur and it’s somewhat more likely to
occur in secondary syphilis as well as an HIV-infected patients. And in this
case when the provider repeated the RPR, or asked the lab to dilute the serum,
the repeat RPR was actually very reactive, 1:1024, with the treponema
specific test that was positive as well. So we can link the rash to the
ocular symptoms and so the retinitis is a manifestation of that patient’s ocular
syphilis and the rash is secondary syphilis. In addition what’s recommended
in any patient who is diagnosed with ocular syphilis is that they get a lumbar
puncture to make sure that they don’t have neurosyphilis as well. And in this
case this patient does have neurosyphilis, his CSF is positive with a
VDRL of 1:16 and he has pleocytosis, so he’s got elevated white blood cells.
So he’s got ocular syphilis, neurosyphilis and secondary syphilis. So now i want to just briefly talk about
the prozone phenomenon. As I said it’s a rare phenomenon but all providers need
to be aware of it, particularly because it may occur somewhat more commonly in
HIV-infected patients and neurosyphilis. So it’s a false negative RPR. This
graphic demonstrates that what you’re looking for in the RPR test is the
complexes that are forming. So it’s an antigen-antibody complex that forms and
that causes clumping of the chromogen. But you can imagine if there’s too much
antibody around, that patient is producing so much antibody that can overwhelm the
antibody antigen reaction, that is what took place in our case patient. So it’s a
false negative but you can ask the laboratorian to dilute the serum and
look for the prozone. As I mentioned this occurs more commonly in HIV-positive and
neurosyphilis, so providers need to be aware of the prozone when they’re thinking about
ocular syphilis. So some other teaching points on
ocular syphilis. Be aware of it and recognize that if you delay diagnosis
you may, this may lead to more serious sequelae in your patient, has led to
blindness in some patients in the cases in Seattle. So patients who are diagnosed
with syphilis, they need to be queried about any visual complaints, you need to ask
them are they having any changes in their vision, are they seeing any floaters, any
flashing lights. If they responded that they’re having visual complaints, they
need to have an immediate ophthalmologic evaluation. All patients with syphilis
and also need a neurologic exam, and that neurologic exam should include
evaluation of their cranial nerves. Similarly, ophthalmologists who are
diagnosing patients with a variety of ophthalmologic manifestations need to
consider syphilis as a possible etiology, particularly if you’ve got a patient
who’s HIV-positive, particularly if you have a patient who’s a male who’s got
male partners. But then that means that the ophthalmologist needs to get a little
history and ask about risk factors for syphilis in their patients, if they have
possible manifestations that could be consistent with syphilis. When they’re
ordering syphilis serologies they need to order both a treponemal and an
nontreponemal test, and that’s because you can have this false negative nontreponemal test called the prozone. So how should patients with syphilis be
managed? All patients with syphilis and ocular complaints, or patients who are
diagnosed with ocular syphilis need to have a lumbar puncture. It’s important that providers realize
that a negative lumbar puncture does not rule out ocular syphilis, you can have a
diagnosis of ocular syphilis and have a completely normal CSF. No matter what, if
you’ve got ocular syphilis you need to be treated with a regimen that covers
neurosyphilis, it’s a 10 to 14 day treatment, IV therapy. All patients who
have syphilis and who have ocular syphilis need to have an HIV test if their HIV status is not known.
And then all patients with syphilis and particularly with ocular syphilis and
neurosyphilis, your local health department wants to be alerted about
these patients and you should report them to local health department within 1
working day. So here’s the regimen for neurosyphilis and for ocular syphilis.
So patients with ocular syphilis get treated with 10 to 14 days of Aqueous
Crystalline Penicillin G at 18 to 24 million units IV daily which is usually
administered as 3 to 4 million units IV q 4 hours for 10 to 14 days. Also at the
completion of this IV therapy it is given a consider recommendation in the
treatment guidelines that these patients get Benzathine Penicillin G at 2.4
million units IM once per week for up to three weeks, and that’s so that the
treatment they receive is a of comparable duration as if they were
treated for late latent syphilis. So finally I want to thank you for your
time and your interest in ocular syphilis and let you know that there are a
host of syphilis resources available to you, whether it be from the CDC, the
California Prevention Training Center, the California Department Public Health
or the National Network of STD HIV Prevention Training Centers. Thank you so much.

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