 Okay, just kind of taking you home here. So many of you know that Lynn just took her board examination and sometimes they ask these really crazy questions like on your board examinations, like what's the box next door and then, so what do Casanova, Idi Amin and Beethoven and Frederick Nietzsche and at least in my clinic, the church lady have in common. So they're all at risk for syphilis and each one of these people had syphilis. So I want to talk to you a little bit about syphilis, it's a very prevalent disease, 18 million cases in 2002 in the World Health Organization and 5.6 prevalent, rather incident cases, but 90% of these are in the developing world and the United States, since they've been keeping records of this in the 40s, there was a very high percentage of cases and which has slowly decreased, decreased, decreased to a with a little blip in the 90s around the HIV AIDS epidemic and then an all-time low in 2000 only to see this resurgence with both an increase, 17 or 18% increase in primary and secondary cases and also in congenital cases since 2000, the year 2000. There have been discrete epidemics of syphilis in the Pacific Northwest and in San Francisco. There is no formal reporting system in the United States, however there is in the United Kingdom and it's interesting, it's not very many cases of syphilitic UVitis that are reported as compared to the number of cases of systemic syphilis and calling the literature in the United States, it represents about 1 to 5% of UVA cases that we see in a tertiary care setting. The thing is that there is a really, HIV and syphilis travel together, so there's a very high rate of co-infection of these two organisms. So if you have patients that are HIV positive, there's a 20% chance that you may have ocular involvement and then conversely, syphilis can be predictive of HIV co-infection, so always test for both when you suspect either one in a patient. Acquired syphilis is divided into three stages, and the primary lesion is the shanker, which occurs two to six weeks after abrasion, the mucous membrane, followed by the secondary stage of syphilis, six to eight weeks later following hematoges spread of the organisms throughout the body lymph nodes and into the central nervous system. And then this is followed by a variable degree of tertiary syphilis, either early, late or latent. You have to know that UVitis can occur in any stage of this disease. And it is called the great masquerader because it can produce pretty much anything and affect any area of the eye. But about 50% of the time, it presents as a posterior UVitis. So that's what we're talking about today, and there are certain clinical presentations that are virtually pathogenomic of syphilis. The first is an acute syphilidic posterior placoid cordyretinitis. It's a mouthful. And this presents as a uniform circular oval outer coroidal lesion. And the typical patient is male HIV positive in about a third of the cases. And this is representative example. One can see this circular placoid lesion at the level of the RPE and coroid. And on fluorescent angiography, it shows this kind of leopard spotting in the early stage of the angiogram with blocked fluorescence and then blocked fluorescence at the leading edge of this lesion, which stains and leaks a little bit later in the later stages of the angiogram. The same patient underwent ICG angiography and ICG angiography shows, although not specific, can be highly suggestive of this disease with a uniform hypo-thoresis in the early and late phases of the angiogram as seen here. And this can actually be helpful in certain cases that are very subtle that present in this placoid lesion as I'll show you in a minute. The OCT of this is also quite helpful and it shows discontinuity of the outer segment ellipsoid with irregular nodular hyperreflectivity at the level of the RPE and sometimes sub-retinal fluid and external limiting membrane disruption. The other distinctive presentation is panneabiasis with superficial pre-retinal exudates. So these are not in the retina, they are just pre-retinal, they're small creamy white lesions that seem to be migratory and may actually be frequently over vessels and may be associated with some syphilitic retinitis which is typically mild opacification of the retina and heals without disruption of the pigment epithelium or necrosis of the retina as Akbar had just described with acute retinal necrosis or necrotizing herpetic retinopathy. And this is seen here in both a patient that's HIV positive and a patient that's HIV negative with these precipitates here that seem to follow the blood vessels. The thing about these precipitates is it's thought to be related to vasculitis and they disappear properly with treatment. Another mode of presentation is really just strictly with optic nerve involvement. This is a gentleman, a 57 year old patient of mine that presented with sores on his hands and his mouth and his tongue. That was a big tip off as to what was going on with him and indeed he was RPR and FDA positive and I showed this hemorrhage around his disc and hyperflorescence of this optic nerve. So there has been a description of a syphilitic outer retinopathy that was described. This is actually a patient of mine that came in with these curvilinear lesions here that were initially described and thought to be Azor but it turns out that many of these patients were RPR positive. So syphilis was a diagnosis and if you look really carefully in these areas there really is a plaqueoid lesion and so it's thought that this syphilitic outer retinopathy is really a variant, a subtle variant of the plaqueoid curvilinear and ICG can be helpful in that post-treatment complete revision and return to normality. In this particular patient. This patient presented three years later with profound reduction in vision and panneuvias as you can see here. So patients with syphilis can become reinfected so that is always something to keep in mind and this patient had a RPR that was positive, he was treated but unfortunately his vision did not recover although his fundoscopic appearance was improved. So syphilis is a clinical diagnosis, always considerate in your work of patients with uveitis. There's highly variable presentation but there are distinctive posterior pole presentations that should make you think of the diagnosis. Always inquire about other sexually transmitted diseases and in the workup one must always order specific serological testing. So traditionally we've ordered both non-tropanamal and tropanamal tests, the RPR and the FTA ABS together. As you know the RPR is positive in the initial stages of the infection and can wane in tertiary syphilis and with treatment, whereas the FTA remains positive for life. The CDC has recently recommended a so-called reverse sequence testing in which enzyme immuno assays and chemiluminescent assays are used to screen for patients with toxoplasma with syphilis as they have increased sensitivity and specificity as a screening test and then the RPR is used to follow the treatment response. So in the case of a patient that is EIA positive and RPR negative, which can happen, then there's kind of a tiebreaker, a very highly specific and sensitive test called the tropanamal pallidum particle agglutination test which is like a tiebreaker which would confirm the diagnosis of syphilis. Further testing, as I said, always test for HIV in a patient with syphilis and vice versa, but patients with syphilis, ocular syphilis are thought to have neurosyphilis. So the CDC recommends that these patients undergo a lumbar puncture and that they have a repeat lumbar puncture if they are positive six months later. The treatment for syphilis is not with a shot of penicillin in the butt, okay? It is a neurosyphilitic regimen with intravenous benzene penicillin for 10 to 14 days or desensitization of penicillin, allergic patient, or prokine penicillin with probenicin. Corticosteroids can be useful for patients with anterior segment inflammation, but very frequently patients with, depending upon the degree of inflammation in the back of the eye, will respond to antibiotic treatment alone. That being said, another board type question is that after or during treatment, one can develop a severe inflammatory, systemic inflammatory reaction and ocular inflammatory reaction known as the aerox. Ericsheimer responds in which steroids are definitely indicated and can be preventative. Also, one would consider systemic steroids in a patient with structural complications and severe inflammation. So in summary, always think about syphilis in every, if I had to order one test, okay, for syphilis would be an FDA because you can actually treat it and cure it. There are certain, it can affect anytime and atomic region in the eye, but there's certain distinctive presentation that should really make you think about the diagnosis. Serologic testing is imperative as is lumbar puncture in patients with acute disease. Multimodal imaging can be helpful and the treatment is always with a neurological dosing. And the visual outcomes are generally pretty good. And there doesn't really seem to be a, it was previously reported that HIV-positive patients did more poorly, but recent evidence suggests that they're about the same as patients that are HIV negative. So that's syphilis, do you, we don't have a whole lot more time, but I'd be happy to entertain any questions about the Grand Rantz presentation. Roger. Very nice. Do you have any pushback from the Health Department about FDA at one point, you had to get an RPR for, were they able to do that? Yeah, I mean, yeah, there was that, there was actually pushback at AREP, but most of the ID people here, you know, don't, first of all, the ID department does not use the reverse sequence testing regularly, and they always order the two tests together. It's imperative that the two are ordered together. So we did, but, you know, we have a conversation with them and try to re-educate them about what Ocular Syphilis is about. All right. Yes, Ashley. So Dr. Lauchel talked about the study showing that there was less recurrence with the toxo of you use Bactrum every other day. Is that something that you guys practice here or? Yeah, we do. So for, so the biggest studies that I know about are, you know, those ones in Brazil in which the effect lasted for as long as people were on prophylactic Bactrum, and they actually have 10-year follow-up on that. And, you know, the effect lasted while they're on the medication, but then the recurrence rates seem to recur after they're off of Bactrum three times a day. Pretty benign. They're 10% sulfa-allergy in Bactrum, you'd have to be aware of. We do, I do routinely prophylox patients for with Bactrum who have lesions that particularly in monocular patients with lesions that are vision-threatening close to the phobia, which many of them are, or to the optic nerve. The other thing is that there is one study that I'm aware of in which treating, so the biggest risk for a reactivation of toxoplasmosis is a previous infection with toxoplasmosis, temporally. So if you've had a recent infection, you're more apt to have a recurrent infection, which is one of the rationales for treating patients with toxoplasmosis. The other thing is pathophysiologically, it is thought that the organisms are assisted throughout the retina, not just in the scarves, okay? And that for cataract surgery, there's one study that suggests that prophyloxically treating patients before an apricatric surgery will reduce the rate of recurrence in the perioperative period for cataract surgery, just as with viral, with herpes. Is that perioperative treatment? Is that full dose Bactrum? Yeah, so I would give him Bactrum twice a day for a week without herpes, and push up a week.