Transcript

MIC CAVAZZINI:                Welcome to Pomegranate Health, a podcast about the culture of medicine. I’m Mic Cavazzini for the Royal Australasian College of Physicians. Syphilis is often thought of as a disease from the historic literature, but in August last year,it was declared a Communicable Disease Incident of National Significance by Australia’s Chief Medical Officer. Case numbers have grown year on year since it became a notifiable disease in 2004, peaking at around six and a half thousand in 2023. 

Syphilis is, of course, a sexually-transmitted infection, but it’s sometimes described as ‘the great imitator’ because it can have so many different presentations. The Treponema pallidum bacterium can invade almost every system of the body leading to neurological symptoms, nephropathy, vascular disorders, arthritis and even cancer mimics. And as we’ll hear later, a concerning number of congenital cases are also observed every year in Australia. The aim of today’s podcast is to add to your cognitive library of differential diagnoses, so that next time you see such a presentation you take a moment to ask, “Could it be syphilis?”. To educate us on this theme, I invited Professor Louise Owen and Dr Janet Towns.

LOUISE OWEN: Thank you. My name is Louise Owen and I'm a sexual health physician and the director of statewide sexual health services in Tasmania. I'm also the president of the Australasian chapter of sexual health medicine and have a clinical appointment at the University of Tasmania Medical School.

MIC CAVAZZINI: Thank you Louise. What about Janet?

JANET TOWNS: Hi, my name is Janet Towns and I'm a sexual health physician and clinical forensic physician. I'm currently based at Melbourne Sexual Health Centre and a post-doc Fellow at Monash University.

MIC CAVAZZINI: Yeah, so this is something I schooled up on very recently, but let's start with bit of epidemiology. So, notifications for infectious syphilis peaked at six and a half thousand in the year 2023 in Australia. This was around four times what it had been a decade prior. Men make up 80% of cases and we know that within the MSM community, men who have sex with men, rates are up to 20 times higher than the general population. But a large part of that increase in recent years has been in the Aboriginal and Torres Strait Islander population, an incidence of 100 cases per 100,000 compared to around 20 for the non-Indigenous population. We'll start with Janet. How should we understand this convergence of risk factors?

JANET TOWNS: You need to consider this as a dual epidemic, because they're both completely different. You've got the heterosexual outbreak disproportionately affecting Aboriginal communities. And this is overwhelmingly heterosexual transmission, primarily affecting young people aged 15 to 34 and with a spike in women of reproductive age. So, there's a high rate of congenital syphilis. So, you've got factors like geographical isolation, difficulty accessing healthcare and gaps in prenatal and antenatal care contributing to that. And then when you look at the urban syphilis epidemic, it's sustained transmission. It's mostly gay and bisexual men, but there is crossover to women and we're starting to see heterosexual transmission there and congenital syphilis. But we've got much better access to healthcare in the cities, but not so much in rural areas and anyone can be at risk.

MIC CAVAZZINI: Thankyou. So, as described at sti.guidelines.org.au, in about a third of people primary syphilis is characterised by a tough sort of ulcer at the site of entry. It’s usually painless and will heal withing a few weeks so it may go unnoticed. After 6 weeks or more, patients enter a secondary stage of syphilis where they may experience a generalised skin rash that can occur anywhere on the body. There can also be oral and genital mucous patches, wart-like growths and even alopecia. Louise, so tell us, you know, how, how these patients typically do present and, how well recognized these symptoms are.

LOUISE OWEN: Thank you. So, Mic, we're talking here initially about early syphilis or infectious syphilis, which is syphilis acquired within the previous two years. And it may be symptomatic or asymptomatic. And the symptoms, as you described, could be in primary syphilis, the shanker at the site of inoculation. And anogenital would be the most common, of course, but included could be an oral lesion, pharyngeal lesion, there have been lesions on the lips.

And then the patient may move to secondary syphilis which can have multiple different dermatological presentations. And so the important thing about the rashes of syphilis is it could replicate any number of dermatological conditions, such as psoriasis, such as a seroconversion illness of HIV, such as an allergic reaction or a simple viral exanthem.

In addition, there can be other mucocutaneous lesions such as condylomata, which could look like warty growths could be misinterpreted for the HPV or wart lesions around the perianal or vulval regions. So, the take-home message initially, I guess, really put syphilis on the radar and have a low threshold for testing.

MIC CAVAZZINI:                I came across a range of case reports that live up to the syphilis as ‘the great imitator.’ One that was seen at John Hunter Hospital in Newcastle described a 38‐year‐old Caucasian man presenting with nephrotic syndrome. He was HIV-positive but this was well-controlled by antiretroviral therapy. He presented with a two-week history of maculopapular rash, lymphadenopathy, oral lesions, nasal congestion and bilateral pitting oedema. Lab tests revealed hypoalbuminemia, abnormal liver function and nephrotic range proteinuria. Renal biopsy revealed membranous nephropathy including mild glomerular basement membrane thickening and granular deposits of immunoglobulin and C3 component. There are many possible causes of membranous nephropathy and syphilis is far from the top of the list. So in this case, what would raise the clinician’s suspicion to test for syphilis? Is it just the HIV status?

JANET TOWNS: I look at that and I see two-week history of rash, lymphadenopathy, oral lesions and nasal congestion and I think, syphilis. And it's very common to have abnormal liver function tests or renal function tests but you have to look what all the symptoms are not just isolate out the kidney function.

LOUISE OWEN: And also I guess the point of our podcast is to really say we need to move it up the list. It's a very easy test to eliminate. And some renal units have this on their syphilis on their pre-transplant workup list. How could we move that onto their exploration of glomerular nephritis list to say this is common enough now to say a very cheap test can rule it out.

MIC CAVAZZINI:                And in about half of T. pallidum infections the bacterium quickly invades the central nervous system. This is usually detectable on CSF examination but only 2% of percent of infections actually result in neurologial symptoms in the first year or so. We’re talking headaches, nausea, fevers, photosensitivity, even hearing loss or tinnitus. But meningeal symptoms can of course have many other aetiologies. So, Janet who needs to be hearing this message to consider neurosyphilis as a diagnosis?

JANET TOWNS: Every clinician. And if I see a patient that's got headaches, nausea, fevers, photosensitivity, they are going straight to the emergency department because it's not possible with those symptoms to differentiate what they are due to without the sort of tests that can usually only be performed in hospital. Syphilis is definitely a differential diagnosis but there are things that could more rapidly cause symptoms like meningococcal meningitis or other types of meningitis. I think with neurosyphilis, the presentations can be protean. Many different types of neurological symptoms, and a variety of specialists, including neurologists, need to consider syphilis as a diagnosis.

MIC CAVAZZINI: To illustrate this complexity let me share a case that was seen at Barwon Health in Victoria and published in the BMJ Case Reports in 2023. A man in his 50s with hypertension presented after having had three episodes of impaired awareness, altered behaviour and post-event confusion. These followed 5 days of lethargy and poor appetite. Structural MRI revealed hyperintensities in the mesial temporal lobe and CSF showed elevated protein and lymphocytes, and a positive test for Herpes Simplex Virus. He was treated with anticonvulsants and acyclovir and remained stable for 6 months apart from some short-term memory loss. But there was no change in the MRI signal or CSF results and the patient developed episodes of focal dyscognitive seizures associated with worsening cognition and personality changes.

He was given a working diagnosis of antibody negative autoimmune limbic encephalitis and admitted for IV methylpred pulse therapy. The pleocytosis persisted, as did the seizures and this progressed to language dysfuction, mild cognitive impairment and auditory hallucinations. But neurological examinations were otherwise normal and the patient was readmitted for evaluation of alternative causes of this chronic meningoencephalitis. That’s when serology and PCR of the cerebrospinal fluid returned a positive result for syphilis which was then treated. The moral of the story is that while neurosyphilis might not be a common aetiology, it should be considered along with other paraneoplastic or autoimmune differentials. 

Another case report I pulled off PubMed spoke to the ocular manifestations of secondary syphilis which are not so uncommon. It was published in 2021 in the RACP’s own Internal Medicine Journal. This patient was a 51-year-old Indigenous man presenting to Princess Alexandra Hospital in Brisbane with a painful red left eye. Symptoms had begun 4 days before and included light sensitivity and reduced acuity. The man had recently developed a widespread non-pruritic rash which he attributed to a course of flucloxacillin he’d been prescribed for a finger cellulitis. Returning to the GP led to identification of deranged liver enzyme function but both of these issues had resolved prior to the ophthalmic presentation.

The eye pain was associated with keratic precipitates on the cornea and a moderately severe iritis with a large fibrin mass overlying his pupil. Also, inflammatory iris adhesions to the anterior lens capsule and a non-pigmented iris stromal mass. As described by the report’s authors, uveitis or intraocular inflammation are the most common ophthalmic symptoms of syphilis and should prompt the clinician to test for it. Note that these can occur as late as 6 months after the initial infection when many of the systemic manifestations have already resolved.

But around 45% of people with early syphilis don’t have any obvious symptoms at all, and may not know they’ve been infected, so the Australian guidelines recommend comprehensive STI testing as part of a regular health check. To confirm a syphilis infection there are several different swabs and serology and PCR. Some tests are specific for the treponema pathogen and others are for non-specific biomarkers. Janet Towns and collaborators across Melbourne institutions published a systematic review showing that 10% of infections remain negative on serologic markers. I asked her to explain how to navigate the strengths and weaknesses of the various diagnostic assays.

JANET TOWNS: So, I'm going to divide this answer into a first episode of syphilis infection or a repeat syphilis infection which are actually quite common and if you've never had syphilis before, you're naive, then you will have no antibodies to syphilis of any kind. And we divide the tests up into direct detection tests and indirect detection tests. The direct tests are PCR, detecting the treponema Pallidum bacteria in a lesion or on a mucosal membrane. And dark ground microscopy. Now dark ground microscopy not used so much, not many labs are still set up for doing that, but PCR is becoming much more widely available.

Then you've got antibodies and indirect detection. And there's two different types of antibody tests. There are the treponemal antibody tests. So specific antibody tests that will be things like an enzyme amino assay or a chemiluminescent immunoassay or a treponema pallidum hemagglutination assay, or maybe even a fluorescent treponemal antibody. And they're all specific to the treponema pallidum.

The other non-specific serology is that of usually an RPR, but occasionally a VDRL. So, an RPR test, a rapid plasma reagent, detects anti-cardiolipin antibodies, which is a response to damage caused by the syphilis bacteria. So, when you've got a higher level of the RPR or VDR, well, you've got a very active case. They can throw up false positives, which makes it tricky.

So, going back to the systematic review and the first episode, we looked at people that had never had syphilis before, had no positive antibodies, either treponemal or non- treponemal, and were picked up on a PCR test. The other half of those people in the systematic review were people that had had syphilis before, had existing positive treponemal antibodies, and usually a low or negative RPR value. So, you then have to use a PCR test because you can't tell whether the antibodies often are from a previous infection or a new infection. You need to do some direct detection because that will be positive before you see the increase in the RPR for subsequent infections.

MIC CAVAZZINI:                Yeah, and I think we both saw a presentation recently from a researcher at the Burnet Institute who was talking of development of a point of care assay that would be able to distinguish active from past infections. Is that worth flagging up? We'll wait to see how well that works.

JANET TOWNS: I think I would wait to see how well that works. They are doing detection using IgA. And while that is showing different responses to the standard serology that we are using, it's not infallible. So, I'll be more interested to see what evolves out of that research project.

MIC CAVAZZINI: Louise, you want to add something?

LOUISE OWEN: Yes, thanks for that explanation, Janet. I guess just to distil it down, our clinicians are really just asking for the blood test syphilis serology noting if the patient has had past history of syphilis they would then just ask for the RPR. And if there are any lesions no matter what you think they are including a rash on the body, the palms, the soles of the feet, the mouth, the bum, please do a PCR using a white top plain swab.

MIC CAVAZZINI: So, I think that the take home message from what you've just told me is that, and that's going to come up a few times today is, “if in doubt test for syphilis”. And that when I heard that I sort of jarred a little bit with some of the conditioning that physicians and GPs have received about over testing and low value care. But are these cheap and available tests that should be occurring alongside any referral to neurology or ophthalmology or wherever.

LOUISE OWEN: Yes, I think so. I guess we're aiming to raise awareness to increase the testing that happens outside sexual health services in people particularly who have symptoms. Certainly in urgent care centres it is expected that they would be having a low threshold to test for syphilis.

MIC CAVAZZINI:                And if a test does come back positive, then who takes responsibility for the treatment plan? Does it typically need to be referred to sexual health medicine or the ID department?

LOUISE OWEN: This is a really great question and certainly it can prevent some clinicians doing a test because they're worried about what to do if they're positive. In many jurisdictions the lab has good relationships with the clinician who's ordered the test, realises this is an important but niche area and will be in touch with the clinician and then put them in touch with either the Australian STI guidelines or a clinician in sexual health or ID who will be able to assist them.

There's also, it's a publicly notifiable condition, so usually public health will be in touch with the clinician as well. But we want people to know that their sexual health physician or their sexual health clinic is really open to being contacted about any queries they have. And in our jurisdiction, someone would contact the clinician for every syphilis diagnosis made outside our service as a courtesy, but we're in a small jurisdiction.

MIC CAVAZZINI:                Treatment for syphilis involves long-acting intramuscular formulation of benzathine benzylpenicillin. For early stages of syphilis, this is given intra-buttock as two injections of 1.2 million units each. For late syphilis or syphilis of unknown duration, three rounds of this treatment are given with intervals of a week or two. And it’s important to get a baseline serology for rapid plasma reagin so that treatment impact can be assessed. A four-fold drop in RGR indicates adequate response to treatment and follow up is performed at 3 months and 6 months. This follow up is now an auditable outcome requiring 100% compliance. If RGR isn’t back down at 12 months after completion of treatment, further specialist advice should be sought.

Without treatment, patients remain most infectious to sexual partners for two years before syphilis enters a latent phase. Syphilis can also be transmitted from a pregnant woman to the unborn foetus. In a woman who has primary or secondary syphilis, the rate of congenital transmission can be 80% or higher, and it remains at 10% even in the latent asymptomatic stage. There have been10 to 20 cases of congenital syphilis in Australia every year for the last six years around a third which resulted in stillbirth or death after live birth. Syphilis is also associated with preterm delivery or low birth weight.

For this part of the conversation I invited, Dr Nele Legge, a neonatologist and general paediatrician who has for a few years generously sat on the podcast editorial group. As head department of the NICU in Liverpool Hospital, she’s seen a few cases of congenital syphilis in recent years that caught her and her team by surprise. I started by presenting her with a case study where a baby was delivered 31 weeks’ gestation by caesarean section because of foetal distress. Only later was an enlarged liver detected and associated thrombocytopenia and an elevated alkaline phosphatase. The baby also had syphilitic periostitis. I asked Dr Legge if there would be any prenatal testing that would reveal the cause of this foetal distress, if you had no idea that the mother was positive for syphilis.

NELE LEGGE:      Well, sometimes we are facing a foetus that is in distress because it's growth restricted. And generally, if you have a scan and your baby is found to be small for age, the obstetricians are very good at doing TORCH serology, which includes a syphilis RPR. And also, these are then women who have had a complete antenatal care package, seeing midwives regularly, going to antenatal clinics, having scans. Generally, or the three cases that I have seen in the last two years of congenital syphilis, the babies that we get are not from pregnancies that have a complete antenatal care package. So, women with minimal or no antenatal care who then turn up and either deliver prematurely, which is a big catastrophe if you have congenital syphilis, or they deliver close to term.

But what I think is really important is what you've already said multiple times, that is to think of syphilis, which we as the neonatologists hardly ever do, or didn't do until two years ago when we had our first case. We always think of CMV, we sometimes think of other viruses, so we don't think of syphilis. And if you have a baby where they just don't behave like you expect them to behave or they have symptoms that just don't fit with the usual stuff that we see, then check that mum had her serology antenatally, and if she hasn't, then think of syphilis straight away.

Because you can then talk to your sexual health clinic which is the first thing that I did. So I had this case where I had a term baby born who was unwell and it didn't fit with the story and we ended up and the obstetrician was very clever and did psychology pretty much when mum turned up and revealed that she might have syphilis and my first call was to Chris Carmody who is the head of our sexual health clinic and saying what's happening what am I supposed to do, all those abbreviations which one do I do first what is the most important test and they were extremely helpful and as Louise said before already. Public health are also a fantastic resource. So I certainly felt very out of my depth, but I definitely didn't feel alone and as we kind of figured it out together the baby got the best care that it could. And if you treat congenital syphilis quickly decisively and consistently the outcomes should be pretty good

MIC CAVAZZINI:                Congenital syphilis is greatly overrepresented in the Aboriginal and Torres Strait Islander population, and the case I’ve described was managed at the Child and Adolescent Health Service in Perth. But, as Nele has described, are cases in southwestern Sydney and non-Indigenous families as well. So, Louise, what's the message then for improving detection of syphilis? Are we talking about testing every mother or is there a trigger in high risk groups?

LOUISE OWEN: Thanks, Mic. Certainly the Australian Pregnancy Care Guidelines have recently been updated to include a minimum of three tests per pregnancy for every pregnant person in Australia. This is also endorsed by the Communicable Disease Network of Australia's National Guidelines and also the RANZCOG and the RACGP recommendations. In addition to that, there will be jurisdictional additional testing recommendations, particularly high prevalence populations which could include some specific jurisdictions or indeed broad groups such as Aboriginal and Torres Strait Islander people.

MIC CAVAZZINI:                And of course, penicillin is considered safe in pregnancy, but not doxycycline, which is the alternative normally given in people who have penicillin allergy. One of my reviewers in New Zealand, Dr Marion Leighton, described how she needed to desensitize a pregnant woman with increasing doses of penicillin over eight hours just to be able to treat for syphilis. Nele, have you explored this? What else do need to know about alternatives to treatment more generally?

NELE LEGGE:      I think the most important thing is to find out that the woman has syphilis and then worry about allergies later. I think the biggest issue is that these, or certainly the cases that I have seen, these are not people who seek out health practitioners. These are not people who come to appointments. These are people that you have to be opportunistic and you have to be kind of like, “Oh gosh, they're here, let's just do everything”. And certainly we were lucky that most of our patients, they're obstetric and antenatal team were really good in picking up that it was missed. But I think when we talk about treatment of syphilis, I think we need to talk about detection of syphilis first.

MIC CAVAZZINI:                And speaking, going back, pushing on with treatment, Janet, I know that there's a supply shortage of the pre-filled syringes of benzathine benzylpenicillin that's expected to continue until November at least. That's what the TGA says. How is this being managed?

JANET TOWNS: This has actually been going on and off since about 2016. So, this is not the first time this has happened. Our pharmacists are very good at sourcing the penicillin that we need from other countries, flying it in and trying to keep a stockpile. But yes, it is outrageous that we've got a disease with 8 million cases globally and we have penicillin shortages.

LOUISE OWEN: I think there's an awareness that the, it's centrally in Australia, that the public health units in each state will prioritise the use of this penicillin for rheumatic fever and for syphilis. And so each state and territory do have mechanisms in place and there have been some other formulations available when there's been acute shortage. Right at the moment, I think we're okay. But a clinician would be best to speak to their local sexual health physicians for advice.

MIC CAVAZZINI:                Thankyou, I was going to ask Nele—I don't have any more questions specifically for you unless—do you have other examples you want to share or do you have questions while you've got the sexual health medicine professors on the line that come from your practice.

NELE LEGGE:      I actually do have a question. So, we had four cases of congenital syphilis in southwestern Sydney over the last two years, which I believe is about a quarter of all cases in Australia over those two years, which is quite shocking. And since most of the mothers that I looked after are a bit shy of the health system, we had big problems continuing the treatment for the babies for the recommended time period and do the repeat tests including repeat lumbar punctures.

There's very, very good pathways established for hepatitis, whether it's B or C, for children. So, they go to the infectious diseases department in the kids' hospital and get all of their serology and stuff repeated in the first 18 months. There doesn't seem to be anything for syphilis yet, or I might not know about, so was wondering whether Louise or Janet have got any information on their  district, where they work, whether they've got better pathways to engage these patients.

LOUISE OWEN: I think that's a really great question, Nele. And while some jurisdictions have had infections in people who have been low healthcare-seeking, others have actually had women who had their antenatal initial test, which was all that was required, and were found to have syphilis acquired later in the pregnancy and still could have a negative outcome for the baby. So, I think, again, there's usually a very strong collaboration between neonates, obstetrics, ID, sexual health and public health. And in many states there is a multidisciplinary team conversion to try and best manage this. But you're right there isn't an established pathway and that's something that we could definitely be promulgating and I may well be able to do that through my role is in the adult medicine division and you might have a role there too. But otherwise, it is an area by area basis and I can imagine that may not always be smooth. And we forgot the GP of course in the care plan for the follow up as well.

MIC CAVAZZINI:                It's a very good example of one of those sort of systems problems that can very easily fall through the gaps.

LOUISE OWEN: And I have a question for Nele, if I may.

MIC CAVAZZINI:                Of course.

LOUISE OWEN: There is, you know, the recommendations on the ASID guidelines for when the placenta is sent off for examination and so on. Is that clear to your colleagues when that is required or is that something also that could be more tightly organized?

NELE LEGGE:      I know how important that is now after having looked after three of these kids somehow but I'm certain that lots of obstetricians don't know and many neonatologists won’t know. I mean once you end up in a NICU as a baby, you will probably be diagnosed, you probably get the tests and you will probably have your placenta sent. But if you are born if you are a normal vaginal delivery with no risk factors—and  we had one of those cases where it was latent syphilis and mum and baby was only diagnosed because they had prolonged jaundice and they did some LFTs and then kind of went searching, by that point the placenta was truly in the bin so there was absolutely no way to send that off and I know that it's a super important puzzle piece.

So, I think important still for an neonatologist to know; if you suspect syphilis, your first course should be to sexual health, second call should be to birthing you to say please send the placenta for histopath because you can't retrospectively go back and that's basically the final puzzle piece to say yes, this is congenital syphilis.

MIC CAVAZZINI: At this point in the interview we farewelled Nele Legge, who told me she had babies coming out of her ears. But it was great to see the podcast interview panel become a place for crossdisciplinary brainstorming. We moved on from congenital transmission, to the to the symptoms of syphilis that arise later in the course of the disease. Without treatment, syphilis can go into hiding for many years but after this latent phase, patients may start to experience various forms of tertiary disease. In developed countries these have become quite rare since the advent of the antibiotic era, but certainly not abolished, as we’ll hear in a minute. And Janet Towns told me that in China, for example, there are wards full of such patients.

Starting from about five years after infection, some people experience what is known as meningovascular syphilis. So, this may include stroke, seizures and myelopathy as well as the neurological symptoms we mentioned earlier. And from ten years onwards, cardiovascular involvement occurs in about half of untreated patients. The corkscrew-shaped treponema spirochetes lodge in the vasa vasorum, those tiny blood vessels that supply the walls of large arteries and veins. This causes inflammation of the arterial walls, leading to aortitis, stenosis, aneurysms and blood clots.

Tertiary syphilis can also present with worsening neurological syndromes. General paresis, dementia-like changes in cognition, mood, and judgment. Impairments with memory and language. And if neurodegeneration and demyelination progresses further there’s something called tabes dorsalis.

JANET TOWNS: When you've got late syphilis, and you've got an example here of the tabes dorsalis, this is a condition that affects the posterior columns of the spinal cord and comes on about 15 to 50 years after the contraction of the disease. The body doesn't have a real sense of itself in space, so you've got proprioception affected. And you can also get damage to sensory nerves as well, so you can get lightening pains, particularly around the trunk, and a very staggering broad-based sort of walk.

So that would be what you would see, and it takes many, many years to progress. And if you think of when the syphilis epidemic first started showing itself in Australia, which should be we had our first new case in 2001, I think that we're probably going to see more of this late tertiary syphilis in decades to come. Maybe not as much because there's lots of incidental antisyphilitic antibiotics used in medicine. But I think we have to be very aware that we're in an epidemic now and some of these late presentations will make themselves more clear later.

MIC CAVAZZINI: Is it helpful to discuss here the more complex treatment pathways, so not just penicillin but other…

JANET TOWNS: Penicillin is the mainstay of treatment. And when you've got neurosyphilis, it's quite aggressive treatment. You're talking benzylpenicillin IV four times a day. And the aim is to get rid of all the spirochetes, all the treponemes around the body. When you've got this very late tertiary syphilis stages, you may be able to clear the spirochetes, you may get some improvement in function but there may be permanent nerve damage.

MIC CAVAZZINI: Yeah, and even central damage as well. Another, very different, presentation I read about came from the Department of General Surgery at Griffith Base Hospital. This involved 39-year-old man presented to ED with worsening tenesmus and diarrhoea and tenderness. He had non-specific bloods and a contrast CT that demonstrated irregular thickening of the rectal wall, bilateral lymphadenopathy and multiple hypoattenuating liver lesions. Colonoscopy revealed a concerning ulcer in the lower rectum that when biopsied showed an atypical crypt epithelium more consistent with chronic inflammation than any neoplastic change. The liver lesions looked more like scattered granulomas with extensive areas of necrosis.

From there it was actually the patient’s background that steered the diagnosis. He identified as homosexual and as an occasional user of intravenous methamphetamine and it was the patient’s HIV doctor who mentioned a history with syphilis. The rectal lesion was considered a chancre resulting from reinfection while the liver lesions were presumed to be the gummata that can come with tertiary syphilis. This was described by the authors as the “the first reported case of syphilis masquerading as both a primary rectal malignancy and hepatic metastases.” A rare mimic but what should we take from this case study?

JANET TOWNS: I will talk to that one. A 39-year-old man presented to emergency with worsening tinnitus and diarrhea and tenderness. To me, that just screams proctitis. And I immediately think of gonorrhea, chlamydia, herpes, syphilis, and M. pox. And all the other things are consistent with that. But going back to that initial presentation, never forget that.

LOUISE OWEN: We would like to give a plug for the Australian STI guidelines here, Mic, because these are a great reference, easy to access. You can look up syndrome, example, at proctitis and it will tell you which tests to do, or you can look up a specific infection and it will talk about which tests to do and how to treat.

MIC CAVAZZINI:                Also at the ASHM website, were some nice decision trees and online tools for working through. And as complicated a spread that we've described of presentations, actually the take home message is quite simple.

LOUISE OWEN: Test, test, test.

MIC CAVAZZINI:                And as Janet has said, there are some primary symptoms that you should never miss.

JANET TOWNS: Everything is syphilis until proven otherwise.

MIC CAVAZZINI:                Yes, nice. There’s a retrospective cohort study from academics in Melbourne that looks at concomitant STIs and other risk factors in the MSM community. For some reason that I didn’t understand HIV has a much higher hazard ration than chlamydia and gonorrhoea. Injecting drug much moreso than condomless anal sex. Can you explain whether we're talking about biological determinants here or behavioral factors?

JANET TOWNS: I think there are some biological reasons, so I'll start with those. The base of the syphilitic ulcer has all the target cells for HIV infection. So, you do get this sort of symbiosis and co-infection between syphilis and HIV.

LOUISE OWEN: One more little grab if you can. Anytime that you're doing a syphilis test, and particularly if your syphilis test is positive, a HIV test should be done in those people who are not already aware of their HIV status. And that's really important to know that part of routine STI testing includes HIV and syphilis testing as a package. So, if our listeners can keep that in mind, that would be great.

MIC CAVAZZINI:                And another thing to consider when diagnosing a case of syphilis is contact tracing. So again, which department is responsible for following up prior sexual partners for testing and how far back do you need to go?

LOUISE OWEN: That's a really good question, Mic. And importantly, the ASHM contact tracing guidelines are a great reference for the clinicians. But basically, the clinician who's diagnosed the condition talks with the patient about contact tracing and for early syphilis, as in less than two years, depending if it's a primary syphilis, three month contact tracing and if it's secondary, six to 12 months. And then there may be assistance that can be given the patient. For example, there's an online anonymous STI notification platform through the Melbourne Sexual Health website called LetThemKnow and occasionally public health services may assist the clinician to find contact trace partners. Importantly, certainly in people of reproductive years or partners of pregnant people, we really take the contact tracing seriously.

I was just going to mention about the management of partners of people who have early syphilis. It's really important and ideal that those people in addition to testing are offered treatment on the day because it can take some months for their syphilis serology to become positive and it's much better to treat them before they may be going to move on to symptoms.

JANET TOWNS: It's absolutely essential, treatment of contacts, because we're not sure what the outer limit is, the seroconversion, but it can be delayed. So all doctors should be aware that in the early stages, patients can be negative, they still need treatment or follow up, but preferably treatment on the day they attend.

MIC CAVAZZINI:                I think we've covered a lot and that hour just flew by. Let me just read one more case study and if you’ve got any gut reactions to it will make the cut. So latent syphilis can wait even 20 or 30 years to reactivate as some form of tertiary syphilis. I came across one case study from Princess Alexandra Hospital published in 2022 which described a 64-year-old man who presented to the ED department with an acutely ischemic right lower limb. CT angiography revealed a partially thrombosed pseudoaneurysm in the wall of the right above-knee popliteal artery and the patient was commenced on aspirin and heparin with a plan for surgical repair. The lack of atherosclerosis made them suspect an infective cause and syphilis was the only test of many that came back positive. Though the patient denied any history of primary symptoms, intravenous drug use and had had a stable sexual partner for the last ten years. So, the diagnosis of tertiary syphilis was a tentative aetiology for this late vascular presentation. Is that kind of thing come up often enough where it's a diagnosis of last resort?

JANET TOWNS: I think with this case, their syphilis may be the causative agent, but it may also be there incidentally. This person could have had it as a much younger person, could have been incidentally treated with other antibiotics. So, I think I would be looking for more evidence. You would treat the suspected syphilis if there was no history of syphilis treatment, but this could be due to other things. So don't assume that it's syphilis just because you've got a positive test.

LOUISE OWEN: As the cause of that clinical presentation. Yeah, but also I think there's probably a reason to include syphilis testing back on early dementia screens, that it was fading off because, “well, we're not really finding any syphilis”. But as Janet mentioned, we do need to have that on as an easily identifiable and treatable condition if it was found. It may or may not change their clinical outcome, but it's important.

JANET TOWNS: And in the older population where there are higher rates of dementia, it's important to think of syphilis in them because they may not have caught it within the last 20 years, but there was a massive spike in the 1930s and 1940s around the Second World War time. And yes, that penicillin came in around that time, but there's a lot of syphilis. And so, this may be incidental relating back to that time.

MIC CAVAZZINI:                Yep.

LOUISE OWEN: You’ve done a lot of good research, Mic.

MIC CAVAZZINI:                Oh, it was too much. Sometimes I can't stop myself going down every rabbit hole.

LOUISE OWEN: Yeah, I think we've got a in priority we've got test test test, use the guidelines, multidisciplinary team for the antenatal care of anybody who's found to have syphilis who's pregnant, treat the contacts and if in doubt phone one of us.

MIC CAVAZZINI: I’ll be handing out your phone number.

LOUISE OWEN: Not literally!      

MIC CAVAZZINI: Many thanks indeed to Professor Louise Owen, Dr Janet Towns and Dr Nele Legge for contributing to this episode of Pomegranate Health. I’m also very grateful to the members of the podcast editorial group who kindly gave their time to provide feedback. They were doctors Aidan Tan, Courtney Dowd, Marion Leighton, Lauren Gomes, Rahul Barmanray and Rachel Murdoch. Dissemination of this podcast was supported by the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine. ASHM is the peak body representing healthcare professionals working in this sector and has some excellent decision-supports and conversations guides at their website. ashm.org.au/stopsyphilis/

At our website, I’ll link to heaps of academic literature, and information on the syphilis epidemic provided by the Australian Centre for Disease Control and the Kirby Institute. Just go to racp.edu.au/podcast and then click on episode number 149. If you’ve got an interest in sexual health medicine, please also check out episode 93 from the back catalogue, titled “the rise and fall of mpox”. And have a play with the new search tool on the archive page, that lets you filter episodes by specialty and domain of professional practice. Hopefully this helps you tick of your CPD requirements and areas of clinical interest. Do tell is what you think in the comments section, or via the email address podcast@racp.edu.au. This podcast was produced on the lands of the Gadigal clans of the Yura nation. I’m Mic Cavazzini, thanks for listening.