We review the history of syphilis, current trends, evaluation and treatment of pregnant women with syphilis and their newborns. We are joined by Muraleedharan Sivarajan, MD, Assistant Professor of Neonatal-Perinatal Medicine at the University of Texas Southwestern Medical Center.
Dr. Neeta Goli:
Welcome to Newborn News, a podcast where we discuss educational topics for medical professionals who care for newborns. I'm your host, Dr. Neeta Goli, a pediatrician in the UT Southwestern newborn nursery. Welcome back to the podcast. In today's episode, we'll be discussing congenital syphilis. We're recording remotely due to the ongoing COVID pandemic. We're joined today by Dr. Muraleedharan Sivarajan, Assistant Professor of Neonatal-Perinatal Medicine at UT Southwestern, and a colleague in the newborn nursery, who has over 35 years of experience caring for children and a career spanning three continents.
Dr. Muralee Sivarajan:
Hello.
Dr. Neeta Goli:
Hi, Dr. Sivarajan. Thanks for joining us today.
Dr. Muralee Sivarajan:
Hi Dr. Goli, good morning. How are you?
Dr. Neeta Goli:
Good, thank you.
Dr. Muralee Sivarajan:
Thanks for inviting me to discuss this rather vexing public health issue.
Dr. Neeta Goli:
Thanks so much for coming and talking to us today.
Dr. Muralee Sivarajan:
My pleasure.
Dr. Neeta Goli:
So syphilis is a sexually transmitted infection caused by the bacteria Treponema pallidum. If a pregnant woman has syphilis, which is not treated, her infant might be affected by congenital syphilis, which we will discuss today. What are the trends in syphilis prevalence both nationally and locally for us here in Texas?
Dr. Muralee Sivarajan:
Good question. That's a rather disturbing piece of evidence we have in the US because syphilis per se has been rising steadily since 2001. If you look at the last batch of statistics from 2018, we have around 115,000 or so of cases of syphilis, which, if you look from the block from 2014, it's a 71% increase.
Dr. Muralee Sivarajan:
And if you go down to congenital syphilis, we have seen a sharp rise from 2012. In 2018, there were around 1,306 cases in the USA, which boils down to around 33 per 100,000 live births. And if you look from the statistics from 2014 it’s a 185% increase.And the news gets even more grim. We are here in Texas, we have around 367 cases. And if you look at the national average 33.1 per 100,000, we are at 92.2 per 100,000 live births and that sadly ranks us as number one, nationally for both case rate and case number. On a worldwide basis, syphilis affects around one million pregnancies, and a case of congenital syphilis should be viewed as a sentinel event, because it shows multiple missed opportunities.
Dr. Neeta Goli:
And to get back to the basics, what does the word syphilis actually mean?
Dr. Muralee Sivarajan:
That's a really interesting question now, because syphilis now, as we all know, refers to the disease caused by Treponema pallidum. This is a double walled bacteria, which belongs to the phylum of spirochetes.
Dr. Muralee Sivarajan:
If we go back into history, this organism was first isolated in 1905. However, there's mention of this organism dating back to antiquity, when we have the earliest records from Europe. We have an instance when the French troops were besieging Naples in Italy, there was a thought process that the French brought it to Italy. And then the Italians were calling it the French disease. Of course, the French returned the favor, calling it the Italian disease. So this mudslinging went on like the Dutch calling it the Spanish disease, and the Russians the Polish disease, and the Turks the Christian disease, and so forth till we got a little bit of a truce when there was this Italian physician and poet. His name was Girolamo Fracastoro. In 1530, he wrote a poem called Syphilis, where the hero of his poem Syphilus, was afflicted by this disease. And since then this disease came to be known as syphilis.
Dr. Neeta Goli:
Dubious honor. I love the history. So currently, right now in the US in 2020, every pregnant woman receives syphilis screening as part of her routine prenatal care. State laws vary, but most mandate screening in the first trimester and in certain circumstances repeat screening in the third trimester as well. How do OBs screen pregnant women for syphilis, and can you explain the difference between the different types of tests: the nontreponemal versus treponemal tests for syphilis?
Dr. Muralee Sivarajan:
Sure, first of all, let me talk about some of the blood tests for syphilis to get an overview. So broadly speaking, we have two categories. One is the nontreponemal. These are the quantitative tests. And then we have the treponemal, which are the qualitative tests. These are all IgG tests, so the bottom line from a pediatrician's perspective is they will cross the transplacental barrier and will result in a positive test as well, which they may result in a positive test without actual infection going on in the newborn.
Dr. Muralee Sivarajan:
The commonly known nontreponemal tests we have, are the VDRL and the RPR. They're pretty sensitive but not specific. But however, they are useful because we use them to monitor the progress of the disease, because they are semi-quantitative tests. VDRL stands for Venereal Disease Research Laboratory, and what this detects is anti-cardiolipin antibodies produced by the organism, which will react with ox heart diphosphatidyl glycerol.
Dr. Muralee Sivarajan:
RPR stands for rapid plasma reagin. This is a newer, more rapid and sensitive test, it takes some time to turn positive - around one to four weeks after getting infected in the mom. And generally they're around one- to two-fold higher than the VDRL test. It detects antibodies against substances released by cells which have been damaged by the organism. Now these two tests should not be substituted for each other when you're following the titers, because the RPR is around a couple of titers higher than the VDRL. It is also important to note that these titers can fluctuate during the course of follow-up of a patient. However, it should not be more than a fourfold rise.
Dr. Muralee Sivarajan:
Now, a sustained drop in titers after treatment, it generally suggests that there was an adequate treatment. This usually occurs in 6-12 months. However, if you have a fourfold increase, this is either a relapse or reinfection and when you treat early, these tests turn to become negative by one year, but may take up to two years for congenital syphilis, often the titers are very high.
Dr. Muralee Sivarajan:
Moving on to the specific tests, the two treponemal tests, they are the qualitative tests, they actually take a little bit longer to become positive. However, the generally speaking tend to stay positive for life. However, some studies show that around 15-25%, can serorevert to a negative status in two to three years time, especially when you treat them early or if you're immunosuppressed as those who have HIV. Some of the examples of the specific tests are the CIA, which is what we use in our hospital. It's also known as the chemiimmunoluminescence assay. Then we have the EIA, enzyme-linked immunoassay, the TP-PA, which is the Treponema pallidum particle agglutination, and so forth.
Dr. Muralee Sivarajan:
The guideline from CDC and AAP is no baby should be discharged from hospital till there is a documentation of maternal syphilis serology at least once and ideally again at delivery. So that's the national guideline. However, and typically, all the moms are screened at the first visit. Now, if you're in a high risk population or in a high risk area, which basically is Texas, and the Texas law is, you need to have additional screenings at 28 to 32 weeks, and again at delivery.
Dr. Muralee Sivarajan:
So, that's the lab evidence. Then we have other supporting evidence, like you can use ultrasound. Around 20 weeks of gestation, you might see hydrops fetalis, hepatosplenomegaly, placentomegaly, polyhydramnios, ascites, and if the baby becomes really anemic, you can even do a fetal middle cerebral artery Doppler to look for flow rates.
Dr. Muralee Sivarajan:
Once the baby is born, the placenta shows a few changes. They typically are large pale edematous, they may show inflammation, which is called necrotizing funisitis of the cord. It gives you a characteristic barber pole appearance. I don't know if you remember the old barber poles we used to have outside the barber shops. It looks like a Christmas, peppermint candy twisted around. So, it gives you that funny appearance. Now for moms who have primarily syphilis, they should be retested for HIV after three months if the first HIV test is negative. So, this goes in line with the thought process that all patients with syphilis should be tested for other sexually transmitted infections.
Dr. Neeta Goli:
And you mentioned a fourfold change in titer, would you be able to explain exactly what that means?
Dr. Muralee Sivarajan:
Yeah, this sometimes is a source of confusion, but if you just remember, it generally means a change in two dilutions. For example, 1:8 becomes 1:32. So, it changed from 1:8 to 1:16 and 1:16 became 1:32. Same way 1:16 might become 1:64. So, that's a fourfold change in titers. Now, these titers tend to fluctuate a little bit change by one dilution like 1:8 became 1:4, or 1:2 became 1:1 can happen, this is usually not significant.
Dr. Neeta Goli:
And on the other side, what does a serofast syphilis mean in the mom?
Dr. Muralee Sivarajan:
Right, this is another source of confusion for this essentially complex algorithm to look at congenital syphilis. So, some people they keep a low titer of either RPR or VDRL test, even after one year of effective therapy. And these people are known as serofast. So low titer for RPR will be 1:4 or less. And for VDRL, it would be 1:2 or less. So they are considered to be just maintaining the titers, it doesn't necessarily mean that they are infected still.
Dr. Neeta Goli:
And when we are assessing the results of these tests, what are some possible false positives and false negatives we might run into?
Dr. Muralee Sivarajan:
Right, so as we mentioned, these nontreponemal tests are not specific tests. So that means a lot of other things can give you positive tests and the list is pretty big for RPR or VDRL. So viral infections are a big offender like varicella, hepatitis, measles, Epstein-Barr virus, they can easily give you a false positive test. Malignancies like lymphoma, exotic infections like TB, malaria, leprosy, other inflammatory disorders like connective tissue disorders, endocarditis, those who are IV drug abusers, certain prescription drugs or even contamination with the Wharton's jelly, which is the jelly in the umbilical cord if you happen to take a cord sample. It can also be lab error or contamination with the maternal blood, or even recent immunization. False negatives are when you happen to do the test during the incubation period, so it doesn't have time to seroconvert yet. And also sometimes in late congenital syphilis, it actually tends to burn out even though you didn't treat the patient and these tend to sometimes turn negative. So, that can be also in long standing latent syphilis. There's also another phenomenon called prozone phenomenon. This is where you have really high titers of the antibody and it will initially test negative. However, if you dilute it down, it becomes positive. So, that's another source of error.
Dr. Muralee Sivarajan:
For the Treponemal tests they are generally specific however, there still are some caveats, that the treponemal tests like the TP-PA and CIA, they can cross react with infections due to some other spirochetes like yaws , other organisms like leptospirosis, rat bite fever, relapsing fever, and even Lyme disease. A false negative here would be again, early incubating syphilis.
Dr. Neeta Goli:
So if the diagnosis of syphilis is made prenatally in a mom, what is the recommended treatment?
Dr. Muralee Sivarajan:
Okay, so to understand this as a pediatrician, we have to have a basic understanding of the stages of syphilis, because when you are trying to ascertain a mom had appropriate treatment, we need to know that. So let me just run a brief overview about syphilis. So one can get infected after around on average three weeks, you develop the primary chancre. So this is the stage of primary syphilis, you may have some local lymphadenopathy. And this heals in around three to six weeks.
Dr. Muralee Sivarajan:
And then after around 30 to 60 days, you go into the stage of secondary syphilis, where you have the classic rash, which can be basically any type. It can be macular or maculopapular, pustular, or anything. Typically, it tends to affect the soles and the palms. Then we have a classic mucocutaneous lesions, you can also have a whole bunch of other things like lymphadenopathy, arthritis, nephrotic syndrome. Then we have the lesions known as condyloma lata, typically in the perianal region. So these symptoms can come and go for around 3-12 weeks. And of interest, this is something I tend to ask my medical students, so what stage is congenital syphilis? So I try to invoke their thought process there. And we get a variety of answers, but the answer is: it is a secondary stage of syphilis.
Dr. Muralee Sivarajan:
Now, well after the secondary stage, up to one year, you can have a period where it goes into what is known as early latent syphilis, here you're asymptomatic, and it tends to be pretty quiescent, but you may still be infected. So that's the early syphilis stage.
Dr. Muralee Sivarajan:
Then you get to the late stage, where you have after one year, it becomes late latent syphilis. So this is, again, an asymptomatic, those who have unknown status are lumped together in this category for treatment purposes. And then around 15-30 years later, you have then tertiary syphilis, where you have the classic lesions of gummas, cardiovascular syphilis, often aortic aneurysms and aortic insufficiency.
Dr. Muralee Sivarajan:
And what's important to note is at any stage during this, you can get neurosyphilis. So this doesn't necessarily have to be in tertiary syphilis, though that's a common stage. Early neurosyphilis can be like meningitis, chorioretinitis, optic neuritis, or late when you usually see this in the adult population, you have general paresis of the tabes dorsalis and you have that interesting pupil known as Argyll Robertson pupil, and you can have seizures, dementia, loss of vibration sense, and even psychiatric symptoms.
Dr. Muralee Sivarajan:
So, all these can be lumped into three groups for treatment purposes: early, late or unknown, and neurosyphilis. Early would be the primary, secondary and early latent, which is up to one year from infection. These moms get a dose of benzathine penicillin G, around 2.4 million units as a deep IM shot. To add to the confusion, our obstetric department sometimes gives them two doses. This is for a safety purpose, but that tends to confuse us sometimes thinking, "Oh, well, she was supposed to get the next stage of treatment, which would be three doses, and didn't go there." So, again, it's important to look at what stage they were treating. Then we have the late or the unknown. So this includes everything after the early latent. So that will be the late latent and tertiary and the unknowns. Here the benzathine penicillin is bumped up to three shots at weekly intervals. They're pretty strict in the requirements. You have to repeat the course if it was given less than one week apart or more than 14 days between two shots.
Dr. Muralee Sivarajan:
If you are in the state of neurosyphilis, then you can't do any of these long acting penicillins. You have to do aqueous crystalline penicillin, usually as an IV infusion over 10 to 14 days. So it's important to check history of treatment if you need documentation. So we typically will call up the Department of Health. Locally they do not treat moms after 20 weeks, they leave the obstetricians to treat them because of slightly higher risk of a certain reaction called the Jarisch-Herxheimer reaction. So we need to check both the obstetric records and the Department of Health to get some valid dates.
Dr. Muralee Sivarajan:
In the US, non-penicillin drugs are not recommended. Penicillin is the drug of choice. This is one instance where if the mom gives a history of allergy to penicillin, you may need to do a skin test to confirm that, and if she is truly allergic, you have to desensitize the mom, and then treat with penicillin. So in other parts of the world, the WHO does recommend non-penicillin regimes where you may not have easy access to benzathine penicillin. So, such regimes are not recommended in the US, so we have to be careful about that.
Dr. Neeta Goli:
If we have a baby born to a mother with syphilis, how do we determine whether her treatment was adequate?
Dr. Muralee Sivarajan:
Yes, so this would mainly come from the documentation. We have to make sure it was a penicillin treatment, it was more than four weeks from delivery, and it was appropriate for her stage of disease, and there have been no concerns of reinfection.
Dr. Neeta Goli:
And what risk factors are associated with the infant acquiring congenital syphilis from the mom?
Dr. Muralee Sivarajan:
So unfortunately, syphilis is higher in the Black population, followed by Native Hawaiian and Pacific Islanders, and generally points to socioeconomic issues. Also other risk factors are IV drug abusers, sex workers, lack of insurance and healthcare, and living in areas of high morbidity.
Dr. Neeta Goli:
Is congenital syphilis typically transmitted during pregnancy or the actual delivery process?
Dr. Muralee Sivarajan:
So, congenital syphilis is usually a vertical transmission, which means it crosses the placenta. And the transmission rates approach around 60-100%, depending on the stage, if it’s primary or secondary. If it’s early latent, it becomes around 40%, and falls even more to 8% for late latent syphilis.
Dr. Muralee Sivarajan:
In untreated early syphilis, up to 40% of pregnancies will abort or may be a stillbirth. And in treated cases, the transmission can be dropped around 1-2% on average. Rarely, you can get horizontal transmission, which means the mom passing on an infant around 30% on an average, though, if the mom has mucocutaneous lesions, these may be more infectious.
Dr. Neeta Goli:
You mentioned earlier that congenital syphilis is considered a secondary rather than primary stage. Why is that?
Dr. Muralee Sivarajan:
Yeah, so for congenital syphilis, there's obviously no primary chancre because the organism is crossing the placenta and entering into the bloodstream and spirochetal phase directly and it is seeding the various sites. So the features you see are typical of secondary syphilis, like you have a rash, basically it can affect almost any part of the body. And those are the typical symptoms you see in secondary syphilis.
Dr. Neeta Goli:
Okay. What is our approach to evaluation of babies whose moms have a history of syphilis?
Dr. Muralee Sivarajan:
Okay, this is where we go hunting for the Red Book for the congenital syphilis algorithm. So it's a complex algorithm, because it's a treacherous way of driving, I would say. You have so many caveats there that you have to really be an expert driver or for the average person who may not be dealing with this very often, dust off your Red Book and then go through it.
Dr. Muralee Sivarajan:
So you need to ask four questions before you assess the issue. So these four questions are:
Dr. Muralee Sivarajan:
So, once you have this data, then you hit the algorithm. So, the AAP's algorithm is there in the Red Book, which is pretty much what we use for infectious diseases in pediatric practice in the US. This will give you the different possibilities for treatment. So, there is a risk stratification and appropriate treatment from the algorithm. So, to go through this, typically, one will screen a mom with a nontreponemal test like an RPR. And if this is positive, you would confirm that with a specific test like the Treponemal TP-PA test, keeping in mind false positives and negatives.
Dr. Muralee Sivarajan:
Now, of late, we have something called reverse sequence screening, which is what our hospital is doing currently. And this is a situation where you do it the other way around. So you do the specific test first. So, you start with the treponemal test. And the reason for this is because these tests can be automated and they are more cost effective. And there's also a clinical benefit. They help to detect the late and late latent syphilis, because the RPR may turn negative in these late situations. The issue with doing the specific test is that they can miss incubating syphilis as they take a little bit longer to seroconvert. And if you look at the false positive rates, they can be a little bit higher in low prevalence populations.
Dr. Muralee Sivarajan:
Now, once the treponemal test is positive, you have to remember it does not differentiate active from treated cases. So you still have to do the RPR. If the RPR is positive, it comes from syphilis, then you have to check for history of treatment, and what were the previous titers. If the RPR is negative, then what you do is do a second specific test.
Dr. Muralee Sivarajan:
In our hospital, you start off with the CIA, you do the RPR, and then if you have to do the second treponemal test, it’s something called TP-PA on the same specimen of blood. If the second test is also positive, what it tells you is it is either a past or current syphilis. So this can be either untreated late latent, you analyze otherwise by exam of history. If negative, the initial treponemal test was a false positive.
Dr. Muralee Sivarajan:
However, to add to the confusion, you can repeat this in 2-4 weeks in case you have a situation where early syphilis was incubating. Now, from our algorithm, this will bring us into four categories for evaluation and treatment. It is either one, your proven are highly probable, two possible, three less likely, four unlikely congenital syphilis. So these are the four situations and for that there is again another chart, which lumps what are the situations you will find from proven to unlikely.
Dr. Muralee Sivarajan:
When you screen the newborn, it is recommended you draw the blood directly from the baby rather than a cord sample, because of a potential false positive from contamination of Wharton’s jelly. And then of course, when you're screening a baby, it may include other tests like x-rays, LP, CBC, LFT, and hearing test. If you do an LP, one should remember if you cannot interpret it because it's technically sometimes challenging to do an LP on a newborn and you may get a traumatic tap or you may get a dry tap. And if you cannot interpret the CSF, you should be considering it as a positive tap and treat the baby accordingly.
Dr. Neeta Goli:
What signs should we look for on physical exam of babies born to mothers with a history of syphilis?
Dr. Muralee Sivarajan:
So, it's important to realize that only 50% may show any signs or symptoms of congenital syphilis. This disease has been labeled the great masquerader because you can have a plethora of signs and symptoms when they do present. And this has prompted Sir William Osler to quote, “the physician who knows syphilis, knows medicine.” Now, we can lump them again into early congenital syphilis, which is up to two years, and late, which is after two years. Early congenital syphilis, it could be asymptomatic as we talked about earlier, or it could be baby with stillbirth, or a preterm baby, or baby with hydrops fetalis, or a low birth weight baby.
Dr. Muralee Sivarajan:
And then you could have a whole bunch of other conditions like hepatosplenomegaly, jaundice, snuffles, so these babies have a lot of secretions coming out of the nose, and a rash which can be pretty much any type, lymphadenopathy especially the epitrochlear nodes may be enlarged, and then you may have a whole bunch of skeletal abnormalities. You can find some fissures around the lips, the nose, the anus, mucous patches, condyloma lata, failure to thrive. You can have what is known as pneumonia alba. An interesting condition is something called pseudoparalysis apparent. These babies sometimes don't move their arms, because they have a lot of pain due to the bony involvement.
Dr. Muralee Sivarajan:
They can have myocarditis, chorioretinitis, glaucoma, ileitis, necrotizing enterocolitis, nephrotic syndrome, they can have pituitary gland being affected causing hypoglycemia, diabetes insipidus, they can have a Coombs-negative anemia, low platelets, high or low white count, and the placenta also may show you some findings as we talked about earlier. Late syphilis are the typical features we know of, you have the abnormal faces that can be a frontal bossing, a saddle nose, a sharp maxilla, protuberant mandible. Actually, there's a Rembrandt painting which depicts this situation.
Dr. Muralee Sivarajan:
You can have interstitial keratitis, glaucoma, scarring of the cornea or optic atrophy. You can also have sensorineural hearing loss. Interestingly, even though we screen all newborns for hearing loss, this can manifest around 8-10 years of age. We have the classics Hutchinson’s teeth, they’re hypoplastic, notched, and tapering, widely spaced permanent incisors, and mulberry molars. These are the hypoplastic molars, they have many cusps in them. And we have a whole bunch of symptoms which are secondary to gummas which can destroy an organ or cause pressure symptoms. So like it can destroy the hard palate. Then we have things like the rhagades, the saber shin, we have an interesting sign called Higoumenakis’ sign, which is an X ray finding on the clavicle, Clutton joints which are basically painless. We can have paroxysmal cold hemoglobinuria. And then there's something called the Hutchison's triad, which is a three symptoms: the interstitial keratitis, sensorineural hearing loss and the Hutchison's teeth. 40% of patients with congenital syphilis can have neurosyphilis also.
Dr. Neeta Goli:
Okay, so truly the great masquerader.
Dr. Muralee Sivarajan:
Absolutely.
Dr. Neeta Goli:
So how might we expect the newborns' lab parameters to be affected by congenital syphilis?
Dr. Muralee Sivarajan:
So classically, we get hold of the RPR or if you're doing a VDRL, that would be the nontreponemal or the nonspecific test. So we do that. We don't have to necessarily do the specific tests because usually that's going to be positive because of transplacental transfer. What you're doing is trying to look at the titers of the RPR. So the RPR should not be greater than the mom's RPR, because if it is, that's a problem. If it is equal to a less than the mom's RPR, it can be just a transplacental transfer of the mom's antibodies. Of course, you have to look at the whole picture if there are other reasons to think that may not be the situation, then you have to do a whole bunch of labs and possible treatment.
Dr. Muralee Sivarajan:
The other things you can find, they can have deranged LFT with raised alkaline phosphatase, ALT, AST, direct bilirubin, or gamma glutamyl transferase increase, can also sometimes bump up the prothrombin time. And these results tend to normalize slowly, even without treatment. And CSF is again a part of the evaluation whenever you evaluate a baby if you have to do an LP. And this can be a little bit of confusion because the cell count per CDC should be less than 5 WBCs per microliter, though normally you can see up to 25 in newborns. And the protein is another thing you look at in the CSF and per CDC, it should be less than 40 milligrams per dL, but up to 250 can be seen in term, and 170 can be seen in preterm. So, even though that can be seen situation, for practical purposes, we should use the CDC cutoff, which I just mentioned.
Dr. Muralee Sivarajan:
From a CBC perspective, you may see low platelets, low hemoglobin, low white cell count or even higher white cell count. And there's a whole bunch of other things, abnormal findings in x-rays or abnormal neuroimaging and an abnormal hearing screen.
Dr. Neeta Goli:
And if the baby does fall into category, which requires an LP, why do we only send the CSF for VDRL and not RPR?
Dr. Muralee Sivarajan:
Yes, thanks for asking that question. That's something I always wondered and had to ask an infectious disease person. So we should not be doing the RPR because it's not been standardized for CSF, and there's little available data. The VDRL on the CSF has around 54% sensitivity and 90% specificity. You can still get a false positive, like if you have a traumatic LP, it can be just a baby's blood passing over and contaminating and giving a positive result. Or sometimes even maternal antibodies can cross over unfortunately. So it's not that clear cut always.
Dr. Neeta Goli:
And can you describe some X-ray findings we might see in congenital syphilis?
Dr. Muralee Sivarajan:
Yes. So we quite often do wonder where should we screen the baby for X ray findings and sometimes we end up taking a babygram, but you're looking mainly at the long bones. So you can see pathological fractures, metaphyseal lucency or demineralization. You can have something known as the Wimberger sign, where you have medial proximal tibial metaphases involvement. The metaphases can sometimes give us what is known as a celery stalk appearance. Then you may see the Wegner sign, this is where you have a metaphyseal serration on the X ray. You might get diaphyseal periostitis or sclerosis, or sometimes even a moth-eaten appearance. And then you have the Higoumenakis’ sign. This is where you have the medial end of the clavicle is enlarged and this is a late sign that may not be seen in the term babies.
Dr. Neeta Goli:
Okay. Per the AAP Redbook 2018 guidelines, if the baby falls under either congenital syphilis less likely or congenital syphilis unlikely, the only lab evaluation we do on baby is a one-time RPR. If the RPR comes back nonreactive or less than fourfold greater than the maternal RPR, what are our next steps in treatment of the baby?
Dr. Muralee Sivarajan:
Right. So as per the Redbook, we have these four categories we talked about earlier, which is proven or highly probable, possible, less likely, and unlikely. So you're asking specifically for what to do in the less likely scenario. So here, we don't have to do all the investigations. We do the RPR, as you correctly mentioned, and we assume that the infant exam was also normal here, and we clarified that mom had adequate treatment. If there’s no evidence of a reinfection, then what we can do is give the baby a shot of Bicillin, which is benzathine penicillin, 50,000 units per kilogram, IM, as a single dose. So this is the preferred scenario.
Dr. Muralee Sivarajan:
The basic thought process is, if you're in doubt, treat, because syphilis is so easily prevented by an appropriate shot of penicillin, whereas when you miss it, the consequences are devastating, and some of them can be lifelong. There are some caveats to remember in this, you might need to follow up the baby closely in the outpatient clinic and see what these titers are also doing.
Dr. Neeta Goli:
And then if the baby falls under the AAP Redbook categories of either proven or highly likely congenital syphilis or possible congenital syphilis, or if they have abnormal physical exam findings, or an RPR that's greater than fourfold maternal RPR, what are our next steps in management and treatment of those babies?
Dr. Muralee Sivarajan:
Okay, so these categories proven/highly probable or possible, the treatment is a little bit different. We have to do a better workup in terms of an LP and doing a CBC and LFTs and some long bone x-rays. Once we arrive at that conclusion, it fits into one of these two categories, then we have to go aqueous crystalline penicillin. So it's not a long-acting preparation anymore, around 50,000 units per kg IV every 12 hours till they're one week old. And then after one week, it can go up to every eight hours for infants older than one week. For a total of 10 days is what is given. So that's the gold standard. Now, there are some caveats where you might consider procaine penicillin, but most people favor the aqueous crystalline penicillin, because the penetration of procaine penicillin into CSF may not be that good.
Dr. Neeta Goli:
What complications might we see from the treatment?
Dr. Muralee Sivarajan:
Okay, so in terms of complications, you might see some allergic reactions. It's very unusual to see an allergic reaction with a first shot, because usually the babies haven't been sensitized to it. But that's certainly something which may develop in the coming days when you have a 10-day treatment.
Dr. Muralee Sivarajan:
The other thing you might see, and this is more common in the adult population, there's something called the Jarisch-Herxheimer reaction. So this is a situation where you get fever and exaggeration of symptoms, or you may have a rash and fever. If it's an older population, they may complain of a headache, myalgia, they can also be hypertension, cardiovascular class, this is due to release of large amounts of the treponemal liposaccharide, which elicits a cytokine response. You see this within a couple of hours, and it can go up to eight days and then resolve after around 24 to 48 days after you treat.
Dr. Neeta Goli:
What are the follow up recommendations for these babies?
Dr. Muralee Sivarajan:
So this is a very important point. We sometimes think we have treated the baby and we are done with it. And we always err on the side of caution just to bypass that situation where you might encounter a poor follow-up, and then miss potential infection growing in the baby. So most babies in the US here get regular well child visits around two, four, six, nine, and 12 months. So once you have treated the baby, you follow the baby both by physical exam and serology. So during one of these visits, you can check the RPR which should be checked at around two to three monthly intervals till they turn negative.
Dr. Muralee Sivarajan:
It is recommended that you retest an infant RPR at three months, even if the baby was initially negative, if the mom was positive and congenital syphilis is unlikely. An example of that would be the serofast syphilis. So neonates with a negative RPR at birth and whose moms were positive at delivery, need to be retested at three months to rule out a serologically negative incubating congenital syphilis.
Dr. Muralee Sivarajan:
Now, the RPR titers tend to usually drop by around three months, and they become negative by around six months and very rare for them to persist beyond 12 months. If it persists, this necessitates another full workup and retreatment. Now, the specific tests is not something we usually check for, but if you should check them, they usually turn negative around 15 months. And this is because these are transplacental transfer of antibody, and they usually get degraded by this timeframe. However, if they're positive at 15 months, it is suggested you repeat it again at 18 months. And if it is still there, it means the baby actually had congenital syphilis. So that is generated from the baby and not from the mom. But this is not something you use to check a treatment response.
Dr. Muralee Sivarajan:
Now, if you have done an LP and that is abnormal, then it is required to repeat the CSF every six months until it reaches normalcy. If the CSF was initially normal, that's okay. You don't have to keep repeating it.
Dr. Muralee Sivarajan:
A treatment failure is indicated by the RPR not declining by 6-12 months or rising at any time after treatment. So these babies should be rescreened. This includes an LP and then treated again for 10 days. Before you assume that this was a treatment failure, we as pediatricians, we have to be cautious. We should consider a new infection as a potential sexual abuse and we want to screen the siblings because they are also at risk. The other source of infection could be a new episode of syphilis in the mom and the horizontal transmission of the organism.
Dr. Muralee Sivarajan:
An absence of more than four-fold titers does not rule out congenital syphilis. One interesting fact about congenital syphilis, it does not give protection for subsequent syphilis infections in later life like some viral infections may. And even if you treat this condition in the first three months, they can still manifest some of the late signs like saber shins or interstitial keratitis.
Dr. Neeta Goli:
To end the episode today, do you have any advice for our listeners while they care for newborns?
Dr. Muralee Sivarajan:
Yeah. Always approach this in a holistic way. Look at the needs of the newborn in conjunction with the family. Confidentiality is certainly an issue, the family or the partner may be unaware. Remember, this is a reportable disease. In our hospital, our labs do this directly on our behalf to the Department of Health, but you are still responsible for that. Contact tracing and treatment is important. Again, the social services get involved, the public health authorities get involved, we can sometimes get the Child Life services involved to help the parents who may be facing some distress.
Dr. Muralee Sivarajan:
Partners who were exposed within 90 days preceding the diagnosis of primary, secondary or even early latent syphilis in the index patient should be treated presumptively for syphilis, even if they are seronegative. There are some situations in different parts of the world where there may be penicillin shortage, so these patients may come in to the US from different parts of the world and not get that medication. So you can look at the CDC website or the FDA website when you encounter certain drug shortages.
Dr. Muralee Sivarajan:
Our policy is for some babies to be covered with ampicillin and gentamicin in a rule-out chorioamnionitis situation while the blood cultures are cooking. And so you might think, oh the baby already got some ampicillin, would that be enough? The answer is no, you still have to give that particular dosage we mentioned and the particular type of penicillin. So, depending on the stage we are looking at, if it is crystalline penicillin, you have a certain dosage, and if it is benzathine penicillin, it's a long-acting form which keeps the serum levels for around three weeks or so. So the ampicillin dose you got is not sufficient. It might partially treated or suppress it, but you haven't essentially treated the condition. We already talked about this, but I'll touch on it again. There's a lot of subtlety and variation in signs and symptoms, so we always use the safety first approach and we err on the side of treatment especially if follow-up is unsure.
Dr. Muralee Sivarajan:
Other thing to remember is transmission to healthcare workers. So we generally say contact isolation of the index case until 24 hours of antibiotics and usually is not contagious after that. Remember, you should be using your gloves; these lesions on the baby are secondary syphilis and they're very contagious. You can acquire them also from the lab specimen. So, all the nursing staff collecting any specimens have to be very careful as should the laboratory workers.
Dr. Muralee Sivarajan:
Syphilis serological test should be performed to exclude pre-existing syphilis and exposed persons may also receive prophylactic penicillin. So you can give them a shot of benzathine penicillin, 2.4 million units maximum typically is 50,000 units per kg intramuscularly. This will prevent the health care worker who was exposed, seroconverting to the treponemal-specific test which can persist for life. Alternatively, you don't have to give the penicillin, you can just closely monitor them clinically and do an RPR in three months or earlier if there are symptoms, and treat only if required.
Dr. Neeta Goli:
Thank you so much for joining us today for this discussion, Dr. Sivarajan.
Dr. Muralee Sivarajan:
You're most welcome. Thank you for championing our podcast Dr. Goli. Thank you so much.
Dr. Neeta Goli:
Thank you. Have a good day.
Dr. Muralee Sivarajan:
You too. Thanks. Bye.
Dr. Neeta Goli:
Thanks for listening to Newborn News. We hope you'll join us next time. If you like what you hear, make sure to subscribe and leave us a review. If you have questions, comments, feedback or suggestions for future episodes, please email me at NewbornNews@utsouthwestern.edu. As a reminder, this content is educational and is not meant to be used as medical advice. Views or opinions expressed in this podcast are those of myself and my guests and do not necessarily reflect the views of the university.