Epstein-Barr Virus: Diagnosis, Management, and Return to Play – PediaCast CME 122
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Show Notes
Description
Dr Jason Newland visits the studio as we explore Epstein-Barr Virus and infectious mononucleosis. When should this diagnosis be considered? What diagnostic tests are most helpful? When are corticosteroids appropriate? And what should we tell student-athletes about their return to sports? Tune in for answers to these questions… and more!
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Topics
Epstein-Barr Virus (EBV)
Infectious Mononucleosis
Presenters
Dr Mike Patrick
PediaCast and PediaCast CME
Nationwide Children’s Hospital
Dr Jason Newland
Chief of Pediatric Infectious Diseases
Nationwide Children’s Hospital
Learning Objectives
At the end of this activity, participants should be able to:
- Describe the virology, transmission, and natural history of Epstein-Barr virus infection.
- Interpret common laboratory studies, including heterophile antibody testing and EBV-specific serologies.
- Differentiate uncomplicated infectious mononucleosis from important complications requiring additional evaluation or intervention.
- Apply evidence-based recommendations for management, corticosteroid use, and return-to-play counseling.
Links
Pediatric Infectious Diseases at Nationwide Children’s Hospital
Epstein-Barr Virus (EBV): Biology and Clinical Disease (Cell)
Epstein-Barr Virus Infections (Infectious Mononucleosis) (Red Book)
Infectious Mononucleosis (NCH Patient Information)
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Episode Transcript
[Dr Mike Patrick]
This episode of PediaCast is brought to you by Pediatric Infectious Diseases at Nationwide Children’s Hospital.
[MUSIC]
[Dr Mike Patrick]
Hello everyone, and welcome to another episode of PediaCast CME. We are a pediatric podcast for healthcare providers.
This is Dr. Mike coming to you from the campus of Nationwide Children’s Hospital. We’re in Columbus, Ohio. It’s episode 122.
We’re calling this one Epstein-Barr virus diagnosis, management and return to play. I want to welcome all of you to the program. We are so happy to have you with us.
You know, Epstein-Barr virus is one of the most common viral infections. In fact, most everyone shows evidence of past infection at some point during their life, whether you remember having the disease or not. So, it can definitely be mild versus moderate versus pretty severe.
And it does generate a lot of important clinical questions along the way. You know, when should we suspect EBV? Which diagnostic tests are most helpful?
When are corticosteroids appropriate? How long should patients avoid sports? And what should providers know about the viruses association with malignancy and other long-term conditions?
Today, we are going to review the science, clinical presentation, diagnosis, management and complications of Epstein-Barr virus infections in children and adolescents. Plus, we’ll answer the question on the minds of student athletes. When can I return to playing sports after a case of infectious mononucleosis?
Of course, in our usual PediaCast fashion, we have a terrific guest joining us in the studio to discuss the topic. Dr. Jason Newland. He is chief of pediatric infectious diseases at Nationwide Children’s.
Don’t forget after listening to this episode, you can claim free category one continuing medical education credit. Really easy to do. Just head over to the show notes for this episode.
Again, this is one 22 episode one 22 over at PediaCast CME.org. You’ll find a link to the post-test in the show notes. Follow that link to cloud CME, click on the materials tab and taken past the post-test.
And then the category one credit is yours. And we do offer credit of course, to physicians, but also nurse practitioners, physician assistants, nurses, pharmacists, psychologists, social workers, and dentists. And since Nationwide Children’s is jointly accredited by all of those professional organizations, it is likely we offer the credits you need to fulfill your state’s continuing medical education requirements.
Of course, you want to be sure the content of this episode matches your scope of practice. Complete details are available at PediaCast CME.org. Also want to remind you the information presented in every episode of our podcast is for general educational purposes only.
We do not diagnose medical conditions or formulate treatment plans for specific individuals. Also, your use of this audio program is subject to the PediaCast CME terms of use agreement, which you can find at PediaCast CME.org.
So, let’s take a quick break. We’ll get Dr. Jason Newland settled into the studio, and then we will be back to talk about Epstein-Barr virus and infectious mononucleosis. It’s coming up right after this.
[MUSIC]
[Dr Mike Patrick]
Our guest today is Dr. Jason Newland. He is chief of infectious diseases at Nationwide Children’s Hospital and a professor of pediatrics at the Ohio State University College of Medicine. And he is an internationally respected clinician, educator, and infectious disease expert. Today, he will help us explore one of the world’s most common and interesting human viruses, the Epstein-Barr virus.
Before we dive in, let’s offer a warm PediaCast CME welcome to our guest, Dr. Jason Newland. Thank you so much for stopping by the studio today.
[Dr Jason Newland]
Dr. Mike, thank you for having me. It’s a true pleasure. And I appreciate I get to come back on and do one of your podcasts.
[Dr Mike Patrick]
I am excited to have you here. And I’m also really looking forward to this conversation because I think that as teenagers, whether we know it or not, the Epstein-Barr virus actually is one of the things, probably one of the first viruses that really can impact us as we think about teens getting mono is sort of the classic example. But I do know that the Epstein-Barr virus expresses itself in many ways.
And so, let’s just start with the basics. Can you sort of explain where Epstein-Barr virus fits in the world of viruses? Sort of what exactly is it and why is it important for us to consider?
[Dr Jason Newland]
Well, I think, you know, Epstein-Barr virus, as you mentioned, it’s just, it’s part of being a pediatrician. And I think your audience, as you know, I mean, they’re the experts at this. They can probably teach us sometimes you and all of that, because you see it all the time.
And as a pediatric infectious diseases doctor, I’d say I probably neglected it in my career until I joined the faculty here at Nationwide Children’s. And as an infectious diseases doctor, I take care of some of these patients on our dedicated infectious diseases work. And I’m like, this thing is unbelievable.
But so, Epstein-Barr virus probably first described clinically in 1885. And then again, in 1889, where they described this glandular fever in 1920, they identified that the lymphocytes were atypical, which we all learn, right? They look and say, hey, they’re too, but they still hadn’t identified the virus until 1964 in Burkitt’s lymphoma.
And again, we’ve all learned this, right? We can all trigger back that piece. Now it’s a DNA virus.
And it’s a herpes virus. And I think, right, why is that important for you? For you all is that, well, if it’s a herpes virus, that means you always have it, right?
Once you get it, you don’t get rid of it. It has a lytic phase, right? Where it’s killing cells, but then it has a latent phase where it just kind of goes in a dormant, right?
So, once you have it, you always have it. And it is so prevalent. They all say that in childhood about 50% will have had a contact with her in fact, I should say infected with it.
And by teenage years, it’s about 87% and worldwide, it’ll be up to 95% will have had EBV, right? Seroprevalence meaning antibodies to EBV. I mean, it is so prevalent and it does all kinds of things that frankly, I think we probably need to learn and learn and learn.
And how do we deal with it is an ongoing thing that I feel like there’s even more work to be done.
[Dr Mike Patrick]
Yeah. Yeah. Now, as we think about that latency period and the herpes virus family, you know, regular herpes, herpes simplex virus and varicella zoster virus, those kind of hang out in their latent phase in nerve cell bodies, right?
So, what about the EBV virus? Where does it hang out when it’s latent?
[Dr Jason Newland]
I want to give you the keys are we think of lymphoma. So, it latens in the B cell, right? So it goes in these important immune cells, but it’s also an epithelial cell.
So, I going back to my reading to be ready for this, Dr. Mike, right? Nasopharyngeal carcinoma associated with EBV and in certain countries and certain ancestries, a greater risk that, so the epithelial cells could also be a place where it sets up its latency. But to your point, which is important, right?
These herpes viruses, they go dormant in different cells, herpes simplex, varicella zoster, and nerve cells. EBV goes into your B cells, epithelial cells. And what’s intriguing about this, Dr. Mike, is that while we see reactivation in herpes where you can get, you know, zoster, which I don’t want, that’s why I’m going to be vaccinated and obviously herpes simplex was cold source and such. You can see in ICU patients that you might find viremic with EBV. We don’t know what that means, but we know if you become immunocompromised, EBV can be a problem because you can get a like post-transplant lymphoproliferative disorder because you have this EBV in your cells. Now I’ve knocked down my normal immune system and now that thing gets going.
[Dr Mike Patrick]
Yeah. Yeah. You know, you mentioned that by late adulthood, virtually everybody has been, shows evidence that they have had a past EBV viral infection, but the vast majority of people, if you just, you know, took a hundred people off the street, probably the majority of them are not going to remember them ever having had EBV.
What is, is it viral load? Is it the, the immune system? Is it a combination of those things that makes it different from one person to another in terms of what that infection looks like?
[Dr Jason Newland]
Well, I find this an intriguing question cause I’m not sure it’s as well delineated as I wish I could find. Right. And I’ll give you some more resources to put up on the notes and for people to look at, you know, this notion that if you get EBV when you’re four or five, you won’t even recognize it, right?
Like as a pediatrician, it you maybe if you had a big lymph node, but that’s not how it presents. It presents was like a non-sub-acute febrile illness that may not even come to your office to be seen versus if you’re a teenager, right? That’s the kid that shows up like, Oh, five, seven days of kind of indolent and then this horrible sore throat, right?
Like it’s, and that makes sense, right? Cause we know the transmission is saliva base, right? So, saliva is the primary transmission kissing disease, right?
We’ve all heard that, right? That, that piece. Then it replicates in the salivary glands, it hits your tonsils.
And I’m telling you, I’ve seen the worst sore throats ever in regard to this. And they all get admitted to the hospital to the ID ward and they won’t want to eat or drink at all because it’s so terrible. And you look in their throats and you’ve all eyes have done this and you’re like, what has happened, right?
You’re thinking this has to be group-based stress. Oh my gosh, there must be a peritonitis or abscess. But the reality of it is that’s the person is teenage years, whether it’s development, whether it’s hormonal, these pieces that that response is much greater there than you see in the infant, the, the, I say infants or the childhood age.
And, and I think that, and I don’t, there’s other diseases we’ve seen that one might argue that some of the long COVID stuff, right. We’ve seen more in teenagers and adults, probably some immune mediated piece, but I don’t feel like it’s delineated as clearly as I wished, but we all know that the teenager’s the one we worry about and that we see.
[Dr Mike Patrick]
Yeah. Yeah. Is, is some of that, the vigorous response of the immune system.
So, you know, when we, when we think about viral infection, you can have symptoms that are from the damage the virus is doing at the cellular level, but you can also have symptoms that are really your immune system, sort of over responding maybe, although maybe it needed to be that strong to eradicate the virus. I don’t know.
[Dr Jason Newland]
Well, I think this is in lies, these questions around where steroids come into effect, right? Where is the importance of really knocking down the immune system versus not? Because it’s clearly part of this is immune mediated versus is it all virus?
And this is, we can talk about a number of ours, right? Let’s talk about inner viruses. We’re sitting here in summertime and we see myocarditis.
Well, we don’t always find the virus, but we find immune cells similar here. I think this is this notion of this interplay between the viral pathogen and the immune system’s response. And let’s be frank, like in all of our careers, I’m, I’m started year 21 as an attending physician, as a pediatric infectious disease doctor, that the understanding and science of immune system and then all the different factors is only been exploded over this time.
And I think that’s why it’s not just the virus. There are clearly immune reactions and look, this virus goes after your immune cells, right? It goes after B cells.
It goes after T cells, natural killer cells. We know that’s one of the places it likes to infect. Yeah.
Yeah.
[Dr Mike Patrick]
What makes this different than HIV in terms of the cells that it infects?
[Dr Jason Newland]
Yeah. This one’s more B cell versus more of the T cell pieces in regard to that. And then obviously does a way more impact on those key viruses.
And it continues to kind of destroy those virus, those cells versus EBV as a herpes virus just goes latency, right? It’s not going to kill all of it though, right? We know that once you have HIV, you always have HIV.
And can you kind of get rid of some of those, those reservoirs? But I think that’s kind of the bigger piece B cell versus T cell though, though EBV can hit some of your T cells. Hence why we’ll see T cell lymphomas or T cell leukemias associated with EBV, which we can get into why the steroid thing becomes scary for people.
[Dr Mike Patrick]
Yeah. Yeah, absolutely. In terms of, of the degree of symptoms and then I think about reactivation.
So, you have that latency period. And as physicians we know when someone has herpes simplex virus, when they’re stressed out or their immune system is taking a hit, then it reactivates and the, you know, the virus travels down and causes problems again. Do you see that also with latent EBV?
[Dr Jason Newland]
Not, not in the normal host, right? Like we don’t see this notion of reactivation in the normal host. Where we see it is if you get a transplant, if you have leukemia potentially these other features that could, you know, change your immune system to kind of well contain this virus to just keep it as part of what you’re living with.
I think this, this, this is why I’m so intrigued by this virus, right? Like we know that if you have multiple sclerosis, a hundred percent, we’ll have had EBV. Now is that association causation?
Where does that fit? We know EBV attacks B cells. We know that multiple sclerosis is an auto immune sort of phenomenon, right?
Attacking these things. So, lupus, right? Another sort of complication.
We know you that pretty much everyone with lupus has had EBV. Now 95% of the population is, yes EBV, but so you can see this. And you can see why there’s more and more like look into this notion of EBV and association with these chronic diseases.
There’s a recent science paper that further delineated why maybe the molecular mechanisms of why this might be the explanation for lupus and get it more at causation than association. So, it’s a really intriguing piece about what this virus means for long-term health in regards for people, but it’s very common, right? We’ve all had it.
I’ve had it. I know I’ve tested monospot positive, which by the way, I know we will get to, but for that in regards. Yes.
[Dr Mike Patrick]
In terms of diagnosis. So, the first thing is who do you diagnose? You know, if this is something that can be, you know, especially in younger kids, sort of a mild to medium febrile viral infection, we’re not testing all of those kids for EBV.
So how do you decide when to test and then what is the best way to accomplish that?
[Dr Jason Newland]
Yeah, well, I mean, I think to your point, sometimes is how I’ve had the person come here to my, you know, this is a second or third visit and I’m like, and I’ve done the viralness. I think EBV is a very appropriate virus to be testing for because of its wide range of constellation of symptoms. And the monospot test is a good test for most individuals, though it doesn’t have the sensitivity we can get that.
There’s no doubt the teenager that one might say looks like a duck, sounds like a duck, is probably a duck. I think it’s reasonable to test, right, because we know that helps the family. And we also know there’s significant complications as well as precautions one might need to do in regard to having acute EBV that we will talk about.
So, to me, the five, six-year-old who comes in with a febrile illness, you don’t have to test for EBV. I mean, like we know that these could be a self-limit and it’s probably not worth it with facing the tests. And do we need to do blood?
That’s OK. The teenager that shows up probably needs to be tested for the potential for what the complications could be, especially around the precautions regarding the spleen, which we’ll talk about.
[Dr Mike Patrick]
Yeah, yeah. Let’s kind of walk through EBV serologies, because when we order well, well, actually, let me take a step back. Let’s start with the monospot.
This is a heterophile antibody test. What the heck does that mean?
[Dr Jason Newland]
Well, you know, Dr. Mike, as a pediatric infectious diseases doctor, I was sitting to myself, well, what’s the heterophile antibody? Then I realized maybe today I didn’t even know what heterophile was. And so, thank you for having me on so that I can learn.
But the heterophile means that we have antibodies that will cross react with other species, so other antigens, other species. So, our monospot test is testing for an antibody that will respond to either sheep, red blood cell antigens or horse equine antigens. Most tests now are horse.
And what happens is it’s an IgM antibody that agglutinates, right? Clumps up the red cells. And we all, you guys have them in your offices.
You have the monospot. It probably has a line. It’s just showing agglutination.
And so that’s it. It’s just basically our antibodies respond, react with another species antigens.
[Dr Mike Patrick]
So, it just so happens that when we have an active mono infection, that the antibodies that we’re making will attach to horse red blood cells. And how in the world, you’re not going to know the answer to this, who figured that out and how did that come to pass?
[Dr Jason Newland]
I think the person is, it’s the Brunel. I think it’s Paul Brunel, because I was reading more. I think they kind of recognize this, right?
If I take blood from this person and put it on these, I don’t know the back history, I wish I did, Dr. Mike, because that would be a pretty awesome story to be able to tell everybody. And maybe I’ll let you know, and you can share it with, uh, on another episode or some other time.
[Dr Mike Patrick]
Or, you know, we’ll have you back on to talk about another virus. And when we open, we’ll say, hey, let’s revisit enteroviral antibodies.
[Dr Jason Newland]
I’m all for it, right? Some of the history stuff is super fun to see how we got to where we are, but it’s an amazing discovery and obviously was super helpful and is super helpful, right? I can just do it in the office.
It’s rapid. Now, I think it’s important to know the limitations. Number one limitation is it’s sensitivities can be between 50 and 80%, meaning, right?
You’re going to have a lot of false negatives in regard to that. Under four years of age, it doesn’t operate as well. It is a very specific test.
Meaning if it is positive, you can feel pretty good, right? Like you can feel pretty good that you’re going to not, it’s the false negative. I should say the false negative rate is wrong there.
Sensitivity means, right? Like you, it’s just not good. You can miss some for sure.
So, but good and specific test, great specific test.
[Dr Mike Patrick]
So, if your monospot is positive, you can guarantee that whoever you tested it on has an active case of mono, not latent, but the active version.
[Dr Jason Newland]
That’s exactly right.
[Dr Mike Patrick]
And as kids get older into the teenage years, it does become more reliable. The younger that kids are, the less likely that they make those particular antibodies, which by the way, then you could correlate that with disease severity. Because when we say that, you know, those younger kids, it’s not, they don’t have quite the immune response or, you know, to the virus being there.
So, their symptoms are mild. And so maybe that, that antibody that we’re testing is partially responsible for more severe illness.
[Dr Jason Newland]
There is an interesting thing too, that the monospot can stay positive for a while. And I think that’s important. It could be positive in some cases up to six months, which again can get tricky, right?
Like you have this and you’re like, what does that mean in regard to that? So, I think you have to take that. It is this notion of pretest probability.
I think it’s important, right? I think it’s highly likely you have EBV and therefore, but again, EBV is tough because it can have such a constellation of symptoms, but that also means if you have a high pretest probability, the teenager coming out with bad sore throat, you know, and if it’s positive, it’s probably positive, but if it’s negative, you might be missing, right? We know the sensitivity is poor, right?
So, you should probably keep looking. And that’s where the serologies come into account.
[Dr Mike Patrick]
And at our hospital, you can order the monospot to reflex to the EBV serology panel if it comes back negative. So, you’re going to get that back a couple of days later. So, let’s talk about that.
It kind of reminds me of the hepatitis B panel. So, we’re looking at antigens that are in the nucleus or they’re on the surface. And then we’re going to look at IgG versus IgM.
So, can you kind of just walk us through all of these and what they mean?
[Dr Jason Newland]
Well, I think we’re lucky that the Henleys, a husband-wife team from Philadelphia, the Children’s Hospital of Philadelphia, I kind of came up with this serology and instead of just having IgM and IgG to just one thing, we have really two things. And so, let’s talk about it. Well, I like to, I love, this is one of my favorite things to talk to the residents about.
And if you were with us on rounds, I’d probably try to find a piece of paper and I’d draw this thing out, but I would draw it in this way. Think of a virus as a circle, right? Think of the virus as a circle and you have these antigens or proteins that are on the outside, right?
So, you have this circle, you have an antigen on the outside, right? That’s a viral capsid antigen, VCA. And as we all know, we’ve all been trained in medical school, all medical students know this, right?
The first antibodies we make when we’re fighting something is IgMs, right? And the beauty of this is, is that we have this viral capsid antigen IgM, boom, it’s going to the outside. Then we, not surprisingly, right?
The IgMs are going to convert to IgGs, the IgM is going to go away. And lo and behold, right? We’re going to have a viral capsid antigen IgG.
So, when you guys have ordered those serologies, you’ve seen that. You’ve seen a VCA IgM and a VCA IgG. Super important to know that they both can come up at the same time.
And so, that doesn’t, you could have an IgG and the IgM’s gone away, but you still could be in an acute phase of the infection, so this is where we’re Because the Henleys realized that there were also nuclear antigens, right? So, you can imagine why the nuclear antigens might show up later, right? Because they’re on the inside.
So, the first thing you’re going to attack is the outside, things open up. Now, I have nuclear antigens available, so now I develop antibodies to the nuclear antigens, also known as Epstein-Barr Virus Nuclear Antigens or EBNA, right? So, now, and we only look at IgGs, they come later.
So, as an infectious diseases doctor, when someone shows me serologies, the first thing I look at is to see if it’s EBNA positive, right? Nuclear antigens positive. Because if it’s EBNA positive, that’s past infection.
That is not acute. I’m not worried about it. If I have IgM, VCA, viral capsid antigen, I’m like, ah, that’s acute.
As long as I don’t get some weird stuff. And by the way, I realize, you’re like, well, I’ve had them all positive at one time. I hear you.
That in those scenarios, I’m like, that doesn’t make sense. Let’s rethink and look, and there’s some other pieces, but then, right? Like what you should end up having, especially in past infection is IgG, viral capsid antigen, positive, right?
Cause it’s the outside. Once you have IgG, you always have Ig, and positive EBNA, Epstein-Barr nuclear antigen, IgG positive, right? Cause it’s the inside.
That’s it. You see those two, you can say past, I’m moving on. If I just have viral capsid antigen, IgG, no EBNA.
Oh, this is probably pretty acute. So how does that, how does that work for you, Mike, Dr. Mike, does that explain it?
[Dr Mike Patrick]
It does. Yeah. Yeah. So those, those antigens or proteins that are on the surface, they’re the ones you’re going to make antibodies against first.
And the first ones you’re going to make are IgM. Then those will slowly turn into, well, not turn into IgG, but then you start making IgG and to give you sort of lifelong protection and what those things are doing are keeping the EBV at bay since it’s going to enter into a latent phase. And all of this is only really important when we have to know, like if a kid is really sick and we want to know, is this EBV or is it something else that we need to treat in a different way, that’s when this is going to become important.
So, this trying to distinguish serologies, you know, in your run of the mill kid with a fever for a few days, this, you know, it’s not as important, right?
[Dr Jason Newland]
Exactly right. And I mean, if we want to get right, like to your point, exactly. If I have a fever of unknown origin, right, meaning greater than seven days, if we were to go down that topic, I’m going to send EBV serologies, it causes all kinds of things in that understanding that interpretation really helps because we know EBV can be a major player within this sort of fever of unknown.
[Dr Mike Patrick]
Yeah. Yeah. Now, as we think about presentation, we’ve, we’ve talked about the sort of mild febrile, mild to moderate febrile virus scenario, the teenagers who get the big tonsils and swollen lymph nodes in their neck and fever, and they just feel miserable, oftentimes come in dehydrated because they’re not able to eat and drink very well.
What other presentations and complications should we think about? You know, the spleen I think comes to a lot of our minds. Does the liver also get enlarged or have problems with that too?
Just sort of your, your abdominal organs.
[Dr Jason Newland]
So, this notion of abdominal pain, right. I think that’s, you know, right. Having some abdominal pain, that fatigue and malaise.
I think we also associate some of these, these extreme fatigue sort of pieces with that, no doubter. I think if you look at like, okay, I have this kid coming with fever, malaise, horrible fatigue, maybe, maybe they don’t have a sore throat, but you’re like, man, this seems right. EBV is a great example.
What would you might find on a lab test? Well, liver enzymes, ALT and ASTs will be elevated. Many people will use that as markers to say, oh, this is even more likely.
You can see pancytopenia. You can see a hemolytic anemia, right? You can see thrombocytopenia.
And I was a fellow many years ago. I mean, we had this kid that had pancytopenia, had traveled from somewhere else and got quarantined because all the blood cells look crazy. And you’re like, whoa, what is this?
It was EBV, right? It’s this notion that you can have these; it can impact so many things. You can have encephalitis.
They talk about this Alice in Wonderland encephalitis where they’re kind of hallucinating in pieces. I haven’t seen that as much, but kind of a, I like as an ID person, these encephalitis, I find them fascinating, but it can do that as well. So, as you all know, you’ve probably seen it.
It can do all kinds of things. Hence why you talk to the ID doctors, like, I just talked to the ID. They said, do EBV.
That’s pretty common for us. Cause it can do so many things.
[Dr Mike Patrick]
Yeah. Yeah. It’s a great masquerader kind of like stress in that sense.
But you don’t want to mix those up because for whatever reason, if you have an Epstein Barr virus, active infection, and then you take amoxicillin, you can get a rash and that’s some complex interplay between the antibiotic and your immune system and the virus when the three of those are together. And we’re seeing that with other viruses too. And that’s probably the rash that a lot of people call a penicillin allergy, that’s not really a penicillin allergy.
It’s probably more of a viral slash drug rash.
[Dr Jason Newland]
You know, Mike, we’re, I have some, I have some med students, I have some undergrad students looking at all of our EBVs in the hospital over a number of years, and they just showed me some of the data yesterday as they finally got it all collected. And interestingly only had a really low percentage that had received amoxicillin and had a rash. So, I mean, I haven’t delved into it, but I found that intriguing because some will say in some of these teenagers, it could happen in up to 85%.
If they receive amoxicillin. So, I was like, oh, that’s fast.
[Dr Mike Patrick]
Yeah. Yeah. No, very, that is very interesting for sure.
And I’m sure that there are, now that I think about it, I haven’t seen or heard about a study that actually looked at the incidence. It’s just one of those mantras that you learn in medical school and then you remember, you know, and then you remember regardless of how significant it really is.
[Dr Jason Newland]
Yeah. It’s kind of fun, right? Like this virus, why is this happening?
No, I totally agree.
[Dr Mike Patrick]
Yeah. In terms of the spleen, this becomes an issue as we think about sports and keeping kids out of sports and off the playing field, which can be from a mental health standpoint, like that really impacts teenagers a lot. So how common, how big of a problem is this really?
And what should we as primary care physicians be telling our families in terms of precautions and such?
[Dr Jason Newland]
Yeah, Dr. Mike, thank you. This is important, I think, because to your point about some of the mental health and the pieces of how activity matters for children, teens, especially, right, this is a teenage disease and you receive a diagnosis of EBV and you go to, I’m going to bring it up guys, right? Everyone knows we got the red book, right?
And the red book will say, cause Jason Newland has read this a few times. Cause maybe one of his children got acute EBV who might’ve been a soccer player, thankfully not in season, but you know, right. And you have acute EBV, your, your, your school isn’t going to tell you you’re not playing.
And this basically says strenuous activity in contact sports should be avoided for at least 21 days after onset of symptoms of infectious mononucleosis. I’m going to skip down clearance to participate in contact sports is appropriate after four to seven weeks following the onsets of symptoms. If the athlete is better is asymptomatic has no avert splenomegaly.
Now we don’t recommend doing ultrasounds. You can have spontaneous rupture without anything happening, which thing goes. And so, the big reason for not participation, right.
Is this splenic rupture, which goes in why, why are we so focused and what is that incident? So, I love sports, everybody. I love activity.
COVID was brutal on people that lost those abilities to do those things. Cause you could even argue playing in the band, being in drama, being in dance, doing that could be considered student strenuous activity. It is not clear exactly.
And that’s the data is very intriguing. The incidents have been reported to between 0.1 and 0.5%. I’ve had med student and a resident go try to find out where this came from. I again, went to try to find out today.
I think it comes from military recruits, but it is buried in regard to this. I just told you, we have this ongoing study retrospective look back. I got to see the data yesterday.
I went, Ooh, I wonder how many splenic ruptures in our EBV confirmed cases. One in 600 do the math. It’s about 0.3%. So, it fits in here. The data would suggest if there is going to be splenic rupture on review, like systematic reviews, looking at case reports, median age 22, usually within the first two weeks, but could be go as long as 31 days, only about 15 to 25%. It will be associated with trauma. So, you can’t do that.
Now this recommendation also says, well, what’s the consequence of a splenic rupture? In one report, one of the ones probably driving some of this, it was 9% mortality. Like that you could see why you’d be like, yeah, I’m putting that in though.
In another report, there was no fatalities and there’s not been anything recent. So, I think this is an intriguing question that it is rare. It is 0.3% is rare. But that complication is somewhat could be bad. And I, and I do think that there, we, I think we need to kind of do more analyses because to your point, Dr. Mike, the kid that comes in with rhinos and cough, they, oh, I did a monospot and, they were positive. You have to be out at least four weeks and no strenuous for maybe up to seven weeks, but they’re better within two weeks.
That child is probably way more. And if you’re a 17-year-old senior in there, let’s, I mean, my, I don’t, like I said, and there’s there, she’s in her final soccer season and wants to crush it. You now have to say, look, sorry, you can’t play.
And they’re like, I feel fine. And, and, and, and I’m not, and I think that’s a hard thing. And I think that it’s, I’m the red book says this, right?
And so that’s what the standard is at this point in time. But I’m hoping that as we do more work, we can see that. And I, and I still tell people, I said, you should, you should follow this based on the data that we have.
But I think it’s important for us as pediatricians who cared most about the health and wellbeing of our kids. There are some that maybe don’t need to do that. Now I can tell you the 17-year-old who ends up in the hospital with bad pharyngitis and horrible fatigue.
They’re not going to want it. They’re not going to be able to play for seven weeks. It’s just not possible.
There’s going to be too much fatigue and that piece and that one’s going to make sense. Right? So, can we figure that out?
I have told people that if I can get the data, I would love to maybe end my career on saying I changed the red book because we found the data that really got more specific on this because I think it does the mental health piece. And some of that matters for these kids that are doing all kinds of activities. It’s not just sports.
There’s a lot of strenuous activities that are beyond sports. And I think that’s important too.
[Dr Mike Patrick]
Yeah. Yeah. I mean, even just roughhousing with your siblings.
[Dr Jason Newland]
Well, and actually I think that would, and I don’t, I think this case was 10, 15 years ago, I think that was what led to the splenic rupture.
[Dr Mike Patrick]
Yeah. Yeah.
[Dr Jason Newland]
But I think it’s intriguing that only like 15%. I’ve even asked, so college age kids, right. Is a common place to get EDB, right?
I mean, they’re all together. They’re shit. Like it’s all, we know this.
I asked some football players and say, hey, can you hear anybody ever had splenic rupture that you’ve been in football? Like, no, I’ve never seen one. I’ve asked a number of ID docs.
You’ve ever seen splenic rupture? I’ve had one tell me, yes. I mean, now maybe we aren’t consulted.
I’ve asked a surgeon. It’s like, yeah, not really. So, it’s just really rare.
And I’ve said, it’s harder to get back from EBV than it is to get back from a concussion. And that kind of.
[Dr Mike Patrick]
The sports medicine people might argue that, but yeah.
[Dr Jason Newland]
Yeah. Yeah. Right.
I mean, I, you could argue, I mean, that’s a piece. And I think this is where, again, I think collaboration with sports medicine is key and we have great sports medicine docs and I’m working. We’re seeing maybe in a couple of years, we’ll have a new update on we can get.
[Dr Mike Patrick]
But I don’t know.
[Dr Jason Newland]
We’ll see.
[Dr Mike Patrick]
I, I feel like the problem is that once that becomes the standard of care for something that is rare, but significant when it happens, then it’s kind of hard to change that because to test it, you would need to expose kids to risk. And that, that risk is, you know, do you want to do that? And, and even though it’s probably fine, but it might not be.
[Dr Jason Newland]
Yeah. And I think this is where medical decision-making and is this where, right? Can we have conversations about, hey, here’s what we know.
And, and I don’t, and I think we need to have more contemporary data, even about splenic rupture and that notion of mortality, I mean, these are old. I mean, let’s look back to the 1980s. Are we really at that place?
But when I’m in, in this business for 20 years, I’ve never had one is, again, there’s reasons why that might be the case. And so, you know, I think we need more data so that we, to your point, Dr. Mike, like I say mortality, that makes sense, right? Like you need to, that that’s not trivial and how do we manage that?
And, but how can we give structure around conversation that helps us really do that in a safe, appropriate way that treats our children at the, at the highest level that we can’t, I just, I think that’s still there. I could be totally wrong by the way. And I’m willing to say my hypothesis is wrong, but I really feel like we can do better with that.
And I, and that’s on us when I say us infectious diseases, because that’s what we should be doing, right? This is how we help you all really kind of try the best care for, for wonderful children around the world. So, and especially here.
[Dr Mike Patrick]
And we’re really talking about contact sports, right? I mean, you know, you could still bowl, you could still.
[Dr Jason Newland]
Now it is mainly contact, but because of spontaneous rupture, they will say strenuous exercise, right? So, if you’re a cross-country runner, they’ll say no, right? That’s too strenuous for those four weeks after that piece, right?
That’s three weeks out after that, then you can three to four, then you can say, but it’s really because of spontaneous rupture, they’ll say strenuous, it’s really shut yourself down. So, you can imagine you’re a cross-country runner and you get EBV in end of October and maybe it’s, you’re done. And that’s, that’s hard.
And that makes me sad for people.
[Dr Mike Patrick]
Yeah. Yeah. And you know, it is different families have different risk tolerances.
And I, you know, that shared decision-making is going to be important. You know, did they have abdominal pain? Although, you know, you can get like a mesenteric adenitis with EBV that causes, you know, pretty significant abdominal pain, but it’s, you know, not their spleen.
And so, it’s just, it is unfortunate. It really is. But we don’t, we also don’t want to gamble with teenagers.
You know what I’m saying?
[Dr Jason Newland]
I mean, it’s like, it is, it’s where science matters, right? These are those questions where science really matters. And my hope is in five, 10 years, I can come back, Dr. Mike, and we’d be like, hey, here’s what we found. And here’s what, here’s why we feel this is good. And here’s a more specific way of handling this for all these guys.
[Dr Mike Patrick]
So, let’s, let’s focus on steroids. I think, especially from, from a primary care standpoint, you’ve got a kid with pretty significant Epstein-Barr virus, so mononucleosis, but maybe not sick enough to be in the hospital. So, they’re not necessarily seeing an infectious disease specialist.
When do we think about steroids or do we?
[Dr Jason Newland]
Yeah. So, you know, there’s an interesting conversation. And I think in the outpatient setting, I don’t think you need to use them.
And in here, let me read it specifically where the indications are reported within the red book. And I think this is important. So short course indicated for impending airway obstruction.
So, these horrible sore throats, big tonsils pressing on that. Steroid support, right? We’re going to knock down the inflammation within those tonsillar tissues.
And we know that B cells and that’s going to do it. Massive splenomegaly, myocarditis, hemolytic anemia, hemophagocytic syndrome, lymphocytic histiocytosis, or severe thrombocytopenia are the recommendations within the red book. So, I really think number one on the outpatient side, not indicating.
On the inpatient side, the question is, is a kid with a severe sore throat that maybe doesn’t have these other things, does that potentially be okay to give steroids? Because right now, most of us in ID will tell you, well, most of us are just going to tell you, no, don’t do steroids. And, but would that help with some of the symptomatology?
Would that help maybe even with splenic involvement? And would that help with maybe knocking down this inflammation? The big concern, as I kind of alluded to earlier, is could you have a T cell lymphoma or, right?
Because EBV could be marker of then having lymphoma or these other things where we know steroids is key for treatment. And if you give steroids without the other antineoplastics, you now ruin one of the best modalities of treatment. And so that’s the biggest fear is that if I give a steroid and if you, a steroid in that setting, so if you ask the Nationwide Children’s Hospital group of infectious disease doctors, acute EBV on the floor, maybe one of your patients, we are really mixed on when we’re going to give steroids, not all of us will be to the red, but because of how severe it can be.
And I think this is where there’s still not enough data in pediatrics to suggest where you should go on the use of steroids on the critical inpatient that doesn’t have like the real severe cases, right? The kid that’s in the hospital for six or seven days because their throat’s so bad that sometimes you think they even have peritonsillar abscess. It’s so severe.
[Dr Mike Patrick]
Yeah. Yeah. When the specialists don’t agree, I feel like that’s when shared decision-making with parents becomes even more important because, you know, if you had, you had a young adult woman who is getting ready to have her wedding and it is a week before the wedding and they are diagnosed with acute mono, you know, you might be a little more inclined to use a steroid so she’s feeling better by wedding day. And this may or may not be an actual scenario that happened in my own family.
[Dr Jason Newland]
Dr. Mike, I think that to your point, there is probably a lot of people who have received steroids for EBV, right? And I can say I’ve actually, even I’ve had severe, I should even say I’ve given corticosteroids one time to someone who was graduating from college, same scenario. Gave steroids because it was so bad.
They didn’t need to be admitted because I thought, but there’s probably a lot more people that have done that. I’m not sure that’s the right decision all the time, but I, but I think the risk might be a lot lower than what we put you just like the splenomegaly. Just, we don’t have enough data about that and that complication, right?
You really change someone’s life on therapies for lymphomas if you give steroids. And I think that scares all of us.
[Dr Mike Patrick]
Yeah. Yeah. And it’s, as you mentioned, it is T-cell lymphomas.
[Dr Jason Newland]
Well, you can see B-cells and T-cell lymphomas, it can be both. And natural killer cells can be impacted so that it is not just as simple. I think even T-cell leukemias can be associated with EBV and it’s just not trivial.
[Dr Mike Patrick]
And Burkitt lymphoma, Hodgkin lymphoma. And you had mentioned nasopharyngeal carcinomas are associated with it as well. So, all, so it’s rare, but when, when these things happen, they’re not trivial.
Nope. For, for sure.
[Dr Jason Newland]
Exactly.
[Dr Mike Patrick]
So, as we think about treatment and I think, okay, this is a herpes virus. And I know that there are antiviral medications that, I mean, work pretty well for if you get them started quick enough in the right clinical scenario, they can be helpful that, you know, things like acyclovir and their analogs. Are those kind of antiviral medications helpful for EBV since it’s the same family or not so much?
[Dr Jason Newland]
They haven’t been. Though you’ve seen some people tried and like post-transplant lymphoproliferative disorders stuff, but they haven’t been helpful. Especially in a normal healthy host, they’re not helpful.
And so, we haven’t been recommending those in that scenario.
[Dr Mike Patrick]
Okay. So, as we, as we wrap up on EBV and then I’m going to have you stick around because I have one more question for you after this, a non-EBV question. So, what, what take-home messages do you have here for primary care docs?
What are the most important things we should keep in mind when we are diagnosing EBV and then walking families through their journey with that viral illness?
[Dr Jason Newland]
Number one, you guys know this, EBV is common and many kids will get EBV four or five-year-olds and never have symptoms. It’s so common. 50% will have already been positive.
Number two, the teenagers are probably way, and you guys know this as most, and that key there is that fatigue, pharyngitis, abdominal pain is going to be important. I think number three is knowing the precautions. And I think it is fair to have those frank conversations that we do the precautions because of the risk of splenic rupture, that splenic rupture doesn’t even have to be because I can feel a big spleen or not.
It is, can be spontaneous. And that because of that, we have precautions of up to 21 days. Most times it happened within 15 days, only about a 15% to 25% are associated with trauma.
So, I think that’s important but also be aware that there’s still data to become. So that’s it. And lastly, is there’s no real treatment supportive care is the best.
Those steroids have been effective in knocking down some of the symptomatology, but the current recommendations are really for severe admitted patients with these complications.
[Dr Mike Patrick]
And for folks who want to learn lots more about Epstein-Barr virus, we are going to have some links in the show notes for you. So, if you head over to pediacastcme.org, look for the show notes for this particular episode, and you will find links to lots of stuff, actually. We have patient information on infectious mononucleosis that may be helpful for your patients and families to share.
We’ll have a link to the EBV and mono section of the Redbook. So, the Redbook is available online. So, if you’re an AAP member, you should have access to that.
And then also the journal Cell in 2022 had a nice review of EBV, the biology and the clinical manifestations of a viral infection with EBV. So, we’ll have a link to that. And then of course, Pediatric Infectious Diseases at Nationwide Children’s Hospital.
You guys are such a great group. And this is where I wanted to ask a one-off question. We had a recent episode where we had actually the authors of an article that was published.
It was a pediatric emergency medicine folks looking at fever in babies who are less than 28 days old. And their study had showed that if you do a procalcitonin, you check the A and C, you check a urine, and if those things all look good and the kid looks clinically well, then maybe you don’t need to do a lumbar puncture because they did a multi-country, huge confirmatory study that showed one case of bacterial meningitis in a less than 28 day old with the fever. There were some more bacteremia.
You know, you still want to get a blood culture, but do we need to do LPs in these babies? And you know, it’s still in our clinical pathway here at Children’s. Is that something that you guys are looking into or is this too dangerous of an area for you?
[Dr Jason Newland]
No, I think you got to address what’s out there, right? I mean, I think in the first seven, I think the question is where? I think the first seven days of life, like I think the LPs probably still, I would still do the LP.
Now again, I’m an ID doctor, right? So, we’re always at, I think after that, it does become now a little better as we’ve gotten some of these biomarkers, but I think you also have to remember that what they look like also matters, right? So, we’re also saying you’re clinically well, they have it.
Now, I think when we run into some trouble is when we get the ANC, the procalcitonin and the CRP, right? The, the guideline in a lot of this is just looking at procalcitonin and ANC, right? So, what happened, what do you do when I want to get the elevated CRP and now what are you saying?
Because that we do see the discordance. I do think that there’s room for this. I think there’s room to discuss further with the data.
Does everyone need it in regard to that? And does this shared decision-making matter? And of course, because of the, you know, the risk to the, and the check treatment of meningitis is different.
I think that’s okay. The next question would be, it’s the summertime, right? We see a lot of enterovirus meningitis and enterovirus for these fevers.
Do you, do you not do the LP and now you don’t have enterovirus because you don’t do, I don’t know, right? Because you now don’t know, maybe know that epidemiologist. Well, maybe that that’s not the right answer with a family.
But I, but I do think that as these data continue, where do we think it’s okay? And then making sure we’re still paying attention to the notion that babies can trick you, especially the first month of life and, and being careful there. But I, I, I mean, I’m doing what ID doctors do.
I’m talking circles. I’m coming to the point. And my point will be is that I think there’s opportunity to potentially not do LPs in all babies, less than 28 days.
I think less than seven days, I would totally do it. But I think there is, there’s give there in those. And I think the guideline gives you some of that, that the national AP guideline gives you some of that don’t have to do LP in all of them.
Yeah.
[Dr Mike Patrick]
Yeah. That helped. Yeah.
Oh, very much so. And what I really love is that we’re asking these questions because for a lot of my career, there have been certain things in pediatrics that you do not question that you just do it because we’ve always done it, but that doesn’t necessarily make it correct or not without its own issues and problems. So, I think just asking these questions like LPs in babies, less than 28 days with fever, like splenic rupture with EBV, like the, you know, the chance of getting a lymphoma because you had steroids with your EBV, all of these things, like we still have to keep asking questions and having a wondering attitude toward human health.
[Dr Jason Newland]
Yep. And in this day and age with large electronic health record systems, we should be able to answer some of these questions going forward with good, rigorous study designs that utilize the, what we have. And I think that’s the exciting part of our future within caring for kids with infectious diseases that we know, right?
That’s our, that’s our, that’s your guys’ practice. You guys do infectious diseases way more than I do on a daily basis. And can we make it better for you and actually treating and managing and providing the, the necessary education because you guys are the ones that do the most important work and I, and that’s what my, well, I think that’s why for me, I love what I do and I love being able to support everyone in what you’re doing on a daily basis.
So that’s why I like coming on the show too, Dr. Mike.
[Dr Mike Patrick]
Well, we will say your work is also very important and very difficult. And we do, we appreciate you and your group so very much. So, and we will, you know, we need to have you back.
Let’s pick another virus. And we’ll, we’ll do it again. Once again, Dr. Jason Newland, Chief of Pediatric Infectious Diseases here at Nationwide Children’s Hospital. Thank you so much for stopping by and chatting with us today.
[Dr Jason Newland]
Always a pleasure. I wish you and your family the best and I look forward to the next time.
[MUSIC]
[Dr Mike Patrick]
We are back with just enough time to say thanks once again, to all of you for taking time out of your day and making PediaCast CME a part of it. We really do appreciate your support. Also, thanks again to our guests this week, Dr. Jason Newland, Chief of Pediatric Infectious Diseases at Nationwide Children’s Hospital. Don’t forget. You can find us wherever podcasts are found. We are in the Apple podcast app, Spotify, iHeartRadio, Amazon music, audible, YouTube, and most other podcast apps for iOS and Android.
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And then a one more podcast that I host is called fame cast. This one is a faculty development podcast from the center for faculty advancement, mentoring, and engagement at the Ohio state university college of medicine. So, if you are a teacher in academic medicine or a faculty member in any of the health sciences, then this is a podcast for you.
You know, we talk about work-life balance, promotion and tenure, mentoring, teaching, really just all of those things you don’t learn in medical school that are still important in terms of having a career in academic medicine. You can find fame cast at fame cast.org and wherever podcasts are found by searching for fame cast. Thanks again for stopping by.
And until next time, this is Dr. Mike saying, stay informed, keep it evidence-based and take care of those kids. So long, everybody.
[MUSIC]
