“Eye” See There is a Problem

Dr. Kade Goepferd: This is Talking Pediatrics, a clinical podcast by Children’s Minnesota, home to the Kid Experts, where the complex is our every day. Each episode, we bring you intriguing stories and relevant pediatric health care information as we partner with you in the care of your patients. Our guests, data, ideas and practical tips will surprise, challenge, and perhaps change, how you care for kids.

Welcome to Talking Pediatrics. I’m your host Dr. Kade Goepferd. On today’s segment, Evidence-Based Charm, Guidelines with Courtney. Hospitalist Dr. Courtney Herring informs us of the latest evidence-based expert-driven clinical practice guidelines. Alongside her informative guests, she takes us through all the steps of care from ambulatory to inpatient and back again with a sizable dose of southern charm.

Dr. Courtney Herring: Welcome everyone. I’m Courtney Herring, and this is Evidence-Based Charm. Periorbital infections epidemiologically dominate in pediatric versus adult healthcare worldwide. A natural anatomic boundary of a thin fiber septum placed center stage to how we investigate and manage these infections with leveled clinical decision-making based on sequential pathways including some diagnostics. The phrase, “the source is in the telling,” reveals the truth in this drama via history and physical exam of this somewhat ambiguous storyboard that has major plot twists if misinterpreted.

While periorbital, commonly referred to as preseptal cellulitis, has the potential to be managed in the outpatient setting. A bigger badder villain sits just millimeters away. Orbital cellulitis is considered an urgent medical diagnosis requiring quick interdisciplinary and hospital-based care. To talk more about this topic, today’s guest is an amazing example of giving back selflessly in the name of providing best evidence clinical care for children. Dr. Nadia Maccabee-Ryaboy is a pediatric hospitalist at Children’s Minnesota and also the University of Minnesota Pediatric Hospital Medicine Fellowship Associate Program Director. She is quickly tallying quite the repertoire of guidelines under her ownership here at Children’s. Nadia, welcome to Evidence-Based Charm.

Dr. Nadia Maccabee-Ryaboy: Thank you so much for having me.

Dr. Courtney Herring: It’s always good to share space with you, by the way.

Dr. Nadia Maccabee-Ryaboy: I’m excited.

Dr. Courtney Herring: Well, if you’re fine, we’re going to get right into it. This diagnostic bucket of periorbital infections encompasses quite the variety of etiology or causes as well as disease severity, however clinical presentation may be or is similar. Nadia, when you were leading this work group, what was your methodology following your research and getting started or where did you find those pivotal decision points to begin the guidelines?

Dr. Nadia Maccabee-Ryaboy: It’s a similar process for all of the guidelines that I’ve worked on. After identifying a disease process that I think is ripe for a clinical guideline, then I just sit down and think through what are the questions that tend to come up when we take care of these patients and where do we wish we had more evidence to guide our decisions? And then also, where have I seen differences when I look at how providers manage these diseases and where would standardization actually improve outcomes, because we don’t always have to do the same thing, but where would actually standardization improve the care of our patients?

And so, once asking those questions, the first place I look is existing guidelines out there. There’s some beautiful guidelines put out by Wisconsin Medical Children’s and CHOP and Connecticut, so we don’t have to reinvent the wheel. I look through their guidelines and then see where do they differ, where are they the same, what reasoning do they use for the decisions that they make?

And then is the fun part, and I got to delve into PubMed and Google Scholar, and then try to answer those same questions myself and see as I take pieces from those different guidelines and then pieces from the evidence, where do we come to at Children’s Hospital of Minnesota? And then I got to meet with some amazing experts in our infectious disease department, our pharmacy, emergency department, primary care docs, ENT and ophthalmology, and sometimes lively debate those nuances and those questions so that we could all come to a consensus for some clinical guideline that felt meaningful and true.

Dr. Courtney Herring: As a segue for our primary care and emergency medicine colleagues, first seeing that child with a swollen red eye, in order to determine next steps, how can they best distinguish between periorbital versus orbital cellulitis?

Dr. Nadia Maccabee-Ryaboy: It really is a clinical diagnosis. We talk about imaging later in the guideline once we know there’s orbital cellulitis, but distinguishing orbital versus that preseptal periorbital cellulitis, it is based on a really good exam and a really good history. It’s up to the diagnostician who’s seeing that child and looking for things like is there photophobia, is there pain with eye movement? Is there ophthalmoplegia? There’s limitations in any direction for the ocular movement, those would all be signs of orbital cellulitis.

Looking at the child and seeing is there proptosis, actual bulging of the globe, or chemosis, redness of the conjunctiva. Are there any changes to the child’s vision? Either visual acuity changes, strabismus, so is misalignment of the eyes, diplopia? Are they seeing double? Those would all be signs of orbital cellulitis. And then if the provider feels confident looking at the optic disc, if they see pallor, they see swelling, those would also be signs of orbital cellulitis. That combination of a great history and exam is what distinguishes periorbital from orbital cellulitis.

Dr. Courtney Herring: Yeah. One dogma that hasn’t changed, right?

Dr. Nadia Maccabee-Ryaboy: Exactly.

Dr. Courtney Herring: Taking a step deeper into the guidance, as you already alluded to, specifically around diagnostics per se, what recommendations are there around laboratory and or medical imaging to assist us in advancing this diagnosis?

Dr. Nadia Maccabee-Ryaboy: In terms of imaging, we do recommend getting a CT for all children where there’s a suspicion of orbital cellulitis really to look for abscess and to see is there an indication for surgery? And so our ENT and our ophthalmology folks would look at that picture along with the emergency department doctor, the hospitalist and say, “Is this something that can be managed with IV antibiotics alone or do we need to operate?” Also, there can be a utility for imaging if the diagnosis is uncertain, if it’s a child particularly less than 12 months old, where sometimes it can be hard to get that really good eye exam, hard to ask and get that history, does it hurt to move your eye around? That imaging can also help distinguish the periorbital from the orbital cellulitis.

Labs, there’s a little bit less utility to labs, particularly if you are certain that it’s a preseptal cellulitis. Just like our other cellulitis guidelines at Children’s, and I think there was another podcast episode on cellulitis here, that there really isn’t good data for blood cultures for CBC in straightforward cellulitis or preseptal cellulitis. Once you get to orbital cellulitis, some studies have found anywhere from four to 15% will have a positive blood culture. And so in that case, getting a blood culture may actually help reveal the cause of organism and help guide antibiotic therapy. For orbital cellulitis, the more invasive infection, labs can be helpful.

Similarly, in addition to blood culture for orbital cellulitis, sometimes a CRP might be helpful if one needs to trend inflammatory markers, that one data point isn’t going to be useful in making the diagnostic decision. But if one’s wondering, “Gosh, is this patient improving or not?” We don’t repeat imaging in these kids usually. We’re looking for clinical improvement, and so also looking at that inflammatory marker downtrend may be other evidence that the antibiotics are working.

Dr. Courtney Herring: The clinical guideline advises that all patients with orbital cellulitis be admitted to the hospital for intravenous antibiotics and potentially other multidisciplinary need. But when do the patients with preseptal cellulitis need to be sent to the hospital?

Dr. Nadia Maccabee-Ryaboy: Often patients who come to clinic or emergency department with preseptal cellulitis can be started on oral antibiotics and watched at home and follow closely as an outpatient, but they should be sent to the hospital if it’s rapidly progressive, if they are really ill appearing. If the kid just looks sick, high fevers, that might suggest, well, maybe I need to watch them a little bit closer. If they’ve already tried oral antibiotics and we say given it a good go. A dose or two isn’t enough of an oral antibiotic trial, but if they’ve been on appropriate antibiotics for 48 hours and they’re just not improving, that would be a reason to admit for IV antibiotics. Or if they just can’t tolerate it, maybe the kid is feeling so sick, they’re not taking it, they’re vomiting, they’re throwing up those oral antibiotics, they should be admitted for IV.

And then we do say in our guideline to consider admission for IV antibiotics in a kiddo less than 12 months old. And it goes back to the fact that sometimes that distinction between periorbital and orbital cellulitis can be tricky in that age group. And so if there’s a little bit of uncertainty in the diagnosis, maybe consider being a little cautious and admitting that kiddo.

Dr. Courtney Herring: In segue to talking about treatment, even though preseptal and orbital cellulitis are combined in this guideline, which is very common, more specific to this question, antibiotic recommendations are different. Can you tell me more about the clinical logic behind these decision points?

Dr. Nadia Maccabee-Ryaboy: I have to admit that before working on this guideline, I often treated these conditions the same and I would use Augmentin or Unison for both preseptal and orbital cellulitis. And it was really only delving into this literature that I educated myself and learned that that’s really not appropriate antibiotic stewardship. And the Red Book, put together by the Infectious Disease Committee, specifically says that preseptal cellulitis is usually due to direct skin inoculation. You’re thinking of your gram-positive staph, strep and can usually very appropriately be covered with a first generation cephalosporin like Keflex or Cefazolin if they’re being admitted.

There are some exceptions. If the cause of the preseptal cellulitis was an animal bite, then you have to cover differently. But generally speaking, thinking of direct skin inoculation, you may or may not see that mode of entry. You might see a little mosquito bite that the kid itched that then progressed to preseptal cellulitis, you might not, versus orbital cellulitis where it’s usually a complication of sinusitis. And so your organism is there, you’re thinking of the gram-positives. It’s usually polymicrobials. You’re also thinking of hemophilus and anaerobes. And so that’s why we go to Unison as a typical monotherapy or Augmentin once they go home on oral antibiotics because you’re covering different bacteria.

Dr. Courtney Herring: It’s fascinating because again, all the same area, everybody. But knowing again, that source brings really to the forefront of how you move forward in the pathway. And I will say, we always talk about antibiotic stewardship. I think this guideline tries to really hone in on that. It’s a necessary consideration when you’re creating these infectious disease clinical guidelines. The clinical practice guideline we have here has obvious investment in diagrammatically calling out potential etiology and associated, as you already mentioned, microbiological target. Was it an insect bite? Was it a dog bite? And then obviously, was it more orbital considering pansinusitis, sinusitis. Importantly, when navigating a disease that has high risk of staphylococcal disease though, specifically staph aureus, the subject of community MRSA inevitably will need to be addressed. Where did these guidelines situate when it comes to MRSA considerations?

Dr. Nadia Maccabee-Ryaboy: That was a point of a lot of debate and research-

Dr. Courtney Herring: Ooh, hot topic here.

Dr. Nadia Maccabee-Ryaboy: It was hot. Is do we need to cover empirically for MRSA or not? And when we do need to cover for MRSA, what do we use? And so what our guideline recommends is if there is a history of MRSA or MRSA risk factors, instead of using that Unison, to go to Clindamycin, and that is based on our children’s antibiogram where actually Clindamycin will cover your gram positives and anaerobes that I talked about, but also will have pretty good MRSA coverage. And we did an informal review of the last five years of patients admitted to Children’s with orbital cellulitis who tested positive for MRSA and they all were Clinda-sensitive. I think it’s important to note that we’re saying Clinda for those with MRSA risk factors, but that really is based on our local antibiogram. And so in other places, that may or may not be what needs to be used for MRSA coverage.

And also important to note are the exceptions in this guideline. If there’s CNS penetration or CNS involvement, those kids are off this guideline and almost certainly would need vancomycin. Similarly, when I looked at that informal five-year review, kids less than 60 days old were much more likely to have more aggressive MRSA and do also often need that vancomycin. Kids less than 60 days old, CNS involvement or what we call imminent site-threatening infection where maybe there’s an abscess and it’s more progressive, more aggressive, they also would need vancomycin. Yes, we’re being thoughtful about the antibiotic stewardship, but also I never want people to use these guidelines as a one-size-fits-all.

Dr. Courtney Herring: I think trying to complete that circle of treatment and management opportunities. There’s mixed evidence we’ll say around adjunctive therapies in the management of specifically orbital cellulitis. Not to over-dramatize the controversy, but one such hot topic circles around whether to consider systemic steroids in the treatment pathway. I know you did work and have continued to investigate this question post-guideline publication. Tell us where we’re currently at regarding recommendations around steroids.

Dr. Nadia Maccabee-Ryaboy: Yeah, there have been studies that have looked at adding systemic steroids for patients with orbital cellulitis with a thought that if we can decrease the inflammation while of course concurrently treating with IV antibiotics that maybe will hasten the clinical improvement and get those kids feeling better and getting out of the hospital sooner and improve their recovery. There have been a handful of studies that have shown that when pediatric patients are admitted with orbital cellulitis and prescribed systemic steroids, they do have a faster recovery. But there are also a handful of studies that have shown that systemic steroids really don’t make a difference in these patients. The trials that have looked at systemic steroids, however, have shown no adverse effects.

I think that’s good to note that these aren’t massive doses of steroids that have been used. And we do know that this is both an infectious and an inflammatory process. Our ophthalmology group at Children’s Minnesota has now decided they would like all children with orbital cellulitis who don’t have CNS involvement, don’t have immuno compromise, that they do get started on systemic steroids shortly after presentation, and we will study it. And that’s part of the beauty of these guidelines is our ophthalmology group thinks that that will help, and in five years ask me and we’ll see what our data shows, but we don’t think it will cause harm and it may help. And so we’re going to see if the data pans out here.

Dr. Courtney Herring: Well, still along the same vein, but maybe not as controversial by any means, is sliding into benign topic around nasal sprays. I think this is a great topic for all translational ambulatory and our side of things in the hospital. What’s your take on nasal sprays and when do you use them and how do we teach families to do this?

Dr. Nadia Maccabee-Ryaboy: There have not been studies that specifically look at the utility of nasal sprays in orbital cellulitis. Because there aren’t studies on it specifically, when I discuss this with our ENT group, and our entire Children’s ENT group really strongly recommends that all children with orbital cellulitis be started on nasal sprays on Flo-Nase, Afrin and nasal saline, and they say that is because the source, the cause of the orbital cellulitis is acute sinusitis. And so you’ve got to get at the source control and essentially, particularly if there’s no surgery to address an abscess, the source control is sprays and clearing out those sinuses. And so they strongly recommend it because there have been studies that have shown utility of nasal sprays in acute sinusitis and extrapolating that to orbital cellulitis.

One of our ENT experts recently told me his recommendation in terms of the order of the sprays, which was interesting. He said that he would start with the Afrin because that de-congests the tissue, so then subsequent medications can pass more freely, and then he’d recommend nasal saline and washing out the mucus that has pro-inflammatory components. And then finally, to give the Flo-Nase because we’ve cleared the space, cleared the way for the Flo-Nase to work its full anti-inflammatory effect. That was the order of operation that he would recommend.

Dr. Courtney Herring: Nasal sprays are one of those things where even in the hospital trying to accomplish this in a two-year-old versus a 12-year-old, which I would say sometimes equally difficult, there is some evidence around nasal-based steroid delivery. It’s limited. It’s mainly an outpatient setting and it’s small power, but at the same time, I agree, it’s one of those you’re using the physiology we understand or the pathophysiology. This is basically acute sinusitis at its worst, and this is really one of the limited things we can do. Encouraging and giving good advice to families of how to accomplish these I think is always one of the hardest parts of the job because our families are doing the hard work here, not us.

I would say from your takeaway, and this is a little off the hip here, if you had three main points you wanted to share about this guideline that if you could walk away knowing your audience is broad, what do you want people to take away from what I would say is an amazing guideline with so many nuances of understanding the true pathophysiology and sources of preseptal and orbital cellulitis?

Dr. Nadia Maccabee-Ryaboy: One is distinguishing preseptal versus orbital cellulitis. It’s all about that good exam and history, but cluing into the signs of eye involvement and also making sure that families are aware of those signs. Really partnering to make sure you’re not missing pain with eye movement, redness of the conjunctiva, limited eye movement to distinguish whether a patient has orbital cellulitis.

The second key takeaway, I think, is thinking about the causative organism and that the way we treat these two infections is really just by looking back to our micro and thinking about what bacteria do we need to cover, and then that should always guide our management.

And then thirdly, I think a big takeaway is really thinking about MRSA coverage because that’s one thing that I saw in the informal review of children admitted to Children’s with orbital cellulitis is there was just a huge variety of whether MRSA was covered with vancomycin, with clindamycin and for how long and when it was stopped. And so I think also as we’re becoming focused on antibiotic stewardship is really thinking about what are MRSA risk factors? Do we ask those questions of all of our patients? And how do we think, how can we be thoughtful about when and how we cover for MRSA infections?

Dr. Courtney Herring: As we’re wrapping up, my takeaways today are periorbital and orbital infections are pediatric-centric diseases, and we need to be aware of them. Whereas periorbital cellulitis, a majority may be treated in the outpatient setting, orbital cellulitis requires urgent management in a hospital setting. The mainstay of treatment is accurate antibiotic targeting based on the etiology. And then at Children’s Minnesota, we are recommending systemic steroids for patients with orbital cellulitis.

And I think my last point is always around looking at the greater piece, which is education for families around nasal sprays or just the idea of periorbital preseptal versus orbital cellulitis is always key to bring cooperation and best management planning together no matter what phase of clinical care that our children are being seen. Thank you so much, Nadia, for being here.

Dr. Nadia Maccabee-Ryaboy: Thanks for having me, Courtney.

Dr. Courtney Herring: You’re my first guest on this podcast that I’ve newly taken over for the elegant and amazing Dr. Gabby Hester, shout-out to her, who really paved the way under Dr. Kade Goepferd’s stewardship. For all of you out there listening today, I welcome and I’m grateful for your attention and hope to hear from you soon.

Dr. Kade Goepferd: Thank you for listening to Talking Pediatrics. Come back next time for a new episode with our caregivers and experts in pediatric health. Our showrunner is Cora Nelson. Episodes are produced, engineered and edited by Jake Beaver and Patrick Bixler. Our marketing representatives are Amie Juba and Krithika Devanathan. For information and additional episodes, check us out on your favorite podcast platform or go to childrensmn.org/talkingpediatrics.