What do you do when faced with a set of symptoms that has two contradictory courses of treatment?
Steven Chen, MD, MPH
Steven T. Chen is a board-certified internist and dermatologist at Massachusetts General Hospital. He is Assistant Professor of Dermatology at Harvard Medical School.
Dr. Chen graduated with Honors from Johns Hopkins University where he earned a BS in Biology. He subsequently earned a Masters in Public Health (MPH) and a medical degree (MD) at Johns Hopkins, and was elected to the Alpha Omega Alpha Honor Society. He then pursued residency training at Harvard, where he completed an Internal Medicine residency at Beth Israel Deaconess Medical Center and a Dermatology residency in the Harvard Combined Dermatology Program. He served as Administrative Chief Resident during his final year of combined training.
He belongs to several professional organizations, including the American Academy of Dermatology, the United States Cutaneous Lymphoma Consortium, and the International Society for Cutaneous Lymphomas. He pursues clinical and education research and has co-authored peer-reviewed articles in medical education and complex dermatology. His clinical interests include cutaneous lymphomas, complex medical dermatology, inpatient dermatology, and medical education.
Dr. Chen attends on both the dermatology and internal medicine services. He is the Co-director of the Comprehensive Cutaneous Lymphoma Program, and serves as Director of Medical Education and Director of the Blistering Orders Clinic in the Department of Dermatology.
DDx SEASON 2, EPISODE 3 TRANSCRIPT
Raj: The patient is a 45-year-old male who had contracted a skin and soft tissue infection while at the gym. He was prescribed antibiotics and the infection started to clear. But towards the end of the treatment, he suddenly developed a rash and flu-like symptoms so severe that he presented to the emergency room.
Raj: This is DDx, a podcast from Figure 1 about how doctors think. This season is all about dermatology. I’m Dr. Raj Bhardwaj. Today’s case comes from Dr. Steven Chen.
Steven Chen: I am a dermatologist and an internist at Massachusetts General Hospital in Boston, Mass. I practice complex medical dermatology for the bulk of my clinical work.
Raj: The patient was young, otherwise healthy, and just finishing a course of antibiotics to treat his skin infection. So what was going on?
Steven Chen: When I first saw him, he was, you know, I think often in medicine we always talk about our ability to identify someone as being sick or not sick. And he was definitely someone who is sick. He’s lying in bed, barely could open his eyes, barely could talk. Actually, his wife was in the room and she did a lot of the talking when I first met him because he was feeling so out of it and so sick.
Raj: Dr. Chen was brought in to help. He noticed right away something that hadn’t been spotted.
Steven Chen: His rash was… he just was red all over. And it would have been very easy to actually miss the rash completely. But if you looked really, really carefully and looked really close, you could actually see that he had a lot of small 2 to 3 millimeter erythematous bumps or papules that coalesced. So they all come together and they create these larger plaques. And the reason I say that it’s easy to miss is because he was covered head to toe in them. And so I think someone who’s not looking for it could easily say could easily gloss over that and say, oh, maybe that’s his normal skin and he’s just red.
Raj: The patient had all the typical symptoms of infection. But it could have also been an allergic reaction to the drugs he was prescribed.
Dr. Chen checked the patient’s file, and saw that he was prescribed an antibiotic known as trimethoprim-sulfamethoxazole.
Dr. Chen checked the patient’s file, and saw that he was prescribed an antibiotic known to cause adverse reactions in some patients.
Steven Chen: I think at that moment you have to make a decision, because if you think this is a drug reaction, that’s from the Bactrim, you treat it one particular way. But if you think about the fact that there’s a person in front of you with a rash, feels ill and has a fever, the natural inclination is to think that they have an infection. The history for this patient was really helpful because knowing that he had taken Bactrim for a while and knowing that he had cleared his infection before completely and was just finishing off his antibiotic course, I think really helped me push toward a drug reaction as being the most likely reason for his symptoms. So we actually toyed with the idea of sending him, sending him to the intensive care unit.
Raj: This was a serious decision. If the patient was having an allergic reaction and was given more of the antibiotic that triggered the reaction, he would get worse. But if he was fighting a severe infection, and was given steroids to suppress his immune system, he would also get worse.
Steven Chen: I think unless you know about the diseases that are possible, when you think of this constellation of symptoms, it’s sometimes easy to miss. And the Bactrim is, we know, a very common culprit for drug allergies. And so that was something that was a red flag just to start. When he got admitted and I first saw him, he looked miserable. He had a fine kind of sandpaper red rash throughout the body. He looked just kind of what we call edematous or swollen all over. And his blood pressure was starting to tank. His blood pressure, I remember, was in the 70s, over 40s, which is certainly not something that we’re used to seeing on a regular medicine floor.
Raj: Dr. Chen recognized these symptoms, and made a decision.
Steven Chen: And to be honest, for the first few hours, we really didn’t know which way he was going to go, because if we were wrong and this was actually an infection, giving steroids can certainly make that worse as we’re immunosuppressing the patient and making their immune system kind of go to sleep in some sense. It really increases the risk that infection can take off. Luckily for him, though, and luckily for us, I should say, our suspicions were correct. And he started to turn the corner. His blood pressure came up and he could stay on the regular medical floor after getting this whopping dose of steroids. And then it became once we kind of knew that we were dealing with this drug reaction, it became more of a question of how do we take care of him on a longer term basis.
Raj: The diagnosis was DRESS syndrome.
Steven Chen: Which is a drug rash with eosinophilia and systemic symptoms. This is an important thing not to miss because the mortality rate from this is 10 percent. So one out of every 10 patients who gets this disease will actually die from it.
Raj: What might have happened if Dr. Chen hadn’t recognized these symptoms?
Steven Chen: You know, I think that if we had missed it, if we had not realized that this was a drug reaction. The potential is that he could have gone to the intensive care unit or stayed on the floor, provided his blood pressure was stable, but if no one had started steroids for him, then the next move probably would have been antibiotics, because the next highest thing on your differential would be an infection. We already know that his entire drug syndrome was set off by an antibiotic. And certainly antibiotics don’t cross react that frequently. But you can imagine that if you’re adding more and more unnecessary drugs and unnecessary medications to the equation, you certainly not only miss your opportunity to treat this in an expedient and quick way, but you could potentially compound the problem if you accidentally pick something that has some cross reactivity with the original drug that may have caused the syndrome in the first place.
The worst case scenario, of course, is that you don’t catch this and then they end up…their liver failure ends up getting worse. There are cases of these patients who end up needing a liver transplant from DRESS syndrome. And obviously in a worst case scenario, these patients do end up dying from their fulminant liver failure.
Raj: DRESS syndrome is easy to miss. One factor complicating the diagnosis is that the rash can show up as late as 2 to 8 weeks after exposure to the drug that triggered it. And sometimes, there isn’t even a rash…
You might not think you’ve seen it… but maybe it has seen you.
Steven Chen: The name is a little misleading because it’s drug rash eosinophilia and systemic symptoms. And ironically, you actually don’t need to eosinophilia and you don’t need a rash to actually make this diagnosis. But you can actually still have an intense systemic drug hypersensitivity syndrome that gives you atypical lymphocytes, feeling ill, fever, all those things and not necessarily have the rash or that you eosinophils on your CBC.
Raj: Depending on the individual patient and their symptoms, DRESS syndrome doesn’t always hit as hard.
Steven Chen: I’ve seen cases where patients have been admitted to the hospital and discharged and told that they had a viral syndrome, and reviewing their chart, it’s rather clear that they actually had DRESS syndrome and no one picked it up. And these patients were lucky enough to be able to get discharged without systemic steroids and to basically recover at home with time.
Raj: But there can be serious consequences to missing the diagnosis.
Steven Chen: But I also think that I think about those cases and I think about the fact that these patients, if a dermatologist weren’t to see them and to recognize that they actually had DRESS, they wouldn’t know that they had this severe drug allergy and could re-expose themselves to those drugs in the future. I should say a physician could expose them to one of these culprit drugs in the future. And so I still think it’s important to think about this case. If anything, for education for our patients so that they know what drugs to avoid, to try to avoid some terrible sequelae like we’ve talked about.
Raj: After starting on steroids, the patient began to improve.
Steven Chen: He ended up doing fine, usually after dress syndrome, you have to be on steroids for six to eight weeks. And then after that slow taper, after slowly peeling back the steroid dose, we can finally get the patient off of it. And then the patient then has a lot of work to do.
Raj: Being on steroids for a long time always comes with complications.
Steven Chen: You can imagine taking systemic steroids for up to eight weeks wreaks havoc on your on your body in terms of bone health, fat deposition, blood sugars, blood pressure, all those kinds of things that we always think about when we’re prescribing something like prednisone. And so this particular person is young and healthy, went back, really took another six to 12 months to kind of build everything back up again. I’m still in touch with this person. And this person actually was very open with the fact that it did take a long time to finally feel like he was back to normal again. And now he’s, you know, living his best life. He will always avoid Bactrim at all costs. But I think that it’s in my mind and in his — I think we both think that, you know, we’re really fortunate that he was able to dodge a bullet in some ways, obviously still afflicted with DRESS syndrome, but at least now understanding what to avoid and standing on the other side, doing much better now.
Thanks to Dr. Steven Chen for speaking to us.
This is DDx, a podcast by Figure 1.
Figure 1 is an app that lets doctors share clinical images and knowledge about difficult-to-diagnose cases.
I’m Doctor Raj Bhardwaj, host and story editor of DDx. You can follow me on Twitter at RajBhardwajMD
Ddx is produced by David Crosbie for Earshot Podcasts.
Sound design and mixing by Chandra Bulucon.
Our theme music is by Nathan Burley.
The executive producers of DDx are Jesse Brown and Kevin Sexton.
Head to Figure1.com/ddx, where you can find full show notes, photos and speaker bios.
Thanks for listening.