Drug Eruptions: TEN tips to help you adDRESS them

Good evening and thank you all so much for joining us in our latest clinical education webinar, "Drug Eruption: 10 Tips to Help You Address Them." My name is Dr. Art Prepare, and I'm the CEO and co-founder of VisualDx. We're honored and humbled by the overwhelmingly positive response we've had to these clinical lectures during the pandemic, and probably tonight, where it's cold in certain parts of the country. We hope that these educational webinars provide value to your training or and/or your practice, and we're thrilled to host today's presentation on cutaneous drug eruptions across diverse skin types.

Before I introduce our presenter, I have a few housekeeping notes. We encourage questions from the audience, so while you're all muted, we do hope you will submit questions through the Q&A box, and we'll get to as many as we can after the presentation. Also, this webinar will be recorded and we'll share it with the registrants. And following the clinical presentation, we'll test your skills with a Kahoot quiz, awarding a prize to the winner. So you want to have, you want to have the app downloaded. So you go to the App Store or Google Play for Android, and you search Kahoot, which is K-A-H-O-O-T, and download the app. We also ask you take our survey at the end to provide feedback and give us ideas for future topics.

Now, I'd like to introduce you to Roxanna, Dr. Roxanna Donashu. Dr. Donashu is a clinical scholar in dermatology at Stanford University. She completed her medical school and residency at Stanford. Dr. Donashu's interests include equity in dermatology and bias in artificial intelligence. Take it away, Dr. Donashu.

Thank you so much. All right, hi everyone out there. I'm going to go ahead and share my PowerPoint. It's always the most tenuous part of any Zoom meeting is finding your share screen, especially if you're like me, who's one of those terrible people who keeps a million tabs open. So, I'm Roxanna Donashu, and I came up with this very punny title. And unfortunately, I think I used all my pun energy on the title, so there are unfortunately no more puns in the rest of the talk. So, "Drug Eruptions: 10 Tips to Help You Address Them." And if you didn't know, TEN and DRESS syndrome are two, uh, um, sort of drug eruptions that we will talk about today. I will also add that I am on Twitter and love to have conversations on there. I don't answer medical questions or give medical advice on Twitter, but I'm happy to talk about, um, dermatology in general or disease states in general and have conversations around that. And Derm Twitter is a pretty active community, so we're always happy to engage with our colleagues across different specialties. So with that, we'll go ahead and get started.

So, conflicts of interest. I'm on the advisory board for VisualDx, and all photos in this presentation are used with the permission of VisualDx. So thank you very much for that. So, why do we care? We care because there are different numbers out there, but about 5% of patients who are on antibiotics or aromatic anticonvulsants, um, will have a cutaneous eruption, and about 2% of all cutaneous drug eruptions are serious. There are certain patient groups that are higher risk. These include the immunosuppressed, so people with HIV or systemic lupus, for example, lymphoma, of course, these are just some of the examples, um, elderly patients, and there are certain genetic HLA subtypes that are also associated with higher risk of drug eruptions.

So, adverse drug reactions come through several different, different mechanisms. They can be immunologic, meaning that they are mediated by the immune system. They can be non-immunologic, meaning that they can be from the drug, like a drug overdose or drug accumulation. Think of like silver accumulation and argyria. They can also be idiosyncratic, meaning that they just randomly happen and we don't quite understand why. We don't know if it's the immune system or something else. And I know that can be kind of scary clinically, but that's just the fact of the matter. Many things that we see are immune, uh, mediated. So there's the Type 1 IgE mediated drug reactions, and of course, this has been in the news because of COVID, right? We worry about anaphylaxis with the COVID vaccine, even though studies have shown now that it's pretty rare. But if you've had your vaccine, you know that there's a 15-minute waiting period where they monitor you to make sure that you don't have this kind of Type 1 reaction to the vaccine. There's a Type 2 cytotoxic drug-induced reaction, there's immune complex deposition, like we see with serum sickness, and then there are T-cell mediated reactions, um, where the T cells get involved.

So after I made this title, I realized that I have to come up with a framework that includes 10 things in order to keep the pun going throughout. And so, I, I wrote up this framework as just one framework for thinking about drug eruptions. There, you can think of sort of your own framework based on, you know, uh, reading the literature or what we talk about today. And I think this is the first, the first thing is like, pretty much something we all do with every patient, which is just ask, is the patient sick or not sick? What kind of emergency situation are we in? Is this something that needs to, you know, be sent to the ED immediately, or is it something we can monitor on an outpatient basis? And then, as a dermatologist, of course, I ask, what is the morphology? And I know that this is mostly a non-derm audience, so I will say, as a dermatologist, we are incredibly forgiving of people not knowing all the right terms to use for describing rashes. We often tell people, you know, you don't have to describe it as macular or papular, just tell us what you see or send us a photo. So I, I don't want anyone to be, uh, scared about that. And I know David Harker has given a lecture previously that covers some of these things, but that's just one thing I wanted to say. And then, what is the distribution? So what parts of the body are involved? Are the mucous membranes involved? And what are the associated symptoms? Are there any extra-cutaneous exam findings, systemic symptoms? And then the number one thing with drugs is you have to think about drugs. So you got to ask about drugs, over-the-counter drugs, and supplements. And then you have to think about the timing between the medication or drug and the drug eruption. And then finally, of course, what do I need to do for management? And well, I will discuss a little bit of management here. A lot of these cases are complex and require sort of multidisciplinary care. So please do not hold this to be like the end-all for for management. Um, I think the most important thing to sort of take away from this is to just have some of these things on your differential, especially the ones that are dangerous or potentially life-threatening, so that you can move quickly, act fast, and get the patient the help that they need.

So with that, what are some of the warning signs? So anyone appearing ill or having high fever, systemic symptoms, facial involvement and facial edema, blistering and erosions, mucosal involvement, lesions that are dusky, and then Nikolsky skin, which is if you apply lateral pressure, it actually starts dislodging layers of skin. That's that's not a good thing. And then of course, if you have new lab abnormalities, um, in the patient, sort of renal issues, hepatic, elevated eosinophils, these are all sort of concerning warning signs that indicate that this is something that probably shouldn't be managed on an outpatient basis and should be assessed and monitored in the inpatient setting.

And with that, we'll go into the cases. I'm going to have to sit here and agree with, uh, you know, I think Misha Rosenbach gave one of the talks in the past and said it's very interesting to sort of just like talk into the void. So, um, if you please feel free to ask questions in the Q&A, and, um, you can also tweet at me, and I will look at the comments afterwards and try to respond.

Our first case is a 55-year-old presenting with a diffuse rash and fever. The rash is itchy. He also feels like his face is more swollen. And so for each one of these cases, you will notice this is obviously not the same person, but what I'm trying to do here is make sure that you see different manifestations of the same disease so that you can kind of create a picture that's inclusive and not just one photo of the disease process. So, um, dermatology is very visual, so we will be having a lot of photos, and I also encourage you after this talk to go look at more photos because these photos only represent a small snapshot of what things may look like. So we'll go through our 10 things to help address the drug eruptions. Is this patient sick or not sick? So if this patient were sitting across from me, I would be a little bit concerned because this patient has a fever, facial swelling, and that's not something that you generally see in your run-of-the-mill drug eruption.

So, what is the morphology? So she has coalescing erythematous patches and plaques with fine scale. Many times this looks like a more morbilliform eruption, meaning measles-like. What is the distribution? So his face is involved, his trunk is involved, and you notice when you're doing your exam, his extremities are involved. And I just want to highlight the importance of doing a full body skin exam for a patient that's coming in with a new drug eruption, just to make sure that you've assessed all the areas involved because sometimes the patient may not know or realize that the rash has spread or exactly where it is. Are the mucous membranes involved? So we're going to say you did your exam and you looked in the mouth, um, you looked in the groin area, you looked at the eyes, you looked in the nose, and the answer is no, they're not involved. So, what are the associated symptoms? So you ask them a little bit more about what's been going on. He says he's itchy, he mentions he's been having fevers, and he's noticed his face looks a little bit more swollen. Any extra-cutaneous exam findings? So face and hands with mild edema. You do a lymph node exam, and you notice that he also has cervical lymphadenopathy.

So, um, you, you decide to ask about any medications. Um, he says that he's been on simvastatin and lisinopril for five years. He, in addition, he occasionally takes a vitamin D supplement. Um, he does suffer from gout, and he started allopurinol four weeks ago. Was fine up until, you know, a couple days when this started. So I, uh, really love the VisualDx flags that they have at the top of certain diseases. So I've actually copied them into my talk, which is, this is a drug rash, with eosinophilia and systemic symptoms, or DRESS syndrome, also known as drug hypersensitivity syndrome. And if you look it up on VisualDx, it has this flag that says, "Emergency, requires immediate attention." So, um, this is not a common condition, but it is something that I saw many, many times in training. And the important thing is to just think about it. It can have a milder presentation that has rash, eosinophilia, lymphadenopathy, um, and then it can, it can have a more severe presentation which has multi-organ dysfunction. Dysfunction. If you suspect this, this is a case where you want to monitor the patient very closely, and probably in the inpatient setting. The important thing to know about this is that the latency period is two to six weeks from drug exposure. Note for any, any sort of drug eruption, if they've been exposed to the medication before, they can actually have the reaction sooner than what is the reported latency period. And the symptoms can actually persist for weeks, even after the drug is discontinued. So that's another important thing to mention is that when you're getting that drug history, make sure you find out if they were on a medication and they stopped it for some reason a couple weeks ago, because, um, that might actually be the culprit.

So these are common offending drugs, but honestly, uh, a lot of different medications. There are case reports out there that have caused this. So I wouldn't necessarily, you know, just say, oh, if it's not on this list, it can't be it. Um, there are Japanese research committee criteria for DRESS syndrome. To be honest, I don't usually go through and check off the boxes. If I see that kind of extensive drug eruption with facial edema and fever and any kind of lab abnormalities, I start getting very concerned for DRESS syndrome. They do have HHV-6 reactivation as one of the criteria. And the reason for that is it's thought, we don't know, there is some school of thought that some kind of viral reactivation happens in this process. Um, but the problem is that usually if you test for that, the result comes back so many days after, like it doesn't really make a clinical difference. So what do you need to do if you suspect DRESS? You want to get a CBC with a differential and possibly a peripheral smear because you can either see, you don't have to see eosinophilia, you may not see it, but you may see atypical lymphocytes on the peripheral smear, and that is another clue. You want to get liver enzymes, creatinine, UA to assess for the kidneys. And the thing is, you can, I have seen DRESS do some very strange things. So definitely can get cardiac involvement and pulmonary involvement. There are certain drugs that are, um, more likely to do that. So minocycline is one that is more likely to have cardiac and pulmonary involvement. And for instance, allopurinol is more likely to have renal involvement. There's no reason for you to sort of memorize these things because you're going to test all of these things. And in very rare cases, as well, I have seen DRESS cause encephalopathy. And the other thing to just be aware of is that the rash can be really subtle. One of the most dramatic cases that I think I saw in residency was a patient that was actually transferred to our care for a liver transplant because they were in liver failure, and the ICU team came and called us and said, "Hey, you know, we don't know what's going on with this person. They're not cognitively with it. They're in liver failure. They're young. It doesn't make any sense. There's no infectious source." There's a really faint rash, and we biopsied the rash. A biopsy will not clinch the diagnosis, but there are findings that can be suggestive of sort of a drug reaction. And the pathologist called us, the dramatic pathologist, and said, "Hey, do you know anything about the medication history?" And sure enough, when we asked the medication, there had been a new, actually, what had happened is, so with anticonvulsants, it can either be like a new start or any kind of dose change that sets it off. And so here was a patient coming in that was supposedly coming in for a liver transplant workup, and once we started the, uh, proper treatment for DRESS, which was stop the offending agent, put it on the allergies, and we started, uh, systemic steroids, she actually completely recovered. And the thing to know with this is you have to taper these steroids very, very slowly, and you have to monitor the labs, um, because they will re-flare as you're tapering. So you just have to keep monitoring labs during re-flare, even after they're out of the hospital. Many times, we're still tapering on an outpatient basis. The other thing to be aware of is that some organ involvement is actually delayed. So you can get thyroid disease. It usually presents three to six months after initial presentation. So good outpatient follow-up, check thyroid labs. Um, these are the kinds of things that we do for the syndrome. And also remember that there can be cross-reacting medications. So, so sort of the anti-epileptics, you have to be careful because they can cross-react with one another.

All right, next case. So a 30-year-old woman comes in with this new rash of two days' duration. She's slightly itchy. She looks, she looks well, she looks fine. So she appears well. So again, this rash actually looks really similar to the last rash, and I, I kind of want you to note that. And the thing to note with it is that actually a lot of rashes that end up being fine or really scary may all begin the same way. Um, so she has coalescing erythematous papules and plaques in a sort of more morbilliform look. That word seems measles-like. And sorry, it looks like the top photo and the bottom photo is flipped, so I apologize for it, because the top photo is the subtle coalescing erythematous patches and papules, and that's what I think is important of studying what rashes look like on different skin tones because of the fact that it can be really subtle. Distribution: she's trunk and extremities. You look at her face, it's not involved. No mucous membrane involvement. A little bit of itching. No fever. No facial or limb edema. No lymphadenopathy. You ask her about drugs. She has been on birth control for a year, and, uh, she started to take Keflex seven days ago for a UTI. She started vitamin C three months ago.

So in this case, you don't have systemic symptoms. She's doing well. She's actually getting kind of better. Um, and so this is what we call the morbilliform drug eruption, or, um, what's often called like, "Oh, it's a macular papular eruption." It's the most common cutaneous drug eruption, like 75 to 90% of cases, usually 7 to 14 days after drug exposure. So in this case, like the Keflex is probably the most likely culprit. Antibiotics are a top culprit, NSAIDs, anticonvulsants, calcium channel blockers. A little bit itchy, sometimes low-grade fever, but they are not going to come in looking sick. They're not going to come in with a high-grade fever and other things. You have to think about is like, I said, there's a lot of things that start out looking this way. So ask about viral illnesses because this can be caused by a recent viral illness. We've definitely seen rashes like this post-COVID. We've even seen it post-COVID vaccine. DRESS syndrome, early SJS, and acute GVHD can all start out looking like this. But of course, DRESS syndrome then progresses to have more of those like systemic symptoms, and SJS also progresses. We'll talk about that a little bit later.

And so, what do you need to do for management? If at all concerned for DRESS syndrome, one, tell your patient what to watch for. Like, if they have any change in systemic symptoms, um, you know, look for facial swelling, ask them about fevers, tell them to watch for fevers, assess for lymphadenopathy. And if I'm concerned, like if this is a patient who is in the inpatient setting, who is high risk, such as they're immunosuppressed or older, I will just go ahead and get the labs if I have any, you know, concern because that will kind of just reassure me. You can hold the necessary medications and, uh, also the suspected trigger. I get, we get asked this question a lot in the hospital setting. If the suspected medication is absolutely required, like such that they're in the inpatient setting and, you know, they have to have it because you're treating a multi-drug resistant infection and this was the only antibiotic that was going to work, um, you can treat through with monitoring and treating the symptoms with antihistamines and topical steroids. One note on topical steroids, make sure that you're using a good strength amount of topical steroids. So lower potency steroids for like the face, the groin, and the armpits, and at least medium potency, like a triamcinolone 0.1 ointment on the rest of the body. And make sure that you order enough. So not like a small, tiny tube. Like we, we, if it's an inpatient, we get a tub and we put it at the bedside.

So our next case, we're moving right along. I, I hope you're enjoying this and getting something out of it. I do feel like I am talking into the void a little bit, but, um, you admit a 60-year-old man to the hospital. He comes in, he says, "Man, I don't feel good. I've been having a fever. I've been having a runny nose, just feel tired." And he has the rash noted above. Uh, he also mentions that his skin burns, and that he noticed that when he has to urinate, it also burns. So all of these things, you should be like, red, you know, red flags, sirens going off in your head. His skin is burning, he has burning with urination, he has fevers. Like, like, you know, and if I see a rash like this, I mean, even when I was, uh, on VisualDx, trying to pick the photos, I felt like I was getting heart palpitations just looking at these photos because your patient walks in looking like this, you, you are concerned.

And so, what is the morphology here? Um, so I want you to notice here these sort of targetoid macules and patches that kind of just look really dusky in the center. And this is kind of followed by the development of blisters and erosions. And if you put lateral pressure on the skin here that hasn't come off, it's probably going to slough off. That's the Nikolsky sign we were talking about. Um, and then in the middle photo, we have these dusky coalescing macules. We may say, "Where's the duskiness?" But if you look at it, you can kind of see that this isn't just red. There's kind of a grayish hue to it. Now, remember that red can look more purple, like inflammation can look more purple and darker skin tones, but this is a lighter skin tone here, and you're kind of seeing this grayish color. You shouldn't really be seeing gray. Um, and you also are beginning to see erosions there. And the bottom photo, you have significant erosions and ulcerations on the lip with crusting. Um, you do the exam, and you see there's trunk involvement, extremity involvement, the lip, as I said, you have burning on urination, and so you see there's actually penile involvement. The mucous membranes are involved. What are the associated symptoms? For him, in this case, he's having fever, he's having rhinorrhea, he's having burning on urination. And, you know, these are the extra-cutaneous. So if you see this picture, your mind should jump to medication-induced. He says that he's been on simvastatin and amlodipine, um, for years. He occasionally takes ibuprofen for headaches, and he started on phenytoin about three weeks ago after new onset, uh, seizures. So I threw that ibuprofen in there actually as, like, to throw you off because sometimes it's not like you look at that history and say, "Well, it must be, you know, the phenytoin," and it probably is, but it's never really like, in with real patients, it's never that straightforward. And so, of course, you know, NSAIDs can cause this too. So I threw that in there because I just wanted to be realistic. Like, a lot of times you'll be scratching your head being like, "I, you know, it could be this drug, it could be that drug." And we'll talk a little bit more about that at the end.

So this is Stevens-Johnson syndrome, toxic epidermal necrolysis, and I love the VisualDx banner on that, which is like, "Life-threatening emergencies." And so whenever people make fun of, uh, dermatologists as being Dr. Pimple Poppers, I love to send, uh, them photos of this condition to say, basically, no, we, we do take care of some really serious disease. So it's a life-threatening condition. You have cutaneous and mucous membranes that have massive keratinocyte death. So the skin cells are just dying, and you're losing the epidermal barrier. It can actually start with this upper respiratory infection-like prodrome, which we see in this case, where he had a little bit of rhinorrhea and fever. These patients are really at high risk of secondary infection, fluid electrolyte shifts due to loss of the epidermal barrier, and scarring. It exists on a spectrum. That's why we call it sort of SJS-TEN because it's, you know, how much of the body surface area is involved. 95% of the time, it's medication-associated, and usually the timing is 7 to 21 days. Earlier previously exposed to medication, over 100 drugs have been implicated. You'll notice that the same drugs keep coming up over and over again with all these different conditions, but the fact of the matter is, you have to just take a good medication history. It may not be one of the ones on this list. The mortality is 5% for SJS and 25 to 50% for TEN. It's pretty terrible. I have seen patients die from this. It does not feel good. Um, you need to find the medication culprit and stop it. And if that means stopping all medications that they're on, usually that's what we do. If it's not some required medication to, you know, keep the person alive, you, you just, just stop everything that you can. And the other thing you want to do is you want to make sure to, if you know what the culprit is, make sure it gets added to the allergy list because, you know, that has happened before where that's not conveyed. You don't want them to get anything like that. It's a hospital admission, you know, usually ICU, and in some cases, depending, they need burn unit type care because they've lost their epidermal barrier. And it's a multidisciplinary thing. So for him, like definitely urology, um, you may even need to get ENT in there because you can get, um, esophageal involvement, you can get tracheal involvement, you get inside the nasal, uh, passages as well. And make sure to get an ophthalmology consult because even if it looks like the eyes look okay, there is a very high rate of ocular scarring. So you do not want to make that determination.

So, sorry, clicked a little fast there. So we're jumping from that very scary entity to something else. Um, I feel like I just got heart palpitations even talking about that condition, as I got flashbacks to several patients that I saw with it. To be honest, I think that's like, uh, you want to get a dermatologist jumping out of bed at 4 AM and rushing to the emergency room. I feel like we, we get consulted for this, like we get a page, "Rule out SJS," and I'm just like, jumping out of the bed and just running to to get to the hospital. Most of the time, thankfully, it is not, but a couple, you know, it has definitely shown up. Um, so here we have, this is probably something you guys see a lot too. A 35-year-old woman coming with the rash above. It's itchy. She says the spots come and go. It started yesterday after she took ibuprofen for a headache. Um, given the pandemic and quarantine, I feel for her. I'm sure we're all having a lot of headaches and Zoom fatigue and things like that. But she's otherwise doing well. No recent illness. So she looks fine. She's not sick. She's got these edematous pink plaques without any epidermal change. Areas that have resolved look normal. Like she said, they come and go within less than 24 hours. They disappear. She gets new ones. It's on the trunk and extremities. She has no mucous membrane involvement. A little bit of itching. No difficulty breathing. No tongue swelling. Look in her mouth. No tongue swelling, lip swelling. You gotta assess here for angioedema. And of course, you ask about medications. She takes a multivitamin every day for the past six months. She uses hormonal birth control, and then she took the ibuprofen yesterday.

So this is acute urticaria. It's an IgE-mediated Type 1 hypersensitivity reaction. Lesions come and go. They should not last. A lesion should not last for 24 hours. The process itself certainly lasts more than 24 hours. Um, a little warning sign if a lesion is lasting more than 24 hours, if it's painful or it leaves behind bruises, this should raise suspicion for urticarial vasculitis, and this needs a skin biopsy and further workup. This can be associated with other autoimmune conditions. So those are kind of little pearls of things that I look for when I have a patient come in with this condition. And of course, I always screen for angioedema, tongue swelling, lip swelling, difficulty breathing, anything that puts your airway at risk, you know, that's an emergency room visit for me. Um, acute urticaria, it's often caused by medications or infection. And actually, we have seen this with COVID as well. Um, it can also be idiopathic. If it starts lasting more than six weeks, then there is a workup associated with chronic urticaria, which is beyond the scope of this talk. But I will say that most of the time with chronic urticaria, we don't find a cause. So, um, stop any triggers, screen for systemic symptoms, fever, and joint pain. So joint pain, you can see this with serum sickness where they have the urticaria and they have joint pains. You know, as I mentioned, lesions that persist more than 24 hours, any of them that burn or leave bruising, um, you can do a skin biopsy if you're concerned that it's not just your run-of-the-mill urticaria or hives. And of course, airway and peri-oral involvement require close monitoring. And, uh, if all of the warning signs are not there, everything seems fine, you can give them antihistamines, usually a long-acting one combined with like a short-acting one on top of it for any breakthrough. And make sure to avoid mast cell degranulators like NSAIDs or aspirin. It can happen at any time. Like I said, she's probably, this patient's probably taking ibuprofen for headaches before, for some reason, it can trigger at any, you know, time.

So I'm just checking our time. I think we do have like 10 more minutes. So I'm just going to move along to the next case, which is really fun. Um, I think it's a, it's a really interesting disease entity that I've seen a couple of times. A 48-year-old with a history of high blood pressure and angina complains of a red rash that started on the face and in the body folds and then spread throughout the body over the past day. She felt like she had a fever as well. Now she's noticing all these pus bumps everywhere, which is very strange. Like this probably might look more morbilliform in the beginning, but then these little pus bumps come up, and that's just very strange compared to everything else we've seen. So she's, she's like borderline. She's not like super sick, but she's sick. She has a fever and she has like this sort of diffuse process going on. Um, and we're seeing these erythematous patches with overlying pustules. Um, there will be no big red banner for this one, like, uh, SJS or or DRESS, but, but you know, you want to watch her. Um, and it's particularly on the face and intertriginous areas, but also generalized. No mucous membrane involvement, though you can rarely have it with this condition. She has some fever, some itchiness, no lymphadenopathy. Ask about drugs. So occasional ibuprofen, lisinopril, simvastatin. Started diltiazem two days ago, prior to the first symptoms.

So, um, this is acute generalized exanthematous pustulosis, or AGEP. And this one actually has a much shorter latency period. You may have noticed the other ones were like seven days, couple weeks. This one usually happens within one to two days of drug exposure. And the skin lesions start on the face and the intertriginous areas and then can generalize, and then you get all these non-follicular sterile pustules. And there's actually a localized variant of this as well that recently showed up on Twitter and was called HSV. So, um, if you see the localized variant, it's rare, but like, you can swap for HSV, just, just keep that in mind. That there can be a localized variant of this. So this looks very much like pustular psoriasis. So ask psoriasis history to make sure that that's not what's going on. Um, the causes include antibiotics, calcium channel blockers, diltiazem, which I mentioned in this case, is a particularly, um, bad actor here. Um, antimalarials, radio contrast dye. There is an AGEP-DRESS overlap, and I have actually seen it where you have like the systemic involvement that you see in DRESS, and they also look like they have AGEP. Um, so, you know, fever, lymphadenopathy, edema, rarely muscle involvement with this. But you won't, again, identify, it's very repetitive, sorry, like you definitely, you want to identify the culprit drug and you want to stop it. And in this case, you do want to check labs just to make sure that there's not that overlap syndrome. Um, and, uh, you can see neutrophilia because these pustules are kind of a, it's a neutrophilic, uh, process. And as I said, to watch for the overlap. And then many of these patients, if there's no systemic, uh, involvement, you can just treat them with, uh, topical steroids.

So this is one of my favorite entities. Um, I actually diagnosed a friend, uh, through this by just like, they sent me a photo and they like gave me a history, and my friend's picture is not on here, obviously, but these are all from VisualDx. So this 30-year-old is coming in with an oval-shaped, deep gray plaque on the neck. No fever, feeling well. So I'm pointing the arrow because that's, that's our patient in this clinical scenario, but I wanted to show you the spectrum of what this can present like. So look fine, they're just got this round plaque there. It's round, deep gray, it's a little bit scaly, just on the neck. Um, no mucous membranes involved. So you can have this on the lips and the, uh, the oral mucous membranes, which is actually a common spot for it to occur. And then no real associated symptoms. His only medication is doxycycline, started when he could go for acne. I wish life were this easy. It's never this easy, but I, I just wanted to sort of write the case in a way that, you know, would kind of be more a little bit more simplistic when thinking about it.

So this is what we call a fixed drug eruption. So I just want you to just take a look. It's very sharply demarcated, and they can be so nice and round sometimes. Like, sometimes I ask the patient, so, you know, there's alternative medicine techniques like cupping. So I do ask about that if it ever seems like, because they're just so nice and round. Um, there is a linear variant. And the thing is, is, uh, with re-challenge, it'll actually reappear on the same site. It may also generalize more broadly with re-challenge. It's very interesting because there's thought that like these memory T cells are involved and that live in the skin and so maybe some, it's something about those memory T cells in the exact same spot will like kind of flare up if they see that same drug again. Um, and by generalized, I was talking like, you, you get it all over the body. So there's a bullous variant, and I show in the photos, I kind of showed that, you know, blistering. Um, and I have seen a case where they had generalized bullous fixed drug eruption, and it can be very scary in terms of confusing this with SJS. A biopsy will help you, you know, kind of distinguish. Um, it does favor the lips, the face, the hands, the feet, and the genitalia. And it's usually one to two weeks after first drug exposure. But like with anything, if it's a re-challenge or if they've seen it before, you know, all those, the time windows go out the window.

So what do you need to do? Stop the medication. Can use topical steroids. And then, you know, particularly in skin of color, where, uh, post-inflammatory pigmentary changes happen, discuss expectations for that because after it goes away, it may leave hyperpigmentation or hypopigmentation for some months to come. I know I'm someone who hyperpigments very easily with any inflammation, and so I just always try to set the expectations like, "Listen, the hyperpigmentation part's going to last for months. You're gonna hate it. Just cover it, keep it out of the sun," and wait for it to sort of resolve.

So those are all our cases. I have some final quick pearls. Do I have time, Art, to do my final pearls? Okay, great. Drug charts, the bane of every dermatology resident. But now that I've been attending, like, I'm like, "You need those drug charts." Which is basically, if you're worried about it, particularly in DRESS syndrome, SJS, those serious ones, and you need to do some detective work to figure out what's going on. You sit down and you write down, you look at the hospital chart, you pull up all the medications they've been on, you look at what dates they've been administered, and you make this beautiful chart, and you try to figure out that timing. And, um, this is just an approximation. This is not like, you know, the gospel in terms of how, but those drug charts coupled with this can kind of help you figure out which drugs, if any, are not likely to be the culprit for whatever disease condition that you're dealing with. Like, you know, AGEP and urticaria that happen quickly. Um, the other ones, there's a longer latency period. Again, everything goes out the window if they've been exposed to the drug before. These latency periods can be shorter. There are some medications like allopurinol where the latency period can be months down the line, according to some case reports. So it can be sometimes frustrating. And I, the question I get all the time is like, "Well, if you can't figure out the drug, what can we do to test?" So there is patch testing, but unfortunately, like with certain conditions, the patch testing is more likely to find the culprit. So with like AGEP, you have a higher chance, but like for SJS-TEN, it, you know, it's not as likely. So sometimes it can be really, um, difficult to find the culprit, and patch testing is one tool that we have as dermatologists to maybe try to help, but it's not perfect.

So I will end with that. I think it's 4:45. Oh, I just want to thank you and say recommended resources: VisualDx, and then I use this book by Misha Rosenbach a lot. It's, it's very, it's written in a very parsable way, so I feel like both dermatologists and non-dermatologists can really benefit, especially if you're doing things in the inpatient setting. And I'm not getting paid anything to say that, or, you know, I don't get any money from that. I just really do like that book.

Thanks so much, Roxanna. It's a difficult subject and really great explanations. We have a whole bunch of questions. We only can get to a few. So I'm going to select a few and shoot them at you and for some quick responses. So one question was, can you explain more about the dusky lesions as a warning sign?

Yeah, so, um, dusky lesions usually indicate that there's cell death and necrosis happening. So sometimes you see this like grayish color because the keratinocytes are dying off, and that's why it's a warning sign is because it usually means that there's, uh, keratinocyte death happening. And in particular, I remember a case where our attending took us, and there were just macules on the patient, those were flat lesions all over the patient, kind of pink in color. It was very early SJS that they had caught, and he pointed to the lesion and said, "Look at this lesion. Do you see how it looks kind of grayish, purplish, dying in the middle? I want you to burn this into your memory because SJS, when it starts, doesn't look, you know, it might not look like much, but if you start, if you, you gotta, you want to really like take a good look at that lesion." Like I said, you can do those kind of tests, and if you're suspecting it's early, like just get, uh, get a biopsy. And in some cases, um, I, you know, I recognize that people are in different setting practice settings and it's not feasible. So like for us, we have a protocol where you can send like a frozen section and it can be like an emergency turnaround. And I recognize that that's like not the case everywhere. Um, but it's a rare condition, you want to be thinking about it, and if you're suspecting it, then it's like, stop the medications, do what you can to to make that diagnosis.

One more question, um, differentiating hypereosinophilic syndrome from DRESS, could you speak to that?

Yeah, I'm not sure that, so like with hypereosinophilic syndromes, which I personally don't, haven't like dealt with, I have one patient that I'm like currently working up for that. Um, I would say that I think it's like a multidisciplinary, uh, situation where you want to get like, like if I'm worried about that, I usually get hematology involved too, because I'm not an expert in that. And, and so like the one case of that I have, I have, it's been more chronic, and I've gotten heme involved. I think I'm not sure if hypereosinophilic syndromes have like sort of like the dramatic edema and like presentation that DRESS has. Um, but of course, with any of these conditions, like we were obviously very drug-focused, but you have to like rule out infection. And so like that very dramatic case that I mentioned, we had hematology involved as well, like ruling out HLH or other, you know, other things. The other thing is DRESS does not always have super, super, super high eosinophils. So, and I think there is like a cutoff for what hypereosinophilic syndrome has to have. So I've definitely seen borderline eosinophils in a lot of DRESS cases, and those atypical lymphocytes on the peripheral smear are always another huge, uh, clue.

Fantastic. Well, thanks again, Dr. Donashu. And we're going to segue to the Kahoot quiz. Kim's going to get that set up now. And while she's setting that up, I'll kind of preview what we're going to do. We'll do the quiz. We ask that dermatology residents and dermatologists do not participate in the quiz. This session was really targeted at advanced practice professionals. So we're going to wait for you to log in to your app, and we'll start showing you slides. And the idea of the quiz is to try to get to the correct answer as quickly as possible. If you haven't played a quiz before. And shortly after that, what I'm going to do is share my screen and show you how you can use VisualDx to check drug reactions. And, you know, drug reactions, you can't memorize all the medication to disease relationships. So we've built a database off of PubMed of all the case reports and articles that point between drugs and the diseases they predispose to or cause. And you can search in either direction. So I'm going to show you. There was also a comment about Dr. Donashu's lecture giving her kudos for skin of color. We actually have over 14,000 images of disease and patients of color, and I'll share that with you as well. We'll just take about five to ten minutes to give some quick power user tips for those that use VisualDx. I'll show you how you can use it for medication adverse events, and then we'll move on to just one or two diagnostic searches, and we'll wish you a good night and to stay warm if you're in a cold part of the country tonight. So I asked Kim when you, I think I think we can get started again. You know, Dr. Papier will give a presentation when this is over, and we also have a survey at the end of this, which is always valuable to know other topics that would be of interest to our VisualDx audience. So let's begin again. There will be eight questions. It'll be multiple choice. Good luck.

Well, it looks like Test G was the speediest. You all did so great on that. I think it was a great review of the presentation. What I'm going to do next is share my screen and go ahead and give some pearls and tips on using a knowledge tool to really help you think through drug reactions. So hopefully you all are seeing the home screen of VisualDx. And what I want to present are two different ways to approach drug eruptions with a knowledge tool. And so the idea here is you can't memorize it all, and that you need a tool that you can use right in the exam room. So you can either search by the medication looking for the possible reactions, or you can search by the reaction looking for the medications. So if I went in and I said, the patient I suspect has fixed drug eruption, I can search by fixed drug eruption. It will take me to the right upon fixed drug eruption. Let me orient you to the screen. There's a "View All Images." So I can say, "View All Images," and see the spectrum. It could be sorted by skin of color or sorted for all skin types. And you'll notice that we're showing the spectrum. So one of the key teaching points is that a lot of diagnostic error occurs because of variation of the comet. So as you saw in the lecture, the classic look of fixed drug eruption is about a three-centimeter, either erythematous with a dusky, slightly dusky center, or brown patch.

or slightly elevated plaque, but they can be larger. They can be multiple, and there's a variant called bullous drug fixed drug eruption. And remember, fixed drug eruptions are common. They're triggered by non-steroidals, and you can see the spectrum here. Sometimes you have quite large lesions with bullae. So VisualDx will show you the spectrum of a disease.

And then in the write-up, there's a point-of-care summary, so you can read a very quick synopsis. And then there's an important field, drug reaction data. So take note on the left, and the table of contents on the left, drug reaction data. It will show you alphabetically every medication the literature says can trigger fixed drug eruption with a number next to it. So you see acetaminophen has 21 case reports and articles in the literature, and these are clickable into PubMed that defend the notion that acetaminophen can cause fixed drug eruption. So some only have one citation, some have many. You can click citations and it will resort to list and show you the class and the individual medications that have the most citations, or you can toggle again to the least. So you can look at this alphabetically, or you can go and quickly check to see which medications have the most evidence in the literature that they cause that problem.

And so all the diseases that can be triggered or predisposed to by a medication are or individual Dx. And you can search, you know, DRESS or Stevens-Johnson or TEN or, you know, pseudoporphyria, lupus, and see which drugs trigger the diseases. Now you can go in the other direction and search the medication. So if I went in, I said the patient's on allopurinol, and I'm not going to put in a skin clue, I'm just going to put in a lab. I'm going to say, your clinical question is, my patient has elevated liver enzymes. Allopurinol was started. I'm wondering, does allopurinol cause elevated liver enzymes? When I click view the differential, it gives me some diagrams first: drug-induced hepatic toxicity, acute liver failure, drug-induced hypersensitivity syndrome, and Stevens-Johnson. So if you look here, you'll see that you have nine citations for drug-induced hepatic toxicity, 24 for drug-induced hypersensitivity syndrome, and 10 citations for Stevens-Johnson. So if your patient didn't have a rash, they probably don't have drug hypersensitivity or Stevens-Johnson because those diagnoses are defined by having a skin rash. Where obviously with drug-induced hepatic toxicity, you might just have nausea, vomiting, hepatomegaly, etc.

So the drug eruption database that's in VisualDx is not limited to skin. So you can put in other factors. You can go in and say, you know, we'll go in and say the patient's on dapsone, and we'll, we'll say the patient has lymphadenopathy, and we can say the patient has hepatomegaly. And you'll know where I'm heading from the lecture, and it's going to give us a differential. And there's drug-induced hypersensitivity, but also cervical lymphadenitis only has one finding. So you would then, of course, be looking to see if the lymph nodes were at the neck versus the other conditions.

So very, very quickly, because we're running out of time, VisualDx covers 3200 diagnoses. Though the founders are dermatologists, we're working with cross-specialty emergency physicians, primary care physicians to develop a technology where you can search by any chief complaint. It's particularly rich for dermatology, and you can have this on your iPhone or Android. And there's a machine learning component where you can take a photo of the rash, and the machine learning will help to analyze the rash as well. There's demos online that you can watch.

But of particular interest is the work we're doing in disparity. So we've been focused for 20 years on having an equitable image collection. As I mentioned, there's over 14,000 images of skin of color. And when you go to build a differential this way, you'll see the icons are in patients of color. And I could say there's a scaly plaque, and the scaly plaques, they are on the leg, and I can say the patient has pruritis or itching. So you can type in symptoms, signs, labs, anything, and then get to a differential. And because I started with skin of color, you're going to see the imagery in skin of color. So we'll show you nummular dermatitis, and you'll see the imagery starts in skin of color, and then you can scroll down to lighter skin.

And VisualDx includes the summary, what to look for in exam, the tests that you can do, management pearls, and treatment of the diseases. So I wanted to give that quick overview, particularly of how to use VisualDx for medication adverse events. There are many web, there's many YouTube videos, we host webinars, we bring VisualDx to many nurse practitioners and physician assistants. We had a wonderful nurse practitioner in Oregon diagnose shiitake mushroom dermatitis with VisualDx. I've been practicing dermatology for 27 years, I've never made that diagnosis. An NP in Oregon made that diagnosis with VisualDx help. And so we're believers here in augmenting the exam room decisions. And people use VisualDx right at the point of care. They share images with patients, and it settles down anxious patients. And I got to underscore that in these times of stress and uncertainty with COVID, we have lots of anxious patients. Showing them an image that looks like them, looks like their rash, you have a patient of color, you can show them an image of a patient of color, or light-skinned patient, similar image. You can print a handout, you can email a handout.

So with that, I'd like to thank everyone for their attention. Please, when you log out, fill out the questionnaire. We want to know what other topics you'd like us to cover for advanced practice professionals. And please feel free to email us. There was a raised hand. Questions here. I just want to make sure that we cover all the questions. All right, so we've covered all the questions. And thanks everyone. Kim, any closing remarks from you, or we're all set? No, I think we're set. Um, also, future events, you can go to VisualDx.com/events for upcoming webinars. And again, thank you to Dr. Repair and Dr. Roxanna Duchino. And thank you guys so much. And this has been recorded, and we will be sharing the recording to all of you, um, tomorrow. Thanks so much. Have a good evening.