Thank you, Dr. Johnson, that was wonderful. Dr. Gerlach will give his talk, and again, last but not least, so let's. Thank you, and for one, I learned a lot from both of our speakers, and thanks for this opportunity. So I'm here today to talk about Not Another Rash. I have no conflicts of interest to disclose, and it's really just describing some of the practical benefits, what we see in these patients. And I think, as Dr. Johnson said, this is a recent case of someone who was billed as Stevens-Johnson syndrome, but since I'm not in that talk, they didn't have it. But this was someone who I took care of, actually, in September. It was a 63-year-old obese female who had kind of this prodromal syndrome, and she was diagnosed with a fungal rash and a UTI, and giving Cefalexin and a nice statin cream. And really, those were the only drugs that had changed in dose or in anything in over six months. But her rash was worsening, especially under the right breast and abdomen. She had pancytopenia, ocular pain, and acute kidney injury. So as you can see why this might have been considered Stevens-Johnson's. And then she really has a complex history, including cervical cancer that was in remission. And when you look at the differential diagnosis, I think, as alluded to, especially by Dr. May, there's a lot of reasons in there, and includes infection. And it's probably what we're used to similar, at least in my clinical practice, is an STI. But there's also acute skin failure, which I think Dr. Johnson spoke of really well. Cancer-related effects, that might be due to their chemotherapy agents, or it might be due to the cancer itself. The immunobolus diseases, rheumatological diseases, and a lot of drug rashes, or drug response reactions that we can see. And not only that, it might also be a response of some sort of medical device, or pressure injuries as well. Now as Dr. May alluded to, primary reasons people come in the ICU are few and far between. This is probably the largest study of almost 500,000 people in the UK, spanning a 10-year period. And it was mostly, I think, from England, Wales, and Northern Ireland. And the reason for admission was only about a half of 1%. And when you look at the reasons for dermatologic manifestations, by far and away, infectious complications are what we see. And those were over 85%. With, of all the infectious complications, over half were an STI, and something that we at least see a lot of in Ohio at my practice. And about 30% was cutaneous cellulitis. Acute skin failure, such as Stevens-Johnson's, is actually very rare. It's only about 9% of it, and 6% of all is a Stevens-Johnson's. So as you allude to, there's a lot in there with the diagnosis of it. And I think this is one of the things we do need to look at in the history. And it's really involved as a detailed history of the patient. It takes a lot of time, but it's one of the things that we really need to do with these people. And as Dr. Johnson said, did they have any flu-like syndromes? And are there any other intracranial symptoms? Making sure we assess the whole body and all the mucous membranes. And really getting a detailed medication history, including any new medications in the last two or three months, or if any doses have changed. And some other things to keep in mind. Any new wounds, bites, or surgery, are they postpartum? Because a lot happens during pregnancy, and any recent travel. Because what we see in Ohio might be different than if someone just came back from India. Now as Dr. May did too, it's always nice to make sure that we're speaking the same language. Being a pharmacist, I was really never taught a lot of this. I never learned dermatologic words, but I think there's some things that's important for us to know. And really some of this is somatics. The difference between a papule and a plaque is just the size of it. But really making sure, is it a vesicle? So is that a lesion that's small that contains fluid, versus a bullae, which is large that contains fluid, versus a pustule, does it contain pus? And really what I think we all need to look at, especially for the ones that come in the ICU, is there erosion, or are you losing some, or the entire part of the epidermis? And acute skin failure, what are some of the common causes of it? As it was alluded to, about 3 4ths of them are between drugs and infection. And only about 20%, as Dr. May said, is really due to some sort of skin disease. But there's a high morbidity associated with these patients that do have acute skin failure. Their length of stay tends to be, in the hospital, double that if it was due to infection or conditions. And these people have a really high mortality rate associated with it, with about a third dying in the ICU, and about a half dying in the hospital. Now what are some of these life-threatening skin conditions? There's an immunobolus group, or the Penphagous group. And these are the mucus, or the blisters that break easily and become erosions. And as Dr. Johnston showed perfectly, is the Narkoski sign, where you have that skin detachment. There's also generalized pustule psoriasis. It's also known as von Zimbabwe disease. And these are plaques with sterile pustules alone that are followed by discriminative areas, and it's really associated with some systemic inflammatory response syndromes. And then erythrodema, which is more of an exfoliative dermatitis, but it happens on more than 90% of the skin. So there's a variety of degrees of discrimination. Sorry, I butchered that word. But there's a lot of skin diseases, drugs, and cancers that are associated with it. And one of the things that we do are starting to see is this new condition called DRESS, or drug reaction with eosinophilia and systemic symptoms. And these are more of like a measles-like rash, but it's associated with a pretty high fever, greater than 38 degrees Celsius, and typically starts two to six weeks after the initiation of the drug. And when you look at the drugs that cause it, it's actually relatively few. Abcavavir, which is typically used for HIV. Allopurinol, a lot of the antibiotics. Anticonvulsants, azathioprine, maxillotine, norepinephrine, and the PPIs. So always remember that there are over-the-counter drugs that can do it too. The bad thing about this is we often get virus reactivation, specifically herpes, but you can also get Epstein-Barr or CMV too. And I think, as Dr. Johnson alluded to, to look at some of these diseases, there is an onset with the drugs. With AGAEP, typically a short duration, but you'll see with DRESS and erythroderma and Steven Johnson's, there might be much longer. And the duration also depends on what it is. I think one of the big things to keep in mind is the mucosal involvement, which is severe in Steven Johnson's TEN, and it's none to minimal in all the other ones. And also the fevers that you see. You get the higher fevers in DRESS and AGAEP. And then finally, what is this skin pathology? In Steven Johnson's syndrome, you have this necrolysis of the epidermal, and everything else is a little bit different. And it's why it's important to get dermatology in there and get your skin biopsies. Now, I think part of this is our thought about chemotherapy. I do also practice one of the surgical ICUs is a cancer ICU. And in the last few years, chemotherapy has dramatically changed with the immunotherapy. Traditionally, we have our alkylating agents, the mustards, antimetabolites, and the spindle inhibitors, the taxines and vinca alkaloids. But now we have the NIBS and the MABS, as I like to call them, right? And they work a lot on different areas, right? Oftentimes, you have the BRAF or VRAF, murine, sarcoma, viral oncogene inhibitors. And there's two of them mainly out. But what we really are seeing are a lot of the single transduction inhibitors or the tyrosine kinase inhibitors. And they're really broken down into three types. And those include both the NIBS and MABS being monoclonal antibodies. But there's a lot of dermatological side effects that we do see with those. And it's not something that we're often talked about. And when we look at those diseases, there's typically three types that I like to think about, papular, postural eruptions. And you see those a lot with the spindle or the tyrosine kinase inhibitors. Most of them, the mTOR inhibitors, which are similar to immunosuppressants that we use after transplantations and then the BRAF inhibitors. Or the BRAF inhibitors, I said it wrong, sorry. Then there's also hand, foot, skin syndrome, which is also known as pulmonary plantar erythrodysesia, acral erythemia, or Bergdorf syndrome. And really what this is, is it starts with a rash on your hands and feet. And it can lead to ulceration, swelling, and blistering. And you see those with both some of the newer chemotherapy agents and some of the older ones, as I have listed there. And then always remember, most of these drugs are very toxic and you can get skin necrosis with extravasation, especially with some of the, a lot of the older agents. So always keep that back in mind too. Now what's the treatment? I think as we saw, especially if you have greater than 10% surface area, is really consider either transfer to a burn center or having that high level of care that you can get your dermatology consult and have all the players there. Because these people do need not only physicians, dermatologists, pharmacists, great nurses, and nursing care and nurse practitioners, but we need dieticians there to help with it. We need that barrier control, fluids as appropriate, and that might be a lot depending on how much of your skin, as Dr. Johnson said. Definitely early nutrition support and then pain control. And really, it's best done by an interprofessional team and we in the ICU excel at that. Now there are some specific treatments out there depending on what is the cause and what the diagnosis is. For AGEP, it's really stopping the offending agents. Most of the time, they just need topical steroids for symptomatic relief. But in severe cases, you might need systemic steroids or cyclophosphamide. For the chemotherapy, it really depends on what's causing it and what chemotherapy. If it's the papule pustule eruptions, sometimes they give oral tetracyclines to decrease the rash severity, especially with the EGRF inhibitors. For the Hannan-Fitts syndrome, ceterabine, you actually wanna give a COX-2 inhibitor, doxorubicin, DSMO, and then obviously you wanna treat extravasation early once it's found. And then really for the DRESS syndrome, going out here, you typically wanna give them systemic steroids, typically a milligram per kilo per day of prednisone or its equivalents, and then you taper over a pretty long time of one and a half to two months. And in severe cases, you might do plasmapheresis, cyclophosphamide, cytoxan, or rituximab, and then you'll always wanna make sure you're addressing the need for antivirals and you might be on some prophylactic agents. Now to kinda get back to my cases, she had some of these signs that, well, maybe she had early Stephen Johnson's in there and she had that worsening rash specifically under her right breast and abdomen, but she also had pancytopenia, ocular pain, and AKI. Now, there was a lot going on, so I actually went up to the unit early that day, and as soon as I got there, like three different doctors are like, I'm not sure this is Stephen Johnson's. We really need help in her medication reconciliation. Like, okay, because saying that she's on allopurinol for rheumatoid arthritis never made sense to me. It's not an indication, right? So when the listed meds, which I think were like four or five years ago, are in the chart, are listed under the orange side, of those, only three of them were actually meds she was on. They were completely different. Over there on the green side under the pills were actually a lot of the meds she was on, and so she wasn't even getting allopurinol, so we listed it out, but I wrote my note and looked at those people, and this is just when you really look at the patient case. What were her symptoms and what was she complaining of? She had these hemorrhagic erosions, and specifically in her inframammary and suprapubic folds, she had mucosal eruptions, clustered hemorrhagic papules on the face, and it kind of looked like this, but this was more of a picture I got from the internet, ocular pain, AKI, and this pancytopenia. So what is the diagnosis? So out there, what do you think might be the drug cause? Because it was a drug cause here, because I'm the pharmacist. She actually had methotrexate toxicity. She had rheumatoid arthritis, and she was getting 17.5 milligrams every week. She came on on a Thursday night, and Friday was supposed to be her day of getting it. Luckily, we didn't give it. Her last dose was at six days ago. At that time, you shouldn't have a detectable level, and when we measured it, it was detectable. So she got started on lucavorin rescue therapy until the limit was under the lower limit of detection, and over the next about two weeks or so, she was hospitalized for about four weeks. Her rash approved, and her mucosal erosions healed. It took her about three weeks for her AKI to resolve, and then her skin biopsy was consistent with the drug-induced dermatitis. So with that, thank you very much, and I think it's time for some questions.

skin conditions

diagnosis

treatment

patient history

DRESS