1 00:00:03,350 --> 00:00:04,260 Sara Dong: Hi, everyone. 2 00:00:04,300 --> 00:00:08,600 Welcome to Febrile, a cultured podcast about all things infectious disease. 3 00:00:09,190 --> 00:00:13,099 We use consult questions to dive into ID clinical reasoning, diagnostics, 4 00:00:13,099 --> 00:00:14,320 and antimicrobial management. 5 00:00:14,559 --> 00:00:17,639 I'm Sara Dong, your host and a MedPeds ID doc. 6 00:00:17,900 --> 00:00:21,909 Today, we have a team visiting from the University of Wisconsin, Madison. 7 00:00:22,080 --> 00:00:23,269 First, let's meet Dr. 8 00:00:23,269 --> 00:00:24,349 Michael Moran. 9 00:00:24,805 --> 00:00:28,915 Michael is an adult Infectious Diseases Fellow at the University of Wisconsin. 10 00:00:29,074 --> 00:00:30,714 Michael Moran: Hi, my name is Michael Moran. 11 00:00:30,725 --> 00:00:32,115 I'm excited to be on the podcast. 12 00:00:32,225 --> 00:00:33,625 Sara Dong: Also joining is Dr. 13 00:00:33,625 --> 00:00:34,755 Swapnil Lanjewar. 14 00:00:35,145 --> 00:00:39,814 Swapnil is a Clinical Assistant Professor in ID at the University of Wisconsin. 15 00:00:40,015 --> 00:00:44,134 He completed his medical schooling in India and pursued his IM residency 16 00:00:44,155 --> 00:00:45,754 at the Cleveland Clinic in Ohio. 17 00:00:46,050 --> 00:00:49,629 He did his fellowship in ID at the University of Wisconsin Madison. 18 00:00:49,780 --> 00:00:52,360 Swapnil Lanjewar: Hi, this is Swapnil Lanjewar, and I'm 19 00:00:52,489 --> 00:00:53,989 super excited to be here. 20 00:00:54,499 --> 00:00:59,349 Both me and Michael, we are big fans of the Febrile podcast, so we are absolutely 21 00:00:59,349 --> 00:01:01,109 thrilled to join you here today, Sara. 22 00:01:01,660 --> 00:01:03,470 Sara Dong: Well, I'm very excited to have you. 23 00:01:03,780 --> 00:01:08,580 Of course, before we jump into the case, we always ask one question. 24 00:01:08,620 --> 00:01:12,550 We are everyone's favorite cultured podcast, so I'd love to hear about a 25 00:01:12,550 --> 00:01:17,240 little piece of culture, something non medical that you've enjoyed recently 26 00:01:17,250 --> 00:01:19,979 or like to do in your free time. 27 00:01:20,220 --> 00:01:21,009 Michael, what do you got? 28 00:01:21,160 --> 00:01:23,919 Michael Moran: Yeah, I mean, so in fellowship, I think I've been 29 00:01:23,940 --> 00:01:27,289 trying to find a lot of things to like kind of dump my brain. 30 00:01:27,479 --> 00:01:32,709 And I was just recently introduced to 90 Day Fiancé, which I had 31 00:01:32,779 --> 00:01:34,559 until now never watched before. 32 00:01:34,559 --> 00:01:37,649 And it was like this week and it is absolutely wild. 33 00:01:37,660 --> 00:01:42,360 And so I've been kind of going down a rabbit hole in that of just that's 34 00:01:42,360 --> 00:01:44,369 the opposite of anything medicine. 35 00:01:45,719 --> 00:01:47,810 So I understand all the hype now. 36 00:01:47,860 --> 00:01:48,030 Yeah. 37 00:01:48,030 --> 00:01:49,240 Sara Dong: What about you Swapnil? 38 00:01:49,555 --> 00:01:53,524 Swapnil Lanjewar: One of my biggest hobbies is playing table tennis. 39 00:01:53,945 --> 00:01:57,714 I grew up in India and I used to train formally in table tennis. 40 00:01:57,714 --> 00:02:01,674 And I used to play competitively at the state and national level tournaments. 41 00:02:01,675 --> 00:02:04,784 But these days it's mostly limited to playing with some 42 00:02:04,794 --> 00:02:05,784 friends over the weekend. 43 00:02:05,954 --> 00:02:07,154 Sara Dong: Do you get really aggressive? 44 00:02:07,164 --> 00:02:08,154 You're very competitive. 45 00:02:08,174 --> 00:02:09,004 Swapnil Lanjewar: I am actually. 46 00:02:12,244 --> 00:02:12,874 Sara Dong: Awesome. 47 00:02:12,934 --> 00:02:15,674 Well, I will hand it over to Michael. 48 00:02:15,714 --> 00:02:16,514 Tell us about the case. 49 00:02:16,890 --> 00:02:21,270 Michael Moran: So today we are getting a call from the medicine team to get 50 00:02:21,270 --> 00:02:25,750 some help looking at a patient for the management of someone they admitted 51 00:02:25,750 --> 00:02:30,420 overnight with a fever and a rash, and this occurred this past March. 52 00:02:30,719 --> 00:02:34,030 When they called us, they gave us a little story about our patient. 53 00:02:34,039 --> 00:02:39,530 She's a 47 year old female, has a past medical history of gout and hypertension, 54 00:02:40,090 --> 00:02:44,080 and notably about eight weeks ago, she was seen by rheumatology due to a 55 00:02:44,080 --> 00:02:48,769 one year history of polyarthralgia and was diagnosed with seronegative RA. 56 00:02:49,120 --> 00:02:53,420 At that appointment, she was started on sulfazalazine and low dose oral prednisone 57 00:02:53,430 --> 00:02:57,999 of about five milligrams a day, resulting in significant symptomatic improvement. 58 00:02:58,750 --> 00:03:02,459 In regards to her current presentation, the medicine team tells us that 59 00:03:02,459 --> 00:03:07,179 about three weeks ago, she started experiencing high grade fevers to 103 to 60 00:03:07,189 --> 00:03:12,225 104 degrees Fahrenheit with associated night sweats and some loss of appetite 61 00:03:12,225 --> 00:03:13,965 and bilateral upper abdominal pain. 62 00:03:14,545 --> 00:03:19,435 About 10 days prior to this presentation, these symptoms were persisting, so she 63 00:03:19,435 --> 00:03:22,044 presented to her local ER for evaluation. 64 00:03:23,045 --> 00:03:27,614 Her exam at that time, along with routine labs like a CBC and CMP, 65 00:03:27,614 --> 00:03:31,325 were within normal limits, although she did have an elevated CRP. 66 00:03:32,045 --> 00:03:37,090 They tell us a CT chest abdomen pelvis was performed and was negative, and as 67 00:03:37,090 --> 00:03:42,280 this was late winter, early spring, a respiratory pathogen panel multiplex PCR, 68 00:03:42,289 --> 00:03:47,099 was done and negative, but with no other explanation, she was discharged home 69 00:03:47,109 --> 00:03:50,980 with a tentative diagnosis of a viral syndrome, as she was otherwise well. 70 00:03:52,445 --> 00:03:56,454 At home, her fever still continued on a daily basis without improvement, 71 00:03:56,855 --> 00:03:59,904 which brings us to our current hospital admission, where she is now 72 00:03:59,904 --> 00:04:03,104 presenting with the new development of a rash, which started about 73 00:04:03,104 --> 00:04:04,944 three days prior to presentation. 74 00:04:06,274 --> 00:04:09,454 The primary team tells us the rash is pink, macular, and 75 00:04:09,454 --> 00:04:11,914 patchy, located all over her body. 76 00:04:12,594 --> 00:04:14,794 The rash is not itchy and non painful. 77 00:04:15,055 --> 00:04:17,855 They tell us there have been no new medications in the last one 78 00:04:17,855 --> 00:04:19,395 to two weeks to explain this. 79 00:04:20,845 --> 00:04:24,935 The team tells us the patient is currently hemodynamically stable, but 80 00:04:24,945 --> 00:04:27,075 has a temp of 102 degrees Fahrenheit. 81 00:04:28,085 --> 00:04:33,835 So far, her repeat labs and new CT chest abdomen pelvis are still unremarkable. 82 00:04:34,764 --> 00:04:37,424 The team is planning to hold off on any antibiotics because 83 00:04:37,425 --> 00:04:38,835 she otherwise looks good. 84 00:04:39,025 --> 00:04:39,605 Swapnil Lanjewar: All right. 85 00:04:39,784 --> 00:04:41,404 Thank you so much for the case, Michael. 86 00:04:41,830 --> 00:04:44,080 So I will summarize what I gathered here. 87 00:04:44,140 --> 00:04:48,680 So it looks like we have a 47 year old female with past medical history of 88 00:04:48,680 --> 00:04:53,770 gout and recently diagnosed seronegative rheumatoid arthritis for which she was 89 00:04:53,780 --> 00:04:58,859 started on treatment about two months ago and she's now presenting due to fever of 90 00:04:58,909 --> 00:05:03,199 unknown etiology over the last four weeks and a new rash since last three days. 91 00:05:03,700 --> 00:05:07,930 And this is in the setting of nearly normal labs and imaging about 10 days ago? 92 00:05:07,980 --> 00:05:08,550 Michael Moran: Exactly. 93 00:05:09,219 --> 00:05:12,909 So Swapnil, if you were called about a case like this, how would you approach 94 00:05:12,909 --> 00:05:17,190 developing an evaluation and treatment plan for a patient with fever and rash? 95 00:05:17,209 --> 00:05:20,669 Swapnil Lanjewar: Fever with rash is an important topic and it's quite 96 00:05:20,669 --> 00:05:23,630 a challenging one, actually, for the infectious disease clinician. 97 00:05:24,219 --> 00:05:27,729 This is because the list of differentials is quite big. 98 00:05:28,159 --> 00:05:32,379 So I remember that as a trainee, this topic used to be pretty intimidating 99 00:05:32,379 --> 00:05:36,580 for me, And even sometimes I struggle with a patient with fever and rash. 100 00:05:37,120 --> 00:05:40,880 But over the years, I developed a structured and organized approach 101 00:05:40,890 --> 00:05:42,779 for myself that I can share today. 102 00:05:43,200 --> 00:05:45,320 And this is my personalized approach. 103 00:05:45,640 --> 00:05:49,789 If you already have an approach nailed down which works well for you, then I 104 00:05:49,809 --> 00:05:51,269 think you should keep doing that one. 105 00:05:51,840 --> 00:05:57,669 For the purposes of this podcast, I will break down my approach in three parts. 106 00:05:58,159 --> 00:06:02,920 First is what I do before I see the patient, second is what I do while I'm 107 00:06:02,950 --> 00:06:07,549 seeing a patient, and third is what I do after I'm done seeing the patient. 108 00:06:08,090 --> 00:06:10,760 Let's come to what I do before I see the patient. 109 00:06:11,340 --> 00:06:14,929 I try to get a few questions answered absolutely before I hang 110 00:06:14,930 --> 00:06:16,890 up the phone with the primary team. 111 00:06:17,505 --> 00:06:21,465 When they're telling me about the case, I try not to interrupt them, and this is 112 00:06:21,475 --> 00:06:25,725 because I want to make sure that they're not losing their train of thought, and 113 00:06:26,395 --> 00:06:30,845 they don't forget giving me an important piece of information, and then I pay 114 00:06:30,845 --> 00:06:33,165 attention to how sick is the patient. 115 00:06:33,194 --> 00:06:36,975 Like, am I getting a call from the ICU, or is the patient's primary 116 00:06:36,975 --> 00:06:38,715 care physician calling me about this? 117 00:06:39,370 --> 00:06:43,950 If the patient is in ICU, super sick, hemodynamically unstable, 118 00:06:44,460 --> 00:06:48,529 then I want to make sure that I'm not missing a never miss diagnosis. 119 00:06:49,010 --> 00:06:51,280 For example, you know, is it a surgical disease? 120 00:06:51,599 --> 00:06:54,169 Is it necrotizing fasciitis? 121 00:06:54,250 --> 00:06:58,259 Or is this a hemorrhagic rash because of septicemia from either a 122 00:06:58,259 --> 00:07:03,760 perforated viscus or a really terrible bad piomyositis or a huge abscess 123 00:07:03,760 --> 00:07:05,040 which requires emergent surgery? 124 00:07:06,370 --> 00:07:10,440 Or is it related to a toxic shock syndrome from a retained foreign body like a 125 00:07:10,440 --> 00:07:16,010 tampon or a line or device infection which is causing the septic shock? 126 00:07:16,610 --> 00:07:22,160 These are some never miss diagnoses and then if the season and location 127 00:07:22,160 --> 00:07:26,050 are right, I will also think about tick borne infections like Babesia 128 00:07:26,090 --> 00:07:29,420 and Rocky Mountain Spotted Fever that I want to make sure I'm not missing. 129 00:07:29,810 --> 00:07:33,130 And if the patient is immune compromised, I absolutely don't want 130 00:07:33,140 --> 00:07:35,300 to miss any terrible fungal infection. 131 00:07:36,044 --> 00:07:41,745 So, apart from that, I also want to make sure whether or not I need to put 132 00:07:41,745 --> 00:07:43,805 this patient into prompt isolation. 133 00:07:44,534 --> 00:07:48,954 If there's anything like a meningococcal disease or a viral hemorrhagic fever 134 00:07:48,954 --> 00:07:53,584 like Ebola based on epidemiologic risk factors for the patient, then you 135 00:07:53,585 --> 00:07:57,234 want to make sure you put the patient in isolation as soon as possible. 136 00:07:57,825 --> 00:08:02,835 Sometimes, somebody who's really sick with HIV and miliary TB can 137 00:08:02,835 --> 00:08:04,305 actually have a skin rash too. 138 00:08:04,935 --> 00:08:08,035 So, these are some considerations regarding whether they 139 00:08:08,035 --> 00:08:09,225 need prompt isolation. 140 00:08:09,795 --> 00:08:14,875 And lastly, if this is an exotic disease, you know, like malaria or so, based on 141 00:08:14,904 --> 00:08:17,484 their epidemiologic risk factors again. 142 00:08:18,025 --> 00:08:21,564 Technically, the textbook approach is also to think of bioterrorism, 143 00:08:21,565 --> 00:08:25,365 but I really hope that none of us in real life have to think about that. 144 00:08:25,365 --> 00:08:29,665 So, these are things I do before I see the patient while I'm still on 145 00:08:29,665 --> 00:08:31,034 the phone with the primary team. 146 00:08:31,580 --> 00:08:34,930 If they don't have a never miss diagnosis and you receive such a 147 00:08:34,930 --> 00:08:38,900 call in middle of night, then it will make me feel comfortable. 148 00:08:38,900 --> 00:08:39,549 Okay, fine. 149 00:08:39,549 --> 00:08:40,740 I think I covered everything. 150 00:08:40,740 --> 00:08:42,379 I can go back to sleep safely. 151 00:08:42,830 --> 00:08:45,950 Next comes what I do while I'm seeing the patient. 152 00:08:46,379 --> 00:08:49,389 So obviously this, I'll divide this between two parts, 153 00:08:49,399 --> 00:08:51,370 history taking and examination. 154 00:08:51,990 --> 00:08:55,940 History taking is one of the most important skills for any 155 00:08:55,950 --> 00:08:57,460 infectious disease clinician. 156 00:08:58,010 --> 00:09:01,520 When you have so many questions that you need to ask to the patient. 157 00:09:01,974 --> 00:09:05,734 It's very easy to forget some crucial pieces of information, 158 00:09:06,275 --> 00:09:10,395 so over the years, I've developed a personal template for myself. 159 00:09:10,844 --> 00:09:14,714 I try to follow this template just so that I don't miss anything 160 00:09:14,715 --> 00:09:16,225 important to ask the patient. 161 00:09:16,865 --> 00:09:19,885 After I'm done asking them relevant questions about the 162 00:09:19,904 --> 00:09:25,015 HPI, I'll ask five main group of questions to elicit differentials. 163 00:09:25,465 --> 00:09:30,565 First group is occupational history, second group is outdoor exposures, 164 00:09:30,995 --> 00:09:35,750 then indoor exposures, then regarding something they ingested or injected, 165 00:09:36,190 --> 00:09:40,179 and the fifth one would be non exposure related differentials. 166 00:09:41,070 --> 00:09:45,630 Going to occupational exposures, this is important to elicit because if 167 00:09:45,630 --> 00:09:49,389 they are a butcher, let's say, there have been periodic outbreaks of Staph 168 00:09:49,389 --> 00:09:51,379 and Strep infection amongst butchers. 169 00:09:51,919 --> 00:09:56,569 If somebody's a chef who's handling raw meat, then I'll think about Salmonella. 170 00:09:56,599 --> 00:10:00,299 And if they are routinely tasting raw oysters, then you 171 00:10:00,299 --> 00:10:01,750 also have to consider Vibrio. 172 00:10:02,550 --> 00:10:06,030 If they are a taxidermist, I know that there have been some 173 00:10:06,040 --> 00:10:08,020 outbreaks of Q fever before. 174 00:10:08,630 --> 00:10:13,099 So if they're a fisherman, I would think about something like Vibrio 175 00:10:13,109 --> 00:10:16,780 if they are on the coast and are having a lot of exposures there. 176 00:10:17,330 --> 00:10:19,549 So that's about occupational exposures. 177 00:10:20,150 --> 00:10:24,299 Coming to outdoor exposures, I tend to categorize them 178 00:10:24,299 --> 00:10:26,190 in three main subcategories. 179 00:10:26,560 --> 00:10:33,415 Travel related and then hiking or camping related, or water body related exposures. 180 00:10:33,965 --> 00:10:36,505 Hiking and camping related outdoor activities. 181 00:10:36,505 --> 00:10:38,575 You know, what, what were they doing outside? 182 00:10:38,944 --> 00:10:42,175 Were they doing something that involved turning of soil? 183 00:10:42,185 --> 00:10:43,895 Were they out exploring caves? 184 00:10:44,245 --> 00:10:47,485 Were they in contact with wild animals like, you know, flying 185 00:10:47,485 --> 00:10:50,184 squirrels and snakes and bears? 186 00:10:50,715 --> 00:10:54,275 Or were they in contact with any farm animals? 187 00:10:54,600 --> 00:10:58,890 And then, have they been annoyed by some insects or arthropods like 188 00:10:58,940 --> 00:11:02,110 ticks or lice or mosquitoes or flies? 189 00:11:02,599 --> 00:11:06,570 Because all of these can contribute to your list of differentials as well. 190 00:11:07,170 --> 00:11:11,289 Now, with regards to travel related exposures, then I ask 191 00:11:11,289 --> 00:11:12,750 them where exactly they travel. 192 00:11:12,760 --> 00:11:15,530 Was it a domestic travel or international travel? 193 00:11:16,050 --> 00:11:19,725 Of course, we all know domestic travel related exposures differentials you have 194 00:11:19,725 --> 00:11:21,545 to consider like in the southwest U. 195 00:11:21,545 --> 00:11:21,685 S. 196 00:11:21,685 --> 00:11:22,985 you think about Cocci[dioides]. 197 00:11:23,265 --> 00:11:26,665 Here in the Midwest we always think about Histo[plasma] and Blasto[myces]. 198 00:11:27,145 --> 00:11:30,094 In New England you would consider things like Lyme disease 199 00:11:30,125 --> 00:11:31,604 based on the season as well. 200 00:11:32,284 --> 00:11:36,295 And then when it comes to international travel, my first 201 00:11:36,295 --> 00:11:39,895 question is always did you check the CDC website before you traveled? 202 00:11:40,645 --> 00:11:44,715 Regardless of the answer, I will always pull up my phone and I'll go 203 00:11:44,715 --> 00:11:50,480 on cdc.gov/travel and and pick their destination of travel and see what 204 00:11:50,480 --> 00:11:54,160 all exposures that can occur in those particular areas of the world because 205 00:11:54,240 --> 00:11:58,109 I can never remember, you know, specifics regarding to each country. 206 00:11:58,109 --> 00:12:01,490 Like for example, if somebody traveled to India, you have to think about 207 00:12:01,500 --> 00:12:07,639 typhoid, you have to think about malaria, even kala azar or leishmaniasis. 208 00:12:07,719 --> 00:12:09,000 The list is pretty extensive. 209 00:12:09,720 --> 00:12:11,459 That's in with regards to travel. 210 00:12:11,840 --> 00:12:14,819 Next is outdoor exposure is water bodies, right? 211 00:12:14,840 --> 00:12:20,605 So it could be oceans or You know, ponds, lakes, uh, streams and rivers, 212 00:12:20,665 --> 00:12:24,864 or it could be flood water as well, and then recreational outdoor water 213 00:12:24,864 --> 00:12:29,275 body exposures like swimming pools, or even water parks, and have they had any 214 00:12:29,285 --> 00:12:34,044 injuries in the water, because there will be very specific bacterial and parasitic 215 00:12:34,044 --> 00:12:38,114 infections that I would be considering with exposure to such water bodies. 216 00:12:38,695 --> 00:12:43,005 In terms of indoor exposures, I asked them about have they had sick 217 00:12:43,015 --> 00:12:49,435 contacts, like sick contacts with other adults or children or indoor animals. 218 00:12:49,805 --> 00:12:53,555 So adults as in you can get of course you know all types of respiratory 219 00:12:53,555 --> 00:12:56,005 infections and URIs from adults as well. 220 00:12:56,404 --> 00:13:02,294 STDs would be a big thing from adults like syphilis and then gonococcal infection. 221 00:13:02,644 --> 00:13:06,655 All of these can cause fever and rash and then risk factors for TB 222 00:13:06,655 --> 00:13:08,445 as well would be elicited here. 223 00:13:09,065 --> 00:13:15,385 Then in terms of contact with kids or little humans, you know, they are sources 224 00:13:15,385 --> 00:13:19,275 of all kinds of viral and bacterial infections like vaccine preventable 225 00:13:19,275 --> 00:13:26,975 diseases, measles, rubella, or parvovirus B19, HHV6, CMV, EBV, the list goes on. 226 00:13:27,494 --> 00:13:32,814 Indoor animals, you could either think about pets as well as insects 227 00:13:32,814 --> 00:13:34,725 as well, annoying indoor insects. 228 00:13:35,235 --> 00:13:39,094 Some people have, you know, all kinds of exotic pets, like including. 229 00:13:39,555 --> 00:13:44,145 Uh, you know, salamanders, and turtles, and snakes, and so obviously that's 230 00:13:44,145 --> 00:13:46,025 going to make you think about salmonella. 231 00:13:46,535 --> 00:13:49,515 And then indoor annoying bugs, like you know, have they had bed 232 00:13:49,515 --> 00:13:51,935 bugs, or spiders, or rodents? 233 00:13:52,585 --> 00:13:57,474 All of these can be associated with some, some other, uh, pathology 234 00:13:57,474 --> 00:13:58,895 that will give you fever and rash. 235 00:13:59,489 --> 00:14:05,280 And then, uh, coming next to something they ingested or injected, so injection 236 00:14:05,280 --> 00:14:10,040 was injection drug use or if they have any recent vaccines that were injected that 237 00:14:10,040 --> 00:14:15,579 can cause fever and rash too, or recent tattoos, and then something they ingested 238 00:14:15,579 --> 00:14:20,949 would be, you know, drugs or food, and so in terms of drugs, there can be Steven 239 00:14:20,949 --> 00:14:26,550 Johnson and toxic epidermal necrolysis, DRESS syndrome, small vessel vasculitis, 240 00:14:27,270 --> 00:14:30,870 In terms of some food they ate, like raw oysters, again, you 241 00:14:30,870 --> 00:14:32,160 have to think about Vibrio. 242 00:14:32,590 --> 00:14:36,790 Raw meat would make you think about salmonella again, or unpasteurized 243 00:14:36,800 --> 00:14:40,600 cheese and dairy products make you think about either brucella or Q fever too. 244 00:14:41,309 --> 00:14:44,140 Non exposure related would be the next big category. 245 00:14:44,180 --> 00:14:49,899 So autoimmune diseases, SLE, rheumatoid arthritis, or cutaneous 246 00:14:49,899 --> 00:14:54,240 vasculitis, or erythema nodosum, cancer, especially liquid malignancies, 247 00:14:54,240 --> 00:14:58,189 or cutaneous T cell lymphomas, and then other diseases like sarcoid. 248 00:14:58,825 --> 00:15:03,735 Kawasaki, GVHD, HLH, so these are some of the differentials that come to my mind. 249 00:15:04,745 --> 00:15:09,485 Michael, could you perhaps provide us with some HPI obtained by ID here? 250 00:15:09,625 --> 00:15:11,594 Michael Moran: Thanks for all that explanation Swapnil. 251 00:15:12,055 --> 00:15:15,225 When we went and saw the patient, she tells us the fever started 252 00:15:15,225 --> 00:15:19,144 about three weeks ago, occurring on almost a daily basis, but no 253 00:15:19,144 --> 00:15:20,734 particular timing during the day. 254 00:15:21,684 --> 00:15:24,314 She does get occasional drenching night sweats though. 255 00:15:24,954 --> 00:15:29,224 She also describes having no energy and poor appetite over the last four to five 256 00:15:29,224 --> 00:15:33,564 weeks, as well as a frontal headache which occurs on and off during these fevers. 257 00:15:34,095 --> 00:15:38,685 She rates these headaches as a 4 out of 5 out of 10 in intensity, but has no 258 00:15:38,685 --> 00:15:41,245 associated photophobia or neck stiffness. 259 00:15:41,765 --> 00:15:45,624 In addition to this, she notes some abdominal pain on and off in 260 00:15:45,625 --> 00:15:50,634 her bilateral upper quadrants, as well as a sharp 5 out of 6 out of 261 00:15:50,634 --> 00:15:52,574 10 intensity without radiation. 262 00:15:52,754 --> 00:15:55,234 She has no associated nausea, vomiting, or diarrhea. 263 00:15:55,825 --> 00:15:59,845 With regards to her rash, she has trouble telling us exactly when it was started. 264 00:16:00,275 --> 00:16:04,035 She is of African American ethnicity and notes that it's possible the 265 00:16:04,035 --> 00:16:07,954 rash could have been there in early stages without her being able to tell. 266 00:16:08,430 --> 00:16:12,400 She does recollect having some local skin sensitivity over her anterior 267 00:16:12,400 --> 00:16:14,859 thighs, but no pain or pruritis. 268 00:16:15,370 --> 00:16:20,730 She believes that this started about three days ago on her thighs and chest, and 269 00:16:20,730 --> 00:16:24,590 her husband's in the room with us, and he tells us that the rash is also on her 270 00:16:24,600 --> 00:16:27,400 upper back, abdomen, and posterior thighs. 271 00:16:28,155 --> 00:16:31,175 She denies any mucosal pain or skin breakdown. 272 00:16:31,635 --> 00:16:34,415 Otherwise, review of systems is unremarkable. 273 00:16:34,575 --> 00:16:38,455 With regards to exposure history, she lives in the Midwest with her husband in a 274 00:16:38,455 --> 00:16:40,754 single family home for the last 15 years. 275 00:16:41,275 --> 00:16:42,175 They have no kids. 276 00:16:42,715 --> 00:16:46,034 She has always been in a monogamous relationship and has no history of 277 00:16:46,035 --> 00:16:48,035 prior sexually transmitted infections. 278 00:16:48,965 --> 00:16:52,585 She works as a software engineer, with the majority of her work being remote. 279 00:16:53,385 --> 00:16:57,194 She is a never smoker and only drinks socially with no illicit drug use. 280 00:16:57,895 --> 00:17:01,505 She reports no new medications in the last two months aside from the 281 00:17:01,505 --> 00:17:03,975 sulfasalazine and prednisone for her RA. 282 00:17:04,805 --> 00:17:07,294 She does not take any other supplements or over the counter 283 00:17:07,294 --> 00:17:11,214 meds, although she has been taking Tylenol and Ibuprofen for her fevers. 284 00:17:11,815 --> 00:17:15,124 She has no pets or any exotic animal exposures. 285 00:17:15,545 --> 00:17:18,265 She has never noticed any rodents or insects in the home. 286 00:17:18,819 --> 00:17:21,589 And in terms of travel, she has never been to the Southwest U. 287 00:17:21,589 --> 00:17:25,780 S., but she did say that she went to Cancun with her family about six weeks ago 288 00:17:26,079 --> 00:17:27,929 and swam in the ocean while she was there. 289 00:17:29,609 --> 00:17:32,659 She reports that she has not spent any time outdoors here in the 290 00:17:32,659 --> 00:17:35,720 Midwest in the last five months because she hates being in the cold. 291 00:17:36,440 --> 00:17:40,560 And before that, she used to go hiking on nearby trails and lakes with her husband. 292 00:17:41,280 --> 00:17:44,320 She does not garden and has no soil exposures. 293 00:17:44,810 --> 00:17:48,399 Her neighbor recently had COVID two weeks ago, and there was no family 294 00:17:48,399 --> 00:17:49,919 history of recurrent infections. 295 00:17:50,385 --> 00:17:54,015 Her sister in law's family did recently visit them for about three days, and 296 00:17:54,015 --> 00:17:57,415 they have two kids of the ages of three and nine, and both kids had 297 00:17:57,675 --> 00:17:59,015 the sniffles while they were here. 298 00:17:59,825 --> 00:18:04,025 So Swapnil, based off this history alone, any differentials going through your mind? 299 00:18:04,125 --> 00:18:06,794 Swapnil Lanjewar: Yeah, so Michael, fever with rash is actually a unique 300 00:18:06,794 --> 00:18:11,004 entity in ID where I often do not start thinking of the differentials 301 00:18:11,025 --> 00:18:13,145 until I lay my eyes on the patient. 302 00:18:13,655 --> 00:18:17,645 This is because the examination of rash is actually going to 303 00:18:17,725 --> 00:18:21,750 significantly influence my thought process regarding differentials. 304 00:18:22,200 --> 00:18:27,400 While examining the rash, I'm looking at is it macular, papular, or maculopapular? 305 00:18:27,439 --> 00:18:29,990 Do they have plaques or nodules? 306 00:18:30,610 --> 00:18:35,179 I also look for secondary features into the rash, like do they have crusting 307 00:18:35,200 --> 00:18:39,269 or scaling there or excoriation or any other important secondary 308 00:18:39,270 --> 00:18:41,710 features like ulcers or eschars? 309 00:18:42,290 --> 00:18:46,530 And this is because appearance of the rash is going to help you narrow 310 00:18:46,530 --> 00:18:48,930 down your differential significantly. 311 00:18:49,385 --> 00:18:53,605 There are multiple viral infections that will cause a maculopapular rash, 312 00:18:53,905 --> 00:19:00,485 like herpes virus infections, EBV, CMV, HHV 6, then vaccine preventable viruses 313 00:19:00,485 --> 00:19:05,745 and childhood infections like measles, rubella, parvirus B19, and adeno. 314 00:19:06,224 --> 00:19:09,745 You can see maculopapular rash in some bacterial infections as well, 315 00:19:09,745 --> 00:19:13,545 like some STDs like syphilis and gonorrhea, and then you can see 316 00:19:13,545 --> 00:19:18,425 that in other bacterial infections like mycoplasma, relapsing fevers. 317 00:19:18,835 --> 00:19:22,165 Even some rickettsial infections like Rocky Mountain spotted fever 318 00:19:22,165 --> 00:19:25,685 and some tick borne infections will give you a maculopapular rash. 319 00:19:26,195 --> 00:19:31,155 When there are secondary features to the rash like skin necrosis, then there are 320 00:19:31,155 --> 00:19:35,175 some very specific bacterial infections that will come to my mind like pseudomonas 321 00:19:35,195 --> 00:19:40,225 which can cause ecthyma gangrenosum and then the Rickettsia typhi group like the 322 00:19:40,225 --> 00:19:45,415 murine and scrub typhus group, then the rat bite fevers like from Spirillum minus 323 00:19:45,455 --> 00:19:48,025 and from Streptobacillus monoliformis. 324 00:19:48,595 --> 00:19:52,915 And then some endemic fungal infections as well will cause some 325 00:19:52,915 --> 00:19:54,555 necrotic appearance to the rash. 326 00:19:55,195 --> 00:20:00,315 Other secondary features like vesicles will make me think about viral etiology 327 00:20:00,325 --> 00:20:07,055 like a Coxsackievirus or HSV or VZV, um, even smallpox and monkeypox. 328 00:20:07,435 --> 00:20:11,675 And then bacterial causes like rickettsial pox can also cause vesicles. 329 00:20:12,149 --> 00:20:15,040 And then Vibrio, uh, can cause bullae. 330 00:20:15,199 --> 00:20:20,429 And then lastly, if the rash is petechial or perpiric rash, then the biggest viral 331 00:20:20,429 --> 00:20:24,569 differentials would be viral hemorrhagic fevers, especially if they have this low 332 00:20:24,569 --> 00:20:27,429 epidemiologic risk factors of travel. 333 00:20:27,850 --> 00:20:32,290 I would think about dengue and then viral hemorrhagic fevers, like Ebola, 334 00:20:32,290 --> 00:20:38,040 Marburg, chikungunya as well, yellow fever can cause petechial or perpiral rash. 335 00:20:38,430 --> 00:20:42,600 And then certain important bacterial causes of petechial rash would be 336 00:20:42,640 --> 00:20:48,319 meningococcal infections, even sometimes severe Capnocytophaga infections, and 337 00:20:48,319 --> 00:20:52,780 then rat bite fever can also cause a petechial or perpireal rash, and then 338 00:20:53,340 --> 00:20:58,330 Staph aureus, and then relapsing fever, and rickettsial infections, again, like 339 00:20:58,330 --> 00:21:03,390 Rocky Mountain spotted fever, or epidemic typhus, or from Rickettsia prowazekii. 340 00:21:03,610 --> 00:21:07,060 These can all cause the petechial rash as well. 341 00:21:08,000 --> 00:21:11,480 So, Michael, can you share the exam findings with us for the rash? 342 00:21:11,600 --> 00:21:12,490 Michael Moran: Yeah, certainly. 343 00:21:12,850 --> 00:21:17,889 On exam, we repeated her vitals, and she had a low grade temp of 100. 344 00:21:17,889 --> 00:21:18,800 6 degrees Fahrenheit. 345 00:21:19,390 --> 00:21:24,429 Her heart rate was 108, but she had a normal respiratory rate, blood 346 00:21:24,429 --> 00:21:26,320 pressure, and oxygen saturation. 347 00:21:26,810 --> 00:21:28,709 And her BMI is 33. 348 00:21:29,190 --> 00:21:33,190 And on exam, she's alert and oriented times three and in no acute distress. 349 00:21:34,300 --> 00:21:37,490 Some pertinent positives and negatives on her exam, she has 350 00:21:37,490 --> 00:21:42,540 a mild periorbital edema and has evidence of cervical lymphadenopathy, 351 00:21:42,550 --> 00:21:44,050 which was non tender on palpation. 352 00:21:45,229 --> 00:21:48,370 Her heart sounds are normal and her respiratory exam is benign. 353 00:21:49,089 --> 00:21:52,649 Her abdomen was soft, obese, with normal bowel sounds and 354 00:21:52,659 --> 00:21:54,419 no organomegaly appreciated. 355 00:21:55,370 --> 00:21:56,870 She had a normal neuro exam. 356 00:21:57,840 --> 00:22:01,899 In regards to her skin exam, there was a symmetric, macular, and patchy 357 00:22:01,899 --> 00:22:06,935 widespread erythematous rash over her cheeks, anterior and posterior 358 00:22:06,935 --> 00:22:09,945 thighs, legs, chest, and back. 359 00:22:10,455 --> 00:22:14,764 She had no mucosal involvement and notes the rash was mildly blanching. 360 00:22:15,605 --> 00:22:19,095 So, with that exam, are there any other differentials that come to mind? 361 00:22:19,154 --> 00:22:21,144 Swapnil Lanjewar: Yeah, that definitely helps narrow down 362 00:22:21,144 --> 00:22:22,395 the list of differentials. 363 00:22:23,175 --> 00:22:28,335 I will divide my list of differentials according to viral versus bacterial 364 00:22:28,415 --> 00:22:31,495 versus fungal, parasitic, or non infectious etiologies. 365 00:22:32,325 --> 00:22:36,545 Viral wise, herpes viruses come to mind, especially with the history of contact 366 00:22:36,545 --> 00:22:38,145 with little kids who have been sick. 367 00:22:38,495 --> 00:22:41,875 So, EBV and HHV6 would be coming to mind. 368 00:22:42,215 --> 00:22:46,854 Because there are no vesicular features, I'm not thinking of chickenpox or VZV or 369 00:22:46,895 --> 00:22:49,675 HSV or any of the other herpes viruses. 370 00:22:50,295 --> 00:22:54,095 Um, Coxsackie and adenovirus would still be on my list of differentials. 371 00:22:54,655 --> 00:22:58,305 And then, Parvovirus B19 again, because of the risk associated 372 00:22:58,305 --> 00:22:59,735 with contact with little kids. 373 00:23:00,280 --> 00:23:04,080 I assume the kids are vaccinated, otherwise I would think of 374 00:23:04,139 --> 00:23:05,520 measles and rubella too. 375 00:23:06,130 --> 00:23:10,240 Uh, in terms of bacterial causes, if this was the appropriate 376 00:23:10,240 --> 00:23:13,990 season, I would have considered tick borne infections definitely. 377 00:23:14,349 --> 00:23:19,579 But it's March, and typically incubation period for most tick borne infections 378 00:23:19,579 --> 00:23:21,409 tends to be around two weeks or so. 379 00:23:21,410 --> 00:23:24,060 So I don't think this is tick borne infection. 380 00:23:24,530 --> 00:23:27,810 Unless the patient has any recent history of blood transfusion or 381 00:23:27,810 --> 00:23:31,060 so, but I don't think there was any such history, so I wouldn't 382 00:23:31,090 --> 00:23:32,800 consider tick borne infections here. 383 00:23:33,330 --> 00:23:37,539 STDs would still remain on my list of differential, even though she states that 384 00:23:37,540 --> 00:23:41,829 she is in a monogamous relationship, I would still consider syphilis, and then 385 00:23:41,859 --> 00:23:47,100 Neisseria gonorrhoeae, and then some non STD infections like Mycoplasma can 386 00:23:47,170 --> 00:23:49,260 still be on the differential for me. 387 00:23:49,970 --> 00:23:55,550 I don't think that the rash sounds fungal or any kind of parasitic infection, so 388 00:23:55,580 --> 00:23:57,450 I think we can safely rule those out. 389 00:23:58,379 --> 00:24:02,459 In terms of non infectious etiologies, I would consider possibility of DRESS 390 00:24:02,499 --> 00:24:06,989 syndrome or autoimmune disease, of course, given her recent history of 391 00:24:07,320 --> 00:24:12,590 rheumatoid arthritis, cancer, possibly hematologic malignancies could still 392 00:24:12,600 --> 00:24:14,149 be in the list of differentials. 393 00:24:14,990 --> 00:24:16,629 That would be my list so far. 394 00:24:17,460 --> 00:24:20,550 Do we have any labs and imaging results back so far, Michael? 395 00:24:20,580 --> 00:24:21,300 Michael Moran: We do. 396 00:24:22,070 --> 00:24:26,669 So, on a CBC with differential, she has a white count of 7. 397 00:24:26,670 --> 00:24:32,209 9 with a mildly elevated lymphocyte count of 3, 670, but 398 00:24:32,209 --> 00:24:34,430 a normal eosinophil count at 110. 399 00:24:35,480 --> 00:24:36,360 Her hemoglobin is 9. 400 00:24:36,360 --> 00:24:40,520 3 and her platelet count is 116, so mildly low. 401 00:24:42,340 --> 00:24:46,340 The pathology department did a formal read on her blood smear, which 402 00:24:46,340 --> 00:24:51,449 shows numerous reactive appearing immunoblasts, and they note a reactive 403 00:24:51,449 --> 00:24:55,279 process is favored, but correlation with flow studies is necessary. 404 00:24:55,729 --> 00:24:58,459 Serum chemistry studies are all within normal limits. 405 00:24:59,139 --> 00:25:02,649 In liver function testings, note an elevated ALT at 430, 406 00:25:02,650 --> 00:25:09,439 AST at 345, and Alk phos 180. 407 00:25:10,320 --> 00:25:15,000 A total bilirubin elevated at 3.8 with a direct bilirubin 2.8. 408 00:25:15,930 --> 00:25:21,790 In terms of other labs, she has a normal uric acid and an elevated LDH at 1, 317. 409 00:25:22,280 --> 00:25:26,200 On her repeat CT chest abdomen and pelvis, they do note a mild 410 00:25:26,209 --> 00:25:30,860 thickening in her urinary bladder as evidence of possible cystitis. 411 00:25:31,455 --> 00:25:36,035 As well as some mild splenomegaly and mild enlargement of the axillary 412 00:25:36,065 --> 00:25:39,555 lymph nodes, presumably reactive without lymphadenopathy in the chest. 413 00:25:40,634 --> 00:25:43,655 So Swapnil, given these findings so far, what would be your 414 00:25:43,655 --> 00:25:46,535 recommendations to the team for any further workup of this patient? 415 00:25:46,805 --> 00:25:50,379 Swapnil Lanjewar: My next set of recommendations would be that we 416 00:25:50,379 --> 00:25:54,090 should check for, you know, the routine things, like multiple blood cultures, 417 00:25:54,650 --> 00:26:00,299 and then I'll recommend serology for EBV and CMV, and of course viral 418 00:26:00,300 --> 00:26:02,790 loads for EBV and CMV as well here. 419 00:26:03,230 --> 00:26:09,260 I'll recommend PCR for HHV6, Parvovirus B19, given the history 420 00:26:09,270 --> 00:26:12,860 that was provided, and then Adenovirus PCR from the blood tube. 421 00:26:13,400 --> 00:26:16,870 Given that this patient had transaminitis, I will screen 422 00:26:16,880 --> 00:26:19,330 her for hepatitis A, B, and C. 423 00:26:19,960 --> 00:26:25,119 I'll still recommend STD workup here by screening for syphilis, so 424 00:26:25,119 --> 00:26:29,490 treponemal antibody, and then the urine gonorrhea and chlamydia screen. 425 00:26:30,110 --> 00:26:31,930 I'll also screen for HIV here. 426 00:26:32,430 --> 00:26:36,409 I'll add some workup for culture negative endocarditis by checking for Bartonella 427 00:26:36,409 --> 00:26:39,629 PCR and Q fever serologies as well. 428 00:26:40,249 --> 00:26:44,889 Since there was this concern for HLH that I was thinking about because of 429 00:26:44,889 --> 00:26:49,399 the splenomegaly and cytopenias and these weird fevers, I'll also recommend 430 00:26:49,429 --> 00:26:55,520 screening for HLH by sending ferritin and triglycerides, soluble IL 2, and 431 00:26:55,520 --> 00:27:00,920 also check for flow cytometry because of the presence of those atypical or 432 00:27:00,930 --> 00:27:04,600 cells or immunoblasts that were mentioned earlier on the peripheral smear. 433 00:27:05,010 --> 00:27:09,070 And last but not the least, I'll recommend dermatology consultation 434 00:27:09,070 --> 00:27:10,909 as well for a skin biopsy here. 435 00:27:10,969 --> 00:27:14,409 Michael Moran: Yeah, so the lab was working quick this week, so we 436 00:27:14,409 --> 00:27:16,059 have lots of results to talk about. 437 00:27:16,379 --> 00:27:19,409 We have multiple sets of blood cultures that were drawn and are negative. 438 00:27:19,870 --> 00:27:23,860 The Q fever phase 1 and phase 2 serologies were negative, as 439 00:27:23,860 --> 00:27:28,070 well as serologies for Bartonella quintana and Mycoplasma serology. 440 00:27:28,409 --> 00:27:31,649 Her urine gonorrhea and chlamydia screen was negative, as well as a 441 00:27:31,649 --> 00:27:37,060 treponemal antibody, and an HIV fourth generation combo assay was negative. 442 00:27:37,979 --> 00:27:41,550 We repeated the nasopharyngeal swab for respiratory viral panel, which was 443 00:27:41,550 --> 00:27:49,375 negative, which included parvovirus B19, an adenovirus, a CMV serum viral 444 00:27:49,375 --> 00:27:54,935 load was negative, and EBV serologies note a positive IgG, but a negative 445 00:27:54,935 --> 00:27:58,544 IgM and a negative EBV viral load. 446 00:27:58,965 --> 00:28:02,365 The hepatitis A, B, and C screens are negative. 447 00:28:02,985 --> 00:28:06,854 In regards to the HLH workup, her ferritin is elevated at 6, 448 00:28:06,854 --> 00:28:16,844 883, and elevated triglycerides at 226, a soluble IL 2 of 7, 252. 449 00:28:17,495 --> 00:28:21,405 With a reference range of the upper limit of normal being 858. 450 00:28:22,105 --> 00:28:25,975 So with those findings so far, how would you further narrow your differential? 451 00:28:26,095 --> 00:28:28,374 Swapnil Lanjewar: This definitely helps me further narrow down 452 00:28:28,374 --> 00:28:29,775 on my list of differentials. 453 00:28:30,345 --> 00:28:34,154 And quite frankly now, I don't think this is any kind of 454 00:28:34,184 --> 00:28:36,364 infectious process going on. 455 00:28:36,874 --> 00:28:40,814 My concern is strongly for non infectious processes. 456 00:28:41,615 --> 00:28:46,115 You know, DRESS would still be on my list of differentials, like drug related 457 00:28:46,865 --> 00:28:48,784 eosinophilia and systemic, uh, symptoms. 458 00:28:49,414 --> 00:28:53,064 I would think about autoimmune pathology still, so at this point, 459 00:28:53,115 --> 00:28:57,195 I might consider engaging our rheumatology colleagues as well. 460 00:28:57,855 --> 00:29:01,825 And hematologic malignancies are still on my list of differential, 461 00:29:02,155 --> 00:29:07,845 so I hope that the team now formally consults, uh, hematology based on 462 00:29:07,845 --> 00:29:13,285 the elevated soluble IL 2 and super elevated ferritin of more than 6, 000. 463 00:29:13,295 --> 00:29:17,755 Now HLH has jumped high on my list of differentials here. 464 00:29:18,285 --> 00:29:22,785 So, Michael, do you have any results so far regarding the skin biopsy? 465 00:29:22,845 --> 00:29:23,625 Michael Moran: We do. 466 00:29:24,125 --> 00:29:28,854 The pathology department tells us that her right thigh skin biopsy pathology 467 00:29:28,855 --> 00:29:33,985 shows an unusual constellation of findings with spongiosis, lichenoid 468 00:29:33,995 --> 00:29:38,345 interface features, and a mixed dermal infiltrate with focal hemorrhage. 469 00:29:38,940 --> 00:29:42,410 Eosinophils are not present in number, but these findings are 470 00:29:42,410 --> 00:29:45,830 consistent with a reaction to a medication or other ingestant. 471 00:29:46,120 --> 00:29:50,120 So dermatology is now suspecting DRESS syndrome, likely related to the 472 00:29:50,120 --> 00:29:52,050 sulfosalazine that she was prescribed. 473 00:29:53,265 --> 00:29:57,005 But, with our concern for HLH, hematology has a few other 474 00:29:57,005 --> 00:29:59,445 additional workup to obtain. 475 00:29:59,545 --> 00:30:03,715 They did do a flow cytometry on the peripheral blood, which showed polytypic 476 00:30:03,745 --> 00:30:09,375 T cells with increased CD8 T cells and polyclonal B cells without evidence of 477 00:30:09,405 --> 00:30:11,485 a B cell lymphoproliferative disorder. 478 00:30:11,945 --> 00:30:14,405 These findings are consistent with the reactive process, 479 00:30:14,415 --> 00:30:15,735 such as a viral infection. 480 00:30:16,155 --> 00:30:19,995 They recommended the bone marrow biopsy, which was done, and showed cellular 481 00:30:19,995 --> 00:30:25,425 marrow with trilineage hematopoiesis, with increased megakaryocytes, 1 percent 482 00:30:25,425 --> 00:30:29,585 BLAST, and small aggregates of T cells consistent with reactive process. 483 00:30:30,295 --> 00:30:32,985 No evidence of a lymphoproliferative disorder. 484 00:30:33,970 --> 00:30:37,860 They also did a PET CT, which showed hypermetabolic lymph nodes throughout 485 00:30:37,860 --> 00:30:43,070 the neck, chest, abdomen, and pelvis, with an enlarged and abnormally avid 486 00:30:43,070 --> 00:30:47,110 spleen, which would be concordant with lymphoma if clinically suspected. 487 00:30:48,380 --> 00:30:52,970 So right now, our final diagnosis is DRESS, and dermatology was considering a 488 00:30:52,970 --> 00:30:58,210 DRESS and HLH overlap, but hematology did not feel that it was consistent with HLH. 489 00:30:58,950 --> 00:31:03,120 So Swapnil, can you discuss DRESS and why we were thinking HLH and why we 490 00:31:03,120 --> 00:31:04,730 could possibly have an overlap here? 491 00:31:05,080 --> 00:31:05,410 Swapnil Lanjewar: Yeah. 492 00:31:05,450 --> 00:31:09,990 So DRESS syndrome, the DRESS word stands for drug reaction with 493 00:31:10,320 --> 00:31:12,220 eosinophilia and systemic symptoms. 494 00:31:12,930 --> 00:31:17,590 I don't really like that name DRESS that much because you can actually 495 00:31:17,630 --> 00:31:19,610 have DRESS without eosinophilia. 496 00:31:20,020 --> 00:31:24,210 That's why a better term for it is drug induced hypersensitivity syndrome. 497 00:31:24,730 --> 00:31:28,785 It's a rare and potentially life threatening disorder that can occur 498 00:31:28,785 --> 00:31:32,975 about two to eight weeks from the initial exposure to the offending drug. 499 00:31:33,505 --> 00:31:36,975 And the typical pathogenesis for DRESS is that it's a T cell 500 00:31:36,975 --> 00:31:39,085 mediated hypersensitivity reaction. 501 00:31:39,625 --> 00:31:43,275 And then another thing we often see in DRESS is that there 502 00:31:43,275 --> 00:31:48,565 is simultaneous evidence of reactivation of HHV 6 or EBV or CMV. 503 00:31:49,025 --> 00:31:52,665 These group of herpes viruses, there is this controversy whether this is 504 00:31:53,150 --> 00:31:58,130 reactivation in the setting of DRESS or are they actually playing any role 505 00:31:58,150 --> 00:32:00,180 in the pathogenesis of DRESS itself? 506 00:32:00,610 --> 00:32:05,520 In terms of manifestations, the classic one is a morbilliform rash 507 00:32:05,990 --> 00:32:09,770 and the word morbilliform means that it essentially looks like measles. 508 00:32:09,830 --> 00:32:15,660 It's a faint pink maculopapular rash which can be circular or elliptical 509 00:32:15,960 --> 00:32:17,930 and it's typically symmetric rash. 510 00:32:18,410 --> 00:32:20,850 This can be associated with fevers. 511 00:32:21,890 --> 00:32:25,010 Lymphadenopathy as well, and some patients might have facial, 512 00:32:25,020 --> 00:32:26,720 hand, or feet swelling too. 513 00:32:27,300 --> 00:32:31,910 Another significant hallmark is visceral organ involvement like, you 514 00:32:31,910 --> 00:32:36,060 know, hepatitis, like our patient had, or renal, or pulmonary, or 515 00:32:36,060 --> 00:32:40,350 cardiac involvement, and when there's pulmonary or cardiac involvement, it's 516 00:32:40,390 --> 00:32:42,080 pretty severe stress at that point. 517 00:32:42,770 --> 00:32:47,470 Common culprits for DRESS tend to be anti epileptic drugs like phenytoin, 518 00:32:47,490 --> 00:32:49,850 or carbamazepine, or lamotrigine. 519 00:32:50,430 --> 00:32:54,370 In terms of antibiotics, sulfa group antibiotics are also a known culprit here. 520 00:32:54,690 --> 00:32:58,170 Tetracycline group antibiotics, especially like minocycline or 521 00:32:58,190 --> 00:33:02,230 minocycline, however you want to say it, penicillins and vancomycin. 522 00:33:02,730 --> 00:33:06,970 And then other important drug that is described for DRESS is allopurinol. 523 00:33:07,510 --> 00:33:11,500 But again, this list continues to grow along with our experience. 524 00:33:12,150 --> 00:33:16,160 Now for the diagnosis of DRESS, There's a really good scoring 525 00:33:16,160 --> 00:33:20,630 system called as RegiSCAR Scoring System, which stands for Registry of 526 00:33:20,630 --> 00:33:23,240 Severe Cutaneous Adverse Reactions. 527 00:33:23,710 --> 00:33:28,700 So that's why RegiSCAR it, it is readily available on Med Calc. 528 00:33:29,140 --> 00:33:33,010 You have to go through this questionnaire regarding whether your patient has fever, 529 00:33:33,010 --> 00:33:39,380 lymphadenopathy, atypical lymphocytes, or eosinophilia, and what's the extent 530 00:33:39,380 --> 00:33:44,080 of their skin involvement and what's their pathology on biopsy of the skin. 531 00:33:44,505 --> 00:33:47,245 Do they have involvement of internal organs, and what's the 532 00:33:47,245 --> 00:33:49,585 resolution time for their rash? 533 00:33:50,075 --> 00:33:55,185 So a score of 6 or more is supposed to be definitive diagnosis for DRESS. 534 00:33:56,045 --> 00:34:00,415 When it comes to treatment, the first line is supportive care, and if the 535 00:34:00,435 --> 00:34:05,500 disease is severe, like if there's end organ involvement as well, then you can 536 00:34:05,500 --> 00:34:07,669 consider glucocorticoids at a dose of 0. 537 00:34:07,670 --> 00:34:11,790 5 to 1 milligram per kg per day of prednisone equivalent. 538 00:34:12,270 --> 00:34:15,900 And then you taper it over the next 8 to 12 weeks or so. 539 00:34:16,600 --> 00:34:19,590 When you're giving them steroids, you absolutely make sure that 540 00:34:19,600 --> 00:34:23,030 you're also giving PJP prophylaxis because you're giving high dose 541 00:34:23,280 --> 00:34:25,835 steroids for more than a month or so. 542 00:34:26,395 --> 00:34:28,015 This is the first line treatment. 543 00:34:28,035 --> 00:34:31,765 Second line treatment is you could consider immunosuppressive drugs like 544 00:34:31,765 --> 00:34:36,955 cyclosporine and you could add IVIG and consider other immunosuppressants like 545 00:34:36,985 --> 00:34:42,435 JAK inhibitors, but typically I also let dermatology drive the ship on that. 546 00:34:42,705 --> 00:34:44,185 That's about DRESS syndrome. 547 00:34:44,785 --> 00:34:49,895 And then other thing which dermatology and myself, we were thinking about HLH. 548 00:34:50,205 --> 00:34:53,975 HLH is a life threatening hyper inflammatory syndrome where there is 549 00:34:54,045 --> 00:34:59,575 intense immune activation characterized by fever, cytopenias, and hepatosplenomegaly, 550 00:34:59,605 --> 00:35:02,025 and highly elevated inflammatory markers. 551 00:35:02,525 --> 00:35:06,215 This is definitely a life threatening condition, and if you are thinking 552 00:35:06,215 --> 00:35:10,565 about HLH, you should work fast on whether or not you can rule in or 553 00:35:10,565 --> 00:35:14,875 rule out this diagnosis because time is of the essence in such patients. 554 00:35:15,665 --> 00:35:22,045 So there are basically 9 criteria for HLH out of which you need at least 5 of them. 555 00:35:22,545 --> 00:35:27,745 Criteria include fever, splenomegaly, and then peripheral blood cytopenias with 556 00:35:27,745 --> 00:35:30,305 at least 2 of the following, you know. 557 00:35:30,645 --> 00:35:34,795 There should be hemoglobin less than 9 or platelets less 558 00:35:34,795 --> 00:35:37,665 than 100 or ANC less than 1000. 559 00:35:38,420 --> 00:35:43,500 Then hypertriglyceridemia is one criteria, so fasting triglycerides 560 00:35:43,500 --> 00:35:50,560 more than 265, or low or absent NK cell activity, or ferritin required is at 561 00:35:50,560 --> 00:35:54,990 least more than 500, but in reality most patients with HLH are going to have 562 00:35:55,290 --> 00:35:57,080 their ferritin in multiple thousands. 563 00:35:57,610 --> 00:36:03,409 And then elevated soluble IL 2 as well, and then elevated CXCL 9, 564 00:36:03,590 --> 00:36:08,100 and evidence of hemophagocytosis on biopsy from bone marrow. 565 00:36:08,535 --> 00:36:12,935 But you can also see that from biopsy from spleen, lymph nodes, or liver. 566 00:36:13,425 --> 00:36:17,145 Our patient, after discussion with hematology, did not 567 00:36:17,185 --> 00:36:18,825 meet all of these criteria. 568 00:36:18,845 --> 00:36:23,555 Our patient had only evidence of fever, and then the splenomegaly was there. 569 00:36:23,585 --> 00:36:25,005 Technically, it was pretty mild. 570 00:36:25,835 --> 00:36:31,335 She did have ferritin elevation of more than 500 and elevated soluble IL 2. 571 00:36:31,935 --> 00:36:36,745 But, the bone marrow biopsy did not show any concern for hemophagocytosis. 572 00:36:37,595 --> 00:36:43,475 Based on all of this, only four criteria were met, and that's why hematology 573 00:36:43,475 --> 00:36:45,695 did not think that this was HLH. 574 00:36:46,275 --> 00:36:48,415 So, Michael, what happened finally with the patient? 575 00:36:48,495 --> 00:36:51,685 Michael Moran: Yeah, so, coming back to our patient, she was initially treated 576 00:36:51,695 --> 00:36:57,585 with IV dexamethasone at dose equivalent of about 1 mg per kg of prednisone, and 577 00:36:57,585 --> 00:37:01,055 later switched to PO prednisone, which was tapered over the next eight weeks. 578 00:37:01,605 --> 00:37:05,645 The team used atovaquone for PJP prophylaxis to avoid any sulfa 579 00:37:05,665 --> 00:37:09,975 drugs, and her symptoms improved very quickly, and she made a full recovery. 580 00:37:10,185 --> 00:37:13,765 Sara Dong: This is such a great ID related topic. 581 00:37:14,235 --> 00:37:18,135 The other thing I just wanted to add that I think you've said and implied, but 582 00:37:18,135 --> 00:37:23,615 just to deliberately say aloud, is the mainstay of treatment is also stopping 583 00:37:23,615 --> 00:37:27,965 the offending drug or agent, or whatever it is you think that is inducing DRESS. 584 00:37:27,965 --> 00:37:32,395 And I think we all know that, but maybe just also saying that again out 585 00:37:32,395 --> 00:37:36,885 loud, because oftentimes it's a bit of a conversation, you know, if these 586 00:37:36,895 --> 00:37:41,425 patients are sick for other reasons, to also avoid giving them new meds, 587 00:37:41,455 --> 00:37:45,785 like new empiric antibiotics, if you are in a place to be able to do so. 588 00:37:46,095 --> 00:37:48,905 I think sometimes that's a hard conversation if these, because often 589 00:37:48,915 --> 00:37:53,605 these patients are in the ICU, they have these very impressive rash, they can 590 00:37:53,665 --> 00:37:59,365 look quite ill, but yeah, I just wanted to re emphasize that because sometimes 591 00:37:59,365 --> 00:38:03,105 it's actually not that easy because the drug that's causing it isn't that clear. 592 00:38:03,585 --> 00:38:07,079 If they look unwell, people want to add new things, so balancing all of that. 593 00:38:07,590 --> 00:38:09,630 Do you guys want to do take home points? 594 00:38:09,630 --> 00:38:12,210 Like, each of you have one thing that you emphasize. 595 00:38:12,750 --> 00:38:15,750 Swapnil Lanjewar: I will say that one of the biggest take home points from my 596 00:38:15,750 --> 00:38:21,520 standpoint here would be that this case shows the importance of not anchoring to 597 00:38:21,600 --> 00:38:26,350 infectious etiologies as the diagnosis every time you hear the word fever. 598 00:38:27,090 --> 00:38:30,980 Oftentimes, it is infectious disease clinicians who are also diagnosing 599 00:38:30,980 --> 00:38:36,610 non infectious causes of fever like DRESS syndrome or autoimmune pathology, 600 00:38:37,785 --> 00:38:39,695 rheumatological diagnosis as well. 601 00:38:40,145 --> 00:38:44,515 So it is important to keep non infectious etiologies in mind as 602 00:38:44,515 --> 00:38:46,675 well for patients having fever. 603 00:38:47,090 --> 00:38:50,470 Michael Moran: Yeah, I think the takeaway that I've had from this case is that, 604 00:38:50,500 --> 00:38:54,110 you know, anytime you're called from the primary team for a rash, which 605 00:38:54,480 --> 00:39:00,810 happens fairly often in ID, is really doing a comprehensive med list look and 606 00:39:00,820 --> 00:39:05,135 getting that good exposure history, and then always just looking at UpToDate or 607 00:39:05,345 --> 00:39:09,425 another resource for those medication lists or offending agents like Swapnil 608 00:39:09,445 --> 00:39:12,885 talked about to kind of jog your memory so you aren't missing something. 609 00:39:12,915 --> 00:39:18,285 Since the differential is so broad, it can really be so many different things. 610 00:39:19,445 --> 00:39:22,565 Sara Dong: Thanks again to Michael and Swapnil for joining Febrile today. 611 00:39:22,965 --> 00:39:25,665 Febrile is produced with support from the Infectious Diseases 612 00:39:25,675 --> 00:39:27,305 Society of America or IDSA. 613 00:39:27,985 --> 00:39:30,355 Don't forget to check out the website, febrilepodcast. 614 00:39:30,355 --> 00:39:34,185 com, where you can find the consult notes, which are written compliments 615 00:39:34,185 --> 00:39:38,615 of the show with links to references, our library of ID infographics, 616 00:39:38,935 --> 00:39:40,145 and a link to our merch store. 617 00:39:40,485 --> 00:39:43,395 Please reach out if you have any suggestions for future shows or want 618 00:39:43,395 --> 00:39:44,665 to be more involved with Febrile. 619 00:39:45,265 --> 00:39:47,705 Thanks for listening, stay safe, and I'll see you next time.