1 00:00:03,389 --> 00:00:04,300 Sara Dong: Hi, everyone. 2 00:00:04,390 --> 00:00:08,250 Welcome to Febrile, a cultured podcast about all things infectious disease. 3 00:00:09,020 --> 00:00:12,759 We use consult questions to dive into ID clinical reasoning, diagnostics, 4 00:00:12,760 --> 00:00:14,009 and antimicrobial management. 5 00:00:14,290 --> 00:00:16,910 I'm Sara Dong, your host and a MedPeds ID doc. 6 00:00:17,200 --> 00:00:20,659 We are joined by a team from the University of Chicago today. 7 00:00:21,080 --> 00:00:24,230 I'll first introduce our co host, Dr. 8 00:00:24,230 --> 00:00:26,699 John Flores, but he goes by Jack. 9 00:00:26,710 --> 00:00:27,769 Jack Flores: Thank you for having me, Sara. 10 00:00:28,810 --> 00:00:33,045 Sara Dong: Jack is a third year MedPeds ID fellow at University of Chicago, who's 11 00:00:33,045 --> 00:00:38,285 passionate about all things ID, but sees himself as an academic MedPeds ID provider 12 00:00:38,285 --> 00:00:43,464 focusing on adolescent, young adult, and maternal fetal infections, along with 13 00:00:43,525 --> 00:00:46,655 HIV syndemic care and travel medicine. 14 00:00:47,085 --> 00:00:48,545 Joining him is Dr. 15 00:00:48,555 --> 00:00:49,455 Madan Kumar. 16 00:00:49,695 --> 00:00:50,085 Madan Kumar: Hey, Sara. 17 00:00:50,144 --> 00:00:50,584 How are you? 18 00:00:50,925 --> 00:00:54,630 Sara Dong: Madan is a Pediatric Infectious Disease Specialist and Assistant Professor 19 00:00:54,630 --> 00:00:58,140 in Pediatrics at the University of Chicago's Comer Children's Hospital. 20 00:00:58,550 --> 00:01:03,319 His various scholarly focuses are with immunocompromised hosts, the intersection 21 00:01:03,339 --> 00:01:07,340 of ID and immune dysregulation, and the study of the microbiome. 22 00:01:07,630 --> 00:01:09,650 Very excited to have you guys here today. 23 00:01:10,209 --> 00:01:14,950 As everyone's favorite culture podcast, we do ask our guests to share a little piece 24 00:01:14,960 --> 00:01:16,720 of culture that brings you happiness. 25 00:01:17,250 --> 00:01:18,440 Jack, maybe I'll start with you. 26 00:01:18,500 --> 00:01:19,089 Jack Flores: Sure. 27 00:01:19,110 --> 00:01:22,100 So, most of my time when I'm not in the hospital or clinic 28 00:01:22,100 --> 00:01:23,600 is spent with my two young kids. 29 00:01:23,600 --> 00:01:27,285 I have a four year old and a two year old, and they take up a lot of time and a lot 30 00:01:27,285 --> 00:01:31,545 of energy in the best way possible, but when I'm not obsessing over University 31 00:01:31,545 --> 00:01:35,314 of Notre Dame sports, which is my alma mater, I have to, you know, I have to say 32 00:01:35,314 --> 00:01:37,855 right off the bat that I went to Notre Dame, of course, like any Notre Dame grad. 33 00:01:38,625 --> 00:01:41,674 Most people don't realize this, but I actually like to make 34 00:01:41,705 --> 00:01:43,404 riddles, like homemade riddles. 35 00:01:43,590 --> 00:01:45,480 Sara Dong: Did you bring one to share with everyone? 36 00:01:46,960 --> 00:01:48,110 Jack Flores: I can if you want. 37 00:01:48,400 --> 00:01:51,519 My mom actually worked at the Art Institute of Chicago for many 38 00:01:51,519 --> 00:01:55,480 decades, and she tried her best to instill art into her children. 39 00:01:55,590 --> 00:01:58,560 My sister thrived, my brother not at all. 40 00:01:58,999 --> 00:02:02,359 So I have no talents and terrible dexterity, so I tried like 41 00:02:02,370 --> 00:02:03,629 painting and didn't do well. 42 00:02:03,829 --> 00:02:07,395 I tried poetry and I don't think I did well, but I kind of ventured 43 00:02:07,395 --> 00:02:11,595 into the riddle world and I tested those out with like various friends 44 00:02:11,595 --> 00:02:12,735 and family and they enjoyed it. 45 00:02:13,154 --> 00:02:17,025 I mean, I could do a riddle now or at the end of the podcast, 46 00:02:17,034 --> 00:02:18,015 if you want, it's up to you. 47 00:02:18,095 --> 00:02:18,945 Sara Dong: Oh, okay. 48 00:02:18,984 --> 00:02:20,475 We'll make people wait till the end. 49 00:02:20,665 --> 00:02:21,174 Jack Flores: Sounds good. 50 00:02:21,194 --> 00:02:21,464 Yeah. 51 00:02:22,325 --> 00:02:23,294 Sara Dong: What about you Madan? 52 00:02:23,524 --> 00:02:28,255 Madan Kumar: I don't make riddles, but I have a side hobby where I really 53 00:02:28,255 --> 00:02:30,505 am a very, very amateur woodworker. 54 00:02:31,019 --> 00:02:34,749 I don't have children, but we are expecting our first in April, so I've 55 00:02:34,749 --> 00:02:39,119 been able to flex that a little bit as we've started to make some furniture 56 00:02:39,119 --> 00:02:43,260 and basic wooden toys for our upcoming son, so that's been fun for me. 57 00:02:43,750 --> 00:02:44,580 Sara Dong: Very nice. 58 00:02:45,290 --> 00:02:48,650 Well, I am going to hand it over to Jack to tell us about the case. 59 00:02:49,050 --> 00:02:49,720 Jack Flores: All right. 60 00:02:50,020 --> 00:02:55,079 So, we are paged late in the afternoon from the emergency room in the pediatric 61 00:02:55,080 --> 00:02:59,130 hospital, our children's hospital, about a concern for a fever without a source. 62 00:02:59,230 --> 00:03:03,000 Upon calling back the resident in the ER, They state that the patient 63 00:03:03,010 --> 00:03:07,770 is a previously healthy two year old male who's had a fever for six days. 64 00:03:08,320 --> 00:03:12,429 On day two of fever, he presented to his primary care pediatrician and 65 00:03:12,429 --> 00:03:17,220 was prescribed a five day course of cefdinir for presumed left sided otitis 66 00:03:17,250 --> 00:03:21,299 media in the setting of a reported amoxicillin allergy with a rash. 67 00:03:21,979 --> 00:03:26,009 Despite the antibiotics, he continued to have fevers, so mom brought him to the ER. 68 00:03:26,495 --> 00:03:28,765 The resident asks our thoroughts on the matter if any 69 00:03:28,765 --> 00:03:30,265 additional workup we would like. 70 00:03:30,675 --> 00:03:30,985 Dr. 71 00:03:30,985 --> 00:03:35,484 Kumar, I'd like to give you some more objective data in a bit, but before that, 72 00:03:35,495 --> 00:03:38,774 can you kind of describe your thought process when you receive a call like this 73 00:03:39,355 --> 00:03:42,265 about your differential diagnosis of a patient with prolonged fever and what sort 74 00:03:42,265 --> 00:03:44,274 of workup you may consider performing? 75 00:03:44,415 --> 00:03:48,325 Madan Kumar: You know, anytime I get a call about a protracted fever, 76 00:03:48,775 --> 00:03:53,695 immediately, I get a huge grain slash boulder of salt on my shoulder 77 00:03:53,695 --> 00:03:57,025 where I'm really trying to parse what I'm getting for validity, right? 78 00:03:57,265 --> 00:04:01,454 Because protracted fever can include things from the spectrum of intermittent 79 00:04:01,454 --> 00:04:05,834 fever that was gone for two days and then it's back now, or it can truly be 80 00:04:05,834 --> 00:04:09,654 high grade fevers every day, or it may just be a very short amount of time that 81 00:04:09,654 --> 00:04:12,644 people personally feel, feels protracted. 82 00:04:13,060 --> 00:04:17,310 There's really a lot to parse through in terms of the calendar and timeline 83 00:04:17,390 --> 00:04:20,289 of fevers when you get a call like this to make sure that you're on the same 84 00:04:20,289 --> 00:04:23,890 page as the person who's consulting you and that you understand exactly 85 00:04:23,890 --> 00:04:25,800 what kind of category this falls in. 86 00:04:26,290 --> 00:04:30,240 In this sort of story, this isn't the protracted fever without a source 87 00:04:30,240 --> 00:04:34,750 where most of our counseling comes from saying, you know, it's okay and 88 00:04:34,760 --> 00:04:38,219 as long as they're well, that we can do some rudimentary workup, but not 89 00:04:38,219 --> 00:04:39,729 get too far down the rabbit hole. 90 00:04:40,120 --> 00:04:42,840 In this case, it sounds like they did have a focus, and that focus might 91 00:04:42,840 --> 00:04:44,270 have been an acute otitis media. 92 00:04:44,599 --> 00:04:48,919 That's another one where diagnostics from a primary team can sometimes be 93 00:04:48,929 --> 00:04:53,039 challenging, and a lot of interrater reliability isn't quite there. 94 00:04:53,539 --> 00:04:58,340 So if I have this story, I start to think, well, maybe they were on the wrong track, 95 00:04:58,340 --> 00:05:02,090 and that may not have been the focus since it didn't respond to antibiotic 96 00:05:02,090 --> 00:05:07,879 therapy with the caveat that they did use suboptimal antibiotic therapy, right? 97 00:05:07,879 --> 00:05:10,989 Cefdinir and pneumococcal coverage is always a concern. 98 00:05:10,989 --> 00:05:13,150 And so those are my sort of initial thoughts. 99 00:05:13,659 --> 00:05:16,689 Really, what we're looking for is coming up soon, Jack, which is a 100 00:05:16,689 --> 00:05:20,580 little more objective data so we can start anchoring in on exactly 101 00:05:20,580 --> 00:05:21,890 where the source of this might be. 102 00:05:21,969 --> 00:05:22,969 Jack Flores: Thank you so much for that. 103 00:05:22,989 --> 00:05:25,879 I'll give you some more information that the resident was able to give us over the 104 00:05:25,879 --> 00:05:27,809 phone and then elicit from the family. 105 00:05:28,179 --> 00:05:31,879 The resident mentions that four days into the fever, the patient did note 106 00:05:31,879 --> 00:05:37,770 a new red rash presented on the dorsal and palmar surfaces of the hand and 107 00:05:37,770 --> 00:05:39,599 the plantar surfaces of the feet. 108 00:05:40,325 --> 00:05:43,304 They also felt that the patient's eyes were maybe bloodshot and 109 00:05:43,304 --> 00:05:47,674 maybe had some new oral findings or ulcers that were slightly painful. 110 00:05:48,075 --> 00:05:52,135 Additionally, he had decreased intake of both liquid and solids 111 00:05:52,144 --> 00:05:53,734 with reduced urine output. 112 00:05:54,164 --> 00:05:56,924 And he did have some loose stools that began when he started the 113 00:05:56,924 --> 00:06:00,394 cefdinir, and they've persisted while he's been on the cefdinir. 114 00:06:00,775 --> 00:06:04,335 At this point, we do go down to the ER to see the family and the patient and we get 115 00:06:04,435 --> 00:06:06,365 a little bit more deep into the history. 116 00:06:06,815 --> 00:06:10,435 He lives at home with his parents and three school age siblings. 117 00:06:10,505 --> 00:06:15,344 He does not attend daycare and the parents don't report any sick contacts. 118 00:06:15,885 --> 00:06:18,965 His vaccinations are up to date and he's had no previous 119 00:06:18,965 --> 00:06:20,385 issues reported by the PCP. 120 00:06:20,385 --> 00:06:25,335 He had a normal birth history, full term, no NICU stay, no oxygen, no 121 00:06:25,335 --> 00:06:27,375 phototherapy for hyperbilirubinemia. 122 00:06:27,945 --> 00:06:30,895 Additionally, the family reports there's been no recent travel. 123 00:06:31,235 --> 00:06:34,145 They live in a nice, clean, reported suburban home just 124 00:06:34,145 --> 00:06:35,545 outside of the city of Chicago. 125 00:06:36,050 --> 00:06:39,740 They do have a dog at home, and there's no family history of immune 126 00:06:39,740 --> 00:06:41,830 deficiency or recurrent infections. 127 00:06:42,469 --> 00:06:47,039 So, how does this information affect your differential, and what now additional 128 00:06:47,039 --> 00:06:50,150 diagnostic workup would you like the patient to receive at this point? 129 00:06:50,659 --> 00:06:53,749 Madan Kumar: If a fellow was reporting this to me, they might have the tendency 130 00:06:53,750 --> 00:06:55,919 to call this social history quite boring. 131 00:06:55,919 --> 00:07:00,520 Because from our standpoint, there isn't a lot to inform any esoteric or 132 00:07:00,520 --> 00:07:04,650 more interesting infectious diseases diagnosis, but we have some nice 133 00:07:04,650 --> 00:07:08,890 information on symptomology that we can now sort of anchor into here a little bit. 134 00:07:09,200 --> 00:07:15,369 So whenever I hear rash and then eyes with some conjunctival changes, we've 135 00:07:15,369 --> 00:07:19,750 got potential mucous membrane changes when I hear about these new oral ulcers, 136 00:07:20,139 --> 00:07:23,640 you have to sort of wonder whether this is something non infectious, right? 137 00:07:23,640 --> 00:07:27,570 Whether that's something more like a Stevens Johnson syndrome, a TEN, even 138 00:07:27,580 --> 00:07:31,970 serum sickness with oral ulcers obviously being a little bit odd there, but those 139 00:07:31,970 --> 00:07:35,140 are the kind of things that come up to my head, but we have to start by ruling 140 00:07:35,140 --> 00:07:36,940 out more common infectious pieces. 141 00:07:37,490 --> 00:07:39,150 You can always go with the old standby. 142 00:07:39,259 --> 00:07:43,270 You can say it's likely viral, which will always get you points in the ID world. 143 00:07:43,440 --> 00:07:45,100 And in this case, it might be true. 144 00:07:45,400 --> 00:07:48,700 We have adenovirus and other adenovirus families that can 145 00:07:48,700 --> 00:07:50,230 present very much like this. 146 00:07:50,240 --> 00:07:52,150 It's very reasonable to test them. 147 00:07:52,520 --> 00:07:56,240 And in this story where they do have some persistence of symptoms and, you 148 00:07:56,240 --> 00:07:59,220 know, they're obviously in a healthcare setting or a more acute healthcare 149 00:07:59,220 --> 00:08:02,190 setting, it makes sense to send it, in my opinion, a respiratory viral 150 00:08:02,190 --> 00:08:06,360 panel, a respiratory pathogen panel, whatever your institution provides. 151 00:08:07,159 --> 00:08:11,020 On that same note, as maybe some folks have been hinted to by the title of 152 00:08:11,020 --> 00:08:15,840 this podcast, I'm going to guess there is the concern that this is Kawasaki's 153 00:08:15,840 --> 00:08:22,050 disease based on the rash, some changes to the conjunctivae, and then of course 154 00:08:22,050 --> 00:08:23,929 these mucous membrane changes as well. 155 00:08:23,940 --> 00:08:26,490 So that has to be a part of your differential and workup. 156 00:08:26,870 --> 00:08:30,380 This is the child that's going to get their screening labs. 157 00:08:30,380 --> 00:08:32,839 This is the child that's going to get a blood culture to ensure there's 158 00:08:32,839 --> 00:08:37,569 nothing we're missing there, probably respiratory viral testing and a 159 00:08:37,579 --> 00:08:39,209 formal infectious disease consult. 160 00:08:39,490 --> 00:08:40,539 Jack Flores: Yeah, sounds great. 161 00:08:40,650 --> 00:08:44,189 You know, despite the incidence or maybe slightly lower incidence of KD 162 00:08:44,189 --> 00:08:47,800 or Kawasaki disease, I'll probably just refer it to KD as here on out. 163 00:08:47,849 --> 00:08:50,979 The ER loves to bring that up in the initial differential, almost 164 00:08:50,979 --> 00:08:54,140 at the top every time they call the kid who's had five days of fever, 165 00:08:54,469 --> 00:08:55,839 regardless of other symptoms. 166 00:08:56,280 --> 00:08:58,589 So we were worried about a variety of viral infections. 167 00:08:59,025 --> 00:09:01,925 Many you already mentioned, you know, adenoviruses, enterovirus 168 00:09:01,925 --> 00:09:05,415 family, Epstein Barr virus, or other mononucleosis type illnesses. 169 00:09:05,885 --> 00:09:09,205 Perhaps a toxin producing bacterial infections such as Staphylococcus 170 00:09:09,205 --> 00:09:13,725 aureus or Streptococcus pyogenes, and perhaps also a drug related 171 00:09:13,725 --> 00:09:14,995 incident due to the cefdinir. 172 00:09:15,974 --> 00:09:19,745 However, also in the differential diagnosis was KD or incomplete 173 00:09:19,745 --> 00:09:23,335 Kawasaki disease, formerly called atypical Kawasaki disease. 174 00:09:23,805 --> 00:09:26,344 And once again, I want to dive a little bit into KD before 175 00:09:26,345 --> 00:09:27,275 we get back to our case. 176 00:09:28,030 --> 00:09:31,510 Kawasaki disease is a vasculitis of the medium sized arteries. 177 00:09:31,540 --> 00:09:35,380 The etiology is unknown, but there are some fascinating science that's kind 178 00:09:35,380 --> 00:09:39,180 of been coming out, and I'll let Madan describe that in a bit that may suggest 179 00:09:39,220 --> 00:09:42,359 the true or an evolving true origin of it. 180 00:09:42,399 --> 00:09:45,409 Epidemiologic and clinical features suggest an infectious origin, 181 00:09:45,699 --> 00:09:49,250 and, or perhaps an environmental cause or trigger in genetically 182 00:09:49,250 --> 00:09:53,060 susceptible individuals or perhaps within family lines or environments. 183 00:09:53,760 --> 00:09:57,839 The peak age of occurrence in the United States is 6 to 24 months. 184 00:09:57,900 --> 00:10:02,129 50 percent of patients are younger than 2, and 80 percent are younger than 185 00:10:02,129 --> 00:10:05,360 5 years old, so this is definitely a disease of the younger child for the 186 00:10:05,360 --> 00:10:09,860 most part, but there are cases that can be older than 8 years old, and very 187 00:10:09,860 --> 00:10:11,530 rarely they've occurred even in adults. 188 00:10:12,210 --> 00:10:14,839 There is a described definition of KD. 189 00:10:15,339 --> 00:10:20,615 It's the fever of five days at least in addition to the presence of at least four 190 00:10:20,615 --> 00:10:22,795 of the following five clinical criteria. 191 00:10:23,045 --> 00:10:27,245 And this is kind of where the subjectivity of the clinical exam does come in to play. 192 00:10:27,295 --> 00:10:30,754 So you can have bilateral injection of the bulbar conjunctivate with 193 00:10:30,795 --> 00:10:32,875 limbic sparing and without exudate. 194 00:10:32,914 --> 00:10:34,795 I feel like that was something I got pimped on a lot as a 195 00:10:34,805 --> 00:10:36,535 resident, the limbic sparing part. 196 00:10:37,125 --> 00:10:41,520 Erythematous mouth and pharynx, strawberry tongue, and or red 197 00:10:41,520 --> 00:10:43,140 cracked lips, that's the second one. 198 00:10:43,200 --> 00:10:49,460 Third is a polymorphous, generalized, erythematous rash, often with accentuation 199 00:10:49,470 --> 00:10:54,160 in the groin, which can be morbilliform, maculopapular, scarlatiniform, 200 00:10:54,210 --> 00:10:55,969 or erythema-multiforme like. 201 00:10:56,390 --> 00:11:00,280 The fourth is changes in the peripheral extremities consisting of erythema 202 00:11:00,300 --> 00:11:04,819 of the hands and soles and firm, sometimes painful, indurations of the 203 00:11:04,819 --> 00:11:08,750 hands and feet, often with periungual desquamation, usually beginning 204 00:11:08,770 --> 00:11:10,849 10 to 14 days after fever onset. 205 00:11:10,849 --> 00:11:15,500 So this can be a little bit more delayed and kind of a more transitionary finding. 206 00:11:15,569 --> 00:11:21,830 And then the fifth one is acute non suppurative, usually unilateral, anterior 207 00:11:21,830 --> 00:11:25,824 cervical lymphadenopathy with at least one node greater than or equal to 1. 208 00:11:25,825 --> 00:11:27,735 5 centimeters in diameter. 209 00:11:28,395 --> 00:11:32,955 So that's the traditional KD, but I want to move on to incomplete or atypical KD. 210 00:11:32,975 --> 00:11:36,305 So this is our children with greater than or equal to five days of fever. 211 00:11:36,664 --> 00:11:40,035 And then you might have two or three of the clinical criteria, which I think 212 00:11:40,035 --> 00:11:45,375 is what we often find more often, or, you can have infants with a fever for 213 00:11:45,375 --> 00:11:48,510 greater than, uh, are equal to seven days without explanation, which I'll have Dr. 214 00:11:48,510 --> 00:11:49,670 Kumar describe in a bit. 215 00:11:50,109 --> 00:11:53,689 And now you want to get some basic labs, so you want to get a CRP and ESR. 216 00:11:53,689 --> 00:11:58,629 I'm going to describe kind of what the AAP Redbook uses for their numbers and 217 00:11:58,640 --> 00:12:06,585 their types of CRP and ESR, but if you have a CRP less than 3 mg/dL and an ESR 218 00:12:06,625 --> 00:12:11,385 less than 40 mm per hour, they recommend serial, clinical, and laboratory re 219 00:12:11,385 --> 00:12:15,625 evaluation if the fever persists, or you can consider an echocardiogram if 220 00:12:15,795 --> 00:12:17,424 peeling develops, interestingly enough. 221 00:12:17,735 --> 00:12:20,575 This can be done in the inpatient or outpatient setting, but I feel 222 00:12:20,575 --> 00:12:23,475 like more often than not we do admit the kids overnight for observation. 223 00:12:23,865 --> 00:12:28,125 If the CRP is greater than 3 mg/dL, or the ESR is greater than or equal 224 00:12:28,125 --> 00:12:32,574 to 40 mm per hour, then you need three or more of laboratory findings. 225 00:12:32,584 --> 00:12:34,874 So, one is anemia for age. 226 00:12:35,294 --> 00:12:38,614 Two is platelet count greater than or equal to 450, 000 227 00:12:38,615 --> 00:12:40,725 after the seventh day of fever. 228 00:12:41,504 --> 00:12:45,845 The third is albumin less than or equal to 3 g/dL. 229 00:12:46,215 --> 00:12:50,525 If you have an elevated ALT level, if your white count is, white blood 230 00:12:50,525 --> 00:12:54,445 cell count is greater than or equal to 15, 000 per millimeter cubed, and 231 00:12:54,445 --> 00:12:57,624 then if your urine white blood cell count is greater than or equal to 10 232 00:12:57,635 --> 00:12:59,295 white blood cells per high power field. 233 00:12:59,819 --> 00:13:03,630 Or, if you simply have a positive echocardiogram for 234 00:13:03,680 --> 00:13:05,010 coronary artery dilation. 235 00:13:05,090 --> 00:13:06,660 At that point, then you move on to treatment. 236 00:13:06,660 --> 00:13:08,960 So I just want to go back to our case really quick. 237 00:13:09,440 --> 00:13:12,880 So the patient did end up getting an IV fluid bolus as he appeared dehydrated. 238 00:13:13,250 --> 00:13:17,259 A rapid group A streptococcal throat swab was performed in return negative. 239 00:13:17,840 --> 00:13:22,430 On our physical exam, the ID consultant physical exam, he was ill appearing, he 240 00:13:22,430 --> 00:13:24,700 was fussy and notable for sunken features. 241 00:13:25,150 --> 00:13:29,899 He did have the erythematous hands and feet, non purulent conjunctival injection. 242 00:13:30,310 --> 00:13:33,869 The oropharynx was erythematous and swollen with bloody and cracked 243 00:13:33,870 --> 00:13:37,744 lips and with areas of bleeding around the right posterior pharynx. 244 00:13:38,275 --> 00:13:41,165 He was also noted to have small, shoddy cervical lymphadenopathy 245 00:13:41,165 --> 00:13:42,295 and was tachycardic. 246 00:13:42,365 --> 00:13:46,745 Interestingly enough though, there was no rash in the patients outside of 247 00:13:46,745 --> 00:13:50,845 the hands and feet, so no trunk, body, arms, or legs, just the hands and feet. 248 00:13:51,795 --> 00:13:56,065 We did get some blood tests, included an elevated white blood cell count of 18, 249 00:13:56,065 --> 00:13:59,775 100, which is greater than the 15, 000 cutoff, with a neutrophilic predominance. 250 00:13:59,945 --> 00:14:03,135 He had an elevated platelet count of 550, 000. 251 00:14:03,565 --> 00:14:05,964 He did have a normal hemoglobin for his age. 252 00:14:05,985 --> 00:14:10,145 He had an elevated ESR to 112 millimeters per hour and a very 253 00:14:10,145 --> 00:14:14,275 high CRP of 77 milligrams per deciliter, well above the 3. 254 00:14:14,275 --> 00:14:14,705 0 cutoff. 255 00:14:15,345 --> 00:14:20,035 The patient's alkaline transferase, or ALT, was elevated to 263. 256 00:14:20,520 --> 00:14:23,660 And his remaining comprehensive metabolic panel was within normal limits. 257 00:14:24,220 --> 00:14:27,030 He also had a urinalysis performed which noted significant pyuria 258 00:14:27,030 --> 00:14:31,819 for 26 to 100 cells per high power field, and negative for nitrites 259 00:14:31,819 --> 00:14:34,849 or bacteria, and urine and blood cultures did remain no growth to date. 260 00:14:35,420 --> 00:14:39,480 He did have a respiratory pathogen panel on nasal PCR swab, which was negative, 261 00:14:39,520 --> 00:14:41,570 and chest X ray was unremarkable. 262 00:14:42,250 --> 00:14:46,140 At this point, we did feel that he met three of the five compatible criteria, 263 00:14:46,140 --> 00:14:50,839 including the erythematous oropharynx features, non purulent conjunctivitis and 264 00:14:50,840 --> 00:14:52,889 changes in the peripheral extremities. 265 00:14:53,140 --> 00:14:57,685 He also had thrombocytosis, a low albumin, elevated ALT, the 266 00:14:57,685 --> 00:15:01,555 leukocytosis, and the pyuria, along with inflammatory markers, to meet a 267 00:15:01,555 --> 00:15:04,325 clinical diagnosis of incomplete KD. 268 00:15:04,935 --> 00:15:08,114 Transthoracic echocardiogram was performed, which did show 269 00:15:08,145 --> 00:15:10,394 elevated Z scores of plus 2. 270 00:15:10,394 --> 00:15:10,724 4 and plus 2. 271 00:15:10,725 --> 00:15:14,965 1, respectively, and dilation of the left anterior descending and left 272 00:15:14,965 --> 00:15:18,805 medial coronary arteries, consistent with a diagnosis of Kawasaki disease. 273 00:15:19,325 --> 00:15:19,725 So, Dr. 274 00:15:19,725 --> 00:15:22,435 Kumar, can you give us thoughts on the clinical findings on the case, and 275 00:15:22,435 --> 00:15:25,435 I would also love if you wanted any more additional thoughts just on the 276 00:15:25,435 --> 00:15:27,834 diagnostic algorithms I described earlier. 277 00:15:28,035 --> 00:15:29,015 Madan Kumar: Yeah, happy to. 278 00:15:29,015 --> 00:15:29,785 Thanks, Jack. 279 00:15:29,805 --> 00:15:34,135 So, as far as the clinical findings go, one of the challenges of Kawasaki's 280 00:15:34,135 --> 00:15:38,485 disease is that to date, we don't have an objective test where we can send 281 00:15:38,635 --> 00:15:42,795 and confirm the diagnosis if we suspect it, and we're relying on these clinical 282 00:15:42,795 --> 00:15:44,575 and associated laboratory parameters. 283 00:15:45,245 --> 00:15:49,944 So when we do that, sometimes trainees get caught in a memorization 284 00:15:49,944 --> 00:15:53,395 pattern and it makes it difficult to understand the mechanism of the 285 00:15:53,395 --> 00:15:57,055 disease, which really should be at the forefront in evaluating this disease. 286 00:15:57,405 --> 00:16:00,274 So if you go back to the basics and just remember that this is a 287 00:16:00,274 --> 00:16:03,895 medium to small vessel vasculitis, it's much better and easier to 288 00:16:03,895 --> 00:16:05,525 remember where that might manifest. 289 00:16:05,525 --> 00:16:09,555 You might see redness in the eyes, but of course you shouldn't see purulence, 290 00:16:09,615 --> 00:16:13,935 not because you have to memorize it, but because this isn't a primary bacterial 291 00:16:14,200 --> 00:16:19,030 or virological purulent mechanism, it is a blood vessel inflammation. 292 00:16:19,100 --> 00:16:22,290 Similarly, with the rash, you can know that you're going to see a 293 00:16:22,290 --> 00:16:26,240 rash, and you can also know that if it is a vasculitis, that rash can be 294 00:16:26,410 --> 00:16:31,029 polymorphous, morbilliform, a lot of ways to say anything, any sort of red 295 00:16:31,029 --> 00:16:33,419 rash can fit with the parameters of KD. 296 00:16:33,420 --> 00:16:37,840 The lymphadenopathy, it used to be a preeminent piece of the disease. 297 00:16:37,840 --> 00:16:42,160 We usually see it unilaterally again, of course, because it's not the same typical 298 00:16:42,520 --> 00:16:44,730 infectious lymphadenopathy process. 299 00:16:45,209 --> 00:16:47,900 And then the mucous membrane changes are other areas where 300 00:16:47,909 --> 00:16:50,500 hyperemia can be eminently visible. 301 00:16:51,000 --> 00:16:53,820 So those things can kind of help you just categorize why you're 302 00:16:53,820 --> 00:16:56,980 seeing what you're seeing and make it a little bit easier to remember. 303 00:16:57,750 --> 00:17:02,879 The piece that's tough, and if we put, uh, caveats about where we're 304 00:17:02,879 --> 00:17:06,050 stepping away from the guideline verbally, this would be it. 305 00:17:06,390 --> 00:17:08,909 The piece that's tough is recognizing that not all of 306 00:17:08,910 --> 00:17:10,779 these parameters are made equal. 307 00:17:11,259 --> 00:17:15,450 If we're trying to diagnose someone with incomplete Kawasaki's disease, you're 308 00:17:15,450 --> 00:17:19,530 functionally trying to differentiate them from viral NOS, because you haven't 309 00:17:19,895 --> 00:17:21,754 established another clear diagnosis. 310 00:17:21,754 --> 00:17:25,194 If you have, it's easier to step away from Kawasaki's disease. 311 00:17:25,865 --> 00:17:29,514 In a viral NOS, you're going to have a lot of overlapping lab parameters and 312 00:17:29,604 --> 00:17:32,774 clinical parameters, but there's some that kind of should jump out at you as 313 00:17:32,784 --> 00:17:35,775 being a typical for a viral process. 314 00:17:35,835 --> 00:17:39,860 So, for me, some of the things that help clinch the diagnosis, if we're 315 00:17:39,870 --> 00:17:43,780 sort of on the fence, are things like the sterile pyuria, right? 316 00:17:43,780 --> 00:17:47,570 We don't really see sterile pyuria as part of your typical adenovirus 317 00:17:47,610 --> 00:17:49,090 upper respiratory infection. 318 00:17:49,520 --> 00:17:53,849 Something that's very hepatotropic, where we have elevated ALT, and then it's 319 00:17:53,859 --> 00:17:56,500 not necessarily part of the parameters, but it's something I always look for. 320 00:17:56,510 --> 00:18:01,129 Elevated GGT as well can also be indicative of something more in the 321 00:18:01,129 --> 00:18:06,040 KD pathway, or KD that's more likely to be resistant to initial therapy. 322 00:18:06,040 --> 00:18:09,875 There's some data to suggest that those things are genetically linked. 323 00:18:10,645 --> 00:18:14,365 When you're dealing with Kawasaki's disease, you kind of have to make an 324 00:18:14,395 --> 00:18:20,425 internal judgment whether you're going to follow the criteria to the staunchest, 325 00:18:20,425 --> 00:18:27,264 most strict possible interpretation, or whether there may be children who look 326 00:18:27,434 --> 00:18:32,105 pathophysiologically like Kawasaki's disease, look miserable like most of 327 00:18:32,105 --> 00:18:38,995 these kids do, and warrant treatment based on meeting the incomplete criteria and 328 00:18:39,125 --> 00:18:42,035 fitting the mechanisms that you suspect. 329 00:18:42,365 --> 00:18:46,754 In this case, it's a little bit easier to make the decision to treat. 330 00:18:46,755 --> 00:18:49,985 You've talked about the initial echocardiogram having elevated 331 00:18:49,985 --> 00:18:51,345 coronary artery scores. 332 00:18:52,099 --> 00:18:57,059 Oftentimes, variable cutoffs are used for the z score, and for trainees who are 333 00:18:57,069 --> 00:19:00,529 unfamiliar, the z score is essentially a measure of standard deviation. 334 00:19:00,529 --> 00:19:03,999 You're looking at the internal diameter of the artery itself and 335 00:19:03,999 --> 00:19:07,899 seeing how many standard deviations above the mean you are, respective to 336 00:19:07,909 --> 00:19:09,999 your body size or body surface area. 337 00:19:10,279 --> 00:19:12,309 And if you're more than 2, that's meaningful. 338 00:19:12,309 --> 00:19:17,070 If you're more than 2.5, that's often used as even more meaningful of a cutoff point. 339 00:19:17,100 --> 00:19:19,235 This person was on the border for 2. 340 00:19:19,274 --> 00:19:19,715 4. 341 00:19:20,365 --> 00:19:23,495 So besides making the diagnosis a little easier, it actually puts them into 342 00:19:23,495 --> 00:19:26,100 potentially a higher risk stratification. 343 00:19:26,510 --> 00:19:29,140 We can get into a little more when we talk about therapy, but in the 344 00:19:29,140 --> 00:19:32,930 initial diagnosis, risk stratification is important as well because it can 345 00:19:32,930 --> 00:19:35,049 inform your therapeutic decisions. 346 00:19:35,659 --> 00:19:39,969 Unfortunately, because of just the way that the data is stratified and where 347 00:19:39,969 --> 00:19:45,100 this tends to be more prevalent, there's very clearly a underlying risk factor in 348 00:19:45,100 --> 00:19:48,189 the Asian population, which makes them more likely to get Kawasaki's disease. 349 00:19:48,810 --> 00:19:53,139 When that happens, most of our data from Kawasaki's disease risk stratification 350 00:19:53,179 --> 00:19:56,969 comes from Asian countries, and it's unclear if our children in America 351 00:19:57,069 --> 00:20:03,569 follow the same risk profile or pattern, but in generality, infants 352 00:20:03,569 --> 00:20:07,815 less than six months and those with initial echocardiogram changes tend to 353 00:20:07,815 --> 00:20:11,815 be higher risk and require high risk stratification and high risk therapy. 354 00:20:11,904 --> 00:20:12,645 Jack Flores: That was amazing. 355 00:20:12,654 --> 00:20:13,995 Thank you so much, Madan for that. 356 00:20:14,105 --> 00:20:17,495 Before I move on to additional clinical features and treatment and 357 00:20:17,495 --> 00:20:20,960 prognosis, do you kind of want to, uh, tell me about like some of the 358 00:20:20,970 --> 00:20:24,530 evolving science of what they think might be causing Kawasaki disease. 359 00:20:24,530 --> 00:20:27,450 I know things are kind of changing almost on an annual basis, but I'd love 360 00:20:27,450 --> 00:20:28,809 to hear what your thoughts are on that. 361 00:20:28,990 --> 00:20:33,560 Madan Kumar: One of the interesting things about the peak pandemic era 362 00:20:33,929 --> 00:20:38,744 is that we had a lot of COVID cases, of course, but we had a very, very 363 00:20:39,044 --> 00:20:42,685 significant paucity of other viral infections for a small window there, 364 00:20:42,695 --> 00:20:44,324 or for a pretty long window actually. 365 00:20:44,574 --> 00:20:47,405 During that time, it was kind of neat because we got to see a lot 366 00:20:47,405 --> 00:20:50,735 of these diagnoses where we didn't quite know if they had a viral 367 00:20:50,735 --> 00:20:55,305 etiology or not and get really good epidemiologic data on their incidence. 368 00:20:55,724 --> 00:21:00,655 Theoretically, if Kawasaki's disease was purely genetic and had no infectious 369 00:21:00,685 --> 00:21:04,335 trigger, the rates would be entirely consistent throughout the pandemic. 370 00:21:04,645 --> 00:21:06,285 And then, of course, the converse is true. 371 00:21:06,445 --> 00:21:10,424 And that's what we found is that when our general viral rates plummeted, 372 00:21:10,445 --> 00:21:13,994 when people were masking, when people were staying at home, similarly, our 373 00:21:13,994 --> 00:21:16,035 rates of Kawasaki's disease plummeted. 374 00:21:16,115 --> 00:21:20,605 So epidemiologically, that presents a really compelling amount of data that 375 00:21:20,775 --> 00:21:26,355 even though there's clearly a genetic component to both risk for onset 376 00:21:26,375 --> 00:21:28,365 of disease and severity of disease. 377 00:21:28,574 --> 00:21:31,715 There is also an infectious trigger that we haven't identified. 378 00:21:32,164 --> 00:21:36,914 It sort of sets the chain off, which makes a lot of sense, in the pathophys 379 00:21:36,914 --> 00:21:39,055 of other similar disease processes. 380 00:21:39,405 --> 00:21:42,945 The other big pieces, um, you know, of course, at this last national 381 00:21:42,945 --> 00:21:48,125 ID conference, we were presented data on partial sequencing of 382 00:21:48,135 --> 00:21:49,775 the causative virus as well. 383 00:21:49,775 --> 00:21:51,385 And that was very compelling. 384 00:21:51,394 --> 00:21:55,585 And it does look like within the next 5 years, we'll be able to have 385 00:21:55,595 --> 00:22:00,865 a little more substantive sequencing data of the causative virus. 386 00:22:00,955 --> 00:22:05,445 So at this point, personally, I think we've sort of clenched it, that this is 387 00:22:05,465 --> 00:22:10,645 a two fold process with a viral trigger and a secondary genetic predisposition. 388 00:22:10,805 --> 00:22:14,105 Jack Flores: Yeah, I just feel like, you know, with KD, we think we know everything 389 00:22:14,105 --> 00:22:16,695 in medicine, but then you have something like KD come along and you're like, 390 00:22:16,695 --> 00:22:19,644 wow, there's still a lot of, you know, discovery to be happened in medicine, 391 00:22:19,815 --> 00:22:21,254 which makes things fun and exciting. 392 00:22:21,665 --> 00:22:24,165 I'll give a little more clinical features, then I'm gonna talk about treatment, 393 00:22:24,165 --> 00:22:26,854 and then I'll come back to you, Madan, if you have any additional thoughts. 394 00:22:27,365 --> 00:22:30,085 Clinicians should consider KD in their differential diagnosis 395 00:22:30,085 --> 00:22:33,175 before the fifth day of course, if several of the features are present 396 00:22:33,184 --> 00:22:35,055 without an alternative explanation. 397 00:22:35,505 --> 00:22:38,625 One of the issues that you've mentioned is that different things can have different 398 00:22:38,625 --> 00:22:42,335 temporalities, so certain things may present earlier in the course and some 399 00:22:42,335 --> 00:22:46,135 may present later in the course, and it's absolutely possible to have a concurrent 400 00:22:46,325 --> 00:22:49,974 viral upper respiratory infection in a patient with KD, particularly 401 00:22:49,985 --> 00:22:53,895 if it's during certain epidemiologic months of the year, like in the winter. 402 00:22:54,125 --> 00:22:57,175 The average duration of fever for untreated KD is 10 days. 403 00:22:57,265 --> 00:22:59,325 However, fever can last two weeks or longer. 404 00:22:59,849 --> 00:23:03,739 After the fever resolves though, patient can remain anorexic and irritable with 405 00:23:03,739 --> 00:23:07,579 decreased energy for two weeks, and I feel like that's something we've encountered 406 00:23:07,579 --> 00:23:09,889 oftentimes in the outpatient setting after we see them in the hospital. 407 00:23:09,889 --> 00:23:12,569 The parents are really concerned because they're still not eating, they're 408 00:23:12,569 --> 00:23:14,919 still very tired, but it's something we kind of have to describe to them. 409 00:23:14,919 --> 00:23:16,339 It's, it's a natural phenomenon. 410 00:23:16,760 --> 00:23:20,240 Also during this kind of recovery phase, the brawny desquamation of the 411 00:23:20,240 --> 00:23:22,290 fingers, toes, hands, and feet may occur. 412 00:23:22,700 --> 00:23:25,330 Transverse lines across the nails or Beau's lines sometimes are 413 00:23:25,330 --> 00:23:26,810 noted to occur even months later. 414 00:23:27,129 --> 00:23:31,240 The most serious complication, of course, is the coronary artery abnormalities. 415 00:23:31,620 --> 00:23:35,200 It occurs in about 20-25 percent of untreated children. 416 00:23:35,520 --> 00:23:39,080 Certain increased risk factors for coronary artery abnormalities, 417 00:23:39,080 --> 00:23:43,310 there appears to be a biologic sex predisposition for males over females, 418 00:23:43,469 --> 00:23:46,170 if you're less than 12 months of age or greater than 8 years, so 419 00:23:46,170 --> 00:23:47,360 the very young or the very old. 420 00:23:47,740 --> 00:23:51,200 If your fever does last more than 10 days, if your white count is greater 421 00:23:51,200 --> 00:23:55,010 than 15, 000 with a high neutrophil predominance, If you're anemic, if 422 00:23:55,010 --> 00:23:57,650 you have a low albumin, if you have a low sodium, interestingly enough, 423 00:23:57,710 --> 00:23:59,130 and if you have high platelet count. 424 00:23:59,689 --> 00:24:04,290 And then, additionally, if your fever persists greater than 36 hours, despite 425 00:24:04,580 --> 00:24:08,320 proper therapy, that also increases risk for coronary artery abnormalities. 426 00:24:08,719 --> 00:24:12,959 Aneurysms of the coronary arteries usually occur between 1 and 4 427 00:24:12,960 --> 00:24:14,550 weeks after the onset of disease. 428 00:24:15,045 --> 00:24:17,395 Onset later than six weeks is extremely uncommon. 429 00:24:18,225 --> 00:24:22,475 If the coronary artery aneurysm or ectasia is evident, as you mentioned 430 00:24:22,475 --> 00:24:26,264 before, a Z score greater than two, but really above two and a half, in 431 00:24:26,264 --> 00:24:29,834 any patient evaluated for fever, a presumptive diagnosis should be made. 432 00:24:30,085 --> 00:24:34,155 A normal early echocardiogram study is typical and does not exclude 433 00:24:34,165 --> 00:24:36,835 the diagnosis, but it might be useful in patients with suspected 434 00:24:36,845 --> 00:24:39,775 incomplete KD, perhaps that's the patient where you'd want to repeat 435 00:24:39,775 --> 00:24:41,615 the echo within 24 to 48 hours. 436 00:24:42,105 --> 00:24:45,835 There was one study that showed that 80 percent of patients with KD who ultimately 437 00:24:45,835 --> 00:24:49,915 developed coronary artery disease had abnormalities in echocardiograms obtained 438 00:24:49,925 --> 00:24:51,254 during the first 10 days of illness. 439 00:24:51,265 --> 00:24:54,365 So, that is still a possibility before the 10 days. 440 00:24:54,955 --> 00:24:59,845 Other exam findings, in many patients you might find urethritis, so pain with 441 00:24:59,845 --> 00:25:04,605 urination along with the sterile pyuria, a mild anterior uveitis, less likely 442 00:25:04,605 --> 00:25:09,285 you might have elevated serum, you know, transferase concentrations, arthralgias, 443 00:25:09,290 --> 00:25:14,360 or arthritis, perhaps CSF pleocytosis, and then even more rare would be hydrops of 444 00:25:14,360 --> 00:25:19,050 the gallbladder, a pericardial effusion, myocarditis, cranial nerve palsies. 445 00:25:19,050 --> 00:25:21,309 These are all kind of much less common things. 446 00:25:21,750 --> 00:25:25,000 The current case fatality rate, fortunately, in the United States 447 00:25:25,000 --> 00:25:28,399 and Japan, where most of the studies are performed, is less than 0. 448 00:25:28,399 --> 00:25:29,409 2 percent at this time. 449 00:25:29,729 --> 00:25:32,989 Primary cause of death is myocardial infarction resulting from coronary 450 00:25:33,000 --> 00:25:36,360 artery occlusion, attributable to thrombosis or progressive stenosis. 451 00:25:36,970 --> 00:25:40,695 The relative risk of mortality is highest within six weeks of of onset of acute 452 00:25:40,695 --> 00:25:44,545 symptoms, but that can occur many months to even years after the acute episode. 453 00:25:45,095 --> 00:25:48,535 The prevalence of higher abnormalities is when you delay treatment beyond 454 00:25:48,535 --> 00:25:51,805 10 days of illness, so that's kind of where we have our 10 day cutoff. 455 00:25:51,885 --> 00:25:55,515 The first line treatment is IVIG, 2 grams per kilogram, 456 00:25:55,515 --> 00:25:57,235 administered over 10 to 12 hours. 457 00:25:57,855 --> 00:26:01,064 It's important, particularly depending on the unit in the hospital, that they 458 00:26:01,065 --> 00:26:02,784 understand this prolonged infusion rate. 459 00:26:03,214 --> 00:26:05,024 A secondary cornerstone is aspirin. 460 00:26:05,034 --> 00:26:11,684 There's the high dose aspirin, 80-100 mg per kg, or the middle to lower dose, 30-50 461 00:26:12,024 --> 00:26:15,034 mg per kg per day, in 4 divided doses. 462 00:26:15,044 --> 00:26:17,624 In severe cases, you can consider steroids. 463 00:26:18,104 --> 00:26:20,964 If you have recurrence of fever after 36 hours of that first 464 00:26:20,964 --> 00:26:24,965 dose of IVIG, we recommend infliximab as one additional dose. 465 00:26:24,975 --> 00:26:25,665 So actually, Dr. 466 00:26:25,665 --> 00:26:30,050 Kumar, can you chat about the two different doses of aspirin I described, 467 00:26:30,050 --> 00:26:34,300 and actually why infliximab is used instead of a second dose of IVIG. 468 00:26:34,450 --> 00:26:37,499 Madan Kumar: KD treatment pathways have evolved and continue to evolve 469 00:26:37,500 --> 00:26:40,910 just like restratification has evolved and continued to evolve. 470 00:26:40,919 --> 00:26:44,340 In the early years of KD, steroids were obviously a hallmark of therapy and 471 00:26:44,340 --> 00:26:48,125 then found to either be ineffective or potentially even harmful and now 472 00:26:48,125 --> 00:26:53,300 they're reserved for use in conjunction with IVIG where they are meaningfully 473 00:26:53,310 --> 00:26:54,890 helpful in our high risk patients. 474 00:26:55,300 --> 00:26:59,150 The aspirin piece has also been an area where we've traditionally had a 475 00:26:59,150 --> 00:27:03,980 paucity of data, and now, now finding more and more data to suggest that lower 476 00:27:03,980 --> 00:27:08,899 doses of aspirin do not have a higher risk of a lot of those complications, 477 00:27:08,909 --> 00:27:12,359 those coronary artery complications, that we were traditionally worried 478 00:27:12,359 --> 00:27:17,889 about when you have thrombocytosis and a artery abnormality or a aneurysm. 479 00:27:18,360 --> 00:27:23,845 So from that high dose of aspirin, a lot of institutions now feel safe 480 00:27:23,865 --> 00:27:27,605 and comfortable switching to medium dose aspirin, and there's actually 481 00:27:27,605 --> 00:27:31,535 been even a push to reduce it even further and to start with the low 482 00:27:31,535 --> 00:27:33,125 dose aspirin and continue there. 483 00:27:33,134 --> 00:27:35,885 Although again, that hasn't made it into the general guidance yet. 484 00:27:36,105 --> 00:27:38,804 I suspect that that will be where we end up. 485 00:27:39,205 --> 00:27:42,174 As far as the infliximab, that's been an interesting piece. 486 00:27:42,224 --> 00:27:46,555 So traditionally, if you refractory to a single dose of IVIG, we'd 487 00:27:46,555 --> 00:27:48,345 often give a 2nd dose of IVIG. 488 00:27:48,680 --> 00:27:50,940 And to be fair, many institutions still do that. 489 00:27:51,389 --> 00:27:55,370 There was a multi center study that we were a part of that evaluated 490 00:27:55,379 --> 00:28:00,349 the respective risks for secondary coronary artery abnormalities, along 491 00:28:00,349 --> 00:28:08,180 with adverse events with each approach, and we found that there was a general 492 00:28:08,190 --> 00:28:11,569 overlap in terms of outcomes, and there was no stratification for outcomes 493 00:28:11,570 --> 00:28:15,969 with use of infliximab, but we had a much better safety profile compared to 494 00:28:15,970 --> 00:28:19,965 second dose of IVIG, particularly with things like autoimmune hemolytic anemia, 495 00:28:20,265 --> 00:28:23,755 which we had a far higher incidence of with our second dose of IVIG. 496 00:28:24,055 --> 00:28:28,514 So we've made the choice to switch over to infliximab for our refractory patients. 497 00:28:28,644 --> 00:28:32,065 Jack Flores: Mysterious disease and once again, you know, therapies can differ 498 00:28:32,125 --> 00:28:33,375 depending on where you are in the world. 499 00:28:33,955 --> 00:28:36,824 Just a few more brief points about follow up. 500 00:28:36,845 --> 00:28:40,945 So echocardiogram should be performed at the time of suspected diagnosis, 501 00:28:41,465 --> 00:28:45,435 oftentimes at our institution, we repeat it at two weeks, then six to 502 00:28:45,435 --> 00:28:49,925 eight weeks after diagnosis with normal coronary arteries on initial evaluation. 503 00:28:50,275 --> 00:28:54,275 If they do have abnormal coronary arteries, though, we oftentimes defer to 504 00:28:54,275 --> 00:28:56,955 our neighborhood friendly cardiologists, and they oftentimes will help monitor 505 00:28:56,955 --> 00:29:00,435 their patients for that and closely see them in the outpatient setting. 506 00:29:00,515 --> 00:29:04,975 If you develop a giant coronary artery aneurysm or very large one with a luminal 507 00:29:04,985 --> 00:29:09,955 diameter of greater than or equal to eight millimeters, or perhaps larger in 508 00:29:09,955 --> 00:29:13,105 our infants with a z score of greater than or equal to 10, that usually 509 00:29:13,105 --> 00:29:16,825 requires the addition of anticoagulant therapy such as warfarin or low molecular 510 00:29:16,825 --> 00:29:18,955 weight heparin to prevent thrombosis. 511 00:29:19,355 --> 00:29:22,815 Another interesting tidbit that I think is fair game for the ID board exam 512 00:29:22,815 --> 00:29:26,794 and it might have even been a practice question for my Pediatric board exam 513 00:29:26,804 --> 00:29:32,114 is the measles, mumps, rubella, and varicella containing vaccines should be 514 00:29:32,114 --> 00:29:36,474 deferred until 11 months after receipt of IVIG for treatment of KD because of the 515 00:29:36,474 --> 00:29:39,504 possible interference of the development of an adequate immune response. 516 00:29:40,295 --> 00:29:43,055 Just to wrap up our case, the patient received a single dose of 517 00:29:43,055 --> 00:29:47,565 IVIG, 2 grams per kg, administered over 10 to 12 hours, in addition 518 00:29:47,565 --> 00:29:49,495 to initiating medium dose aspirin. 519 00:29:49,495 --> 00:29:52,455 The patient was noted to defervesce within 36 hours and did not 520 00:29:52,455 --> 00:29:55,895 require an additional dose of IVIG or infliximab, which is great. 521 00:29:56,425 --> 00:29:59,445 He did go home, but interestingly enough, he returned to the hospital 522 00:29:59,455 --> 00:30:02,985 10 days later with low grade fever and upper respiratory infection symptoms, 523 00:30:02,985 --> 00:30:04,925 just a runny nose and a sore throat. 524 00:30:05,655 --> 00:30:08,905 He did notice a desquamation of the hands and feet, so the ER 525 00:30:09,165 --> 00:30:12,155 asked us if this is actually the return of the Kawasaki disease. 526 00:30:12,525 --> 00:30:16,105 He was diagnosed with rhinovirus on nasal PCR swab, and his sibling 527 00:30:16,105 --> 00:30:17,825 was also sick and diagnosed too. 528 00:30:18,205 --> 00:30:21,665 We described to them that this was an expected finding on the 10-14 529 00:30:21,685 --> 00:30:24,655 day range later, and patient was discharged to him with a close 530 00:30:24,705 --> 00:30:25,775 follow up and ended up doing well. 531 00:30:25,825 --> 00:30:28,515 He had a follow up echocardiogram at 6 weeks of age, which showed 532 00:30:28,515 --> 00:30:31,535 complete resolution of coronary artery dilation, which was great. 533 00:30:31,535 --> 00:30:32,059 So this was a good thing. 534 00:30:32,110 --> 00:30:33,310 Good success story. 535 00:30:33,990 --> 00:30:34,290 Dr. 536 00:30:34,290 --> 00:30:37,330 Kumar, do you have any closing comments on KD or the 537 00:30:37,330 --> 00:30:37,740 Madan Kumar: case? 538 00:30:37,810 --> 00:30:38,470 I do. 539 00:30:38,490 --> 00:30:41,690 And this is a really good take home, I think, for our trainees who are 540 00:30:41,690 --> 00:30:45,460 listening to this, which is our tendencies as people, and especially 541 00:30:45,460 --> 00:30:49,050 as we're learning medicine, and we're learning about so many disease processes 542 00:30:49,050 --> 00:30:52,380 all at once, is to try to try to close the loop on them as quickly as we can. 543 00:30:52,560 --> 00:30:55,600 The easiest thing to do and the most effective thing to do is 544 00:30:55,610 --> 00:30:59,840 say, well, this isn't X because of Y, and then be able to move on. 545 00:30:59,860 --> 00:31:01,780 And there are diseases where you can do that. 546 00:31:01,810 --> 00:31:03,840 And unfortunately, Kawasaki's is not one of them. 547 00:31:04,130 --> 00:31:06,540 You hit the nail on the head here, Jack, when you talk about these 548 00:31:06,550 --> 00:31:08,540 concomitant viral positivities, right? 549 00:31:08,540 --> 00:31:11,800 It would be really nice if we could use those as a reason to say you 550 00:31:11,800 --> 00:31:13,280 don't have Kawasaki's disease. 551 00:31:13,850 --> 00:31:19,780 But we know kids who are in the right time and place are likely to 552 00:31:19,780 --> 00:31:21,560 have multiple viral positivities. 553 00:31:21,850 --> 00:31:25,700 So since the causative trigger for this is viral, if you are Rhino Entero 554 00:31:25,700 --> 00:31:29,900 positive or some other viral positive, it may actually allude to the fact that 555 00:31:29,900 --> 00:31:32,910 you are more likely to have Kawasaki's disease because you're in daycare 556 00:31:32,910 --> 00:31:36,830 settings or around other children or other social risk factors that make you 557 00:31:36,840 --> 00:31:40,580 more likely to have these repeat viral positivities as this case highlights. 558 00:31:41,165 --> 00:31:44,745 The other piece is that the clinical phenotype can be very varied as well. 559 00:31:45,065 --> 00:31:48,865 We have Kawasaki's disease that can be fairly mild, although those kids still 560 00:31:48,865 --> 00:31:51,115 tend to be fairly miserable and unhappy. 561 00:31:51,455 --> 00:31:55,055 But we also have Kawasaki's disease that presents with shock, that presents 562 00:31:55,055 --> 00:31:58,535 with macrophage activation syndrome, that presents quite fulminantly in 563 00:31:58,535 --> 00:32:02,875 children that end up in the ICU on pressers, and the root etiology is still 564 00:32:02,875 --> 00:32:06,555 Kawasaki, or what we sometimes sort of colloquially call "Kawa-shock-i". 565 00:32:06,915 --> 00:32:09,665 So it's nice to try to close the loop. 566 00:32:09,675 --> 00:32:12,565 But this is one of those diagnoses that you shouldn't do that and shouldn't 567 00:32:12,565 --> 00:32:16,035 anchor and should still keep an open mind on, particularly since the outcome 568 00:32:16,035 --> 00:32:19,855 differences with treatment can be so substantial and preventing children 569 00:32:19,855 --> 00:32:24,275 from having long term coronary artery aneurysms is so very meaningful. 570 00:32:24,785 --> 00:32:25,995 So thank you for this case. 571 00:32:26,205 --> 00:32:26,555 Sara Dong: Yeah. 572 00:32:26,595 --> 00:32:27,785 Thank you guys both so much. 573 00:32:27,785 --> 00:32:31,865 I, and we'll of course put some resources about some of these recent papers that you 574 00:32:31,865 --> 00:32:38,825 guys are talking about as far as trying to understand the causes of Kawasaki, and 575 00:32:38,975 --> 00:32:43,045 I also want to add, I'm very glad that you covered a lot of the specifics, which 576 00:32:43,045 --> 00:32:48,255 are, of course, board review, typical questions, but also highlighted the 577 00:32:48,255 --> 00:32:53,925 nuance and the thing that stands out to me the most from seeing these patients in 578 00:32:53,945 --> 00:32:58,105 residency and beyond was that irritability that isn't really captured in that. 579 00:32:58,105 --> 00:33:01,985 But I remember, you know, talking through these cases with my clinical team and 580 00:33:01,985 --> 00:33:04,855 the attendings and learning a ton. 581 00:33:05,035 --> 00:33:05,905 Madan Kumar: Couldn't agree more. 582 00:33:05,905 --> 00:33:09,305 I don't think there's such thing as a happy Kawasaki's disease patient. 583 00:33:09,305 --> 00:33:13,215 I think the irritability is sort of a independent clinical risk 584 00:33:13,215 --> 00:33:15,195 profile that that must be present. 585 00:33:15,205 --> 00:33:15,525 Sara Dong: Yeah. 586 00:33:18,025 --> 00:33:21,225 I have these like very clear pictures of patients that I saw. 587 00:33:21,785 --> 00:33:26,775 Everyone would love it you If we had a perfect test or checkboxes, and this 588 00:33:26,775 --> 00:33:28,755 just isn't one of those illnesses. 589 00:33:29,395 --> 00:33:30,865 Jack, thanks for walking me through the case. 590 00:33:30,895 --> 00:33:35,095 I realize we have to come back to your riddle to close us out. 591 00:33:35,245 --> 00:33:36,135 Jack Flores: Oh, yeah. 592 00:33:36,745 --> 00:33:38,805 I'll give you probably one of more lyrical ones. 593 00:33:38,955 --> 00:33:39,875 All of them rhyme. 594 00:33:39,875 --> 00:33:42,095 That's like the only rule I have of them. 595 00:33:42,515 --> 00:33:42,995 But you're here. 596 00:33:42,995 --> 00:33:43,745 I got one pulled up. 597 00:33:44,265 --> 00:33:49,105 I can be a tree, a bridge, a lily pond, a battle, or a shelf. 598 00:33:49,105 --> 00:33:53,595 I can be pieces of fruit, a chair, a woman, or even God themselves. 599 00:33:54,395 --> 00:33:57,535 These are just a few of the things that often make me sublime. 600 00:33:57,595 --> 00:34:01,585 I'm simply a snapshot of someone's emotions and perceptions of 601 00:34:01,585 --> 00:34:02,885 their world at that time. 602 00:34:03,075 --> 00:34:06,185 Most of the time I'm free, but occasionally I can 603 00:34:06,185 --> 00:34:07,635 be a pretty price to pay. 604 00:34:07,645 --> 00:34:12,065 You can find me almost anywhere from Dublin to New York or Paris to Mumbai. 605 00:34:12,925 --> 00:34:16,265 Sara Dong: Thank you to Jack and Madan for joining Febrile today. 606 00:34:16,465 --> 00:34:20,115 As always, don't forget to check out the website, febrilepodcast. 607 00:34:20,145 --> 00:34:23,695 com, where you can find the Consult Notes, which are written complements of 608 00:34:23,695 --> 00:34:28,715 the show with links to references, and in today's case, the answer to the riddle 609 00:34:28,725 --> 00:34:32,345 from Jack, our library of ID infographics, and a link to our merch store. 610 00:34:32,575 --> 00:34:36,425 Febrile is produced with support from the Infectious Diseases Society of America. 611 00:34:36,635 --> 00:34:39,275 Audio editing and mixing is provided by Bentley Brown. 612 00:34:39,485 --> 00:34:42,515 Please reach out if you have any suggestions for future shows or want 613 00:34:42,515 --> 00:34:43,825 to be more involved with Febrile. 614 00:34:44,195 --> 00:34:46,535 Thanks for listening, stay safe, and I'll see you next time.