Drs. Jack Flores and Madan Kumar chat about the nuances of Kawasaki disease (and provide a mystery riddle!! solution in the Consult Notes!)

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Febrile is produced with support from the Infectious Diseases Society of America (IDSA)

Hi, everyone.

Welcome to Febrile, a cultured podcast about all things infectious disease.

We use consult questions to dive into ID clinical reasoning, diagnostics,

and antimicrobial management.

I'm Sara Dong, your host and a MedPeds ID doc.

We are joined by a team from the University of Chicago today.

I'll first introduce our co host, Dr.

John Flores, but he goes by Jack.

Thank you for having me, Sara.

Jack is a third year MedPeds ID fellow at University of Chicago, who's

passionate about all things ID, but sees himself as an academic MedPeds ID provider

focusing on adolescent, young adult, and maternal fetal infections, along with

HIV syndemic care and travel medicine.

Joining him is Dr.

Madan Kumar.

Hey, Sara.

How are you?

Madan is a Pediatric Infectious Disease Specialist and Assistant Professor

in Pediatrics at the University of Chicago's Comer Children's Hospital.

His various scholarly focuses are with immunocompromised hosts, the intersection

of ID and immune dysregulation, and the study of the microbiome.

Very excited to have you guys here today.

As everyone's favorite culture podcast, we do ask our guests to share a little piece

of culture that brings you happiness.

Jack, maybe I'll start with you.

Sure.

So, most of my time when I'm not in the hospital or clinic

is spent with my two young kids.

I have a four year old and a two year old, and they take up a lot of time and a lot

of energy in the best way possible, but when I'm not obsessing over University

of Notre Dame sports, which is my alma mater, I have to, you know, I have to say

right off the bat that I went to Notre Dame, of course, like any Notre Dame grad.

Most people don't realize this, but I actually like to make

riddles, like homemade riddles.

Did you bring one to share with everyone?

I can if you want.

My mom actually worked at the Art Institute of Chicago for many

decades, and she tried her best to instill art into her children.

My sister thrived, my brother not at all.

So I have no talents and terrible dexterity, so I tried like

painting and didn't do well.

I tried poetry and I don't think I did well, but I kind of ventured

into the riddle world and I tested those out with like various friends

and family and they enjoyed it.

I mean, I could do a riddle now or at the end of the podcast,

if you want, it's up to you.

Oh, okay.

We'll make people wait till the end.

Sounds good.

Yeah.

What about you Madan?

I don't make riddles, but I have a side hobby where I really

am a very, very amateur woodworker.

I don't have children, but we are expecting our first in April, so I've

been able to flex that a little bit as we've started to make some furniture

and basic wooden toys for our upcoming son, so that's been fun for me.

Very nice.

Well, I am going to hand it over to Jack to tell us about the case.

All right.

So, we are paged late in the afternoon from the emergency room in the pediatric

hospital, our children's hospital, about a concern for a fever without a source.

Upon calling back the resident in the ER, They state that the patient

is a previously healthy two year old male who's had a fever for six days.

On day two of fever, he presented to his primary care pediatrician and

was prescribed a five day course of cefdinir for presumed left sided otitis

media in the setting of a reported amoxicillin allergy with a rash.

Despite the antibiotics, he continued to have fevers, so mom brought him to the ER.

The resident asks our thoroughts on the matter if any

additional workup we would like.

Dr.

Kumar, I'd like to give you some more objective data in a bit, but before that,

can you kind of describe your thought process when you receive a call like this

about your differential diagnosis of a patient with prolonged fever and what sort

of workup you may consider performing?

You know, anytime I get a call about a protracted fever,

immediately, I get a huge grain slash boulder of salt on my shoulder

where I'm really trying to parse what I'm getting for validity, right?

Because protracted fever can include things from the spectrum of intermittent

fever that was gone for two days and then it's back now, or it can truly be

high grade fevers every day, or it may just be a very short amount of time that

people personally feel, feels protracted.

There's really a lot to parse through in terms of the calendar and timeline

of fevers when you get a call like this to make sure that you're on the same

page as the person who's consulting you and that you understand exactly

what kind of category this falls in.

In this sort of story, this isn't the protracted fever without a source

where most of our counseling comes from saying, you know, it's okay and

as long as they're well, that we can do some rudimentary workup, but not

get too far down the rabbit hole.

In this case, it sounds like they did have a focus, and that focus might

have been an acute otitis media.

That's another one where diagnostics from a primary team can sometimes be

challenging, and a lot of interrater reliability isn't quite there.

So if I have this story, I start to think, well, maybe they were on the wrong track,

and that may not have been the focus since it didn't respond to antibiotic

therapy with the caveat that they did use suboptimal antibiotic therapy, right?

Cefdinir and pneumococcal coverage is always a concern.

And so those are my sort of initial thoughts.

Really, what we're looking for is coming up soon, Jack, which is a

little more objective data so we can start anchoring in on exactly

where the source of this might be.

Thank you so much for that.

I'll give you some more information that the resident was able to give us over the

phone and then elicit from the family.

The resident mentions that four days into the fever, the patient did note

a new red rash presented on the dorsal and palmar surfaces of the hand and

the plantar surfaces of the feet.

They also felt that the patient's eyes were maybe bloodshot and

maybe had some new oral findings or ulcers that were slightly painful.

Additionally, he had decreased intake of both liquid and solids

with reduced urine output.

And he did have some loose stools that began when he started the

cefdinir, and they've persisted while he's been on the cefdinir.

At this point, we do go down to the ER to see the family and the patient and we get

a little bit more deep into the history.

He lives at home with his parents and three school age siblings.

He does not attend daycare and the parents don't report any sick contacts.

His vaccinations are up to date and he's had no previous

issues reported by the PCP.

He had a normal birth history, full term, no NICU stay, no oxygen, no

phototherapy for hyperbilirubinemia.

Additionally, the family reports there's been no recent travel.

They live in a nice, clean, reported suburban home just

outside of the city of Chicago.

They do have a dog at home, and there's no family history of immune

deficiency or recurrent infections.

So, how does this information affect your differential, and what now additional

diagnostic workup would you like the patient to receive at this point?

If a fellow was reporting this to me, they might have the tendency

to call this social history quite boring.

Because from our standpoint, there isn't a lot to inform any esoteric or

more interesting infectious diseases diagnosis, but we have some nice

information on symptomology that we can now sort of anchor into here a little bit.

So whenever I hear rash and then eyes with some conjunctival changes, we've

got potential mucous membrane changes when I hear about these new oral ulcers,

you have to sort of wonder whether this is something non infectious, right?

Whether that's something more like a Stevens Johnson syndrome, a TEN, even

serum sickness with oral ulcers obviously being a little bit odd there, but those

are the kind of things that come up to my head, but we have to start by ruling

out more common infectious pieces.

You can always go with the old standby.

You can say it's likely viral, which will always get you points in the ID world.

And in this case, it might be true.

We have adenovirus and other adenovirus families that can

present very much like this.

It's very reasonable to test them.

And in this story where they do have some persistence of symptoms and, you

know, they're obviously in a healthcare setting or a more acute healthcare

setting, it makes sense to send it, in my opinion, a respiratory viral

panel, a respiratory pathogen panel, whatever your institution provides.

On that same note, as maybe some folks have been hinted to by the title of

this podcast, I'm going to guess there is the concern that this is Kawasaki's

disease based on the rash, some changes to the conjunctivae, and then of course

these mucous membrane changes as well.

So that has to be a part of your differential and workup.

This is the child that's going to get their screening labs.

This is the child that's going to get a blood culture to ensure there's

nothing we're missing there, probably respiratory viral testing and a

formal infectious disease consult.

Yeah, sounds great.

You know, despite the incidence or maybe slightly lower incidence of KD

or Kawasaki disease, I'll probably just refer it to KD as here on out.

The ER loves to bring that up in the initial differential, almost

at the top every time they call the kid who's had five days of fever,

regardless of other symptoms.

So we were worried about a variety of viral infections.

Many you already mentioned, you know, adenoviruses, enterovirus

family, Epstein Barr virus, or other mononucleosis type illnesses.

Perhaps a toxin producing bacterial infections such as Staphylococcus

aureus or Streptococcus pyogenes, and perhaps also a drug related

incident due to the cefdinir.

However, also in the differential diagnosis was KD or incomplete

Kawasaki disease, formerly called atypical Kawasaki disease.

And once again, I want to dive a little bit into KD before

we get back to our case.

Kawasaki disease is a vasculitis of the medium sized arteries.

The etiology is unknown, but there are some fascinating science that's kind

of been coming out, and I'll let Madan describe that in a bit that may suggest

the true or an evolving true origin of it.

Epidemiologic and clinical features suggest an infectious origin,

and, or perhaps an environmental cause or trigger in genetically

susceptible individuals or perhaps within family lines or environments.

The peak age of occurrence in the United States is 6 to 24 months.

50 percent of patients are younger than 2, and 80 percent are younger than

5 years old, so this is definitely a disease of the younger child for the

most part, but there are cases that can be older than 8 years old, and very

rarely they've occurred even in adults.

There is a described definition of KD.

It's the fever of five days at least in addition to the presence of at least four

of the following five clinical criteria.

And this is kind of where the subjectivity of the clinical exam does come in to play.

So you can have bilateral injection of the bulbar conjunctivate with

limbic sparing and without exudate.

I feel like that was something I got pimped on a lot as a

resident, the limbic sparing part.

Erythematous mouth and pharynx, strawberry tongue, and or red

cracked lips, that's the second one.

Third is a polymorphous, generalized, erythematous rash, often with accentuation

in the groin, which can be morbilliform, maculopapular, scarlatiniform,

or erythema-multiforme like.

The fourth is changes in the peripheral extremities consisting of erythema

of the hands and soles and firm, sometimes painful, indurations of the

hands and feet, often with periungual desquamation, usually beginning

10 to 14 days after fever onset.

So this can be a little bit more delayed and kind of a more transitionary finding.

And then the fifth one is acute non suppurative, usually unilateral, anterior

cervical lymphadenopathy with at least one node greater than or equal to 1.

5 centimeters in diameter.

So that's the traditional KD, but I want to move on to incomplete or atypical KD.

So this is our children with greater than or equal to five days of fever.

And then you might have two or three of the clinical criteria, which I think

is what we often find more often, or, you can have infants with a fever for

greater than, uh, are equal to seven days without explanation, which I'll have Dr.

Kumar describe in a bit.

And now you want to get some basic labs, so you want to get a CRP and ESR.

I'm going to describe kind of what the AAP Redbook uses for their numbers and

their types of CRP and ESR, but if you have a CRP less than 3 mg/dL and an ESR

less than 40 mm per hour, they recommend serial, clinical, and laboratory re

evaluation if the fever persists, or you can consider an echocardiogram if

peeling develops, interestingly enough.

This can be done in the inpatient or outpatient setting, but I feel

like more often than not we do admit the kids overnight for observation.

If the CRP is greater than 3 mg/dL, or the ESR is greater than or equal

to 40 mm per hour, then you need three or more of laboratory findings.

So, one is anemia for age.

Two is platelet count greater than or equal to 450, 000

after the seventh day of fever.

The third is albumin less than or equal to 3 g/dL.

If you have an elevated ALT level, if your white count is, white blood

cell count is greater than or equal to 15, 000 per millimeter cubed, and

then if your urine white blood cell count is greater than or equal to 10

white blood cells per high power field.

Or, if you simply have a positive echocardiogram for

coronary artery dilation.

At that point, then you move on to treatment.

So I just want to go back to our case really quick.

So the patient did end up getting an IV fluid bolus as he appeared dehydrated.

A rapid group A streptococcal throat swab was performed in return negative.

On our physical exam, the ID consultant physical exam, he was ill appearing, he

was fussy and notable for sunken features.

He did have the erythematous hands and feet, non purulent conjunctival injection.

The oropharynx was erythematous and swollen with bloody and cracked

lips and with areas of bleeding around the right posterior pharynx.

He was also noted to have small, shoddy cervical lymphadenopathy

and was tachycardic.

Interestingly enough though, there was no rash in the patients outside of

the hands and feet, so no trunk, body, arms, or legs, just the hands and feet.

We did get some blood tests, included an elevated white blood cell count of 18,

100, which is greater than the 15, 000 cutoff, with a neutrophilic predominance.

He had an elevated platelet count of 550, 000.

He did have a normal hemoglobin for his age.

He had an elevated ESR to 112 millimeters per hour and a very

high CRP of 77 milligrams per deciliter, well above the 3.

0 cutoff.

The patient's alkaline transferase, or ALT, was elevated to 263.

And his remaining comprehensive metabolic panel was within normal limits.

He also had a urinalysis performed which noted significant pyuria

for 26 to 100 cells per high power field, and negative for nitrites

or bacteria, and urine and blood cultures did remain no growth to date.

He did have a respiratory pathogen panel on nasal PCR swab, which was negative,

and chest X ray was unremarkable.

At this point, we did feel that he met three of the five compatible criteria,

including the erythematous oropharynx features, non purulent conjunctivitis and

changes in the peripheral extremities.

He also had thrombocytosis, a low albumin, elevated ALT, the

leukocytosis, and the pyuria, along with inflammatory markers, to meet a

clinical diagnosis of incomplete KD.

Transthoracic echocardiogram was performed, which did show

elevated Z scores of plus 2.

4 and plus 2.

1, respectively, and dilation of the left anterior descending and left

medial coronary arteries, consistent with a diagnosis of Kawasaki disease.

So, Dr.

Kumar, can you give us thoughts on the clinical findings on the case, and

I would also love if you wanted any more additional thoughts just on the

diagnostic algorithms I described earlier.

Yeah, happy to.

Thanks, Jack.

So, as far as the clinical findings go, one of the challenges of Kawasaki's

disease is that to date, we don't have an objective test where we can send

and confirm the diagnosis if we suspect it, and we're relying on these clinical

and associated laboratory parameters.

So when we do that, sometimes trainees get caught in a memorization

pattern and it makes it difficult to understand the mechanism of the

disease, which really should be at the forefront in evaluating this disease.

So if you go back to the basics and just remember that this is a

medium to small vessel vasculitis, it's much better and easier to

remember where that might manifest.

You might see redness in the eyes, but of course you shouldn't see purulence,

not because you have to memorize it, but because this isn't a primary bacterial

or virological purulent mechanism, it is a blood vessel inflammation.

Similarly, with the rash, you can know that you're going to see a

rash, and you can also know that if it is a vasculitis, that rash can be

polymorphous, morbilliform, a lot of ways to say anything, any sort of red

rash can fit with the parameters of KD.

The lymphadenopathy, it used to be a preeminent piece of the disease.

We usually see it unilaterally again, of course, because it's not the same typical

infectious lymphadenopathy process.

And then the mucous membrane changes are other areas where

hyperemia can be eminently visible.

So those things can kind of help you just categorize why you're

seeing what you're seeing and make it a little bit easier to remember.

The piece that's tough, and if we put, uh, caveats about where we're

stepping away from the guideline verbally, this would be it.

The piece that's tough is recognizing that not all of

these parameters are made equal.

If we're trying to diagnose someone with incomplete Kawasaki's disease, you're

functionally trying to differentiate them from viral NOS, because you haven't

established another clear diagnosis.

If you have, it's easier to step away from Kawasaki's disease.

In a viral NOS, you're going to have a lot of overlapping lab parameters and

clinical parameters, but there's some that kind of should jump out at you as

being a typical for a viral process.

So, for me, some of the things that help clinch the diagnosis, if we're

sort of on the fence, are things like the sterile pyuria, right?

We don't really see sterile pyuria as part of your typical adenovirus

upper respiratory infection.

Something that's very hepatotropic, where we have elevated ALT, and then it's

not necessarily part of the parameters, but it's something I always look for.

Elevated GGT as well can also be indicative of something more in the

KD pathway, or KD that's more likely to be resistant to initial therapy.

There's some data to suggest that those things are genetically linked.

When you're dealing with Kawasaki's disease, you kind of have to make an

internal judgment whether you're going to follow the criteria to the staunchest,

most strict possible interpretation, or whether there may be children who look

pathophysiologically like Kawasaki's disease, look miserable like most of

these kids do, and warrant treatment based on meeting the incomplete criteria and

fitting the mechanisms that you suspect.

In this case, it's a little bit easier to make the decision to treat.

You've talked about the initial echocardiogram having elevated

coronary artery scores.

Oftentimes, variable cutoffs are used for the z score, and for trainees who are

unfamiliar, the z score is essentially a measure of standard deviation.

You're looking at the internal diameter of the artery itself and

seeing how many standard deviations above the mean you are, respective to

your body size or body surface area.

And if you're more than 2, that's meaningful.

If you're more than 2.5, that's often used as even more meaningful of a cutoff point.

This person was on the border for 2.

4.

So besides making the diagnosis a little easier, it actually puts them into

potentially a higher risk stratification.

We can get into a little more when we talk about therapy, but in the

initial diagnosis, risk stratification is important as well because it can

inform your therapeutic decisions.

Unfortunately, because of just the way that the data is stratified and where

this tends to be more prevalent, there's very clearly a underlying risk factor in

the Asian population, which makes them more likely to get Kawasaki's disease.

When that happens, most of our data from Kawasaki's disease risk stratification

comes from Asian countries, and it's unclear if our children in America

follow the same risk profile or pattern, but in generality, infants

less than six months and those with initial echocardiogram changes tend to

be higher risk and require high risk stratification and high risk therapy.

That was amazing.

Thank you so much, Madan for that.

Before I move on to additional clinical features and treatment and

prognosis, do you kind of want to, uh, tell me about like some of the

evolving science of what they think might be causing Kawasaki disease.

I know things are kind of changing almost on an annual basis, but I'd love

to hear what your thoughts are on that.

One of the interesting things about the peak pandemic era

is that we had a lot of COVID cases, of course, but we had a very, very

significant paucity of other viral infections for a small window there,

or for a pretty long window actually.

During that time, it was kind of neat because we got to see a lot

of these diagnoses where we didn't quite know if they had a viral

etiology or not and get really good epidemiologic data on their incidence.

Theoretically, if Kawasaki's disease was purely genetic and had no infectious

trigger, the rates would be entirely consistent throughout the pandemic.

And then, of course, the converse is true.

And that's what we found is that when our general viral rates plummeted,

when people were masking, when people were staying at home, similarly, our

rates of Kawasaki's disease plummeted.

So epidemiologically, that presents a really compelling amount of data that

even though there's clearly a genetic component to both risk for onset

of disease and severity of disease.

There is also an infectious trigger that we haven't identified.

It sort of sets the chain off, which makes a lot of sense, in the pathophys

of other similar disease processes.

The other big pieces, um, you know, of course, at this last national

ID conference, we were presented data on partial sequencing of

the causative virus as well.

And that was very compelling.

And it does look like within the next 5 years, we'll be able to have

a little more substantive sequencing data of the causative virus.

So at this point, personally, I think we've sort of clenched it, that this is

a two fold process with a viral trigger and a secondary genetic predisposition.

Yeah, I just feel like, you know, with KD, we think we know everything

in medicine, but then you have something like KD come along and you're like,

wow, there's still a lot of, you know, discovery to be happened in medicine,

which makes things fun and exciting.

I'll give a little more clinical features, then I'm gonna talk about treatment,

and then I'll come back to you, Madan, if you have any additional thoughts.

Clinicians should consider KD in their differential diagnosis

before the fifth day of course, if several of the features are present

without an alternative explanation.

One of the issues that you've mentioned is that different things can have different

temporalities, so certain things may present earlier in the course and some

may present later in the course, and it's absolutely possible to have a concurrent

viral upper respiratory infection in a patient with KD, particularly

if it's during certain epidemiologic months of the year, like in the winter.

The average duration of fever for untreated KD is 10 days.

However, fever can last two weeks or longer.

After the fever resolves though, patient can remain anorexic and irritable with

decreased energy for two weeks, and I feel like that's something we've encountered

oftentimes in the outpatient setting after we see them in the hospital.

The parents are really concerned because they're still not eating, they're

still very tired, but it's something we kind of have to describe to them.

It's, it's a natural phenomenon.

Also during this kind of recovery phase, the brawny desquamation of the

fingers, toes, hands, and feet may occur.

Transverse lines across the nails or Beau's lines sometimes are

noted to occur even months later.

The most serious complication, of course, is the coronary artery abnormalities.

It occurs in about 20-25 percent of untreated children.

Certain increased risk factors for coronary artery abnormalities,

there appears to be a biologic sex predisposition for males over females,

if you're less than 12 months of age or greater than 8 years, so

the very young or the very old.

If your fever does last more than 10 days, if your white count is greater

than 15, 000 with a high neutrophil predominance, If you're anemic, if

you have a low albumin, if you have a low sodium, interestingly enough,

and if you have high platelet count.

And then, additionally, if your fever persists greater than 36 hours, despite

proper therapy, that also increases risk for coronary artery abnormalities.

Aneurysms of the coronary arteries usually occur between 1 and 4

weeks after the onset of disease.

Onset later than six weeks is extremely uncommon.

If the coronary artery aneurysm or ectasia is evident, as you mentioned

before, a Z score greater than two, but really above two and a half, in

any patient evaluated for fever, a presumptive diagnosis should be made.

A normal early echocardiogram study is typical and does not exclude

the diagnosis, but it might be useful in patients with suspected

incomplete KD, perhaps that's the patient where you'd want to repeat

the echo within 24 to 48 hours.

There was one study that showed that 80 percent of patients with KD who ultimately

developed coronary artery disease had abnormalities in echocardiograms obtained

during the first 10 days of illness.

So, that is still a possibility before the 10 days.

Other exam findings, in many patients you might find urethritis, so pain with

urination along with the sterile pyuria, a mild anterior uveitis, less likely

you might have elevated serum, you know, transferase concentrations, arthralgias,

or arthritis, perhaps CSF pleocytosis, and then even more rare would be hydrops of

the gallbladder, a pericardial effusion, myocarditis, cranial nerve palsies.

These are all kind of much less common things.

The current case fatality rate, fortunately, in the United States

and Japan, where most of the studies are performed, is less than 0.

2 percent at this time.

Primary cause of death is myocardial infarction resulting from coronary

artery occlusion, attributable to thrombosis or progressive stenosis.

The relative risk of mortality is highest within six weeks of of onset of acute

symptoms, but that can occur many months to even years after the acute episode.

The prevalence of higher abnormalities is when you delay treatment beyond

10 days of illness, so that's kind of where we have our 10 day cutoff.

The first line treatment is IVIG, 2 grams per kilogram,

administered over 10 to 12 hours.

It's important, particularly depending on the unit in the hospital, that they

understand this prolonged infusion rate.

A secondary cornerstone is aspirin.

There's the high dose aspirin, 80-100 mg per kg, or the middle to lower dose, 30-50

mg per kg per day, in 4 divided doses.

In severe cases, you can consider steroids.

If you have recurrence of fever after 36 hours of that first

dose of IVIG, we recommend infliximab as one additional dose.

So actually, Dr.

Kumar, can you chat about the two different doses of aspirin I described,

and actually why infliximab is used instead of a second dose of IVIG.

KD treatment pathways have evolved and continue to evolve

just like restratification has evolved and continued to evolve.

In the early years of KD, steroids were obviously a hallmark of therapy and

then found to either be ineffective or potentially even harmful and now

they're reserved for use in conjunction with IVIG where they are meaningfully

helpful in our high risk patients.

The aspirin piece has also been an area where we've traditionally had a

paucity of data, and now, now finding more and more data to suggest that lower

doses of aspirin do not have a higher risk of a lot of those complications,

those coronary artery complications, that we were traditionally worried

about when you have thrombocytosis and a artery abnormality or a aneurysm.

So from that high dose of aspirin, a lot of institutions now feel safe

and comfortable switching to medium dose aspirin, and there's actually

been even a push to reduce it even further and to start with the low

dose aspirin and continue there.

Although again, that hasn't made it into the general guidance yet.

I suspect that that will be where we end up.

As far as the infliximab, that's been an interesting piece.

So traditionally, if you refractory to a single dose of IVIG, we'd

often give a 2nd dose of IVIG.

And to be fair, many institutions still do that.

There was a multi center study that we were a part of that evaluated

the respective risks for secondary coronary artery abnormalities, along

with adverse events with each approach, and we found that there was a general

overlap in terms of outcomes, and there was no stratification for outcomes

with use of infliximab, but we had a much better safety profile compared to

second dose of IVIG, particularly with things like autoimmune hemolytic anemia,

which we had a far higher incidence of with our second dose of IVIG.

So we've made the choice to switch over to infliximab for our refractory patients.

Mysterious disease and once again, you know, therapies can differ

depending on where you are in the world.

Just a few more brief points about follow up.

So echocardiogram should be performed at the time of suspected diagnosis,

oftentimes at our institution, we repeat it at two weeks, then six to

eight weeks after diagnosis with normal coronary arteries on initial evaluation.

If they do have abnormal coronary arteries, though, we oftentimes defer to

our neighborhood friendly cardiologists, and they oftentimes will help monitor

their patients for that and closely see them in the outpatient setting.

If you develop a giant coronary artery aneurysm or very large one with a luminal

diameter of greater than or equal to eight millimeters, or perhaps larger in

our infants with a z score of greater than or equal to 10, that usually

requires the addition of anticoagulant therapy such as warfarin or low molecular

weight heparin to prevent thrombosis.

Another interesting tidbit that I think is fair game for the ID board exam

and it might have even been a practice question for my Pediatric board exam

is the measles, mumps, rubella, and varicella containing vaccines should be

deferred until 11 months after receipt of IVIG for treatment of KD because of the

possible interference of the development of an adequate immune response.

Just to wrap up our case, the patient received a single dose of

IVIG, 2 grams per kg, administered over 10 to 12 hours, in addition

to initiating medium dose aspirin.

The patient was noted to defervesce within 36 hours and did not

require an additional dose of IVIG or infliximab, which is great.

He did go home, but interestingly enough, he returned to the hospital

10 days later with low grade fever and upper respiratory infection symptoms,

just a runny nose and a sore throat.

He did notice a desquamation of the hands and feet, so the ER

asked us if this is actually the return of the Kawasaki disease.

He was diagnosed with rhinovirus on nasal PCR swab, and his sibling

was also sick and diagnosed too.

We described to them that this was an expected finding on the 10-14

day range later, and patient was discharged to him with a close

follow up and ended up doing well.

He had a follow up echocardiogram at 6 weeks of age, which showed

complete resolution of coronary artery dilation, which was great.

So this was a good thing.

Good success story.

Dr.

Kumar, do you have any closing comments on KD or the

case?

I do.

And this is a really good take home, I think, for our trainees who are

listening to this, which is our tendencies as people, and especially

as we're learning medicine, and we're learning about so many disease processes

all at once, is to try to try to close the loop on them as quickly as we can.

The easiest thing to do and the most effective thing to do is

say, well, this isn't X because of Y, and then be able to move on.

And there are diseases where you can do that.

And unfortunately, Kawasaki's is not one of them.

You hit the nail on the head here, Jack, when you talk about these

concomitant viral positivities, right?

It would be really nice if we could use those as a reason to say you

don't have Kawasaki's disease.

But we know kids who are in the right time and place are likely to

have multiple viral positivities.

So since the causative trigger for this is viral, if you are Rhino Entero

positive or some other viral positive, it may actually allude to the fact that

you are more likely to have Kawasaki's disease because you're in daycare

settings or around other children or other social risk factors that make you

more likely to have these repeat viral positivities as this case highlights.

The other piece is that the clinical phenotype can be very varied as well.

We have Kawasaki's disease that can be fairly mild, although those kids still

tend to be fairly miserable and unhappy.

But we also have Kawasaki's disease that presents with shock, that presents

with macrophage activation syndrome, that presents quite fulminantly in

children that end up in the ICU on pressers, and the root etiology is still

Kawasaki, or what we sometimes sort of colloquially call "Kawa-shock-i".

So it's nice to try to close the loop.

But this is one of those diagnoses that you shouldn't do that and shouldn't

anchor and should still keep an open mind on, particularly since the outcome

differences with treatment can be so substantial and preventing children

from having long term coronary artery aneurysms is so very meaningful.

So thank you for this case.

Yeah.

Thank you guys both so much.

I, and we'll of course put some resources about some of these recent papers that you

guys are talking about as far as trying to understand the causes of Kawasaki, and

I also want to add, I'm very glad that you covered a lot of the specifics, which

are, of course, board review, typical questions, but also highlighted the

nuance and the thing that stands out to me the most from seeing these patients in

residency and beyond was that irritability that isn't really captured in that.

But I remember, you know, talking through these cases with my clinical team and

the attendings and learning a ton.

Couldn't agree more.

I don't think there's such thing as a happy Kawasaki's disease patient.

I think the irritability is sort of a independent clinical risk

profile that that must be present.

Yeah.

I have these like very clear pictures of patients that I saw.

Everyone would love it you If we had a perfect test or checkboxes, and this

just isn't one of those illnesses.

Jack, thanks for walking me through the case.

I realize we have to come back to your riddle to close us out.

Oh, yeah.

I'll give you probably one of more lyrical ones.

All of them rhyme.

That's like the only rule I have of them.

But you're here.

I got one pulled up.

I can be a tree, a bridge, a lily pond, a battle, or a shelf.

I can be pieces of fruit, a chair, a woman, or even God themselves.

These are just a few of the things that often make me sublime.

I'm simply a snapshot of someone's emotions and perceptions of

their world at that time.

Most of the time I'm free, but occasionally I can

be a pretty price to pay.

You can find me almost anywhere from Dublin to New York or Paris to Mumbai.

Thank you to Jack and Madan for joining Febrile today.

As always, don't forget to check out the website, febrilepodcast.

com, where you can find the Consult Notes, which are written complements of

the show with links to references, and in today's case, the answer to the riddle

from Jack, our library of ID infographics, and a link to our merch store.

Febrile is produced with support from the Infectious Diseases Society of America.

Audio editing and mixing is provided by Bentley Brown.

Please reach out if you have any suggestions for future shows or want

to be more involved with Febrile.

Thanks for listening, stay safe, and I'll see you next time.