93: Rash Decisions

Sara Dong: 00:00:03

Hi, everyone.

Sara Dong: 00:00:04

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

Sara Dong: 00:00:09

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

Sara Dong: 00:00:13

and antimicrobial management.

Sara Dong: 00:00:14

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

Sara Dong: 00:00:17

Today, we have a team visiting from the University of Wisconsin, Madison.

Sara Dong: 00:00:22

First, let's meet Dr.

Sara Dong: 00:00:23

Michael Moran.

Sara Dong: 00:00:24

Michael is an adult Infectious Diseases Fellow at the University of Wisconsin.

Michael Moran: 00:00:29

Hi, my name is Michael Moran.

Michael Moran: 00:00:30

I'm excited to be on the podcast.

Sara Dong: 00:00:32

Also joining is Dr.

Sara Dong: 00:00:33

Swapnil Lanjewar.

Sara Dong: 00:00:35

Swapnil is a Clinical Assistant Professor in ID at the University of Wisconsin.

Sara Dong: 00:00:40

He completed his medical schooling in India and pursued his IM residency

Sara Dong: 00:00:44

at the Cleveland Clinic in Ohio.

Sara Dong: 00:00:46

He did his fellowship in ID at the University of Wisconsin Madison.

Swapnil Lanjewar: 00:00:49

Hi, this is Swapnil Lanjewar, and I'm

Swapnil Lanjewar: 00:00:52

super excited to be here.

Swapnil Lanjewar: 00:00:54

Both me and Michael, we are big fans of the Febrile podcast, so we are absolutely

Swapnil Lanjewar: 00:00:59

thrilled to join you here today, Sara.

Sara Dong: 00:01:01

Well, I'm very excited to have you.

Sara Dong: 00:01:03

Of course, before we jump into the case, we always ask one question.

Sara Dong: 00:01:08

We are everyone's favorite cultured podcast, so I'd love to hear about a

Sara Dong: 00:01:12

little piece of culture, something non medical that you've enjoyed recently

Sara Dong: 00:01:17

or like to do in your free time.

Sara Dong: 00:01:20

Michael, what do you got?

Michael Moran: 00:01:21

Yeah, I mean, so in fellowship, I think I've been

Michael Moran: 00:01:23

trying to find a lot of things to like kind of dump my brain.

Michael Moran: 00:01:27

And I was just recently introduced to 90 Day Fiancé, which I had

Michael Moran: 00:01:32

until now never watched before.

Michael Moran: 00:01:34

And it was like this week and it is absolutely wild.

Michael Moran: 00:01:37

And so I've been kind of going down a rabbit hole in that of just that's

Michael Moran: 00:01:42

the opposite of anything medicine.

Michael Moran: 00:01:45

So I understand all the hype now.

Michael Moran: 00:01:47

Yeah.

Sara Dong: 00:01:48

What about you Swapnil?

Swapnil Lanjewar: 00:01:49

One of my biggest hobbies is playing table tennis.

Swapnil Lanjewar: 00:01:53

I grew up in India and I used to train formally in table tennis.

Swapnil Lanjewar: 00:01:57

And I used to play competitively at the state and national level tournaments.

Swapnil Lanjewar: 00:02:01

But these days it's mostly limited to playing with some

Swapnil Lanjewar: 00:02:04

friends over the weekend.

Sara Dong: 00:02:05

Do you get really aggressive?

Sara Dong: 00:02:07

You're very competitive.

Swapnil Lanjewar: 00:02:08

I am actually.

Sara Dong: 00:02:12

Awesome.

Sara Dong: 00:02:12

Well, I will hand it over to Michael.

Sara Dong: 00:02:15

Tell us about the case.

Michael Moran: 00:02:16

So today we are getting a call from the medicine team to get

Michael Moran: 00:02:21

some help looking at a patient for the management of someone they admitted

Michael Moran: 00:02:25

overnight with a fever and a rash, and this occurred this past March.

Michael Moran: 00:02:30

When they called us, they gave us a little story about our patient.

Michael Moran: 00:02:34

She's a 47 year old female, has a past medical history of gout and hypertension,

Michael Moran: 00:02:40

and notably about eight weeks ago, she was seen by rheumatology due to a

Michael Moran: 00:02:44

one year history of polyarthralgia and was diagnosed with seronegative RA.

Michael Moran: 00:02:49

At that appointment, she was started on sulfazalazine and low dose oral prednisone

Michael Moran: 00:02:53

of about five milligrams a day, resulting in significant symptomatic improvement.

Michael Moran: 00:02:58

In regards to her current presentation, the medicine team tells us that

Michael Moran: 00:03:02

about three weeks ago, she started experiencing high grade fevers to 103 to

Michael Moran: 00:03:07

104 degrees Fahrenheit with associated night sweats and some loss of appetite

Michael Moran: 00:03:12

and bilateral upper abdominal pain.

Michael Moran: 00:03:14

About 10 days prior to this presentation, these symptoms were persisting, so she

Michael Moran: 00:03:19

presented to her local ER for evaluation.

Michael Moran: 00:03:23

Her exam at that time, along with routine labs like a CBC and CMP,

Michael Moran: 00:03:27

were within normal limits, although she did have an elevated CRP.

Michael Moran: 00:03:32

They tell us a CT chest abdomen pelvis was performed and was negative, and as

Michael Moran: 00:03:37

this was late winter, early spring, a respiratory pathogen panel multiplex PCR,

Michael Moran: 00:03:42

was done and negative, but with no other explanation, she was discharged home

Michael Moran: 00:03:47

with a tentative diagnosis of a viral syndrome, as she was otherwise well.

Michael Moran: 00:03:52

At home, her fever still continued on a daily basis without improvement,

Michael Moran: 00:03:56

which brings us to our current hospital admission, where she is now

Michael Moran: 00:03:59

presenting with the new development of a rash, which started about

Michael Moran: 00:04:03

three days prior to presentation.

Michael Moran: 00:04:06

The primary team tells us the rash is pink, macular, and

Michael Moran: 00:04:09

patchy, located all over her body.

Michael Moran: 00:04:12

The rash is not itchy and non painful.

Michael Moran: 00:04:15

They tell us there have been no new medications in the last one

Michael Moran: 00:04:17

to two weeks to explain this.

Michael Moran: 00:04:20

The team tells us the patient is currently hemodynamically stable, but

Michael Moran: 00:04:24

has a temp of 102 degrees Fahrenheit.

Michael Moran: 00:04:28

So far, her repeat labs and new CT chest abdomen pelvis are still unremarkable.

Michael Moran: 00:04:34

The team is planning to hold off on any antibiotics because

Michael Moran: 00:04:37

she otherwise looks good.

Swapnil Lanjewar: 00:04:39

All right.

Swapnil Lanjewar: 00:04:39

Thank you so much for the case, Michael.

Swapnil Lanjewar: 00:04:41

So I will summarize what I gathered here.

Swapnil Lanjewar: 00:04:44

So it looks like we have a 47 year old female with past medical history of

Swapnil Lanjewar: 00:04:48

gout and recently diagnosed seronegative rheumatoid arthritis for which she was

Swapnil Lanjewar: 00:04:53

started on treatment about two months ago and she's now presenting due to fever of

Swapnil Lanjewar: 00:04:58

unknown etiology over the last four weeks and a new rash since last three days.

Swapnil Lanjewar: 00:05:03

And this is in the setting of nearly normal labs and imaging about 10 days ago?

Michael Moran: 00:05:07

Exactly.

Michael Moran: 00:05:09

So Swapnil, if you were called about a case like this, how would you approach

Michael Moran: 00:05:12

developing an evaluation and treatment plan for a patient with fever and rash?

Swapnil Lanjewar: 00:05:17

Fever with rash is an important topic and it's quite

Swapnil Lanjewar: 00:05:20

a challenging one, actually, for the infectious disease clinician.

Swapnil Lanjewar: 00:05:24

This is because the list of differentials is quite big.

Swapnil Lanjewar: 00:05:28

So I remember that as a trainee, this topic used to be pretty intimidating

Swapnil Lanjewar: 00:05:32

for me, And even sometimes I struggle with a patient with fever and rash.

Swapnil Lanjewar: 00:05:37

But over the years, I developed a structured and organized approach

Swapnil Lanjewar: 00:05:40

for myself that I can share today.

Swapnil Lanjewar: 00:05:43

And this is my personalized approach.

Swapnil Lanjewar: 00:05:45

If you already have an approach nailed down which works well for you, then I

Swapnil Lanjewar: 00:05:49

think you should keep doing that one.

Swapnil Lanjewar: 00:05:51

For the purposes of this podcast, I will break down my approach in three parts.

Swapnil Lanjewar: 00:05:58

First is what I do before I see the patient, second is what I do while I'm

Swapnil Lanjewar: 00:06:02

seeing a patient, and third is what I do after I'm done seeing the patient.

Swapnil Lanjewar: 00:06:08

Let's come to what I do before I see the patient.

Swapnil Lanjewar: 00:06:11

I try to get a few questions answered absolutely before I hang

Swapnil Lanjewar: 00:06:14

up the phone with the primary team.

Swapnil Lanjewar: 00:06:17

When they're telling me about the case, I try not to interrupt them, and this is

Swapnil Lanjewar: 00:06:21

because I want to make sure that they're not losing their train of thought, and

Swapnil Lanjewar: 00:06:26

they don't forget giving me an important piece of information, and then I pay

Swapnil Lanjewar: 00:06:30

attention to how sick is the patient.

Swapnil Lanjewar: 00:06:33

Like, am I getting a call from the ICU, or is the patient's primary

Swapnil Lanjewar: 00:06:36

care physician calling me about this?

Swapnil Lanjewar: 00:06:39

If the patient is in ICU, super sick, hemodynamically unstable,

Swapnil Lanjewar: 00:06:44

then I want to make sure that I'm not missing a never miss diagnosis.

Swapnil Lanjewar: 00:06:49

For example, you know, is it a surgical disease?

Swapnil Lanjewar: 00:06:51

Is it necrotizing fasciitis?

Swapnil Lanjewar: 00:06:54

Or is this a hemorrhagic rash because of septicemia from either a

Swapnil Lanjewar: 00:06:58

perforated viscus or a really terrible bad piomyositis or a huge abscess

Swapnil Lanjewar: 00:07:03

which requires emergent surgery?

Swapnil Lanjewar: 00:07:06

Or is it related to a toxic shock syndrome from a retained foreign body like a

Swapnil Lanjewar: 00:07:10

tampon or a line or device infection which is causing the septic shock?

Swapnil Lanjewar: 00:07:16

These are some never miss diagnoses and then if the season and location

Swapnil Lanjewar: 00:07:22

are right, I will also think about tick borne infections like Babesia

Swapnil Lanjewar: 00:07:26

and Rocky Mountain Spotted Fever that I want to make sure I'm not missing.

Swapnil Lanjewar: 00:07:29

And if the patient is immune compromised, I absolutely don't want

Swapnil Lanjewar: 00:07:33

to miss any terrible fungal infection.

Swapnil Lanjewar: 00:07:36

So, apart from that, I also want to make sure whether or not I need to put

Swapnil Lanjewar: 00:07:41

this patient into prompt isolation.

Swapnil Lanjewar: 00:07:44

If there's anything like a meningococcal disease or a viral hemorrhagic fever

Swapnil Lanjewar: 00:07:48

like Ebola based on epidemiologic risk factors for the patient, then you

Swapnil Lanjewar: 00:07:53

want to make sure you put the patient in isolation as soon as possible.

Swapnil Lanjewar: 00:07:57

Sometimes, somebody who's really sick with HIV and miliary TB can

Swapnil Lanjewar: 00:08:02

actually have a skin rash too.

Swapnil Lanjewar: 00:08:04

So, these are some considerations regarding whether they

Swapnil Lanjewar: 00:08:08

need prompt isolation.

Swapnil Lanjewar: 00:08:09

And lastly, if this is an exotic disease, you know, like malaria or so, based on

Swapnil Lanjewar: 00:08:14

their epidemiologic risk factors again.

Swapnil Lanjewar: 00:08:18

Technically, the textbook approach is also to think of bioterrorism,

Swapnil Lanjewar: 00:08:21

but I really hope that none of us in real life have to think about that.

Swapnil Lanjewar: 00:08:25

So, these are things I do before I see the patient while I'm still on

Swapnil Lanjewar: 00:08:29

the phone with the primary team.

Swapnil Lanjewar: 00:08:31

If they don't have a never miss diagnosis and you receive such a

Swapnil Lanjewar: 00:08:34

call in middle of night, then it will make me feel comfortable.

Swapnil Lanjewar: 00:08:38

Okay, fine.

Swapnil Lanjewar: 00:08:39

I think I covered everything.

Swapnil Lanjewar: 00:08:40

I can go back to sleep safely.

Swapnil Lanjewar: 00:08:42

Next comes what I do while I'm seeing the patient.

Swapnil Lanjewar: 00:08:46

So obviously this, I'll divide this between two parts,

Swapnil Lanjewar: 00:08:49

history taking and examination.

Swapnil Lanjewar: 00:08:51

History taking is one of the most important skills for any

Swapnil Lanjewar: 00:08:55

infectious disease clinician.

Swapnil Lanjewar: 00:08:58

When you have so many questions that you need to ask to the patient.

Swapnil Lanjewar: 00:09:01

It's very easy to forget some crucial pieces of information,

Swapnil Lanjewar: 00:09:06

so over the years, I've developed a personal template for myself.

Swapnil Lanjewar: 00:09:10

I try to follow this template just so that I don't miss anything

Swapnil Lanjewar: 00:09:14

important to ask the patient.

Swapnil Lanjewar: 00:09:16

After I'm done asking them relevant questions about the

Swapnil Lanjewar: 00:09:19

HPI, I'll ask five main group of questions to elicit differentials.

Swapnil Lanjewar: 00:09:25

First group is occupational history, second group is outdoor exposures,

Swapnil Lanjewar: 00:09:30

then indoor exposures, then regarding something they ingested or injected,

Swapnil Lanjewar: 00:09:36

and the fifth one would be non exposure related differentials.

Swapnil Lanjewar: 00:09:41

Going to occupational exposures, this is important to elicit because if

Swapnil Lanjewar: 00:09:45

they are a butcher, let's say, there have been periodic outbreaks of Staph

Swapnil Lanjewar: 00:09:49

and Strep infection amongst butchers.

Swapnil Lanjewar: 00:09:51

If somebody's a chef who's handling raw meat, then I'll think about Salmonella.

Swapnil Lanjewar: 00:09:56

And if they are routinely tasting raw oysters, then you

Swapnil Lanjewar: 00:10:00

also have to consider Vibrio.

Swapnil Lanjewar: 00:10:02

If they are a taxidermist, I know that there have been some

Swapnil Lanjewar: 00:10:06

outbreaks of Q fever before.

Swapnil Lanjewar: 00:10:08

So if they're a fisherman, I would think about something like Vibrio

Swapnil Lanjewar: 00:10:13

if they are on the coast and are having a lot of exposures there.

Swapnil Lanjewar: 00:10:17

So that's about occupational exposures.

Swapnil Lanjewar: 00:10:20

Coming to outdoor exposures, I tend to categorize them

Swapnil Lanjewar: 00:10:24

in three main subcategories.

Swapnil Lanjewar: 00:10:26

Travel related and then hiking or camping related, or water body related exposures.

Swapnil Lanjewar: 00:10:33

Hiking and camping related outdoor activities.

Swapnil Lanjewar: 00:10:36

You know, what, what were they doing outside?

Swapnil Lanjewar: 00:10:38

Were they doing something that involved turning of soil?

Swapnil Lanjewar: 00:10:42

Were they out exploring caves?

Swapnil Lanjewar: 00:10:44

Were they in contact with wild animals like, you know, flying

Swapnil Lanjewar: 00:10:47

squirrels and snakes and bears?

Swapnil Lanjewar: 00:10:50

Or were they in contact with any farm animals?

Swapnil Lanjewar: 00:10:54

And then, have they been annoyed by some insects or arthropods like

Swapnil Lanjewar: 00:10:58

ticks or lice or mosquitoes or flies?

Swapnil Lanjewar: 00:11:02

Because all of these can contribute to your list of differentials as well.

Swapnil Lanjewar: 00:11:07

Now, with regards to travel related exposures, then I ask

Swapnil Lanjewar: 00:11:11

them where exactly they travel.

Swapnil Lanjewar: 00:11:12

Was it a domestic travel or international travel?

Swapnil Lanjewar: 00:11:16

Of course, we all know domestic travel related exposures differentials you have

Swapnil Lanjewar: 00:11:19

to consider like in the southwest U.

Swapnil Lanjewar: 00:11:21

S.

Swapnil Lanjewar: 00:11:21

you think about Cocci[dioides].

Swapnil Lanjewar: 00:11:23

Here in the Midwest we always think about Histo[plasma] and Blasto[myces].

Swapnil Lanjewar: 00:11:27

In New England you would consider things like Lyme disease

Swapnil Lanjewar: 00:11:30

based on the season as well.

Swapnil Lanjewar: 00:11:32

And then when it comes to international travel, my first

Swapnil Lanjewar: 00:11:36

question is always did you check the CDC website before you traveled?

Swapnil Lanjewar: 00:11:40

Regardless of the answer, I will always pull up my phone and I'll go

Swapnil Lanjewar: 00:11:44

on cdc.gov/travel and and pick their destination of travel and see what

Swapnil Lanjewar: 00:11:50

all exposures that can occur in those particular areas of the world because

Swapnil Lanjewar: 00:11:54

I can never remember, you know, specifics regarding to each country.

Swapnil Lanjewar: 00:11:58

Like for example, if somebody traveled to India, you have to think about

Swapnil Lanjewar: 00:12:01

typhoid, you have to think about malaria, even kala azar or leishmaniasis.

Swapnil Lanjewar: 00:12:07

The list is pretty extensive.

Swapnil Lanjewar: 00:12:09

That's in with regards to travel.

Swapnil Lanjewar: 00:12:11

Next is outdoor exposure is water bodies, right?

Swapnil Lanjewar: 00:12:14

So it could be oceans or You know, ponds, lakes, uh, streams and rivers,

Swapnil Lanjewar: 00:12:20

or it could be flood water as well, and then recreational outdoor water

Swapnil Lanjewar: 00:12:24

body exposures like swimming pools, or even water parks, and have they had any

Swapnil Lanjewar: 00:12:29

injuries in the water, because there will be very specific bacterial and parasitic

Swapnil Lanjewar: 00:12:34

infections that I would be considering with exposure to such water bodies.

Swapnil Lanjewar: 00:12:38

In terms of indoor exposures, I asked them about have they had sick

Swapnil Lanjewar: 00:12:43

contacts, like sick contacts with other adults or children or indoor animals.

Swapnil Lanjewar: 00:12:49

So adults as in you can get of course you know all types of respiratory

Swapnil Lanjewar: 00:12:53

infections and URIs from adults as well.

Swapnil Lanjewar: 00:12:56

STDs would be a big thing from adults like syphilis and then gonococcal infection.

Swapnil Lanjewar: 00:13:02

All of these can cause fever and rash and then risk factors for TB

Swapnil Lanjewar: 00:13:06

as well would be elicited here.

Swapnil Lanjewar: 00:13:09

Then in terms of contact with kids or little humans, you know, they are sources

Swapnil Lanjewar: 00:13:15

of all kinds of viral and bacterial infections like vaccine preventable

Swapnil Lanjewar: 00:13:19

diseases, measles, rubella, or parvovirus B19, HHV6, CMV, EBV, the list goes on.

Swapnil Lanjewar: 00:13:27

Indoor animals, you could either think about pets as well as insects

Swapnil Lanjewar: 00:13:32

as well, annoying indoor insects.

Swapnil Lanjewar: 00:13:35

Some people have, you know, all kinds of exotic pets, like including.

Swapnil Lanjewar: 00:13:39

Uh, you know, salamanders, and turtles, and snakes, and so obviously that's

Swapnil Lanjewar: 00:13:44

going to make you think about salmonella.

Swapnil Lanjewar: 00:13:46

And then indoor annoying bugs, like you know, have they had bed

Swapnil Lanjewar: 00:13:49

bugs, or spiders, or rodents?

Swapnil Lanjewar: 00:13:52

All of these can be associated with some, some other, uh, pathology

Swapnil Lanjewar: 00:13:57

that will give you fever and rash.

Swapnil Lanjewar: 00:13:59

And then, uh, coming next to something they ingested or injected, so injection

Swapnil Lanjewar: 00:14:05

was injection drug use or if they have any recent vaccines that were injected that

Swapnil Lanjewar: 00:14:10

can cause fever and rash too, or recent tattoos, and then something they ingested

Swapnil Lanjewar: 00:14:15

would be, you know, drugs or food, and so in terms of drugs, there can be Steven

Swapnil Lanjewar: 00:14:20

Johnson and toxic epidermal necrolysis, DRESS syndrome, small vessel vasculitis,

Swapnil Lanjewar: 00:14:27

In terms of some food they ate, like raw oysters, again, you

Swapnil Lanjewar: 00:14:30

have to think about Vibrio.

Swapnil Lanjewar: 00:14:32

Raw meat would make you think about salmonella again, or unpasteurized

Swapnil Lanjewar: 00:14:36

cheese and dairy products make you think about either brucella or Q fever too.

Swapnil Lanjewar: 00:14:41

Non exposure related would be the next big category.

Swapnil Lanjewar: 00:14:44

So autoimmune diseases, SLE, rheumatoid arthritis, or cutaneous

Swapnil Lanjewar: 00:14:49

vasculitis, or erythema nodosum, cancer, especially liquid malignancies,

Swapnil Lanjewar: 00:14:54

or cutaneous T cell lymphomas, and then other diseases like sarcoid.

Swapnil Lanjewar: 00:14:58

Kawasaki, GVHD, HLH, so these are some of the differentials that come to my mind.

Swapnil Lanjewar: 00:15:04

Michael, could you perhaps provide us with some HPI obtained by ID here?

Michael Moran: 00:15:09

Thanks for all that explanation Swapnil.

Michael Moran: 00:15:12

When we went and saw the patient, she tells us the fever started

Michael Moran: 00:15:15

about three weeks ago, occurring on almost a daily basis, but no

Michael Moran: 00:15:19

particular timing during the day.

Michael Moran: 00:15:21

She does get occasional drenching night sweats though.

Michael Moran: 00:15:24

She also describes having no energy and poor appetite over the last four to five

Michael Moran: 00:15:29

weeks, as well as a frontal headache which occurs on and off during these fevers.

Michael Moran: 00:15:34

She rates these headaches as a 4 out of 5 out of 10 in intensity, but has no

Michael Moran: 00:15:38

associated photophobia or neck stiffness.

Michael Moran: 00:15:41

In addition to this, she notes some abdominal pain on and off in

Michael Moran: 00:15:45

her bilateral upper quadrants, as well as a sharp 5 out of 6 out of

Michael Moran: 00:15:50

10 intensity without radiation.

Michael Moran: 00:15:52

She has no associated nausea, vomiting, or diarrhea.

Michael Moran: 00:15:55

With regards to her rash, she has trouble telling us exactly when it was started.

Michael Moran: 00:16:00

She is of African American ethnicity and notes that it's possible the

Michael Moran: 00:16:04

rash could have been there in early stages without her being able to tell.

Michael Moran: 00:16:08

She does recollect having some local skin sensitivity over her anterior

Michael Moran: 00:16:12

thighs, but no pain or pruritis.

Michael Moran: 00:16:15

She believes that this started about three days ago on her thighs and chest, and

Michael Moran: 00:16:20

her husband's in the room with us, and he tells us that the rash is also on her

Michael Moran: 00:16:24

upper back, abdomen, and posterior thighs.

Michael Moran: 00:16:28

She denies any mucosal pain or skin breakdown.

Michael Moran: 00:16:31

Otherwise, review of systems is unremarkable.

Michael Moran: 00:16:34

With regards to exposure history, she lives in the Midwest with her husband in a

Michael Moran: 00:16:38

single family home for the last 15 years.

Michael Moran: 00:16:41

They have no kids.

Michael Moran: 00:16:42

She has always been in a monogamous relationship and has no history of

Michael Moran: 00:16:46

prior sexually transmitted infections.

Michael Moran: 00:16:48

She works as a software engineer, with the majority of her work being remote.

Michael Moran: 00:16:53

She is a never smoker and only drinks socially with no illicit drug use.

Michael Moran: 00:16:57

She reports no new medications in the last two months aside from the

Michael Moran: 00:17:01

sulfasalazine and prednisone for her RA.

Michael Moran: 00:17:04

She does not take any other supplements or over the counter

Michael Moran: 00:17:07

meds, although she has been taking Tylenol and Ibuprofen for her fevers.

Michael Moran: 00:17:11

She has no pets or any exotic animal exposures.

Michael Moran: 00:17:15

She has never noticed any rodents or insects in the home.

Michael Moran: 00:17:18

And in terms of travel, she has never been to the Southwest U.

Michael Moran: 00:17:21

S., but she did say that she went to Cancun with her family about six weeks ago

Michael Moran: 00:17:26

and swam in the ocean while she was there.

Michael Moran: 00:17:29

She reports that she has not spent any time outdoors here in the

Michael Moran: 00:17:32

Midwest in the last five months because she hates being in the cold.

Michael Moran: 00:17:36

And before that, she used to go hiking on nearby trails and lakes with her husband.

Michael Moran: 00:17:41

She does not garden and has no soil exposures.

Michael Moran: 00:17:44

Her neighbor recently had COVID two weeks ago, and there was no family

Michael Moran: 00:17:48

history of recurrent infections.

Michael Moran: 00:17:50

Her sister in law's family did recently visit them for about three days, and

Michael Moran: 00:17:54

they have two kids of the ages of three and nine, and both kids had

Michael Moran: 00:17:57

the sniffles while they were here.

Michael Moran: 00:17:59

So Swapnil, based off this history alone, any differentials going through your mind?

Swapnil Lanjewar: 00:18:04

Yeah, so Michael, fever with rash is actually a unique

Swapnil Lanjewar: 00:18:06

entity in ID where I often do not start thinking of the differentials

Swapnil Lanjewar: 00:18:11

until I lay my eyes on the patient.

Swapnil Lanjewar: 00:18:13

This is because the examination of rash is actually going to

Swapnil Lanjewar: 00:18:17

significantly influence my thought process regarding differentials.

Swapnil Lanjewar: 00:18:22

While examining the rash, I'm looking at is it macular, papular, or maculopapular?

Swapnil Lanjewar: 00:18:27

Do they have plaques or nodules?

Swapnil Lanjewar: 00:18:30

I also look for secondary features into the rash, like do they have crusting

Swapnil Lanjewar: 00:18:35

or scaling there or excoriation or any other important secondary

Swapnil Lanjewar: 00:18:39

features like ulcers or eschars?

Swapnil Lanjewar: 00:18:42

And this is because appearance of the rash is going to help you narrow

Swapnil Lanjewar: 00:18:46

down your differential significantly.

Swapnil Lanjewar: 00:18:49

There are multiple viral infections that will cause a maculopapular rash,

Swapnil Lanjewar: 00:18:53

like herpes virus infections, EBV, CMV, HHV 6, then vaccine preventable viruses

Swapnil Lanjewar: 00:19:00

and childhood infections like measles, rubella, parvirus B19, and adeno.

Swapnil Lanjewar: 00:19:06

You can see maculopapular rash in some bacterial infections as well,

Swapnil Lanjewar: 00:19:09

like some STDs like syphilis and gonorrhea, and then you can see

Swapnil Lanjewar: 00:19:13

that in other bacterial infections like mycoplasma, relapsing fevers.

Swapnil Lanjewar: 00:19:18

Even some rickettsial infections like Rocky Mountain spotted fever

Swapnil Lanjewar: 00:19:22

and some tick borne infections will give you a maculopapular rash.

Swapnil Lanjewar: 00:19:26

When there are secondary features to the rash like skin necrosis, then there are

Swapnil Lanjewar: 00:19:31

some very specific bacterial infections that will come to my mind like pseudomonas

Swapnil Lanjewar: 00:19:35

which can cause ecthyma gangrenosum and then the Rickettsia typhi group like the

Swapnil Lanjewar: 00:19:40

murine and scrub typhus group, then the rat bite fevers like from Spirillum minus

Swapnil Lanjewar: 00:19:45

and from Streptobacillus monoliformis.

Swapnil Lanjewar: 00:19:48

And then some endemic fungal infections as well will cause some

Swapnil Lanjewar: 00:19:52

necrotic appearance to the rash.

Swapnil Lanjewar: 00:19:55

Other secondary features like vesicles will make me think about viral etiology

Swapnil Lanjewar: 00:20:00

like a Coxsackievirus or HSV or VZV, um, even smallpox and monkeypox.

Swapnil Lanjewar: 00:20:07

And then bacterial causes like rickettsial pox can also cause vesicles.

Swapnil Lanjewar: 00:20:12

And then Vibrio, uh, can cause bullae.

Swapnil Lanjewar: 00:20:15

And then lastly, if the rash is petechial or perpiric rash, then the biggest viral

Swapnil Lanjewar: 00:20:20

differentials would be viral hemorrhagic fevers, especially if they have this low

Swapnil Lanjewar: 00:20:24

epidemiologic risk factors of travel.

Swapnil Lanjewar: 00:20:27

I would think about dengue and then viral hemorrhagic fevers, like Ebola,

Swapnil Lanjewar: 00:20:32

Marburg, chikungunya as well, yellow fever can cause petechial or perpiral rash.

Swapnil Lanjewar: 00:20:38

And then certain important bacterial causes of petechial rash would be

Swapnil Lanjewar: 00:20:42

meningococcal infections, even sometimes severe Capnocytophaga infections, and

Swapnil Lanjewar: 00:20:48

then rat bite fever can also cause a petechial or perpireal rash, and then

Swapnil Lanjewar: 00:20:53

Staph aureus, and then relapsing fever, and rickettsial infections, again, like

Swapnil Lanjewar: 00:20:58

Rocky Mountain spotted fever, or epidemic typhus, or from Rickettsia prowazekii.

Swapnil Lanjewar: 00:21:03

These can all cause the petechial rash as well.

Swapnil Lanjewar: 00:21:08

So, Michael, can you share the exam findings with us for the rash?

Michael Moran: 00:21:11

Yeah, certainly.

Michael Moran: 00:21:12

On exam, we repeated her vitals, and she had a low grade temp of 100.

Michael Moran: 00:21:17

6 degrees Fahrenheit.

Michael Moran: 00:21:19

Her heart rate was 108, but she had a normal respiratory rate, blood

Michael Moran: 00:21:24

pressure, and oxygen saturation.

Michael Moran: 00:21:26

And her BMI is 33.

Michael Moran: 00:21:29

And on exam, she's alert and oriented times three and in no acute distress.

Michael Moran: 00:21:34

Some pertinent positives and negatives on her exam, she has

Michael Moran: 00:21:37

a mild periorbital edema and has evidence of cervical lymphadenopathy,

Michael Moran: 00:21:42

which was non tender on palpation.

Michael Moran: 00:21:45

Her heart sounds are normal and her respiratory exam is benign.

Michael Moran: 00:21:49

Her abdomen was soft, obese, with normal bowel sounds and

Michael Moran: 00:21:52

no organomegaly appreciated.

Michael Moran: 00:21:55

She had a normal neuro exam.

Michael Moran: 00:21:57

In regards to her skin exam, there was a symmetric, macular, and patchy

Michael Moran: 00:22:01

widespread erythematous rash over her cheeks, anterior and posterior

Michael Moran: 00:22:06

thighs, legs, chest, and back.

Michael Moran: 00:22:10

She had no mucosal involvement and notes the rash was mildly blanching.

Michael Moran: 00:22:15

So, with that exam, are there any other differentials that come to mind?

Swapnil Lanjewar: 00:22:19

Yeah, that definitely helps narrow down

Swapnil Lanjewar: 00:22:21

the list of differentials.

Swapnil Lanjewar: 00:22:23

I will divide my list of differentials according to viral versus bacterial

Swapnil Lanjewar: 00:22:28

versus fungal, parasitic, or non infectious etiologies.

Swapnil Lanjewar: 00:22:32

Viral wise, herpes viruses come to mind, especially with the history of contact

Swapnil Lanjewar: 00:22:36

with little kids who have been sick.

Swapnil Lanjewar: 00:22:38

So, EBV and HHV6 would be coming to mind.

Swapnil Lanjewar: 00:22:42

Because there are no vesicular features, I'm not thinking of chickenpox or VZV or

Swapnil Lanjewar: 00:22:46

HSV or any of the other herpes viruses.

Swapnil Lanjewar: 00:22:50

Um, Coxsackie and adenovirus would still be on my list of differentials.

Swapnil Lanjewar: 00:22:54

And then, Parvovirus B19 again, because of the risk associated

Swapnil Lanjewar: 00:22:58

with contact with little kids.

Swapnil Lanjewar: 00:23:00

I assume the kids are vaccinated, otherwise I would think of

Swapnil Lanjewar: 00:23:04

measles and rubella too.

Swapnil Lanjewar: 00:23:06

Uh, in terms of bacterial causes, if this was the appropriate

Swapnil Lanjewar: 00:23:10

season, I would have considered tick borne infections definitely.

Swapnil Lanjewar: 00:23:14

But it's March, and typically incubation period for most tick borne infections

Swapnil Lanjewar: 00:23:19

tends to be around two weeks or so.

Swapnil Lanjewar: 00:23:21

So I don't think this is tick borne infection.

Swapnil Lanjewar: 00:23:24

Unless the patient has any recent history of blood transfusion or

Swapnil Lanjewar: 00:23:27

so, but I don't think there was any such history, so I wouldn't

Swapnil Lanjewar: 00:23:31

consider tick borne infections here.

Swapnil Lanjewar: 00:23:33

STDs would still remain on my list of differential, even though she states that

Swapnil Lanjewar: 00:23:37

she is in a monogamous relationship, I would still consider syphilis, and then

Swapnil Lanjewar: 00:23:41

Neisseria gonorrhoeae, and then some non STD infections like Mycoplasma can

Swapnil Lanjewar: 00:23:47

still be on the differential for me.

Swapnil Lanjewar: 00:23:49

I don't think that the rash sounds fungal or any kind of parasitic infection, so

Swapnil Lanjewar: 00:23:55

I think we can safely rule those out.

Swapnil Lanjewar: 00:23:58

In terms of non infectious etiologies, I would consider possibility of DRESS

Swapnil Lanjewar: 00:24:02

syndrome or autoimmune disease, of course, given her recent history of

Swapnil Lanjewar: 00:24:07

rheumatoid arthritis, cancer, possibly hematologic malignancies could still

Swapnil Lanjewar: 00:24:12

be in the list of differentials.

Swapnil Lanjewar: 00:24:14

That would be my list so far.

Swapnil Lanjewar: 00:24:17

Do we have any labs and imaging results back so far, Michael?

Michael Moran: 00:24:20

We do.

Michael Moran: 00:24:22

So, on a CBC with differential, she has a white count of 7.

Michael Moran: 00:24:26

9 with a mildly elevated lymphocyte count of 3, 670, but

Michael Moran: 00:24:32

a normal eosinophil count at 110.

Michael Moran: 00:24:35

Her hemoglobin is 9.

Michael Moran: 00:24:36

3 and her platelet count is 116, so mildly low.

Michael Moran: 00:24:42

The pathology department did a formal read on her blood smear, which

Michael Moran: 00:24:46

shows numerous reactive appearing immunoblasts, and they note a reactive

Michael Moran: 00:24:51

process is favored, but correlation with flow studies is necessary.

Michael Moran: 00:24:55

Serum chemistry studies are all within normal limits.

Michael Moran: 00:24:59

In liver function testings, note an elevated ALT at 430,

Michael Moran: 00:25:02

AST at 345, and Alk phos 180.

Michael Moran: 00:25:10

A total bilirubin elevated at 3.8 with a direct bilirubin 2.8.

Michael Moran: 00:25:15

In terms of other labs, she has a normal uric acid and an elevated LDH at 1, 317.

Michael Moran: 00:25:22

On her repeat CT chest abdomen and pelvis, they do note a mild

Michael Moran: 00:25:26

thickening in her urinary bladder as evidence of possible cystitis.

Michael Moran: 00:25:31

As well as some mild splenomegaly and mild enlargement of the axillary

Michael Moran: 00:25:36

lymph nodes, presumably reactive without lymphadenopathy in the chest.

Michael Moran: 00:25:40

So Swapnil, given these findings so far, what would be your

Michael Moran: 00:25:43

recommendations to the team for any further workup of this patient?

Swapnil Lanjewar: 00:25:46

My next set of recommendations would be that we

Swapnil Lanjewar: 00:25:50

should check for, you know, the routine things, like multiple blood cultures,

Swapnil Lanjewar: 00:25:54

and then I'll recommend serology for EBV and CMV, and of course viral

Swapnil Lanjewar: 00:26:00

loads for EBV and CMV as well here.

Swapnil Lanjewar: 00:26:03

I'll recommend PCR for HHV6, Parvovirus B19, given the history

Swapnil Lanjewar: 00:26:09

that was provided, and then Adenovirus PCR from the blood tube.

Swapnil Lanjewar: 00:26:13

Given that this patient had transaminitis, I will screen

Swapnil Lanjewar: 00:26:16

her for hepatitis A, B, and C.

Swapnil Lanjewar: 00:26:19

I'll still recommend STD workup here by screening for syphilis, so

Swapnil Lanjewar: 00:26:25

treponemal antibody, and then the urine gonorrhea and chlamydia screen.

Swapnil Lanjewar: 00:26:30

I'll also screen for HIV here.

Swapnil Lanjewar: 00:26:32

I'll add some workup for culture negative endocarditis by checking for Bartonella

Swapnil Lanjewar: 00:26:36

PCR and Q fever serologies as well.

Swapnil Lanjewar: 00:26:40

Since there was this concern for HLH that I was thinking about because of

Swapnil Lanjewar: 00:26:44

the splenomegaly and cytopenias and these weird fevers, I'll also recommend

Swapnil Lanjewar: 00:26:49

screening for HLH by sending ferritin and triglycerides, soluble IL 2, and

Swapnil Lanjewar: 00:26:55

also check for flow cytometry because of the presence of those atypical or

Swapnil Lanjewar: 00:27:00

cells or immunoblasts that were mentioned earlier on the peripheral smear.

Swapnil Lanjewar: 00:27:05

And last but not the least, I'll recommend dermatology consultation

Swapnil Lanjewar: 00:27:09

as well for a skin biopsy here.

Michael Moran: 00:27:10

Yeah, so the lab was working quick this week, so we

Michael Moran: 00:27:14

have lots of results to talk about.

Michael Moran: 00:27:16

We have multiple sets of blood cultures that were drawn and are negative.

Michael Moran: 00:27:19

The Q fever phase 1 and phase 2 serologies were negative, as

Michael Moran: 00:27:23

well as serologies for Bartonella quintana and Mycoplasma serology.

Michael Moran: 00:27:28

Her urine gonorrhea and chlamydia screen was negative, as well as a

Michael Moran: 00:27:31

treponemal antibody, and an HIV fourth generation combo assay was negative.

Michael Moran: 00:27:37

We repeated the nasopharyngeal swab for respiratory viral panel, which was

Michael Moran: 00:27:41

negative, which included parvovirus B19, an adenovirus, a CMV serum viral

Michael Moran: 00:27:49

load was negative, and EBV serologies note a positive IgG, but a negative

Michael Moran: 00:27:54

IgM and a negative EBV viral load.

Michael Moran: 00:27:58

The hepatitis A, B, and C screens are negative.

Michael Moran: 00:28:02

In regards to the HLH workup, her ferritin is elevated at 6,

Michael Moran: 00:28:06

883, and elevated triglycerides at 226, a soluble IL 2 of 7, 252.

Michael Moran: 00:28:17

With a reference range of the upper limit of normal being 858.

Michael Moran: 00:28:22

So with those findings so far, how would you further narrow your differential?

Swapnil Lanjewar: 00:28:26

This definitely helps me further narrow down

Swapnil Lanjewar: 00:28:28

on my list of differentials.

Swapnil Lanjewar: 00:28:30

And quite frankly now, I don't think this is any kind of

Swapnil Lanjewar: 00:28:34

infectious process going on.

Swapnil Lanjewar: 00:28:36

My concern is strongly for non infectious processes.

Swapnil Lanjewar: 00:28:41

You know, DRESS would still be on my list of differentials, like drug related

Swapnil Lanjewar: 00:28:46

eosinophilia and systemic, uh, symptoms.

Swapnil Lanjewar: 00:28:49

I would think about autoimmune pathology still, so at this point,

Swapnil Lanjewar: 00:28:53

I might consider engaging our rheumatology colleagues as well.

Swapnil Lanjewar: 00:28:57

And hematologic malignancies are still on my list of differential,

Swapnil Lanjewar: 00:29:02

so I hope that the team now formally consults, uh, hematology based on

Swapnil Lanjewar: 00:29:07

the elevated soluble IL 2 and super elevated ferritin of more than 6, 000.

Swapnil Lanjewar: 00:29:13

Now HLH has jumped high on my list of differentials here.

Swapnil Lanjewar: 00:29:18

So, Michael, do you have any results so far regarding the skin biopsy?

Michael Moran: 00:29:22

We do.

Michael Moran: 00:29:24

The pathology department tells us that her right thigh skin biopsy pathology

Michael Moran: 00:29:28

shows an unusual constellation of findings with spongiosis, lichenoid

Michael Moran: 00:29:33

interface features, and a mixed dermal infiltrate with focal hemorrhage.

Michael Moran: 00:29:38

Eosinophils are not present in number, but these findings are

Michael Moran: 00:29:42

consistent with a reaction to a medication or other ingestant.

Michael Moran: 00:29:46

So dermatology is now suspecting DRESS syndrome, likely related to the

Michael Moran: 00:29:50

sulfosalazine that she was prescribed.

Michael Moran: 00:29:53

But, with our concern for HLH, hematology has a few other

Michael Moran: 00:29:57

additional workup to obtain.

Michael Moran: 00:29:59

They did do a flow cytometry on the peripheral blood, which showed polytypic

Michael Moran: 00:30:03

T cells with increased CD8 T cells and polyclonal B cells without evidence of

Michael Moran: 00:30:09

a B cell lymphoproliferative disorder.

Michael Moran: 00:30:11

These findings are consistent with the reactive process,

Michael Moran: 00:30:14

such as a viral infection.

Michael Moran: 00:30:16

They recommended the bone marrow biopsy, which was done, and showed cellular

Michael Moran: 00:30:19

marrow with trilineage hematopoiesis, with increased megakaryocytes, 1 percent

Michael Moran: 00:30:25

BLAST, and small aggregates of T cells consistent with reactive process.

Michael Moran: 00:30:30

No evidence of a lymphoproliferative disorder.

Michael Moran: 00:30:33

They also did a PET CT, which showed hypermetabolic lymph nodes throughout

Michael Moran: 00:30:37

the neck, chest, abdomen, and pelvis, with an enlarged and abnormally avid

Michael Moran: 00:30:43

spleen, which would be concordant with lymphoma if clinically suspected.

Michael Moran: 00:30:48

So right now, our final diagnosis is DRESS, and dermatology was considering a

Michael Moran: 00:30:52

DRESS and HLH overlap, but hematology did not feel that it was consistent with HLH.

Michael Moran: 00:30:58

So Swapnil, can you discuss DRESS and why we were thinking HLH and why we

Michael Moran: 00:31:03

could possibly have an overlap here?

Swapnil Lanjewar: 00:31:05

Yeah.

Swapnil Lanjewar: 00:31:05

So DRESS syndrome, the DRESS word stands for drug reaction with

Swapnil Lanjewar: 00:31:10

eosinophilia and systemic symptoms.

Swapnil Lanjewar: 00:31:12

I don't really like that name DRESS that much because you can actually

Swapnil Lanjewar: 00:31:17

have DRESS without eosinophilia.

Swapnil Lanjewar: 00:31:20

That's why a better term for it is drug induced hypersensitivity syndrome.

Swapnil Lanjewar: 00:31:24

It's a rare and potentially life threatening disorder that can occur

Swapnil Lanjewar: 00:31:28

about two to eight weeks from the initial exposure to the offending drug.

Swapnil Lanjewar: 00:31:33

And the typical pathogenesis for DRESS is that it's a T cell

Swapnil Lanjewar: 00:31:36

mediated hypersensitivity reaction.

Swapnil Lanjewar: 00:31:39

And then another thing we often see in DRESS is that there

Swapnil Lanjewar: 00:31:43

is simultaneous evidence of reactivation of HHV 6 or EBV or CMV.

Swapnil Lanjewar: 00:31:49

These group of herpes viruses, there is this controversy whether this is

Swapnil Lanjewar: 00:31:53

reactivation in the setting of DRESS or are they actually playing any role

Swapnil Lanjewar: 00:31:58

in the pathogenesis of DRESS itself?

Swapnil Lanjewar: 00:32:00

In terms of manifestations, the classic one is a morbilliform rash

Swapnil Lanjewar: 00:32:05

and the word morbilliform means that it essentially looks like measles.

Swapnil Lanjewar: 00:32:09

It's a faint pink maculopapular rash which can be circular or elliptical

Swapnil Lanjewar: 00:32:15

and it's typically symmetric rash.

Swapnil Lanjewar: 00:32:18

This can be associated with fevers.

Swapnil Lanjewar: 00:32:21

Lymphadenopathy as well, and some patients might have facial,

Swapnil Lanjewar: 00:32:25

hand, or feet swelling too.

Swapnil Lanjewar: 00:32:27

Another significant hallmark is visceral organ involvement like, you

Swapnil Lanjewar: 00:32:31

know, hepatitis, like our patient had, or renal, or pulmonary, or

Swapnil Lanjewar: 00:32:36

cardiac involvement, and when there's pulmonary or cardiac involvement, it's

Swapnil Lanjewar: 00:32:40

pretty severe stress at that point.

Swapnil Lanjewar: 00:32:42

Common culprits for DRESS tend to be anti epileptic drugs like phenytoin,

Swapnil Lanjewar: 00:32:47

or carbamazepine, or lamotrigine.

Swapnil Lanjewar: 00:32:50

In terms of antibiotics, sulfa group antibiotics are also a known culprit here.

Swapnil Lanjewar: 00:32:54

Tetracycline group antibiotics, especially like minocycline or

Swapnil Lanjewar: 00:32:58

minocycline, however you want to say it, penicillins and vancomycin.

Swapnil Lanjewar: 00:33:02

And then other important drug that is described for DRESS is allopurinol.

Swapnil Lanjewar: 00:33:07

But again, this list continues to grow along with our experience.

Swapnil Lanjewar: 00:33:12

Now for the diagnosis of DRESS, There's a really good scoring

Swapnil Lanjewar: 00:33:16

system called as RegiSCAR Scoring System, which stands for Registry of

Swapnil Lanjewar: 00:33:20

Severe Cutaneous Adverse Reactions.

Swapnil Lanjewar: 00:33:23

So that's why RegiSCAR it, it is readily available on Med Calc.

Swapnil Lanjewar: 00:33:29

You have to go through this questionnaire regarding whether your patient has fever,

Swapnil Lanjewar: 00:33:33

lymphadenopathy, atypical lymphocytes, or eosinophilia, and what's the extent

Swapnil Lanjewar: 00:33:39

of their skin involvement and what's their pathology on biopsy of the skin.

Swapnil Lanjewar: 00:33:44

Do they have involvement of internal organs, and what's the

Swapnil Lanjewar: 00:33:47

resolution time for their rash?

Swapnil Lanjewar: 00:33:50

So a score of 6 or more is supposed to be definitive diagnosis for DRESS.

Swapnil Lanjewar: 00:33:56

When it comes to treatment, the first line is supportive care, and if the

Swapnil Lanjewar: 00:34:00

disease is severe, like if there's end organ involvement as well, then you can

Swapnil Lanjewar: 00:34:05

consider glucocorticoids at a dose of 0.

Swapnil Lanjewar: 00:34:07

5 to 1 milligram per kg per day of prednisone equivalent.

Swapnil Lanjewar: 00:34:12

And then you taper it over the next 8 to 12 weeks or so.

Swapnil Lanjewar: 00:34:16

When you're giving them steroids, you absolutely make sure that

Swapnil Lanjewar: 00:34:19

you're also giving PJP prophylaxis because you're giving high dose

Swapnil Lanjewar: 00:34:23

steroids for more than a month or so.

Swapnil Lanjewar: 00:34:26

This is the first line treatment.

Swapnil Lanjewar: 00:34:28

Second line treatment is you could consider immunosuppressive drugs like

Swapnil Lanjewar: 00:34:31

cyclosporine and you could add IVIG and consider other immunosuppressants like

Swapnil Lanjewar: 00:34:36

JAK inhibitors, but typically I also let dermatology drive the ship on that.

Swapnil Lanjewar: 00:34:42

That's about DRESS syndrome.

Swapnil Lanjewar: 00:34:44

And then other thing which dermatology and myself, we were thinking about HLH.

Swapnil Lanjewar: 00:34:50

HLH is a life threatening hyper inflammatory syndrome where there is

Swapnil Lanjewar: 00:34:54

intense immune activation characterized by fever, cytopenias, and hepatosplenomegaly,

Swapnil Lanjewar: 00:34:59

and highly elevated inflammatory markers.

Swapnil Lanjewar: 00:35:02

This is definitely a life threatening condition, and if you are thinking

Swapnil Lanjewar: 00:35:06

about HLH, you should work fast on whether or not you can rule in or

Swapnil Lanjewar: 00:35:10

rule out this diagnosis because time is of the essence in such patients.

Swapnil Lanjewar: 00:35:15

So there are basically 9 criteria for HLH out of which you need at least 5 of them.

Swapnil Lanjewar: 00:35:22

Criteria include fever, splenomegaly, and then peripheral blood cytopenias with

Swapnil Lanjewar: 00:35:27

at least 2 of the following, you know.

Swapnil Lanjewar: 00:35:30

There should be hemoglobin less than 9 or platelets less

Swapnil Lanjewar: 00:35:34

than 100 or ANC less than 1000.

Swapnil Lanjewar: 00:35:38

Then hypertriglyceridemia is one criteria, so fasting triglycerides

Swapnil Lanjewar: 00:35:43

more than 265, or low or absent NK cell activity, or ferritin required is at

Swapnil Lanjewar: 00:35:50

least more than 500, but in reality most patients with HLH are going to have

Swapnil Lanjewar: 00:35:55

their ferritin in multiple thousands.

Swapnil Lanjewar: 00:35:57

And then elevated soluble IL 2 as well, and then elevated CXCL 9,

Swapnil Lanjewar: 00:36:03

and evidence of hemophagocytosis on biopsy from bone marrow.

Swapnil Lanjewar: 00:36:08

But you can also see that from biopsy from spleen, lymph nodes, or liver.

Swapnil Lanjewar: 00:36:13

Our patient, after discussion with hematology, did not

Swapnil Lanjewar: 00:36:17

meet all of these criteria.

Swapnil Lanjewar: 00:36:18

Our patient had only evidence of fever, and then the splenomegaly was there.

Swapnil Lanjewar: 00:36:23

Technically, it was pretty mild.

Swapnil Lanjewar: 00:36:25

She did have ferritin elevation of more than 500 and elevated soluble IL 2.

Swapnil Lanjewar: 00:36:31

But, the bone marrow biopsy did not show any concern for hemophagocytosis.

Swapnil Lanjewar: 00:36:37

Based on all of this, only four criteria were met, and that's why hematology

Swapnil Lanjewar: 00:36:43

did not think that this was HLH.

Swapnil Lanjewar: 00:36:46

So, Michael, what happened finally with the patient?

Michael Moran: 00:36:48

Yeah, so, coming back to our patient, she was initially treated

Michael Moran: 00:36:51

with IV dexamethasone at dose equivalent of about 1 mg per kg of prednisone, and

Michael Moran: 00:36:57

later switched to PO prednisone, which was tapered over the next eight weeks.

Michael Moran: 00:37:01

The team used atovaquone for PJP prophylaxis to avoid any sulfa

Michael Moran: 00:37:05

drugs, and her symptoms improved very quickly, and she made a full recovery.

Sara Dong: 00:37:10

This is such a great ID related topic.

Sara Dong: 00:37:14

The other thing I just wanted to add that I think you've said and implied, but

Sara Dong: 00:37:18

just to deliberately say aloud, is the mainstay of treatment is also stopping

Sara Dong: 00:37:23

the offending drug or agent, or whatever it is you think that is inducing DRESS.

Sara Dong: 00:37:27

And I think we all know that, but maybe just also saying that again out

Sara Dong: 00:37:32

loud, because oftentimes it's a bit of a conversation, you know, if these

Sara Dong: 00:37:36

patients are sick for other reasons, to also avoid giving them new meds,

Sara Dong: 00:37:41

like new empiric antibiotics, if you are in a place to be able to do so.

Sara Dong: 00:37:46

I think sometimes that's a hard conversation if these, because often

Sara Dong: 00:37:48

these patients are in the ICU, they have these very impressive rash, they can

Sara Dong: 00:37:53

look quite ill, but yeah, I just wanted to re emphasize that because sometimes

Sara Dong: 00:37:59

it's actually not that easy because the drug that's causing it isn't that clear.

Sara Dong: 00:38:03

If they look unwell, people want to add new things, so balancing all of that.

Sara Dong: 00:38:07

Do you guys want to do take home points?

Sara Dong: 00:38:09

Like, each of you have one thing that you emphasize.

Swapnil Lanjewar: 00:38:12

I will say that one of the biggest take home points from my

Swapnil Lanjewar: 00:38:15

standpoint here would be that this case shows the importance of not anchoring to

Swapnil Lanjewar: 00:38:21

infectious etiologies as the diagnosis every time you hear the word fever.

Swapnil Lanjewar: 00:38:27

Oftentimes, it is infectious disease clinicians who are also diagnosing

Swapnil Lanjewar: 00:38:30

non infectious causes of fever like DRESS syndrome or autoimmune pathology,

Swapnil Lanjewar: 00:38:37

rheumatological diagnosis as well.

Swapnil Lanjewar: 00:38:40

So it is important to keep non infectious etiologies in mind as

Swapnil Lanjewar: 00:38:44

well for patients having fever.

Michael Moran: 00:38:47

Yeah, I think the takeaway that I've had from this case is that,

Michael Moran: 00:38:50

you know, anytime you're called from the primary team for a rash, which

Michael Moran: 00:38:54

happens fairly often in ID, is really doing a comprehensive med list look and

Michael Moran: 00:39:00

getting that good exposure history, and then always just looking at UpToDate or

Michael Moran: 00:39:05

another resource for those medication lists or offending agents like Swapnil

Michael Moran: 00:39:09

talked about to kind of jog your memory so you aren't missing something.

Michael Moran: 00:39:12

Since the differential is so broad, it can really be so many different things.

Sara Dong: 00:39:19

Thanks again to Michael and Swapnil for joining Febrile today.

Sara Dong: 00:39:22

Febrile is produced with support from the Infectious Diseases

Sara Dong: 00:39:25

Society of America or IDSA.

Sara Dong: 00:39:27

Don't forget to check out the website, febrilepodcast.

Sara Dong: 00:39:30

com, where you can find the consult notes, which are written compliments

Sara Dong: 00:39:34

of the show with links to references, our library of ID infographics,

Sara Dong: 00:39:38

and a link to our merch store.

Sara Dong: 00:39:40

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

Sara Dong: 00:39:43

to be more involved with Febrile.

Sara Dong: 00:39:45

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