UA-184069179-1 93: Rash Decisions - Febrile

Episode 93

93: Rash Decisions

Drs. Michael Moran and Swapnil Lanjewar from the University of Wisconsin-Madison walk through a case and their approach to the common ID consult for fever and rash.

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Febrile is produced with support from the Infectious Diseases Society of America (IDSA). Audio editing/mixing by Bentley Brown.

Transcript
Sara Dong:

Hi, everyone.

Sara Dong:

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

Sara Dong:

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

Sara Dong:

and antimicrobial management.

Sara Dong:

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

Sara Dong:

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

Sara Dong:

First, let's meet Dr.

Sara Dong:

Michael Moran.

Sara Dong:

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

Michael Moran:

Hi, my name is Michael Moran.

Michael Moran:

I'm excited to be on the podcast.

Sara Dong:

Also joining is Dr.

Sara Dong:

Swapnil Lanjewar.

Sara Dong:

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

Sara Dong:

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

Sara Dong:

at the Cleveland Clinic in Ohio.

Sara Dong:

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

Swapnil Lanjewar:

Hi, this is Swapnil Lanjewar, and I'm

Swapnil Lanjewar:

super excited to be here.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

thrilled to join you here today, Sara.

Sara Dong:

Well, I'm very excited to have you.

Sara Dong:

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

Sara Dong:

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

Sara Dong:

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

Sara Dong:

or like to do in your free time.

Sara Dong:

Michael, what do you got?

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

until now never watched before.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

the opposite of anything medicine.

Michael Moran:

So I understand all the hype now.

Michael Moran:

Yeah.

Sara Dong:

What about you Swapnil?

Swapnil Lanjewar:

One of my biggest hobbies is playing table tennis.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

friends over the weekend.

Sara Dong:

Do you get really aggressive?

Sara Dong:

You're very competitive.

Swapnil Lanjewar:

I am actually.

Sara Dong:

Awesome.

Sara Dong:

Well, I will hand it over to Michael.

Sara Dong:

Tell us about the case.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

and bilateral upper abdominal pain.

Michael Moran:

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

Michael Moran:

presented to her local ER for evaluation.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

three days prior to presentation.

Michael Moran:

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

Michael Moran:

patchy, located all over her body.

Michael Moran:

The rash is not itchy and non painful.

Michael Moran:

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

Michael Moran:

to two weeks to explain this.

Michael Moran:

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

Michael Moran:

has a temp of 102 degrees Fahrenheit.

Michael Moran:

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

Michael Moran:

The team is planning to hold off on any antibiotics because

Michael Moran:

she otherwise looks good.

Swapnil Lanjewar:

All right.

Swapnil Lanjewar:

Thank you so much for the case, Michael.

Swapnil Lanjewar:

So I will summarize what I gathered here.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

gout and recently diagnosed seronegative rheumatoid arthritis for which she was

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Michael Moran:

Exactly.

Michael Moran:

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

Michael Moran:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

This is because the list of differentials is quite big.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

for myself that I can share today.

Swapnil Lanjewar:

And this is my personalized approach.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

think you should keep doing that one.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

up the phone with the primary team.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

attention to how sick is the patient.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

care physician calling me about this?

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

Is it necrotizing fasciitis?

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

which requires emergent surgery?

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

to miss any terrible fungal infection.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

this patient into prompt isolation.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

actually have a skin rash too.

Swapnil Lanjewar:

So, these are some considerations regarding whether they

Swapnil Lanjewar:

need prompt isolation.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

their epidemiologic risk factors again.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

the phone with the primary team.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

Okay, fine.

Swapnil Lanjewar:

I think I covered everything.

Swapnil Lanjewar:

I can go back to sleep safely.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

history taking and examination.

Swapnil Lanjewar:

History taking is one of the most important skills for any

Swapnil Lanjewar:

infectious disease clinician.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

important to ask the patient.

Swapnil Lanjewar:

After I'm done asking them relevant questions about the

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

and the fifth one would be non exposure related differentials.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

and Strep infection amongst butchers.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

And if they are routinely tasting raw oysters, then you

Swapnil Lanjewar:

also have to consider Vibrio.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

outbreaks of Q fever before.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

So that's about occupational exposures.

Swapnil Lanjewar:

Coming to outdoor exposures, I tend to categorize them

Swapnil Lanjewar:

in three main subcategories.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

Hiking and camping related outdoor activities.

Swapnil Lanjewar:

You know, what, what were they doing outside?

Swapnil Lanjewar:

Were they doing something that involved turning of soil?

Swapnil Lanjewar:

Were they out exploring caves?

Swapnil Lanjewar:

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

Swapnil Lanjewar:

squirrels and snakes and bears?

Swapnil Lanjewar:

Or were they in contact with any farm animals?

Swapnil Lanjewar:

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

Swapnil Lanjewar:

ticks or lice or mosquitoes or flies?

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

them where exactly they travel.

Swapnil Lanjewar:

Was it a domestic travel or international travel?

Swapnil Lanjewar:

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

Swapnil Lanjewar:

to consider like in the southwest U.

Swapnil Lanjewar:

S.

Swapnil Lanjewar:

you think about Cocci[dioides].

Swapnil Lanjewar:

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

Swapnil Lanjewar:

In New England you would consider things like Lyme disease

Swapnil Lanjewar:

based on the season as well.

Swapnil Lanjewar:

And then when it comes to international travel, my first

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

The list is pretty extensive.

Swapnil Lanjewar:

That's in with regards to travel.

Swapnil Lanjewar:

Next is outdoor exposure is water bodies, right?

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

infections and URIs from adults as well.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

as well would be elicited here.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

of all kinds of viral and bacterial infections like vaccine preventable

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

as well, annoying indoor insects.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

going to make you think about salmonella.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

bugs, or spiders, or rodents?

Swapnil Lanjewar:

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

Swapnil Lanjewar:

that will give you fever and rash.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

have to think about Vibrio.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

Non exposure related would be the next big category.

Swapnil Lanjewar:

So autoimmune diseases, SLE, rheumatoid arthritis, or cutaneous

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Michael Moran:

Thanks for all that explanation Swapnil.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

particular timing during the day.

Michael Moran:

She does get occasional drenching night sweats though.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

associated photophobia or neck stiffness.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

10 intensity without radiation.

Michael Moran:

She has no associated nausea, vomiting, or diarrhea.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

She does recollect having some local skin sensitivity over her anterior

Michael Moran:

thighs, but no pain or pruritis.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

upper back, abdomen, and posterior thighs.

Michael Moran:

She denies any mucosal pain or skin breakdown.

Michael Moran:

Otherwise, review of systems is unremarkable.

Michael Moran:

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

Michael Moran:

single family home for the last 15 years.

Michael Moran:

They have no kids.

Michael Moran:

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

Michael Moran:

prior sexually transmitted infections.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

sulfasalazine and prednisone for her RA.

Michael Moran:

She does not take any other supplements or over the counter

Michael Moran:

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

Michael Moran:

She has no pets or any exotic animal exposures.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

and swam in the ocean while she was there.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

She does not garden and has no soil exposures.

Michael Moran:

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

Michael Moran:

history of recurrent infections.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

the sniffles while they were here.

Michael Moran:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

until I lay my eyes on the patient.

Swapnil Lanjewar:

This is because the examination of rash is actually going to

Swapnil Lanjewar:

significantly influence my thought process regarding differentials.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

Do they have plaques or nodules?

Swapnil Lanjewar:

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

Swapnil Lanjewar:

or scaling there or excoriation or any other important secondary

Swapnil Lanjewar:

features like ulcers or eschars?

Swapnil Lanjewar:

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

Swapnil Lanjewar:

down your differential significantly.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

that in other bacterial infections like mycoplasma, relapsing fevers.

Swapnil Lanjewar:

Even some rickettsial infections like Rocky Mountain spotted fever

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

and from Streptobacillus monoliformis.

Swapnil Lanjewar:

And then some endemic fungal infections as well will cause some

Swapnil Lanjewar:

necrotic appearance to the rash.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

And then Vibrio, uh, can cause bullae.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

epidemiologic risk factors of travel.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

And then certain important bacterial causes of petechial rash would be

Swapnil Lanjewar:

meningococcal infections, even sometimes severe Capnocytophaga infections, and

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

These can all cause the petechial rash as well.

Swapnil Lanjewar:

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

Michael Moran:

Yeah, certainly.

Michael Moran:

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

Michael Moran:

6 degrees Fahrenheit.

Michael Moran:

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

Michael Moran:

pressure, and oxygen saturation.

Michael Moran:

And her BMI is 33.

Michael Moran:

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

Michael Moran:

Some pertinent positives and negatives on her exam, she has

Michael Moran:

a mild periorbital edema and has evidence of cervical lymphadenopathy,

Michael Moran:

which was non tender on palpation.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

no organomegaly appreciated.

Michael Moran:

She had a normal neuro exam.

Michael Moran:

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

Michael Moran:

widespread erythematous rash over her cheeks, anterior and posterior

Michael Moran:

thighs, legs, chest, and back.

Michael Moran:

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

Michael Moran:

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

Swapnil Lanjewar:

Yeah, that definitely helps narrow down

Swapnil Lanjewar:

the list of differentials.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

versus fungal, parasitic, or non infectious etiologies.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

with little kids who have been sick.

Swapnil Lanjewar:

So, EBV and HHV6 would be coming to mind.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

HSV or any of the other herpes viruses.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

with contact with little kids.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

measles and rubella too.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

season, I would have considered tick borne infections definitely.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

tends to be around two weeks or so.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

Unless the patient has any recent history of blood transfusion or

Swapnil Lanjewar:

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

Swapnil Lanjewar:

consider tick borne infections here.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

still be on the differential for me.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

I think we can safely rule those out.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

rheumatoid arthritis, cancer, possibly hematologic malignancies could still

Swapnil Lanjewar:

be in the list of differentials.

Swapnil Lanjewar:

That would be my list so far.

Swapnil Lanjewar:

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

Michael Moran:

We do.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

a normal eosinophil count at 110.

Michael Moran:

Her hemoglobin is 9.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

shows numerous reactive appearing immunoblasts, and they note a reactive

Michael Moran:

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

Michael Moran:

Serum chemistry studies are all within normal limits.

Michael Moran:

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

Michael Moran:

AST at 345, and Alk phos 180.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

thickening in her urinary bladder as evidence of possible cystitis.

Michael Moran:

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

Michael Moran:

lymph nodes, presumably reactive without lymphadenopathy in the chest.

Michael Moran:

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

Michael Moran:

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

Swapnil Lanjewar:

My next set of recommendations would be that we

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

loads for EBV and CMV as well here.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

Given that this patient had transaminitis, I will screen

Swapnil Lanjewar:

her for hepatitis A, B, and C.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

I'll also screen for HIV here.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

PCR and Q fever serologies as well.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

as well for a skin biopsy here.

Michael Moran:

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

Michael Moran:

have lots of results to talk about.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

well as serologies for Bartonella quintana and Mycoplasma serology.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

IgM and a negative EBV viral load.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Swapnil Lanjewar:

This definitely helps me further narrow down

Swapnil Lanjewar:

on my list of differentials.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

infectious process going on.

Swapnil Lanjewar:

My concern is strongly for non infectious processes.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

eosinophilia and systemic, uh, symptoms.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

I might consider engaging our rheumatology colleagues as well.

Swapnil Lanjewar:

And hematologic malignancies are still on my list of differential,

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Michael Moran:

We do.

Michael Moran:

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

Michael Moran:

shows an unusual constellation of findings with spongiosis, lichenoid

Michael Moran:

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

Michael Moran:

Eosinophils are not present in number, but these findings are

Michael Moran:

consistent with a reaction to a medication or other ingestant.

Michael Moran:

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

Michael Moran:

sulfosalazine that she was prescribed.

Michael Moran:

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

Michael Moran:

additional workup to obtain.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

a B cell lymphoproliferative disorder.

Michael Moran:

These findings are consistent with the reactive process,

Michael Moran:

such as a viral infection.

Michael Moran:

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

Michael Moran:

marrow with trilineage hematopoiesis, with increased megakaryocytes, 1 percent

Michael Moran:

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

Michael Moran:

No evidence of a lymphoproliferative disorder.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

could possibly have an overlap here?

Swapnil Lanjewar:

Yeah.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

eosinophilia and systemic symptoms.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

have DRESS without eosinophilia.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

mediated hypersensitivity reaction.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

in the pathogenesis of DRESS itself?

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

and it's typically symmetric rash.

Swapnil Lanjewar:

This can be associated with fevers.

Swapnil Lanjewar:

Lymphadenopathy as well, and some patients might have facial,

Swapnil Lanjewar:

hand, or feet swelling too.

Swapnil Lanjewar:

Another significant hallmark is visceral organ involvement like, you

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

pretty severe stress at that point.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

or carbamazepine, or lamotrigine.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

Tetracycline group antibiotics, especially like minocycline or

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

Severe Cutaneous Adverse Reactions.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

resolution time for their rash?

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

consider glucocorticoids at a dose of 0.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

steroids for more than a month or so.

Swapnil Lanjewar:

This is the first line treatment.

Swapnil Lanjewar:

Second line treatment is you could consider immunosuppressive drugs like

Swapnil Lanjewar:

cyclosporine and you could add IVIG and consider other immunosuppressants like

Swapnil Lanjewar:

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

Swapnil Lanjewar:

That's about DRESS syndrome.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

HLH is a life threatening hyper inflammatory syndrome where there is

Swapnil Lanjewar:

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

Swapnil Lanjewar:

and highly elevated inflammatory markers.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

at least 2 of the following, you know.

Swapnil Lanjewar:

There should be hemoglobin less than 9 or platelets less

Swapnil Lanjewar:

than 100 or ANC less than 1000.

Swapnil Lanjewar:

Then hypertriglyceridemia is one criteria, so fasting triglycerides

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

their ferritin in multiple thousands.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

and evidence of hemophagocytosis on biopsy from bone marrow.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

Our patient, after discussion with hematology, did not

Swapnil Lanjewar:

meet all of these criteria.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

Technically, it was pretty mild.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

did not think that this was HLH.

Swapnil Lanjewar:

So, Michael, what happened finally with the patient?

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

The team used atovaquone for PJP prophylaxis to avoid any sulfa

Michael Moran:

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

Sara Dong:

This is such a great ID related topic.

Sara Dong:

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

Sara Dong:

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

Sara Dong:

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

Sara Dong:

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

Sara Dong:

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

Sara Dong:

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

Sara Dong:

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

Sara Dong:

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

Sara Dong:

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

Sara Dong:

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

Sara Dong:

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

Sara Dong:

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

Sara Dong:

Do you guys want to do take home points?

Sara Dong:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

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

Swapnil Lanjewar:

Oftentimes, it is infectious disease clinicians who are also diagnosing

Swapnil Lanjewar:

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

Swapnil Lanjewar:

rheumatological diagnosis as well.

Swapnil Lanjewar:

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

Swapnil Lanjewar:

well for patients having fever.

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

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

Michael Moran:

another resource for those medication lists or offending agents like Swapnil

Michael Moran:

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

Michael Moran:

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

Sara Dong:

Thanks again to Michael and Swapnil for joining Febrile today.

Sara Dong:

Febrile is produced with support from the Infectious Diseases

Sara Dong:

Society of America or IDSA.

Sara Dong:

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

Sara Dong:

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

Sara Dong:

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

Sara Dong:

and a link to our merch store.

Sara Dong:

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

Sara Dong:

to be more involved with Febrile.

Sara Dong:

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

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