Sara Dong: Hi, everyone.
Welcome to Febrile, a cultured podcast about all things infectious disease.
We use consult questions to dive into ID clinical reasoning, diagnostics,
and antimicrobial management.
I'm Sara Dong, your host and a MedPeds ID doc.
Today, we have a team visiting from the University of Wisconsin, Madison.
First, let's meet Dr.
Michael Moran.
Michael is an adult Infectious Diseases Fellow at the University of Wisconsin.
Michael Moran: Hi, my name is Michael Moran.
I'm excited to be on the podcast.
Sara Dong: Also joining is Dr.
Swapnil Lanjewar.
Swapnil is a Clinical Assistant Professor in ID at the University of Wisconsin.
He completed his medical schooling in India and pursued his IM residency
at the Cleveland Clinic in Ohio.
He did his fellowship in ID at the University of Wisconsin Madison.
Swapnil Lanjewar: Hi, this is Swapnil Lanjewar, and I'm
super excited to be here.
Both me and Michael, we are big fans of the Febrile podcast, so we are absolutely
thrilled to join you here today, Sara.
Sara Dong: Well, I'm very excited to have you.
Of course, before we jump into the case, we always ask one question.
We are everyone's favorite cultured podcast, so I'd love to hear about a
little piece of culture, something non medical that you've enjoyed recently
or like to do in your free time.
Michael, what do you got?
Michael Moran: Yeah, I mean, so in fellowship, I think I've been
trying to find a lot of things to like kind of dump my brain.
And I was just recently introduced to 90 Day Fiancé, which I had
until now never watched before.
And it was like this week and it is absolutely wild.
And so I've been kind of going down a rabbit hole in that of just that's
the opposite of anything medicine.
So I understand all the hype now.
Yeah.
Sara Dong: What about you Swapnil?
Swapnil Lanjewar: One of my biggest hobbies is playing table tennis.
I grew up in India and I used to train formally in table tennis.
And I used to play competitively at the state and national level tournaments.
But these days it's mostly limited to playing with some
friends over the weekend.
Sara Dong: Do you get really aggressive?
You're very competitive.
Swapnil Lanjewar: I am actually.
Sara Dong: Awesome.
Well, I will hand it over to Michael.
Tell us about the case.
Michael Moran: So today we are getting a call from the medicine team to get
some help looking at a patient for the management of someone they admitted
overnight with a fever and a rash, and this occurred this past March.
When they called us, they gave us a little story about our patient.
She's a 47 year old female, has a past medical history of gout and hypertension,
and notably about eight weeks ago, she was seen by rheumatology due to a
one year history of polyarthralgia and was diagnosed with seronegative RA.
At that appointment, she was started on sulfazalazine and low dose oral prednisone
of about five milligrams a day, resulting in significant symptomatic improvement.
In regards to her current presentation, the medicine team tells us that
about three weeks ago, she started experiencing high grade fevers to 103 to
104 degrees Fahrenheit with associated night sweats and some loss of appetite
and bilateral upper abdominal pain.
About 10 days prior to this presentation, these symptoms were persisting, so she
presented to her local ER for evaluation.
Her exam at that time, along with routine labs like a CBC and CMP,
were within normal limits, although she did have an elevated CRP.
They tell us a CT chest abdomen pelvis was performed and was negative, and as
this was late winter, early spring, a respiratory pathogen panel multiplex PCR,
was done and negative, but with no other explanation, she was discharged home
with a tentative diagnosis of a viral syndrome, as she was otherwise well.
At home, her fever still continued on a daily basis without improvement,
which brings us to our current hospital admission, where she is now
presenting with the new development of a rash, which started about
three days prior to presentation.
The primary team tells us the rash is pink, macular, and
patchy, located all over her body.
The rash is not itchy and non painful.
They tell us there have been no new medications in the last one
to two weeks to explain this.
The team tells us the patient is currently hemodynamically stable, but
has a temp of 102 degrees Fahrenheit.
So far, her repeat labs and new CT chest abdomen pelvis are still unremarkable.
The team is planning to hold off on any antibiotics because
she otherwise looks good.
Swapnil Lanjewar: All right.
Thank you so much for the case, Michael.
So I will summarize what I gathered here.
So it looks like we have a 47 year old female with past medical history of
gout and recently diagnosed seronegative rheumatoid arthritis for which she was
started on treatment about two months ago and she's now presenting due to fever of
unknown etiology over the last four weeks and a new rash since last three days.
And this is in the setting of nearly normal labs and imaging about 10 days ago?
Michael Moran: Exactly.
So Swapnil, if you were called about a case like this, how would you approach
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
a challenging one, actually, for the infectious disease clinician.
This is because the list of differentials is quite big.
So I remember that as a trainee, this topic used to be pretty intimidating
for me, And even sometimes I struggle with a patient with fever and rash.
But over the years, I developed a structured and organized approach
for myself that I can share today.
And this is my personalized approach.
If you already have an approach nailed down which works well for you, then I
think you should keep doing that one.
For the purposes of this podcast, I will break down my approach in three parts.
First is what I do before I see the patient, second is what I do while I'm
seeing a patient, and third is what I do after I'm done seeing the patient.
Let's come to what I do before I see the patient.
I try to get a few questions answered absolutely before I hang
up the phone with the primary team.
When they're telling me about the case, I try not to interrupt them, and this is
because I want to make sure that they're not losing their train of thought, and
they don't forget giving me an important piece of information, and then I pay
attention to how sick is the patient.
Like, am I getting a call from the ICU, or is the patient's primary
care physician calling me about this?
If the patient is in ICU, super sick, hemodynamically unstable,
then I want to make sure that I'm not missing a never miss diagnosis.
For example, you know, is it a surgical disease?
Is it necrotizing fasciitis?
Or is this a hemorrhagic rash because of septicemia from either a
perforated viscus or a really terrible bad piomyositis or a huge abscess
which requires emergent surgery?
Or is it related to a toxic shock syndrome from a retained foreign body like a
tampon or a line or device infection which is causing the septic shock?
These are some never miss diagnoses and then if the season and location
are right, I will also think about tick borne infections like Babesia
and Rocky Mountain Spotted Fever that I want to make sure I'm not missing.
And if the patient is immune compromised, I absolutely don't want
to miss any terrible fungal infection.
So, apart from that, I also want to make sure whether or not I need to put
this patient into prompt isolation.
If there's anything like a meningococcal disease or a viral hemorrhagic fever
like Ebola based on epidemiologic risk factors for the patient, then you
want to make sure you put the patient in isolation as soon as possible.
Sometimes, somebody who's really sick with HIV and miliary TB can
actually have a skin rash too.
So, these are some considerations regarding whether they
need prompt isolation.
And lastly, if this is an exotic disease, you know, like malaria or so, based on
their epidemiologic risk factors again.
Technically, the textbook approach is also to think of bioterrorism,
but I really hope that none of us in real life have to think about that.
So, these are things I do before I see the patient while I'm still on
the phone with the primary team.
If they don't have a never miss diagnosis and you receive such a
call in middle of night, then it will make me feel comfortable.
Okay, fine.
I think I covered everything.
I can go back to sleep safely.
Next comes what I do while I'm seeing the patient.
So obviously this, I'll divide this between two parts,
history taking and examination.
History taking is one of the most important skills for any
infectious disease clinician.
When you have so many questions that you need to ask to the patient.
It's very easy to forget some crucial pieces of information,
so over the years, I've developed a personal template for myself.
I try to follow this template just so that I don't miss anything
important to ask the patient.
After I'm done asking them relevant questions about the
HPI, I'll ask five main group of questions to elicit differentials.
First group is occupational history, second group is outdoor exposures,
then indoor exposures, then regarding something they ingested or injected,
and the fifth one would be non exposure related differentials.
Going to occupational exposures, this is important to elicit because if
they are a butcher, let's say, there have been periodic outbreaks of Staph
and Strep infection amongst butchers.
If somebody's a chef who's handling raw meat, then I'll think about Salmonella.
And if they are routinely tasting raw oysters, then you
also have to consider Vibrio.
If they are a taxidermist, I know that there have been some
outbreaks of Q fever before.
So if they're a fisherman, I would think about something like Vibrio
if they are on the coast and are having a lot of exposures there.
So that's about occupational exposures.
Coming to outdoor exposures, I tend to categorize them
in three main subcategories.
Travel related and then hiking or camping related, or water body related exposures.
Hiking and camping related outdoor activities.
You know, what, what were they doing outside?
Were they doing something that involved turning of soil?
Were they out exploring caves?
Were they in contact with wild animals like, you know, flying
squirrels and snakes and bears?
Or were they in contact with any farm animals?
And then, have they been annoyed by some insects or arthropods like
ticks or lice or mosquitoes or flies?
Because all of these can contribute to your list of differentials as well.
Now, with regards to travel related exposures, then I ask
them where exactly they travel.
Was it a domestic travel or international travel?
Of course, we all know domestic travel related exposures differentials you have
to consider like in the southwest U.
S.
you think about Cocci[dioides].
Here in the Midwest we always think about Histo[plasma] and Blasto[myces].
In New England you would consider things like Lyme disease
based on the season as well.
And then when it comes to international travel, my first
question is always did you check the CDC website before you traveled?
Regardless of the answer, I will always pull up my phone and I'll go
on cdc.gov/travel and and pick their destination of travel and see what
all exposures that can occur in those particular areas of the world because
I can never remember, you know, specifics regarding to each country.
Like for example, if somebody traveled to India, you have to think about
typhoid, you have to think about malaria, even kala azar or leishmaniasis.
The list is pretty extensive.
That's in with regards to travel.
Next is outdoor exposure is water bodies, right?
So it could be oceans or You know, ponds, lakes, uh, streams and rivers,
or it could be flood water as well, and then recreational outdoor water
body exposures like swimming pools, or even water parks, and have they had any
injuries in the water, because there will be very specific bacterial and parasitic
infections that I would be considering with exposure to such water bodies.
In terms of indoor exposures, I asked them about have they had sick
contacts, like sick contacts with other adults or children or indoor animals.
So adults as in you can get of course you know all types of respiratory
infections and URIs from adults as well.
STDs would be a big thing from adults like syphilis and then gonococcal infection.
All of these can cause fever and rash and then risk factors for TB
as well would be elicited here.
Then in terms of contact with kids or little humans, you know, they are sources
of all kinds of viral and bacterial infections like vaccine preventable
diseases, measles, rubella, or parvovirus B19, HHV6, CMV, EBV, the list goes on.
Indoor animals, you could either think about pets as well as insects
as well, annoying indoor insects.
Some people have, you know, all kinds of exotic pets, like including.
Uh, you know, salamanders, and turtles, and snakes, and so obviously that's
going to make you think about salmonella.
And then indoor annoying bugs, like you know, have they had bed
bugs, or spiders, or rodents?
All of these can be associated with some, some other, uh, pathology
that will give you fever and rash.
And then, uh, coming next to something they ingested or injected, so injection
was injection drug use or if they have any recent vaccines that were injected that
can cause fever and rash too, or recent tattoos, and then something they ingested
would be, you know, drugs or food, and so in terms of drugs, there can be Steven
Johnson and toxic epidermal necrolysis, DRESS syndrome, small vessel vasculitis,
In terms of some food they ate, like raw oysters, again, you
have to think about Vibrio.
Raw meat would make you think about salmonella again, or unpasteurized
cheese and dairy products make you think about either brucella or Q fever too.
Non exposure related would be the next big category.
So autoimmune diseases, SLE, rheumatoid arthritis, or cutaneous
vasculitis, or erythema nodosum, cancer, especially liquid malignancies,
or cutaneous T cell lymphomas, and then other diseases like sarcoid.
Kawasaki, GVHD, HLH, so these are some of the differentials that come to my mind.
Michael, could you perhaps provide us with some HPI obtained by ID here?
Michael Moran: Thanks for all that explanation Swapnil.
When we went and saw the patient, she tells us the fever started
about three weeks ago, occurring on almost a daily basis, but no
particular timing during the day.
She does get occasional drenching night sweats though.
She also describes having no energy and poor appetite over the last four to five
weeks, as well as a frontal headache which occurs on and off during these fevers.
She rates these headaches as a 4 out of 5 out of 10 in intensity, but has no
associated photophobia or neck stiffness.
In addition to this, she notes some abdominal pain on and off in
her bilateral upper quadrants, as well as a sharp 5 out of 6 out of
10 intensity without radiation.
She has no associated nausea, vomiting, or diarrhea.
With regards to her rash, she has trouble telling us exactly when it was started.
She is of African American ethnicity and notes that it's possible the
rash could have been there in early stages without her being able to tell.
She does recollect having some local skin sensitivity over her anterior
thighs, but no pain or pruritis.
She believes that this started about three days ago on her thighs and chest, and
her husband's in the room with us, and he tells us that the rash is also on her
upper back, abdomen, and posterior thighs.
She denies any mucosal pain or skin breakdown.
Otherwise, review of systems is unremarkable.
With regards to exposure history, she lives in the Midwest with her husband in a
single family home for the last 15 years.
They have no kids.
She has always been in a monogamous relationship and has no history of
prior sexually transmitted infections.
She works as a software engineer, with the majority of her work being remote.
She is a never smoker and only drinks socially with no illicit drug use.
She reports no new medications in the last two months aside from the
sulfasalazine and prednisone for her RA.
She does not take any other supplements or over the counter
meds, although she has been taking Tylenol and Ibuprofen for her fevers.
She has no pets or any exotic animal exposures.
She has never noticed any rodents or insects in the home.
And in terms of travel, she has never been to the Southwest U.
S., but she did say that she went to Cancun with her family about six weeks ago
and swam in the ocean while she was there.
She reports that she has not spent any time outdoors here in the
Midwest in the last five months because she hates being in the cold.
And before that, she used to go hiking on nearby trails and lakes with her husband.
She does not garden and has no soil exposures.
Her neighbor recently had COVID two weeks ago, and there was no family
history of recurrent infections.
Her sister in law's family did recently visit them for about three days, and
they have two kids of the ages of three and nine, and both kids had
the sniffles while they were here.
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
entity in ID where I often do not start thinking of the differentials
until I lay my eyes on the patient.
This is because the examination of rash is actually going to
significantly influence my thought process regarding differentials.
While examining the rash, I'm looking at is it macular, papular, or maculopapular?
Do they have plaques or nodules?
I also look for secondary features into the rash, like do they have crusting
or scaling there or excoriation or any other important secondary
features like ulcers or eschars?
And this is because appearance of the rash is going to help you narrow
down your differential significantly.
There are multiple viral infections that will cause a maculopapular rash,
like herpes virus infections, EBV, CMV, HHV 6, then vaccine preventable viruses
and childhood infections like measles, rubella, parvirus B19, and adeno.
You can see maculopapular rash in some bacterial infections as well,
like some STDs like syphilis and gonorrhea, and then you can see
that in other bacterial infections like mycoplasma, relapsing fevers.
Even some rickettsial infections like Rocky Mountain spotted fever
and some tick borne infections will give you a maculopapular rash.
When there are secondary features to the rash like skin necrosis, then there are
some very specific bacterial infections that will come to my mind like pseudomonas
which can cause ecthyma gangrenosum and then the Rickettsia typhi group like the
murine and scrub typhus group, then the rat bite fevers like from Spirillum minus
and from Streptobacillus monoliformis.
And then some endemic fungal infections as well will cause some
necrotic appearance to the rash.
Other secondary features like vesicles will make me think about viral etiology
like a Coxsackievirus or HSV or VZV, um, even smallpox and monkeypox.
And then bacterial causes like rickettsial pox can also cause vesicles.
And then Vibrio, uh, can cause bullae.
And then lastly, if the rash is petechial or perpiric rash, then the biggest viral
differentials would be viral hemorrhagic fevers, especially if they have this low
epidemiologic risk factors of travel.
I would think about dengue and then viral hemorrhagic fevers, like Ebola,
Marburg, chikungunya as well, yellow fever can cause petechial or perpiral rash.
And then certain important bacterial causes of petechial rash would be
meningococcal infections, even sometimes severe Capnocytophaga infections, and
then rat bite fever can also cause a petechial or perpireal rash, and then
Staph aureus, and then relapsing fever, and rickettsial infections, again, like
Rocky Mountain spotted fever, or epidemic typhus, or from Rickettsia prowazekii.
These can all cause the petechial rash as well.
So, Michael, can you share the exam findings with us for the rash?
Michael Moran: Yeah, certainly.
On exam, we repeated her vitals, and she had a low grade temp of 100.
6 degrees Fahrenheit.
Her heart rate was 108, but she had a normal respiratory rate, blood
pressure, and oxygen saturation.
And her BMI is 33.
And on exam, she's alert and oriented times three and in no acute distress.
Some pertinent positives and negatives on her exam, she has
a mild periorbital edema and has evidence of cervical lymphadenopathy,
which was non tender on palpation.
Her heart sounds are normal and her respiratory exam is benign.
Her abdomen was soft, obese, with normal bowel sounds and
no organomegaly appreciated.
She had a normal neuro exam.
In regards to her skin exam, there was a symmetric, macular, and patchy
widespread erythematous rash over her cheeks, anterior and posterior
thighs, legs, chest, and back.
She had no mucosal involvement and notes the rash was mildly blanching.
So, with that exam, are there any other differentials that come to mind?
Swapnil Lanjewar: Yeah, that definitely helps narrow down
the list of differentials.
I will divide my list of differentials according to viral versus bacterial
versus fungal, parasitic, or non infectious etiologies.
Viral wise, herpes viruses come to mind, especially with the history of contact
with little kids who have been sick.
So, EBV and HHV6 would be coming to mind.
Because there are no vesicular features, I'm not thinking of chickenpox or VZV or
HSV or any of the other herpes viruses.
Um, Coxsackie and adenovirus would still be on my list of differentials.
And then, Parvovirus B19 again, because of the risk associated
with contact with little kids.
I assume the kids are vaccinated, otherwise I would think of
measles and rubella too.
Uh, in terms of bacterial causes, if this was the appropriate
season, I would have considered tick borne infections definitely.
But it's March, and typically incubation period for most tick borne infections
tends to be around two weeks or so.
So I don't think this is tick borne infection.
Unless the patient has any recent history of blood transfusion or
so, but I don't think there was any such history, so I wouldn't
consider tick borne infections here.
STDs would still remain on my list of differential, even though she states that
she is in a monogamous relationship, I would still consider syphilis, and then
Neisseria gonorrhoeae, and then some non STD infections like Mycoplasma can
still be on the differential for me.
I don't think that the rash sounds fungal or any kind of parasitic infection, so
I think we can safely rule those out.
In terms of non infectious etiologies, I would consider possibility of DRESS
syndrome or autoimmune disease, of course, given her recent history of
rheumatoid arthritis, cancer, possibly hematologic malignancies could still
be in the list of differentials.
That would be my list so far.
Do we have any labs and imaging results back so far, Michael?
Michael Moran: We do.
So, on a CBC with differential, she has a white count of 7.
9 with a mildly elevated lymphocyte count of 3, 670, but
a normal eosinophil count at 110.
Her hemoglobin is 9.
3 and her platelet count is 116, so mildly low.
The pathology department did a formal read on her blood smear, which
shows numerous reactive appearing immunoblasts, and they note a reactive
process is favored, but correlation with flow studies is necessary.
Serum chemistry studies are all within normal limits.
In liver function testings, note an elevated ALT at 430,
AST at 345, and Alk phos 180.
A total bilirubin elevated at 3.8 with a direct bilirubin 2.8.
In terms of other labs, she has a normal uric acid and an elevated LDH at 1, 317.
On her repeat CT chest abdomen and pelvis, they do note a mild
thickening in her urinary bladder as evidence of possible cystitis.
As well as some mild splenomegaly and mild enlargement of the axillary
lymph nodes, presumably reactive without lymphadenopathy in the chest.
So Swapnil, given these findings so far, what would be your
recommendations to the team for any further workup of this patient?
Swapnil Lanjewar: My next set of recommendations would be that we
should check for, you know, the routine things, like multiple blood cultures,
and then I'll recommend serology for EBV and CMV, and of course viral
loads for EBV and CMV as well here.
I'll recommend PCR for HHV6, Parvovirus B19, given the history
that was provided, and then Adenovirus PCR from the blood tube.
Given that this patient had transaminitis, I will screen
her for hepatitis A, B, and C.
I'll still recommend STD workup here by screening for syphilis, so
treponemal antibody, and then the urine gonorrhea and chlamydia screen.
I'll also screen for HIV here.
I'll add some workup for culture negative endocarditis by checking for Bartonella
PCR and Q fever serologies as well.
Since there was this concern for HLH that I was thinking about because of
the splenomegaly and cytopenias and these weird fevers, I'll also recommend
screening for HLH by sending ferritin and triglycerides, soluble IL 2, and
also check for flow cytometry because of the presence of those atypical or
cells or immunoblasts that were mentioned earlier on the peripheral smear.
And last but not the least, I'll recommend dermatology consultation
as well for a skin biopsy here.
Michael Moran: Yeah, so the lab was working quick this week, so we
have lots of results to talk about.
We have multiple sets of blood cultures that were drawn and are negative.
The Q fever phase 1 and phase 2 serologies were negative, as
well as serologies for Bartonella quintana and Mycoplasma serology.
Her urine gonorrhea and chlamydia screen was negative, as well as a
treponemal antibody, and an HIV fourth generation combo assay was negative.
We repeated the nasopharyngeal swab for respiratory viral panel, which was
negative, which included parvovirus B19, an adenovirus, a CMV serum viral
load was negative, and EBV serologies note a positive IgG, but a negative
IgM and a negative EBV viral load.
The hepatitis A, B, and C screens are negative.
In regards to the HLH workup, her ferritin is elevated at 6,
883, and elevated triglycerides at 226, a soluble IL 2 of 7, 252.
With a reference range of the upper limit of normal being 858.
So with those findings so far, how would you further narrow your differential?
Swapnil Lanjewar: This definitely helps me further narrow down
on my list of differentials.
And quite frankly now, I don't think this is any kind of
infectious process going on.
My concern is strongly for non infectious processes.
You know, DRESS would still be on my list of differentials, like drug related
eosinophilia and systemic, uh, symptoms.
I would think about autoimmune pathology still, so at this point,
I might consider engaging our rheumatology colleagues as well.
And hematologic malignancies are still on my list of differential,
so I hope that the team now formally consults, uh, hematology based on
the elevated soluble IL 2 and super elevated ferritin of more than 6, 000.
Now HLH has jumped high on my list of differentials here.
So, Michael, do you have any results so far regarding the skin biopsy?
Michael Moran: We do.
The pathology department tells us that her right thigh skin biopsy pathology
shows an unusual constellation of findings with spongiosis, lichenoid
interface features, and a mixed dermal infiltrate with focal hemorrhage.
Eosinophils are not present in number, but these findings are
consistent with a reaction to a medication or other ingestant.
So dermatology is now suspecting DRESS syndrome, likely related to the
sulfosalazine that she was prescribed.
But, with our concern for HLH, hematology has a few other
additional workup to obtain.
They did do a flow cytometry on the peripheral blood, which showed polytypic
T cells with increased CD8 T cells and polyclonal B cells without evidence of
a B cell lymphoproliferative disorder.
These findings are consistent with the reactive process,
such as a viral infection.
They recommended the bone marrow biopsy, which was done, and showed cellular
marrow with trilineage hematopoiesis, with increased megakaryocytes, 1 percent
BLAST, and small aggregates of T cells consistent with reactive process.
No evidence of a lymphoproliferative disorder.
They also did a PET CT, which showed hypermetabolic lymph nodes throughout
the neck, chest, abdomen, and pelvis, with an enlarged and abnormally avid
spleen, which would be concordant with lymphoma if clinically suspected.
So right now, our final diagnosis is DRESS, and dermatology was considering a
DRESS and HLH overlap, but hematology did not feel that it was consistent with HLH.
So Swapnil, can you discuss DRESS and why we were thinking HLH and why we
could possibly have an overlap here?
Swapnil Lanjewar: Yeah.
So DRESS syndrome, the DRESS word stands for drug reaction with
eosinophilia and systemic symptoms.
I don't really like that name DRESS that much because you can actually
have DRESS without eosinophilia.
That's why a better term for it is drug induced hypersensitivity syndrome.
It's a rare and potentially life threatening disorder that can occur
about two to eight weeks from the initial exposure to the offending drug.
And the typical pathogenesis for DRESS is that it's a T cell
mediated hypersensitivity reaction.
And then another thing we often see in DRESS is that there
is simultaneous evidence of reactivation of HHV 6 or EBV or CMV.
These group of herpes viruses, there is this controversy whether this is
reactivation in the setting of DRESS or are they actually playing any role
in the pathogenesis of DRESS itself?
In terms of manifestations, the classic one is a morbilliform rash
and the word morbilliform means that it essentially looks like measles.
It's a faint pink maculopapular rash which can be circular or elliptical
and it's typically symmetric rash.
This can be associated with fevers.
Lymphadenopathy as well, and some patients might have facial,
hand, or feet swelling too.
Another significant hallmark is visceral organ involvement like, you
know, hepatitis, like our patient had, or renal, or pulmonary, or
cardiac involvement, and when there's pulmonary or cardiac involvement, it's
pretty severe stress at that point.
Common culprits for DRESS tend to be anti epileptic drugs like phenytoin,
or carbamazepine, or lamotrigine.
In terms of antibiotics, sulfa group antibiotics are also a known culprit here.
Tetracycline group antibiotics, especially like minocycline or
minocycline, however you want to say it, penicillins and vancomycin.
And then other important drug that is described for DRESS is allopurinol.
But again, this list continues to grow along with our experience.
Now for the diagnosis of DRESS, There's a really good scoring
system called as RegiSCAR Scoring System, which stands for Registry of
Severe Cutaneous Adverse Reactions.
So that's why RegiSCAR it, it is readily available on Med Calc.
You have to go through this questionnaire regarding whether your patient has fever,
lymphadenopathy, atypical lymphocytes, or eosinophilia, and what's the extent
of their skin involvement and what's their pathology on biopsy of the skin.
Do they have involvement of internal organs, and what's the
resolution time for their rash?
So a score of 6 or more is supposed to be definitive diagnosis for DRESS.
When it comes to treatment, the first line is supportive care, and if the
disease is severe, like if there's end organ involvement as well, then you can
consider glucocorticoids at a dose of 0.
5 to 1 milligram per kg per day of prednisone equivalent.
And then you taper it over the next 8 to 12 weeks or so.
When you're giving them steroids, you absolutely make sure that
you're also giving PJP prophylaxis because you're giving high dose
steroids for more than a month or so.
This is the first line treatment.
Second line treatment is you could consider immunosuppressive drugs like
cyclosporine and you could add IVIG and consider other immunosuppressants like
JAK inhibitors, but typically I also let dermatology drive the ship on that.
That's about DRESS syndrome.
And then other thing which dermatology and myself, we were thinking about HLH.
HLH is a life threatening hyper inflammatory syndrome where there is
intense immune activation characterized by fever, cytopenias, and hepatosplenomegaly,
and highly elevated inflammatory markers.
This is definitely a life threatening condition, and if you are thinking
about HLH, you should work fast on whether or not you can rule in or
rule out this diagnosis because time is of the essence in such patients.
So there are basically 9 criteria for HLH out of which you need at least 5 of them.
Criteria include fever, splenomegaly, and then peripheral blood cytopenias with
at least 2 of the following, you know.
There should be hemoglobin less than 9 or platelets less
than 100 or ANC less than 1000.
Then hypertriglyceridemia is one criteria, so fasting triglycerides
more than 265, or low or absent NK cell activity, or ferritin required is at
least more than 500, but in reality most patients with HLH are going to have
their ferritin in multiple thousands.
And then elevated soluble IL 2 as well, and then elevated CXCL 9,
and evidence of hemophagocytosis on biopsy from bone marrow.
But you can also see that from biopsy from spleen, lymph nodes, or liver.
Our patient, after discussion with hematology, did not
meet all of these criteria.
Our patient had only evidence of fever, and then the splenomegaly was there.
Technically, it was pretty mild.
She did have ferritin elevation of more than 500 and elevated soluble IL 2.
But, the bone marrow biopsy did not show any concern for hemophagocytosis.
Based on all of this, only four criteria were met, and that's why hematology
did not think that this was HLH.
So, Michael, what happened finally with the patient?
Michael Moran: Yeah, so, coming back to our patient, she was initially treated
with IV dexamethasone at dose equivalent of about 1 mg per kg of prednisone, and
later switched to PO prednisone, which was tapered over the next eight weeks.
The team used atovaquone for PJP prophylaxis to avoid any sulfa
drugs, and her symptoms improved very quickly, and she made a full recovery.
Sara Dong: This is such a great ID related topic.
The other thing I just wanted to add that I think you've said and implied, but
just to deliberately say aloud, is the mainstay of treatment is also stopping
the offending drug or agent, or whatever it is you think that is inducing DRESS.
And I think we all know that, but maybe just also saying that again out
loud, because oftentimes it's a bit of a conversation, you know, if these
patients are sick for other reasons, to also avoid giving them new meds,
like new empiric antibiotics, if you are in a place to be able to do so.
I think sometimes that's a hard conversation if these, because often
these patients are in the ICU, they have these very impressive rash, they can
look quite ill, but yeah, I just wanted to re emphasize that because sometimes
it's actually not that easy because the drug that's causing it isn't that clear.
If they look unwell, people want to add new things, so balancing all of that.
Do you guys want to do take home points?
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
standpoint here would be that this case shows the importance of not anchoring to
infectious etiologies as the diagnosis every time you hear the word fever.
Oftentimes, it is infectious disease clinicians who are also diagnosing
non infectious causes of fever like DRESS syndrome or autoimmune pathology,
rheumatological diagnosis as well.
So it is important to keep non infectious etiologies in mind as
well for patients having fever.
Michael Moran: Yeah, I think the takeaway that I've had from this case is that,
you know, anytime you're called from the primary team for a rash, which
happens fairly often in ID, is really doing a comprehensive med list look and
getting that good exposure history, and then always just looking at UpToDate or
another resource for those medication lists or offending agents like Swapnil
talked about to kind of jog your memory so you aren't missing something.
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.
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