Time Stamps

  • 0:30 New features in this episode 
  • 1:09 Case one: 66M w RUQ pain 
  • 9:26 Case two: 41M w Afib in RVR 
  • 14:33 Case three: 50M w Syncope 
  • 19:57 Reveal 
  • 22:29 Retrieving illness scripts 
  • 26:12 Typical versus Atypical presentation of diseases

Show Notes

  • When faced with a complex case, it is useful take an intermediate step and speculate which “domain” the case involves first, Instead of jumping straight from raw clinical data to specific diagnosis – a domain being a structural or functional component of the human body. Narrowing down the correct domain(s) is often the first, and sometimes the most important step of the diagnostic reasoning process.
  • Lone atrial fibrillation, or idiopathic atrial fibrillation in young individuals without clear cardiac or other causes, warrants additional work up for risk factors traditionally not thought to be associated with atrial fibrillation.  
  • Adapting and individualizing diagnostic schema for common clinical problems allows practitioners to perfect a logical framework that help them avoid missing diagnosis
  • Illness scripts formation and refinement require both clinical knowledge and practice experience. It is worthwhile to take an active role in the continuing development of illness scripts even for entities you think you know well.


CINDY Hi everyone, Cindy Fang here. And welcome back to another episode of Hoofbeats, where we challenge you to solve diagnostically difficult, real-world cases alongside experienced clinicians. As always, I’m here with my partner, Dr. John Hwang.

JOHN Hi everyone, this is John Hwang. So if you remember, last episode we tried a different format to spice things up a bit. We presented a case in a reductive format with sequentially provided chunks of information. We also had two discussants instead of one tackling the case together.

CINDY We are going to try something different this time too. For this episode, our discussant is going to tackle not one, not two, but THREE cases!!! Again, the cases are very short and only the bare minimal information is provided for each one. At the end of this episode, the diagnoses for all three cases will be revealed – of course not until we hear from our discussant first.

JOHN Without further ado, let’s hear the first case from our chief executive producer of core IM, Dr. Shreya Trivedi.

Case 1

66M presented for abdominal pain for two days

  • RUQ pain worse with movements and deep inspiration, associated with nausea
  • PMH: mild intermittent asthma, OSA, HTN/HLD
  • SH: 45 pack year smoker quit 5 years ago
  • VS afebrile HR94 144/74 18 96% RA 81kg
  • Exam + R CVA tenderness, RLL rales
  • CXR small atelectasis at lung bases
  • Rest of exam and basic admission labs wnl

CINDY And that’s all the information you will get for the first case. I know it is not a lot to go on, but what would you have said if you were our expert discussant? What would you have done as this patient’s provider on presentation? Make sure to pause and give yourself room for some active thinking, we will compare notes after the break.

Musical Interlude

CINDY Welcome back! This week John and I sat down with Dr. David Kudlowitz, a hybrid internist who is both a hospitalist and a primary care provider here at NYU. Let’s see what he thinks about this case. As usual, he is getting exactly the same information you are getting, and nothing more.

DAVID KUDLOWITZ So the more that I learned about medicine, the more that I realized that what we mostly see are classic or typical presentations of atypical diseases or atypical presentations of typical diseases. So that’s how I separated my differential diagnosis here.

So first when you’re thinking about typical presentations of typical diseases, something like just a musculoskeletal type of back pain comes up, there’s no history of trauma. Then you start to think of all the other types of things that can give you right upper quadrant pain, biliary colic, again, not associated with food. Acute cholecystitis, again, there’s no fever and the pain is mostly with inspiration. Cholangitis, there’s no jaundice. Hepatitis, the labs are normal. There’s no ascites. Um, I think even, you know, more interestingly, pneumonia is something that comes up to me, especially with the right upper quadrant pain. And you know, the atelectasis that’s there. But again, there’s, there is no fever

I’m thinking about kidney pathology. So to me this fits very well with pyelonephritis and a kidney stone because the patient has nausea, but again, there’s no fever and assumingly there’s no blood on, on the UA, which would be key for a diagnosis of a kidney stone.

Finally the patient’s a smoker. So, you know, could, could this atelectasis be disguising a lung cancer of some sort? I don’t, I don’t think that’s, that’s probable here, but that’s just starting to talk about some of the typical things that this, this may or may not be.

Atypical things or atypical presentations of typical diseases is where I want to next. And I thought of a few different things here. So the first thing that I thought of was, was actually a pulmonary embolism. So the patient has borderline tachycardia, borderline hypoxia, um, they have this risk of a possible cancer.Now, smoking puts you at risk for more than just lung cancer, puts you at risk for other cancers as well. Um, the acuteness of this picture also makes PE more likely and could this atelectasis be a disguising and infarct of some sort which is causing the pain, which again, we described as pleuritic, but in the abdomen. The wells score is zero, but I think there’s at least enough evidence here to send a d dimer.

Another thought would be perhaps a renal infarct. Um, again, I don’t see any risk factors for a renal infarct. There’s no history of cardiac disease. There’s no a Fib Two other quick things that I thought about where pid, pelvic inflammatory disease, maybe a with the fitzhugh Curtis Syndrome in the right upper quadrant and also a mesenteric ischemia, but again, hard to relate with, with a little bit more without a little bit more information.

CINDY That’s a relatively long list from not a lot of information.

JOHN If you listen closely, though, it’s clearly not a random list.

DAVID KUDLOWITZ I think relying on certain tricks or probably what the literature would call it, a schemas, right? Of how you’re thinking and like, oh, right upper quadrant pain. I go through my all the things in the right upper quadrant and if those don’t fit, then I started thinking about things that aren’t in the right upper quadrant can cause right upper quadrant pain. Like pneumonia,PE, pleural effusion, retroperitoneal stuff.

CINDY Remember we mentioned the idea of diagnostic hierarchy in one of our previous episode?

JOHN Yes we did. That when faced with a complex case, experts generally don’t jump straight from the raw clinical data to a specific diagnosis. They start by characterizing their illness in relatively broad, abstract terms. Often the clinician speculates about which domains are involved in the patient’s illness — a “domain” being a structural or functional component of the human body.

CINDY These domains could be organ based, ie the heart versus the lungs

JOHN They can be systems, like the hematopoietic system, or the immune system.

CINDY Or just an anatomical region of the body, chest versus abdomen. Choosing the correct domain is crucial, it is often the first step in the reasoning process and it determines the directionality of your reasoning. A lot of diagnostic errors stem from moving to the incorrect domain.

JOHN For example, when encountering a chief complaint of dyspnea, a lot of people reflexively think, is it cardiac or is it pulmonary?  That might be enough to diagnose a pna in a patient w/ lobar infiltrate and fever, but when the patient fails to extubate by hospital day 3 multiple times- you may realize there are other domains that you didn’t consider – in this case neurologic, this patient is suffering from MG exacerbation in the setting of pna.

If you think about it, we can think of many diagnosis – anemia, metabolic acidosis, hyperthyroidism – we can think of many processes that don’t belong either cardiac or pulmonary domains.

CINDY Another common mistake is thinking the body is composed of anatomically distinct boxes. It’s easy to think in terms of chest versus abdomen, is it above or below the diaphragm – but in reality we know its not the case. An epigastric pain is very often MI for some patients, splenic infarction may present as left lower chest pain. Anatomy 101 in med school: left shoulder pain could be referred from diaphragmatic irritation.

JOHN I know these are things we’ve been all taught but its nice to see how Dr. Kudlowitz models for us here: When a symptom is close to the diaphragm, make sure to think about what’s on the other side of the diaphragm too. A patient with RUQ pain? Thinking about the liver and biliary tree is obvious, but can’t forget the lower chest and retroperitoneal space as well.  Considering each and all of these domains allowed him to come up with the specific diagnoses such as biliary colic, pulmonary embolism, renal infarcts, respectively.

CINDY Alright, let’s stop singing praises, we all know Dr. Kudlowitz is brilliant and definitely not paying us to say this on air.

JOHN We do have to move on unfortunately to case 2. I know it’s frustrating to leave this patient without a diagnosis but deal with it – delayed gratification is a good virtue for an internist to have.

Musical Interlude

Case 2

  • 41M referred by pre-op clinic for afib w/ RVR
  • Bilateral Wrist fracture from a trip and fall one week ago
  • PMH/PSH/Meds/SH/FH: none
  • VS Afebrile HR156 122/76 16 99% 97kg
  • Exam wrists in soft cast, tachycardic
  • EKG afib/flutter w/ RVR
  • CXR no overt edema or pneumonia, possible vascular congestion exaggerated by reduced depth of inspiration

JOHN Alright hoofbeat listeners, you should know the drill by now. Pause, think, come up with your own differential. We’ll play you some relaxing music as usual, but don’t fall asleep, pretend we are interviewing you and the pressure is on you to sound smart when we come back.

Musical Interlude

JOHN Alright, 41M here for new onsert afib w/ rvr.  Again Dr. Kudlowitz?

DAVID KUDLOWITZ First question, why does such a young guy have afib? Second question, why is he 97 kilograms and what’s his BMI? And my third question is, how did he get, how did he fall? How does a guy who’s 41 just trip and fall and break both of his wrists?

I’m very uneasy with sending this patient to surgery. I’m uneasy for three reasons. So number one, am I satisfied that this is a fib that’s idiopathic and not related to anything else or just related to his obesity? Number two, did he just trip and fall and happen to break both of his wrists? Does he actually just need a good primary care doctor and a DEXA scan when all this is over? Or did he actually syncopize? And then finally if he is going to go to surgery, I think, you know, figuring out what his rate control medication is going to be as very important. And as far as I know he doesn’t have diabetes so you know, his chads-vasc is probably zero and, and he doesn’t need anything like anticoagulation preoperatively.

CINDY To answer Dr. Kudlowitz’s question, we sent a medical student into the patient’s room and thoroughly interrogated him for an hour. It was definitely a mechanical fall, and the wrist fractures were results of both the very crowded environment and very bad luck. I mean, it makes sense for him to come in tachycardic, right? He broke his wrists, there’s a lot of pain and maybe anxiety with going through surgery…

DAVID KUDLOWITZ But I’m not really 100 percent satisfied as to why he could possibly have a fib. At 41 years old. Like, you know, I think it is very possible that it could just be idiopathic and you know, we have enough evidence here to at least check a TSH, which means maybe you have for me, but as far as doing further testing, I think a chest x Ray, um, is, is reasonable here as well, which we have with no, no overt pneumonia, possible vascular congestion, which I read as actually obesity. Right, he’s not taking a deep breath and he probably has a lot of, subcutaneous tissue.

At least putting on my hospital is hat, you know, anytime someone has new afib, PE always crosses my mind so I don’t see why it wouldn’t cross my mind in the clinic as well and obesity is a risk factor for, for pe and sometimes the only one that we discover in patient.

JOHN To be fair you do occasionally see this — a young healthy patient who comes in with new afib for no apparent reason and no evidence of structural heart disease. Lone afib is a well-described entity.

CINDY I wonder what made him immediately skeptical – is it a quote on quote spidey sense?

DAVID KUDLOWITZ  I don’t know if I’m good enough to rely on my spidey sense yet. I liked it. I like to try and rely on my spidey sense, but when I try and rely on that I feel like it’s sometimes getting, getting lazy or you know, it’s not really feeling lazy. It’s really actually just being overworked and tired and, and you know, trying to take a mental break when I can and that’s a dangerous path to follow

CINDY And that’s a recurrent theme that reminds me of many of our prior episodes: the way expert clinicians habitually ask themselves “what doesn’t fit”? It might take years of experience to hone your system 1/pattern recognition for the “spidey sense” to become reliable, but. Getting into the habit of questioning myself is something i can start doing today.

JOHN  I agree, Cindy. I think there’s a lot more we can say about this case, but we’re going to have to move on to our third case, and again, we’ll get to the answers at the end of this episode.

Musical Interlude

Case 3

50M here for tremor and syncope on day of admission

  • Smelled burnt toast then felt dizzy and lost consciousness at work desk
  • Similar admission one month ago treated for withdrawal
  • PSH: 3 vodka drinks daily, current everyday smoker
  • VS Afebrile HR97 141/89 14 96% RA 59Kg
  • Exam mild hand tremor
  • Rest of admission labs wnl

JOHN Listeners, you know what to do. Enjoy the music interlude.

Musical Interlude

DAVID KUDLOWITZ  So to me, initial thoughts. So weird smell plus loss of consciousness is not a, it’s not syncope to me. It’s a seizure to me until proven otherwise. So I’m surprised that the patient didn’t get any EEG or we didn’t hear about the EEG from the, from um, the last admission if the presenting symptoms were similar. So it says that he was treated for withdrawal but he drinks three vodka drinks per day. So having trained at Bellevue three shots of vodka is not enough to cause alcohol withdrawal. So I’m wondering if, you know, these were actually just like, you know, big glasses of vodka that he was drinking, but it’s very reasonable that, you know, he could have had an alcohol withdrawal seizure. This time, this kind of burnt toast smell, which leads me towards seizure. But then dizziness kind of makes me think maybe a little bit more cardiac and hey, maybe did this patient have, have an arrhythmia possibly as well here and p prior to his syncope…other thing… or seizure, which, which I’m going to talk a little bit more about.

So for me, what I fall back on here is syncope and what’s my differential diagnosis for syncope, since we see syncope quite often I have a specific way that I think about it.

So the first, it’s divided into four parts. So the first part is what I’m thinking about. My differential diagnosis for syncope is number one, not syncope. So all the things that are not syncope that we include in our syncope category when we’re talking about the differential in the first one of course is a seizure. Hypoglycemia, intoxication. There’s this also this thing that I like to bring up, especially when I’m teaching people for, vertibral-basolar insufficiency, which only way I’m able to remember what that is, is because it’s also called beauty parlor syndrome. (What? Do tell!) So you like lean your head back like this and you occlude those vertebral arteries makes you very dizzy and you could syncopize. And then finally, my favorite not syncope, cause of syncope is sleeping, which rapid responses have been called for!

Second category to me is a reflex syncope. So lots of people just say Vasovagal, I like to say reflex because I include vasovagal on that, but I also include, um, situational syncope like coughing, micturition, etc. Third is orthostasis, which is usually due to, hypovolemia, medications, or underlying neurologic disease. And four is a big category and it’s cardiac. So arrhythmia as myocardial diseases, structural diseases, a third is vascular disease and fourth would be an obstructive type of disease, like a tamponade, or PE- something that’s causing hypoxia.

There was that study that was, was debatably done very well or not well, um, where, you know, one out of six people who are admitted to the hospital for undifferentiated syncopy have a pe. Um, but the question is, was that study too biased or where they’ll have those incidental findings. So this patient had loss of consciousness and you know, did, did this patient have a PE?

JOHN Look at the way he frames the problem. We tell him it’s syncope, but syncope is not just a symptom — it’s a diagnosis — the cause of the LOC is hypoperfusion of the brain. He recognizes it is premature to make that assumption. He is dealing with transient loss of consciousness.

CINDY I really love the diagnostic schema he has for syncope (when he’s convinced it is in fact syncope). It’s very similar to the ones we all learned in med school, but you can tell   he has added additional extra wings to the bare scaffolds he inherited as he learns more from additional experience and reading. That’s something I strive to do for all the common problems I see

Brief Musical Interlude

JOHN So to recap, we presented our discussant with three patients: a 66M w/ significant smoking history here for acute abdominal pain, a 41M w/ obesity and recent wrist fractures here for new asymptomatic afib, and a 50M w/ tobacco/etoh abuse here for recurrent syncope. Dr. Kudlowitz gave a thoughtful and robust differential diagnosis for each case. But in the end, he concluded that the diagnosis was the same in all three cases.

So Cindy, do you want to tell us what happened?

CINDY In the first case, the 41M with acute abdomen pain underwent abdominal imaging with contrast and was incidentally found to have a acute lobar pulmonary embolism on the lung cut, and a dedicated PE study confirmed the lobar PE, RLE pulmonary infarction, with a pulmonary mass highly concerning for invasive carcinoma.

JOHN  Yicks, that’s not good

CINDY The patient with wrist fracture and new afib w/ RVR? You guessed it, bilateral lobar PEs.

DAVID KUDLOWITZ So why did that patient have PE?

CINDY The patient reported relative immobility and new chairbound or chair bound status for a week because his wrist fx prevented him from going to work and performing his usual tasks. You got to wonder though, is that enough to cause a acute DVT and PE? Or is it more like what Dr. Kudlowitz said earlier, that obesity plays a big role here?

JOHN Ha, I see what you did there. My understanding is that  upper extremity fractures do have a weak association with VTEs, but the incidence seems to be higher w/ humerus or clavicular fractures and its very rare in patients with wrist fractures. Unclear if its a result of degree of inactivity or disturbance in venous blood flow.

CINDY It’s quite interesting right? If this patient presented with a lower extremity, say, a hip fracture, combined with the tachycardia, that would definitely trigger a PE scan for most providers. But with the wrist fracture, I do not know if I am necessarily sensitive enough to think of it if I saw this patient in the busy ER myself, especially when there are other factors that could explain his tachycardia. Kudos to the ED physician who decided to obtain a d-dimer and then ultimately a PE scan.

JOHN  Retrieving illness scripts in response to clinical cues that is a process is fast, basically subconscious.

Some authors have argued that the reason why expert clinicians can extract relevant clinical information that triggering the correct script through this process because much of the information is focused on the conditions that contribute to (or protect against) certain diseases, rather than the signs or symptoms themselves.

CINDY Conversely, using a rigid, limited illness script is almost like using a stupid search engine, the search results only comes up if you enter the key phrases completely correctly. I still think this patient got lucky here – if the presentation was different here – if he was 75 or had a prior history of atrial fibrillation, his PE really could have gone undiagnosed.

JOHN And the patient with recurrent syncope vs. seizure episodes?

CINDY You guessed it, acute bilateral lobar PE. It is unclear why, but he is undergoing malignancy workup for some pulmonary nodules on imaging as well as hypercoagulability work up now. I omitted this information to make this harder for Dr. Kudlowitz, but this patient actually had a remote history of DVT a few years ago, unclear circumstances or prior work up, but he had not taken AC in years.

JOHN Just to be clear, these are lobar PEs, right? Not these crappy subsegmental ones that come up incidentally sometimes? [Cindy: Yes.] And it is still unclear if you can attribute both of the syncopal episodes to PE, right? Still could be primary seizure disorder?

CINDY I completely agree, but I still love how on admission the hospitalist thought his symptoms and etoh history just don’t fit the previous diagnosis of withdrawal seizures, and made the call to scan him. Not necessarily all providers would have pulled the trigger based on his presentation (even with the history of dvt known to them!) would have pulled the trigger and that’s why I included the case here. So, yup, I intentionally collected three middle age man w/ PE who presented very differently to trick Dr. Kudlowitz, but it was obviously too easy for him.

DAVID KUDLOWITZ Can I pick this mic up and drop it?

JOHN For those getting wrong impression, David is actually quite modest and humble; he did not actually drop the mic.

Musical Interlude

CINDY I do wonder, how did Dr. Kudlowitz arrive at the diagnosis of PE so effortlessly in these three cases?

DAVID KUDLOWITZ I’m always surprised by diagnosis of PE and I’m often annoyed by a diagnosis of PE. I feel like PE is the classic, atypical presentation of a typical disease, which is what I was reading into these three cases.

Well, I think what’s, what’s interesting is you read these three cases separately. You don’t necessarily think of PE, but when you read them together you try and you try and put a thread through them, it’s not my bad experiences or, or you know, or things that have happened to me, but it’s things that have happened to other people as far as, you know, PE  always being in a morbidity and mortality. It makes you very hyper aware of, of this as a possible diagnosis.

CINDY Now that we all know the diagnosis, let’s come back to the discussion of typical versus atypical presentation of diseases. In an ideal world, all PE patients should just read the med school textbook and present with the dyspnea, pleuritic chest pain, tachycardia/hypoxia, maybe trace hemoptysis. But what happens when our patients forget to read the textbook?

Is it a legit diagnostic strategy if I just gather a list of diagnosis that tend to have variable presentations and tend to trick people up? And use it as a cheat sheet?

JOHN If you remember in our past episode on hyperthyroidism, we said that disease entities that could have multi-organ involvements, like hyperthyroidism or tb, are things to watch out for atypical presentations.

CINDY Well now, I feel I am going to add PE to my list now. Not a multi-organ process, but definitely can look like anything. You know, when I first heard of the phrase “the great imitator” in medical school, it was just a few select entities. Now it’s TB, lymphoma, sarcoidosis, amyloidosis, lupus, lyme, PE, thyroid disorders, leptospirosis,…the list goes on and on now.

JOHN That’s why they are common answers to CPCs and M&Ms, right? And every conference you go to, or every case report you read, the take home message they give you is “remember to keep a high index of suspicion for XYZ”.

CINDY Uhh, how am i supposed to keep a high index of suspicion for so many “great imitators” at the same time? I guess keeping a list of ddx to watch out for might work for other clinicians, but it’s not really working for me.

JOHN Yeah. I agree.

CINDY Instead of having a list of offending diseases, is it then a legit strategy to just think harder about certain types of patients who tend to present atypically? Say, geriatrics pts who dysuria/fever/leukocytosis when they have a UTI

JOHN I get what you’re saying. Like how we learn to be careful with diabetics or women who present with things like nausea or gas pain because they might having an MI.

CINDY Or medications, I always remember my Crohn’s patient getting high dose steroids, developed c diff toxic megacolon overnight and perfed – was not screaming in pain and abd exam was so subtle, the only clue was the acute rise in leukocytosis, which, hey, could also be explained by the steroids. Almost missed the perforation.

JOHN Cindy I acknowledge this strategy again only seems useful up to a point. As my paranoia increases, I could justify adding more and more groups of patients to this list. You mentioned your patient on steroids, well what about other immunosuppressed patients, have a transplant, have AIDS, are malnourished, have CVID, hematological cancer. Every patient who doesn’t speak English as a first language. Every patient who has a psychiatric diagnosis. At a certain point, the list of people to worry about just becomes too long to be useful.

CINDY To make the strategy even harder to adapt, these patients don’t necessarily tell you when they are part of these “high risk” groups for atypical presentation – they don’t tell you they have undiagnosed DM or metastatic malignancy, etc, thats just annoying! So I guess watching out for specific patient populations, just as a general strategy its not working out for me either…

JOHN In this episode we presented three middle age, baseline healthy males, so the above factors are not even at play. This is why we have to stress the importance of building and developing /maintaining robust  illness script

DAVID KUDLOWITZ I think the problem, the problem is with these, um, these typical diseases, right? So you separate everything that typical and atypical diseases like we’ve been talking about, right? So like PE is a typical disease, but something like gpa for me isn’t a typical disease. So my illness script for an atypical disease that I haven’t seen as much I have less experience with is very small. Uh, almost like, you know, for instance, a medical students illness script would be for a typical disease. So for me, since PE is a typical disease, and I’ve seen it a lot, the illness script is huge. It’s more than just someone who recently has surgery or is tachycardic and hypoxic and as pleuridic chest pain, um, and you know, S1Q3T3, it’s more than that. It’s, it’s, um, someone who has something wrong with them, but you can’t necessarily figure out what it is and it’s not necessarily obvious from just all the information that you have.

DAVID KUDLOWITZ I think my illness scripts or organized in groups of illness scripts. So I actually think that I’m a big believer in horizontal reading. So taking several diseases that have similarities and taking each of their illness scripts and comparing the components of their illness scripts to one another

CINDY And know which disease entities are common to US – so you know which illness scripts need to be worked on. Once we build our illness script based on the most typical presentation, we need to continue to expand and adapt to incorporate the atypical but very possible presentations. Illness script building should be an ongoing process throughout your training, even for the disease entities you think you know pretty well.

JOHN An going process and an active process. Can’t rely on seeing many cases.

CINDY Being a still an inexperienced novice myself, I am hoping my conscious effort in the process can speed things up.  While we are gaining on patient exposure by following up on your own patients, reading case reports, going to conferences, talking to your colleagues and gathering cool cases – the focus is not just learning some disease entities I have never heard before, but also learning how atypical presentations of certain diseases can still trick me.

Musical Interlude

CINDY Alright listeners, that should do it for this episode. Just to recap, this week we had three previously healthy, middle age men presenting with abdominal pain, atrial fibrillation with rapid rate, and recurrent syncope. All three had one diagnosis in common – pulmonary embolism. Something we see commonly, but an entity I learned to respect and its still very sexy in my mind.

JOHN Speak for yourself, I am so over PE


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