April 30, 2026 VMR with Rabih & Lourenço - headache and blurry vision

Ajouté : 2026-05-07

[00:00:01]All righty, before we get started I just wanted to share an observation that I've had I have had the privilege of hanging out with three uh new Academy recruits this week. It's been our busiest week uh bringing in new team team members.

[00:00:17]Uh it is not a coincidence. This is a time of transition for many folks, especially in the United States as we go from uh the end of the academic year to the beginning one. We are about to bid farewell to 11 team members who are soon to be interns who we know so well and will will miss deeply.

[00:00:37]And so as a as a direct consequences of that there are a lot more there's a lot more space in the Academy and so we've had more and more people join and three of three have said to me almost quoted that there is no way I thought I could be in the Academy because the people here are just too smart.

[00:00:57]Um and I will tell you that is the only thing that they are completely wrong about. There's nothing uh uh nothing here that is not earned.

[00:01:06]There is no gift from above that gives people facts or knowledge. The only gift that people have here it's actually a a gift of two things. It's a relentless drive to be the best version you can be uh and a tremendous amount of humility and kindness.

[00:01:22]So I only will tell you one thing that if you uh listen to this VMR and don't think that you're up to par um now you know that that is actually a requirement to join it seems because three of the three newest team members have all felt that feeling. So if you don't have it maybe this isn't the place for you. And I I say that both in just but also in seriousness because um the people who think that that maybe they're not good enough are often the people who really want to try the hardest and actually that's the secret sauce.

[00:01:52]Everyone you see here in the Academy is somebody who's willing to put in 120 130% and that includes everybody you're going to see today. Um Now I'm very very excited to pivot to that because today is a day of firsts.

[00:02:05]Uh we have somebody who's been part of the CP Solvers orbit for some time. Uh Lorenzo who's bamboozled bamboozled us with case after case after case. Now I think it's his time to be bamboozled.

[00:02:17]Um uh by our case presenter Varsha who has a case for us today.

[00:02:24]Um but first I'd love to shed light on the folks who are making the session happen in part because there are two people that we're going to have to bid a temporary goodbye to in the near future and I will miss them dearly.

[00:02:36]So I'm glad they're here.

[00:02:37]Um beginning with Sarah who is scribing today. Mike to you Sarah.

[00:02:42]Hello hello. Happy to be scribing this morning. It's a little bit rainy outside so it it is much nicer in here.

[00:02:52]>> [laughter] >> Good day to be indoors and stay warm, huh? Yep. Awesome. Well thanks for hanging out with us.

[00:02:58]I've gotten used to saying this line and and Eugene on teaching points on Thursday.

[00:03:02]Mike to you Eugene.

[00:03:04]Yeah. Hello everybody. I'm Eugene. I'm from Ghana and now we doing teaching points. But I hope Ravi wasn't mentioning that I will be leaving soon cuz I'm still here for life. Yeah. No no I I I think it's a temporary leave of absence.

[00:03:23]You're going to be a little bit different.

[00:03:25]We'll see about that. Okay. All righty.

[00:03:28]Sounds good. Sounds good. You're doing your intern year at the CP Solvers residency. I love it. That that would be a dream come true.

[00:03:34]Uh well thank you both. I really appreciate you being here and very excited for the learning that you're going to get a lot next year. Um Yeah thrilled that one of our newest Academy members Varsha is presenting a case.

[00:03:49]Varsha maybe I can hand the mic to you to tell people a little bit about yourself who are getting to know you and then we can hand the mic to Lorenzo to say hi.

[00:03:58]Hi everyone. I'm joining from India today and I'm one of the new members of this incredible Academy. Um I will be presenting a really interesting and fun case today for us to discuss. I will give you a disclaimer that I did not see this patient so I'm all the more interested to see the discussion go around and I will give a shout out at the end of the session who to the physician who gave me this opportunity and shared his wonderful journey with us.

[00:04:23]Wonderful. That's so cool. You know bringing somebody else's story to life is another skill but it's also a testament to another person's work. So thank you so much for doing that. And before that I hand the mic to Lorenzo I have to say that I I vividly remember the phone call that I had with him when we were discussing his potential involvement in the Academy and he was he was in a car in an Uber I think >> [laughter] >> on the way on the way to dinner and you know [snorts] when when you do this for a long time you you become better and better at spotting presumed nervousness.

[00:04:49]And my whole goal was to try to diffuse it and I know I'm tasked with that skill again today cuz Lorenzo mentioned that he's a little bit nervous before the session. I have to tell you I think he is one of uh the brightest young minds in the space and I think we see incontrovertible evidence of that this week when you saw him tell us a story on Tuesday that I highly highly recommend you check out.

[00:05:09]In fact if you're watching this video on YouTube stop and go ahead and watch Tuesday and then of course come back and learn from Varsha. But it's been a treat to get to know you and see you uh uh Lorenzo and I think I'm making you even more nervous now but as the case goes I promise we'll have we'll have a ton of fun.

[00:05:24]But I hand you the mic to say hello and then we can jump in.

[00:05:28]Thank you for the kind words Ravi. Hello everyone. My name is Lorenzo Garcia. I'm an internal medicine resident from Portugal. Hopefully the case won't bamboozle me too much but if it does so I'll lean on your knowledge Ravi. Thank you for the care.

[00:05:45]All right Varsha I think we're ready to rock and roll. Take it away.

[00:05:49]All right.

[00:05:51]We have our first dialogue box here. We have a 55 year old male that presents with headache and blurry vision. The symptom was gradual in onset confined mainly to the temporal and retro orbital region for the last eight days. It increased in intensity and peaked at 24 hours and has remained constant since. The pain is also aggravated by extraocular movements and he also reports developing gradual blurring of vision of his peripheral field.

[00:06:20]Um he also has a significant ocular history from his past that I'd like to mention now and then I'll stop for discussion.

[00:06:27]He had a severe orbital ocular trauma from a surfboard injury at the age of 17 that required surgery and a placement of a Teflon um Teflon support plate.

[00:06:39]He recalled being told that the vision in his left eye would eventually stabilize but the right eye would become dominant over time and I will now stop here.

[00:06:49]Fascinating. Yeah. Lorenzo how are how are you thinking about all this?

[00:06:54]So whenever we have headache it's usually something uh on the primary spectrum and usually those types of headaches come along with only pain but here we have something that's subacute in terms of progression and we also have blurry vision which we always have to be careful about. Um I don't actually have a really good approach to this but whenever I see blurry vision and headache I'm usually prone to think about intracranial hypertension since we have um the subarachnoid space involving the optic nerve and that usually leads to repercussion when we have intracranial hypertension. Another thing that we have to be wary about is the fact that the patient has pain with eye movement. Uh whenever we have pain it's usually something that's localized. So either we have something on the orbit orbit cavity that's causing pain. Either we have swollen muscles either we have a foreign body either we have edema or inflammation or we could have some type of ischemia of the optic nerve itself uh some type of arthritis or ischemic heart arthritis that's causing the pain. Um with the eye trauma the past eye trauma and the fact that the patient has some sort of if I um got it correctly some sort of um some sort of type of plate foreign body inside the orbit that makes me believe that it might be somewhat related to this but I'm not yet putting too much stock in it just knowing that there's point of vulnerability in the patient's eyes that we have to be on the lookout for.

[00:08:46]Aside from that we would really want to um rule out other types of focality associated with this headache uh which seems to be particularly concerning at this point. What do you think Ravi?

[00:09:03]Yeah I'm right there with you. I think that you're analyzing this super superbly. You know what is my role after digesting all the data that you have is to try to offer simplicity through studying a paradox without any real comment to the substances commented that you've made just to help people see the space with a little bit more clarity.

[00:09:20]And I will tell you that when you think about the eye and the reason you have to think about the eye here is evident. The patient's reporting blurry vision. It's helpful to divide the eye into two anatomical compartments the anterior and posterior parts of the eye with the lens being the site of division. And in general the anterior part of the eye is extremely sensitive and radiates pain.

[00:09:39]The back of the eye is relatively insensate.

[00:09:42]How can you remember that? Corneal ulcerations and corneal trauma is excruciatingly painful and in stark contrast ischemia to the retina when patients have amaurosis fugax is completely painless.

[00:09:56]So you might ask yourself, um, how does that does that how does that help us make progress?

[00:10:05]Um, the fact that the patient doesn't seem to have redness of the eye is the first clue that the back of the eye is responsible for the change in vision.

[00:10:16]Most patients who have anterior eye disease have pain as we just alluded to, but also have redness.

[00:10:21]So, you might immediately say, "Okay, well, hmm, I don't think there's redness. We'll see." And so, that tells me there's a problem in the back of the eye, but the back of the eye is relatively insensate, and yet this patient is reporting pain. What significance does that paradox have? And the significance of that paradox is fundamentally pressure, pressure, pressure.

[00:10:43]With the idea being that if somebody is really hurting in this area, has vision changes, and you cannot see why, um, unlike pressure coming from inside the eye, i.e., glaucoma, that often is a often a reason concern that there's pressure coming from our in and around the eye, i.e., the pressure is in the orbit, not in the actual globe.

[00:11:05]And so, when I hear the story of somebody who has headache and blurry vision, I really worry about pressure radiating from outside. And I think that's where your instinct and the reflex teaching point that you've been taught, Lorenzo, of intracranial hypertension doing this, it but it just illustrates the concept that the back of the eye only really feels pain when it's under pressure. And so, you might immediately translate this phenomenon to where is the pressure coming from, and you have two fundamental options. The pressure is radiating from the brain down the optic nerve and affecting the eye, or there's actually pressure in the orbit itself. And that there is pressure between the bones, i.e., here the plate, and the patient's actual eye.

[00:11:52]The only exception to this rule is the dull, vague pain of optic neuritis.

[00:12:01]So, this eye is under pressure until proven otherwise. Where? From the brain radiating into the orbit or intrinsically from the orbit itself. And the only way, the only diagnosis that is a satisfactory one that does not invoke pressure is optic neuritis.

[00:12:22]So, when you hear the story, you should be worried, and the journey that you can go on is where is the pressure? And a good physical exam can help you make a lot of progress. I'm not talking about a good funduscopic exam, which I'm not good at, but I think you have to really pay attention to is there restriction in ocular motility? Is there a proptosis or enophthalmosis also enophthalmos, sorry.

[00:12:46]Things that suggest there's something in the orbit or in stark contrast, are there neurological abnormalities such as the problems in the brain?

[00:12:55]So, I'm really curious to see where this case goes, and I think as you said, we're on the hunt for where the pressure is, and only after that do we think maybe there's a maybe there's inflammation of the nerve.

[00:13:06]I should say I this is the first time I've said I vocalized this on VMR, so are there any clarifying thoughts or questions, Lorenzo, about that about that maybe oversimplification? Okay.

[00:13:17]All right, Varsha, mic to you. What do you have next?

[00:13:20]Um, that was incredible. Um, to give you a little bit more context, um, 6 months prior to the presentation he currently has, he developed a diffuse rash on his trunk, back, and extremities, which he describes as bruise-like after working down in a mine.

[00:13:37]He recalled that he was working on some cables which were covered by a muddy brown liquid, and the following day he developed burning sensation in his hands, followed shortly by welts that progressed to blistering lesions. He described these lesions as forming subcutaneous channels that later broke open and ultimately impaired his ability to use his hands.

[00:13:59]Um, he sought care for these when it did not resolve spontaneously after a week, and he was given antibiotics and a steroid taper for a possible hypersensitivity reaction, with some improvement in the rash, and it eventually faded over time. He later noticed that in the creases of his arms at sites of previous blood draws, he had developed pustules that remained open without discharge.

[00:14:23]There were also pustules of similar appearance, um, present on the dorsum of his MCPs bilaterally. There was no improvement after multiple rounds of antibiotics, but steroids improved some of these lesions. These pustules would not diffuse, but a total of four to five small pustules were spread throughout his upper extremities.

[00:14:43]Um, he denies any ocular discharge, eye redness, or vision darkening or graying.

[00:14:50]There is no double vision. He denies any jaw pain, fatigue, scalp tenderness, hearing changes, muscle weakness, etc. He denies any neck stiffness, numb- numbness or tingling, um, denies nausea, vomiting. There are no bleeding manifestations, and none of his symptoms have any relief with over-the-counter analgesics at this point.

[00:15:11]Review of systems also shed some light.

[00:15:14]Um, he, um, reported to have polyarticular joint pain with stiffness.

[00:15:20]Um, there is a new bilateral calf pain which he has had for the last 5 days associated with progressive swelling of his lower extremities. His left, um, ear had pain and some tinnitus. He also reports an undiagnosed illness consisting of intermittent drenching night sweats and subjective fevers over the last 6 months associated with a 25-lb unintentional weight loss, which he attributes to alcohol withdrawal. So, I'm going to give you a little history about his alcohol consumption.

[00:15:52]He previously reported drinking up to 40 beers weekly, but on several occasions he felt the urge to quit, and he would relapse again.

[00:16:01]He has a 25-pack-year smoking history.

[00:16:04]Um, he used to work as a bartender, but currently works as a plant technician.

[00:16:09]He denies any significant travel history or animal exposure, and his past medical history is significant for type 2 DM and CAD. And I'll stop here for discussion.

[00:16:22]Uh, hey Sarah, I think it's raining more indoors than it is outdoors. Oh my gosh.

[00:16:27]This case is unreal. Um, I have Varsha, I have a I'm starting to get a sneaky suspicion who this illustrious physician might be based on many things in this case, but we'll see.

[00:16:36]I only I know that better than I think I know where this case is going.

[00:16:40]But yeah, Lorenzo has a lot of information. How how are you processing it all?

[00:16:45]I just have to say this is way easier looking from the outside.

[00:16:50]>> [laughter] >> There's too much to catch.

[00:16:52]Uh, uh, I'll try to tackle some of the uh, symptoms and some of the findings, but uh, I'll need your assist, Robbie.

[00:16:59]So, the main point that I, uh, got out from the second outlook was that there's inflammation, a backdrop of inflammation. We have subjective fevers, we have sweating, um, the patient has night sweats, uh, and we also have a diffuse disease, um, and a marker of exposure.

[00:17:18]Um, the main thing that caught my eye and that Ravi was, uh, saying about in the chat was the fact that there's uh, there's something that points to a Pathergy sign or a positive Pathergy test where we have pustules in previous venous puncture sites, uh, and that aligned with the fact that the patient has polyarthralgia or polyarthritis, we yet don't know, uh, can, uh, make us think of autoimmune diseases, mainly, uh, Behcet's disease, but I won't put too much stock in that, uh, as of now.

[00:17:48]Uh, we also have cutaneous findings.

[00:17:52]Uh, I'm trying to, uh, other cutaneous findings, I mean. I'm trying to see, uh, their distribution. I I heard that they were, uh, affecting the trunk, and bruise-like after working cables with a muddy liquid. So, we have some exposure, some toxic exposure, possibly.

[00:18:09]Um, for example, copper wires or copper exposure, lead exposure.

[00:18:15]Um, don't see lead. I believe that it can give off cutaneous manifestations and some neurological manifestations.

[00:18:22]Copper, I'm not so sure, apart from, uh, myelopathy and some anemia.

[00:18:27]Um, don't yet know how to connect that with the eyes, uh, as of now, and the headache. Um, and other other things that we have to, uh, rule out with the fact that we have polyarticular, uh, symptoms, we have a rash, we have, uh, eye symptoms is some some infections or STDs that we have to be on the lookout for, for example, Reiter's syndrome caused either by chlamydia or gonorrhea. Um, so we have to have a good, uh, um, uh, sexual history from the patient.

[00:19:04]Um, and, uh, apart from that, nothing comes to my mind. How to, uh, pair that with the eye?

[00:19:13]Not yet sure.

[00:19:14]Maybe the physical exam will give us more, uh, to work with.

[00:19:20]What do you think, Robbie? No, there's a real struggle here. I'm I'm not I'm not, um, uh, not not for this to be a cop-out, but I'll tell you exactly what I would do in real time.

[00:19:29]I would be like, "Oh my gosh, I'm so sorry you're going through all this.

[00:19:33]That's a lot. Why don't we put that aside for a moment and study what's happening in your eye to try to get clarity on that?"

[00:19:41]And, um, I would explain to the patient that many, many diseases that cause such profound problems, um, can be very difficult to diagnose.

[00:19:51]But, um, there's an opportunity at finally making clarity whenever a disease takes off.

[00:19:56]And it's very, very common to not be able to really have put your finger around something that is slowly causing somebody trouble, but when somebody has uh an entity arise to the surface as dramatically and aggressively as his eye pain and visual discomfort over the last 24 hours, that is finally an opportunity to potentially put together these uh complex um both superficial pustules and arthritis, but also visceral weight loss uh elements.

[00:20:23]So, what am I actually doing? I'm cheating. I'm completely ignoring all that information, except I've made a note that this isn't just an eye story.

[00:20:31]And so, once we figure out what the eye issue is, we then can paint it back. And I encourage all of you to resist the temptation that is that is sort of ingrained in the default educational pathway of taking this as a boards question and saying, "Eye pain plus pustules plus this plus that."

[00:20:47]You may you may be a supercomputer and able to do that, but in real life, the number of possibilities here is so infinite um because you are trying to connect dots.

[00:20:58]Uh uh but you don't know what each dot actually represents. So, you have this illusion that the pustules and the arthritis and the eye pain are actual individual dots.

[00:21:08]But, if you zoom in, you might change those dots to neutrophilic dermatosis, arthralgia, uh and uveitis. And those are very different dots than what else they could be.

[00:21:18]So, the first thing in medicine is to clarify each individual component to a much more precise dot and then connect them rather than connect the balloons um uh and uh larger structures. So, the eye element is hectic and progressive, and I think finally potentially a window to begin clarity on this. So, my mind hasn't thought of anything except what's up with the eye, and the progress we made in that domain is what we suspected, I think, based on how patients typically tell the story, the fact that there's no redness, the fact that there's no discharge.

[00:21:49]We're in the back of the eye, and um I think the exam will help us a lot, and I'm really looking forward to to seeing how we can ultimately connect the dots, but I think the eye is where the money's at for now.

[00:22:00]All right, Varsha. Link to you.

[00:22:03]Um for the examination, we have the vitals, um and he was hemodynamically stable um with a heart rate of uh 104.

[00:22:13]Respiratory rate was normal um and he uh was afebrile.

[00:22:18]Systemic examination, the cardiovascular system revealed a regular heart rate rhythm without any murmurs, rubs, or gallops. Respiratory system, the lungs were clear to auscultation bilaterally.

[00:22:29]The abdomen was soft to touch, non-tender, non-distended without organomegaly. CNS showed no abnormalities um on motor, sensory, or cranial nerve exam.

[00:22:40]For the head and neck exam, um there was no conjunctival injection or scleral icterus. Mild upper eyelid swelling was present. Extraocular movements were intact, but move uh the movement had reproduced pain on the left eye.

[00:22:55]The oropharynx was clear with moist mucous membrane and no oral ulcers or thrush. A firm erythematous nodule was noted along the right helix um with surrounding erythema that did not spare the pinna.

[00:23:08]And the left ear was normal. The neck was supple with no cervical, supraclavicular um lymphadenopathy, no axillary lymphadenopathy present. With the skin examination, the skin um was notable for slowly healing lesions over the right hypothenar eminence at the site of a prior biopsy he had had.

[00:23:28]Small pustules were present over the right second and third MCP joints.

[00:23:34]Extremities uh revealed um bilateral uh pain uh the calves were painful to palpation bilaterally, and there was a localized linear area with some surrounding um erythema.

[00:23:48]Similar uh linear erythema was notable over the ankle regions um on the right side more than the left. There was um one plus bilateral uh pitting pedal edema.

[00:24:00]The MSK examination revealed uh a right uh greater than the left carpal metacarpal squaring and uh Heberden nodes on multiple fingers.

[00:24:11]There was tenderness um of the right fourth proximal interphalangeal joint without signovitis, and I'll stop.

[00:24:21]Oh my gosh, what an incredibly detailed exam.

[00:24:24]Yeah, Lorenzo, if we if we stay true to the exercise of studying the eye and then um picking up things thereafter, what progress do you think you're able to make around the initial chief concern the patient had?

[00:24:36]So, now we have the upper eyelid swelling and intact movements, but left eye pain.

[00:24:44]I was trying to see if the Teflon plate was in both eyes or just in one eye uh to see if that's somehow related. If it's just a foreign body causing discomfort or if it's something more uh related to the vessels behind the eye the the eye, and this uh makes it more asymmetrical in terms of affection.

[00:25:07]Uh I did not uh hear in terms of uh vision problems per se if we had scotomas, if we had color vision problems.

[00:25:16]Uh that would make me more inclined to think that there's a problem with the retina, either um structural problem uh or an a vascular problem affecting the retina itself. Uh I think what's key in this case is trying to grasp onto something that's more specific and using that to to get to the final diagnosis, and uh somehow my gut feeling is telling me to either join to try and join the skin and the eye um and the inflammation background. Um the fact that we have um uh palmar involvement, there's not many diseases that cause a skin rash uh either in the in the soles of the feet or in the palmar aspect of the hands.

[00:26:02]Uh usually uh we either have uh something like uh rickettsia, like Sweet's syndrome or Behçet's. We have uh gonorrhea, uh we have endocarditis, syphilis.

[00:26:17]Uh that that's a very narrow spectrum of differentials. Uh all of those can lead to eye problems and um cutaneous problems, and even with a polyarticular involvement. So, um right now I can't make much progress that that I can't see from the physical exam. Uh apart from that, uh labs will probably help. Um let me see.

[00:26:43]The pa- the fact that the patient has edema, I'm not put- putting much stock into that because we have a vulnerability in the past medical history that can um explain that uh without being too much involved in the present illness with the fact that the patient has a alcohol use disorder and uh has smoking habits, uh which could impair the heart or the liver.

[00:27:05]And the proximal interphalangeal joint swelling with Heberden nodes, not really familiar with those ones.

[00:27:15]Um and that's what's going through my mind right now.

[00:27:21]Ooh ooh ooh yeah. Can I ask you a quick question?

[00:27:23]So, you see many patients, right? How long into a average clinical encounter do you think we are in right now when a patient starts and how much time has elapsed in real life, you think?

[00:27:36]Maybe an hour. Hour to hours. Oh, you're Yeah, right. You know, it's probably like 45 minutes with the patient and an hour really deep chart review, right?

[00:27:49]I will tell you a simple rule of thumb.

[00:27:51]For every day the patient has a disease, you have an hour to figure it out.

[00:27:57]How long has this patient been suffering from?

[00:28:00]Many, many, many, many, many days.

[00:28:03]There is no way in real life you can have specific, concrete diagnostic hypotheses. That's very different than, "Hi, Lorenzo, I have apoplectic sudden onset 3 seconds ago chest pain."

[00:28:19]You have 2 seconds to figure it out.

[00:28:22]Right? This is a disease that is brewing and building and and has grown so much complexity in it for that for you to really understand it, you have to disentangle so many different pieces.

[00:28:35]And so, there's a prominent surface component. And I think the observation that I have is that the patient has a lot of symptoms at the surface.

[00:28:44]A lot of rashes, a lot of arthritis, a lot of things that you see here or there, but the truth is that the most uh concerning abnormality is that two things are compromised. His vision, at least in a subjective sense that it's blurry, and that his weight is compromised.

[00:29:04]And so, I ask myself, how could somebody with a disease that's localizing in the extremities lose weight?

[00:29:10]Why why would those nodules, that rash, those arthritis cause somebody to be consumed? And if you look at the base rate of wasting syndromes that exist in the extremities, there's like three diseases that live just on the surface and somehow impact caloric ingestion, digestion, and absorption.

[00:29:30]Doesn't happen.

[00:29:32]So, for me, I'm really interested to say, "Okay, I'm cool, and these are a lot of like tantalizing little nodules on the surface, but this person's lost 25 lb. Where is that coming from?"

[00:29:42]And so, for me, there's a major vacuum in this case, which is what's happening in his chest and his belly.

[00:29:46]And an exam is interesting, but I think visceral imaging is going to be really, really key, but that starts with the labs. Because you expect that if somebody just has a disease at the surface that their labs will be underwhelming. Blood-based testing is designed to help you understand if a patient has a systemic fingerprint to their disease. So, I'm right there with you. I'm not thinking about this case in terms of trying to figure out what a upside-down oozing erythematous nodule on the left ear tells me.

[00:30:14]This person's lost 25 lb of weight.

[00:30:16]That's way more important.

[00:30:18]And this person's vision potentially is at risk of being lost. That's way, way, way more important.

[00:30:24]So, I am telling you that if you are if you are thinking of a very specific diagnosis in this case, odds are that if I if I present 100 cases like this, you'll get it right maybe twice.

[00:30:36]That right now you really need to understand what's the problem, and there are two major issues. Weight loss and vision changes. The rest are decorating pieces.

[00:30:45]So, I'm right there with you. I think we have to understand the vision loss better, and the progress we've made is there doesn't seem to be orbital pressure. Um there's no restriction with motion. There's no proptosis. So, I'm wondering is there something is there something happening in the back of the eye? Is this a itis in the back of the eye? Optic neuritis is the most common. But you can also have posterior uveitis. You can have posterior scleritis. You can have necrotizing retinitis. So, I think having somebody look at the back of his eyes really, really crucial. And then having uh starting a systemic evaluation with blood work and then potentially imaging.

[00:31:19]So, we're very much in the what is this problem rather than what is this answered. 2 hours into a 6-month-long saga. We have plenty of time to make progress.

[00:31:31]All right, Varsha, mic to you.

[00:31:35]Um I have some of his initial labs. Um we have the WBC, which was 4.6.

[00:31:41]Hemoglobin was 13.8. Platelets was 239.

[00:31:45]Um for the renal profile, we have a creatinine of 0.8 and a BUN of 15. His glucose was 268. Um for the electrolytes, we have a sodium of 136, potassium of 3.9, chloride of 102, bicarb of 23, and calcium of 9.4.

[00:32:03]With the liver panel, we have an AST of 12, ALT of 17, and phosphorus of 82.

[00:32:09]His total bili was 0.4. Um total protein was 8.3 with an albumin of 3.1.

[00:32:16]His thyroid panel came back normal. Um urine analysis um uh showed a 2+ protein.

[00:32:23]ESR was 40. Um CRP was 4.3. CK was 105.

[00:32:29]Uric acid was 8.6. And just to summarize, we have elevated inflammatory markers, high serum uric acid levels, and protein.

[00:32:39]I can stop here or I can give you more labs if Uh Varsha, maybe I can just ask um do you know how many uploads you have left until the reveal? Just to pace ourselves for it's very >> just two more and um the third one will reveal the diagnosis.

[00:32:53]I see. So, two more rounds of information and then a final reveal.

[00:32:57]Okay.

[00:32:58]Um yeah, Lawrence, maybe we can just stop here. I'm curious what what your reflections are on the on the data that you were looking for.

[00:33:04]Um I didn't catch the CRP and ESR if you have given us. I couldn't make the value.

[00:33:12]Um the ESR was 40 and CRP was 4.3.

[00:33:17]4.3, okay, got you. So, from this blood work up till now, we have nothing to go off for and unless the inflammation or the slight touching inflammatory markers.

[00:33:30]Uh and what caught my eye, but I'm not yet making much progress into that is the albumin and the total protein. I also think I heard that the UA also had protein in it, but I'm not making I'm not sure if I heard that correctly. But it's 2+ protein. 2+ protein. Okay, no no RBCs?

[00:33:50]No RBCs.

[00:33:52]Okay. So, um we have proteinuria.

[00:33:57]We have no kidney damage.

[00:33:59]We don't have we have albumin that's lower than 3.5.

[00:34:05]Uh usually we we can make progress with this. Um we could even think about nephrotic syndrome.

[00:34:15]But only with a good with a good measurement of the protein ratios or total protein in the urine in the 24-hour urine could we make that assessment or say that with 100% sure.

[00:34:29]As of now, not nothing much to go on. Only that we have a multi-systemic disease that's impairing the eye, that's impairing the kidneys most likely, that's impairing the skin. Um And the fact that we have weight loss.

[00:34:44]So, we have to trigger our our weight loss schema and we either divide the inflammatory causes and non-inflammatory or end organ causes.

[00:34:53]And in inflammation bucket, we have the inflammatory or autoimmune {slash} infection diseases infectious diseases or cancers.

[00:35:03]Um Nothing jumps out to my mind as of now that could be the cause of of inflammation in this picture.

[00:35:12]I'm still stuck in the infection {slash} autoimmune bucket. Uh nothing screams out cancer as of now. We have a very normal CBC.

[00:35:23]I'm not sure if there was an LDH, but if there was, I'm not thinking that it would would be too high at this point.

[00:35:30]And the uric acid as of now, I'm not putting too much stock into it.

[00:35:36]Um Yeah.

[00:35:38]Those are my thoughts.

[00:35:40]Yeah, I share those. You know, if you're listening to our conversation, you're seeing that there's a lot of friction towards making a diagnostic progress, and I think you can see why.

[00:35:48]Um uh Lawrence, so this is a very, very difficult case to discuss, but it's even more difficult case to diagnose in real life. And I think all that I have to offer is just to reinforce what we said earlier. We're seeing evidence that this is a slowly smoldering disease. The white count is normal, the hemoglobin is normal. How many patients with 25 25 lb of weight loss have a normal hemoglobin?

[00:36:09]So, you can see why this disease evaded diagnosis for the the time that this person is suffering. It's a very gentle disease. And I think acknowledging that is really, really key. But its gentleness seems to have been broken by this 24 hours of my head really hurts and my vision is blurry. And so, I think that remains the most likely way to finally provide some clarity and hopefully a path to healing for this patient. And so, I think Varsha has shed light on the subacute disease elements.

[00:36:40]Um and viscerally in terms of blood work, there doesn't seem to be uh uh need for recalibration of how serious and severe that is. It's been smoldering on, and these labs suggest that there is that smoldering. And so, now I'm just like on the phone with the ophthalmologist to be like, "Hey, we have finally an opportunity to crack this case. Help, please."

[00:37:02]Um yeah.

[00:37:04]All right, Varsha, mic mic to you. What do you have next?

[00:37:07]Okay. Um like you mentioned, I have some of the autoimmune and the infectious labs that came back. Um HIV was negative. TB Quantiferon was negative.

[00:37:18]Hep B and Hep C was negative.

[00:37:21]Um ANA came back negative. ENA panel came back negative. Rheumatoid factor came back negative. CCP was negative.

[00:37:28]ANCA was negative. And the complements were normal.

[00:37:32]IgG was um 1850, which was elevated. IgA was 933, which was elevated. IgM was normal.

[00:37:41]Serum free light chain ratio was normal with an SPEP being negative and a UPEP being negative.

[00:37:47]The blood cultures were negative. Fungal blood cultures were sent, which came back negative. And serum cryptococcal antigen came back negative. Um we also had a CSF analysis done with a normal study with a normal opening pressure, no WBCs, 32 protein, glucose of 50, and an RBC count of three.

[00:38:06]Um I could share the imaging um in this upload and the next one will reveal the diagnosis if that's okay.

[00:38:20]Dr. Abe, I think you're muted.

[00:38:22]Wow, thank you, Lira. That's the first time you bailed me out. Thank you.

[00:38:25]Um I'm going to keep a list of people who rescue me from the mute failures. Uh Yeah, Varsha, I think the imaging is going to be really, really helpful. Um so, I yeah, please go ahead and share it, and then we can just um do a long breakout room to try to see what progress we can make.

[00:38:40]So, go ahead.

[00:38:42]We have the X-ray of hands, which showed joint space narrowing and osteophytes of the PIP and the DIPs.

[00:38:50]A CT of the chest, abdomen, and pelvis came back normal.

[00:38:53]Lower extremity venous ultrasound was done, which revealed bilateral superficial thrombophlebitis without any DVTs.

[00:39:01]MRI of the brain and orbits revealed optic perineuritis of the left eye and bilateral dacryoadenitis.

[00:39:08]Um Further workup was done to understand this ocular pathology, and IgG4 level was sent, which came back high with a value of 2.6.

[00:39:18]Um a toxoplasma IgM antibody was done, which came back positive with a negative IgG antibody.

[00:39:26]I'll stop here.

[00:39:29]Oh, sorry. I just to clarify one thing, Varsha. The last thing you said, I missed what toxo something was positive and something was negative, but I missed that cuz I was creating the breakout room. So, what was it again?

[00:39:39]Toxo IgM antibodies were positive and IgG were negative. Okay. All right.

[00:39:44]Thank you.

[00:39:48]All right, Lorenzo. Any uh I figured we would you know, we have 20 minutes so we can kind of mix our thoughts in a breakout room. Is there anything you want to clarify from Varsha before we uh go ahead and do that?

[00:39:57]Uh just the immunoglobulin levels. Uh again, I think I caught everything else, but those I didn't.

[00:40:06]We have an IgG of 1850 and an IgA of 933. And then IgM was normal.

[00:40:15]Okay. Thank you. Yeah, Varsha, please correct me if I'm wrong. My mental model is that the IgG is elevated and the IgE is elevated. So, uh G and E are uh uh yeah.

[00:40:25]>> G and E were elevated G and A's I Okay.

[00:40:29]Got you. That's very helpful. Sorry.

[00:40:30]Okay. All right.

[00:40:31]All right. Let's sort it out together.

[00:40:35]I'll see you all in like 5 minutes or so.

[00:40:45]You're muted, Robbie.

[00:40:47]Oh my gosh. Like uh what am I going to learn? Sorry, I had a I had a late night shift, so I woke up like 30 minutes before the session. So, I uh I appreciate uh the the assistance here. Uh Lorenzo, I what I was saying was that unfortunately your wish did not come true about not being bamboozled. I think both you and I are a little bit uh a little bit struck by the the uh awesomeness of this case. So, I'll hand the mic to you to see where your thoughts are. We can we can have a little conversation to see what progress you can make. Take it away.

[00:41:18]Uh I'm very lost right now.

[00:41:21]>> [laughter] >> Oh no.

[00:41:22]>> There's nothing that there there isn't a single thing that I'm keeping track of or that I'm holding on to uh to follow that through till the end. Uh we had the the I um the eye involvement. We also we have that on imaging with perineuritis or with optic neuritis. We have dacryocystitis.

[00:41:44]We also have skin involvement. Uh I'm also like everyone else in the chat dying for an RPR test. Um but the dacryocystitis itself makes me think of uh with the IgG4 uh levels uh make me think of IgG4 related disease.

[00:42:02]Not that I think that it explains everything uh that the patient has, but at least it could be a Mikulicz syndrome uh with the uh gland lacrimal gland involvement and possibly some uh some uh salivary glands involvement. Uh although I don't think the patient has any of that.

[00:42:26]Wouldn't really explain, I believe, um the proteinuria or isolated proteinuria.

[00:42:31]Uh we also have that serology for toxoplasmosis. Uh not really sure what to make of it.

[00:42:38]I read about a case in NEJM uh last year or 2 years ago where the patient also only had optic neuritis and we it was I don't remember the specific conclusion of that case, but it was some sort of uh vasculitis that was affecting the optic nerve sheath alone and it was causing uh sort [snorts] of ocular presentation similar to this one, but it what it didn't have that much of systemic involvement. Uh so, I don't really know how to make much more progress uh with this. Um the thrombophlebitis itself uh superficial if it was migratory, I would think of true sole syndrome uh with an occult malignancy that could be affecting uh could have multisystemic involvement, uh but we don't really have any particular sign to that, I believe.

[00:43:29]Uh the LP was normal. The MRI didn't show anything apart from the lacrimal gland involvement and optic neuritis.

[00:43:37]Um I'm all over the place. That's the conclusion.

[00:43:40]>> Not at all.

[00:43:41]You're not all over the place at all. I think that um Yeah, I think that your thoughts are tracking exactly with what I what I'm thinking. And I you know, I'm anchoring myself in actually the ocular findings cuz I find them very very dominant.

[00:43:52]And I think they ring true to the idea that when something's smoldering and then explodes, as I've said three times now, uh let's go go where the acute action is to help you crack chronic mysteries. And I think you need to have a rich understanding of what optic perineuritis is to be able to make a lot of progress.

[00:44:07]And I think that um fundamentally, uh optic neuritis is an extremely different disease than optic neuritis. And let me just take a moment to share with you a simplification.

[00:44:17]Optic neuritis are a set of diseases that extend from the brain into the uh into the optic nerve.

[00:44:24]So, these are conditions that Sarah will be diagnosing left, right, and center in a couple of years from now.

[00:44:29]Um where she will say this person has MS or neuromyelitis optica spectrum disease or uh or a MOG and so on and so forth.

[00:44:38]However, she'll spend her intern year diagnosing conditions that cause optic perineuritis because this optic perineuritis is an internal medicine diagnosis.

[00:44:47]Instead of the disease radiating from the brain into the optic nerve, which causes optic neuritis, optic perineuritis, which refers to the inflammation of the sheath around the optic nerve, is a systemic internal medicine condition that goes to the sheath as opposed to a neurological condition that goes to the middle of the optic nerve. And you are seeing that play out by seeing elements not of a brain condition cuz the MRI is completely normal, but swelling of the lacrimal glands um uh and involvement of the skin and the joints. So, you can tell immediately that this is a systemic internal medicine condition that is infiltrating the eye and then right there up to the nerve sheath. This is not MS. This is not neuromyelitis myelitis optica. In fact, the only neurological condition that causes perineuritis is anti-MOG, which is fascinating, but this is not the case.

[00:45:37]So, this becomes really what is what kind of systemic diseases have a tropism to affect both nerve sheaths on both sides? And I will tell you a simple rule of thumb, which you know, whenever you have symmetry whenever you have symmetry the answer is almost always autoimmunity.

[00:45:54]Infections result in asymmetry. Cancers result in asymmetry. And if we took a picture CT abdomen pelvis and found a large cavitary lung lesion or a dominant liver mass, then there's asymmetry. So, here this is an autoimmune disease until proven otherwise. But the question is, are there exceptions to the rule? Are there infections that are chronic and symmetric?

[00:46:20]And I think the answer is yes. It's chronic viral infections like that devastating diagnosis of HIV, which was negative here.

[00:46:27]And the other chronic and asymmetric uh condition are spirochetes, especially syphilis. So, I think for me if I could only get one test for this patient, it would be syphilis testing.

[00:46:39]Why is syphilis lower on my radar as a complete explanatory lesion? Is it doesn't explain the arthritis definitively and it doesn't explain the dacryoadenitis.

[00:46:50]And so, while I would not move beyond getting an RPR, I even if it was positive, I would still proceed with the workup of what other underlying autoimmune disease a patient might synchronously have.

[00:47:02]And uh Lorenzo, there's only three space-occupying autoimmune diseases.

[00:47:10]And I think that's another leap, right?

[00:47:13]We're saying that this person has an autoimmune condition that's taking up space.

[00:47:17]And I think we see that the space is taken up by having a space-occupying rash which are these pustules, not a flat macular rash or a popular rash or purpuric rash, but also that there's space occupation in the bilateral lacrimal glands.

[00:47:33]And you mentioned them, IgG4 disease histiocytic diseases and sarcoidosis.

[00:47:40]There's a fourth category of the ANCA vasculitides that can take up space, but um I think for many reasons, including something that you specifically looked for, the lack of hematuria, that's less likely. So, when whenever I'm leaping into this world of space-occupying diseases, I ask myself like um uh is this IgG4 disease, sarcoidosis, or histiocytic disease? And the truth is that the patient can easily have any one of those things. The only way to make progress on a space-occupying autoimmune disease is to is to do high-quality histopathological analysis.

[00:48:14]Uh you have your leading suspicion as to which one it is, and I agree. I think IgG4 disease is a great fit for optic perineuritis for lacrimal gland involvement. The friction for IgG4 disease is um the arthritis and the pustules.

[00:48:29]Uh sarcoidosis is a great fit for optic perineuritis and lacrimal gland involvement, but the major counterargument against sarcoid as finding this present in 90% of cases is pulmonary findings.

[00:48:41]Uh what about histiocytic diseases? And I think this is where the beauty of hanging out with too many rheumatologists, including uh someone who will be named shortly, uh and um and my wife is that um that and there's a lot of overlap in the world of histiocytic diseases and IgG4 disease, a tremendous amount. And I've come to believe that histiocytic diseases and IgG4 disease are actually part of the same umbrella spectrum. And my wife, Cara, recently presented to the Academy a case of AA POx uh which is adult-onset asthma with periocular xanthogranulomas, a histiocytic disease that has strong overlap with IgG4 disease.

[00:49:20]And here uh the arthritis, especially the DIP involvement uh and the skin lesions have me wonder whether the patient has a specific kind of histiocytic disease called multicentric reticulohistiocytosis.

[00:49:35]All that to say who cares? You need a biopsy, I think, to make progress and I suspect that if this person's syphilis testing is negative, uh immunosuppression, probably in the form of rituximab, is uh is going to be uh really helpful for him.

[00:49:53]Um So, yeah, that was a lot to digest. I'm I'm It's really a lot outside. I'm curious what uh questions or clarifications you have from that reflection, but I'm fully aligned with your syphilis as a place to start and then autoimmunity, IgG4 disease, histiocytic diseases where I think for him. What's your >> Nothing to say to add to that.

[00:50:14]All right, Varsha, educate us, please.

[00:50:16]What happened?

[00:50:17]Um we had an RPR done, which came back negative. Um we also did a bone marrow biopsy, which showed normal cellular bone marrow with a trilineage hematopoiesis. Occasional myeloid precursors with cytoplasmic vacuoles were present. Um negative for increased blast, significant dysplasia, or a monoclonal plasma cells. And due to his um clinical uh presentation and his bone marrow findings, we also did a gene testing for UBA1 gene, which came back positive and the patient was diagnosed to have VEXAS.

[00:50:51]Fascinating. Oh my gosh. Lorenzo, what do you think?

[00:50:55]As soon as I heard vacuoles, I was like, okay, we have skin, we have autoimmunity, we have everything. He's a male, 50 years old. Okay, VEXAS fits really well.

[00:51:06]Um What a masterful class presentation, Varsha. Thank you for the case. I will have to do much studying after this session, and I'll have to do a cognitive autopsy to better understand what could have made me uh better understand the patient. Thank you.

[00:51:25]Yeah, there's a lot of reflecting to do.

[00:51:26]I think uh in retrospect, um when if you represent this problem as uh a man over 50 who has superficial venous thrombophlebitis and orbital VEXAS is a really, really good fit. Um I think, yeah, we're chronically under-diagnosing this condition and I think we symbolize that again today, just the power of Um I think the the deeper uh truth here about VEXAS is um that it, too, is a disease under the myeloid uh uh realm of conditions and Jeffrey and uh and Kirtan continue to teach us about the depth and the reality of a lot of these diseases, including uh what I thought this disease was as a histiocytic disease, and many patients with histiocytic diseases harbor uh mutations in the myeloid uh uh in the myeloid spectrum of diseases. So, yeah, I think, ultimately, uh it makes so much sense. Uh I think the uh real-time kind of autopsy that I have is pustules equals neutrophilic dermatosis, which is a very uh characteristic feature of VEXAS.

[00:52:36]Um the uh hypercoagulability is a feature of VEXAS, and then many, many patients with VEXAS have prominent orbital manifestation. So, when you slice this really complicated case with the neutrophilic dermatosis, eye findings, and hypercoagulability, I think VEXAS is a fantastic fit and a really, really humbling lesson for me, cuz it was not at all on my radar, even though I have uh recognized we we miss it a lot.

[00:53:04]Varsha, I'm really curious what you you went through all this to put this case together, refine it, present it, and learn from it. What what stuck with you?

[00:53:12]Um it was an incredible experience, cuz the first time I came across the diagnosis, there was a lot of learning for me, and I'm assuming you all figured out who the case was shared by. It was Dr. Jeffrey, um who did an incredible job and caught on to the diagnosis very early on. Um he also um shared an incredible um fact, which I was not aware of, which I'd like to share, which is um any new autoimmune skin disease or a refractory disease, um especially if it is a vasculitis in someone who's elderly, like 60 or mid-50s, um it's always concerning for a paraneoplastic um it's a paraneoplastic manifestation. And if no cancer can be found um by regular imaging, it's always important to look for occult cause, which um Lorenzo actually mentioned in our breakout rooms as well.

[00:54:01]And um in this patient, um we got on to the VEXAS very early on before um any such diagnosis was made, but he later did um go on to develop myelodysplastic syndrome, which was very interesting.

[00:54:16]Yeah, it's incredible to me that uh you know, you you and Jeffrey had never met a month prior, and here you are exchanging knowledge and wisdom. Um I think Jeffrey is uh reason number one to join the Academy, an incredibly kind human being who's so passionate about medicine. Yesterday, he was teaching uh about uh about electrolytes, and today he's teaching about VEXAS syndrome through the lens of two learners, Varsha and Sarah, which is just so cool. So, big, big shout-out to uh to Jeffrey and uh Yeah, thank you for awesome hour.

[00:54:49]Lorenzo, this was a really, really tough case, and I'm glad I had uh I had you. I'm sorry that I didn't live up to your hope that I would try to help you.

[00:54:58]But, I think there's no uh there's no bigger joy for me than to be able to have the opportunity to learn from a case, and gosh, I I think like you, I'm going to be lost in the world of reading on this case. Is there anything that you wanted to emphasize or say that you Yeah, I wanted to just hand you the mic for any final thoughts before we learn from you, Jean.

[00:55:18]Uh just trying to uh better understand what can be specific enough to latch on to. I think in these types of cases where we have too much going on. This case was hectic.

[00:55:32]Uh we have to latch on either to the primary or chief complaint and follow that through, or uh find something either in the exam or in the testing that we do that's specific enough for us to reach the final conclusion. Um unfortunately, there was nothing that I could latch on to until the final bone marrow, but yeah, every kind of learning is good learning, so Yeah, agreed. I think that um yeah, I I I I I I I I I I I I I don't think I have anything to add to that. This case was a lot about like signal and noise and a lot of difficult signal to grasp. Um I think the bone marrow really gave us a lot of momentum, so I completely agree.

[00:56:13]All right, Eugene, mic to you, my friend.

[00:56:18]Yeah, very fantastic case. I don't know where to begin. Um because I usually I have a pattern of latching on to probably the history, lab findings, to be able to try to make sense of the case, but um this case we had VEXAS, which you mentioned that is a somatic mutation in the UBA1 um gene that uh affects the hematopoietic cells, and so there's um overproduction of myeloid myeloid lineage. And it seems to um lie in between inflammatory and autoimmune, but not really with um production of um autoantibodies.

[00:57:05]Um you mentioned that in retrospect, if we have patient with uh eye signs pointing to vitis, and then superficial thrombophlebitis, VEXAS can fit.

[00:57:19]Uh but uh some very important um key messages that I think we can all take home with is that when you have a patient complaining of um headache, and um mentions that it's worse since with eye movement, you could start thinking about causes of eye pain.

[00:57:40]And to localize eye pain for anterior eye diseases, corneal ulcerations, conjunctivitis, they usually transmit pain. So, that can be one of your buckets of thinking. Um you could also think about posterior eye diseases, um but they are usually painless, but if especially when you're looking at the ischemia to the the um to the retina or detachments, you're you're not thinking about pain.

[00:58:13]But, if there's inflammatory causes, so uveitis, um optic neuritis, you can have um pain.

[00:58:22]Um when you have pain in the eye and there's no redness, the likelihood of a superficial anterior eye disease comes down. However, it's still possible, especially when there's corneal stretch.

[00:58:35]And so, we put together the eye pain plus blurry vision plus the headache, we thought that this may suggest um so, Lorenzo mentioned it earlier on, this may suggest a raised intraocular or um intracranial pressures.

[00:58:52]Um but it fitted more for the raised intraocular pressures because of um the the the the differential of glaucoma, but partly for raised um um intracranial pressures or inflammatory causes, so the inflammatory causes, like the vitis and optic neuritis, um they may not cause headache, but they raise intracranial pressures, they may not cause the eye pain.

[00:59:20]And then we had some systemic fingerprint. So, we had a patient having weight loss. I mean, there was a whole lot going on, but what did we latch on to make sense of this case? It was weight loss, there was polyarticular pain, and there was some skin lesions.

[00:59:36]There was papilledema where with trauma, the patient has a lesion there. There was popliteal thrombophlebitis.

[00:59:43]And then we came to the labs. We had raised um inflammatory markers. And so we were thinking about a systemic inflammatory process, whether autoimmune, whether autoimmune. And with autoimmune, Dr. Ravi mentioned about the space-occupying types, example the IgG myeloma disease or multiple myeloma disease. And we were also thinking about infectious causes, which was hinted by Lorenzo Anea.

[01:00:07]Um but the labs took out the the common infectious causes cuz we were thinking HIV could do this. It could really manifest very like the syphilis could do this to some extent.

[01:00:19]But not too much with the arthritis and then vasculitis.

[01:00:24]But they all came back negative.

[01:00:26]And um it was also that we should consider as less malignant in this case, although there was the weight loss.

[01:00:33]Um so what could help us? We also had some noise which I wanted to take notes of. If you have toxo IgGm, there's a lot of false positives, so you don't latch on that simply think there's toxoplasmosis going on there.

[01:00:48]Um cryptococcal IgG IgA raised with negative crypto antigen, you need to interpret that carefully.

[01:00:55]And then we were looking at doing a biopsy. I wasn't expecting diagnosis.

[01:01:00]Initially, I was thinking vasculitis. I think that's a lot of what many people were thinking, especially Behcet's, which could have fitted very well with this um this particular condition. However, we ended up having the the the Dexus, which is, like said in the um from the beginning, that's somatic mutation in UBA1 gene leading to overproduction of myeloid. Moreover, after the myeloid line is still sick, that's where I'll I'll put my teaching points.

[01:01:29]Thank you.

[01:01:31]Uh yeah, I think you know, discussing this case is hard, but trying to recap learning from such a uh topsy-turvy case is a skill of its own. Uh you're more than ready to hop in and do this every day in an intern year. Kudos to you. Uh yeah, I think we're going to be spending a lot of time reflecting on this case in our own heads and probably uh internally in the academy. So I'm sure I'll see some of you there. Uh for the rest of you, I hope you'll hop on to VMR 15 minutes early. Uh we have a I have a really fun uh case for you all for our uh public academy session tomorrow. So I hope to see some of you there.

[01:02:04]Thanks, everyone.

[01:02:05]Bye.