Episode 440: Subspecialty Episode – Pelvic & Joint Pain

(upbeat music) - Welcome back clinical problem solvers. Maddie and Yusuf here. At CP solvers, our mission is to make clinical reasoning accessible to learners worldwide. We invite you to join us for our live virtual morning reports where we break down cases and sharpen our diagnostic reasoning together. Now over to you, Yusuf. - Thanks, Maddie. Just a quick reminder, this podcast is for educational purposes only and is not a substitute for medical advice. Patient details haven't modified to protect their privacy and the views express your own not those of our employers. Now, let's dive into the case. - Enjoy the show. (upbeat music) - Okay, welcome to the clinical problem solvers. Thanks for joining us in the holiday week. I know you guys must be either busy with working or spending time with family. So thanks to everyone who's joining with us. Today we have a really special guest, Greg, who is going to be presenting a case to us. So I'm gonna let Greg, you know, for those of you who don't know I'm introduced himself. - Hi y'all, my name is Greg Kirshin. I am a current second year Maternal Field Medicine Fellow in Philadelphia. My clinical interests include diagnostic reasoning, pregnancy physiology, pharmacology and pregnancy. This is not gonna be a pregnancy related case, but I thought it was a very interesting case. So, very excited to be presenting it to Jeffrey. - Yeah, amazing. And then I believe we have Siva who's scribing. Siva, do you wanna introduce yourself? How are you doing? - Hi, I'm doing good. I'm Siva. I'm originally from India, currently based in Buffalo, excited for the case today. - Awesome. And I think Julia's doing teaching points. How are you doing, Julia? - Hello, everyone. I'm Julia. I'm at coverage from Brazil, actually, in Arizona. And yeah, I'm doing great. I'm excited for Greg's case. - Awesome. All right, well, why don't we get started, Greg? - All right, let's do it. So Alpah 1 just could be the chief complaint. So this is a 30 year old male who originally presents to your clinic with a constellation of several symptoms. He has had lower abdominal pain, pelvic pain, perianal numbness and tingling, as well as aches and pains in his, both his upper and lower extremities bilaterally, especially in his fingers that have been going on for actually several years, months to years duration. - Okay, awesome. - Let's stop there. - So yeah, I'll start with this, this really interesting chief complaint. So I guess being a rheumatologist, we often see patients for complaints of chronic pain, chronic fatigue. And it seems like we're dealing with a young man who was coming in with a lot of different complaints, but one of the main complaints there is diffuse pain. As we will see with neurology, one of the big aspects of pain that is taught classically neurology is how to localize where this is. So I think that's gonna be one of the important things that we're probably have to do as we go through the history and as we go through the exam. And keeping in mind that in rheumatology because diseases are chronic, and we often see patients after a chronic history, that there can be actually multiple different complaints at the same time. So multiple different localizations, or you can even have one localization and have multiple different contributing factors to it. So we only need to keep that in mind. Kind of just starting in the beginning thoughts of what kind of things that I would be interesting to know in the history. So most people who have pain and aches in many different areas of the body don't also have a symptom of numbness or tingling. When you have numbness or tingling, that is a little bit of a suggestion that partially some of this may be due to nerve involvement. Now this is a little bit complicated because nerve involvement doesn't mean that this necessarily has to be a primary neurological process. For example, you can have lumbar spinal stenosis and that's more of a degenerative or orthopedic process and secondary nerve involvement. So right now I'm trying to figure out, is this a primary neurological process or is this a secondary neurological process? The other thing I'll point out is this complaint of perianal numbness is quite specific, unique, and it's not something that people typically complain of when they just have a pain. So what could be the cause of this? I think that will be another thing that we will want to key in. When did that specific symptoms start? All right, Greg. - All right, thanks so much, Jeffrey. Very rich discussion already. I'm about to hit you with a lot of information here on this history of present illness. So he had been in his usual state of health until he actually had back to back only mildly symptomatic COVID-19 infections. This was about three years ago. At which time, he was noted to have high COVID-19 antibody titers. Just a couple of weeks after resolution of the infections, he noted pain in his buttocks, anus, penis, and scrotum, as well as his right lower quadrant. He reported some dysuria, but no hemateria, some urinary hesitancy with some midstream involuntary urethral sphincter contraction, no incontinence. This was associated with some perianal tingling, but no loss of bowel function, and he is also able to empty his bladder. On review of systems, he also reports that around this time, he has been experiencing aches in his fingers, especially with stretching, myalges in his arms and legs, and some tingling in his feet. The pain in his buttock has limited his ability to sit for a long period of time. Your reports periodic dysysthegias and paracetegias in his upper and lower extremities, as well as some shooting pain in his feet, which he was told was consistent with plantar fasciitis. He interestingly also has had kind of waxing and waning redness in his right foot, denies any rain out phenomenon. At the time of his initial evaluation, he was recommended to see a physical therapist for pelvic floor dysfunction, and was prescribed pregabaline, gabapentin, and ibuprofen for suspected neuropathic pain, as well as pelvic floor Botox injections. His pain and his paracetegias have now persisted for several years waxing and waning in severity. Also of notes, a few months after his initial evaluation, he had a protracted episode of pain in his right elbow after just a minor fall, limiting his ability to play sports, throw a ball or care groceries. He was diagnosed with tennis elbow and has been working with a physical therapist, although he feels that his pain is really only about 25% improved. In the intervening months, he's also experienced protracted pain in his left elbow, and the ulnar aspect of his hand, after a minor fall in the left arm. He now has to take steps slowly when climbing stairs. He was of note very previously athletic, playing baseball, running, and lifting weights without any functional limitations. Now he says if he were to grip an object with strong force, he feels like sort of like a shooting nerve pain in his fingers and palms at last a few days. As far as his medical history is concerned, he has a history of GERD. We talked about pelvic floor dysfunction, insomnia, separate dermatitis, that affects his scalp and his beard, and he also, which I'll get to a little further on, has had some MRIs showing tendon up at the in the large joints, and he does carry a working diagnosis of psoriatic arthritis. In terms of his medications, he is taking gabapentin, pre-gagabalin, ibuprofen, the Botox injections. He has PRN diazepam for insomnia, and he also takes toxin and chastone for the insomnia. He has no known allergies. His past surgical history, he had a right inguinal herner repair with mesh as a child. For his family history, his mother has a history of mesothelioma. He does have type one diabetes in his maternal aunt. He has a cousin with hypothyroidism, and he has two cousins with celiac disease. Finally, in terms of his social history, he has a remote history of chlamydia, treated in 2017, otherwise unremarkable. And I'll stop there. - Wow, such a rich history, eloquent over here that we have. So definitely a lot of things that we're gonna try to have to see, whether they tie together, or are these different things that are happening at the same time, given that it's a chronic disease that we're kind of looking for, chronic conditions that we're looking for, that's one of the most important things to be able to try to figure out. So a lot of times, let a rheumatologist has to evaluate a patient. What we're looking for, what we're gonna ask to do is to identify a pattern. And one of the most important things that can confuse a pattern is that something that can be a sequence of events can coincidentally look like a pattern. So that's one of the things that I'm trying to keep in mind. For example, this all started after COVID, is this something that we need to take into account and is part of the pattern, or is this just a sequence of events where he happened to have COVID and then the symptoms developed afterwards? So that's something that will keep into consideration. Now, I will focus again on what jumps out to me specifically because we have a lot of complaints that can we say be nonspecific and what nonspecific really means is there's a wide variety of etiologies that can cause it. So I think still at this point, the thing that I wanna understand the best is the pelvic symptoms, the pelvic anal symptoms, where he's noticing issues with pain there, but also tingling. So the question that I'm going to try to understand there is what type of pathology are we really dealing with there? And when I think of pathologies that involve numbness or tingling there and pain, the first thing that jumps to my mind is gonna be looking at the spine. Now, if this was an acute presentation, right? And you had someone who came acutely to you with an acute onset of back pain, especially with urinary and pelvic numbness tingling complaints and problems with either retention or other issues like incontinence, one thing you would be worried about is some type of spinal cord compression syndrome or caudaquina. Given this is so chronic, I would be thinking about a different type of etiology, something a little bit more chronic. So one thing I would be curious asked to look at is does the distribution of his numbness or tingling on the exam correlate with the spinal cord pathology? And then you can ask why would somebody who's young have a spinal cord issue? Why would that be happening, right? And so typically in my experience, when this happens, we can ask, is this patient that we're dealing with a weight lifter? And I've seen so far that several times that people who lift weights that are very active, they can have small disc herniations. And that can sometimes cause issues with ridiculous apathy, can cause issues in the pelvic area. So that's one thing that I'm gonna try to figure out is does this pain different in different areas with the numbness and tingling really localized to the spinal cord or not? And one thing that can be helpful with that on a neurological exam is gonna be the reflexes. And then what should we do with the other symptoms that we're dealing with? So in addition, he's not just noticing that there is changes in sensation and pain there, but he's also noticing that there's issues with things like dyseria, hematuria, and changes to his urination. So the question there is are we dealing with a primary pathology that's in the GU tract? Or are we dealing with something secondary, right? So I think that's another part. If we are doing a thorough evaluation of the spine of the neurological issues, and we don't notice that there's a neurological cause for these GU complaints, right? 'Cause you can have, for example, UTIs, secondary things, prostocytis, and that can be secondary to having issues with the neurological sensation there. But if we don't have evidence for that, then we will have to look primarily is there a problem in the GU tract itself? Or is there a problem in this surrounding anatomy there? Now then after that, what should we do with these arthralogias, these changes in color that we're dealing with in multiple different areas? And also documented exam findings previously with plantar fasciitis, erythema of the foot, and even epiconolitis or maybe tendonitis of the elbow. So what we're dealing with here is we're dealing with inflammatory arthritis, but not necessarily of the actual joint, but around the joint. So in rheumatology, we term this inflammatory periarthritis. And what's gonna be really important to tease out here is is there also true inflammatory arthritis? Or is it just mostly periarthritis around the joint? And why is that important? Because inflammation around the joint can have many different ideologies, the most common of which is gonna be working out too much overuse, right? So if you think about the last time maybe that you introduce your shoulder and it feels like it's hurt and it's swollen or red, right? It's because that you have what we think of this mechanical or traumatic overuse and that causes periarthritis and that can be inflammatory. But that will be around the joint and not actually inside the joint. Furthermore, just because if the joint inflammation is kind of not indirectly in the joint, but around it, doesn't mean that it's not a rheumatoid disease either, right? So any actual problems with the joints, the muscles, the nerves can make it harder for someone to do what's normal, right? So for example, let's say you have somebody with neuropathy in both of their legs, it's gonna be easier for them to fall, it's gonna be easier for them to injure themselves. With those injuries, you can have complications like periarthritis. So that's another thing that we're gonna have to tease out. The distribution of these locations, if they were to be a rheumatologic cause, correlate a lot better with a spondylorethropathy than with pure rheumatoid arthritis. Even though rheumatoid arthritis can occasionally have issues like versitis or periarthritis, it's much, much more likely or classic for it to have true inflammatory arthritis. And those complaints are not something that we're seeing technically here. With the involvement of plantar fasciitis, one of the things that will come to mind is to differentiate whether this tendonitis is really just tendonitis or is it enthousitis, which means that there's specific tenderness at the points of insertion. If you have enthousitis, again, mechanical issues can still cause that, but that's where the question of seronegative spondylorethropathy's rise. And then if we look at the seborrheic dermatitis, there's two ways to analyze that. One is it's just seborrheic dermatitis, which can be common, right? And it can cause things like dandruff, dandruff by itself in seborrheic dermatitis is common or one other possibility is that it looks like seborrheic dermatitis, but it may be a different rash. In the classic rash that looks like that would be psoriasis, right? So I can understand why this patient was a evaluative biometologist putting these together, they would think, is it possible that this patient has psoriatic arthritis? Now, one thing that can be missed sometimes in people that are not specifically looking for it is the fingernails. So in people with psoriatic arthritis, they have a much higher incidence of fingernail problems than people with just psoriasis and osteoarthritis, two different things, right? It's not 100% going to guarantee that they have psoriatic arthritis, it's not perfectly sensitive or specific, but it can be a huge hint. So what I'd be asking for looking for is are there changes of the nails, do they crack on their own, things like that? And I'm excited to see what the exemptions. - Awesome, thank you so much, Jeffrey. This is a master class. I think similar to you, when I've thought about this case, it's so hard to sift through all the data figure out, is this an Occam's razor or a Hickam's Dictum, kind of thing, and I think you've done a beautiful job so far of dissecting it. So I'll give you the physical exam, and I also have some images to share with you. So on exam, his vital signs were all within normal limits. He was a febrile, he's no acute distress. In terms of his head and neck exam, he had a clear congenitiva and no scalp tenderness. Let me just share my screen real quick, and I'll show you a couple of pictures. Okay, so this was his ear area. You can see a little bit of a rash, maybe a little bit of redness, flakiness, and then his hard lung exams within normal limits. I'll just quickly show you. This was one of the episodes where his right foot had that erythema. It was non-tender to palpation, however. And then as far as the rest of his exam, his abdomen was soft, non-tender, non-distended. His skin, he had no digital ulcerations, no paler, no cyanosis, no erythema, no plaque or nail pitting. He had full range of motion to his neck, full range of motion to his shoulders. In his arm exam, he had intact sensation to light touch and the radial median ulter nerve distributions, provocative testing for a trigger finger was negative. There was no tenderness to palpation at the base joint of the MP joint or the IP joints of the thumb on either side, no triggering. They did note some thickening of the flexor tendons, middle and right at the A1 pulley bilaterally, left greatest at the middle finger without triggering again with provocative maneuvers with minimal tenderness. There was no, excuse me, no tenderness over the lateral epicondiles on either side, no pain with resisted wrist or middle finger extension while the elbows were maximally extended. Normal back alignment without tenderness to palpation. He had full range of motion in the hips without groin pain, no tenderness in the knees or no swelling, no, and then his feet, as I mentioned, were non-tender to palpation as well. I think the last thing is just his neurological exam. So he was A and O times four, attentive, normal concentration, fluent speech, normal cranial nerves. He had normal bulk, tone, no faciculations, negative prone air drift, formal power testing, showed full strength in all muscle groups. As a sensation, he had slightly reduced the pin prick bilaterally in the mid-shin. Temperature vibration and proprioception were all intact in all dermatomes. He had two plus biceps bricarialis triceps patellar and Achilles tendon reflexes without clonus, hoffman's or crossed a doctor sign response. It was negative planter responses where flexor bilaterally. For his coordination, he had no tremor, negative rhomburg, and then for his gait was standard with normal stride, arm swing and turning, and heel the toe, walking, and tandem gait were normal. And I'll stop there. - Okay, awesome. Wow, what an extensive physical exam and very comprehensive. So I guess I'll just start by going back to what I was most concerned about, which is what is causing these odd symptoms that he's having kind of in the pelvic area. And are those odd symptoms neurologic or are they primarily non neurologic with the secondary neurologic kind of issue? So I think what we're seeing here with the neurological exam is that there's not really, there's not really much in the lower extremities that's showing that there's a neurological issue essential. And that can be tricky sometimes, as sometimes that you can have actual, but still you can have ridiculous apathy that's intermittent or it's very mild. But because we're not having a lot of signal there, it makes me think that it may be more likely that it's a secondary issue. So then what do we do about the other symptoms that we saw? So one of the symptoms or one of the areas that we're looking at is the rash. And I'll say just, you know, of course I'm not a dermatologist, but taking a look at the rash to see whether this is psoriasis or subarietic dermatitis. What would make me think or heavily favor psoriasis in the circumstances would be if it was very scaly. And so the rash that, you know, we're seeing right now, it's a little bit erythematous, it's a little bit scaly. It's hard to really say that it's more than just subarietic dermatitis and actually does go into psoriasis area. I think if it was much more extensive or that there's other locations involved, it would help us understand more. And sometimes a dermatologist can take a look and look at the scalp to see if, you know, which one of those two are more likely. And that being said, you know, you can have severe negative spondylorethopathy, even without psoriasis. So for example, a patient can have angolosing spondylitis or inflammatory bowel disease. And you don't need the psoriasis lesions to have arthritis from those. One other thing to think about, especially in the context of a pre-sitting infection is could this be reactive arthritis, right? Usually when we have patients that have reactive arthritis, in the original description, we learn this kind of phenomenon where we say, can't see, can't pee, climb a tree, right? So the triad there is you have GI or GU infection causing the urinary abnormalities. So the can't see part is usually due to eye inflammation, which often is either conjunctivitis or can even be UVitis or carotitis. And then third, the can't climb a tree is due to the arthritis. And the arthritis is actually usually in a pariarthritis plus an inflammatory arthritis. Now given that in an infection such as COVID was occurring before this, definitely reactive arthritis is something to think about. Most cases of reactive arthritis do go away eventually over time. However, it's thought that up to maybe one-third or one-fourth of cases can be persistent. So that's one thing that we should also keep in our mind. Is there something that activated that? And COVID can cause reactive arthritis, but it would be a little bit unusual for COVID to be causing the GU symptoms because we don't really typically think of COVID causing things like UTR or prostititis. So one of the questions is could it be that when he came in with COVID, he also had either a UTI, prostititis or some type of infection in the pelvic area as well. And that infection was actually the primary driver of the reactive arthritis. There's not many infections in that area that can produce a longstanding history of reactive arthritis, but some of them that can be missed and are a little bit kind of subacute to chronic, would be mycoplasma or urea plasma. And both these infections are atypical infections. They would be negative on blood cultures and can cause pulmonary symptoms that would look or respiratory viral symptoms that would look like COVID. So it's something that we can think about. In addition, what are we going to do with these findings of the unilateral leg changes of where we're not having pain, but we're having changes in the color. And we can take a look at that foot and we can say that this is not rain notes. And because it's not painful, this is probably not complex regional pain syndrome. So what could be the cause for unilateral changes there? So I'm not definitely not an expert in the different type of neurological issues that can cause skin changes there and it won't comment necessarily on the skin part of the issues. But when I've seen this in my experience, there are a couple of things that can cause this discoloration. Probably the most common thing that I see that causes this discoloration is just severe inflammatory arthritis previously. So I presented a case internally before a person who came for intermittent or even permanent discoloration of his vessels and that would occur from time to time. And that patient had really bad gout. And the gout flare causes can cause so much inflammation. It causes hyperenia, which is essentially when the blood vessels get engorged and that can lead to discoloration almost even permanently through hyperpigmentation there. So one possible question is, did he have severe inflammation of that entire foot area, or especially around the ankle? What else could that be? The other thing that's really important to make sure that we're not missing is could this be vascular disease, right? So we didn't get many symptoms of when he's walking, does the foot hurt more than, right? That would be one question to ask if you're thinking about peripheral arterial disease. Now we'll say we were dealing with a younger man. So it'd be unusual to have peripheral arterial disease. But we also have a patient that has had a lot of symptoms after COVID. So we know that COVID can rarely cause problems in the blood flow. And we hear this bluto syndrome. So a similar thought is, could he have had a vascular component of attack from the COVID, that's leading to the changes there, right? So I'm thinking of secondary to inflammatory arthritis. I'm thinking of could this be vascular arterium, which is usually a little bit more dangerous than venous, but both of them can cause it? And then lastly, again, back to the neurogenic, neurogenic clotication or neurogenic issues can also cause changes in the foot, right? We talk about complex reusional pain syndrome, which is unlikely because there's no pain. It's usually very severe pain. But again, it makes me wonder, could he have some type of compression, intermittent lean, one of the nerves that goes down to the foot there? And the area that's affected the dorsum and the bottom of the foot would be consistent with L5S1. So if we haven't had imaging in the back, that's something that we can think of as well. If it's not in the back, you can also have kind of focal compression in different areas, something that's common and it's easy to misdiagnose, that looks like sciatica, for example, is paraformis syndrome. That would also make sense of why it would be unilateral. So those are the kind of the things I'm thinking in terms of the color changes. And then finally, we're not getting any on the exam. We're not getting any signs of inflammatory arthritis. And we're specifically not even getting many signs of peri-earthritis. But we do have signs that there has been chronic inflammation there. So what do we do with those results in terms of a rheumatologic disease? So again, if we really think about the primary inflammatory arthritis that is chronic. So in rheumatology, there are three big buckets of primary inflammatory arthritis. And what I mean by primary is that there is no systemic involvement. Because any rheumatologic condition can cause inflammatory arthritis, right? And lupus can cause inflammatory arthritis. But we think of it as a secondary involvement. You have a systemic disease and you have secondary arthritis. But there's really only three big groups that almost only show up as arthritis. And number one is going to be rheumatoid arthritis. Number two is going to be the sear-negative spondylarthritis. And number three is going to be crystalline arthritis. Now out of these three, if we take a picture and we look at which one of these is most likely to cause arthritis that comes and goes and flares and is completely normal in between, the most common one to cause that is crystalline orthopedies. However, the important thing that we have to know about that is usually crystalline orthopedies, things like gout, pseudogout, are very painful when they come in the flare. They require treatment, often eating, go to the ER urgent care. And then after a couple of days, after treatment, the patient is feeling totally normal. Over here, we're not getting necessarily that story. We're getting a story of where we have some chronic type of pain. So it's almost like there's an underlying chronic issue with flares, not saying that they can't be gout or pseudogout. But because of that, it makes it a little bit more likely as well to consider sear-negative spondylarthritis. And why is it important to consider that is because the flares, again, in sear-negative spondylarthritis, there's multiple different types. One type of flair is the type that causes tenonitis, bursinus, or enticitis. Again, these is periarthritis. These always come and go. They can eventually become chronic. And one of the important things to know is that when in rheumatology, we talk about inflammatory arthritis, right? And we talk about it gets better with movement. It gets better with activity. For sear-negative spondylarthritis, it often gets worse with activity. It's triggered by activity. So that's why I think it's important not to just, you know, memorize that if it's an inflammatory, it will necessarily improve with activity. But in the sear-negative arthritis realm, it's often very complicated because you have multiple different types of arthritis that we're dealing with. So I think what we'd be dealing with here is, what I would say is a milder version. And what I mean by mild is just that we don't have chronic inflammatory arthritis that we're dealing with on exam. But a milder version, possibly, of the sear-negative spondylarthropathy. And I would want to get x-rays of the affected joints, possibly ultrasound to see if there's inflammation as well in the synovium. Then HLAB27, and then uric acid. And if he has actually effusions, it would be important to get an arthrocentesis to look for chrysalis. - Excellent discussion, Jeffrey. This is just amazing. This is a really complex case. And I feel like you're distilling it very logically. And as you mentioned, so in his case, his pain is certainly triggered by activity. So maybe that's a key differentiating factor 'cause I'm certainly no rheumatologist, but I remember in medical school, we learn rheumatoid arthritis. They wake up with joint pain to get better throughout the day versus other types of arthritis may get worse with activity. So I think that's also an important point that you made. You requested some imaging and some lab. So I'm gonna give you some of that information now. So he was evaluated by orthopaedics, neurology, and rheumatology. And I'll give you his imaging first, and I'll go through some of his labs. So he had an MRI spine that showed a small T2 hyperintensity within the central aspect of the spinal cord at C6, C7, measuring one millimeter in diameter, compatible with just prominence of the central canal. Otherwise, there was no evidence of cladaquina. He had a multi-planar T2 MRI of the pelvis, which showed that he had a hernia repair, possibly tiny, recurrent, fat-containing, a right inguinal hernia with no adenopathy. He did have an x-ray of the right elbow which showed no osseus or articular abnormality. There was minimal soft tissue swelling over the olecronon, no effusion. He also had a follow-up MRI of the elbow without contrast that showed chronic appearing mild to moderate, common-extensor tendinopathy, common flexor tendin was intact. There was mild to moderate biceps insertional tendinopathy, mild brachialis insertional tendinopathy, triceps tendin was intact, no macroscopic cartilage defect was seen and no effusion. He underwent an EMG nerve conduction study, which demonstrated no evidence of cervical radiculopathy, brachial plexopathy or peripheral nerve entrapment. And he underwent a skin biopsy with did not show any evidence of small fiber neuropathy. As far as his labs, he had a under-markable CBC, his white count was seven, he had a little bit of 14. His MCV was 86 and a platelet count of 182. On his CMP, he had normal electrolytes. His creatinine was 0.9, normal glucose, normal protein. His ovum was 0.9. He had normal ALT/AST. His alkyphosphate was normal at 59. His T-billion was 1.3. He had a normal anion gap. He also had a normal hemogloin A1c. He had a urinalysis and a urine culture, which were unremarkable. He had a CRP, which was 0.7. The reference range being less than five. And an ESR that was two with the reference range being less than 10. And he had a CK that was 44. He had an ANA that was 40 with the reference range upper-limit of normal being 40 with a speckled pattern. He was anti-smith negative, anti-double strain DNA negative, protein A3, antibody negative, myeloproxidase negative, TPO, antibody negative, CCPIGG negative, RNP, antibody negative, RF negative. Ancotider was negative, his SSA and SSB antibodies were negative. He had a negative anti-cardiolipin antibody, and he did have an HLAV27 that was negative. He also had a cytokine panel, which had a bunch of interleukins, TNF, that were all normal. He had a Lyme antibody screen that was negative. He also had a negative HIV and a negative RPR. He had an SPEP, which was normal. They checked some of his vitamins, his vitamin B1, B6, and B12 levels were normal. He had normal seroloplasmon and serum copper level. He had a normal blood mercury level, and a normal negative, myelin associated glycoprotein. Just in terms of his course, he was treated with an impaired course of oral steroids, and an NSAID nebumatone with little response after two weeks. Reporting that his pain is mostly improved with physical therapy, not with any of the pharmacological therapy, and then his rheumatologist is considering adding on a biologic agent next. I'll stop there. - Okay, yeah, this is a lot of good data, and this is a challenging situation to be in. And so I guess I'll just go through my thoughts starting from the labs. So I think a lot of things that are good to know here in the labs is that the basic labs are unremarkable, right? So, you know, so far, what I've been discussing is mostly the common causes. If we were to look at much more rare causes, we would look at if they're small, subtle hints, in basic labs like the CBC, the CMP, things like opphosph, things like CK, maybe LDH, to see like, is there anything very abnormal that would make us concerned? And we're not seeing any of that. So in this situation by far, like maybe a hundred times more common than a rare cause would be a common cause that we're not able to figure out yet because it's in the transition of being mild to moderate. And then looking at kind of the other things that as you notice, like I didn't ask for inflamed form markers, but that is something that we usually get. The reason I didn't ask for inflamed form markers is because I have such a strong suspicion in this patient, even before I even get to have some imaging that they have a seroneg responsible orthodoxy that I expect them to be normal. If they are abnormal, it's still wouldn't race concern that it's not a seroneg responsible orthodoxy, unless the levels are very high. And what do I mean by very high? This is, you know, again, there's not a specific cutoff, but if, for example, yes, there was a hundred, now that would be something that would make me more concerned about something like GAL, or something like something atypical that we're dealing with, that's not a common thing, right? But because even the, you know, all the labs that we're getting here, your analysis, A and A are checked, and the RFCCP and they're all normal, that even strengthens that this is not something like a rheumatoid arthritis, not something like lupus, but it is in the seroneg responsible orthodoxy category. Now, I think one of the challenges here is what to make again of the symptoms that he's having with his GU symptoms, right? He has issues with pain in that area, he has dysuria, he has this issue with contraction of the sphincter, you know, midway. So is this somehow tied to the disease that we're dealing with? Or are we dealing with two separate things, right? So I think it's important to clarify that. I think one good thing that we notice is that he's, you know, he's gotten infectious testing probably several times for ETIs, prostititis, that's not what we're dealing with, right? It'll also be very unlikely to have prostititis or ETI something like that for three years, for multiple years. So I think that the likely have, that is, is very low. So what we're dealing with here, it's, it's seeming more and more likely that the symptoms in the urinary area are secondary symptoms, either to something in the back, but we're not catching it on MRI or something in the actual musculature there. So how could we tie musculature there with a question of could this be seronegative smell orthopathy? Well, one of the things that you can get with these seronegative smell orthopathy is sacrilyitis. And it can be hard sometimes for people to tease apart what that is because it feels a little bit different in each patient. In many patients, it does feel like back pain or hip pain. And when it occurs like that, it's easier to diagnose it. However, I have also seen some patients complain of burning sensation in that area or complain of butt pain or only butt pain when they're sitting, right? And usually when we think of those things, first of all, not many things come to mind because it's not a very common complaint. But we don't necessarily think of sacrilyact joint. But the sacrilyact joint is actually something that will flare or will get worse in that area in the butt. And we can also understand that if you have sacrilyitis, you may not present with actually the sacrilyact inflammation from a complaint perspective. But it may be secondary gluteal tendonopathy, for example, that you get. So I'm almost wondering, could he have pelvic floor muscle dysfunction in that area from the inflammation of the tendons around the sacrilyact joint? So that's one thing that I'll be curious about. Another thing that we'll look at is the MRI of the elbow. So the good thing is we have a lot of x-rays and it's not showing something called erosions. So what we look at in flammatory arthritis that's chronic, like been going on for three years is their erosions. Erosions mean that we have severe enough inflammation that there's scar damage to the bones. We're not seeing that, which again supports our theory that this is not a primary arthritis in the joint itself, but it's a periarthritis around it. And that is the word it even further by the MRI, right? The MRI is showing that we have tendonopathy, not only tendonopathy, but in the biceps, we're showing insertional site tendonopathy. Biceps insertional tendonopathy is not very common. In a young patient, if there was nothing else going on, we would be asking, like, is he just working out doing biceps curls way too much, right? But if he's not doing that, that really points towards an enthocitis, which again, further increases our concern if we could this be a serious dysbondyl orthopathy. So I think the MRI perfectly is compatible with that as well. We're looking at the other symptoms we had thought about could this be neurologic? The EMG is normal. The MRI pelvis isn't showing much, just maybe some reactive things there. There is, however, one, there's one entity in that area that can also be neurologic that we haven't necessarily seen and may not be caught on the EMG. And that is a plexopathy there. But the issue with that is that it's usually much more painful, severe and constant. After it's resolved, it may be not as painful anymore, but although I'm not a neurologist, I've never seen a plexopathy not present with severe pain enough to go to the ER. So unless it's a chronic plexopathy, I'm thinking that it's probably also less likely to go further down in the neurological workup. And right now, I'm gonna focus almost all my energy in this peri-arthritis workup. Now, what do you do with an HLAB-27 that's negative? When you get an HLAB-27, one thing it helps us do is support our theory that this is a seronegative spinal orthography. But what a lot of people may not realize is that a lot of people, patients with seronegative spinal orthography, may not have a positive HLAB-27. So while it's a good confirmatory test, right? Like let's say he has the entire picture and we have an HLAB-27 positive, that would be helpful in confirming the diagnosis. A negative test doesn't rule it out. We use the joint complaints to look at what type of joint problem we're dealing with, which in this case is a peri-arthritis and specifically hints of enthocitis. And that really puts us towards a seronegative spinal orthography there. Now, out of the seronegative spinal orthropathy, there are several different types again. One is seronegative arthritis, one is ankylosing spinalitis, one is IBD, and one is reactive arthritis. What are the important questions that are necessary to tease these apart and to change management? So one is we have no inflammation of the eyes, so that's really important. Because if there's inflammation of the eyes, suddenly nothing else in the body is really that important. The eyes are the only thing we need to focus on, right? Because if there's inflammation there, we're already about saving vision. So that's really good. The second question then is, is there GI involvement? And why is it important to know if there's GI involvement? It's because that we're considering whether this patient needs immunosuppressive therapy, right? If we're starting things like N-sense, if we're starting things like biologics, there are certain biologics that will increase the risk of GI disease, especially if the patient already has inflammatory bowel disease. So that's one thing to really ask about is, are we sure that none of these symptoms are actually GI in nature, right? Confirm he has no diarrhea. We confirm he doesn't have the abdominal pain, things like malabsorption that would make us concerned for Crohn's disease, okay? And then after that, in terms of the involvement of the joints, the number one most important question is, is there axial involvement? What axial means is the center, the spine, or the sacral iliac joints are involved. And the reason is because when this is involved, for first of all, it's a lot more difficult to control. And as you can imagine, let's say if you have a patient who has pain in their elbow, they're still able to function most of the time. But if you really have inflammation in the back and scarring there, lots of things are important in the back. The nerves, of course, the joints and the muscles there. And even when we're seeing sometimes GI complications, this requires a higher level of treatment and also responds less towards things like metatrexate. So what I would be doing here is, I would be getting an X-ray at least, or if got an MRI for the SI joints, to look if they're sacral Iliitis or not. And once we know those things, we can determine whether he needs, what type of treatment he needs and whether which biologic, if we aren't a sort of biologically reasonable adapt. - Wow, Jeffrey, that was just phenomenal. Thank you so much for all of your insights. This is just an amazing discussion. I will tell you, he has not had diarrhea, no weight loss, no symptoms to suggest like a Crohn's or IBD picture. I don't, he hasn't yet undergone ever, I have the SI joints, so I don't have that piece of data for you yet. I do have one final lab result that I wanna know what your opinion is of. So he had a gangly aside, GD1A IgG antibody, which was highly positive with a tighter of one to 800, normal being less than one to 100. IgM negative. And for my reading, that has been associated with Guillon-Barray syndrome. So I'm wondering if you think that this is a red herring or is this something that is important to it, is that do you ever, even though they're considered zero negative, spondaloarthropathies, are any of these kind of cross-reacting antibodies ever at play? That's a good, yeah, that's a good question. And very interesting finding. I will say that although I'm not a neurologist, I can share some of my thoughts as a rheumatologist of what I would be doing in rheumatology clinic if I saw that antibody come back positive in the work of. So as he said that, typically what we think of with anti-gangly side antibodies is something like Guillon-Barray. And typically Guillon-Barray, the history we have is a ascending paralysis. So again, this would not already be the typical story for that. Now, a thing that some of us may not be as familiar with is that they're actually variants of the embryo, and these can cause different types of symptoms. So like one variant, for example, is something called Miller Fisher, which instead of going up, down to up, kind of goes from top to bottom. And there are other kind of rare variants of Guillon-Barray. Some of them are purely motor, some of them are purely sensory, right? So the question I think I would have here is that, is this consistent with the neurological exam that we're seeing in this patient? And if we look at the neurological exam, we're seeing that there's no more reflexes. There's not really evidence of motor weakness. There's no really any evidence of even like sensory weakness in the kind of peripheral areas. So for this to be Guillon-Barray, I would think that maybe what would make sense is if you had lumbosacral involvement with radiculopathy there, just like kind of in that area. And maybe that could explain some of the GU symptoms that we're dealing with. But does it explain the enthocides that, or arthritis that we're dealing with? I would say it'd be very unlikely, because again, we're having issues with the elbow, with the biceps. These are really focal areas. Even if you had a neurological issue there, you wouldn't have insertional site tendinopathy there. It'd be very unlikely. And it would, it's so multifocal and asymmetric, it makes it a lot less likely. I would think for this to be a primary neurological process, right? And in rheumatology, sometimes we deal with neurological processes that do involve scattered nerves and what the thing that we call that is mononuritis multiplex. However, I would say that mononuritis multiplex really is not a primary consideration in this case, because we have a normal nerve conduction study. And furthermore, in my experience, usually people with that who have infarcted their nerves, they don't actually tend to resolve. So you have neurological evidence of the deficits of neuropathy. And often, unfortunately, you have severe debilits and in pain that you can't really deal with. You can't really treat or cure besides using pain medication. So I think that like a primary neurological process in here would be a lot less likely. I'd be curious to see what neurology says, but I think that this is still almost all completely consistent with the seronectrospong neuropathy. And I'm curious to see if they're going to do an MRI of the sicker Iliak joints and hopefully that he does well with the treatment that they give him. This has been a wonderful discussion. You know, I don't know if we have quite a final diagnosis because it's still a work in progress, but my thought, and I want to get your opinion on this, could this be a post-COVID-19 related seronegative inflammatory arthritis, or is the COVID-19 also just sort of coincident, true, true, unrelated? - Yeah, that's a great question. I think with the history that we're getting here, it really does suggest that it's a post-COVID-19 reactive arthritis. I think the one thing that we'll have to just, it will just take time to see is sometimes, and when I look at back into the cases that I've seen, sometimes what you have is you actually have a patient who's already gonna have serietic arthritis, or who's already have angolistine spinalitis, and then the COVID-19, it triggers their immune system, and it actually brings it out early. So that's why it's really important to follow this longitudinally, but with this history that we're getting here, it fits really well with a post-COVID-19 reactive arthritis. - Wow, and how would you treat this differently than, I guess, your garden variety seronegative spinal arthritis? - So that's a really good question as well. And I think the important thing from my experience to know is that usually a post-infectious reactive arthritis is less likely to be chronic and easier to treat overall than a primary angolistine spinalitis or IBD. So what I would hope here is that if he would need escalation of treatment, he may only need it for a couple of years before we can actually wean. In patients that actually have seronegative arthritis angolistine spinalitis, the current guidelines say that you need to be on this for lifelong because we want to prevent progression. But I think the fact that this could be reactive arthritis makes me lean towards treatment that is proportional to the dysfunction and consideration of weaning once there's resolution of inflammation. - Wow, phenomenal. Thank you so much, Jeffrey. This has been just an amazing discussion, such a treat and you were just a brilliant diagnostician. The way that you parse this case, I am just forward. - Thanks so much. I'm really flattered. I'm not sure if I did anything much. It looks like that, you know, I agree. I think that everyone already did the right thing and they were very thorough and comprehensive. So I'm glad that he got such great care and I hope the best for him. Thank you so much for bringing this case. - Yes, and thanks everyone. - All right, happy holidays. - Happy holidays, everyone. (upbeat music) - That's a wrap, everyone. Thanks for tuning in. - If you enjoyed this episode and want to be part of our community, join us for our live virtual morning report where we can present the case or discuss with us. This is our website for details. You would love to have you.