Chapters Transcript The Swollen Knee and JIA Bradley Ornstein, MD, presents on how to be able to identify when to refer joint swelling to a pediatric rheumatologist. So, um I'm gonna talk to you about, you know, ji a juvenile idiopathic arthritis, uh a little bit more broadly but kind of in the context of, of a patient who presented with a swollen knee, um which is the most common presentation for JI A. Um I have no financial disclosures. Um I must disclose, I am sitting in my house in my dining room and a child or cat may pop into the talk. So I apologize for that in advance. Um But I will also be discussing some non FDA approved uses for medications just briefly. So the objectives of the talk are to recognize the presentation of arthritis in Ji A and be able to differentiate this from a septic joint. I just think that's an important distinction to make in your office. Um And to make a quick decision about that, but to also appreciate a little bit more the different types in the spectrum of Ji A and that uveitis, um inflammatory eye condition is a frequent complication of JI A. So it's not just a joint disease. Um And then also to identify maybe when to refer to rheumatology. So just a a briefcase spin yet that I, I think shows the most typical ji a type patient that we'll see in clinic. So, uh, a two year old girl previously healthy, who developed a right leg limp after tripping and falling about two months prior. Um, her knee was mildly swollen but was never red and never really seemed overly painful to her. Um, but she never really wanted to straighten that leg completely though. She would get up and walk on it. She would just limp around. And her parents commented that especially in the mornings or after naps, she would walk around like a an old woman for about 30 or 40 minutes. But despite that, she remained active and again, never really seemed to be in much distress despite the knee swelling and her abnormal gait. But I think it's kind of helpful just to kind of understand maybe how we define uh arthritis or more specifically in inflammatory arthritis. So, you know, first you have to have swelling or extra fluid and a fusion in a joint. Um But we also look for limitations in the range of motion of the joint tenderness to palpation around the joint or pain with motion of the joint. And then we often look for increased heat in the joint, which is a little bit subjective. Um Of course, but I'm often that kind of feeling around the joint itself. You can detect some increased warmth in the joint, then especially I, I think it's, I think it's good to just think about this particular scenario, um, with this girl where she presented with a single inflamed joint, um, in JI A which I'll, I'll get into a little bit more. A single, swollen knee is the most common presentation. And I, I think it just has a, an interesting differential that's important to keep in mind. So, when I'm presented with a swollen single joint, I tend to think about kind of two broad categories. One is, is it acute or two? Is it chronic? And I guess we could argue about what's acute versus chronic. But, you know, if it's been there for a few weeks, it's probably chronic. Um, certainly acute in the last day or two, would be how I would kind of different, differentiate things a little bit in the acute category. I think the, the decision tree is always most important. Um when you're thinking about is this a septic joint? Um And, and it's usually not too hard, I think to make that distinction, this, this knee that I have pictured over here, which is red, swollen. Um You could even see maybe some small little pustules around it. I mean, I think, I, I hope everyone can sort of appreciate that. That's probably an infected knee. Um That's not what AJ I A knee looks like. But when you get a call about, hey, there's a kid with a swollen single joint a swollen knee. I think the first thought is always gonna have to be, do we have to rule out an infection in it? Um, and you can usually get a pretty good clue just by looking at it. Um, but there's certainly different kinds of infections. You know, this would probably be a staph or a group, a strep infected knee, but you can have uh infection triggered arthritis like a reactive arthritis. Um, Lyme is not endemic here in Missouri, but certainly seeing patients who have traveled, who come back, who do present subsequently with uh Lyme arthritis and the most common presentation for that would be a single knee. Um And that can look very much like AJ I A joint actually. Uh but also considering, you know, other symptoms and do you have to worry about malignancy like leukemia or neuroblastoma which could present with a single um swollen joint bleeding into the knee and patients with hemophilia, obviously, trauma could cause swelling and ji a certainly fits into this category too. Um chronic arthritis, there are some other, you know, rare or more interesting things like pigmented villonodular synovitis, which is an overgrowth of the synovium of the joint. Um Other autoimmune diseases like sarcoidosis, um There's a congenital or genetic form called blau syndrome, could present with a single joint. Tuberculosis again, wouldn't present like the classic staph or strep infected joint and would be a much more chronic kind of arthritis. Then you got some other interesting, interesting things like hemangioma that could cause an enlarged knee and, and again, ji a could fit into the chronic picture as well. Um So this, this is just how I think about things, this is not an evidence based medicine kind of flow chart. Um It's just kind of like big picture things that I think about when I hear or see a kid with a single swollen knee. Um So my first question is, is the kid having fever? Um, if they are, is the joint red, if it's a febrile child with a red joint septic arthritis is always the top of the differential. Um, you know, there are other things that could present with a red swollen joint in the febrile child, you know, acute rheumatic fever or some viral arthritis is um reactive arthritis, but most of those are more likely to be more than one joint. Um So like polyarticular kind of process. Um, so one single joint that's read in a febrile child. I mean, you need to call orthopedics, we need imaging labs including a blood culture and probably starting antibiotics. So, you know, that's, that's a trip to the, er, for sure. I mean, a febrile child who has a single swollen joint but the joint isn't red. Um I think, you know, the differential broadens a little bit more. Um you know, some autoimmune things could fit into there. I have like systemic J A lupus inflammatory b uh bowel disease associated arthritis. But again, most of those things are much more likely to be polyarticular. Um, so they could start with a single joint. So I think, you know, you just have to keep an open mind, but malignancy would certainly be in the differential in this case and, and you're gonna be doing some sort of evaluation in those kids as well. Um, so if they're not having a fever, then the next thing I think about is, well, is there a history of trauma? Um II I think this gets really tricky in kids um especially in our clinic. Um We see a lot of toddlers who are presenting with a single knee and I, I'll get into kind of the demographics of ji A and the parents can always recount a story of a fall or some sort of trauma to like basically any part of their body. So I, I don't think a history of trauma necessarily means that the swelling is due to trauma, but you at least have to think about it and that might kind of drive some initial imaging or perhaps a referral to Ortho first. But again, I think there are some other details about the story that can help kind of make the decision for you. Um Then we'll get into some of that later. So Afebrile, no history of trauma, I think ja a certainly has to be in that list. Uh But some of the more chronic rare infections like lyme or TB, some of the overgrowth, things like the pigmented vlo nodular synovitis, malignancy and some metabolic diseases can be in that list too. So, again, I think it just kind of categorizes things a little bit in my mind as to like, what kind of things do I need to be thinking about ordering? Um, but in your office, I think the big thing is always gonna be if there's a fever in a red joint, that's more of an emergent situation and they should be going to the, er for a septic um arthritis evaluation. Um So to kind of shift back into JIA a little bit more. So there, there is some confusion about what is, what do we call Ji A and that's because the name has changed over time a little bit. So if you were in Europe a couple of decades ago, um it was called JC A Juvenile Chronic arthritis here in the US, we called it juvenile rheumatoid arthritis for a long time or JR A. Um and a lot of the older literature here still definitely uses that phrase and family members um or families who have older family members with Ji A. Um we'll call it JR A. So they're a little interchangeable in my mind, but technically now it is called JI A. There was an international consensus about using this nomenclature and that happened in the late nineties. So that's those are the terms that, that I use at this point. So in, in kind of overarching broad strokes because Ji A has a lot of nuances to it. Um But typically you have to have certain criteria to consider this diagnosis. Um You have to be actually less than 16 years of age at onset of illness. Why? 16 and not 18? I don't know, but that's the story. Um You obviously have to have arthritis, it has to have been present for at least six weeks and you have to exclude all other forms or causes of arthritis. Of course. Um These criteria are really most useful for clinical trials and studies. I think, you know, in the clinic space when we're seeing patients, you don't need to wait six weeks to make a diagnosis of ji A. Um, you know, if it's only been a week, I think we'd be pretty hesitant to call it that unless there's some other extenuating circumstance. Um So usually if it's been like in the 3 to 4 week range, most of us would feel pretty comfortable making that diagnosis. Assuming, you know, we've kind of felt like we've ruled other things out, but you don't need to like, have your patient tell them like, hey, you've only had arthritis for four weeks. We can't send you yet. Like, you know, we have to wait a little bit longer. Um That's, that's not necessary. Plus it will probably take longer than that to get in to see us. Uh So in this international classification consensus that was made, um back in the nineties, there are a variety of different types of JI A and I, I'm only gonna talk about two of these in more depth in the rest of the talk. Um But I just wanted to kind of list them all out here. So there's systemic onset ji A and I think when most people hear the word Ji A or the the term JI A, this is the one they're most commonly thinking of. And this is really would probably be better classified in a completely separate as a completely separate disorder. It's a different path of physiology which I'll talk about briefly and and really isn't sort of the typical Ji A that we see most commonly systemic concept is about 10% of Ji A and everything else is made up of these other categories. Um So the type that we see the most is oligo arthritis. So that's four or fewer joints. There's some subtypes of that that are broken down based on whether or not you develop more joints as time goes on. Um there's polyarthritis. So that's five or more joints and that's subdivided into rheumatoid factor, negative or rheumatoid factor, positive disease. And those have some prognostic kind of value to them to kind of make that differentiation. There's also juvenile psoriatic arthritis, um emphasis related arthritis, which is uh more of a spondyloarthropathy, kind of like ankylosing spondylitis and then an undifferentiated arthritis category if you just don't meet criteria for any of the other categories. Um, so the overall incidence of JI A is, is pretty high for autoimmune diseases. I I kind of gave some other diseases that are in, you know, a similar range like inflammatory bowel disease is about 10 in 100,000. Um, type one diabetes is about 20 to 30 per 100,000 and JI A is about 10 to 20 per 100,000. Depending on the study you look at. Um because of all the different subtypes of JI A, the age of onset is really quite variable. Each one of them is, is almost its own distinct entity. Um So it really doesn't make a lot of sense to give an overall age of onset for the disease. But you kind of look at the subcategories more individually. Um But you know, taken as a whole, girls are more likely to develop it than boys. Though the the spondyloarthropathy type that emphasizes related arthritis is more common than boys. So again, there's a lot of variability even in the gender ratios in these different subtypes. Um Similarly, there's a lot of racial variability. So Caucasians are more likely to have oligo arthritis or psoriatic arthritis. Um A lot of Eastern Asian populations are more likely to have emphasis related arthritis and African American patients are more likely to have rheumatoid factor positive polyarticular arthritis, but of course, anyone could have any of them, but in broad strokes, those things are a little bit more common in those, um, different groups. You know, what causes? J, I don't know. Um, you know, I think that's generally true for most autoimmune diseases. You know, it's some combination of genetics environment. And again, because of the different types of JI A, there's different kind of associations within those too. So I've been mentioning this sort of emphasis related arthritis. One that's more like ankylosing spondylitis, that is a very high association with the HL A marker HLAB 27. Um that's also found at higher rates in juvenile psoriatic arthritis and also the rheumatoid factor, negative polyarticular arthritis. Um I also mentioned a little bit earlier, this kind of difference between systemic JI A which we think of as more of an autoinflammatory disease, which I'll talk about um briefly. Um and then all the other types which we think of as more of autoimmune diseases. And it's just kind of differentiating which arms of the immune system seem to be most active in those disorders. Um When we talk about oligoarticular arthritis, so four or fewer joints, um we do see, again, that's the most common type, we see that there is, you know, genetics to this, even if it's not associated with this B 27 marker that I mentioned. So in twin studies that looked at this um monos psychotics or identical twins had about a 44% chance. Um, of if one twin had it, the other was going to develop it. Um, whereas dizygotic non identical twins, it was only 4%. Now, that's well above the background rate. Um, but that is the number that we would generally quote to a family because they, they usually ask like, well, if one child has it, what's the risk that is gonna happen to another? Um So about 4% unless they're identical twins, but that's only for the oligoarticular variety. Um Other types like psoriatic arthritis and the emphasis related arthritis, they do seem to have much higher rates, you know, within families. So again, it just depends what kind of arthritis are we talking about here. Um Relatively speaking across the board, if you look though at what's happening within the joint of these disorders, you do see a preponderance of um CD four positive T cells and macrophages, you know, actively causing the inflammation in there. Um And if you test the fluid, you'll see high levels of inflammatory molecules like T neala interleukin one interleukin six and those are molecules that we're targeting. Now with um biologic therapy, which I'll, I'll touch on briefly closer to the end. Um And again, just because this is the kind of arthritis that most people really think of. When you say JIA, I thought it'd be helpful to talk a little bit about the systemic onset variety. Um So I mentioned it earlier, but this only accounts for about 10% of ji A patients. Um, so relatively rare in our clinic. Um It, it's definitely the most dramatic form of it. Um So I think that's why it kind of sticks out in people's minds even if it is on the rare side. Um, it tends to occur um, in younger Children, but there is an adult corollary called Still's Disease. Um, The prognosis, you know, generally is that about the way we think about is half are going to develop actually into more of this chronic persistent arthritis after the more inflammatory stage is done and they'll actually look like a more typical ji a patient. And then the other half is kind of split between this. They have one single episode and it kind of dies out and then they're good or they have this waxing and waning kind of course with um flare ups in their systemic symptoms. Um which I'll, I'll talk about in a second. Um But this is a very unique disorder within JI A. Um And I think the big distinguishing thing from it um is fever no other ji a subtype presents with fever. Um But I think sometimes we kind of get referrals or, you know, consults within the hospital about, oh, there's a kid with, you know, like a single joint and has a fever and, you know, that's generally not gonna be a systemic JIA a patient. Um they might have fever for another reason. Um and then they have a single joint or we're worried about systemic JI A but they have arthritis without fever. So, you know, fever is, is really typically distinguishing for systemic, but they're usually fairly sick Children overall, which isn't the case for any other um ji A subtype and systemic J A is really more this what we call an autoinflammatory disorder. So, autoinflammatory disorders um include some interesting diseases. Um like the periodic fever syndromes. Um The prototypical one is familial mediterranean fever. Um Some people would classify Bichette syndrome as an autoinflammatory syndrome. But these are diseases that really are being driven more by the um more primitive innate immune system. Um versus, you know, the, the smarter, more advanced um antigen dependent um mechanisms that you see with the humoral immune system. Um So this is more neutrophils, macrophages, natural killer cells as opposed to the other types of JI A which you think more about T cells and B cells. Um you know, in the end, the inflammation is very similar. You know, this still has high levels of T neala and interleukin one, but interleukin one in particular is, is very high um in these autoinflammatory disorders and we treat them really by targeting that molecule fairly specifically. Um though other medications do work as well, but that's been one of the breakthroughs in managing um a lot of these disorders. Um So these diseases really have fever as a hallmark to most of them. And, and again, that kind of fits with systemic JI A as opposed to all the other types of JI A. So the criteria for systemic Ji A are arthritis and fever. Um the fever has to be present for at least two weeks and classically it should be quotidian. Um meaning usually it has a single spike, maybe two spikes every day around the same time, the fever usually goes up and comes down fairly quickly. Um That only has to occur for a few days. Um But it typically is fairly persistent. It has a classic evanescent rash which I've kind of pictured over here. It's called the Stills rash. Um classically described, described as a salmon colored rash. It will typically come with the fevers or a classic story is when I gave them a bath, the fever popped up. So anything that kind of raises their body temperature seems to make the rash pop up and then it'll fade away when their temperature drops. They will often have generalized lymphadenopathy, um organomegaly. So I've had a splenomegaly, they can have sidis or pericardial effusions, um you know, pleural effusions. So they look quite ill. Um And you know, the differential kind of is a bit different for systemic JI A than it is for essentially any other type of JI A. So that differential includes, you know, a lot of other autoimmune diseases. Um things like lupus, polyarteritis, dosa, serum sickness, sarcoid could present with all those symptoms, other auto inflammatory diseases, you know, other periodic fever syndromes. Kawasaki's disease is frequently in the differential. Again, just given the length of the fever or the rash and some of the other symptoms that can come with it. I certainly infections have to be considered and malignancy is always uh a high level, a high concern for us. And we very commonly will ask um oncology to do bone marrow biopsies on kids where we're thinking about systemic ji A just because there's so much overlap um in how leukemia um could present um with how a systemic ji A patient does. So, laboratory studies are, are usually pretty dramatic. Um typically, they'll have very high white counts, you know, often over 30,000 with a neutrophil predominance. Um their platelet count can go over a million at times. Um They're typically anemic um you know, more from like anemia of chronic disease. Um their inflammatory markers are generally very high, you know, ESRCRP are very elevated, the complement levels are high and all these other markers are usually elevated. Um And again, unlike most other kinds of JI A, if you send things like a nas rheumatoid factors, they're generally negative in a systemic ji A patient. Um again, just different mechanisms um than what we associate with all the other subtypes of JI A. There, there is um sort of a twist to systemic J that can sometimes make the diagnosis a little bit more challenging. Um And that is in the sickest of the patients, they can develop something called MA S or macrophage Activation syndrome, which I'll, I'll talk to about in a second. But this can paradoxically create a normalized ESR and a low white count and platelets. So even PMY AIA is pretty common. So this is essentially um a secondary form of HLH. Um it can be triggered by EBV and um systemic JI A patients. Um much like classic HLH can and this is a very life-threatening condition in a systemic ji A patient. Um it can be seen in other autoimmune diseases too. Um like lupus, sometimes in Kawasaki. Um you know, misc polyarticular ji A um can very rarely present like this. It's not something I would strongly think about probably lupus. Um or Kawasakis would be the ones where we would see it maybe most commonly, but that would be extraordinarily rare. Um But about 5 to 10% of systemic ji A patients in their presentation will develop macrophage activation syndrome. Um But this is really just uncontrolled cytokine storm um and can be quite devastating. So they'll have unremitting fever, again, organo medically, adenopathy, they can become encephalopathic, develop her and bleeding really just kind of multiorgan failure. Um And again, and sort of like as a big difference to the typical systemic patient um who usually has high levels of white, you know, white blood cells and platelets. These patients develop cytopenias as their macrophages kind of chew through their bone marrow. Um they become coagulopathic and just from um all the destruction of the um proteins in their system, like their ESR will actually drop. Um they develop very high ferritin levels. Well above 5000 is typical hyper um triglyceride. They have elevated cil two receptor levels and lower absent natural pillar cell activity. Again, this looks just like an HLH patient. Um and staining for CD um 163 positive cells um in the bone marrow, you know, is frequently positive though it can be missed, you know, on single samples. Um but just evidence of hemos by macrophages that are um CD 163 positive is would be classic for it. I treat pretty aggressively with steroids. Um and interleukin one blockade, as I mentioned, um typically with Anakinra, which is a short acting agent. Um but there are some newer treatments um like an uh interferon gamma blocker. Um And then cyclosporin used to be used quite a bit in this condition. I would say we use it less now with the advent of the um IL one blockers just because of side effects. And um the and Ain in particular is very quick on and off. So it's you can feel relatively comfortable like trying it, you usually get a quick response and you haven't really burned any major bridges by using it up front, sometimes we worry about using steroids when we're really concerned about malignancy. Um, an Amic can, uh, you know, usually doesn't set you back if you end up having a patient who ends up, you know, having, um, a malignancy instead. Um So just to shift gears now to your articulate ji A. So this is the most common form of JI A that we see and it involves four or fewer joints, um, at least over the first six months of the disease. So you can't even officially classify most Ji A patients until they've had um disease, you know, a diagnosis of JI A of some kind for six months. Um There is this persistent versus extended subs subtype, um which I don't think we really need to go into. Um, but exclusions for this are, you know, if you have psoriasis, um either in the patient or in a first degree relative. Um if it's a first degree relative with psoriasis, that patient actually will have psoriatic arthritis, even if they never develop psoriasis themselves. Um I mentioned that this hr A B 27 associated type of Ji A that emphasis related arthritis. Um, it's more common in boys and if you are a male patient and you're older than six and you're b 27 positive, you cannot be diagnosed with oligoarticular ji A, you'd be diagnosed with, er, a, um, family history of er, a spa inflammatory bowel disease associated arthritis or classic uh reactive arthritis, um or anterior uveitis puts you more into that category of er, a as well rather than articulate. So, you know, there are lots of little kind of nuances to the diagnosis. Um but in the end, this is the most common type that we see and the most common age of presentation is about two and at that age, girls are about 4 to 5 times more likely than boys to be presenting. So our, our classic new diagnosis of JI A is usually a, a two year old blonde haired, blue eyed girl coming in with one swollen knee. Um So that's, that's just typical why the blonde hair and blue eyes, I don't know, but clearly there's something genetic about it. Um But that's what we see most commonly. So this is well over half to three quarters of Ji A and Caucasians ends up being a go articular, um and much lower percentage in other ethnicities. So this is our classic patient here. Um, a little girl in all likelihood, and you can see on their face, but presenting with one swollen knee here that they're holding slightly flexed, but she's still standing on it, which generally you wouldn't see in someone who has a septic joint just be too painful for them. The knee is the most common joint to be involved, uh followed by the ankles, fingers and toes are much less common. Um And then elbows, the hip, wrists and the temporal mandibular joints are less common. Um still but monoarticular disease. So a single knee is about half of oligoarticular ji a patients at least at presentation. Um As I mentioned, the hip is really rare. It would be much more likely that if you have a patient coming in with hip pain, that it's gonna be a transient synovitis or possibly a a septic hip, a septic joint. So if you feel this joint here, you know, it would obviously feel swollen, it would generally feel warm, but you could see it's not red. And again, I mentioned like she's still standing on it. I mean, she's not putting her full weight on it, but she is using it and just a, a classic appearance for an old of a particular ji a patient. Um as I mentioned in the initial case presentation, you would expect to hear a story that when she wakes up in the morning or after naps, the joint seems stiff and she has a harder time getting around. But as she moves around more, it sort of loosens up and she does better. Um Typically patients only have arthritis um really for the most part, other organ systems else who have systemic ji A um are pretty rarely involved except for one thing. Um and those are the eyes. So uveitis, particularly um anterior uveitis. So, you know, upfront in the eye, potentially involving the ciliary body. Um and um the iris is relatively common in ji a about 20% overall of patients, um, will develop uveitis at some point in their disease course, most commonly in the first few years after diagnosis. Um, it can be very asymptomatic. And again, because our most common patient is a two year old, they're probably not gonna tell you that their vision is blurry. Um, sometimes you might notice that they are becoming a little bit more light sensitive, but again, it's a little bit challenging. The sort of most common patient is usually a blue eyed person. Um and they're often very light sensitive to begin with. So pretty minimal um symptoms to kind of clue into and, and really, it just ends up being they need to have their eyes examined pretty frequently, especially in the early stage of their disease. Um There can be a lot of complications from untreated uveitis and it can involve both eyes. So you can develop sneaky, um which I'll show you some pictures of, but they're basically attachments from the iris onto the lens. You could develop calcifications in a band across um the cornea and then you could develop increased pressure in the eye sometimes from the treatment itself, which can often involve a lot of topical steroids, but also from the inflammatory process that's occurring. Um So here's a picture of a couple of eyes. So hopefully you're able to see it, but you could see that the people here isn't totally round there are these little like projections, those are the syne, those are little strands from the iris that are actually adhering to the lens and that's from the inflammation that's occurring. Um And, and something else that you might see though, I've never actually seen it in clinic and I look for it. So you could see here there's a thin layer of white blood cells that actually, that have accumulated from the inflammation. So uh a hypo on um but in pretty um active disease, you could potentially see that. But I look at I've never seen it. Um Down here, you can see that band Katy that I mentioned. So that's just calcification from all the inflammation going across there. And obviously, that's gonna really affect um this person's visual acuity. So we wanna prevent all these things. Um So treatment is often driven at least initially by our um ophthalmology and optometry colleagues. So topical steroids can be helpful for anterior uveitis. Some of the diseases we take care of um like sarcoidosis have more posterior inflammation and topical steroids really just won't penetrate back far enough to manage that. So we often have to resort to systemic therapy sooner. Um but in most ji a patients steroid drops can be very helpful. Um the dra to to help dilate the eye and try and break some of these um extra connections, um can often be helpful too and failing that. Uh those more localized treatments we often will resort to systemic immune suppression. Um Even if their joint disease is quiescent, I mean, in remission, um we sometimes do have to start them back on very similar treatment just because their eye disease is um not responding like it should or like we would hope it would. So, um these patients really need um a good eye specialist to monitor them. They need slit lamp exams. They really should be a pediatric person because doing a slit lamp exam on a two year old, I think, takes a different skill set. Um And even if their joints are totally fine, they still need regular eye exams. And the highest risk group are the youngest patients who are a N A positive. So a newly diagnosed two year old who has a positive A N A, they need eye exams every three months for the first four years. And then after that, they go to every six months for another three years and then still, once a year after that, um systemic ji A has a very low risk of U Vitis, but we still suggest a once a year exam in those patients. Um So again, there's, there's some guidelines about when you do what, but that's always something that we would manage and, and recommend, you know, follow up for, with, with our eye specialists. Um So to touch on some of the labs that um we frequently would get or look at in an oligoarticular ji a patient. So, very commonly sed rates and CRPS are normal in these patients. They might be a little bit elevated, but I usually expect them to be pretty normal. CV CS are frequently normal too. Maybe they'll be a little anemic from the inflammation. Um A rheumatoid factor and AC CP, um which is another test kind of similar to a rheumatoid factor should be negative. Um, if they're positive, they're probably not an oligoarticular ji a patient. Though sometimes you'll have some false positives and we'll repeat them in a few months. Um If they stay positive, I think our how we watch this expectation that they might really develop into more of a polyarticular type disease. Um on occasion, you know, we will get fluid out of those joints, sometimes it's part of the treatment. Um but sometimes this happens before they come to us diagnostically, you know, and this is just a table looking at sort of different values you might expect to see um depending on what process is occurring in the joint. So normal fluid is yellow, it's clear, it's very viscous. Um on occasion, some will leak out and there used to be something called a strand test where if you took some of the fluid between your fingers, it would kind of like stretch out and strand between them. Um once inflammation starts to occur, all those kind of proteins really break down and it loses that sort of stickiness Um And so if you draw fluid into a tube and there's an air bubble in it, it'll just kind of flow through it like water. Whereas if it was normal fluid, it would move very slowly through the fluid. That's usually more what, what I look at when I draw fluid out during like a joint injection. Um, normal synovial fluids have a very low white blood cell count in JIA, a common value would be like 15 to 20,000 cells. Whereas in a septic joint, you'd see well above 100,000, that being said, sometimes those ji A joints get up in the 100,000 range. So you can't just look at the absolute number. Ji A joints have very high levels of um neutrophils in them and I've seen well above 75%. So sometimes it can be a little bit tricky to look at that fluid and make a determination about. Do we really think that this is not infected or not? Um But that's usually where the history and the back story are are most helpful. So just the the elephant in the room when it comes to labs. Um So a nas so this is like our best friend in the bane of our existence sometimes. So a a stands for anti nuclear antibody. I'm sure you all know um in oligoarticular ji A patients. So just in that particular group, about 60 to 80% of them will test positive for an A N A. Um as I mentioned before, having that positive A N A does increase the risk for developing U Vitis. It also seems to probably increase the chances that they'll respond really well to treatment. So it's a little bit of a double edged sword. Um You always get a tighter back with your A N A. Um Usually a 1 to 40 isn't gonna really be seen in someone who has an autoimmune disease. Um, 1 to 80 maybe. But usually we're seeing at least a 1 to 160 if not higher in patients. Um You'll frequently get a pattern back um describing, you know how the A N A lights up. That's what these um little pictures over here represent just different A N A patterns. I think they're sort of academically interesting to think about. But from a practical standpoint, I never really look at the pattern like it doesn't matter all that much to me. Most of the time I'm more interested in is the A N A positive. And what are the symptoms? And what other tests do we need to do? Like, I've never diagnosed someone with lupus based on their A N A pattern. Uh But it, it's sort of interesting to think about. Um But A NAS do represent a break in immune tolerance. Um They themselves are not clearly pathogenic. Um And 10 to 15% of the population, if you check them is going to be positive at any time. And most of them don't have an autoimmune disease, probably means they're at some increased risk for developing one, but it certainly isn't a death sentence for them. Um So it's just one piece of information and doesn't make a diagnosis. Um So other studies that often get done imaging, so x rays are frequently obtained, I would say in a new onset patient, we almost never expect to see much on an X ray. Just the disease hasn't been present long enough typically to cause any issues. Um This series of x rays over here shows the progression of disease in a patient over time. This was a patient. I don't know how old this study was or this is from one of our textbooks. So this was from decades ago when our treatments weren't very good. And you could see over time this is like early on in, in the disease course that there's a lot of space in between. Um you know, the femur and the tibia here. But over time that space gets narrower and then basically disappears. So this is progressive arthritis, the bones start to look more sclerotic um and maybe a little bit more osteopenic. So that's what occurs with untreated inflammatory disease in the joints and that's what we really wanna prevent. Um We've gotten pretty good at that, but I'll get into that in a little bit. So sometimes it's a little unclear what's going on um especially with some of the other subtypes of J A particularly when we're more concerned about the spine. Um and we will often resort to an MRI um to look at those joints. Um often with smaller finger joints too, it can just be hard on exam at times to really appreciate swelling there. You can get inflammation um in the tendons as well and get a tenosynovitis and that can be a little challenging to really appreciate on exams. So MRI studies often with contrast, um can be helpful for us at times. Um ultrasound is becoming increasingly more established as a useful tool um in the clinic. Um And I think more of us are getting trained on using that to actually see active inflammatory disease, you know, just at the bedside. So that that's a growing tool for us. So our goals of treatment um in our gi a patients are to, you know, relieve discomfort, obviously preserve function, prevent deformities, promote normal growth and, you know, all through controlling inflammation once we've controlled it to keep it controlled, hopefully off of medication though we're variably successful with that. Um And, and to really use treatments that minimize side effects, um you know, we do wanna obviously get kids functional again and educate families about, you know, monitoring things like UV I dis and the risk of flare and things of that nature. So our typical approach um is usually to start with some men says while we're working things out. Um You know, it's a quick thing to do. It might provide a little bit of relief, but it almost is never going to fix things in the patient that I presented upfront who had a single joint. Our favorite treatment is to inject that knee with steroids. Um We used to use a formulation that was available in the US um Tram hexacetonide. It no longer is um it worked a little bit better than typical Kao which is tramel onedin, but still in a fraction of patients, a single injection might lead to prolonged disease remission and the arthritis may never come back. That is not typical, but it's possible. So we usually try it if that fails. Like they get a very minimal response, just not a long lasting response. Our next step is usually to start systemic immune suppression with the disease, modifying anti rheumatic drug classically methotrexate. This is also something we would do if they come in with many joints involved and it's just not practical to inject them all if that isn't adequate. We move to a newer class of medications that have been out now for a couple of decades. These are the biologics. So these are frequently monoclonal antibodies that are designed to target specific inflammatory or signaling molecules um in the immune system and this is super busy. You don't need to like look at all the details of it. I think it's just to give a general sense of, there's a lot of stuff going on and we over time have developed a lot of different antibodies biologics to target very specific receptors, inflammatory molecules cells. So our, our um Armamentarium has grown and this is just a few of the things that we have now. So this is a list of some of the biologics that um we use most frequently I would say. And the things that they target, um the ones that are underlined are ones that actually do have FDA approval in pediatric patients. Um in certain types of JI A, the ones that are not underlined or not FDA approved, but we will use them in certain situations and usually you just have to fight with insurance about it. Um But major molecules that we target are TNF alpha um is probably the most common one. So Etanercept is Enbrel. Adalimumab is humera infliximab is Remicade, those are some of the most common medications that we use um in interleukin one blockers. Um I mentioned more in a systemic JI A and that's usually where we would use those. So they have maybe some utility and other kinds of JI A um tosol lium or Tere is used as well, um that was used in some misc patients. Um So another kind of interesting inflammatory condition but the list goes on and on and each of these things targets the immune system in a different way. Um You know, I kind of came up through training at the time that these were really hitting the scene. And I recall in fellowship, when I started fellowship, we actually had a physical therapist in clinic with us because we used to do things like serial casting to try and get kids joint straighter by kind of moving them, casting them, moving, casting a little bit more. And by the end of fellowship, we didn't actually need her anymore because of how successful treatment tends to be with the use of these biologics. So it really has changed the face of the management of Ji A and having a family come in with a story of, well, you know, Uncle Bobby ended up in a wheelchair from his JR A like that just doesn't happen anymore. It would be extraordinarily rare. So it's uh makes a lot more fun, I think to work in the clinic because we're usually fixing kids quite well. The problem with these meds is they're silly expensive. Um 2030 40 $1000 a year, Ken and Kad is about a quarter million dollars a year. So just insane prices for these things. Um I mean, that's a function of, I think our system here, there are biosimilars now, kind of like generics for biologics, which are supposed to provide a lot of cost, cost savings but hasn't really materialized yet. They still cost about the same, but a lot of insurance companies are making a switch to them because they probably get some mild um cost savings on them. But um the prognosis nowadays, as I said is generally pretty good, but having fewer joints involved is always better. Having a negative rheumatoid factor is better being A N A positive might be better for the joints but might be higher risk for the eyes. Um But you know, as I mentioned, we're really limiting now the negative outcomes of like major leg length discrepancies, short stature, chronic contractures and joints. Um just because we've become pretty darn effective at at managing this disease. So just to quickly revisit our case because I know we're getting a little bit long here. Um So these are the things that kind of clue me in to this child having ji A and I think of things to kind of keep in mind when you're seeing a patient in clinic. So again, a toddler, a two year old girl has been limping around for two months. So a chronic arthritis, the knee is swollen but not red or painful. She has that kind of post nap, early morning, more prominent symptomatology where she's walking around and limping more, then it kind of warms up, but she's still active and she looks ok, even though she's limping in clinic, that's AJ I A patient like in my mind until proven otherwise. So just briefly what to do, you know, again, I think I mentioned our most common patients, a toddler they fall and hurt themselves all the time. So that can kind of confuse the picture sometimes, but particularly in our patient, this sounds just much more like ji A like that's not a torn AC L, right. She probably wouldn't be walking around on that. Imaging can sometimes be helpful again with that story of trauma in this child. I mean, you could get one, I'd be sort of plus minus on it honestly. Um just given the whole clinical picture um labs, you could get them. We're always fine having you send them to us and we'll get the labs that we want to save them a poke. But I think, you know, at the end here, I just mentioned, you're always welcome to call us and ask for advice. Um you know, in your clinic, as you're trying to get them over to us, starting some naproxen or ibuprofen regularly would be a very easy thing to do. It might provide a little bit of relief. Um But then kind of making a judgment about things or a strong family history of a particular kind of autoimmune disease that might just color the picture a little bit for us and maybe push us one way or the other about how quickly to see the kid. But as I said, always welcome to call for advice. Um So here's just some resources that you can use in your clinic. Um The Arthritis Foundation is a wonderful organization. They have a lot of resources on their website and we send families to their website for a lot of information. Um It's a good resource. Um Ny MS has some things and, and you just mentioned. So a lot of the information from the talk came from our, our sort of our Bible uh the Cassidy textbook and that concludes my talk. So, thank you. Created by Presenters Bradley Ornstein, MD Pediatric Emergency Medicthe View full profile
