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Trancriptions
[00:00:07] Dr Sylvia Kamphuis: So, hello, good afternoon everyone. My name is Sylvia Kamphuis . I'm a pediatric rheumatologist in the Netherlands, in Rotterdam. And today I'm going to teach you about metabolic diseases and specific metabolic diseases that actually can interfere with your diagnostic process, because some metabolic diseases really look in patients as they would have chronic arthritis or JIA. Here are some basic slides that you know what we're doing. Just technically, I mean, for the webinar. Don't take any screenshots, not necessary. Not reproduce all the slides. It's going to be around 20 to 25 minutes. Please post your questions at the end, and you can type them in, and I'll read them out and answer the questions. Always nice, because that's actually how you learn, I think, and get to know the subject. What I'm actually trying to learn you today is that you can recognize when it's not JIA. So when a child with chronic arthritis presents, and you don't need or should not think of JIA. I'm going to help you to show you some key features, which makes you able to distinguish the genetic disorders from JIA. Also, if you think about it, what's to do to really diagnose a patient with that disease or exclude the disease? I'm going to start off with the first case. This is a girl. She was referred at six years to our unit. She had a swollen wrist for quite some time. Normally, I see a swollen wrist at six weeks or 12 weeks, and hardly any longer. So this was really extraordinary, and it also made me think. I always think doctors are doing a good job, and why would this kid be around, walking around with one and a half year of a swollen wrist? Anyway, she was now referred also to a new doctor, because it was getting worse. So I think in the beginning, that's also what she said. She didn't feel that much pain. It was just limited. It was swollen, but not much pain. Remarkably, in her history, was a trigger finger. So she couldn't move one of her fingers, and it needed to be operatively, by a surgeon, corrected. Sorry. Corrected, and so it went away, the trigger finger. She has been seen by a neurologist, a rehabilitation specialist, a new neurologist, a new rehabilitation specialist, and in the end, she was referred to the plastic surgeon in our hospital in Rotterdam. She came from the southern part of the Netherlands, and she was shown to the plastic surgeon, because they are specialized in hands, and they didn't know what to do. And I have a good connection with the hands team in Rotterdam, and that's how she came to our pediatric rheumatology ward. The swollen wrist actually was the only joint problem she was referred to with me. In general, she had general stiffness in the morning. She also complained when asked about other joints, her shoulders, her hand, but you know, for six years, she did well at school, but she also moved well, and no one actually had noticed that there was a problem with her locomotor system, except for the wrists. And then as I saw her, I was actually quite shocked. I saw several limitations in her wrists, elbows, shoulders, in her fingers, but also in her knees. Only the wrists were swollen, but the limitation of motion was clear in the other joints, and she didn't walk nicely. She walked insecure, and she actually could not stretch out completely when walking. And other internal exams or other joints not mentioned were all normal. And of course, what do you do? You do some diagnostics, and first I did a, especially for the wrists, I did an x-ray, and normally I would ask the public, what do you see? So wonder in your head, what do you see? What do you see in the picture in the x-rays? And I can actually show you with my, hopefully you'll notice, this is her left wrist, this is her right wrist.
[00:04:45] Dr Sylvia Kamphuis: As you can see, she's six years, and normally you can count the bones in a developing skeleton, you can count the wrist bones by the age. So this is maybe a fifth one, so five, but six years, that's okay. Here you can see her right wrist is actually not looking well. It's matured more early, and also the bones don't look well. So this is a damaged wrist. This was reported by the radiologist. I'm not sure if anyone sees any other things, but this was how I got the picture back from the radiologist. No more wrist, no other abnormalities seen. So then the question is, of course, what can it be? And the swelling of the wrist, the joints that were limited, made us think of JIA. But what really struck us is that she didn't have any pain, which we know that doesn't need to be there with JIA, but the most striking thing at physical examination was actually her stiffness in a lot of other joints. And that made us think, and we thought, maybe this could be a metabolic disease. So we consulted our metabolic specialist, and she actually said, there's no metabolic disease. This kid is doing well at school She has no psychological delay, her motor function. No, it's not something that I would think of a metabolic disease. But we also looked ourselves and looked a bit into literature, and we were not convinced that it was not a metabolic disease. And actually, we did very directed investigations to enzymes in blood, in white blood cells. And indeed, the girl turned out to have a disease called mucolipidosis, and then she had the type II- III. And what's here in Dutch is that it actually says there's normal activity of this enzyme, iduronidase, I'm not a metabolic doctor, so it's hard to pronounce. But here with, it's not mucopolysaccharidosis type I, but the other ones, you see all the stars, are very much elevated. And that's how they know, the lab knows, it's this disease. To tell you the truth, I had not heard for it before, but if you look well, and that's gonna be one of the key messages of this talk, if you look well in specific papers or specific things, it's just too easy to not miss it. So the big thing is, with these diseases, think about it, look it up in some key papers that you have, and I'll provide you with one, and a tip for a second one. And then you can actually make the diagnosis. Just to get a bit of epidemiology, here you see the prevalence of pediatric autoimmune diseases and JIA, of course, is the most prevalent rheumatic disease in childhood, followed by lupus, and then the severe, sorry, the systemic vasculitis. And if you put in lysosomal storage diseases, as this disease is a lysosomal storage disease, it's actually in between. So it's less frequent in JIA, but it's more frequent than lupus. So for sure, you should have some patients in your clinic presenting at any time during your career with this disease. You have to know, though, because you'll say, well, I don't have 25 patients. Do you? I don't either. I had two patients now in my 20- year career, so that's not a lot. But this is the number, it's the combines of all diseases, and not all lysosomal storage diseases or metabolic diseases present with this phenotype, with joint problems, stiffness, so with symptoms that actually, they get referred to us. Most of the metabolic diseases, of course, retarded patients, very abnormal, investigations by physical examinations, and they get the diagnosis before anything else. So this number is a little bit flattered. It's not the ones that we see. So probably, I think, in your career, again, you'll have, if you look well, maybe five patients. So yes, the subject of this talk are just the lysosomal storage diseases, and that's because these, as I said, present mostly with mild phenotypes that actually may resemble JI. There are four subtypes, mucopolysaccharidosis, Gaucher or Fabry, then the mucolipidosis, as this patient had, and there's another disease called Farber disease. If you look at all four of them, the severity is very variable. So Gaucher, of course, I think most will know, will be much easier to recognize than, for example, some of the milder mucopolysaccharidoses or the mucolipidosis. And one of the key messages, these diseases, specifically these four groups, can actually present as a JIA patient. So, where do you look for, when should you be between all of your patients with JIA? Think about the disease and not only at the point that you notice that your treatment isn't working. The whole thing, the whole idea of this talk is that you'll be able to at the start, you get a patient referred, recognize that there's something different about this kid. And I actually set four main points, four key points to think about, to memorize. First of all, in these diseases, the kids are more stiff. They have a bit of joint swelling, but mostly they are stiff throughout their body, so not just one joint. And it may be missed because a lot of people don't even look and check the whole locomotor system. Second, pain is not prominent in most of these diseases. It's actually a bit hard because most JIA patients don't complain about pain. But if you ask them, they can do sports, they can do other things. And then if you go in, they'll say, well, you know, there's some aching, there's some, so most you'll get some pain in your further history. But these kids don't have pain, it's mostly stiffness where they complain about. They can do things, they can reach out as much as they would like to with their hands or shoulders, so the pain, again, it's not prominent. The third thing, and that's for many of the lysosomal diseases, they have an early infancy carpal tunnel syndrome or trigger fingers. And I hope you're all familiar with what a trigger finger is, but it's when your finger, and mostly it's the thumb or the smaller fingers, if they just contract, and it needs to be surgically removed, like the tendon needs to be loosened, and then it's repaired. So these kids often have in their history a trigger finger, and that's, when you hear about that, that must actually direct you towards lysosomal diseases. And the fourth key point is that you have to look for x- ray abnormalities of the bones. And something in your mind should also be there that maybe at presentation when you see the kids with the problems of the locomotor system, they not always already have those abnormalities. So that can develop throughout the disease. Then some more general things, so those four, I'm just going to go back, those four main points will lead you to find whether a girl or boy that you suspect of having JIA actually doesn't make it quite typical. This makes your case of a kid with a chronic arthritis atypical and needs further examination. And further examination actually is to ask a bit more and know about that they can have normal psychomotor developments. So that's not a reason not to check for metabolic diseases. So actually our metabolic doctor did not have that much experience, yet, what's wrong? You can perfectly have normal psychomotor developments at the age of six, maybe even eight, and still have a metabolic disease. Also you need to know that facial appearance, so most of the lysosomal diseases, they have a broadened face, as you might know, but most at younger age look normal. They don't have yet a different face. There's no morning stiffness, which you would expect for a JIA. Really take a careful history for this, because a lot of kids won't recognize if you ask, are you stiff in the morning? Really have to ask what they do, if they get up, if they need help, if they can dress themselves, if they make their own bread or breakfast themselves, use their hands, really go into detail. But if there's no morning stiffness, that's really odd for a kid with JIA. Blood work can be normal, but of course that's with JIA the case as well. JIA mostly is in girls, but these diseases are just as much in boys and girls. So you'll see with a boy, maybe you should even be more suspicious of these diseases. And also important to know that there's not just the young kids that you need to suspect for these diseases. They can also be in their teenage years, specifically Fabry disease develops later. So also the age is not a limitation. Even in a teenage girl or teenage boy, you have to think about it. And just go back to the four key points that I listed before. So, just to teach you a bit more about the bone abnormalities that you can see, mostly you do see that the kids are relatively short. So if you look at the parents and you look and you check what their height should be expected from the height of the parents, you see that they are always a bit short. Not abnormally short, so it's not that they fall off the curve, but they are a little bit short when compared to what you would expect with their parents. As I said, they can have a claw hand, that's the trigger fingers, but also the limitations in the joints of the fingers, so in the MCPs or the PIPs, they make the fingers stretch out less easily. And then, your radiologist will often call the bone abnormalities that you see dysostosis multiplex. And for the Latin knowers around you, so that know Latin, this just means it's wrong, this is just not how a bone would look, this is bone, so this is actually translated as a wrong bone on multiple places. So it's actually no diagnosis, it's just something that your radiologist says if they don't really know what's going on. They won't always call it dysplasia, because maybe with dysplasia, you would think more of metabolic diseases or genetic diseases, but this is often a terminology that your radiologist would use. And this is actually a table from the key paper that I want you to really all store in your clinic, and if you can just take a peek at it if you suspect something is wrong, but not your A in a kit. I won't go to all the details, but here you see the head, the thorax, the spine, the legs, the hands, the hips, and the knees. They can all have specific abnormalities, and in this paper, you can actually see them listed. It can also be missed by your radiologist, because they're not focused. If you say JIA, they'll look at JIA, but they can miss other things. And just to show you what you actually can see, here you see the skeletal bone, and what's actually the remarkable thing about this picture is that the bone here is widened, so it's too big for a normal kit, and it's one of the signs in the skull of a lysosomal storage disease. What you see here is that the femur heads are just not right. They don't look well, they're irregular, and often you also see irregular acetabulars. So here you see sclerosis here as well, and they're not as deep as they should be. Maybe they would call this a bit of dysplasia as well, but this is actually a kid with a lysosomal storage disease. This is a much more known abnormality. It's from Gaucher's disease, and it's called the Erlenflask, just because it looks like an Erlenmeyer flask. You see here, it's pretty clear. Here maybe too. But if you look at this picture, if you're not suspected, maybe a few years earlier, you would have missed it. So also, lesson is repeat. If you have a patient, you don't expect the things to go that you should be going. In a kid's thought of JIA, just make extra x- rays, new x- rays, and see what they look like. So what you actually see in the lysosomal disease, specifically also with the girl that we're talking about in our case one, is that the metacarpals, but also the phalanges, they are just too broad. As you can see here, they're short. You can see the hand here. And they're very broad. If we look at the picture again of our girl, again, you see this is wrist. These are the abnormal wrists. But when I teach this, I've teached this before, and some actually within the audience said it looks a bit weird here. This is too broad. And one of the signs is that actually this part is actually broader than the part here or the part here. So the diaphysis is broader than the epiphysis that's adjacent. So that's in general what you see. But again, my radiologist missed it. I didn't see it either at that point, as I said, because I only thought this is not a typical case of JIA, and we have to look further. This is the key paper that I need you to collect. paper and put it somewhere in a folder next to you in your office. It's a very practical paper. It's one of my colleagues, Nico Wulffraat, from the Netherlands. And this is a metabolic doctor. This is an orthopedic surgeon. And this is a resident. And they wrote this really comprehensive paper with very nice tables. It actually helps you to think whether it would fit between the different diseases. I specifically said lysosomal diseases. I don't want you to memorize or know what is a Hurler exactly, what is a Sanfilippo exactly, because you'll forget. It's too rare to know all the systems, but just, I promise you with this paper, it's very easy to see, just look at the symptoms here and see whether it fits with the patients that you have in front of you. And I just listed for the four different Lusosomal diseases that can mimic JIA, the most permanent and most frequent features. You see in the first two, it's the stiffness really that stands out. Trigger fingers also in the first two. And this is actually very, can be otherwise very mild, and only the stiffness may trigger you towards this disease. But in some other mycobacterial sarcoidosis, you actually have the claw hands.
[00:20:59] Dr Sylvia Kamphuis: You can have, not in all patients, organomegaly, so a liver or spleen that's enlarged, a broad facies or a coarse facies, and a psychomotor retardation. If you go to Fabry and Gaucher, we all know that they can have the Gaucher bone crisis, so they have pain. And Fabry is actually known for the pain crisis as well, and that's specifically in the hands. It's all written down in the paper. Just look and check the tables. Farber's disease is one of the actually only metabolic disease that actually can have an elevated CRP and ESR, and they can have subcutaneous nodules. So maybe you think of irritable nodosum, where it's actually Farber's disease with elevated ESR and these nodules. And again, these also can have joint swelling. The others as well, but not much in front, mostly the stiffness and some joints that may be swollen. And for all four, just pay attention to the x- rays and ask specifically if your clinic is not liking to be JIA, just list them to, sorry, just do extensive x- rays and ask radiologists, can this be a lysosomal disease? Again, use the paper and check it. Then to end this case one with lysosomal storage disease and this part of the talk, you have to know how to diagnose them. And again, how nice this paper. In table three, they actually list what you do, because our patients, we wouldn't have found our patients if we had done just a blood screening test for GAGs, that's how they call it. That would not be enough to make the disease. So then again, if we would have done only that and it would have said by the lab, there's no metabolic disease, then maybe we would have a delay of another few years. Now you really have to look for these specific diseases. So you go to table two or table one and you list the diseases that can actually fit with the phenotype of your patient. Then you can take the paper and you go to table three and you look what you need to do and also some extra comments that make you certain that you sometimes really need to do these expensive investigations. So again, for three and four, you need enzyme that's expensive, but that's the only way to really find it. Fabry and Gaucher, you need enzyme, but it can also be DNA that you actually do need specifically in girls. And this is what I said before, mucolipidosis, also enzyme diagnostics necessary. Therapy unfortunately only for a few, we have enzyme replacement therapy, but for our patients, there was no enzyme therapy available. And the only thing we can do for her is help her and just support her in the progression of the disease itself. But for the other diseases, as you see above, if you diagnose them early, and that's why it's so important that you do have the option, then it's not a typical case of JIA that you have the option of this lysosomal storage disease in your head and act appropriately and in time. Okay, we'll move on now to the next case, and this is a. I'm just gonna tell in front, up front that it's not a metabolic disease. This is actually a genetic disease, and there are- this is not the only genetic disease that's around. There are many more genetic disease, but this is actually a disease. That is something that also you should approach a few cases in your career. This is a boy. He presented at seven years and he was referred to me by the orthopedic surgeon. He had a swollen knee for a year and again the same with the other. Don't think that the doctor didn't do a good job. He probably didn't complain at all. It was just swollen. He could do what he would like to do and there was not much of a hurry and they just waited and waited to it to disappear. However, it didn't disappear and the reason for referral now was that it actually got a bit of painful when he was sitting. It wasn't, but it was when he was doing exercise. So during the year actually it did get a bit painful and also that's a reason why they really felt that something needed to be done- is that the walking was not good as it used to be. His previous history was actually unremarkable. I didn't see any other things, any abnormalities in any other organ system, but what was remarkable was his family history. So both sorry, his family. He came from Pakistan, where it's very useful, very used to marry within families. So his father, his grandpa were brothers, his both grandfathers were brothers from the father and the mother, but also from another side, from the mother, they were related. So this was typically a consanguineous family from Pakistan. And the mom said: well, his sister is also with orthopedic surgeon, she has also swollen knees, but that's once in a while and actually she has a disease called something with epithesial whatever. She didn't really know. But she said this is different, this is not as he has, because he only has a swollen knee. And then she also said that her sister had rheumatism. There was not much not treated by any medication and also not too much swelling. And also she thought the mother that this was not something that would fit with the disease of her son. So when I investigated them- and that's something I think with the ones of you that have experience with rheumatic diseases and know how to and see swollen joints- that often happens they get a kid referred with one joint and if you look closely there are actually more, and this boy clearly had one knee with both ankles and both wrists that were swollen. There were no limitations. I would say yes, but at that point I saw no limitations and this is something that you not always experience, but actually also the mom said it. That she said sometimes when he moves his legs it's a bit of rubbery, so it's not a necking or a nicking, what you do with, like with playing with the fingers. But she said he makes noise, sometimes friction noise. That's how she actually called it. Well, these are his knees, because I told you you have to do x- rays and just take a sec to look at it and as you can see the bones, I'd say pretty normal, they look nice. There's maybe a bit of difference. This one is broader than this one, but I'm not sure if that's just not because the knee was a bit more up front. You know the space in between the bones is large enough, so probably the cartilage is fine as well. Again, the tibia looks nice as well, but you can actually see that subcutaneously there's some swelling. That's not why he did the x- ray, because you saw that at the physical examination, but you see it here as well. So we did his hips as well, and actually what you see? Not his femur head, it's pretty normal. But you can see here that this is not what it should be. There's actually sclerosis, and here there's also sclerosis, and this is already a direction or a hint towards a diagnosis. But you don't see coxa vara, which means that the angle of the femoral head is more of varus, the vara region, than in the valgus region. But in this case it was still normal. So only the thing that you see at the hips is that it's a bit sclerotic. So then the question, of course, is what kind of disease should you think of? And to recapitalize, he had only a spinal node, but the history actually should make you worry and think of another disease. And what I actually did is ask for the sister, and if I, because she was actually in our hospital as well with the orthopedic surgeon, if I was able, if I was allowed by the mother to see her disease, because maybe the sister, I thought, with this family that was much related, consanguineous, I mean, that maybe the sister would point me towards the diagnosis that the boy would have. So the mom said, yeah, sure, you can look in her files. And she was 13 years, and it all started at two years. So it was, you can actually read everything, I'm not going to read everything out, but it started at two years, and then it progressed later on, much more extensive. She had polyarticular involvement. She did have chlorine, but only at a later age, but she was operated on at two already for chlorine of the thumbs, trigger fingers, you should say. And then, again, polyarticular disease, and I can't see why the mom didn't think of the same, that her daughter would have the same disease as her boy. So if you looked at her joints, her joints are worse. So you see this, it's a little bit tight, so the cartilage is not as well, and the bone doesn't look as nice. This is all a bit edgy, the wrists, not too much cartilage in between, and it all, well, you can hear I'm not a radiologist, but I think that's just summarizing it very well. It's just too close together, not too much joist pains. It's a bit edgy, it's not nicely rounded, and it's also osteopenia. And the same goes here, it's a bit, you know, these are flattened. It's just not specifically abnormal, but it's what they said, epiphyseal abnormalities, epiphyseal dysostosis. And her hips were actually worse, and she had a lot of limitations. You could barely move her hips, she had hardly any rotations, and a bit of flexion left. And you can see it's completely abnormal. She had coxa vara, and she also has this extensive sclerosis of the acetabulum. The feet are actually not that bad. You only can see a bit of broadening of the metacarpals. So what's her disease? And actually, with the trigger fingers, with the hip abnormalities, and the swelling of the joints, that's the extensive swelling of the joints, that should actually trigger you to this disease, namely CACP, Camptodactyly-Arthropathy-Coxa Vara-Pericarditis. And again, yes, I didn't tell you about pericarditis. So both these kids did not have pericarditis. And it's important to realize that the disease, as we often have in childhood with genetic diseases, it accumulates over time. So at presentation, often this disease is shown in an incomplete phenotype yet. And indeed, this is a genetic disease, and it's actually a genetic disorder of the tissue. It's lubricin- called, but of the fibromuscular tissue, so the fibrous tissue, I should say. And both had a homozygous mutation. This to let you know how frequent it is, it's less frequent. But if you compare it to a specific like mucolipidosis in the first case, it's actually more frequent. So it's as frequent as you see you get with polyarteritis nodosa or with scleroderma. Just with this disease its an autosomal recessive disease and it should be in boys and girls. And specifically, if you have families that are interrelated, you should think of, and it's an atypical case, think of genetic disorders and specifically think of CACP syndrome. As I said, it's often incomplete at presentation. Disease is almost always universally present at the moment that they present to you, because this happens early in life, and the arthropathy only develops later in life. But now, as we recognize it better, you can see even within families that the severity really can vary, because I've seen these two, the boy and the girl, the sister and the brother, for quite some years now. I think five years since the first time I saw them. The boy is actually still doing very well. He has his runnings, but he hardly has x- ray abnormalities, and he hardly has limitations. I think only his knees are limited, and the girl is progressing, but also at a quite stable rate. So again, the boy is now 11 years and still has swollen joints, but no limitations. So again, it can be very varying. The clinical phenotype that you see, even within families- pericarditis- is only sometimes. At the first description of this disease, all the patients had it. But now if you read about it more and more, this is only sometimes present, again, only sometimes in some studies. More often, and also this is a later symptom- you don't see it right at the start. This is something that you don't read a lot about it. But with the case that I had, I have around six patients with this disease and in some you actually hear that if you move the joint, specifically the knee, that you can hear the bends, that they make a bit of a sound. It's different. You hear it sometimes here too. What should be the key points for our thinking of CACP is again, no morning stiffness- that's odd for a kid with JIA- positive family history and if they're related, if the mom and the dad are related, our family are related. Again, the trigger fingers are the contradictory- and no blood abnormalities. But you all know in JIA you don't have to have blood abnormalities. And again, here it's: do your X- rays. You can have abnormalities here as well. So this key list is not too different from the lysosomal storage diseases if you recalibrate the other key points that I mentioned before. And so if you think of lysosomal diseases you should also think of CACP, as I said. No, I did not say this yet, but it's only symptomatic therapy. We cannot have any. There's no causal therapy, and many of the patients from studies that you can read about have had methotrexate. They have had sometimes even biologicals and because they were misdiagnosed as having JIA. And maybe it's good, because at least we know that it wouldn't make sense that it would work because of the genetic defects in the fibrous tissue. But at least we know that anti- inflammatory medication doesn't help them. And they really have to be frequently- like three, four times a year- go to a rehabilitation specialist that can actually support them and help them to keep on to limit the limitations, so to limit the progression of the joint contractures, and you know so these kids should be at a physiotherapist every two weeks just to be stretched and keep, hopefully optimally help them to keep their joint mobility. And that makes me coming to the end of the session. I said the key paper already, but this is also something I really would like you to well, actually to take part of. This is a chapter in the PRESS online course in pediatric rheumatology and EULAR and PRESS. EULAR is the adult association for rheumatic diseases and PRESS is the pediatric European organization for rheumatic diseases, and actually they developed an online course. It's very cheap, it's- I'd say so. It's- I think it's 100 euros, maybe 150 euros, and it's... a year. You get it's an e- learning course so you can do it from any place in the world and it teaches you about all rheumatic diseases in childhood and this is a chapter. It's a very good chapter. I can tell I have no influence because I didn't write it myself, but it's a very good chapter where actually the things that I mentioned you summarized today, you can actually read more about. This is the paper that you all need to have, but you don't have right now, and thank you for listening and I'm open to any questions that you might have and for your knowledge, I'm just looking a bit into the screen, otherwise I can't read the questions because the questions appear on my right side and I see one of you post a question: why do you emphasize the lysosomal diseases and not other metabolic diseases? Yeah, well, that's a very interesting question because, of course, there are a ton of metabolic diseases and until I knew about that paper, I always felt a bit lost and I thought, you know what, I'm just going to consult my metabolic doctor and that's it. But what actually, if you read a bit more about metabolic diseases, many of the other diseases have a much more severe phenotype, that clearly it's not just JIA. They have joint problems, but they have so much more that they will never be referred to us or we see that there are so many more other symptoms that it's not a rheumatic disease. And that's actually the reason why I'm focusing on lysosomal diseases because the lysosomal diseases actually can mimic JIA and that makes them stand apart from many of the other metabolic diseases. So I'd say with the rarity of the metabolic diseases, I'd focus if you get a kid that's presented with joint problems, check lysosomal for the lysosomal disease. If the phenotype is not fitting with JIA, just check just for the lysosomal diseases because most of the other metabolic diseases have a much clearer phenotype, much more severe and you probably won't even get consulted then. Next question. It's another nice question, I think.
[00:40:40] Dr Sylvia Kamphuis: It's not clear to me why the patients have swelling of the joints and may have abnormalities that resemble JIA. Yeah, I didn't mention that. Thank you for the question. Well, it's a lysosomal storage disease. I just focused on the message and on what you see, but actually the pathogenesis I left out, but what's happening is that it's a storage disease, so the lysosomes don't work well. And the breakdown products that normally disappear in your body and get removed, the breakdown products are just too large and they stay in certain places.
[00:41:18] Dr Sylvia Kamphuis: And one of the places that they stay is in the bones, but also in the joints. Having those breakdown products that are not normal, that should not be there, those breakdown products that come from the lysosomes that won't work well actually give rise to inflammation. So the products themselves give rise to inflammation and the inflammation attracts some cells, some bloods and they can actually make the joints swollen. And again, also if you have something, you may give for the inflammation status also may be pain. Not always, but there may be pain.
[00:42:02] Dr Sylvia Kamphuis: Again anti-inflammatory medication will not solve it because those products will stay there. So you can only symptomatically treat with painkillers, but you can actually really remove those products and adding a methotrexate or adding a TNF blocker won't help the patients. But that's the reason why the joints get swollen. Another question, oh this one I did answer, but maybe you missed it. How often have you diagnosed lysosomal diseases in your career? So that's two times for now and I've worked 18 years in rheumatology, so that's not that often. And maybe to add a new thing on, why is it important to know about if it's just so rare? Well, it's that these patients can be helped earlier and better and you can actually prevent damage if you recognize them. And also they can have problems with medication and no one wants to take medication that they don't need. So I think it's just good that you know, you know, typical case of JIA., that's JIA., but if it's not typical, please think of the other diseases. And I see, that's it. No more questions I see from the organizers. Well, I would really like to thank you for listening. It was my first experience doing a webinar and I must say it's kind of weird to just talk and talk and talk and not see or hear any of your listeners or your audience. I hope you enjoyed it and I hope you agree that you met the learning objectives of this session. Thank you. Bye-bye.