My name is Sarah Johnson, and I have had lupus since I was a teenager. When I was fourteen fifteen, I started having this series of fevers, and they were kind of a couple days a week once a month, and then all of a sudden, they were for a whole week each month, and then they just the time in between them started getting smaller and smaller. I couldn't find any source of infection or reason that I would be having any fevers. For some reason, these fevers would get extremely high in like one O two, one oh three. I would be really nauseous. I wasn't able to eat. I wasn't really able to keep food down or liquid down, and I ate a lot of popsicles because it was the only thing that I could eat for a long time. With these fevers would come a lot of soreness. It was difficult to get up and walk around, especially in my ankles and my knees and my hip. It was uncomfortable to sleep. After a while, it just had been months of this type of back and forth fevering, not being able to keep a lot down, and the fevers got high enough and I got weak enough that I had to go to the hospital and I stayed in the hospital for probably about two months. So I was around fifteen at this time, so you know, leaving school at the age of fifteen it is extremely traumatic because your friends are.

My name is Sarah Johnson, and I have had lupus since I was a teenager. When I was fourteen fifteen, I started having this series of fevers, and they were kind of a couple days a week once a month, and then all of a sudden, they were for a whole week each month, and then they just the time in between them started getting smaller and smaller. I couldn't find any source of infection or reason that I would be having any fevers. For some reason, these fevers would get extremely high in like one O two, one oh three. I would be really nauseous. I wasn't able to eat. I wasn't really able to keep food down or liquid down, and I ate a lot of popsicles because it was the only thing that I could eat for a long time. With these fevers would come a lot of soreness. It was difficult to get up and walk around, especially in my ankles and my knees and my hip. It was uncomfortable to sleep. After a while, it just had been months of this type of back and forth fevering, not being able to keep a lot down, and the fevers got high enough and I got weak enough that I had to go to the hospital and I stayed in the hospital for probably about two months. So I was around fifteen at this time, so you know, leaving school at the age of fifteen it is extremely traumatic because your friends are.

Pretty much the most important thing to you.

Pretty much the most important thing to you.

So going into the hospital, I had to start fluids, and this was basically just to get me up to a baseline where I felt semi normal again. And then with those fluids, I had too many fluids. I had pleurisy in my lungs, which is inflammation of the tissue around your lungs. So then I had a really difficult time breathing and they had to help drain fluids out of my lungs and give me LASiS to help me kind of shed that fluid. So that was kind of the first little bit of my introduction to whatever we thought was going on with my body. At the time, I didn't know anything about lupus. And at the hospital I was at the Children's hospital, they did a lot of different tests. They tested me for all sorts of different blood disorders, lime disease, rocky mountains, spotted fever, if I had a spinal tap to see if I had some sort of infection, really anything that you could think of. I was having blood drawn all the time, and really it didn't It wasn't until I started seeing a rheumatologist at the hospital that she started suggesting that it could be something called adult onset Stills disease or juvenile Stills disease, where you have sometimes when I would have these fevers, I would have this under this skin, not quite a rash, but it was like a modeling where almost when you get a bruise and you have like a speckley red under your skin. So I'd have that on the back of my upper arms and on the inside of my knees, and when I would when I would shower actually is when they would get most prominent, so almost like when there was heat and kind of inflammation in those areas, and so she noticed that as a sign that, oh, that's sometimes related to this rheumatoid condition, so maybe that's what's going on, and so kind of that was just my diagnosis for a long time, and really the only way I got better was by staying in the hospital, getting tons of fluids and eventually starting a course of steroids or pread and zone and taking that for a very, very very long time. I think I was probably on sixty milligrams or more of premazone for six months to a year, and based on all the things that had happened to me in the hospital, the stress to my body and my immune system for that long, I remember having like on my sixteenth birthday, I have pictures of me with different colored roots in my hair because my hair started growing a different color. So anyways, really that time just kind of passed, and then after all of this course of medication, I got a lot better. I would say the biggest thing that I can remember coming out of that was I had very very intense anxiety for a long time after that, for a few years, and I was fortunate enough to see a therapist who focused on chronic diseases, especially with people like my age, and just learn how to use a lot of coping skills to not be really scared all the time, because when you have something like this that you don't know where it came from or how it was spurred, you never know when it's going to happen again, or what's going to cause it, or what you're doing that's going to make it harder for you. One big thing is stress in my life was very stressful in my preteen years. There's a lot going on in my life and at home, and you're told to manage your stress, but when you're fifteen sixteen, it seems almost impossible. So that took me a long time to adjust. But now at thirty five years old, I feel like I'm doing a lot better with it. So from fifteen sixteen, I didn't really have any issues with this. Again, I think probably until I was around twenty one. I probably treated my body pretty poorly in my twenties, so I just assumed that whatever was going on with me was just me being run down and tired and started getting fevers again and then having a lot of the same issues. So I found a new roomatologist at that time basically said, oh, it's just this stills disease. You're going to grow out of it. Don't worry about it. So I moved on to another rheumatologist because I did not believe that whatsoever, And they looked at a lot of my past history which the previous roomatologists had not done, and said, you know, a lot of this really looks like lupus. There's this new test out there now where we can search for this essentially if you're more likely to have lupus or not, and it came back positive. So this is the best we can do at trying to figure out if it's potentially lupus. But at the end of the day, most of the trees treatments for this type of illness are the same. So I started hydroxychloroquin or plaquino when I was around twenty one, and I've been on it for fifteen years now pretty much with very few.

So going into the hospital, I had to start fluids, and this was basically just to get me up to a baseline where I felt semi normal again. And then with those fluids, I had too many fluids. I had pleurisy in my lungs, which is inflammation of the tissue around your lungs. So then I had a really difficult time breathing and they had to help drain fluids out of my lungs and give me LASiS to help me kind of shed that fluid. So that was kind of the first little bit of my introduction to whatever we thought was going on with my body. At the time, I didn't know anything about lupus. And at the hospital I was at the Children's hospital, they did a lot of different tests. They tested me for all sorts of different blood disorders, lime disease, rocky mountains, spotted fever, if I had a spinal tap to see if I had some sort of infection, really anything that you could think of. I was having blood drawn all the time, and really it didn't It wasn't until I started seeing a rheumatologist at the hospital that she started suggesting that it could be something called adult onset Stills disease or juvenile Stills disease, where you have sometimes when I would have these fevers, I would have this under this skin, not quite a rash, but it was like a modeling where almost when you get a bruise and you have like a speckley red under your skin. So I'd have that on the back of my upper arms and on the inside of my knees, and when I would when I would shower actually is when they would get most prominent, so almost like when there was heat and kind of inflammation in those areas, and so she noticed that as a sign that, oh, that's sometimes related to this rheumatoid condition, so maybe that's what's going on, and so kind of that was just my diagnosis for a long time, and really the only way I got better was by staying in the hospital, getting tons of fluids and eventually starting a course of steroids or pread and zone and taking that for a very, very very long time. I think I was probably on sixty milligrams or more of premazone for six months to a year, and based on all the things that had happened to me in the hospital, the stress to my body and my immune system for that long, I remember having like on my sixteenth birthday, I have pictures of me with different colored roots in my hair because my hair started growing a different color. So anyways, really that time just kind of passed, and then after all of this course of medication, I got a lot better. I would say the biggest thing that I can remember coming out of that was I had very very intense anxiety for a long time after that, for a few years, and I was fortunate enough to see a therapist who focused on chronic diseases, especially with people like my age, and just learn how to use a lot of coping skills to not be really scared all the time, because when you have something like this that you don't know where it came from or how it was spurred, you never know when it's going to happen again, or what's going to cause it, or what you're doing that's going to make it harder for you. One big thing is stress in my life was very stressful in my preteen years. There's a lot going on in my life and at home, and you're told to manage your stress, but when you're fifteen sixteen, it seems almost impossible. So that took me a long time to adjust. But now at thirty five years old, I feel like I'm doing a lot better with it. So from fifteen sixteen, I didn't really have any issues with this. Again, I think probably until I was around twenty one. I probably treated my body pretty poorly in my twenties, so I just assumed that whatever was going on with me was just me being run down and tired and started getting fevers again and then having a lot of the same issues. So I found a new roomatologist at that time basically said, oh, it's just this stills disease. You're going to grow out of it. Don't worry about it. So I moved on to another rheumatologist because I did not believe that whatsoever, And they looked at a lot of my past history which the previous roomatologists had not done, and said, you know, a lot of this really looks like lupus. There's this new test out there now where we can search for this essentially if you're more likely to have lupus or not, and it came back positive. So this is the best we can do at trying to figure out if it's potentially lupus. But at the end of the day, most of the trees treatments for this type of illness are the same. So I started hydroxychloroquin or plaquino when I was around twenty one, and I've been on it for fifteen years now pretty much with very few.

Issues or side effects.

Issues or side effects.

I'm at a stage with my loopus where I really only seemed to have a flare up every three years or so. Seemed like I had a flare up in twenty fourteen, twenty fifteen, then again in twenty seventeen, twenty eighteen, and then again twenty twenty twenty twenty one, which was a very strange time to have a flare up. A strange but also very positive time to have a flare up because I didn't have anywhere that I had to go, you know, I really could focus on taking care of myself. I spent a lot of time in my garden. But it was a really brutal flare up. The challenge for me has been. When you move and you see a different rheumatologist, you kind of have to explain your whole story to them over and over again. So for anyone who has this or has anything similar, being your own ad and keeping really good records is crucial because when I had this issue again in twenty twenty, I had to find a new doctor. I had different insurance at that time, and when you're well, you don't think to deal with any of this stuff. They came in handy when I was sick because I could take all this information to my new doctor in twenty twenty and say, this feels similar but different, and here's all the information that I have. So I stayed on premozone for most of the rest of the year, and I finally started feeling a lot better. And then phasing out of prednozone was equally as difficult, I feel like as going onto the prednizone because your body then kind of adjusts to this elevated level of incredibleness, which is feeling amazing. So since then I've been pretty well. Like I said, I was fortunate that I didn't have a lot requiring my attention that year. I didn't need to do field work for grad school. For a lot of people, those are very limiting factors to a disease like lupus, where you just can't expect what your schedule is going to look like or be able to anticipate these events in your life that may need to completely be canceled or changed because you don't know when or where you're going to have a flare up. Personally, I've chosen probably one of the worst fields to be in for someone with a chronic inflammatory disorder. I'm a field biologist. I spend a lot of time outside in the sun, physically active, but I love it and it's what matters to me. So I've over the years found ways to have a more flexible schedule or a schedule that's more adapted to what I need and when I'm capable. I also take really good care of myself in terms of wearing protective clothing. I treat all of my clothing with sunnguard, and I wear long sleeves, and I wear big hats, and I wear a ton of sunscreen and so all of those things in addition to therapy and you know, making sure I keep my stress at a good level and trying to get a lot of sleep. So yeah, I guess that's most of my life with lucas. I think that I'm very fortunate to have whatever version of this chronic disease that I have, because I can lead a pretty normal life. It's tough when I'm in a flare up, but I do feel like over time, I've built this kind of anthology of wisdom and knowledge that has helped me manage it so much better than I could have ever dreamed of when I was fifteen and things really felt terrible.

I'm at a stage with my loopus where I really only seemed to have a flare up every three years or so. Seemed like I had a flare up in twenty fourteen, twenty fifteen, then again in twenty seventeen, twenty eighteen, and then again twenty twenty twenty twenty one, which was a very strange time to have a flare up. A strange but also very positive time to have a flare up because I didn't have anywhere that I had to go, you know, I really could focus on taking care of myself. I spent a lot of time in my garden. But it was a really brutal flare up. The challenge for me has been. When you move and you see a different rheumatologist, you kind of have to explain your whole story to them over and over again. So for anyone who has this or has anything similar, being your own ad and keeping really good records is crucial because when I had this issue again in twenty twenty, I had to find a new doctor. I had different insurance at that time, and when you're well, you don't think to deal with any of this stuff. They came in handy when I was sick because I could take all this information to my new doctor in twenty twenty and say, this feels similar but different, and here's all the information that I have. So I stayed on premozone for most of the rest of the year, and I finally started feeling a lot better. And then phasing out of prednozone was equally as difficult, I feel like as going onto the prednizone because your body then kind of adjusts to this elevated level of incredibleness, which is feeling amazing. So since then I've been pretty well. Like I said, I was fortunate that I didn't have a lot requiring my attention that year. I didn't need to do field work for grad school. For a lot of people, those are very limiting factors to a disease like lupus, where you just can't expect what your schedule is going to look like or be able to anticipate these events in your life that may need to completely be canceled or changed because you don't know when or where you're going to have a flare up. Personally, I've chosen probably one of the worst fields to be in for someone with a chronic inflammatory disorder. I'm a field biologist. I spend a lot of time outside in the sun, physically active, but I love it and it's what matters to me. So I've over the years found ways to have a more flexible schedule or a schedule that's more adapted to what I need and when I'm capable. I also take really good care of myself in terms of wearing protective clothing. I treat all of my clothing with sunnguard, and I wear long sleeves, and I wear big hats, and I wear a ton of sunscreen and so all of those things in addition to therapy and you know, making sure I keep my stress at a good level and trying to get a lot of sleep. So yeah, I guess that's most of my life with lucas. I think that I'm very fortunate to have whatever version of this chronic disease that I have, because I can lead a pretty normal life. It's tough when I'm in a flare up, but I do feel like over time, I've built this kind of anthology of wisdom and knowledge that has helped me manage it so much better than I could have ever dreamed of when I was fifteen and things really felt terrible.

Wow, like wow, thank you, Sarah, thank you so much for sharing your story with us.

Wow, like wow, thank you, Sarah, thank you so much for sharing your story with us.

Yeah, Sarah, thank you that, I mean thanks for having to go through that by telling us this story and then sharing it with everyone. Just yeah, yeah, thanks, We're really grateful. Hi. I'm Erin Welsh and I'm Erin Almond Updike And this is this podcast will kill.

Yeah, Sarah, thank you that, I mean thanks for having to go through that by telling us this story and then sharing it with everyone. Just yeah, yeah, thanks, We're really grateful. Hi. I'm Erin Welsh and I'm Erin Almond Updike And this is this podcast will kill.

You And today if you haven't figured it out, we're talking about lupus.

You And today if you haven't figured it out, we're talking about lupus.

We are. This is a okay, this is probably the what is this our sixth episode? So the sixth time this season that we have said it's gonna be a big one. Yeah, and we've been right in every case. There's a lot to cover here, So should we get straight down to business? We should. It's quarantiny time. Excellent. What are we drinking this week? We're drinking the Butterfly smash. Love this why is the favorite?

We are. This is a okay, this is probably the what is this our sixth episode? So the sixth time this season that we have said it's gonna be a big one. Yeah, and we've been right in every case. There's a lot to cover here, So should we get straight down to business? We should. It's quarantiny time. Excellent. What are we drinking this week? We're drinking the Butterfly smash. Love this why is the favorite?

So shout out Sarah love this quarantiny title. She came up with it because she's amazing. It's butterfly smash because there is a very typical rash that you can see in lupus that is often called a butterfly rash.

So shout out Sarah love this quarantiny title. She came up with it because she's amazing. It's butterfly smash because there is a very typical rash that you can see in lupus that is often called a butterfly rash.

But it's a great it's a really good name, it really is. And a good drink erin what's in it? Yeah, So this is actually a listener suggestion, So thank you so much for sending this over because it is delicious. So it is a bourbon fizz, so bourbon and then strawberry puree and lime juice topped with ginger beer. So refreshing, so delightful, so so so so yum.

But it's a great it's a really good name, it really is. And a good drink erin what's in it? Yeah, So this is actually a listener suggestion, So thank you so much for sending this over because it is delicious. So it is a bourbon fizz, so bourbon and then strawberry puree and lime juice topped with ginger beer. So refreshing, so delightful, so so so so yum.

And we'll post the full recipe for that quarantine as well as our non alcoholic plasy but Rita on our website.

And we'll post the full recipe for that quarantine as well as our non alcoholic plasy but Rita on our website.

This podcast will kill you dot com and all of our visual media channels. We certainly will. Yeah. On our website you can find the things that you can always find there transcripts, the sources for each and every one of our episodes. We've got links to bookshop dot org, to goodreads list to music by Bloodmobile. Just go check it out. It's great everything. Yeah. Great.

This podcast will kill you dot com and all of our visual media channels. We certainly will. Yeah. On our website you can find the things that you can always find there transcripts, the sources for each and every one of our episodes. We've got links to bookshop dot org, to goodreads list to music by Bloodmobile. Just go check it out. It's great everything. Yeah. Great.

We do have a small piece of business to announce before we get into the content of this episode, and that is that you will notice a slight schedule change coming up in our episode, really schedule because I Aaron Almann Updike am having another baby and we'll be taking a leave of absence for a short time.

We do have a small piece of business to announce before we get into the content of this episode, and that is that you will notice a slight schedule change coming up in our episode, really schedule because I Aaron Almann Updike am having another baby and we'll be taking a leave of absence for a short time.

It's amazing. I'm super excited. It's going to be an adventure. But Aaron Welsh has covered because she's.

It's amazing. I'm super excited. It's going to be an adventure. But Aaron Welsh has covered because she's.

Got tons of bonus episode content that's going to be filling in any gaps.

Got tons of bonus episode content that's going to be filling in any gaps.

So yeah, So episodes will be coming out every other week, but instead of one regular season episode every other week, it'll be regular season episode two weeks later, bonus episode two weeks later regular episode. And this is just for a short amount of time, so we'll be back to our regularly scheduled programming briefly, all right, Well, any other business, I don't think so. I think that we should get started on this massive topic. I can't wait right after this break.

So yeah, So episodes will be coming out every other week, but instead of one regular season episode every other week, it'll be regular season episode two weeks later, bonus episode two weeks later regular episode. And this is just for a short amount of time, so we'll be back to our regularly scheduled programming briefly, all right, Well, any other business, I don't think so. I think that we should get started on this massive topic. I can't wait right after this break.

So lupus, or as it's more properly called, systemic lupus arithematosis, the first question that you may have listeners is what is this?

So lupus, or as it's more properly called, systemic lupus arithematosis, the first question that you may have listeners is what is this?

And the truth of the matter is we still simply don't know. Will we have a better understanding forty minutes from now, Yeah, yeah, we will for sure for sure.

And the truth of the matter is we still simply don't know. Will we have a better understanding forty minutes from now, Yeah, yeah, we will for sure for sure.

But I want to start with a quote which I don't do very often, but I read a paper from like twenty years ago, was published in two thousand and three, and that really just highlighted how little we knew then about the path of physiology of lupus, and I was like, well, surely when I get to the more recent papers. So then there was a paper that came out in twenty nineteen in the Lancet that started off strong with this quote. Quote Systemic lupus arithematosis is not only the prototypic systemic autoimmune disease, but also one of the most heterogeneous illnesses treated by physicians.

But I want to start with a quote which I don't do very often, but I read a paper from like twenty years ago, was published in two thousand and three, and that really just highlighted how little we knew then about the path of physiology of lupus, and I was like, well, surely when I get to the more recent papers. So then there was a paper that came out in twenty nineteen in the Lancet that started off strong with this quote. Quote Systemic lupus arithematosis is not only the prototypic systemic autoimmune disease, but also one of the most heterogeneous illnesses treated by physicians.

End quote. It doesn't really tell you much, doesn't. Nope, it doesn't.

End quote. It doesn't really tell you much, doesn't. Nope, it doesn't.

And also just like it really underscores just how okay we need to just keep going because it's going to be too much Okay, I am a little worried that for some people this biology section might feel very unsatisfying, But the truth is that that's because lupus is a disorder that we still just don't fully understand. And I really wonder if we will find in the years to come that what we now call loopus or even systemic lupus arithematosis, is actually this very very large umbrella under which we might have in the future many different disorders as we understand more of the genetics and everything that underpin this disease.

And also just like it really underscores just how okay we need to just keep going because it's going to be too much Okay, I am a little worried that for some people this biology section might feel very unsatisfying, But the truth is that that's because lupus is a disorder that we still just don't fully understand. And I really wonder if we will find in the years to come that what we now call loopus or even systemic lupus arithematosis, is actually this very very large umbrella under which we might have in the future many different disorders as we understand more of the genetics and everything that underpin this disease.

But in any case, we will try our best.

But in any case, we will try our best.

So what I'm going to do is first highlight some of the most common symptoms, which there are a lot, how we diagnose lupus, what we know so far about both the big picture, you know, risk factors and contributing factors, as well as the nitty gritty path of physiology of what's happening in our bodies in someone with lupus, and then at least a little bit about how it's treated or managed, which is a lot of ground to cover. So, like I said, already, lupus, which is how I'm going to refer to it from now on, is a chronic systemic autoimmune disease. There are, and I'll mention all of these, some other forms of lupus that are sometimes lumped within lupus, and sometimes they're very separated, and I'll at least mention all of them. But there is cutaneous loopus, which means that you might only have skin findings without any systemic symptoms. There is a drug induced lupus that is brought on by medications, but generally not something that turns into a chronic disease. It usually resolves with stopping that medication. And then there's also neonatal loopus, which can happen to infants that are born to people with lupus.

So what I'm going to do is first highlight some of the most common symptoms, which there are a lot, how we diagnose lupus, what we know so far about both the big picture, you know, risk factors and contributing factors, as well as the nitty gritty path of physiology of what's happening in our bodies in someone with lupus, and then at least a little bit about how it's treated or managed, which is a lot of ground to cover. So, like I said, already, lupus, which is how I'm going to refer to it from now on, is a chronic systemic autoimmune disease. There are, and I'll mention all of these, some other forms of lupus that are sometimes lumped within lupus, and sometimes they're very separated, and I'll at least mention all of them. But there is cutaneous loopus, which means that you might only have skin findings without any systemic symptoms. There is a drug induced lupus that is brought on by medications, but generally not something that turns into a chronic disease. It usually resolves with stopping that medication. And then there's also neonatal loopus, which can happen to infants that are born to people with lupus.

Huh.

Huh.

But today our focus is sle systemic loopus. Henceforth, again I'm just gonna call loopus. And we have covered on this podcast a number of other autoimmune diseases in the past. We've talked about MS, We've talked about type one diabetes. But to refresh everyone, autoimmune simply means that one of the main pathologic drivers of a disease is the production of antibodies that are attacking one's self rather than only attacking non self. And this auto antibody as they're called production is associated with a whole bunch of other immune system dysregulation that can lead to inflammation and damage to various parts of the body. In the case of the other autoimmune diseases that we have covered on the podcast, for example, MS, it's predominantly just affecting our central nervous system right, destroying our nerve axon sheets. Type one diabetes is auto antibodies destroying the insulin producing cells of our pancreas. These are you can think of as like very targeted, localized autoimmune disorders. They're affecting a single organ or a single organ system. Lupus, on the other hand, is systemic. It does not discriminate, and it has the capacity to affect any and every organ or organ system or part of our body. And that is what makes it so incredibly difficult. It's not the only systemic autoimmune disease, rheumatoid arthritis, chogrin syndrome, there are a lot of others, but lupus is probably the most heterogeneous and difficult to get a handle on. So of course it's the first one that we're going to cover on this podcast.

But today our focus is sle systemic loopus. Henceforth, again I'm just gonna call loopus. And we have covered on this podcast a number of other autoimmune diseases in the past. We've talked about MS, We've talked about type one diabetes. But to refresh everyone, autoimmune simply means that one of the main pathologic drivers of a disease is the production of antibodies that are attacking one's self rather than only attacking non self. And this auto antibody as they're called production is associated with a whole bunch of other immune system dysregulation that can lead to inflammation and damage to various parts of the body. In the case of the other autoimmune diseases that we have covered on the podcast, for example, MS, it's predominantly just affecting our central nervous system right, destroying our nerve axon sheets. Type one diabetes is auto antibodies destroying the insulin producing cells of our pancreas. These are you can think of as like very targeted, localized autoimmune disorders. They're affecting a single organ or a single organ system. Lupus, on the other hand, is systemic. It does not discriminate, and it has the capacity to affect any and every organ or organ system or part of our body. And that is what makes it so incredibly difficult. It's not the only systemic autoimmune disease, rheumatoid arthritis, chogrin syndrome, there are a lot of others, but lupus is probably the most heterogeneous and difficult to get a handle on. So of course it's the first one that we're going to cover on this podcast.

Uh, tell me what you mean by heterogeneous In this context.

Uh, tell me what you mean by heterogeneous In this context.

Let me tell you by going over the symptoms, that'll do it. Yeah, And that's really what I mean is that the way that this can present, both in terms of the symptoms and in terms of the laboratory findings that we see very a ton person to person. So one person's experience with lupus might be higherly different than another person's experience with lupus.

Let me tell you by going over the symptoms, that'll do it. Yeah, And that's really what I mean is that the way that this can present, both in terms of the symptoms and in terms of the laboratory findings that we see very a ton person to person. So one person's experience with lupus might be higherly different than another person's experience with lupus.

Okay, So when it comes.

Okay, So when it comes.

To the symptoms, because of that, I can't give you, like I often do this timeline of events of what happens in terms of symptoms, like first we see this and then this, Because somebody with loopus can present with any or all of the symptoms that I'm going to go over. It's unlikely that someone would have all of these symptoms at once, but it is entirely possible that they could have all or nearly all of them throughout their lifetime at different times. So the diagnosis of lupus is really challenging. Because of that, it is easy to both under attribute symptoms, to not recognize symptoms as related to lupus, as well as over a tribute, especially if somebody has a previous diagnosis of lupus, to just assume that everything someone's experiencing is related only to lupus, like a la house.

To the symptoms, because of that, I can't give you, like I often do this timeline of events of what happens in terms of symptoms, like first we see this and then this, Because somebody with loopus can present with any or all of the symptoms that I'm going to go over. It's unlikely that someone would have all of these symptoms at once, but it is entirely possible that they could have all or nearly all of them throughout their lifetime at different times. So the diagnosis of lupus is really challenging. Because of that, it is easy to both under attribute symptoms, to not recognize symptoms as related to lupus, as well as over a tribute, especially if somebody has a previous diagnosis of lupus, to just assume that everything someone's experiencing is related only to lupus, like a la house.

So how then is some thing determined to be over or under attributed, right, Like, how do you know that it's correctly attributed to lupus? Oh, Aaron, if I had an answer to that, we don't have any sort of cellular diagnostics, so we do for a lot of these.

So how then is some thing determined to be over or under attributed, right, Like, how do you know that it's correctly attributed to lupus? Oh, Aaron, if I had an answer to that, we don't have any sort of cellular diagnostics, so we do for a lot of these.

So let's get into what some of the most common symptoms are and then we can talk about kind of that. Okay, okay, Yeah, So one of the most common symptoms that we see is arthritis. Arthritis is a major symptom of loopus, with about eighty five percent of people with loopus having symptoms of inflammation and pain in the joints. Joint involvement is actually one of the most universal symptoms of systemic autoimmune diseases. Why our joints specifically are so susceptible to this type of autoimmune inflammation, we don't know, but they definitely are. So Arthritis pain in your joints, especially in the hands, in the wrists, but it could be any joint in your d higher body. That's one huge one. Then there are a whole host of skin manifestations, and these can vary widely. I'll talk about some of the most common ones. Many of these are brought on or exacerbated by exposure to the sun. So a new rash or a new skin finding that's brought on after sun exposure is something that might make someone think lupus. And as I mentioned early on, some of these skin findings are also found in people that have cutaneous lupus, arithematosis or cle That doesn't necessarily mean that they have any systemic symptoms of lupus, so it's it's a lot, but the skin involvement happens in again about seventy to eighty percent of people that have lupus systemic lupus, and they can be classified by how quickly they appear or how long they last. So there's some rashes like the malar rash or the butterfly rash. This is like a reddish, not very raised rash that goes across the nose and onto the cheeks and really looks kind of like a butterfly, like if your nose was the body of a butterfly, and then your cheeks are like the wings. And it doesn't usually go into the nasolabial folds like right, interesting, that's your smile lines. Yeah, so that's one type of rash that we can see, very often brought on by being in the sun or by sun exposure. Sometimes the skin findings might be ulcers in the mouth or other mucous membranes. You could have just disseminated like splotchy red bumps kind of all over, or a number of different discrete patches on the skin, especially on sun exposed areas, that look round like discoid is one very common finding. Maybe a little bit like a psoriasis plaque, so something that's like raised and kind of scaly. That's a common one. You could also have blisters that aren't very superficial but are kind of underneath that first layer of skin. There are a few other things that we might see. Leveto reticularis one of my favorite words. This is a lacy pattern of purple like modeling that you might see usually on the lower legs, or rainode syndrome, which is where in the cold, the tips of your fingers or your toes turn white or even blue or purple and it's incredibly painful.

So let's get into what some of the most common symptoms are and then we can talk about kind of that. Okay, okay, Yeah, So one of the most common symptoms that we see is arthritis. Arthritis is a major symptom of loopus, with about eighty five percent of people with loopus having symptoms of inflammation and pain in the joints. Joint involvement is actually one of the most universal symptoms of systemic autoimmune diseases. Why our joints specifically are so susceptible to this type of autoimmune inflammation, we don't know, but they definitely are. So Arthritis pain in your joints, especially in the hands, in the wrists, but it could be any joint in your d higher body. That's one huge one. Then there are a whole host of skin manifestations, and these can vary widely. I'll talk about some of the most common ones. Many of these are brought on or exacerbated by exposure to the sun. So a new rash or a new skin finding that's brought on after sun exposure is something that might make someone think lupus. And as I mentioned early on, some of these skin findings are also found in people that have cutaneous lupus, arithematosis or cle That doesn't necessarily mean that they have any systemic symptoms of lupus, so it's it's a lot, but the skin involvement happens in again about seventy to eighty percent of people that have lupus systemic lupus, and they can be classified by how quickly they appear or how long they last. So there's some rashes like the malar rash or the butterfly rash. This is like a reddish, not very raised rash that goes across the nose and onto the cheeks and really looks kind of like a butterfly, like if your nose was the body of a butterfly, and then your cheeks are like the wings. And it doesn't usually go into the nasolabial folds like right, interesting, that's your smile lines. Yeah, so that's one type of rash that we can see, very often brought on by being in the sun or by sun exposure. Sometimes the skin findings might be ulcers in the mouth or other mucous membranes. You could have just disseminated like splotchy red bumps kind of all over, or a number of different discrete patches on the skin, especially on sun exposed areas, that look round like discoid is one very common finding. Maybe a little bit like a psoriasis plaque, so something that's like raised and kind of scaly. That's a common one. You could also have blisters that aren't very superficial but are kind of underneath that first layer of skin. There are a few other things that we might see. Leveto reticularis one of my favorite words. This is a lacy pattern of purple like modeling that you might see usually on the lower legs, or rainode syndrome, which is where in the cold, the tips of your fingers or your toes turn white or even blue or purple and it's incredibly painful.

Those last two, the levito.

Those last two, the levito.

Reticularis and the rain nods are related more to vasospasm of blood vessels, but you see those skin manifestations with them. And then we also can see hair loss or what's called non scarring alopecia, So in various patches you might have hair loss or sometimes kind of diffusely see that people are kind of losing a lot of hair that eventually we'll grow back. It's not causing scarring across the skin.

Reticularis and the rain nods are related more to vasospasm of blood vessels, but you see those skin manifestations with them. And then we also can see hair loss or what's called non scarring alopecia, So in various patches you might have hair loss or sometimes kind of diffusely see that people are kind of losing a lot of hair that eventually we'll grow back. It's not causing scarring across the skin.

And so any one of these things that you've mentioned so far, because I know you're not done. I know happen sequentially or at the same time, or you see one and not the other. It's just a complete mixed bag. It's a complete mixed bag. And I'm not even close to done if you do.

And so any one of these things that you've mentioned so far, because I know you're not done. I know happen sequentially or at the same time, or you see one and not the other. It's just a complete mixed bag. It's a complete mixed bag. And I'm not even close to done if you do.

Fever is another really common manifestation or something that we see a lot. About thirty one percent of people with lupus will have fevers at some point with a flare or maybe like the first time that they're diagnosed. We also can see various forms of saracitis, which are generalized inflammation of our sorrosal membrane. So this means the layers in our body that are like between organs, so say the plura, the lining of your lungs or the pericardium, the lining of your heart, or even the lining of your abdomen, though that's a little bit less common. So what this is going to cause, especially in the case of inflammation in the lining of the heart or the lining of the lungs, is incredible chest pain, especially what's called pluritic chest pain. This pain that gets a lot worse if you try and take a deep breath, because that's stretching these linings and causing a lot of pain because of all of that inflammation. That sounds horrible, I know, it's really awful. There's a lot more. Lupus can also affect the nervous system, so it can cause neurologic symptoms, and these can vary incredibly widely because it's not just affecting one particular part of the nervous system or another. So it could mean things like seizures, could mean things like neuropathies, or having various kind of numbness or tinglings, or like unusual sensations because of nerve damage. It could mean cognitive dysfunction, severe fatigue, brain fog. Lupus also has a significantly increased risk for stroke as well as cardiovascular disease. In general, people living with lupus have a twofold increased risk for cardiovascular disease and an increased risk of high blood pressure. One of the other biggest and most important in terms of morbidity and mortality signs or symptoms of loopus is what's called lupis nephritis, and this is what happens when lupus affects the kidneys. This happens to most papers that I read estimated more than half of people with lupus, so about sixty percent of people with lupus within a decade of their first diagnosis, although some papers have slightly lower estimates. But the damage that lupus can cause to the kidneys in particular is very significant. So lupus nephritis can end up leading to end stage kidney disease, which can result in somebody needing dialysis or even a kidney transplant. It can also lead to a lot of issues with blood pressure because your kidneys are really integral in the maintenance of blood pressure. So with lupus nephritis, the main way that this is confirmed to be inflammation and damage to the kidneys caused by lupus and not anything else, which is a question that you asked earlier. Aaron is by biopsy, kidney biopsy, and that is something that we can do in several of these other cases as well. For example, a lot of the skin manifestations, we can take a biopsy and look for specific histological findings that are associated with lupus. That's not true for everything, in part because we don't want to biopsy, you know, your heart if we don't absolutely have to, et cetera. But when we have some of these findings, we can do biopsies and that can tell us a lot about whether this is lupus or something different. In terms of what the symptoms might be with someone with lupus nephritis, what we usually see is protein in the urine or sometimes just small amounts of blood or white blood cells that are just continuously there in the urine, and then other lab findings that are just suggesting general kidney damage. But the biopsy is really pretty important to actually look at the vessels and see the type of damage that's specific.

Fever is another really common manifestation or something that we see a lot. About thirty one percent of people with lupus will have fevers at some point with a flare or maybe like the first time that they're diagnosed. We also can see various forms of saracitis, which are generalized inflammation of our sorrosal membrane. So this means the layers in our body that are like between organs, so say the plura, the lining of your lungs or the pericardium, the lining of your heart, or even the lining of your abdomen, though that's a little bit less common. So what this is going to cause, especially in the case of inflammation in the lining of the heart or the lining of the lungs, is incredible chest pain, especially what's called pluritic chest pain. This pain that gets a lot worse if you try and take a deep breath, because that's stretching these linings and causing a lot of pain because of all of that inflammation. That sounds horrible, I know, it's really awful. There's a lot more. Lupus can also affect the nervous system, so it can cause neurologic symptoms, and these can vary incredibly widely because it's not just affecting one particular part of the nervous system or another. So it could mean things like seizures, could mean things like neuropathies, or having various kind of numbness or tinglings, or like unusual sensations because of nerve damage. It could mean cognitive dysfunction, severe fatigue, brain fog. Lupus also has a significantly increased risk for stroke as well as cardiovascular disease. In general, people living with lupus have a twofold increased risk for cardiovascular disease and an increased risk of high blood pressure. One of the other biggest and most important in terms of morbidity and mortality signs or symptoms of loopus is what's called lupis nephritis, and this is what happens when lupus affects the kidneys. This happens to most papers that I read estimated more than half of people with lupus, so about sixty percent of people with lupus within a decade of their first diagnosis, although some papers have slightly lower estimates. But the damage that lupus can cause to the kidneys in particular is very significant. So lupus nephritis can end up leading to end stage kidney disease, which can result in somebody needing dialysis or even a kidney transplant. It can also lead to a lot of issues with blood pressure because your kidneys are really integral in the maintenance of blood pressure. So with lupus nephritis, the main way that this is confirmed to be inflammation and damage to the kidneys caused by lupus and not anything else, which is a question that you asked earlier. Aaron is by biopsy, kidney biopsy, and that is something that we can do in several of these other cases as well. For example, a lot of the skin manifestations, we can take a biopsy and look for specific histological findings that are associated with lupus. That's not true for everything, in part because we don't want to biopsy, you know, your heart if we don't absolutely have to, et cetera. But when we have some of these findings, we can do biopsies and that can tell us a lot about whether this is lupus or something different. In terms of what the symptoms might be with someone with lupus nephritis, what we usually see is protein in the urine or sometimes just small amounts of blood or white blood cells that are just continuously there in the urine, and then other lab findings that are just suggesting general kidney damage. But the biopsy is really pretty important to actually look at the vessels and see the type of damage that's specific.

To lupus and what type of damage is that. Yeah, let's this is a really good question.

To lupus and what type of damage is that. Yeah, let's this is a really good question.

So that question, Aaron gets really into the nitty gritty of the path of physiology of this disease. Right, So if we zoom in and look at what is happening in your body when you're living with lupus, how exactly is this disease causing all of these different effects. We do actually know at least a little bit of detail, but it's still probably not going to be very satisfying herein But the central mechanism of damage, like I mentioned when I was just talking about autoimmune diseases in general, is this autoantibody production. So in lupus, we're making these antibodies that target our own cells or things and structures within our own cells. In the case of lupus, it's most often antibodies against the nucleus or against our DNA, but there are a whole bunch of other specific antibodies that can be associated with lupus as well. What happens is that these autoantibodies are binding to stuff various things our DNA, our nucleus, et cetera in our cells, and then they're triggering inappropriate immune responses. So what we see are increases in things like B cell activation, remember our B cells, or what are making antibodies. We're seeing increases in T cell activation as well, because our T cells are what are activated often by our antibodies to start reacting and blocking off or killing whatever pathogen they're supposed to be defending against. And really we can see this just generalized pattern of inflammation. The places in our body that this inflammation often ends up causing damage very commonly are in our blood vessels, but also in any possible organ so in our joint space. I know your face is so unsatisfied with this exploration.

So that question, Aaron gets really into the nitty gritty of the path of physiology of this disease. Right, So if we zoom in and look at what is happening in your body when you're living with lupus, how exactly is this disease causing all of these different effects. We do actually know at least a little bit of detail, but it's still probably not going to be very satisfying herein But the central mechanism of damage, like I mentioned when I was just talking about autoimmune diseases in general, is this autoantibody production. So in lupus, we're making these antibodies that target our own cells or things and structures within our own cells. In the case of lupus, it's most often antibodies against the nucleus or against our DNA, but there are a whole bunch of other specific antibodies that can be associated with lupus as well. What happens is that these autoantibodies are binding to stuff various things our DNA, our nucleus, et cetera in our cells, and then they're triggering inappropriate immune responses. So what we see are increases in things like B cell activation, remember our B cells, or what are making antibodies. We're seeing increases in T cell activation as well, because our T cells are what are activated often by our antibodies to start reacting and blocking off or killing whatever pathogen they're supposed to be defending against. And really we can see this just generalized pattern of inflammation. The places in our body that this inflammation often ends up causing damage very commonly are in our blood vessels, but also in any possible organ so in our joint space. I know your face is so unsatisfied with this exploration.

Like in our blood vessels that I'm like, Okay, finally we're getting down to some like a little bit more specifics said, and any other organ it is, though, I know it's reality.

Like in our blood vessels that I'm like, Okay, finally we're getting down to some like a little bit more specifics said, and any other organ it is, though, I know it's reality.

So like in the case of serositis, then this is inflammation caused by you know, auto antibodies and generalized white blood cell and cytokine production and inflammation that's attacking the lining specifically, right, so it's attacking our peracardial cells.

So like in the case of serositis, then this is inflammation caused by you know, auto antibodies and generalized white blood cell and cytokine production and inflammation that's attacking the lining specifically, right, so it's attacking our peracardial cells.

Right.

Right.

In the case of our kidneys, you have inflammation that's attacking the tubules of the kidneys as well as the blood vessels that lead into the kidneys.

In the case of our kidneys, you have inflammation that's attacking the tubules of the kidneys as well as the blood vessels that lead into the kidneys.

But these are not this is not one cell type or one target. There are different antibodies targeting different things that can be involved. How is this one disease.

But these are not this is not one cell type or one target. There are different antibodies targeting different things that can be involved. How is this one disease.

Such a good question, And it goes even further because it's not just targeting cells, because the other thing that can happen that's really important in lupus is that these auto antibodies themselves can lead to what's called immune complex deposition. You can think of this as clumps of our highly active immune cells, as well as various debris and just things that are in our body that ends up sticking to the walls of stuff, sticking to the walls of our blood vessels, sticking to the tubules of our kidneys, getting deposited in our skin, getting deposited in our joints, right.

Such a good question, And it goes even further because it's not just targeting cells, because the other thing that can happen that's really important in lupus is that these auto antibodies themselves can lead to what's called immune complex deposition. You can think of this as clumps of our highly active immune cells, as well as various debris and just things that are in our body that ends up sticking to the walls of stuff, sticking to the walls of our blood vessels, sticking to the tubules of our kidneys, getting deposited in our skin, getting deposited in our joints, right.

Out of the organs. Yeah.

Out of the organs. Yeah.

I like that, except it's not crystals. It's just these immune complexes slumps.

I like that, except it's not crystals. It's just these immune complexes slumps.

Yeah.

Yeah.

But these things are going to then cause even more inflammation, right because they're going to just continue triggering our immune response. And all of these things together, this generalized inflammation, the immune complex deposition, the vasculitis, or the inflammation happening in our blood vessels, all of these are causing damage to whatever organ they're affecting at the time, And like I mentioned, there are specific histological changes that we can see in some kinds of cutaneous lupus, those skin manifestations, certainly in kidney biopsies.

But these things are going to then cause even more inflammation, right because they're going to just continue triggering our immune response. And all of these things together, this generalized inflammation, the immune complex deposition, the vasculitis, or the inflammation happening in our blood vessels, all of these are causing damage to whatever organ they're affecting at the time, And like I mentioned, there are specific histological changes that we can see in some kinds of cutaneous lupus, those skin manifestations, certainly in kidney biopsies.

And I'm not.

And I'm not.

Going to get into the detail of what those look like because they're quite honestly, unless you're a histologist, like they're very boring.

Going to get into the detail of what those look like because they're quite honestly, unless you're a histologist, like they're very boring.

It's like this type of die bines blah blah blah. All the histologists out there are like shaking their fists, like, come on, these are almost.

It's like this type of die bines blah blah blah. All the histologists out there are like shaking their fists, like, come on, these are almost.

Sorry, it's just because I'm bad at histology, that's the real answer. But that that's kind of what's happening on the inside. In as much detail as I can provide, which I know is not is not a satisfying amount.

Sorry, it's just because I'm bad at histology, that's the real answer. But that that's kind of what's happening on the inside. In as much detail as I can provide, which I know is not is not a satisfying amount.

I guess I kind of have a question. I'm honestly just so taking it all in that it's hard to form questions, but I think I do have one, okay, and that is, what are some other things that could look like lupus or other things that lupus looks like ooh oof.

I guess I kind of have a question. I'm honestly just so taking it all in that it's hard to form questions, but I think I do have one, okay, and that is, what are some other things that could look like lupus or other things that lupus looks like ooh oof.

Aaron, huh yeah, And like how do we even diagnose this?

Aaron, huh yeah, And like how do we even diagnose this?

Right? Like that's kind of getting at that question or the boundaries that solid or are they permeable. They are, they're not that solid.

Right? Like that's kind of getting at that question or the boundaries that solid or are they permeable. They are, they're not that solid.

How one actually gets diagnosed with lupus is a is a very difficult question, and that's in part because, like you kind of alluded to, there are a lot of things that can look like lupus or that lupus can look like. But let's kind of maybe go over some of the things that might make it seem more like lupus and less like, say, an infection, right, Because someone might come in with a rash and a fever, and that might be their initial presentation that might seem like it's an infection. They might also have abnormalities in like their blood cell counts, so we might say that they have really high white blood cells and those things are going to make you think that they have an infection initially, right, Or or someone might come in with, you know, generalized joint pain in a number of their joints. That could be any number of different kinds of arthritis. Not necessarily lupus is going to be the first thing that you think of. So let's kind of see if we can figure out some of it part of the diagnosis of lupus that can be helpful is that about seventy percent of people with lupus have a relapsing remitting course of disease. So that means that they'll have flares of these symptoms and then they'll have periods of remission. The issue is that flares could be anyone or any combination of those symptoms, and they might not be the same every time, and so sometimes a flare might be if someone has arthritis, they kind of kind of always have at least some joint pain. A flare might be a worsening of those chronic symptoms that might be a flare, or a flare might be a brand new symptom, a new rash that you've never had before, with no changes in maybe any other symptoms that you may or may not have. So there's no perfect way to diagnose lupus, and it often takes a really long time to diagnose because of that.

How one actually gets diagnosed with lupus is a is a very difficult question, and that's in part because, like you kind of alluded to, there are a lot of things that can look like lupus or that lupus can look like. But let's kind of maybe go over some of the things that might make it seem more like lupus and less like, say, an infection, right, Because someone might come in with a rash and a fever, and that might be their initial presentation that might seem like it's an infection. They might also have abnormalities in like their blood cell counts, so we might say that they have really high white blood cells and those things are going to make you think that they have an infection initially, right, Or or someone might come in with, you know, generalized joint pain in a number of their joints. That could be any number of different kinds of arthritis. Not necessarily lupus is going to be the first thing that you think of. So let's kind of see if we can figure out some of it part of the diagnosis of lupus that can be helpful is that about seventy percent of people with lupus have a relapsing remitting course of disease. So that means that they'll have flares of these symptoms and then they'll have periods of remission. The issue is that flares could be anyone or any combination of those symptoms, and they might not be the same every time, and so sometimes a flare might be if someone has arthritis, they kind of kind of always have at least some joint pain. A flare might be a worsening of those chronic symptoms that might be a flare, or a flare might be a brand new symptom, a new rash that you've never had before, with no changes in maybe any other symptoms that you may or may not have. So there's no perfect way to diagnose lupus, and it often takes a really long time to diagnose because of that.

I was just about to ask if we had numbers. I remember the only other one where we've talked about this, I think was endometriosis. Yeah, that's a good question.

I was just about to ask if we had numbers. I remember the only other one where we've talked about this, I think was endometriosis. Yeah, that's a good question.

I actually didn't see that, like time from initial symptoms to diagnosis, I didn't see numbers on that, but I would guess it's very long, and it's often many many different doctors and specialists before somebody actually gets that diagnosis, except in cases when someone presents with maybe very kind of classic findings like lupus nephritis and a rash and a fever with these specific blood findings, right, if it kind of fits a very classic picture, be easier to diagnose, But a lot of times it doesn't. But there do exist classification criteria. The American College of Rheumatology and the European League against Rheumatism, which I think has recently been renamed the European Alliance of Associations for Rheumatology I don't know anyways, have classification criteria that they updated in twenty nineteen.

I actually didn't see that, like time from initial symptoms to diagnosis, I didn't see numbers on that, but I would guess it's very long, and it's often many many different doctors and specialists before somebody actually gets that diagnosis, except in cases when someone presents with maybe very kind of classic findings like lupus nephritis and a rash and a fever with these specific blood findings, right, if it kind of fits a very classic picture, be easier to diagnose, But a lot of times it doesn't. But there do exist classification criteria. The American College of Rheumatology and the European League against Rheumatism, which I think has recently been renamed the European Alliance of Associations for Rheumatology I don't know anyways, have classification criteria that they updated in twenty nineteen.

And in general, to meet.

And in general, to meet.

Criteria for this classification, you have to have a combination of symptoms. Right, some of these clinical criteria, it could be any various combination, And there's kind of different points for different symptoms that are more likely associated with lupus versus less likely. Because I did not go over all of the possible symptoms, there are more. Then there are also immunologic criteria, so specific lab findings that may or may not be present and give you kind of points on this scale as well.

Criteria for this classification, you have to have a combination of symptoms. Right, some of these clinical criteria, it could be any various combination, And there's kind of different points for different symptoms that are more likely associated with lupus versus less likely. Because I did not go over all of the possible symptoms, there are more. Then there are also immunologic criteria, so specific lab findings that may or may not be present and give you kind of points on this scale as well.

Does duration matter duration of of like a symptom during a flare up?

Does duration matter duration of of like a symptom during a flare up?

Good question, Not in this particular classification scheme that I know of, Okay, Yeah, but certainly like history of past flares is going to be a really important thing that also isn't necessarily like a point scale, but is going to make someone be more suspicious that it is lupus versus something else if they've had similar episodes in the past.

Good question, Not in this particular classification scheme that I know of, Okay, Yeah, but certainly like history of past flares is going to be a really important thing that also isn't necessarily like a point scale, but is going to make someone be more suspicious that it is lupus versus something else if they've had similar episodes in the past.

Okay.

Okay.

One of the most important lab findings that in this classification criteria is the gateway to be able to even get a classification of lupus to begin with, is called anti nuclear antibody. This is a very general antibody that's directed against the nucleus. Some studies say it's present in like ninety five to ninety nine point five percent of people with lupus, so it's considered very sensitive, although it can be negative even in people with lupus, especially if it's very well controlled lupus. But anti nuclear antibodies ANA are also present in like fifteen percent of people without lupus or any other autoimmune disease, as well as in plenty of people with other autoimmune diseases, so it's not a specific antibody. So then beyond that one, there are also a number of other autoantibodies that do tend to be more specific that we usually only see in loopus, but they're not always present in loopus.

One of the most important lab findings that in this classification criteria is the gateway to be able to even get a classification of lupus to begin with, is called anti nuclear antibody. This is a very general antibody that's directed against the nucleus. Some studies say it's present in like ninety five to ninety nine point five percent of people with lupus, so it's considered very sensitive, although it can be negative even in people with lupus, especially if it's very well controlled lupus. But anti nuclear antibodies ANA are also present in like fifteen percent of people without lupus or any other autoimmune disease, as well as in plenty of people with other autoimmune diseases, so it's not a specific antibody. So then beyond that one, there are also a number of other autoantibodies that do tend to be more specific that we usually only see in loopus, but they're not always present in loopus.

I mean, I know erin I know.

I mean, I know erin I know.

Yeah, So it's unsurprising that it's difficult to diagnose, incredibly frustrating if you're just living with joint pain, if you're living with chronic fatigue, if you're living with all of these symptoms that you don't have an answer for yet, right, Yeah, So I guess the next question that I wanted to try and answer is like what causes this?

Yeah, So it's unsurprising that it's difficult to diagnose, incredibly frustrating if you're just living with joint pain, if you're living with chronic fatigue, if you're living with all of these symptoms that you don't have an answer for yet, right, Yeah, So I guess the next question that I wanted to try and answer is like what causes this?

Not on the you know, cellular.

Not on the you know, cellular.

Level, but like on the big picture level, what do we know about the risk factors and all of that. We know that there is absolutely a huge amount of genetic.

Level, but like on the big picture level, what do we know about the risk factors and all of that. We know that there is absolutely a huge amount of genetic.

Basis to loopus.

Basis to loopus.

There is an increased in frequency in twin studies, there's an increased risk in siblings. But it's definitely a polygenic risk. There are dozens or more different genes that have been identified to contribute to increased risk of loopus, and in some rare cases there have been like monogenic so like one gene susceptibility, but a lot of times what we see is that it actually is multiple genes, multiple genetic changes that are necessary prior to resulting in loopus.

There is an increased in frequency in twin studies, there's an increased risk in siblings. But it's definitely a polygenic risk. There are dozens or more different genes that have been identified to contribute to increased risk of loopus, and in some rare cases there have been like monogenic so like one gene susceptibility, but a lot of times what we see is that it actually is multiple genes, multiple genetic changes that are necessary prior to resulting in loopus.

If that makes sense. What do these genes do? Are they all doing the same thing or are they doing a lot of different things?

If that makes sense. What do these genes do? Are they all doing the same thing or are they doing a lot of different things?

Great question, there's a lot. So they are doing a lot of different things. But in general they're all related to our immune response. So a lot of the genes that we've identified are related to our major histocompatibility complexes or various human leukocyte antigen changes or polymorphisms. So we see these all kind of being related to the propensity to develop auto antibodies and like immune system regulation for the most.

Great question, there's a lot. So they are doing a lot of different things. But in general they're all related to our immune response. So a lot of the genes that we've identified are related to our major histocompatibility complexes or various human leukocyte antigen changes or polymorphisms. So we see these all kind of being related to the propensity to develop auto antibodies and like immune system regulation for the most.

Part, Aaron, do other mammals get lupus? I don't know. Should we do a quick google? Yeah, let's do a quick goog. Yes, that was a very quick goog.

Part, Aaron, do other mammals get lupus? I don't know. Should we do a quick google? Yeah, let's do a quick goog. Yes, that was a very quick goog.

Well, like first line sees various animals such as cats, rats, dogs, hamsters, guinea pigs, rabbits, horses, minx pigs, and primates have been described lupus like phenotype. So I don't know if it's exactly the same.

Well, like first line sees various animals such as cats, rats, dogs, hamsters, guinea pigs, rabbits, horses, minx pigs, and primates have been described lupus like phenotype. So I don't know if it's exactly the same.

So interesting, what unites every one of these What is.

So interesting, what unites every one of these What is.

Our immune systems? I guess I mean yeah, but ugh, I will I'll post this paper that I've found real quick. Obviously haven't read it, but looks interesting. Back to genes, Yeah, back to genes or rather other things that we can get into about the kind of causes of lupus or risks for lupus. There is also some good evidence that there are associations with lupus and estrogen and testosterone metabolism. Testosterone to a lesser extent, estrogen to a larger extent, so some of the evidence that we have for this. In general, lupus is significantly more prevalent in females. Ninety percent of people who get diagnosed with lupus are assigned female at birth. And also people with Kleinfelter syndrome, which is a genetic condition where someone is born with forty seven xxy chromosomes so an extra X chromosome have an increased risk for lupus, and people who are born with Turner syndrome, which we covered last season, who are We talked about it a lot of different possible phenotypes, but in general, missing one X chromosome have a lower risk for.

Our immune systems? I guess I mean yeah, but ugh, I will I'll post this paper that I've found real quick. Obviously haven't read it, but looks interesting. Back to genes, Yeah, back to genes or rather other things that we can get into about the kind of causes of lupus or risks for lupus. There is also some good evidence that there are associations with lupus and estrogen and testosterone metabolism. Testosterone to a lesser extent, estrogen to a larger extent, so some of the evidence that we have for this. In general, lupus is significantly more prevalent in females. Ninety percent of people who get diagnosed with lupus are assigned female at birth. And also people with Kleinfelter syndrome, which is a genetic condition where someone is born with forty seven xxy chromosomes so an extra X chromosome have an increased risk for lupus, and people who are born with Turner syndrome, which we covered last season, who are We talked about it a lot of different possible phenotypes, but in general, missing one X chromosome have a lower risk for.

Lupus, So it's definitely got to be some sort of a dose thing with the X chromosome and estrogen.

Lupus, So it's definitely got to be some sort of a dose thing with the X chromosome and estrogen.

Right, So there's a lot of evidence that there must be at least some degree of kind of X linkage, that is that a lot of these genes that may be involved are located on the X chromosome, and or having two copies rather than one copy of this X chromosome somehow is part of this inherent risk. But again, it's not sufficient to cause lupus because plenty of people with multiple X chromosomes don't have lupis, so it's fascinating. We also can see a risk specifically associated with estrogen, where we see sometimes an increase in flares in people that are taking exogenous estrogen things like birth control or hormone replacement therapy. So there's some thought too that it could be alterations in either estrogen metabolism or the hypothalamic pituitary axis, which is the axis between our brain and our gonads that kind of regulates sex hormone production in general. So there's a lot of potential genetic components that we don't fully understand but we know are really fascinating and interesting and need for their research, but there are also likely a lot of environmental factors that work in combination to then produce the disease that we know of as lupus. When it comes to environmental factors, we don't have one. Course, in our MS episode, we spent a lot of time talking about EBV infection in the context of trying to identify like the one environmental thing, the one exposure that might result in MS. Unsurprisingly, for a disease as heterogeneous as lupus, we don't have one, and I don't know that we'll ever have just one.

Right, So there's a lot of evidence that there must be at least some degree of kind of X linkage, that is that a lot of these genes that may be involved are located on the X chromosome, and or having two copies rather than one copy of this X chromosome somehow is part of this inherent risk. But again, it's not sufficient to cause lupus because plenty of people with multiple X chromosomes don't have lupis, so it's fascinating. We also can see a risk specifically associated with estrogen, where we see sometimes an increase in flares in people that are taking exogenous estrogen things like birth control or hormone replacement therapy. So there's some thought too that it could be alterations in either estrogen metabolism or the hypothalamic pituitary axis, which is the axis between our brain and our gonads that kind of regulates sex hormone production in general. So there's a lot of potential genetic components that we don't fully understand but we know are really fascinating and interesting and need for their research, but there are also likely a lot of environmental factors that work in combination to then produce the disease that we know of as lupus. When it comes to environmental factors, we don't have one. Course, in our MS episode, we spent a lot of time talking about EBV infection in the context of trying to identify like the one environmental thing, the one exposure that might result in MS. Unsurprisingly, for a disease as heterogeneous as lupus, we don't have one, and I don't know that we'll ever have just one.

A few things that.

A few things that.

We know are associated with either flares or with lupus diagnosis in general are UV light, So exposure to the sun is strongly associated with both the onset of symptoms as well as with flares. There's some thought because I can see your face being like what why?

We know are associated with either flares or with lupus diagnosis in general are UV light, So exposure to the sun is strongly associated with both the onset of symptoms as well as with flares. There's some thought because I can see your face being like what why?

Hell? Well? Also, wasn't that the opposite with MS there was a latitudinal gradient. There was a latitude in no ingradient. That's fascinating.

Hell? Well? Also, wasn't that the opposite with MS there was a latitudinal gradient. There was a latitude in no ingradient. That's fascinating.

Yeah, But there's some thought that in the case of loopus, it's the UV light damage to our skin cells because there's a lot of skin manifestations in loopus that then ends up causing like increased inflammation and increased antibody production. That that's the kind of mechanism there. And then the only other two things that have been associated with an increased risk of loopus are smoking, so like cigarette or tobacco smoking. And then, like I mentioned briefly, there are a whole bunch of different medications in almost every medication class, like anti arrhythmic medications, blood pressure medicines, anti tuberculosis medicines, like over one hundred different medicines that can cause a drug induced lupus, but that loopus generally doesn't lead to systemic loopus aerythematosis what okay?

Yeah, But there's some thought that in the case of loopus, it's the UV light damage to our skin cells because there's a lot of skin manifestations in loopus that then ends up causing like increased inflammation and increased antibody production. That that's the kind of mechanism there. And then the only other two things that have been associated with an increased risk of loopus are smoking, so like cigarette or tobacco smoking. And then, like I mentioned briefly, there are a whole bunch of different medications in almost every medication class, like anti arrhythmic medications, blood pressure medicines, anti tuberculosis medicines, like over one hundred different medicines that can cause a drug induced lupus, but that loopus generally doesn't lead to systemic loopus aerythematosis what okay?

So, like I have a question about these other lupuses? Uh huh? What makes them all loopus?

So, like I have a question about these other lupuses? Uh huh? What makes them all loopus?

So we see similar antibody production, okay, and then we see similar signs and symptoms oka and laboratory findings.

So we see similar antibody production, okay, and then we see similar signs and symptoms oka and laboratory findings.

Yeah, for drug induced how does that happen? And how long does that take or how long does it last?

Yeah, for drug induced how does that happen? And how long does that take or how long does it last?

It usually doesn't happen unless someone has been on a medication for a pretty prolonged period of time. So it's not like I started a med and then I got lupus, like right, away. It's usually someone who's been on a medicine for a very long time, months if not years, and then it usually goes away within six months of stopping the medication. So if someone, for example, comes in with all of these symptoms that look a lot like lupus, then one of the first things to do is look through what medicines they're taking and say, is there any way that this could have just been a drug induced lupus versus you know, kind of true lupus or systemic loopus. So if you see numbers for lupus in general, that means systemic lupus arithematosis, Okay, drug induce lupus is always going to be kind of separated out from that. I don't have numbers on like how many cases of that a year, et cetera. When it comes to cutaneous loopus, about ten to twenty five percent of people who have cutaneous loopus will then go on to develop systemic loopus, so it's actually pretty small amount. But like I mentioned, about seventy to eighty percent of people with systemic loopis will have some kind of skin manifestation. Okay, and then there's the last one that I hadn't even mentioned yet, which is neonatal lupus. Yeah, and this happens due to a few different types of antibodies, not every possible type of lupus antibody, crossing the placenta during pregnancy and then being present in the fetus. So once the baby is born, those autoantibodies that are already present can lead to liver problems or problems with their blood or platelet function That tends to be transient and usually resolves within a few months, as those autoantibodies are kind of just like getting out of the system because remember that baby hasn't made those antibodies themselves, they were passed through the placenta. However, the most dangerous thing that neont loopus can result in is complete heart block, which means that the electrical system of their heart isn't working correctly. This is very very rare, but does end up causing damage earlier to the point where these babies often need pacemakers eventually. And I don't have an exact number on how rare, but in general, neonatal loopus is very rare. Though loopus in general can have huge effects on pregnancy and can sometimes make it very difficult to become pregnant or can result in recurrent miscarriage and things like that as well.