Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with a variety of immunologic and laboratory abnormalities as well as numerous clinical manifestations. It can affect almost every organ and has the potential to cause severe organ damage. Most patients experience flares of the disease alternating with periods of remission. Lupus is much more common in women than in men and there are significant geographic and ethnic differences in the incidence and eventual outcome of the disease. Lupus is known as the great imitator because it can mimic a variety of other diseases. It's not uncommon for patients to have symptoms for over five years before a diagnosis of lupus is established. The topic for this podcast is SLE and our guest is Ali A. Duarte Garcia, M.D. , a rheumatologist at Mayo Clinic.
Rheumatologic problems are some of the most common health conditions we see as primary care professionals. They can become frustrating for both the provider and the patient, as in many cases it may take months and sometimes even years to establish a correct diagnosis. There are a variety of new tests available to help us confirm a diagnosis, as well as multiple new and effective treatment options. This episode is part of a seven-episode miniseries on Mayo Clinic talks dedicated to rheumatologic health problems to aid in the recognition, diagnosis, and treatment of your patients. Please find these additional episodes where you listen to podcasts or on CE.mail.edu. This is Mayo Clinic Docs, a curated weekly podcast for physicians and healthcare providers. I'm your host, Darryl Chetka, a general internist at Mayo Clinic in Rochester, Minnesota. Systemic lupus erythematosis, it's a chronic systemic autoimmune disease with the variety of immunological and laboratory abnormalities, as well as numerous clinical manifestations. It can affect almost any organ and has the potential to cause severe organ damage. Most patients experience flares of the disease, alternating with periods of remission. And it's much more common in women than men, and there are significant geographical and ethnic differences in the incidences and the eventual outcome of the disease. It's known as the Great Imitator because it can mimic a variety of other conditions, and it's not uncommon for patients to have symptoms for over 5 years before a diagnosis of lupus is established. Today's topic is systemic lupus, and our guest is Doctor Ali Duarte, a rheumatologist from the Mayo Clinic. You're listening to Mayo Clinic Talks. Ali, welcome and thank you for joining me today. Thank you for inviting me. Let's start by describing lupus, and I'm gonna ask you to Tell me what the typical patient is who has lupus. What do they look like? Sure. So, you, you actually already mentioned some of who is the typical patient in your introduction. So, lupus is a very heterogeneous disease, but it does affect certain populations more than others. So, lupus predominantly affect women. And women in the reproductive years. So that means from the menarchy to menopause. And it also affects more frequently patients who have a minority background. So, patients who are Asian, black, Hispanic, or indigenous Americans. All of the minority groups have higher incidence of lupus than the white population. It doesn't mean that lupus doesn't affect white males, it happens, but it's just less frequent. In general. The frequency of lupus in males is 10 times less or you can see it differently like in women it's 10 times more frequent than in men. Yeah, I don't think I can recall seeing a male with lupus. I've had uh quite a few females, but you're right, it is much more common in women. What are the risk factors for lupus? Who's more likely to get this? We don't know exactly what I, you know, if there's a, a specific reason why people develop systemic lupus. There are some risk factors that are slightly associated with the risk of developing lupus. So one of them is smoking. We know that patients or individuals who smoke have a slightly higher risk of developing SLE.er Exposure to infections, for example, Epstein virus or monocleosis, patients who have had EBV are more likely to develop our immune diseases, lupus is one of them, but as you know, the majority of us get EBV throughout our lives and we don't develop an autoimmune disease. And then exposure to UV light, so and also something that is very common, is associated with the development of lupus. And then there are some more recent associations that have been described that are interesting. So patients who experience severe trauma, for example, like people who went through an episode of being exposed to war or even intense psychological trauma can be associated with the development of autoimmune diseases, not only lupus but other autoimmune diseases as well. Is there a genetic component to this? There have been a lot of studies looking into the genetics of SLE and there are 100, or at least 100 genes that have been associated with the development of lupus. But as today, these genes explain around 30% of the susceptibility to lupus, so that means that 70% is either to environmental factors that are not identified yet or genes that haven't been identified. I will say that from the clinical perspective, it's not unusual that patients mention that they have and their mother or an aunt or usually somebody in, in the female side of their family or the women in their family who have an autoimmune disease. It doesn't need to be lupus, but maybe they have rheumatoid arthritis, scleroderma or, or even autoimmune thyroid disease. Well, most of the patients with new symptoms of lupus are probably gonna present to their primary care provider before a rheumatologist. So what should we be alert for in terms of the history and physical exam that should at least make us suspect they might have lupus? Sure, so that, that's a very good question. So, when you read in a textbook about lupus, it gets very complicated because they describe that it affects basically head to toe. But there are some manifestations that are much more frequent than others. There are 4 or 5 cardinal manifestations that one can keep in mind. So, one of them is arthritis, so having inflammation or at least a pain in the, in the joints and more frequently in the hands. The other one is the, the skin rashes. The most famous one is the malar rash, but they, they can also get other types of rashes, usually in the upper parts of the body. The development of lupus nephritis, this is usually identified as proteinuria, the patients won't have pain, so one has to check urinalysis to identify it. Another one is cytopenia, so leukopenia is very frequent. And thrombocytopenia is also very frequent, so cytopenias and a little bit less frequent, but also we see it frequent often and I think it's also seen in general practices pericarditis. So patients who develop chest pain, they often go to the emergency department, so this is maybe more frequently seen in, in an acute setting like an acute, in acute care or, or in the ED but the pericarditis is also one manifestation that is more frequently seen in SLE. When I think back to the lectures I've heard on lupus, uh, mostly in medical school and residency, it seems like they always show a picture of a patient with this classic butterfly rash on the face. How common is that? Is it in most patients or not so much? Yes, the butterfly rash is basically the, the icon of lupus. It's what people very quickly identify or associate with, but really it's not, it's not as common as other manifestations. So rashes in general, when a patient has a new diagnosis, show up in around 20% of the patients and the malar rash is not the only rash that they can have. Some patients may have. The traditional mail rash that you were describing that doesn't cross the neolabial folds, but some patients may have a rash that is predominantly affecting, for example, like the upper chest or the upper back or areas that are exposed to the sun, the neck. So I will say that around 20% or less of the patients will present with the butterfly rash. So that means that 80% don't have it, right. Well, I, I know lupus can affect so many different organ systems, but what are the most common organs that are involved in lupus? So the most common one is the joints, so it's uh arthritis. Arthritis is present in around 50 or 60% of the patients in, within their, you know, when, around the time of diagnosis or when they are starting to experience symptoms. The other one that is very important and also fairly frequent, so around the 20% of the patients is the, the lupus nephritis that shows as proteinuria. You've mentioned the arthritis associated with lupus and with osteoarthritis, the arthritis typically is in the distal joints of the fingers, rheumatoid arthritis more the proximal joints. Does lupus have any predilection for certain joints and also, are there any radiologic findings that are specific for lupus like RA? Yeah, so the arthritis that we see in systemic lupus has a similar distribution as the one in rheumatoid arthritis. So, it will affect predominantly the hands and it will be predominantly the metacarpal phalangeal joints, so the proximal joints of the phalanges. The difference with rheumatoid arthritis is that it's arthritis that is non-erosive, and that means that when you do an X-ray, You're not going to see these changes in the bones in an erosion looks like a piece of bone was scooped out. So you don't see these destructive changes in the joints that you see in rheumatoid arthritis. The patients may still develop some degree of deformity in the hands, and some changes in the hands, but it's mostly due to laxity in the ligaments or lacks in the joint capsule rather than destruction of the joint. So the, the X-rays make a big difference or help you to make the differential diagnosis between rheumatoid arthritis and systemic lupus. OK. Let's talk a little bit about the laboratory tests associated with lupus, and I think the one that we think of most commonly is the uh anti-nuclear antibody or ANA. How specific is a positive ANA for lupus? Yeah, so the ANA, the anti nuclear antibody is a screening test that is not specific for any disease. It is more frequently seen in our immune diseases, and ANA is telling you, an anti-nuclear antibody is telling you that there's an antibody directed against the nucleus, but it's not telling you which one. So, in lupus, you have antibodies directed against the DNA and then another antibodies called the Smith antibody directed against the protein in the nucleus. But there are other anti-nuclear antibodies that are not related to lupus and can be related to a different disease. For example, in scleroderma, you see anti-centrome antibodies. And then to make things a little bit more complicated is 10% or more recently, the reports are up to 15% of the general population have a positive ANA. So, the ANA helps you to steer your diagnosis towards an autoimmune disease, but it's not diagnostic of any autoimmune disease. And that just happened with a patient of mine last week. Their primary care provider checked an ANA for some reason. I don't know why, but it came back positive and they really had no symptoms of uh lupus or any other arthritis and That that's relatively common. I don't know what percent of the population has a positive ANA, but it certainly doesn't mean they've got lupus. So what laboratory tests are useful? What should we be checking when we suspect lupus? Yeah, so if you, if you have that the patient with the symptoms that we just diagnosed and that we just mentioned and then also positive ANA, the next step, for sure, always check a CBC because the patients often have low platelets or low white blood cell count. And the most common is lympopenia of the, of the white blood cells. And then also always check uh urinalysis looking for proteinuria. Those are, you know, just to complete the workup in terms of what organs might be affected. Now, to confirm the diagnosis, the laboratories that are very helpful are anti-DNA antibodies and anti-SM antibodies. And basically, you know, the chances that a patient has SLE are very high if you have those antibodies and the clinical manifestations that we mentioned before. Could you go over the typical course of lupus? What's a patient likely to experience over their lifetime? The most common pattern of the trajectory of the disease activity is uh relapsing remitting, so, A relapsing remitting pattern is that the patients will have an episode of flare and then you get treated and get an episode of quiescence and it can be some months or even years, and then we'll have all again episodic flares and those are sometimes difficult to prevent because The patients may get an infection and they have to stop their medications and you know, that brings a flare. So, that's the most common, most common pattern. I will say that less common is that the patients get one-time episode or so like just very severe SLE once and then they, they get remission that lasts for years. And there's still another pattern that there are patients that have persistent active disease that we cannot get them into remission. And that's it's a little bit less frequent. The most common one is, is that the patients enter into remission and then have episodic flares. Do we have any idea what sets off these flares? The most common reason is uh not taking the medications, and it might be just as I was saying, like, for example, if the patients have to have a procedure, sometimes we may stop the medication or may, we may ask them to lower the doses in the context of a surgery, or also when they have an infection and they need to take antibiotics, oftentimes we may reduce the immunosuppression. So, an infections themselves, when the immune system gets activated, they may also cause a flare. Those are some of the most common reasons. I know patients who have uh rheumatoid arthritis and they've had it for many years. Many of them will eventually um have the disease go in remission and not come back, and we often call that a burnt out rheumatoid patient, but does that happen in lupus? Does this go away and uh it's gone forever? In some patients, they may enter remission, but what we have seen is even patients who have been on long standing remission, you know, and by that I mean, you know, for 4 or 5 years. And then they are still at least only on hydroxychloroquine or Plaquenil, which is the most common medication and that medication gets tapered or stopped that day the disease comes back, that they start to develop like at least arthralgia or the skin starts to get the rashes. So there are some patients who will have long remissions, but I will say that is remissions without medications is very rare. OK. All right. So what are the more common complications of lupus? I will say the most serious complication is actually accelerated or cardiovascular disease. Cardiovascular disease is the most common cause of death in patients with SLE, and both MIs and strokes are, are more frequent in patients with lupus. And then the other complication that we worry a lot about is lupus nephritis. Some patients may start with lupus nephritis, you know, that may be the initial manifestation, but a lot of patients also will develop lupus nephritis over the years. That's another serious manifestation that we are often looking, you know, monitoring for it by doing urinalysis in every visit. Mhm. Well, lupus is called the great imitator because there's, it takes a while for many patients to get an established diagnosis. What are some of the other medical conditions that are often mistaken for lupus? The differential diagnosis is very broad and it depends what is the organ or, or system that is predominantly affecting the patient initially. So, it's not unusual, for example, that the patients besides having arthritis may have like fever or they may have weight loss in the, in those cases, the differential, for example, goes to into infections or looking even in for malignancy if the patients are losing weight. But you can imagine that if, if somebody, for example, that is presenting with uh arthritis mainly, the differential diagnosis will be geared towards that. So they, you have to make sure that they don't have rheumatoid arthritis or even these are mostly young women, so maybe parvovirus like B19 infection or, you know, other potential causes of, of uh arthritis and same if they have serositis, uh by that meaning pericarditis, uh, the, the Patients may have, you have to look into alternative causes of chest pain, of course, an MI but look into viral pericarditis or other causes of pericarditis. So, because the disease is very heterogeneous, the differential diagnosis is also very heterogeneous and, and very diverse. Let's finish up by talking about the management of lupus. How is it treated? lupus is an autoimmune disease, as you initially mentioned, and the main treatment of lupus is immunosuppression. The medication that is the foundation for lupus of the, the foundation of the treatment is hydroxychloroquine or, or also known as Plaquenil. And this is anti-malarial that has been around now for several decades, but over the years, uh, it has been shown that patients who, who are on Plaquenil, persistently on Plaquenil or hydroxychloroquine. They are less likely to have an episode of flare. They have longer life spans and also they have less thrombotic events and you know, the patients with lupus, as I mentioned, have moreI or stroke, so that's also an important protective factor of the hydroxychloroquine. Now, many patients, they will still have symptoms, the majority will still have symptoms while on hydroxychloroquine. So, other medications that we use is, of course, glucocorticoids. We try to use the least possible, but it's a useful medication for sure. And then the other immunosuppressants like a zathioprine or mycophenolate and biologics like the limoa. From the pharmacologic standpoint, those are the medications that are more frequently used. OK. Well, hydroxychloroquine, corticosteroids, azathioprine, they've been around a long time. Is there anything new in the management of lupus or anything? That you see as potential for the near future. Yeah, so the lupus field is growing a lot and it's accelerating very rapidly. 10 years ago, there was a new approval. I was this drug called Belimumab is a biologic. But more recently, this drug, and this is in 2021 or so, got approved for the treatment of lupus nephritis. So this is a biologic that is approvals often come for systemic lupus and for lupus nephritis. So this drug was recently approved for both. There's another drug that got approved in the last couple of years uh for systemic lupus called aroma so. That's a new bio biologic and a new calcineurin inhibitor, so similar to tacrolimus that is used in transplant is vocallosporin, and that one got approved for lupus nephritis also 2 years ago. And there are a lot of clinical trials going on. I expect that the number of drugs that we're using will go up substantially in the next decade or so. OK. Well, Ollie, you've given us lots of good information about lupus. Can you summarize our discussion maybe with 2 or 3 key points? Sure, so, lupus is a heterogeneous disease. It, it has a lot of clinical manifestations. I think you're more likely to get the diagnosis correct if you focus on, in the key cardinal manifestations of the disease such as arthritis, the patients are having rashes, patients who have these symptoms and proteinuria or cytopenia such as thrombocytopenia, and leukopenia. That combined with a positive ANA and a positive anti-double stranded DNA and SM antibody, it is very, very likely that the diagnosis is correct and it's very likely that this patient has systemic lupus. Another point I would like to mention is that hydroxychloroquine is the foundation of the treatment and the current thinking about lupus is that all the patients should be on hydroxychloroquine only. They develop an allergy. And something that I would like to mention is that especially during the pandemic, the hydroxychloroquine became very popular and there was a concern about retinopathy or eye toxicity, but the studies have been very reassuring. There's, with the doses that we use for lupus is negligible. It's extraordinarily rare that somebody will develop retinopathy. So hydroxychloroquine is the foundation of treatment. The last point is the main complications are cardiovascular disease and lupus nephritis, and cardiovascular disease, even though it's very frequent, we know even, it's more frequent even than in patients with diabetes. Patients with lupus are not treated for hypercholesterolemia or hypertension as frequently. So I encourage primary care physicians that if you see a patient with lupus, just think of them as patients who have diabetes and check the hypertension, like patients who have diabetes that we're always trying to decrease their cardiovascular risk, treat the hypertension, treat the hyperlipidemia, and always check a protein to make sure that they don't have renal involvement. That we will, will be the parallel with diabetic nephropathy. Always checking patients with lupus that they don't have proteinuria, looking for lupus nephritis. We've been discussing systemic lupus with Doctor Ali Duarte from the division of Rheumatology at the Mayo Clinic. Ollie, thank you so much for sharing your expertise with us today. Thank you so much for the invitation. You can now listen to several 100 different medical topics developed for primary care providers on Mayo Clinic Talks podcasts. Find them at c.mail.edu or your favorite podcasting app. If you've enjoyed Mayo Clinic Talks podcasts, please follow us. We're honored to have you as a listener. Tune in again next week and stay well.
