Megan Clowse, MD, Associate Professor of Medicine , Division of Rheumatology & Immunology at Duke University talks about lupus pregnancies.
Interview conducted by Ivanhoe Broadcast News in October 2018.
You work with patients with certain condition such as lupus, tell us some of the patients you work with.
Dr. Clowse: Absolutely. So I’m a rheumatologist so I take care of patients with autoimmune diseases, in particular women with lupus but also women with rheumatoid arthritis and other autoimmune diseases.
When it comes to lupus tell us what lupus is exactly and how many people are affected in this country.
Dr. Clowse: Sure. Systemic lupus erythematosus is the official name sometimes we call it SLE and sometimes we call it lupus. It is a systemic disease so it can affect multiple different parts of a person’s body. It’s caused by the immune system attacking the body. It’s like the body has decided that your immune system has decided there are parts that aren’t supposed to be there and they’re attacking them trying to make them go away. That causes the inflammation in different parts of the body and that leads to the symptoms that we see with lupus. Some of the symptoms are things like joint pain and arthritis, rashes are also really common, and then we also see internal organ problems. We’ll see kidney inflammation which can actually cause kidney failure in some situations. It can cause we can see inflammation around the heart and the lungs. Occasionally we can even see inflammation in the brain. It really presents with a lot of different symptoms in a lot of different people. It primarily affects women so actually ninety percent of all people with lupus are women. It primarily hits when women are young. Most commonly in the late teens to twenties to maybe the early thirties is really for most women when this gets going. When they’re young, it’s particularly when it’s the most severe.
It would be important also in the case of Emily her symptoms started when she was like sixteen but she wasn’t officially diagnosed for like ten years. So sometimes there can be a delay it’s important to get—
Dr. Clowse: Absolutely, absolutely. Lupus can be really challenging to diagnose in part because the symptoms can sort of go along with lots of other things. Sometimes women will come in and talk about how tired they are and fatigued that can really be part of lupus. But fatigue can be part of many things it can just be part of normal life, it can be part of working really hard, part of not sleeping well. So it’s sort of a vague symptom that doesn’t lead people down the road to lupus. Almost every lupus patient presents with a somewhat different story. There’s not just a textbook everybody shows up the same way so sometimes it can take a long time to end up in the hands of the right doctor who thinks of lupus and can run all the right tests and really knows enough about lupus to give a diagnosis.
So it’s very unique to each case? Also when it comes to treatment what can be done to manage the lupus, what do most of these patients need to do?
Dr. Clowse: Fortunately for lupus we have some medications that can be pretty effective. But we don’t really have enough medications to really fix everything. Hydroxychloroquine is the medicine that we use the most. It’s also called placqunel. It’s actually a medicine that’s been around for decades. I always tell my patients that back World War II when we sent all the guys off to war taking hydroxychloroquine or a medicine very much like I, because it’s actually and anti-malaria drug, it’s almost like an antibiotic. All these guys went off taking their anti-malaria pills and the ones who had joint pain, particularly like had stiffness and hand pain, got better. They came back and they told all the doctors and everybody sort of scratched their heads but at that point we started using it for arthritis and eventually we figured out that it was really great for lupus. Some of us call it lupus life insurance because it’s actually been shown to reduce the risk of death from lupus. Decreases the risk of kidney disease, decreases the severity of kidney disease plus it also helps manage things like joint pains and rashes. So hydroxychloroquine is like the main stay of our treatment. But it’s really not strong enough to fix everything. We have lots of other medicines that we use, sometimes we use prednisone that’s the thing that works the fastest. We use a fair amount of prednisone when people are really particularly sick. We also use medicines like azathioprine or imuran is a medicine that is turns down the activity of the immune system. So immunosuppressants are really what we tend to use. Those are medicines that basically dial back your immune system right. If you think about lupus, is your immune system too active and attacking your body (end of tape one—tape two started here) is to turn down the immune system so that you stop attacking your own body.
I should have asked you because people with lupus they may not be sick every day, they experience flairs is that what they’re called, and tell us what that is.
Dr. Clowse: Yeah, so many of our lupus patients their symptoms go up and down. And actually if you go back decades before we really had medicines to treat lupus symptoms went up and down no matter what. So there are some periods of time when people will be really sick, there will be other periods of time when people will be less sick. Sometimes occasionally people will go back to feeling normal but most people sort of feel baseline not great but then there are periods of time when they seem to be worse.
For women too I’ve heard and I think in Emily’s case she said maybe with her menstrual cycle it can come and go then.
Dr. Clowse: There are some studies that suggest that, actually sure I’m not even there are studies. Some patients report that they feel that their symptoms get worse when they’re having their period. I would say it’s unclear at this point as to whether that’s actually change in the amount of inflammation they have in their body or if it’s just an increase in the sense of symptoms of swelling and fatigue and so on. It’s hard if you have lupus to know what’s lupus versus what’s everybody else’s premenstrual symptom. But it’s possible that some patients feel worse during their period.
With these medications that manage, basically help manage, the disease in patients. Is there or was there a concern then especially for women when it came to pregnancy because we heard concerns from women saying they have lupus or this autoimmune condition, I don’t think I can have a family. Is that true or are we looking at some sort of breakthrough in that area?
Dr. Clowse: Certainly! Several decades ago women were told, particularly women with lupus, that they should not have children, they should never get pregnant. The earliest data about pregnancy for women with lupus suggested that lupus became more active so they had more kidney disease and more inflammation in their body. That led to both damage to the woman’s body but also it really strongly impacted the pregnancy. They are high rates of pregnancy loss and really high rates of preterm delivery so delivering the baby well before the due date such that the baby could have lifelong consequences so initially people were very nervous about women with lupus having babies, back in the nineteen eighteens or so (women) started actually collecting data about these lupus pregnancies. Michele Petre at John’s Hopkins Hospital is actually one of the first people to really start collecting data and to start realizing that actually these pregnancies were not as disastrous always as we thought. Certainly we’ve seen plenty that have gone poorly for women with lupus. But we’ve also see many, many pregnancies for women with lupus that go really well. And so I think we’ve now come to sort of a new approach to lupus pregnancy management, but experts in the field have sort of been doing this approach for the last fifteen years or so. But I think, I’m hoping, that’s it really reaching the general rheumatology patient the country at this point. And the approach is basically to continue pregnancy compatible medications, and thereby control their disease so the lupus doesn’t become active during the pregnancy. And with that combination we really see very good pregnancy outcomes. We see a lot of live births and we see a lot of deliveries close to the due date, we see fewer preterm deliveries. We also see less harm to the woman. We see less women having active kidney disease during pregnancy, less pain that sort of thing. So, my approach here at Dukes I continue almost everybody on hydroxychloroquine almost all of my pregnancies are for women with lupus take hydroxychloroquine unless they already have an allergy to it. If they’ve had active disease in the recent past or if they’re on a stronger immunosuppressant medication prior to pregnancy or if they’ve had kidney disease in the past, I generally treat them with azathioprine or imuran. Azathioprine is a medication that we have been using for several decades in pregnancy particularly women with kidney transplants. As you can imagine if you’ve had a kidney transplant, and you get pregnant you really can’t stop your medicines because then you would reject your kidney. Therefore we continue transplant medications during pregnancy and so there’s actually a lot of great data showing that azathioprine or imuran is very safe. We use that a lot in our pregnancies, about twenty percent of my lupus pregnancies the women take azathioprine during pregnancy.
So even if they were not on that before this might be something you put them on during pregnancy?
Dr. Clowse: Absolutely, absolutely, so I have some women who show up and their lupus is kind of active. They’ve been needing prednisone recently to control their disease for example, and I’ll actually start them on azathioprine while they’re pregnant, ideally I like to see them before they get pregnant and we start them on azathioprine ahead of time. The data really suggests that actually azathioprine is probably safer than prednisone for the pregnancy. My goal is to keep lupus as well controlled as possible on the lowest doses of medication and particularly lowest dose of prednisone that we can get away with.
So far what you’ve seen in the women you’ve treated have you seen any side effects or anything to the medication at all or so far this has been very successful in managing?
Dr. Clowse: Yeah, I’ve managed about a hundred and fifty lupus pregnancies over the past decade and when we look at those pregnancies what we see is pregnancy loss rates a little bit higher than the general population but not a lot higher. We see that about one five maybe will have activeness on their lupus become more active, and we’ll need to use more medications for them. About half of our patients end up taking prednisone. We also have preterm delivery. We have probably about thirty percent of our pregnancies deliver early. Often that’s just a couple weeks early and it’s not a big problem. Occasionally it’s very early and the babies are in the NICU for a long time. Those tend to occur in women who get pregnant while their lupus is very active. the hardest pregnancies I’ve had to manage and the pregnancies that ended up with the most harm to the mother, and the most harm to the pregnancy are in women who get pregnant while their lupus is active often not taking the medications that we anticipate or sometimes even taking medications at the time of conception that are we know cause birth defects or cause problems to the fetus. In my experience planned lupus pregnancies go great. That’s our key really and always sort of my key when I’m talking to women is that our goal is to plan the pregnancy so we plan it when there’s not lupus activity going on, they’re already on the right medications for lupus for pregnancy. And then we have a good running start to have a really successful pregnancy.
If someone sees this and they become pregnant and they do have lupus should they not stop—with the idea you don’t stop taking your medication?
Dr. Clowse: That’s a great question. Alright, if you’ve gotten pregnant without planning and you have lupus then there’s a couple of first things to do. Number one, call your rheumatologist office first and let them know that you are pregnant and talk through with the nurse or your rheumatologist the medications that you’re taking. Know that hydroxychloroquine can be continued. Azathioprine can be continued. Prednisone can be continued and should probably be continued at least at the beginning with the dose that you’re already taking because your doctor already thought that you needed that dose so stay on that dose for now. If you’re talking one of the few medications that we know cause birth defects then you need to stop those right away, and get in to see your doctor soon to see if they need to switch your medicines around. The medicines I recommend stopping like, oh my goodness I have a positive pregnancy test stop today. Methotrexate that should be stopped right away, micophenolate mofelil also called cellcept that medicine is the medicine we use commonly for women with kidney disease with lupus. It is a major teratogen one out of every four babies that are exposed and are born alive can have effect. So if you’re taking micophenolate and you find out your pregnant you should stop it right away. And cyclophosphamide or cytoxan that’s a medicine that we don’t use quite as much anymore and it’s usually given as an IV infusion. So if you think you might be pregnant,(or) if there’s a chance you might be pregnant and you’re showing up to get your IV infusion that day make them do a pregnancy test before they give you the medication. Those are really the three drugs that are most commonly used in lupus that cause birth defects, and those need to be stopped immediately. And then you need to talk to your rheumatologist and you probably need to talk to a high risk obstetrician. Often the high risk obstetrician is the best person to give you advice about what to do at this point. Often if you would like to keep the pregnancy then they can monitor to look for any kind of birth effects a little bit earlier than otherwise knowing that they might not see all the birth defects that are possibly there. But they’ll also talk to you about the risks of having those birth defects are and they can really help you make a good informed decision about what to do next.
Once they give birth should they continue their normal regiment and I believe Emily would just continue to take her medication.
Dr. Clowse: Absolutely, absolutely. So after delivery we recommend continuing the medications you were taking during pregnancy. Basically all the medicines that we use for lupus during pregnancy are compatible with breast feeding. Prednisone is fine really pretty much at any dose hydroxychloroquine is fine, azathioprine is fine so very minimal transfer of any of those drugs if any get in to breast milk. The baby would really not get any exposure that we think would be worrisome with those three drugs. If your lupus is flaring and you need to add something like methotrexate or micophenolate back then you would talk about whether or not you want to stop breast feeding at that point. It’s a very personal decision about how long you go without treatment with those medications versus how long you breast feed. For our patients with lupus who have things like kidney disease my strong recommendation would be to stop breast feeding and go to important medications. If it’s more like a rash and then you might want to consider going back on then you can wait a little bit longer. But if it’s something that’s going to cause you permanent physical harm then, we would recommend stopping breast feeding for that.
So it depends on the severity of the condition at the time?
Dr. Clowse: It does yeah. Let me say this one more time.
Sure.
Dr. Clowse: The vast majority of our women with lupus can breast feed and they can breast feed safely. Most or our medications are very safe it’s really only the very sickest women who need to go back on the risky medications after they deliver who we would be more hesitant to have them breast feed.
(talking) And in Emily’s case she told us honestly that she never felt better than when she was pregnant. So is that something too along with the lupus, is that a phenomenon of lupus of is that——
Dr. Clowse: For a long time we’ve actually known that rheumatoid arthritis is a different rheumatologic disease improve in pregnancy. It’s actually how one of the Nobel prizes was awarded was based on that discovery and the reason behind that discovery. But lupus has always historically been more of a concern in pregnancy. And people always felt like it worsened in pregnancy. So we actually have some data that our group published recently looking at the John’s Hopkins lupus cohort and actually found that as long as women were taking the hydroxychloroquine their lupus did not flare during pregnancy If they weren’t taking hydroxychloroquine then yes they did have a higher risk of flare. Flaring is not as big a problem as we thought. in rheumatoid ——Let me start because that wasn’t your question.
What you said was a very good point.
Dr. Clowse: For decades we’ve talked about rheumatoid arthritis getting better in pregnancy that is a well-known sort of thing that we all learn in rheumatology and many women will be aware of. Lupus improving during pregnancy is not something that people generally talk about. But I can tell you after following a hundred and fifty pregnancies for the last decade many woman feel better when they’re pregnant when they have lupus. The stuff that gets better is achiness and fatigue. I think the reason that we sort of missed this getting better during pregnancy is that those aren’t actually the symptoms that the physicians are recording on the disease activity measures. You know we’re recording how active your kidneys are, and how many joints are really swollen. Not just how you generally feel and so I don’t think we’ve measured it really before. But I can tell you that our patients frequently say that they felt better during pregnancy than they ever felt before. I think actually with Emily it’s interesting because I think before she got pregnant I think really Emily sort of felt like she only had skin disease with her lupus. When I first met her I thought oh yeah, it’s really just skin disease and she’s really high functioning and you know, does lots of work and is really active and she doesn’t really have what we call systemic lupus erythematosus. But then following her during this pregnancy and actually seeing how much better she has felt it has actually made both of us reassess her diagnosis. And I suspect that actually she does have a component of systemic lupus but that she’s sort of been in denial and the doctors have been in denial for a long time. We’re actually planning on switching up her medications after she delivers, At this point and really switching up so that we treat her lupus a little more aggressively than we had before in order to see if we can get some of that improvement that she felt during pregnancy back in her daily life.
So having the baby has really changed her life a hundred percent. And the bottom line is that young women which make up a great population of those with lupus, can safely get pregnant, safely have healthy babies and go on to have families.
Dr. Clowse: Absolutely, I think that the message for women with lupus is that you can have a family; you can have a safe pregnancy. The key is to talk to your rheumatologist now, make plans, make sure that as you make choices about medications your doctor your rheumatologist and an obstetrician is informed about what you want and what you’re planning on and just don’t jump ahead and get pregnant when everybody else isn’t ready. Make sure you have a plan and that you follow it closely.
You are really only one of six rheumatologists that are focused with pregnancy in the country, am I saying this properly?
Dr. Clowse: So six is hard to call right?
But you’re one of those?
Dr. Clowse: Yes. I would say that right, so there’s not very many rheumatologists in there are not very many rheumatologists in this country who really focus their career on pregnancy management and women with rheumatic diseases. I’m pretty much the only person in the southeast. There certainly people at several different universities across the country, but what we do and what I do here is not necessarily what all rheumatologists are doing across the country. It is one of my goals however, and projects that we actually get what we do, there’s expert level of care and the protocols that we follow actually out in to the hands of all rheumatologists across the country,
So the people who are not steering people in the wrong direction saying you can’t do this?
Dr. Clowse: Absolutely.
That’s good news doctor is there a website that we can add?
Dr. Clowse: Yes. Through an independent medical education grant from Glasgow-Smith-Kline we’ve actually this year been building a website for directed to both patients and rheumatologists to help better plan and manage lupus pregnancies. It’s called hop step, and I’m happy to share the link with you all.
Please do.
END OF INTERVIEW
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