“Positive ANA” is one of the most common reasons for referral to the pediatric rheumatology clinic. The antinuclear antibody (ANA) is often mistakenly considered a good screening test for rheumatic disease.
Dr. Ashley Cooper, Interim Division Director of Pediatric Rheumatology, discusses what it means when a child has a positive anti-nuclear antibody test, when ANA should be checked, and how to talk about the test results with the family.
Selected Podcast
Positive Antinuclear Antibody: What Now?
Featured Speaker:
Ashley Cooper, MD
Ashley Cooper, MD, is a pediatric rheumatologist and Interim Division Director of Pediatric Rheumatology at Children’s Mercy and Assistant Professor of Pediatrics at the University of Missouri-Kansas City School of Medicine. Dr. Cooper completed medical school, residency in pediatrics and fellowship in pediatric rheumatology at the University of Texas Southwestern Medical School in Dallas, TX. Her academic interests include medical education and pediatric uveitis. Transcription:
Positive Antinuclear Antibody: What Now?
Dr. Michael Smith (Host): So our topic today is positive antinuclear antibody, what now? My guest is Dr. Ashley Cooper. Dr. Cooper is a pediatric rheumatologist and Intern Division Director of Pediatric Rheumatology at Children’s Mercy. Dr. Cooper, welcome to the show.
Dr. Ashley Cooper (Guest): Yes, thanks for having me.
Dr. Smith: So let’s – how about a nice little review? Right, so we have a lot of community physicians and nurse practitioners that listen into this show so first of all, nice review of ANA. What is it? Why is it something we look at in autoimmune disorders?
Dr. Cooper: So an ANA, which is also called an antinuclear antibody is really just an antibody against anything in the cell – in the nucleus of our cells. So if you think about that, it’s a pretty nonspecific test. We have lots of things that float around in our cell nucleus and an antibody against any one of those things can make an ANA test be positive. So some examples would be in a person who carries an antibody to double stranded DNA like lupus patients often do then an ANA would come up positive, or if you had antibodies against a protein called SEL70 like people with scleroderma would have, then your ANA would be positive and list is really long, it goes on and on.
Dr. Smith: Right.
Dr. Cooper: So the ANA can really pick up a lot of autoimmunity but because it’s so nonspecific unfortunately it kind of picks up a lot of distractors or junk along the way too.
Dr. Smith: Which is what kind of poses the challenge, right? When we’re practicing medicine, maybe a patient comes in, has an ANA test, maybe they had some symptoms and the ANA test comes back positive. What is your advice at that stage? What would be the appropriate workup at that point and when does the patient just need to go see the specialist?
Dr. Cooper: So I think that’s a great question and it’s one of the most common questions we get in rheumatology from primary care providers who call us for advice. In my mind the answer to this question really comes down to why you do the ANA in the first place, so what symptoms brought the patient to your practice. If this is a patient who has symptoms that are really concerning for lupus or a serious condition like scleroderma or mixed connective tissue disease and then the ANA comes back positive, that’s probably a patient we’re going to want to see a lot more quickly in the rheumatology practice. So an example of this would be if you saw a patient in your practice and they had painful joint swelling and a real malar rash and maybe some cytopenia, you’d be worried about lupus in that patient. An ANA just further supports that diagnosis, so we’d want to see them really quickly. So here in our practice at Children’s Mercy, when we get calls about patients like this we often try to add them on within a week to our clinic so that we can assess them really quickly, and that’s really what I would recommend to any primary care provider who had a patient like this would be to call the local rheumatologist and ask for advice about how soon to see a patient that seems that sick. On the flip side if you drew an ANA for really any other reason other than a true concern for lupus or related condition like mixed connective tissue disease, I would say maybe take a step back and question whether you should have done that ANA in the first place. So I urge people to try to avoid ANA testing, at least in the primary care setting, unless you have a really specific reason for doing it and the reason for that is that although an ANA can be helpful in some situations, we run into lots of problems with kids having positive ANAs that were drawn for nonspecific reasons and then we’re not really sure what to do with them.
Dr. Smith: Are you seeing that the ANA test is being done more and more in community practices? Is this something that is becoming more of an issue in your opinion?
Dr. Cooper: Yeah probably so. I mean I’ve only been practicing rheumatology for about five years, but I think at least in that time frame we see a lot of referrals for positive ANA and sometimes there was a really good reason for doing it, and sometimes it was done for a really nonspecific symptom.
Dr. Smith: Well it’s interesting because the way you described the classic patient, that’s textbook, and we both know when you get out of the classroom and the exams and you get into practicing real medicine, no one looks like the textbook –
Dr. Cooper: It seems to simple right? But the thing is in pediatrics, actually what’s interesting about our pediatric patients, at least the ones with lupus, is that a lot of them do have really classic findings, so kids with lupus in general are sicker than adults with lupus when they present and they tend to have more criteria. So it’s going to be unusual to find a kid who will end up having lupus that you can’t find anything on their exam or anything on more routine labs like a CBC and a urinalysis.
Dr. Smith: Something’s going to come out, right?
Dr. Cooper: Exactly.
Dr. Smith: So what do you suggest for a general pediatrician or maybe a nurse practitioner that’s listening and they’re not quite sure and it’s kind of nonspecific, do they just – can they just call up Children’s Mercy and talk to somebody like you to get some advice right there live while the patients waiting or is there a different process for that kind of information?
Dr. Cooper: Actually here at Children’s Mercy we do offer that service. We always have someone on call for community calls, and a lot of pediatric rheumatology practices across the country are similar in that sense. We’re kind of a small specialty and we want to make sure our kids get in as quickly as they need to when they’re sick and that we avoid unnecessary testing, so that is what I would recommend if you have that available. A lot of the kid that we see positive ANAs on had reasons for testing like chronic fatigue or “full body pain” or hypermobility related pain, and unfortunately because the ANA is positive in up to 20% of the healthy population at some point in their life, that leads to a lot of false positives, and so if you obtain that test for one of those nonspecific reasons and it comes up positive you’re kind of stuck, and unfortunately, as great as it is that we have such easy access to information on the internet now, once you have a child with a positive ANA, no matter how much you try to explain it away, their family will be worried that they have lupus or something really serious. So they’ll probably end up coming to see us anyway at that point.
Dr. Smith: I kind of want to – knowing what you do at Children’s Mercy, Dr. Cooper, can you run us or walk us through a little bit of the patient experience once somebody refers a positive ANA to you, and let’s say it is a patient with some of these classic signs, walk us through what the patient and the family is now going to go through.
Dr. Cooper: So if we had someone referred to us who had classic clinical signs of lupus for example. They had inflammatory arthritis, painful swollen joints, a malar rash, and a positive ANA, if we got that call from a pediatrician, we’d probably try to work that patient into our practice that week or if not the following week. In our initial visit, we would take a really detailed history. So one of the things that drew me to rheumatology that even with all our advanced testing that we have available, we still really rely a lot on our history and physical exam. So we would start by seeing that patient, taking a lot of detailed history about the symptoms they’re having, and we do a really thorough review of systems because sometimes patients are experiencing symptoms that they haven’t really recognized might be pertinent, that when we hear them we think, well goodness maybe we need to work that up a little bit more, maybe that ties into what else they’re here for, and then we would do a really careful physical exam. So often times in a patient with lupus for example, we might find things on physical exam that they haven’t noticed. They might have a painless ulcer on their hard palate, that’s sort of a pathognomonic finding for lupus or they might have a discoid rash that’s hiding inside their ears or behind their ears that no one has noticed. So we sort of do a head to toe look for any signs that would support that diagnosis, and then most likely if we truly suspected a diagnosis of lupus, we would do additional laboratory testing. So that’s one of the reasons that sometimes even if you think about a diagnosis like lupus, it might be better to call ahead and say do you want us to get labs or do you want us to just wait and have the child seen urgently because often we still need to stick them again for additional laboratory testing at that point. So we would send not only an ANA but more specific antibodies as well and other markers of disease activity.
Dr. Smith: So Dr. Cooper, knowing that the topic of our conversation is a positive antinuclear antibody, just to kind of summarize it, what would you like the primary care physician, the general pediatrician to know about a positive ANA?
Dr. Cooper: I would probably like them to know that it, unfortunately, is not specific for anything, so you can see a positive ANA in autoimmune diseases like lupus, you can see it in children with juvenile arthritis. You can see it in other autoimmune diseases that aren’t truly rheumatic like thyroid disease, type 1 diabetes, things like that or you can see it in healthy people or even in conditions that maybe mimic a rheumatic disease but are even more serious. So you could see a child with severe painful joint swelling, get an ANA and it’s positive, but maybe that child turns out to have leukemia or something else, so unfortunately it’s really not specific at all. But on the flip side it’s only really sensitive for a very things, so it’s very, very sensitive for lupus, positive in more than 90% of kids with lupus, but it’s not sensitive for conditions like juvenile arthritis. So while some kids with JIA have a positive ANA, there’s lots of kids who don’t so you can’t rule out arthritis by drawing an ANA and that’s another sort of trap that I think people fall into.
Dr. Smith: And the good news is if they need help they have people like you, the experts, Dr. Cooper and Children’s Mercy that they can call right?
Dr. Cooper: Exactly, yep. We see lots of kids for this reason and we’re happy to help either provide reassurance or help the family down the right path in terms of further workup and management.
Dr. Smith: Dr. Cooper I want to thank you for the work that you are doing at Children’s Mercy and also thank you for coming on the show today. You’re listening to Pediatrics in Practice with Children’s Mercy Kansas City. For more information you can go to childrensmercy.org, that’s childrensmercy.org. I’m Dr. Mike Smith, thanks for listening.
Positive Antinuclear Antibody: What Now?
Dr. Michael Smith (Host): So our topic today is positive antinuclear antibody, what now? My guest is Dr. Ashley Cooper. Dr. Cooper is a pediatric rheumatologist and Intern Division Director of Pediatric Rheumatology at Children’s Mercy. Dr. Cooper, welcome to the show.
Dr. Ashley Cooper (Guest): Yes, thanks for having me.
Dr. Smith: So let’s – how about a nice little review? Right, so we have a lot of community physicians and nurse practitioners that listen into this show so first of all, nice review of ANA. What is it? Why is it something we look at in autoimmune disorders?
Dr. Cooper: So an ANA, which is also called an antinuclear antibody is really just an antibody against anything in the cell – in the nucleus of our cells. So if you think about that, it’s a pretty nonspecific test. We have lots of things that float around in our cell nucleus and an antibody against any one of those things can make an ANA test be positive. So some examples would be in a person who carries an antibody to double stranded DNA like lupus patients often do then an ANA would come up positive, or if you had antibodies against a protein called SEL70 like people with scleroderma would have, then your ANA would be positive and list is really long, it goes on and on.
Dr. Smith: Right.
Dr. Cooper: So the ANA can really pick up a lot of autoimmunity but because it’s so nonspecific unfortunately it kind of picks up a lot of distractors or junk along the way too.
Dr. Smith: Which is what kind of poses the challenge, right? When we’re practicing medicine, maybe a patient comes in, has an ANA test, maybe they had some symptoms and the ANA test comes back positive. What is your advice at that stage? What would be the appropriate workup at that point and when does the patient just need to go see the specialist?
Dr. Cooper: So I think that’s a great question and it’s one of the most common questions we get in rheumatology from primary care providers who call us for advice. In my mind the answer to this question really comes down to why you do the ANA in the first place, so what symptoms brought the patient to your practice. If this is a patient who has symptoms that are really concerning for lupus or a serious condition like scleroderma or mixed connective tissue disease and then the ANA comes back positive, that’s probably a patient we’re going to want to see a lot more quickly in the rheumatology practice. So an example of this would be if you saw a patient in your practice and they had painful joint swelling and a real malar rash and maybe some cytopenia, you’d be worried about lupus in that patient. An ANA just further supports that diagnosis, so we’d want to see them really quickly. So here in our practice at Children’s Mercy, when we get calls about patients like this we often try to add them on within a week to our clinic so that we can assess them really quickly, and that’s really what I would recommend to any primary care provider who had a patient like this would be to call the local rheumatologist and ask for advice about how soon to see a patient that seems that sick. On the flip side if you drew an ANA for really any other reason other than a true concern for lupus or related condition like mixed connective tissue disease, I would say maybe take a step back and question whether you should have done that ANA in the first place. So I urge people to try to avoid ANA testing, at least in the primary care setting, unless you have a really specific reason for doing it and the reason for that is that although an ANA can be helpful in some situations, we run into lots of problems with kids having positive ANAs that were drawn for nonspecific reasons and then we’re not really sure what to do with them.
Dr. Smith: Are you seeing that the ANA test is being done more and more in community practices? Is this something that is becoming more of an issue in your opinion?
Dr. Cooper: Yeah probably so. I mean I’ve only been practicing rheumatology for about five years, but I think at least in that time frame we see a lot of referrals for positive ANA and sometimes there was a really good reason for doing it, and sometimes it was done for a really nonspecific symptom.
Dr. Smith: Well it’s interesting because the way you described the classic patient, that’s textbook, and we both know when you get out of the classroom and the exams and you get into practicing real medicine, no one looks like the textbook –
Dr. Cooper: It seems to simple right? But the thing is in pediatrics, actually what’s interesting about our pediatric patients, at least the ones with lupus, is that a lot of them do have really classic findings, so kids with lupus in general are sicker than adults with lupus when they present and they tend to have more criteria. So it’s going to be unusual to find a kid who will end up having lupus that you can’t find anything on their exam or anything on more routine labs like a CBC and a urinalysis.
Dr. Smith: Something’s going to come out, right?
Dr. Cooper: Exactly.
Dr. Smith: So what do you suggest for a general pediatrician or maybe a nurse practitioner that’s listening and they’re not quite sure and it’s kind of nonspecific, do they just – can they just call up Children’s Mercy and talk to somebody like you to get some advice right there live while the patients waiting or is there a different process for that kind of information?
Dr. Cooper: Actually here at Children’s Mercy we do offer that service. We always have someone on call for community calls, and a lot of pediatric rheumatology practices across the country are similar in that sense. We’re kind of a small specialty and we want to make sure our kids get in as quickly as they need to when they’re sick and that we avoid unnecessary testing, so that is what I would recommend if you have that available. A lot of the kid that we see positive ANAs on had reasons for testing like chronic fatigue or “full body pain” or hypermobility related pain, and unfortunately because the ANA is positive in up to 20% of the healthy population at some point in their life, that leads to a lot of false positives, and so if you obtain that test for one of those nonspecific reasons and it comes up positive you’re kind of stuck, and unfortunately, as great as it is that we have such easy access to information on the internet now, once you have a child with a positive ANA, no matter how much you try to explain it away, their family will be worried that they have lupus or something really serious. So they’ll probably end up coming to see us anyway at that point.
Dr. Smith: I kind of want to – knowing what you do at Children’s Mercy, Dr. Cooper, can you run us or walk us through a little bit of the patient experience once somebody refers a positive ANA to you, and let’s say it is a patient with some of these classic signs, walk us through what the patient and the family is now going to go through.
Dr. Cooper: So if we had someone referred to us who had classic clinical signs of lupus for example. They had inflammatory arthritis, painful swollen joints, a malar rash, and a positive ANA, if we got that call from a pediatrician, we’d probably try to work that patient into our practice that week or if not the following week. In our initial visit, we would take a really detailed history. So one of the things that drew me to rheumatology that even with all our advanced testing that we have available, we still really rely a lot on our history and physical exam. So we would start by seeing that patient, taking a lot of detailed history about the symptoms they’re having, and we do a really thorough review of systems because sometimes patients are experiencing symptoms that they haven’t really recognized might be pertinent, that when we hear them we think, well goodness maybe we need to work that up a little bit more, maybe that ties into what else they’re here for, and then we would do a really careful physical exam. So often times in a patient with lupus for example, we might find things on physical exam that they haven’t noticed. They might have a painless ulcer on their hard palate, that’s sort of a pathognomonic finding for lupus or they might have a discoid rash that’s hiding inside their ears or behind their ears that no one has noticed. So we sort of do a head to toe look for any signs that would support that diagnosis, and then most likely if we truly suspected a diagnosis of lupus, we would do additional laboratory testing. So that’s one of the reasons that sometimes even if you think about a diagnosis like lupus, it might be better to call ahead and say do you want us to get labs or do you want us to just wait and have the child seen urgently because often we still need to stick them again for additional laboratory testing at that point. So we would send not only an ANA but more specific antibodies as well and other markers of disease activity.
Dr. Smith: So Dr. Cooper, knowing that the topic of our conversation is a positive antinuclear antibody, just to kind of summarize it, what would you like the primary care physician, the general pediatrician to know about a positive ANA?
Dr. Cooper: I would probably like them to know that it, unfortunately, is not specific for anything, so you can see a positive ANA in autoimmune diseases like lupus, you can see it in children with juvenile arthritis. You can see it in other autoimmune diseases that aren’t truly rheumatic like thyroid disease, type 1 diabetes, things like that or you can see it in healthy people or even in conditions that maybe mimic a rheumatic disease but are even more serious. So you could see a child with severe painful joint swelling, get an ANA and it’s positive, but maybe that child turns out to have leukemia or something else, so unfortunately it’s really not specific at all. But on the flip side it’s only really sensitive for a very things, so it’s very, very sensitive for lupus, positive in more than 90% of kids with lupus, but it’s not sensitive for conditions like juvenile arthritis. So while some kids with JIA have a positive ANA, there’s lots of kids who don’t so you can’t rule out arthritis by drawing an ANA and that’s another sort of trap that I think people fall into.
Dr. Smith: And the good news is if they need help they have people like you, the experts, Dr. Cooper and Children’s Mercy that they can call right?
Dr. Cooper: Exactly, yep. We see lots of kids for this reason and we’re happy to help either provide reassurance or help the family down the right path in terms of further workup and management.
Dr. Smith: Dr. Cooper I want to thank you for the work that you are doing at Children’s Mercy and also thank you for coming on the show today. You’re listening to Pediatrics in Practice with Children’s Mercy Kansas City. For more information you can go to childrensmercy.org, that’s childrensmercy.org. I’m Dr. Mike Smith, thanks for listening.