RheumNow Podcast Vasculitis And Strange Bedfellows %2812.14.18%29 Save
RheumNow Podcast Vasculitis And Strange Bedfellows %2812.14.18%29 by Dr. Cush
Transcription
This is the RheumNow podcast for 12/14/2018. This week in the news, we will reveal to you the incidence and frequency of statin associated toxicities. We're gonna ask the big question, is there such a thing as ANA positive pauci articular JIA in the adults? And will we, the diagnosticians, ultimately be replaced by genetic studies, GWAS and whole exome sequencing? Oh my, say it ain't so.
We're gonna start the news with a discussion of GPA in both kids and adults is a comparison study, a cohort study looking at about 200 kids with GPA and over 5,000 adults with a diagnosis showing that for many of the parameters one would look at, turns out that they're almost the same except kids tend to have more severe disease as measured by more hospitalizations and maybe as much as thirty percent more hospitalizations and a two to threefold increased risk of complications such as leukopenia, neutropenia, and hypogammaglobulinemia. Surprisingly, they don't have more infections or more major relapses or renal disease than do adults, it's about equal. So it's a bad disease in both, but like in lupus, sometimes kids who get these adult diseases tend to have more severe manifestations. An interesting look, came from a comparative study, that analyzed the risk of cardiovascular events, major adverse cardiovascular events called MACE, in RA patients, axial spondyloarthritis patients, and psoriatic arthritis patients. After all is said and done in a fairly large cohort study shows that the risk of cardiovascular disease is elevated in all three suggesting it is inflammation and not the disease or the specific disease that lends to an increased cardiovascular risk, suggesting that we should be worried about all our inflammatory diseases, not just RA and PSA for whom much of this has been written about the cardiovascular risk, etc.
I threw out a tweet this week about a case I was working on that really was peaking my interest. And here's the case, and I'm gonna ask the question, what's the diagnosis and tell you what the answers are from at least 100 of your peers. So the case is a 27 year old female who has a chronic left knee effusion going on for four months and then becomes a right knee effusion. So bilateral knee effusions for the last three months. It's inflammatory, there's 22,000 white cells, negative cultures.
MRI done only shows synovitis and large effusion. She gets worked up and treated, nothing responds, intraocular steroids don't help, nonsteroidals don't help, has not received a DMARD. Labs only show that she is ANA positive one to one hundred sixty in a speckled and homogeneous pattern. Negative lab tests include IgM parvovirus, rheumatoid factor, B27, CCP, hepatitis C and hepatitis B, RPR, SedRite and CRP are actually normal. So the question is, what would you call it at this point and how would you treat it?
So I threw it out there wondering what the community would think and on Twitter with almost a 100 responses, here's the vote. The top answer was that the, and there's only four choices I laid out there, there was no write in. Forty nine percent said this was probably an occult IBD, PSA or SPA diagnosis that would ultimately reveal itself. Twenty six percent said this is probably seronegative RA. Eighteen percent, what I thought this could be, which is adult onset postarticular JIA, which is ANA positive.
I've got several of these patients, however, they do not seem to develop uveitis like the kids do, but that's something I'm watching for. And seven percent call this incomplete lupus. I think that's wrong. There's nothing about this that looks like or smells like lupus. So usually time ultimately makes a diagnosis in cases like this.
The question is, what are you gonna do until you make the diagnosis? I'm gonna treat what's present and move on. So let's move on to the next report. This is on statin safety coming from the American Heart Association, a very large study that basically shows with thousands and thousands of patients, almost forty percent or more, is that the number? Forty percent, one in four, I'm sorry, twenty five percent of adults over the age of 40 are taking a statin currently.
We know that statins save lives, we know statins lower lipid levels or LDL levels by 55 to 65%. What is the real numbers? What should you be quoting to your patients? They're always asking you, should I be on a statin? You're always wondering why they're stopping their statin.
The risk of statin induced rhabdo is one in a thousand, and probably that's the high end. The risk of severe hepatotoxicity from a statin is probably less than more than one in ten thousand. And the risk of a statin induced new diabetes, something I was really unaware of, is about two point two percent per year. So again, these numbers are really low. It seems like if properly monitored statins can be a significant advantage for patients who need them.
So there's two interesting studies that looked at comorbidities and vasculitis that I found interesting, and taught me something. And one report talks about the risk of developing vasculitis if you have an auto inflammatory disease. We know that FMF patients, for instance, get, PAN like disease and IgA, deposition vasculitis. We know that, small vessel vasculitis can be seen in patients with CAPS, the Cryopyran associated periodic syndromes, TRAPS, Hyper IgD syndrome, DIR, the deficiency of the IL-one, in, receptor, POPA and Behcet's, all small vessel vasculitis can occur. And then there's the Savi syndrome described recently by, Dan, Kastner and colleagues, that's the, DAD2 deficiency where they have sting associated vasculopathy with onset in infancy.
These kids, again, genetic it's disorder, do respond really, really well to Enbrel and TNF inhibitors. So that's kind of interesting and we should maybe watch out for that. Another meta analysis looked at the risk of developing comorbidities in patients with polymyalgia rheumatica, elderly, obviously they're going steroids. What other things do occur in these people? Well, CVA, coronary artery disease, peripheral artery disease, diverticular disease, hyperthyroidism are all significantly increased.
What is not so clear is whether there's an association between PMR and cancer risk there that's not borne out in these meta analyses of at least 41 papers studied by the authors. An interesting study looks at, the outcomes in systemic sclerosis patients, specifically looking at what lends to poor outcomes, specifically the risk of death. And they show in their study that early severe GI involvement, and that's seen by up to nine percent of people in the first two years, is associated with a twofold increased risk of death in patients with systemic sclerosis. Again, early, severe GI involvement, poor TENS, other bad things, including the risk of inflammatory myositis is fourfold higher, telangiectasis is two and a half fold higher, rapid and progression of skin disease again, twofold higher or more. So this is one of the bad prognostic signs in patients with scleroderma.
We need better markers, we need better therapies. This still is the great unmet need in rheumatology. A nice study looked at pregnancy in psoriasis patients, specifically psoriatic arthritis patients. This comes from Daphne Gleidman and colleagues and they looked at patients in Tel Aviv and in Toronto and enrolled seventy four PSA patients and seventy four match controls. And roughly each of these patients and controls had about two pregnancies.
And in the end, the outcomes were the same. The numbers of pregnancies, live births, gestational age, maternal and fetal complications, breastfeeding, breastfeeding outcomes, the same between the controls and PSA, which is an important message. And it's also good data, a lot of these patients continue to do pretty well, actually do well, and only minority get worse during their pregnancy. So this is encouraging data for those of you who manage psoriatic arthritis patients, telling them that they can get pregnant. Again, whether or not they're on therapies is really contingent upon their activity going into the pregnancy.
Healthy mother is needed to make a healthy baby, treat them if you need to, there's a lot of good therapies you can still use during pregnancy and not rely on steroids. There's another interesting article that we covered, which is really a spin off of the Washington newspapers report on, all I want for Christmas is my Shingrix vaccine. We called it no end in sight for the Shingrix vaccine shortage. As you know, this was approved about a year ago. It's outsold its projections, they've done very, very well.
It's estimated that in The United States, we will sell about 900,000,000 to a billion dollars worth of Shingrix in the first year. The problem is that there's a significant number of individuals, who have been unable to either get the vaccine or get their second dose of the vaccine. The manufacturer GSK makes this in Belgium, they said they've stepped up the production. As much as they say they're dealing with this, they don't give any real projections on when it's going to end. This problem started in May 2018, and is expected to continue into early twenty nineteen.
The manufacturer says that of all the people who've been prescribed this seventy percent have received the full two doses of the drug. But there still are a lot of patients and a lot of pharmacies are dealing with this. Pharmacies are no longer taking a waiting list because they don't know when this is going to end. The bottom line appears to be, maybe you should wait until unless the patient really needs it and you can get it, it's okay to wait until it becomes available. And the other thing is, we'd like to know about more about its safety in our patients with rheumatoid arthritis and lupus.
Not likely that's gonna be resolved anytime soon. The manufacturer has not indicated any interest in doing those studies. But again, this is not a live virus vaccine theoretically should be used. The question is, would our patients get worse on that? My opinion is I haven't seen that yet with a lot of inadvertent use and even out my instructions to go ahead and use it.
Again, it's two injections list price about $140 per injection. And again, we need more information, we need more vaccine. An interesting report also appeared this week in the New England Journal, brought to my attention by my partner, Doctor. Catherine Dow. And it's about the use of genetic diagnoses in patients with previously undiagnosed disorders.
The NIH has an undiagnosed disease network. They've taken in over 600 patients and accepted forty percent of them for evaluation. About a third of these people underwent exome genome sequencing prior to getting in. In the end, half of them underwent a complete evaluation. And that included again, exome sequencing, and they were able to achieve a diagnosis in thirty three percent.
Eleven percent were diagnosed clinically based on clinical grounds, but the majority of patients needed the exome and genome sequencing to make that diagnose. They made a diagnosis of thirty one new syndromes, one in five led to a change in therapy, thirty seven percent led to changes in diagnostic testing. Again, this might be the future. Other academic centers and, leaders in the community have talked about very difficult patients, undiagnosed patients, patients with fever even have undergone this whole exome sequencing. Used to be this with thousands and thousands of dollars.
I'm reading that the price has come way down, I wanna say $500 but don't quote me on that. It could even get cheaper as it gets more widely used. You may wanna consider this, for the future. There's a nice report about patients not telling the truth that appeared in MedPage today. This comes from two different surveys that were done of largely white individuals, mostly elderly, finding a sixty to eighty percent of patients, admit to not fully revealing the truth to their physicians.
And that includes up to eighty one percent said they avoided disclosing at least one type of information. Forty six percent disagreeing with the clinician's recommendation. Thirty one percent not understanding the clinician's instruction. Again, to eighty percent did not disclose this because they didn't wanna be judged or lectured to. Up to seventy five percent not wanting to hear how harmful their behavior was that they didn't want to reveal.
Sixty percent not wanting to be embarrassed during the visit. The bottom line is that those who are more likely to withhold information tend to be women and those who are younger and those who tended to rate their own health as being somewhat poor. Again, patients said things like I didn't want the provider to think I was difficult or stupid. I didn't wanna take up any more of the provider's time. I didn't think it mattered.
I didn't want this information in my medical record. This is scary. I tweeted this week all too often physicians think their job is to know the answer, fix the problem, when instead, much to our surprise, patients really need to be listened to, wanna know someone cares, want someone who won't judge their behaviors, and someone who actually displays a personality in caring. Then once you develop this bond, you might actually solve their problems. I think it's something we need to work on.
Again, I think we're great diagnosticians, we're really good at what we do, but we really need to meet the patient's needs and involves a lot more listening. I want to close with a reminder about RheumNow Live, 03/22/2019 in Fort Worth, Texas. We're going to have all the big names, all the big companies, all the big topics. I think you should attend. I think it's gonna be unlike any other meeting you've ever seen.
We did a survey of US rheumatologists on RheumNow and asked them what you want most from your CME programs. You said at the top of your list, topic reviews, online access, digital handouts, case presentations, Q and As, panels and a meeting recap were the most common things cited as things they'd like to see. What was least desirable were debates, promotional lectures or dinners, breakouts, working lunches and paper handouts. RheumNow Live is going to have reviews of JAKs, psoriatic arthritis therapies, comorbidities, dactylitis, enthesitis. There's gonna be online access, the lectures are shorter, everything's maxed out at thirty minutes.
We're having thirty minute panel discussions, there's digital handouts. All of the lectures have to have case presentations and then I can't see why you really would enjoy this meeting. Come, we'll enjoy seeing you there.
We're gonna start the news with a discussion of GPA in both kids and adults is a comparison study, a cohort study looking at about 200 kids with GPA and over 5,000 adults with a diagnosis showing that for many of the parameters one would look at, turns out that they're almost the same except kids tend to have more severe disease as measured by more hospitalizations and maybe as much as thirty percent more hospitalizations and a two to threefold increased risk of complications such as leukopenia, neutropenia, and hypogammaglobulinemia. Surprisingly, they don't have more infections or more major relapses or renal disease than do adults, it's about equal. So it's a bad disease in both, but like in lupus, sometimes kids who get these adult diseases tend to have more severe manifestations. An interesting look, came from a comparative study, that analyzed the risk of cardiovascular events, major adverse cardiovascular events called MACE, in RA patients, axial spondyloarthritis patients, and psoriatic arthritis patients. After all is said and done in a fairly large cohort study shows that the risk of cardiovascular disease is elevated in all three suggesting it is inflammation and not the disease or the specific disease that lends to an increased cardiovascular risk, suggesting that we should be worried about all our inflammatory diseases, not just RA and PSA for whom much of this has been written about the cardiovascular risk, etc.
I threw out a tweet this week about a case I was working on that really was peaking my interest. And here's the case, and I'm gonna ask the question, what's the diagnosis and tell you what the answers are from at least 100 of your peers. So the case is a 27 year old female who has a chronic left knee effusion going on for four months and then becomes a right knee effusion. So bilateral knee effusions for the last three months. It's inflammatory, there's 22,000 white cells, negative cultures.
MRI done only shows synovitis and large effusion. She gets worked up and treated, nothing responds, intraocular steroids don't help, nonsteroidals don't help, has not received a DMARD. Labs only show that she is ANA positive one to one hundred sixty in a speckled and homogeneous pattern. Negative lab tests include IgM parvovirus, rheumatoid factor, B27, CCP, hepatitis C and hepatitis B, RPR, SedRite and CRP are actually normal. So the question is, what would you call it at this point and how would you treat it?
So I threw it out there wondering what the community would think and on Twitter with almost a 100 responses, here's the vote. The top answer was that the, and there's only four choices I laid out there, there was no write in. Forty nine percent said this was probably an occult IBD, PSA or SPA diagnosis that would ultimately reveal itself. Twenty six percent said this is probably seronegative RA. Eighteen percent, what I thought this could be, which is adult onset postarticular JIA, which is ANA positive.
I've got several of these patients, however, they do not seem to develop uveitis like the kids do, but that's something I'm watching for. And seven percent call this incomplete lupus. I think that's wrong. There's nothing about this that looks like or smells like lupus. So usually time ultimately makes a diagnosis in cases like this.
The question is, what are you gonna do until you make the diagnosis? I'm gonna treat what's present and move on. So let's move on to the next report. This is on statin safety coming from the American Heart Association, a very large study that basically shows with thousands and thousands of patients, almost forty percent or more, is that the number? Forty percent, one in four, I'm sorry, twenty five percent of adults over the age of 40 are taking a statin currently.
We know that statins save lives, we know statins lower lipid levels or LDL levels by 55 to 65%. What is the real numbers? What should you be quoting to your patients? They're always asking you, should I be on a statin? You're always wondering why they're stopping their statin.
The risk of statin induced rhabdo is one in a thousand, and probably that's the high end. The risk of severe hepatotoxicity from a statin is probably less than more than one in ten thousand. And the risk of a statin induced new diabetes, something I was really unaware of, is about two point two percent per year. So again, these numbers are really low. It seems like if properly monitored statins can be a significant advantage for patients who need them.
So there's two interesting studies that looked at comorbidities and vasculitis that I found interesting, and taught me something. And one report talks about the risk of developing vasculitis if you have an auto inflammatory disease. We know that FMF patients, for instance, get, PAN like disease and IgA, deposition vasculitis. We know that, small vessel vasculitis can be seen in patients with CAPS, the Cryopyran associated periodic syndromes, TRAPS, Hyper IgD syndrome, DIR, the deficiency of the IL-one, in, receptor, POPA and Behcet's, all small vessel vasculitis can occur. And then there's the Savi syndrome described recently by, Dan, Kastner and colleagues, that's the, DAD2 deficiency where they have sting associated vasculopathy with onset in infancy.
These kids, again, genetic it's disorder, do respond really, really well to Enbrel and TNF inhibitors. So that's kind of interesting and we should maybe watch out for that. Another meta analysis looked at the risk of developing comorbidities in patients with polymyalgia rheumatica, elderly, obviously they're going steroids. What other things do occur in these people? Well, CVA, coronary artery disease, peripheral artery disease, diverticular disease, hyperthyroidism are all significantly increased.
What is not so clear is whether there's an association between PMR and cancer risk there that's not borne out in these meta analyses of at least 41 papers studied by the authors. An interesting study looks at, the outcomes in systemic sclerosis patients, specifically looking at what lends to poor outcomes, specifically the risk of death. And they show in their study that early severe GI involvement, and that's seen by up to nine percent of people in the first two years, is associated with a twofold increased risk of death in patients with systemic sclerosis. Again, early, severe GI involvement, poor TENS, other bad things, including the risk of inflammatory myositis is fourfold higher, telangiectasis is two and a half fold higher, rapid and progression of skin disease again, twofold higher or more. So this is one of the bad prognostic signs in patients with scleroderma.
We need better markers, we need better therapies. This still is the great unmet need in rheumatology. A nice study looked at pregnancy in psoriasis patients, specifically psoriatic arthritis patients. This comes from Daphne Gleidman and colleagues and they looked at patients in Tel Aviv and in Toronto and enrolled seventy four PSA patients and seventy four match controls. And roughly each of these patients and controls had about two pregnancies.
And in the end, the outcomes were the same. The numbers of pregnancies, live births, gestational age, maternal and fetal complications, breastfeeding, breastfeeding outcomes, the same between the controls and PSA, which is an important message. And it's also good data, a lot of these patients continue to do pretty well, actually do well, and only minority get worse during their pregnancy. So this is encouraging data for those of you who manage psoriatic arthritis patients, telling them that they can get pregnant. Again, whether or not they're on therapies is really contingent upon their activity going into the pregnancy.
Healthy mother is needed to make a healthy baby, treat them if you need to, there's a lot of good therapies you can still use during pregnancy and not rely on steroids. There's another interesting article that we covered, which is really a spin off of the Washington newspapers report on, all I want for Christmas is my Shingrix vaccine. We called it no end in sight for the Shingrix vaccine shortage. As you know, this was approved about a year ago. It's outsold its projections, they've done very, very well.
It's estimated that in The United States, we will sell about 900,000,000 to a billion dollars worth of Shingrix in the first year. The problem is that there's a significant number of individuals, who have been unable to either get the vaccine or get their second dose of the vaccine. The manufacturer GSK makes this in Belgium, they said they've stepped up the production. As much as they say they're dealing with this, they don't give any real projections on when it's going to end. This problem started in May 2018, and is expected to continue into early twenty nineteen.
The manufacturer says that of all the people who've been prescribed this seventy percent have received the full two doses of the drug. But there still are a lot of patients and a lot of pharmacies are dealing with this. Pharmacies are no longer taking a waiting list because they don't know when this is going to end. The bottom line appears to be, maybe you should wait until unless the patient really needs it and you can get it, it's okay to wait until it becomes available. And the other thing is, we'd like to know about more about its safety in our patients with rheumatoid arthritis and lupus.
Not likely that's gonna be resolved anytime soon. The manufacturer has not indicated any interest in doing those studies. But again, this is not a live virus vaccine theoretically should be used. The question is, would our patients get worse on that? My opinion is I haven't seen that yet with a lot of inadvertent use and even out my instructions to go ahead and use it.
Again, it's two injections list price about $140 per injection. And again, we need more information, we need more vaccine. An interesting report also appeared this week in the New England Journal, brought to my attention by my partner, Doctor. Catherine Dow. And it's about the use of genetic diagnoses in patients with previously undiagnosed disorders.
The NIH has an undiagnosed disease network. They've taken in over 600 patients and accepted forty percent of them for evaluation. About a third of these people underwent exome genome sequencing prior to getting in. In the end, half of them underwent a complete evaluation. And that included again, exome sequencing, and they were able to achieve a diagnosis in thirty three percent.
Eleven percent were diagnosed clinically based on clinical grounds, but the majority of patients needed the exome and genome sequencing to make that diagnose. They made a diagnosis of thirty one new syndromes, one in five led to a change in therapy, thirty seven percent led to changes in diagnostic testing. Again, this might be the future. Other academic centers and, leaders in the community have talked about very difficult patients, undiagnosed patients, patients with fever even have undergone this whole exome sequencing. Used to be this with thousands and thousands of dollars.
I'm reading that the price has come way down, I wanna say $500 but don't quote me on that. It could even get cheaper as it gets more widely used. You may wanna consider this, for the future. There's a nice report about patients not telling the truth that appeared in MedPage today. This comes from two different surveys that were done of largely white individuals, mostly elderly, finding a sixty to eighty percent of patients, admit to not fully revealing the truth to their physicians.
And that includes up to eighty one percent said they avoided disclosing at least one type of information. Forty six percent disagreeing with the clinician's recommendation. Thirty one percent not understanding the clinician's instruction. Again, to eighty percent did not disclose this because they didn't wanna be judged or lectured to. Up to seventy five percent not wanting to hear how harmful their behavior was that they didn't want to reveal.
Sixty percent not wanting to be embarrassed during the visit. The bottom line is that those who are more likely to withhold information tend to be women and those who are younger and those who tended to rate their own health as being somewhat poor. Again, patients said things like I didn't want the provider to think I was difficult or stupid. I didn't wanna take up any more of the provider's time. I didn't think it mattered.
I didn't want this information in my medical record. This is scary. I tweeted this week all too often physicians think their job is to know the answer, fix the problem, when instead, much to our surprise, patients really need to be listened to, wanna know someone cares, want someone who won't judge their behaviors, and someone who actually displays a personality in caring. Then once you develop this bond, you might actually solve their problems. I think it's something we need to work on.
Again, I think we're great diagnosticians, we're really good at what we do, but we really need to meet the patient's needs and involves a lot more listening. I want to close with a reminder about RheumNow Live, 03/22/2019 in Fort Worth, Texas. We're going to have all the big names, all the big companies, all the big topics. I think you should attend. I think it's gonna be unlike any other meeting you've ever seen.
We did a survey of US rheumatologists on RheumNow and asked them what you want most from your CME programs. You said at the top of your list, topic reviews, online access, digital handouts, case presentations, Q and As, panels and a meeting recap were the most common things cited as things they'd like to see. What was least desirable were debates, promotional lectures or dinners, breakouts, working lunches and paper handouts. RheumNow Live is going to have reviews of JAKs, psoriatic arthritis therapies, comorbidities, dactylitis, enthesitis. There's gonna be online access, the lectures are shorter, everything's maxed out at thirty minutes.
We're having thirty minute panel discussions, there's digital handouts. All of the lectures have to have case presentations and then I can't see why you really would enjoy this meeting. Come, we'll enjoy seeing you there.
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